Three patients with signs of acute flail mitral leaflet seen on emergency department echo: a critical constellation within the focused cardiac exam

PubMed Central

Stephenson, George; Wallace, Craig; Mao, Pras; Moore, Chris

2015-01-01

Abstract Acute flail mitral leaflet is a time‐sensitive, reversible cause of cardiogenic shock. Transthoracic echocardiography (echo) is increasingly becoming a vital tool for non‐cardiologist physicians who treat patients with undifferentiated chest pain and dyspnoea. The sonographic abnormalities seen in acute flail mitral leaflet are within the boundaries of a focused echo. Individually, these findings are non‐specific. As a constellation, however, they are highly suggestive of this disease process. We present a case series of three patients with acute flail mitral leaflet seen on emergency department echo along with a discussion of the findings and the disease itself. PMID:28191212

Hypoplasia or Absence of Posterior Leaflet: A Rare Congenital Anomaly of The Mitral Valve in Adulthood - Case Series.

PubMed

Parato, Vito Maurizio; Masia, Stefano Lucio

2018-01-01

We present a case series of two adult patients with almost complete absence of the posterior mitral valve leaflet and who are asymptomatic or mildly symptomatic, with two different degrees of mitral regurgitation.

Distribution of the microelastic properties within the human anterior mitral leaflet.

PubMed

Jensen, Anne Skakkebaek; Baandrup, Ulrik; Hasenkam, J Michael; Kundu, Tribikram; Jørgensen, Claus Schiøtt

2006-12-01

Knowledge of the biomechanical properties of the mitral valve leaflets and their relation to histologic structure is of importance for understanding the leaflet movement characteristics under normal and pathologic conditions, but such knowledge is not yet available. The aim of this study was to determine biomechanical properties of the human anterior mitral leaflet on a microscopic scale. We used scanning acoustic microscopy (SAM) to examine the human anterior mitral leaflet. Sections of fixed human anterior mitral leaflet tissue were obtained from postmortem human anterior mitral leaflets (n = 5). We measured the speed of sound (nu(L)) in each histologic layer in three regions-of-interest (ROIs): these were at the annular edge, at the valve midpoint and close to the free edge. nu(L) varied in the three histologic layers (p < 0.01). It was higher in the fibrous layer (1.76 km/s) compared with the atrial layer (1.75 km/s) and ventricular layer (1.73 km/s). Also, nu(L) differed between positions along the length of the annulus-free edge line (p < 0.01), showing a decline from the annular edge (1.76 km/s) to the free edge (1.73 km/s), both as a whole and also within the atrial and the fibrous layer. These results demonstrate that the fibrous layer is stiffer than the atrial and ventricular layer and that the leaflet as a whole and within the atrial and the fibrous layer is stiffer at the annulus part in comparison with those near the free edge. (E-mail: ).

Treatment of severe mitral regurgitation caused by lesions in both leaflets using multiple mitral valve plasty techniques in a small dog

PubMed Central

Yokoyama, Satoko; Kanemoto, Isamu; Mihara, Kippei; Ando, Takanori; Kawase, Koudai; Sahashi, Yasuaki; Iguchi, Kazuhito

2017-01-01

Mitral valve plasty (MVP) is preferred over mitral valve replacement (MVR) for mitral regurgitation in humans because of its favorable effect on quality of life. In small dogs, it is difficult to repair multiple lesions in both leaflets using MVP. Herein, we report a case of severe mitral regurgitation caused by multiple severe lesions in the posterior leaflet (PL) in a mixed Chihuahua. Initially, we had planned MVR with an artificial valve. However, MVP combined with artificial chordal reconstruction of both leaflets, semicircular suture annuloplasty, and valvuloplasty using a newly devised direct scallop suture for the PL was attempted in this dog. The dog recovered well and showed no adverse cardiac signs, surviving two major operations. The dog died 4 years and 10 months after the MVP due to non-cardiovascular disease. Our additional technique of using a direct scallop suture seemed useful for PL repair involving multiple scallops in a small dog. PMID:29201662

Severe mitral regurgitation due to mitral leaflet aneurysm diagnosed by three-dimensional transesophageal echocardiography: a case report.

PubMed

Konishi, Takao; Funayama, Naohiro; Yamamoto, Tadashi; Hotta, Daisuke; Kikuchi, Kenjiro; Ohori, Katsumi; Nishihara, Hiroshi; Tanaka, Shinya

2016-11-22

A small mitral valve aneurysm (MVA) presenting as severe mitral regurgitation (MR) is uncommon. A 47-year-old man with a history of hypertension complained of exertional chest discomfort. A transthoracic echocardiogram (TTE) revealed the presence of MR and prolapse of the posterior leaflet. A 6-mm in diameter MVA, not clearly visualized by TTE, was detected on the posterior leaflet on a three-dimensional (3D) transesophageal echocardiography (TEE). The patient underwent uncomplicated triangular resection of P2 and mitral valve annuloplasty, and was discharged from postoperative rehabilitation, 2 weeks after the operation. Histopathology of the excised leaflet showed myxomatous changes without infective vegetation or signs of rheumatic heart disease. A small, isolated MVA is a cause of severe MR, which might be overlooked and, therefore, managed belatedly. 3D TEE was helpful in imaging its morphologic details.

Partial hammock valve: surgical repair in adulthood.

PubMed

Aramendi, José I; Rodríguez, Miguel A; Voces, Roberto; Pérez, Pedro; Rodrigo, David

2006-09-01

We describe a forme frustrée of hammock valve involving only the posterior mitral leaflet. Three adult patients were referred to surgery with the diagnosis of severe mitral regurgitation due to fibrosis of the posterior mitral leaflet. The final diagnosis was done intraoperatively. In all of them the posterior leaflet was attached to some accessory papillary muscles arranged en palisade, with three to four fused muscle heads producing restrictive leaflet motion in systole. Repair consisted in division of the papillary muscles, patch augmentation, and ring annuloplasty. This previously unreported lesion is congenital but manifests itself in adulthood.

Hypoplasia or Absence of Posterior Leaflet: A Rare Congenital Anomaly of The Mitral Valve in Adulthood – Case Series

PubMed Central

Parato, Vito Maurizio; Masia, Stefano Lucio

2018-01-01

We present a case series of two adult patients with almost complete absence of the posterior mitral valve leaflet and who are asymptomatic or mildly symptomatic, with two different degrees of mitral regurgitation. PMID:29629259

Efficacy of chordal cutting in alleviating ischemic mitral regurgitation: insights from 3-dimensional echocardiography

PubMed Central

Sai-Sudhakar, Chittoor B; Vandse, Rashmi; Armen, Todd A; Bickle, Katherine M; Nathan, Nadia S

2007-01-01

Background Ischemic mitral regurgitation often complicates severe ischemic heart disease and adversely affects the prognosis in these patients. There is wide variation in the clinical spectrum of ischemic mitral regurgitation due to varying location and chronicity of ischemia and anomalies in annular and ventricular remodeling. As a result, there is lack of consensus in treating these patients. Treatment has to be individualized for each patient. Most of the available surgical options do not consistently correct this condition in all the patients. Chordal cutting is one of the newer surgical approaches in which cutting a limited number of critically positioned basal chordae have found success by relieving the leaflet tethering and thereby improving the coaptation of leaflets. Three-dimensional echocardiography is a potentially valuable tool in identifying the specific pattern of tethering and thus the suitability of this procedure in a given clinical scenario. Case Presentation A 66-year-old man with cardiomyopathy and ischemic mitral regurgitation presented to us with the features of congestive heart failure. The three-dimensional echocardiography revealed severe mitral regurgitation associated with the tethering of the lateral (P1) and medial (P3) scallops of the posterior leaflet of the mitral valve due to secondary chordal attachments. The ejection fraction was only 15% with severe global systolic and diastolic dysfunction. Mitral regurgitation was successfully corrected with mitral annuloplasty and resection of the secondary chordae tethering the medial and lateral scallops of the posterior leaflet of the mitral valve. Conclusion Cutting the second order chordae along with mitral annuloplasty could be a novel method to remedy Ischemic mitral regurgitation by relieving the tethering of the valve leaflets. The preoperative three-dimensional echocardiography should be considered in all patients with Ischemic mitral regurgitation to assess the complex three-dimensional interactions between the mitral valve apparatus and the left ventricle. This aids in timely surgical planning. PMID:17894872

Efficacy of chordal cutting in alleviating ischemic mitral regurgitation: insights from 3-dimensional echocardiography.

PubMed

Sai-Sudhakar, Chittoor B; Vandse, Rashmi; Armen, Todd A; Bickle, Katherine M; Nathan, Nadia S

2007-09-25

Ischemic mitral regurgitation often complicates severe ischemic heart disease and adversely affects the prognosis in these patients. There is wide variation in the clinical spectrum of ischemic mitral regurgitation due to varying location and chronicity of ischemia and anomalies in annular and ventricular remodeling. As a result, there is lack of consensus in treating these patients. Treatment has to be individualized for each patient. Most of the available surgical options do not consistently correct this condition in all the patients. Chordal cutting is one of the newer surgical approaches in which cutting a limited number of critically positioned basal chordae have found success by relieving the leaflet tethering and thereby improving the coaptation of leaflets. Three-dimensional echocardiography is a potentially valuable tool in identifying the specific pattern of tethering and thus the suitability of this procedure in a given clinical scenario. A 66-year-old man with cardiomyopathy and ischemic mitral regurgitation presented to us with the features of congestive heart failure. The three-dimensional echocardiography revealed severe mitral regurgitation associated with the tethering of the lateral (P1) and medial (P3) scallops of the posterior leaflet of the mitral valve due to secondary chordal attachments. The ejection fraction was only 15% with severe global systolic and diastolic dysfunction. Mitral regurgitation was successfully corrected with mitral annuloplasty and resection of the secondary chordae tethering the medial and lateral scallops of the posterior leaflet of the mitral valve. Cutting the second order chordae along with mitral annuloplasty could be a novel method to remedy Ischemic mitral regurgitation by relieving the tethering of the valve leaflets. The preoperative three-dimensional echocardiography should be considered in all patients with Ischemic mitral regurgitation to assess the complex three-dimensional interactions between the mitral valve apparatus and the left ventricle. This aids in timely surgical planning.

[TECHNIQUES IN MITRAL VALVE REPAIR VIA A MINIMALLY INVASIVE APPROACH].

PubMed

Ito, Toshiaki

2016-03-01

In mitral valve repair via a minimally invasive approach, resection of the leaflet is technically demanding compared with that in the standard approach. For resection and suture repair of the posterior leaflet, premarking of incision lines is recommended for precise resection. As an alternative to resection and suture, the leaflet-folding technique is also recommended. For correction of prolapse of the anterior leaflet, neochordae placement with the loop technique is easy to perform. Premeasurement with transesophageal echocardiography or intraoperative measurement using a replica of artificial chordae is useful to determine the appropriate length of the loops. Fine-tuning of the length of neochordae is possible by adding a secondary fixation point on the leaflet if the loop is too long. If the loop is too short, a CV5 Gore-Tex suture can be passed through the loop and loosely tied several times to stack the knots, with subsequent fixation to the edge of the leaflet. Finally, skill in the mitral valve replacement technique is necessary as a back-up for surgeons who perform minimally invasive mitral valve repair.

Robotic Posterior Mitral Leaflet Repair: Neochordal versus Resectional Techniques

PubMed Central

Mihaljevic, Tomislav; Pattakos, Gregory; Gillinov, A. Marc; Bajwa, Gurjyot; Planinc, Mislav; Williams, Sarah J.; Blackstone, Eugene H.

2013-01-01

Background Resectional techniques are the established method of posterior mitral valve leaflet repair for degenerative disease; however, use of neochordae in a robotically assisted approach is gaining acceptance because of its versatility for difficult multi-segment disease. The purposes of this study were to compare the versatility, safety, and effectiveness of neochordal vs. resectional techniques for robotic posterior mitral leaflet repair. Methods From 12/2007 to 7/2010, 334 patients underwent robotic posterior mitral leaflet repair for degenerative disease by a resectional (n=248) or neochordal (n=86) technique. Outcomes were compared unadjusted and after propensity score matching. Results Neochordae were more likely to be used than resection in patients with two (28% vs. 13%, P=.002) or three (3.7% vs. 0.87%, P=.08) diseased posterior leaflet segments. Three resection patients (0.98%) but no neochordal patient required reoperation for hemodynamically significant systolic anterior motion (SAM). Residual mitral regurgitation (MR) at hospital discharge was similar for matched neochordal vs. resection patients (P=.14) (MR 0+, 82% vs. 89%; MR 1+, 14% vs. 8.2%; MR 2+, 2.3% vs. 2.6%; one neochordal patient had 4+ MR and was reoperated). Among matched patients, postoperative mortality and morbidity were similarly low. Conclusion Compared with a resectional technique, robotic posterior mitral leaflet repair with neochordae is associated with shorter operative times and no occurrence of SAM. The versatility, effectiveness, and safety of this repair make it a good choice for patients with advanced multi-segment disease. PMID:23103008

Acute Mitral Valve Dysfunction Due to Escape of Prosthetic Mechanical Leaflet and Peripheral Leaftlet Embolization.

PubMed

Calik, Eyup Serhat; Limandal, Husnu Kamil; Arslan, Umit; Tort, Mehmet; Yildiz, Ziya; Bayram, Ednan; Dag, Ozgur; Kaygin, Mehmet Ali; Erkut, Bilgehan

2015-12-14

Leaflet escape of prosthetic valve is rare but potentially life threatening. Early diagnosis is essential on account of avoiding mortality, and emergency surgical correction is compulsory. This complication has previously been reported for both monoleaflet and bileaflet valve models. A 30-year-old man who had undergone mitral valve replacement with a bileaflet valve 8 years prior at another center was admitted with acute-onset with cardiogenic shock as an emergency case. Transthoracic echocardiograms showed acute-starting severe mitral regurgitation associated with prosthetic mitral valve. There was a suspicious finding of a single prosthetic mitral leaflet. But the problem related with the valve wasn't specifically determined. The patient underwent emergent surgery for replacement of the damaged prosthetic valves immediately. There was no tissue impingement and thrombosis, one of the two leaflets was absent, and there were no signs of endocarditis or pannus formation in the prosthetic valve. The missing leaflet could not be found within the cardiac cavity. The abdominal fluoroscopic study and plain radiography were unable to detect the escaped leaflet during surgery. The damaged valve was removed and a replacement 29 mm bileaflet mechanical valve was inserted by right lateral thoracotomy. After post-operative week one, the abdominal computed tomography scan and the ultrasound showed the escaped leaflet in the left femoral artery. Fifteen days after the surgery the escaped leaflet was removed safely from the left femoral artery and the patient made a complete recovery. The escaped leaflet showed a fracture of one of the pivot systems caused by structural failure. Early cardiac surgery should be applied because of life-threatening problems.

A Ruptured Mitral Valve Aneurysm as Complication of a Bicuspid Aortic Valve Endocarditis.

PubMed

Muscente, Francesca; Scarano, Michele; Clemente, Daniela; Pezzuoli, Franco; Parato, Vito Maurizio

2017-01-01

We present a case of a ruptured mitral valve (MV) aneurysm as a complication of a bicuspid aortic valve (BAV) endocarditis. It is about a young 35-year-old man, admitted to Cardiology Unit because of unexpected heart failure picture. We found a BAV endocarditis complicated by anterior MV-anterior leaflet aneurysm formation and subsequent severe MV regurgitation caused by aneurysm perforation. It was a particular and rare situation characterized by an infection of anterior mitral leaflet secondary to an infected regurgitant jet of a primary aortic infective endocarditis due to a BAV. A resulting aneurysm formation on the atrial side of the mitral anterior leaflet leads later to mitral perforation. In this article, we review the more relevant medical literature on this topic.

Mitral valve repair using ePTFE sutures for ruptured mitral chordae tendineae: a computational simulation study.

PubMed

Rim, Yonghoon; Laing, Susan T; McPherson, David D; Kim, Hyunggun

2014-01-01

Mitral valve (MV) repair using expanded polytetrafluoroethylene sutures is an established and preferred interventional method to resolve the complex pathophysiologic problems associated with chordal rupture. We developed a novel computational evaluation protocol to determine the effect of the artificial sutures on restoring MV function following valve repair. A virtual MV was created using three-dimensional echocardiographic data in a patient with ruptured mitral chordae tendineae (RMCT). Virtual repairs were designed by adding artificial sutures between the papillary muscles and the posterior leaflet where the native chordae were ruptured. Dynamic finite element simulations were performed to evaluate pre- and post-repair MV function. Abnormal posterior leaflet prolapse and mitral regurgitation was clearly demonstrated in the MV with ruptured chordae. Following virtual repair to reconstruct ruptured chordae, the severity of the posterior leaflet prolapse decreased and stress concentration was markedly reduced both in the leaflet tissue and the intact native chordae. Complete leaflet coaptation was restored when four or six sutures were utilized. Computational simulations provided quantitative information of functional improvement following MV repair. This novel simulation strategy may provide a powerful tool for evaluation and prediction of interventional treatment for RMCT.

Isolated effect of geometry on mitral valve function for in silico model development.

PubMed

Siefert, Andrew William; Rabbah, Jean-Pierre Michel; Saikrishnan, Neelakantan; Kunzelman, Karyn Susanne; Yoganathan, Ajit Prithivaraj

2015-01-01

Computational models for the heart's mitral valve (MV) exhibit several uncertainties that may be reduced by further developing these models using ground-truth data-sets. This study generated a ground-truth data-set by quantifying the effects of isolated mitral annular flattening, symmetric annular dilatation, symmetric papillary muscle (PM) displacement and asymmetric PM displacement on leaflet coaptation, mitral regurgitation (MR) and anterior leaflet strain. MVs were mounted in an in vitro left heart simulator and tested under pulsatile haemodynamics. Mitral leaflet coaptation length, coaptation depth, tenting area, MR volume, MR jet direction and anterior leaflet strain in the radial and circumferential directions were successfully quantified at increasing levels of geometric distortion. From these data, increase in the levels of isolated PM displacement resulted in the greatest mean change in coaptation depth (70% increase), tenting area (150% increase) and radial leaflet strain (37% increase) while annular dilatation resulted in the largest mean change in coaptation length (50% decrease) and regurgitation volume (134% increase). Regurgitant jets were centrally located for symmetric annular dilatation and symmetric PM displacement. Asymmetric PM displacement resulted in asymmetrically directed jets. Peak changes in anterior leaflet strain in the circumferential direction were smaller and exhibited non-significant differences across the tested conditions. When used together, this ground-truth data-set may be used to parametrically evaluate and develop modelling assumptions for both the MV leaflets and subvalvular apparatus. This novel data may improve MV computational models and provide a platform for the development of future surgical planning tools.

Fluid-Structure Interaction and Structural Analyses using a Comprehensive Mitral Valve Model with 3D Chordal Structure

PubMed Central

Toma, Milan; Einstein, Daniel R.; Bloodworth, Charles H.; Cochran, Richard P.; Yoganathan, Ajit P.; Kunzelman, Karyn S.

2016-01-01

Over the years, three-dimensional models of the mitral valve have generally been organized around a simplified anatomy. Leaflets have been typically modeled as membranes, tethered to discrete chordae typically modeled as one-dimensional, non-linear cables. Yet, recent, high-resolution medical images have revealed that there is no clear boundary between the chordae and the leaflets. In fact, the mitral valve has been revealed to be more of a webbed structure whose architecture is continuous with the chordae and their extensions into the leaflets. Such detailed images can serve as the basis of anatomically accurate, subject-specific models, wherein the entire valve is modeled with solid elements that more faithfully represent the chordae, the leaflets, and the transition between the two. These models have the potential to enhance our understanding of mitral valve mechanics, and to re-examine the role of the mitral valve chordae, which heretofore have been considered to be “invisible” to the fluid and to be of secondary importance to the leaflets. However, these new models also require a rethinking of modeling assumptions. In this study, we examine the conventional practice of loading the leaflets only and not the chordae in order to study the structural response of the mitral valve apparatus. Specifically, we demonstrate that fully resolved 3D models of the mitral valve require a fluid-structure interaction analysis to correctly load the valve even in the case of quasi-static mechanics. While a fluid-structure interaction mode is still more computationally expensive than a structural-only model, we also show that advances in GPU computing have made such models tractable. PMID:27342229

Fluid-structure interaction and structural analyses using a comprehensive mitral valve model with 3D chordal structure.

PubMed

Toma, Milan; Einstein, Daniel R; Bloodworth, Charles H; Cochran, Richard P; Yoganathan, Ajit P; Kunzelman, Karyn S

2017-04-01

Over the years, three-dimensional models of the mitral valve have generally been organized around a simplified anatomy. Leaflets have been typically modeled as membranes, tethered to discrete chordae typically modeled as one-dimensional, non-linear cables. Yet, recent, high-resolution medical images have revealed that there is no clear boundary between the chordae and the leaflets. In fact, the mitral valve has been revealed to be more of a webbed structure whose architecture is continuous with the chordae and their extensions into the leaflets. Such detailed images can serve as the basis of anatomically accurate, subject-specific models, wherein the entire valve is modeled with solid elements that more faithfully represent the chordae, the leaflets, and the transition between the two. These models have the potential to enhance our understanding of mitral valve mechanics and to re-examine the role of the mitral valve chordae, which heretofore have been considered to be 'invisible' to the fluid and to be of secondary importance to the leaflets. However, these new models also require a rethinking of modeling assumptions. In this study, we examine the conventional practice of loading the leaflets only and not the chordae in order to study the structural response of the mitral valve apparatus. Specifically, we demonstrate that fully resolved 3D models of the mitral valve require a fluid-structure interaction analysis to correctly load the valve even in the case of quasi-static mechanics. While a fluid-structure interaction mode is still more computationally expensive than a structural-only model, we also show that advances in GPU computing have made such models tractable. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Posterior leaflet preservation during mitral valve replacement for rheumatic mitral stenosis.

PubMed

Djukić, P L; Obrenović-Kirćanski, B B; Vranes, M R; Kocica, M J; Mikić, A Dj; Velinović, M M; Kacar, S M; Kovacević, N S; Parapid, B J

2006-01-01

Mitral valve replacement with posterior leaflet preservation was shown beneficial for postoperative left vetricular (LV) performance in patients with mitral regurgitation. Some authors find it beneficial even for the long term LV function. We investigated a long term effect of this technique in patients with rheumatic mitral stenosis. We studied 20 patents with mitral valve replacement due to rheumatic mitral stenosis, in the period from January 1988 to December 1989. In group A (10 patients) both leaflets and coresponding chordal excision was performed, while in group B (10 patients) the posterior leaflet was preserved. In all patients a Carbomedics valve was inserted. We compared clinical pre and postoperative status, as well as hemodynamic characteristics of the valve and left ventricle in both groups. Control echocardiographyc analysis included: maximal (PG) and mean (MG) gradients; effective valve area (AREA); telediastolic (TDV) and telesystolic (TSV) LV volume; stroke volume (SV); ejection fraction (EF); fractional shortening (FS) and segmental LV motion. The mean size of inserted valve was 26.6 in group A and 27.2 in group B. Hemodynamic data: PG (10.12 vs 11.1); MG (3.57 vs 3.87); AREA (2.35 vs 2.30); TDV 126.0 vs 114.5); TSV (42.2 vs 36.62); SV (83.7 vs 77.75); EF (63.66 vs 67.12); FS (32.66 vs 38.25). Diaphragmal segmental hypokinesis was evident in one patient from group A and in two patients from group B. In patients with rheumatic stenosis, posterior leaflet preservation did not have increased beneficial effect on left ventricular performance during long-term follow-up. An adequate posterior leaflet preservation does not change hemodynamic valvular characteristics even after long-term follow-up.

Tissue Doppler imaging and echo-Doppler findings associated with a mitral valve stenosis with an immobile posterior valve leaflet in a bull terrier.

PubMed

Tidholm, A; Nicolle, A P; Carlos, C; Gouni, V; Caruso, J L; Pouchelon, J L; Chetboul, V

2004-04-01

A mitral valve stenosis was diagnosed in a 2-year-old female Bull Terrier by use of two-dimensional (2-D) and M-mode echocardiography, colour-flow imaging and spectral Doppler examinations. Tissue Doppler Imaging was also performed to assess the segmental radial myocardial motion. The mitral valve stenosis was characterized by a decreased mitral orifice area/left ventricle area ratio (0.14), an increased early diastolic flow velocity (E wave = 1.9 m/s), a prolonged pressure half-time (106 ms) and a decreased E-F slope (4.5 cm/s) on pulsed-wave Doppler examination. This mitral stenosis was associated with an immobile posterior leaflet, as seen on 2-D and M-mode echocardiography. Immobility of the posterior mitral leaflet is considered to be a rare finding in humans and, to our knowledge, has not been precisely documented in dogs with mitral valve stenosis.

Early Activation of Growth Pathways in Mitral Leaflets Exposed to Aortic Regurgitation: New Insights from an Animal Model.

PubMed

Marsit, Ons; Royer, Olivier; Drolet, Marie-Claude; Arsenault, Marie; Couet, Jacques; Morin, Stéphane; Levine, Robert A; Pibarot, Philippe; Beaudoin, Jonathan

2017-05-01

Mitral leaflet enlargement in patients with chronic aortic regurgitation (AR) has been identified as an adaptive mechanism potentially able to prevent functional mitral regurgitation (FMR) in response to left ventricular (LV) dilatation. The timing of valve enlargement is not known, and the related mechanisms are largely unexplored. AR was induced in 58 rats, and another 54 were used as sham controls. Animals were euthanized at different time points after AR creation (48 h, one week, and three months), and AR severity, FMR and LV dilatation were assessed using echocardiography. Mitral valves were harvested to document the reactivation of embryonic growth pathways. AR animals had increased LV dimensions and mitral annulus size. No animal developed FMR. No change in leaflet length or thickness was seen at 48 h; however, anterior mitral leaflets were longer and thicker in AR animals at one week and three months. Molecular changes were present early (at 48 h and at one week), with positive staining for transforming growth factor-b1 (TGF-b1), Alpha-smooth muscle actin (α-SMA) and matrix metalloproteinase-2 (MMP-2), which suggested active matrix remodeling. Increased gene expression for collagen 1, TGF-β1, α-SMA and MMP-2 was found in the mitral valve at 48 h and at one week, but after three months their expression had returned to normal. This model of AR induces active expansion and thickening of the mitral leaflets. Growth signals are expressed acutely, but not at three months, which suggests that most of this enlargement occurs at an early stage. The stimulation of valvular growth could represent a new strategy for the prevention of FMR.

Correction of anterior mitral prolapse: the parachute technique.

PubMed

Zannis, Konstantinos; Mitchell-Heggs, Laurens; Di Nitto, Valentina; Kirsch, Matthias E W; Noghin, Milena; Ghorayeb, Gabriel; Lessana, Arrigo

2012-04-01

To evaluate a new surgical technique for the correction of anterior mitral leaflet prolapse. From October 2006 to November 2011, 44 consecutive patients (28 males, mean age 55 ± 13 years) underwent mitral valve repair because of anterior mitral leaflet prolapse. Echocardiography was performed to evaluate the distance from the tip of each papillary muscle to the annular plane. A specially designed caliper was used to manufacture a parachute-like device, by looping a 4-0 polytetrafluoroethylene suture between a Dacron strip and Teflon felt pledget, according to the preoperative echocardiographic measurements. This parachute was then used to resuspend the anterior mitral leaflet to the corresponding papillary muscle. Of the 44 patients, 35 (80%) required concomitant posterior leaflet repair. Additional procedures were required in 16 patients (36%). The preoperative logistic European System for Cardiac Operative Risk Evaluation was 4.3 ± 6.9. The clinical and echocardiographic follow-up were complete. The total follow-up was 1031 patient-months and averaged 23.4 ± 17.2 months per patient. The overall mortality rate was 4.5% (n = 2). Also, 2 patients (4.5%) with recurrent mitral regurgitation required mitral valve replacement, 1 on the first postoperative day and 1 after 13 months. In the latter patient, histologic analysis showed complete endothelialization of the Dacron strip. At follow-up, all non-reoperated survivors (n = 40) were in New York Heart Association class I, with no regurgitation in 40 patients (93%) and grade 2+ mitral regurgitation in 3 (7%). This technique offers a simple and reproducible solution for correction of anterior leaflet prolapse. Echocardiography can reliably evaluate the length of the chordae. However, the long-term results must be evaluated and compared with other surgical strategies. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Flow-Induced Mitral Leaflet Motion in Hypertrophic Cardiomyopathy

NASA Astrophysics Data System (ADS)

Meschini, Valentina; Mittal, Rajat; Verzicco, Roberto

2017-11-01

Hypertrophic cardiomyopathy (HCM) is considered the cause of sudden cardiac death in developed countries. Clinically it is found to be related to the thickening of the intra-ventricular septum combined with elongated mitral leaflets. During systole the low pressure, induced by the abnormal velocities in the narrowed aortic channel, can attract one or both the mitral leaflets causing the aortic obstruction and sometimes instantaneous death. In this paper a fluid structure interaction model for the flow in the left ventricle with a native mitral valve is employed to investigate the physio-pathology of HCM. The problem is studied using direct numerical simulations of the Navier-Stokes equations with a two-way coupled structural solver based on interaction potential approach for the structure dynamics. Simulations are performed for two different degrees of hypertrophy, and two values of pumping efficiency. The leaflets dynamics and the ventricle deformation resulting from the echocardiography of patients affected by HCM are well captured by the simulations. Moreover, the procedures of leaflets plication and septum myectomy are simulated in order to get insights into the efficiency and reliability of such surgery.

Isolated Effect of Geometry on Mitral Valve Function for In-Silico Model Development

PubMed Central

Siefert, Andrew William; Rabbah, Jean-Pierre Michel; Saikrishnan, Neelakantan; Kunzelman, Karyn Susanne; Yoganathan, Ajit Prithivaraj

2013-01-01

Computational models for the heart’s mitral valve (MV) exhibit several uncertainties which may be reduced by further developing these models using ground-truth data sets. The present study generated a ground-truth data set by quantifying the effects of isolated mitral annular flattening, symmetric annular dilatation, symmetric papillary muscle displacement, and asymmetric papillary muscle displacement on leaflet coaptation, mitral regurgitation (MR), and anterior leaflet strain. MVs were mounted in an in vitro left heart simulator and tested under pulsatile hemodynamics. Mitral leaflet coaptation length, coaptation depth, tenting area, MR volume, MR jet direction, and anterior leaflet strain in the radial and circumferential directions were successfully quantified for increasing levels of geometric distortion. From these data, increasing levels of isolated papillary muscle displacement resulted in the greatest mean change in coaptation depth (70% increase), tenting area (150% increase), and radial leaflet strain (37% increase) while annular dilatation resulted in the largest mean change in coaptation length (50% decrease) and regurgitation volume (134% increase). Regurgitant jets were centrally located for symmetric annular dilatation and symmetric papillary muscle displacement. Asymmetric papillary muscle displacement resulted in asymmetrically directed jets. Peak changes in anterior leaflet strain in the circumferential direction were smaller and exhibited non-significant differences across the tested conditions. When used together, this ground-truth data may be used to parametrically evaluate and develop modeling assumptions for both the MV leaflets and subvalvular apparatus. This novel data may improve MV computational models and provide a platform for the development of future surgical planning tools. PMID:24059354

Basic Mechanisms of Mitral Regurgitation

PubMed Central

Dal-Bianco, Jacob P.; Beaudoin, Jonathan

2014-01-01

Any structural or functional impairment of the mitral valve (MV) apparatus that exhausts MV tissue redundancy available for leaflet coaptation will result in mitral regurgitation (MR). The mechanism responsible for MV malcoaptation and MR can be dysfunction or structural change of the left ventricle, the papillary muscles, the chordae tendineae, the mitral annulus and the MV leaflets. The rationale for MV treatment depends on the MR mechanism and therefore it is essential to identify and understand normal and abnormal MV and MV apparatus function. PMID:25151282

Calcification of the mitral valve and annulus: systematic evaluation of effects on valve anatomy and function.

PubMed

Movva, Rajesh; Murthy, Kinnari; Romero-Corral, Abel; Seetha Rammohan, Harish Raj; Fumo, Peter; Pressman, Gregg S

2013-10-01

Mitral annular calcification (MAC) is common in chronic kidney disease. It is associated with cardiovascular events and can cause valvular dysfunction, but it has not been systematically characterized. The aim of this prospective study was to assess the prevalence and distribution of MAC, its effects on leaflet motion, and its association with mitral stenosis and mitral regurgitation (MR) in a hemodialysis population. Echocardiograms were obtained in 75 consecutive hemodialysis outpatients. MAC extent and distribution were graded semiquantitatively using two-dimensional and three-dimensional echocardiography. Associations with the presence and severity of mitral stenosis and MR were explored. The mean age was 60 ± 14 years; 60% were men, and 87% were African American. MAC was present in 64% (moderate to severe in 48%). Calcium extended more than halfway onto the leaflet in 37% and beyond the annulus in 40%. Leaflet motion was restricted in 37%. Mitral stenosis was present in 28%, and the extent of calcification was associated with mean mitral valve gradient (P < .0001). MR was prevalent (present in 81%) but was severe in none. The severity of MAC was greater in patients with moderate MR than in those with no or mild MR (P = .04). Three-dimensional analysis suggested an uneven distribution of annular calcium; the middle and lateral anterior segments were less often calcified than the anterior-medial or posterior segments. Calcification in any annular segment was highly associated with restricted motion of the attached leaflet segment. MAC is common and often extensive in hemodialysis patients. Calcium may be unevenly distributed among the annular segments. When present, annular calcification reduces the angle of leaflet opening and can cause valvular dysfunction. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Measured posterior annuloplasty for repair of non-ischemic mitral regurgitation. A single unit follow-up.

PubMed

Jyrala, Aarne; Gatto, Nicole M; Kay, Gregory L

2010-01-01

The aim of this report is to evaluate short- and long-term outcomes of annuloplasty method of our choice: measured posterior annuloplasty (MPA). MPA is a piece of a Duran ring cut to the length of free-edge of anterior mitral leaflet (AML) and anchored with multiple pledgeted U-sutures from trigone to trigone into the posterior annulus. From 1988 to 2000, 103 consecutive patients with non-ischemic mitral regurgitation were scheduled preoperatively to be repaired by MPA. Preoperative mitral valve regurgitation (MR) grade was 3.8+/-0.5 and decreased to 0.1+/-0.3 (P<0.0001) after repair. One patient was converted to insertion of mechanical prosthesis after grade 3 MR persisted after septal myectomy and MPA. Three patients needed instant revision of the repair one due to SAM and two due to stenosis. No patient had a stenosis or unacceptable (>1) MR after the procedure. There was one operative death (1.0%) and 3 hospital/30-day deaths (2.9%). Sixteen patients (16.3%) expired during the follow-up to 91 months (mean 57.4+/-19.5, median 60 months) none due to failure of MPA. There were no reoperations due to failure of MPA. Three patients had a reoperation, one for dehiscence of reconstruction after P2 resection and two patients due to progression of anterior leaflet degeneration and calcification with 4+ MR. New York Heart Association (NYHA) functional classification decreased from 2.3+/-0.8 to 1.4+/-0.6 (P<0.0001) and only one patient had an increase from II to III. Eighty-eight patients (96.7%) were in NYHA class I-II. Ten patients had an increase of MR from 0 to trace or 1 and one from 0 to 2. Two patients were diagnosed with mild stenosis without need of reoperation. MPA is a durable and stable alternative for repair of non-ischemic mitral regurgitation of different etiologies. The technique gives an objective measure of the length of the band and no patient is left with a significant MR or mitral valve stenosis (MS). First-time success rate is very high and instant repairs few and minor. Freedom of MPA related reoperations is 100%.

Finite element analysis for edge-to-edge technique to treat post-mitral valve repair systolic anterior motion.

PubMed

Zhong, Qi; Zeng, Wenhua; Huang, Xiaoyang; Zhao, Xiaojia

2014-01-01

Systolic anterior motion of the mitral valve is an uncommon complication of mitral valve repair, which requires immediate supplementary surgical action. Edge-to-edge suture is considered as an effective technique to treat post-mitral valve repair systolic anterior motion by clinical researchers. However, the fundamentals and quantitative analysis are vacant to validate the effectiveness of the additional edge-to-edge surgery to repair systolic anterior motion. In the present work, finite element models were developed to simulate a specific clinical surgery for patients with posterior leaflet prolapse, so as to analyze the edge-to-edge technique quantificationally. The simulated surgery procedure concluded several actions such as quadrangular resection, mitral annuloplasty and edge-to-edge suture. And the simulated results were compared with echocardiography and measurement data of the patients under the mitral valve surgery, which shows good agreement. The leaflets model with additional edge-to-edge suture has a shorter mismatch length than that of the model merely under quadrangular resection and mitral annuloplasty actions at systole, which assures a better coaptation status. The stress on the leaflets after edge-to-edge suture is lessened as well.

Mechanism of valvular regurgitation.

PubMed

Khoo, Nee S; Smallhorn, Jeffery F

2011-10-01

Despite improvements in surgical techniques, valvular regurgitation results in major morbidity in children with heart disease. Functional anatomy, mechanisms of valve closure and adaptation to changing hemodynamic stress in normal mitral and tricuspid valves are complex and only partially understood. As well, pathology of atrioventricular valve regurgitation is further complicated by congenital valve abnormalities involving leaflet tissue, supporting chordal apparatus and displaced papillary muscles. This review provides a current understanding of the mechanisms that result in atrioventricular valve failure. Mitral valve leaflets have contractile elements, in addition to atrial muscle modulation of leaflet tension. When placed under mechanical tethering stress, the mitral valve adapts by leaflet expansion, which increases coaptation surface reserve and chordal thickening. Both pediatric and adult studies are increasingly reporting on the importance of subvalvar apparatus function in maintaining valve competency. The maintenance of efficient valve function is accomplished by a complex series of events involving atrial and annular contraction, annular deformation, active leaflet tension, chordal transmission of papillary muscle contractions and ventricular contraction.

Mitral stenosis in 15 dogs.

PubMed

Lehmkuhl, L B; Ware, W A; Bonagura, J D

1994-01-01

Mitral stenosis was diagnosed in 15 young to middle-aged dogs. There were 5 Newfoundlands and 4 bull terriers affected, suggesting a breed predisposition for this disorder. Clinical signs included cough, dyspnea, exercise intolerance, and syncope. Soft left apical diastolic murmurs were heard only in 4 dogs, whereas 8 dogs had systolic murmurs characteristic of mitral regurgitation. Left atrial enlargement was the most prominent radiographic feature. Left-sided congestive heart failure was detected by radiographs in 11 dogs within 1 year of diagnosis. Electrocardiographic abnormalities varied among dogs and included atrial and ventricular enlargement, as well as atrial and ventricular arrhythmias. Abnormalities on M-mode and two-dimensional echocardiograms included abnormal diastolic motion of the mitral valve characterized by decreased leaflet separation, valve doming, concordant motion of the parietal mitral valve leaflet, and a decreased E-to-F slope. Increased mitral valve inflow velocities and prolonged pressure half-times were detected by Doppler echocardiography. Cardiac catheterization, performed in 8 dogs, documented a diastolic pressure gradient between the left atrial, pulmonary capillary wedge, or pulmonary artery diastolic pressures and the left ventricular diastolic pressure. Necropsy showed mitral stenosis caused by thickened, fused mitral valve leaflets in 5 dogs and a supramitral ring in another dog. The outcome in affected dogs was poor; 9 of 15 dogs were euthanatized or died by 2 1/2 years of age.

Annulus fibrosus of the mitral valve: reality or myth.

PubMed

Berdajs, Denis; Zünd, Gregor; Camenisch, Colette; Schurr, Ulrich; Turina, Marko I; Genoni, Michele

2007-01-01

Surgical repair of the mitral valve is in most cases limited to the posterior leaflet of the mitral valve and to the annulus fibrosus. The term annulus fibrosus is still used in anatomical and clinical terminology and is described as a cord like structure providing the attachment of the mitral vale. However, to date no evidence exists of a ring-or cord-like structure at this area. Herein, we describe the attachment of the mitral valve by using the macroscopical and microscopical techniques. The ventricular attachment of the posterior mitral valve leaflet was investigated in 10 human hearts. In dry dissected specimens, the intraventricular illumination was used to identify the attachment of the mitral valve to the left ventricular muscle. Using the histological techniques, we verified the position of the annulus fibrosus. The attachment of the posterior mitral valve leaflet is a band-like structure positioned between the left ventricular muscle and the left atrium. This fibrous band illustrates the morphological attachment of the mitral valve and, as thus, was interpreted as the annulus fibrosus of the mitral valve. Based on our data, no ring-like structure was found corresponding to the anatomical description of the annulus fibrosus, instead the band-like fibrous tissue was identified positioned between the mitral valve and the left ventricle. Histologicaly, we detected that this structure is part of the greater structural system that is directly connected to the membranous septum, to the left and right fibrous trigone and the attachment aortic root to the left ventricular muscle.

Tricuspid and Mitral Valve Regurgitation with Bi-fascicular Block Following a Horse Kick.

PubMed

Kokubun, Tomoki; Oikawa, Masayoshi; Ichijo, Yasuhiro; Matsumoto, Yoshiyuki; Yokokawa, Tetsuro; Nakazato, Kazuhiko; Sato, Yoshiyuki; Takase, Shinya; Shinjo, Hiroharu; Yokoyama, Hitoshi; Suzuki, Hitoshi; Saitoh, Shu-Ichi; Takeishi, Yasuchika

2018-06-01

A 40-year-old man was transferred to our hospital following an isolated horse kick injury to the anterior chest wall. The case showed bi-fascicular block, severe tricuspid valve regurgitation due to ruptured chordae tendineae of the anterior leaflet, moderate mitral valve regurgitation due to prolapse of mitral anterior leaflet, and hypokinetic motion of the inferior septal wall. Both tricuspid and mitral insufficiency were completely repaired by a surgical operation. Fortunately, these injuries were not fatal in this case, but the comprehensive assessment of cardiac damage and careful observation are important for managing patients with cardiac injury.

Mitral stenosis and hypertrophic obstructive cardiomyopathy: An unusual combination.

PubMed

Hong, Joonhwa; Schaff, Hartzell V; Ommen, Steve R; Abel, Martin D; Dearani, Joseph A; Nishimura, Rick A

2016-04-01

Systolic anterior motion of mitral valve (MV) leaflets is a main pathophysiologic feature of left ventricular outflow tract (LVOT) obstruction in hypertrophic obstructive cardiomyopathy. Thus, restricted leaflet motion that occurs with MV stenosis might be expected to minimize outflow tract obstruction related to systolic anterior motion. From January 1993 through February 2015, we performed MV replacement and septal myectomy in 12 patients with mitral stenosis and hypertrophic obstructive cardiomyopathy at Mayo Clinic Hospital in Rochester, Minn. Preoperative data, echocardiographic images, operative records, and postoperative outcomes were reviewed. Mean (standard deviation) age was 70 (7.6) years. Preoperative mean (standard deviation) maximal LVOT pressure gradient was 75.0 (35.0) mm Hg; MV gradient was 13.7 (2.8) mm Hg. From echocardiographic images, 4 mechanisms of outflow tract obstruction were identified: systolic anterior motion without severe limitation in MV leaflet excursion, severe limitation in MV leaflet mobility with systolic anterior motion at the tip of the MV anterior leaflet, septal encroachment toward the LVOT, and MV displacement toward the LVOT by calcification. Mitral valve replacement and extended septal myectomy relieved outflow gradients in all patients, with no death or serious morbidity. Patients with mitral stenosis and hypertrophic obstructive cardiomyopathy have multiple LVOT obstruction mechanisms, and MV replacement may not be adequate treatment. We favor septal myectomy and MV replacement in this complex subset of hypertrophic obstructive cardiomyopathy. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Design considerations and quantitative assessment for the development of percutaneous mitral valve stent.

PubMed

Kumar, Gideon Praveen; Cui, Fangsen; Phang, Hui Qun; Su, Boyang; Leo, Hwa Liang; Hon, Jimmy Kim Fatt

2014-07-01

Percutaneous heart valve replacement is gaining popularity, as more positive reports of satisfactory early clinical experiences are published. However this technique is mostly used for the replacement of pulmonary and aortic valves and less often for the repair and replacement of atrioventricular valves mainly due to their anatomical complexity. While the challenges posed by the complexity of the mitral annulus anatomy cannot be mitigated, it is possible to design mitral stents that could offer good anchorage and support to the valve prosthesis. This paper describes four new Nitinol based mitral valve designs with specific features intended to address migration and paravalvular leaks associated with mitral valve designs. The paper also describes maximum possible crimpability assessment of these mitral stent designs using a crimpability index formulation based on the various stent design parameters. The actual crimpability of the designs was further evaluated using finite element analysis (FEA). Furthermore, fatigue modeling and analysis was also done on these designs. One of the models was then coated with polytetrafluoroethylene (PTFE) with leaflets sutured and put to: (i) leaflet functional tests to check for proper coaptation of the leaflet and regurgitation leakages on a phantom model and (ii) anchorage test where the stented valve was deployed in an explanted pig heart. Simulations results showed that all the stents designs could be crimped to 18F without mechanical failure. Leaflet functional test results showed that the valve leaflets in the fabricated stented valve coapted properly and the regurgitation leakage being within acceptable limits. Deployment of the stented valve in the explanted heart showed that it anchors well in the mitral annulus. Based on these promising results of the one design tested, the other stent models proposed here were also considered to be promising for percutaneous replacement of mitral valves for the treatment of mitral regurgitation, by virtue of their key features as well as effective crimping. These models will be fabricated and put to all the aforementioned tests before being taken for animal trials. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Finite element modeling of mitral leaflet tissue using a layered shell approximation

PubMed Central

Ratcliffe, Mark B.; Guccione, Julius M.

2012-01-01

The current study presents a finite element model of mitral leaflet tissue, which incorporates the anisotropic material response and approximates the layered structure. First, continuum mechanics and the theory of layered composites are used to develop an analytical representation of membrane stress in the leaflet material. This is done with an existing anisotropic constitutive law from literature. Then, the concept is implemented in a finite element (FE) model by overlapping and merging two layers of transversely isotropic membrane elements in LS-DYNA, which homogenizes the response. The FE model is then used to simulate various biaxial extension tests and out-of-plane pressure loading. Both the analytical and FE model show good agreement with experimental biaxial extension data, and show good mutual agreement. This confirms that the layered composite approximation presented in the current study is able to capture the exponential stiffening seen in both the circumferential and radial directions of mitral leaflets. PMID:22971896

Reproducibility of a novel echocardiographic 3D automated software for the assessment of mitral valve anatomy.

PubMed

Aquila, Iolanda; González, Ariana; Fernández-Golfín, Covadonga; Rincón, Luis Miguel; Casas, Eduardo; García, Ana; Hinojar, Rocio; Jiménez-Nacher, José Julio; Zamorano, José Luis

2016-05-17

3D transesophageal echocardiography (TEE) is superior to 2D TEE in quantitative anatomic evaluation of the mitral valve (MV) but it shows limitations regarding automatic quantification. Here, we tested the inter-/intra-observer reproducibility of a novel full-automated software in the evaluation of MV anatomy compared to manual 3D assessment. Thirty-six out of 61 screened patients referred to our Cardiac Imaging Unit for TEE were retrospectively included. 3D TEE analysis was performed both manually and with the automated software by two independent operators. Mitral annular area, intercommissural distance, anterior leaflet length and posterior leaflet length were assessed. A significant correlation between both methods was found for all variables: intercommissural diameter (r = 0.84, p < 0.01), mitral annular area (r = 0.94, p > 0, 01), anterior leaflet length (r = 0.83, p < 0.01) and posterior leaflet length (r = 0.67, p < 0.01). Interobserver variability assessed by the intraclass correlation coefficient was superior for the automatic software: intercommisural distance 0.997 vs. 0.76; mitral annular area 0.957 vs. 0.858; anterior leaflet length 0.963 vs. 0.734 and posterior leaflet length 0.936 vs. 0.838. Intraobserver variability was good for both methods with a better level of agreement with the automatic software. The novel 3D automated software is reproducible in MV anatomy assessment. The incorporation of this new tool in clinical MV assessment may improve patient selection and outcomes for MV interventions as well as patient diagnosis and prognosis stratification. Yet, high-quality 3D images are indispensable.

Obstructed bi-leaflet prosthetic mitral valve imaging with real-time three-dimensional transesophageal echocardiography.

PubMed

Shimbo, Mai; Watanabe, Hiroyuki; Kimura, Shunsuke; Terada, Mai; Iino, Takako; Iino, Kenji; Ito, Hiroshi

2015-01-01

Real-time three-dimensional transesophageal echocardiography (RT3D-TEE) can provide unique visualization and better understanding of the relationship among cardiac structures. Here, we report the case of an 85-year-old woman with an obstructed mitral prosthetic valve diagnosed promptly by RT3D-TEE, which clearly showed a leaflet stuck in the closed position. The opening and closing angles of the valve leaflets measured by RT3D-TEE were compatible with those measured by fluoroscopy. Moreover, RT3D-TEE revealed, in the ring of the prosthetic valve, thrombi that were not visible on fluoroscopy. RT3D-TEE might be a valuable diagnostic technique for prosthetic mitral valve thrombosis. © 2014 Wiley Periodicals, Inc.

Mechanisms of valve competency after mitral valve annuloplasty for ischaemic mitral regurgitation using the Geoform ring: insights from three-dimensional echocardiography.

PubMed

Armen, Todd A; Vandse, Rashmi; Crestanello, Juan A; Raman, Subha V; Bickle, Katherine M; Nathan, Nadia S

2009-01-01

Left ventricular remodelling leads to functional mitral regurgitation resulting from annular dilatation, leaflet tethering, tenting, and decreased leaflet coaptation. Mitral valve annuloplasty restores valve competency, improving the patient's functional status and ventricular function. This study was designed to evaluate the mechanisms underlying mitral valve competency after the implantation of a Geoform annuloplasty ring using three-dimensional (3D) echocardiography. Seven patients (mean age of 65 years) with ischaemic mitral regurgitation underwent mitral valve annuloplasty with the Geoform ring and coronary artery bypass surgery. Pre- and post-operative 3D echocardiograms were performed. Following mitral annuloplasty, mitral regurgitation decreased from 3.4+/-0.2 to 0.9+/-0.3 (P-value<0.0001), mitral valve tenting volume from 13+/-1.7 to 3.2+/-0.3 mL (P-value<0.001), annulus area from 12.6+/-1.0 to 3.3+/-0.2 cm2 (P-value<0.0001), valve circumference from 13+/-0.5 to 7.3+/-0.3 cm (P-value<0.0001), septolateral distance from 2.1+/-0.1 to 1.4+/-0.06 cm (P-value<0.01) and intercommissural distance from 3.4+/-0.1 to 2.7+/-0.03 cm (P-value<0.03). There was significant decrease in the septolateral distance at the level of A2-P2 with respect to other regions. These geometric changes were associated with the improvement in the NYHA class from 3.1+/-0.3 to 1.3+/-0.3 (P-value<0.002). The mitral valve annuloplasty with the Geoform ring restores leaflet coaptation and eliminates mitral regurgitation by effectively modifying the mitral annular geometry.

Surgical treatment of functional ischemic mitral regurgitation.

PubMed

Jensen, Henrik

2015-03-01

In many ways we are at a crossroad in terms of what constitutes optimal FIMR treatment: is CABG combined with mitral valve ring annuloplasty better than CABG alone in moderate FIMR? Is mitral valve repair really better than replacement? And does adding a valvular repair or subvalvular reverse remodeling procedure shift that balance? In the present thesis I aim to shed further light on these questions by addressing the current status and future perspectives of the surgical treatment of FIMR. CURRENT SURGICAL TREATMENT FOR FIMR. CABG alone: The overall impression from the literature is that patients are left with a high grade of persistent/recurrent FIMR from isolated CABG. CABG is most effective to treat FIMR in patients with viable myocardium (at least five viable segments) and absence of dyssynchrony between papillary muscles (< 60 ms). Mitral valve ring annuloplasty. A vast number of different designs are available to perform mitral valve ring annuloplasty with variations over the theme of complete/partial and rigid/semi-rigid/flexible. Also, the three-dimensional shape of the rigid and semi-rigid rings is the subject of great variation. A rigid or semi-rigid down-sized mitral valve ring annuloplasty is the most advocated treatment in chronic FIMR grade 2+ or higher. Combined CABG and mitral valve ring annuloplasty: CABG combined with mitral valve ring annuloplasty leads to reverse LV remodeling and reduced volumes. Despite this, the recurrence rate after combined CABG and mitral valve ring annuloplasty is 20-30% at 2-4 years follow-up. This is also true for studies strictly using down-sized mitral valve ring annuloplasty by two sizes. A number of preoperative risk factors to develop recurrent FIMR were identified, e.g. LVEDD > 65-70 mm, coaptation depth > 10 mm, anterior leaflet angle > 27-39.5°, posterior leaflet angle > 45° and interpapillary muscle distance > 20 mm. CABG alone vs. combined CABG and mitral valve ring annuloplasty: The current available literature, including three randomized studies and a meta analysis, indicate that combined CABG and mitral valve ring annuloplasty has no late survival difference compared with CABG alone, and early mortality might even be higher. Meanwhile, adding a mitral valve ring annuloplasty results in a lower NYHA functional class, most likely as a consequence of a lower incidence of persistent or recurrent FIMR. More randomized studies are being conducted to further address this topic. Mitral valve ring annuloplasty vs. mitral valve replacement. The early survival may be higher after repair compared with replacement, meanwhile, the literature is more ambiguous in terms of late survival advantages, and recent reports find no late survival advantage from repair over replacement. The recurrence rates after ring annuloplasty addressed above were also present in this subset of patients, whereas the incidence of recurrent FIMR after valve replacement is scarcely reported. There was an overall tendency of slightly higher incidence of reoperations after ring annuloplasty. The mitral valve annulus: Innovations in mitral valve ring annuloplasty: The latest innovation in mitral valve ring annuloplasty design includes adjustable rings, allowing adjustment of septo-lateral dimensions intra- or postoperatively. Minimally invasive ring annuloplasty using indirect coronary sinus devices, has been introduced, but so far have produced suboptimal results in terms of safety and efficacy. Also, first in man testing of direct percutaneous catheter based mitral annuloplasty techniques have been conducted. Leaflets and chordae: Direct repair techniques: Surgical methods have been developed to directly address the mitral valve leaflets and chordae tendineae to correct leaflet tethering in FIMR. Both the Alfieri stich and the minimally invasive MitraClip attaches the anterior and posterior leaflets, typically the A2-P2 region, to correct incomplete leaflet coaptation. Patch augmentation of the posterior leaflet in the P2-P3 region increases coaptation in the area most prone to cause FIMR. Chordal cutting of the secondary "strut" chordae releases the anterior leaflet from the tethering due to papillary muscle displacement and improves mitral valve geometry. The mitral subvalvular apparatus: Numerous subvalvular approaches to improve outcome in patients with FIMR have been introduced. They include very invasive techniques such as surgical ventricular restoration procedure, surgical techniques directly addressing the papillary muscle dis-placement, and beating heart procedures using transventricular and epicardial devices applied in a few minutes. The role of the transventricular and epicardial devices still remains to be defined and many of these devices seem to have a hard time ganing their footing in the clinical practise and until now only constitute a footnote in the surgical literature. Meanwhile, the current results with adjunct techniques to CABG and ring annuloplasty, such as the papillary muscle approximation technique introduced by Hvass et al and the papillary muscle relocation technique introduced by Kron et al and further developed by Langer et al are gaining continuing support in the surgical community since these techniques can be used with only little added time consumption but with very good clinical outcome.

Effect of the Mitral Valve's Anterior Leaflet on Axisymmetry of Transmitral Vortex Ring.

PubMed

Falahatpisheh, Ahmad; Pahlevan, Niema M; Kheradvar, Arash

2015-10-01

The shape and formation of transmitral vortex ring are shown to be associated with diastolic function of the left ventricle (LV). Transmitral vortex ring is a flow feature that is observed to be non-axisymmetric in a healthy heart and its inherent asymmetry in the LV assists in efficient ejection of the blood during systole. This study is a first step towards understanding the effects of the mitral valve's anterior leaflet on transmitral flow. We experimentally study a single-leaflet model of the mitral valve to investigate the effect of the anterior leaflet on the axisymmetry of the generated vortex ring based on the three-dimensional data acquired using defocusing digital particle image velocimetry. Vortex rings form downstream of a D-shaped orifice in presence or absence of the anterior leaflet in various physiological stroke ratios. The results of the statistical analysis indicate that the formed vortex ring downstream of a D-shaped orifice is markedly non-axisymmetric, and presence of the anterior leaflet improves the ring's axisymmetry. This study suggests that the improvement of axisymmetry in presence of the anterior leaflet might be due to coupled dynamic interaction between rolling-up of the shear layer at the edges of the D-shaped orifice and the borders of the anterior leaflet. This interaction can reduce the non-uniformity in vorticity generation, which results in more axisymmetric behavior compared to the D-shaped orifice without the anterior leaflet.

Novel pathogenetic mechanisms and structural adaptations in ischemic mitral regurgitation.

PubMed

Silbiger, Jeffrey J

2013-10-01

Ischemic mitral regurgitation (MR) is a common complication of myocardial infarction thought to result from leaflet tethering caused by displacement of the papillary muscles that occurs as the left ventricle remodels. The author explores the possibility that left atrial remodeling may also play a role in the pathogenesis of ischemic MR, through a novel mechanism: atriogenic leaflet tethering. When ischemic MR is hemodynamically significant, the left ventricle compensates by dilating to preserve forward output using the Starling mechanism. Left ventricular dilatation, however, worsens MR by increasing the mitral valve regurgitant orifice, leading to a vicious cycle in which MR begets more MR. The author proposes that several structural adaptations play a role in reducing ischemic MR. In contrast to the compensatory effects of left ventricular enlargement, these may reduce, rather than increase, its severity. The suggested adaptations involve the mitral valve leaflets, the papillary muscles, the mitral annulus, and the left ventricular false tendons. This review describes the potential role each may play in reducing ischemic MR. Therapies that exploit these adaptations are also discussed. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Adjunctive intracardiac echocardiography imaging from the left ventricle to guide percutaneous mitral valve repair with the MitraClip in patients with failed prior surgical rings.

PubMed

Saji, Mike; Rossi, Ann M; Ailawadi, Gorav; Dent, John; Ragosta, Michael; Lim, D Scott

2016-02-01

We evaluated intracardiac echocardiography (ICE) for adjunctively guiding the MitraClip procedure in patients with prior surgical rings. Transesophageal echocardiography (TEE) is the standard imaging modality used to guide the MitraClip procedure (Abbott Vascular, CA). However, in patients with post-surgical anatomy, clear imaging of the mitral valve leaflets may be complex because of shadowing from the surgical ring. In these patients, TEE may be suboptimal for guiding the procedure, even using three-dimensional imaging. This retrospective analysis included data from 121 consecutive patients with mitral regurgitation who underwent MitraClip procedures at the University of Virginia. ICE was used adjunctively when there was difficulty with TEE, particularly for assessing the insertion of the posterior leaflet into the MitraClip's arms. The ICE catheter was introduced transarterially into the left ventricle and flexed to obtain the short-axis view. Six patients had prior surgical rings, and in five, we used adjunctive ICE. The etiology of the mitral regurgitation was prolapse of the posterior leaflet in one patient and restriction of the posterior leaflet due to ischemic tethering in the remainder. All images were obtained from the left ventricle, and were adequate for assessing posterior leaflet insertion and the perpendicularity of the MitraClip arms. The procedural success rate was 80%. There was no adverse event related to the ICE procedure. Mitral valve repair with the MitraClip system assisted by ICE is feasible in patients with prior surgical rings, achieving an excellent risk profile and satisfactory procedural success. © 2015 Wiley Periodicals, Inc.

FLUID-STRUCTURE INTERACTION MODELS OF THE MITRAL VALVE: FUNCTION IN NORMAL AND PATHOLOGIC STATES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kunzelman, K. S.; Einstein, Daniel R.; Cochran, R. P.

2007-08-29

Successful mitral valve repair is dependent upon a full understanding of normal and abnormal mitral valve anatomy and function. Computational analysis is one such method that can be applied to simulate mitral valve function in order to analyze the roles of individual components, and evaluate proposed surgical repair. We developed the first three-dimensional, finite element (FE) computer model of the mitral valve including leaflets and chordae tendineae, however, one critical aspect that has been missing until the last few years was the evaluation of fluid flow, as coupled to the function of the mitral valve structure. We present here ourmore » latest results for normal function and specific pathologic changes using a fluid-structure interaction (FSI) model. Normal valve function was first assessed, followed by pathologic material changes in collagen fiber volume fraction, fiber stiffness, fiber splay, and isotropic stiffness. Leaflet and chordal stress and strain, and papillary muscle force was determined. In addition, transmitral flow, time to leaflet closure, and heart valve sound were assessed. Model predictions in the normal state agreed well with a wide range of available in-vivo and in-vitro data. Further, pathologic material changes that preserved the anisotropy of the valve leaflets were found to preserve valve function. By contrast, material changes that altered the anisotropy of the valve were found to profoundly alter valve function. The addition of blood flow and an experimentally driven microstructural description of mitral tissue represent significant advances in computational studies of the mitral valve, which allow further insight to be gained. This work is another building block in the foundation of a computational framework to aid in the refinement and development of a truly noninvasive diagnostic evaluation of the mitral valve. Ultimately, it represents the basis for simulation of surgical repair of pathologic valves in a clinical and educational setting.« less

Catheter Entrapment During Posterior Mitral Leaflet Pushing Maneuver for MitraClip Implantation.

PubMed

Castrodeza, Javier; Amat-Santos, Ignacio J; Tobar, Javier; Varela-Falcón, Luis H

2016-06-01

MitraClip (Abbott Vascular) therapy has been reported to be an effective procedure for mitral regurgitation, especially in high-risk patients. Recently, the novel pushing maneuver technique has been described for approaching restricted and short posterior leaflets with a pigtail catheter in order to facilitate grasping of the clip. However, complications or unexpected situations may occur. We report the case of an 84-year-old patient who underwent MitraClip implantation wherein the pushing maneuver was complicated by the clip accidentally gripping the pigtail catheter along with the two leaflets.

Evolving Techniques for Mitral Valve Reconstruction

PubMed Central

Galloway, Aubrey C.; Grossi, Eugene A.; Bizekis, Costas S.; Ribakove, Greg; Ursomanno, Patricia; Delianides, Julie; Baumann, F. Gregory; Spencer, Frank C.; Colvin, Stephen B.

2002-01-01

Objective To analyze the effectiveness of new techniques of mitral valve reconstruction (MVR) that have evolved over the last decade, such as aggressive anterior leaflet repair and minimally invasive surgery using an endoaortic balloon occluder. Summary Background Data MVR via conventional sternotomy has been an established treatment for mitral insufficiency for over 20 years, primarily for the treatment of patients with posterior leaflet prolapse. Methods Between June 1980 and June 2001, 1,195 consecutive patients had MVR with ring annuloplasty. Conventional sternotomy was used in 843 patients, minimally invasive surgery in 352 (since June 1996). Anterior leaflet repair was performed in 374 patients, with increasing use over the last 10 years. Follow-up was 100% complete (mean 4.6 years, range 0.5–20.5). Results Hospital mortality was 4.7% overall and 1.4% for isolated MVR (1.1% for minimally invasive surgery vs. 1.6% for conventional sternotomy;P = .4). Multivariate analysis showed the factors predictive of increased operative risk to be age, NYHA functional class, concomitant procedures, and previous cardiac surgery. The 5-year results for freedom from cardiac death, reoperation, and valve-related complications among the 782 patients with degenerative etiology are, respectively, as follows (P > .05 for all end points): for anterior leaflet repair, 93%, 94%, 90%; for no anterior leaflet repair, 91%, 92%, 91%; for minimally invasive surgery, 97%, 89%, 93%; and for conventional sternotomy, 93%, 94%, 90%. Conclusions These findings indicate that late results of MVR after minimally invasive surgery and after anterior leaflet repair are equivalent to those achievable with conventional sternotomy and posterior leaflet repair. These options significantly expand the range of patients suitable for mitral valve repair surgery and give further evidence to support wider use of minimally invasive techniques. PMID:12192315

Prosthetic Mitral Valve Leaflet Escape

PubMed Central

Kim, Darae; Hun, Sin Sang; Cho, In-Jeong; Shim, Chi-Young; Ha, Jong-Won; Chung, Namsik; Ju, Hyun Chul; Sohn, Jang Won

2013-01-01

Leaflet escape of prosthetic valve is rare but potentially life threatening. It is essential to make timely diagnosis in order to avoid mortality. Transesophageal echocardiography and cinefluoroscopy is usually diagnostic and the location of the missing leaflet can be identified by computed tomography (CT). Emergent surgical correction is mandatory. We report a case of fractured escape of Edward-Duromedics mitral valve 27 years after the surgery. The patient presented with symptoms of acute decompensated heart failure and cardiogenic shock. She was instantly intubated and mechanically ventilated. After prompt evaluation including transthoracic echocardiography and CT, the escape of the leaflet was confirmed. The patient underwent emergent surgery for replacement of the damaged prosthetic valves immediately. Eleven days after the surgery, the dislodged leaflet in iliac artery was removed safely and the patient recovered well. PMID:23837121

Nonlinear solid finite element analysis of mitral valves with heterogeneous leaflet layers

NASA Astrophysics Data System (ADS)

Prot, V.; Skallerud, B.

2009-02-01

An incompressible transversely isotropic hyperelastic material for solid finite element analysis of a porcine mitral valve response is described. The material model implementation is checked in single element tests and compared with a membrane implementation in an out-of-plane loading test to study how the layered structures modify the stress response for a simple geometry. Three different collagen layer arrangements are used in finite element analysis of the mitral valve. When the leaflets are arranged in two layers with the collagen on the ventricular side, the stress in the fibre direction through the thickness in the central part of the anterior leaflet is homogenized and the peak stress is reduced. A simulation using membrane elements is also carried out for comparison with the solid finite element results. Compared to echocardiographic measurements, the finite element models bulge too much in the left atrium. This may be due to evidence of active muscle fibres in some parts of the anterior leaflet, whereas our constitutive modelling is based on passive material.

Effects of suture position on left ventricular fluid mechanics under mitral valve edge-to-edge repair.

PubMed

Du, Dongxing; Jiang, Song; Wang, Ze; Hu, Yingying; He, Zhaoming

2014-01-01

Mitral valve (MV) edge-to-edge repair (ETER) is a surgical procedure for the correction of mitral valve regurgitation by suturing the free edge of the leaflets. The leaflets are often sutured at three different positions: central, lateral and commissural portions. To study the effects of position of suture on left ventricular (LV) fluid mechanics under mitral valve ETER, a parametric model of MV-LV system during diastole was developed. The distribution and development of vortex and atrio-ventricular pressure under different suture position were investigated. Results show that the MV sutured at central and lateral in ETER creates two vortex rings around two jets, compared with single vortex ring around one jet of the MV sutured at commissure. Smaller total orifices lead to a higher pressure difference across the atrio-ventricular leaflets in diastole. The central suture generates smaller wall shear stresses than the lateral suture, while the commissural suture generated the minimum wall shear stresses in ETER.

Mitral valve plasty for mitral regurgitation after blunt chest trauma.

PubMed

Kumagai, H; Hamanaka, Y; Hirai, S; Mitsui, N; Kobayashi, T

2001-06-01

A 21 year-old woman was admitted to our hospital because of chest and back pain after blunt chest trauma. On admission, consciousness was clear and a physical examination showed labored breathing. Her vital signs were stable, but her breathing gradually worsened, and artificial respiration was started. The chest roentgenogram and a subsequent chest computed tomographic scans revealed contusions, hemothorax of the left lung and multiple rib fractures. A transthoracic echocardiography (TTE) revealed normal left ventricular wall motion and mild mitral regurgitation (MR). TTE was carried out repeatedly, and revealed gradually progressive MR and prolapse of the posterior medial leaflet, although there was no congestive heart failure. After her general condition had recovered, surgery was performed. Intraoperative transesophageal echocardiography (TEE) revealed torn chordae at the posterior medial leaflet. The leaflet where the chorda was torn was cut and plicated, and posterior mitral annuloplasty was performed using a prosthetic ring. One month later following discharge, the MR had disappeared on TTE.

Anatomic characteristics of bileaflet mitral valve prolapse--Barlow disease--in patients undergoing mitral valve repair.

PubMed

Rostagno, Carlo; Droandi, Ginevra; Rossi, Alessandra; Bevilacqua, Sergio; Romagnoli, Stefano; Montesi, Gian Franco; Stefàno, Pier Luigi

2014-01-01

Barlow disease is a still challenging pathology for the surgeon. Aim of the present study is to report anatomic abnormalities of mitral valve in patients undergoing mitral valve repair. Between January 1st, 2007, and December 31st, 2010, 85 consecutive patients (54 men and 31 women, mean age 59 +/- 14 years--range: 28-85 years) with the features of a Barlow mitral valve disease underwent mitral repair Forty seven percent of patients were in New York Heart Association functional class III or IV. Preoperative transesophageal echocardiography was compared with anatomical findings at the moment of surgery. Transthoracic echocardiography diagnosis of Barlow disease according to the criteria described by Carpentier was confirmed at anatomical inspection. Annular calcifications were found in 28 patients while 7 patients presented single or multiple clefts. A flail posterior mitral leaflet was detected in 32 subjects, while a flail anterior leaflet in 8. Elongation of chordae tendineae was demonstrated in 45 patients and chordal rupture in 31. All patients showed at trans esophageal echocardiography the typical features of Barlow disease. Seventy-seven (90.6%) patients had severe mitral valve regurgitation, in the remaining 9.4% it was moderate to severe. Transesophageal echocardiography failed to identify clefts in 2/7 and chordal rupture in 4/31. bileaflet prolapse > 2 mm, billowing valve with excess tissue and thickened leaflets > or = 3 mm, and severe annular dilatation, are characteristics of Barlow disease, however the identification of the associated and complex abnormalities of mitral valve is necessary to obtain optimal valve repair.

Fast image-based mitral valve simulation from individualized geometry.

PubMed

Villard, Pierre-Frederic; Hammer, Peter E; Perrin, Douglas P; Del Nido, Pedro J; Howe, Robert D

2018-04-01

Common surgical procedures on the mitral valve of the heart include modifications to the chordae tendineae. Such interventions are used when there is extensive leaflet prolapse caused by chordae rupture or elongation. Understanding the role of individual chordae tendineae before operating could be helpful to predict whether the mitral valve will be competent at peak systole. Biomechanical modelling and simulation can achieve this goal. We present a method to semi-automatically build a computational model of a mitral valve from micro CT (computed tomography) scans: after manually picking chordae fiducial points, the leaflets are segmented and the boundary conditions as well as the loading conditions are automatically defined. Fast finite element method (FEM) simulation is carried out using Simulation Open Framework Architecture (SOFA) to reproduce leaflet closure at peak systole. We develop three metrics to evaluate simulation results: (i) point-to-surface error with the ground truth reference extracted from the CT image, (ii) coaptation surface area of the leaflets and (iii) an indication of whether the simulated closed leaflets leak. We validate our method on three explanted porcine hearts and show that our model predicts the closed valve surface with point-to-surface error of approximately 1 mm, a reasonable coaptation surface area, and absence of any leak at peak systole (maximum closed pressure). We also evaluate the sensitivity of our model to changes in various parameters (tissue elasticity, mesh accuracy, and the transformation matrix used for CT scan registration). We also measure the influence of the positions of the chordae tendineae on simulation results and show that marginal chordae have a greater influence on the final shape than intermediate chordae. The mitral valve simulation can help the surgeon understand valve behaviour and anticipate the outcome of a procedure. Copyright © 2018 John Wiley & Sons, Ltd.

Supravalvar mitral ring with a parachute mitral valve and subcoarctation of the aorta in a child with hemodynamically significant VSD. A study of the morphology, echocardiographic diagnostics and surgical therapy.

PubMed

Mądry, Wojciech; Karolczak, Maciej A; Grabowski, Krzysztof

2017-09-01

The authors present a case of echocardiographic diagnosis of supravalvar mitral ring (a fibromembranous structure that arose from the atrial surface of the mitral leaflets) in a child with a parachute mitral valve, a ventricular septal defect, and mild narrowing of the aortic isthmus. The supravalvar mitral stenosis is a typical but very infrequently detected element of the complex of anatomical abnormalities located within the left heart and the proximal aorta, called the Shone's complex (syndrome). Diagnosing an additional, hemodynamically significant anatomic defect during echocardiography was possible thanks to the detection of marked mobility limitation of the ring-adjacent part of the mitral valve mural leaflet as well as of an atypical image of turbulence occurring during the inflow from the left atrium to the left ventricle. The early diagnosis made it possible to perform complete correction of this complex congenital defect within a single operation.

Premeasured Chordal Loops for Mitral Valve Repair.

PubMed

Gillinov, Marc; Quinn, Reed; Kerendi, Faraz; Gaudiani, Vince; Shemin, Richard; Barnhart, Glenn; Raines, Edward; Gerdisch, Marc W; Banbury, Michael

2016-09-01

Premeasured expanded polytetrafluoroethylene chordal loops with integrated sutures for attachment to the papillary muscle and leaflet edges facilitate correction of mitral valve prolapse. Configured as a group of 3 loops (length range 12 to 24 mm), the loops are attached to a pledget that is passed through the papillary muscle and tied. Each of the loops has 2 sutures with attached needles; these needles are passed through the free edge of the leaflet and then the sutures are tied to each other, securing the chordal loop to the leaflet. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Idiopathic mitral valve disease in a patient presenting with Axenfeld-Rieger syndrome.

PubMed

Antevil, Jared; Umakanthan, Ramanan; Leacche, Marzia; Brewer, Zachary; Solenkova, Natalia; Byrne, John G; Greelish, James P

2009-05-01

A 33-year-old, previously healthy male presented with respiratory distress and underwent intubation. A physical examination revealed a holosystolic murmur and pupillary abnormalities. Echocardiography revealed a flail anterior mitral valve leaflet with ruptured chordae and severe mitral regurgitation. The patient underwent urgent mitral valve replacement and tolerated the procedure well. The mitral valve leaflet was myxomatous and calcified -- an unusual find in such a patient. An ophthalmology consultation was obtained and the patient diagnosed with Axenfeld-Rieger syndrome, a disorder of the anterior ocular chamber that has been associated with cardiac malformations. The present case report adds to the body of literature which suggests a correlation between Axenfeld-Rieger syndrome and valvular abnormalities. Hence, it is believed prudent that patients with Axenfeld-Rieger syndrome should undergo echocardiographic screenings for valvular abnormalities.

A Novel Left Heart Simulator for the Multi-modality Characterization of Native Mitral Valve Geometry and Fluid Mechanics

PubMed Central

Rabbah, Jean-Pierre; Saikrishnan, Neelakantan; Yoganathan, Ajit P.

2012-01-01

Numerical models of the mitral valve have been used to elucidate mitral valve function and mechanics. These models have evolved from simple two-dimensional approximations to complex three-dimensional fully coupled fluid structure interaction models. However, to date these models lack direct one-to-one experimental validation. As computational solvers vary considerably, experimental benchmark data are critically important to ensure model accuracy. In this study, a novel left heart simulator was designed specifically for the validation of numerical mitral valve models. Several distinct experimental techniques were collectively performed to resolve mitral valve geometry and hemodynamics. In particular, micro-computed tomography was used to obtain accurate and high-resolution (39 µm voxel) native valvular anatomy, which included the mitral leaflets, chordae tendinae, and papillary muscles. Threedimensional echocardiography was used to obtain systolic leaflet geometry for direct comparison of resultant leaflet kinematics. Stereoscopic digital particle image velocimetry provided all three components of fluid velocity through the mitral valve, resolved every 25 ms in the cardiac cycle. A strong central filling jet was observed during peak systole, with minimal out-of-plane velocities (V~0.6m/s). In addition, physiologic hemodynamic boundary conditions were defined and all data were synchronously acquired through a central trigger. Finally, the simulator is a precisely controlled environment, in which flow conditions and geometry can be systematically prescribed and resultant valvular function and hemodynamics assessed. Thus, these data represent the first comprehensive database of high fidelity experimental data, critical for extensive validation of mitral valve fluid structure interaction simulations. PMID:22965640

Modeling the Mitral Valve

NASA Astrophysics Data System (ADS)

Kaiser, Alexander

2016-11-01

The mitral valve is one of four valves in the human heart. The valve opens to allow oxygenated blood from the lungs to fill the left ventricle, and closes when the ventricle contracts to prevent backflow. The valve is composed of two fibrous leaflets which hang from a ring. These leaflets are supported like a parachute by a system of strings called chordae tendineae. In this talk, I will describe a new computational model of the mitral valve. To generate geometry, general information comes from classical anatomy texts and the author's dissection of porcine hearts. An MRI image of a human heart is used to locate the tips of the papillary muscles, which anchor the chordae tendineae, in relation to the mitral ring. The initial configurations of the valve leaflets and chordae tendineae are found by solving solving an equilibrium elasticity problem. The valve is then simulated in fluid (blood) using the immersed boundary method over multiple heart cycles in a model valve tester. We aim to identify features and mechanisms that influence or control valve function. Support from National Science Foundation, Graduate Research Fellowship Program, Grant DGE 1342536.

Live 3D TEE demonstrates and guides the management of prosthetic mitral valve obstruction.

PubMed

Chahal, Mangeet; Pandya, Utpal; Adlakha, Satjit; Khouri, Samer J

2011-08-01

A 43-year-old woman, with a remote history of rheumatic mitral stenosis and a St. Jude prosthetic mitral valve replacement, presented with shortness of breath and palpitations, shortly after a long flight. On admission, atrial fibrillation with a rapid ventricular response was noted in the setting of a long history of noncompliance with her anticoagulation. Transesophageal echocardiography (TEE) demonstrated multiple laminated thrombi in the left atrial appendage. Live three-dimensional (3D) TEE confirmed this diagnosis and demonstrated an immobile posterior leaflet of the mitral prosthesis, which had direct implications in her management. She successfully underwent surgery for mitral valve replacement, left atrial appendage ligation, and a Maze procedure on the following day. The multiple thrombi within the atrial appendage were confirmed intraoperatively and pannus formation was determined to be the etiology of the leaflet immobility. © 2011, Wiley Periodicals, Inc.

Malformation of the canine mitral valve complex.

PubMed

Litu, S K; Tilley, L P

1975-09-15

Twenty-nine dogs, including 13 Great Danes and 5 German Shepherd Dogs and averaging 7.3 months age, were diagnosed clinically and radiographically as having mitral regurgitation. Alterations of the mitral valve complex included enlarged anulus; short thick leaflets, with an occasional cleft; short and stout or long and thin chordae tendineae; upward malposition of atrophic or hypertrophic papillary muscles; insertion of one papillary muscle directly into one or both leaflets; and diffuse endocardial fibrosis, occasionally with jet lesions in te left atrium. Other cardiac anomalies included dysplasia of the tricuspid valve (5 dogs), patent ductus afteriosus (2 dogs), aortic stenosis (2 dogs), and ventricular septal defect (1 dog).

Contribution of mitral valve leaflet length and septal wall thickness to outflow tract obstruction in patients with hypertrophic cardiomyopathy.

PubMed

Morant, Kareem; Mikami, Yoko; Nevis, Immaculate; McCarty, David; Stirrat, John; Scholl, David; Rajchl, Martin; Giannoccaro, Peter; Kolman, Louis; Heydari, Bobby; Lydell, Carmen; Howarth, Andrew; Grant, Andrew; White, James A

2017-08-01

We sought to examine whether elongation of the mitral valve leaflets in patients with hypertrophic cardiomyopathy (HCM) is synergistic to septal wall thickness (SWT) in the development of left ventricular outflow tract obstruction (LVOTO). HCM is a common genetic cardiac disease characterized by asymmetric septal hypertrophy and predisposition towards LVOTO. It has been reported that elongation of the mitral valve leaflets may be a primary phenotypic feature and contribute to LVOTO. However, the relative contribution of this finding versus SWT has not been studied. 152 patients (76 with HCM and 76 non-diseased age, race and BSA-matched controls) and 18 young, healthy volunteers were studied. SWT and the anterior mitral valve leaflet length (AMVLL) were measured using cine MRI. The combined contribution of these variables (SWT × AMVLL) was described as the Septal Anterior Leaflet Product (SALP). Peak LVOT pressure gradient was determined by Doppler interrogation and defined as "obstructive" if ≥ 30 mmHg. Patients with HCM were confirmed to have increased AMVLL compared with controls and volunteers (p < 0.01). Among HCM patients, both SWT and SALP were significantly higher in patients with LVOTO (N = 17) versus without. SALP showed modest improvement in predictive accuracy for LVOTO (AUC = 0.81) among the HCM population versus SWT alone (AUC = 0.77). However, in isolated patients this variable identified patients with LVOTO despite modest SWT. Elongation of the AMVLL is a primary phenotypic feature of HCM. While incremental contributions to LVOTO appear modest at a population level, specific patients may have dominant contribution to LVOTO. The combined marker of SALP allows for maintained identification of such patients despite modest increases in SWT.

Mitral valve morphology assessed by three-dimensional transthoracic echocardiography in healthy dogs and dogs with myxomatous mitral valve disease.

PubMed

Menciotti, G; Borgarelli, M; Aherne, M; Wesselowski, S; Häggström, J; Ljungvall, I; Lahmers, S M; Abbott, J A

2017-04-01

To assess differences in morphology of the mitral valve (MV) between healthy dogs and dogs affected by myxomatous mitral valve disease (MMVD) using real-time transthoracic three-dimensional echocardiography (RT3DE). Thirty-four were normal dogs and 79 dogs were affected by MMVD. Real-time transthoracic three-dimensional echocardiography mitral datasets were digitally recorded and analyzed using dedicated software. The following variables were obtained and compared between healthy dogs and dogs with MMVD at different stages: antero-posterior annulus diameter, anterolateral-posteromedial annulus diameter, commissural diameter, annulus height, annulus circumference, annulus area, anterior leaflet length, anterior leaflet area, posterior leaflet length, posterior leaflet area, non-planar angle, annulus sphericity index, tenting height, tenting area, tenting volume, the ratio of annulus height and commissural diameter. Dogs with MMVD had a more circular MV annulus compared to healthy dogs as demonstrated by an increased annulus sphericity index (p=0.0179). Affected dogs had a less saddle-shaped MV manifest as a decreased annulus height to commissural width ratio (p=0.0004). Tenting height (p<0.0001), area (p<0.0001), and volume (p<0.0001) were less in affected dogs. Real-time transthoracic three-dimensional echocardiography analysis demonstrated that dogs affected by MMVD had a more circular and less saddle-shaped MV annulus, as well as reduced tenting height area and volume, compared to healthy dogs. Multiple variables differed between dogs at different stages of MMVD. Diagnostic and prognostic utility of these variables, and the significance of these changes in the pathogenesis and natural history of MMVD, require further attention. Copyright © 2017 Elsevier B.V. All rights reserved.

Mitral regurgitation after previous aortic valve surgery for bicuspid aortic valve insufficiency.

PubMed

Girdauskas, Evaldas; Disha, Kushtrim; Espinoza, Andres; Misfeld, Martin; Reichenspurner, Hermann; Borger, Michael A; Kuntze, Thomas

2017-06-01

Regurgitant bicuspid aortic valves (BAV) are reported to be associated with myxomatous degeneration of the anterior mitral leaflet. We examined the risk of late new-onset mitral regurgitation (MR) in patients who underwent aortic valve/aortic root surgery for BAV regurgitation and concomitant root dilatation. A total of 97 consecutive patients (47±11 years, 94% men) were identified from our institutional BAV database (N.=640) based on the following criteria: 1) BAV regurgitation; 2) aortic root diameter >40 mm; 3) no relevant mitral valve disease (i.e., MR<2+) and no simultaneous mitral intervention at the time of BAV surgery. All patients underwent isolated aortic valve replacement (AVR subgroup, N.=59) or aortic root replacement with a composite graft (i.e., for root aneurysm >50 mm) (ARR subgroup, N.=38) from 1995 through 2008. Echocardiographic follow-up (1009 patient-years) was obtained for all 96 (100%) hospital survivors. The primary endpoint was freedom from new-onset MR>2+ and redo mitral valve surgery. Nine patients (9.4%) showed new-onset MR>2+ after mean echocardiographic follow-up of 10.4±4.0 years postoperatively. Myxomatous degeneration and prolapse of the anterior mitral leaflet was found in all 9 patients, and the posterior leaflet was involved in 3 of them. Two patients (2%) in AVR subgroup underwent re-do mitral surgery. No MR>2+ occurred in ARR subgroup. Freedom from MR>2+ or mitral surgery at 15 years was significantly lower in AVR subgroup vs. ARR subgroup (i.e., 38% vs. 100%, P=0.01). The risk of new-onset MR is significantly increased in patients with BAV regurgitation and aortic root dilatation who undergo isolated AVR rather than root replacement. The mechanism by which aortic root replacement may prevent the occurrence of late MR in BAV root phenotype patients is to be determined.

Improved mitral valve coaptation and reduced mitral valve annular size after percutaneous mitral valve repair (PMVR) using the MitraClip system.

PubMed

Patzelt, Johannes; Zhang, Yingying; Magunia, Harry; Ulrich, Miriam; Jorbenadze, Rezo; Droppa, Michal; Zhang, Wenzhong; Lausberg, Henning; Walker, Tobias; Rosenberger, Peter; Seizer, Peter; Gawaz, Meinrad; Langer, Harald F

2017-08-01

Improved mitral valve leaflet coaptation with consecutive reduction of mitral regurgitation (MR) is a central goal of percutaneous mitral valve repair (PMVR) with the MitraClip® system. As influences of PMVR on mitral valve geometry have been suggested before, we examined the effect of the procedure on mitral annular size in relation to procedural outcome. Geometry of the mitral valve annulus was evaluated in 183 patients undergoing PMVR using echocardiography before and after the procedure and at follow-up. Mitral valve annular anterior-posterior (ap) diameter decreased from 34.0 ± 4.3 to 31.3 ± 4.9 mm (P < 0.001), and medio-lateral (ml) diameter from 33.2 ± 4.8 to 32.4 ± 4.9 mm (P < 0.001). Accordingly, we observed an increase in MV leaflet coaptation after PMVR. The reduction of mitral valve ap diameter showed a significant inverse correlation with residual MR. Importantly, the reduction of mitral valve ap diameter persisted at follow-up (31.3 ± 4.9 mm post PMVR, 28.4 ± 5.3 mm at follow-up). This study demonstrates mechanical approximation of both mitral valve annulus edges with improved mitral valve annular coaptation by PMVR using the MitraClip® system, which correlates with residual MR in patients with MR. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Balloon valvuloplasty of congenital mitral stenosis.

PubMed

Arndt, Jason W; Oyama, Mark A

2013-06-01

Radiographic, echocardiographic, fluoroscopic, and angiographic images from 2 dogs with severe congenital mitral valve stenosis that underwent cardiac catheterization and balloon valvuloplasty are presented. Both dogs displayed systolic doming of the mitral valve leaflets, increased diastolic pressure gradient across the left atrium and ventricle, and decreased mitral inflow E to F slope. Balloon valvuloplasty was performed on both dogs using atrial transeptal puncture. Copyright © 2013 Elsevier B.V. All rights reserved.

Transapical endovascular implantation of neochordae using a suction and suture device.

PubMed

Maisano, Francesco; Michev, Iassen; Rowe, Stanton; Addis, Alessandro; Campagnol, Marino; Guidotti, Andrea; Colombo, Antonio; Alfieri, Ottavio

2009-07-01

Neochordae implantation is a standard method for treatment of mitral valve prolapse. We describe a transcatheter technology enabling transapical endovascular chordal implantation. Six adult pigs were anesthetized. Two 10F sheaths were introduced in the femoral vessels for monitoring and intracardiac echo. After midline sternotomy, the pericardium was opened, the apex was punctured inside two 2-0 polypropylene purse strings. A 0.035 in J tipped guidewire was introduced in the left ventricle and an ultra stiff 14F sheath (guide catheter) inserted through the apex. A suction-and-suture device was introduced in the left ventricle. The mitral valve was crossed under echo guidance. Using suction, either the anterior (two cases) or posterior (four cases) leaflet was captured and a loop of 4-0 polypropylene was thrown at the edge of the leaflet. The loop, with a pledget, was exteriorized through the introducer. The introducer was removed and the purse-string tied. Under echo guidance, the neochordae suture was pulled and tied over a pledget to evoke leaflet tethering. The animals were sacrificed and gross anatomy reviewed. Leaflet capture was feasible in the intended location in all cases. Following suture tethering, variable degrees of MR were obtained. At gross anatomy, the neochordae were positioned at 1-4mm from the leaflet free edge, and were firmly attached to the leaflets. Transcatheter endovascular neochordae implantation is feasible. A prolapse model is needed to further demonstrate feasibility under pathologic conditions. The apical approach allows easy and direct route to transcatheter beating heart minimally invasive mitral repair.

Rapid pannus formation after few months of obstructing aortic mechanical prosthesis.

PubMed

Al-Alao, Bassel; Simoniuk, Urszula; Heron, Brian; Parissis, Haralabos

2015-11-01

We report a rare case of a prosthetic aortic valve obstruction due to pannus formation only 3 months following aortic and mitral valve replacement. Fragments of asymmetrical pannus formation affected one of the leaflets of the bi-leaflet mechanical valve; the leaflet appeared immobile due to pannus ingrowth into the mechanical skeleton resulting in encroachment of the leaflet, which in turn became immobile. The patient successfully underwent emergency redo-aortic valve replacement.

Development of an off bypass mitral valve repair.

PubMed

Morales, D L; Madigan, J D; Choudhri, A F; Williams, M R; Helman, D N; Elder, J B; Naka, Y; Oz, M C

1999-01-01

The Bow Tie Repair (BTR), a single edge-to-edge suture opposing the anterior and posterior leaflets of the mitral valve (MV), has led to satisfactory reduction of mitral regurgitation (MR) with few re-operations and excellent hemodynamic results. The simplicity of the repair lends itself to minimally invasive approaches. A MV grasper has been developed that will coapt both leaflets and fasten the structures with a graduated spiral screw. Eleven explanted adult human MVs were mounted in a mock circulatory loop created for simulating a variety of hemodynamic conditions. The MV grasper was used to place a screw in each valve, which was then continuously run for 300,000 to 1,000,000 cycles with a fixed transvalvular pressure gradient. At the completion of these studies, the valves were stressed to a maximal transvalvular gradient for ten minutes. In seven cases, MR was induced and subsequently repaired using the MV screw. In vivo, the MV screw was tested in nine male canines. Through a subcostal incision, the MV grasper entered the left ventricle, approximated the mitral leaflets and deployed the MV screw under direct visualization via an atriotomy. Follow-up transthoracic echocardiograms were done at postoperative week 1, 6, and 12 to identify screw migration, MV regurgitation/stenosis or clot formation. Dogs were sacrificed up to postoperative week 12 to allow gross and histologic assessment. In vitro, no MV screw detached from the valve leaflets or migrated during the durability testing period of 6.8 million cycles, including periods of stress load testing up to 350 mm Hg. The percent regurgitant flow used to assess MR statistically decreased with the placement of the screw from 72 +/- 7% to 34 +/- 17%; p = 0.0025. In vivo, seven dogs whose valves were examined within the first 48 hours revealed leaflet coaptation with an intact MV screw and no evidence of MR. Two dogs, followed for a prolonged period, had serial postoperative echocardiograms demonstrating consistent coaptation, no screw migration, no clot, and no regurgitation or stenosis. In the animal sacrificed at 12 weeks, the MV screw was integrated into the tissue of both leaflets. The MV screw has provided durable leaflet coaptation and has reduced regurgitation in human MVs. Initial data on the MV screw's biocompatibility and interactions with living valve tissue is promising. Our early success supports further efforts towards the maturation of this prototype into off bypass mitral valve repair technology.

Retrieval of a leaflet escaped in a Tri-technologies bileaflet mechanical prosthetic valve.

PubMed

Cianciulli, Tomás F; Lax, Jorge A; Saccheri, María C; Guidoin, Robert; Salvado, César M; Fernández, Adrián J; Prezioso, Horacio A

2008-01-01

The escape of the prosthetic heart valve disc is one of the causes of prosthetic dysfunction that requires emergency surgery. The removal of the embolized disc should be carried out because of the risk of a progressive extrusion on the aortic wall. Several imaging techniques can be used for the detection of the missing disc localization. In this report we describe a 32-year-old man who underwent mitral valve replacement with a Tri-technologies bileaflet valve three years ago, and was admitted in cardiogenic shock. Transesophageal echocardiography showed acute-onset massive mitral regurgitation. The patient underwent emergency replacement of the prosthetic valve. Only one of the two leaflets remained in the removed prosthetic valve. The missing leaflet could not be found within the cardiac cavity. The abdominal fluoroscopic study and plain radiography were unable to detect the escaped leaflet. The abdominal computed tomography scan and the ultrasound showed the escaped leaflet in the terminal portion of the aortic bifurcation. To retrieve the embolized disc laparotomy and aortotomy were performed three months later. The escaped leaflet shows a fracture of one of the pivot systems caused by structural failure. This kind of failure mode is usually the result of high stress concentration.

The Impact of Fluid Inertia on In Vivo Estimation of Mitral Valve Leaflet Constitutive Properties and Mechanics.

PubMed

Bark, David L; Dasi, Lakshmi P

2016-05-01

We examine the influence of the added mass effect (fluid inertia) on mitral valve leaflet stress during isovolumetric phases. To study this effect, oscillating flow is applied to a flexible membrane at various frequencies to control inertia. Resulting membrane strain is calculated through a three-dimensional reconstruction of markers from stereo images. To investigate the effect in vivo, the analysis is repeated on a published dataset for an ovine mitral valve (Journal of Biomechanics 42(16): 2697-2701). The membrane experiment demonstrates that the relationship between pressure and strain must be corrected with a fluid inertia term if the ratio of inertia to pressure differential approaches 1. In the mitral valve, this ratio reaches 0.7 during isovolumetric contraction for an acceleration of 6 m/s(2). Acceleration is reduced by 72% during isovolumetric relaxation. Fluid acceleration also varies along the leaflet during isovolumetric phases, resulting in spatial variations in stress. These results demonstrate that fluid inertia may be the source of the temporally and spatially varying stiffness measurements previously seen through inverse finite element analysis of in vivo data during isovolumetric phases. This study demonstrates that there is a need to account for added mass effects when analyzing in vivo constitutive relationships of heart valves.

Echocardiographic assessment of mitral valve morphology and performance after triangular resection of the prolapsing posterior leaflet for degenerative myxomatous disease.

PubMed

Chiappini, Bruno; Gregorini, Renato; De Remigis, Franco; Petrella, Licia; Villani, Carmine; Di Pietrantonio, Fabrizio; Pavicevic, Srdan; Mazzola, Alessandro

2009-08-01

The gold standard for the surgical treatment of prolapse of the posterior leaflet of the mitral valve (MV) for degenerative myxomatous disease has been represented by the quadrangular resection of the leaflet, according to the Carpentier technique. Since 2006 we performed a triangular resection of the prolapsing leaflet in 20 patients with myxomatous mitral regurgitation (MR). Seventeen patients (85%) underwent the triangular resection of P2; one patient (5%) had a triple scallops triangular resection (P1, P2, P3) and two (10%) a double scallops (P2, P3) resection. In this study, we report the immediate and mid-term clinical and echocardiographic results of a cohort of 20 patients, who underwent this technique. Thirty-day mortality was 0. Acute renal failure occurred in three patients (15%) and they resolved with conservative management. One patient (5%) required re-exploration for bleeding. At the mean follow-up of 13.1+/-4.2 months survival was 95%; one patient died of lymphoma during the follow-up time. All the cases were in New York Heart Association (NYHA) class I. Nineteen survivors underwent transthoracic echocardiography (TTE) (5), or transesophageal echocardiography (TEE) (13), performed by two skilled cardiologists. All patients showed no or trivial MV regurgitation. We believe that triangular resection of posterior MV leaflet (PMVL) provides excellent mid-term results providing the surgeon with a reliable and reproducible surgical option for myxomatous degenerative MV regurgitation.

Rare Combination of Pathologies Causing Mitral Stenosis and Mitral Regurgitation: A Case Report.

PubMed

Nair, Anupama K; Chowdhuri, Kuntal Roy; Radhakrishnan, Sitaraman; Iyer, Krishna S; Saxena, Manish

2018-01-01

A supramitral ring is a rare cause of mitral stenosis, while an isolated mitral valve cleft is a rare cause of congenital mitral regurgitation. Fortunately, both the lesions are known to have good outcomes after surgical correction. Although each is known to be associated with a variety of other structural heart defects, their coexistence has not been reported previously. We report a case of a three- and half-year-old boy detected to have a rare combination of supramitral ring producing severe mitral stenosis with a coexisting cleft in the anterior leaflet of mitral valve causing severe mitral regurgitation. The patient underwent successful surgical repair with resolution of both mitral stenosis and regurgitation.

The 'respect rather than resect' principle in mitral valve repair: the lateral dislocation of the P2 technique.

PubMed

Zanobini, Marco; Ricciardi, Gabriella; Mammana, Francesco Liborio; Kassem, Samer; Poggio, Paolo; Di Minno, Alessandro; Cavallotti, L; Saccocci, Matteo

2017-09-01

Leaflet resection represents the reference standard for surgical treatment of mitral valve (MV) regurgitation. New approaches recently proposed place emphasis on respecting, rather than resecting, the leaflet tissue to avoid the drawbacks of the 'resection' approach. The lateral dislocation of mid portion of mitral posterior leaflet (P2) technique for MV repair is a nonresectional technique in which the prolapsed P2 segment is sutured to normal P1 segment. Our study evaluates the effectiveness of this technique. We performed the procedure on seven patients. Once ring annular sutures were placed, the prolapsed P2 segment was dislocated toward the normal P1 segment with a rotation of 90° and without any resection. If present, residual clefts between P2 and P3 segments were closed. Once the absence of residual mitral regurgitation is confirmed by saline pressure test, ring annuloplasty was completed. The valve was evaluated using transesophageal echocardiography in the operating room and by transthoracic echocardiography before discharge. At the last follow-up visit, transthoracic echocardiography revealed no mitral regurgitation and normal TRANSVALVULAR gradients. The lateral dislocation of P2 is an easily fine-tuned technique for isolated P2 prolapse, with the advantage of short aortic cross-clamp and cardiopulmonary bypass times. We think it might be very favorable in older and frail patients. Long-term follow-up is necessary to assess the durability of this technique.

Transapical off-pump mitral valve repair. First experience with the NeoChord system in Poland (report of two cases).

PubMed

Wróbel, Krzysztof; Kurnicka, Katarzyna; Zygier, Marcin; Dyk, Wojciech; Wojdyga, Ryszard; Zieliński, Dariusz; Jarzębska, Małgorzata; Juraszyński, Zbigniew; Lichodziejewska, Barbara; Pruszczyk, Piotr; Biederman, Andrzej; Speziali, Giovanni; Kasten, Uwe

2017-01-01

Artificial chord implantation to repair a flail or prolapsing mitral valve leaflet requires open heart surgery and cardiopulmonary bypass. Transapical off-pump artificial chordae implantation is a new surgical technique proposed to treat degenerative mitral valve regurgitation. The procedure is performed using the NeoChord DS1000 system (NeoChord, Inc., St. Louis Park, MN, USA), which facilitates both implantation and lenght adjustment of the artificial chordae under two (2D)- and three (3D)-dimensional transoesophageal echocardiographic (TEE) guidance on a beating heart. Two male patients aged 60 and 55 years with severe mitral regurgitation due to posterior leaflet prolapse underwent transapical off-pump artificial chordae implantation on September 3, 2015. The procedure was performed by left minithoracotomy under general anaesthesia in a cardiac surgical theatre, using 2D and 3D TEE guidance. Early procedural success as confirmed by 3D TEE was achieved in both patients, with implantation of 6 artificial chordae in the first patient and 3 artificial chordae in the second patient. Both procedures were uneventful, and no postoperative complications were noted. The patients were discharged home on the 8th and 6th postoperative day, respectively. The NeoChord DS1000 system allows both implantation and lenght adjustment of artificial chordae under 2D and 3D TEE guidance on a beating heart. Our initial experience in 2 patients with posterior mitral leaflet prolapse indicates that the procedure is feasible and safe.

Collagen birefringence assessment in heart chordae tendineae through PS-OCT

NASA Astrophysics Data System (ADS)

Real, Eusebio; Revuelta, José M.; González-Vargas, Nieves; Pontón, Alejandro; Calvo-Díez, Marta; López-Higuera, José M.; Conde, Olga M.

2017-02-01

Degenerative mitral regurgitation is a serious and frequent human heart valve disease. Malfunctioning of this valve brings the left-sided heart through a significant increase of pressure and volume overload. Severe degenerative mitral incompetence generally requires surgical repair or valve replacement with a bioprosthesis or mechanical heart valve. Degenerative disease affects the leaflets or/and the chordae tendineae, which link both leaflets to the papillary muscles. During mitral valve surgical repair, reconstruction of the valve leaflets, annulus and chordae are provided to prevent postoperative recurrence of valve regurgitation. The operative evaluation of the diseased and apparently normal chordae tendineae mainly depends of the surgeońs experience, without any other objective diagnosis tool. In this work, PS-OCT (Polarization Sensitive-Optical Coherence Tomography) is applied for the first time to evaluate the pathological condition of human chordae coming from the mitral valve. It consists on a prospective study to test the viability of this technique for the evaluation of the collagen core of chords. This core presents a strong birefringence due to the longitudinal and organized arrangement of its collagen bundles. Different densities and organizations of the collagen core translate into different birefringence indicators whose measurement become an objective marker of the core structure. Ex-vivo mitral degenerative chordae tendineae have been analyzed with PS-OCT. Intensity OCT is used to obtain complementary morphological information of the chords. Birefringence results correlate with the previously reported values for human tendinous tissue.

Robotic artificial chordal replacement for repair of mitral valve prolapse.

PubMed

Brunsting, Louis A; Rankin, J Scott; Braly, Kimberly C; Binford, Robert S

2009-07-01

Artificial chordal replacement (ACR) has emerged as a superior method of mitral valve repair with excellent early and late efficacy. It is also ideal to combine with robotic techniques for correction of mitral prolapse, and this article presents a current method of robotic Gore-Tex ACR. Patients with isolated posterior leaflet prolapse are approached with the fourth-generation DaVinci robotic system and endoaortic balloon occlusion. A pledgetted anchor stitch is placed in a papillary muscle, and a 2-o Gore-Tex suture is passed through the anchor pledget. After full annuloplasty ring placement, the Gore-Tex suture is woven into the prolapsing segment and positioned temporarily with robotic forceps. Chordal length is then "adjusted" by lengthening or shortening the temporary knot over 1-cm increments as the valve is tested by injection of cold saline into the ventricle. After achieving good leaflet position and valve competence, the chord is tied permanently. The "adjustable" ACR procedure preserves leaflet surface area and produces a competent valve in the majority of patients. Postoperative transesophageal echo shows a large surface area of coaptation. Patient recovery is facilitated by the minimally invasive approach, while long-term stability of similar open ACR techniques have been excellent with a 2% to 3% failure rate over 10 years of follow-up. Robotic Gore-Tex ACR without leaflet resection is a reproducible procedure that simplifies mitral repair for prolapse. The outcomes observed in early robotic applications have been excellent. It is suggested that most patients with simple prolapse might validly be approached in this manner.

Transcatheter mitral direct annuloplasty: state of the art.

PubMed

Maisano, F; Kuck, K H

2014-06-01

Transcatheter mitral interventions are emerging as a novel therapy for patients with severe symptomatic mitral regurgitation who are deemed to be high risk or inoperable. Surgical treatment of mitral regurgitation includes a wide spectrum of therapies, ranging from leaflet and annular repair, to mitral valve replacement. Annuloplasty plays a fundamental role in open heart mitral valve repair, since it is associated with longer durability and higher degree of mitral regurgitation reduction. Direct annuloplasty is the interventional methodology most closely reproducing open heart annular repair. We describe the challenges and opportunities of the most promising technologies currently under development which will become available in clinical practice in the next future.

Outlet strut fracture and leaflet escape of Bjork-Shiley convexo-concave valve.

PubMed

Uchino, Gaku; Yoshida, Hideo; Sakoda, Naoya; Hattori, Shigeru; Kawabata, Takuya; Saiki, Munehiro; Fujita, Yasufumi; Yunoki, Keiji; Hisamochi, Kunikazu; Mine, Yoshinari

2017-06-01

Prosthetic valve fracture is a serious complication and may arise in patient post-valve replacement. We experienced an outlet strut fracture and leaflet escape of a Bjork-Shiley convexo-concave valve. We performed an emergency redo mitral valve replacement and successfully retrieved the fractured strut and escaped leaflet from superficial femoral artery and the abdominal aorta. The patient showed an uneventful postoperative recovery.

The dynamic cardiac biosimulator: A method for training physicians in beating-heart mitral valve repair procedures.

PubMed

Leopaldi, Alberto M; Wrobel, Krzysztof; Speziali, Giovanni; van Tuijl, Sjoerd; Drasutiene, Agne; Chitwood, W Randolph

2018-01-01

Previously, cardiac surgeons and cardiologists learned to operate new clinical devices for the first time in the operating room or catheterization laboratory. We describe a biosimulator that recapitulates normal heart valve physiology with associated real-time hemodynamic performance. To highlight the advantages of this simulation platform, transventricular extruded polytetrafluoroethylene artificial chordae were attached to repair flail or prolapsing mitral valve leaflets. Guidance for key repair steps was by 2-dimensional/3-dimensional echocardiography and simultaneous intracardiac videoscopy. Multiple surgeons have assessed the use of this biosimulator during artificial chordae implantations. This simulation platform recapitulates normal and pathologic mitral valve function with associated hemodynamic changes. Clinical situations were replicated in the simulator and echocardiography was used for navigation, followed by videoscopic confirmation. This beating heart biosimulator reproduces prolapsing mitral leaflet pathology. It may be the ideal platform for surgeon and cardiologist training on many transcatheter and beating heart procedures. Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.

Increased frequency of mitral valve prolapse in patients with deviated nasal septum.

PubMed

Arslan, Hasan Huseyin; Aparci, Mustafa; Arslan, Zekeriya; Ozturk, Cengiz; Isilak, Zafer; Balta, Sevket; Celik, Turgay; Iyisoy, Atila

2015-07-01

Any abnormality of collagen may affect the tissues with higher collagen content, e.g., joints, heart valves, and great arteries. Mitral valve prolapse (MVP) is a characteristic of generalized collagen abnormality. Nasal septum (NS) is constituted by osseous and cartilaginous septums that are highly rich in collagen. We evaluated the co-existence of deviation of NS (DNS) in patients with MVP. We retrospectively evaluated the recordings of echocardiographic and nasal examinations of subjects with MVP and DNS. We analyzed the features of MVP and anatomical classification of DNS among subjects. Totally, 74 patients with DNS and 38 subjects with normal nasal passage were enrolled to the study. Presence of MVP was significantly higher in patients with DNS compared to normal subjects (63 vs 26%, p < 0.001). Prolapse of anterior, posterior and both leaflets was higher in patients with DNS. Thickness of anterior mitral leaflet was significantly increased in patients with DNS (3.57 ± 0.68 vs 4.59 ± 1.1 mm, p < 0.001) compared to normal subjects. Type I, II, and III, IV DNS were higher in frequency in patients with MVP while type V and VI were higher in normal subjects. DNS is highly co-existent with MVP and increased thickness of mitral anterior leaflet. Generalized abnormality of collagen which is the main component of mitral valves and nasal septum may be accounted for co-existence of MVP and DNS. Also co-existence of them may exaggerate the symptoms of patients with MVP due to limited airflow through the nasal passage.

Multiplanar visualization in 3D transthoracic echocardiography for precise delineation of mitral valve pathology.

PubMed

Kuppahally, Suman S; Paloma, Allan; Craig Miller, D; Schnittger, Ingela; Liang, David

2008-01-01

A novel multiplanar reformatting (MPR) technique in three-dimensional transthoracic echocardiography (3D TTE) was used to precisely localize the prolapsed lateral segment of posterior mitral valve leaflet in a patient symptomatic with mitral valve prolapse (MVP) and moderate mitral regurgitation (MR) before undergoing mitral valve repair surgery. Transesophageal echocardiography was avoided based on the findings of this new technique by 3D TTE. It was noninvasive, quick, reproducible and reliable. Also, it did not need the time-consuming reconstruction of multiple cardiac images. Mitral valve repair surgery was subsequently performed based on the MPR findings and corroborated the findings from the MPR examination.

Quantification of mitral and tricuspid regurgitation by the proximal flow convergence method using two-dimensional colour Doppler and colour Doppler M-mode: influence of the mechanism of regurgitation.

PubMed

Grossmann, G; Giesler, M; Stein, M; Kochs, M; Höher, M; Hombach, V

1998-10-30

In patients with mitral (n=77: organic=49, functional=28) and tricuspid regurgitation (n=55: functional=54) quantified by angiography, the temporal variation of the proximal flow convergence region throughout systole was assessed by colour Doppler M-Mode, and peak and mean radius of the proximal isovelocity surface area for 28 cm/s blood flow velocity were measured. Additionally, the peak radius derived from two-dimensional colour Doppler was obtained. About 50% of the patients with mitral and tricuspid regurgitation showed a typical temporal variation of the flow convergence region related to the mechanism of regurgitation. The different proximal isovelocity surface area radii were similarly correlated to the angiographic grade in mitral and tricuspid regurgitation (rank correlation coefficients 0.55-0.89) and they differentiated mild to moderate (grade < or =II) from severe (grade > or =III) mitral and tricuspid regurgitation with comparable accuracy (82-96%). However, moderate mitral regurgitation due to leaflet prolapse in two patients was correctly classified by the mean M-mode radius and overestimated by both peak radii. Only half of the patients showed a typical variation of the flow convergence region related to the mechanism of regurgitation. The different proximal isovelocity surface area radii were suitable to quantify mitral and tricuspid regurgitation in most patients. However, in mitral regurgitation due to leaflet prolapse the use of the mean M-mode radius may avoid overestimation.

Impact of mitral valve geometry on hemodynamic efficacy of surgical repair in secondary mitral regurgitation.

PubMed

Padala, Muralidhar; Gyoneva, Lazarina I; Thourani, Vinod H; Yoganathan, Ajit P

2014-01-01

Mitral valve geometry is significantly altered secondary to left ventricular remodeling in non-ischemic and ischemic dilated cardiomyopathies. Since the extent of remodeling and asymmetry of dilatation of the ventricle differ significantly between individual patients, the valve geometry and tethering also differ. The study aim was to determine if mitral valve geometry has an impact on the efficacy of surgical repairs to eliminate regurgitation and restore valve closure in a validated experimental model. Porcine mitral valves (n = 8) were studied in a pulsatile heart simulator, in which the mitral valve geometry can be precisely altered and controlled throughout the experiment. Baseline hemodynamics for each valve were measured (Control), and the valves were tethered in two distinct ways: annular dilatation with 7 mm apical papillary muscle (PM) displacement (Tether 1, symmetric), and annular dilatation with 7 mm apical, 7 mm posterior and 7 mm lateral PM displacement (Tether 2, asymmetric). Mitral annuloplasty was performed on each valve (Annular Repair), succeeded by anterior leaflet secondary chordal cutting (Sub-annular Repair). The efficacy of each repair in the setting of a given valve geometry was quantified by measuring the changes in mitral regurgitation (MR), leaflet coaptation length, tethering height and area. At baseline, none of the valves was regurgitant. Significant leaflet tethering was measured in Tether 2 over Tether 1, but both groups were significantly higher compared to baseline (60.9 +/- 31 mm2 for Control versus 129.7 +/- 28.4 mm2 for Tether 1 versus 186.4 +/- 36.3 mm2 for Tether 2). Consequently, the MR fraction was higher in Tether 2 group (23.0 +/- 5.7%) than in Tether 1 (10.5 +/- 5.5%). Mitral annuloplasty reduced MR in both groups, but remnant regurgitation after the repair was higher in Tether 2. After chordal cutting a similar trend was observed with trace regurgitation in Tether 1 group at 3.6 +/- 2.8%, in comparison to 18.6 +/- 4.2% in the Tether 2 group. In this experimental model, the tethering geometry of the mitral valve impacts the valve hemodynamics after annuloplasty and chordal cutting. The quantitative assessment of valve geometry may help in tailoring a repair to the specific tethering pattern.

A novel left heart simulator for the multi-modality characterization of native mitral valve geometry and fluid mechanics.

PubMed

Rabbah, Jean-Pierre; Saikrishnan, Neelakantan; Yoganathan, Ajit P

2013-02-01

Numerical models of the mitral valve have been used to elucidate mitral valve function and mechanics. These models have evolved from simple two-dimensional approximations to complex three-dimensional fully coupled fluid structure interaction models. However, to date these models lack direct one-to-one experimental validation. As computational solvers vary considerably, experimental benchmark data are critically important to ensure model accuracy. In this study, a novel left heart simulator was designed specifically for the validation of numerical mitral valve models. Several distinct experimental techniques were collectively performed to resolve mitral valve geometry and hemodynamics. In particular, micro-computed tomography was used to obtain accurate and high-resolution (39 μm voxel) native valvular anatomy, which included the mitral leaflets, chordae tendinae, and papillary muscles. Three-dimensional echocardiography was used to obtain systolic leaflet geometry. Stereoscopic digital particle image velocimetry provided all three components of fluid velocity through the mitral valve, resolved every 25 ms in the cardiac cycle. A strong central filling jet (V ~ 0.6 m/s) was observed during peak systole with minimal out-of-plane velocities. In addition, physiologic hemodynamic boundary conditions were defined and all data were synchronously acquired through a central trigger. Finally, the simulator is a precisely controlled environment, in which flow conditions and geometry can be systematically prescribed and resultant valvular function and hemodynamics assessed. Thus, this work represents the first comprehensive database of high fidelity experimental data, critical for extensive validation of mitral valve fluid structure interaction simulations.

Mitral stenosis due to dynamic clip-leaflet interaction during the MitraClip procedure: Case report and review of current knowledge.

PubMed

Singh, Gagan D; Smith, Thomas W; Rogers, Jason H

2017-06-01

The goal of MitraClip therapy is to achieve mitral regurgitation reduction without iatrogenic creation of clinically significant MS. In some series, up to 35% of patients are left with mild MS. There are many contributors to the final transmitral gradient achieved in patients undergoing MitraClip therapy. Additionally, there are many modalities used for the intraprocedural assessment of MS with no one modality considered to be the benchmark. We herein describe a case which illustrates the dynamic nature of clip-leaflet interaction, and review intraprocedural techniques for invasively and noninvasively assessing MS. Copyright © 2016 Elsevier Inc. All rights reserved.

Intravalvular Implantation of Mitral Valve Prostheses

PubMed Central

Cooley, Denton A.; Ingram, Michael T.

1987-01-01

We describe a technique of intravalvular implantation of a low-profile prosthesis that has been used in nine patients with mitral valve lesions. This technique preserves the anterior and posterior chordae and papillary mechanisms, which may decrease the incidence of postoperative left ventricular dysfunction that has been noted following standard mitral valve replacement. The technique may also be useful in some patients with aortic and tricuspid regurgitation when the annulus and leaflets are relatively normal pathologically. (Texas Heart Institute Journal 1987;14:188-193) PMID:15229740

Mitral valve-sparing procedures and prosthetic heart valve failure: A case report

PubMed Central

Khan, Nasir A; Butany, Jagdish; Leong, Shaun W; Rao, Vivek; Cusimano, Robert J; Ross, Heather J

2009-01-01

Prosthetic heart valve dysfunction due to thrombus or pannus formation can be a life-threatening complication. The present report describes a 47-year-old woman who developed valvular cardiomyopathy after chorda-sparing mitral valve replacement, and subsequently underwent heart transplantation for progressive heart failure. The explanted mitral valve prosthesis showed significant thrombus and pannus leading to reduced leaflet mobility and valvular stenosis. The present report illustrates the role of the subvalvular apparatus and pannus in prosthesis dysfunction. PMID:19279993

Finite Element Analysis of Patient-Specific Mitral Valve with Mitral Regurgitation.

PubMed

Pham, Thuy; Kong, Fanwei; Martin, Caitlin; Wang, Qian; Primiano, Charles; McKay, Raymond; Elefteriades, John; Sun, Wei

2017-03-01

Functional mitral regurgitation (FMR) is a significant complication of left ventricular dysfunction and strongly associated with a poor prognosis. In this study, we developed a patient-specific finite element (FE) model of the mitral apparatus in a FMR patient which included: both leaflets with thickness, annulus, chordae tendineae, and chordae insertions on the leaflets and origins on the papillary muscles. The FE model incorporated human age- and gender-matched anisotropic hyperelastic material properties, and MV closure at systole was simulated. The model was validated by comparing the FE results from valve closure simulation with the in vivo geometry of the MV at systole. It was found that the FE model could not replicate the in vivo MV geometry without the application of tethering pre-tension force in the chordae at diastole. Upon applying the pre-tension force and performing model optimization by adjusting the chordal length, position, and leaflet length, a good agreement between the FE model and the in vivo model was established. Not only were the chordal forces high at both diastole and systole, but the tethering force on the anterior papillary muscle was higher than that of the posterior papillary muscle, which resulted in an asymmetrical gap with a larger orifice area at the anterolateral commissure resulting in MR. The analyses further show that high peak stress and strain were found at the chordal insertions where large chordal tethering forces were found. This study shows that the pre-tension tethering force plays an important role in accurately simulating the MV dynamics in this FMR patient, particularly in quantifying the degree of leaflet coaptation and stress distribution. Due to the complexity of the disease, the patient-specific computational modeling procedure of FMR patients presented should be further evaluated using a large patient cohort. However, this study provides useful insights into the MV biomechanics of a FMR patient, and could serve as a tool to assist in pre-operative planning for MV repair or replacement surgical or interventional procedures.

Functional and Biomechanical Effects of the Edge-to-Edge Repair in the Setting of Mitral Regurgitation: Consolidated Knowledge and Novel Tools to Gain Insight into Its Percutaneous Implementation.

PubMed

Sturla, Francesco; Redaelli, Alberto; Puppini, Giovanni; Onorati, Francesco; Faggian, Giuseppe; Votta, Emiliano

2015-06-01

Mitral regurgitation is the most prevalent heart valve disease in the western population. When severe, it requires surgical treatment, repair being the preferred option. The edge-to-edge repair technique treats mitral regurgitation by suturing the leaflets together and creating a double-orifice valve. Due to its relative simplicity and versatility, it has become progressively more widespread. Recently, its percutaneous version has become feasible, and has raised interest thanks to the positive results of the Mitraclip(®) device. Edge-to-edge features and evolution have stimulated debate and multidisciplinary research by both clinicians and engineers. After providing an overview of representative studies in the field, here we propose a novel computational approach to the most recent percutaneous evolution of the edge-to-edge technique. Image-based structural finite element models of three mitral valves affected by posterior prolapse were derived from cine-cardiac magnetic resonance imaging. The models accounted for the patient-specific 3D geometry of the valve, including leaflet compound curvature pattern, patient-specific motion of annulus and papillary muscles, and hyperelastic and anisotropic mechanical properties of tissues. The biomechanics of the three valves throughout the entire cardiac cycle was simulated before and after Mitraclip(®) implantation, assessing the biomechanical impact of the procedure. For all three simulated MVs, Mitraclip(®) implantation significantly improved systolic leaflets coaptation, without inducing major alterations in systolic peak stresses. Diastolic orifice area was decreased, by up to 58.9%, and leaflets diastolic stresses became comparable, although lower, to systolic ones. Despite established knowledge on the edge-to-edge surgical repair, latest technological advances make its percutanoues implementation a challenging field of research. The modeling approach herein proposed may be expanded to analyze clinical scenarios that are currently critical for Mitraclip(®) implantation, helping the search for possible solutions.

Vector flow mapping in obstructive hypertrophic cardiomyopathy to assess the relationship of early systolic left ventricular flow and the mitral valve.

PubMed

Ro, Richard; Halpern, Dan; Sahn, David J; Homel, Peter; Arabadjian, Milla; Lopresto, Charles; Sherrid, Mark V

2014-11-11

The hydrodynamic cause of systolic anterior motion of the mitral valve (SAM) is unresolved. This study hypothesized that echocardiographic vector flow mapping, a new echocardiographic technique, would provide insights into the cause of early SAM in obstructive hypertrophic cardiomyopathy (HCM). We analyzed the spatial relationship of left ventricular (LV) flow and the mitral valve leaflets (MVL) on 3-chamber vector flow mapping frames, and performed mitral valve measurements on 2-dimensional frames in patients with obstructive and nonobstructive HCM and in normal patients. We compared 82 patients (22 obstructive HCM, 23 nonobstructive HCM, and 37 normal) by measuring 164 LV pre- and post-SAM velocity vector flow maps, 82 maximum isovolumic vortices, and 328 2-dimensional frames. We observed color flow and velocity vector flow posterior to the MVL impacting them in the early systolic frames of 95% of obstructive HCM, 22% of nonobstructive HCM, and 11% of normal patients (p < 0.001). In both pre- and post-SAM frames, we measured a high angle of attack >60° of local vector flow onto the posterior surface of the leaflets whether the flow was ejection (59%) or the early systolic isovolumic vortex (41%). Ricochet of vector flow, rebounding off the leaflet into the cul-de-sac, was noted in 82% of the obstructed HCM, 9% of nonobstructive HCM, and none (0%) of the control patients (p < 0.001). Flow velocities in the LV outflow tract on the pre-SAM frame 1 and 2 mm from the tip of the anterior leaflet were low: 39 and 43 cm/s, respectively. Early systolic flow impacts the posterior surfaces of protruding MVL initiating SAM in obstructive HCM. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Haemodynamic improvement of older, previously replaced mechanical mitral valves by removal of the subvalvular pannus in redo cardiac surgery.

PubMed

Kim, Jong Hun; Kim, Tae Youn; Choi, Jong Bum; Kuh, Ja Hong

2017-01-01

Patients requiring redo cardiac surgery for diseased heart valves other than mitral valves may show increased pressure gradients and reduced valve areas of previously placed mechanical mitral valves due to subvalvular pannus formation. We treated four women who had mechanical mitral valves inserted greater than or equal to 20 years earlier and who presented with circular pannus that protruded into the lower margin of the valve ring but did not impede leaflet motion. Pannus removal improved the haemodynamic function of the mitral valve. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Leaflet escape in a new bileaflet mechanical valve: TRI technologies.

PubMed

Bottio, Tomaso; Casarotto, Dino; Thiene, Gaetano; Caprili, Luca; Angelini, Annalisa; Gerosa, Gino

2003-05-13

Leaflet escape is a mode of structural valve failure for mechanical prostheses. This complication previously has been reported for both monoleaflet and bileaflet valve models. We report 2 leaflet escape occurrences observed in 2 patients who underwent valve replacement with a TRI Technologies valve prosthesis. At the University of Padua, between November 2000 and February 2002, 36 TRI Technologies valve prostheses (26 aortic and 10 mitral) were implanted in 34 patients (12 women and 22 men) with a mean age of 59.9+/-10.3 years (range, 30 to 75 years). There were 5 deaths: 3 in hospital, 1 early after discharge, and 1 late. Two patients experienced a catastrophic prosthetic leaflet escape; the first patient was a 52-year-old man who died 10 days after aortic valve and ascending aorta replacement, and the second was a 58-year-old man who underwent a successful emergency reoperation 20 months after mitral valve replacement. Examination of the explanted prostheses showed in both cases a leaflet escape caused by a leaflet's pivoting system fracture. Prophylactic replacement was then successfully accomplished so far in 12 patients, without evidence of structural valve failure in any of them. Among other significant postoperative complications, we observed 3 major thromboembolisms, 1 hemorrhage, and 1 paravalvular leak. These catastrophes prompted us to interrupt the implantation program, and they cast a shadow on the durability of the TRI Technologies valve prosthesis because of its high risk of structural failure.

Collagen organization in canine myxomatous mitral valve disease: an x-ray diffraction study.

PubMed

Hadian, Mojtaba; Corcoran, Brendan M; Han, Richard I; Grossmann, J Günter; Bradshaw, Jeremy P

2007-10-01

Collagen fibrils, a major component of mitral valve leaflets, play an important role in defining shape and providing mechanical strength and flexibility. Histopathological studies show that collagen fibrils undergo dramatic changes in the course of myxomatous mitral valve disease in both dogs and humans. However, little is known about the detailed organization of collagen in this disease. This study was designed to analyze and compare collagen fibril organization in healthy and lesional areas of myxomatous mitral valves of dogs, using synchrotron small-angle x-ray diffraction. The orientation, density, and alignment of collagen fibrils were mapped across six different valves. The findings reveal a preferred collagen alignment in the main body of the leaflets between two commissures. Qualitative and quantitative analysis of the data showed significant differences between affected and lesion-free areas in terms of collagen content, fibril alignment, and total tissue volume. Regression analysis of the amount of collagen compared to the total tissue content at each point revealed a significant relationship between these two parameters in lesion-free but not in affected areas. This is the first time this technique has been used to map collagen fibrils in cardiac tissue; the findings have important applications to human cardiology.

Mitral Valve Structure in Addition to Myocardial Viability Determines the Outcome of Functional Mitral Regurgitation After Coronary Artery Bypass Grafting.

PubMed

Yoshida, Shohei; Fukushima, Satsuki; Miyagawa, Shigeru; Nakamura, Teruya; Yoshikawa, Yasushi; Hata, Hiroki; Saito, Shunsuke; Yoshioka, Daisuke; Domae, Keitaro; Kashiyama, Noriyuki; Yamamoto, Kouji; Shintani, Ayumi; Nakatani, Satoshi; Toda, Koichi; Sawa, Yoshiki

2017-10-25

Coronary artery bypass grafting (CABG) reduces functional mitral regurgitation (MR) associated with ischemic heart disease, although the predictive factors or mechanisms of reversibility of functional MR after CABG are not fully understood.We investigated whether mitral valve structure is associated with the outcome of functional MR after CABG.Methods and Results:From a consecutive series of 98 patients with mild-moderate functional MR preoperatively who underwent isolated CABG, we enrolled 66 patients who were followed up for >1 year postoperatively using echocardiography. The degree of MR was reduced in 34 patients (52%) postoperatively, in association with a lower rate of in-hospital treatment for cardiac failure in the long term, compared with the 32 patients (48%) with residual MR postoperatively. The patients with reduced MR postoperatively had longer estimated coaptation length and more anteriorly or centrally directed MR jets than those without reduced MR. On statistical analysis, the addition of estimated coaptation length and jet direction to the reported predictors (ejection fraction, left ventricular end-diastolic dimension, and tenting height) more accurately predicted changes in post-CABG MR than the reported 3 factors alone. Residual MR was associated with the emergence of congestive heart failure in the long term after CABG. A specific mitral valve structure, such as large mitral leaflet size or predominant tethering of the posterior leaflet, was a predictive factor for the reversibility of post-CABG functional MR.

Acquired discrete subaortic stenosis late after mitral valve replacement.

PubMed

Mohan, Jagdish C; Shukla, Madhu; Mohan, Vishwas; Sethi, Arvind

2016-09-01

Although acquired left ventricular outflow obstruction has been reported in a variety of conditions, there are scant reports of its occurrence following mitral valve replacement (MVR). This study describes two female patients, who developed severe discrete subaortic stenosis, five years following MVR. In both cases, the mitral valve was replaced by a porcine Carpentier-Edwards 27-mm bioprosthesis with preservation of mitral valve leaflets. The risk of very late left ventricular outflow tract obstruction after bio-prosthetic MVR with preservation of subvalvular apparatus needs to be kept in mind in symptomatic patients. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Effect of Losartan on Mitral Valve Changes After Myocardial Infarction.

PubMed

Bartko, Philipp E; Dal-Bianco, Jacob P; Guerrero, J Luis; Beaudoin, Jonathan; Szymanski, Catherine; Kim, Dae-Hee; Seybolt, Margo M; Handschumacher, Mark D; Sullivan, Suzanne; Garcia, Michael L; Titus, James S; Wylie-Sears, Jill; Irvin, Whitney S; Messas, Emmanuel; Hagège, Albert A; Carpentier, Alain; Aikawa, Elena; Bischoff, Joyce; Levine, Robert A

2017-09-05

After myocardial infarction (MI), mitral valve (MV) tethering stimulates adaptive leaflet growth, but counterproductive leaflet thickening and fibrosis augment mitral regurgitation (MR), doubling heart failure and mortality. MV fibrosis post-MI is associated with excessive endothelial-to-mesenchymal transition (EMT), driven by transforming growth factor (TGF)-β overexpression. In vitro, losartan-mediated TGF-β inhibition reduces EMT of MV endothelial cells. This study tested the hypothesis that profibrotic MV changes post-MI are therapeutically accessible, specifically by losartan-mediated TGF-β inhibition. The study assessed 17 sheep, including 6 sham-operated control animals and 11 with apical MI and papillary muscle retraction short of producing MR; 6 of the 11 were treated with daily losartan, and 5 were untreated, with flexible epicardial mesh comparably limiting left ventricular (LV) remodeling. LV volumes, tethering, and MV area were quantified by using three-dimensional echocardiography at baseline and at 60 ± 6 days, and excised leaflets were analyzed by histopathology and flow cytometry. Post-MI LV dilation and tethering were comparable in the losartan-treated and untreated LV constraint sheep. Telemetered sensors (n = 6) showed no significant losartan-induced changes in arterial pressure. Losartan strongly reduced leaflet thickness (0.9 ± 0.2 mm vs. 1.6 ± 0.2 mm; p < 0.05; 0.4 ± 0.1 mm sham animals), TGF-β, and downstream phosphorylated extracellular-signal-regulated kinase and EMT (27.2 ± 12.0% vs. 51.6 ± 11.7% α-smooth muscle actin-positive endothelial cells, p < 0.05; 7.2 ± 3.5% sham animals), cellular proliferation, collagen deposition, endothelial cell activation (vascular cell adhesion molecule-1 expression), neovascularization, and cells positive for cluster of differentiation (CD) 45, a hematopoietic marker associated with post-MI valve fibrosis. Leaflet area increased comparably (17%) in constrained and losartan-treated sheep. Profibrotic changes of tethered MV leaflets post-MI can be modulated by losartan without eliminating adaptive growth. Understanding the cellular and molecular mechanisms could provide new opportunities to reduce ischemic MR. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

A new definition for an old entity: improved definition of mitral valve prolapse using three-dimensional echocardiography and color-coded parametric models.

PubMed

Addetia, Karima; Mor-Avi, Victor; Weinert, Lynn; Salgo, Ivan S; Lang, Roberto M

2014-01-01

Differentiating between mitral valve (MV) prolapse (MVP) and MV billowing (MVB) on two-dimensional echocardiography is challenging. The aim of this study was to test the hypothesis that color-coded models of maximal leaflet displacement from the annular plane into the atrium derived from three-dimensional transesophageal echocardiography would allow discrimination between these lesions. Three-dimensional transesophageal echocardiographic imaging of the MV was performed in 50 patients with (n = 38) and without (n = 12) degenerative MV disease. Definitive diagnosis of MVP versus MVB was made using inspection of dynamic three-dimensional renderings and multiple two-dimensional cut planes extracted from three-dimensional data sets. This was used as a reference standard to test an alternative approach, wherein the color-coded parametric models were inspected for integrity of the coaptation line and location of the maximally displaced portion of the leaflet. Diagnostic interpretations of these models by two independent readers were compared with the reference standard. In all cases of MVP, the color-coded models depicted loss of integrity of the coaptation line and maximal leaflet displacement extending to the coaptation line. MVB was depicted by preserved leaflet apposition with maximal displacement away from the coaptation line. Interpretation of the 50 color-coded models by novice readers took 5 to 10 min and resulted in good agreement with the reference technique (κ = 0.81 and κ = 0.73 for the two readers). Three-dimensional color-coded models provide a static display of MV leaflet displacement, allowing differentiation between MVP and MVB, without the need to inspect multiple planes and while taking into account the saddle shape of the mitral annulus. Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Insufficient Leaflet Remodeling in Patients With Atrial Fibrillation: Association With the Severity of Mitral Regurgitation.

PubMed

Kagiyama, Nobuyuki; Hayashida, Akihiro; Toki, Misako; Fukuda, Shota; Ohara, Minako; Hirohata, Atsushi; Yamamoto, Keizo; Isobe, Mitsuaki; Yoshida, Kiyoshi

2017-03-01

The relationship between annular dilatation caused by atrial fibrillation (AF) and mitral regurgitation (MR) remains controversial. We hypothesized that the small ratio of total leaflet area/annulus area (TLA/AA), reflecting insufficient leaflet remodeling to annular dilatation, is a main component of MR in patients with AF. Three-dimensional transesophageal echocardiographic data of the mitral valve were analyzed in 28 AF patients with moderate or severe MR (MR group), age- and sex-matched 56 AF patients with mild or less MR (non-MR group), and 16 control subjects. AA was significantly greater in both the MR (645±126 mm 2 /m 2 , P <0.001) and non-MR groups (568±121 mm 2 /m 2 , P =0.001) compared with control subjects (444±108 mm 2 /m 2 ). However, TLA/AA was significantly smaller in the MR (1.29±0.10, P <0.001), but not in the non-MR group (1.65±0.24, P >0.99), compared with control subjects (1.70±0.29). In linear regression analysis, TLA/AA was inversely associated with the effective regurgitant orifice ( r =-0.73, P <0.001). The area under the receiver-operating-characteristics curve of TLA/AA was significantly greater than that of AA (0.95 versus 0.72, P <0.001). Multivariable analysis revealed that small TLA/AA ( P <0.001) was independently associated with significant MR, while AA was not ( P =0.26). In patients with AF, insufficient leaflet remodeling to annular dilatation, rather than crude annular dilatation, was strongly associated with the severity of MR. © 2017 American Heart Association, Inc.

Artificial chordae for degenerative mitral valve disease: critical analysis of current techniques

PubMed Central

Ibrahim, Michael; Rao, Christopher; Athanasiou, Thanos

2012-01-01

The surgical repair of degenerative mitral valve disease involves a number of technical points of importance. The use of artificial chordae for the repair of degenerative disease has increased as a part of the move from mitral valve replacement to repair of the mitral valve. The use of artificial chordae provides an alternative to the techniques pioneered by Carpentier (including the quadrangular resection, transfer of native chordae and papillary muscle shortening/plasty), which can be more technically difficult. Despite a growth in their uptake and the indications for their use, a number of challenges remain for the use of artificial chordae in mitral valve repair, particularly in the determination of the correct length to ensure optimal leaflet coaptation. Here, we analyse over 40 techniques described for artificial chordae mitral valve repair in the setting of degenerative disease. PMID:22962321

Four decades of experience with mitral valve repair: analysis of differential indications, technical evolution, and long-term outcome.

PubMed

DiBardino, Daniel J; ElBardissi, Andrew W; McClure, R Scott; Razo-Vasquez, Ozwaldo A; Kelly, Nicole E; Cohn, Lawrence H

2010-01-01

To determine the long-term outcomes of mitral valvuloplasty for myxomatous valve disease, rheumatic valve disease, and functional mitral regurgitation. A total of 1503 patients underwent mitral valvuloplasty by a single surgeon between February 1972 and April 2008 and were retrospectively reviewed for short- and long-term results. Overall mean age was 60.3 + or - 13.7 years, and 57% were male. The cause was rheumatic in 193 patients, myxomatous in 1042 patients, and ischemic and nonischemic functional mitral regurgitation in 236 patients. Ring annuloplasty was performed in 1306 patients (87%). Commissurotomy was the primary repair for rheumatic valves, posterior leaflet resection and reconstruction was the most common repair for myxomatous valves (527/1042 [51%]), and ring reduction annuloplasty was the primary operation for functional mitral regurgitation. The 30-day mortality was 19 of 1503 patients (1.3%) and significantly higher in the functional mitral regurgitation group (11/236 patients, 4.7% vs 0.5% in the rheumatic group and 0.6% in the myxomatous group, P < .01). The 10-, 20-, and 30-year survivals were similar for the rheumatic and myxomatous groups (77%, 56%, and 39% vs 79%, 62%, and 52%, respectively) but significantly less for the functional mitral regurgitation group (44%, 4%, and 0%, respectively, log-rank P < .0001). The 10- and 20-year freedom from reoperation rates were significantly better for the myxomatous group than for the rheumatic group (90% and 82% vs 66% and 34%, log-rank P < .0001), with a 30-year freedom from reoperation of only 10% for rheumatic repair. In the myxomatous group, freedom from reoperation was lower in patients with anterior leaflet pathology (P = .0008). Follow-up data to 36 years demonstrate that cause strongly determines survival and durability of mitral valvuloplasty; patients with rheumatic valve disease who survive more than 20 years require reoperation, whereas functional mitral regurgitation carries the highest short- and long-term mortality rates and lowest freedom from reoperation. Mitral valvuloplasty for myxomatous valves demonstrates the longest durability, with many patients free from reoperation at 30 years. Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Mitral Valve Disease

MedlinePlus

... leaflets) that open and close, allowing blood to flow from your left atrium to your left ventricle ... does not open enough to allow sufficient blood flow. Usually this is the result of hardening (calcification) ...

Modified edge-to-edge technique for correction of congenital mitral regurgitation in infants and children.

PubMed

Zhang, Gang; Zhang, Fusheng; Zhu, Mei; Zhang, Wenlong; Fan, Quanxin; Zou, Chengwei; Wang, Anbiao

2011-10-01

Since 2008, 28 patients with congenital mitral regurgitation have undergone mitral valve repair with a modified edge-to-edge technique at our institution. The regurgitant mitral leaflet was sutured with a pledget-reinforced, horizontal mattress suture with No. 4-0 polypropylene on the ventricle side and a pledget-reinforced mattress suture with Gore-Tex sutures (W.L. Gore & Associates, Flagstaff, AZ) and Dacron pledgets (Chest, Shanghai) placed on the anterior and posterior annulus corresponding to the edge-to-edge suturing site. Early results are encouraging, but a longer follow-up is needed. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Mechanism of reduction of mitral regurgitation with vasodilator therapy.

PubMed

Yoran, C; Yellin, E L; Becker, R M; Gabbay, S; Frater, R W; Sonnenblick, E H

1979-04-01

Acute mitral regurgitation was produced in six open chest dogs by excising a portion of the anterior valve leaflet. Electromagnetic flow probes were placed in the left atrium around the mitral anulus and in the ascending aorta to determine phasic left ventricular filling volume, regurgitant volume and stroke volume. The systolic pressure gradient was calculated from simultaneously measured high fidelity left atrial and left ventricular pressures. The effective mitral regurgitant orifice area was calculated from Gorlin's hydraulic equation. Infusion of nitroprusside resulted in a significant reduction in mitral regurgitation. No significant change occurred in the systolic pressure gradient between the left ventricle and the left atrium because both peak left ventricular pressure and left atrial pressure were reduced. The reduction of mitral regurgitation was largely due to reduction in the size of the mitral regurgitant orifice. Reduction of ventricular volume rather than the traditional concept of reduction of impedance of left ventricular ejection may explain the effects of vasodilators in reducing mitral regurgitation.

A biomimetic bi-leaflet mitral prosthesis with enhanced physiological left ventricular swirl restorative capability

NASA Astrophysics Data System (ADS)

Tan, Sean Guo-Dong; Kim, Sangho; Leo, Hwa Liang

2016-06-01

Mechanical heart valve prostheses are often implanted in young patients due to their durability and long-term reliability. However, existing designs are known to induce elevated levels of blood damage and blood platelet activation. As a result, there is a need for patients to undergo chronic anti-coagulation treatment to prevent thrombosis, often resulting in bleeding complications. Furthermore, recent studies have suggested that the implantation of a mechanical prosthetic valve at the mitral position results in a significant alteration of the left ventricular flow field which may contribute to flow turbulence. This study proposes a bi-leaflet mechanical heart valve design (Bio-MHV) that mimics the geometry of a human mitral valve, with the aim of reducing turbulence levels in the left ventricle by replicating physiological flow patterns. An in vitro three-dimensional particle velocimetry imaging experiment was carried out to compare the hemodynamic performance of the Bio-MHV with that of the clinically established ATS valve. The Bio-MHV was found to replicate physiological left ventricular flow patterns and produced lower turbulence levels.

Computational Modeling of Blood Flow and Valve Dynamics in Hearts with Hypertrophic Cardiomyopathy

NASA Astrophysics Data System (ADS)

Zheng, Xudong; Mittal, Rajat; Abraham, Theodore; Pinheiro, Aurelio

2010-11-01

Hypertrophic Cardiomyopathy (HCM) is a cardiovascular disease manifested by the thickening of the ventricular wall and often leads to a partial obstruction to the blood flow out of the left ventricle. HCM is recognized as one of the most common causes of sudden cardiac death in athletes. In a heart with HCM, the hypertrophy usually narrows the blood flow pathway to the aorta and produces a low pressure zone between the mitral valve and the hypertrophy during systole. This low pressure can suck the mitral valve leaflet back and completely block the blood flow into the aorta. In the current study, a sharp interface immersed boundary method flow solver is employed to study the hemodynamics and valve dynamics inside a heart with HCM. The three-dimensional motion and configuration of the left ventricle including mitral valve leaflets and aortic valves are reconstructed based on echo-cardio data sets. The mechanisms of aortic obstruction associated with HCM are investigated. The long term objective of this study is to develop a computational tool to aid in the assessment and surgical management of HCM.

Very long-term results (more than 20 years) of valve repair with carpentier's techniques in nonrheumatic mitral valve insufficiency.

PubMed

Braunberger, E; Deloche, A; Berrebi, A; Abdallah, F; Celestin, J A; Meimoun, P; Chatellier, G; Chauvaud, S; Fabiani, J N; Carpentier, A

2001-09-18

Mitral valve repair is considered the gold standard in surgery of degenerative mitral valve insufficiency (MVI), but the long-term results (>20 years) are unknown. We reviewed the first 162 consecutive patients who underwent mitral valve repair between 1970 and 1984 for MVI due to nonrheumatic disease. The cause of MVI was degenerative in 146 patients (90%) and bacterial endocarditis in 16 patients (10%). MVI was isolated or, in 18 cases, associated with tricuspid insufficiency. The mean age of the 162 patients (104 men and 58 women) was 56+/-10 years (age range 22 to 77 years). New York Heart Association functional class was I, II, III, and IV in 2%, 39%, 52%, and 7% of patients, respectively. The mean cardiothoracic ratio was 0.58+/-0.07 (0.4 to 0.8), and 72 (45%) patients had atrial fibrillation. Valve analysis showed that the main mechanism of MVI was type II Carpentier's functional classification in 152 patients. The leaflet prolapse involved the posterior leaflet in 93 patients, the anterior leaflet in 28 patients, and both leaflets in 31 patients. Surgical technique included a Carpentier's ring annuloplasty in all cases, a valve resection in 126 patients, and shortening or transposition of chordae in 49 patients. During the first postoperative month, there were 3 deaths (1.9%) and 3 reoperations (2 valve replacements and 1 repeat repair [1.9%]). Six patients were lost to follow-up. The remaining 151 patients with mitral valve repair were followed during a median of 17 years (range 1 to 29 years; 2273 patient-years). The 20-year Kaplan-Meier survival rate was 48% (95% CI 40% to 57%), which is similar to the survival rate for a normal population with the same age structure. The 20-year rates were 19.3% (95% CI 11% to 27%) for cardiac death and 26% (95% CI 17% to 35%) for cardiac morbidity/mortality (including death from a cardiac cause, stroke, and reoperation). During the 20 years of follow-up, 7 patients were underwent surgery at 3, 7, 7, 8, 8, 10, or 12 years after the initial operation. Valve replacement was carried out in 5 patients, and repeat repair was carried out in 2 patients. At the end of the study, 65 patients remained alive (median follow-up 19 years). Their median age was 76 years (age range 41 to 95 years). All except 1 were in New York Heart Association functional class I/II. Mitral valve repair using Carpentier's technique in patients with nonrheumatic MVI provides excellent long-term results with a mortality rate similar to that of the general population and a very low incidence of reoperation.

Cardiac Calcified Amorphous Tumor of the Mitral Valve Presenting as Transient Ischemic Attack

PubMed Central

Abbasi Teshnizi, Mohammad; Ghorbanzadeh, Atefeh; Zirak, Nahid; Manafi, Babak

2017-01-01

Cardiac calcified amorphous tumors (CATs) are an extremely rare nonneoplastic intracardiac masses. They have been reported in the literature in only a few cases. Thus, the incidence, pathogenesis, and best approach to the treatment are not certain. We report a case of CATs on the atrial surface of the anterior mitral valve leaflet in a 37-year-old female who was diagnosed by histopathological examination after surgical removal. PMID:28194283

Cardiac Calcified Amorphous Tumor of the Mitral Valve Presenting as Transient Ischemic Attack.

PubMed

Abbasi Teshnizi, Mohammad; Ghorbanzadeh, Atefeh; Zirak, Nahid; Manafi, Babak; Moeinipour, Aliasghar

2017-01-01

Cardiac calcified amorphous tumors (CATs) are an extremely rare nonneoplastic intracardiac masses. They have been reported in the literature in only a few cases. Thus, the incidence, pathogenesis, and best approach to the treatment are not certain. We report a case of CATs on the atrial surface of the anterior mitral valve leaflet in a 37-year-old female who was diagnosed by histopathological examination after surgical removal.

Probe for production and measurement of acute mitral regurgitant flow in dog.

PubMed

Kléber, A G; Simon, R; Rutishauser, W

1976-02-01

A probe for production and measurement of acute mitral regurgitation in dogs is described. It consists of a tube that is introduced into the mitral valve through the left atrial appendage. Regurgitant flow through the tube is measured by an electromagnetic device. Variation of flow and zero flow are achieved by narrowing or occluding the tube with a rubber cuff. In animals weighing 30-50 kg, the probe does not produce significant mitral stenosis and the mitral leaflets fit closely around the probe during ventricular systole. The instantaneous relationship between mitral regurgitant flow (MRF) and the gradient between left ventricular and left atrial pressure shows a marked delay of MRF at the beginning and end of regurgitation. This delay can be attributed to some extent to electrical phase lag and to the small movement of the probe relative to the mitral valve during the cardiac cycle. Measurement of regurgitant stroke volume is affected by this movement only to a small extent.

Postcaesarean open-heart surgery for Streptococcus sanguinis infective endocarditis

PubMed Central

Kongwattanakul, Kiattisak; Tribuddharat, Sirirat; Prathanee, Sompop; Pachirat, Orathai

2013-01-01

A 33-week pregnant (gravida 3), 29-year-old woman was transferred for management of Streptococcus sanguinis infective endocarditis. A vegetation was present on the posterior leaflet of the mitral valve with moderate mitral regurgitation. On admission (day 1), the ultrasound examination revealed splenic abscesses and retarded intrauterine growth albeit with normal vessels. The fetal heart rate was 140 bpm. On day 11, the baby was delivered by Caesarean, and then the mother underwent tubal ligation followed by a mitral valve repair. The splenic abscess was treated with antibiotics. The woman was clinically stable and recovered uneventfully. This successful outcome was achieved by a strategic (optimal and sequential) timeline for selecting the mode of delivery and type of mitral valve correction. PMID:24234426

A neonate with mitral stenosis due to accessory mitral valve, ventricular septal defect, and patent ductus arteriosus: changes in echocardiographical findings during the neonatal period.

PubMed

Ito, Tadahiko; Okubo, Tadashi

2002-12-01

A female neonate with mitral stenosis due to accessory mitral valve with ventricular septal defect and patent ductus arteriosus is described. She was referred to our hospital because of neonatal asphyxia. Asphyxia was improved by ventilator support, but rapid deterioration of respiration with pulmonary congestion and hemorrhage appeared 8 days after birth. Echocardiography revealed an accessory mitral valve attached to the anterior mitral leaflet with a perimembranous ventricular septal defect and patent ductus arteriosus. Although there were no echocardiographical findings indicating mitral stenosis on admission, the mitral stenosis blood flow patterns were detected by color and pulsed Doppler examination performed on the eighth day after admission. Transaortic resection of accessory mitral valve tissue was performed with patch closure of the ventricular septal defect and ligation of the ductus arteriosus 35 days after birth. After operation, pulmonary congestion and hemorrhage were improved. Postoperative echocardiography showed complete resection of the accessory mitral valve and no mitral insufficiency. We concluded that the combination of the accessory mitral valve and left-to-right shunt due to ventricular septal defect or patent ducturs arteriosus might have led to a critical hemodynamic condition due to relative mitral stenosis in the neonatal period with the decrease in pulmonary vascular resistance.

Complete Atrioventricular Block Complicating Mitral Infective Endocarditis Caused by Streptococcus Agalactiae.

PubMed

Arai, Masaru; Nagashima, Koichi; Kato, Mahoto; Akutsu, Naotaka; Hayase, Misa; Ogura, Kanako; Iwasawa, Yukino; Aizawa, Yoshihiro; Saito, Yuki; Okumura, Yasuo; Nishimaki, Haruna; Masuda, Shinobu; Hirayama, Astushi

2016-09-08

BACKGROUND Infective endocarditis (IE) involving the mitral valve can but rarely lead to complete atrioventricular block (CAVB). CASE REPORT A 74-year-old man with a history of infective endocarditis caused by Streptococcus gordonii (S. gordonii) presented to our emergency room with fever and loss of appetite, which had lasted for 5 days. On admission, results of serologic tests pointed to severe infection. Electrocardiography showed normal sinus rhythm with first-degree atrioventricular block and incomplete right bundle branch block, and transthoracic echocardiography and transesophageal echocardiography revealed severe mitral regurgitation caused by posterior leaflet perforation and 2 vegetations (5 mm and 6 mm) on the tricuspid valve. The patient was initially treated with ceftriaxone and gentamycin because blood and cutaneous ulcer cultures yielded S. agalactiae. On hospital day 2, however, sudden CAVB requiring transvenous pacing occurred, and the patient's heart failure and infection worsened. Although an emergent surgery is strongly recommended, even in patients with uncontrolled heart failure or infection, surgery was not performed because of the Child-Pugh class B liver cirrhosis. Despite intensive therapy, the patient's condition further deteriorated, and he died on hospital day 16. On postmortem examination, a 2×1-cm vegetation was seen on the perforated posterior mitral leaflet, and the infection had extended to the interventricular septum. Histologic examination revealed extensive necrosis of the AV node. CONCLUSIONS This rare case of CAVB resulting from S. agalactiae IE points to the fact that in monitoring patients with IE involving the mitral valve, clinicians should be aware of the potential for perivalvular extension of the infection, which can lead to fatal heart block.

An uncommon cause of tricuspid regurgitation: three-dimensional echocardiographic incremental value, surgical and genetic insights.

PubMed

Theron, Alexis; Pinard, Amélie; Riberi, Alberto; Zaffran, Stéphane

2016-07-01

Congenital tricuspid valve disease is a rare defect that includes regurgitation, stenosis and Ebstein's anomaly. We report a case of severe tricuspid regurgitation associated with functional mitral regurgitation in a 47-year-old man with congestive heart failure. Transthoracic echocardiography (TTE) ruled out any Ebstein's anomaly. Three-dimensional TTE revealed a 'tricuspid hole' into the anterior leaflet that was only attached to the tricuspid annulus next to both anteroseptal and anteroposterior commissures. There was no sign of leaflet tear or perforation. The surgical repair of the tricuspid and mitral valves was performed with an optimal result. No sign of endocarditis or rheumatic disease was observed during the intervention. Sequence analysis of GATA4, HEY2 and ZFPM2 genes was performed, but no causative mutation was identified. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

A rare native mitral valve endocarditis successfully treated after surgical correction

PubMed Central

Garcia, Daniel C; Nascimento, Rhanderson; Soto, Victor; Mendoza, Cesar E

2014-01-01

Mycobacterium abscessus and Kocuria species are rare causes of infections in humans. Endocarditis by these agents has been reported in only 11 cases. M. abscessus is a particularly resistant organism and treatment requires the association of antibiotics for a prolonged period of time. We report a case of native mitral valve bacterial endocarditis due to M. abscessus and Kocuria species in a 48-year-old man with a history of intravenous drug use. The case was complicated by a perforation of the posterior mitral valve leaflet, leading to surgical mitral valve replacement. Cultures from the blood and mitral valve disclosed M. abscessus and Kocuria species. The patient was treated for 6 months with clarithromycin, imipenem and amikacin, with resolution of symptoms. Repeated blood cultures were negative. Acid-fast staining should be done in subacute endocarditis in order to identify rapidly growing mycobacteria. PMID:25270154

The mechanobiology of mitral valve function, degeneration, and repair

PubMed Central

Richards, Jennifer M.; Farrar, Emily J.; Kornreich, Bruce G.; Moïse, N. Sydney; Butcher, Jonathan T.

2013-01-01

In degenerative valve disease, the highly organized mitral valve leaflet matrix stratification is progressively destroyed and replaced with proteoglycan rich, mechanically inadequate tissue. This is driven by the actions of originally quiescent valve interstitial cells that become active contractile and migratory myofibroblasts. While treatment for myxomatous mitral valve disease in humans ranges from repair to total replacement, therapies in dogs focus on treating the consequences of the resulting mitral regurgitation. The fundamental gap in our understanding is how the resident valve cells respond to altered mechanical signals to drive tissue remodeling. Despite the pathological similarities and high clinical occurrence, surprisingly little mechanistic insight has been gleaned from the dog. This review presents what is known about mitral valve mechanobiology from clinical, in vivo, and in vitro data. There are a number of experimental strategies already available to pursue this significant opportunity, but success requires the collaboration between veterinary clinicians, scientists, and engineers. PMID:22366572

The "Polar Light Sign" is a useful tool to detect discrete membranous supravalvular mitral stenosis.

PubMed

Hertwig, Christine; Haas, Nikolaus A; Habash, Sheeraz; Hanslik, Andreas; Kececioglu, Deniz; Sandica, Eugen; Laser, Kai-Thorsten

2015-02-01

Mitral valve stenosis caused by a discrete supravalvular membrane is a rare congenital malformation haemodynamically leading to significant mitral valve stenosis. When the supravalvular mitral stenosis consists of a discrete supravalvular membrane adherent to the mitral valve, it is usually not clearly detectable by routine echocardiography. We report about the typical echocardiographic finding in three young patients with this rare form of a discrete membranous supravalvular stenosis caused by a membrane adherent to the mitral valve. These cases present a typical echocardiographic feature in colour Doppler generated by the pathognomonic supramitral flow acceleration. Whereas typical supravalvular mitral stenosis caused by cor triatriatum or a clearly visible supravalvular ring is easily detectable by echocardiography, a discrete supravalvular membrane adjacent to the mitral valve leaflets resembling valvular mitral stenosis is difficult to differentiate by routine echocardiography. In our opinion, this colour phenomenon does resemble the visual impression of polar lights in the northern hemisphere; owing to its typical appearance, it may therefore be named as "Polar Light Sign". This phenomenon may help to detect this anatomical entity by echocardiography in time and therefore improve the prognosis for repair.

Mitral valve disease—morphology and mechanisms

PubMed Central

Levine, Robert A.; Hagége, Albert A.; Judge, Daniel P.; Padala, Muralidhar; Dal-Bianco, Jacob P.; Aikawa, Elena; Beaudoin, Jonathan; Bischoff, Joyce; Bouatia-Naji, Nabila; Bruneval, Patrick; Butcher, Jonathan T.; Carpentier, Alain; Chaput, Miguel; Chester, Adrian H.; Clusel, Catherine; Delling, Francesca N.; Dietz, Harry C.; Dina, Christian; Durst, Ronen; Fernandez-Friera, Leticia; Handschumacher, Mark D.; Jensen, Morten O.; Jeunemaitre, Xavier P.; Le Marec, Hervé; Le Tourneau, Thierry; Markwald, Roger R.; Mérot, Jean; Messas, Emmanuel; Milan, David P.; Neri, Tui; Norris, Russell A.; Peal, David; Perrocheau, Maelle; Probst, Vincent; Pucéat, Michael; Rosenthal, Nadia; Solis, Jorge; Schott, Jean-Jacques; Schwammenthal, Ehud; Slaugenhaupt, Susan A.; Song, Jae-Kwan; Yacoub, Magdi H.

2016-01-01

Mitral valve disease is a frequent cause of heart failure and death. Emerging evidence indicates that the mitral valve is not a passive structure, but—even in adult life—remains dynamic and accessible for treatment. This concept motivates efforts to reduce the clinical progression of mitral valve disease through early detection and modification of underlying mechanisms. Discoveries of genetic mutations causing mitral valve elongation and prolapse have revealed that growth factor signalling and cell migration pathways are regulated by structural molecules in ways that can be modified to limit progression from developmental defects to valve degeneration with clinical complications. Mitral valve enlargement can determine left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and might be stimulated by potentially modifiable biological valvular–ventricular interactions. Mitral valve plasticity also allows adaptive growth in response to ventricular remodelling. However, adverse cellular and mechanobiological processes create relative leaflet deficiency in the ischaemic setting, leading to mitral regurgitation with increased heart failure and mortality. Our approach, which bridges clinicians and basic scientists, enables the correlation of observed disease with cellular and molecular mechanisms, leading to the discovery of new opportunities for improving the natural history of mitral valve disease. PMID:26483167

Pathology of myxomatous mitral valve disease in the dog.

PubMed

Fox, Philip R

2012-03-01

Mitral valve competence requires complex interplay between structures that comprise the mitral apparatus - the mitral annulus, mitral valve leaflets, chordae tendineae, papillary muscles, and left atrial and left ventricular myocardium. Myxomatous mitral valve degeneration is prevalent in the canine, and most adult dogs develop some degree of mitral valve disease as they age, highlighting the apparent vulnerability of canine heart valves to injury. Myxomatous valvular remodeling is associated with characteristic histopathologic features. Changes include expansion of extracellular matrix with glycosaminoglycans and proteoglycans; valvular interstitial cell alteration; and attenuation or loss of the collagen-laden fibrosa layer. These lead to malformation of the mitral apparatus, biomechanical dysfunction, and mitral incompetence. Mitral regurgitation is the most common manifestation of myxomatous valve disease and in advanced stages, associated volume overload promotes progressive valvular regurgitation, left atrial and left ventricular remodeling, atrial tears, chordal rupture, and congestive heart failure. Future studies are necessary to identify clinical-pathologic correlates that track disease severity and progression, detect valve dysfunction, and facilitate risk stratification. It remains unresolved whether, or to what extent, the pathobiology of myxomatous mitral valve degeneration is the same between breeds of dogs, between canines and humans, and how these features are related to aging and genetics. Copyright © 2012 Elsevier B.V. All rights reserved.

Early beneficial effect of preservation of papillo-annular continuity in mitral valve replacement on left ventricular function.

PubMed

Dilip, D; Chandra, A; Rajashekhar, D; Padmanabhan, M

2001-05-01

Impairment of left ventricular (LV) function after mitral valve replacement (MVR) has been the most important factor to determine morbidity and mortality. With this in mind, LV performance in the postoperative period was assessed with and without preservation of papillo-annular continuity in MVR. Between March 1994 and August 1998, a total of 383 valve prostheses (202 MVR, 65 AVR, 58 MVR+AVR) were implanted in 325 patients, 177 of whom underwent MVR with Starr Edwards ball cage prostheses (the study group). Of these 177 patients, 105 had MVR with preservation of the posterior mitral leaflet (group I), and 72 had conventional MVR (group II). Predominant lesions were mitral stenosis in 81, mitral regurgitation in 42, and mixed mitral lesion (MS/MR) in 54. Concomitant tricuspid valve annuloplasty was performed in 13, and atrial septal defect repair in five. Sixteen patients underwent MVR for mitral restenosis. In-vivo performance of the prostheses and LV function was evaluated by M-mode and Doppler echocardiography. At 3-6 months clinical improvement was seen in NYHA class, with reduction in cardiothoracic ratio among patients with preserved papillo-annular continuity, irrespective of lesion type. Significant reductions (p <0.05) were seen in left atrial dimensions (54.10 +/- 8.79 preop. versus 44.64 +/- 8.54 postop.; p <0.05), left ventricular end-diastolic dimensions (LVEDD) (50.84 +/- 10.42 preop. versus 41.21 +/- 7.16 postop.; p <0.05) and end-systolic dimensions (LVESD) (34.76 +/- 7.94 preop. versus 28.81 +/- 5.79 postop.; p <0.05) in patients who had their posterior mitral leaflet preserved with significant improvement in ejection fraction (60.31 +/- 8.22 versus 64.47 +/- 7.93; p <0.05). Further analysis of data in group I patients showed significant reductions in left atrial dimensions, LVESD and peak gradient, along with improved ejection fraction compared with conventional (group II) patients. Deterioration in LV function in patients undergoing conventional MVR indicates chordal resection as a putative mechanism. This study supports the concept that maintenance of continuity between the mitral annulus and papillary muscles has a beneficial effect on postoperative LV function, and is particularly important in patients with mitral stenosis with depressed preoperative LV systolic function.

Vent-induced prosthetic leaflet thrombosis treated by open-heart valve-in-valve implantation.

PubMed

Stamm, Christof; Pasic, Miralem; Buz, Semih; Hetzer, Roland

2015-09-01

A patient required emergency mitral valve replacement and extracorporeal membrane oxygenation (ECMO) support for acute biventricular failure. The left ventricular (LV) vent inserted via the left upper pulmonary vein induced thrombotic immobilization of a prosthetic valve leaflet, with significant intra-prosthesis regurgitation after ECMO explantation. Therefore, the left atrium was opened on the beating heart during conventional extracorporeal circulation, all prosthesis leaflets were excised and a 29-mm expandable Edwards Sapien prosthesis was inserted within the scaffold of the original prosthesis under direct vision. This case illustrates the benefits and potential problems of LV venting on ECMO support, and a rapid and safe way of replacing the prosthesis leaflets in a critical situation. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

A Case of Post Myocardial Infarction Papillary Muscle Rupture.

PubMed

Anuwatworn, Amornpol; Milnes, Christopher; Kumar, Vishesh; Raizada, Amol; Nykamp, Verlyn; Stys, Adam

2016-06-01

Papillary muscle rupture is a rare, life-threatening post myocardial infarction mechanical complication. Without surgical intervention, prognosis is very poor. Clinicians need to recognize this complication early, as prompt therapy is crucial. We present a case of inferior ST elevation myocardial infarction complicated by posteromedial papillary muscle rupture resulting in severe acute mitral regurgitation (flail anterior mitral leaflet), acute pulmonary edema and cardiogenic shock. In our patient, a new mitral regurgitation murmur suggested this mechanical complication. Complete disruption of papillary muscle was visualized by transesophageal echocardiography. This case illustrates the importance of good physical examination for early diagnosis of papillary muscle rupture, so that life-saving treatment can be administered without delay.

Transcatheter mitral valve repair in osteogenesis imperfecta associated mitral valve regurgitation.

PubMed

van der Kley, Frank; Delgado, Victoria; Ajmone Marsan, Nina; Schalij, Martin J

2014-08-01

Osteogenesis imperfecta is associated with increased prevalence of significant mitral valve regurgitation. Surgical mitral valve repair and replacement are feasible but are associated with increased risk of bleeding and dehiscence of implanted valves may occur more frequently. The present case report describes the outcomes of transcatheter mitral valve repair in a patient with osteogenesis imperfecta. A 60 year-old patient with osteogenesis imperfecta and associated symptomatic moderate to severe mitral regurgitation underwent transthoracic echocardiography which showed a nondilated left ventricle with preserved systolic function and moderate to severe mitral regurgitation. On transoesophageal echocardiography the regurgitant jet originated between the anterolateral scallops of the anterior and posterior leaflets (A1-P1). Considering the comorbidities associated with osteogenesis imperfecta the patient was accepted for transcatheter mitral valve repair using the Mitraclip device (Abbott vascular, Menlo, CA). Under fluoroscopy and 3D transoesophageal echocardiography guidance, a Mitraclip device was implanted between the anterolateral and central scallops with significant reduction of mitral regurgitation. The postoperative evolution was uneventful. At one month follow-up, transthoracic echocardiography showed a stable position of the Mitraclip device with no mitral regurgitation. Transcatheter mitral valve repair is feasible and safe in patients with osteogenesis imperfecta and associated symptomatic significant mitral regurgitation. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Anterior Leaflet Augmentation With CorMatrix Porcine Extracellular Matrix in Twenty-Five Patients: Unexpected Patch Failures and Histologic Analysis.

PubMed

Kelley, Thomas M; Kashem, Mohammed; Wang, He; McCarthy, James; Carroll, Nels D; Moser, G William; Guy, T Sloane

2017-01-01

This study reported on the treatment of Carpentier type IIIa and type IIIb mitral regurgitation (MR) with a large patch anterior mitral valve leaflet augmentation technique using CorMatrix (CorMatrix Cardiovascular Inc, Alpharetta, GA) extracellular matrix (ECM). A single-site chart review was conducted on patients who underwent anterior leaflet augmentation performed with the Da Vinci surgical robot (Intuitive Surgical, Sunnyvale, CA) or through a median sternotomy. Only patients who had anterior leaflet augmentation with porcine intestine ECM or autologous pericardium were included. Follow-up echocardiography was performed on all patients. Histologic specimens were available on ECM patches from a subset of patients who required reoperation. Between August 2011 and April 2014, 44 patients (mean age, 62.6 ± 12.2 years) underwent anterior leaflet augmentation with either porcine intestinal ECM or autologous pericardium at the Temple University Hospital in Philadelphia. Two (4%) late deaths occurred, one in each group. One patient who underwent ECM augmentation died of non-cardiac-related causes 7 months after discharge as a result of complications of chronic renal failure. The second late death occurred 5 months after discharge because of complications of a stroke in a patient in the pericardial augmentation group. Eight (32%) of the patients with ECM had recurrence of severe MR on echocardiography at an average time of 201 ± 98 days. Seven (28%) patients required reoperation because of failure of the ECM patch including perforation (4%), excessive patch dilation (20%), and suture line dehiscence (4%). In contrast, none of the patients with pericardial augmentation developed severe MR or required operation. Statistical analysis of the patients with ECM augmentation demonstrated no correlation of the following: age; sex; comorbid conditions such as diabetes, chronic obstructive pulmonary disease, and hypertension; left ventricular ejection fraction; surgical approach; annuloplasty size; or type of MR with patch failure. A lower body mass index was the only factor associated with recurrent severe regurgitation on univariate analysis (p = 0.039). Histologic study of the four available explants demonstrated intense inflammation without evidence of host integration. The remaining 15 (60%) patients had normal mitral leaflet structure and function on follow-up echocardiograms out to 12 months. For type III MR, a large anterior leaflet patch technique with porcine ECM was associated with a 32% recurrence rate of severe MR related directly to patch failure. Further research and development should be performed on the use of ECM materials with a goal to decrease the failure rate experienced in this study. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Advanced technologies for cardiac valvular replacement, transcatheter innovations and reconstructive surgery.

PubMed

Jamieson, W R Eric

2006-01-01

Since the 2002 Surgical Technology International monograph on valvular prostheses, there have been significant developmental and investigative advances. Aortic bioprostheses and mechanical prostheses have undergone design changes to optimize hemodynamics and prevent patient-prosthesis mismatch to have a potential satisfactory influence on survival. There has been continual technological improvements striving to bring forward advances that improve the durability of bioprostheses and reduce the thrombogenicity of mechanical prostheses. There also has been a continuance to preserve biological tissue with glutaraldehyde, rather than clinically evaluate other cross-linking technologies, by controlling or retarding calcification with therapies to control phospholipids and residual aldehydes. The techniques of mitral valve reconstruction have now been well established and new annuloplasty rings have been designed for the potential of maintaining the anatomical and physiological characteristics of the mitral annulus. Several objectives exist for annuloplasty, namely remodeling of the length and shape of the dilated annulus, prevention of dilatation of the annulus, and support for the potentially fragile area after partial-leaflet resection. Currently, there exists an emergence of catheter-based therapies for management of aortic stenosis and mitral regurgitation. For management of selected populations with critical aortic stenosis, techniques for aortic valve substitution have been developed for both antegrade and retrograde catheter techniques, as well as apical transventricular implantation. Mitral regurgitation has been addressed by experimental transcoronary sinus, stent-like devices and transventricular, edge-to-edge leaflet devices. The devices, descriptions and pictorial images comprise this monograph.

Quantification of annular dilatation and papillary muscle separation in functional mitral regurgitation: role of anterior mitral leaflet length as reference.

PubMed

Jorapur, Vinod; Voudouris, Apostolos; Lucariello, Richard J

2005-07-01

We hypothesized that anterior mitral leaflet length (ALL) does not differ significantly between normal subjects and patients with functional mitral regurgitation (FMR) and hence may be used as a reference measurement to quantify annular dilatation and papillary muscle separation. We prospectively studied 50 controls, 15 patients with systolic left ventricular dysfunction (LVD) with significant FMR, and 15 patients with LVD without significant FMR. Significant MR was defined as an effective regurgitant orifice area > or = 0.2 cm2 as measured by the flow convergence method. Annular diameter, interpapillary distance, and ALL were measured, and the following ratios were derived: annular diameter indexed to ALL (ADI) and interpapillary distance indexed to ALL (IPDI). There was no significant difference in ALL among the three groups. The mean ADI was 1.26 times controls in patients with LVD without significant FMR compared to 1.33 times controls in patients with LVD with significant FMR (P = 0.06, no significant difference between groups). The mean IPDI was 1.42 times controls in patients with LVD without significant FMR compared to 2.1 times controls in patients with LVD with significant FMR (P < 0.0001, significant difference between groups). There was no significant difference in ALL between controls and patients with LVD. ALL can be used as a reference measurement to quantify annular dilatation and papillary muscle separation in patients with FMR. Interpapillary distance but not annular diameter indexed to ALL correlates with severity of FMR.

Saddle-shaped mitral valve annuloplasty rings experience lower forces compared with flat rings.

PubMed

Jensen, Morten O; Jensen, Henrik; Smerup, Morten; Levine, Robert A; Yoganathan, Ajit P; Nygaard, Hans; Hasenkam, J Michael; Nielsen, Sten L

2008-09-30

New insight into the 3D dynamic behavior of the mitral valve has prompted a reevaluation of annuloplasty ring designs. Force balance analysis indicates correlation between annulus forces and stresses in leaflets and chords. Improving this stress distribution can intuitively enhance the durability of mitral valve repair. We tested the hypothesis that saddle-shaped annuloplasty rings have superior uniform systolic force distribution compared with a nonuniform force distribution in flat annuloplasty rings. Sixteen 80-kg pigs had a flat (n=8) or saddle-shaped (n=8) mitral annuloplasty ring implanted. Mitral annulus 3D dynamic geometry was obtained with sonomicrometry before ring insertion. Strain gauges mounted on dedicated D-shaped rigid flat and saddle-shaped annuloplasty rings provided the intraoperative force distribution perpendicular to the annular plane. Average systolic annular height to commissural width ratio before ring implantation was 14.0%+/-1.6%. After flat and saddle shaped ring implantation, the annulus was fixed in the diastolic (9.0%+/-1.0%) and systolic (14.3%+/-1.3%) configuration, respectively (P<0.01). Force accumulation was seen from the anterior (0.72N+/-0.14N) and commissural annular segments (average 1.38N+/-0.27N) of the flat rings. In these segments, the difference between the 2 types of rings was statistically significant (P<0.05). The saddle-shaped annuloplasty rings did not experience forces statistically significantly larger than zero in any annular segments. Saddle-shaped annuloplasty rings provide superior uniform annular force distribution compared to flat rings and appear to represent a configuration that minimizes out-of-plane forces that could potentially be transmitted to leaflets and chords. This may have important implications for annuloplasty ring selections.

Complete Atrioventricular Block Complicating Mitral Infective Endocarditis Caused by Streptococcus Agalactiae

PubMed Central

Arai, Masaru; Nagashima, Koichi; Kato, Mahoto; Akutsu, Naotaka; Hayase, Misa; Ogura, Kanako; Iwasawa, Yukino; Aizawa, Yoshihiro; Saito, Yuki; Okumura, Yasuo; Nishimaki, Haruna; Masuda, Shinobu; Hirayama, Atsushi

2016-01-01

Patient: Male, 74 Final Diagnosis: Infective endocarditis Symptoms: Apetite loss • fever Medication: — Clinical Procedure: Transesophageal echocardiography Specialty: Cardiology Objective: Rare co-existance of disease or pathology Background: Infective endocarditis (IE) involving the mitral valve can but rarely lead to complete atrioventricular block (CAVB). Case Report: A 74-year-old man with a history of infective endocarditis caused by Streptococcus gordonii (S. gordonii) presented to our emergency room with fever and loss of appetite, which had lasted for 5 days. On admission, results of serologic tests pointed to severe infection. Electrocardiography showed normal sinus rhythm with first-degree atrioventricular block and incomplete right bundle branch block, and transthoracic echocardiography and transesophageal echocardiography revealed severe mitral regurgitation caused by posterior leaflet perforation and 2 vegetations (5 mm and 6 mm) on the tricuspid valve. The patient was initially treated with ceftriaxone and gentamycin because blood and cutaneous ulcer cultures yielded S. agalactiae. On hospital day 2, however, sudden CAVB requiring transvenous pacing occurred, and the patient’s heart failure and infection worsened. Although an emergent surgery is strongly recommended, even in patients with uncontrolled heart failure or infection, surgery was not performed because of the Child-Pugh class B liver cirrhosis. Despite intensive therapy, the patient’s condition further deteriorated, and he died on hospital day 16. On postmortem examination, a 2×1-cm vegetation was seen on the perforated posterior mitral leaflet, and the infection had extended to the interventricular septum. Histologic examination revealed extensive necrosis of the AV node. Conclusions: This rare case of CAVB resulting from S. agalactiae IE points to the fact that in monitoring patients with IE involving the mitral valve, clinicians should be aware of the potential for perivalvular extension of the infection, which can lead to fatal heart block. PMID:27604147

Aortic valve sclerosis as a marker of coronary artery atherosclerosis; a multicenter study of a large population with a low prevalence of coronary artery disease.

PubMed

Rossi, Andrea; Gaibazzi, Nicola; Dandale, Raje; Agricola, Eustachio; Moreo, Antonella; Berlinghieri, Nicola; Sartorio, Daniele; Loffi, Marco; De Chiara, Benedetta; Rigo, Fausto; Vassanelli, Corrado; Faggiano, Pompilio

2014-03-15

There are no studies analyzing the association between aortic valve sclerosis (AVS) and coronary artery disease (CAD) in a large and multicenter patient population with an overall low prevalence of CAD. We hypothesized that AVS could predict the presence and degree of CAD in patients with severe organic mitral regurgitation. We retrospectively analyzed consecutive patients with flail mitral leaflet who had coronary angiography for pre-surgical screening and not because suspect of CAD. End-points were considered: 1) any degree of CAD (stenosis>20%) and 2) obstructive CAD (stenosis>75% of at least one coronary artery). AVS was defined as focal areas of increased echogenicity and thickening of the leaflets. Traditional clinical risk factors were considered: age, male gender, hypertension (>140/90 mmHg or medical therapy), hypercholesterolemia (total cholesterol>200 mg/dl or statin), diabetes, family history of CAD and smoking habit. 675 patients (mean age: 64±12; 27% female) formed the study population. Among patients with AVS, 60% and 39% had any-CAD and ob-CAD respectively, on the opposite among patients without AVS 12% and 7% had any-CAD and ob-cad. After adjustment for clinical risk factors, AVS was associated with a 22.7 fold increased risk of any degree of CAD (95% CI 8.1 63.6 p<0.0001) and with a 21.8 fold increased risk of obstructive-CAD (95% CI 6.6 71.9; p<0.0001). In a large and multicenter sample of patient with flail mitral leaflet, AVS was strongly associated with the presence and degree of CAD independently of clinical risk factors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Percutaneous Mitral Valve Dilatation: Single Balloon versus Double Balloon - A Finite Element Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schievano, Silvia; Kunzelman, Karyn; Nicosia, Mark

2009-01-01

Background: Percutaneous mitral valve (MV) dilatation is performed with either a single balloon (SB) or double balloon (DB) technique. The aim of this study was to compare the two balloon system results using the finite element (FE) method. Methods and Results: An established FE model of the MV was modified by fusing the MV leaflet edges at commissure level to simulate a stenotic valve (orifice area=180mm2). A FE model of a 30mm SB (low-pressure, elastomeric balloon) and an 18mm DB system (high-pressure, non-elastic balloon) was created. Both SB and DB simulations resulted in splitting of the commissures and subsequent stenosismore » dilatation (final MV area=610mm2 and 560mm2 respectively). Stresses induced by the two balloon systems varied across the valve. At the end of inflation, SB showed higher stresses in the central part of the leaflets and at the commissures compared to DB simulation, which demonstrated a more uniform stress distribution. The higher stresses in the SB analysis were due to the mismatch of the round balloon shape with the oval mitral orifice. The commissural split was not easily accomplished with the SB due to its high compliance. The high pressure applied to the DB guaranteed the commissural split even when high forces were required to break the commissure welds. Conclusions: The FE model demonstrated that MV dilatation can be accomplished by both SB and DB techniques. However, the DB method resulted in higher probability of splitting of the fused commissures and less damage caused to the MV leaflets by overstretching.« less

Mitral valve repair in dogs using an ePTFE chordal implantation device: a pilot study.

PubMed

Borgarelli, M; Lanz, O; Pavlisko, N; Abbott, J A; Menciotti, G; Aherne, M; Lahmers, S M; Lahmers, K K; Gammie, J S

2017-06-01

Mitral valve (MV) regurgitation due to degenerative MV disease is the leading cause of cardiac death in dogs. We carried out preliminary experiments to determine the feasibility and short-term effects of beating-heart MV repair using an expanded polytetrafluorethylene (ePTFE) chordal implantation device (Harpoon TSD-5) in dogs. This study involved six healthy purpose-bred Beagles (weight range 8.9-11.4 kg). Following a mini-thoracotomy performed under general anesthesia, the TSD-5 was used to place 1 or 2 artificial ePTFE cords on the anterior MV leaflet or the posterior MV leaflet via a left-ventricular transapical approach. The procedure was guided and monitored by transesophageal echocardiography. Postoperative antithrombotic treatment consisted of clopidogrel or a combination of clopidogrel and apixaban. Dogs were serially evaluated by transthoracic echocardiography at day 1, 7, 14, 21, and 30. The hearts were then examined for evaluation of tissues reactions and to detect signs of endothelialization. One or two chords were successfully implanted in five dogs. Four dogs completed the 30 days follow-up. One dog died intra-operatively because of aortic perforation. One dog died early post-operatively from a hemorrhagic pleural effusion attributed to overly aggressive antithrombotic treatment. One dog developed a thrombus surrounding both the knot and the synthetic cord. Postmortem exam confirmed secure placement of ePTFE knots in the mitral leaflets in all dogs and the presence of endothelialization of the knots and chords. These preliminary results demonstrate the feasibility of artificial chordal placement using an ePTFE cordal implantation device in dogs. Copyright © 2017 Elsevier B.V. All rights reserved.

Early Results of Rheumatic Mitral Valve Repair.

PubMed

Petrone, Giuseppe; Theodoropoulos, Panagiotis; Punjabi, Prakash P

2016-11-01

Mitral valve repair (MVr) in rheumatic heart disease (RHD) remains challenging. The present authors' surgical experience of MVr in 56 patients with RHD operated in between January 2011 and September 2014 is reported. Among the patients (mean age 32 ± 11 years), 11 were in NYHA functional class II, 32 in class III, and seven in class IV. An adequate or oversized autologous pericardial patch was sutured to extend the coaptating edge of both the anterior leaflet (in 18 patients) and the posterior leaflet (in 30 patients). Neochordae were implanted as needed (n = 43), and leaflet thinning (n = 13), commissurotomy (n = 15) and chordal splitting (n = 9) were also performed. A rigid annuloplasty ring was implanted in 32 patients, and in 24 patients a complete flexible annuloplasty ring made from pericardium, 4 mm Gore-Tex tube graft or a Dacron patch was constructed. Repair was not attempted in 16 patients, with replacement using a mechanical bileaflet prosthesis being considered the only option. Intraoperative post-repair transesophageal echocardiography demonstrated competency, with trivial mitral regurgitation (MR) up to grade I in all patients and a minimum coaptation depth ≥5 mm. There were no intraoperative or in-hospital deaths. Clinical and echocardiographic evaluations were performed up to six weeks after surgery, at which time 51 patients were in NYHA classes I-II and five were in class III. Residual mild MR up to grade I was identified in six patients. No recurrence of MR was observed in any of the patients, and no patients were reoperated on. The lack of adequate access to anticoagulation medication and monitoring, in addition to religious/cultural bias to the type of prosthetic valve used in low-income countries, necessitates an increase in the numbers of rheumatic MVr.

Examination of mitral regurgitation with a goat heart model for the development of intelligent artificial papillary muscle.

PubMed

Shiraishi, Y; Yambe, T; Yoshizawa, M; Hashimoto, H; Yamada, A; Miura, H; Hashem, M; Kitano, T; Shiga, T; Homma, D

2012-01-01

Annuloplasty for functional mitral or tricuspid regurgitation has been made for surgical restoration of valvular diseases. However, these major techniques may sometimes be ineffective because of chamber dilation and valve tethering. We have been developing a sophisticated intelligent artificial papillary muscle (PM) by using an anisotropic shape memory alloy fiber for an alternative surgical reconstruction of the continuity of the mitral structural apparatus and the left ventricular myocardium. This study exhibited the mitral regurgitation with regard to the reduction in the PM tension quantitatively with an originally developed ventricular simulator using isolated goat hearts for the sophisticated artificial PM. Aortic and mitral valves with left ventricular free wall portions of isolated goat hearts (n=9) were secured on the elastic plastic membrane and statically pressurized, which led to valvular leaflet-papillary muscle positional change and central mitral regurgitation. PMs were connected to the load cell, and the relationship between the tension of regurgitation and PM tension were measured. Then we connected the left ventricular specimen model to our hydraulic ventricular simulator and achieved hemodynamic simulation with the controlled tension of PMs.

Surgical treatment of atrioventricular canal defect.

PubMed

Hardesty, R L; Zuberbuhler, J R; Bahnson, H T

1975-11-01

Fifty-nine patients with congenital anomalies of the atrioventricular canal underwent operation and all survivors were followed up. In 42 patients with partial atrioventricular canal defects, ten had preoperative congestive heart failure. Three, or 7.1%, died of endomyocardial fibroelastosis, high pulmonary vascular resistance, and severe mitral regurgitation. A fourth patient later died of Wolff-Parkinson-White syndrome and fibrilation. Reoperations in five patients were all successful. No patients had persistent atrioventricular blocks, and all patients are asymptomatic. Two of these subjects continue to receive digoxin therapy, and one of them is believed to have substantial mitral insufficiency. Of the 17 patients who had complete atrioventricular canal defects, 13 had a divided common anterior leaflet attached to the septum by chordae tendineae, and four had undivided and unattached anterior leaflets. Two had previously undergone pulmonary banding, and nine were treated for congestive heart failure. Six died after operation. There were no reoperations. No patient presently has required a pacemaker. Two subjects have persistent cardiomegaly.

Clinical Significance of Markers of Collagen Metabolism in Rheumatic Mitral Valve Disease

PubMed Central

Banerjee, Tanima; Mukherjee, Somaditya; Ghosh, Sudip; Biswas, Monodeep; Dutta, Santanu; Pattari, Sanjib; Chatterjee, Shelly; Bandyopadhyay, Arun

2014-01-01

Background Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. It is a major public health concern in developing countries. In RHD, mostly the valves get affected. The present study investigated whether extracellular matrix remodelling in rheumatic valve leads to altered levels of collagen metabolism markers and if such markers can be clinically used to diagnose or monitor disease progression. Methodology This is a case control study comprising 118 subjects. It included 77 cases and 41 healthy controls. Cases were classified into two groups- Mitral Stenosis (MS) and Mitral Regurgitation (MR). Carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), total Matrix Metalloproteinase-1(MMP-1) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) were assessed. Histopathology studies were performed on excised mitral valve leaflets. A p value <0.05 was considered statistically significant. Results Plasma PICP and PIIINP concentrations increased significantly (p<0.01) in MS and MR subjects compared to controls but decreased gradually over a one year period post mitral valve replacement (p<0.05). In MS, PICP level and MMP-1/TIMP-1 ratio strongly correlated with mitral valve area (r = −0.40; r = 0.49 respectively) and pulmonary artery systolic pressure (r = 0.49; r = −0.49 respectively); while in MR they correlated with left ventricular internal diastolic (r = 0.68; r = −0.48 respectively) and systolic diameters (r = 0.65; r = −0.55 respectively). Receiver operating characteristic curve analysis established PICP as a better marker (AUC = 0.95; 95% CI = 0.91−0.99; p<0.0001). A cut-off >459 ng/mL for PICP provided 91% sensitivity, 90% specificity and a likelihood ratio of 9 in diagnosing RHD. Histopathology analysis revealed inflammation, scarring, neovascularisation and extensive leaflet fibrosis in diseased mitral valve. Conclusions Levels of collagen metabolism markers correlated with echocardiographic parameters for RHD diagnosis. PMID:24603967

Intraoperative Two- and Three-Dimensional Transesophageal Echocardiography in Combined Myectomy-Mitral Operations for Hypertrophic Cardiomyopathy.

PubMed

Nampiaparampil, Robert G; Swistel, Daniel G; Schlame, Michael; Saric, Muhamed; Sherrid, Mark V

2018-03-01

Transesophageal echocardiography is essential in guiding the surgical approach for patients with obstructive hypertrophic cardiomyopathy. Septal hypertrophy, elongated mitral valve leaflets, and abnormalities of the subvalvular apparatus are prominent features, all of which may contribute to left ventricular outflow tract obstruction. Surgery aims to alleviate the obstruction via an extended myectomy, often with an intervention on the mitral valve and subvalvular apparatus. The goal of intraoperative echocardiography is to assess the anatomic pathology and pathophysiology in order to achieve a safe intraoperative course and a successful repair. This guide summarizes the systematic evaluation of these patients to determine the best surgical plan. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Fluid-Structure Interaction Analysis of Ruptured Mitral Chordae Tendineae.

PubMed

Toma, Milan; Bloodworth, Charles H; Pierce, Eric L; Einstein, Daniel R; Cochran, Richard P; Yoganathan, Ajit P; Kunzelman, Karyn S

2017-03-01

The chordal structure is a part of mitral valve geometry that has been commonly neglected or simplified in computational modeling due to its complexity. However, these simplifications cannot be used when investigating the roles of individual chordae tendineae in mitral valve closure. For the first time, advancements in imaging, computational techniques, and hardware technology make it possible to create models of the mitral valve without simplifications to its complex geometry, and to quickly run validated computer simulations that more realistically capture its function. Such simulations can then be used for a detailed analysis of chordae-related diseases. In this work, a comprehensive model of a subject-specific mitral valve with detailed chordal structure is used to analyze the distinct role played by individual chordae in closure of the mitral valve leaflets. Mitral closure was simulated for 51 possible chordal rupture points. Resultant regurgitant orifice area and strain change in the chordae at the papillary muscle tips were then calculated to examine the role of each ruptured chorda in the mitral valve closure. For certain subclassifications of chordae, regurgitant orifice area was found to trend positively with ruptured chordal diameter, and strain changes correlated negatively with regurgitant orifice area. Further advancements in clinical imaging modalities, coupled with the next generation of computational techniques will enable more physiologically realistic simulations.

Fluid-Structure Interaction Analysis of Ruptured Mitral Chordae Tendineae

PubMed Central

Toma, Milan; Bloodworth, Charles H.; Pierce, Eric L.; Einstein, Daniel R.; Cochran, Richard P.; Yoganathan, Ajit P.; Kunzelman, Karyn S.

2016-01-01

The chordal structure is a part of mitral valve geometry that has been commonly neglected or simplified in computational modeling due to its complexity. However, these simplifications cannot be used when investigating the roles of individual chordae tendineae in mitral valve closure. For the first time, advancements in imaging, computational techniques, and hardware technology make it possible to create models of the mitral valve without simplifications to its complex geometry, and to quickly run validated computer simulations that more realistically capture its function. Such simulations can then be used for a detailed analysis of chordae-related diseases. In this work, a comprehensive model of a subject-specific mitral valve with detailed chordal structure is used to analyze the distinct role played by individual chordae in closure of the mitral valve leaflets. Mitral closure was simulated for 51 possible chordal rupture points. Resultant regurgitant orifice area and strain change in the chordae at the papillary muscle tips were then calculated to examine the role of each ruptured chorda in the mitral valve closure. For certain subclassifications of chordae, regurgitant orifice area was found to trend positively with ruptured chordal diameter, and strain changes correlated negatively with regurgitant orifice area. Further advancements in clinical imaging modalities, coupled with the next generation of computational techniques will enable more physiologically realistic simulations. PMID:27624659

Can the learning curve of totally endoscopic robotic mitral valve repair be short-circuited?

PubMed

Yaffee, David W; Loulmet, Didier F; Kelly, Lauren A; Ward, Alison F; Ursomanno, Patricia A; Rabinovich, Annette E; Neuburger, Peter J; Krishnan, Sandeep; Hill, Frederick T; Grossi, Eugene A

2014-01-01

A concern with the initiation of totally endoscopic robotic mitral valve repair (TERMR) programs has been the risk for the learning curve. To minimize this risk, we initiated a TERMR program with a defined team and structured learning approach before clinical implementation. A dedicated team (two surgeons, one cardiac anesthesiologist, one perfusionist, and two nurses) was trained with clinical scenarios, simulations, wet laboratories, and "expert" observation for 3 months. This team then performed a series of TERMRs of varying complexity. Thirty-two isolated TERMRs were performed during the first programmatic year. All operations included mitral valve repair, left atrial appendage exclusion, and annuloplasty device implantation. Additional procedures included leaflet resection, neochordae insertion, atrial ablation, and papillary muscle shortening. Longer clamp times were associated with number of neochordae (P < 0.01), papillary muscle procedures (P < 0.01), and leaflet resection (P = 0.06). Sequential case number had no impact on cross-clamp time (P = 0.3). Analysis of nonclamp time demonstrated a 71.3% learning percentage (P < 0.01; ie, 28.7% reduction in nonclamp time with each doubling of case number). There were no hospital deaths or incidences of stroke, myocardial infarction, unplanned reoperation, respiratory failure, or renal failure. Median length of stay was 4 days. All patients were discharged home. Totally endoscopic robotic mitral valve repair can be safely performed after a pretraining regimen with emphasis on experts' current practice and team training. After a pretraining regimen, cross-clamp times were not subject to learning curve phenomena but were dependent on procedural complexity. Nonclamp times were associated with a short learning curve.

Three-dimensional prototyping for procedural simulation of transcatheter mitral valve replacement in patients with mitral annular calcification.

PubMed

El Sabbagh, Abdallah; Eleid, Mackram F; Matsumoto, Jane M; Anavekar, Nandan S; Al-Hijji, Mohammed A; Said, Sameh M; Nkomo, Vuyisile T; Holmes, David R; Rihal, Charanjit S; Foley, Thomas A

2018-01-23

Three-dimensional (3D) prototyping is a novel technology which can be used to plan and guide complex procedures such as transcatheter mitral valve replacement (TMVR). Eight patients with severe mitral annular calcification (MAC) underwent TMVR. 3D digital models with digital balloon expandable valves were created from pre-procedure CT scans using dedicated software. Five models were printed. These models were used to assess prosthesis sizing, anchoring, expansion, paravalvular gaps, left ventricular outflow tract (LVOT) obstruction, and other potential procedure pitfalls. Results of 3D prototyping were then compared to post procedural imaging to determine how closely the achieved procedural result mirrored the 3D modeled result. 3D prototyping simulated LVOT obstruction in one patient who developed it and in another patient who underwent alcohol septal ablation prior to TMVR. Valve sizing correlated with actual placed valve size in six out of the eight patients and more than mild paravalvular leak (PVL) was simulated in two of the three patients who had it. Patients who had mismatch between their modeled valve size and post-procedural imaging were the ones that had anterior leaflet resection which could have altered valve sizing and PVL simulation. 3D printed model of one of the latter patients allowed modification of anterior leaflet to simulate surgical resection and was able to estimate the size and location of the PVL after inserting a valve stent into the physical model. 3D prototyping in TMVR for severe MAC is feasible for simulating valve sizing, apposition, expansion, PVL, and LVOT obstruction. © 2018 Wiley Periodicals, Inc.

Percutaneous direct mitral annuloplasty using the Mitralign Bident system: description of the method and a case report.

PubMed

Siminiak, Tomasz; Dankowski, Rafał; Baszko, Artur; Lee, Christopher; Firek, Ludwik; Kałmucki, Piotr; Szyszka, Andrzej; Groothuis, Adam

2013-01-01

Functional mitral regurgitation (FMR) is known to contribute to a poor prognosis in patients with heart failure (HF). Current guidelines do not recommend cardiac surgery in patients with FMR and impaired ejection fraction due to the high procedural risk. Percutaneous techniques aimed at mitral valve repair may constitute an alternative to currently used routine medical treatment. To provide a description of a novel percutaneous suture-based technique of direct mitral annuloplasty using the Mitralign Bident system, as well as report our first case successfully treated with this method. A deflectable guiding catheter is advanced via the femoral route across the aortic valve to the posterior wall of the ventricle. A nested deflectable catheter is advanced through the guide toward the mitral annulus that allows the advancement of an insulated radiofrequency wire to cross the annulus. The wire is directed across the annulus in a target area that is 2-5 mm from the base of the leaflet into the annulus, as assessed by real-time 3D transoesophageal echocardiography. After placement of the first wire, another wire is positioned using a duel lumen bident delivery catheter, which provides a predetermined separation between wires (i.e. 14, 17 or 21 mm). Each wire provides a guide rail for implantation of sutured pledget implants within the annulus. Two pairs of pledgets are implanted, one pair in each of the P1 and P3 scallop regions of the posterior mitral annulus. A dedicated plication lock device is used to provide a means for plication of the annulus within each pair of the pledgets, and to retain the plication by delivering a suture locking implant. The plications result in improved leaflet coaptation and a reduction of the regurgitant orifice area. A 60-year-old female with diagnosed dilated cardiomyopathy, concomitant FMR class III and congestive HF was successfully treated with the Mitralign Bident system. Two pairs of pledgets were implanted resulting in an improvement of transoesophageal echocardiographic parameters, including proximal isovelocity surface area radius (0.7 cm to 0.4 cm), effective regurgitant orfice area (0.3 cm² to 0.1 cm²) and mitral regurgitant volume (49 mL to 10 mL). Percutaneous mitral annuloplasty with the Mitralign Bident system is feasible. Future clinical trials are needed to assess its safety and efficacy.

Annular dynamics of memo3D annuloplasty ring evaluated by 3D transesophageal echocardiography.

PubMed

Nishi, Hiroyuki; Toda, Koichi; Miyagawa, Shigeru; Yoshikawa, Yasushi; Fukushima, Satsuki; Yoshioka, Daisuke; Sawa, Yoshiki

2018-04-01

We assessed the mitral annular motion after mitral valve repair with the Sorin Memo 3D® (Sorin Group Italia S.r.L., Saluggia, Italy), which is a unique complete semirigid annuloplasty ring intended to restore the systolic profile of the mitral annulus while adapting to the physiologic dynamism of the annulus, using transesophageal real-time three-dimensional echocardiography. 17 patients (12 male; mean age 60.4 ± 14.9 years) who underwent mitral annuloplasty using the Memo 3D ring were investigated. Mitral annular motion was assessed using QLAB®version8 allowing for a full evaluation of the mitral annulus dynamics. The mitral annular dimensions were measured throughout the cardiac cycle using 4D MV assessment2® while saddle shape was assessed through sequential measurements by RealView®. Saddle shape configuration of the mitral annulus and posterior and anterior leaflet motion could be observed during systole and diastole. The mitral annular area changed during the cardiac cycle by 5.7 ± 1.8%.The circumference length and diameter also changed throughout the cardiac cycle. The annular height was significantly higher in mid-systole than in mid-diastole (p < 0.05). The Memo 3D ring maintained a physiological saddle-shape configuration throughout the cardiac cycle. Real-time three-dimensional echocardiography analysis confirmed the motion and flexibility of the Memo 3D ring upon implantation.

Mitral Annular Calcium and Mitral Stenosis Determined by Multidetector Computed Tomography in Patients Referred for Aortic Stenosis.

PubMed

Mejean, Simon; Bouvier, Erik; Bataille, Vincent; Seknadji, Patrick; Fourchy, Dominique; Tabet, Jean-Yves; Lairez, Olivier; Cormier, Bertrand

2016-10-15

Mitral annular calcium (MAC) is a common finding in older patients referred for transcatheter aortic valve implantation (TAVI). Multidetector computed tomography (MDCT) allows fine quantification of the calcific deposits. Our objective was to estimate the prevalence of MAC and associated mitral stenosis (MS) in patients referred for TAVI using MDCT. A cohort of 346 consecutive patients referred for TAVI evaluation was screened by MDCT for MAC: 174 had MAC (50%). Of these patients, 165 patients (95%) had mitral valve area (MVA) assessable by MDCT planimetry (age 83.8 ± 5.9 years). Median mitral calcium volume and MVA were 545 mm 3 (193 to 1,253 mm 3 ) and 234 mm 2 (187 to 297 mm 2 ), respectively. The MS was very severe, severe, and moderate in 2%, 22%, and 10% patients, respectively. By multivariate analysis, MVA was independently correlated to mitral calcium volume, aortic annular area, and some specific patterns of mitral leaflet calcium. Based on these findings, a formula was elaborated to predict the presence of a significant MS. In conclusion, MDCT allows detailed assessment of MAC in TAVI populations, demonstrating a high prevalence. Mitral analysis should become routine during MDCT screening before TAVI as it may alter therapeutic strategy. Copyright © 2016 Elsevier Inc. All rights reserved.

When what appears to be mitral stenosis is not: diagnostic and therapeutic implications.

PubMed

Almeida, Inês; Caetano, Francisca; Trigo, Joana; Mota, Paula; Cachulo, Maria do Carmo; Antunes, Manuel; Leitão Marques, António

2014-01-01

The authors report the case of a 53-year-old man, with a long-standing history of mild mitral stenosis, admitted for worsening fatigue. Transthoracic echocardiography (limited by poor image quality) showed mitral annular calcification, leaflets that were difficult to visualize and an estimated mitral valve area of 1.8 cm(2) by the pressure half-time method. However, elevated mean transmitral and right ventricle/right atrium gradients were identified (39 and 117 mmHg, respectively). This puzzling discrepancy in the echocardiographic findings prompted investigation by transesophageal echocardiography, which revealed an echogenic structure adjacent to the mitral annulus, causing severe obstruction (effective orifice area 0.7 cm(2)). The suspicion of supravalvular mitral ring was confirmed during surgery. Following ring resection and mitral valve replacement there was significant improvement in the patient's clinical condition and normalization of the left atrium/left ventricle gradient. Supravalvular mitral ring is an unusual cause of congenital mitral stenosis, characterized by an abnormal ridge of connective tissue on the atrial side of the mitral valve, which often obstructs mitral valve inflow. Few cases have been reported, most of them in children with concomitant congenital abnormalities. Diagnosis of a supravalvular mitral ring is challenging, since it is very difficult to visualize in most diagnostic tests. It was the combination of clinical and various echocardiographic findings that led us to suspect this very rare condition, enabling appropriate treatment, with excellent long-term results. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Unusual course of infective endocarditis: acute renal failure progressing to chronic renal failure.

PubMed

Sevinc, Alper; Davutoglu, Vedat; Barutcu, Irfan; Kocoglu, M Esra

2006-04-01

Infective endocarditis is an infection of the endocardium that usually involves the valves and adjacent structures. The classical fever of unknown origin presentation represents a minority of infective endocarditis. The presented case was a 21-yearold young lady presenting with acute renal failure and fever to the emergency room. Cardiac auscultation revealed a soft S1 and 4/6 apical holosystolic murmur extended to axilla. Echocardiography showed mobile fresh vegetation under the mitral posterior leaflet. She was diagnosed as having infective endocarditis. Hemodialysis was started with antimicrobial therapy. However, because of the presence of severe mitral regurgitation with left ventricle dilatation and large mobile vegetation, mitral prosthetic mechanical valve replacement was performed. Although treated with antibiotics combined with surgery, renal functions were deteriorated and progressed to chronic renal failure.

Leaflet embolisation from Duromedics valves: a report of two cases.

PubMed

Kumar, N; Balasundaram, S; Rickard, M; al Halees, Z; Duran, C M

1991-12-01

Embolization of parts of mechanical valves has been reported since the inception of prosthetic valve implantation. We report here two cases of embolization of one hemileaflet of a Duromedic bileaflet prosthesis in the mitral position due to a pivot fracture. Both presented with moderately severe mitral regurgitation and pulmonary edema and were successfully managed by replacement of the malfunctioning prostheses. The embolised disc was located in the left common iliac artery by abdominal ultrasound and removed by an inguinal, retroperitoneal approach with low morbidity. Both patients left hospital and are doing well to-date.

Mitral Valve Chordae Tendineae: Topological and Geometrical Characterization.

PubMed

Khalighi, Amir H; Drach, Andrew; Bloodworth, Charles H; Pierce, Eric L; Yoganathan, Ajit P; Gorman, Robert C; Gorman, Joseph H; Sacks, Michael S

2017-02-01

Mitral valve (MV) closure depends upon the proper function of each component of the valve apparatus, which includes the annulus, leaflets, and chordae tendineae (CT). Geometry plays a major role in MV mechanics and thus highly impacts the accuracy of computational models simulating MV function and repair. While the physiological geometry of the leaflets and annulus have been previously investigated, little effort has been made to quantitatively and objectively describe CT geometry. The CT constitute a fibrous tendon-like structure projecting from the papillary muscles (PMs) to the leaflets, thereby evenly distributing the loads placed on the MV during closure. Because CT play a major role in determining the shape and stress state of the MV as a whole, their geometry must be well characterized. In the present work, a novel and comprehensive investigation of MV CT geometry was performed to more fully quantify CT anatomy. In vitro micro-tomography 3D images of ovine MVs were acquired, segmented, then analyzed using a curve-skeleton transform. The resulting data was used to construct B-spline geometric representations of the CT structures, enriched with a continuous field of cross-sectional area (CSA) data. Next, Reeb graph models were developed to analyze overall topological patterns, along with dimensional attributes such as segment lengths, 3D orientations, and CSA. Reeb graph results revealed that the topology of ovine MV CT followed a full binary tree structure. Moreover, individual chords are mostly planar geometries that together form a 3D load-bearing support for the MV leaflets. We further demonstrated that, unlike flow-based branching patterns, while individual CT branches became thinner as they propagated further away from the PM heads towards the leaflets, the total CSA almost doubled. Overall, our findings indicate a certain level of regularity in structure, and suggest that population-based MV CT geometric models can be generated to improve current MV repair procedures.

Ultrasound based mitral valve annulus tracking for off-pump beating heart mitral valve repair

NASA Astrophysics Data System (ADS)

Li, Feng P.; Rajchl, Martin; Moore, John; Peters, Terry M.

2014-03-01

Mitral regurgitation (MR) occurs when the mitral valve cannot close properly during systole. The NeoChordtool aims to repair MR by implanting artificial chordae tendineae on flail leaflets inside the beating heart, without a cardiopulmonary bypass. Image guidance is crucial for such a procedure due to the lack of direct vision of the targets or instruments. While this procedure is currently guided solely by transesophageal echocardiography (TEE), our previous work has demonstrated that guidance safety and efficiency can be significantly improved by employing augmented virtuality to provide virtual presentation of mitral valve annulus (MVA) and tools integrated with real time ultrasound image data. However, real-time mitral annulus tracking remains a challenge. In this paper, we describe an image-based approach to rapidly track MVA points on 2D/biplane TEE images. This approach is composed of two components: an image-based phasing component identifying images at optimal cardiac phases for tracking, and a registration component updating the coordinates of MVA points. Preliminary validation has been performed on porcine data with an average difference between manually and automatically identified MVA points of 2.5mm. Using a parallelized implementation, this approach is able to track the mitral valve at up to 10 images per second.

Fluid-structure interaction in the left ventricle of the human heart coupled with mitral valve

NASA Astrophysics Data System (ADS)

Meschini, Valentina; de Tullio, Marco Donato; Querzoli, Giorgio; Verzicco, Roberto

2016-11-01

In this paper Direct Numerical Simulations (DNS), implemented using a fully fluid-structure interaction model for the left ventricle, the mitral valve and the flowing blood, and laboratory experiments are performed in order to cross validate the results. Moreover a parameter affecting the flow dynamics is the presence of a mitral valve. We model two cases, one with a natural mitral valve and another with a prosthetic mechanical one. Our aim is to understand their different effects on the flow inside the left ventricle in order to better investigate the process of valve replacement. We simulate two situations, one of a healthy left ventricle and another of a failing one. While in the first case the flow reaches the apex of the left ventricle and washout the stagnant fluid with both mechanical and natural valve, in the second case the disturbance generated by the mechanical leaflets destabilizes the mitral jet, thus further decreasing its capability to penetrate the ventricular region and originating heart attack or cardiac pathologies in general.

Patient-specific pediatric silicone heart valve models based on 3D ultrasound

NASA Astrophysics Data System (ADS)

Ilina, Anna; Lasso, Andras; Jolley, Matthew A.; Wohler, Brittany; Nguyen, Alex; Scanlan, Adam; Baum, Zachary; McGowan, Frank; Fichtinger, Gabor

2017-03-01

PURPOSE: Patient-specific heart and valve models have shown promise as training and planning tools for heart surgery, but physically realistic valve models remain elusive. Available proprietary, simulation-focused heart valve models are generic adult mitral valves and do not allow for patient-specific modeling as may be needed for rare diseases such as congenitally abnormal valves. We propose creating silicone valve models from a 3D-printed plastic mold as a solution that can be adapted to any individual patient and heart valve at a fraction of the cost of direct 3D-printing using soft materials. METHODS: Leaflets of a pediatric mitral valve, a tricuspid valve in a patient with hypoplastic left heart syndrome, and a complete atrioventricular canal valve were segmented from ultrasound images. A custom software was developed to automatically generate molds for each valve based on the segmentation. These molds were 3D-printed and used to make silicone valve models. The models were designed with cylindrical rims of different sizes surrounding the leaflets, to show the outline of the valve and add rigidity. Pediatric cardiac surgeons practiced suturing on the models and evaluated them for use as surgical planning and training tools. RESULTS: Five out of six surgeons reported that the valve models would be very useful as training tools for cardiac surgery. In this first iteration of valve models, leaflets were felt to be unrealistically thick or stiff compared to real pediatric leaflets. A thin tube rim was preferred for valve flexibility. CONCLUSION: The valve models were well received and considered to be valuable and accessible tools for heart valve surgery training. Further improvements will be made based on surgeons' feedback.

Pregnancy-induced remodeling of heart valves.

PubMed

Pierlot, Caitlin M; Moeller, Andrew D; Lee, J Michael; Wells, Sarah M

2015-11-01

Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves. Copyright © 2015 the American Physiological Society.

Initial Experience With a New Mitral Ring Designed to Simplify Length Determination of Neochords.

PubMed

Prinzing, Anatol; Bleiziffer, Sabine; Krane, Markus; Lange, Ruediger

2018-06-01

Artificial chord implantation has become one of the most applied techniques for mitral valve repair (MVR). Many techniques have been described, with the goal of optimizing neochord implantation. A new annuloplasty device designed to simplify the determination of the appropriate neochord length has been recently introduced. We describe our initial experience with this new device. The semirigid device is equipped with removable loops on the posterior aspect of the ring. Neochords are tied to the loops, which are subsequently removed. The device was implanted in 47 symptomatic patients from January 2015 to August 2016 through a median sternotomy in 33 patients (70.2%) and a right anterolateral minithoracotomy in 14 (29.8%). The cause of mitral valve insufficiency was degenerative in all patients, and most patients presented with isolated prolapse of the posterior leaflet. Before and after cardiopulmonary bypass, all patients underwent evaluation with transesophageal echocardiography, and transthoracic echocardiography was performed at discharge. A median of 2 neochords were implanted (minimum, 1; maximum, 6). Mean cardiopulmonary bypass time and aortic cross-clamp times were 141.7 ± 32.3 and 104.8 ± 28.5 minutes for combined and 133 ± 53.9 and 98.3 ± 41.6 minutes for isolated MVR. At discharge, echocardiography revealed no or only mild mitral insufficiency in 45 patients (mean gradient, 2.9 ± 1.3 mm Hg). This new annuloplasty ring facilitated determination of appropriate neochord length and was used to successfully treat different degenerative pathologies affecting both leaflets. This new device simplified length determination of the neochords. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Antiphospholipid antibody-associated non-infective mitral valve endocarditis successfully treated with medical therapy.

PubMed

Contractor, Tahmeed; Bell, Adrian; Khasnis, Atul; Silverberg, Bruce J; Martinez, Matthew W

2013-01-01

Non-bacterial endocarditis lesions associated with antiphospholipid antibodies (aPLs) in the absence of other criteria for antiphospholipid syndrome or systemic lupus erythematosus is termed an aPL-associated cardiac valve disease. Evidence regarding the management of this condition is sparse. A rare case is described of a 20-year-old female who presented with an incidental finding of 'vegetations on a heart valve'. Echocardiography revealed mitral valve leaflet thickening and echodensities with moderate mitral regurgitation. She had an elevated partial thromboplastin time that did not correct with a mixing study, and elevated levels of antiocardiolipin antibodies. Hence, a diagnosis of aPL-associated cardiac valve disease was made, and the patient commenced on warfarin, hydroxychloroquine, and a short course of oral prednisone. At one year after diagnosis the patient remained symptom-free, and follow up echocardiography revealed resolution of the vegetations with minimal mitral regurgitation. Further evidence is needed to guide the therapy of this rare condition.

Changes in mitral annular and left ventricular dimensions and left ventricular pressure-volume relations after off-pump treatment of mitral regurgitation with the Coapsys device.

PubMed

Fukamachi, Kiyotaka; Popović, Zoran B; Inoue, Masahiro; Doi, Kazuyoshi; Schenk, Soren; Ootaki, Yoshio; Kopcak, Michael W; McCarthy, Patrick M

2004-03-01

The objective of this study was to evaluate the changes in mitral annular and left ventricular dimensions and left ventricular pressure-volume relations produced by the Myocor Coapsys device that has been developed to treat functional mitral regurgitation (MR) off-pump. The Coapsys device, which consists of anterior and posterior epicardial pads connected by a sub-valvular chord, was implanted in seven dogs with functional MR resulting from pacing induced cardiomyopathy. The Coapsys device was then sized by drawing the posterior leaflet and annulus toward the anterior leaflet. During sizing, MR grade was assessed using color flow Doppler echocardiography. Final device size was selected when MR was eliminated or minimized. Following implantation, heart failure was maintained by continued pacing for a period of 8 weeks. Mitral annular and left ventricular dimensions and left ventricular pressure-volume relations were evaluated by two-dimensional echocardiography and a conductance catheter, respectively, at pre-sizing, post-sizing, and after 8 weeks. All implants were performed on beating hearts without cardiopulmonary bypass. Mean MR grade was reduced from 2.9+/-0.7 at pre-sizing to 0.7+/-0.8 at post-sizing (P<0.001), and was maintained at 0.8+/-0.8 after 8 weeks (P<0.01). The septal-lateral dimensions were significantly reduced at both mitral annular level [2.4+/-0.2 cm at pre-sizing, 1.5+/-0.3 cm at post-sizing (P<0.001) and 1.8+/-0.3 cm after 8 weeks (P<0.05)] and mid-papillary level [4.1+/-0.4 cm at pre-sizing, 2.4+/-0.2 cm at post-sizing (P<0.001) and 3.3+/-0.4 cm after 8 weeks (P<0.001)]. The end-systolic pressure-volume relation shifted leftward at post-sizing with a significantly steeper slope (P=0.03). There was a significant (P=0.03) leftward shift of the end-diastolic pressure-volume relation at post-sizing. After 8 weeks, these changes in pressure-volume relations tended to return to pre-sizing relations. The Coapsys device significantly reduced MR by treating both the mitral annular dilatation and the papillary muscle displacement. Despite these significant dimensional changes, the Coapsys device did not negatively affect the left ventricular pressure-volume relations.

Quantification of mitral regurgitation using proximal isovelocity surface area method in dogs.

PubMed

Choi, Hojung; Lee, Kichang; Lee, Heechun; Lee, Youngwon; Chang, Dongwoo; Eom, Kidong; Youn, Hwayoung; Choi, Mincheol; Yoon, Junghee

2004-06-01

The present study was performed to determine the accuracy and reproducibility of calculating the mitral regurgitant orifice area with the proximal isovelocity surface area (PISA) method in dogs with experimental mitral regurgitation and in canine patients with chronic mitral insufficiency and to evaluate the effect of general anesthesia on mitral regurgitation. Eight adult, Beagle dogs for experimental mitral regurgitation and 11 small breed dogs with spontaneous mitral regurgitation were used. In 8 Beagle dogs, mild mitral regurgitation was created by disrupting mitral chordae or leaflets. Effective regurgitant orifice (ERO) area was measured by the PISA method and compared with the measurements simultaneously obtained by quantitative Doppler echocardiography 4 weeks after creation of mitral regurgitation. The same procedure was performed in 11 patients with isolated mitral regurgitation and in 8 Beagle dogs under two different protocols of general anesthesia. ERO and regurgitant stroke volume (RSV) by the PISA method correlated well with values by the quantitative Doppler technique with a small error in experimental dogs (r = 0.914 and r = 0.839) and 11 patients (r = 0.990 and r = 0.996). The isoflurane anesthetic echocardiography demonstrated a significant decrease of RSV, and there was no significant change in fractional shortening (FS), ERO area, LV end-diastolic and LV end-systolic volume. ERO area showed increasing tendency after ketamine-xylazine administration, but not statistically significant. RSV, LV end-systolic and LV end-diastolic volume increased significantly (p < 0.01), whereas FS significantly decreased (p < 0.01). The PISA method is accurate and reproducible in experimental mitral regurgitation model and in a clinical setting. ERO area is considered and preferred as a hemodynamic-nondependent factor than other traditional measurements.

Percutaneous repair or surgery for mitral regurgitation.

PubMed

Feldman, Ted; Foster, Elyse; Glower, Donald D; Glower, Donald G; Kar, Saibal; Rinaldi, Michael J; Fail, Peter S; Smalling, Richard W; Siegel, Robert; Rose, Geoffrey A; Engeron, Eric; Loghin, Catalin; Trento, Alfredo; Skipper, Eric R; Fudge, Tommy; Letsou, George V; Massaro, Joseph M; Mauri, Laura

2011-04-14

Mitral-valve repair can be accomplished with an investigational procedure that involves the percutaneous implantation of a clip that grasps and approximates the edges of the mitral leaflets at the origin of the regurgitant jet. We randomly assigned 279 patients with moderately severe or severe (grade 3+ or 4+) mitral regurgitation in a 2:1 ratio to undergo either percutaneous repair or conventional surgery for repair or replacement of the mitral valve. The primary composite end point for efficacy was freedom from death, from surgery for mitral-valve dysfunction, and from grade 3+ or 4+ mitral regurgitation at 12 months. The primary safety end point was a composite of major adverse events within 30 days. At 12 months, the rates of the primary end point for efficacy were 55% in the percutaneous-repair group and 73% in the surgery group (P=0.007). The respective rates of the components of the primary end point were as follows: death, 6% in each group; surgery for mitral-valve dysfunction, 20% versus 2%; and grade 3+ or 4+ mitral regurgitation, 21% versus 20%. Major adverse events occurred in 15% of patients in the percutaneous-repair group and 48% of patients in the surgery group at 30 days (P<0.001). At 12 months, both groups had improved left ventricular size, New York Heart Association functional class, and quality-of-life measures, as compared with baseline. Although percutaneous repair was less effective at reducing mitral regurgitation than conventional surgery, the procedure was associated with superior safety and similar improvements in clinical outcomes. (Funded by Abbott Vascular; EVEREST II ClinicalTrials.gov number, NCT00209274.).

Assessment of insulin-like growth factor-1 (IGF-I) level in patients with rheumatic mitral stenosis.

PubMed

Deveci, Onur S; Yavuz, Bunyamin; Sen, Omer; Deniz, Ali; Ozkan, Selcuk; Dal, Kursat; Ata, Naim; Baser, Salih; Akin, Kadir O; Kucukazman, Metin; Beyan, Esin; Ertugrul, Derun T

2015-03-01

Insulin-like growth factor-1 may serve some regulatory function in the immune system. Rheumatic mitral stenosis is related to autoimmune heart valve damage after streptococcal infection. The aim of this study was to assess the level of insulin-like growth factor-1 and its correlation with the Wilkins score in patients with rheumatic mitral stenosis. A total of 65 patients with rheumatic mitral stenosis and 62 age- and sex-matched control subjects were enrolled in this study. All subjects underwent transthoracic echocardiography. The mitral valve area and Wilkins score were evaluated for all patients. Biochemical parameters and serum insulin-like growth factor-1 levels were measured. Demographic data were similar in the rheumatic mitral stenosis and control groups. The mean mitral valve area was 1.6±0.4 cm2 in the rheumatic mitral stenosis group. The level of insulin-like growth factor-1 was significantly higher in the rheumatic mitral stenosis group than in the control group (104 (55.6-267) versus 79.1 (23.0-244.0) ng/ml; p=0.039). There was a significant moderate positive correlation between insulin-like growth factor-1 and thickening of leaflets score of Wilkins (r=0.541, p<0.001). The present study demonstrated that serum insulin-like growth factor-1 levels were significantly higher in the rheumatic mitral stenosis group compared with control subjects and that insulin-like growth factor-1 level was also correlated with the Wilkins score. It can be suggested that there may be a link between insulin-like growth factor-1 level and immune pathogenesis of rheumatic mitral stenosis.

Echocardiographic Assessment of Degenerative Mitral Stenosis: A Diagnostic Challenge of an Emerging Cardiac Disease.

PubMed

Oktay, Ahmet Afşşin; Gilliland, Yvonne E; Lavie, Carl J; Ramee, Stephen J; Parrino, Patrick E; Bates, Michael; Shah, Sangeeta; Cash, Michael E; Dinshaw, Homeyar; Qamruddin, Salima

2017-03-01

Degenerative mitral stenosis (DMS) is characterized by decreased mitral valve (MV) orifice area and increased transmitral pressure gradient due to chronic noninflammatory degeneration and subsequent calcification of the fibrous mitral annulus and the MV leaflets. The "true" prevalence of DMS in the general population is unknown. DMS predominantly affects elderly individuals, many of whom have multiple other comorbidities. Transcatheter MV replacement techniques, although their long-term outcomes are yet to be tested, have been gaining popularity and may emerge as more effective and relatively safer treatment option for patients with DMS. Echocardiography is the primary imaging modality for evaluation of DMS and related hemodynamic abnormalities such as increased transmitral pressure gradient and pulmonary arterial pressure. Classic echocardiographic techniques used for evaluation of mitral stenosis (pressure half time, proximal isovelocity surface area, continuity equation, and MV area planimetry) lack validation for DMS. Direct planimetry with 3-dimensional echocardiography and color flow Doppler is a reasonable technique for determining MV area in DMS. Cardiac computed tomography is an essential tool for planning potential interventions or surgeries for DMS. This article reviews the current concepts on mitral annular calcification and its role in DMS. We then discuss the epidemiology, natural history, differential diagnosis, mechanisms, and echocardiographic assessment of DMS. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of bileaflet mitral valve prolapse on quantification of mitral regurgitation with cardiac magnetic resonance: a single-center study.

PubMed

Vincenti, Gabriella; Masci, Pier Giorgio; Rutz, Tobias; De Blois, Jonathan; Prša, Milan; Jeanrenaud, Xavier; Schwitter, Juerg; Monney, Pierre

2017-07-27

To quantify mitral regurgitation (MR) with CMR, the regurgitant volume can be calculated as the difference between the left ventricular (LV) stroke volume (SV) measured with the Simpson's method and the reference SV, i.e. the right ventricular SV (RVSV) in patients without tricuspid regurgitation. However, for patients with prominent mitral valve prolapse (MVP), the Simpson's method may underestimate the LV end-systolic volume (LVESV) as it only considers the volume located between the apex and the mitral annulus, and neglects the ventricular volume that is displaced into the left atrium but contained within the prolapsed mitral leaflets at end systole. This may lead to an underestimation of LVESV, and resulting an over-estimation of LVSV, and an over-estimation of mitral regurgitation. The aim of the present study was to assess the impact of prominent MVP on MR quantification by CMR. In patients with MVP (and no more than trace tricuspid regurgitation) MR was quantified by calculating the regurgitant volume as the difference between LVSV and RVSV. LVSV uncorr was calculated conventionally as LV end-diastolic (LVEDV) minus LVESV. A corrected LVESV corr was calculated as the LVESV plus the prolapsed volume, i.e. the volume between the mitral annulus and the prolapsing mitral leaflets. The 2 methods were compared with respect to the MR grading. MR grades were defined as absent or trace, mild (5-29% regurgitant fraction (RF)), moderate (30-49% RF), or severe (≥50% RF). In 35 patients (44.0 ± 23.0y, 14 males, 20 patients with MR) the prolapsed volume was 16.5 ± 8.7 ml. The 2 methods were concordant in only 12 (34%) patients, as the uncorrected method indicated a 1-grade higher MR severity in 23 (66%) patients. For the uncorrected/corrected method, the distribution of the MR grades as absent-trace (0 vs 11, respectively), mild (20 vs 18, respectively), moderate (11 vs 5, respectively), and severe (4 vs 1, respectively) was significantly different (p < 0.001). In the subgroup without MR, LVSV corr was not significantly different from RVSV (difference: 2.5 ± 4.7 ml, p = 0.11 vs 0) while a systematic overestimation was observed with LVSV uncorr (difference: 16.9 ± 9.1 ml, p = 0.0007 vs 0). Also, RVSV was highly correlated with aortic forward flow (n = 24, R 2  = 0.97, p < 0.001). For patients with severe bileaflet prolapse, the correction of the LVSV for the prolapse volume is suggested as it modified the assessment of MR severity by one grade in a large portion of patients.

[Valvuloplasty with balloon catheter in biologic prosthesis. Reality or illusion].

PubMed

Ledesma Velasco, M; Verdín Vázquez, R; Acosta Valdez, J L; Munayer Calderón, J; Salgado Escobar, J L; Arias Monroy, L; Flores Mendoza, J

1989-01-01

We performed catheter balloon valvuloplasty (CBV) on 8 stenotic operatively-excised bioprosthetic valves (2 Hancock and 6 Ionescu Shiley). Pathology of valves before CBV included degenerative changes: commissural fusion by mounds of calcific deposits (2 valves), fibrotic and focally calcified leaflets (7 valves) and stiff and thick valves (1 valve). Inflation of the balloon resulted in commissural splitting (2 valves), leaflet cracks and fractures (3 valves). Removal of the deflated balloon catheter was associated with debris dislodgement (3 valves). In one case the valve was unable to close with potential for acute regurgitation. Thus, CBV of bioprosthetic valves can split fused commissures by similar mechanisms as in native valves. CBV may fracture calcific deposits causing acute emboli. It can also disrupt the leaflets causing acute insufficiency. The findings suggest a limited role of CBV in the treatment of stenotic bioprosthetic valves in mitral and aortic position.

Relief of mitral leaflet tethering following chronic myocardial infarction by chordal cutting diminishes left ventricular remodeling.

PubMed

Messas, Emmanuel; Bel, Alain; Szymanski, Catherine; Cohen, Iris; Touchot, Bernard; Handschumacher, Mark D; Desnos, Michel; Carpentier, Alain; Menasché, Philippe; Hagège, Albert A; Levine, Robert A

2010-11-01

one of the key targets in treating mitral regurgitation (MR) is reducing the otherwise progressive left ventricular (LV) remodeling that exacerbates MR and conveys adverse prognosis. We have previously demonstrated that severing 2 second-order chordae to the anterior mitral leaflet relieves tethering and ischemic MR acutely. The purpose of this study was to test whether this technique reduces the progression of LV remodeling in the chronic ischemic MR setting. a posterolateral MI was created in 18 sheep by obtuse marginal branch ligation. After chronic remodeling and MR development at 3 months, 6 sheep were randomized to sham surgery (control group) and 12 to second-order chordal cutting (6 each to anterior leaflet [AntL] and bileaflet [BiL] chordal cutting, techniques that are in clinical application). At baseline, chronic infarction (3 months), and follow-up at a mean of 6.6 months post-myocardial infarction (MI) (euthanasia), we measured LV end-diastolic (EDV) and end-systolic volume (ESV), ejection fraction, wall motion score index, and posterior leaflet (PL) restriction angle relative to the annulus by 2D and 3D echocardiography. All measurements were comparable among groups at baseline and chronic MI. At euthanasia, AntL and BiL chordal cutting limited the progressive remodeling seen in controls. LVESV increased relative to chronic MI by 109±8.7% in controls versus 30.5±6.1% with chordal cutting (P<0.01) (LVESV in controls, 82.5±2.6 mL; in AntL, 60.6±5.1 mL; in BiL, 61.8±4.1 mL). LVEDV increased by 63±2.0% in controls versus 26±5.5% and 22±3.4% with chordal cutting (P<0.01). LV ejection fraction and wall motion score index were not significantly different at follow-up among the chordal cutting and control groups. MR progressively increased to moderate in controls but decreased to trace-mild with AntL and BiL chordal cutting (MR vena contracta in controls, 5.9±1.1 mm; in AntL, 2.6±0.1 mm; in BiL, 1.7±0.1 mm; P<0.01). BiL chordal cutting provided greater PL mobility (decreased PL restriction angle to 54.2±5.0° versus 83±3.2° with AntL chordal cutting; P<0.01). reduced leaflet tethering by chordal cutting in the chronic post-MI setting substantially decreases the progression of LV remodeling with sustained reduction of MR over a chronic follow-up. These benefits have the potential to improve clinical outcomes.

Assessment of transmitral flow after mitral valve edge-to-edge repair using High-speed particle image velocimetry

NASA Astrophysics Data System (ADS)

Jeyhani, Morteza; Shahriari, Shahrokh; Labrosse, Michel; Kadem, Lyes

2013-11-01

Approximately 500,000 people in North America suffer from mitral valve regurgitation (MR). MR is a disorder of the heart in which the mitral valve (MV) leaflets do not close securely during systole. Edge-to-edge repair (EtER) technique can be used to surgically treat MR. This technique produces a double-orifice configuration for the MV. Under these un-physiological conditions, flow downstream of the MV forms a double jet structure that may disturb the intraventricular hemodynamics. Abnormal flow patterns following EtER are mainly characterized by high-shear stress and stagnation zones in the left ventricle (LV), which increase the potential of blood component damage. In this study, a custom-made prosthetic bicuspid MV was used to analyze the LV flow patterns after EtER by means of digital particle image velocimetry (PIV). Although the repair of a MV using EtER technique is an effective approach, this study confirms that EtER leads to changes in the LV flow field, including the generation of a double mitral jet flow and high shear stress regions.

Effects of Mechanical Ventilation on Heart Geometry and Mitral Valve Leaflet Coaptation During Percutaneous Edge-to-Edge Mitral Valve Repair.

PubMed

Patzelt, Johannes; Zhang, Yingying; Seizer, Peter; Magunia, Harry; Henning, Andreas; Riemlova, Veronika; Patzelt, Tara A E; Hansen, Marc; Haap, Michael; Riessen, Reimer; Lausberg, Henning; Walker, Tobias; Reutershan, Joerg; Schlensak, Christian; Grasshoff, Christian; Simon, Dan I; Rosenberger, Peter; Schreieck, Juergen; Gawaz, Meinrad; Langer, Harald F

2016-01-25

This study sought to evaluate a ventilation maneuver to facilitate percutaneous edge-to-edge mitral valve repair (PMVR) and its effects on heart geometry. In patients with challenging anatomy, the application of PMVR is limited, potentially resulting in insufficient reduction of mitral regurgitation (MR) or clip detachment. Under general anesthesia, however, ventilation maneuvers can be used to facilitate PMVR. A total of 50 consecutive patients undergoing PMVR were included. During mechanical ventilation, different levels of positive end-expiratory pressure (PEEP) were applied, and parameters of heart geometry were assessed using transesophageal echocardiography. We found that increased PEEP results in elevated central venous pressure. Specifically, central venous pressure increased from 14.0 ± 6.5 mm Hg (PEEP 3 mm Hg) to 19.3 ± 5.9 mm Hg (PEEP 20 mm Hg; p < 0.001). As a consequence, the reduced pre-load resulted in reduction of the left ventricular end-systolic diameter from 43.8 ± 10.7 mm (PEEP 3 mm Hg) to 39.9 ± 11.0 mm (PEEP 20 mm Hg; p < 0.001), mitral valve annulus anterior-posterior diameter from 32.4 ± 4.3 mm (PEEP 3 mm Hg) to 30.5 ± 4.4 mm (PEEP 20 mm Hg; p < 0.001), and the medio-lateral diameter from 35.4 ± 4.2 mm to 34.1 ± 3.9 mm (p = 0.002). In parallel, we observed a significant increase in leaflet coaptation length from 3.0 ± 0.8 mm (PEEP 3 mm Hg) to 5.4 ± 1.1 mm (PEEP 20 mm Hg; p < 0.001). The increase in coaptation length was more pronounced in MR with functional or mixed genesis. Importantly, a coaptation length >4.9 mm at PEEP of 10 mm Hg resulted in a significant reduction of PMVR procedure time (152 ± 49 min to 116 ± 26 min; p = 0.05). In this study, we describe a novel ventilation maneuver improving mitral valve coaptation length during the PMVR procedure, which facilitates clip positioning. Our observations could help to improve PMVR therapy and could make nonsurgical candidates accessible to PMVR therapy, particularly in challenging cases with functional MR. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

A technique of snaring method for fitting a prosthetic valve into the annulus.

PubMed

Nagasaka, Shigeo; Kawata, Tetsuji; Matsuta, Masahiro; Taniguchi, Shigeki

2005-01-01

Tourniquetting technique to fit a prosthetic valve (PV) into the annulus in valve replacement surgery has been previously reported. We modified the previously reported method and designed a simpler tying technique. We performed 11 aortic (AVR: including four cases for calcified aortic stenosis (AS) with a small annulus and one cases for infective endocarditis with intramuscular abscess cavity), eight mitral valve replacements (MVR), and one tricuspid valve replacement (TVR: for corrected transposition of the great arteries). A PV was implanted using 2-0 polyester mattress sutures with a pledget. Each of the two tourniquets held a suture at the bottom of the annulus and at the opposite position to fit a PV. The sutures between each snare were tied down from the bottom to the top. In MVR, after seating of a PV with two tourniquets, we could make sure that no native tissue of any preserved mitral apparatus disturbed PV leaflet motion. In calcific AS, a PV had a good fitting into the annulus because of tourniquets applied to unseated part during tying sutures. In AVR for infective endocarditis, mattress sutures supported by a Teflon pledget were placed to close the abscess cavity. After snaring on one of these sutures, we tied down the sutures, ensuring that they did not cut through the friable tissues. In TVR, we found that native leaflets interfered with PV motion after seating down the prosthesis and those leaflets were resected before tying down the sutures. Postoperative transesophageal echocardiography showed no paravalvular leakage in any patients and excellent PV functions.

Spatiotemporal Segmentation and Modeling of the Mitral Valve in Real-Time 3D Echocardiographic Images.

PubMed

Pouch, Alison M; Aly, Ahmed H; Lai, Eric K; Yushkevich, Natalie; Stoffers, Rutger H; Gorman, Joseph H; Cheung, Albert T; Gorman, Joseph H; Gorman, Robert C; Yushkevich, Paul A

2017-09-01

Transesophageal echocardiography is the primary imaging modality for preoperative assessment of mitral valves with ischemic mitral regurgitation (IMR). While there are well known echocardiographic insights into the 3D morphology of mitral valves with IMR, such as annular dilation and leaflet tethering, less is understood about how quantification of valve dynamics can inform surgical treatment of IMR or predict short-term recurrence of the disease. As a step towards filling this knowledge gap, we present a novel framework for 4D segmentation and geometric modeling of the mitral valve in real-time 3D echocardiography (rt-3DE). The framework integrates multi-atlas label fusion and template-based medial modeling to generate quantitatively descriptive models of valve dynamics. The novelty of this work is that temporal consistency in the rt-3DE segmentations is enforced during both the segmentation and modeling stages with the use of groupwise label fusion and Kalman filtering. The algorithm is evaluated on rt-3DE data series from 10 patients: five with normal mitral valve morphology and five with severe IMR. In these 10 data series that total 207 individual 3DE images, each 3DE segmentation is validated against manual tracing and temporal consistency between segmentations is demonstrated. The ultimate goal is to generate accurate and consistent representations of valve dynamics that can both visually and quantitatively provide insight into normal and pathological valve function.

Tricuspid Regurgitation Associated With Ischemic Mitral Regurgitation: Characterization, Evolution After Mitral Surgery, and Value of Tricuspid Repair.

PubMed

Navia, José L; Elgharably, Haytham; Javadikasgari, Hoda; Ibrahim, Ahmed; Koprivanac, Marijan; Lowry, Ashley M; Blackstone, Eugene H; Klein, Allan L; Gillinov, A Marc; Roselli, Eric E; Svensson, Lars G

2017-08-01

Tricuspid regurgitation (TR) often accompanies ischemic mitral regurgitation and is generally assumed to be a secondary consequence of altered hemodynamics of the left-sided regurgitation. We hypothesized that it may also be a direct consequence of right-sided ischemic disease. Therefore, our objectives were to (1) characterize the nature of this TR and (2) describe its time course after mitral valve surgery for ischemic mitral regurgitation, with or without concomitant tricuspid valve repair. From 2001 to 2011, 568 patients with ischemic mitral regurgitation underwent mitral valve surgery. They had varying degrees of TR and altered right-side heart morphology and function; 131 had concomitant tricuspid valve repair. Postoperatively, 1,395 echocardiograms were available to assess residual and recurrent TR. Greater severity of preoperative TR was accompanied by larger tricuspid valve diameter, greater leaflet tethering, worse right ventricular function, and higher right ventricular pressure (all p [trend] ≤ 0.002). Without tricuspid valve repair, 31% of patients with no preoperative TR had moderate or greater TR by 5 years, as did 62% with moderate TR. With tricuspid valve repair, 25% with moderate preoperative TR remained in that grade at 5 years, but 11% had severe TR. Tricuspid regurgitation accompanying ischemic mitral regurgitation is associated with right-side heart remodeling and dysfunction often mirroring that occurring in the left side of the heart-ischemic TR. Tricuspid valve repair is effective initially, but as with mitral valve repair, TR progressively returns. Therefore, when the severity of TR and right-sided remodeling reaches the point of irreversibility, it may be an indication to eliminate the TR by replacing the tricuspid valve. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Simple versus complex degenerative mitral valve disease.

PubMed

Javadikasgari, Hoda; Mihaljevic, Tomislav; Suri, Rakesh M; Svensson, Lars G; Navia, Jose L; Wang, Robert Z; Tappuni, Bassman; Lowry, Ashley M; McCurry, Kenneth R; Blackstone, Eugene H; Desai, Milind Y; Mick, Stephanie L; Gillinov, A Marc

2018-07-01

At a center where surgeons favor mitral valve (MV) repair for all subsets of leaflet prolapse, we compared results of patients undergoing repair for simple versus complex degenerative MV disease. From January 1985 to January 2016, 6153 patients underwent primary isolated MV repair for degenerative disease, 3101 patients underwent primary isolated MV repair for simple disease (posterior prolapse), and 3052 patients underwent primary isolated MV repair for complex disease (anterior or bileaflet prolapse), based on preoperative echocardiographic images. Logistic regression analysis was used to generate propensity scores for risk-adjusted comparisons (n = 2065 matched pairs). Durability was assessed by longitudinal recurrence of mitral regurgitation and reoperation. Compared with patients with simple disease, those undergoing repair of complex pathology were more likely to be younger and female (both P values < .0001) but with similar symptoms (P = .3). The most common repair technique was ring/band annuloplasty (3055/99% simple vs 3000/98% complex; P = .5), followed by leaflet resection (2802/90% simple vs 2249/74% complex; P < .0001). Among propensity-matched patients, recurrence of severe mitral regurgitation 10 years after repair was 6.2% for simple pathology versus 11% for complex pathology (P = .007), reoperation at 18 years was 6.3% for simple pathology versus 11% for complex pathology, and 20-year survival was 62% for simple pathology versus 61% for complex pathology (P = .6). Early surgical intervention has become more common in patients with degenerative MV disease, regardless of valve prolapse complexity or symptom status. Valve repair was associated with similarly low operative risk and time-related survival but less durability in complex disease. Lifelong annual echocardiographic surveillance after MV repair is recommended, particularly in patients with complex disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

[Hyperthyroidism, eosinophilia, and fever in a 64-year-old patient].

PubMed

Tack, C; Stierle, U; Heydrich, D; Petersohn, S; Sievers, H H; Feller, A C; Schneider, B

2012-10-01

We report on a male patient suffering from loss of weight, fatigue, fever, eosinophilia, and hyperthyreoidism. The echocardiogram revealed a left atrial mass originating from the posterior mitral leaflet. In combination with the constitutional symptoms a left atrial myxoma was diagnosed. The tumor was surgically removed. Postoperatively therapy with corticosteroids and thiamazole was stopped. During follow-up, eosinophilia and hyperthyreodism could no longer be detected.

AN INVERSE MODELING APPROACH FOR STRESS ESTIMATION IN MITRAL VALVE ANTERIOR LEAFLET VALVULOPLASTY FOR IN-VIVO VALVULAR BIOMATERIAL ASSESSMENT

PubMed Central

Lee, Chung-Hao; Amini, Rouzbeh; Gorman, Robert C.; Gorman, Joseph H.; Sacks, Michael S.

2013-01-01

Estimation of regional tissue stresses in the functioning heart valve remains an important goal in our understanding of normal valve function and in developing novel engineered tissue strategies for valvular repair and replacement. Methods to accurately estimate regional tissue stresses are thus needed for this purpose, and in particular to develop accurate, statistically informed means to validate computational models of valve function. Moreover, there exists no currently accepted method to evaluate engineered heart valve tissues and replacement heart valve biomaterials undergoing valvular stresses in blood contact. While we have utilized mitral valve anterior leaflet valvuloplasty as an experimental approach to address this limitation, robust computational techniques to estimate implant stresses are required. In the present study, we developed a novel numerical analysis approach for estimation of the in-vivo stresses of the central region of the mitral valve anterior leaflet (MVAL) delimited by a sonocrystal transducer array. The in-vivo material properties of the MVAL were simulated using an inverse FE modeling approach based on three pseudo-hyperelastic constitutive models: the neo-Hookean, exponential-type isotropic, and full collagen-fiber mapped transversely isotropic models. A series of numerical replications with varying structural configurations were developed by incorporating measured statistical variations in MVAL local preferred fiber directions and fiber splay. These model replications were then used to investigate how known variations in the valve tissue microstructure influence the estimated ROI stresses and its variation at each time point during a cardiac cycle. Simulations were also able to include estimates of the variation in tissue stresses for an individual specimen dataset over the cardiac cycle. Of the three material models, the transversely anisotropic model produced the most accurate results, with ROI averaged stresses at the fully-loaded state of 432.6±46.5 kPa and 241.4±40.5 kPa in the radial and circumferential directions, respectively. We conclude that the present approach can provide robust instantaneous mean and variation estimates of tissue stresses of the central regions of the MVAL. PMID:24275434

Occluder closing behavior: a key factor in mechanical heart valve cavitation.

PubMed

Wu, Z J; Wang, Y; Hwang, N H

1994-04-01

A laser sweeping technique developed in this laboratory was found to be capable of monitoring the leaflet closing motion with microsecond precision. The leaflet closing velocity was measured inside the last three degrees before impact. Mechanical heart valve (MHV) leaflets were observed to close with a three-phase motion; the approaching phase, the decelerating phase, and the rebound phase, all of which take place within one to two milliseconds. The leaflet closing behavior depends mainly on the leaflet design and the hinge mechanism. Bileaflet and monoleaflet types of mechanical heart valves were tested in the mitral position in a physiologic mock circulatory flow loop, which incorporated a computer-controlled magnetic drive and an adjustable afterload system. The test loop was tuned to produce physiologic ventricular and aortic pressure wave forms at 70-120 beats/min, with the maximum ventricular dp/dt varying between 1500-5600 mmHg/sec. The experiments were conducted by controlling the cardiac output at a constant level between 2.0-9.0 liters/min. The measured time-displacement curve of each tested MHV leaflet and its geometry were taken as the input for computation of the squeeze flow field in the narrow gap space between the approaching leaflet and the valve housing. The results indicated rapid build-up of both the pressure and velocity in the gap field within microsecs before the impact. The pressure build-up in the gap space is apparently responsible for the leaflet deceleration before the impact. When the concurrent water hammer pressure reduction at closure was combined with the high energy squeeze jet ejected from the gap space, there were strong indications of the environment which favors micro cavitation inceptions in certain types of MHV.

Is minimally invasive mitral valve repair with artificial chords reproducible and applicable in routine surgery?

PubMed

Panos, Aristotelis; Vlad, Sylvio; Milas, Fotios; Myers, Patrick O

2015-06-01

Traditional resectional techniques and chordal transfer are difficult to apply in video-assisted mitral valve repair. Using artificial chords appears easier in this setting. The purpose of this study was to review the effectiveness and reproducibility of neochordal repair as a routine approach to minimally invasive mitral repair, and to assess the stability of neochord implantation using the figure-of-eight suture without pledgets in this setting. This is a retrospective review of all patients who underwent minimally invasive video-assisted mitral valve repair from 2008 to 2013. The primary endpoints were recurrent mitral regurgitation and reoperation. A total of 426 consecutive patients were included during the study period, with a mean age of 55 ± 18 years. Neochords were used in all patients, and in association with leaflet resection in 47 patients. One patient was not repairable and underwent valve replacement (repair rate, 99.8%). Fifteen patients had Grade I (3.5%) regurgitation, whereas the remainder had none. Patients were fast-tracked, with 25% extubated in the operation theatre and the remainder within 6 h. There were 5 deaths within 30 days (1.2%). Follow-up ranged 3-60 months, during which all of the patients remained with no or trace mitral regurgitation. No de-insertion or rupture of any neochords was found, and no patients required a reoperation. Minimally invasive mitral valve repair using neochords provided a high rate of repair, reproducible results in a routine cardiac surgery setting and stable repair during follow-up. This has become our preferred technique for mitral valve surgery. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Mitral valve reconstruction in Barlow disease: long-term echographic results and implications for surgical management.

PubMed

Jouan, Jérôme; Berrebi, Alain; Chauvaud, Sylvain; Menasché, Philippe; Carpentier, Alain; Fabiani, Jean-Noël

2012-04-01

Owing to the complexity of the underlying lesions, Barlow disease remains a challenge for surgeons performing mitral valve repair. We aimed to assess whether our most recent results involving several surgeons were comparable with those of a previous experience in which mitral valve repair was performed by a more limited group of surgeons. From September 2000 to January 2007, 200 patients with Barlow disease (135 men and 65 women; mean age, 56 ± 13 years) were referred to our institution for surgical treatment of their mitral regurgitation. We retrospectively analysed the mitral lesions characteristics, the surgical techniques used, and clinical outcomes. Follow-up echocardiograms were biannually reviewed. Lesions comprised annular dilatation, excess tissue, and leaflet prolapse in all cases. The most frequent prolapsed segments were P2 (88.5%; n = 177) and A2 (55.5%; n = 111). Annular calcifications and restrictive valvular motion were associated in 20% (n = 40). Repair was feasible in 94.7% (n = 179/189) of non-redo interventions. Immediate postoperative echocardiography showed residual mitral regurgitation greater than 1+ in 6 cases; these patients were all reoperated on within the next months. Operative mortality was 1.5% (n = 3). Mean follow-up was 77.5 ± 25.6 months. At 8 years postoperatively, overall survival was 88.6% ± 3.1%, freedom from reintervention was 95.3% ± 1.7%, and freedom from late recurrent moderate mitral regurgitation (>2+) was 90.2% ± 3.1% Provided that the fundamental principles of mitral valve reconstruction are respected, the surgical techniques are highly reproducible with good long-term results, similar to those published during the pioneering phase of this surgery. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Echocardiographic predictors of survival in dogs with myxomatous mitral valve disease.

PubMed

Sargent, Julia; Muzzi, Ruthnea; Mukherjee, Rajat; Somarathne, Sharlene; Schranz, Katherine; Stephenson, Hannah; Connolly, David; Brodbelt, David; Fuentes, Virginia Luis

2015-03-01

To evaluate vena contracta and other echocardiographic measures of myxomatous mitral valve disease (MMVD) severity in a multivariable analysis of survival in dogs. 70 dogs diagnosed with MMVD from stored echocardiographic images that met study inclusion criteria. Left heart dimensions were measured as well as mitral regurgitant jet area/left atrial area (JAR), early mitral filling velocity (Evel), extent of mitral valve prolapse in right and left views (ProlR, ProlL), Prol indexed to aortic diameter (ProlR:Ao, ProlL:Ao), presence of a flail leaflet (FlailR, FlailL), and mitral regurgitation vena contracta diameter (VCR, VCL) indexed to aortic diameter (VCR:Ao, VCL:Ao). Follow-up from referring veterinarians was obtained by questionnaire or telephone to determine survival times. Inter- and intra-observer agreement was evaluated with Bland-Altman plots and weighted Kappa analysis. Survival was analyzed using Kaplan-Meier curves, logrank tests and Cox's proportional hazards. Logrank analysis showed VCL:Ao, VCR:Ao, FlailL, ProlR:Ao, ProlL:Ao, left ventricular internal dimension in diastole indexed to aortic diameter (LVIDD:Ao) >2.87, left atrium to aorta ratio (LA/Ao) >1.6, and Evel >1.4 m/s were predictors of cardiac mortality. In a multivariable analysis, the independent predictors of cardiac mortality were Evel >1.4 m/s [hazard ratio (HR) 5.0, 95% confidence interval (CI) 2.5-10.3], FlailL (HR 3.1, 95% CI 1.3-7.9), and ProlR:Ao (HR 2.8, 95% CI 1.3-6.3). Echocardiographic measures of mitral regurgitation severity and mitral valve pathology provide valuable prognostic information independent of chamber enlargement in dogs with MMVD. Copyright © 2014 Elsevier B.V. All rights reserved.

Mechanisms and Predictors of Mitral Regurgitation after High-Risk Myocardial Infarction

PubMed Central

Meris, Alessandra; Amigoni, Maria; Verma, Anil; Thune, Jens Jakob; Køber, Lars; Velazquez, Eric; McMurray, John J. V.; Pfeffer, Marc A.; Califf, Robert; Levine, Robert A.; Solomon, Scott D.

2012-01-01

Background Mitral regurgitation (MR) has been associated with adverse outcomes after myocardial infarction (MI). Without structural valve disease, functional MR has been related to left ventricular (LV) remodeling and geometric deformation of the mitral apparatus. The aims of this study were to elucidate the mechanistic components of MR after high-risk MI and to identify predictors of MR progression during follow-up. Methods The Valsartan in Acute Myocardial Infarction Echo substudy prospectively enrolled 610 patients with LV dysfunction, heart failure, or both after MI. MR at baseline, 1 month, and 20 months was quantified by mapping jet expansion in the left atrium in 341 patients with good-quality echocardiograms. Indices of LV remodeling, left atrial size, and diastolic function and parameters of mitral valve deformation, including tenting area, coaptation depth, anterior leaflet concavity, annular diameters, and contractility, were assessed and related to baseline MR. The progression of MR was further analyzed, and predictors of worsening among the baseline characteristics were identified. Results Tenting area, coaptation depth, annular dilatation, and left atrial size were all associated with the degree of baseline MR. Tenting area was the only significant and independent predictor of worsening MR; a tenting area of 4 cm2 was a useful cutoff to identify worsening of MR after MI and moderate to severe MR after 20 months. Conclusions Increased mitral tenting and larger mitral annular area are determinants of MR degree at baseline, and tenting area is an independent predictor of progression of MR after MI. Although LV remodeling itself contributes to ischemic MR, this influence is directly dependent on alterations in mitral geometry. PMID:22305962

Simple repair approach for mitral regurgitation in Barlow disease.

PubMed

Ben Zekry, Sagit; Spiegelstein, Dan; Sternik, Leonid; Lev, Innon; Kogan, Alexander; Kuperstein, Rafael; Raanani, Ehud

2015-11-01

Mitral valve repair for myxomatous Barlow disease is a challenging procedure requiring complex surgery with less than optimal results. The use of ring-only repair has been previously reported but never analyzed or followed-up. We investigated this simple valve repair approach for patients with Barlow disease and multisegment involvement causing mainly central jet. Of 572 patients who underwent mitral valve repair for mitral regurgitation at our medical center, 24 with Barlow disease (aged 47 ± 14 years; 46% male) underwent ring-only repair. Patients were characterized by severely enlarged mitral valve annulus, multisegment prolapse involving both leaflets, and demonstrated mainly a central wide regurgitant jet. Surgical technique included only the implantation of a large mitral annuloplasty ring. Early and late outcome results were compared with those of the remaining patients who underwent conventional mitral valve repair for degenerative disease (controls). All ring-only patients presented with moderate-severe/severe mitral regurgitation (vena contracta, 0.6 ± 0.1 cm; regurgitation volume, 52 ± 17 mL), with mainly a central jet and almost preserved ejection fraction (59% ± 6%). Cardiopulmonary bypass and crossclamp times were significantly shorter compared with controls (P < .0001). At follow-up (ring-only, 38 ± 36 months and controls, 36 ± 29 months), there were no late deaths in the ring-only group compared with 19 (4%) in the controls. Late follow-up revealed New York Heart Association functional class I or II in 95% of ring-only patients, compared with 90% of controls. Freedom from recurrent moderate or severe mitral regurgitation was 100% and 89% in the ring-only and control groups, respectively. Mitral annuloplasty for Barlow disease patients with multisegment involvement and mainly central regurgitant jet is both simple and reproducible with excellent late outcomes. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Clinical outcomes and economic impact of transcatheter mitral leaflet repair in heart failure patients.

PubMed

Asgar, Anita W; Khairy, Paul; Guertin, Marie-Claude; Cournoyer, Daniel; Ducharme, Anique; Bonan, Raoul; Basmadjian, Arsene; Tardif, Jean-Claude; Cohen, David J

2017-01-01

Mitral regurgitation (MR) is a common valvular heart disorder requiring intervention once it becomes severe. Transcatheter mitral repair with the MitraClip device is a safe and effective therapy for selected patients denied surgery. The authors sought to evaluate the clinical outcomes and economic impact of this therapy compared to medical management in heart-failure patients with symptomatic mitral regurgitation. The study was comprised of two phases; an observational study of patients with heart failure and mitral regurgitation treated with either medical therapy or the MitraClip, and an economic model. Results of the observational study were used to estimate parameters for the decision model, which estimated costs, and benefits in a hypothetical cohort of patients with heart failure and moderate-to-severe mitral regurgitation treated with either standard medical therapy or MitraClip. The cohort of patients treated with the MitraClip was propensity matched to a population of heart failure patients, and their outcomes compared. At a mean follow-up of 22 months, all-cause mortality was 21% in the MitraClip cohort and 42% in the medical management cohort (p = .007). The decision model demonstrated that MitraClip increased life expectancy from 1.87-3.60 years and quality-adjusted life years (QALY) from 1.13-2.76 years. The incremental cost was $52,500 Canadian dollars, corresponding to an incremental cost-effectiveness ratio (ICER) of $32,300.00 per QALY gained. Results were sensitive to the survival benefit. In heart failure patients with symptomatic moderate-severe mitral regurgitation, therapy with the MitraClip is associated with superior survival and is cost-effective compared to medical therapy.

Geometric differences of the mitral apparatus between ischemic and dilated cardiomyopathy with significant mitral regurgitation: real-time three-dimensional echocardiography study

NASA Technical Reports Server (NTRS)

Kwan, Jun; Shiota, Takahiro; Agler, Deborah A.; Popovic, Zoran B.; Qin, Jian Xin; Gillinov, Marc A.; Stewart, William J.; Cosgrove, Delos M.; McCarthy, Patrick M.; Thomas, James D.

2003-01-01

BACKGROUND: This study was conducted to elucidate the geometric differences of the mitral apparatus in patients with significant mitral regurgitation caused by ischemic cardiomyopathy (ICM-MR) and by idiopathic dilated cardiomyopathy (DCM-MR) by use of real-time 3D echocardiography (RT3DE). METHODS AND RESULTS: Twenty-six patients with ICM-MR caused by posterior infarction, 18 patients with DCM-MR, and 8 control subjects were studied. With the 3D software, commissure-commissure plane and 3 perpendicular anteroposterior (AP) planes were generated for imaging the medial, central, and lateral sides of the mitral valve (MV) during mid systole. In 3 AP planes, the angles between the annular plane and each leaflet (anterior, Aalpha; posterior, Palpha) were measured. In ICM-MR, Aalpha measured in the medial and central planes was significantly larger than that in the lateral plane (39+/-5 degrees, 34+/-6 degrees, and 27+/-5 degrees, respectively; P<0.01), whereas Palpha showed no significant difference in any of the 3 AP planes (61+/-7 degrees, 57+/-7 degrees, and 56+/-7 degrees, P>0.05). In DCM-MR, both Aalpha (38+/-8 degrees, 37+/-9 degrees, and 36+/-7 degrees, P>0.05) and Palpha (59+/-6 degrees, 58+/-5 degrees, and 57+/-6 degrees, P>0.05) revealed no significant differences in the 3 planes. CONCLUSIONS: The pattern of MV deformation from the medial to the lateral side was asymmetrical in ICM-MR, whereas it was symmetrical in DCM-MR. RT3DE is a helpful tool for differentiating the geometry of the mitral apparatus between these 2 different types of functional mitral regurgitation.

Patient-specific indirectly 3D printed mitral valves for pre-operative surgical modelling

NASA Astrophysics Data System (ADS)

Ginty, Olivia; Moore, John; Xia, Wenyao; Bainbridge, Dan; Peters, Terry

2017-03-01

Significant mitral valve regurgitation affects over 2% of the population. Over the past few decades, mitral valve (MV) repair has become the preferred treatment option, producing better patient outcomes than MV replacement, but requiring more expertise. Recently, 3D printing has been used to assist surgeons in planning optimal treatments for complex surgery, thus increasing the experience of surgeons and the success of MV repairs. However, while commercially available 3D printers are capable of printing soft, tissue-like material, they cannot replicate the demanding combination of echogenicity, physical flexibility and strength of the mitral valve. In this work, we propose the use of trans-esophageal echocardiography (TEE) 3D image data and inexpensive 3D printing technology to create patient specific mitral valve models. Patient specific 3D TEE images were segmented and used to generate a profile of the mitral valve leaflets. This profile was 3D printed and integrated into a mold to generate a silicone valve model that was placed in a dynamic heart phantom. Our primary goal is to use silicone models to assess different repair options prior to surgery, in the hope of optimizing patient outcomes. As a corollary, a database of patient specific models can then be used as a trainer for new surgeons, using a beating heart simulator to assess success. The current work reports preliminary results, quantifying basic morphological properties. The models were assessed using 3D TEE images, as well as 2D and 3D Doppler images for comparison to the original patient TEE data.

Development of mitral stenosis after single MitraClip insertion for severe mitral regurgitation.

PubMed

Cockburn, James; Fragkou, Paraskevi; Hildick-Smith, David

2014-02-01

We report the first case of mitral stenosis following Mitra-Clip insertion in a patient with symptomatic NYHA IV heart failure, secondary to severe mitral regurgitation (MR). A 79-year-old female with a history of prior aortic valve replacement underwent percutaneous mitral valve (MV) repair. A single clip was advanced coaxially down onto the MV under TOE guidance, with the anterior and posterior leaflets clipped together between A2 and P2. TOE confirmed a significant reduction in MR (grade 4 to grade 1). Despite initial symptomatic relief, she represented 3 months later with similar symptoms. Repeat TOE confirmed a well positioned Mitra-Clip with mild residual MR. However, the possibility of significant mitral stenosis was raised due to the presence of significant turbulence through the bi-orifice valve, with a peak gradient of 25 mm Hg. In addition there was evidence of severe functional tricuspid valve (TV) regurgitation with elevated pulmonary artery pressures (PAP 90 mm Hg), confirmed on subsequent right heart catheterization. After repeated heart team discussions and a failure of optimal medical therapy, and despite a logistic EuroScore of 35.5, minimally invasive surgical replacement of the MV and simultaneous TV repair was undertaken via a right thoracotomy. Despite procedural success and initial good postoperative response, the patient died subsequently from a combination of hospital-acquired pneumonia and significant gastrointestinal bleeding (post operative day 35). Mitra-Clip is a promising novel approach to MV repair. The establishment of further clinical and echocardiographic based selection criteria will help identify the correct patients for this treatment. Copyright © 2013 Wiley Periodicals, Inc.

Fluid-Structure Interaction Analysis of Papillary Muscle Forces Using a Comprehensive Mitral Valve Model with 3D Chordal Structure.

PubMed

Toma, Milan; Jensen, Morten Ø; Einstein, Daniel R; Yoganathan, Ajit P; Cochran, Richard P; Kunzelman, Karyn S

2016-04-01

Numerical models of native heart valves are being used to study valve biomechanics to aid design and development of repair procedures and replacement devices. These models have evolved from simple two-dimensional approximations to complex three-dimensional, fully coupled fluid-structure interaction (FSI) systems. Such simulations are useful for predicting the mechanical and hemodynamic loading on implanted valve devices. A current challenge for improving the accuracy of these predictions is choosing and implementing modeling boundary conditions. In order to address this challenge, we are utilizing an advanced in vitro system to validate FSI conditions for the mitral valve system. Explanted ovine mitral valves were mounted in an in vitro setup, and structural data for the mitral valve was acquired with [Formula: see text]CT. Experimental data from the in vitro ovine mitral valve system were used to validate the computational model. As the valve closes, the hemodynamic data, high speed leaflet dynamics, and force vectors from the in vitro system were compared to the results of the FSI simulation computational model. The total force of 2.6 N per papillary muscle is matched by the computational model. In vitro and in vivo force measurements enable validating and adjusting material parameters to improve the accuracy of computational models. The simulations can then be used to answer questions that are otherwise not possible to investigate experimentally. This work is important to maximize the validity of computational models of not just the mitral valve, but any biomechanical aspect using computational simulation in designing medical devices.

Mitral Annular Calcification as a Possible Nidus for Endocarditis: A Descriptive Series with Bacteriological Differences Noted.

PubMed

Pressman, Gregg S; Rodriguez-Ziccardi, Mary; Gartman, Charles H; Obasare, Edinrin; Melendres, Emmanuel; Arguello, Vivian; Bhalla, Vikas

2017-06-01

Mitral annular calcification (MAC) is a chronic inflammatory process with similarities to atherosclerosis. It is common in elderly patients and those with renal dysfunction. Although MAC is associated with cardiovascular morbidity, its relationship to infective endocarditis is unclear. The aim of this study was to test the hypothesis that MAC would be prevalent in patients with mitral valve vegetations and that vegetations would frequently occur on calcific nodules. A secondary aim was to look for possible bacteriological differences between vegetations attached to the calcified annulus versus leaflet vegetations. We retrospectively reviewed all echocardiographic studies of patients with native mitral valve vegetations from January 2007 to August 2015 (N = 56). We searched for (1) presence of MAC, (2) location of MAC, and (3) vegetation location (on calcium deposits or distant). MAC was defined as focal echo brightness in a nodular or band-like pattern. The modified Duke criteria were used to confirm the diagnosis of infective endocarditis. Transthoracic, transesophageal, and three-dimensional echocardiograms (when available) at the time of infection were evaluated by a single reader. Twenty-eight subjects were infected with Staphylococcus aureus, 17 with a streptococcal species, and five with other organisms; blood cultures were sterile in 6. Thirty-four (61%) subjects had some degree of MAC, while 22 (39%) had none. Among those with MAC, the vegetation was located on the calcium deposits in 22 (65%), versus in 12 (35%) where it was not. Among all 56 subjects, when S. aureus was the infecting organism it was present on MAC in 16/28 (57%) versus 6/28 (21%; P = .01) for other bacterial species. By contrast, streptococcal infections more frequently involved the leaflets (16/17 [94%]) versus nonstreptococcal infections (18/39 [46%]; P = .0008). MAC may act as a nidus for infection especially with S. aureus. Differences in mechanism of attachment between S. aureus and streptococci may account for the observed difference in frequency of attachment of vegetations to MAC. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

An experimental-computational analysis of MHV cavitation: effects of leaflet squeezing and rebound.

PubMed

Makhijani, V B; Yang, H Q; Singhal, A K; Hwang, N H

1994-04-01

A combined experimental-computational study was performed to investigate the flow mechanics which could cause cavitation during the squeezing and rebounding phases of valve closure in the 29 mm mitral bileaflet Edwards-Duromedics (ED) mechanical heart valve (MHV). Leaflet closing motion was measured in vitro, and input into a computational fluid mechanics software package, CFD-ACE, to compute flow velocities and pressures in the small gap space between the occluder tip and valve housing. The possibility of cavitation inception was predicted when fluid pressures dropped below the saturated vapor pressure for blood plasma. The computational analysis indicated that cavitation is more likely to be induced during valve rebound rather than the squeezing phase of valve closure in the 29 mm ED-MHV. Also, there is a higher probability of cavitation at lower values of the gap width at the point of impact between the leaflet tip and housing. These predictions of cavitation inception are not likely to be significantly influenced by the water-hammer pressure gradient that develops during valve closure.

Postural Tachycardia Syndrome and Vasovagal Syncope: A Hidden Case of Obstructive Cardiomyopathy without Severe Septal Hypertrophy

PubMed Central

Ho, Natalie; Shields, Robert W.; Cremer, Paul; Rodriguez, L. Leonardo

2018-01-01

A 36-year-old female with symptoms of orthostatic intolerance and syncope was diagnosed with vasovagal syncope on a tilt table test and with postural tachycardia syndrome (POTS) after a repeat tilt table test. However, an echocardiogram at our institution revealed obstructive cardiomyopathy without severe septal hypertrophy, with a striking increase in left ventricular outflow tract gradient from 7 mmHg at rest to 75 mmHg during Valsalva, with a septal thickness of only 1.3 cm. Cardiac MRI showed an apically displaced multiheaded posteromedial papillary muscle with suggestion of aberrant chordal attachments to the anterior mitral leaflet contributing to systolic anterior motion of the mitral valve. She underwent surgery with reorientation of the posterior medial papillary muscle head, resection of the tethering secondary chordae to the A1 segment of the mitral valve, chordal shortening and tacking of the chordae to the A1 and A2 segments of the mitral valve, and gentle septal myectomy. After surgery, she had significant improvement in her prior symptoms. To our knowledge, this is the first reported case of obstructive cardiomyopathy without severe septal hypertrophy with abnormalities in papillary muscle and chordal attachment, in a patient diagnosed with vasovagal syncope and POTS. PMID:29850268

Postural Tachycardia Syndrome and Vasovagal Syncope: A Hidden Case of Obstructive Cardiomyopathy without Severe Septal Hypertrophy.

PubMed

Mayuga, Kenneth A; Ho, Natalie; Shields, Robert W; Cremer, Paul; Rodriguez, L Leonardo

2018-01-01

A 36-year-old female with symptoms of orthostatic intolerance and syncope was diagnosed with vasovagal syncope on a tilt table test and with postural tachycardia syndrome (POTS) after a repeat tilt table test. However, an echocardiogram at our institution revealed obstructive cardiomyopathy without severe septal hypertrophy, with a striking increase in left ventricular outflow tract gradient from 7 mmHg at rest to 75 mmHg during Valsalva, with a septal thickness of only 1.3 cm. Cardiac MRI showed an apically displaced multiheaded posteromedial papillary muscle with suggestion of aberrant chordal attachments to the anterior mitral leaflet contributing to systolic anterior motion of the mitral valve. She underwent surgery with reorientation of the posterior medial papillary muscle head, resection of the tethering secondary chordae to the A1 segment of the mitral valve, chordal shortening and tacking of the chordae to the A1 and A2 segments of the mitral valve, and gentle septal myectomy. After surgery, she had significant improvement in her prior symptoms. To our knowledge, this is the first reported case of obstructive cardiomyopathy without severe septal hypertrophy with abnormalities in papillary muscle and chordal attachment, in a patient diagnosed with vasovagal syncope and POTS.

Initial Experience and Early Results of Mitral Valve Repair with Cardiocel Pericardial Patch.

PubMed

Tomšič, Anton; Bissessar, Daniella D; van Brakel, Thomas J; Marsan, Nina Ajmone; Klautz, Robert J M; Palmen, Meindert

2018-06-07

To assess the performance of a tissue engineering process-treated bovine pericardium patch (CardioCel) in the setting of reconstructive mitral valve surgery. Between 3/2014 and 4/2016, 30 patients (57.2±14.3 years, 27% female) underwent mitral valve leaflet repair with a CardioCel patch. Perioperative mortality was 7% (2 patients, non-graft-related). In 28 remaining patients, pre-discharge echocardiography demonstrated good repaired valve function. At a mean follow-up of 1.7±0.9 years, 3 additional deaths occurred (2 due to infective endocarditis, 1 non-cardiac related). On follow-up echocardiography [follow-up time 1.7±0.8 years, available for 26/28 (93%) hospital survivors], recurrent regurgitation was seen in 2 patients (both infective endocarditis) and 1 underwent reoperation (no infection at the level of patch repair was observed). In the remaining patients, the most recent echocardiogram demonstrated ≤mild regurgitation and stable gradients. The thickness and echodensity of the implanted patch on follow-up echocardiograms were comparable with postoperative echocardiograms. Initial results of the CardioCel patch in mitral valve repair surgery are satisfactory. The resistance to infection and late degeneration will need to be assessed in the future. Copyright © 2018. Published by Elsevier Inc.

Ex Vivo Methods for Informing Computational Models of the Mitral Valve

PubMed Central

Bloodworth, Charles H.; Pierce, Eric L.; Easley, Thomas F.; Drach, Andrew; Khalighi, Amir H.; Toma, Milan; Jensen, Morten O.; Sacks, Michael S.; Yoganathan, Ajit P.

2016-01-01

Computational modeling of the mitral valve (MV) has potential applications for determining optimal MV repair techniques and risk of recurrent mitral regurgitation. Two key concerns for informing these models are (1) sensitivity of model performance to the accuracy of the input geometry, and, (2) acquisition of comprehensive data sets against which the simulation can be validated across clinically relevant geometries. Addressing the first concern, ex vivo micro-computed tomography (microCT) was used to image MVs at high resolution (~40 micron voxel size). Because MVs distorted substantially during static imaging, glutaraldehyde fixation was used prior to microCT. After fixation, MV leaflet distortions were significantly smaller (p<0.005), and detail of the chordal tree was appreciably greater. Addressing the second concern, a left heart simulator was designed to reproduce MV geometric perturbations seen in vivo in functional mitral regurgitation and after subsequent repair, and maintain compatibility with microCT. By permuting individual excised ovine MVs (n=5) through each state (healthy, diseased and repaired), and imaging with microCT in each state, a comprehensive data set was produced. Using this data set, work is ongoing to construct and validate high-fidelity MV biomechanical models. These models will seek to link MV function across clinically relevant states. PMID:27699507

[Aortic stenosis and mitral regurgitation complicated by hemolytic anemia and positive Direct Coombs test: a case report].

PubMed

Tamura, Shinjiro; Kitaoka, Hiroaki; Yamasaki, Naohito; Okawa, Makoto; Kubo, Toru; Matsumura, Yoshihisa; Furuno, Takashi; Takata, Jun; Nishinaga, Masanori; Sasaguri, Shiro; Doi, Yoshinori

2005-09-01

A 83-year-old man was admitted because of heart failure due to severe aortic stenosis and mitral regurgitation secondary to chordal rupture of the anterior leaflet. Mild anemia and elevated serum lactate dehydrogenase were present with reticulocytosis and haptoglobinemia. Direct Coombs test was positive. Coexistence of autoimmune hemolytic anemia was identified, but the main cause of his hemolysis was thought to be mechanical hemolysis due to stenotic valve and/or ruptured chordae because of the presence of red cell fragmentation. The patient successfully underwent double valve replacement. Improvement of anemia was coupled with reduction of the serum lactate dehydrogenase level. Valvular shear stress on the red cells and reduction of red cell deformability secondary to autoimmune hemolytic anemia were thought to be responsible for his hemolysis.

Assessment of deformation of the mitral valve complex during off-pump coronary artery bypass surgery using three-dimensional echocardiography in a porcine model.

PubMed

Igarashi, Takashi; Iwai-Takano, Masumi; Wakamatsu, Hiroki; Haruta, Mineyuki; Omata, Sadao; Yokoyama, Hitoshi

2018-01-01

This study aimed to assess the deformation of the mitral valve complex during the displacement of the beating heart by using three-dimensional echocardiography in a porcine off-pump coronary artery bypass grafting (OPCAB) model. In nine healthy swine, we positioned the beating heart as an OPCAB model, i.e. control, left anterior descending artery (LAD), right coronary artery (RCA), and left circumflex artery (LCX) positions. In each position, three-dimensional echocardiography was performed to assess the mitral valve complex with hemodynamic parameters. We analyzed the deformation of the mitral valve and the three-dimensional coordinates of the papillary muscles. There was a significant increase in maximum tenting length and tenting volume (control 0.70±0.30, LAD 0.65±0.27, RCA 0.79±0.23, LCX 0.95±0.34cm 3 , p<0.05) in the LCX position compared with the other positions. The posterior papillary muscle (PPM) angle had a significant relationship with the tenting volume (r=-0.643, p<0.001). The PPM was displaced to the medial side in the LAD and LCX positions (p<0.01). The prime cause of the deformation of the mitral leaflets is suggested to be the displacement of the PPM associated with the change in geometry of the left ventricle in a porcine model. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Anatomical considerations of percutaneous transvenous mitral annuloplasty: a novel procedure for treatment of functional mitral regurgitation.

PubMed

Mehra, Lalit; Raheja, Shashi; Agarwal, Sneh; Rani, Yashoda; Kaur, Kulwinder; Tuli, Anita

2016-03-01

Percutaneous transvenous mitral annuloplasty (PTMA) has evolved as a latest procedure for the treatment of functional mitral regurgitation. It reduces mitral valve annulus (MVA) size and increases valve leaflet coaptation via compression of coronary sinus (CS). Anatomical considerations for this procedure were elucidated in the present study. In 40 formalin fixed adult cadaveric human hearts, relation of the venous channel formed by CS and great cardiac vein (GCV) to MVA and the adjacent arteries was described, at 6 points by making longitudinal sections perpendicular to the plane of MVA, numbered 1-6 starting from CS ostium. CS/GCV formed a semicircular venous channel on the atrial side of MVA. Based on the distance of CS/GCV from MVA, two patterns were identified. In 37 hearts, the venous channel at point 2 was widely separated from the MVA compared to the two ends and in three hearts a nonconsistent pattern was observed. GCV crossed circumflex artery superficially. GCV or CS crossed the left marginal artery and ventricular branches of circumflex artery superficially in 17 and 23 hearts, respectively. As the venous channel was related more to the left atrial wall, PTMA devices probably exert an indirect traction on MVA. The arteries crossing deep to the venous channel may be compressed by PTMA device leading to myocardial ischemia. Knowledge of the spatial relations of MVA and a preoperative and postoperative angiogram may help to reduce such complications during PTMA.

Brucella endocarditis: an occupational hazard!

PubMed

Agarwal, Sanjeev Kumar; Rajani, Ali Raza; Hussain, Kosar; Dande, Mangesh Manoharrao

2013-04-22

A young man presented with a 2-month history of fever and malaise. Cardiac auscultation revealed the presence of a diastolic murmur. Subsequently, a cardiac echocardiogram was done, which showed a large vegetation adherent to an anterior mitral leaflet. The blood culture was positive for Brucella species. The patient was given antibiotic therapy for brucellosis and referred for surgery. Brucella endocarditis is one of the rarest, yet most notorious complications of this infection. This condition requires a high degree of clinical suspicion in order to facilitate prompt diagnosis and treatment.

TexMi: Development of Tissue-Engineered Textile-Reinforced Mitral Valve Prosthesis

PubMed Central

Moreira, Ricardo; Gesche, Valentine N.; Hurtado-Aguilar, Luis G.; Schmitz-Rode, Thomas; Frese, Julia

2014-01-01

Mitral valve regurgitation together with aortic stenosis is the most common valvular heart disease in Europe and North America. Mechanical and biological prostheses available for mitral valve replacement have significant limitations such as the need of a long-term anticoagulation therapy and failure by calcifications. Both types are unable to remodel, self-repair, and adapt to the changing hemodynamic conditions. Moreover, they are mostly designed for the aortic position and do not reproduce the native annular-ventricular continuity, resulting in suboptimal hemodynamics, limited durability, and gradually decreasing ventricular pumping efficiency. A tissue-engineered heart valve specifically designed for the mitral position has the potential to overcome the limitations of the commercially available substitutes. For this purpose, we developed the TexMi, a living textile-reinforced mitral valve, which recapitulates the key elements of the native one: annulus, asymmetric leaflets (anterior and posterior), and chordae tendineae to maintain the native annular-ventricular continuity. The tissue-engineered valve is based on a composite scaffold consisting of the fibrin gel as a cell carrier and a textile tubular structure with the twofold task of defining the gross three-dimensional (3D) geometry of the valve and conferring mechanical stability. The TexMi valves were molded with ovine umbilical vein cells and stimulated under dynamic conditions for 21 days in a custom-made bioreactor. Histological and immunohistological stainings showed remarkable tissue development with abundant aligned collagen fibers and elastin deposition. No cell-mediated tissue contraction occurred. This study presents the proof-of-principle for the realization of a tissue-engineered mitral valve with a simple and reliable injection molding process readily adaptable to the patient's anatomy and pathological situation by producing a patient-specific rapid prototyped mold. PMID:24665896

Predictors of ischaemic mitral regurgitation recurrence in patients undergoing combined surgery: additional value of cardiovascular magnetic resonance imaging.

PubMed

Glaveckaite, Sigita; Uzdavinyte-Gateliene, Egle; Petrulioniene, Zaneta; Palionis, Darius; Valeviciene, Nomeda; Kalinauskas, Gintaras; Serpytis, Pranas; Laucevicius, Aleksandras

2018-03-09

We aimed to evaluate (i) the effectiveness of combined surgery (coronary artery bypass grafting with restrictive mitral valve annuloplasty) and (ii) the late gadolinium enhancement cardiovascular magnetic resonance-based predictors of ischaemic mitral regurgitation (IMR) recurrence. The prospective analysis included 40 patients with multivessel coronary artery disease, IMR >II° and left ventricular (LV) dysfunction undergoing combined surgery. The degree of IMR and LV parameters were assessed preoperatively by transthoracic echocardiography, 3D transoesophageal echocardiography and cardiovascular magnetic resonance and postoperatively by transthoracic echocardiography. The effective mitral valve repair group (n = 30) was defined as having recurrent ischaemic mitral regurgitation (RIMR) ≤II° at the end of follow-up (25 ± 11 months). The surgery was effective: freedom from RIMR >II° at 1 and 2 years after surgery was 80% and 75%, respectively. Using multivariable logistic regression, 2 independent predictors of RIMR >II° were identified: ≥3 non-viable LV segments (odds ratio 22, P = 0.027) and ≥1 non-viable segment in the LV posterior wall (odds ratio 11, P = 0.026). Using classification trees, the best combinations of cardiovascular magnetic resonance-based and 3D transoesophageal echocardiography-based predictors for RIMR >II° were (i) posterior mitral valve leaflet angle >40° and LV end-systolic volume index >45 ml/m2 (sensitivity 100%, specificity 89%) and (ii) scar transmurality >68% in the inferior LV wall and EuroSCORE II >8 (sensitivity 83%, specificity 78%). There is a clear relationship between the amount of non-viable LV segments, especially in the LV posterior and inferior walls, and the recurrence of IMR after the combined surgery.

Red flag in the emergency department: fracture and primary failure of a prosthetic valve.

PubMed

Ozsarac, Murat; Karcioglu, Ozgur; Ayrik, Cuneyt; Bozkurt, Seyran; Turkcuer, Ibrahim; Gumrukcu, Serhat

2005-07-01

This case report concerns a patient with fracture and primary dysfunction of a prosthetic valve. A 40-year-old man presented to the Emergency Department with a chief complaint of breakthrough pleuritic back pain and shortness of breath. Past surgical history was significant only for an aortic valve replacement and mitral valve replacement performed 16 years prior. The transthoracic echocardiography raised suspicion of prosthesis malposition. The patient was taken to the operating room by cardiothoracic surgeons for valve replacement. Operative findings revealed that a prosthetic valve leaflet in the mitral position had broken off. Primary prosthetic valve failure should not be overlooked in the differential diagnosis of patients with valve replacement and a rapidly deteriorating clinical course. Emergency echocardiography is a guide to convenient diagnosis and management. Early surgical consultation and early reparative surgery might prevent unnecessary morbidity and mortality.

Preoperative left ventricular ejection fraction and left atrium reverse remodeling after mitral regurgitation surgery.

PubMed

Machado, Lucia R; Meneghelo, Zilda M; Le Bihan, David C S; Barretto, Rodrigo B M; Carvalho, Antonio C; Moises, Valdir A

2014-11-06

Left atrium enlargement has been associated with cardiac events in patients with mitral regurgitation (MR). Left atrium reverse remodeling (LARR) occur after surgical correction of MR, but the preoperative predictors of this phenomenon are not well known. It is therefore important to identify preoperative predictors for postoperative LARR. We enrolled 62 patients with chronic severe MR (prolapse or flail leaflet) who underwent successful mitral valve surgery (repair or replacement); all with pre- and postoperative echocardiography. LARR was defined as a reduction in left atrium volume index (LAVI) of ≥ 25%. Stepwise multiple regression analysis was used to identify independent predictors of LARR. LARR occurred in 46 patients (74.2%), with the mean LAVI decreasing from 85.5 mL/m2 to 49.7 mL/m2 (p <0.001). These patients had a smaller preoperative left ventricular systolic volume (p =0.022) and a higher left ventricular ejection fraction (LVEF) (p =0.034). LVEF was identified as the only preoperative variable significantly associated with LARR (odds ratio, 1.086; 95% confidence interval, 1.002-1.178). A LVEF cutoff value of 63.5% identified patients with LARR of ≥ 25% with a sensitivity of 71.7% and a specificity of 56.3%. LARR occurs frequently after mitral valve surgery and is associated with preoperative LVEF higher than 63.5%.

Endoscopic feature tracking for augmented-reality assisted prosthesis selection in mitral valve repair

NASA Astrophysics Data System (ADS)

Engelhardt, Sandy; Kolb, Silvio; De Simone, Raffaele; Karck, Matthias; Meinzer, Hans-Peter; Wolf, Ivo

2016-03-01

Mitral valve annuloplasty describes a surgical procedure where an artificial prosthesis is sutured onto the anatomical structure of the mitral annulus to re-establish the valve's functionality. Choosing an appropriate commercially available ring size and shape is a difficult decision the surgeon has to make intraoperatively according to his experience. In our augmented-reality framework, digitalized ring models are superimposed onto endoscopic image streams without using any additional hardware. To place the ring model on the proper position within the endoscopic image plane, a pose estimation is performed that depends on the localization of sutures placed by the surgeon around the leaflet origins and punctured through the stiffer structure of the annulus. In this work, the tissue penetration points are tracked by the real-time capable Lucas Kanade optical flow algorithm. The accuracy and robustness of this tracking algorithm is investigated with respect to the question whether outliers influence the subsequent pose estimation. Our results suggest that optical flow is very stable for a variety of different endoscopic scenes and tracking errors do not affect the position of the superimposed virtual objects in the scene, making this approach a viable candidate for annuloplasty augmented reality-enhanced decision support.

Anatomic, histologic, and two-dimensional-echocardiographic evaluation of mitral valve anatomy in dogs.

PubMed

Borgarelli, Michele; Tursi, Massimiliano; La Rosa, Giuseppe; Savarino, Paolo; Galloni, Marco

2011-09-01

To compare echocardiographic variables of dogs with postmortem anatomic measurements and histologic characteristics of the mitral valve (MV). 21 cardiologically normal dogs. The MV was measured echocardiographically by use of the right parasternal 5-chamber long-axis view. Dogs were euthanized, and anatomic measurements of the MV annulus (MVa) were performed at the level of the left circumflex coronary artery. Mitral valve leaflets (MVLs) and chordae tendineae were measured. Structure of the MVLs was histologically evaluated in 3 segments (proximal, middle, and distal). Echocardiographic measurements of MVL length did not differ significantly from anatomic measurements. A positive correlation was detected between body weight and MVa area. There was a negative correlation between MVa area and the percentage by which the MVL area exceeded the MVa area. Anterior MVLs had a significantly higher number of chordae tendineae than did posterior MVLs. Histologically, layering of MVLs was less preserved in the distal segment, whereas the muscular component and adipose tissue were significantly more diffuse in the proximal and middle segments. The MV in cardiologically normal dogs had wide anatomic variability. Anatomic measurements of MVL length were correlated with echocardiographic measurements.

Surgical revision after percutaneous mitral valve repair by edge-to-edge device: when the strategy fails in the highest risk surgical population.

PubMed

Alozie, Anthony; Westphal, Bernd; Kische, Stephan; Kaminski, Alexander; Paranskaya, Liliya; Bozdag-Turan, Ilkay; Ortak, Jasmin; Schubert, Jochen; Steinhoff, Gustav; Ince, Hüseyin

2014-07-01

Percutaneous edge-to-edge devices for non-surgical repair of mitral valve regurgitation are under clinical evaluation in high-risk patients deemed not suitable for conventional surgery. To address guidelines for initial therapy decision, we here report on 13 cases of surgery after failed percutaneous edge-to-edge mitral valve repair or attempted repair, and discuss methodology and prognostic factors for operative outcome in this high-risk situation. Thirteen patients referred to our cardiothoracic unit after failed percutaneous mitral valve repair or attempted repair using the edge-to-edge technique, were treated surgically for mitral valve failure between June 2010 and December 2012. Pathology of mitral valve before and after interventional mitral valve repair (especially prevalent mode of failure) was evaluated and classified for each individual patient by echocardiography and intraoperative direct visualization. Number of implanted edge-to-edge devices were identified. Preoperative risk scores were matched with intraoperative observations and histopathological findings of valve tissue. Postoperative morbidity and mortality were analysed with respect to mitral valve and patient-related data. Three of 10 patients were referred with severe mitral valve regurgitation/stenosis after initially successful percutaneous edge-to-edge therapy or attempted therapy. In 3 patients, ≥ 2 edge-to-edge devices were implanted leading to very tight edge-to-edge leaflet connection and fibrosis. All patients underwent successful surgical mitral valve replacement and concomitant complete cardiac surgery (CABG, aortic or tricuspid valve surgery, ASD closure and pulmonary vein isolation for atrial fibrillation). The likelihood of repair was reduced with respect to multiple edge-to-edge technology. One device could not be harvested surgically because of embolization. One patient died on the second postoperative day due to sepsis with multiple organ failure. The remaining 12 patients were discharged with excellent valve prosthesis function and followed up to 2 years post-surgery. The current long-term survival rate is 77%. Our series demonstrate that highest risk patients can survive mitral valve surgery after failed multiple edge-to-edge interventional mitral valve repair. As long-term results of the MitraClip therapy are pending, we recommend close meshed follow-up of patients treated with the MitraClip device, especially within the first year of the index procedure as delays in salvage management, interventional or surgical, when the index procedure fails may increase morbidity and mortality. © The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Mitral Regurgitation after Percutaneous Balloon Mitral Valvotomy in Patients with Rheumatic Mitral Stenosis: A Single-Center Study

PubMed Central

Aslanabadi, Naser; Toufan, Mehrnoush; Salehi, Rezvaneyeh; Alizadehasl, Azin; Ghaffari, Samad; Sohrabi, Bahram; Separham, Ahmad; Manafi, Ataolaah; Mehdizadeh, Mohammad Bagher; Habibzadeh, Afshin

2014-01-01

Abstract Background: Percutaneous balloon mitral valvotomy (BMV) is the gold standard treatment for rheumatic mitral stenosis (MS) in that it causes significant changes in mitral valve area (MVA) and improves leaflet mobility. Development of or increase in mitral regurgitation (MR) is common after BMV. This study evaluated MR severity and its changes after BMV in Iranian patients. Methods: We prospectively evaluated consecutive patients with severe rheumatic MS undergoing BMV using the Inoue balloon technique between February 2010 and January 2013 in Madani Heart Center, Tabriz, Iran. New York Heart Association (NYHA) functional class and echocardiographic and catheterization data, including MVA, mitral valve mean and peak gradient (MVPG and MVMG), left atrial (LA) pressure, pulmonary artery systolic pressure (PAPs), and MR severity before and after BMV, were evaluated. Results: Totally, 105 patients (80% female) at a mean age of 45.81 ± 13.37 years were enrolled. NYHA class was significantly improved after BMV: 55.2% of the patients were in NYHA functional class III before BMV compared to 36.2% after the procedure (p value < 0.001). MVA significantly increased (mean area = 0.64 ± 0.29 cm2 before BMV vs. 1.90 ± 0.22 cm2 after BMV; p value < 0.001) and PAPs, LA pressure, MVPG, and MVMG significantly decreased. MR severity did not change in 82 (78.1%) patients, but it increased in 18 (17.1%) and decreased in 5 (4.8%) patients. Patients with increased MR had a significantly higher calcification score (2.03 ± 0.53 vs.1.50 ± 0.51; p value < 0.001) and lower MVA before BMV (0.81 ± 0.23 vs.0.94 ± 0.18; p value = 0.010). There were no major complications. Conclusion: In our study, BMV had excellent immediate hemodynamic and clinical results inasmuch as MR severity increased only in some patients and, interestingly, decreased in a few. Our results, underscore BMV efficacy in severe MS. The echocardiographic calcification score was useful for identifying patients likely to have MR development or MR increase after BMV. PMID:25870627

Progression of degenerative mitral stenosis: insights from a cohort of 254 patients.

PubMed

Tyagi, Gaurav; Dang, Patricia; Pasca, Ioana; Patel, Reena; Pai, Ramdas G

2014-11-01

Degenerative mitral stenosis (DMS) is an increasingly common echocardiographic finding, yet the clinical and biological behavior and rate of progression of the condition are unknown. A total of 254 patients was identified from the authors' echocardiographic database with DMS, defined as severe mitral annular calcification with extension into the mitral leaflets resulting in transmitral flow acceleration with a mean diastolic gradient of >2 mmHg in the absence of commissural fusion. Each patient required paired echocardiograms to have been recorded at least three months apart. Clinical, biochemical and pharmacological data were collected from each patient and related to the annualized rate of increase in mean diastolic mitral gradient and stenosis severity on a scale of 0 to 3. The characteristics of the patients were as follows: mean age 71 +/- 15 years; female gender 73%; and left ventricular ejection fraction 66 +/- 13%. Diabetes was present in 50% of patients, renal insufficiency in 40%, and coronary artery disease in 50%. Over a follow up period of 2.6 +/- 2.2 years, the mean gradient was increased by 0.8 +/- 2.4 mmHg (range: 0-15 mmHg) per year, while the stenosis grade was increased by 0.18 +/- 0.5 (range: 0-3) per year. The rate of progression was faster in patients with lesser degrees of stenosis (p = 0.01) and low serum albumen levels (p = 0.04), and slower in those receiving beta-blockers (p = 0.01). Milder stenosis, diabetes mellitus and lack of beta-blocker use were independent predictors of faster DMS progression. DMS progression is highly variable, but generally slow; its progression is accelerated in the presence of diabetes mellitus, but is retarded by beta-blocker use. DMS may be an active biological process offering potentially modifiable targets for intervention.

Repair for Congenital Mitral Valve Stenosis.

PubMed

Delmo Walter, Eva Maria; Hetzer, Roland

2018-03-01

We report the techniques and long-term outcome of mitral valve (MV) repair to correct congenital mitral stenosis in children. Between 1986 and 2014, 137 children (mean age 4.1 ± 5.0, range 1 month-16.8 years) underwent repair of congenital mitral stenosis (CMS). In 48 patients, CMS is involved in Shone's anomaly. The typical congenital MS (type I) was seen in 56 patients. Hypoplastic MV (type II, n = 15) was associated with severe left ventricular outflow tract abnormalities and hypoplastic left ventricular cavity and muscle mass. Supravalvar ring (type III, n = 48) ranged from a thin membrane to a thick discrete fibrous ridge. Parachute MV (type IV, n = 10) have 2 leaflets and barely distinguishable commissures, but all chordae merged either into 1 major papillary muscle or asymmetric papillary muscles-1 dominant and the other minuscule. Hammock valve (type IV, n = 8) appeared dysplastic with shortened chordae directly inserted into the posterior left ventricular muscle mass. MV repair was performed using commissurotomy, chordal division, papillary muscle splitting and fenestration, and mitral ring resection, each applied according to the presenting morphology. During the 28-year follow-up period, 23 patients underwent repeat MV repair and 3 underwent MV replacement after failed attempts at repeat repair. At 1 and 15 years postoperatively, freedom from reoperation was 89.3 ± 5.1% and 52.8 ± 11.8%, and cumulative survival rates were 92.3 ± 4.3% and 70.3 ± 8.9, respectively. Mortality unrelated to repair accounted for 9 (20%) deaths. Long-term functional outcome of MV repair in children with CMS is satisfactory. Repeat repair or replacement may be deemed necessary during the course of follow-up. Copyright © 2017 Elsevier Inc. All rights reserved.

Learning curve analysis of mitral valve repair using telemanipulative technology.

PubMed

Charland, Patrick J; Robbins, Tom; Rodriguez, Evilio; Nifong, Wiley L; Chitwood, Randolph W

2011-08-01

To determine if the time required to perform mitral valve repairs using telemanipulation technology decreases with experience and how that decrease is influenced by patient and procedure variables. A single-center retrospective review was conducted using perioperative and outcomes data collected contemporaneously on 458 mitral valve repair surgeries using telemanipulative technology. A regression model was constructed to assess learning with this technology and predict total robot time using multiple predictive variables. Statistical analysis was used to determine if models were significantly useful, to rule out correlation between predictor variables, and to identify terms that did not contribute to the prediction of total robot time. We found a statistically significant learning curve (P < .01). The institutional learning percentage∗ derived from total robot times† for the first 458 recorded cases of mitral valve repair using telemanipulative technology is 95% (R(2) = .40). More than one third of the variability in total robot time can be explained through our model using the following variables: type of repair (chordal procedures, ablations, and leaflet resections), band size, use of clips alone in band implantation, and the presence of a fellow at bedside (P < .01). Learning in mitral valve repair surgery using telemanipulative technology occurs at the East Carolina Heart Institute according to a logarithmic curve, with a learning percentage of 95%. From our regression output, we can make an approximate prediction of total robot time using an additive model. These metrics can be used by programs for benchmarking to manage the implementation of this new technology, as well as for capacity planning, scheduling, and capital budget analysis. Copyright © 2011 The American Association for Thoracic Surgery. All rights reserved.

First percutaneous Micra leadless pacemaker implantation and tricuspid valve repair with MitraClip NT for lead-associated severe tricuspid regurgitation.

PubMed

Tang, Gilbert H L; Kaple, Ryan; Cohen, Martin; Dutta, Tanya; Undemir, Cenap; Ahmad, Hasan; Poniros, Angelica; Bennett, Joanne; Feng, Cheng; Lansman, Steven

2017-02-03

Pacemaker lead-associated severe tricuspid regurgitation (TR) can lead to right heart failure and poor prognosis. Surgery in these patients carries significant morbidities. We describe a successful treatment of symptomatic severe TR by leadless pacemaker implantation followed by tricuspid valve (TV) repair with the MitraClip NT. A 71-year-old frail female with poor functional status, chronic atrial fibrillation and permanent pacemaker implantation in 2012 presented with symptomatic moderate-severe mitral regurgitation (MR) and severe TR with the pacemaker lead as the culprit. She was deemed extreme risk for double valve surgery and, because of her pacemaker dependency, the decision was to stage her interventions first with transcatheter mitral repair, then laser lead extraction and leadless pacemaker implantation to free the TV from tethering, then TV repair. An obstructive LAD lesion was identified and treated during mitral repair with the MitraClip NT. The Micra leadless pacemaker implantation and subsequent TV repair with the MitraClip NT were successful and the patient's MR improved to mild and TR to moderate, respectively. We report here a first successful transcatheter strategy to treat lead-associated severe TR by leadless pacemaker and MitraClip. Removing the pacemaker lead relieved leaflet tethering and improved the reparability of the TV.

Treatment of Heart Failure With Associated Functional Mitral Regurgitation Using the ARTO System: Initial Results of the First-in-Human MAVERIC Trial (Mitral Valve Repair Clinical Trial).

PubMed

Rogers, Jason H; Thomas, Martyn; Morice, Marie-Claude; Narbute, Inga; Zabunova, Milana; Hovasse, Thomas; Poupineau, Mathieu; Rudzitis, Ainars; Kamzola, Ginta; Zvaigzne, Ligita; Greene, Samantha; Erglis, Andrejs

2015-07-01

MAVERIC (Mitral Valve Repair Clinical Trial) reports the safety and efficacy of the ARTO system in patients with symptomatic heart failure and functional mitral regurgitation (FMR). The ARTO system percutaneously modifies the mitral annulus to improve leaflet coaptation in FMR. The MAVERIC trial is a prospective, nonrandomized first-in-human study. Key inclusion criteria were systolic heart failure New York Heart Association functional classes II to IV, FMR grade ≥2+, left ventricular (LV) ejection fraction ≤40%, LV end-diastolic diameter >50 mm and ≤75 mm. Exclusion criteria were clinical variables that precluded feasibility of the ARTO procedure. Primary outcomes were safety (30-day major adverse events) and efficacy (MR reduction, LV volumes, and functional status). Eleven patients received the ARTO system, and there were no procedural adverse events. From baseline to 30 days, there were meaningful improvements. Effective regurgitant orifice area decreased from 30.3 ± 11.1 mm(2) to 13.5 ± 7.1 mm(2) and regurgitant volumes from 45.4 ± 15.0 ml to 19.5 ± 10.2 ml. LV end-systolic volume index improved from 77.5 ± 24.3 ml/m(2) to 68.5 ± 21.4 ml/m(2), and LV end-diastolic volume index 118.7 ± 28.6 ml/m(2) to 103.9 ± 21.2 ml/m(2). Mitral annular anteroposterior diameter decreased from 45.0 ± 3.3 mm to 38.7 ± 3.0 mm. Functional status was 81.8% New York Heart Association functional class III/IV improving to 54.6% functional class I/II. At 30 days, there were 2 adverse events: 1 pericardial effusion requiring surgical drainage; and 1 asymptomatic device dislodgement. The ARTO system is a novel transcatheter device that can be used safely with meaningful efficacy in the treatment of FMR. (Mitral Valve Repair Clinical Trial [MAVERIC]; NCT02302872). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Loop technique.

PubMed

Seeburger, Joerg; Noack, Thilo; Winkfein, Michael; Ender, Joerg; Mohr, Friedrich Wilhelm

2010-01-01

The loop technique facilitates mitral valve repair for leaflet prolapse by implantation of Gore-Tex neo-chordae. The key feature of the technique is a premade bundle of four loops made out of one suture. The loops are available in different lengths ranging from 10 to 26 mm. After assessment of the ideal length of neo-chordae with a caliper the loops are then secured to the body of the papillary muscle over an additional felt pledget. In the following step, the free ends of the loops are distributed along the free margin of the prolapsing segment using one additional suture for each loop.

Extrinsic mechanism obstructing the opening of a prosthetic mitral valve: an unusual case of suture entrapment.

PubMed

Ozkan, Mehmet; Astarcioglu, Mehmet Ali; Karakoyun, Suleyman; Balkanay, Mehmet

2012-02-01

Obstruction to a prosthetic cardiac valve is a well-recognized complication of cardiac valve replacement. Malfunction of the mobile component of a prosthetic valve to open or close correctly may occur in consequence of intrinsic or extrinsic causes (thrombus, vegetation, entrapment of left ventricular myocardium, suture entanglement, and pannus formation) that may result prosthetic valve stenosis and/or insufficiency. In the case we report a 48-year-old female with valve dysfunction occurred early after surgery, as one valve leaflet was only able to partially open due to suture entrapment. © 2011, Wiley Periodicals, Inc.

Prevalence and clinical characteristics of degenerative mitral stenosis.

PubMed

Ukita, Yasuyuki; Yuda, Satoshi; Sugio, Hideaki; Yonezawa, Ayaka; Takayanagi, Yuka; Masuda-Yamamoto, Hitomi; Tanaka-Saito, Norie; Ohnishi, Hirofumi; Miura, Tetsuji

2016-09-01

Degenerative mitral stenosis (DMS) is found in the elderly population. However, there are a few reports regarding the prevalence rate of DMS and, its clinical characteristics. The aim of this study was to determine the relationship between age, gender, and the prevalence rate of DMS. Patients with DMS and rheumatic mitral stenosis (RMS) were searched retrospectively in consecutive patients who underwent echocardiography from January 2011 to December 2013 in a community hospital. DMS was defined as presence of both turbulent antegrade flow with a mean transmitral pressure gradient (PG) of ≥2mmHg and mitral annular calcification without restriction of leaflets tip motion. We identified 19 patients (17 female and 2 male) with DMS (0.22%) and 19 patients with RMS in 8683 patients. The prevalence rate of DMS significantly increased with aging, especially in patients >90 years old. There was no significant difference in the prevalence rates of RMS among the age groups. Patients with DMS were older (86±8 years vs. 73±10 years, p<0.01) and had higher rates of hypertension and aortic stenosis, larger left ventricular mass index, and mean PG of aortic valve, smaller aortic valve area, less degree of left atrial dilatation, and lower rate of atrial fibrillation, compared with those values in patients with RMS. DMS is rare (0.22%) and almost exclusively found in females in routine echocardiography. The prevalence of DMS increases with aging to 2.5% in patients >90 years of age, and DMS is often associated with aortic valve stenosis. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Thyrotoxic Valvulopathy: Case Report and Review of the Literature

PubMed Central

Pierre, Keniel; Gadde, Sushee; Omar, Bassam; Awan, G. Mustafa; Malozzi, Christopher

2017-01-01

We report a 42-year-old female who was admitted for abdominal pain, and also endorsed dyspnea, fatigue and chronic palpitations. Past medical history included asthma, patent ductus arteriosus repaired in childhood and ill-defined thyroid disease. Physical examination revealed blood pressure of 136/88 mm Hg and heart rate of 149 beats per minute. Cardiovascular exam revealed an irregularly irregular rhythm, and pulmonary exam revealed mild expiratory wheezing. Abdomen was tender. Electrocardiogram revealed atrial fibrillation with rapid ventricular response which responded to intravenous diltiazem. Labs revealed TSH of < 0.1 mU/L and free T4 of 2.82 ng/dL, a positive TSH-receptor and thyroid peroxidase antibodies suggesting Grave’s thyrotoxicosis. A transthoracic echocardiogram reported an ejection fraction of 55-60%, with mild to moderate mitral regurgitation (MR) and moderate to severe tricuspid regurgitation (TR) and dilated right heart chambers. Pulmonary artery systolic pressure was 52 mm Hg. Transesophageal echocardiogram revealed a myxomatous tricuspid valve with thickening and malcoaptation of the leaflets and moderate to severe TR, mild to moderate MR with mild thickening of the mitral valve leaflets. Abdominal ultrasound revealed wall thickening of the gall bladder concerning for acute cholecystitis. She underwent laparoscopic cholecystectomy and was discharged in stable condition on methimazole for her thyroid disease, and on oral diltiazem for rate control and anticoagulation for atrial fibrillation. Follow-up visit with her cardiologist few months later documented absence of cardiac symptoms, and no murmurs were reported on physical examination. This case underscores the importance of maintaining a high index of suspicion for hyperthyroidism when faced with significant newly diagnosed pulmonary hypertension and TR, as treatment of the thyroid abnormalities can reverse these cardiac findings. PMID:28725332

Cardiac findings in Quarter Horses with heritable equine regional dermal asthenia.

PubMed

Brinkman, Erin L; Weed, Benjamin C; Patnaik, Sourav S; Brazile, Bryn L; Centini, Ryan M; Wills, Robert W; Olivier, Bari; Sledge, Dodd G; Cooley, Jim; Liao, Jun; Rashmir-Raven, Ann M

2017-03-01

OBJECTIVE To compare biomechanical and histologic features of heart valves and echocardiographic findings between Quarter Horses with and without heritable equine regional dermal asthenia (HERDA). DESIGN Prospective case-control study. ANIMALS 41 Quarter Horses. PROCEDURES Ultimate tensile strength (UTS) of aortic and mitral valve leaflets was assessed by biomechanical testing in 5 horses with HERDA and 5 horses without HERDA (controls). Histologic evaluation of aortic and mitral valves was performed for 6 HERDA-affected and 3 control horses. Echocardiography was performed in 14 HERDA-affected and 11 control horses. Biomechanical data and echocardiographic variables of interest were compared between groups by statistical analyses, RESULTS Mean values for mean and maximum UTS of heart valves were significantly lower in HERDA-affected horses than in controls. Blood vessels were identified in aortic valve leaflets of HERDA-affected but not control horses. Most echocardiographic data did not differ between groups. When the statistical model for echocardiographic measures was controlled for body weight, mean and maximum height and width of the aorta at the valve annulus in short-axis images were significantly associated with HERDA status and were smaller for affected horses. CONCLUSIONS AND CLINICAL RELEVANCE Lower UTS of heart valves in HERDA-affected horses, compared with those of control horses, supported that tissues other than skin with high fibrillar collagen content are abnormal in horses with HERDA. Lack of significant differences in most echocardiographic variables between affected and control horses suggested that echocardiography may not be useful to detect a substantial loss of heart valve tensile strength. Further investigation is warranted to confirm these findings. Studies in horses with HERDA may provide insight into cardiac abnormalities in people with collagen disorders.

Evidence of subannular and left ventricular morphological differences in patients with bicuspid versus tricuspid aortic valve stenosis: magnetic resonance imaging-based analysis.

PubMed

Disha, Kushtrim; Dubslaff, Georg; Rouman, Mina; Fey, Beatrix; Borger, Michael A; Barker, Alex J; Kuntze, Thomas; Girdauskas, Evaldas

2017-03-01

Prospective analysis of left ventricular (LV) morphological/functional parameters in patients with bicuspid versus tricuspid aortic valve (TAV) stenosis undergoing aortic valve replacement (AVR) surgery. A total of 190 consecutive patients with BAV ( n  = 154) and TAV stenosis ( n  = 36) (mean age 61 ± 8 years, 65% male) underwent AVR ± concomitant aortic surgery from January 2012 through May 2015. All patients underwent preoperative cardiac magnetic resonance imaging in order to evaluate: (i) left ventricular outflow tract (LVOT) dimensions, (ii) length of anterior mitral leaflet (AML), (iii) end-systolic and end-diastolic LV wall thickness, (iv) LV area, (v) LV end-systolic and end-diastolic diameters (LVESD, LVEDD), (vi) LV end-diastolic and end-systolic volumes (LVEDV, LVESV) and (vii) maximal diameter of aortic root. These parameters were compared between the two study groups. The LVOT diameter was significantly larger in BAV patients (21.7 ± 3 mm in BAV vs 18.9 ± 3 mm in TAV, P  < 0.001). Moreover, BAV patients had significantly longer AML (24 ± 3 mm in BAV vs 22 ± 4 mm in TAV, P  = 0.009). LVEDV and LVESV were significantly larger in BAV patients (LVEDV: 164.9 ± 68.4 ml in BAV groups vs 126.5 ± 53.1 ml in TAV group, P  = 0.037; LVESV: 82.1 ± 57.9 ml in BAV group vs 52.9 ± 25.7 ml in TAV group, P  = 0.008). A strong linear correlation was found between LVOT diameter and aortic annulus diameter in BAV patients ( r  = 0.7, P  < 0.001), whereas significantly weaker correlation was observed in TAV patients ( r  = 0.5, P  = 0.006, z  = 1.65, P  = 0.04). Presence of BAV morphology was independently associated with larger LVOT diameters (OR 9.0, 95% CI 1.0-81.3, P  = 0.04). We found relevant differences in LV morphological/functional parameters between BAV and TAV stenosis patients. Further investigations are warranted in order to determine the cause of these observed differences. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Polymer Injection Therapy to Reverse Remodel the Papillary Muscles: Efficacy in Reducing Mitral Regurgitation in a Chronic Ischemic Model

PubMed Central

Solis, Jorge; Levine, Robert A.; Johnson, Benjamin; Guerrero, J. Luis; Handschumacher, Mark D.; Suzanne, Suzanne; Lam, Kaitlyn; Berlin, Jason; Braithwaite, Gavin J.C.; Muratoglu, Orhun K.; Vlahakes, Gus J.; Hung, Judy

2010-01-01

Ischemic mitral regurgitation (IMR) results from displacement of the papillary muscles due to ischemic ventricular distortion. Recurrent IMR is frequent after annuloplasty, particularly when left ventricular remodeling continues to progress. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced left ventricular remodeling. Methods Nine sheep underwent ligation of circumflex branches to produce chronic ischemic MR over eight weeks. Once MR developed, PVA was injected into the myocardium underlying the infarcted PM. 2D and 3D echocardiograms and hemodynamic data were obtained pre infarct (baseline), pre PVA (Chronic MR) and post PVA. Results One animal died early, one did not develop MR, and the remaining 7 developed moderate MR. PVA injection significantly decreased the MR from moderate to trace. This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (32.6 ± 4.4 to 27.6 ± 4.2 mm, P<0.05), tenting volume (2.1±0.3 to 1.6 ± 0.3 mm2 P<0.05) and leaflet closure area (9.3 ± 0.8 to 8.2 ± 0.7 mm2, P<0.04). PVA was not associated with significant decreases in LVEF (42 ± 3 % vs 40 ± 2 %, p=ns) or end-systolic elastance. Measures of left ventricular diastolic function, tau (99 ± 55 ms to 87 ± 36;) and left ventricular stiffness coefficient (0.04 ± 0.03 to 0.05 ± 0.03) did not increase post PVA. Conclusions PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving ischemic mitral regurgitation by correcting papillary muscle position, thus relieving tethering that causes ischemic mitral regurgitation. PMID:20736444

Impact of moderate functional mitral insufficiency in patients undergoing surgical revascularization.

PubMed

Grossi, Eugene A; Crooke, Gregory A; DiGiorgi, Paul L; Schwartz, Charles F; Jorde, Ulrich; Applebaum, Robert M; Ribakove, Greg H; Galloway, Aubrey C; Grau, Juan B; Colvin, Stephen B

2006-07-04

Mild and moderate functional ischemic mitral insufficiency present at the time of surgical revascularization present clinical uncertainty. It is unclear whether the relatively poor outcomes in this cohort are dependent on valvular function or related to left ventricular dysfunction. The purpose of this study was to examine the early and late outcomes in patients with less-than-severe functional ischemic mitral insufficiency at the time of isolated coronary artery bypass grafting (CABG). From 1996 through 2004, 2242 consecutive patients undergoing isolated CABG were identified as having none to moderate mitral regurgitation (MR) and no valve leaflet pathology. All of the patients at this single institution routinely had an intraoperative transesophageal echocardiography, prospectively quantified MR, and ejection fraction (EF). The New York State Cardiac Surgery Reporting System infrastructure was used to prospectively collect in-hospital patient variables and outcomes. Social Security Death Benefit Index was used to determine long-term survival. Odds ratio and significance (P value) are presented for each determined risk factor. There were 841 patients (37.5%) with no MR, 1137 (50.7%) with mild MR, and 264 (11.8%) with moderate MR. The patients with moderate MR were more likely to be older, female, and have more renal disease, previous MI, congestive heart failure, previous cardiac surgery, and lower EFs. Hospital mortality was independently and significantly associated with renal disease, decreasing EF, increasing age, previous cardiac operation, and cerebral vascular disease. Multivariable analysis revealed decreased survival with increasing age, previous operation, congestive heart failure, diabetes, nonelective operation, decreasing EF, and the presence of moderate MR (expbeta = 1.49; P=0.007) and mild MR (expbeta = 1.34; P=0.033). Independent of ventricular function, mild and moderate functional mitral insufficiency are associated with significantly decreased survival in patients undergoing CABG. Whether correction of moderate functional MR at the time of CABG improves outcome still needs to be determined.

[Anesthetic management of a patient with HOCM even after PTSMA].

PubMed

Fujimoto, Hiroko; Kamiya, Yoshinori; Ohki, Hiroshi; Goto, Takahisa

2008-10-01

A 74-year-old woman previously treated with percutaneous transluminnal septal myocardial ablation (PTSMA) for severe hypertrophic obstructive cardiomyopathy (HOCM) underwent laparoscopic cholecystectomy under general anesthesia. The PTSMA was performed for HOCM 5 month before surgery and the left ventricular outflow pressure gradient (LVOTG) was reduced from 100 mmHg to 30 mmHg. After anesthetic induction, severe hypotension occurred concomitantly with asymmetrical septal hypertrophy (ASH) and systolic anterior movement of the mitral valve leaflet (SAM). Hypotension was treated with fluid therapy and the vasopressors (methoxamine and noradrenaline). Care should be taken for the anesthetic management of a patient with HOCM even after PTSMA.

MitraClip in CRT non-responders with severe mitral regurgitation.

PubMed

Seifert, Martin; Schau, Thomas; Schoepp, Maren; Arya, Anita; Neuss, Michael; Butter, Christian

2014-11-15

Severe mitral regurgitation (MR) ≥ 3+ and left ventricular dyssynchrony in heart failure patients are markers of CRT non response. The MitraClip (MC) implantation is a therapy for MR ≥ 3+ in patients with high surgical risk of mitral valve reconstruction. We investigated 42 patients with CRT and MR ≥ 3+ who received an MC device at our center. One and two year mortality rates were compared with the predicted mortality by Seattle Heart Failure Model (SHFM) and meta-analysis global group in chronic heart failure (MAGGIC), using the baseline characteristics of patients at the time of MC implantation. The median time interval between CRT and MC implantation was 20.1 (4.5-43.3) months. In 19 patients we observed a functional regurgitation with normal leaflets and in 23 patients a degenerative mechanism for mitral regurgitation. There was no change in mean QRS duration by biventricular pacing or MC implantation. The use of MC led to significant reductions in: median N-terminal pro-brain natriuretic peptide (NT-proBNP) level (pg/ml) from 3923 to 2636 (p = 0.02), tricuspid regurgitation pressure gradient (TRPG) from 43 to 35 mmHg (p = 0.019) and in left ventricular end-diastolic volume (LVEDV) by MC (p = 0.008). At the 2 year follow-up interval the all-cause mortality was 25%. MC implantation leads to an improvement of NT-proBNP level, TRPG and LVEDV in both functional and degenerative MR but does not influence QRS duration. Two year all-cause mortality was 25% and did not differ significantly from that predicted by SHFM and MAGGIC. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Successful balloon dilatation of both orifices in a case of double-orifice mitral valve with severe rheumatic stenosis.

PubMed

Nath, Ranjit Kumar; Soni, Dheeraj Kumar

2016-08-01

A 24-year-old female patient presented to us with progressive dyspnea on exertion for last three year. She was not a known case of rheumatic heart disease. Her physical examination showed regular pulse and her blood pressure was 100/76 mm Hg. Cardiac palpation showed grade 3 parasternal heave and auscultation revelled an accentuated first heart sound, loud P2 and mid-diastolic long rumbling murmur at apex and pansystolic murmur of tricuspid regurgitation at lower left sterna border. Chest X-ray showed evidence of grade 3 pulmonary venous congestion. Transthoracic and transesophageal two-dimensional echocardiography revealed a double-orifice mitral valve of complete bridge type at the leaflet level. Both orifice sizes were unequal, with the anterolateral orifice being smaller than its counterpart. There was moderate subvalvular fusion and both commisures were fused. Color doppler examination showed two separate mitral diastolic flows with mean gradients of 22 mm and 20 mm of Hg, respectively. There was no mitral regurgitation and no left atrial or appendage clot was seen by transesophageal echocardiography. Transseptal puncture was done by the modified fluoroscopic method. Posteromedial orifice was crossed with a 24 mm Inoue balloon and dilated using the stepwise dilation technique. Anterolateral orifice was not crossed by Inuoe balloon after multiple attempts. A TYSHAK (NuMAD Canada Inc.) balloon (16 × 40mm) was taken over the wire and inflated successfully across the anterolateral orifice with the help of transthoracic echocardiography guidance. Mean gradient become 9 and 8 mm across the medial and lateral orifice. Patient was discharged in stable condition after two day. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Triple-orifice valve repair in severe Barlow disease with multiple-jet mitral regurgitation: report of mid-term experience.

PubMed

Fucci, Carlo; Faggiano, Pompilio; Nardi, Matilde; D'Aloia, Antonio; Coletti, Giuseppe; De Cicco, Giuseppe; Latini, Leonardo; Vizzardi, Enrico; Lorusso, Roberto

2013-09-10

Barlow disease represents a surgical challenge for mitral valve repair (MR) in the presence of mitral insufficiency (MI) with multiple regurgitant jets. We hereby present our mid-term experience using a modified edge-to-edge technique to address this peculiar MI. From March 2003 till December 2010, 25 consecutive patients (mean age 54 ± 7 years, 14 males) affected by severe Barlow disease with multiple regurgitant jets were submitted to MR. Preoperative transesophageal echo (TEE) in all the cases showed at least 2 regurgitant jets, involving one or both leaflets in more than one segment. In all the patients, a triple orifice valve (TOV) repair with annuloplasty was performed. Intra-operative TEE and postoperative transthoracic echocardiography (TTE) were carried out to evaluate results of the TOV repair. There was no in-hospital death and one late death (non-cardiac related). At intra-operative TEE, the three orifices showed a mean total valve area of 2.9 ± 0.1cm(2) (range 2.5-3.3 cm(2)) with no residual regurgitation (2 cases of trivial MI) and no sign of valve stenosis (mean transvalvular gradient 4.6 ± 1.5 mmHg). At follow up (mean 38 ± 22 months), TTE showed favourable MR and no recurrence of significant MI (6 cases of trivial and 1 of mild MI). Stress TTE was performed in 5 cases showing persistent effective valve function (2 cases of trivial MI at peak exercise). All the patients showed significant NYHA functional class improvement. This report indicates that the TOV technique is effective in correcting complex Barlow mitral valves with multiple jets. Further studies are required to confirm long-term applicability and durability in more numerous clinical cases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Alarming atrioventricular block and mitral valve prolapse in the Kearns-Sayre syndrome.

PubMed

Katsanos, Konstantinos H; Pappas, Christos J; Patsouras, Dimitrios; Michalis, Lambros K; Kitsios, Georgios; Elisaf, Moses; Tsianos, Epameinondas V

2002-05-01

Kearns-Sayre syndrome (KSS) is a multisystem mitochondrial disorder characterized by the invariant triad: onset before 20, progressive external ophthalmoplegia and pigmentary retinal degeneration, plus at least one of the following: complete (or not) heart block, cereberal dysfunction and CSF protein above 100 mg/dl. Autopsies from patients with KSS revealed widespread tissue distribution mtDNA deletions. These deletions result in significantly lower activities of the enzymes of the respiratory chain. The same deletion of mitochondrial DNA present in skeletal muscle is found in myocardial tissue. An 18-year-old girl diagnosed with the KSS was admitted to our hospital because of an upper respiratory tract infection and dysphagia. ECG showed cardiac conduction defects. The patient had no history of syncope. At her surface ECG there was a complete RBBB (QRS duration approximately 130 ms), a clockwise rotation with an axis of approximately 90 degrees and a slight QT prolongation (420 ms). Echocardiography showed prolapse with thickening and degeneration of both mitral valve leaflets but without mitral regurgitation. The patient was started on a diet rich in potassium and pharmaceutical therapy with magnesium oxide (240 mg of elemental Mg p.o. per day), 1 g of calcium carbonate t.i.d., vitamin D (calcitriol 0.25 microg p.o. per day) and coenzyme Q(10) 100 mg daily and discharged 6 days later with slightly improved biochemical profile but apparent clinical improvement. Urgent pacemaker implantation was decided but unfortunately the patient died due to acute cardiac arrest 10 days later.

Adult women with mitral valve prolapse are more flexible

PubMed Central

Araujo, C; Chaves, C

2005-01-01

Background: Mitral valve prolapse (MVP) is common in women. Other clinical features such as flexibility and hyperlaxity are often associated with MVP, as there is a common biochemical and histological basis for collagen tissue characteristics, range of joint motion, and mitral leaflet excursion. Objective: To confirm whether adult women with MVP are more flexible and hypermobile than those without. Methods: Data from 125 women (mean age 50 years), 31 of them with MVP, were retrospectively analysed with regard to clinical and kinanthropometric aspects. Passive joint motion was evaluated in 20 body movements using Flexitest and three laxity tests. Flexitest individual movements (0 to 4) and overall Flexindex scores were obtained in all subjects by the same investigator. Results: Women with MVP were lighter, less endomorphic and mesomorphic, and more linear. The Flexindex was significantly higher in the women with MVP, both absolute (48 (1.6) v 41 (1.3); p<0.01) and centile for age (67 v 42; p<0.01) values. In 13 out of 20 movements, the Flexitest scores were significantly higher for the women with MVP. Signs of hyperlaxity were about five times more common in these women: 74% v 16% (p<0.01). Scores of 0 and 1 in elbow extension, absence of hyperlaxity, and a Flexindex centile below 65 were almost never found in women with MVP. Conclusion: Flexitest, alone or combined with hyperlaxity tests, may be useful in the assessment of adult women with MVP. PMID:16183767

Transcatheter Mitral Valve Replacement for Patients With Symptomatic Mitral Regurgitation: A Global Feasibility Trial.

PubMed

Muller, David W M; Farivar, Robert Saeid; Jansz, Paul; Bae, Richard; Walters, Darren; Clarke, Andrew; Grayburn, Paul A; Stoler, Robert C; Dahle, Gry; Rein, Kjell A; Shaw, Marty; Scalia, Gregory M; Guerrero, Mayra; Pearson, Paul; Kapadia, Samir; Gillinov, Marc; Pichard, Augusto; Corso, Paul; Popma, Jeffrey; Chuang, Michael; Blanke, Philipp; Leipsic, Jonathon; Sorajja, Paul

2017-01-31

Symptomatic mitral regurgitation (MR) is associated with high morbidity and mortality that can be ameliorated by surgical valve repair or replacement. Despite this, many patients with MR do not undergo surgery. Transcatheter mitral valve replacement (TMVR) may be an option for selected patients with severe MR. This study aimed to examine the effectiveness and safety of TMVR in a cohort of patients with native valve MR who were at high risk for cardiac surgery. Patients underwent transcatheter, transapical delivery of a self-expanding mitral valve prosthesis and were examined in a prospective registry for short-term and 30-day outcomes. Thirty patients (age 75.6 ± 9.2 years; 25 men) with grade 3 or 4 MR underwent TMVR. The MR etiology was secondary (n = 23), primary (n = 3), or mixed pathology (n = 4). The Society of Thoracic Surgeons Predicted Risk of Mortality was 7.3 ± 5.7%. Successful device implantation was achieved in 28 patients (93.3%). There were no acute deaths, strokes, or myocardial infarctions. One patient died 13 days after TMVR from hospital-acquired pneumonia. Prosthetic leaflet thrombosis was detected in 1 patient at follow-up and resolved after increased oral anticoagulation with warfarin. At 30 days, transthoracic echocardiography showed mild (1+) central MR in 1 patient, and no residual MR in the remaining 26 patients with valves in situ. The left ventricular end-diastolic volume index decreased (90.1 ± 28.2 ml/m 2 at baseline vs. 72.1 ± 19.3 ml/m 2 at follow-up; p = 0.0012), as did the left ventricular end-systolic volume index (48.4 ± 19.7 ml/m 2 vs. 43.1 ± 16.2 ml/m 2 ; p = 0.18). Seventy-five percent of the patients reported mild or no symptoms at follow-up (New York Heart Association functional class I or II). Successful device implantation free of cardiovascular mortality, stroke, and device malfunction at 30 days was 86.6%. TMVR is an effective and safe therapy for selected patients with symptomatic native MR. Further evaluation of TMVR using prostheses specifically designed for the mitral valve is warranted. This intervention may help address an unmet need in patients at high risk for surgery. (Early Feasibility Study of the Tendyne Mitral Valve System [Global Feasibility Study]; NCT02321514). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Value of Robotically Assisted Surgery for Mitral Valve Disease

PubMed Central

Mihaljevic, Tomislav; Koprivanac, Marijan; Kelava, Marta; Goodman, Avi; Jarrett, Craig; Williams, Sarah J.; Gillinov, A. Marc; Bajwa, Gurjyot; Mick, Stephanie L.; Bonatti, Johannes; Blackstone, Eugene H.

2014-01-01

Importance The value of robotically assisted surgery for mitral valve disease is questioned because the high cost of care associated with robotic technology may outweigh its clinical benefits. Objective To investigate conditions under which benefits of robotic surgery mitigate high technology costs. Design Clinical cohort study comparing costs of robotic vs. three contemporaneous conventional surgical approaches for degenerative mitral disease. Surgery was performed from 2006–2011, and comparisons were based on intent-to-treat, with propensity-matching used to reduce selection bias. Setting Large multi-specialty academic medical center. Participants 1,290 patients aged 57±11 years, 27% women, underwent mitral repair for regurgitation from posterior leaflet prolapse. Robotic surgery was used in 473, complete sternotomy in 227, partial sternotomy in 349, and anterolateral thoracotomy in 241. Three propensity-matched groups were formed based on demographics, symptoms, cardiac and noncardiac comorbidities, valve pathophysiology, and echocardiographic measurements: robotic vs. sternotomy (n=198 pairs) vs. partial sternotomy (n=293 pairs) vs. thoracotomy (n=224 pairs). Interventions Mitral valve repair. Main Outcome Measures Cost of care, expressed as robotic capital investment, maintenance, and direct technical hospital cost, and benefit of care, based on differences in recovery time. Results Median cost of care for robotically assisted surgery exceeded the cost of alternative approaches by 27% (−5%, 68%), 32% (−6%, 70%), and 21% (−2%, 54%) (median [15th, 85th percentiles]) for complete sternotomy, partial sternotomy, and anterolateral thoracotomy, respectively. Higher operative costs were partially offset by lower postoperative costs and earlier return to work: median 35 days for robotic surgery, 49 for complete sternotomy, 56 for partial sternotomy, and 42 for anterolateral thoracotomy. Resulting net differences in cost of robotic surgery vs. the three alternatives were 16% (−15%, 55%), 16% (−19%, 51%), and 15% (−7%, 49%), respectively. Beyond a volume threshold of 55–100 robotic cases per year, confidence limits for the cost of robotic surgery broadly overlapped those of conventional approaches. Conclusions In exchange for higher procedural costs, robotically assisted mitral valve surgery offers the clinical benefit of least invasive surgery, lowest postoperative cost, and fastest return to work. The value of robotically assisted surgery comparable to conventional approaches can only be realized in high-volume centers. PMID:24848944

Pivot design in bileaflet valves.

PubMed

Vallana, F; Rinaldi, S; Galletti, P M; Nguyen, A; Piwnica, A

1992-01-01

The design criteria leading to the development of a new bileaflet valve (Sorin Bicarbon) were derived from the analysis of functional requirements, the performance of existing prostheses, and the availability of an advanced carbon coating technology (Carbofilm). The hinge is the critical element affecting fluid dynamics, durability, and thrombus formation in bileaflet valves. A comparative study of three existing models led to a new hinge design that was based on coupling two spheric surfaces with different radii of curvature (leaflet pivot and hinge recess) and obtained by electroerosion into a Carbofilm-coated metallic housing. In this valve, the point of contact moves continuously by rolling, not sliding. This minimizes friction and wear and allows uninterrupted washing of the blood exposed surfaces even during diastole (a finding established in patients using transesophageal echocardiography). Tricuspid implantation without anticoagulation in 33 sheep did not lead to thrombotic events (follow-up, 40-400 days). In the first 36 clinical implants observed for 15 months (mitral position, size 29; two unrelated deaths), the mean diastolic gradient by echo Doppler was 4 +/- 1.25 mmHg; the functional area was 3.2 +/- 0.6 cm2. No leaflet fracture and no thrombotic or embolic complications were observed clinically using a standard anticoagulant regimen.

Prosthetic Tricuspid Valve Thrombosis: Three Case Reports and Literature Review

PubMed Central

Yaminisharif, Ahmad; Alemzadeh-Ansari, Mohammad Javad; Ahmadi, Seyed Hossein

2012-01-01

A common complication of prosthetic heart valves is thrombosis. Although the incidence of prosthetic valve thrombosis (PVT) in the tricuspid position is high, there are not enough data on the management of it, in contrast to left-sided PVT. Here, we describe three cases of tricuspid PVT with three different management approaches: thrombolytic therapy; close observation with oral anticoagulants; and surgery. The first case was a woman who suffered from recurrent PVT, for which we successfully used Tenecteplase for second and third episodes. We employed Tenecteplase in this case for the first time in the therapy of tricuspid PVT. The second case had fixed leaflets in open position while being symptomless. At six months' follow-up, with the patient having taken oral anticoagulants, the motion of the leaflets was restricted and she was symptomfree. The last case was a woman who had a large thrombus in the right atrium immediately after mitral and tricuspid valvular replacement. The patient underwent re-replacement surgery and a new biological valve was implanted in the tricuspid position. Also, we review the literature on the pathology, signs and symptoms, diagnosis, and management of tricuspid PVT. PMID:23323074

On the Presence of Affine Fibril and Fiber Kinematics in the Mitral Valve Anterior Leaflet

PubMed Central

Lee, Chung-Hao; Zhang, Will; Liao, Jun; Carruthers, Christopher A.; Sacks, Jacob I.; Sacks, Michael S.

2015-01-01

In this study, we evaluated the hypothesis that the constituent fibers follow an affine deformation kinematic model for planar collagenous tissues. Results from two experimental datasets were utilized, taken at two scales (nanometer and micrometer), using mitral valve anterior leaflet (MVAL) tissues as the representative tissue. We simulated MVAL collagen fiber network as an ensemble of undulated fibers under a generalized two-dimensional deformation state, by representing the collagen fibrils based on a planar sinusoidally shaped geometric model. The proposed approach accounted for collagen fibril amplitude, crimp period, and rotation with applied macroscopic tissue-level deformation. When compared to the small angle x-ray scattering measurements, the model fit the data well, with an r2 = 0.976. This important finding suggests that, at the homogenized tissue-level scale of ∼1 mm, the collagen fiber network in the MVAL deforms according to an affine kinematics model. Moreover, with respect to understanding its function, affine kinematics suggests that the constituent fibers are largely noninteracting and deform in accordance with the bulk tissue. It also suggests that the collagen fibrils are tightly bounded and deform as a single fiber-level unit. This greatly simplifies the modeling efforts at the tissue and organ levels, because affine kinematics allows a straightforward connection between the macroscopic and local fiber strains. It also suggests that the collagen and elastin fiber networks act independently of each other, with the collagen and elastin forming long fiber networks that allow for free rotations. Such freedom of rotation can greatly facilitate the observed high degree of mechanical anisotropy in the MVAL and other heart valves, which is essential to heart valve function. These apparently novel findings support modeling efforts directed toward improving our fundamental understanding of tissue biomechanics in healthy and diseased conditions. PMID:25902446

Left ventricular inflow tract obstruction secondary to a myxoma in a dog.

PubMed

Fernandez-del Palacio, M Josefa; Sanchez, Joaquin; Talavera, Jesus; Martínez, Carlos

2011-01-01

This is the first description of a left ventricular inflow tract obstruction secondary to a myxoma in a dog. A 4 yr old, male fox terrier presented with a 1 mo history of cough and exercise intolerance. Expiratory dyspnea, pulmonary crackles, irregular cardiac rhythm, and a grade 4/6 pansystolic cardiac murmur over the left cardiac apex were the most important features on physical examination. The electrocardiogram revealed atrial fibrillation. Thoracic radiographs showed left-sided cardiac enlargement and mild pulmonary edema, especially in the hilar area. Two-dimensional transthoracic echocardiography showed severe left atrial dilation and a homogenous, echodense mass involving both leaflets of the mitral valve and the posteromedial papillary muscle, inducing mitral stenosis. Spectral Doppler echocardiography was consistent with severe left ventricular inflow tract obstruction secondary to a mass. Therapy for congestive heart failure was prescribed. Follow-up examinations of the dog 1 mo, 2 mo, and 6 mo after diagnosis showed an improvement in clinical signs, but similar echocardiographic features. Eleven months after diagnosis, the dog was euthanized at the owner's request because of recurrent congestive heart failure. The postmortem examination showed the cardiac tumor was consistent with a myxoma.

An unusual case of infective endocarditis presenting as acute myocardial infarction.

PubMed

Chen, Zhong; Ng, Francesca; Nageh, Thuraia

2007-06-01

A 39-year-old Zimbabwean man presented with a 1 week history of fever, general malaise and acute-onset chest pain. He had a urethral stricture, which had been managed with an indwelling supra-pubic catheter. The electrocardiography on admission showed inferior ST-T segments elevation. His chest pain and electrocardiography changes resolved subsequent to thrombolysis, and he remained haemodynamically stable. The 12-h troponin I was increased at 10.5 microg/l (NR <0.04 microg/l). Echocardiography confirmed severe mitral regurgitation and a flail anterior mitral valve leaflet with an independently oscillating mobile vegetation. Enterococci faecalis were grown on blood cultures. A diagnosis of enterococci infective endocarditis with concomitant acute myocardial infarction due to possible septic emboli was made. Despite the successful outcome from thrombolysis in the setting of acute myocardial infarction with infective endocarditis, the case highlights the current lack of definitive data on the optimal acute management of such an unusual clinical scenario. Although there is serious concern that thrombolytic treatment for myocardial infarction in the setting of infective endocarditis may be associated with higher risk of cerebral haemorrhage, there is little documented evidence supporting the safety of primary percutaneous coronary intervention with these patients.

Percutaneous edge-to-edge mitral valve repair in high-surgical-risk patients: do we hit the target?

PubMed

Van den Branden, Ben J L; Swaans, Martin J; Post, Martijn C; Rensing, Benno J W M; Eefting, Frank D; Jaarsma, Wybren; Van der Heyden, Jan A S

2012-01-01

This study sought to assess the feasibility and safety of percutaneous edge-to-edge mitral valve (MV) repair in patients with an unacceptably high operative risk. MV repair for mitral regurgitation (MR) can be accomplished by use of a clip that approximates the free edges of the mitral leaflets. All patients were declined for surgery because of a high logistic EuroSCORE (>20%) or the presence of other specific surgical risk factors. Transthoracic echocardiography was performed before and 6 months after the procedure. Differences in New York Heart Association (NYHA) functional class, quality of life (QoL) using the Minnesota questionnaire, and 6-min walk test (6-MWT) distances were reported. Fifty-five procedures were performed in 52 patients (69.2% male, age 73.2 ± 10.1 years, logistic EuroSCORE 27.1 ± 17.0%). In 3 patients, partial clip detachment occurred; a second clip was placed successfully. One patient experienced cardiac tamponade. Two patients developed inguinal bleeding, of whom 1 needed surgery. Six patients (11.5%) died during 6-month follow-up (5 patients as a result of progressive heart failure and 1 noncardiac death). The MR grade before repair was ≥3 in 100%; after 6 months, a reduction in MR grade to ≤2 was present in 79% of the patients. Left ventricular (LV) end-diastolic diameter, LV ejection fraction, and systolic pulmonary artery pressure improved significantly. Accompanied improvements in NYHA functional class, QoL index, 6-MWT distances, and log N-terminal pro-B-type natriuretic peptide were observed. In a high-risk population, MR reduction can be achieved by percutaneous edge-to-edge valve repair, resulting in LV remodeling with improvement of functional capacity after 6 months. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

How Heart Valves Evolve to Adapt to an Extreme-Pressure System: Morphologic and Biomechanical Properties of Giraffe Heart Valves.

PubMed

Amstrup Funder, Jonas; Christian Danielsen, Carl; Baandrup, Ulrik; Martin Bibby, Bo; Carl Andelius, Ted; Toft Brøndum, Emil; Wang, Tobias; Michael Hasenkam, J

2017-01-01

Heart valves which exist naturally in an extreme-pressure system must have evolved in a way to resist the stresses of high pressure. Giraffes are interesting as they naturally have a blood pressure twice that of humans. Thus, knowledge regarding giraffe heart valves may aid in developing techniques to design improved pressure-resistant biological heart valves. Heart valves from 12 giraffes and 10 calves were explanted and subjected to either biomechanical or morphological examinations. Strips from the heart valves were subjected to cyclic loading tests, followed by failure tests. Thickness measurements and analyses of elastin and collagen content were also made. Valve specimens were stained with hematoxylin and eosin, elastic van Gieson stain, Masson's trichrome and Fraser-Lendrum stain, as well as immunohistochemical reactions for morphological examinations. The aortic valve was shown to be 70% (95% CI 42-103%) stronger in the giraffe than in its bovine counterpart (p <0.001). No significant difference was found between mitral or pulmonary valves. After normalization for collagen, no significant differences were found in strength between species. The giraffe aortic valve was found to be significantly stiffer than the bovine aortic valve (p <0.001), with no significant difference between mitral and pulmonary valves. On a dry weight basis, the aortic (10.9%), pulmonary (4.3%), and mitral valves (9.6%) of giraffes contained significantly more collagen than those of calves. The elastin contents of the pulmonary valves (2.5%) and aortic valves (1.5%) were also higher in giraffes. The greater strength of the giraffe aortic valve is most likely due to a compact collagen construction. Both, collagen and elastin contents were higher in giraffes than in calves, which would make giraffe valves more resistant to the high-pressure forces. However, collagen also stiffens and thickens the valves. The mitral leaflets showed similar (but mostly insignificant) trends in strength, stiffness, and collagen content.

Thrombolysis Is an Effective and Safe Therapy in Stuck Mitral Valves With Delayed Presentation as Well as Hemodynamically Unstable Patients: A Single Centre Study

PubMed Central

Bade, Arun Shivajirao; Shaikh, Shakil Sattar Ahmed; Khemani, Hemant; Singh, Gurkirat; Bansal, Narender Omprakash

2018-01-01

Background Thrombosis is a complication of prosthetic valves on oral anticoagulants which is associated with significant morbidity and mortality. A re-operation carries a substantial risk, with mortality rate from 10% to 15% in selected series, which may be 2- or 3-folds higher in critically ill patients. This study conducted in a tertiary care cardiology unit aimed to evaluate the effectiveness and safety of thrombolytic therapy in stuck mitral bileaflet heart valves. Methods As a prospective observational study, clinical symptoms and fluoroscopy were the mainstay in diagnosis of stuck mitral valve. Gradient across the valve by transthoracic echocardiography was used to monitor the therapy every 6 h. Fall of mean gradient more than 50% was considered as successful thrombolysis. And final results were again checked by fluoroscopy with documentation of improved leaflet movement. Results Totally we studied 34 patients. Patients receiving thrombolytic therapy with streptokinase achieved an overall 91.2% freedom from a repeat operation or major complications, a large subcutaneous hematoma occurred in one ( 2.9%), reoperation required in two due to failure of treatment (5.9%), allergic reaction in one (2.9%), one patient developed transient neurologic dysfunction (2.9%) and one patient died during therapy due to refractory cardiogenic shock(2.9%). All patients including those with delayed presentation (> 14 days) and hemodynamically unstable patients had good results similar to those who presented within 14 days and hemodynamically stable. Mortality was higher in unstable patients and reoperation was higher with delayed presentation. Conclusions Thrombolysis with streptokinase is highly successful and safe therapy in hemodynamically stable as well as unstable patients, or those with early or delayed presentation with stuck bileaflet mitral valves, especially in centers where round the clock cardiothoracic surgery backup is not available. PMID:29904451

The Murine Model of Mucopolysaccharidosis IIIB Develops Cardiopathies over Time Leading to Heart Failure

PubMed Central

De Pasquale, Valeria; Cocchiaro, Pasquale; Paciello, Orlando; Avallone, Luigi; Belfiore, Maria Paola; Iacobellis, Francesca; Di Napoli, Daniele; Magliulo, Fabio; Perrino, Cinzia; Trimarco, Bruno; Esposito, Giovanni; Di Natale, Paola; Pavone, Luigi Michele

2015-01-01

Mucopolysaccharidosis (MPS) IIIB is a lysosomal disease due to the deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU) required for heparan sulfate (HS) degradation. The disease is characterized by mild somatic features and severe neurological disorders. Very little is known on the cardiac dysfunctions in MPS IIIB. In this study, we used the murine model of MPS IIIB (NAGLU knockout mice, NAGLU-/-) in order to investigate the cardiac involvement in the disease. Echocardiographic analysis showed a marked increase in left ventricular (LV) mass, reduced cardiac function and valvular defects in NAGLU-/- mice as compared to wild-type (WT) littermates. The NAGLU-/- mice exhibited a significant increase in aortic and mitral annulus dimension with a progressive elongation and thickening of anterior mitral valve leaflet. A severe mitral regurgitation with reduction in mitral inflow E-wave-to-A-wave ratio was observed in 32-week-old NAGLU-/- mice. Compared to WT mice, NAGLU-/- mice exhibited a significantly lower survival with increased mortality observed in particular after 25 weeks of age. Histopathological analysis revealed a significant increase of myocardial fiber vacuolization, accumulation of HS in the myocardial vacuoles, recruitment of inflammatory cells and collagen deposition within the myocardium, and an increase of LV fibrosis in NAGLU-/- mice compared to WT mice. Biochemical analysis of heart samples from affected mice showed increased expression levels of cardiac failure hallmarks such as calcium/calmodulin-dependent protein kinase II, connexin43, α-smooth muscle actin, α-actinin, atrial and brain natriuretic peptides, and myosin heavy polypeptide 7. Furthermore, heart samples from NAGLU-/- mice showed enhanced expression of the lysosome-associated membrane protein-2 (LAMP2), and the autophagic markers Beclin1 and LC3 isoform II (LC3-II). Overall, our findings demonstrate that NAGLU-/- mice develop heart disease, valvular abnormalities and cardiac failure associated with an impaired lysosomal autophagic flux. PMID:26147524

Intra-Aortic Missile After Gunshot Wound to Chest: An Interesting Case of Traumatic Cardiac Injury.

PubMed

Fraser, Charles D; Goeddel, Lee; Patel, Nishant D; Azoury, Said C; Grimm, Joshua C; Sheinberg, Rosanne B; Sciortino, Christopher M

2017-05-01

Missile embolus to the heart, although uncommon, is one of the most challenging scenarios in trauma. We describe a 36-year-old man who presented with a gunshot wound to the left chest and a chest x-ray revealing a foreign body in the mediastinum. A median sternotomy was performed and an injury to the left ventricle was identified. After intraoperative echocardiography and fluoroscopy confirmed a foreign body in the aortic root, cardiopulmonary bypass was implemented. A bullet was retrieved from the noncoronary sinus of the aortic valve. Injuries to the anterior leaflet of the mitral valve and left ventricle were repaired. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Nonbacterial Thrombotic Endocarditis in a Patient with Bowel Infarction due to Mesenteric Vein Thrombosis.

PubMed

Kim, Hyue Mee; Kim, Hack-Lyoung; Lee, Hak Seung; Jung, Ji-Hyun; Kim, Chee Hae; Oh, Sooyeon; Kim, Jung Ho; Zo, Joo-Hee

2014-05-01

Ante mortem cases of venous thrombosis in patients with nonbacterial thrombotic endocarditis (NBTE) have not yet been reported. We describe a rare case of NBTE in a patient with mesenteric vein thrombosis. A healthy 37-year-old man with abdominal pain and fever underwent emergency small bowel resection due to bowel ischemia resulting from mesenteric vein thrombosis. Transthoracic echocardiography revealed multiple mobile masses attached to the anterior leaflet of the mitral valves and their chordae tendineae. On suspicion of infective endocarditis, the cardiac masses were excised through open-heart surgery. However, pathologic reviews were compatible with NBTE. The patient was stable after the cardiac surgery and was treated with warfarin. Laboratory and imaging findings regarding his hypercoagulable condition were all negative.

On the effects of leaflet microstructure and constitutive model on the closing behavior of the mitral valve

PubMed Central

Lee, Chung-Hao; Rabbah, Jean-Pierre; Yoganathan, Ajit P.; Gorman, Robert C.; Gorman, Joseph H.

2016-01-01

Recent long-term studies showed an unsatisfactory recurrence rate of severe mitral regurgitation 3–5 years after surgical repair, suggesting that excessive tissue stresses and the resulting strain-induced tissue failure are potential etiological factors controlling the success of surgical repair for treating mitral valve (MV) diseases. We hypothesized that restoring normal MV tissue stresses in MV repair techniques would ultimately lead to improved repair durability through the restoration of MV normal homeostatic state. Therefore, we developed a micro- and macro- anatomically accurate MV finite element model by incorporating actual fiber microstructural architecture and a realistic structure-based constitutive model. We investigated MV closing behaviors, with extensive in vitro data used for validating the proposed model. Comparative and parametric studies were conducted to identify essential model fidelity and information for achieving desirable accuracy. More importantly, for the first time, the interrelationship between the local fiber ensemble behavior and the organ-level MV closing behavior was investigated using a computational simulation. These novel results indicated not only the appropriate parameter ranges, but also the importance of the microstructural tuning (i.e., straightening and re-orientation) of the collagen/elastin fiber networks at the macroscopic tissue level for facilitating the proper coaptation and natural functioning of the MV apparatus under physiological loading at the organ level. The proposed computational model would serve as a logical first step toward our long-term modeling goal—facilitating simulation-guided design of optimal surgical repair strategies for treating diseased MVs with significantly enhanced durability. PMID:25947879

A new method for the adjustment of neochordal length: the adjustable slip knot technique.

PubMed

Yano, Mitsuhiro; Sakaguchi, Syuuhei; Furukawa, Kohji; Nakamura, Eisaku

2015-08-01

The use of expanded polytetrafluoroethylene (ePTFE) sutures for the correction of mitral valve prolapse has become a standardized procedure. Adjustment of neochordal length is crucial to the efficacy of this technique. Various methods have been described for this purpose; however, the fine adjustment of neochordal length is technically challenging. We describe a simple and effective technique for the implantation of neochordae, which we have termed the 'adjustable slip knot technique'. The first step of this technique is reinforcement of the papillary muscle by a Teflon pledget with or without polytetrafluoroethylene (CV-4) loops. The second step is the formation of a neochordal loop by introducing an ePTFE suture between the affected mitral leaflet and the papillary muscle or ePTFE loops. The third step is the adjustment of the length of neochordae. The formation of a slip knot in one arm of the ePTFE suture is the pivot of this technique. The neochordal loop can be constricted by the application of tension to one arm of the suture. We applied this technique in 5 patients with satisfactory results. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

No patch technique for complete atrioventricular canal repair.

PubMed

Aramendi, José Ignacio; Rodriguez, Miguel Angel; Luis, Teresa; Voces, Roberto

2006-08-01

We describe our initial experience with a new technique, consisting in direct closure of the ventricular septal defect component of the AV canal, by directly attaching the common bridging leaflets to the crest of the ventricular septum with interrupted sutures. After closure of the cleft, the ostium primum defect was closed with a running suture suturing the border of the septum primum to the newly created AV valve annulus. Three patients were operated upon. There was no mortality. Mean ischemic time was 39 min and mean pump time 77 min. All patients remained in sinus rhythm. At follow-up only trivial or mild mitral regurgitation was observed. This new technique permits the repair of complete AV canal without the need for any patch. It is fast, simple and reproducible.

Outcome after percutaneous edge-to-edge mitral repair for functional and degenerative mitral regurgitation: a systematic review and meta-analysis.

PubMed

Chiarito, Mauro; Pagnesi, Matteo; Martino, Enrico Antonio; Pighi, Michele; Scotti, Andrea; Biondi-Zoccai, Giuseppe; Latib, Azeem; Landoni, Giovanni; Mario, Carlo Di; Margonato, Alberto; Maisano, Francesco; Feldman, Ted; Alfieri, Ottavio; Colombo, Antonio; Godino, Cosmo

2018-02-01

Differences in terms of safety and efficacy of percutaneous edge-to-edge mitral repair between patients with functional and degenerative mitral regurgitation (MR) are not well established. We performed a systematic review and meta-analysis to clarify these differences. PubMed, EMBASE, Google scholar database and international meeting abstracts were searched for all studies about MitraClip. Studies with <25 patients or where 1-year results were not delineated between MR aetiology were excluded. This study is registered with PROSPERO. A total of nine studies investigating the mid-term outcome of percutaneous edge-to-edge repair in patients with functional versus degenerative MR were included in the meta-analysis (n=2615). At 1 year, there were not significant differences among groups in terms of patients with MR grade≤2 (719/1304 vs 295/504; 58% vs 54%; risk ratio (RR) 1.12; 95% CI: 0.86 to 1.47; p=0.40), while there was a significantly lower rate of mitral valve re-intervention in patients with functional MR compared with those with degenerative MR (77/1770 vs 80/818; 4% vs 10%; RR 0.60; 95% CI: 0.38 to 0.97; p=0.04). One-year mortality rate was 16% (408/2498) and similar among groups (RR 1.26; 95% CI: 0.90 to 1.77; p=0.18). Functional MR group showed significantly higher percentage of patients in New York Heart Association class III/IV (234/1480 vs 49/583; 16% vs 8%; p<0.01) and re-hospitalisation for heart failure (137/605 vs 31/220; 23% vs 14%; p=0.03). No differences were found in terms of single leaflet device attachment (25/969 vs 20/464; 3% vs 4%; p=0.81) and device embolisation (no events reported in both groups) at 1 year. This meta-analysis suggests that percutaneous edge-to-edge repair is likely to be an efficacious and safe option in patients with both functional and degenerative MR. Large, randomised studies are ongoing and awaited to fully assess the clinical impact of the procedure in these two different MR aetiologies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Plasma proANP and SDMA and microRNAs are associated with chronic mitral regurgitation in a pig model

PubMed Central

Cirera, Susanna; Moesgaard, Sophia G; Zois, Nora E; Ravn, Nathja; Goetze, Jens P; Cremer, Signe E; Teerlink, Tom; Leifsson, Páll S; Honge, Jesper L; Hasenkam, J Michael; Olsen, Lisbeth H

2013-01-01

Objective Non-ischemic mitral regurgitation (MR) is primarily caused by myxomatous mitral valve (MV) disease leading to adaptive remodeling, enlargement, and dysfunction of the left ventricle. The aim of this study was to examine the regulation of plasma markers and several cardiac key genes in a novel porcine model of non-ischemic MR. Methods and results Twenty-eight production pigs (Sus scrofa) were randomized to experimental MR or sham surgery controls. MR was induced by external suture(s) through the posterior MV leaflet and quantified using echocardiography. The experimental group was subdivided into mild MR (mMR, MR=20–50%, n=10) and moderate/severe MR (sMR, MR >50%, n=6) and compared with controls (CON, MR ≤10%, n=12). Eight weeks postoperatively, follow-up examinations were performed followed by killing. Circulating concentrations of pro-atrial natriuretic peptide (proANP), l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine (SDMA) were measured. MV, anterior papillary muscle, and left ventricular free wall tissues were collected to quantify mRNA expression of eNOS (NOS3), iNOS (NOS2), MMP9, MMP14, ANP (NPPA), BNP (NPPB), and TGFB1, 2, and 3 and five microRNAs by quantitative real-time PCR. Pigs with sMR displayed markedly increased plasma proANP and SDMA concentrations compared with both controls and mMR (P<0.05). The expression of all genes examined differed significantly between the three localizations in the heart. miR-21 and miR-133a were differently expressed among the experimental groups (P<0.05). Conclusions Plasma proANP and SDMA levels and tissue expression of miR-21 and miR-133a are associated with severity of chronic MR in an experimental porcine model. PMID:24029364

Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease.

PubMed

Borgarelli, M; Savarino, P; Crosara, S; Santilli, R A; Chiavegato, D; Poggi, M; Bellino, C; La Rosa, G; Zanatta, R; Haggstrom, J; Tarducci, A

2008-01-01

There are few studies evaluating the natural history and prognostic variables in chronic mitral valve disease (CMVI) in a heterogeneous population of dogs. To estimate survival and prognostic value of clinical and echocardiographic variables in dogs with CMVI of varying severity. Five hundred and fifty-eight dogs belonging to 36 breeds were studied. Dogs were included after clinical examination and echocardiography. Long-term outcome was assessed by telephone interview with the owner. The mean follow-up time was 22.7 +/- 13.6 months, and the median survival time was 19.5 +/- 13.2 months. In univariate analysis, age>8 years, syncope, HR>140 bpm, dyspnea, arrhythmias, class of heart failure (International Small Animal Cardiac Health Council), furosemide therapy, end-systolic volume-index (ESV-I)>30 mL/m(2), left atrial to aortic root ratio (LA/Ao)>1.7, E wave transmitral peak velocity (Emax)>1.2 m/s, and bilateral mitral valve leaflet engagement were associated with survival time when all causes of death were included. For the cardiac-related deaths, all the previous variables except dyspnea and EDV-I>100 mL/m(2) were significantly associated with survival time. Significant variables in multivariate analysis (all causes of death) were syncope, LA/Ao>1.7 m/s, and Emax>1.2 m/s. For cardiac-related death, the only significant variable was LA/Ao>1.7. Mild CMVI is a relatively benign condition in dogs. However, some clinical variables can identify dogs at a higher risk of death; these variables might be useful to identify individuals that need more frequent monitoring or therapeutic intervention.

Expression of transforming growth factor-beta1, -beta2 and -beta3 in normal and diseased canine mitral valves.

PubMed

Aupperle, H; März, I; Thielebein, J; Schoon, H-A

2008-01-01

The pathogenesis of chronic valvular disease (CVD) in dogs remains unclear, but activation and proliferation of valvular stromal cells (VSC) and their transdifferentiation into myofibroblast-like cells has been described. These alterations may be influenced by transforming growth factor-beta (TGF-beta), a cytokine involved in extracellular matrix (ECM) regulation and mesenchymal cell differentiation. The present study investigates immunohistochemically the expression of TGF-beta1, -beta2, -beta3 and smooth muscle alpha actin (alpha-SMA) in normal canine mitral valves (MVs) (n=10) and in the valves of dogs with mild (n=7), moderate (n=14) and severe (n=9) CVD. In normal mitral valves there was no expression of alpha-SMA but VSC displayed variable expression of TGF-beta1 (10% of VSC labelled), TGF-beta2 (1-5% labelled) and TGF-beta3 (50% labelled). In mild CVD the affected atrialis contain activated and proliferating alpha-SMA-positive VSC, which strongly expressed TGF-beta1 and -beta3, but only 10% of these cells expressed TGF-beta2. In unaffected areas of the leaflet there was selective increase in expression of TGF-beta1 and -beta3. In advanced CVD the activated subendothelial VSC strongly expressed alpha-SMA, TGF-beta1 and -beta3. Inactive VSC within the centre of the nodules had much less labelling for TGF-beta1 and -beta3. TGF-beta1 labelling was strong within the ECM. These data suggest that TGF-beta plays a role in the pathogenesis of CVD by inducing myofibroblast-like differentiation of VSC and ECM secretion. Changed haemodynamic forces and expression of matrix metalloproteinases (MMPs) may in turn regulate TGF-beta expression.

Transthoracic echocardiography in patients undergoing mitral valve repair: comparison of new transthoracic 3D techniques to 2D transoesophageal echocardiography in the localization of mitral valve prolapse.

PubMed

Gripari, Paola; Mapelli, Massimo; Bellacosa, Ilaria; Piazzese, Concetta; Milo, Maria; Fusini, Laura; Muratori, Manuela; Ali, Sarah Ghulam; Tamborini, Gloria; Pepi, Mauro

2018-02-26

Successful mitral valve (MV) repair for degenerative mitral regurgitation (DMR) is mainly related to surgical expertise and MV anatomy. Although 2D echocardiography, specifically transoesophageal (TOE), provides precise information regarding MV anatomy, recent advancements in matrix technology meant a decisive step forward to the point where segmental MV analysis can be accurately performed from a noninvasive 3D transthoracic (TTE) approach. The aims of this study were: (a) to evaluate the feasibility and time required for real-time 3D TTE in a large consecutive cohort of patients with severe DMR in the assessment of MV anatomy; (b) to compare the accuracy of 3D TTE and 2D TOE versus surgical inspection in the recognition and localization of all components of the MV leaflets; (c) to establish the added diagnostic value of 3D colourDoppler examination to pure 3D morphologic evaluation. 149 consecutive patients with severe DMR underwent complete 3D TTE before surgery and 2D TOE in the operating room. Echocardiographic data obtained by the different techniques were compared with surgical inspection. 3D TTE was feasible in a relatively short time (8 ± 4 min), with good (49%) and optimal (33%) imaging quality in the majority of cases. 3D TTE had significant better overall accuracy compared to 2D TOE (93 and 91%, p < 0.05, respectively). 2D TOE was significantly more specific than 3D TTE in the identification of A3 prolapse (99 vs. 96%). The colourDoppler mode did not improve significantly the accuracy of 3D TTE, albeit it determined a better sensitivity in the detection of A2 prolapse if compared to 2D TOE (95 vs. 85%). 3D TTE with or without colourDoppler is a feasible and useful method in the analysis of MV prolapse; it allows a preoperative and noninvasive description of the pathology as accurate as the 2D TOE.

Tricuspid regurgitation after successful mitral valve surgery

PubMed Central

Katsi, Vasiliki; Raftopoulos, Leonidas; Aggeli, Constantina; Vlasseros, Ioannis; Felekos, Ioannis; Tousoulis, Dimitrios; Stefanadis, Christodoulos; Kallikazaros, Ioannis

2012-01-01

The tricuspid valve (TV) is inseparably connected with the mitral valve (MV) in terms of function. Any pathophysiological condition concerning the MV is potentially a threat for the normal function of the TV as well. One of the most challenging cases is functional tricuspid regurgitation (TR) after surgical MV correction. In the past, TR was considered to progressively revert with time after left-sided valve restoration. Nevertheless, more recent studies showed that TR could develop and evolve postoperatively over time, as well as being closely associated with a poorer prognosis in terms of morbidity and mortality. Pressure and volume overload are usually the underlying pathophysiological mechanisms; structural alterations, like tricuspid annulus dilatation, increased leaflet tethering and right ventricular remodelling are almost always present when regurgitation develops. The most important risk factors associated with a higher probability of late TR development involve the elderly, female gender, larger left atrial size, atrial fibrillation, right chamber dilatation, higher pulmonary artery systolic pressures, longer times from the onset of MV disease to surgery, history of rheumatic heart disease, ischaemic heart disease and prosthetic valve malfunction. The time of TR manifestation can be up to 10 years or more after an MV surgery. Echocardiography, including the novel 3D Echo techniques, is crucial in the early diagnosis and prognosis of future TV disease development. Appropriate surgical technique and timing still need to be clarified. PMID:22457188

COMPUTATIONAL MITRAL VALVE EVALUATION AND POTENTIAL CLINICAL APPLICATIONS

PubMed Central

Chandran, Krishnan B.; Kim, Hyunggun

2014-01-01

The mitral valve (MV) apparatus consists of the two asymmetric leaflets, the saddle-shaped annulus, the chordae tendineae, and the papillary muscles. MV function over the cardiac cycle involves complex interaction between the MV apparatus components for efficient blood circulation. Common diseases of the MV include valvular stenosis, regurgitation, and prolapse. MV repair is the most popular and most reliable surgical treatment for early MV pathology. One of the unsolved problems in MV repair is to predict the optimal repair strategy for each patient. Although experimental studies have provided valuable information to improve repair techniques, computational simulations are increasingly playing an important role in understanding the complex MV dynamics, particularly with the availability of patient-specific real-time imaging modalities. This work presents a review of computational simulation studies of MV function employing finite element (FE) structural analysis and fluid-structure interaction (FSI) approach reported in the literature to date. More recent studies towards potential applications of computational simulation approaches in the assessment of valvular repair techniques and potential pre-surgical planning of repair strategies are also discussed. It is anticipated that further advancements in computational techniques combined with the next generations of clinical imaging modalities will enable physiologically more realistic simulations. Such advancement in imaging and computation will allow for patient-specific, disease-specific, and case-specific MV evaluation and virtual prediction of MV repair. PMID:25134487

High-resolution subject-specific mitral valve imaging and modeling: experimental and computational methods.

PubMed

Toma, Milan; Bloodworth, Charles H; Einstein, Daniel R; Pierce, Eric L; Cochran, Richard P; Yoganathan, Ajit P; Kunzelman, Karyn S

2016-12-01

The diversity of mitral valve (MV) geometries and multitude of surgical options for correction of MV diseases necessitates the use of computational modeling. Numerical simulations of the MV would allow surgeons and engineers to evaluate repairs, devices, procedures, and concepts before performing them and before moving on to more costly testing modalities. Constructing, tuning, and validating these models rely upon extensive in vitro characterization of valve structure, function, and response to change due to diseases. Micro-computed tomography ([Formula: see text]CT) allows for unmatched spatial resolution for soft tissue imaging. However, it is still technically challenging to obtain an accurate geometry of the diastolic MV. We discuss here the development of a novel technique for treating MV specimens with glutaraldehyde fixative in order to minimize geometric distortions in preparation for [Formula: see text]CT scanning. The technique provides a resulting MV geometry which is significantly more detailed in chordal structure, accurate in leaflet shape, and closer to its physiological diastolic geometry. In this paper, computational fluid-structure interaction (FSI) simulations are used to show the importance of more detailed subject-specific MV geometry with 3D chordal structure to simulate a proper closure validated against [Formula: see text]CT images of the closed valve. Two computational models, before and after use of the aforementioned technique, are used to simulate closure of the MV.

Are anticoagulant independent mechanical valves within reach-fast prototype fabrication and in vitro testing of innovative bi-leaflet valve models.

PubMed

Scotten, Lawrence N; Siegel, Rolland

2015-08-01

Exploration for causes of prosthetic valve thrombogenicity has frequently focused on forward or post-closure flow detail. In prior laboratory studies, we uncovered high amplitude flow velocities of short duration close to valve closure implying potential for substantial shear stress with subsequent initiation of blood coagulation pathways. This may be relevant to widely accepted clinical disparity between mechanical and tissue valves vis-à-vis thrombogenicity. With a series of prototype bi-leaflet mechanical valves, we attempt reduction of closure related velocities with the objective of identifying a prototype valve with thrombogenic potential similar to our tissue valve control. This iterative design approach may find application in preclinical assessment of valves for anticoagulation independence. Tested valves included: prototype mechanical bi-leaflet BVs (n=56), controls (n=2) and patented early prototype mechanicals (n=2) from other investigators. Pulsatile and quasi-steady flow systems were used for testing. Projected dynamic valve area (PDVA) was measured using previously described novel technology. Flow velocity over the open and closing periods was determined by volumetric flow rate/PDVA. For the closed valve interval, use was made of data obtained from quasi-steady back pressure/flow tests. Performance was ranked by a proposed thrombogenicity potential index (TPI) relative to tissue and mechanical control valves. Optimization of the prototype valve designs lead to a 3-D printed model (BV3D). For the mitral/aortic site, BV3D has lower TPI (1.10/1.47) relative to the control mechanical valve (3.44/3.93) and similar to the control tissue valve (ideal TPI ≤1.0). Using unique technology, rapid prototyping and thrombogenicity ranking, optimization of experimental valves for reduced thrombogenic potential was expedited and simplified. Innovative mechanical valve configurations were identified that merit consideration for further development which may bring the anti-coagulation independent mechanical valve within reach.

Are anticoagulant independent mechanical valves within reach—fast prototype fabrication and in vitro testing of innovative bi-leaflet valve models

PubMed Central

Siegel, Rolland

2015-01-01

Background Exploration for causes of prosthetic valve thrombogenicity has frequently focused on forward or post-closure flow detail. In prior laboratory studies, we uncovered high amplitude flow velocities of short duration close to valve closure implying potential for substantial shear stress with subsequent initiation of blood coagulation pathways. This may be relevant to widely accepted clinical disparity between mechanical and tissue valves vis-à-vis thrombogenicity. With a series of prototype bi-leaflet mechanical valves, we attempt reduction of closure related velocities with the objective of identifying a prototype valve with thrombogenic potential similar to our tissue valve control. This iterative design approach may find application in preclinical assessment of valves for anticoagulation independence. Methods Tested valves included: prototype mechanical bi-leaflet BVs (n=56), controls (n=2) and patented early prototype mechanicals (n=2) from other investigators. Pulsatile and quasi-steady flow systems were used for testing. Projected dynamic valve area (PDVA) was measured using previously described novel technology. Flow velocity over the open and closing periods was determined by volumetric flow rate/PDVA. For the closed valve interval, use was made of data obtained from quasi-steady back pressure/flow tests. Performance was ranked by a proposed thrombogenicity potential index (TPI) relative to tissue and mechanical control valves. Results Optimization of the prototype valve designs lead to a 3-D printed model (BV3D). For the mitral/aortic site, BV3D has lower TPI (1.10/1.47) relative to the control mechanical valve (3.44/3.93) and similar to the control tissue valve (ideal TPI ≤1.0). Conclusions Using unique technology, rapid prototyping and thrombogenicity ranking, optimization of experimental valves for reduced thrombogenic potential was expedited and simplified. Innovative mechanical valve configurations were identified that merit consideration for further development which may bring the anti-coagulation independent mechanical valve within reach. PMID:26417581

Infective endocarditis of native valve after anterior nasal packing.

PubMed

Jayawardena, Suriya; Eisdorfer, Jacob; Indulkar, Shalaka; Zarkaria, Muhammad

2006-01-01

We present a case report of a patient who was previously treated for spontaneous epistaxis with a petroleum jelly gauze (0.5 in x 72 in) anterior nasal packing filled with an antibiotic ointment, along with prophylactic oral clindamycin. The patient presented with fever and hypotension 3 days after the nasal packing. Her blood cultures grew methicillin-resistant Staphylococcus aureus and the transesophageal echocardiography showed vegetation on the atrial surface of the posterior mitral valve leaflet, confirming the diagnosis of bacterial endocarditis attributable to nasal packing. Several case reports discuss toxic shock syndrome after nasal packing, but none describe endocarditis of the native heart valves subsequent to anterior nasal packing. Current guidelines on endocarditis prophylaxis produced by the American Heart Association, European Cardiac Society, and British Cardiac Society together with published evidence do not recommend endocarditis prophylaxis for patients with native heart valves undergoing anterior nasal packing.

Subaortic membrane mimicking hypertrophic cardiomyopathy.

PubMed

Anderson, Mark Joseph; Arruda-Olson, Adelaide; Gersh, Bernard; Geske, Jeffrey

2015-11-04

A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM. 2015 BMJ Publishing Group Ltd.

Subaortic membrane mimicking hypertrophic cardiomyopathy

PubMed Central

Anderson, Mark Joseph; Arruda-Olson, Adelaide; Gersh, Bernard; Geske, Jeffrey

2015-01-01

A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM. PMID:26538250

Transcatheter aortic valve implantation using anatomically oriented, marrow stromal cell-based, stented, tissue-engineered heart valves: technical considerations and implications for translational cell-based heart valve concepts.

PubMed

Emmert, Maximilian Y; Weber, Benedikt; Behr, Luc; Sammut, Sebastien; Frauenfelder, Thomas; Wolint, Petra; Scherman, Jacques; Bettex, Dominique; Grünenfelder, Jürg; Falk, Volkmar; Hoerstrup, Simon P

2014-01-01

While transcatheter aortic valve implantation (TAVI) has rapidly evolved for the treatment of aortic valve disease, the currently used bioprostheses are prone to continuous calcific degeneration. Thus, autologous, cell-based, living, tissue-engineered heart valves (TEHVs) with regeneration potential have been suggested to overcome these limitations. We investigate the technical feasibility of combining the concept of TEHV with transapical implantation technology using a state-of-the-art transcatheter delivery system facilitating the exact anatomical position in the systemic circulation. Trileaflet TEHVs fabricated from biodegradable synthetic scaffolds were sewn onto self-expanding Nitinol stents seeded with autologous marrow stromal cells, crimped and transapically delivered into the orthotopic aortic valve position of adult sheep (n = 4) using the JenaValve transapical TAVI System (JenaValve, Munich, Germany). Delivery, positioning and functionality were assessed by angiography and echocardiography before the TEHV underwent post-mortem gross examination. For three-dimensional reconstruction of the stent position of the anatomically oriented system, a computed tomography analysis was performed post-mortem. Anatomically oriented, transapical delivery of marrow stromal cell-based TEHV into the orthotopic aortic valve position was successful in all animals (n = 4), with a duration from cell harvest to TEHV implantation of 101 ± 6 min. Fluoroscopy and echocardiography displayed sufficient positioning, thereby entirely excluding the native leaflets. There were no signs of coronary obstruction. All TEHV tolerated the loading pressure of the systemic circulation and no acute ruptures occurred. Animals displayed intact and mobile leaflets with an adequate functionality. The mean transvalvular gradient was 7.8 ± 0.9 mmHg, and the mean effective orifice area was 1.73 ± 0.02 cm(2). Paravalvular leakage was present in two animals, and central aortic regurgitation due to a single-leaflet prolapse was detected in two, which was primarily related to the leaflet design. No stent dislocation, migration or affection of the mitral valve was observed. For the first time, we demonstrate the technical feasibility of a transapical TEHV delivery into the aortic valve position using a commercially available and clinically applied transapical implantation system that allows for exact anatomical positioning. Our data indicate that the combination of TEHV and a state-of-the-art transapical delivery system is feasible, representing an important step towards translational, transcatheter-based TEHV concepts.

Loss of Axin2 results in impaired heart valve maturation and subsequent myxomatous valve disease.

PubMed

Hulin, Alexia; Moore, Vicky; James, Jeanne M; Yutzey, Katherine E

2017-01-01

Myxomatous valve disease (MVD) is the most common aetiology of primary mitral regurgitation. Recent studies suggest that defects in heart valve development can lead to heart valve disease in adults. Wnt/β-catenin signalling is active during heart valve development and has been reported in human MVD. The consequences of increased Wnt/β-catenin signalling due to Axin2 deficiency in postnatal valve remodelling and pathogenesis of MVD were determined. To investigate the role of Wnt/β-catenin signalling, we analysed heart valves from mice deficient in Axin2 (KO), a negative regulator of Wnt/β-catenin signalling. Axin2 KO mice display enlarged mitral and aortic valves (AoV) after birth with increased Wnt/β-catenin signalling and cell proliferation, whereas Sox9 expression and collagen deposition are decreased. At 2 months in Axin2 KO mice, the valve extracellular matrix (ECM) is stratified but distal AoV leaflets remain thickened and develop aortic insufficiency. Progressive myxomatous degeneration is apparent at 4 months with extensive ECM remodelling and focal aggrecan-rich areas, along with increased BMP signalling. Infiltration of inflammatory cells is also observed in Axin2 KO AoV prior to ECM remodelling. Overall, these features are consistent with the progression of human MVD. Finally, Axin2 expression is decreased and Wnt/β-catenin signalling is increased in myxomatous mitral valves in a murine model of Marfan syndrome, supporting the importance of Wnt/β-catenin signalling in the development of MVD. Altogether, these data indicate that Axin2 limits Wnt/β-catenin signalling after birth and allows proper heart valve maturation. Moreover, dysregulation of Wnt/β-catenin signalling resulting from loss of Axin2 leads to progressive MVD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Polymer injection therapy to reverse remodel the papillary muscles: efficacy in reducing mitral regurgitation in a chronic ischemic model.

PubMed

Solis, Jorge; Levine, Robert A; Johnson, Benjamin; Guerrero, J Luis; Handschumacher, Mark D; Sullivan, Suzanne; Lam, Kaitlyn; Berlin, Jason; Braithwaite, Gavin J C; Muratoglu, Orhun K; Vlahakes, Gus J; Hung, Judy

2010-10-01

Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P=0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P=0.01), and leaflet closure area (8.8±1.3 cm(2)to 7.6±1.3 cm(2), P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P=NS), end-systolic elastance, τ (82±36 ms to 72±26, P=NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.

Electrical conduction disturbance effects on dynamic changes of functional mitral regurgitation.

PubMed

Fukuda, Shota; Grimm, Richard; Song, Jong-Min; Kihara, Takashi; Daimon, Masao; Agler, Deborah A; Wilkoff, Bruce L; Natale, Andrea; Thomas, James D; Shiota, Takahiro

2005-12-20

The aim of this study was to investigate the relationship between dynamics of functional mitral regurgitation (MR) and the degree of electrical conduction disturbance, and to evaluate the impact of cardiac resynchronization therapy (CRT) on MR severity and its phasic pattern. Mechanisms of phasic changes of functional MR, which may be determined by annulus dilation and tethering of the leaflet, remain unclear. Transthoracic two-dimensional echocardiography was performed in 60 patients with functional MR. A biventricular pacemaker was implanted in 19 patients. The mitral annulus area (MAA) and the tenting area (TA) were measured from apical views. The MR volume and fraction were assessed by the quantitative pulsed Doppler method. Instantaneous regurgitation flow rate was measured by proximal flow convergence method. A dynamic change in MR flow rate was evaluated by frame-by-frame analysis throughout systole. A phasic pattern with two peaks at early- and late-systole and decrease in mid-systole was noticed in 57 patients. The early-systolic peak of MR was larger than the late-systolic peak (128.4 +/- 64.3 ml/s vs. 73.9 +/- 55.1 ml/s, p < 0.001). The ratio of flow rate at these two peaks correlated with QRS duration (r = 0.55, p < 0.001). Early-systolic flow rate reduced after CRT (143.9 +/- 60.8 ml/s to 90.7 +/- 54.1 ml/s, p < 0.05), but late-systolic flow rate did not (61.5 +/- 55.0 ml/s to 51.2 +/- 40.9 ml/s, p = NS). A similar pattern was observed for TA, whereas MAA did not change after CRT. Biphasic pattern was found in functional MR, and the ratio of flow rate at two peaks correlated with QRS duration. The CRT decreased regurgitation flow volume by reducing early-systolic MR but not late-systolic MR, resulting in the change in phasic pattern of functional MR.

Tuna cornea as biomaterial for cardiac applications.

PubMed

Parravicini, Roberto; Cocconcelli, Flavio; Verona, Alessandro; Parravicini, Valeriano; Giuliani, Enrico; Barbieri, Alberto

2012-01-01

Among available biomaterials, cornea is almost completely devoid of cells and is composed only of collagen fibers oriented in an orderly pattern, which contributes to low antigenicity. Thunnus thynnus, the Atlantic bluefin tuna, is a fish with large eyes that can withstand pressures of approximately 10 MPa. We evaluated the potential of this tuna cornea in cardiac bioimplantation. Eyes from freshly caught Atlantic bluefin tuna were harvested and preserved in a fixative solution. Sterilized samples of corneal stroma were embedded in paraffin and stained with hematoxylin and eosin, and the histologic features were studied. Physical and mechanical resistance tests were performed in comparison with bovine pericardial strips and porcine mitral valves. Corneal material was implanted subcutaneously in 7 rats, to evaluate in vivo calcification rates. Mitral valves made from tuna corneal leaflets were implanted in 9 sheep. We found that the corneal tissue consisted only of parallel collagen fibers without evidence of vascular or neural structures. In tensile strength, the tuna corneal specimens were substantially similar to bovine pericardium. After 23 days, the rat-implanted samples showed no calcium or calcium salt deposition. Hydrodynamic and fatigue testing of valve prototypes yielded acceptable functional and long-term behavioral results. In the sheep, valvular performance was stable during the 180-day follow-up period, with no instrumental sign of calcification at the end of observation. We conclude that low antigenicity and favorable physical properties qualify tuna cornea as a potential material for durable bioimplantation. Further study is warranted.

Kocuria kristinae endocarditis related to diabetic foot infection.

PubMed

Citro, Rodolfo; Prota, Costantina; Greco, Luigi; Mirra, Marco; Masullo, Alfonso; Silverio, Angelo; Bossone, Eduardo; Piscione, Federico

2013-06-01

We report an unusual case of endocarditis occurring in a 74-year-old man with a history of systemic hypertension, diabetes mellitus and minor amputation for left forefoot ulcer. The patient was hospitalized for vacuum-assisted closure therapy to aid in wound healing. After the first treatment session, the patient reported abdominal pain with haematemesis and fever (40 °C). Owing to persistent fever, three blood cultures were performed, all positive for Kocuria kristinae. The identification was based on biochemical tests and automated systems. The speciation of the micro-organism was achieved with MALDI-TOF and then confirmed by 16S rRNA gene sequencing. Transthoracic echocardiographic examination showed the presence of a large vegetation (38×20 mm) on the posterior mitral leaflet and moderate mitral regurgitation. Since there are no current guidelines for the treatment of K. kristinae endocarditis, empiric antibiotic therapy with intravenous sulbactam/ampicillin (1.5 g twice daily) and gentamicin (6 mg kg(-1) per day) was started. After 7 days of hospitalization, the patient's condition suddenly worsened because of the occurrence of haemorrhagic stroke. Despite inotropic support and rifampicin infusion, the haemodynamic status progressively deteriorated. After an initial improvement, he worsened again, becoming stuporous, hypotensive and dyspnoeic. In the following days, the patient developed compartment syndrome resulting in right foot ischaemia. Unfortunately, 25 days after hospitalization, the patient died of multiple organ failure from overwhelming sepsis. To the best of our knowledge, this is the first case of K. kristinae endocarditis on a native valve that is not related to a central venous catheter but associated with diabetic foot infection.

Transcatheter Treatment of Tricuspid Regurgitation Using Edge-to-Edge Repair: Procedural Results, Clinical Implications and Predictors for Success.

PubMed

Lurz, Philipp; Besler, Christian; Noack, Thilo; Forner, Anna Flo; Bevilacqua, Carmine; Seeburger, Joerg; Rommel, Karl-Philipp; Blazek, Stephan; Hartung, Philipp; Zimmer, Marion; Mohr, Friedrich; Schuler, Gerhard; Linke, Axel; Ender, Joerg; Thiele, Holger

2018-04-10

To analyze the feasibility, safety and effectiveness of Tricuspid valve (TV) repair using the MitraClip system in patients at high surgical risk. Forty-two elderly high-risk patients (76.8±7.3 years, EuroScore II 8.1±5.7) with isolated TR or combined TR and mitral regurgitation (MR) underwent edge-to-edge repair of the TV (n=11) or combined edge-to-edge repair of the TV and mitral valve (n=31). Procedural details, success rate, impact on TR severity and predictors for success at 30 day follow-up were analyzed. Successful edge-to-edge repair of TR was achieved in 35/42 patients (83%, 68 clips in total, 94% in the anteroseptal commissure, 6% in the posteroseptal commissure). In 5 patients, grasping of the leaflets was impossible and two patients had no decrease in TR after clipping. In those with procedural success, clipping of the TV led to a reduction in effective regurgitant orifice area by -62,5 % (from 0.8±0.4 to 0.3±0.2 cm2; p<0.0001). In both, patients with isolated TV and combined procedures, 6 minute walking distance improved (from 285±118 to 344±81 and 225±113 to 261±130 m, p=0.02 and 0.03, respectively). Predominant anteroseptal or central TR was identified as predictor of procedural success (p=0.025). Edge-to-edge repair of the TV is feasible with promising reduction in TR, which could result in clinical improvement.

The Double-Orifice Valve Technique to Treat Tricuspid Valve Incompetence.

PubMed

Hetzer, Roland; Javier, Mariano; Delmo Walter, Eva Maria

2016-01-01

A straightforward tricuspid valve (TV) repair technique was used to treat either moderate or severe functional (normal valve with dilated annulus) or for primary/organic (Ebstein's anomaly, leaflet retraction/tethering and chordal malposition/tethering, with annular dilatation) TV incompetence, and its long-term outcome assessed. A double-orifice valve technique was employed in 91 patients (mean age 52.6 ± 23.2 years; median age 56 years; range: 0.6-82 years) with severe tricuspid regurgitation. Among the patients, three had post-transplant iatrogenic chordal rupture, five had infective endocarditis, 11 had mitral valve insufficiency, 23 had Ebstein's anomaly, and 47 had isolated severe TV incompetence. The basic principle was to reduce the distance between the coapting leaflets, wherein the most mobile leaflet could coapt to the opposite leaflet, by creating two orifices, ensuring valve competence. The TV repair was performed through a median sternotomy or right anterior thoracotomy in the fifth intercostal space under cardiopulmonary bypass. The degree and extent of creating a double-valve orifice was determined by considering the minimal body surface area (BSA)-related acceptable TV diameter. Repair was accomplished by passing pledgeted mattress sutures from the middle of the true anterior annulus to a spot on the opposite septal annulus, located approximately two-thirds of the length of the septal annulus to avoid injury to the bundle of His. The annular apposition divides the TV into a larger anterior and a smaller posterior orifices, enabling valve closure, on both sides. In adults, the diameter of the anterior valve orifice should be 23-25 mm, and the posterior orifice 15-18 mm; thus, the total valve orifice area is 5-6 cm2. In children, the total valve orifice should be a standard deviation of 1.7 mm for a BSA of <1. 0m2, and 1.5 mm for a BSA of >1.0m2. During a mean follow up of 8.7 ± 1.34 years (median 10 years; range: 1.5-25.9 years) there have been no reoperations for TV insufficiency or stenosis. Reoperations on three patients (mean age 42.5 ± 8.7 years) were indicated for aortic valve replacement at 14 months postoperatively (n = 1) and for assist device implantation (n = 2) who eventually underwent heart transplant at 18 and 20 months after TV repair, respectively. The cumulative 12-year survival rate was 86.9%. This double-orifice technique is technically a straightforward repair to abolish TV incompetence with highly satisfactory results, particularly in patients with severe annular dilatation or with leaflet and chordal tethering. In the present series, the technique provided no pitfalls (if the location of the conduction system was borne in mind), requiring only a gentle placement of sutures. It also led to no residual regurgitation or reoperation during the follow up period.

Pulsed cavitational ultrasound for non-invasive chordal cutting guided by real-time 3D echocardiography.

PubMed

Villemain, Olivier; Kwiecinski, Wojciech; Bel, Alain; Robin, Justine; Bruneval, Patrick; Arnal, Bastien; Tanter, Mickael; Pernot, Mathieu; Messas, Emmanuel

2016-10-01

Basal chordae surgical section has been shown to be effective in reducing ischaemic mitral regurgitation (IMR). Achieving this section by non-invasive mean can considerably decrease the morbidity of this intervention on already infarcted myocardium. We investigated in vitro and in vivo the feasibility and safety of pulsed cavitational focused ultrasound (histotripsy) for non-invasive chordal cutting guided by real-time 3D echocardiography. Experiments were performed on 12 sheep hearts, 5 in vitro on explanted sheep hearts and 7 in vivo on beating sheep hearts. In vitro, the mitral valve (MV) apparatus including basal and marginal chordae was removed and fixed on a holder in a water tank. High-intensity ultrasound pulses were emitted from the therapeutic device (1-MHz focused transducer, pulses of 8 µs duration, peak negative pressure of 17 MPa, repetition frequency of 100 Hz), placed at a distance of 64 mm under 3D echocardiography guidance. In vivo, after sternotomy, the same therapeutic device was applied on the beating heart. We analysed MV coaptation and chordae by real-time 3D echocardiography before and after basal chordal cutting. After sacrifice, the MV apparatus were harvested for anatomical and histological post-mortem explorations to confirm the section of the chordae. In vitro, all chordae were completely cut after a mean procedure duration of 5.5 ± 2.5 min. The procedure duration was found to increase linearly with the chordae diameter. In vivo, the central basal chordae of the anterior leaflet were completely cut. The mean procedure duration was 20 ± 9 min (min = 14, max = 26). The sectioned chordae was visible on echocardiography, and MV coaptation remained normal with no significant mitral regurgitation. Anatomical and histological post-mortem explorations of the hearts confirmed the section of the chordae. Histotripsy guided by 3D echo achieved successfully to cut MV chordae in vitro and in vivo in beating heart. We hope that this technique will open the door in the near future to the non-invasive treatment of functional IMR. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Long-term effects of sildenafil in a rat model of chronic mitral regurgitation: benefits of ventricular remodeling and exercise capacity.

PubMed

Kim, Kyung-Hee; Kim, Yong-Jin; Ohn, Jung-Hun; Yang, Jimin; Lee, Sang-Eun; Lee, Sae-Won; Kim, Hyung-Kwan; Seo, Jeong-Wook; Sohn, Dae-Won

2012-03-20

We tested the hypothesis that chronic treatment with sildenafil attenuates left ventricular (LV) remodeling and prevents exercise intolerance in chronic mitral regurgitation (MR). MR was created in Sprague-Dawley rats by making a hole on the mitral leaflet. Two weeks after MR creation, MR and LV dilatation were confirmed by echocardiography, and rats were randomly assigned to sildenafil treatment (MR+sildenafil group; 50 mg/kg PO twice a day; n=16) or normal saline only (MR group; n=16) and continued for 4 months. Sixteen sham rats were compared with MR rats. After 4 months, LV size was smaller in the MR+sildenafil compared with the MR group (LV end-systolic dimension, 4.7±0.3 for sham versus 5.9±0.3 for MR+sildenafil versus 7.4±0.5 mm for MR; P<0.05; LV end-diastolic dimension, 8.3±0.4 versus 10.5±0.2 versus 11.7±0.61 mm, respectively; P<0.05). LV ejection fraction was greater in the MR+sildenafil group than in the MR group (70.2±2.2 for sham versus 67.0±4.2 for MR+sildenafil versus 58.9±2.5 for MR; P=0.01). Serial treadmill test revealed that exercise capacity was reduced in the MR but not in the MR+sildenafil group. Transcriptional profiling of cardiac apical tissues revealed that gene sets related to inflammatory response, DNA damage response, cell cycle checkpoint, and cellular signaling pathways were significantly enriched by genes with reciprocal changes. Pathological analysis showed that perivascular fibrosis was more prominent in the MR than in the MR+sildenafil group and that the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells was 2-fold greater in the MR compared with the MR+sildenafil group. Sildenafil significantly attenuates LV remodeling and prevents exercise intolerance in a rat model of chronic MR. This benefit may be associated with the antiapoptotic, anti-inflammatory effects of sildenafil.

Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease.

PubMed

Marjanovic, Irena; Kostic, Jelena; Stanic, Bojana; Pejanovic, Nadja; Lucic, Bojana; Karan-Djurasevic, Teodora; Janic, Dragana; Dokmanovic, Lidija; Jankovic, Srdja; Vukovic, Nada Suvajdzic; Tomin, Dragica; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Pavlovic, Sonja; Tosic, Natasa

2016-10-01

The age-specific differences in the genetic mechanisms of myeloid leukemogenesis have been observed and studied previously. However, NGS technology has provided a possibility to obtain a large amount of mutation data. We analyzed DNA samples from 20 childhood (cAML) and 20 adult AML (aAML) patients, using NGS targeted sequencing. The average coverage of high-quality sequences was 2981 × per amplicon. A total of 412 (207 cAML, 205 aAML) variants in the coding regions were detected; out of which, only 122 (62 cAML and 60 aAML) were potentially protein-changing. Our results confirmed that AML contains small number of genetic alterations (median 3 mutations/patient in both groups). The prevalence of the most frequent single gene AML associated mutations differed in cAML and aAML patient cohorts: IDH1 (0 % cAML, 5 % aAML), IDH2 (0 % cAML, 10 % aAML), NPM1 (10 % cAML, 35 % aAML). Additionally, potentially protein-changing variants were found in tyrosine kinase genes or genes encoding tyrosine kinase associated proteins (JAK3, ABL1, GNAQ, and EGFR) in cAML, while among aAML, the prevalence is directed towards variants in the methylation and histone modifying genes (IDH1, IDH2, and SMARCB1). Besides uniform genomic profile of AML, specific genetic characteristic was exclusively detected in cAML and aAML.

Cyclic Mechanical Loading Is Essential for Rac1-Mediated Elongation and Remodeling of the Embryonic Mitral Valve.

PubMed

Gould, Russell A; Yalcin, Huseyin C; MacKay, Joanna L; Sauls, Kimberly; Norris, Russell; Kumar, Sanjay; Butcher, Jonathan T

2016-01-11

During valvulogenesis, globular endocardial cushions elongate and remodel into highly organized thin fibrous leaflets. Proper regulation of this dynamic process is essential to maintain unidirectional blood flow as the embryonic heart matures. In this study, we tested how mechanosensitive small GTPases, RhoA and Rac1, coordinate atrioventricular valve (AV) differentiation and morphogenesis. RhoA activity and its regulated GTPase-activating protein FilGAP are elevated during early cushion formation but decreased considerably during valve remodeling. In contrast, Rac1 activity was nearly absent in the early cushions but increased substantially as the valve matured. Using gain- and loss-of-function assays, we determined that the RhoA pathway was essential for the contractile myofibroblastic phenotype present in early cushion formation but was surprisingly insufficient to drive matrix compaction during valve maturation. The Rac1 pathway was necessary to induce matrix compaction in vitro through increased cell adhesion, elongation, and stress fiber alignment. Facilitating this process, we found that acute cyclic stretch was a potent activator of RhoA and subsequently downregulated Rac1 activity via FilGAP. On the other hand, chronic cyclic stretch reduced active RhoA and downstream FilGAP, which enabled Rac1 activation. Finally, we used partial atrial ligation experiments to confirm in vivo that altered cyclic mechanical loading augmented or restricted cushion elongation and thinning, directly through potentiation of active Rac1 and active RhoA, respectively. Together, these results demonstrate that cyclic mechanical signaling coordinates the RhoA to Rac1 signaling transition essential for proper embryonic mitral valve remodeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cardiac Calcifications on Echocardiography Are Associated with Mortality and Stroke.

PubMed

Lu, Marvin Louis Roy; Gupta, Shuchita; Romero-Corral, Abel; Matejková, Magdaléna; De Venecia, Toni; Obasare, Edinrin; Bhalla, Vikas; Pressman, Gregg S

2016-12-01

Calcium deposits in the aortic valve and mitral annulus have been associated with cardiovascular events and mortality. However, there is no accepted standard method for scoring such cardiac calcifications, and most existing methods are simplistic. The aim of this study was to test the hypothesis that a semiquantitative score, one that accounts for all visible calcium on echocardiography, could predict all-cause mortality and stroke in a graded fashion. This was a retrospective study of 443 unselected subjects derived from a general echocardiography database. A global cardiac calcium score (GCCS) was applied that assigned points for calcification in the aortic root and valve, mitral annulus and valve, and submitral apparatus, and points for restricted leaflet mobility. The primary outcome was all-cause mortality, and the secondary outcome was stroke. Over a mean 3.8 ± 1.7 years of follow-up, there were 116 deaths and 34 strokes. Crude mortality increased in a graded fashion with increasing GCCS. In unadjusted proportional hazard analysis, the GCCS was significantly associated with total mortality (hazard ratio, 1.26; 95% CI, 1.17-1.35; P < .0001) and stroke (hazard ratio, 1.23; 95% CI, 1.07-1.40; P = .003). After adjusting for demographic and clinical factors (age, gender, body mass index, diabetes, hypertension, dyslipidemia, smoking, family history of coronary disease, chronic kidney disease, history of atrial fibrillation, and history of stroke), these associations remained significant. The GCCS is easily applied to routinely acquired echocardiograms and has clinically significant associations with total mortality and stroke. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Association of A Dilated Coronary Sinus in the Fetus with Actual and Apparent Coarctation of the Aorta and Diminutive Left Heart Structures.

PubMed

Ramaswamy, Prema; Rafii, Daniela; Osmolovsky, Marina; Agarwal, Arpit; Amirtharaj, Cynthia

2016-12-01

Evidence suggests an association between left heart obstructive lesions and dilated coronary sinus (DCS), but this has not been studied in fetuses. A retrospective review of fetal echocardiograms (FE) over an 8-year period was conducted, and patients with DCS were identified and confirmed postnatally. There were 5840 FE performed on 4920 women during this period. Of 49 patients with DCS, 22 had normal intracardiac anatomy and 27 patients had congenital heart disease (CHD) yielding an incidence of 4.6 % in the presence of CHD (27/584). Of 27 patients with DCS and CHD, approximately a third had either hypoplastic left ventricles and/or coarctations (10/27, 37 %). The incidence of left heart obstructive lesions was much higher in the presence of a DCS (37 % vs 45/557, 8 %, p < 0.0001). The odds ratio of left heart hypoplasia in fetuses with CHD and a DCS was 6.6 (95 % CI 2.8-15.3). Comparison of patients with postnatally confirmed coarctation with those with normal intracardiac anatomy with DCS, revealed that in the former, the right ventricle (p = 0.005), pulmonic valve annulus (p = 0.0001) and the tricuspid inflow were larger (p = 0.001) compared to corresponding left-sided structures. The size of the DCS was not significantly different between the two groups, but in the former, the DCS was more closely related to the posterior leaflet of the mitral valve and caused a significant diminution of the mitral inflow. Our study suggests a strong association, possibly causal, between left heart obstructive lesions and DCS in utero.

Impact of timing and surgical approach on outcomes after mitral valve regurgitation operations.

PubMed

Stevens, Louis-Mathieu; Rodriguez, Evelio; Lehr, Eric J; Kindell, Linda C; Nifong, L Wiley; Ferguson, T Bruce; Chitwood, W Randolph

2012-05-01

This study investigated whether the timing of mitral valve (MV) repair or surgical approach affects outcomes in patients with MV regurgitation. Between 1992 and 2009, 2,255 patients underwent MV operations, including 1,305 with isolated MV regurgitation operations (1,054 repairs, 251 replacements). Surgical approaches were sternotomy in 377, video-assisted right minithoracotomy in 481, or robot-assisted in 447. Mean follow-up was 6.4±4.5 years (maximum, 19 years). Sternotomy MV repairs decreased during the study while minimally invasive MV repairs increased. Robotic MV repair patients were younger, with fewer women, had better left ventricular ejection fractions, and were more likely to have myxomatous degeneration (all p<0.001). The robotic approach led to a higher MV repair rate and increased use of leaflet/chordal procedures but had longer cardiopulmonary bypass and aortic cross-clamp times (all p<0.001). The 30-day mortality for isolated MV repair was similar for all approaches (p=0.409). Fewer neurological events were observed in the videoscopic and robotic groups (p=0.013). Adjusted survival was similar for all approaches (p=0.357). Survival in patients in New York Heart Association class I to II with myxomatous degeneration or annular dilatation was similar to a matched population but was worse for patients in class III to IV or undergoing MV replacement. MV repair in patients with severe MV regurgitation should be performed before New York Heart Association class III to IV symptoms develop. Minimally invasive MV repair techniques render similar outcomes as the sternotomy approach. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Recurrent left atrial myxoma in Carney complex

PubMed Central

Wang, Liaoyuan; Wang, Qing; Zhou, Yue; Xue, Qian; Sun, Xiao; Wang, Zhinong; Ji, Guangyu

2018-01-01

Abstract Rationale: Carney complex (CNC) accounts for up to two-thirds of familial cardiac myxoma, which is a rare autosomal dominant syndrome characterized by multiple mucocutaneous lesions and endocrine tumors. Mutation in the cAMP-dependent protein kinase A (PKA) regulatory (R) subunit 1 (PRKAR1A) gene has been identified as a cause of CNC. In this article, we report 3 first-degree relatives with cardiac myxoma who were diagnosed with CNC and underwent surgical resection. Presenting concerns: The recurrence of cardiac myxoma was detected in a 45-year-old male by echocardiography 5 years after the resection was carried out, without any additional symptoms. Family screening indicated that his brother and his brother's son also had a history of cardiac myxoma. Diagnosis: The echocardiography of the patient showed a 43 mm × 28 mm echo mass at the bottom of the atrial septum near anterior mitral leaflet. Sequencing of the patient's genomic DNA obtained from peripheral blood identified a p.E17X (c.491-492delTG) mutation in PRKAR1A, which encodes the type Iα regulatory subunit of protein kinase A. Interventions: The patient received redo cardiac myxoma resection and mitral valve repair under cardiopulmonary bypass. Echocardiographic surveillance was conducted after the surgery. Outcomes: The patient recovered quickly after the surgery and was discharged without any abnormality detected by echocardiography. Follow-up after 1 year showed no recurrence of the cardiac myxoma. Main lesson: We recommend echocardiographic surveillance of the affected individuals and their first-degree relatives at regular intervals, given the high risk of recurrence and the morbidity and mortality associated with cardiac tumors in any location. PMID:29561454

Rapidly Progressive Seeding of a Community Acquired Pathogen in an Immune-competent Host--End Organ Damage from Head to Bone.

PubMed

Torres-Miranda, Daisy; Al-Saffar, Farah; Ibrahim, Saif; Font-Diaz, Stephanie

2015-01-01

This report describes a 64-years-old male patient that presented to our hospital with a chief complaint of acute worsening of his usual chronic lower back pain, progressive weakness in lower extremities and subjective fevers at home. Spine CT failed to demonstrate any infectious foci but showed partially visualized lung cavitary lesion and renal pole abnormalities. Blood cultures grew methicillin-sensitive Staphylococcus Aureus (MSSA). Transthoracic echocardiogram (TTE) showed no signs of infective endocarditis (IE). Later, the patient experienced an acute deterioration on clinical status and examination showed development of a new murmur. He also developed new hemiparesis with up-going babinski reflex. A head MRI showed multiple infarcts. MRI spine displayed osteomyelitis at T12-L1. Cerebro-spinal fluid was positive for meningitis. A transesophageal echocardiogram (TEE) was performed demonstrating new severe mitral and mild tricuspid regurgitations with a definitive 1.5 cm mobile vegetation on posterior mitral leaflet. We present is a very interesting case of a rapidly progressive MSSA infection. MSSA meningitis is a rare disease; there are only few reported cases in the literature to date. We describe a case of MSSA bacteremia, of questionable source, that resulted in MSSA endocarditis affecting right and left heart in a patient who did not have a history of intravenous drug use (IVDU) or immunosuppression. The case was complicated by septic emboli to systemic circulation involving the kidneys, vertebral spine (osteomyelitis), lungs and brain with consequent meningitis and stroke. Even when MSSA infections are well known, to our knowledge there are no previous case reports describing such an acute-simultaneous-manifestation of multi-end-organ failure, including meningitis and stroke. These latter are rarely reported, even individually.

Vortex shedding in bileaflet heart valve prostheses.

PubMed

Gross, J M; Shermer, C D; Hwang, N H

1988-01-01

A dynamic study of two geometrically similar bileaflet heart valve prostheses (HVP) was performed using a physiologic mock circulatory flow loop. The HVPs studied were the 25 mm St. Jude Medical (SJM) and the 25 mm Carbomedics (CMI) in the aortic position and the 27 mm SJM and 27 mm CMI in the mitral position. All data were collected at a heart rate of 70 beats/min and a cardiac output of 5.0 L/min. Flow visualization was conducted in the transparent flow chambers of the pulsatile mock circulatory flow loop using a 15 mW He-Ne laser light source. A cylindrical lens and optics system converted the incident laser beam into a thin parallel light plane, and 420 microns tracer particles were suspended in the testing fluid to illuminate the flow field at selected planes. Frame-by-frame analysis of the 16 mm high-speed cine provides detailed phasic flow patterns in the vicinity of the HVP. A series of still photographs of flow patterns, taken at approximately 22.5 degrees phase intervals, are sequentially presented for each HVP. In the aortic position, a Karman-like vortex pattern appears downstream of the SJM at the end of the ejection phase. The CMI exhibits a rather symmetrical ejection flow pattern that turns into random motion immediately after the onset of ejection. In the mitral position, the SJM again exhibits a strong core flow during ventricular filling, whereas the CMI produces a more diffuse pattern during the same period. A pair of vortices shed from both the SJM and CMI are clearly visible toward the end of the ventricular filling phase. The vortex mechanisms are discussed in light of leaflet boundary layer formation.

High frequency of AML1/RUNX1 point mutations in radiation-associated myelodysplastic syndrome around Semipalatinsk nuclear test site.

PubMed

Zharlyganova, Dinara; Harada, Hironori; Harada, Yuka; Shinkarev, Sergey; Zhumadilov, Zhaxybay; Zhunusova, Aigul; Tchaizhunusova, Naylya J; Apsalikov, Kazbek N; Kemaikin, Vadim; Zhumadilov, Kassym; Kawano, Noriyuki; Kimura, Akiro; Hoshi, Masaharu

2008-09-01

It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, we investigated the AML1 mutations in radiation-exposed patients with MDS/AML among the residents near the Semipalatinsk Nuclear Test Site (SNTS), where the risk of solid cancers and leukemias was increased due to the radiation effects. AML1 mutations were identified in 7 (39%) of 18 radiation-exposed MDS/AML patients. In contrast, no AML1 mutation was found in 13 unexposed MDS/AML cases. The frequency of AML1 mutations in radiation-exposed patients with MDS/AML was significantly higher compared with unexposed patients (p < 0.05).We also found a significant correlation between individual estimated doses and AML1 mutations (p < 0.05). Considering these results, AML1 point mutations might be a useful biomarker that differentiates radio-induced MDS/AML from spontaneous MDS/AML.

Doctors and pharmacists provision and opinions of medicines information leaflets in New Zealand.

PubMed

Young, Amber; Tordoff, June; Leitch, Sharon; Smith, Alesha

2018-06-01

Background Providing verbal medicines information to patients may be insufficient. Providing medicine information leaflets could support verbal information, however New Zealand health professionals' opinions or use of leaflets is unknown. Objective To examine self-reported provision and health professionals' views about medicine information leaflets and to determine their support for tailoring patient leaflets. Setting A cross sectional survey of general practitioners (GPs) and community pharmacists in New Zealand primary care. Method GPs and pharmacists completed validated questionnaires. Data was collected using SurveyMonkey® and where applicable, Chi squared analysis was carried out. Main outcome measures Frequency of leaflet provision, how leaflets are used in practice and why, likes and dislikes of available leaflets, and opinions on providing tailored information. Results 143 GPs and 126 pharmacists responded. For new medicines, significantly more pharmacists than GPs reported providing leaflets all or most of the time. For repeat medicines, leaflets were more likely to be given only on request. Leaflets were given to ensure patients are well-informed. Most GPs and pharmacists report discussing sections of leaflets with patients. The likes and dislikes of leaflets were mostly about design and content. Both professions support tailoring leaflets to meet individual's requirements. Conclusions Provision of medicines information needs to be re-evaluated. Relying on verbal communication is inadequate and leaflet provision appears to be suboptimal. Making leaflets more patient-centred and accessible could improve health professionals' perceptions and use of them. Automated creation and provision of tailored summary leaflets would be beneficial. Further advantage could be gained by digital patient access.

Allometric scaling of echocardiographic measurements in healthy Spanish foals with different body weight.

PubMed

Rovira, S; Muñoz, A; Rodilla, V

2009-04-01

Scaling in biology is usually allometric, and therefore, the size of the heart may be expressed as a power function of body weight (BW). The present research analyses the echocardiographic measurements in 68 healthy Spanish foals weighed between 70 and 347kg in order to determine the correct scaling exponent for the allometric equation. The echocardiographic parameters measured were: left ventricular internal dimensions (LVID), free wall thickness (LVFWT), interventricular septum thickness (IVST) at systole (s) and diastole (d), EPSS (distance between the point E of the mitral valve and the interventricular septum), and aorta diameters at the level of the aortic valve (AOD), base of valve leaflets (ABS), sinus of Valsalva (ASV) and sino-tubular junction (AJT). Indices of left ventricular performance were calculated. It was found that LVIDd, IVSTs, AOD, and ASV have a relationship to BW raised to 0.300-0.368 power, whereas left ventricular end-diastolic volume and stroke volume scaled to BW raised to 0.731-0.712 power. With these data, appropriate values can be calculated for normal Spanish foals.

Medicine information leaflets for non-steroidal anti-inflammatory drugs in Thailand.

PubMed

Phueanpinit, Pacharaporn; Pongwecharak, Juraporn; Krska, Janet; Jarernsiripornkul, Narumol

2016-02-01

The importance of promoting the use of patient-oriented medicines leaflets is recognized in many countries. Leaflets should include basic information plus specific warnings, and be provided with all medicines, but there is little attempt at enforcement of these requirements in Thailand. To determine content and availability of Thai information leaflets for nonsteroidal anti-inflammatory drugs (NSAIDs). Leaflets for all NSAIDs available for purchase from 34 pharmacies in a large city were evaluated against a checklist and number of leaflets assessed against number of medicine packs available in each pharmacy. Of the 76 leaflets for ten different NSAIDs, 67 (88 %) were for locally manufactured products. Only 22 % of 76 leaflets were sufficient in number for distribution with medicines, while only 4 % had patient-oriented leaflets. No leaflet covered all topics in the checklist. Less than half included safety information, such as contraindications (46 %), precautions (47 %), and adverse drug reactions (34 %). Locally-produced leaflets provided less information than those for originator products and no leaflet included all the warnings required by Thai regulations. This study illustrates the variable availability and quality of NSAID information leaflets. The lack of accessible essential information about medicines in Thailand requires urgent attention to enable patients to minimise adverse reactions.

Impact of Clinically Relevant Elliptical Deformations on the Damage Patterns of Sagging and Stretched Leaflets in a Bioprosthetic Heart Valve.

PubMed

Sritharan, Deepa; Fathi, Parinaz; Weaver, Jason D; Retta, Stephen M; Wu, Changfu; Duraiswamy, Nandini

2018-06-12

After implantation of a transcatheter bioprosthetic heart valve its original circular circumference may become distorted, which can lead to changes in leaflet coaptation and leaflets that are stretched or sagging. This may lead to early structural deterioration of the valve as seen in some explanted transcatheter heart valves. Our in vitro study evaluates the effect of leaflet deformations seen in elliptical configurations on the damage patterns of the leaflets, with circular valve deformation as the control. Bovine pericardial tissue heart valves were subjected to accelerated wear testing under both circular (N = 2) and elliptical (N = 4) configurations. The elliptical configurations were created by placing the valve inside custom-made elliptical holders, which caused the leaflets to sag or stretch. The hydrodynamic performance of the valves was monitored and high resolution images were acquired to evaluate leaflet damage patterns over time. In the elliptically deformed valves, sagging leaflets experienced more damage from wear compared to stretched leaflets; the undistorted leaflets of the circular valves experienced the least leaflet damage. Free-edge thinning and tearing were the primary modes of damage in the sagging leaflets. Belly region thinning was seen in the undistorted and stretched leaflets. Leaflet and fabric tears at the commissures were seen in all valve configurations. Free-edge tearing and commissure tears were the leading cause of valve hydrodynamic incompetence. Our study shows that mechanical wear affects heart valve pericardial leaflets differently based on whether they are undistorted, stretched, or sagging in a valve configuration. Sagging leaflets are more likely to be subjected to free-edge tear than stretched or undistorted leaflets. Reducing leaflet stress at the free edge of non-circular valve configurations should be an important factor to consider in the design and/or deployment of transcatheter bioprosthetic heart valves to improve their long-term performance.

The Relation Between Collagen Fibril Kinematics and Mechanical Properties in the Mitral Valve Anterior Leaflet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao,J.; Yang, L.; Grashow, J.

2007-01-01

We have recently demonstrated that the mitral valve anterior leaflet (MVAL) exhibited minimal hysteresis, no strain rate sensitivity, stress relaxation but not creep (Grashow et al., 2006, Ann Biomed Eng., 34(2), pp. 315-325; Grashow et al., 2006, Ann Biomed. Eng., 34(10), pp. 1509-1518). However, the underlying structural basis for this unique quasi-elastic mechanical behavior is presently unknown. As collagen is the major structural component of the MVAL, we investigated the relation between collagen fibril kinematics (rotation and stretch) and tissue-level mechanical properties in the MVAL under biaxial loading using small angle X-ray scattering. A novel device was developed and utilizedmore » to perform simultaneous measurements of tissue level forces and strain under a planar biaxial loading state. Collagen fibril D-period strain ({epsilon}{sub D}) and the fibrillar angular distribution were measured under equibiaxial tension, creep, and stress relaxation to a peak tension of 90 N/m. Results indicated that, under equibiaxial tension, collagen fibril straining did not initiate until the end of the nonlinear region of the tissue-level stress-strain curve. At higher tissue tension levels, {epsilon}{sub D} increased linearly with increasing tension. Changes in the angular distribution of the collagen fibrils mainly occurred in the tissue toe region. Using {epsilon}{sub D}, the tangent modulus of collagen fibrils was estimated to be 95.5{+-}25.5 MPa, which was {approx}27 times higher than the tissue tensile tangent modulus of 3.58{+-}1.83 MPa. In creep tests performed at 90 N/m equibiaxial tension for 60 min, both tissue strain and D remained constant with no observable changes over the test length. In contrast, in stress relaxation tests performed for 90 min {epsilon}{sub D} was found to rapidly decrease in the first 10 min followed by a slower decay rate for the remainder of the test. Using a single exponential model, the time constant for the reduction in collagen fibril strain was 8.3 min, which was smaller than the tissue-level stress relaxation time constants of 22.0 and 16.9 min in the circumferential and radial directions, respectively. Moreover, there was no change in the fibril angular distribution under both creep and stress relaxation over the test period. Our results suggest that (1) the MVAL collagen fibrils do not exhibit intrinsic viscoelastic behavior, (2) tissue relaxation results from the removal of stress from the fibrils, possibly by a slipping mechanism modulated by noncollagenous components (e.g. proteoglycans), and (3) the lack of creep but the occurrence of stress relaxation suggests a 'load-locking' behavior under maintained loading conditions. These unique mechanical characteristics are likely necessary for normal valvular function.« less

Chromosomal Minimal Critical Regions in Therapy-Related Leukemia Appear Different from Those of De Novo Leukemia by High-Resolution aCGH

PubMed Central

Itzhar, Nathalie; Dessen, Philippe; Toujani, Saloua; Auger, Nathalie; Preudhomme, Claude; Richon, Catherine; Lazar, Vladimir; Saada, Véronique; Bennaceur, Anelyse; Bourhis, Jean Henri; de Botton, Stéphane; Bernheim, Alain

2011-01-01

Therapy-related acute leukemia (t-AML), is a severe complication of cytotoxic therapy used for primary cancer treatment. The outcome of these patients is poor, compared to people who develop de novo acute leukemia (p-AML). Cytogenetic abnormalities in t-AML are similar to those found in p-AML but present more frequent unfavorable karyotypes depending on the inducting agent. Losses of chromosome 5 or 7 are observed after alkylating agents while balanced translocations are found after topoisomerase II inhibitors. This study compared t-AML to p-AML using high resolution array CGH in order to find copy number abnormalities (CNA) at a higher resolution than conventional cytogenetics. More CNAs were observed in 30 t-AML than in 36 p-AML: 104 CNAs were observed with 63 losses and 41 gains (mean number 3.46 per case) in t-AML, while in p-AML, 69 CNAs were observed with 32 losses and 37 gains (mean number of 1.9 per case). In primary leukemia with a previously “normal” karyotype, 18% exhibited a previously undetected CNA, whereas in the (few) t-AML with a normal karyotype, the rate was 50%. Several minimal critical regions (MCRs) were found in t-AML and p-AML. No common MCRs were found in the two groups. In t-AML a 40kb deleted MCR pointed to RUNX1 on 21q22, a gene coding for a transcription factor implicated in frequent rearrangements in leukemia and in familial thrombocytopenia. In de novo AML, a 1Mb MCR harboring ERG and ETS2 was observed from patients with complex aCGH profiles. High resolution cytogenomics obtained by aCGH and similar techniques already published allowed us to characterize numerous non random chromosome abnormalities. This work supports the hypothesis that they can be classified into several categories: abnormalities common to all AML; those more frequently found in t-AML and those specifically found in p-AML. PMID:21339820

Chromosomal minimal critical regions in therapy-related leukemia appear different from those of de novo leukemia by high-resolution aCGH.

PubMed

Itzhar, Nathalie; Dessen, Philippe; Toujani, Saloua; Auger, Nathalie; Preudhomme, Claude; Richon, Catherine; Lazar, Vladimir; Saada, Véronique; Bennaceur, Anelyse; Bourhis, Jean Henri; de Botton, Stéphane; Bernheim, Alain

2011-02-14

Therapy-related acute leukemia (t-AML), is a severe complication of cytotoxic therapy used for primary cancer treatment. The outcome of these patients is poor, compared to people who develop de novo acute leukemia (p-AML). Cytogenetic abnormalities in t-AML are similar to those found in p-AML but present more frequent unfavorable karyotypes depending on the inducting agent. Losses of chromosome 5 or 7 are observed after alkylating agents while balanced translocations are found after topoisomerase II inhibitors. This study compared t-AML to p-AML using high resolution array CGH in order to find copy number abnormalities (CNA) at a higher resolution than conventional cytogenetics. More CNAs were observed in 30 t-AML than in 36 p-AML: 104 CNAs were observed with 63 losses and 41 gains (mean number 3.46 per case) in t-AML, while in p-AML, 69 CNAs were observed with 32 losses and 37 gains (mean number of 1.9 per case). In primary leukemia with a previously "normal" karyotype, 18% exhibited a previously undetected CNA, whereas in the (few) t-AML with a normal karyotype, the rate was 50%. Several minimal critical regions (MCRs) were found in t-AML and p-AML. No common MCRs were found in the two groups. In t-AML a 40 kb deleted MCR pointed to RUNX1 on 21q22, a gene coding for a transcription factor implicated in frequent rearrangements in leukemia and in familial thrombocytopenia. In de novo AML, a 1 Mb MCR harboring ERG and ETS2 was observed from patients with complex aCGH profiles. High resolution cytogenomics obtained by aCGH and similar techniques already published allowed us to characterize numerous non random chromosome abnormalities. This work supports the hypothesis that they can be classified into several categories: abnormalities common to all AML; those more frequently found in t-AML and those specifically found in p-AML.

High incidence of biallelic point mutations in the Runt domain of the AML1/PEBP2 alpha B gene in Mo acute myeloid leukemia and in myeloid malignancies with acquired trisomy 21.

PubMed

Preudhomme, C; Warot-Loze, D; Roumier, C; Grardel-Duflos, N; Garand, R; Lai, J L; Dastugue, N; Macintyre, E; Denis, C; Bauters, F; Kerckaert, J P; Cosson, A; Fenaux, P

2000-10-15

The AML1 gene, situated in 21q22, is often rearranged in acute leukemias through t(8;21) translocation, t(12;21) translocation, or less often t(3;21) translocation. Recently, point mutations in the Runt domain of the AML1 gene have also been reported in leukemia patients. Observations for mutations of the Runt domain of the AML1 gene in bone marrow cells were made in 300 patients, including 131 with acute myeloid leukemia (AML), 94 with myelodysplastic syndrome (MDS), 28 with blast crisis chronic myeloid leukemia (CML), 3 with atypical CML, 41 with acute lymphoblastic leukemia (ALL), and 3 with essential thrombocythemia (ET). Forty-one of the patients had chromosome 21 abnormalities, including t(8;21) in 6 of the patients with AML, t(12;21) in 8 patients with ALL, acquired trisomy 21 in 17 patients, tetrasomy 21 in 7 patients, and constitutional trisomy 21 (Down syndrome) in 3 patients. A point mutation was found in 14 cases (4.7%), including 9 (22%) of the 41 patients with AML of the Mo type (MoAML) (none of them had detectable chromosome 21 rearrangement) and 5 (38%) of the 13 myeloid malignancies with acquired trisomy 21 (1 M1AML, 2 M2AML, 1 ET, and 1 atypical CML). In at least 8 of 9 mutated cases of MoAML, both AML alleles were mutated: 3 patients had different stop codon mutations of the 2 AML1 alleles, and 5 patients had the same missense or stop codon mutation in both AML1 alleles, which resulted in at least 3 of the patients having duplication of the mutated allele and deletion of the normal residual allele, as shown by FISH analysis and by comparing microsatellite analyses of several chromosome 21 markers on diagnosis and remission samples. In the remaining mutated cases, with acquired trisomy 21, a missense mutation of AML1, which involved 2 of the 3 copies of the AML1 gene, was found. Four of the 7 mutated cases could be reanalyzed in complete remission, and no AML1 mutation was found, showing that mutations were acquired in the leukemic clone. In conclusion, these findings confirm the possibility of mutations of the Runt domain of the AML1 gene in leukemias, mainly in MoAML and in myeloid malignancies with acquired trisomy 21. AML1 mutations, in MoAML, involved both alleles and probably lead to nonfunctional AML1 protein. As AML1 protein regulates the expression of the myeloperoxidase gene, the relationship between AML1 mutations and Mo phenotype in AML will have to be further explored. (Blood. 2000;96:2862-2869)

Osteolytic Bone Lesions - A Rare Presentation of AML M6.

PubMed

Geetha, N; Sreelesh, K P; Priya, M J; Lali, V S; Rekha, N

2015-01-01

Acute myeloid leukemia (AML) M6 is a rare form of AML accounting for < 5 % of all AML. Extramedullary involvement is very rarely seen in this entity. Skeletal lesion has not been described in AML M6 before. We discuss the case of a 17 year old boy with AML M6, who presented with osteolytic lesion of right humerus. He was treated with induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.

A new self-expandable aortic valved stent deployed above native leaflets for aortic insufficiency: an in vitro study.

PubMed

Huang, H; Zhou, Y; Shao, J; Cai, J; Mei, Y; Wang, Y

2012-12-01

The aim of this paper was to develop a new self-expandable aortic valved stent following the shape of the sinus of Valsalva, which can be deployed above native leaflets for aortic regurgitation, and study it's effect on coronary artery flow when orthotopic implantation in and above native leaflets. New self-expandable aortic valved stent consist of nitinol stent and bovine pericardium, and was designed following the shape of the sinus of Valsalva, the bovine pericardium was tailed as native leaflet. Thirty-six swine hearts were divided into three equal groups of twelve. In Group A (N.=12), the new self-expandable aortic valved stents deployed in native leaflets. In Group B (N.=12), the new self-expandable aortic valved stents deployed above native leaflets. In Group C (N.=12), the cylinder-like valved stents deployed only in native leaflets. The measurements of each coronary flow rate and endoscopic inspections were repeated post-implantation. In Group A and C, valve implantation in native leaflets resulted in a significant decrease in both left and right coronary flows. In Group B, no significant change in either right or left coronary flow was found after new self-expandable aortic valved stent placement. Endoscopic inspections showed that in group A and C the native leaflets sandwiched between valved stent and aortic wall, whereas, in group B the native leaflets were under the artificial leaflets. Two kinds of stents deployed in native leaflets affect left and right coronary flows significantly. No significant effect was found when the new self-expandable aortic valved stent deployed above native leaflets. This new self-expandable aortic valved stent can be deployed above the native leaflets, which avoids the obstruction of native leaflets on coronary flow.

[Acute myeloid leukemia].

PubMed

Tabuchi, Ken

2007-02-01

The annual incident rate of pediatric acute myeloid leukemia (AML) is now 10 per million in Japan, against 5 to 9 per million in the USA and Europe. Overall long-term survival has now been achieved for more than 50% of pediatric patients with AML in the USA and in Europe. The prognostic factors of pediatric AML were analyzed,and patients with AML were classified according to prognostic factors. The t(15;17), inv(16) and t(8;21) have emerged as predictors of good prognosis in children with AML. Monosomy 7, monosomy 5 and del (5 q) abnormalities showed a poor prognosis. In addition to chromosomal deletions, FLT 3/ITD identifies pediatric patients with a particularly poor prognosis. Clinical trials of AML feature intensive chemotherapy with or without subsequent stem cell transplantation. Risk group stratification is becoming increasingly important in planning AML therapy. APL can be distinguished from other subtypes of AML by virtue of its excellent response and overall outcome as a result of differentiation therapy with ATRA. Children with Down syndrome and AML have been shown to have a superior prognosis to AML therapy compared to other children with AML. The results of the Japan Cooperative Study Group protocol ANLL 91 was one of the best previously reported in the literature. With the consideration of quality of life (QOL), risk-adapted therapy was introduced in the AML 99 trial conducted by the Japanese Childhood AML Cooperative Study Group. A high survival rate of 79% at 3 years was achieved for childhood de novo AML in the AML 99 trial. To evaluate the efficacy and safety of the treatment strategy according to risk stratification based on leukemia cell biology and response to the initial induction therapy in children with AML, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) has organized multi-center phase II trials in children with newly diagnosed AML.

Aml1 gene rearrangements and mutations in radiation-associated acute myeloid leukemia and myelodysplastic syndromes.

PubMed

Klymenko, Sergiy; Trott, Klaus; Atkinson, Michael; Bink, Karin; Bebeshko, Vladimir; Bazyka, Dimitry; Dmytrenko, Iryna; Abramenko, Iryna; Bilous, Nadia; Misurin, Andrei; Zitzelsberger, Horst; Rosemann, Michael

2005-06-01

Several studies suggested a causal link between AML1 gene rearrangements and both radiation-induced acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Fifty-three AML samples were analyzed for the presence of AML1 abnormalities using fluorescent in-situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR). Of these patients, 24 had experienced radiation exposure due to the Chernobyl accident, and 29 were non-irradiated spontaneous AML cases and served as controls. AML1/ETO translocations were found in 9 of 29 spontaneous AML but only in 1 of 24 radiation-associated AML cases. This difference between translocation frequencies is statistically significant in the age-unstratified cohorts (p=0.015). Following age stratification, the difference becomes less pronounced but remains on borderline significance (p=0.053). AML1 mutation status was assessed in 5 clean-up workers at Chernobyl NPP with MDS, or AML following MDS, by direct sequencing of genomic DNA from the coding region (exon 3 through 8). In one patient who developed MDS following an acute radiation syndrome, a hexanucleotide duplication of CGGCAT in exon 8 was found, inserted after base position 1502. Our results suggest that AML1 gene translocations are infrequent in radiation-induced leukemogenesis but are consistent with the idea that radiation may contribute to the development of MDS through AML1 gene mutation.

The readability and suitability of sexual health promotion leaflets.

PubMed

Corcoran, Nova; Ahmad, Fatuma

2016-02-01

To investigate the readability and suitability of sexual health promotion leaflets. Application of SMOG, FRY and SAM tests to assess the readability and suitability of a selection of sexual health leaflets. SMOG and FRY scores illustrate an average reading level of grade 9. SAM scores indicate that 59% of leaflets are superior in design and 41% are average in design. Leaflets generally perform well in the categories of content, literacy demand, typography and layout. They perform poorly in use of graphics, learning stimulation/motivation and cultural appropriateness. Sexual health leaflets have a reading level that is too high. Leaflets perform well on the suitability scores indicating they are reasonably suitable. There are a number of areas where sexual health leaflets could improve their design. Numerous practical techniques are suggested for improving the readability and suitability of sexual health leaflets. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Simulation of long-term fatigue damage in bioprosthetic heart valves: effects of leaflet and stent elastic properties

PubMed Central

Martin, Caitlin

2014-01-01

One of the major failure modes of bioprosthetic heart valves (BHVs) is noncalcific structural deterioration due to fatigue of the tissue leaflets; yet, the mechanisms of fatigue are not well understood. BHV durability is primarily assessed based on visual inspection of the leaflets following accelerated wear testing. In this study, we developed a computational framework to simulate BHV leaflet fatigue, which is both efficient and quantitative, making it an attractive alternative to traditional accelerated wear testing. We utilize a phenomenological soft tissue fatigue damage model developed previously to describe the stress softening and permanent set of the glutaraldehyde-treated bovine pericardium leaflets in BHVs subjected to cyclic loading. A parametric study was conducted to determine the effects of altered leaflet and stent elastic properties on the fatigue of the leaflets. The simulation results show that heterogeneity of the leaflet elastic properties, poor leaflet coaptation, and little stent-tip deflection may accelerate leaflet fatigue, which agrees with clinical findings. Therefore, the developed framework may be an invaluable tool for evaluating leaflet durability in new tissue valve designs, including traditional BHVs as well as new transcatheter valves. PMID:24092257

Content analysis of nutritional information in paediatric oral health education leaflets.

PubMed

Arora, Amit; Doan, Jenny; Martinez, Jessamine; Phan, Colin; Kolt, Gregory S; Bhole, Sameer; Harris, Mark Fort; Scott, Jane Anne; Hector, Debra

2017-02-20

The aim of this study was to determine if paediatric oral health education leaflets with a food and nutritional focus provide messages that are clear and consistent with the current Australian Dietary Guidelines and the Infant Feeding Guidelines. Forty-three leaflets aimed at parents were sourced from Australian state and territory Health Departments, oral health industry partners and commercial organisations, and a content analysis was performed. Recommendations on food and drink type, consumption frequency and general diet and nutrition advice were considered and cross-referenced with the Australian Dietary Guidelines and the Infant Feeding Guidelines to identify areas of consistency and discrepancy. Twenty leaflets recommended reducing the consumption of sugary and/or acidic food, while 23 leaflets recommended reducing the consumption of sugary and/or acidic drinks. The majority of the leaflets advised water (n = 35) and milk (n = 23) to drink. Although 33 leaflets encouraged a healthy diet, seven of these did not specify what a healthy diet was. Twenty-eight leaflets provided early childhood-related (0-2 years) feeding advice. Confusing messages were found in nine leaflets, with ambiguous recommendations that were open to individual interpretation. There were some inconsistencies between the leaflets and the dietary and infant feeding guidelines in Australia; and across the leaflets, as not all important messages were included in any one leaflet. Government Health Departments and other relevant agencies should ensure that advisory messages regarding diet, particularly those with dental implications, are clear, complete and consistent across all dental educational leaflets.

Crutches, confetti or useful tools? Professionals' views on and use of health education leaflets.

PubMed

Murphy, S; Smith, C

1993-06-01

This paper examines the views on and use of health education leaflets by a number of professional groups: health visitors, midwives, occupational health workers, pharmacists and school health education co-ordinators. Eighty nine percent currently obtain leaflets from health promotion units, with the exception of health visitors, professionals are largely satisfied with the units' service. Seventy six percent use commercial or sponsored leaflets primarily because of the large numbers and topics that are available. The numbers and type of leaflets used were found to vary across the professions. All professionals see an increasingly important role for leaflets in their work. A number of them, pharmacists and occupational health workers in particular, saw the numbers they use rising. These views were accompanied by lower levels of belief in a leaflets ability to increase knowledge and behaviour as well as lower levels of satisfaction with current leaflet use and a concern over the public's reception of leaflets. Methods of leaflet distribution to the public largely reflect the professionals' work contexts. Most popular were handing out leaflets with advice, leaving them in a public place and using them as a back-up to a meeting. A number of contradictions emerge between distribution practices and perceived effectiveness. Few professionals thought leaving leaflets in a public place was effective, and few health visitors and midwives believed giving leaflets to the family of a client was effective despite large numbers doing so. The implications of these findings for health promotion policy and practice are discussed.

Metachronous and Synchronous Presentation of Acute Myeloid Leukemia and Lung Cancer

PubMed Central

Varadarajan, Ramya; Ford, LaurieAnn; Sait, Sheila NJ; Block, AnneMarie W.; Barcos, Maurice; Wallace, Paul K.; Ramnath, Nithya; Wang, Eunice S.; Wetzler, Meir

2009-01-01

Smoking is associated with both acute myeloid leukemia (AML) and lung cancer. We therefore searched our database for concomitant presentation of AML and lung cancer. Among 775 AML cases and 5225 lung cancer cases presenting to Roswell Park Cancer Institute between the years January 1992 and May 2008 we found 12 (1.5% of AML cases; 0.23% of lung cancer cases) cases (seven metachronous and five synchronous) with AML and lung cancer. All but one patient were smokers. There were no unique characteristic of either AML or lung cancer in these patients. Nine patients succumbed to AML, one died from an unrelated cause while undergoing treatment for AML, one died of lung cancer and one patient is alive after allogeneic transplantation for AML. In summary, this study supports the need for effective smoking cessation programs. PMID:19181380

Development of acute myeloid leukemia in patients with untreated chronic lymphocytic leukemia.

PubMed

Ito, Shoko; Fujiwara, Shin-Ichiro; Mashima, Kiyomi; Umino, Kento; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Ashizawa, Masahiro; Yamamoto, Chihiro; Hatano, Kaoru; Okazuka, Kiyoshi; Sato, Kazuya; Oh, Iekuni; Ohmine, Ken; Suzuki, Takahiro; Muroi, Kazuo; Kanda, Yoshinobu

2017-05-01

The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4.2 years. Diagnosis of AML and CLL was made simultaneously in 16 patients. The CR rate of AML was 42.9%, and the median survival was only 1.5 months after the diagnosis of AML. Patients who achieved CR tended to survive longer than those who did not. Our results demonstrated that the development of AML in patients with untreated CLL was associated with a poor response to chemotherapy and an extremely poor prognosis.

Aortic or Mitral Valve Replacement With the Biocor and Biocor Supra

ClinicalTrials.gov

2017-04-26

Aortic Valve Insufficiency; Aortic Valve Regurgitation; Aortic Valve Stenosis; Aortic Valve Incompetence; Mitral Valve Insufficiency; Mitral Valve Regurgitation; Mitral Valve Stenosis; Mitral Valve Incompetence

AML1/ETO induces self-renewal in hematopoietic progenitor cells via the Groucho-related amino-terminal AES protein.

PubMed

Steffen, Björn; Knop, Markus; Bergholz, Ulla; Vakhrusheva, Olesya; Rode, Miriam; Köhler, Gabriele; Henrichs, Marcel-Philipp; Bulk, Etmar; Hehn, Sina; Stehling, Martin; Dugas, Martin; Bäumer, Nicole; Tschanter, Petra; Brandts, Christian; Koschmieder, Steffen; Berdel, Wolfgang E; Serve, Hubert; Stocking, Carol; Müller-Tidow, Carsten

2011-04-21

The most frequent translocation t(8;21) in acute myeloid leukemia (AML) generates the chimeric AML1/ETO protein, which blocks differentiation and induces self-renewal in hematopoietic progenitor cells. The underlying mechanisms mediating AML1/ETO-induced self-renewal are largely unknown. Using expression microarray analysis, we identified the Groucho-related amino-terminal enhancer of split (AES) as a consistently up-regulated AML1/ETO target. Elevated levels of AES mRNA and protein were confirmed in AML1/ETO-expressing leukemia cells, as well as in other AML specimens. High expression of AES mRNA or protein was associated with improved survival of AML patients, even in the absence of t(8;21). On a functional level, knockdown of AES by RNAi in AML1/ETO-expressing cell lines inhibited colony formation. Similarly, self-renewal induced by AML1/ETO in primary murine progenitors was inhibited when AES was decreased or absent. High levels of AES expression enhanced formation of immature colonies, serial replating capacity of primary cells, and colony formation in colony-forming unit-spleen assays. These findings establish AES as a novel AML1/ETO-induced target gene that plays an important role in the self-renewal phenotype of t(8;21)-positive AML.

Advertising, expectations and informed consent: the contents and functions of acupuncture leaflets.

PubMed

Bishop, Felicity L; Salmon, Cathy

2013-12-01

To evaluate the content of patient information leaflets about acupuncture. 401 patient information leaflets were obtained from practising UK acupuncturists and subjected to content and thematic analysis. 59% of included leaflets were from NHS physiotherapists. Almost all the leaflets defined acupuncture and the majority explained how it might work, described the treatment process and placed it in a historical context. Most described possible benefits and risks of acupuncture and discussed contraindications and safety. Just under a third of leaflets (120, 30%) suggested conditions that might be helped by acupuncture, most commonly musculoskeletal pain, arthritis and injuries. By emphasising differences between individuals in acupuncture treatments and responsiveness, the leaflets fostered hope for positive effects without making any guarantees. Information leaflets are broadly consistent with the evidence for acupuncture, but some claims are inconsistent with official advice from advertising regulators. An ethically sound, scientifically grounded and psychologically effective leaflet should accurately convey both benefits and risks of treatment, optimise patients' expectations and allay concerns about needling. This study suggests that acupuncture leaflets might achieve these multiple functions but care should be taken to ensure adequate coverage of risks.

Stent and leaflet stresses in a 26-mm first-generation balloon-expandable transcatheter aortic valve.

PubMed

Xuan, Yue; Krishnan, Kapil; Ye, Jian; Dvir, Danny; Guccione, Julius M; Ge, Liang; Tseng, Elaine E

2017-05-01

Transcatheter aortic valve replacement is established therapy for high-risk and inoperable patients with severe aortic stenosis, but questions remain regarding long-term durability. Valve design influences durability. Increased leaflet stresses in surgical bioprostheses have been correlated with degeneration; however, transcatheter valve leaflet stresses are unknown. From 2007 to 2014, a majority of US patients received first-generation balloon-expandable transcatheter valves. Our goal was to determine stent and leaflet stresses in this valve design using finite element analyses. A 26-mm Sapien Transcatheter Heart Valve (Edwards Lifesciences, Inc, Irvine, Calif) underwent high-resolution microcomputed tomography scanning to develop precise 3-dimensional geometry of the leaflets, the stent, and the polyethylene terephthalate elements. The stent was modeled using 3-dimensional elements and the leaflets were modeled using shell elements. Stent material properties were based on stainless steel, whereas those for leaflets were obtained from surgical bioprostheses. Noncylindrical Sapien valve geometry was also simulated. Pressure loading to 80 mm Hg and 120 mm Hg was performed using ABAQUS finite element software (Dassault Systèmes, Waltham, Mass). At 80 mm Hg, maximum principal stresses on Sapien leaflets were 1.31 megaspascals (MPa). Peak leaflet stress was observed at commissural tips where leaflets connected to the stent. Maximum principal stresses for the stent were 188.91 MPa and located at stent tips where leaflet commissures were attached. Noncylindrical geometry increased peak principal leaflet stresses by 16%. Using exact geometry from high-resolution scans, the 26-mm Sapien Transcatheter Heart Valve showed that peak stresses for both stent and leaflets were present at commissural tips where leaflets were attached. These regions would be prone to leaflet degeneration. Understanding stresses in first-generation transcatheter valves allows comparison to future designs for relative durability. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Inoue Balloon Mitral Valvotomy in a 4-Year-Old Boy

PubMed Central

Kapoor, Aditya; Moorthy, Nagaraja; Kumar, Sudeep

2012-01-01

Mitral stenosis in children often has a fulminant and rapid course. Percutaneous transvenous mitral commissurotomy is accepted as the treatment of choice for mitral stenosis not only in adults, but also in younger patients who have pliable valves. Balloon mitral valvotomy has yielded good immediate and long-term results. Herein, we report successful Inoue balloon mitral valvotomy in a 4-year-old boy who had severe, symptomatic rheumatic mitral stenosis. To our knowledge, our patient is the youngest to have undergone this procedure. In addition to the case description, we discuss the features of juvenile rheumatic mitral stenosis and several technical aspects of performing the Inoue balloon mitral valvotomy procedure in children. PMID:22412242

Successful treatment of congenital acute myeloid leukemia (AML-M6) in a premature infant.

PubMed

van Dongen, Joyce C A; Dalinghaus, Michiel; Kroon, Andre A; de Vries, Andrica C H; van den Heuvel-Eibrink, Marry M

2009-11-01

Congenital acute myeloid leukemia (AML), and especially AML-M6 is a rare disease with a poor prognosis. Moreover, reports of treatment outcome of congenital AML-M6 in premature infants are not available. We report the first treated case of congenital AML-M6 in a premature girl, who received a full AML protocol. She presented with blueberry-muffin spots, anemia, high white blood cell count, and serious cardiopulmonary distress. Peripheral blood smears showed AML-M6 blasts. After treatment with a sequential low-dose cytarabine after birth and full-dose AML treatment according to the MRC-12 protocol at the age of 2 months, she now is in continuous complete remission for 4 years.

Acute myeloid leukemia and diabetes insipidus with monosomy 7.

PubMed

Harb, Antoine; Tan, Wei; Wilding, Gregory E; Battiwalla, Minoo; Sait, Sheila N J; Wang, Eunice S; Wetzler, Meir

2009-04-15

The predisposition of monosomy 7 to diabetes insipidus (DI) in acute myeloid leukemia (AML) led us to ask whether AML associated with monosomy 7 and DI will differ from AML associated with other karyotype aberrations and DI and whether the outcome of patients with AML and DI will differ from those without DI. We describe 2 patients from Roswell Park Cancer Institute and discuss 29 additional cases from the literature. AML with monosomy 7 and DI (n = 25) had a trend towards a lower complete remission (p = 0.0936) and worse survival (p = 0.0480) than AML with other karyotype changes and DI (n = 6). Further, AML with monosomy 7 and DI had worse complete remission rate and overall survival than AML with monosomy 7 but without DI. In conclusion, it appears that AML with monosomy 7 and DI is a disease entity with specifically poor outcome.

Percutaneous transluminal mitral commissurotomy for rheumatic mitral stenosis in a 5-year-old child.

PubMed

Ullah, Maad; Sultan, Mehboob; Akbar, Hajira; Sadiq, Nadeem

2012-06-01

We report a 5-year-old boy weighing 11 kg, with severe mitral valve stenosis of rheumatic aetiology, who underwent successful percutaneous transluminal mitral commissurotomy (PTMC) with valvuloplasty balloon. Postprocedural mean pressure gradient across the mitral valve decreased to 6 mmHg from an initially recorded value of 22 mmHg. In addition to symptomatic improvement, the mitral valvular area increased from 0.4 to 0.8 cm(2) without significant change in mitral regurgitation. At 1- and 3-month follow up, transthoracic echocardiography revealed further improvement with an increase in mitral valve area to 1.0 cm(2), a decrease in pulmonary arterial pressure, and a mean mitral valve pressure gradient of 8 mmHg with trivial mitral regurgitation. To best of our knowledge, this is the first successful PTMC procedure performed in the youngest and smallest ever reported child with rheumatic mitral stenosis (MS). We conclude that PTMC with valvuloplasty balloon could be a logical alternative to surgery in young patients with rheumatic MS.

Effectiveness of Percutaneous Balloon Mitral Valvuloplasty for Rheumatic Mitral Stenosis with Mild to Severe Mitral Regurgitation

PubMed Central

Lu, LinXiang; Hong, Lang; Fang, Jun; Chen, LiangLong

2016-01-01

This study is designed to test whether percutaneous balloon mitral valvuloplasty (PBMV) is effective for rheumatic mitral stenosis in Chinese patients with moderate to severe mitral regurgitation. Fifty-six patients with rheumatic mitral valve stenosis were divided into the mild, moderate, and severe regurgitation groups. Cardiac ultrasonography was measured before and 1 to 2 days after PBMV. Following PBMV, the mitral orifice was enlarged, and the left atrial diameter was reduced in the 3 patient groups. The enlargement of the mitral orifice in the mild regurgitation group was greater than that observed in the moderate and severe regurgitation groups. The size of the regurgitation area increased in the mild regurgitation group and decreased in the moderate and severe regurgitation groups, with the decrease in the severe regurgitation group being greater than that in the moderate regurgitation group. Therefore, PBMV is effective for treating rheumatic mitral stenosis in Chinese patients with mild to severe mitral regurgitation. PMID:27034933

Management of mitral regurgitation in Marfan syndrome: Outcomes of valve repair versus replacement and comparison with myxomatous mitral valve disease.

PubMed

Helder, Meghana R K; Schaff, Hartzell V; Dearani, Joseph A; Li, Zhuo; Stulak, John M; Suri, Rakesh M; Connolly, Heidi M

2014-09-01

The study objective was to evaluate patients with Marfan syndrome and mitral valve regurgitation undergoing valve repair or replacement and to compare them with patients undergoing repair for myxomatous mitral valve disease. We reviewed the medical records of consecutive patients with Marfan syndrome treated surgically between March 17, 1960, and September 12, 2011, for mitral regurgitation and performed a subanalysis of those with repairs compared with case-matched patients with myxomatous mitral valve disease who had repairs (March 14, 1995, to July 5, 2013). Of 61 consecutive patients, 40 underwent mitral repair and 21 underwent mitral replacement (mean [standard deviation] age, 40 [18] vs 31 [19] years; P = .09). Concomitant aortic surgery was performed to a similar extent (repair, 45% [18/40] vs replacement, 43% [9/21]; P = .87). Ten-year survival was significantly better in patients with Marfan syndrome with mitral repair than in those with replacement (80% vs 41%; P = .01). Mitral reintervention did not differ between mitral repair and replacement (cumulative risk of reoperation, 27% vs 15%; P = .64). In the matched cohort, 10-year survival after repair was similar for patients with Marfan syndrome and myxomatous mitral disease (84% vs 78%; P = .63), as was cumulative risk of reoperation (17% vs 12%; P = .61). Patients with Marfan syndrome and mitral regurgitation have better survival with repair than with replacement. Survival and risk of reoperation for patients with Marfan syndrome were similar to those for patients with myxomatous mitral disease. These results support the use of mitral valve repair in patients with Marfan syndrome and moderate or more mitral regurgitation, including those having composite replacement of the aortic root. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

'What do patients want?' Tailoring medicines information to meet patients' needs.

PubMed

Young, Amber; Tordoff, June; Smith, Alesha

2017-11-01

Medicines information leaflets can equip patients to be in control of their own healthcare and support the safe and effective use of medicines. The design and content of leaflets influences patients' willingness to read them, and poor examples can cause patient confusion and anxiety. Researchers examined the literature over the past 8 years to determine the content and design of medicine information leaflets that patients prefer in order to read, understand, and use them effectively. It was found that existing leaflets do not meet patients' needs and appear ineffective. Leaflets lack the information patients seek and may contain non-essential material, affecting patients' perception of, and willingness to read them. Additionally, the acceptable leaflet length varies between patients. Application of good design principles improves readability, comprehension, and ability to locate information. Medicine information leaflets must meet patients' needs and be well designed. Tailoring information leaflets to patient characteristics and requirements would enhance effectiveness. Passive provision of pre-printed leaflets is outdated, unvalued and ineffective. Using automated computer systems for leaflet tailoring with the ability to further adapt patients' information might be the best way forward. Copyright © 2016 Elsevier Inc. All rights reserved.

Charged anaesthetics alter LM-fibroblast plasma-membrane enzymes by selective fluidization of inner or outer membrane leaflets.

PubMed Central

Sweet, W D; Schroeder, F

1986-01-01

The functional consequences of the differences in lipid composition and structure between the two leaflets of the plasma membrane were investigated. Fluorescence of 1,6-diphenylhexa-1,3,5-triene(DPH), quenching, and differential polarized phase fluorimetry demonstrated selective fluidization by local anaesthetics of individual leaflets in isolated LM-cell plasma membranes. As measured by decreased limiting anisotropy of DPH fluorescence, cationic (prilocaine) and anionic (phenobarbital and pentobarbital) amphipaths preferentially fluidized the cytofacial and exofacial leaflets respectively. Unlike prilocaine, procaine, also a cation, fluidized both leaflets of these membranes equally. Pentobarbital stimulated 5'-nucleotidase between 0.1 and 5 mM and inhibited at higher concentrations, whereas phenobarbital only inhibited, at higher concentrations. Cationic drugs were ineffective. Two maxima of (Na+ + K+)-ATPase activation were obtained with both anionic drugs. Only one activation maximum was obtained with both cationic drugs. The maximum in activity below 1 mM for all four drugs clustered about a single limiting anisotropy value in the cytofacial leaflet, whereas there was no correlation between activity and limiting anisotropy in the exofacial leaflets. Therefore, although phenobarbital and pentobarbital below 1 mM fluidized the exofacial leaflet more than the cytofacial leaflet, the smaller fluidization in the cytofacial leaflet was functionally significant for (Na+ + K+)-ATPase. Mg2+-ATPase was stimulated at 1 mM-phenobarbital, unaffected by pentobarbital and slightly stimulated by both cationic drugs at concentrations fluidizing both leaflets. Thus the activity of (Na+ + K+)-ATPase was highly sensitive to selective fluidization of the leaflet containing its active site, whereas the other enzymes examined were little affected by fluidization of either leaflet. PMID:3028369

Adaptation of child oral health education leaflets for Arabic migrants in Australia: a qualitative study.

PubMed

Arora, Amit; Al-Salti, Ibrahim; Murad, Hussam; Tran, Quang; Itaoui, Rhonda; Bhole, Sameer; Ajwani, Shilpi; Jones, Charlotte; Manohar, Narendar

2018-01-10

The purpose of this study was to gain an in-depth understanding of Arabic-speaking mothers views on the usefulness of existing oral health education leaflets aimed at young children and also to record their views on the tailored versions of these leaflets. This qualitative study was nested within a large ongoing birth cohort study in South Western Sydney, Australia. Arabic-speaking mothers (n = 19) with young children were purposively selected and approached for a semi-structured interview. Two original English leaflets giving advice on young children's oral health were sent to mother's prior to the interview. On the day of interview, mothers were given simplified-English and Arabic versions of both the leaflets and were asked to compare the three versions. Interviews were audio-recorded, subsequently transcribed verbatim and analysed by thematic analysis. Ethical approval was obtained from Human Research Ethics Committees of the former Sydney South West Area Health Service, University of Sydney and Western Sydney University. Mothers reported that simplified English together with the Arabic version of the leaflets were useful sources of information. Although many mothers favoured the simplified version over original English leaflets, the majority favoured the leaflets in Arabic. Ideally, a "dual Arabic - simplified English leaflet" was preferred. The understanding of key health messages was optimised through a simple layout and visual images. There is a need to tailor oral health education leaflets for Arabic-speaking migrants. Producers of dental leaflets should also consider a "dual Arabic - simplified English leaflet" to improve oral health knowledge of Arabic-speaking migrants. The use of simple layout and pictures assists Arabic-speaking migrants to understand the content of dental leaflets.

Simulated transcatheter aortic valve deformation: A parametric study on the impact of leaflet geometry on valve peak stress.

PubMed

Li, Kewei; Sun, Wei

2017-03-01

In this study, we developed a computational framework to investigate the impact of leaflet geometry of a transcatheter aortic valve (TAV) on the leaflet stress distribution, aiming at optimizing TAV leaflet design to reduce its peak stress. Utilizing a generic TAV model developed previously [Li and Sun, Annals of Biomedical Engineering, 2010. 38(8): 2690-2701], we first parameterized the 2D leaflet geometry by mathematical equations, then by perturbing the parameters of the equations, we could automatically generate a new leaflet design, remesh the 2D leaflet model and build a 3D leaflet model from the 2D design via a Python script. Approximately 500 different leaflet designs were investigated by simulating TAV closure under the nominal circular deployment and physiological loading conditions. From the simulation results, we identified a new leaflet design that could reduce the previously reported valve peak stress by about 5%. The parametric analysis also revealed that increasing the free edge width had the highest overall impact on decreasing the peak stress. A similar computational analysis was further performed for a TAV deployed in an abnormal, asymmetric elliptical configuration. We found that a minimal free edge height of 0.46 mm should be adopted to prevent central backflow leakage. This increase of the free edge height resulted in an increase of the leaflet peak stress. Furthermore, the parametric study revealed a complex response surface for the impact of the leaflet geometric parameters on the peak stress, underscoring the importance of performing a numerical optimization to obtain the optimal TAV leaflet design. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML.

PubMed

Malani, D; Murumägi, A; Yadav, B; Kontro, M; Eldfors, S; Kumar, A; Karjalainen, R; Majumder, M M; Ojamies, P; Pemovska, T; Wennerberg, K; Heckman, C; Porkka, K; Wolf, M; Aittokallio, T; Kallioniemi, O

2017-05-01

We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample. Cytarabine-resistant SHI-1 variants and a subset of chemorefractory AML patient samples showed increased sensitivity to glucocorticoids that are often used in treatment of lymphoid leukemia but not AML. Paired samples taken from AML patients before treatment and at relapse also showed acquisition of glucocorticoid sensitivity. Enhanced glucocorticoid sensitivity was only seen in AML patient samples that were negative for the FLT3 mutation (P=0.0006). Our study shows that development of cytarabine resistance is associated with increased sensitivity to glucocorticoids in a subset of AML, suggesting a new therapeutic strategy that should be explored in a clinical trial of chemorefractory AML patients carrying wild-type FLT3.

Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML

PubMed Central

Malani, D; Murumägi, A; Yadav, B; Kontro, M; Eldfors, S; Kumar, A; Karjalainen, R; Majumder, M M; Ojamies, P; Pemovska, T; Wennerberg, K; Heckman, C; Porkka, K; Wolf, M; Aittokallio, T; Kallioniemi, O

2017-01-01

We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample. Cytarabine-resistant SHI-1 variants and a subset of chemorefractory AML patient samples showed increased sensitivity to glucocorticoids that are often used in treatment of lymphoid leukemia but not AML. Paired samples taken from AML patients before treatment and at relapse also showed acquisition of glucocorticoid sensitivity. Enhanced glucocorticoid sensitivity was only seen in AML patient samples that were negative for the FLT3 mutation (P=0.0006). Our study shows that development of cytarabine resistance is associated with increased sensitivity to glucocorticoids in a subset of AML, suggesting a new therapeutic strategy that should be explored in a clinical trial of chemorefractory AML patients carrying wild-type FLT3. PMID:27833094

Chaperonin TRiC/CCT Modulates the Folding and Activity of Leukemogenic Fusion Oncoprotein AML1-ETO.

PubMed

Roh, Soung-Hun; Kasembeli, Moses; Galaz-Montoya, Jesús G; Trnka, Mike; Lau, Wilson Chun-Yu; Burlingame, Alma; Chiu, Wah; Tweardy, David J

2016-02-26

AML1-ETO is the most common fusion oncoprotein causing acute myeloid leukemia (AML), a disease with a 5-year survival rate of only 24%. AML1-ETO functions as a rogue transcription factor, altering the expression of genes critical for myeloid cell development and differentiation. Currently, there are no specific therapies for AML1-ETO-positive AML. While known for decades to be the translational product of a chimeric gene created by the stable chromosome translocation t(8;21)(q22;q22), it is not known how AML1-ETO achieves its native and functional conformation or whether this process can be targeted for therapeutic benefit. Here, we show that the biosynthesis and folding of the AML1-ETO protein is facilitated by interaction with the essential eukaryotic chaperonin TRiC (or CCT). We demonstrate that a folding intermediate of AML1-ETO binds to TRiC directly, mainly through its β-strand rich, DNA-binding domain (AML-(1-175)), with the assistance of HSP70. Our results suggest that TRiC contributes to AML1-ETO proteostasis through specific interactions between the oncoprotein's DNA-binding domain, which may be targeted for therapeutic benefit. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Gene expression profiling of acute myeloid leukemia samples from adult patients with AML-M1 and -M2 through boutique microarrays, real-time PCR and droplet digital PCR.

PubMed

Handschuh, Luiza; Kaźmierczak, Maciej; Milewski, Marek C; Góralski, Michał; Łuczak, Magdalena; Wojtaszewska, Marzena; Uszczyńska-Ratajczak, Barbara; Lewandowski, Krzysztof; Komarnicki, Mieczysław; Figlerowicz, Marek

2018-03-01

Acute myeloid leukemia (AML) is the most common and severe form of acute leukemia diagnosed in adults. Owing to its heterogeneity, AML is divided into classes associated with different treatment outcomes and specific gene expression profiles. Based on previous studies on AML, in this study, we designed and generated an AML-array containing 900 oligonucleotide probes complementary to human genes implicated in hematopoietic cell differentiation and maturation, proliferation, apoptosis and leukemic transformation. The AML-array was used to hybridize 118 samples from 33 patients with AML of the M1 and M2 subtypes of the French-American‑British (FAB) classification and 15 healthy volunteers (HV). Rigorous analysis of the microarray data revealed that 83 genes were differentially expressed between the patients with AML and the HV, including genes not yet discussed in the context of AML pathogenesis. The most overexpressed genes in AML were STMN1, KITLG, CDK6, MCM5, KRAS, CEBPA, MYC, ANGPT1, SRGN, RPLP0, ENO1 and SET, whereas the most underexpressed genes were IFITM1, LTB, FCN1, BIRC3, LYZ, ADD3, S100A9, FCER1G, PTRPE, CD74 and TMSB4X. The overexpression of the CPA3 gene was specific for AML with mutated NPM1 and FLT3. Although the microarray-based method was insufficient to differentiate between any other AML subgroups, quantitative PCR approaches enabled us to identify 3 genes (ANXA3, S100A9 and WT1) whose expression can be used to discriminate between the 2 studied AML FAB subtypes. The expression levels of the ANXA3 and S100A9 genes were increased, whereas those of WT1 were decreased in the AML-M2 compared to the AML-M1 group. We also examined the association between the STMN1, CAT and ABL1 genes, and the FLT3 and NPM1 mutation status. FLT3+/NPM1- AML was associated with the highest expression of STMN1, and ABL1 was upregulated in FLT3+ AML and CAT in FLT3- AML, irrespectively of the NPM1 mutation status. Moreover, our results indicated that CAT and WT1 gene expression levels correlated with the response to therapy. CAT expression was highest in patients who remained longer under complete remission, whereas WT1 expression increased with treatment resistance. On the whole, this study demonstrates that the AML-array can potentially serve as a first-line screening tool, and may be helpful for the diagnosis of AML, whereas the differentiation between AML subgroups can be more successfully performed with PCR-based analysis of a few marker genes.

All in the family: matrimonial mitral valve clicks.

PubMed

Desser, K B; Bokhari, S I; Benchimol, A; Romney, D

1981-05-01

Mitral valve clicks with or without late systolic murmurs were detected in genetically unrelated marital partners of 5 families. The first family represented 2 successive nonconsanguineous marital unions with 3 generations of mitral valve clicks. The second family included 1 natural and 2 adopted children with clinical and echographic evidence of mitral valve prolapse. The third family was comprised of asymptomatic parents, both with nonejection clicks and mitral valve prolapse, whose daughter presented 3 years previously with syncope, palpitations, and combined mitral and tricuspid valve prolapse. The fourth family had 3 members with auscultatory and ultrasonic manifestations of billowing mitral valve, whereas the fourth member had "silent mitral valve prolapse." The fifth family represented a mother with auscultatory and echographic evidence of mitral valve prolapse; her 14-year-old daughter had both mitral and tricuspid valve prolapse, whereas the son had a bicuspid aortic valve. Both children were products of a prior marriage, and her husband has symptomatic mitral valve prolapse. We conclude that matrimonial mitral valve prolapse probably reflects the purported (6--10%) prevalence of this disorder in the general population. The consequences of such marital union on progeny is currently unclear and warrants future investigation.

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel.

PubMed

Creutzig, Ursula; van den Heuvel-Eibrink, Marry M; Gibson, Brenda; Dworzak, Michael N; Adachi, Souichi; de Bont, Eveline; Harbott, Jochen; Hasle, Henrik; Johnston, Donna; Kinoshita, Akitoshi; Lehrnbecher, Thomas; Leverger, Guy; Mejstrikova, Ester; Meshinchi, Soheil; Pession, Andrea; Raimondi, Susana C; Sung, Lillian; Stary, Jan; Zwaan, Christian M; Kaspers, Gertjan J L; Reinhardt, Dirk

2012-10-18

Despite major improvements in outcome over the past decades, acute myeloid leukemia (AML) remains a life-threatening malignancy in children, with current survival rates of ∼70%. State-of-the-art recommendations in adult AML have recently been published in this journal by Döhner et al. The primary goal of an international expert panel of the International BFM Study Group AML Committee was to set standards for the management, diagnosis, response assessment, and treatment in childhood AML. This paper aims to discuss differences between childhood and adult AML, and to highlight recommendations that are specific to children. The particular relevance of new diagnostic and prognostic molecular markers in pediatric AML is presented. The general management of pediatric AML, the management of specific pediatric AML cohorts (such as infants) or subtypes of the disease occurring in children (such as Down syndrome related AML), as well as new therapeutic approaches, and the role of supportive care are discussed.

Long-term outcome in dogs undergoing mitral valve repair with suture annuloplasty and chordae tendinae replacement.

PubMed

Mizuno, T; Mizukoshi, T; Uechi, M

2013-02-01

Mitral valve repair under cardiopulmonary bypass was performed in three dogs with clinical signs associated with mitral regurgitation that were not controlled by medication. Mitral valve repair comprised circumferential annuloplasty and chordal replacement with expanded polytetrafluoroethylene. One dog died 2 years after surgery because of severe mitral regurgitation resulting from partial circumferential suture detachment. The others survived for over 5 years, but mild mitral valve stenosis persisted in one. The replaced chordae did not rupture in any dog. Mitral valve repair appears to be an effective treatment for mitral regurgitation in dogs. Chordal replacement with expanded polytetrafluoroethylene is a feasible technique, demonstrating long-term durability in dogs. However, mitral annuloplasty techniques need improvement. © 2012 British Small Animal Veterinary Association.

AML Guide: Information for Patients and Caregivers

MedlinePlus

The AML Guide Information for Patients and Caregivers Acute Myeloid Leukemia Emily , AML survivor Revised 2012 A ... day most people who have been diagnosed with acute myeloid leukemia (AML) will be cured or will ...

The natural history of trilinear myelodysplastic syndrome and erythroleukemia.

PubMed

Michiels, J J; van der Meulen, J; Brederoo, P

1997-01-01

A case of Di Guglielmo's syndrome passed through the three stages of chronic erythromyelosis, erythroleukemia and acute myeloid leukemia (AML). According to the FAB classification the subsequent stages of this syndrome were refractory anemia (RA), RA with excess of blasts (RAEB), AML-M6, AML-M2 and undifferentiated AML-MO as the end-stage disease. Light- and electronmicroscopice findings on peripheral blood and bone marrow slides showed a pronounced trilineage myelodysplastic syndrome (MDS) during the RA, RAEB, AML-M6 and M2 phases of the disease, i.e. dysplastic erythropoiesis with PAS-positive erythroblasts, agranular and hypogranular neutrophils and dysplastic megakaryocytes. It is concluded that this case of Di Guglielmo's syndrome with chronic erythromyelosis, erythroleukemia and AML appears to be a continuum of trilineage MDS, AML-M6 and M2 with dyserythropoiesis which evolved into AML-M0.

Targeting CD157 in AML using a novel, Fc-engineered antibody construct

PubMed Central

Krupka, Christina; Lichtenegger, Felix S.; Köhnke, Thomas; Bögeholz, Jan; Bücklein, Veit; Roiss, Michael; Altmann, Torben; Do, To Uyen; Dusek, Rachel; Wilson, Keith; Bisht, Arnima; Terrett, Jon; Aud, Dee; Pombo-Villar, Esteban; Rohlff, Christian; Hiddemann, Wolfgang; Subklewe, Marion

2017-01-01

Antibody-based immunotherapy represents a promising strategy to eliminate chemorefractory leukemic cells in acute myeloid leukemia (AML). In this study, we evaluated a novel Fc-engineered antibody against CD157 (MEN1112) for its suitability as immunotherapy in AML. CD157 was expressed in 97% of primary AML patient samples. A significant, albeit lower expression level of CD157 was observed within the compartment of leukemia-initiating cells, which are supposed to be the major source of relapse. In healthy donor bone marrow, CD157 was expressed on CD34+ cells. In ex vivo assays, MEN1112 triggered natural killer (NK) cell-mediated cytotoxicity against AML cell lines and primary AML cells. Compared to its parental analogue, the Fc-engineered antibody exhibited higher antibody dependent cellular cytotoxicity responses. Using NK cells from AML patients, we observed heterogeneous MEN1112-mediated cytotoxicity against AML cells, most likely due to well-documented defects in AML-NK cells and corresponding inter-patient variations in NK cell function. Cytotoxicity could not be correlated to the time after completion of chemotherapy. In summary, we could demonstrate that CD157 is strongly expressed in AML. MEN1112 is a promising antibody construct that showed high cytotoxicity against AML cells and warrants further clinical testing. Due to variability in NK-cell function of AML patients, the time of application during the course of the disease as well as combinatorial strategies might influence treatment results. PMID:28415689

Effects of Leaflet Design on Transvalvular Gradients of Bioprosthetic Heart Valves.

PubMed

Dabiri, Yaghoub; Ronsky, Janet; Ali, Imtiaz; Basha, Ameen; Bhanji, Alisha; Narine, Kishan

2016-12-01

Bioprosthetic aortic valves (BAVs) are becoming the prostheses of choice in heart valve replacement. The objective of this paper is to assess the effects of leaflet geometry on the mechanics and hemodynamics of BAVs in a fluid structure interaction model. The curvature and angle of leaflets were varied in 10 case studies whereby the following design parameters were altered: a circular arch, a line, and a parabola for the radial curvature, and a circular arch, a spline, and a parabola for the circumferential curvature. Six different leaflet angles (representative of the inclination of the leaflets toward the surrounding aortic wall) were analyzed. The 3-dimensional geometry of the models were created using SolidWorks, Pointwise was used for meshing, and Comsol Multiphysics was used for implicit finite element calculations. Realistic loading was enforced by considering the time-dependent strongly-coupled interaction between blood flow and leaflets. Higher mean pressure gradients as well as von Mises stresses were obtained with a parabolic or circular curvature for radial curvature or a parabolic or spline curvature for the circumferential curvature. A smaller leaflet angle was associated with a lower pressure gradient, and, a lower von Mises stress. The leaflet curvature and angle noticeably affected the speed of valve opening, and closing. When a parabola was used for circumferential or radial curvature, leaflets displacements were asymmetric, and they opened and closed more slowly. A circular circumferential leaflet curvature, a linear leaflet radial curvature, and leaflet inclination toward the surrounding aortic wall were associated with superior BAVs mechanics.

MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia.

PubMed

Rauch, Philipp J; Ellegast, Jana M; Widmer, Corinne C; Fritsch, Kristin; Goede, Jeroen S; Valk, Peter J M; Löwenberg, Bob; Takizawa, Hitoshi; Manz, Markus G

2016-11-03

Although the molecular pathways that cause acute myeloid leukemia (AML) are increasingly well understood, the pathogenesis of peripheral blood cytopenia, a major cause of AML mortality, remains obscure. A prevailing assumption states that AML spatially displaces nonleukemic hematopoiesis from the bone marrow. However, examining an initial cohort of 223 AML patients, we found no correlation between bone marrow blast content and cytopenia, questioning the displacement theory. Measuring serum concentration of thrombopoietin (TPO), a key regulator of hematopoietic stem cells and megakaryocytes, revealed loss of physiologic negative correlation with platelet count in AML cases with blasts expressing MPL, the thrombopoietin (scavenging) receptor. Mechanistic studies demonstrated that MPL hi blasts could indeed clear TPO, likely therefore leading to insufficient cytokine levels for nonleukemic hematopoiesis. Microarray analysis in an independent multicenter study cohort of 437 AML cases validated MPL expression as a central predictor of thrombocytopenia and neutropenia in AML. Moreover, t(8;21) AML cases demonstrated the highest average MPL expression and lowest average platelet and absolute neutrophil counts among subgroups. Our work thus explains the pathophysiology of peripheral blood cytopenia in a relevant number of AML cases. © 2016 by The American Society of Hematology.

Inhibition of autophagy as a treatment strategy for p53 wild-type acute myeloid leukemia

PubMed Central

Folkerts, Hendrik; Hilgendorf, Susan; Wierenga, Albertus T J; Jaques, Jennifer; Mulder, André B; Coffer, Paul J; Schuringa, Jan Jacob; Vellenga, Edo

2017-01-01

Here we have explored whether inhibition of autophagy can be used as a treatment strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in leukemic cell lines and primary human CD34+ AML cells with a large variability in basal autophagy between AMLs observed. The autophagy flux was higher in AMLs classified as poor risk, which are frequently associated with TP53 mutations (TP53mut), compared with favorable- and intermediate-risk AMLs. In addition, the higher flux was associated with a higher expression level of several autophagy genes, but was not affected by alterations in p53 expression by knocking down p53 or overexpression of wild-type p53 or p53R273H. AML CD34+ cells were more sensitive to the autophagy inhibitor hydroxychloroquine (HCQ) than normal bone marrow CD34+ cells. Similar, inhibition of autophagy by knockdown of ATG5 or ATG7 triggered apoptosis, which coincided with increased expression of p53. In contrast to wild-type p53 AML (TP53wt), HCQ treatment did not trigger a BAX and PUMA-dependent apoptotic response in AMLs harboring TP53mut. To further characterize autophagy in the leukemic stem cell-enriched cell fraction AML CD34+ cells were separated into ROSlow and ROShigh subfractions. The immature AML CD34+-enriched ROSlow cells maintained higher basal autophagy and showed reduced survival upon HCQ treatment compared with ROShigh cells. Finally, knockdown of ATG5 inhibits in vivo maintenance of AML CD34+ cells in NSG mice. These results indicate that targeting autophagy might provide new therapeutic options for treatment of AML since it affects the immature AML subfraction. PMID:28703806

Segmentation and tracking in echocardiographic sequences: active contours guided by optical flow estimates

NASA Technical Reports Server (NTRS)

Mikic, I.; Krucinski, S.; Thomas, J. D.

1998-01-01

This paper presents a method for segmentation and tracking of cardiac structures in ultrasound image sequences. The developed algorithm is based on the active contour framework. This approach requires initial placement of the contour close to the desired position in the image, usually an object outline. Best contour shape and position are then calculated, assuming that at this configuration a global energy function, associated with a contour, attains its minimum. Active contours can be used for tracking by selecting a solution from a previous frame as an initial position in a present frame. Such an approach, however, fails for large displacements of the object of interest. This paper presents a technique that incorporates the information on pixel velocities (optical flow) into the estimate of initial contour to enable tracking of fast-moving objects. The algorithm was tested on several ultrasound image sequences, each covering one complete cardiac cycle. The contour successfully tracked boundaries of mitral valve leaflets, aortic root and endocardial borders of the left ventricle. The algorithm-generated outlines were compared against manual tracings by expert physicians. The automated method resulted in contours that were within the boundaries of intraobserver variability.

Heart valve replacement with the Sorin tilting-disc prosthesis. A 10-year experience.

PubMed

Milano, A; Bortolotti, U; Mazzucco, A; Mossuto, E; Testolin, L; Thiene, G; Gallucci, V

1992-02-01

From 1978 to 1988, 697 patients with a mean age of 48 +/- 11 years (range 5 to 75 years) received a Sorin tilting-disc prosthesis; 358 had had aortic valve replacement, 247 mitral valve replacement, and 92 mitral and aortic valve replacement. Operative mortality rates were 7.8%, 11.3%, and 10.8%, respectively, in the three groups. Cumulative duration of follow-up is 1650 patient-years for aortic valve replacement (maximum follow-up 11.4 years), 963 patient-years for mitral valve replacement (maximum follow-up 9.9 years) and 328 patient-years for mitral and aortic valve replacement (maximum follow-up 9.4 years). Actuarial survival at 9 years is 72% +/- 4% after mitral valve replacement, 70% +/- 3% after aortic valve replacement, and 50% +/- 12% after mitral and aortic valve replacement, and actuarial freedom from valve-related deaths is 97% +/- 2% after mitral valve replacement, 92% +/- 2% after aortic valve replacement, and 62% +/- 15% after mitral and aortic valve replacement. Thromboembolic events occurred in 21 patients with aortic valve replacement (1.3% +/- 0.2%/pt-yr), in 12 with mitral valve replacement (1.2% +/- 0.3% pt-yr), and in seven with mitral and aortic valve replacement (2.1% +/- 0.8%), with one case of prosthetic thrombosis in each group; actuarial freedom from thromboembolism at 9 years is 92% +/- 3% after mitral valve replacement, 91% +/- 3% after aortic valve replacement, and 74% +/- 16% after mitral and aortic valve replacement. Anticoagulant-related hemorrhage was observed in 15 patients after aortic valve replacement (0.9% +/- 0.2%/pt-yr), in 9 after mitral valve replacement (0.9% +/- 0.3%/pt-yr), and in 6 with mitral and aortic valve replacement (0.9% +/- 0.5%/pt-yr); actuarial freedom from this complication at 9 years is 94% +/- 2% after aortic valve replacement, 91% +/- 4% after mitral valve replacement, and 68% +/- 16% after mitral and aortic valve replacement. Actuarial freedom from reoperation at 9 years is 97% +/- 2% after mitral and aortic valve replacement, 92% +/- 4% after mitral valve replacement, and 89% +/- 3% after aortic valve replacement, with no cases of mechanical fracture. The Sorin valve has shown a satisfactory long-term overall performance, comparable with other mechanical prostheses, and an excellent durability that renders it a reliable heart valve substitute for the mitral and aortic positions.

Identification of novel molecular markers for prognosis estimation of acute myeloid leukemia: over-expression of PDCD7, FIS1 and Ang2 may indicate poor prognosis in pretreatment patients with acute myeloid leukemia.

PubMed

Tian, Yiming; Huang, Zoufang; Wang, Zhixiang; Yin, Changxin; Zhou, Lanlan; Zhang, Lingxiu; Huang, Kaikai; Zhou, Hongsheng; Jiang, Xuejie; Li, Jinming; Liao, Libin; Yang, Mo; Meng, Fanyi

2014-01-01

Numerous factors impact on the prognosis of acute myeloid leukemia (AML), among which molecular genetic abnormalities are developed increasingly, however, accurate prediction for newly diagnosed AML patients remains unsatisfied. For further improving the prognosis evaluation system, we investigated the transcripts levels of PDCD7, FIS1, FAM3A, CA6, APP, KLRF1, ATCAY, GGT5 and Ang2 in 97 AML patients and 30 non-malignant controls, and validated using the published microarray data from 225 cytogenetically normal AML (CN-AML) patients treated according to the German AMLCG-1999 protocol. Real-time quantitative polymerase chain reaction and western blot were carried out, and clinical data were collected and analyzed. High Ang2 and FIS1 expression discriminated the CR rate of AML patients (62.5% versus 82.9% for Ang2, P = 0.011; 61.4% versus 82.2% for FIS1, P = 0.029). In CN-AML, patients with high FIS1 expression were more likely to be resistant to two courses of induction (P = 0.035). Overall survival (OS) and relapse-free survival (RFS) were shorter in CN-AML patients with high PDCD7 expression (P<0.001; P = 0.006), and PDCD7 was revealed to be an independent risk factor for OS in CN-AML (P = 0.004). In the analysis of published data from 225 CN-AML patients, PDCD7 remained independently predicting OS in CN-AML (P = 0.039). As a conclusion, Ang2 and FIS1 seem related to decreased CR rate of AML patients, and PDCD7 is associated with shorter OS and RFS in CN-AML. Hence, PDCD7, Ang2 and FIS1 may indicate a more aggressive form and poor prognosis of AML.

Identification of Novel Molecular Markers for Prognosis Estimation of Acute Myeloid Leukemia: Over-Expression of PDCD7, FIS1 and Ang2 May Indicate Poor Prognosis in Pretreatment Patients with Acute Myeloid Leukemia

PubMed Central

Tian, Yiming; Huang, Zoufang; Wang, Zhixiang; Yin, Changxin; Zhou, Lanlan; Zhang, Lingxiu; Huang, Kaikai; Zhou, Hongsheng; Jiang, Xuejie; Li, Jinming; Liao, Libin; Yang, Mo; Meng, Fanyi

2014-01-01

Numerous factors impact on the prognosis of acute myeloid leukemia (AML), among which molecular genetic abnormalities are developed increasingly, however, accurate prediction for newly diagnosed AML patients remains unsatisfied. For further improving the prognosis evaluation system, we investigated the transcripts levels of PDCD7, FIS1, FAM3A, CA6, APP, KLRF1, ATCAY, GGT5 and Ang2 in 97 AML patients and 30 non-malignant controls, and validated using the published microarray data from 225 cytogenetically normal AML (CN-AML) patients treated according to the German AMLCG-1999 protocol. Real-time quantitative polymerase chain reaction and western blot were carried out, and clinical data were collected and analyzed. High Ang2 and FIS1 expression discriminated the CR rate of AML patients (62.5% versus 82.9% for Ang2, P = 0.011; 61.4% versus 82.2% for FIS1, P = 0.029). In CN-AML, patients with high FIS1 expression were more likely to be resistant to two courses of induction (P = 0.035). Overall survival (OS) and relapse-free survival (RFS) were shorter in CN-AML patients with high PDCD7 expression (P<0.001; P = 0.006), and PDCD7 was revealed to be an independent risk factor for OS in CN-AML (P = 0.004). In the analysis of published data from 225 CN-AML patients, PDCD7 remained independently predicting OS in CN-AML (P = 0.039). As a conclusion, Ang2 and FIS1 seem related to decreased CR rate of AML patients, and PDCD7 is associated with shorter OS and RFS in CN-AML. Hence, PDCD7, Ang2 and FIS1 may indicate a more aggressive form and poor prognosis of AML. PMID:24416201

Adult Acute Erythroleukemia: An Analysis of 108 patients treated at a single institution

PubMed Central

Santos, Fabio; Faderl, Stefan; Garcia-Manero, Guillermo; Koller, Charles; Beran, Miloslav; O'Brien, Susan; Pierce, Sherry; Freireich, Emil; Huang, Xuelin; Borthakur, Gautam; Bueso-Ramos, Carlos; de Lima, Marcos; Keating, Michael; Cortes, Jorge; Kantarjian, Hagop; Ravandi, Farhad

2014-01-01

Acute erythroleukemia (AML-M6) is an uncommon subtype of acute myeloid leukemia (AML); it is considered to have a poor prognosis. From January 1st, 1980 to May 21st, 2008, 108 patients with newly diagnosed AML-M6 were seen at the University of Texas – M.D. Anderson Cancer Center (UT-MDACC). Half (50%) had a history of myelodysplatic syndrome (MDS), compared to 41% in our control group (patients with other AML subtypes) (p=0.05). Poor risk cytogenetics was more common in patients with AML-M6 (69% versus 46%, p<0.001). Complete remission rates were 63% for patients with AML-M6, comparing to 58% for the control group (p = 0.285). Median disease free survival (DFS) for patients with AML-M6 was 31 weeks, versus 49 weeks for the control group (p = 0.004). Median overall survival (OS) of patients with AML-M6 was 33 weeks, compared to 42 weeks for the control group (p = 0.13). On multivariate analysis for DFS and OS, AML-M6 was not an independent risk factor. Acute erythroleukemia is commonly associated with a previous diagnosis of MDS and poor risk karyotype. The diagnosis of AML-M6 does not impart by itself a worse prognosis, and treatment decisions on this disease should be guided by well know AML prognostic factors. PMID:19741728

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia.

PubMed

Pillinger, Genevra; Abdul-Aziz, Amina; Zaitseva, Lyubov; Lawes, Matthew; MacEwan, David J; Bowles, Kristian M; Rushworth, Stuart A

2015-08-21

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML.

AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer.

PubMed

Tian, Ying; Wang, Genjie; Hu, Qingzhu; Xiao, Xichun; Chen, Shuxia

2018-04-01

The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. © 2017 Wiley Periodicals, Inc.

Total ellipse of the heart valve: the impact of eccentric stent distortion on the regional dynamic deformation of pericardial tissue leaflets of a transcatheter aortic valve replacement

PubMed Central

Gunning, Paul S.; Saikrishnan, Neelakantan; Yoganathan, Ajit P.; McNamara, Laoise M.

2015-01-01

Transcatheter aortic valve replacements (TAVRs) are a percutaneous alternative to surgical aortic valve replacements and are used to treat patients with aortic valve stenosis. This minimally invasive procedure relies on expansion of the TAVR stent to radially displace calcified aortic valve leaflets against the aortic root wall. However, these calcium deposits can impede the expansion of the device causing distortion of the valve stent and pericardial tissue leaflets. The objective of this study was to elucidate the impact of eccentric TAVR stent distortion on the dynamic deformation of the tissue leaflets of the prosthesis in vitro. Dual-camera stereophotogrammetry was used to measure the regional variation in strain in a leaflet of a TAVR deployed in nominal circular and eccentric (eccentricity index = 28%) orifices, representative of deployed TAVRs in vivo. It was observed that (i) eccentric stent distortion caused incorrect coaptation of the leaflets at peak diastole resulting in a ‘peel-back’ leaflet geometry that was not present in the circular valve and (ii) adverse bending of the leaflet, arising in the eccentric valve at peak diastole, caused significantly higher commissure strains compared with the circular valve in both normotensive and hypertensive pressure conditions (normotension: eccentric = 13.76 ± 2.04% versus circular = 11.77 ± 1.61%, p = 0.0014, hypertension: eccentric = 15.07 ± 1.13% versus circular = 13.56 ± 0.87%, p = 0.0042). This study reveals that eccentric distortion of a TAVR stent can have a considerable impact on dynamic leaflet deformation, inducing deleterious bending of the leaflet and increasing commissures strains, which might expedite leaflet structural failure compared to leaflets in a circular deployed valve. PMID:26674192

Behavior of Bilayer Leaflets in Asymmetric Model Membranes: Atomistic Simulation Studies

DOE PAGES

Tian, Jianhui; Nickels, Jonathan; Katsaras, John; ...

2016-04-27

Spatial organization within lipid bilayers is an important feature for a range of biological processes. Leaflet compositional asymmetry and lateral lipid organization are just two of the ways in which membrane structure appears to be more complex than initially postulated by the fluid mosaic model. This raises the question of how the phase behavior in one bilayer leaflet may affect the apposing leaflet and how one begins to construct asymmetric model systems to investigate these interleaflet interactions. In this paper, we report on all-atom molecular dynamics simulations (a total of 4.1 μs) of symmetric and asymmetric bilayer systems composed ofmore » liquid-ordered (Lo) or liquid-disordered (Ld) leaflets, based on the nanodomain-forming POPC/DSPC/cholesterol system. We begin by analyzing an asymmetric bilayer with leaflets derived from simulations of symmetric Lo and Ld bilayers. In this system, we observe that the properties of the Lo and Ld leaflets are similar to those of the Lo and Ld leaflets in corresponding symmetric systems. However, it is not obvious that mixing the equilibrium structures of their symmetric counterparts is the most appropriate way to construct asymmetric bilayers nor that these structures will manifest interleaflet couplings that lead to domain registry/antiregistry. We therefore constructed and simulated four additional asymmetric bilayer systems by systematically adding or removing lipids in the Ld leaflet to mimic potential density fluctuations. We find that the number of lipids in the Ld leaflet affects its own properties, as well as those of the apposing Lo leaflet. Collectively, the simulations reveal the presence of weak acyl chain interdigitation across bilayer leaflets, suggesting that interdigitation alone does not contribute significantly to the interleaflet coupling in nonphase-separated bilayers of this chemical composition. Finally, however, the properties of both leaflets appear to be sensitive to changes in in-plane lipid packing, possibly providing a mechanism for interleaflet coupling by modulating local density and/or curvature fluctuations.« less

Clonal evolution and devolution after chemotherapy in adult acute myelogenous leukemia

PubMed Central

Parkin, Brian; Ouillette, Peter; Li, Yifeng; Keller, Jennifer; Lam, Cindy; Roulston, Diane; Li, Cheng; Shedden, Kerby

2013-01-01

The frequent occurrence of persistent or relapsed disease after induction chemotherapy in AML necessitates a better understanding of the clonal relationship of AML in various disease phases. In this study, we used SNP 6.0 array-based genomic profiling of acquired copy number aberrations (aCNA) and copy neutral LOH (cnLOH) together with sequence analysis of recurrently mutated genes to characterize paired AML genomes. We analyzed 28 AML sample pairs from patients who achieved complete remission with chemotherapy and subsequently relapsed and 11 sample pairs from patients with persistent disease after induction chemotherapy. Through review of aCNA/cnLOH and gene mutation profiles in informative cases, we demonstrate that relapsed AML invariably represents re-emergence or evolution of a founder clone. Furthermore, all individual aCNA or cnLOH detected at presentation persisted at relapse indicating that this lesion type is proximally involved in AML evolution. Analysis of informative paired persistent AML disease samples uncovered cases with 2 coexisting dominant clones of which at least one was chemotherapy sensitive and one resistant, respectively. These data support the conclusion that incomplete eradication of AML founder clones rather than stochastic emergence of fully unrelated novel clones underlies AML relapse and persistence with direct implications for clinical AML research. PMID:23175688

MicroRNA-155 expression and function in AML: An evolving paradigm.

PubMed

Narayan, Nisha; Bracken, Cameron P; Ekert, Paul G

2018-06-01

Acute myeloid leukemia (AML) arises when immature myeloid blast cells acquire multiple, recurrent genetic and epigenetic changes that result in dysregulated proliferation. Acute leukemia is the most common form of pediatric cancer, with AML accounting for ~20% of all leukemias in children. The genomic aberrations that drive AML inhibit myeloid differentiation and activate signal transduction pathways that drive proliferation. MicroRNAs, a class of small (~22 nucleotide) noncoding RNAs that posttranscriptionally suppress the expression of specifically targeted transcripts, are also frequently dysregulated in AML, which may prove useful for the purposes of disease classification, prognosis, and future therapeutic approaches. MicroRNA expression profiles are associated with patient prognosis and responses to standard chemotherapy, including predicting therapy resistance in AML. miR-155 is the primary focus of this review because it has been repeatedly associated with poorer survival across multiple cohorts of adult and pediatric AML. We discuss some novel features of miR-155 expression in AML, in particular how the levels of expression can critically influence function. Understanding the role of microRNAs in AML and the ways in which microRNA expression influences AML biology is one means to develop novel and more targeted therapies. Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Preparation, validation and user-testing of pictogram-based patient information leaflets for hemodialysis patients.

PubMed

Mateti, Uday Venkat; Nagappa, Anantha Naik; Attur, Ravindra Prabhu; Bairy, Manohar; Nagaraju, Shankar Prasad; Mallayasamy, Surulivelrajan; Vilakkathala, Rajesh; Guddattu, Vasudev; Balkrishnan, Rajesh

2015-11-01

Patient information leaflets are universally-accepted resources to educate the patients/users about their medications, disease and lifestyle modification. The objective of the study was to prepare, validate and perform user-testing of pictogram-based patient information leaflets (P-PILs) among hemodialysis (HD) patients. The P-PILs are prepared by referring to the primary, secondary and tertiary resources. The content and pictograms of the leaflet have been validated by an expert committee consisting of three nephrologists and two academic pharmacists. The Baker Able Leaflet Design has been applied to develop the layout and design of the P-PILs. Quasi-experimental pre- and post-test design without control group was conducted on 81 HD patients for user-testing of P-PILs. The mean Baker Able Leaflet Design assessment score for English version of the leaflet was 28, and 26 for Kannada version. The overall user-testing knowledge assessment mean scores were observed to have significantly improved from 44.25 to 69.62 with p value <0.001. The overall user opinion of content and legibility of the leaflets was good. Pictogram-based patient information leaflets can be considered an effective educational tool for HD patients.

A novel glycogen synthase kinase-3 inhibitor optimized for acute myeloid leukemia differentiation activity

PubMed Central

Stetson, Lindsay; Ignatz-Hoover, James; Moreton, Stephen; Chakrabarti, Amit; Xia, Zhiqiang; Karan, Goutam; de Lima, Marcos; Agrawal, Mukesh K; Wald, David N

2016-01-01

Standard therapies used for the treatment of Acute Myeloid Leukemia (AML) are cytotoxic agents that target rapidly proliferating cells. Unfortunately, this therapeutic approach has limited efficacy and significant toxicity and the majority of AML patients still die of their disease. In contrast to the poor prognosis of most AML patients, most individuals with a rare subtype of AML, Acute Promyelocytic Leukemia (APL), can be cured by differentiation therapy using regimens containing all-trans retinoic acid. GSK3 has previously been identified as a therapeutic target in AML where its inhibition can lead to the differentiation and growth arrest of leukemic cells. Unfortunately, existing GSK3 inhibitors lead to suboptimal differentiation activity making them less useful as clinical AML differentiation agents. Here we describe the discovery of a novel GSK3 inhibitor, GS87. GS87 was discovered in efforts to optimize GSK3 inhibition for AML differentiation activity. Despite GS87's dramatic ability to induce AML differentiation, kinase profiling reveals its high specificity in targeting GSK3 as compared to other kinases. GS87 demonstrates high efficacy in a mouse AML model system and unlike current AML therapeutics, exhibits little effect on normal bone marrow cells. GS87 induces potent differentiation by more effectively activating GSK3-dependent signaling components including MAPK signaling as compared to other GSK3 inhibitors. GS87 is a novel GSK3 inhibitor with therapeutic potential as a differentiation agent for non-promyelocytic AML. PMID:27196775

Relation of Mitral Valve Surgery Volume to Repair Rate, Durability, and Survival.

PubMed

Chikwe, Joanna; Toyoda, Nana; Anyanwu, Anelechi C; Itagaki, Shinobu; Egorova, Natalia N; Boateng, Percy; El-Eshmawi, Ahmed; Adams, David H

2017-04-24

Degenerative mitral valve repair rates remain highly variable, despite established benefits of repair over replacement. The contribution of surgeon-specific factors is poorly defined. This study evaluated the influence of surgeon case volume on degenerative mitral valve repair rates and outcomes. A mandatory New York State database was queried and 5,475 patients were identified with degenerative mitral disease who underwent mitral valve operations between 2002 and 2013. Mitral repair rates, mitral reoperations within 12 months of repair, and survival were analyzed using multivariable Cox modeling and restricted cubic spline function. Median annual surgeon volume of any mitral operations was 10 (range 1 to 230), with a mean repair rate of 55% (n = 20,797 of 38,128). In the subgroup of patients with degenerative disease, the mean repair rate was 67% (n = 3,660 of 5,475), with a range of 0% to 100%. Mean repair rates ranged from 48% (n = 179 of 370) for surgeons with total annual volumes of ≤10 mitral operations to 77% (n = 1,710 of 2,216) for surgeons with total annual volumes of >50 mitral operations (p < 0.001). Higher total annual surgeon volume was associated with increased repair rates of degenerative mitral valve disease (adjusted odds ratio [OR]: 1.13 for every additional 10 mitral operations; 95% confidence interval [CI]: 1.10 to 1.17; p < 0.001); a steady decrease in reoperation risk until 25 total mitral operations annually; and improved 1-year survival (adjusted hazard ratio: 0.95 for every additional 10 operations; 95% CI: 0.92 to 0.98; p = 0.001). For surgeons with a total annual volume of ≤25 mitral operations, repair rates were higher (63.8%; n = 180 of 282) if they operated in the same institution as a surgeon with total annual mitral volumes of >50 and degenerative mitral valve repair rates of >70%, compared with surgeons operating in the other institutions (51.3%; n = 580 of 1,130) (adjusted OR: 1.79; 95% CI: 1.24 to 2.60; p < 0.001). This study suggests that individual surgeon volume is a determinant of not only mitral repair rates, but also freedom from reoperation, and survival. The data from this study support the guideline's concept of reference referral to experienced mitral surgeons to improve outcomes in patients with degenerative mitral valve disease. Copyright © 2017. Published by Elsevier Inc.

Stress Analysis of Transcatheter Aortic Valve Leaflets Under Dynamic Loading: Effect of Reduced Tissue Thickness.

PubMed

Abbasi, Mostafa; Azadani, Ali N

2017-07-01

In order to accommodate transcatheter valves to miniaturized catheters, the leaflet thickness must be reduced to a value which is typically less than that of surgical bioprostheses. The study aim was to use finite-element simulations to determine the impact of the thickness reduction on stress and strain distribution. A 23 mm transcatheter aortic valve (TAV) was modelled based on the Edwards SAPIEN XT (Edwards Lifesciences, Irvine, CA, USA). Finite-element (FE) analysis was performed using the ABAQUS/Explicit solver. An ensemble-averaged transvalvular pressure waveform measured from in-vitro tests conducted in a pulse duplicator was applied to the leaflets. Through a parametric study, uniform TAV leaflet thickness was reduced from 0.5 to 0.18 mm. By reducing leaflet thickness, significantly higher stress values were found in the leaflet's fixed edge during systole, and in the commissures during diastole. Through dynamic FE simulations, the highest stress values were found during systole in the leaflet fixed edge. In contrast, at the peak of diastole high-stress regions were mainly observed in the commissures. The peak stress was increased by 178% and 507% within the leaflets after reducing the thickness of 0.5 mm to 0.18 mm at the peak of systole and diastole, respectively. The study results indicated that, the smaller the leaflet thickness, the higher the maximum principal stress. Increased mechanical stress on TAV leaflets may lead to accelerated tissue degeneration. By using a thinner leaflet, TAV durability may not atch with that of surgical bioprostheses.

Comprehensive mutational profiling of core binding factor acute myeloid leukemia

PubMed Central

Duployez, Nicolas; Marceau-Renaut, Alice; Boissel, Nicolas; Petit, Arnaud; Bucci, Maxime; Geffroy, Sandrine; Lapillonne, Hélène; Renneville, Aline; Ragu, Christine; Figeac, Martin; Celli-Lebras, Karine; Lacombe, Catherine; Micol, Jean-Baptiste; Abdel-Wahab, Omar; Cornillet, Pascale; Ifrah, Norbert; Dombret, Hervé; Leverger, Guy; Jourdan, Eric

2016-01-01

Acute myeloid leukemia (AML) with t(8;21) or inv(16) have been recognized as unique entities within AML and are usually reported together as core binding factor AML (CBF-AML). However, there is considerable clinical and biological heterogeneity within this group of diseases, and relapse incidence reaches up to 40%. Moreover, translocations involving CBFs are not sufficient to induce AML on its own and the full spectrum of mutations coexisting with CBF translocations has not been elucidated. To address these issues, we performed extensive mutational analysis by high-throughput sequencing in 215 patients with CBF-AML enrolled in the Phase 3 Trial of Systematic Versus Response-adapted Timed-Sequential Induction in Patients With Core Binding Factor Acute Myeloid Leukemia and Treating Patients with Childhood Acute Myeloid Leukemia with Interleukin-2 trials (age, 1-60 years). Mutations in genes activating tyrosine kinase signaling (including KIT, N/KRAS, and FLT3) were frequent in both subtypes of CBF-AML. In contrast, mutations in genes that regulate chromatin conformation or encode members of the cohesin complex were observed with high frequencies in t(8;21) AML (42% and 18%, respectively), whereas they were nearly absent in inv(16) AML. High KIT mutant allele ratios defined a group of t(8;21) AML patients with poor prognosis, whereas high N/KRAS mutant allele ratios were associated with the lack of KIT or FLT3 mutations and a favorable outcome. In addition, mutations in epigenetic modifying or cohesin genes were associated with a poor prognosis in patients with tyrosine kinase pathway mutations, suggesting synergic cooperation between these events. These data suggest that diverse cooperating mutations may influence CBF-AML pathophysiology as well as clinical behavior and point to potential unique pathogenesis of t(8;21) vs inv(16) AML. PMID:26980726

Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models.

PubMed

Portwood, Scott; Lal, Deepika; Hsu, Yung-Chun; Vargas, Rodrigo; Johnson, Megan K; Wetzler, Meir; Hart, Charles P; Wang, Eunice S

2013-12-01

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm. Recent evidence has shown the bone marrow microenvironment in patients with AML to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth. We assessed the effects of hypoxia and TH-302 on human AML cells, primary samples, and systemic xenograft models. We observed that human AML cells and primary AML colonies cultured under chronic hypoxia (1% O2, 72 hours) exhibited reduced sensitivity to cytarabine-induced apoptosis as compared with normoxic controls. TH-302 treatment resulted in dose- and hypoxia-dependent apoptosis and cell death in diverse AML cells. TH-302 preferentially decreased proliferation, reduced HIF-1α expression, induced cell-cycle arrest, and enhanced double-stranded DNA breaks in hypoxic AML cells. Hypoxia-induced reactive oxygen species by AML cells were also diminished. In systemic human AML xenografts (HEL, HL60), TH-302 [50 mg/kg intraperitoneally (i.p.) 5 times per week] inhibited disease progression and prolonged overall survival. TH-302 treatment reduced the number of hypoxic cells within leukemic bone marrows and was not associated with hematologic toxicities in nonleukemic or leukemic mice. Later initiation of TH-302 treatment in advanced AML disease was as effective as earlier TH-302 treatment in xenograft models. Our results establish the preclinical activity of TH-302 in AML and provide the rationale for further clinical studies of this and other hypoxia-activated agents for leukemia therapy. ©2013 AACR.

Disrupting Threat Finances: Utilization of Financial Information to Disrupt Terrorist Organization in the Twenty-First Century

DTIC Science & Technology

2007-04-01

with the FATF for conducting comprehensive Anti-Money Laundering/Counter-Financing of Terrorism ( AML / CFT ) assessments of countries’ compliance with... AML / CFT ) (September 2002) • http://www.imf.org/external/np/mae/am/2002/eng/092523.htm (Comprehensive Methodology on AML / CFT ) International...of Rwanda AML : Anti-Money Laundering AML / CFT : Anti-Money Laundering/Counter-Financing of Terrorism ANO: Abu Nidal Organization AOR: Area of

Diet and Colorectal Cancer Risk: Evaluation of a Nutrition Education Leaflet

ERIC Educational Resources Information Center

Dyer, K. J.; Fearon, K. C. H.; Buckner, K.; Richardson, R. A.

2005-01-01

Objective: To evaluate the effect of a needs-based, nutrition education leaflet on nutritional knowledge. Design: Comparison of nutritional knowledge levels before and after exposure to a nutrition education leaflet. Setting: A regional colorectal out-patient clinic in Edinburgh. Method: A nutrition education leaflet, based on an earlier…

Augmentation of autologous T cell reactivity with acute myeloid leukemia (AML) blasts by Toll-like receptor (TLR) agonists

PubMed Central

Zhong, RuiKun; Li, Hongying; Messer, Karen; Lane, Thomas A.; Zhou, Jiehua; Ball, Edward D.

2016-01-01

This study investigated whether TNF-α, Toll-like receptors (TLRs) 7/8 agonist resiquimod (R848), the TLR4 agonist lipopolysaccharide (LPS) and their combinations can enhance autologous AML-reactive T cell generation in an in vitro culture. AML peripheral blood or bone marrow mononuclear cells were cultured in medium supplemented with GM-CSF/IL-4 to induce dendritic cell (DC) differentiation of AML blasts (AML-DC). The impact of TNF-α, LPS, R848 and their combinations on AML-DC cultures was analyzed. Significantly enhanced CD80, CD40, CD83, CD54, HLADR and CD86 expression of AML cells was observed by addition of TNF-α, LPS, R848 alone or combinations. Induced CD80 expression of AML cells was significantly higher through the combination of TNF-α, LPS and R848 (T + L + R) than that by T alone. CTL induced from T + L + R, T + R, T + L, L + R and R, but not T, L alone stimulated cultures showed significantly higher IFN-γ release than the medium control in response to autologous AML cells. IFN-γ release by T + L + R was significantly higher than T or L alone, and T + R was significantly higher than T alone. CTL generated from T + L + R, T + L, T + R, L + R and L alone exerted significantly higher AML cell killing than medium control. AML cell killing by T + L + R and T + R was significantly higher than T or R alone. These results indicate that the combination of T + L + R induces a significantly enhanced antigen presentation effect of AML-DC. We speculate that the complementary effects of reagent combinations may better address the heterogeneity of responses to any single agent in AML cells from different patients. PMID:25795133

Diagnostic and Prognostic Utility of Fluorescence In situ Hybridization (FISH) Analysis in Acute Myeloid Leukemia.

PubMed

Gonzales, Patrick R; Mikhail, Fady M

2017-12-01

Acute myeloid leukemia (AML) is a hematologic neoplasia consisting of incompletely differentiated hematopoietic cells of the myeloid lineage that proliferate in the bone marrow, blood, and/or other tissues. Clinical implementation of fluorescence in situ hybridization (FISH) in cytogenetic laboratories allows for high-resolution analysis of recurrent structural chromosomal rearrangements specific to AML, especially in AML with normal karyotypes, which comprises approximately 33-50% of AML-positive specimens. Here, we review the use of several FISH probe strategies in the diagnosis of AML. We also review the standards and guidelines currently in place for use by clinical cytogenetic laboratories in the evaluation of AML. Updated standards and guidelines from the WHO, ACMG, and NCCN have further defined clinically significant, recurring cytogenetic anomalies in AML that are detectable by FISH. FISH continues to be a powerful technique in the diagnosis of AML, with higher resolution than conventional cytogenetic analysis, rapid turnaround time, and a considerable diagnostic and prognostic utility.

Repression of GSK3 restores NK cell cytotoxicity in AML patients

PubMed Central

Parameswaran, Reshmi; Ramakrishnan, Parameswaran; Moreton, Stephen A.; Xia, Zhiqiang; Hou, Yongchun; Lee, Dean A.; Gupta, Kalpana; deLima, Marcos; Beck, Rose C.; Wald, David N.

2016-01-01

Natural killer cells from acute myeloid leukaemia patients (AML-NK) show a dramatic impairment in cytotoxic activity. The exact reasons for this dysfunction are not fully understood. Here we show that the glycogen synthase kinase beta (GSK3β) expression is elevated in AML-NK cells. Interestingly, GSK3 overexpression in normal NK cells impairs their ability to kill AML cells, while genetic or pharmacological GSK3 inactivation enhances their cytotoxic activity. Mechanistic studies reveal that the increased cytotoxic activity correlates with an increase in AML-NK cell conjugates. GSK3 inhibition promotes the conjugate formation by upregulating LFA expression on NK cells and by inducing ICAM-1 expression on AML cells. The latter is mediated by increased NF-κB activation in response to TNF-α production by NK cells. Finally, GSK3-inhibited NK cells show significant efficacy in human AML mouse models. Overall, our work provides mechanistic insights into the AML-NK dysfunction and a potential NK cell therapy strategy. PMID:27040177

Mitral valve prolapse and hyperthyroidism: effect of patient selection.

PubMed

Zullo, M A; Devereux, R B; Kramer-Fox, R; Lutas, E M; Brown, W T

1985-11-01

Patients with mitral valve prolapse and hyperthyroidism have common symptoms; the most outstanding symptom is palpitation. To determine whether or not common symptoms contributed to the reported association of these conditions, we evaluated 220 patients with symptomatic mitral valve prolapse and 216 first-degree relatives in 72 families; 65 relatives with mitral valve prolapse and 151 relatives without mitral valve prolapse, all greater than or equal to 16 years of age. Thirty subjects, aged 49 +/- 13 years (p less than 0.025 vs entire study group), had thyroid disease (23 subjects had definite thyroid disease, seven subjects had probable); 27 of 30 subjects with thyroid disease (90%) were female (p less than 0.005). The age- and sex-adjusted prevalence of hyperthyroidism was significantly higher in probands with mitral valve prolapse than in family members without mitral valve prolapse (3.5% vs 0%, p = 0.03), while an intermediate prevalence of hyperthyroidism (2.2%) was observed in family members with mitral valve prolapse. Thus, the prevalence of hyperthyroidism is increased among symptomatic patients with mitral valve prolapse as compared to family members without mitral valve prolapse, but the prevalence of thyroid conditions is similar among family members with or without this condition. These findings are explained by the effect of common symptoms on clinical detection of both mitral valve prolapse and hyperthyroidism.

Rheb1 promotes tumor progression through mTORC1 in MLL-AF9-initiated murine acute myeloid leukemia.

PubMed

Gao, Yanan; Gao, Juan; Li, Minghao; Zheng, Yawei; Wang, Yajie; Zhang, Hongyan; Wang, Weili; Chu, Yajing; Wang, Xiaomin; Xu, Mingjiang; Cheng, Tao; Ju, Zhenyu; Yuan, Weiping

2016-04-12

The constitutive hyper-activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways has frequently been associated with acute myeloid leukemia (AML). While many inhibitors targeting these pathways have been developed, the anti-leukemic effect was not as robust as expected. As part of the molecular link between PI3K/Akt and mTOR kinase, the role of Rheb1 in AML remains unexplored. Our study aims to explore the role of Rheb1 in AML and estimate whether Rheb1 could be a potential target of AML treatment. The expressions of Rheb1 and other indicated genes were analyzed using real-time PCR. AML mouse model was established by retrovirus transduction. Leukemia cell properties and related signaling pathways were dissected by in vitro and in vivo studies. The transcriptional changes were analyzed via gene chip analysis. Molecular reagents including mTOR inhibitor and mTOR activator were used to evaluate the function of related signaling pathway in the mouse model. We observed that Rheb1 is overexpressed in AML patients and the change of Rheb1 level in AML patients is associated with their median survival. Using a Rheb1-deficient MLL-AF9 murine AML model, we revealed that Rheb1 deletion prolonged the survival of AML mice by weakening LSC function. In addition, Rheb1 deletion arrested cell cycle progression and enhanced apoptosis of AML cells. Furthermore, while Rheb1 deletion reduced mTORC1 activity in AML cells, additional rapamycin treatment further decreased mTORC1 activity and increased the apoptosis of Rheb1 (Δ/Δ) AML cells. The mTOR activator 3BDO partially rescued mTORC1 signaling and inhibited apoptosis in Rheb1 (Δ/Δ) AML cells. Our data suggest that Rheb1 promotes AML progression through mTORC1 signaling pathway and combinational drug treatments targeting Rheb1 and mTOR might have a better therapeutic effect on leukemia.

Vortex flow during early and late left ventricular filling in normal subjects: quantitative characterization using retrospectively-gated 4D flow cardiovascular magnetic resonance and three-dimensional vortex core analysis.

PubMed

Elbaz, Mohammed S M; Calkoen, Emmeline E; Westenberg, Jos J M; Lelieveldt, Boudewijn P F; Roest, Arno A W; van der Geest, Rob J

2014-09-27

LV diastolic vortex formation has been suggested to critically contribute to efficient blood pumping function, while altered vortex formation has been associated with LV pathologies. Therefore, quantitative characterization of vortex flow might provide a novel objective tool for evaluating LV function. The objectives of this study were 1) assess feasibility of vortex flow analysis during both early and late diastolic filling in vivo in normal subjects using 4D Flow cardiovascular magnetic resonance (CMR) with retrospective cardiac gating and 3D vortex core analysis 2) establish normal quantitative parameters characterizing 3D LV vortex flow during both early and late ventricular filling in normal subjects. With full ethical approval, twenty-four healthy volunteers (mean age: 20±10 years) underwent whole-heart 4D Flow CMR. The Lambda2-method was used to extract 3D LV vortex ring cores from the blood flow velocity field during early (E) and late (A) diastolic filling. The 3D location of the center of vortex ring core was characterized using cylindrical cardiac coordinates (Circumferential, Longitudinal (L), Radial (R)). Comparison between E and A filling was done with a paired T-test. The orientation of the vortex ring core was measured and the ring shape was quantified by the circularity index (CI). Finally, the Spearman's correlation between the shapes of mitral inflow pattern and formed vortex ring cores was tested. Distinct E- and A-vortex ring cores were observed with centers of A-vortex rings significantly closer to the mitral valve annulus (E-vortex L=0.19±0.04 versus A-vortex L=0.15±0.05; p=0.0001), closer to the ventricle's long-axis (E-vortex: R=0.27±0.07, A-vortex: R=0.20±0.09, p=0.048) and more elliptical in shape (E-vortex: CI=0.79±0.09, A-vortex: CI=0.57±0.06; <0.001) compared to E-vortex. The circumferential location and orientation relative to LV long-axis for both E- and A-vortex ring cores were similar. Good to strong correlation was found between vortex shape and mitral inflow shape through both the annulus (r=0.66) and leaflet tips (r=0.83). Quantitative characterization and comparison of 3D vortex rings in LV inflow during both early and late diastolic phases is feasible in normal subjects using retrospectively-gated 4D Flow CMR, with distinct differences between early and late diastolic vortex rings.

Histone deacetylase inhibitors reduce differentiating osteoblast-mediated protection of acute myeloid leukemia cells from cytarabine

PubMed Central

Sterner, Rosalie M.; Kremer, Kimberly N.; Al-Kali, Aref; Patnaik, Mrinal M.; Gangat, Naseema; Litzow, Mark R.; Kaufmann, Scott H.; Westendorf, Jennifer J.; van Wijnen, Andre J.; Hedin, Karen E.

2017-01-01

The bone marrow microenvironment protects acute myeloid leukemia (AML) cells during chemotherapy and is a major factor in relapse. Here, we examined which type(s) of bone marrow cells are responsible for the relapse of AML following treatment with cytarabine (Ara-C), and we identified a means to inhibit this protection. To determine the protective cell type(s), AML cells were treated with Ara-C, and AML cell survival in the presence or absence of osteoblast lineage cells was assessed. Cultured AML cells and patient bone marrow isolates were each significantly protected from Ara-C-induced apoptosis by co-culture with differentiating osteoblasts. Moreover, pretreating differentiating osteoblasts with the histone deacetylase inhibitors (HDACi) vorinostat and panobinostat abrogated the ability of the differentiating osteoblasts to protect AML cells. Together, our results indicate that differentiating osteoblasts have the potential to promote residual AML in the bone marrow following standard chemotherapy and act via a mechanism requiring HDACi-sensitive gene expression. Using HDACi to target the leukemic microenvironment in combination with Ara-C could potentially improve treatment of AML. Moreover, other strategies for manipulating bone marrow osteoblasts may also help eradicate AML cells and reduce relapse. PMID:29212250

Mitral stenosis (image)

MedlinePlus

Mitral stenosis is a heart valve disorder that narrows or obstructs the mitral valve opening. Narrowing of the ... to the body. The main risk factor for mitral stenosis is a history of rheumatic fever but it ...

Acute myeloid leukaemia with myelodysplastic features in children: a report of Japanese Paediatric Leukaemia/Lymphoma Study Group.

PubMed

Kinoshita, Akitoshi; Miyachi, Hayato; Matsushita, Hiromichi; Yabe, Miharu; Taki, Tomohiko; Watanabe, Tomoyuki; Saito, Akiko M; Tomizawa, Daisuke; Taga, Takashi; Takahashi, Hiroyuki; Matsuo, Hidemasa; Kodama, Kumi; Ohki, Kentaro; Hayashi, Yasuhide; Tawa, Akio; Horibe, Keizo; Adachi, Souichi

2014-10-01

The clinical characteristics and prognostic relevance of acute myeloid leukaemia (AML) with myelodysplastic features remains to be clarified in children. We prospectively examined 443 newly diagnosed patients in a multicentre clinical trial for paediatric de novo AML, and found 'AML with myelodysplasia-related changes' (AML-MRC) according to the 2008 World Health Organization classification in 93 (21·0%), in whom 59 were diagnosed from myelodysplasia-related cytogenetics alone, 28 from multilineage dysplasia alone and six from a combination of both. Compared with 111 patients with 'AML, not otherwise specified' (AML-NOS), patients with 'AML-MRC' presented at a younger age, with a lower white blood cell count, higher incidence of 20-30% bone marrow blasts, unfavourable cytogenetics and a lower frequency of Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), NPM1 and CEBPA mutations. Complete remission rate and 3-year probability of event-free survival were significantly worse in 'AML-MRC' patients (67·7 vs. 85·6%, P < 0·01, 37·1% vs. 53·8%, P = 0·02, respectively), but 3-year overall survival and relapse-free survival were comparable with 'AML-NOS' patients. By multivariate analysis, FLT3-ITD was solely associated with worse overall survival. These results support the distinctive features of the category 'AML-MRC' even in children. © 2014 John Wiley & Sons Ltd.

Downregulation of miR‑135a predicts poor prognosis in acute myeloid leukemia and regulates leukemia progression via modulating HOXA10 expression.

PubMed

Xu, Hongwei; Wen, Quan

2018-05-23

MicroRNA‑135a (miR‑135a) has been shown to exert important roles in various human cancer types, such as glioblastoma, thyroid carcinoma and renal carcinoma. However, the function of miR‑135a in acute myeloid leukemia (AML) remains largely unknown. In the present study, it was demonstrated that miR‑135a expression was significantly downregulated in AML cells compared with normal control cells. Furthermore, the downregulation of miR‑135a in patients with AML predicted poor prognosis. Through functional experiments, overexpression of miR‑135a was demonstrated to significantly inhibit the proliferation and cell cycle of AML cells, while it promoted cellular apoptosis. miR‑135a directly targeted HOXA10 in AML cells. miR‑135a overexpression significantly suppressed the mRNA and protein levels of HOXA10 in AML cells. Moreover, there was an inverse association between miR‑135a expression and HOXA10 level in AML samples. Additionally, by ectopic expression of HOXA10, restoration of HOXA10 significantly abolished the effects of miR‑135a overexpression on AML cell proliferation, cell cycle and apoptosis. In conclusion, the present study demonstrated that miR‑135a serves as a tumor suppressor in AML by targeting HOXA10, and miR‑135a may be a promising prognostic biomarker for AML patients.

Promotion of family planning services in practice leaflets.

PubMed

Marshall, M N; Gray, D J; Pearson, V; Phillips, D R; Owen, M

1994-10-08

Providing 75% of family planning services in the United Kingdom, general practitioners are required to produce leaflets which describe the contraceptive services they provide. The authors analyzed information about family planning provided to clients through practice leaflets. 88% of practice leaflets from the 198 practices in Devon were available from the Devon Family Health Services Authority for analysis. It was determined that the leaflets are not being best used to advertise the range and potential of family planning services. Although all practices in Devon offer contraceptive services, only 90% of leaflets mentioned that the services are available. Reference to postcoital contraception and information about services outside the practice for people who might not want to see their family doctor are also sorely lacking. A clear need exists to provide patients with more information. Finally, the authors found that group practices and those with female partners are most likely to give high priority to family planning issues in their leaflets.

Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

PubMed

Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

2016-02-01

Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

Evaluation of the efficacy and tolerability of fixed-dose combination therapy of azilsartan and amlodipine besylate in Japanese patients with grade I to II essential hypertension.

PubMed

Rakugi, Hiromi; Nakata, Emi; Sasaki, Emma; Kagawa, Tomoya

2014-05-01

Guidelines for the management of hypertension recommend using drugs with different mechanisms of action in antihypertensive regimens that include simple single-pill fixed-dose combination (FDC) products. The objective of this study was to compare the efficacy and tolerability of the FDC of azilsartan (AZI) and amlodipine besylate (AML) with those of AZI monotherapy and AML monotherapy in Japanese patients with grade 1 to 2 essential hypertension. This was a multicenter, randomized, double-blind, parallel-group study. After receiving placebo during a 4-week run-in period in a single-blind manner, patients were randomized to receive 1 of the following 5 treatments for 8 weeks: FDC containing AZI 20 mg and AML 5 mg (AZI/AML 20/5 mg), FDC containing AZI 20 mg and AML 2.5 mg (AZI/AML 20/2.5 mg), AZI 20 mg, AML 5 mg, or AML 2.5 mg once daily in a fasting or fed state. The primary end point was the change from baseline (week 0) in the seated trough diastolic blood pressure at week 8 (last observation carried forward [LOCF]), and the secondary end point was the change from baseline in the seated trough systolic blood pressure at week 8 (LOCF). Tolerability was assessed based on adverse events, vital signs, and physical examination findings. Of the 800 patients who provided informed consent, 603 were randomized to receive AZI/AML 20/5 mg (150 patients), AZI/AML 20/2.5 mg (151 patients), AZI 20 mg (151 patients), AML 5 mg (75 patients), or AML 2.5 mg (76 patients). The mean baseline systolic/diastolic blood pressure was 160.7/100.3 mm Hg. The mean change from baseline in seated blood pressure at week 8 (LOCF) was -35.3/-22.3 mm Hg in the AZI/AML 20/5 mg group and -31.4/-19.2 mm Hg in the AZI/AML 20/2.5 mg group, indicating a reduction significantly greater than that in corresponding monotherapy groups (-21.5/-13.9 mm Hg in the AZI 20 mg group, -26.4/-15.5 mm Hg in the AML 5 mg group, and -19.3/-11.6 mm Hg in the AML 2.5 mg group; p < 0.0001 for all contrast tests). No remarkable difference was found in the incidences of adverse events, vital signs, and physical examination findings among the treatment groups. This study found that the FDC of AZI/AML 20/5 mg and 20/2.5 mg exhibited greater antihypertensive effects compared with each monotherapy. The FDC of AZI/AML had a similar safety profile to that of each monotherapy and was tolerable to Japanese patients with grade 1 to 2 essential hypertension. Japic CTI-111606. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group

PubMed Central

Pleyer, Lisa; Döhner, Hartmut; Dombret, Hervé; Seymour, John F.; Schuh, Andre C.; Beach, CL; Swern, Arlene S.; Burgstaller, Sonja; Stauder, Reinhard; Girschikofsky, Michael; Sill, Heinz; Schlick, Konstantin; Thaler, Josef; Halter, Britta; Machherndl Spandl, Sigrid; Zebisch, Armin; Pichler, Angelika; Pfeilstöcker, Michael; Autzinger, Eva M.; Lang, Alois; Geissler, Klaus; Voskova, Daniela; Sperr, Wolfgang R.; Hojas, Sabine; Rogulj, Inga M.; Andel, Johannes; Greil, Richard

2017-01-01

We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214) with AAR patients meeting the same inclusion criteria (“AAR (001-like)” cohort; n = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616) for “AML-001” versus “AAR (001-like)” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95) versus all AAR patients with World Health Organization (WHO)-defined AML (“AAR (WHO-AML)” cohort; n = 193). Within the registry population, median OS for AAR patients meeting trial inclusion criteria versus all WHO-AML patients was 10.8 versus 11.8 months (p = 0.599), respectively. We thus tested and confirmed the efficacy of azacitidine as a front-line agent in patients with AML, >30% BM blasts and WBC ≤ 15 G/L in a routine clinical practice setting. We further show that the efficacy of azacitidine does not appear to be limited to AML patients who meet stringent clinical trial inclusion criteria, but instead appears efficacious as front-line treatment in all patients with WHO-AML. PMID:28212292

[Evaluation of a self-care leaflet].

PubMed

Lystad, N; Heian, F

1989-01-20

A self care leaflet of 50 pages was distributed in Tingvoll, a municipality with 3,500 inhabitants. The leaflet gives advice about self treatment and prevention of common health problems, and guidelines for contacting the health services. In surveys conducted just before and 10 months after the distribution, we documented -- how the leaflet was accepted and used --changes in knowledge about the health problems mentioned in the leaflet. The leaflet was well accepted. It was characterized as easy to read and to use. 10 months after distribution to read and to use. 10 months after distribution 90% found it within five minutes. 63% used the leaflet when they had a health problem. 90% of those using the leaflet felt more sure that they acted correctly after consulting it, and 60% changed their mind about consulting a general practitioner. We consider the level of knowledge about health problems to be low. The evaluation showed increased knowledge in all groups, except for persons "responsible for caring for elderly relatives". The increase was most marked for "men" and for "persons with health education".

Effects of Selective Checkpoint Kinase 1 Inhibition on Cytarabine Cytotoxicity in Acute Myelogenous Leukemia Cells in Vitro

PubMed Central

Schenk, Erin L.; Koh, Brian D.; Flatten, Karen S.; Peterson, Kevin L.; Parry, David; Hess, Allan D.; Smith, B. Douglas; Karp, Judith E.; Karnitz, Larry M.; Kaufmann, Scott H.

2012-01-01

Purpose Previous studies have demonstrated that the replication checkpoint, which involves the kinases ATR and Chk1, contributes to cytarabine resistance in cell lines. In the present study, we examined whether this checkpoint is activated in clinical AML during cytarabine infusion in vivo and then assessed the impact of combining cytarabine with the recently described Chk1 inhibitor SCH 900776 in vitro. Experimental design AML marrow aspirates harvested before and during cytarabine infusion were examined by immunoblotting. Human AML lines treated with cytarabine in the absence or presence of SCH 900776 were assayed for checkpoint activation by immunoblotting, nucleotide incorporation into DNA and flow cytometry. Long-term effects in AML lines, clinical AML isolates, and normal myeloid progenitors were assayed using clonogenic assays. Results Immunoblotting demonstrated increased Chk1 phosphorylation, a marker of checkpoint activation, in over half of Chk1-containing AMLs after 48 h of cytarabine infusion. In human AML lines, SCH 900776 not only disrupted cytarabine-induced Chk1 activation and S phase arrest, but also markedly increased cytarabine-induced apoptosis. Clonogenic assays demonstrated that SCH 900776 enhanced the anti-proliferative effects of cytarabine in AML cell lines and clinical AML samples at concentrations that had negligible impact on normal myeloid progenitors. Conclusions These results not only provide evidence for cytarabine-induced S phase checkpoint activation in AML in the clinical setting, but also show that a selective Chk1 inhibitor can overcome the S phase checkpoint and enhance the cytotoxicity of cytarabine. Accordingly, further investigation of the cytarabine/SCH 900776 combination in AML appears warranted. PMID:22869869

Daunorubicin and Cytarabine Liposome in Newly Diagnosed Therapy-Related Acute Myeloid Leukemia (AML) or AML With Myelodysplasia-Related Changes.

PubMed

Kim, Miryoung; Williams, Sherry

2018-03-01

To evaluate the efficacy and safety of daunorubicin and cytarabine liposome in older adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). A literature search of PubMed and MEDLINE (January 2017 to January 2018) was performed using the terms CPX-351, Vyxeos, daunorubicin and cytarabine liposome, and acute myeloid leukemia. Phase I, II, and III clinical trials evaluating the efficacy and safety of daunorubicin and cytarabine liposome were reviewed with a specific focus on its use in older patients with newly diagnosed AML. All peer-reviewed articles with clinically relevant information were evaluated for inclusion. The phase II trial demonstrated that daunorubicin and cytarabine liposome improved response rates (RR), but there was no difference in event-free survival and overall survival in the overall patient population. However, clinical benefit was most pronounced in secondary AML with an increased RR and survival. The phase III trial illustrated that daunorubicin and cytarabine liposome improved survival and RR with tolerable toxicity compared with standard 7 plus 3 (daunorubicin and cytarabine) in patients 60 to 75 years of age with t-AML or AML-MRC. More patients proceeded to a stem cell transplant, and 30-day and 60-day mortality was lower with daunorubicin and cytarabine liposome. Grade 3 to 5 toxicities were similar between the 2 groups, except daunorubicin and cytarabine liposome had prolonged cytopenia and a higher risk of hemorrhage. Daunorubicin and cytarabine liposome improves RR and survival, with tolerable toxicity in older patients with t-AML or AML-MRC.

Comparison of nested competitive RT-PCR and real-time RT-PCR for the detection and quantification of AML1/MTG8 fusion transcripts in t(8;21) positive acute myelogenous leukemia.

PubMed

Wattjes, M P; Krauter, J; Nagel, S; Heidenreich, O; Ganser, A; Heil, G

2000-02-01

The chromosomal translocation t(8;21)(q22;q22) is one of the most frequent karyotypic aberrations in acute myeloid leukemia (AML) and results in a chimeric fusion transcript AML1/MTG8. Since AML1/MTG8 fusion transcripts remain detectable by RT-PCR in t(8;21) AML patients in long-term hematological remission, quantitative assessment of AML1/MTG8 transcripts is necessary for the monitoring of minimal residual disease (MRD) in these patients. Competitive RT-PCR and recently real-time RT-PCR are increasingly used for detection and quantification of leukemia specific fusion transcripts. For the direct comparison of both methods we cloned a 42 bp DNA fragment into the original AML1/MTG8 sequence. The resulting molecule was used as an internal competitor for our novel competitive nested RT-PCR for AML1/MTG8 and as an external standard for the generation of AML1/MTG8 standard curves in a real-time PCR assay. Using this standard molecule for both PCR techniques, we compared their sensitivity, linearity and reproducibility. Both methods were comparable with regard to all parameters tested irrespective of analyzing serial dilutions of plasmids, cell lines or samples from t(8;21) positive AML patients at different stages of the disease. Therefore, both techniques can be recommended for the monitoring of MRD in these particular AML patients. However, the automatization of the real-time PCR technique offers some technical advantages.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eicher, Barbara; Marquardt, Drew; Heberle, Frederick A.

We measured the effect of intrinsic lipid curvature, J 0, on structural properties of asymmetric vesicles made of palmitoyl-oleoyl-phosphatidylethanolamine (POPE; J 0 < 0) and palmitoyl-oleoyl-phosphatidylcholine (POPC; J 0 ~ 0). Electron microscopy and dynamic light scattering were used to determine vesicle size and morphology, and x-ray and neutron scattering, combined with calorimetric experiments and solution NMR, yielded insights into leaflet-specific lipid packing and melting processes. Below the lipid melting temperature we observed strong interleaflet coupling in asymmetric vesicles with POPE inner bilayer leaflets and outer leaflets enriched in POPC. This lipid arrangement manifested itself by lipids melting cooperatively inmore » both leaflets, and a rearrangement of lipid packing in both monolayers. On the other hand, no coupling was observed in vesicles with POPC inner bilayer leaflets and outer leaflets enriched in POPE. In this case, the leaflets melted independently and did not affect each other’s acyl chain packing. Furthermore, we found no evidence for transbilayer structural coupling above the melting temperature of either sample preparation. Our results are consistent with the energetically preferred location of POPE residing in the inner leaflet, where it also resides in natural membranes, most likely causing the coupling of both leaflets. The loss of this coupling in the fluid bilayers is most likely the result of entropic contributions.« less

Percutaneous transfemoral-transseptal implantation of a second-generation CardiAQ mitral valve bioprosthesis: first procedure description and 30-day follow-up.

PubMed

Ussia, Gian Paolo; Quadri, Arshad; Cammalleri, Valeria; De Vico, Pasquale; Muscoli, Saverio; Marchei, Massimo; Ruvolo, Giovanni; Sondergaard, Lars; Romeo, Francesco

2016-02-01

Transcatheter mitral valve implantation for mitral valve regurgitation is in the very early phase of development because of challenging anatomy and device dimensions. We describe the procedure of a transfemoral-transseptal implantation of the second-generation CardiAQ mitral valve bioprosthesis and 30-day follow-up. The procedure was performed percutaneously, without any left extracorporeal circulatory support. The patient had severe mitral regurgitation with severely depressed ventricular function and other comorbidities. The patient was deemed extreme high risk for conventional cardiac surgery by a multidisciplinary team. The main procedural steps were the creation of an arteriovenous loop with an exchange nitinol wire, and the use of a customised "steerable snare system" to facilitate the catheter delivery system into the mitral annulus. Transoesophageal echocardiography and fluoroscopy were utilised for device positioning and deployment. The mitral valve prosthesis was implanted with mild mitral regurgitation. The postoperative course was uneventful and at 30-day follow-up the patient is in NYHA Class I, with good function of the mitral valve bioprosthesis. This procedure shows that percutaneous transfemoral transcatheter mitral valve implantation is feasible, safe and successful. Further experience is needed to render this procedure clinically available.

Assessment of mitral regurgitation in dogs: comparison of results of echocardiography with magnetic resonance imaging.

PubMed

Sargent, J; Connolly, D J; Watts, V; Mõtsküla, P; Volk, H A; Lamb, C R; Fuentes, V Luis

2015-11-01

Echocardiography is used routinely to assess mitral regurgitation severity, but echocardiographic measures of mitral regurgitation in dogs have not been compared with other quantitative methods. The study aim was to compare echocardiographic measures of mitral regurgitation with cardiac magnetic resonance imaging-derived mitral regurgitant fraction in small-breed dogs. Dogs with myxomatous mitral valve disease scheduled for magnetic resonance imaging assessment of neurological disease were recruited. Correlations were tested between cardiac magnetic resonance imaging-derived mitral regurgitant fraction and the following echocardiographic measures: vena contracta/aortic diameter, transmitral E-wave velocity, amplitude of mitral prolapse/aortic diameter, diastolic left ventricular diameter:aortic diameter, left atrium:aortic diameter, mitral regurgitation jet area ratio and regurgitant fraction calculated using the proximal isovelocity surface area method. Measurement of cardiac magnetic resonance imaging-derived mitral regurgitant fraction was attempted in 21 dogs. Twelve consecutive, complete studies were obtained and 10 dogs were included in the final analysis: vena contracta/aortic diameter (r = 0 · 89, p = 0 · 001) and E-wave velocity (r = 0 · 86, p = 0 · 001) had the strongest correlations with cardiac magnetic resonance imaging-derived mitral regurgitant fraction. E velocity had superior repeatability and could be measured in all dogs. The presence of multiple jets precluded vena contracta/aortic diameter measurement in one dog. Measurement of cardiac magnetic resonance imaging-derived mitral regurgitant fraction is feasible but technically demanding. The echocardiographic measures that correlated most closely with cardiac magnetic resonance imaging-derived mitral regurgitant fraction were vena contracta/aortic diameter and E-wave velocity. © 2015 British Small Animal Veterinary Association.

Association Of Tricuspid Regurgitation And Severity Of Mitral Stenosis In Patients With Rheumatic Heart Disease.

PubMed

Ahmed, Rehan; Kazmi, Nasir; Naz, Farhat; Malik, Saqib; Gillani, Saima

2016-01-01

Rheumatic heart disease is a common ailment in Pakistan and Mitral stenosis is its flag bearer Severity of mitral stenosis is the key factor in deciding for mitral valve surgery. This case series study was conducted at Ayub Teaching Hospital .Cases of Rheumatic heart disease with mitral stenosis were diagnosed clinically. 2D echocardiography was used to find severity of mitral stenosis. Data was entered into SPSS-17.0 and results were recorded and analysed. Pearson's two tailed correlation was used to find the correlation between presence of tricuspid regurgitation in patients with severe mitral stenosis, p was <0.05. A total 35 patients with pure mitral stenosis were included in study, out of which 8 were male and 27 were females. Mean age in males was 34.5±15.85 years while in females it was 31±8 years. Twenty-two out of 35 (62.86%) patients had tricuspid regurgitation while 13 out 35 (37.14%) had no tricuspid regurgitation. Mean (MVA) mitral valve area in patients with tricuspid regurgitation was 0.84±0.3 cm2 while mean (MVA) mitral valve area in patients without tricuspid regurgitation was 1.83±0.7 cm2. Mean left atrial (L.A) size was 45.23±1.5 mm2 in patients with tricuspid regurgitation, while it was 44.13±6.14 mm2 in patients without tricuspid regurgitation. Mean RSVP was 57.5mmHg in patients with tricuspid regurgitation while RSVP could not be calculated in patients without tricuspid regurgitation. It was concluded that tricuspid regurgitation was strongly associated with severe mitral stenosis as almost all patients with severe mitral stenosis had tricuspid regurgitation and none of the patients with mild mitral stenosis had tricuspid regurgitation.

Colposcopy information leaflets: what women want to know and when they want to receive this information.

PubMed

Byrom, J; Dunn, P D J; Hughes, G M; Lockett, J; Johnson, A; Neale, J; Redman, C W E

2003-01-01

To evaluate whether the information leaflets produced by UK colposcopy clinics provide women with the information they desire and to determine when they would like to receive this information. Questionnaire study and structured evaluation. The colposcopy clinic of a UK cancer centre. Forty-two women attending a pre-colposcopy counselling session and 100 consecutive women attending the colposcopy clinic. Thirty-eight standards derived from the concerns/questions asked by women attending a pre-colposcopy counselling session were used to assess locally produced colposcopy clinic leaflets from UK colposcopy clinics, the leaflets produced by the Royal College of Obstetricians and Gynaecologists and the National Health Service Cervical Screening Programme (NHSCSP), and two "leaflets" obtained from internet sites. The Gunning fog test was used to assess the leaflets' readability. A questionnaire survey of 100 women attending the colposcopy clinic was used to determine when women wanted to receive information about colposcopy. Percentage of questions answered by a given leaflet and Gunning fog scores for readability. The information leaflets of 128 colposcopy clinics were received and assessed. Thirty-two clinics only sent women the NHSCSP leaflet. No leaflet answered all 38 questions. Less than half (36/100) of the leaflets answered more than 50% of the questions. In addition to the lack of advice given, different leaflets frequently gave conflicting advice. The average Gunning fog score was 9.7 (range 5.5-15.5). The majority of women (70%) wanted to receive information about colposcopy at or prior to the time of receiving their abnormal smear test result, although only 42% of women actually received information at this time. Many UK colposcopy clinics do not appear to be providing women with the information they require to understand their condition and the procedure that they are about to undergo. Furthermore, this information is often not provided at the appropriate time in the screening process.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Jianhui; Nickels, Jonathan; Katsaras, John

Spatial organization within lipid bilayers is an important feature for a range of biological processes. Leaflet compositional asymmetry and lateral lipid organization are just two of the ways in which membrane structure appears to be more complex than initially postulated by the fluid mosaic model. This raises the question of how the phase behavior in one bilayer leaflet may affect the apposing leaflet and how one begins to construct asymmetric model systems to investigate these interleaflet interactions. In this paper, we report on all-atom molecular dynamics simulations (a total of 4.1 μs) of symmetric and asymmetric bilayer systems composed ofmore » liquid-ordered (Lo) or liquid-disordered (Ld) leaflets, based on the nanodomain-forming POPC/DSPC/cholesterol system. We begin by analyzing an asymmetric bilayer with leaflets derived from simulations of symmetric Lo and Ld bilayers. In this system, we observe that the properties of the Lo and Ld leaflets are similar to those of the Lo and Ld leaflets in corresponding symmetric systems. However, it is not obvious that mixing the equilibrium structures of their symmetric counterparts is the most appropriate way to construct asymmetric bilayers nor that these structures will manifest interleaflet couplings that lead to domain registry/antiregistry. We therefore constructed and simulated four additional asymmetric bilayer systems by systematically adding or removing lipids in the Ld leaflet to mimic potential density fluctuations. We find that the number of lipids in the Ld leaflet affects its own properties, as well as those of the apposing Lo leaflet. Collectively, the simulations reveal the presence of weak acyl chain interdigitation across bilayer leaflets, suggesting that interdigitation alone does not contribute significantly to the interleaflet coupling in nonphase-separated bilayers of this chemical composition. Finally, however, the properties of both leaflets appear to be sensitive to changes in in-plane lipid packing, possibly providing a mechanism for interleaflet coupling by modulating local density and/or curvature fluctuations.« less

Overcoming the knowledge-behavior gap: The effect of evidence-based HPV vaccination leaflets on understanding, intention, and actual vaccination decision.

PubMed

Wegwarth, O; Kurzenhäuser-Carstens, S; Gigerenzer, G

2014-03-10

Informed decision making requires transparent and evidence-based (=balanced) information on the potential benefit and harms of medical preventions. An analysis of German HPV vaccination leaflets revealed, however, that none met the standards of balanced risk communication. We surveyed a sample of 225 girl-parent pairs in a before-after design on the effects of balanced and unbalanced risk communication on participants' knowledge about cervical cancer and the HPV vaccination, their perceived risk, their intention to have the vaccine, and their actual vaccination decision. The balanced leaflet increased the number of participants who were correctly informed about cervical cancer and the HPV vaccine by 33 to 66 absolute percentage points. In contrast, the unbalanced leaflet decreased the number of participants who were correctly informed about these facts by 0 to 18 absolute percentage points. Whereas the actual uptake of the HPV vaccination 14 months after the initial study did not differ between the two groups (22% balanced leaflet vs. 23% unbalanced leaflet; p=.93, r=.01), the originally stated intention to have the vaccine reliably predicted the actual vaccination decision for the balanced leaflet group only (concordance between intention and actual uptake: 97% in the balanced leaflet group, rs=.92, p=.00; 60% in the unbalanced leaflet group, rs=.37, p=.08). In contrast to a unbalanced leaflet, a balanced leaflet increased people's knowledge of the HPV vaccination, improved perceived risk judgments, and led to an actual vaccination uptake, which first was robustly predicted by people's intention and second did not differ from the uptake in the unbalanced leaflet group. These findings suggest that balanced reporting about HPV vaccination increases informed decisions about whether to be vaccinated and does not undermine actual uptake. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A scanning electron microscopy study of the invasion of leaflets of a bloat-safe and a bloat-causing legume by rumen microorganisms.

PubMed

Fay, J P; Cheng, K J; Hanna, M R; Howarth, R E; Costerton, J W

1981-04-01

A newly developed technique using ruthenium red to detect foci of bacterial digestion in mounts of whole leaflets that had been incubated with rumen bacteria was used to compare the digestion of alfalfa, a bloat-causing legume, and sainfoin, a bloat-safe legume. When whole leaflets were suspended in an artificial rumen medium and inoculated with rumen bacteria, massive bacterial adhesion and proliferation were noted at the stomata of alfalfa leaflets after 6 h of incubation, whereas only a few isolated bacteria adhered near the stomata of sainfoin leaflets After 22 h of incubation, the epidermal layers of alfalfa leaflets had peeled away in many areas, revealing an extensive bacterial invasion of the underlying mesophyll tissue in which large bacterial microcolonies had formed in intercellular spaces, and in intracellular spaces in several areas where plant cell walls had broken down. After 22 h of incubation, the surface of sainfoin leaflets resembled that of alfalfa leaflets at 6 h, with bacterial microcolonies adhering to the area surrounding the stomata, but without sloughing of the epidermis. Uninoculated control leaflets of both species showed no surface alteration but part of their normal bacterial flora had proliferated to form microcolonies on the surface after 22 h incubation. Dry matter loss due to leaching or bacterial digestion when whole leaflets of legumes were suspended in an artificial rumen medium, alone or with rumen bacteria, was significantly higher in the bloat-causing group. Values of leaching and of bacterial digestion were positively correlated. We conclude that reported differences in plant anatomy, and in cell wall chemistry, produce distinct rates or organic nutrient release from legume leaflets, and that these same differences produce an equally distinct susceptibility of leaflets to bacterial invasion, plant cell rupture, and the consequent release of intracellular plant components. The rate of release of organic nutrients from legume leaflets may be important in the etiology of foamy pasture bloat. This technique of in vitro digestion of whole leaflets followed by ruthenium red staining shows some promise of providing a rapid and qualitative test to distinguish, within a species, cultivars that may differ in their bloat-related characteristics.

When the gold standard is not always golden: The value of invasive hemodynamic assessment to overcome the pitfalls of echocardiography in challenging cases of mitral stenosis.

PubMed

Harper, Yenal; Salem, Salem A; Alsafwah, Shadwan; Koshy, Santhosh; Garg, Nadish

2018-01-01

Mitral stenosis is a uncommon valvular lesion in the developed countries. Noninvasive evaluation is the first-line modality for assessment of mitral stenosis, however the noninvasive methods may have limitations in certain cases. Invasive hemodynamics can be used as adjunct tool for assessment of mitral stenosis in such difficult cases. Mitral valve using three-dimensional planimetry is a promising technique for assessment of mitral stenosis. © 2018 Wiley Periodicals, Inc.

Role of echocardiography/Doppler in cardiogenic shock: silent mitral regurgitation.

PubMed

Goldman, A P; Glover, M U; Mick, W; Pupello, D F; Hiro, S P; Lopez-Cuenca, E; Maniscalco, B S

1991-08-01

Two cases of cardiogenic shock and pulmonary edema due to acute, severe, silent mitral regurgitation are discussed. The mechanism for the mitral regurgitation was papillary muscle rupture in the setting of acute myocardial infarction. Echocardiography established the presence, severity, and cause of the mitral regurgitation and the associated hyperdynamic left ventricular function in the setting of cardiogenic shock. Transesophageal echocardiography is excellent for assessing the mitral valve in critically ill patients in whom transthoracic echocardiography may be inadequate or misleading. This allowed for emergency mitral valve replacement without prolonged attempts at medical stabilization.

The impact of concomitant pulmonary hypertension on early and late outcomes following surgery for mitral stenosis.

PubMed

Yang, Bo; DeBenedictus, Christina; Watt, Tessa; Farley, Sean; Salita, Alona; Hornsby, Whitney; Wu, Xiaoting; Herbert, Morley; Likosky, Donald; Bolling, Steven F

2016-08-01

To provide initial evidence on the management of mitral stenosis and pulmonary hypertension (PH) based on short-term and long-term outcomes following mitral valve surgery. Consecutive patients with mitral stenosis (n = 317) who had undergone mitral valve surgery between 1992 and 2014 with recorded pulmonary artery pressure (PAP) data were reviewed. PH severity, based on systolic PAP, was categorized as mild (35 to 44 mm Hg), moderate (45 to 59 mm Hg), or severe (>60 mm Hg). Primary outcomes were 30-day mortality and long-term survival. There were no significant between-group differences in age or preoperative comorbidities. Mitral valve surgery included mitral valve replacement (78%) and repair (22%). The severe PH group had more mitral valve replacement (81%; P = .04), severe tricuspid valve regurgitation (31%; P = .003), right heart failure (17%; P = .02), and concomitant tricuspid valve procedures (46%; P < .001). For severe PH, 30-day mortality was 9%, with no significant group differences. Ten- and 12-year survival were significantly worse in the moderate-severe PH group (58% and 51%, respectively) compared with the normal PAP-mild PH group (83% and 79%, respectively) with a hazard ratio of 2.98 (95% confidence interval, 1.55-5.75; P = .001). Ten-year survival after mitral valve surgery for mitral stenosis was inversely associated with preoperative PAP. Mitral valve surgery can be performed with acceptable 30-day mortality for patients with mitral stenosis and moderate to severe PH, but long-term survival is impaired by moderate to severe PH. Patients with mitral stenosis and mild PH (systolic PAP 35-44 mm Hg) should be considered for mitral valve surgery. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

An Investigation of Tenascin-C Levels in Rheumatic Mitral Stenosis and Their Response to Percutaneous Mitral Balloon Valvuloplasty

PubMed Central

Celik, Ahmet; Gunebakmaz, Ozgur; Baran, Oguzhan; Dogdu, Orhan; Elcik, Deniz; Kobat, Mehmet Ali; Balin, Mehmet; Erdem, Kenan; Aydin, Suleyman; Ozdogru, Ibrahim; Topsakal, Ramazan

2012-01-01

Objective The purpose of this study was to evaluate the tenascin-C levels in severe rheumatic mitral stenosis before and after percutaneous mitral balloon valvuloplasty (PMBV). Subjects and Methods Forty patients with severe mitral stenosis requiring PMBV and 20 age-matched healthy subjects were included in the study. The mitral valve areas, mitral gradients and systolic pulmonary artery pressure (sPAP) were measured by echocardiography. The sPAP values and mitral gradients were also measured by catheterization before and after PMBV. The blood tenascin-C levels were measured before PMBV and 1 month after the procedure. Results The echocardiographic mean mitral gradients had a significant decrease after PMBV (11.7 ± 2.8 vs. 5.6 ± 1.7 mm Hg; p < 0.001) and also those of catheterization (13.9 ± 4.4 vs. 4.0 ± 2.4 mm Hg; p < 0.001). Mitral valve areas increased significantly after PMBV (from 1.1 ± 0.1 to 1.8 ± 0.2 cm2, p < 0.001). Tenascin-C levels decreased significantly in patients after PMBV (from 15.0 ± 3.8 to 10.9 ± 3.1 ng/ml; p < 0.001). Tenascin-C levels were higher in patients with mitral stenosis before PMBV than in healthy subjects (15.0 ± 3.8 and 9.4 ± 2.9 ng/ml; p < 0.001, respectively). There were no significant differences between patients with mitral stenosis after PMBV and healthy subjects (10.9 ± 3.1 and 9.4 ± 2.9 ng/ml; p = 0.09, respectively). There was a significant positive correlation between tenascin-C levels and sPAP (r = 0.508, p < 0.001). In multivariant analysis, tenascin-C predicted mitral stenosis (p = 0.004, OR: 2.31). Conclusions Tenascin-C was an independent predictor for rheumatic mitral stenosis. PMID:22889719

[Parenting Renewal. Leaflets and Lessons for Parents of Children Birth to Four.

ERIC Educational Resources Information Center

Clemson Univ., SC. Cooperative Extension Service.

Instructional materials on parenting skills for parents of newborn through 4-year-old children are provided, with teaching guides for extension service agents. Organized as a series of nine leaflets followed by nine corresponding lessons, leaflets for parents concern: (1) an overview of the leaflets; (2) readiness: guiding normal development; (3)…

Flow-induced Flutter of Heart Valves: Experiments with Canonical Models

NASA Astrophysics Data System (ADS)

Dou, Zhongwang; Seo, Jung-Hee; Mittal, Rajat

2017-11-01

For the better understanding of hemodynamics associated with valvular function in health and disease, the flow-induced flutter of heart valve leaflets is studied using benchtop experiments with canonical valve models. A simple experimental model with flexible leaflets is constructed and a pulsatile pump drives the flow through the leaflets. We quantify the leaflet dynamics using digital image analysis and also characterize the dynamics of the flow around the leaflets using particle imaging velocimetry. Experiments are conducted over a wide range of flow and leaflet parameters and data curated for use as a benchmark for validation of computational fluid-structure interaction models. The authors would like to acknowledge Supported from NSF Grants IIS-1344772, CBET-1511200 and NSF XSEDE Grant TG-CTS100002.

Tumor Trp53 status and genotype affect the bone marrow microenvironment in acute myeloid leukemia

PubMed Central

Jacamo, Rodrigo; Davis, R. Eric; Ling, Xiaoyang; Sonnylal, Sonali; Wang, Zhiqiang; Ma, Wencai; Zhang, Min; Ruvolo, Peter; Ruvolo, Vivian; Wang, Rui-Yu; McQueen, Teresa; Lowe, Scott; Zuber, Johannes; Kornblau, Steven M.; Konopleva, Marina; Andreeff, Michael

2017-01-01

The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds. We identified a set of genes whose expression in BM-MSC was modulated by all four AML genotypes tested. In addition, there were sets of differentially-expressed genes in AML-exposed BM-MSC that were unique to the particular AML genotype or Trp53 status. Our findings support the hypothesis that leukemia cells alter the transcriptome of surrounding BM stromal cells, in both common and genotype-specific ways. These changes are likely to be advantageous to AML cells, affecting disease progression and response to chemotherapy, and suggest opportunities for stroma-targeting therapy, including those based on AML genotype. PMID:29137349

Drug targeting of NR4A nuclear receptors for treatment of acute myeloid leukemia.

PubMed

Boudreaux, Seth P; Duren, Ryan P; Call, Steven G; Nguyen, Loc; Freire, Pablo R; Narayanan, Padmini; Redell, Michele S; Conneely, Orla M

2018-06-08

NR4As are AML tumor suppressors that are frequently silenced in human acute myeloid leukemia (AML). Despite their potential as novel targets for therapeutic intervention, mechanisms of NR4A silencing and strategies for their reactivation remain poorly defined. Here we show that NR4A silencing in AML occurs through blockade of transcriptional elongation rather than epigenetic promoter silencing. By intersection of NR4A-regulated gene signatures captured upon acute, exogenous expression of NR4As in human AML cells with in silico chemical genomics screening, we identify several FDA-approved drugs including dihydroergotamine (DHE) that reactivate NR4A expression and regulate NR4A-dependent gene signatures. We show that DHE induces NR4A expression via recruitment of the super elongation complex to enable elongation of NR4A promoter paused RNA polymerase II. Finally, DHE exhibits AML selective NR4A-dependent anti-leukemic activity in cytogenetically distinct human AML cells in vitro and delays AML progression in mice revealing its potential as a novel therapeutic agent in AML.

Global Cell Proteome Profiling, Phospho-signaling and Quantitative 
Proteomics for Identification of New Biomarkers in Acute Myeloid 
Leukemia Patients

PubMed Central

Aasebø, Elise; Forthun, Rakel B.; Berven, Frode; Selheim, Frode; Hernandez-Valladares, Maria

2016-01-01

The identification of protein biomarkers for acute myeloid leukemia (AML) that could find applications in AML diagnosis and prognosis, treatment and the selection for bone marrow transplant requires substantial comparative analyses of the proteomes from AML patients. In the past years, several studies have suggested some biomarkers for AML diagnosis or AML classification using methods for sample preparation with low proteome coverage and low resolution mass spectrometers. However, most of the studies did not follow up, confirm or validate their candidates with more patient samples. Current proteomics methods, new high resolution and fast mass spectrometers allow the identification and quantification of several thousands of proteins obtained from few tens of μg of AML cell lysate. Enrichment methods for posttranslational modifications (PTM), such as phosphorylation, can isolate several thousands of site-specific phosphorylated peptides from AML patient samples, which subsequently can be quantified with high confidence in new mass spectrometers. While recent reports aiming to propose proteomic or phosphoproteomic biomarkers on the studied AML patient samples have taken advantage of the technological progress, the access to large cohorts of AML patients to sample from and the availability of appropriate control samples still remain challenging. PMID:26306748

Phosphatidylserine index as a marker of the procoagulant phenotype of acute myelogenous leukemia cells

NASA Astrophysics Data System (ADS)

Tormoen, Garth W.; Recht, Olivia; Gruber, András; Levine, Ross L.; McCarty, Owen J. T.

2013-10-01

Patients with acute myelogenous leukemia (AML) are at risk for thrombotic complications. Risk to develop thrombosis is closely tied to leukemia subtype, and studies have shown an association between leukocytosis and thrombosis in AML M3. We evaluated the relative roles of cell count and the surface expression of tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a purified system and promoted experimental thrombus formation. In contrast, the TF-negative AML cell line, HEL, exhibited only prothrombinase activity and did not affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14 shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin increased their extrinsic tenase activity and PS expression. Clot initiation time inversely correlated with logarithm of PS index, defined as the product of multiplying leukocyte count with cell surface PS exposure. We propose that leukemia cell PS index may serve as a biomarker for procoagulant activity.

Gemtuzumab ozogamicin for the treatment of acute myeloid leukemia.

PubMed

Baron, Jeffrey; Wang, Eunice S

2018-06-11

Gemtuzumab ozogamicin (GO) is an antibody-drug conjugate consisting of a monoclonal antibody targeting CD33 linked to a cytotoxic derivative of calicheamicin. Despite the known clinical efficacy in relapsed/refractory acute myeloid leukemia (AML), GO was withdrawn from the market in 2010 due to increased early deaths witnessed in newly diagnosed AML patients receiving GO + intensive chemotherapy. In 2017, new data on the clinical efficacy and safety of GO administered on a fractionated-dosing schedule led to re-approval for newly diagnosed and relapsed/refractory AML. Areas covered: Addition of fractionated GO to chemotherapy significantly improved event-free survival of newly diagnosed AML patients with favorable and intermediate cytogenetic-risk disease. GO monotherapy also prolonged survival in newly diagnosed unfit patients and relapse-free survival in relapsed/refractory AML. This new dosing schedule was associated with decreased incidence of hepatotoxicity, veno-occlusive disease, and early mortality. Expert commentary: GO represents the first drug-antibody conjugate approved (twice) in the United States for AML. Its re-emergence adds a valuable agent back into the armamentarium for AML. The approval of GO as well as three other agents for AML in 2017 highlights the need for rapid cytogenetic and molecular characterization of AML and incorporation into new treatment algorithms.

Transcatheter Mitral Valve Replacement for Native and Failed Bioprosthetic Mitral Valves

PubMed Central

Sarkar, Kunal; Reardon, Michael J.; Little, Stephen H.; Barker, Colin M.; Kleiman, Neal S.

2017-01-01

Transcatheter mitral valve replacement (TMVR) is a novel approach for treatment of severe mitral regurgitation. A number of TMVR devices are currently undergoing feasibility trials using both transseptal and transapical routes for device delivery. Overall experience worldwide is limited to fewer than 200 cases. At present, the 30-day mortality exceeds 30% and is attributable to both patient- and device-related factors. TMVR has been successfully used to treat patients with degenerative mitral stenosis (DMS) as well as failed mitral bioprosthesis and mitral repair using transcatheter mitral valve-in-valve (TMViV)/valve-in-ring (ViR) repair. These patients are currently treated with devices designed for transcatheter aortic valve replacement. Multicenter registries have been initiated to collect outcomes data on patients currently undergoing TMViV/ViR and TMVR for DMS and have confirmed the feasibility of TMVR in these patients. However, the high periprocedural and 30-day event rates underscore the need for further improvements in device design and multicenter randomized studies to delineate the role of these technologies in patients with mitral valve disease. PMID:29743999

The complexity of interpreting genomic data in patients with acute myeloid leukemia

PubMed Central

Nazha, A; Zarzour, A; Al-Issa, K; Radivoyevitch, T; Carraway, H E; Hirsch, C M; Przychodzen, B; Patel, B J; Clemente, M; Sanikommu, S R; Kalaycio, M; Maciejewski, J P; Sekeres, M A

2016-01-01

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the accumulation of complex genetic alterations responsible for the initiation and progression of the disease. Translating genomic information into clinical practice remained challenging with conflicting results regarding the impact of certain mutations on disease phenotype and overall survival (OS) especially when clinical variables are controlled for when interpreting the result. We sequenced the coding region for 62 genes in 468 patients with secondary AML (sAML) and primary AML (pAML). Overall, mutations in FLT3, DNMT3A, NPM1 and IDH2 were more specific for pAML whereas UTAF1, STAG2, BCORL1, BCOR, EZH2, JAK2, CBL, PRPF8, SF3B1, ASXL1 and DHX29 were more specific for sAML. However, in multivariate analysis that included clinical variables, only FLT3 and DNMT3A remained specific for pAML and EZH2, BCOR, SF3B1 and ASXL1 for sAML. When the impact of mutations on OS was evaluated in the entire cohort, mutations in DNMT3A, PRPF8, ASXL1, CBL EZH2 and TP53 had a negative impact on OS; no mutation impacted OS favorably; however, in a cox multivariate analysis that included clinical data, mutations in DNMT3A, ASXL1, CBL, EZH2 and TP53 became significant. Thus, controlling for clinical variables is important when interpreting genomic data in AML. PMID:27983727

The complexity of interpreting genomic data in patients with acute myeloid leukemia.

PubMed

Nazha, A; Zarzour, A; Al-Issa, K; Radivoyevitch, T; Carraway, H E; Hirsch, C M; Przychodzen, B; Patel, B J; Clemente, M; Sanikommu, S R; Kalaycio, M; Maciejewski, J P; Sekeres, M A

2016-12-16

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the accumulation of complex genetic alterations responsible for the initiation and progression of the disease. Translating genomic information into clinical practice remained challenging with conflicting results regarding the impact of certain mutations on disease phenotype and overall survival (OS) especially when clinical variables are controlled for when interpreting the result. We sequenced the coding region for 62 genes in 468 patients with secondary AML (sAML) and primary AML (pAML). Overall, mutations in FLT3, DNMT3A, NPM1 and IDH2 were more specific for pAML whereas UTAF1, STAG2, BCORL1, BCOR, EZH2, JAK2, CBL, PRPF8, SF3B1, ASXL1 and DHX29 were more specific for sAML. However, in multivariate analysis that included clinical variables, only FLT3 and DNMT3A remained specific for pAML and EZH2, BCOR, SF3B1 and ASXL1 for sAML. When the impact of mutations on OS was evaluated in the entire cohort, mutations in DNMT3A, PRPF8, ASXL1, CBL EZH2 and TP53 had a negative impact on OS; no mutation impacted OS favorably; however, in a cox multivariate analysis that included clinical data, mutations in DNMT3A, ASXL1, CBL, EZH2 and TP53 became significant. Thus, controlling for clinical variables is important when interpreting genomic data in AML.

Osteoblasts Protect AML Cells from SDF-1-Induced Apoptosis

PubMed Central

Kremer, Kimberly N.; Dudakovic, Amel; McGee-Lawrence, Meghan E.; Philips, Rachael L.; Hess, Allan D.; Smith, B. Douglas; van Wijnen, Andre J.; Karp, Judith E.; Kaufmann, Scott H.; Westendorf, Jennifer J.; Hedin, Karen E.

2014-01-01

The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment. PMID:24851270

Fatty Acid Binding Protein FABP4 Mechanistically Links Obesity with Aggressive AML by Enhancing Aberrant DNA Methylation in AML Cells

PubMed Central

Yan, F; Shen, N; Pang, JX; Zhang, YW; Rao, EY; Bode, AM; Al-Kali, A; Zhang, DE; Litzow, MR; Li, B; Liu, SJ

2016-01-01

Obesity is becoming more prevalent worldwide and is a major risk factor for cancer development. Acute myeloid leukemia (AML), the most common acute leukemia in adults, remains a frequently fatal disease. Here, we investigated the molecular mechanisms by which obesity favors AML growth and uncovered the fatty acid binding protein 4 (FABP4) and DNA methyltransferase 1 (DNMT1) regulatory axis that mediates aggressive AML in obesity. We showed that leukemia burden was much higher in high-fat diet-induced obese mice, which had higher levels of FABP4 and IL-6 in sera. Upregulation of environmental and cellular FABP4 accelerated AML cell growth in both a cell-autonomous and cell-non-autonomous manner. Genetic disruption of FABP4 in AML cells or in mice blocked cell proliferation in vitro and induced leukemia regression in vivo. Mechanistic investigations showed that FABP4 upregulation increased IL-6 expression and STAT3 phosphorylation leading to DNMT1 overexpression and further silencing of the p15INK4B tumor suppressor gene in AML cells. Conversely, FABP4 ablation reduced DNMT1-dependent DNA methylation and restored p15INK4B expression, thus conferring substantial protection against AML growth. Our findings reveal the FABP4/DNMT1 axis in the control of AML cell fate in obesity, and suggest that interference with the FABP4/DNMT1 axis might be a new strategy to treat leukemia. PMID:27885273

Fatty acid-binding protein FABP4 mechanistically links obesity with aggressive AML by enhancing aberrant DNA methylation in AML cells.

PubMed

Yan, F; Shen, N; Pang, J X; Zhang, Y W; Rao, E Y; Bode, A M; Al-Kali, A; Zhang, D E; Litzow, M R; Li, B; Liu, S J

2017-06-01

Obesity is becoming more prevalent worldwide and is a major risk factor for cancer development. Acute myeloid leukemia (AML), the most common acute leukemia in adults, remains a frequently fatal disease. Here we investigated the molecular mechanisms by which obesity favors AML growth and uncovered the fatty acid-binding protein 4 (FABP4) and DNA methyltransferase 1 (DNMT1) regulatory axis that mediates aggressive AML in obesity. We showed that leukemia burden was much higher in high-fat diet-induced obese mice, which had higher levels of FABP4 and interleukin (IL)-6 in the sera. Upregulation of environmental and cellular FABP4 accelerated AML cell growth in both a cell-autonomous and cell-non-autonomous manner. Genetic disruption of FABP4 in AML cells or in mice blocked cell proliferation in vitro and induced leukemia regression in vivo. Mechanistic investigations showed that FABP4 upregulation increased IL-6 expression and signal transducer and activator of transcription factor 3 phosphorylation leading to DNMT1 overexpression and further silencing of the p15 INK4B tumor-suppressor gene in AML cells. Conversely, FABP4 ablation reduced DNMT1-dependent DNA methylation and restored p15 INK4B expression, thus conferring substantial protection against AML growth. Our findings reveal the FABP4/DNMT1 axis in the control of AML cell fate in obesity and suggest that interference with the FABP4/DNMT1 axis might be a new strategy to treat leukemia.

The biologic properties of recombinant human thrombopoietin in the proliferation and megakaryocytic differentiation of acute myeloblastic leukemia cells.

PubMed

Matsumura, I; Kanakura, Y; Kato, T; Ikeda, H; Horikawa, Y; Ishikawa, J; Kitayama, H; Nishiura, T; Tomiyama, Y; Miyazaki, H; Matsuzawa, Y

1996-10-15

Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic leukemia (AML) cells are largely unknown. To determine if recombinant human (rh) TPO has proliferation-supporting and differentiation-inducing activities in AML cells, 15 cases of AML cells that were exclusively composed of undifferentiated leukemia cells and showed growth response to rhTPO in a short-term culture (72 hours) were subjected to long-term suspension culture with or without rhTPO. Of 15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In addition to the proliferation-supporting activity, rhTPO was found to induce AML cells to progress to some degree of megakaryocytic differentiation at both morphologic and surface-phenotypic level in 2 AML cases with M0 and M7 subtypes. The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the expression of erythroid/megakaryocyte-specific transcription factors (GATA-1, GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that showed megakaryocytic differentiation in response to rhTPO. These results suggested that, at least in a fraction of AML cases, TPO could not only support the proliferation of AML cells irrespective of AML subtypes, but could also induce megakaryocytic differentiation, possibly through activation of GATA-1, GATA-2, and NF-E2.

Knockdown of miR-128a induces Lin28a expression and reverts myeloid differentiation blockage in acute myeloid leukemia

PubMed Central

De Luca, Luciana; Trino, Stefania; Laurenzana, Ilaria; Tagliaferri, Daniela; Falco, Geppino; Grieco, Vitina; Bianchino, Gabriella; Nozza, Filomena; Campia, Valentina; D'Alessio, Francesca; La Rocca, Francesco; Caivano, Antonella; Villani, Oreste; Cilloni, Daniela; Musto, Pellegrino; Del Vecchio, Luigi

2017-01-01

Lin28A is a highly conserved RNA-binding protein that concurs to control the balance between stemness and differentiation in several tissue lineages. Here, we report the role of miR-128a/Lin28A axis in blocking cell differentiation in acute myeloid leukemia (AML), a genetically heterogeneous disease characterized by abnormally controlled proliferation of myeloid progenitor cells accompanied by partial or total inability to undergo terminal differentiation. First, we found Lin28A underexpressed in blast cells from AML patients and AML cell lines as compared with CD34+ normal precursors. In vitro transfection of Lin28A in NPM1-mutated OCI-AML3 cell line significantly triggered cell-cycle arrest and myeloid differentiation, with increased expression of macrophage associate genes (EGR2, ZFP36 and ANXA1). Furthermore, miR-128a, a negative regulator of Lin28A, was found overexpressed in AML cells compared with normal precursors, especially in acute promyelocytic leukemia (APL) and in ‘AML with maturation’ (according to 2016 WHO classification of myeloid neoplasms and acute leukemia). Its forced overexpression by lentiviral infection in OCI-AML3 downregulated Lin28A with ensuing repression of macrophage-oriented differentiation. Finally, knockdown of miR-128a in OCI-AML3 and in APL/AML leukemic cells (by transfection and lentiviral infection, respectively) induced myeloid cell differentiation and increased expression of Lin28A, EGR2, ZFP36 and ANXA1, reverting myeloid differentiation blockage. In conclusion, our findings revealed a new mechanism for AML differentiation blockage, suggesting new strategies for AML therapy based upon miR-128a inhibition. PMID:28569789

Correlation between CD34 expression and chromosomal abnormalities but not clinical outcome in acute myeloid leukemia.

PubMed

Fruchart, C; Lenormand, B; Bastard, C; Boulet, D; Lesesve, J F; Callat, M P; Stamatoullas, A; Monconduit, M; Tilly, H

1996-11-01

The hemopoietic stem cell marker CD34 has been reported to be a useful predictor of treatment outcome in acute myeloid leukemia (AML). Previous data suggested that CD34 expression may be associated with other poor prognosis factors in AML such as undifferentiated leukemia, secondary AML (SAML), and clonal abnormalities involving chromosome 5 and 7. In order to analyze the correlations between the clinicopathologic features, cytogenetic and CD34 expression in AML, we retrospectively investigated 99 patients with newly diagnosed AML: 85 with de novo disease and 14 with secondary AML (SAML). Eighty-six patients who received the same induction chemotherapy were available for clinical outcome. Defining a case as positive when > or = 20% of bone marrow cells collected at diagnosis expressed the CD34 antigen, forty-five patients were included in the CD34 positive group. Ninety patients had adequate cytogenetic analysis. Thirty-two patients (72%) with CD34 positive AML exhibited an abnormal karyotype whereas 15 patients (28%) with CD34 negative AML had abnormal metaphases (P < 0.01). Monosomy 7/7q- or monosomy 5/5q- occurred in 10 patients and 8 of them expressed the CD34 antigen (P < 0.05). All patients with t(8;21) which is considered as a favorable factor in AML had levels of CD34 >/= 20% (P < 0.05). We did not find any association between CD34 expression and attainment of complete remission, overall survival, or disease-free survival. In conclusion, the variations of CD34 expression in AML are correlated with cytogenetic abnormalities associated both with poor and favorable outcome. The evaluation of the correlations between CD34 antigen and clinical outcome in AML should take into account the results of pretreatment karyotype.

The rarity of ALDH(+) cells is the key to separation of normal versus leukemia stem cells by ALDH activity in AML patients.

PubMed

Hoang, Van T; Buss, Eike C; Wang, Wenwen; Hoffmann, Isabel; Raffel, Simon; Zepeda-Moreno, Abraham; Baran, Natalia; Wuchter, Patrick; Eckstein, Volker; Trumpp, Andreas; Jauch, Anna; Ho, Anthony D; Lutz, Christoph

2015-08-01

To understand the precise disease driving mechanisms in acute myeloid leukemia (AML), comparison of patient matched hematopoietic stem cells (HSC) and leukemia stem cells (LSC) is essential. In this analysis, we have examined the value of aldehyde dehydrogenase (ALDH) activity in combination with CD34 expression for the separation of HSC from LSC in 104 patients with de novo AML. The majority of AML patients (80 out of 104) had low percentages of cells with high ALDH activity (ALDH(+) cells; <1.9%; ALDH-rare AML), whereas 24 patients had relatively numerous ALDH(+) cells (≥1.9%; ALDH-numerous AML). In patients with ALDH-rare AML, normal HSC could be separated by their CD34(+) ALDH(+) phenotype, whereas LSC were exclusively detected among CD34(+) ALDH(-) cells. For patients with ALDH-numerous AML, the CD34(+) ALDH(+) subset consisted mainly of LSC and separation from HSC was not feasible. Functional analyses further showed that ALDH(+) cells from ALDH-numerous AML were quiescent, refractory to ARA-C treatment and capable of leukemic engraftment in a xenogenic mouse transplantation model. Clinically, resistance to chemotherapy and poor long-term outcome were also characteristic for patients with ALDH-numerous AML providing an additional risk-stratification tool. The difference in spectrum and relevance of ALDH activity in the putative LSC populations demonstrates, in addition to phenotypic and genetic, also functional heterogeneity of leukemic cells and suggests divergent roles for ALDH activity in normal HSC versus LSC. By acknowledging these differences our study provides a new and useful tool for prospective identification of AML cases in which separation of HSC from LSC is possible. © 2014 UICC.

The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from chemotherapy in AML Patients.

PubMed

Dong-Feng, Zeng; Ting, Liu; Yong, Zhang; Cheng, Chang; Xi, Zhang; Pei-Yan, Kong

2014-04-01

Accumulating evidence indicates that the interaction of human LSCs (leukemic stem cells) with the hematopoietic microenvironment, mediated by the thrombopoietin (TPO)/c-MPL pathway, may be an underlying mechanism for resistance to cell cycle-dependent cytotoxic chemotherapy. However, the role of TPO/c-MPL signaling in AML (acute myelogenous leukemia) chemotherapy resistance hasn't been fully understood. The c-MPL and TPO levels in different AML samples were measured by flow cytometry and ELISA. We also assessed the TPO levels in the osteoblasts derived from bone mesenchymal stem cells (BMSCs). The survival rate of an AML cell line that had been co-cultured with different BMSC-derived osteoblasts was measured to determine the IC50 of an AML chemotherapy drug daunorubicin (DNR). The levels of TPO/c-MPL in the initial and relapse AML patients were significantly higher than that in the control (P < 0.05). The osteoblasts derived from AML patients' BMSCs secreted more TPO than the osteoblasts derived from normal control BMSCs (P < 0.05). A strong positive correlation between the TPO level and c-MPL expression was found in the bone marrow mononuclear cells of the relapse AML patients. More importantly, the IC50 of DNR in the HEL + AML-derived osteoblasts was the highest among all co-culture systems. High level of TPO/c-MPL signaling may protect LSCs from chemotherapy in AML. The effects of inhibition of the TPO/c-MPL pathway on enhancing the chemotherapy sensitivity of AML cells, and on their downstream effector molecules that direct the interactions between patient-derived blasts and leukemia repopulating cells need to be further studied.

XPO1 Inhibition Using Selinexor Synergizes With Chemotherapy in Acute Myeloid Leukemia (AML) by Targeting DNA Repair and Restoring Topoisomerase IIα to the Nucleus

PubMed Central

Ranganathan, Parvathi; Kashyap, Trinayan; Yu, Xueyan; Meng, Xiaomei; Lai, Tzung-Huei; McNeil, Betina; Bhatnagar, Bhavana; Shacham, Sharon; Kauffman, Michael; Dorrance, Adrienne M.; Blum, William; Sampath, Deepa; Landesman, Yosef; Garzon, Ramiro

2016-01-01

Purpose Selinexor, a selective inhibitor of XPO1, is currently being tested as single agent in clinical trials in acute myeloid leukemia (AML). However, considering the molecular complexity of AML, it is unlikely that AML can be cured with monotherapy. Therefore we asked whether adding already established effective drugs such as Topoisomerase (Topo) II inhibitors to selinexor will enhance its anti-leukemic effects in AML. Experimental Design The efficacy of combinatorial drug treatment using Topo II inhibitors (idarubicin, daunorubicin, mitoxantrone, etoposide) and selinexor was evaluated in established cellular and animal models of AML. Results Concomitant treatment with selinexor and Topo II inhibitors resulted in therapeutic synergy in AML cell lines and patient samples. Using a xenograft MV4-11 AML mouse model, we show that treatment with selinexor and idarubicin significantly prolongs survival of leukemic mice compared to each single therapy. Conclusions Aberrant nuclear export and cytoplasmic localization of Topo IIα has been identified as one of the mechanisms leading to drug resistance in cancer. Here, we show that in a subset of AML patients that express cytoplasmic Topo IIα, selinexor treatment results in nuclear retention of Topo IIα protein, resulting in increased sensitivity to idarubicin. Selinexor treatment of AML cells resulted in a c-MYC dependent reduction of DNA damage repair genes (Rad51 and Chk1) mRNA and protein expression, and subsequent inhibition of homologous recombination repair and increased sensitivity to Topo II inhibitors. The preclinical data reported here support further clinical studies using selinexor and Topo II inhibitors in combination to treat AML. PMID:27358488

The significance of trilineage myelodysplasia in de novo acute myeloblastic leukemia: clinical and laboratory features.

PubMed

Lima, C S; Vassalo, J; Lorand-Metze, I; Bechelli, A P; Souza, C A

1997-01-01

A prospective study was undertaken to elucidate the clinical and laboratory differences between de novo acute myeloid leukemia (AML) and AML with trilineage myelodysplasia (AML-TMDS). One hundred and seven patients with AML were diagnosed at the University Hospital between January 1987 and July 1992, and were followed until July 1995. TMDS was identified in 17 of them (16%). With regard to age and sex distribution no difference was found between AML patients with and without TMDS (p = 0.43, p = 0.54, respectively). The duration of symptoms at presentation in AML-TMDS was similar to those observed in de novo AML (p = 0.29). Hemoglobin values and platelet counts were similar in both groups of patients (p = 0.45, p = 0.44, respectively). However, peripheral white blood cell and neutrophil counts, as well as blast counts in AML-TMDS patients were lower than those observed in AML without TMDS patients (p < 0.001 for all of them). Bone marrow blast counts in de novo AML were higher than the values observed in AML-TMDS patients (p < 0.001). TMDS occurred predominantly in M2 and M6 FAB types, and was absent in the M3 type. Bone marrow histology showed no particular feature that could be of diagnostic relevance. The remission rates were similar in both groups of patients (p = 0.55). The same was true for the probability of disease-free survival and overall survival during the period of study (p = 0.50, p = 0.33, respectively). These results suggest that: 1) in AML-TMDS patients, leukemia transformation occurs in a more undifferentiated pluripotent stem cell, leading to a dysplastic residual hemopoiesis besides the blast proliferation; 2) the incidence of TMDS in our group of patients did not influence the clinical outcome after treatment of the disease.

SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Li; Weng, Wei; Sun, Zhi-Xin

Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, andmore » concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent. - Highlights: • SKI-II inhibits proliferation and survival of primary and transformed AML cells. • SKI-II induces apoptotic death of AML cells, but is safe to normal PBMCs. • SKI-II is more efficient than two known SphK1 inhibitors in inhibiting AML cells. • SKI-II inhibits SphK1 activity, while increasing ceramide production in AML cells. • SKI-II dose-dependently inhibits U937 xenograft growth in SCID mice.« less

Correlation between p65 and TNF-α in patients with acute myelocytic leukemia.

PubMed

Dong, Qiao-Mei; Ling, Chun; Zhu, Jun-Fang; Chen, Xuan; Tang, Yan; Zhao, L I

2015-11-01

The correlation between the expression levels of p65 and TNF-α in patients with acute myelocytic leukemia (AML) and AML cell lines were investigated. The bone marrow samples of 30 AML patients and 10 non-leukemia controls were studied. The mRNA expression levels of p65 and TNF-α were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Pearson's Correlation test was used to demonstrate the correlation between TNF-α and p65 expression levels in AML specimens. Receiver operating characteristic (ROC) curves were plotted to determine whether TNF-α and p65 expression levels could be used to differentiate AML samples from non-leukemia samples. MG132 and anti-TNF-α antibody were used to inhibit the expression of p65 and TNF-α in the AML cell line, HL-60. The expression of p65 and TNF-α were detected by RT-qPCR and western blot analysis. The mRNA expression levels of p65 and TNF-α were significantly increased in AML patients compared with non-leukemia control bone marrow samples by RT-qPCR, and the two molecules expression pattern's exhibited sufficient predictive power to distinguish AML patients from non-leukemia control samples. Pearson's correlation analysis demonstrated that TNF-α expression was strongly correlated with p65 expression in AML bone marrow samples. In HL-60 cells, inhibition of TNF-α reduced the expression of p65; in addition, inhibition of p65 reduced the expression of TNF-α as assessed by RT-qPCR and western blot analysis. p65 and TNF-α were highly expressed in AML patients, and these 2 molecules were strongly correlated. The present study indicates that p65 and TNF-α have potential as molecular markers to distinguish AML patients from non-leukemia control samples, and that these 2 molecules may be useful prognostic factor for patients with AML.

Comprehensive mutational profiling of core binding factor acute myeloid leukemia.

PubMed

Duployez, Nicolas; Marceau-Renaut, Alice; Boissel, Nicolas; Petit, Arnaud; Bucci, Maxime; Geffroy, Sandrine; Lapillonne, Hélène; Renneville, Aline; Ragu, Christine; Figeac, Martin; Celli-Lebras, Karine; Lacombe, Catherine; Micol, Jean-Baptiste; Abdel-Wahab, Omar; Cornillet, Pascale; Ifrah, Norbert; Dombret, Hervé; Leverger, Guy; Jourdan, Eric; Preudhomme, Claude

2016-05-19

Acute myeloid leukemia (AML) with t(8;21) or inv(16) have been recognized as unique entities within AML and are usually reported together as core binding factor AML (CBF-AML). However, there is considerable clinical and biological heterogeneity within this group of diseases, and relapse incidence reaches up to 40%. Moreover, translocations involving CBFs are not sufficient to induce AML on its own and the full spectrum of mutations coexisting with CBF translocations has not been elucidated. To address these issues, we performed extensive mutational analysis by high-throughput sequencing in 215 patients with CBF-AML enrolled in the Phase 3 Trial of Systematic Versus Response-adapted Timed-Sequential Induction in Patients With Core Binding Factor Acute Myeloid Leukemia and Treating Patients with Childhood Acute Myeloid Leukemia with Interleukin-2 trials (age, 1-60 years). Mutations in genes activating tyrosine kinase signaling (including KIT, N/KRAS, and FLT3) were frequent in both subtypes of CBF-AML. In contrast, mutations in genes that regulate chromatin conformation or encode members of the cohesin complex were observed with high frequencies in t(8;21) AML (42% and 18%, respectively), whereas they were nearly absent in inv(16) AML. High KIT mutant allele ratios defined a group of t(8;21) AML patients with poor prognosis, whereas high N/KRAS mutant allele ratios were associated with the lack of KIT or FLT3 mutations and a favorable outcome. In addition, mutations in epigenetic modifying or cohesin genes were associated with a poor prognosis in patients with tyrosine kinase pathway mutations, suggesting synergic cooperation between these events. These data suggest that diverse cooperating mutations may influence CBF-AML pathophysiology as well as clinical behavior and point to potential unique pathogenesis of t(8;21) vs inv(16) AML. © 2016 by The American Society of Hematology.

Identification of Novel Genomic Aberrations in AML-M5 in a Level of Array CGH

PubMed Central

Zhang, Rui; Lee, Ji-Yun; Wang, Xianfu; Xu, Weihong; Hu, Xiaoxia; Lu, Xianglan; Niu, Yimeng; Tang, Rurong; Li, Shibo; Li, Yan

2014-01-01

To assess the possible existence of unbalanced chromosomal abnormalities and delineate the characterization of copy number alterations (CNAs) of acute myeloid leukemia-M5 (AML-M5), R-banding karyotype, oligonucelotide array CGH and FISH were performed in 24 patients with AML-M5. A total of 117 CNAs with size ranging from 0.004 to 146.263 Mb was recognized in 12 of 24 cases, involving all chromosomes other than chromosome 1, 4, X and Y. Cryptic CNAs with size less than 5 Mb accounted for 59.8% of all the CNAs. 12 recurrent chromosomal alterations were mapped. Seven out of them were described in the previous AML studies and five were new candidate AML-M5 associated CNAs, including gains of 3q26.2-qter and 13q31.3 as well as losses of 2q24.2, 8p12 and 14q32. Amplication of 3q26.2-qter was the sole large recurrent chromosomal anomaly and the pathogenic mechanism in AML-M5 was possibly different from the classical recurrent 3q21q26 abnormality in AML. As a tumor suppressor gene, FOXN3, was singled out from the small recurrent CNA of 14q32, however, it is proved that deletion of FOXN3 is a common marker of myeloid leukemia rather than a specific marker for AML-M5 subtype. Moreover, the concurrent amplication of MLL and deletion of CDKN2A were noted and it might be associated with AML-M5. The number of CNA did not show a significant association with clinico-biological parameters and CR number of the 22 patients received chemotherapy. This study provided the evidence that array CGH served as a complementary platform for routine cytogenetic analysis to identify those cryptic alterations in the patients with AML-M5. As a subtype of AML, AML-M5 carries both common recurrent CNAs and unique CNAs, which may harbor novel oncogenes or tumor suppressor genes. Clarifying the role of these genes will contribute to the understanding of leukemogenic network of AML-M5. PMID:24727659

Intraoperative application of geometric three-dimensional mitral valve assessment package: a feasibility study.

PubMed

Mahmood, Feroze; Karthik, Swaminathan; Subramaniam, Balachundhar; Panzica, Peter J; Mitchell, John; Lerner, Adam B; Jervis, Karinne; Maslow, Andrew D

2008-04-01

To study the feasibility of using 3-dimensional (3D) echocardiography in the operating room for mitral valve repair or replacement surgery. To perform geometric analysis of the mitral valve before and after repair. Prospective observational study. Academic, tertiary care hospital. Consecutive patients scheduled for mitral valve surgery. Intraoperative reconstruction of 3D images of the mitral valve. One hundred and two patients had 3D analysis of their mitral valve. Successful image reconstruction was performed in 93 patients-8 patients had arrhythmias or a dilated mitral valve annulus resulting in significant artifacts. Time from acquisition to reconstruction and analysis was less than 5 minutes. Surgeon identification of mitral valve anatomy was 100% accurate. The study confirms the feasibility of performing intraoperative 3D reconstruction of the mitral valve. This data can be used for confirmation and communication of 2-dimensional data to the surgeons by obtaining a surgical view of the mitral valve. The incorporation of color-flow Doppler into these 3D images helps in identification of the commissural or perivalvular location of regurgitant orifice. With improvements in the processing power of the current generation of echocardiography equipment, it is possible to quickly acquire, reconstruct, and manipulate images to help with timely diagnosis and surgical planning.

The contents of dental implant patient information leaflets available within the UK.

PubMed

Barber, J; Puryer, J; McNally, L; O'Sullivan, D

2015-02-01

Patient information leaflets are designed to provide easy to follow information summaries and first point of contact information about treatment options. This survey reviewed the content of dental implant patient information leaflets, produced by implant companies and available within the UK in 2011. Dental implant companies in the UK were asked to provide samples of their patient information leaflets. The information within the leaflets was then summarised, including the quantity and the types of images used and whether the source of the information was given. Quantitative data was obtained on the amount of information provided, size of images and number of references. A response rate of 71% was obtained and 23 leaflets were studied. Great variation was found between the leaflets, with the word counts ranging from 88 to 5,434, and 44 different topics were identified. The majority of the images used were decorative, and none of the leaflets gave any reference to the sources of their information. Implant treatment was generally described in a positive way, with an emphasis on describing the treatment and the advantages. Much less information was given about the potential disadvantages and risks of complications or failure, including the relevance of periodontal disease or smoking. Implant patient information leaflets provided by dental implant companies should not be solely relied upon to provide patients with all the information they need to give informed consent to treatment.

The development and testing of a brief ('gist-based') supplementary colorectal cancer screening information leaflet.

PubMed

Smith, Samuel G; Wolf, Michael S; Obichere, Austin; Raine, Rosalind; Wardle, Jane; von Wagner, Christian

2013-12-01

To design and user-test a 'gist-based' colorectal cancer screening information leaflet, which promotes comprehension of the screening offer. Twenty-eight individuals approaching screening age were recruited from organisations in deprived areas of England. Using a between-subjects design, we tested iterations of a newly-designed gist-based information leaflet. Participants read the leaflet and answered 8 'true' or 'false' comprehension statements. For the leaflet to be considered fit-for-purpose, all statements had to be answered correctly by at least 80% of participants in each round. Alterations were made if this threshold was not met and additional rounds of testing were undertaken. At round 1, answers to 2/8 statements did not meet the threshold. After changes, answers in round 2 did not reach the threshold for 1/8 statements. In round 3, all answers were adequate and the leaflet was deemed fit-for-purpose. Qualitative data offered solutions such as language and layout changes which led to improved comprehension of the leaflet. User-testing substantially improved the design and subsequent comprehensibility of a theory-driven gist-based colorectal cancer screening information leaflet. This leaflet will be evaluated as part of a large national randomised controlled trial designed to reduce socioeconomic inequalities in colorectal cancer screening participation. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Package leaflets of the most consumed medicines in Portugal: safety and regulatory compliance issues. A descriptive study.

PubMed

Pires, Carla; Vigário, Marina; Cavaco, Afonso

2015-01-01

Package leaflets are necessary for safe use of medicines. The aims of the present study were: 1) to assess the compliance between the content of the package leaflets and the specifications of the pharmaceutical regulations; and 2) to identify potential safety issues for patients. Qualitative descriptive study, involving all the package leaflets of branded medicines from the three most consumed therapeutic groups in Portugal, analyzed in the Department of Pharmacoepidemiology, School of Pharmacy, University of Lisbon. A checklist validated through an expert consensus process was used to gather the data. The content of each package leaflet in the sample was classified as compliant or non-compliant with compulsory regulatory issues (i.e. stated dosage and descriptions of adverse reactions) and optional regulatory issues (i.e. adverse reaction frequency, symptoms and procedures in cases of overdose). A total of 651 package leaflets were identified. Overall, the package leaflets were found to be compliant with the compulsory regulatory issues. However, the optional regulatory issues were only addressed in around half of the sample of package leaflets, which made it possible to identify some situations of potentially compromised drug safety. Ideally, the methodologies for package leaflet approval should be reviewed and optimized as a way of ensuring the inclusion of the minimum essential information for safe use of medicines.

Provision of tricuspid valve leaflets by septal papillary muscles in the right ventricle of human and other mammal hearts.

PubMed

Jezyk, Damian; Jerzemowski, Janusz; Grzybiak, Marek

2003-01-01

Leaflets of the tricuspid valve are provided by tendinous cords extending from the papillary muscles. The situation is complicated with the septal muscles, which generally occur in two groups, one as constant musculus coni arteriosi and the second as other variable septal muscles. We tested whether there is a variability in the provision of the tricuspid valve in different taxonomical groups of mammals. The material examined consisted of 299 hearts of mammals (Primates, Ungulata, Carnivora, Lagomorpha, Rodentia, Marsupialia). The musculus coni arteriosi in the majority of mammals provided only the front leaflet, but among Ungulata and Rodentia it provided simultaneously the front and septal leaflet. The other septal muscles provided the front, septal and even back leaflets. The following regularity was observed: in the hearts of Primates provision of the front leaflet and the front part of the septal leaflet predominated, among Ungulata the muscles provided the middle part of the septal leaflet, but among the other mammals the rest of the septal muscles provided, significantly, the back part of the septal leaflet. Such a provision was characteristic for predators, hares, rodents and marsupials. These circumstances may allow the conclusion to be drawn that there is a taxonomical dependence in the provision of the tricuspid valve in the hearts of the mammals under examination.

Intrinsic Curvature-Mediated Transbilayer Coupling in Asymmetric Lipid Vesicles

DOE PAGES

Eicher, Barbara; Marquardt, Drew; Heberle, Frederick A.; ...

2018-01-09

We measured the effect of intrinsic lipid curvature, J 0, on structural properties of asymmetric vesicles made of palmitoyl-oleoyl-phosphatidylethanolamine (POPE; J 0 < 0) and palmitoyl-oleoyl-phosphatidylcholine (POPC; J 0 ~ 0). Electron microscopy and dynamic light scattering were used to determine vesicle size and morphology, and x-ray and neutron scattering, combined with calorimetric experiments and solution NMR, yielded insights into leaflet-specific lipid packing and melting processes. Below the lipid melting temperature we observed strong interleaflet coupling in asymmetric vesicles with POPE inner bilayer leaflets and outer leaflets enriched in POPC. This lipid arrangement manifested itself by lipids melting cooperatively inmore » both leaflets, and a rearrangement of lipid packing in both monolayers. On the other hand, no coupling was observed in vesicles with POPC inner bilayer leaflets and outer leaflets enriched in POPE. In this case, the leaflets melted independently and did not affect each other’s acyl chain packing. Furthermore, we found no evidence for transbilayer structural coupling above the melting temperature of either sample preparation. Our results are consistent with the energetically preferred location of POPE residing in the inner leaflet, where it also resides in natural membranes, most likely causing the coupling of both leaflets. The loss of this coupling in the fluid bilayers is most likely the result of entropic contributions.« less

Patient assessment of medication information leaflets and validation of the Evaluative Linguistic Framework (ELF).

PubMed

Hirsh, Di; Clerehan, Rosemary; Staples, Margaret; Osborne, Richard H; Buchbinder, Rachelle

2009-11-01

To obtain patient feedback about the structure and quality of medication information leaflets and validate the usefulness of the Evaluative Linguistic Framework (ELF) for improving written communication with patients. Triangulated feedback about a set of rheumatoid arthritis (RA) medication leaflets, some developed with knowledge of the ELF, was obtained from 27 people with RA from interviews, focus group discussion and self-administered questionnaires. The principal elements of the framework were investigated: overall generic structure and functions of each stage, interpersonal relationship between writer and reader, technicality of language and density of information. Participant assessments of the leaflets aligned with the framework in terms of what constituted a good leaflet. While the main purpose of the leaflets was identified as being information provision, participants also wanted clear instructions, benefits to be highlighted and side effects to be comprehensively listed. For comprehensiveness and user-friendliness, leaflets developed with guidance of the ELF were consistently preferred. According to people with RA, leaflets generated from a linguistic framework are clearer and more effective in communicating information about medications. The ELF is a user-friendly, structured analytic system that can assist with the development of effective high quality patient information materials.

Optimal Elastomeric Scaffold Leaflet Shape for Pulmonary Heart Valve Leaflet Replacement

PubMed Central

Fan, Rong; Bayoumi, Ahmed S.; Chen, Peter; Hobson, Christopher M.; Wagner, William R.; Mayer, John E.; Sacks, Michael S.

2012-01-01

Surgical replacement of the pulmonary valve (PV) is a common treatment option for congenital pulmonary valve defects. Engineered tissue approaches to develop novel PV replacements are intrinsically complex, and will require methodical approaches for their development. Single leaflet replacement utilizing an ovine model is an attractive approach in that candidate materials can be evaluated under valve level stresses in blood contact without the confounding effects of a particular valve design. In the present study an approach for optimal leaflet shape design based on finite element (FE) simulation of a mechanically anisotropic, elastomeric scaffold for PV replacement is presented. The scaffold was modeled as an orthotropic hyperelastic material using a generalized Fung-type constitutive model. The optimal shape of the fully loaded PV replacement leaflet was systematically determined by minimizing the difference between the deformed shape obtained from FE simulation and an ex-vivo microCT scan of a native ovine PV leaflet. Effects of material anisotropy, dimensional changes of PV root, and fiber orientation on the resulting leaflet deformation were investigated. In-situ validation demonstrated that the approach could guide the design of the leaflet shape for PV replacement surgery. PMID:23294966

Meningioma of the superior leaflet of the velum interpositum: A case report

PubMed Central

Champagne, Pierre-Olivier; Bojanowski, Michel W.

2015-01-01

Background: Meningiomas of the velum interpositum in the roof of the third ventricle are rare. Knowing from which leaflet the meningioma originates and thus its relationships with the internal cerebral and Galen veins, may help in choosing the surgical approach. Case Description: We report the case of a 40-year-old male with a meningioma arising from the superior leaflet of the velum interpositum. The tumor was resected successfully using the infratentorial-supracerebellar approach. Reviewing the literature, of the 22 reported cases of velum interpositum meningiomas, sufficient information regarding the precise location of the origin of the tumor was provided in 14 cases, all of which were from the inferior leaflet. Conclusion: We report the first case of velum interpositum meningioma arising from the superior leaflet and give a potential explanation as to why meningiomas of the velum interpositum occur more commonly on the inferior leaflet. Distinguishing from which of the two leaflets the tumor originates may influence the surgical strategy. PMID:25949856

Future prospects of therapeutic clinical trials in acute myeloid leukemia

PubMed Central

Khan, Maliha; Mansoor, Armaghan-e-Rehman; Kadia, Tapan M

2017-01-01

Acute myeloid leukemia (AML) is a markedly heterogeneous hematological malignancy that is most commonly seen in elderly adults. The response to current therapies to AML is quite variable, and very few new drugs have been recently approved for use in AML. This review aims to discuss the issues with current trial design for AML therapies, including trial end points, patient enrollment, cost of drug discovery and patient heterogeneity. We also discuss the future directions in AML therapeutics, including intensification of conventional therapy and new drug delivery mechanisms; targeted agents, including epigenetic therapies, cell cycle regulators, hypomethylating agents and chimeric antigen receptor T-cell therapy; and detail of the possible agents that may be incorporated into the treatment of AML in the future. PMID:27771959

Percutaneous Transcatheter Mitral Valve Replacement: Patient-specific Three-dimensional Computer-based Heart Model and Prototyping.

PubMed

Vaquerizo, Beatriz; Theriault-Lauzier, Pascal; Piazza, Nicolo

2015-12-01

Mitral regurgitation is the most prevalent valvular heart disease worldwide. Despite the widespread availability of curative surgical intervention, a considerable proportion of patients with severe mitral regurgitation are not referred for treatment, largely due to the presence of left ventricular dysfunction, advanced age, and comorbid illnesses. Transcatheter mitral valve replacement is a promising therapeutic alternative to traditional surgical valve replacement. The complex anatomical and pathophysiological nature of the mitral valvular complex, however, presents significant challenges to the successful design and implementation of novel transcatheter mitral replacement devices. Patient-specific 3-dimensional computer-based models enable accurate assessment of the mitral valve anatomy and preprocedural simulations for transcatheter therapies. Such information may help refine the design features of novel transcatheter mitral devices and enhance procedural planning. Herein, we describe a novel medical image-based processing tool that facilitates accurate, noninvasive assessment of the mitral valvular complex, by creating precise three-dimensional heart models. The 3-dimensional computer reconstructions are then converted to a physical model using 3-dimensional printing technology, thereby enabling patient-specific assessment of the interaction between device and patient. It may provide new opportunities for a better understanding of the mitral anatomy-pathophysiology-device interaction, which is of critical importance for the advancement of transcatheter mitral valve replacement. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

The geometrical effect of different annuloplasty rings on mitral valve annulus.

PubMed

Al-Maisary, Sameer; Graser, Bastian; Engelhardt, Sandy; Wolf, Ivo; Karck, Matthias; DE Simone, Raffaele

2017-06-01

Different types of mitral annuloplasty rings are commercially available. The aim of this study was to investigate the effect of implantation of six types of annuloplasty rings on the geometry and dynamics of the mitral valve. Three-dimensional echocardiography images of 42 patients were acquired to visualize the mitral valve annulus. Virtual representations of six commercially available annuloplasty rings were matched to anatomical mitral annuli of each patient according to anterolateral-posteromedial diameter. The virtual displacement of each annuloplasty ring after the implantation was measured and compared with the other rings. Patients with severe mitral regurgitation had significantly dilated annuli according to anterolateral-posteromedial diameter, anterior-posterior diameter and to annulus circumference. Anterior and posterior heights of the mitral annuli and non-planarity angle showed no significant differences among different patients with different degree of mitral regurgitation. The ratio of anterior-posterior to anterolateral-posteromedial diameter was almost identical in all groups with identical annular shapes. The implantation of the Carpentier-Edwards Classic Annuloplasty Ring™ led to maximal displacement of mitral annulus, followed by the IM-Ring™, without a statistical significance. In contrary, the implantation of a MyxoETlogix Ring™ was associated with minimal displacement of mitral annulus throughout the groups, but without statistical significance. The implantation of different ring types in patients with different annuli shapes and dimensions did not lead to any significant change in the configuration of mitral annuli after the virtual implantation of the tested annuloplasty rings.

Curved butterfly bileaflet prosthetic cardiac valve

DOEpatents

McQueen, David M.; Peskin, Charles S.

1991-06-25

An annular valve body having a central passageway for the flow of blood therethrough with two curved leaflets each of which is pivotally supported on an accentric positioned axis in the central passageway for moving between a closed position and an open position. The leaflets are curved in a plane normal to the eccentric axis and positioned with the convex side of the leaflets facing each other when the leaflets are in the open position. Various parameters such as the curvature of the leaflets, the location of the eccentric axis, and the maximum opening angle of the leaflets are optimized according to the following performance criteria: maximize the minimum peak velocity through the valve, maximize the net stroke volume, and minimize the mean forward pressure difference, thereby reducing thrombosis and improving the hemodynamic performance.

Effects of Mitral Annulus Remodeling Following MitraClip Procedure on Reduction of Functional Mitral Regurgitation.

PubMed

Hidalgo, Francisco; Mesa, Dolores; Ruiz, Martín; Delgado, Mónica; Rodríguez, Sara; Pardo, Laura; Pan, Manuel; López, Amador; Romero, Miguel A; Suárez de Lezo, José

2016-11-01

The percutaneous mitral valve repair procedure (MitraClip) appears to reduce mitral annulus diameter in patients with functional mitral regurgitation, but the relationship between this and regurgitation severity has not been demonstrated. The aim of this study was to determine the effect of mitral annulus remodeling on the reduction of mitral regurgitation in patients with functional etiology. The study included all patients with functional mitral regurgitation treated with MitraClip at our hospital until January 2015. Echocardiogram (iE33 model, Philips) was performed in all patients immediately after device positioning. Changes in the mitral annulus correlated with mitral regurgitation severity, as assessed using the effective regurgitant orifice area. The study included 23 patients (age, 65±14 years; 74% men; left ventricular ejection fraction, 31%±13%; systolic pulmonary artery pressure, 47±10 mmHg). After the procedure, the regurgitant orifice area decreased by 0.30 cm 2 ±0.04 cm 2 (P<.0005), from a baseline of 0.49 cm 2 ±0.09 cm 2 . Anteroposterior diameter decreased by 3.14 mm±1.01 mm (P<.0005) from a baseline of 28.27 mm±4.9 mm, with no changes in the intercommissural diameter (0.50 mm±0.91 mm vs 40.68 mm±4.7 mm; P=.26). A significant association was seen between anteroposterior diameter reduction and regurgitant orifice area reduction (r=.49; P=.020). In patients with functional mitral regurgitation, the MitraClip device produces an immediate reduction in the anteroposterior diameter. This remodeling may be related to the reduction in mitral regurgitation. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Is mitral valve repair superior to replacement for chronic ischemic mitral regurgitation with left ventricular dysfunction?

PubMed Central

2010-01-01

Background This study was undertaken to compare mitral valve repair and replacement as treatments for ischemic mitral regurgitation (IMR) with left ventricular dysfunction (LVD). Specifically, we sought to determine whether the choice of mitral valve procedure affected survival, and discover which patients were predicted to benefit from mitral valve repair and which from replacement. Methods A total of 218 consecutive patients underwent either mitral valve repair (MVP, n = 112) or mitral valve replacement (MVR, n = 106). We retrospectively reviewed the clinical material, operation methods, echocardiography check during operation and follow-up. Patients details and follow-up outcomes were compared using multivariate and Kaplan-Meier analyses. Results No statistical difference was found between the two groups in term of intraoperative data. Early mortality was 3.2% (MVP 2.7% and MVR 3.8%). At discharge, Left ventricular end-systolic and end-diastolic diameter and left ventricular ejection fraction (LVEF) were improved more in the MVP group than MVR group (P < 0.05), however, in follow-up no statistically significant difference was observed between the MVR and MVP group (P > 0.05). Follow-up mitral regurgitation grade was significantly improved in the MVR group compared with the MVP group (P < 0.05). The Kaplan-Meier survival estimates at 1, 3, and 5 years were simlar between MVP and MVR group. Logistic regression revealed poor survival was associated with old age(#75), preoperative renal insufficiency and low left ventricular ejection fraction (< 30%). Conclusion Mitral valve repair is the procedure of choice in the majority of patients having surgery for severe ischemic mitral regurgitation with left ventricular dysfunction. Early results of MVP treatment seem to be satisfactory, but several lines of data indicate that mitral valve repair provided less long-term benefit than mitral valve replacement in the LVD patients. PMID:21059216

Mitral Valve Clip for Treatment of Mitral Regurgitation: An Evidence-Based Analysis

PubMed Central

Ansari, Mohammed T.; Ahmadzai, Nadera; Coyle, Kathryn; Coyle, Doug; Moher, David

2015-01-01

Background Many of the 500,000 North American patients with chronic mitral regurgitation may be poor candidates for mitral valve surgery. Objective The objective of this study was to investigate the comparative effectiveness, harms, and cost-effectiveness of percutaneous mitral valve repair using mitral valve clips in candidates at prohibitive risk for surgery. Data Sources We searched articles in MEDLINE, Embase, and the Cochrane Library published from 1994 to February 2014 for evidence of effectiveness and harms; for economic literature we also searched NHS EED and Tufts CEA registry. Grey literature was also searched. Review Methods Primary studies were sought from existing systematic reviews that had employed reliable search and screening methods. Newer studies were sought by searching the period subsequent to the last search date of the review. Two reviewers screened records and assessed study validity. We used the Cochrane risk of bias tool for randomized, generic assessment for non-randomized studies, and the Phillips checklist for economic studies. Results Ten studies including 1 randomized trial were included. The majority of the direct comparative evidence compared the mitral valve clip repair with surgery in patients not particularly at prohibitive surgical risk. Irrespective of degenerative or functional chronic mitral regurgitation etiology, evidence of effectiveness and harms is inconclusive and of very low quality. Very-low-quality evidence indicates that percutaneous mitral valve clip repair may provide a survival advantage, at least during the first 1 to 2 years, particularly in medically managed chronic functional mitral regurgitation. Because of limitations in the design of studies, the cost-effectiveness of mitral valve clips in patients at prohibitive risk for surgery also could not be established. Limitations Because of serious concerns of risk of bias, indirectness, and imprecision, evidence is of very low quality. Conclusions No meaningful conclusions can be drawn about the comparative effectiveness, harms, and cost-effectiveness of mitral valve clips in the population with chronic mitral regurgitation who are at prohibitive risk for surgery. PMID:26379810

Preoperative planning with three-dimensional reconstruction of patient's anatomy, rapid prototyping and simulation for endoscopic mitral valve repair.

PubMed

Sardari Nia, Peyman; Heuts, Samuel; Daemen, Jean; Luyten, Peter; Vainer, Jindrich; Hoorntje, Jan; Cheriex, Emile; Maessen, Jos

2017-02-01

Mitral valve repair performed by an experienced surgeon is superior to mitral valve replacement for degenerative mitral valve disease; however, many surgeons are still deterred from adapting this procedure because of a steep learning curve. Simulation-based training and planning could improve the surgical performance and reduce the learning curve. The aim of this study was to develop a patient-specific simulation for mitral valve repair and provide a proof of concept of personalized medicine in a patient prospectively planned for mitral valve surgery. A 65-year old male with severe symptomatic mitral valve regurgitation was referred to our mitral valve heart team. On the basis of three-dimensional (3D) transoesophageal echocardiography and computed tomography, 3D reconstructions of the patient's anatomy were constructed. By navigating through these reconstructions, the repair options and surgical access were chosen (minimally invasive repair). Using rapid prototyping and negative mould fabrication, we developed a process to cast a patient-specific mitral valve silicone replica for preoperative repair in a high-fidelity simulator. Mitral valve and negative mould were printed in systole to capture the pathology when the valve closes. A patient-specific mitral valve silicone replica was casted and mounted in the simulator. All repair techniques could be performed in the simulator to choose the best repair strategy. As the valve was printed in systole, no special testing other than adjusting the coaptation area was required. Subsequently, the patient was operated, mitral valve pathology was validated and repair was successfully done as in the simulation. The patient-specific simulation and planning could be applied for surgical training, starting the (minimally invasive) mitral valve repair programme, planning of complex cases and the evaluation of new interventional techniques. The personalized medicine could be a possible pathway towards enhancing reproducibility, patient's safety and effectiveness of a complex surgical procedure. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Mitral annulus size links ventricular dilatation to functional mitral regurgitation.

PubMed

Popović, Zoran B; Martin, Maureen; Fukamachi, Kiyotaka; Inoue, Masahiro; Kwan, Jun; Doi, Kazuyoshi; Qin, Jian Xin; Shiota, Takahiro; Garcia, Mario J; McCarthy, Patrick M; Thomas, James D

2005-09-01

We compared the impact of annulus size and valve deformation (tethering) on mitral regurgitation in the animal dilated cardiomyopathy model, and assessed if acute left ventricular volume changes affect mitral annulus dimensions. We performed 3-dimensional echocardiography in 30 open-chest dogs with pacing-induced cardiomyopathy. Mitral annulus area was calculated from its two orthogonal diameters, whereas valve tethering was quantified by valve tenting area measurement. Mitral valve regurgitant volume showed the highest correlation with annulus area (r = 0.64, P < .001), left atrial volume (r = 0.40, P < .01), and left ventricular end-diastolic volume (r = 0.37, P < .01). Regurgitant volume showed poorer correlation with valve tethering in both septolateral and intercommissural planes (r = 0.35 and r = 0.31, P < .05 for both). Annulus dimensions correlated with acute changes of left ventricular end-diastolic volume (r = 0.68, P = .002). Mitral annulus dilation is the strongest predictor of functional mitral regurgitation in this animal dilated cardiomyopathy model.

Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML.

PubMed

Liyanage, Sanduni U; Hurren, Rose; Voisin, Veronique; Bridon, Gaëlle; Wang, Xiaoming; Xu, ChangJiang; MacLean, Neil; Siriwardena, Thirushi P; Gronda, Marcela; Yehudai, Dana; Sriskanthadevan, Shrivani; Avizonis, Daina; Shamas-Din, Aisha; Minden, Mark D; Bader, Gary D; Laposa, Rebecca; Schimmer, Aaron D

2017-05-11

Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human acute myeloid leukemia (AML) samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared with normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared with normal hematopoietic samples. Knockdown of cytoplasmic nucleoside kinases reduced mtDNA levels in AML cells, demonstrating their contribution in maintaining mtDNA. To assess cytoplasmic nucleoside kinase pathway activity, we used a nucleoside analog 2'3'-dideoxycytidine (ddC), which is phosphorylated to the activated antimetabolite, 2'3'-dideoxycytidine triphosphate by cytoplasmic nucleoside kinases. ddC is a selective inhibitor of the mitochondrial DNA polymerase γ. ddC was preferentially activated in AML cells compared with normal hematopoietic progenitor cells. ddC treatment inhibited mtDNA replication, oxidative phosphorylation, and induced cytotoxicity in a panel of AML cell lines. Furthermore, ddC preferentially inhibited mtDNA replication in a subset of primary human leukemia cells and selectively targeted leukemia cells while sparing normal progenitor cells. In animal models of human AML, treatment with ddC decreased mtDNA, electron transport chain proteins, and induced tumor regression without toxicity. ddC also targeted leukemic stem cells in secondary AML xenotransplantation assays. Thus, AML cells have increased cytidine nucleoside kinase activity that regulates mtDNA biogenesis and can be leveraged to selectively target oxidative phosphorylation in AML. © 2017 by The American Society of Hematology.

Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML

PubMed Central

Liyanage, Sanduni U.; Hurren, Rose; Voisin, Veronique; Bridon, Gaëlle; Wang, Xiaoming; Xu, ChangJiang; MacLean, Neil; Siriwardena, Thirushi P.; Gronda, Marcela; Yehudai, Dana; Sriskanthadevan, Shrivani; Avizonis, Daina; Shamas-Din, Aisha; Minden, Mark D.; Bader, Gary D.; Laposa, Rebecca

2017-01-01

Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human acute myeloid leukemia (AML) samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared with normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared with normal hematopoietic samples. Knockdown of cytoplasmic nucleoside kinases reduced mtDNA levels in AML cells, demonstrating their contribution in maintaining mtDNA. To assess cytoplasmic nucleoside kinase pathway activity, we used a nucleoside analog 2′3′-dideoxycytidine (ddC), which is phosphorylated to the activated antimetabolite, 2′3′-dideoxycytidine triphosphate by cytoplasmic nucleoside kinases. ddC is a selective inhibitor of the mitochondrial DNA polymerase γ. ddC was preferentially activated in AML cells compared with normal hematopoietic progenitor cells. ddC treatment inhibited mtDNA replication, oxidative phosphorylation, and induced cytotoxicity in a panel of AML cell lines. Furthermore, ddC preferentially inhibited mtDNA replication in a subset of primary human leukemia cells and selectively targeted leukemia cells while sparing normal progenitor cells. In animal models of human AML, treatment with ddC decreased mtDNA, electron transport chain proteins, and induced tumor regression without toxicity. ddC also targeted leukemic stem cells in secondary AML xenotransplantation assays. Thus, AML cells have increased cytidine nucleoside kinase activity that regulates mtDNA biogenesis and can be leveraged to selectively target oxidative phosphorylation in AML. PMID:28283480

AML1 is overexpressed in patients with myeloproliferative neoplasms and mediates JAK2V617F-independent overexpression of NF-E2

PubMed Central

Wang, Wei; Schwemmers, Sven; Hexner, Elizabeth O.

2010-01-01

The transcription factor NF-E2 is overexpressed in the majority of patients with polycythemia vera (PV). Concomitantly, 95% of these patients carry the JAK2V617F mutation. Although NF-E2 levels correlate with JAK2V671F allele burden in some PV cohorts, the molecular mechanism causing aberrant NF-E2 expression has not been described. Here we show that NF-E2 expression is also increased in patients with essential thrombocythemia and primary myelofibrosis independent of the presence of the JAK2V617F mutation. Characterization of the NF-E2 promoter revealed multiple functional binding sites for AML1/RUNX-1. Chromatin immunoprecipitation demonstrated AML1 binding to the NF-E2 promoter in vivo. Moreover, AML1 binding to the NF-E2 promoter was significantly increased in granulocytes from PV patients compared with healthy controls. AML1 mRNA expression was elevated in patients with PV, essential thrombocythemia, and primary myelofibrosis both in the presence and absence of JAK2V617F. In addition, AML1 and NF-E2 expression were highly correlated. RNAi-mediated suppression of either AML1 or of its binding partner CBF-β significantly decreased NF-E2 expression. Moreover, expression of the leukemic fusion protein AML/ETO drastically decreased NF-E2 protein levels. Our data identify NF-E2 as a novel AML1 target gene and delineate a role for aberrant AML1 expression in mediating elevated NF-E2 expression in MPN patients. PMID:20339092

Immunogenic apoptosis in human acute myeloid leukemia (AML): primary human AML cells expose calreticulin and release heat shock protein (HSP) 70 and HSP90 during apoptosis.

PubMed

Fredly, Hanne; Ersvær, Elisabeth; Gjertsen, Bjørn-Tore; Bruserud, Oystein

2011-06-01

Several previous studies have demonstrated that both conventional cytotoxic drugs as well as targeted therapeutics can induce apoptosis in primary human acute myelogenous leukemia (AML) cells. However, the apoptotic phenotype of dying AML cells has been less extensively characterized. Even though specific antileukemic immune reactivity is important in AML, especially for allotransplanted patients, it has not been investigated whether dying primary human AML cells show phenotypic characteristics consistent with immunogenic apoptosis [calreticulin exposure, heat shock protein (HSP) release]. We therefore investigated whether in vitro cultured primary human acute myeloid leukemia (AML) cells show calreticulin exposure and HSP70/HSP90 release during spontaneous (stress-induced) apoptosis when cultured in medium alone and when cultured in the presence of antileukemic drugs. Both surface exposure of calreticulin and release of HSP70 and HSP90 was detected but showed a wide variation between patients. This variation was also maintained when the AML cells were cultured in the presence of cytotoxic drugs (cytarabine, daunorubicin, mitomycin), all-trans retinoic acid (ATRA) and valproic acid. Finally, AML cells collected during in vivo ATRA therapy showed increased calreticulin exposure during spontaneous in vitro apoptosis, suggesting that in vivo pharmacotherapy can modulate the apoptotic phenotype. To conclude, apoptotic AML cells can show phenotypic characteristics consistent with immunogenic apoptosis, but there is a wide variation between patients and the level of calreticulin exposure/HSP release seems to depend on individual patient characteristics rather than the apoptosis-inducing agent.

IL-8 as mediator in the microenvironment-leukaemia network in acute myeloid leukaemia.

PubMed

Kuett, Alexander; Rieger, Christina; Perathoner, Deborah; Herold, Tobias; Wagner, Michaela; Sironi, Silvia; Sotlar, Karl; Horny, Hans-Peter; Deniffel, Christian; Drolle, Heidrun; Fiegl, Michael

2015-12-17

The bone marrow microenvironment is physiologically hypoxic with areas being as low as 1% O2, e.g. the stem cell niche. Acute myeloid leukaemia (AML) blasts misuse these bone marrow niches for protection by the local microenvironment, but also might create their own microenvironment. Here we identify IL-8 as a hypoxia-regulated cytokine in both AML cell lines and primary AML samples that is induced within 48 hours of severe hypoxia (1% O2). IL-8 lacked effects on AML cells but induced migration in mesenchymal stromal cells (MSC), an integral part of the bone marrow. Accordingly, MSC were significantly increased in AML bone marrow as compared to healthy bone marrow. Interestingly, mononuclear cells obtained from healthy bone marrow displayed both significantly lower endogenous and hypoxia-induced production of IL-8. IL-8 mRNA expression in AML blasts from 533 patients differed between genetic subgroups with significantly lower expression of IL-8 in acute promyelocytic leukaemia (APL), while in non APL-AML patients with FLT ITD had the highest IL-8 expression. In this subgroup, high IL-8 expression was also prognostically unfavourable. In conclusion, hypoxia as encountered in the bone marrow specifically increases IL-8 expression of AML, which in turn impacts niche formation. High IL-8 expression might be correlated with poor prognosis in certain AML subsets.

Association of a murine leukaemia stem cell gene signature based on nucleostemin promoter activity with prognosis of acute myeloid leukaemia in patients.

PubMed

Ali, Mohamed A E; Naka, Kazuhito; Yoshida, Akiyo; Fuse, Kyoko; Kasada, Atsuo; Hoshii, Takayuki; Tadokoro, Yuko; Ueno, Masaya; Ohta, Kumiko; Kobayashi, Masahiko; Takahashi, Chiaki; Hirao, Atsushi

2014-07-18

Acute myeloid leukaemia (AML) is a heterogeneous neoplastic disorder in which a subset of cells function as leukaemia-initiating cells (LICs). In this study, we prospectively evaluated the leukaemia-initiating capacity of AML cells fractionated according to the expression of a nucleolar GTP binding protein, nucleostemin (NS). To monitor NS expression in living AML cells, we generated a mouse AML model in which green fluorescent protein (GFP) is expressed under the control of a region of the NS promoter (NS-GFP). In AML cells, NS-GFP levels were correlated with endogenous NS mRNA. AML cells with the highest expression of NS-GFP were very immature blast-like cells, efficiently formed leukaemia colonies in vitro, and exhibited the highest leukaemia-initiating capacity in vivo. Gene expression profiling analysis revealed that cell cycle regulators and nucleotide metabolism-related genes were highly enriched in a gene set associated with leukaemia-initiating capacity that we termed the 'leukaemia stem cell gene signature'. This gene signature stratified human AML patients into distinct clusters that reflected prognosis, demonstrating that the mouse leukaemia stem cell gene signature is significantly associated with the malignant properties of human AML. Further analyses of gene regulation in leukaemia stem cells could provide novel insights into diagnostic and therapeutic approaches to AML. Copyright © 2014 Elsevier Inc. All rights reserved.

Trib2 expression in granulocyte-monocyte progenitors drives a highly drug resistant acute myeloid leukaemia linked to elevated Bcl2

PubMed Central

O’Connor, Caitriona; Yalla, Krishna; Salomé, Mara; Moka, Hothri Ananyambica; Castañeda, Eduardo Gómez; Eyers, Patrick A.; Keeshan, Karen

2018-01-01

Trib2 pseudokinase has oncogenic and tumour suppressive functions depending on the cellular context. We investigated the ability of Trib2 to transform different haemopoietic stem and progenitor cells (HSPCs). Our study identified the granulocyte-macrophage progenitor (GMP) subpopulation as a potent leukaemia initiating cell of Trib2-driven AML in vivo. Trib2 transformed GMPs generated a fully penetrant and short latency AML. AML cells expressing elevated Trib2 led to a chemoresistant phenotype following chemotherapy treatment. We show that Trib2 overexpression results in an increase in BCL2 expression, and high Trib2 expressing cells are highly sensitive to cell killing by BCL2 inhibition (ABT199). Combined treatment with chemotherapeutic agents and BCL2 inhibition resulted in synergistic killing of Trib2+ AML cells. Trib2 transformed GMP AML cells showed more chemoresistance compared with HSPC derived Trib2 AML cells associated with higher Bcl2 expression. There is significant correlation of high TRIB2 and BCL2 expression in patient derived human AML cells. These data demonstrate that the cell of origin influences the leukaemic profile and chemotherapeutic response of Trib2+ AML. Combined TRIB2 and BCL2 expression in AML cells may have clinical utility relevant for monitoring drug resistance and disease relapse. PMID:29599919

Integrated genomic analyses identify WEE1 as a critical mediator of cell fate and novel therapeutic target in acute myeloid leukemia

PubMed Central

Porter, Christopher C.; Kim, Jihye; Fosmire, Susan; Gearheart, Christy M.; van Linden, Annemie; Baturin, Dmitry; Zaberezhnyy, Vadym; Patel, Purvi R.; Gao, Dexiang; Tan, Aik Choon; DeGregori, James

2011-01-01

Acute myeloid leukemia (AML) remains a therapeutic challenge despite increasing knowledge about the molecular origins of the disease, as the mechanisms of AML cell escape from chemotherapy remain poorly defined. We hypothesized that AML cells are addicted to molecular pathways in the context of chemotherapy and used complementary approaches to identify these addictions. Using novel molecular and computational approaches, we performed genome-wide shRNA screens to identify proteins that mediate AML cell fate after cytarabine exposure, gene expression profiling of AML cells exposed to cytarabine to identify genes with induced expression in this context, and examination of existing gene expression data from primary patient samples. The integration of these independent analyses strongly implicates cell cycle checkpoint proteins, particularly WEE1, as critical mediators of AML cell survival after cytarabine exposure. Knockdown of WEE1 in a secondary screen confirmed its role in AML cell survival. Pharmacologic inhibition of WEE1 in AML cell lines and primary cells is synergistic with cytarabine. Further experiments demonstrate that inhibition of WEE1 prevents S-phase arrest induced by cytarabine, broadening the functions of WEE1 that may be exploited therapeutically. These data highlight the power of integrating functional and descriptive genomics, and identify WEE1 as potential therapeutic target in AML. PMID:22289989

Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML.

PubMed

Morgado-Palacin, Isabel; Day, Amanda; Murga, Matilde; Lafarga, Vanesa; Anton, Marta Elena; Tubbs, Anthony; Chen, Hua Tang; Ergan, Aysegul; Anderson, Rhonda; Bhandoola, Avinash; Pike, Kurt G; Barlaam, Bernard; Cadogan, Elaine; Wang, Xi; Pierce, Andrew J; Hubbard, Chad; Armstrong, Scott A; Nussenzweig, André; Fernandez-Capetillo, Oscar

2016-09-13

Among the various subtypes of acute myeloid leukemia (AML), those with chromosomal rearrangements of the MLL oncogene (AML-MLL) have a poor prognosis. AML-MLL tumor cells are resistant to current genotoxic therapies because of an attenuated response by p53, a protein that induces cell cycle arrest and apoptosis in response to DNA damage. In addition to chemicals that damage DNA, efforts have focused on targeting DNA repair enzymes as a general chemotherapeutic approach to cancer treatment. Here, we found that inhibition of the kinase ATR, which is the primary sensor of DNA replication stress, induced chromosomal breakage and death of mouse AML(MLL) cells (with an MLL-ENL fusion and a constitutively active N-RAS independently of p53. Moreover, ATR inhibition as a single agent exhibited antitumoral activity, both reducing tumor burden after establishment and preventing tumors from growing, in an immunocompetent allograft mouse model of AML(MLL) and in xenografts of a human AML-MLL cell line. We also found that inhibition of ATM, a kinase that senses DNA double-strand breaks, also promoted the survival of the AML(MLL) mice. Collectively, these data indicated that ATR or ATM inhibition represent potential therapeutic strategies for the treatment of AML, especially MLL-driven leukemias. Copyright © 2016, American Association for the Advancement of Science.

Trisomy 19 as the sole chromosomal anomaly in hematologic neoplasms.

PubMed

Johansson, B; Billström, R; Mauritzson, N; Mitelman, F

1994-05-01

Trisomy 19 was found as the sole chromosomal aberration in three hematologic malignancies: one chronic myelomonocytic leukemia and two cases of of immunophenotypically immature acute myeloid leukemia (AML). A compilation of previously published hematologic neoplasms with +19 as the only change reveals that this anomaly is strongly associated with myeloid malignancies; 25 of 31 cases have been myelodysplastic syndromes (MDS) or AML. Eight of the 11 MDS cases have been either refractory anemia (RA) or RA with excess of blasts, and four of the 14 AML cases have had preleukemic myelodysplastic cases phase, with the +19 accruing during the time of leukemic transformation. The AML cases have, in general, been either or early maturation arrest, i.e. undifferentiated or AML-M1/M2, or of myelomonocytic-monoblastic origin, i.e., AML-M4/M5. None of the MDS or AML cases with +19 had had a previous history of radio- or chemotherapy. We conclude that trisomy 19, as the sole anomaly, is a characteristic abnormality in de novo myeloid malignancies. No clinical features seem to characterize patients with +19 AML and MDS and the prognostic impact of the aberration remains to be elucidated.

When the good go bad: Mutant NPM1 in acute myeloid leukemia.

PubMed

Kunchala, Preethi; Kuravi, Sudhakiranmayi; Jensen, Roy; McGuirk, Joseph; Balusu, Ramesh

2018-05-01

Nucleophosmin 1 (NPM1) is a nucleolar phosphoprotein that performs diverse biological functions including molecular chaperoning, ribosome biogenesis, DNA repair, and genome stability. Acute myeloid leukemia (AML) is a heterogeneous disease, more than half of the AML cases exhibit normal karyotype (NK). Approximately 50-60 percent of patients with NK-AML carry NPM1 mutations which are characterized by cytoplasmic dislocation of the NPM1 protein. In AML, mutant NPM1 (NPM1c+) acts in a dominant negative fashion and also blocks the differentiation of myeloid cells through gain-of-function for the AML phenotype. Currently, there is limited knowledge on the gain-of-function mechanism of mutant NPM1. Here, we review the known mechanisms of mutant NPM1 in the pathogenesis of AML. We describe genetic abnormalities, the clinical significance of exon-12 mutations in the NPM1 gene, and chromosomal translocations including the recently discovered NPM1-TYK2, and NPM1-HAUS1. Also, we outline the possible therapeutic interventions for the treatment of AML by targeting NPM1. Overall, the review will summarize present knowledge on mutant NPM1 origin, pathogenesis, and therapy in AML. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mitral stenosis and percutaneous mitral valvuloplasty (part 1).

PubMed

Guérios, Enio E; Bueno, Ronaldo; Nercolini, Deborah; Tarastchuk, José; Andrade, Paulo; Pacheco, Alvaro; Faidiga, Alysson; Negrao, Stefan; Barbosa, Antonio

2005-07-01

Although the incidence and severity of rheumatic mitral stenosis have declined in developed countries, the disease is still highly prevalent in many of the poorer and most densely populated areas of the globe, remaining a major public health issue and reflecting the socioeconomic status of the region. In the last 30 years, mitral stenosis therapy has undergone a reorientation with the introduction of percutaneous mitral valvuloplasty. This manuscript is an updated review of percutaneous dilation of mitral stenosis in its different aspects, encompassing traditional techniques, technical innovations, the most significant case loads worldwide, an analysis of the procedure as well as immediate and late outcomes.

Percutaneous Mitral Valvuloplasty in a Mid-Term Pregnant Woman with Severe Rheumatic Mitral Stenosis

PubMed Central

Lee, Myoung Mook; Sohn, Dae-Won; Oh, Byung Hee; Kim, Jung Goo; Park, Young Bae; Choi, Yun Shik; Seo, Jung Don; Lee, Young Woo

1992-01-01

A 28-year-old woman with severe mitral stenosis underwent percutaneous mitral valvuloplasty at 26 weeks’ gestation. Balloon dilation using a double 18-18 mm balloon resulted in improvement in mean mitral pressure gradient (32 to 8 mmHg) and in calculated mitral valve area (0.9 to 2.4 cm2) without complications and any evidence of fetal distress during procedures with an estimated radiation exposure to the fetus of 0.13 rem. This procedure resulted in the disappearance of symptoms of congestive heart failure and allowed for normal full term spontaneous delivery of a 3.51 kg boy without any complication. PMID:1477032

Myectomy and LA-to-LV Conduit for Severe Calcific Mitral Stenosis and Hypertrophic Cardiomyopathy.

PubMed

Meghji, Zahara; Nguyen, Anita; Geske, Jeffrey B; Schaff, Hartzell V

2018-02-26

Severe calcific mitral valve stenosis can rarely occur concomitantly with obstructive hypertrophic cardiomyopathy. In these patients, surgical decalcification of the stenotic mitral valve followed by mitral valve replacement carries significant operative risk and may result in paravalvular leakage, atrioventricular groove disruption, and excessive bleeding. We report the first 2 cases of obstructive hypertrophic cardiomyopathy with severe calcific mitral valve stenosis successfully treated with concomitant transaortic septal myectomy and bypass of the stenotic mitral valve using a valved left atrium to left ventricular conduit. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Snare-assisted anterograde balloon mitral and aortic valvotomy using Inoue balloon catheter.

PubMed

Krishnan, Mangalath N; Syamkumar, M D; Sajeev, C G; Venugopal, K; Johnson, Francis; Vinaykumar, D; Velayudhan, C C; Jayakumar, T G

2007-01-02

We performed concurrent antegrade mitral and aortic valvotomy using Inoue dilatation catheter in 3 cases of combined rheumatic mitral and aortic stenosis. Following mitral valvotomy by standard procedure, aortic valve was crossed with the help of a floatation catheter. Stiff long length guide wire was fixed in descending aorta using a snare. Inoue catheter was threaded over the wire across the aortic valve and aortic valvotomy completed. Mitral valve area increased from mean 1 cm2 to 2 cm2; aortic gradient dropped from mean of 97 mm to 36 mm. Concurrent anterograde balloon mitral and aortic valvotomy may be effective and safe.

Mitral valve replacement with preservation of the subvalvular apparatus.

PubMed

Reardon, M J; David, T E

1999-03-01

The introduction of the Starr-Edwards valve allowed complete replacement of diseased left-sided heart valves. With improved cardiopulmonary bypass, myocardial protection, and surgical techniques the mortality rate from aortic valve replacement decreased substantially, whereas the mortality rate from mitral valve replacement remained high, largely because of low cardiac output syndrome. Increasing use of mitral valve repair techniques resulted in a marked decrease in short-term and long-term morbidity and mortality when treating patients with mitral regurgitation. Some believed that this resulted from maintenance of the mitral annular papillary muscle continuity during mitral valve repair. Subsequent experimental and clinical studies have validated the positive short-term and long-term effects of maintaining the integrity of the mitral valve subvalvular apparatus. This article considers the history of the clinical use of preservation of the subvalvular apparatus, the physiologic studies examining this concept, and the clinical data available on its use. It also examines the following: 1) mitral stenosis versus mitral regurgitation and the preservation of the subvalvular apparatus; 2) whether the anterior, posterior, or both areas of the subvalvular apparatus should be preserved; and 3) the surgical techniques for the preservation of the subvalvular apparatus and valve implantation.

Balloon mitral valvuloplasty during pregnancy--our experience.

PubMed

Salomé, Nuno; Dias, Carla C; Ribeiro, José; Gonçalves, Manuel; Fonseca, Conceição; Ribeiro, Vasco Gama

2002-12-01

Mitral stenosis is the most common valvular heart lesion found in pregnancy. When severe, it leads to significant maternal and fetal morbidity and mortality, since the hemodynamic adaptations to pregnancy are badly tolerated. Pregnancy can lead to development of heart failure in patients with asymptomatic or even unknown mitral stenosis, as a result of the increased mitral valve pressure gradient caused by the physiologic increase in heart rate and blood volume in pregnancy. When symptoms persist despite optimal medical therapy, the poor prognosis justifies the correction of mitral stenosis during pregnancy. To present our experience in treating severe mitral stenosis in women who develop severe heart failure during pregnancy, using percutaneous balloon mitral valvuloplasty. From 1996 to March 2002, in our department, 47 balloon mitral valvuloplasties were successfully performed in women, three of them pregnant. These were patients with congestive heart failure, New York Heart Association (NYHA) functional class III or IV, at the end of the second trimester of pregnancy, who did not respond positively to drug treatment with diuretics and digitalis. We performed percutaneous balloon mitral valvuloplasty using the Inoue technique in the three pregnant patients, with success, at around 25 weeks of gestation. After the procedure, the patients showed clinical improvement, returning to the NYHA functional class that they were in before becoming pregnant (I-II). The previous mitral valve area was 0.9-1.2 cm2, nearly doubling after valvuloplasty. Mean left atrial pressure decreased on average by 42%, and the maximum pressure (V wave) decreased on average by 40%. The mitral valve pressure gradient decreased from 15, 10 and 28 mmHg to 7, 5 and 5 mmHg after valvuloplasty. During the procedure there were no maternal or fetal complications. All patients were discharged 24 to 48 h after valvuloplasty, continuing their pregnancies without complications. One woman had vaginal delivery, and the other two had cesarean sections at 35 weeks of gestation, all without complications with healthy newborns that developed normally. In follow-up, one patient who had moderate mitral regurgitation after valvuloplasty developed severe mitral regurgitation, requiring surgical correction after two years. In pregnant patients who have severe mitral stenosis and persistent congestive heart failure symptoms despite conventional medical treatment, when feasible, percutaneous balloon mitral valvuloplasty is the best treatment.

Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML

PubMed Central

Zaitseva, Lyubov; Murray, Megan Y.; Shafat, Manar S.; Lawes, Matthew J.; MacEwan, David J.; Bowles, Kristian M.; Rushworth, Stuart A.

2014-01-01

Pharmacological targeting of BTK using ibrutinib has recently shown encouraging clinical activity in a range of lymphoid malignancies. Recently we reported that ibrutinib inhibits human acute myeloid leukemia (AML) blast proliferation and leukemic cell adhesion to the surrounding bone marrow stroma cells. Here we report that in human AML ibrutinib, in addition, functions to inhibit SDF1/CXCR4-mediated AML migration at concentrations achievable in vivo. It has previously been shown that SDF1/CXCR4-induced migration is dependent on activation of downstream BTK in chronic lymphocytic leukaemia (CLL) and multiple myeloma. Here we show that SDF-1 induces BTK phosphorylation and downstream MAPK signalling in primary AML blast. Furthermore, we show that ibrutinib can inhibit SDF1-induced AKT and MAPK activation. These results reported here provide a molecular mechanistic rationale for clinically evaluating BTK inhibition in AML patients and suggests that in some AML patients the blasts count may initially rise in response to ibrutinib therapy, analgous to similar clinical observations in CLL. PMID:25294819

Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer?

PubMed Central

Grove, Carolyn S.; Vassiliou, George S.

2014-01-01

Acute myeloid leukaemia (AML) is an uncontrolled clonal proliferation of abnormal myeloid progenitor cells in the bone marrow and blood. Advances in cancer genomics have revealed the spectrum of somatic mutations that give rise to human AML and drawn our attention to its molecular evolution and clonal architecture. It is now evident that most AML genomes harbour small numbers of mutations, which are acquired in a stepwise manner. This characteristic, combined with our ability to identify mutations in individual leukaemic cells and our detailed understanding of normal human and murine haematopoiesis, makes AML an excellent model for understanding the principles of cancer evolution. Furthermore, a better understanding of how AML evolves can help us devise strategies to improve the therapy and prognosis of AML patients. Here, we draw from recent advances in genomics, clinical studies and experimental models to describe the current knowledge of the clonal evolution of AML and its implications for the biology and treatment of leukaemias and other cancers. PMID:25056697

Granulocyte, monocyte and blast immunophenotype abnormalities in acute myeloid leukemia with myelodysplasia-related changes.

PubMed

Ayar, Sonali P; Ravula, Sreelakshmi; Polski, Jacek M

2014-01-01

Little literature exists regarding granulocyte and monocyte immunophenotype abnormalities in Acute Myeloid Leukemia (AML). We hypothesized that granulocyte and monocyte immunophenotype abnormalities are common in AML, and especially in AML with myelodysplasia-related changes (AMLMRC). Bone marrow or peripheral blood specimens from 48 cases of AML and 22 cases of control specimens were analyzed by flow cytometric immunophenotyping. Granulocyte, monocyte, and blast immunophenotype abnormalities were compared between cases of AML versus controls and AMLMRC versus AML without myelodysplasia. The results revealed that granulocyte, monocyte, and blast abnormalities were more common in AMLMRC than in AML without myelodysplasia or control cases. The difference reached statistical significance for abnormalities of granulocytes and abnormalities in all cells of interest. From the numerous individual abnormalities, only CD25 expression in blasts was significantly more prevalent in AMLMRC in this study. We conclude that detection of granulocyte, monocyte, and blast immunophenotype abnormalities can contribute to the diagnosis of AMLMRC.

Acute myeloid leukemia with leukemic pleural effusion.

PubMed

Chang, Hung

2013-10-01

Acute myeloid leukemia (AML) may be associated with extramedullary tumor growth, which is commonly known as myeloid sarcoma. Although AML with leukemic pleural effusion is considered rare, the true incidence is not clear. We report three cases of AML involving pleural effusion in this study. The cases were encountered in a single institute within two years, suggesting that leukemic effusion is more common than previously reported. Leukemic cells showed evidence of monocytic differentiation in all cases. Two patients presented with advanced AML. Both had concurrent myeloid sarcoma. Both were ineligible for intensive treatment and died soon after diagnosis of myeloid sarcoma. The third patient had pleural effusion upon diagnosis of AML. Remission was achieved and the effusion disappeared after treatment. We conclude leukemic effusion may become more common in an era of improved care and prolonged survival for AML patients. The prognostic impact is unclear and patients should be given standard AML treatment whenever possible. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Patch enlargement of the aortic and mitral valve rings with aortic and mitral double valve replacement. Experimental study.

PubMed

Manouguian, S; Abu-Aishah, N; Neitzel, J

1979-09-01

The experimental results of patch enlargement of the aortic and mitral valve rings with aortic and mitral double valve replacement are reported. The operative technique of this new surgical method is described and the indications are discussed.

Immediate Outcome of Balloon Mitral Valvuloplasty with JOMIVA Balloon during Pregnancy

PubMed Central

Ramasamy, Ramona; Kaliappan, Tamilarasu; Gopalan, Rajendiran; Palanimuthu, Ramasmy; Anandhan, Premkrishna

2017-01-01

Introduction Rheumatic mitral stenosis is the most common Valvular Heart Disease encountered during pregnancy. Balloon Mitral Valvuloplasty (BMV) is one of the treatment option available if the symptoms are refractory to the medical management and the valve anatomy is suitable for balloon dilatation. BMV with Inoue balloon is the most common technique being followed worldwide. Over the wire BMV is a modified technique using Joseph Mitral Valvuloplasty (JOMIVA) balloon catheter which is being followed in certain centres. Aim To assess the immediate post procedure outcome of over the wire BMV with JOMIVA balloon. Materials and Methods Clinical and echocardiographic parameters of pregnant women with significant mitral stenosis who underwent elective BMV with JOMIVA balloon in our institute from 2005 to 2015 were analysed retrospectively. Severity of breathlessness (New York Heart Association Functional Class), and duration of pregnancy was included in the analysis. Pre procedural echocardiographic parameters which included severity of mitral stenosis and Wilkin’s scoring were analysed. Clinical, haemodynamic and echocardiographic outcomes immediately after the procedure were analysed. Results Among the patients who underwent BMV in our Institute 38 were pregnant women. Twenty four patients (63%) were in New York Heart Association (NYHA) Class III. All of them were in sinus rhythm except two (5%) who had atrial fibrillation. Thirty four patients (89.5%) were in second trimester of pregnancy at the time of presentation and four (10.5%) were in third trimester. Echocardiographic analysis of the mitral valve showed that the mean Wilkin’s score was 7.3. Mean mitral valve area pre procedure was 0.8 cm2. Mean gradient across the valve was 18 mmHg. Ten patients (26.5%) had mild mitral regurgitation and none had more than mild mitral regurgitation. Thirty six patients had pulmonary hypertension as assessed by tricuspid regurgitation jet velocity. All of them underwent BMV with JOMIVA balloon. Post procedure mean mitral valve area was 1.7 cm2 as assessed by echocardiography. Post procedure mean gradient across the mitral valve as assessed by echocardiography was 5 mmHg. Two patients had moderate to severe mitral regurgitation after the procedure and the rest had either no mitral regurgitation or mild mitral regurgitation after the procedure. None of the patients warranted mitral valve replacement after BMV. No patients had any manifestations of systemic embolism like cerebrovascular accident or limb ischemia after the procedure. None of the patients had preterm delivery or adverse fetal outcome during index hospitalisation. Conclusion Over the wire BMV is safe and effective method during pregnancy. The results are comparable to that of Inoue technique. BMV offers a good symptomatic improvement in pregnant women presenting with symptoms of pulmonary congestion because of Rheumatic mitral stenosis. PMID:28384909

Anaesthesia information--what patients want to know.

PubMed

Garden, A L; Merry, A F; Holland, R L; Petrie, K J

1996-10-01

We developed and introduced into clinical practice a leaflet to improve the delivery of information to patients before obtaining their consent to anaesthesia. The amount of information needs to be what a "reasonable" patient thinks appropriate; therefore we tested patients' responses to three levels of information: "full" disclosure, "standard" disclosure (as contained in our leaflet) and "minimal" disclosure. Forty-five patients scheduled to undergo cardiac surgery were enrolled in the study. None of the information sheets caused a significant change in state anxiety score and only the "full" disclosure significantly increased knowledge about anaesthesia (P = 0.016). All leaflets were easy to understand. When only one leaflet was provided 64-73% of patients thought the content was "just right", whereas when all three leaflets were viewed together, 63% of patients thought the "minimal" leaflet withheld too much information.

Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML.

PubMed

Wei, Andrew H; Tiong, Ing S

2017-12-07

In 2017, 4 drugs received US Food and Drug Administration marketing approval for acute myeloid leukemia (AML) treatment: targeted therapies for mutant FLT3 and IDH2 , a liposomal cytarabine-daunorubicin formulation for therapy-related AML and AML with myelodysplasia-related changes, and resurgence of an antibody-drug conjugate designed to target CD33. Promising results also emerged for the BCL-2 inhibitor venetoclax combined with low-intensity therapy in older patients unfit for intensive chemotherapy. This quintet of new drugs is likely to reshape the therapeutic landscape of AML. © 2017 by The American Society of Hematology.

INPP4B promotes cell survival via SGK3 activation in NPM1-mutated leukemia.

PubMed

Jin, Hongjun; Yang, Liyuan; Wang, Lu; Yang, Zailin; Zhan, Qian; Tao, Yao; Zou, Qin; Tang, Yuting; Xian, Jingrong; Zhang, Shuaishuai; Jing, Yipei; Zhang, Ling

2018-01-17

Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) has been recognized as a distinct leukemia entity in the 2016 World Health Organization (WHO) classification. The genetic events underlying oncogenesis in NPM1-mutated AML that is characterized by a normal karyotype remain unclear. Inositol polyphosphate 4-phosphatase type II (INPP4B), a new factor in the phosphoinositide-3 kinase (PI3K) pathway-associated cancers, has been recently found a clinically relevant role in AML. However, little is known about the specific mechanistic function of INPP4B in NPM1-mutated AML. The INPP4B expression levels in NPM1-mutated AML primary blasts and AML OCI-AML3 cell lines were determined by qRT-PCR and western blotting. The effect of INPP4B knockdown on OCI-AML3 leukemia cell proliferation was evaluated, using the Cell Counting Kit-8 and colony formation assay. After INPP4B overexpression or knockdown, the activation of serum and glucocorticoid-regulated kinase 3 (SGK3) and AKT was assessed. The effects of PI3K signaling pathway inhibitors on the levels of p-SGK3 in OCI-AML3 cells were tested. The mass of PI (3,4) P 2 and PI (3) P was analyzed by ELISA upon INPP4B overexpression. Knockdown of SGK3 by RNA interference and a rescue assay were performed to confirm the critical role of SGK3 in INPP4B-mediated cell survival. In addition, the molecular mechanism underlying INPP4B expression in NPM1-mutated leukemia cells was explored. Finally, Kaplan-Meier survival analysis was conducted on the NPM1-mutated AML cohort stratified into quartiles for INPP4B expression in The Cancer Genome Atlas (TCGA) dataset. High expression of INPP4B was observed in NPM1-mutated AML. Knockdown of INPP4B repressed cell proliferation in OCI-AML3 cells, whereas recovered INPP4B rescued this inhibitory effect in vitro. Mechanically, INPP4B enhanced phosphorylated SGK3 (p-SGK3) status, but did not affect AKT activation. SGK3 was required for INPP4B-induced cell proliferation in OCI-AML3 cells. High levels of INPP4B were at least partially caused by the NPM1 mutant via ERK/Ets-1 signaling. Finally, high expression of INPP4B showed a trend towards lower overall survival and event-free survival in NPM1-mutated AML patients. Our results indicate that INPP4B promotes leukemia cell survival via SGK3 activation, and INPP4B might be a potential target in the treatment of NPM1-mutated AML.

Further insights into normal aortic valve function: role of a compliant aortic root on leaflet opening and valve orifice area.

PubMed

Sripathi, Vangipuram Canchi; Kumar, Ramarathnam Krishna; Balakrishnan, Komarakshi R

2004-03-01

This study aims to find the fundamental differences in the mechanism of opening and closing of a normal aortic valve and a valve with a stiff root, using a dynamic finite element model. A dynamic, finite element model with time varying pressure was used in this study. Shell elements with linear elastic properties for the leaflet and root were used. Two different cases were analyzed: (1) normal leaflets inside a compliant root, and (2) normal leaflets inside a stiff root. A compliant aortic root contributes substantially to the smooth and symmetrical leaflet opening with minimal gradients. In contrast, the leaflet opening inside a stiff root is delayed, asymmetric, and wrinkled. However, this wrinkling is not associated with increased leaflet stresses. In compliant roots, the effective valve orifice area can substantially increase because of increased root pressure and transvalvular gradients. In stiff roots this effect is strikingly absent. A compliant aortic root contributes substantially to smooth and symmetrical leaflet opening with minimal gradients. The compliance also contributes much to the ability of the normal aortic valve to increase its effective valve orifice in response to physiologic demands of exercise. This effect is strikingly absent in stiff roots.

Transcatheter valve underexpansion limits leaflet durability: implications for valve-in-valve procedures

PubMed Central

Martin, Caitlin; Sun, Wei

2016-01-01

Transcatheter aortic valve (TAV) implantation within a failed bioprosthetic valve is a growing trend for high-risk patients. The non-compliant stent of the previous prosthesis may prevent full expansion of the TAV, which has been shown to distort the leaflet configuration, and has been hypothesized to adversely affect durability. In this study, TAV leaflet fatigue damage under cyclic pressurization in the setting of stent underexpansion by 0 (fully expanded), 1, 2 and 3 mm was simulated using finite element analysis to test this hypothesis. In the 2 and 3 mm underexpanded devices, the TAV leaflets exhibited severe pin-wheeling during valve closure, which increased leaflet stresses dramatically, and resulted in accelerated fatigue damage of the leaflets. The leaflet fatigue damage in the 1 mm underexpanded case was similar to that in the fully expanded case. Clinically a range of 10% to 15% underexpansion is generally considered acceptable; however, it was observed in this study that ≥2 mm (≥9.1%) underexpansion, will significantly impact device durability. Further study is necessary to determine the impact of various deployment conditions, i.e. non-uniform and non-circular deployments and different implantation heights, on differing TAV devices, but it is clear that the normal TAV leaflet configuration must be preserved in order to preserve durability. PMID:27734178

Kangaroo versus porcine aortic valve tissue--valve geometry morphology, tensile strength and calcification potential.

PubMed

Neethling, W M; Papadimitriou, J M; Swarts, E; Hodge, A J

2000-06-01

Valve related factors and patient related factors are responsible for calcification of valvular bioprostheses. Recent studies showed different donor and recipient species have different influences on the total calcification rate of bioprostheses. This study was performed to evaluate and compare Kangaroo aortic valve leaflets with porcine aortic valve leaflets. Experimental design. Prospective study. Setting. Cardio-thoracic experimental research of a university department. Glutaraldehyde-fixed Kangaroo and porcine valve leaflets were evaluated in vitro according to valve geometry (internal diameter and leaflet thickness), morphology (light and electron microscopy) and tensile strength. In vivo evaluation consisted of implantation in a rat model for 8 weeks, Von Kossa stain for calcium and atomic absorption spectrophotometry for total extractable calcium content. Kangaroo valves indicated a smaller internal valve diameter as well as a thinner valve leaflet (p<0.01, ANOVA) at corresponding body weight, less proteoglycan spicules in the fibrosa, increased elasticity (p<0.05) and low calcification potential (p<0.01, confidence interval 95%). Kangaroo aortic valve leaflets have different valvular qualities compared to porcine valve tissue. Kangaroo valve leaflets are significantly superior to porcine valve leaflets as far as calcification is concerned. These results are encouraging and suggest further in vivo evaluation in a larger animal model before clinical application can be considered.

Missing the Benefit of Metformin in Acute Myeloid Leukemia: A Problem of Contrast?

PubMed

Ceacareanu, Alice C; Nimako, George K; Wintrob, Zachary A P

2017-01-01

To evaluate whether metformin's cancer-related benefits reported in patients with solid tumors (ST) are also present in acute myeloid leukemia (AML) patients. Baseline demographic and clinical history for all diabetes mellitus patients newly diagnosed with AML or cancer of the breast, ovary, prostate, gastrointestinal tract, lung, or kidney at Roswell Park Cancer Institute in Buffalo, NY (January 2003-December 2010, n = 924) was collected. Overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan-Meier (KM) analysis and Cox proportional hazards regression (hazard ratio [HR]). Baseline metformin use provided significant OS and DFS benefit in ST but not in AML (KM: P ST-OS = 0.003; P ST-DFS = 0.002; P AML-OS = 0.961; P AML-DFS = 0.943). AML median survival was slightly better with metformin use, but users derived no relapse benefit. In ST, metformin nonusers had shorter median survival, 57.7 versus 86 months, and poorer outcomes (HR ST-OS = 1.33; P ST-OS = 0.002; HR ST-DFS = 1.32; P ST-DFS = 0.002). These findings remained significant in age-adjusted models (HR ST-OS = 1.21; P ST-OS = 0.039; HR ST-DFS = 1.23; P ST-DFS = 0.02) but not fully adjusted models (HR ST-OS = 0.96; P ST-OS = 0.688; HR ST-DFS = 1.0; P ST-DFS = 0.94). Higher mortality was noted in AML patients taking insulin versus oral diabetes pharmacotherapy at baseline (HR AML-OS = 2.03; P AML-OS = 0.04). Lack of metformin benefit in AML could be due to advanced age at cancer diagnosis. Metformin substitution with insulin before computed tomography scans with contrast - a frequent AML assessment practice - may also explain the lack of subsequent benefit despite taking metformin at baseline. A temporary metformin substitution is recommended by the package insert due to a possible drug interaction with the contrast dye. Our data suggest that metformin substitution was permanent in many patients. Nonetheless, the observed benefit in other malignancies warrants further investigation of metformin use in AML.

Medication information leaflets for patients: the further validation of an analytic linguistic framework.

PubMed

Clerehan, Rosemary; Hirsh, Di; Buchbinder, Rachelle

2009-01-01

While clinicians may routinely use patient information leaflets about drug therapy, a poorly conceived leaflet has the potential to do harm. We previously developed a novel approach to analysing leaflets about a rheumatoid arthritis drug, using an analytic approach based on systemic functional linguistics. The aim of the present study was to verify the validity of the linguistic framework by applying it to two further arthritis drug leaflets. The findings confirmed the applicability of the framework and were used to refine it. A new stage or 'move' in the genre was identified. While the function of many of the moves appeared to be 'to instruct' the patient, the instruction was often unclear. The role relationships expressed in the text were critical to the meaning. As with our previous study, judged on their lexical density, the leaflets resembled academic text. The framework can provide specific tools to assess and produce medication information leaflets to support readers in taking medication. Future work could utilize the framework to evaluate information on other treatments and procedures or on healthcare information more widely.

Abandoned Mine Lands: Revitalization and Reuse

EPA Pesticide Factsheets

EPA recognizes that reuse opportunities at AMLs may provide the critical impetus to expedite environmental cleanup. EPA’s AML Team is dedicated to providing tools and resources to support the reuse of AMLs.

Transcatheter direct mitral valve annuloplasty with the Cardioband system for the treatment of functional mitral regurgitation.

PubMed

Taramasso, Maurizio; Inderbitzin, Devdas T; Guidotti, Andrea; Nietlispach, Fabian; Gaemperli, Oliver; Zuber, Michel; Maisano, Francesco

2016-01-01

Direct mitral valve annuloplasty is a transcatheter mitral valve repair approach that mimics the conventional surgical approach to treat functional mitral regurgitation. The Cardioband system (Valtech Cardio, Inc., Or-Yehuda, Israel) is delivered by a trans-septal approach and the implant is performed on the atrial side of the mitral annulus, under live echo and fluoroscopic guidance using multiple anchor elements. The Cardioband system obtained CE mark approval in October 2015, and initial clinical experiences are promising with regard to feasibility, safety and efficacy. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Severe mitral stenosis with atypical presentation: hemorrhagic pleural effusion--a case report and literature review.

PubMed

Albalbissi, Kais A; Burress, Jonathan W; Garcia, Israel D; Iskandar, Said B

2009-02-01

Mitral stenosis is a well-described valvular heart disease. We report a 68-year-old patient with an unusual presentation of mitral stenosis. He presented with recurrent episodes of hemorrhagic pleural effusion. Afterwards, an extensive atrial thrombosis complicated his course of illness. We will discuss how the clinical presentation of mitral stenosis is mainly dictated by the underlying pathophysiology of the disease. Also, the need for anticoagulation in the setting of mitral stenosis is often linked to the presence of atrial fibrillation. We will discuss the independent risk factors for thromboembolism in the setting of mitral stenosis. Finally, a review of the current recommendation for anticoagulation is conferred.

Mitral repair and the robot: a revolutionary tool or marketing ploy?

PubMed

Ghoneim, Aly; Bouhout, Ismail; Makhdom, Fahd; Chu, Michael W A

2018-03-01

In this review, we discuss the current evidence supporting each minimally invasive mitral repair approach and their associated controversies. Current evidence demonstrates that minimally invasive mitral repair techniques yield similar mitral repair results to conventional sternotomy with the benefits of shorter hospital stay, quicker recovery, better cosmesis and improved patient satisfaction. Despite this, broad adoption of minimally invasive mitral repair is still not achieved. Two main approaches of minimally invasive mitral repair exist: endoscopic mini-thoracotomy and robotic-assisted approaches. Both minimally invasive approaches share many commonalities; however, most centres are strongly polarized to one approach over another creating controversy and debate about the most effective minimally invasive approach.

Transaortic Alfieri Edge-to-Edge Repair for Functional Mitral Regurgitation.

PubMed

Imasaka, Ken-Ichi; Tayama, Eiki; Morita, Shigeki; Toriya, Ryohei; Tomita, Yukihiro

2018-03-01

There is controversy about handling functional mitral regurgitation in patients undergoing aortic valve or proximal aortic operations. We describe a transaortic Alfieri edge-to-edge repair for functional mitral regurgitation that reduces operative excessive invasion and prolonged cardiopulmonary bypass time. Between May 2013 and December 2016, 10 patients underwent transaortic Alfieri edge-to-edge mitral repair. There were no operative deaths. The severity of mitral regurgitation immediately after the operation by transesophageal echocardiography was none or trivial in all patients. A transaortic Alfieri edge-to-edge repair for functional mitral regurgitation is a simple and safe approach. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

A genome-wide aberrant RNA splicing in patients with acute myeloid leukemia identifies novel potential disease markers and therapeutic targets.

PubMed

Adamia, Sophia; Haibe-Kains, Benjamin; Pilarski, Patrick M; Bar-Natan, Michal; Pevzner, Samuel; Avet-Loiseau, Herve; Lode, Laurence; Verselis, Sigitas; Fox, Edward A; Burke, John; Galinsky, Ilene; Dagogo-Jack, Ibiayi; Wadleigh, Martha; Steensma, David P; Motyckova, Gabriela; Deangelo, Daniel J; Quackenbush, John; Stone, Richard; Griffin, James D

2014-03-01

Despite new treatments, acute myeloid leukemia (AML) remains an incurable disease. More effective drug design requires an expanded view of the molecular complexity that underlies AML. Alternative splicing of RNA is used by normal cells to generate protein diversity. Growing evidence indicates that aberrant splicing of genes plays a key role in cancer. We investigated genome-wide splicing abnormalities in AML and based on these abnormalities, we aimed to identify novel potential biomarkers and therapeutic targets. We used genome-wide alternative splicing screening to investigate alternative splicing abnormalities in two independent AML patient cohorts [Dana-Farber Cancer Institute (DFCI) (Boston, MA) and University Hospital de Nantes (UHN) (Nantes, France)] and normal donors. Selected splicing events were confirmed through cloning and sequencing analysis, and than validated in 193 patients with AML. Our results show that approximately 29% of expressed genes genome-wide were differentially and recurrently spliced in patients with AML compared with normal donors bone marrow CD34(+) cells. Results were reproducible in two independent AML cohorts. In both cohorts, annotation analyses indicated similar proportions of differentially spliced genes encoding several oncogenes, tumor suppressor proteins, splicing factors, and heterogeneous-nuclear-ribonucleoproteins, proteins involved in apoptosis, cell proliferation, and spliceosome assembly. Our findings are consistent with reports for other malignances and indicate that AML-specific aberrations in splicing mechanisms are a hallmark of AML pathogenesis. Overall, our results suggest that aberrant splicing is a common characteristic for AML. Our findings also suggest that splice variant transcripts that are the result of splicing aberrations create novel disease markers and provide potential targets for small molecules or antibody therapeutics for this disease. ©2013 AACR

Hyperforin inhibits Akt1 kinase activity and promotes caspase-mediated apoptosis involving Bad and Noxa activation in human myeloid tumor cells.

PubMed

Merhi, Faten; Tang, Ruoping; Piedfer, Marion; Mathieu, Julie; Bombarda, Isabelle; Zaher, Murhaf; Kolb, Jean-Pierre; Billard, Christian; Bauvois, Brigitte

2011-01-01

The natural phloroglucinol hyperforin HF displays anti-inflammatory and anti-tumoral properties of potential pharmacological interest. Acute myeloid leukemia (AML) cells abnormally proliferate and escape apoptosis. Herein, the effects and mechanisms of purified HF on AML cell dysfunction were investigated in AML cell lines defining distinct AML subfamilies and primary AML cells cultured ex vivo. HF inhibited in a time- and concentration-dependent manner the growth of AML cell lines (U937, OCI-AML3, NB4, HL-60) by inducing apoptosis as evidenced by accumulation of sub-G1 population, phosphatidylserine externalization and DNA fragmentation. HF also induced apoptosis in primary AML blasts, whereas normal blood cells were not affected. The apoptotic process in U937 cells was accompanied by downregulation of anti-apoptotic Bcl-2, upregulation of pro-apoptotic Noxa, mitochondrial membrane depolarization, activation of procaspases and cleavage of the caspase substrate PARP-1. The general caspase inhibitor Z-VAD-fmk and the caspase-9- and -3-specific inhibitors, but not caspase-8 inhibitor, significantly attenuated apoptosis. HF-mediated apoptosis was associated with dephosphorylation of active Akt1 (at Ser(473)) and Akt1 substrate Bad (at Ser(136)) which activates Bad pro-apoptotic function. HF supppressed the kinase activity of Akt1, and combined treatment with the allosteric Akt1 inhibitor Akt-I-VIII significantly enhanced apoptosis of U937 cells. Our data provide new evidence that HF's pro-apoptotic effect in AML cells involved inhibition of Akt1 signaling, mitochondria and Bcl-2 members dysfunctions, and activation of procaspases -9/-3. Combined interruption of mitochondrial and Akt1 pathways by HF may have implications for AML treatment.

Hyperforin Inhibits Akt1 Kinase Activity and Promotes Caspase-Mediated Apoptosis Involving Bad and Noxa Activation in Human Myeloid Tumor Cells

PubMed Central

Merhi, Faten; Tang, Ruoping; Piedfer, Marion; Mathieu, Julie; Bombarda, Isabelle; Zaher, Murhaf; Kolb, Jean-Pierre; Billard, Christian; Bauvois, Brigitte

2011-01-01

Background The natural phloroglucinol hyperforin HF displays anti-inflammatory and anti-tumoral properties of potential pharmacological interest. Acute myeloid leukemia (AML) cells abnormally proliferate and escape apoptosis. Herein, the effects and mechanisms of purified HF on AML cell dysfunction were investigated in AML cell lines defining distinct AML subfamilies and primary AML cells cultured ex vivo. Methodology and Results HF inhibited in a time- and concentration-dependent manner the growth of AML cell lines (U937, OCI-AML3, NB4, HL-60) by inducing apoptosis as evidenced by accumulation of sub-G1 population, phosphatidylserine externalization and DNA fragmentation. HF also induced apoptosis in primary AML blasts, whereas normal blood cells were not affected. The apoptotic process in U937 cells was accompanied by downregulation of anti-apoptotic Bcl-2, upregulation of pro-apoptotic Noxa, mitochondrial membrane depolarization, activation of procaspases and cleavage of the caspase substrate PARP-1. The general caspase inhibitor Z-VAD-fmk and the caspase-9- and -3-specific inhibitors, but not caspase-8 inhibitor, significantly attenuated apoptosis. HF-mediated apoptosis was associated with dephosphorylation of active Akt1 (at Ser473) and Akt1 substrate Bad (at Ser136) which activates Bad pro-apoptotic function. HF supppressed the kinase activity of Akt1, and combined treatment with the allosteric Akt1 inhibitor Akt-I-VIII significantly enhanced apoptosis of U937 cells. Significance Our data provide new evidence that HF's pro-apoptotic effect in AML cells involved inhibition of Akt1 signaling, mitochondria and Bcl-2 members dysfunctions, and activation of procaspases -9/-3. Combined interruption of mitochondrial and Akt1 pathways by HF may have implications for AML treatment. PMID:21998731

Clonal Architecture of Secondary Acute Myeloid Leukemia

PubMed Central

Walter, Matthew J.; Shen, Dong; Ding, Li; Shao, Jin; Koboldt, Daniel C.; Chen, Ken; Larson, David E.; McLellan, Michael D.; Dooling, David; Abbott, Rachel; Fulton, Robert; Magrini, Vincent; Schmidt, Heather; Kalicki-Veizer, Joelle; O’Laughlin, Michelle; Fan, Xian; Grillot, Marcus; Witowski, Sarah; Heath, Sharon; Frater, John L.; Eades, William; Tomasson, Michael; Westervelt, Peter; DiPersio, John F.; Link, Daniel C.; Mardis, Elaine R.; Ley, Timothy J.; Wilson, Richard K.; Graubert, Timothy A.

2012-01-01

BACKGROUND The myelodysplastic syndromes are a group of hematologic disorders that often evolve into secondary acute myeloid leukemia (AML). The genetic changes that underlie progression from the myelodysplastic syndromes to secondary AML are not well understood. METHODS We performed whole-genome sequencing of seven paired samples of skin and bone marrow in seven subjects with secondary AML to identify somatic mutations specific to secondary AML. We then genotyped a bone marrow sample obtained during the antecedent myelodysplastic-syndrome stage from each subject to determine the presence or absence of the specific somatic mutations. We identified recurrent mutations in coding genes and defined the clonal architecture of each pair of samples from the myelodysplastic-syndrome stage and the secondary-AML stage, using the allele burden of hundreds of mutations. RESULTS Approximately 85% of bone marrow cells were clonal in the myelodysplastic-syndrome and secondary-AML samples, regardless of the myeloblast count. The secondary-AML samples contained mutations in 11 recurrently mutated genes, including 4 genes that have not been previously implicated in the myelodysplastic syndromes or AML. In every case, progression to acute leukemia was defined by the persistence of an antecedent founding clone containing 182 to 660 somatic mutations and the outgrowth or emergence of at least one subclone, harboring dozens to hundreds of new mutations. All founding clones and subclones contained at least one mutation in a coding gene. CONCLUSIONS Nearly all the bone marrow cells in patients with myelodysplastic syndromes and secondary AML are clonally derived. Genetic evolution of secondary AML is a dynamic process shaped by multiple cycles of mutation acquisition and clonal selection. Recurrent gene mutations are found in both founding clones and daughter subclones. (Funded by the National Institutes of Health and others.) PMID:22417201

Waveform modeling of the seismic response of a mid-ocean ridge axial melt sill

NASA Astrophysics Data System (ADS)

Xu, Min; Stephen, R. A.; Canales, J. Pablo

2017-12-01

Seismic reflections from axial magma lens (AML) are commonly observed along many mid-ocean ridges, and are thought to arise from the negative impedance contrast between a solid, high-speed lid and the underlying low-speed, molten or partially molten (mush) sill. The polarity of the AML reflection ( P AML P) at vertical incidence and the amplitude vs offset (AVO) behavior of the AML reflections (e.g., P AML P and S-converted P AML S waves) are often used as a diagnostic tool for the nature of the low-speed sill. Time-domain finite difference calculations for two-dimensional laterally homogeneous models show some scenarios make the interpretation of melt content from partial-offset stacks of P- and S-waves difficult. Laterally heterogeneous model calculations indicate diffractions from the edges of the finite-width AML reducing the amplitude of the AML reflections. Rough seafloor and/or a rough AML surface can also greatly reduce the amplitude of peg-leg multiples because of scattering and destructive interference. Mid-crustal seismic reflection events are observed in the three-dimensional multi-channel seismic dataset acquired over the RIDGE-2000 Integrated Study Site at East Pacific Rise (EPR, cruise MGL0812). Modeling indicates that the mid-crustal seismic reflection reflections are unlikely to arise from peg-leg multiples of the AML reflections, P-to- S converted phases, or scattering due to rough topography, but could probably arise from deeper multiple magma sills. Our results support the identification of Marjanović et al. (Nat Geosci 7(11):825-829, 2014) that a multi-level complex of melt lenses is present beneath the axis of the EPR.

Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children's Oncology Group.

PubMed

Barnard, Dorothy R; Alonzo, Todd A; Gerbing, Robert B; Lange, Beverly; Woods, William G

2007-07-01

Myelodysplastic syndromes (MDS), acute erythroleukemia (FAB M6), and acute megakaryocytic leukemia (FAB M7) have overlapping features. Children without Down syndrome or acute promyelocytic leukemia who were newly diagnosed with primary myelodysplastic syndrome or acute myeloid leukemia (AML) M6 or M7 were compared to children with de novo AML M0-M5. All children were entered on the Children's Cancer Group therapeutic research study CCG 2891. The presentation and outcomes of the 132 children diagnosed with MDS (60 children), AML FAB M6 (19 children), or AML FAB M7 (53 children) were similar. Children with AML FAB M7 were diagnosed at a significantly younger age (P = 0.001). Children with MDS, M6, or M7 had significantly lower white blood cell (WBC) counts (P = 0.001), lower peripheral blast counts (P < 0.001), and an increased frequency of -7/7q- (P = 0.003) at presentation. All three groups had significantly inferior overall survival (OS) (P < 0.001) and event free survival (P < 0.001) compared with the 748 children diagnosed with AML FAB M0-M5 when assessed from entry on study. This poor survival was largely attributable to induction death and failure. However, when assessed from successful completion of induction therapy, the 5-year OS (P = 0.090)(49.1 vs. 56.9%) and disease-free survival (DFS) (P = 0.113)(38.0 vs. 46.3%) therapy were not significantly different from other children with AML. Childhood AML FAB M6 and AML M7 resemble MDS in presentation, poor induction success rates, and outcomes.

Effects of triple combination therapy with azilsartan/amlodipine/hydrochlorothiazide on office/home blood pressure: a randomized-controlled trial in Japanese essential hypertensive patients.

PubMed

Rakugi, Hiromi; Shimizu, Kohei; Sano, Yuhei; Nishiyama, Yuya; Kinugawa, Yoshinobu; Terashio, Souhei

2018-04-01

The efficacy and safety of triple therapy with azilsartan (AZI), amlodipine besylate (AML), and hydrochlorothiazide (HCTZ) compared with dual therapy with AZI/AML or HCTZ monotherapy were evaluated in Japanese essential hypertensive patients in a double-blinded manner. A total of 353 patients with office blood pressure (BP) of at least 150/95 mmHg were randomized to a 10-week treatment with AZI/AML/HCTZ 20/5/12.5 mg, AZI/AML/HCTZ 20/5/6.25 mg, AZI/AML 20/5 mg, HCTZ 12.5 mg, or HCTZ 6.25 mg. The mean change from baseline in office diastolic/systolic BPs at week 10 was -25.9/-41.4, -24.9/-38.6, and -22.4/-34.5 mmHg in the AZI/AML/HCTZ 20/5/12.5 mg, AZI/AML/HCTZ 20/5/6.25 mg, and AZI/AML 20/5 mg groups, respectively. AZI/AML/HCTZ 20/5/12.5 mg led to a significantly greater reduction in diastolic and systolic BP than the dual therapy. In addition, the change in home diastolic BP measured with telemetry devices showed a significant difference between the two triple therapy groups. The incidences of adverse events except dizziness postural were similar among the treatment groups in the triple therapy groups. Triple therapy with AZI/AML/HCTZ 20/5/12.5 mg shows a greater antihypertensive effect than the dual therapy and has acceptable safety profiles for Japanese essential hypertensive patients. It was also observed that home BP measurement by automated telemetry could detect changes in BP that were not detected in office BP measurement, although further investigation is needed.

Cannabidiol stimulates Aml-1a-dependent glial differentiation and inhibits glioma stem-like cells proliferation by inducing autophagy in a TRPV2-dependent manner.

PubMed

Nabissi, Massimo; Morelli, Maria Beatrice; Amantini, Consuelo; Liberati, Sonia; Santoni, Matteo; Ricci-Vitiani, Lucia; Pallini, Roberto; Santoni, Giorgio

2015-10-15

Glioma stem-like cells (GSCs) correspond to a tumor cell subpopulation, involved in glioblastoma multiforme (GBM) tumor initiation and acquired chemoresistance. Currently, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population. Recently, the effect of cannabinoids (CBs) in promoting glial differentiation and inhibiting gliomagenesis has been evidenced. Herein, we demonstrated that cannabidiol (CBD) by activating transient receptor potential vanilloid-2 (TRPV2) triggers GSCs differentiation activating the autophagic process and inhibits GSCs proliferation and clonogenic capability. Above all, CBD and carmustine (BCNU) in combination overcome the high resistance of GSCs to BCNU treatment, by inducing apoptotic cell death. Acute myeloid leukemia (Aml-1) transcription factors play a pivotal role in GBM proliferation and differentiation and it is known that Aml-1 control the expression of several nociceptive receptors. So, we evaluated the expression levels of Aml-1 spliced variants (Aml-1a, b and c) in GSCs and during their differentiation. We found that Aml-1a is upregulated during GSCs differentiation, and its downregulation restores a stem cell phenotype in differentiated GSCs. Since it was demonstrated that CBD induces also TRPV2 expression and that TRPV2 is involved in GSCs differentiation, we evaluated if Aml-1a interacted directly with TRPV2 promoters. Herein, we found that Aml-1a binds TRPV2 promoters and that Aml-1a expression is upregulated by CBD treatment, in a TRPV2 and PI3K/AKT dependent manner. Altogether, these results support a novel mechanism by which CBD inducing TRPV2-dependent autophagic process stimulates Aml-1a-dependent GSCs differentiation, abrogating the BCNU chemoresistance in GSCs. © 2015 UICC.

Chronic Immune Stimulation Might Act As a Trigger for the Development of Acute Myeloid Leukemia or Myelodysplastic Syndromes

PubMed Central

Kristinsson, Sigurdur Y.; Björkholm, Magnus; Hultcrantz, Malin; Derolf, Åsa R.; Landgren, Ola; Goldin, Lynn R.

2011-01-01

Purpose Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) often present with infections, but there are little data to assess whether a personal history of selected infections may act as pathogenic triggers. To additionally expand our knowledge on the role of immune stimulation in the causation of AML and MDS, we have conducted a large, population-based study to evaluate the risk of AML and MDS associated with a prior history of a broad range of infections or autoimmune diseases. Patients and Methods By using population-based central registries in Sweden, we included 9,219 patients with AML, 1,662 patients with MDS, and 42,878 matched controls. We used logistic regression to calculate odds ratios (ORs) and 95% CIs for the association of AML or MDS with infectious and/or autoimmune diseases. Results Overall, a history of any infectious disease was associated with a significantly increased risk of both AML (OR, 1.3; 95% CI, 1.2 to 1.4) and MDS (OR, 1.3; 95% CI, 1.1 to 1.5). These associations were significant even when we limited infections to those occurring 3 or more years before AML/MDS. A previous history of any autoimmune disease was associated with a 1.7-fold (95% CI, 1.5 to 1.9) increased risk for AML and 2.1-fold (95% CI, 1.7 to 2.6) increased risk for MDS. A large range of conditions were each significantly associated with AML and MDS. Conclusion Our novel findings indicate that chronic immune stimulation acts as a trigger for AML/MDS development. The underlying mechanisms may also be due to a common genetic predisposition or an effect of treatment for infections/autoimmune conditions. PMID:21690473

Towards an atrio-ventricular delay optimization assessed by a computer model for cardiac resynchronization therapy

NASA Astrophysics Data System (ADS)

Ojeda, David; Le Rolle, Virginie; Tse Ve Koon, Kevin; Thebault, Christophe; Donal, Erwan; Hernández, Alfredo I.

2013-11-01

In this paper, lumped-parameter models of the cardiovascular system, the cardiac electrical conduction system and a pacemaker are coupled to generate mitral ow pro les for di erent atrio-ventricular delay (AVD) con gurations, in the context of cardiac resynchronization therapy (CRT). First, we perform a local sensitivity analysis of left ventricular and left atrial parameters on mitral ow characteristics, namely E and A wave amplitude, mitral ow duration, and mitral ow time integral. Additionally, a global sensitivity analysis over all model parameters is presented to screen for the most relevant parameters that a ect the same mitral ow characteristics. Results provide insight on the in uence of left ventricle and atrium in uence on mitral ow pro les. This information will be useful for future parameter estimation of the model that could reproduce the mitral ow pro les and cardiovascular hemodynamics of patients undergoing AVD optimization during CRT.

Mitral stenosis due to pannus overgrowth after rigid ring annuloplasty.

PubMed

Oda, Takeshi; Kato, Seiya; Tayama, Eiki; Fukunaga, Shuji; Akashi, Hidetoshi; Aoyagi, Shigeaki

2010-03-01

Although mitral stenosis (MS) due to pannus overgrowth after mitral valve repair for rheumatic mitral regurgitation (MR) is not uncommon, it is extremely rare in relation to non-rheumatic mitral regurgitation. Whilst it has been suggested that the rigid annuloplasty ring induces pannus overgrowth in the same manner as the flexible ring, to date only in cases using the flexible ring has pannus formation been confirmed by a pathological examination after redo surgery. The case is described of a woman who had undergone mitral valve repair using a 28 mm rigid ring three years previously because of non-rheumatic MR, and subsequently suffered from MS due to pannus formation over the annuloplasty ring. To the present authors' knowledge, this is the first report of MS due to pannus formation after mitral valve repair using a rigid annuloplasty ring to treat non-rheumatic MR documented at reoperation.

Inhibition of poly(ADP-ribose) polymerase 1 protects against acute myeloid leukemia by suppressing the myeloproliferative leukemia virus oncogene

PubMed Central

Wang, Lingbo; Cai, Weili; Zhang, Wei; Chen, Xueying; Dong, Wenqian; Tang, Dongqi; Zhang, Yun; Ji, Chunyan; Zhang, Mingxiang

2015-01-01

An abnormal expression of poly(ADP-ribose) polymerase 1 (PARP-1) has been described in many tumors. PARP-1 promotes tumorigenesis and cancer progression by acting on different molecular pathways. PARP-1 inhibitors can be used with radiotherapy or chemotherapy to enhance the susceptibility of tumor cells to the treatment. However, the specific mechanism of PARP-1 in acute myeloid leukemia (AML) remains unknown. Our study showed that expression of PARP-1 was upregulated in AML patients. PARP-1 inhibition slowed AML cell proliferation, arrested the cell cycle, induced apoptosis in vitro and improved AML prognosis in vivo. Mechanistically, microarray assay of AML cells with loss of PARP-1 function revealed that the myeloproliferative leukemia virus oncogene (MPL) was significantly downregulated. In human AML samples, MPL expression was increased, and gain-of-function and loss-of-function analysis demonstrated that MPL promoted cell growth. Moreover, PARP-1 and MPL expression were positively correlated in AML samples, and their overexpression was associated with an unfavorable prognosis. Furthermore, PARP-1 and MPL consistently acted on Akt and ERK1/2 pathways, and the anti-proliferative and pro-apoptotic function observed with PARP-1 inhibition were reversed in part via MPL activation upon thrombopoietin stimulation or gene overexpression. These data highlight the important function of PARP-1 in the progression of AML, which suggest PARP-1 as a potential target for AML treatment. PMID:26314963

Is Acute Myeloid Leukemia a Liquid Tumor?

PubMed Central

Ohanian, Maro; Faderl, Stefan; Ravandi, Farhad; Pemmaraju, Naveen; Garcia-Manero, Guillermo; Cortes, Jorge; Estrov, Zeev

2014-01-01

Extramedullary manifestations of acute myeloid leukemia (AML) were described as early as the 19th century. However, the incidence, clinical significance, and pathobiology of extramedullary AML remain ill defined. We reviewed case reports, retrospective case series, pilot studies, and imaging studies of extramedullary leukemia (EML) to determine its frequency, characteristics, clinical presentation, and significance. EML precedes or accompanies development of AML and occurs during or following treatment, even during remission. Although imaging studies are rarely conducted and the true incidence of EML has yet to be verified, authors have reported several estimates based on retrospective and autopsy studies. The incidence of EML in patients with AML of all ages is estimated to be about 9% and EML in children with AML was detected in 40% of patients at diagnosis. The combination of positron emission tomography and computed tomography were the most sensitive and reliable techniques of detecting and monitoring EML. Based on our literature review, the frequency of EML is likely underreported. The well-documented nature of EML in AML patients suggests that AML can manifest as a solid tumor. The extent to which EML accompanies AML and whether EML is derived from bone marrow are unknown. Furthermore, questions remain regarding the role of the microenvironment, which may or may not facilitate the survival and proliferation of EML, and the implications of these interactions with regard to minimal residual disease, tumor cell quiescence, and relapse. Therefore, prospective studies of detection and characterization of EML in AML patients are warranted. PMID:23280377

Is acute myeloid leukemia a liquid tumor?

PubMed

Ohanian, Maro; Faderl, Stefan; Ravandi, Farhad; Pemmaraju, Naveen; Garcia-Manero, Guillermo; Cortes, Jorge; Estrov, Zeev

2013-08-01

Extramedullary manifestations of acute myeloid leukemia (AML) were described as early as the 19th century. However, the incidence, clinical significance and pathobiology of extramedullary AML remain ill defined. We reviewed case reports, retrospective case series, pilot studies and imaging studies of extramedullary leukemia (EML) to determine its frequency, characteristics, clinical presentation and significance. EML precedes or accompanies development of AML and occurs during or following treatment, even during remission. Although imaging studies are rarely conducted and the true incidence of EML has yet to be verified, authors have reported several estimates based on retrospective and autopsy studies. The incidence of EML in patients with AML of all ages is estimated to be about 9% and EML in children with AML was detected in 40% of patients at diagnosis. The combination of positron emission tomography and computed tomography were the most sensitive and reliable techniques of detecting and monitoring EML. Based on our literature review, the frequency of EML is likely underreported. The well-documented nature of EML in patients with AML suggests that AML can manifest as a solid tumor. The extent to which EML accompanies AML and whether EML is derived from bone marrow are unknown. Furthermore, questions remain regarding the role of the microenvironment, which may or may not facilitate the survival and proliferation of EML, and the implications of these interactions with regard to minimal residual disease, tumor cell quiescence and relapse. Therefore, prospective studies of detection and characterization of EML in patients with AML are warranted. Copyright © 2013 UICC.

Autophagy is dispensable for Kmt2a/Mll-Mllt3/Af9 AML maintenance and anti-leukemic effect of chloroquine.

PubMed

Chen, Xiaoyi; Clark, Jason; Wunderlich, Mark; Fan, Cuiqing; Davis, Ashley; Chen, Song; Guan, Jun-Lin; Mulloy, James C; Kumar, Ashish; Zheng, Yi

2017-05-04

Recently, macroautophagy/autophagy has emerged as a promising target in various types of solid tumor treatment. However, the impact of autophagy on acute myeloid leukemia (AML) maintenance and the validity of autophagy as a viable target in AML therapy remain unclear. Here we show that Kmt2a/Mll-Mllt3/Af9 AML (MA9-AML) cells have high autophagy flux compared with normal bone marrow cells, but autophagy-specific targeting, either through Rb1cc1-disruption to abolish autophagy initiation, or via Atg5-disruption to prevent phagophore (the autophagosome precursor) membrane elongation, does not affect the growth or survival of MA9-AML cells, either in vitro or in vivo. Mechanistically, neither Atg5 nor Rb1cc1 disruption impairs endolysosome formation or survival signaling pathways. The autophagy inhibitor chloroquine shows autophagy-independent anti-leukemic effects in vitro but has no efficacy in vivo likely due to limited achievable drug efficacy in blood. Further, vesicular exocytosis appears to mediate chloroquine resistance in AML cells, and exocytotic inhibition significantly enhances the anti-leukemic effect of chloroquine. Thus, chloroquine can induce leukemia cell death in vitro in an autophagy-independent manner but with inadequate efficacy in vivo, and vesicular exocytosis is a possible mechanism of chloroquine resistance in MA9-AML. This study also reveals that autophagy-specific targeting is unlikely to benefit MA9-AML therapy.

Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia.

PubMed

Chen, Lisa S; Redkar, Sanjeev; Taverna, Pietro; Cortes, Jorge E; Gandhi, Varsha

2011-07-21

Pim kinases are Ser/Thr kinases with multiple substrates that affect survival pathways. These proteins are overexpressed in acute myeloid leukemia (AML) blasts and we hypothesized that Pim kinase inhibition would affect AML cell survival. Imidazo[1,2-b]pyridazine compound, SGI-1776 inhibits Pim-1, Pim-2 and Pim-3, and was evaluated in AML-cell line, -xenograft model, and -primary blasts. Treatment of AML cells with SGI-1776 results in a concentration-dependent induction of apoptosis and we investigated its effect on Pim kinase functions. Phosphorylation of traditional Pim kinase targets, c-Myc(Ser62) and 4E-BP1 (Thr36/Thr47), were both decreased in actively cycling AML cell lines MV-4-11, MOLM-13 and OCI-AML-3. Levels of antiapoptotic proteins Bcl-2, Bcl-x(L), XIAP, and proapoptotic Bak and Bax were unchanged; however, a significant reduction in Mcl-1 was observed. This was correlated with inhibition of global RNA and protein synthesis and MCL-1 transcript decline after SGI-1776 treatment. These data suggest that SGI-1776 mechanism in AML involves Mcl-1 protein reduction. Consistent with cell line data, xenograft model studies with mice bearing MV-4-11 tumors showed efficacy with SGI-1776. Importantly, SGI-1776 was also cytotoxic in AML primary cells, irrespective of FLT3 mutation status and resulted in Mcl-1 protein decline. Pim kinase inhibition may be a new strategy for AML treatment.

Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia

PubMed Central

Chen, Lisa S.; Redkar, Sanjeev; Taverna, Pietro; Cortes, Jorge E.

2011-01-01

Pim kinases are Ser/Thr kinases with multiple substrates that affect survival pathways. These proteins are overexpressed in acute myeloid leukemia (AML) blasts and we hypothesized that Pim kinase inhibition would affect AML cell survival. Imidazo[1,2-b]pyridazine compound, SGI-1776 inhibits Pim-1, Pim-2 and Pim-3, and was evaluated in AML-cell line, -xenograft model, and -primary blasts. Treatment of AML cells with SGI-1776 results in a concentration-dependent induction of apoptosis and we investigated its effect on Pim kinase functions. Phosphorylation of traditional Pim kinase targets, c-Myc(Ser62) and 4E-BP1 (Thr36/Thr47), were both decreased in actively cycling AML cell lines MV-4-11, MOLM-13 and OCI-AML-3. Levels of antiapoptotic proteins Bcl-2, Bcl-xL, XIAP, and proapoptotic Bak and Bax were unchanged; however, a significant reduction in Mcl-1 was observed. This was correlated with inhibition of global RNA and protein synthesis and MCL-1 transcript decline after SGI-1776 treatment. These data suggest that SGI-1776 mechanism in AML involves Mcl-1 protein reduction. Consistent with cell line data, xenograft model studies with mice bearing MV-4-11 tumors showed efficacy with SGI-1776. Importantly, SGI-1776 was also cytotoxic in AML primary cells, irrespective of FLT3 mutation status and resulted in Mcl-1 protein decline. Pim kinase inhibition may be a new strategy for AML treatment. PMID:21628411

Olfactory epithelium influences the orientation of mitral cell dendrites during development.

PubMed

López-Mascaraque, Laura; García, Concepción; Blanchart, Albert; De Carlos, Juan A

2005-02-01

We have established previously that, although the olfactory epithelium is absent in the homozygous Pax-6 mutant mouse, an olfactory bulb-like structure (OBLS) does develop. Moreover, this OBLS contains cells that correspond to mitral cells, the primary projection neurons in the olfactory bulb. The current study aimed to address whether the dendrites of mitral cells in the olfactory bulb or in the OBLS mitral-like cells, exhibit a change in orientation in the presence of the olfactory epithelium. The underlying hypothesis is that the olfactory epithelium imparts a trophic signal on mitral and mitral-like cell that influences the growth of their primary dendrites, orientating them toward the surface of the olfactory bulb. Hence, we cultured hemibrains from wild-type and Pax 6 mutant mice from two different embryonic stages (embryonic days 14 and 15) either alone or in coculture with normal olfactory epithelial explants or control tissue (cerebellum). Our results indicate that the final dendritic orientation of mitral and mitral-like cells is directly influenced both by age and indeed by the presence of the olfactory epithelium. Copyright 2004 Wiley-Liss, Inc.

Percutaneous transvenous mitral commissurotomy in patients with mitral stenosis and coexistent hyperthyroidism.

PubMed

Wang, P W; Hung, J S; Fu, M; Yeh, K H; Wu, J J

1996-01-01

Percutaneous transvenous mitral commissurotomy (PTMC) was performed successfully without complications in 3 patients with severe mitral stenosis and hyperthyroidism. All 3 patients had pliable, noncalcified mitral valves. One patient who had been treated with methimazole for 6 months was still in a hyperthyroid state when she presented with intractable congestive heart failure and was found to have severe mitral stenosis. The heart failure improved immediately after PTMC, but the patient remained in New York Heart Association functional class 2 until a euthyroid state was achieved with I131 therapy. In the other 2 patients, hyperthyroidism was unsuspected at the time of PTMC. Unexpectedly suboptimal symptom improvement led to the diagnosis of hyperthyroidism 1 month after the intervention. In all 3 patients, PTMC resulted in an immediate hemodynamic and clinical improvement. However, complete clinical improvement occurred only when euthyroid state was achieved after antithyroid treatment. The present study suggests that PTMC is a safe and effective intervention modality in patients with coexisting hyperthyroidism and severe mitral stenosis. The procedure may be considered a therapeutic option in patients with hyperthyroidism and severe mitral stenosis.

Mechanisms of mechanical heart valve cavitation: investigation using a tilting disk valve model.

PubMed

He, Z; Xi, B; Zhu, K; Hwang, N H

2001-09-01

The induction of mechanical heart valve (MHV) cavitation was investigated using a 27 mm Medtronic Hall (MH27) tilting disk valve. The MH27 valve was mounted in the mitral position of a simulating pulse flow system, and stroboscopic lighting used to visualize cavitation bubbles on the occluder inflow surface at the instant of valve closure. MHV cavitation was monitored using a digital camera with 0.04 mm/pixel resolution sufficient to render the tiny bubbles clearly visible on the computer monitor screen. Cavitation on MH27 valve was classified as five types according to the time, site and shape of the cavitation bubbles. Valve cavitation occurred at the instant of occluder impact with the valve seat at closing. The impact motion was subdivided into three temporal phases: (i) squeezing flow; (ii) elastic collision; and (iii) leaflet rebound. MHV cavitation caused by vortices was found to be initiated by the squeezing jet and/or by the transvalvular leakage jets. By using a tension wave which swept across the occluder surface immediately upon elastic impact, nuclei in the vortex core were expanded to form cavitation bubbles. Analysis of the shape and location of the cavitation bubbles permitted a better understanding of MHV cavitation mechanisms, based on the fluid dynamics of jet vortex and tension wave propagations.

A New Cone-Shaped Aortic Valve Prosthesis for Orthotopic Position: An Experimental Study in Swine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sochman, Jan, E-mail: jan.sochman@medicon.c; Peregrin, Jan H.; Pulda, Zdenek

The aim of this experimental study was to evaluate a newly designed cone-shaped aortic valve prosthesis (CAVP) for one-step transcatheter placement in an orthotopic position. The study was conducted in 15 swine using either the transcarotid (11 animals) or the transfemoral (4 animals) artery approach. A 12- or 13-Fr sheath was inserted via arterial cutdown. The CAVP was deployed under fluoroscopic control and its struts, by design, induced significant native valve insufficiency. CAVP function was evaluated by aortography and aortic pressure curve tracing. In 11 of 15 swine the CAVP was properly deployed and functioned well throughout the scheduled periodmore » of 2-3 h. In three swine the CAVPs were placed lower than intended, however, they were functional even in the left ventricular outflow tract position. One swine expired due to inadvertent low CAVP placement that caused both aortic regurgitation and immobilization of the anterior mitral valve leaflet by the valve struts. We conclude that this design of CAVP is relatively easy to deploy, works well throughout a short time period (2-3 h), and, moreover, seems to be reliable even in a lower-than-orthotopic position (e.g., infra-annulary space). Longer-term studies are needed for its further evaluation.« less

A Genomics-Based Model for Prediction of Severe Bioprosthetic Mitral Valve Calcification.

PubMed

Ponasenko, Anastasia V; Khutornaya, Maria V; Kutikhin, Anton G; Rutkovskaya, Natalia V; Tsepokina, Anna V; Kondyukova, Natalia V; Yuzhalin, Arseniy E; Barbarash, Leonid S

2016-08-31

Severe bioprosthetic mitral valve calcification is a significant problem in cardiovascular surgery. Unfortunately, clinical markers did not demonstrate efficacy in prediction of severe bioprosthetic mitral valve calcification. Here, we examined whether a genomics-based approach is efficient in predicting the risk of severe bioprosthetic mitral valve calcification. A total of 124 consecutive Russian patients who underwent mitral valve replacement surgery were recruited. We investigated the associations of the inherited variation in innate immunity, lipid metabolism and calcium metabolism genes with severe bioprosthetic mitral valve calcification. Genotyping was conducted utilizing the TaqMan assay. Eight gene polymorphisms were significantly associated with severe bioprosthetic mitral valve calcification and were therefore included into stepwise logistic regression which identified male gender, the T/T genotype of the rs3775073 polymorphism within the TLR6 gene, the C/T genotype of the rs2229238 polymorphism within the IL6R gene, and the A/A genotype of the rs10455872 polymorphism within the LPA gene as independent predictors of severe bioprosthetic mitral valve calcification. The developed genomics-based model had fair predictive value with area under the receiver operating characteristic (ROC) curve of 0.73. In conclusion, our genomics-based approach is efficient for the prediction of severe bioprosthetic mitral valve calcification.

A Genomics-Based Model for Prediction of Severe Bioprosthetic Mitral Valve Calcification

PubMed Central

Ponasenko, Anastasia V.; Khutornaya, Maria V.; Kutikhin, Anton G.; Rutkovskaya, Natalia V.; Tsepokina, Anna V.; Kondyukova, Natalia V.; Yuzhalin, Arseniy E.; Barbarash, Leonid S.

2016-01-01

Severe bioprosthetic mitral valve calcification is a significant problem in cardiovascular surgery. Unfortunately, clinical markers did not demonstrate efficacy in prediction of severe bioprosthetic mitral valve calcification. Here, we examined whether a genomics-based approach is efficient in predicting the risk of severe bioprosthetic mitral valve calcification. A total of 124 consecutive Russian patients who underwent mitral valve replacement surgery were recruited. We investigated the associations of the inherited variation in innate immunity, lipid metabolism and calcium metabolism genes with severe bioprosthetic mitral valve calcification. Genotyping was conducted utilizing the TaqMan assay. Eight gene polymorphisms were significantly associated with severe bioprosthetic mitral valve calcification and were therefore included into stepwise logistic regression which identified male gender, the T/T genotype of the rs3775073 polymorphism within the TLR6 gene, the C/T genotype of the rs2229238 polymorphism within the IL6R gene, and the A/A genotype of the rs10455872 polymorphism within the LPA gene as independent predictors of severe bioprosthetic mitral valve calcification. The developed genomics-based model had fair predictive value with area under the receiver operating characteristic (ROC) curve of 0.73. In conclusion, our genomics-based approach is efficient for the prediction of severe bioprosthetic mitral valve calcification. PMID:27589735

Long-term Results After Open Mitral Commissurotomy for a One-Month-Old Infant With Mitral Stenosis.

PubMed

Kitaichi, Takashi; Sugano, Mikio; Arase, Hiroki; Kawatani, Yohei; Kameta, Kanako; Kurobe, Hirotsugu; Fujimoto, Eiki; Ono, Akemi; Hayabuchi, Yasunobu; Fujita, Hiroshi; Sogabe, Hitoshi; Kitagawa, Tetsuya

2017-01-01

The strategy for an infant with congenital mitral stenosis should be determined by three important factors: left ventricular volume, the degree of the systemic outflow tract obstruction, and the type of mitral valve dysfunction. A successful staged biventricular repair in early infancy for a patient who had congenital mitral stenosis with short chordae, hypoplastic left ventricle and coarctation of the aorta, and the long-term results are described. There were the following important hemodynamic factors that led to the successful biventricular repair in the patient. Total systemic output was barely supplied through the hypoplastic left ventricle after closure of the ductus arteriosus on admission. The neonate underwent repair of coarctation of the aorta alone as the initial stage at 9 days after birth. Also, spontaneous closure of the foramen ovale following repair of coarctation of the aorta accelerated the progressive left ventricular growth. Open mitral commissurotomy with an interatrial fenestration using the modified Brawley's approach was performed for a 40-day-old infant. Good left ventricular growth and good mitral valve function have been observed for 18 years after open mitral commissurotomy. Appropriate early augmentation of left ventricular inflow through the mitral valve might be effective for growth of a hypoplastic left ventricle. J. Med. Invest. 64: 187-191, February, 2017.

Percutaneous Transvenous Mitral Annuloplasty (PTMA) with the Viking device reduces pacing-induced mitral regurgitation.

PubMed

Kimblad, Per Ola; Harnek, Jan; Roijer, Anders; Meurling, Carl; Brandt, Johan; Solem, Jan Otto

2005-11-01

The new percutaneous mitral annuloplasty Viking device was evaluated in surviving sheep with pacing-induced mitral regurgitation. Twenty sheep were subjected to rapid ventricular pacing for one to three months, leading to cardiomyopathy and mitral regurgitation. Device implantation could be successfully performed in 11 of these animals after pacemaker treatment for 64+/-7 days. The device-related procedure time was 12+/-2 min. The mean follow-up time was 58+/-8 days after implantation of the device. Mitral annulus septo-lateral diameter was significantly reduced after insertion of the device, from 35+/-1 mm before implantation to 30+/-1 mm at the final follow up intracardiac echocardiography (P = 0.0097). The degree of mitral regurgitation (on a scale from 0 to 4) was 2.6+/-0.2 before device implantation and decreased to 0.8+/-0.2 after treatment (P = 0.0039), and the vena contracta was reduced from 7+/-0.4 mm to 3+/-0.8 mm (P = 0.0019). Angiography showed no signs of impairment of the coronary arteries. No thrombosis was observed. These results indicate that the septo-lateral diameter of the mitral annulus, and the degree of experimentally induced mitral regurgitation, can be significantly reduced with a percutaneous catheter technique in surviving sheep.

A Study on Cerebral Embolism in Mitral Stenosis

PubMed Central

Kwon, Osun; Kim, Myung Hwan; Kim, Kwon Sam; Bae, Jong Hoa; Kim, Myung Shick; Song, Jung Sang

1986-01-01

To evaluate the significance of episodes of cerebral embolism in patients with mitral valve disease in Korea, 128 patients with echocardiographic diagnosis of mitral valve disease were examined. Among these, 82 patients had predominant mitral stenosis. The clinical features of 82 patients with mitral stenosis have been reviewed to elucidate the factors favoring cerebral embolism which occurred in 19 patients, i.e., incidence of 23.2%.Atrial fibrillation was present in 16 of 19 patients with cerebral embolism (84.2%). Cerebral embolic episodes occurred in 16 of 47 patients with atrial fibrillation (34.0%).The mean age (55.3 ± 12.1 years) of patients without cerebral embolism was significantly older than that (43.2 ± 14.6 years) of patients without cerebral embolism (P<0.005).There was no significant relationship between the incidence of embolism and sex, left atrial thrombi, left atrium/aortic root diameter, mitral valvular orifice area, mitral valvular vegetation or calcification, left ventricular enddiastolic dimension or left ventricular posterior wall thickness. Cerebral embolism is common in patients with mitral stenosis in our country. The presence of atrial fibrillation and low cardiac output increase the attack of cerebral emboli whereas the severity of mitral stenosis, as judged by valve area, may not correlate with the occurrence of emboli. The best treatment for cerebral embolism is prevention. Therefore, we believe that more vigorous treatment of patients with mitral valve disease who are old or associated with atrial fibrillation as well as previous embolic history is indicated. PMID:15759378

Echocardiographic versus histologic findings in Marfan syndrome.

PubMed

Gu, Xiaoyan; He, Yihua; Li, Zhian; Han, Jiancheng; Chen, Jian; Nixon, J V Ian

2015-02-01

This retrospective study attempted to establish the prevalence of multiple-valve involvement in Marfan syndrome and to compare echocardiographic with histopathologic findings in Marfan patients undergoing valvular or aortic surgery. We reviewed echocardiograms of 73 Marfan patients who underwent cardiovascular surgery from January 2004 through October 2009. Tissue histology was available for comparison in 29 patients. Among the 73 patients, 66 underwent aortic valve replacement or the Bentall procedure. Histologic findings were available in 29 patients, all of whom had myxomatous degeneration. Of 63 patients with moderate or severe aortic regurgitation as determined by echocardiography, 4 had thickened aortic valves. The echocardiographic findings in 18 patients with mitral involvement included mitral prolapse in 15. Of 11 patients with moderate or severe mitral regurgitation as determined by echocardiography, 4 underwent mitral valve repair and 7 mitral valve replacement. Histologic findings among mitral valve replacement patients showed thickened valve tissue and myxomatous degeneration. Tricuspid involvement was seen echocardiographically in 8 patients, all of whom had tricuspid prolapse. Two patients had severe tricuspid regurgitation, and both underwent repair. Both mitral and tricuspid involvement were seen echocardiographically in 7 patients. Among the 73 patients undergoing cardiac surgery for Marfan syndrome, 66 had moderate or severe aortic regurgitation, although their valves manifested few histologic changes. Eighteen patients had mitral involvement (moderate or severe mitral regurgitation, prolapse, or both), and 8 had tricuspid involvement. Mitral valves were most frequently found to have histologic changes, but the tricuspid valve was invariably involved.

Modulation of the tissue reninangiotensin-aldosterone system in dogs with chronic mild regurgitation through the mitral valve.

PubMed

Fujii, Yoko; Orito, Kensuke; Muto, Makoto; Wakao, Yoshito

2007-10-01

To investigate whether the tissue and plasma renin-angiotensin-aldosterone system (RAAS) is activated in dogs with mild regurgitation through the mitral valve and determine the contribution of chymase and angiotensin-converting enzyme (ACE) to the activation of the RAAS and potential production of angiotensin II during the chronic stage of mild mitral valve regurgitation. 5 Beagles with experimentally induced mild mitral valve regurgitation and 6 clinically normal (control) Beagles. Tissue ACE and chymase-like activities and plasma RAAS were measured and the RAAS evaluated approximately 1,000 days after experimental induction of mitral valve regurgitation in the 5 dogs. Dogs with experimentally induced mitral valve regurgitation did not have clinical signs of the condition, although echocardiography revealed substantial eccentric hyper- trophy. On the basis of these findings, dogs with mitral valve regurgitation were classified as International Small Animal Cardiac Health Council class Ib. Plasma activity of renin and plasma concentrations of angiotensin I, angiotensin II, and aldosterone were not significantly different between dogs with mitral valve regurgitation and clinically normal dogs. Tissue ACE activity was significantly increased and chymase-like activity significantly decreased in dogs with mitral valve regurgitation, compared with values in clinically normal dogs. The tissue RAAS was modulated without changes in the plasma RAAS in dogs with mild mitral valve regurgitation during the chronic stage of the condition. An ACE-dependent pathway may be a major route for production of angiotensin II during this stage of the condition.

Effect of balloon mitral valvotomy on left ventricular function in rheumatic mitral stenosis.

PubMed

Rajesh, Gopalan Nair; Sreekumar, Pradeep; Haridasan, Vellani; Sajeev, C G; Bastian, Cicy; Vinayakumar, D; Kadermuneer, P; Mathew, Dolly; George, Biju; Krishnan, M N

Mitral stenosis (MS) is found to produce left ventricular (LV) dysfunction in some studies. We sought to study the left ventricular function in patients with rheumatic MS undergoing balloon mitral valvotomy (BMV). Ours is the first study to analyze effect of BMV on mitral annular plane systolic excursion (MAPSE), and to quantify prevalence of longitudinal left ventricular dysfunction in rheumatic MS. In this prospective cohort study, we included 43 patients with severe rheumatic mitral stenosis undergoing BMV. They were compared to twenty controls whose distribution of age and gender were similar to that of patients. The parameters compared were LV ejection fraction (EF) by modified Simpson's method, mitral annular systolic velocity (MASV), MAPSE, mitral annular early diastolic velocity (E'), and myocardial performance index (MPI). These parameters were reassessed immediately following BMV and after 3 months of procedure. MASV, MAPSE, E', and EF were significantly lower and MPI was higher in mitral stenosis group compared to controls. Impaired longitudinal LV function was present in 77% of study group. MAPSE and EF did not show significant change after BMV while MPI, MASV, and E' improved significantly. MASV and E' showed improvement immediately after BMV, while MPI decreased only at 3 months follow-up. There were significantly lower mitral annular motion parameters including MAPSE in patients with rheumatic mitral stenosis. Those with atrial fibrillation had higher MPI. Immediately after BMV, there was improvement in LV long axis function with a gradual improvement in global LV function. There was no significant change of MAPSE after BMV. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Long-Term Results of Mitral Valve Repair

PubMed Central

da Costa, Francisco Diniz Affonso; Colatusso, Daniele de Fátima Fornazari; Martin, Gustavo Luis do Santos; Parra, Kallyne Carolina Silva; Botta, Mariana Cozer; Balbi Filho, Eduardo Mendel; Veloso, Myrian; Miotto, Gabriela; Ferreira, Andreia Dumsch de Aragon; Colatusso, Claudinei

2018-01-01

Introduction Current guidelines state that patients with severe mitral regurgitation should be treated in reference centers with a high reparability rate, low mortality rate, and durable results. Objective To analyze our global experience with the treatment of organic mitral regurgitation from various etiologies operated in a single center. Methods We evaluated all surgically treated patients with organic mitral regurgitation from 2004-2017. Patients were evaluated clinically and by echocardiography every year. We determined early and late survival rates, valve related events and freedom from recurrent mitral regurgitation and tricuspid regurgitation. Valve failure was defined as any mitral regurgitation ≥ moderate degree or the need for reoperation for any reason. Results Out of 133 patients with organic mitral regurgitation, 125 (93.9%) were submitted to valve repair. Mean age was 57±15 years and 52 patients were males. The most common etiologies were degenerative disease (73 patients) and rheumatic disease (34 patients). Early mortality was 2.4% and late survival was 84.3% at 10 years, which are similar to the age- and gender-matched general population. Only two patients developed severe mitral regurgitation, and both were reoperated (95.6% at 10 years). Freedom from mitral valve failure was 84.5% at 10 years, with no difference between degenerative and rheumatic valves. Overall, late ≥ moderate tricuspid regurgitation was present in 34% of the patients, being more common in the rheumatic ones. The use of tricuspid annuloplasty abolished this complication. Conclusion We have demonstrated that mitral regurgitation due to organic mitral valve disease from various etiologies can be surgically treated with a high repair rate, low early mortality and long-term survival that are comparable to the matched general population. Concomitant treatment of atrial fibrillation and tricuspid valve may be important adjuncts to optimize long-term results. PMID:29617498

Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism

PubMed Central

Rotin, Lianne E.; Gronda, Marcela; MacLean, Neil; Hurren, Rose; Wang, XiaoMing; Lin, Feng-Hsu; Wrana, Jeff; Datti, Alessandro; Barber, Dwayne L.; Minden, Mark D.; Slassi, Malik; Schimmer, Aaron D.

2016-01-01

Targeting Bruton's tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity. Given the reported expression and constitutive activation of BTK in acute myeloid leukemia (AML) cells, there has been recent interest in investigating the anti-AML activity of ibrutinib. We noted that ibrutinib had limited single-agent toxicity in a panel of AML cell lines and primary AML samples, and therefore sought to identify ibrutinib-sensitizing drugs. Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induced a synergistic increase in reactive oxygen species that was functionally important to explain the observed cell death. Interestingly, synergistic cytotoxicity of ibrutinib and ethacridine was independent of the inhibitory effect of ibrutinib against BTK, as knockdown of BTK did not sensitize TEX and OCI-AML2 cells to ethacridine treatment. Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease. PMID:26624983

Functionally distinct roles for different miR-155 expression levels through contrasting effects on gene expression, in acute myeloid leukaemia.

PubMed

Narayan, N; Morenos, L; Phipson, B; Willis, S N; Brumatti, G; Eggers, S; Lalaoui, N; Brown, L M; Kosasih, H J; Bartolo, R C; Zhou, L; Catchpoole, D; Saffery, R; Oshlack, A; Goodall, G J; Ekert, P G

2017-04-01

Enforced expression of microRNA-155 (miR-155) in myeloid cells has been shown to have both oncogenic or tumour-suppressor functions in acute myeloid leukaemia (AML). We sought to resolve these contrasting effects of miR-155 overexpression using murine models of AML and human paediatric AML data sets. We show that the highest miR-155 expression levels inhibited proliferation in murine AML models. Over time, enforced miR-155 expression in AML in vitro and in vivo, however, favours selection of intermediate miR-155 expression levels that results in increased tumour burden in mice, without accelerating the onset of disease. Strikingly, we show that intermediate and high miR-155 expression also regulate very different subsets of miR-155 targets and have contrasting downstream effects on the transcriptional environments of AML cells, including genes involved in haematopoiesis and leukaemia. Furthermore, we show that elevated miR-155 expression detected in paediatric AML correlates with intermediate and not high miR-155 expression identified in our experimental models. These findings collectively describe a novel dose-dependent role for miR-155 in the regulation of AML, which may have important therapeutic implications.

Small Molecule Inhibition of cAMP Response Element Binding Protein in Human Acute Myeloid Leukemia Cells

PubMed Central

Mitton, Bryan; Chae, Hee-Don; Hsu, Katie; Dutta, Ritika; Aldana-Masangkay, Grace; Ferrari, Roberto; Davis, Kara; Tiu, Bruce C.; Kaul, Arya; Lacayo, Norman; Dahl, Gary; Xie, Fuchun; Li, Bingbing X.; Breese, Marcus R.; Landaw, Elliot M.; Nolan, Garry; Pellegrini, Matteo; Romanov, Sergei; Xiao, Xiangshu; Sakamoto, Kathleen M.

2016-01-01

The transcription factor CREB (cAMP Response Element Binding Protein) is overexpressed in the majority of acute myeloid leukemia (AML) patients, and this is associated with a worse prognosis. Previous work revealed that CREB overexpression augmented AML cell growth, while CREB knockdown disrupted key AML cell functions in vitro. In contrast, CREB knockdown had no effect on long-term hematopoietic stem cell activity in mouse transduction/transplantation assays. Together, these studies position CREB as a promising drug target for AML. To test this concept, a small molecule inhibitor of CREB, XX-650-23, was developed. This molecule blocks a critical interaction between CREB and its required co-activator CBP (CREB Binding Protein), leading to disruption of CREB-driven gene expression. Inhibition of CBP-CREB interaction induced apoptosis and cell cycle arrest in AML cells, and prolonged survival in vivo in mice injected with human AML cells. XX-650-23 had little toxicity on normal human hematopoietic cells and tissues in mice. To understand the mechanism of XX-650-23, we performed RNA-seq, ChIP-seq and Cytometry Time of Flight with human AML cells. Our results demonstrate that small molecule inhibition of CBP-CREB interaction mostly affects apoptotic, cell cycle, and survival pathways, which may represent a novel approach for AML therapy. PMID:27211267

Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism.

PubMed

Rotin, Lianne E; Gronda, Marcela; MacLean, Neil; Hurren, Rose; Wang, XiaoMing; Lin, Feng-Hsu; Wrana, Jeff; Datti, Alessandro; Barber, Dwayne L; Minden, Mark D; Slassi, Malik; Schimmer, Aaron D

2016-01-19

Targeting Bruton's tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity. Given the reported expression and constitutive activation of BTK in acute myeloid leukemia (AML) cells, there has been recent interest in investigating the anti-AML activity of ibrutinib. We noted that ibrutinib had limited single-agent toxicity in a panel of AML cell lines and primary AML samples, and therefore sought to identify ibrutinib-sensitizing drugs. Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induced a synergistic increase in reactive oxygen species that was functionally important to explain the observed cell death. Interestingly, synergistic cytotoxicity of ibrutinib and ethacridine was independent of the inhibitory effect of ibrutinib against BTK, as knockdown of BTK did not sensitize TEX and OCI-AML2 cells to ethacridine treatment. Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease.

Impaired health-related quality of life in acute myeloid leukemia survivors: a single-center study.

PubMed

Leunis, Annemieke; Redekop, William K; Uyl-de Groot, Carin A; Löwenberg, Bob

2014-09-01

The purpose of this study was to assess the impact of acute myeloid leukemia (AML) and its treatment on health-related quality of life (HRQOL) by comparing the HRQOL of AML survivors with the HRQOL in the general population. Two HRQOL questionnaires (EQ-5D and QLQ-C30) were sent to patients diagnosed with AML between 1999 and 2011 at a single academic hospital and still alive in 2012. HRQOL in AML survivors was compared with general population reference values. Multivariate analysis was used to identify factors associated with HRQOL in AML survivors. Questionnaires were returned by 92 of the 103 patients (89%). AML survivors reported significantly worse functioning, more fatigue, pain, dyspnea, appetite loss, and financial difficulties and lower EQ-VAS scores than the general population (P < 0.05). Impaired HRQOL in AML survivors was mainly found in survivors without a paid job. Other factors associated with a poor HRQOL were allogeneic hematopoietic stem cell transplantation and the absence of social support. This single-center study showed that the HRQOL in AML survivors is worse than the HRQOL in the general population. HRQOL in these patients can be improved by adequately treating and preventing fatigue, pain, dyspnea, and appetite loss. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML.

PubMed

Wong, Terrence N; Miller, Christopher A; Klco, Jeffery M; Petti, Allegra; Demeter, Ryan; Helton, Nichole M; Li, Tiandao; Fulton, Robert S; Heath, Sharon E; Mardis, Elaine R; Westervelt, Peter; DiPersio, John F; Walter, Matthew J; Welch, John S; Graubert, Timothy A; Wilson, Richard K; Ley, Timothy J; Link, Daniel C

2016-02-18

There is interest in using leukemia-gene panels and next-generation sequencing to assess acute myelogenous leukemia (AML) response to induction chemotherapy. Studies have shown that patients with AML in morphologic remission may continue to have clonal hematopoiesis with populations closely related to the founding AML clone and that this confers an increased risk of relapse. However, it remains unknown how induction chemotherapy influences the clonal evolution of a patient's nonleukemic hematopoietic population. Here, we report that 5 of 15 patients with genetic clearance of their founding AML clone after induction chemotherapy had a concomitant expansion of a hematopoietic population unrelated to the initial AML. These populations frequently harbored somatic mutations in genes recurrently mutated in AML or myelodysplastic syndromes and were detectable at very low frequencies at the time of AML diagnosis. These results suggest that nonleukemic hematopoietic stem and progenitor cells, harboring specific aging-acquired mutations, may have a competitive fitness advantage after induction chemotherapy, expand, and persist long after the completion of chemotherapy. Although the clinical importance of these "rising" clones remains to be determined, it will be important to distinguish them from leukemia-related populations when assessing for molecular responses to induction chemotherapy. © 2016 by The American Society of Hematology.

Proteogenomics approaches for studying cancer biology and their potential in the identification of acute myeloid leukemia biomarkers.

PubMed

Hernandez-Valladares, Maria; Vaudel, Marc; Selheim, Frode; Berven, Frode; Bruserud, Øystein

2017-08-01

Mass spectrometry (MS)-based proteomics has become an indispensable tool for the characterization of the proteome and its post-translational modifications (PTM). In addition to standard protein sequence databases, proteogenomics strategies search the spectral data against the theoretical spectra obtained from customized protein sequence databases. Up to date, there are no published proteogenomics studies on acute myeloid leukemia (AML) samples. Areas covered: Proteogenomics involves the understanding of genomic and proteomic data. The intersection of both datatypes requires advanced bioinformatics skills. A standard proteogenomics workflow that could be used for the study of AML samples is described. The generation of customized protein sequence databases as well as bioinformatics tools and pipelines commonly used in proteogenomics are discussed in detail. Expert commentary: Drawing on evidence from recent cancer proteogenomics studies and taking into account the public availability of AML genomic data, the interpretation of present and future MS-based AML proteomic data using AML-specific protein sequence databases could discover new biological mechanisms and targets in AML. However, proteogenomics workflows including bioinformatics guidelines can be challenging for the wide AML research community. It is expected that further automation and simplification of the bioinformatics procedures might attract AML investigators to adopt the proteogenomics strategy.

Implantation of personalized, biocompatible mitral annuloplasty rings: feasibility study in an animal model

PubMed Central

Sündermann, Simon H.; Gessat, Michael; Cesarovic, Nikola; Frauenfelder, Thomas; Biaggi, Patric; Bettex, Dominique; Falk, Volkmar; Jacobs, Stephan

2013-01-01

OBJECTIVES Implantation of an annuloplasty ring is an essential component of a durable mitral valve repair. Currently available off-the-shelf rings still do not cover all the variations in mitral annulus anatomy and pathology from subject to subject. Computed tomography (CT) and echo imaging allow for 3-D segmentation of the mitral valve and mitral annulus. The concept of tailored annuloplasty rings has been proposed although, to date, no surgically applicable implementation of patient-specific annuloplasty rings has been seen. The objective of this trial was to prove the concept of surgical implantation of a model-guided, personalized mitral annuloplasty ring, manufactured based on individual CT-scan models. METHODS ECG-gated CT angiography was performed in six healthy pigs under general anaesthesia. Based on the individual shape of the mitral annulus in systole, a customized solid ring with integrated suturing holes was designed and manufactured from a biocompatible titanium alloy by a rapid process using laser melting. The ring was implanted three days later and valve function was assessed by intraoperative echocardiography. The macroscopic annulus–annuloplasty match was assessed after heart explantation. RESULTS CT angiography provided good enough image quality in all animals to allow for segmentation of the mitral annulus. The individually tailored mitral rings were manufactured and successfully implanted in all pigs. In 50%, a perfect matching of the implanted ring and the mitral annulus was achieved. In one animal, a slight deviation of the ring shape from the circumference was seen postoperatively. The rings implanted in the first two animals were significantly oversized but the deviation did not affect valve competence. CONCLUSIONS CT image quality and accuracy of the dimensions of the mitral annulus were sufficient for digital modelling and rapid manufacturing of mitral rings. Implantation of individually tailored annuloplasty rings is feasible. PMID:23287589

Acute myeloid leukemia (AML) - children

MedlinePlus

Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

DNA methylation and targeted sequencing of methyltransferases family genes in canine acute myeloid leukaemia, modelling human myeloid leukaemia.

PubMed

Bronzini, I; Aresu, L; Paganin, M; Marchioretto, L; Comazzi, S; Cian, F; Riondato, F; Marconato, L; Martini, V; Te Kronnie, G

2017-09-01

Tumours shows aberrant DNA methylation patterns, being hypermethylated or hypomethylated compared with normal tissues. In human acute myeloid leukaemia (hAML) mutations in DNA methyltransferase (DNMT3A) are associated to a more aggressive tumour behaviour. As AML is lethal in dogs, we defined global DNA methylation content, and screened the C-terminal domain of DNMT3 family of genes for sequence variants in 39 canine acute myeloid leukaemia (cAML) cases. A heterogeneous pattern of DNA methylation was found among cAML samples, with subsets of cases being hypermethylated or hypomethylated compared with healthy controls; four recurrent single nucleotide variations (SNVs) were found in DNMT3L gene. Although SNVs were not directly correlated to whole genome DNA methylation levels, all hypomethylated cAML cases were homozygous for the deleterious mutation at p.Arg222Trp. This study contributes to understand genetic modifications of cAML, leading up to studies that will elucidate the role of methylome alterations in the pathogenesis of AML in dogs. © 2016 John Wiley & Sons Ltd.

Novel agents in acute myeloid leukemia.

PubMed

Ungewickell, Alexander; Medeiros, Bruno C

2012-08-01

Although complete remissions can be achieved in most patients younger than 60 years of age with untreated acute myeloid leukemia (AML), only 30-40 % of patients remain long-term survivors. Furthermore, long-term survivors represent only 10-15 % of all AML patients older than 60 years of age and <10 % of all patients with relapsed AML. The development of new treatments for AML is therefore needed. Novel therapies should target specific mechanisms and pathways implicated in the development and maintenance of AML, should strive to have better tolerability than conventional combination chemotherapy, be associated with improved quality of life and minimize utilization of health care resources. In this manuscript, we discuss the role of epigenetic regulators and immunomodulatory agents in the treatment of AML. Also, we review the data on inhibitors of protein homeostasis and its synergistic effect to DNA methyltransferase inhibitors, the potential role for inhibitors of heat shock proteins and the mitotic machinery and a novel formulation of conventional chemotherapeutic agents given at a fixed molar concentration. Finally, we briefly share our views on optimal clinical trial design and patient selection for future studies in AML.

Study of the S427G polymorphism and of MYBL2 variants in patients with acute myeloid leukemia.

PubMed

Dolz, Sandra; García, Paloma; Llop, Marta; Fuster, Óscar; Luna, Irene; Ibáñez, Mariam; Gómez, Inés; López, María; Such, Esperanza; Cervera, José; Sanz, Miguel A; De Juan, Inmaculada; Palanca, Sarai; Murria, Rosa; Bolufer, Pascual; Barragán, Eva

2015-06-19

Dysregulation of MYBL2 has been associated to tumorigenesis and the S427G polymorphism could induce partial inactivation of MYBL2, associating it with cancer risk. It has previously been shown that MYBL2 was over-expressed in some acute myeloid leukemias (AML), portending poor prognosis. However, to date no studies have investigated the S427G or other genetic variants of MYBL2 in AML. This study analyzed the S427G in 197 AML patients and 179 controls and screened the MYBL2 sequence in patients. In contrast to other studies in solid tumors, the S427G was not associated with the incidence of AML. This study detected four unannotated genetic alterations, of which the Q67X could be involved in MYBL2 dysfunction. Eight polymorphisms were identified, among which the rs73116571, located in a splicing region, was associated with higher incidence in AML and weaker MYBL2 expression, suggesting pre-disposition to AML. Additional functional studies should be performed to verify these genetic variations as possible targets in AML.

Proteasome inhibition enhances the efficacy of volasertib-induced mitotic arrest in AML in vitro and prolongs survival in vivo.

PubMed

Schnerch, Dominik; Schüler, Julia; Follo, Marie; Felthaus, Julia; Wider, Dagmar; Klingner, Kathrin; Greil, Christine; Duyster, Justus; Engelhardt, Monika; Wäsch, Ralph

2017-03-28

Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and ineligible to undergo intensive treatment, have a dismal prognosis. The small molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like kinase 1 and has shown remarkable anti-leukemic activity when combined with low-dose cytarabine. We have demonstrated that AML cells are highly vulnerable to cell death in mitosis yet manage to escape a mitotic block through mitotic slippage by sustained proteasome-dependent slow degradation of cyclin B. Therefore, we tested whether interfering with mitotic slippage through proteasome inhibition arrests and kills AML cells more efficiently during mitosis. We show that therapeutic doses of bortezomib block the slow degradation of cyclin B during a volasertib-induced mitotic arrest in AML cell lines and patient-derived primary AML cells. In a xenotransplant mouse model of human AML, mice receiving volasertib in combination with bortezomib showed superior disease control compared to mice receiving volasertib alone, highlighting the potential therapeutic impact of this drug combination.

Expression of microRNA-181 determines response to treatment with azacitidine and predicts survival in elderly patients with acute myeloid leukaemia.

PubMed

Butrym, Aleksandra; Rybka, Justyna; Baczyńska, Dagmara; Poręba, Rafał; Mazur, Grzegorz; Kuliczkowski, Kazimierz

2016-10-01

MicroRNAs (miRs) are small non-coding RNAs that play important roles in cell differentiation and survival. Abnormal expression of miRs has been demonstrated in numerous types of cancer, including acute myeloid leukaemia (AML). The aim of the present study was to evaluate miR-181 expression at diagnosis and following the completion of chemotherapy in AML patients, with regard to clinical response and outcome, particularly in patients treated with azacitidine. miR-181 expression was analysed using reverse transcription-quantitative polymerase chain reaction in 95 bone marrow specimens from newly diagnosed AML patients and in 20 healthy subjects for comparison. The results revealed upregulated miR-181 expression in the total cohort of AML patients, which was correlated with longer survival. However, in a subset of older AML patients treated with azacitidine, low miR-181 expression at diagnosis was a predictor for complete remission and prolonged survival. The findings indicated that miR-181 has an important role in AML and determines response to azacitidine treatment in older AML patients.

Expression of microRNA-181 determines response to treatment with azacitidine and predicts survival in elderly patients with acute myeloid leukaemia

PubMed Central

Butrym, Aleksandra; Rybka, Justyna; Baczyńska, Dagmara; Poręba, Rafał; Mazur, Grzegorz; Kuliczkowski, Kazimierz

2016-01-01

MicroRNAs (miRs) are small non-coding RNAs that play important roles in cell differentiation and survival. Abnormal expression of miRs has been demonstrated in numerous types of cancer, including acute myeloid leukaemia (AML). The aim of the present study was to evaluate miR-181 expression at diagnosis and following the completion of chemotherapy in AML patients, with regard to clinical response and outcome, particularly in patients treated with azacitidine. miR-181 expression was analysed using reverse transcription-quantitative polymerase chain reaction in 95 bone marrow specimens from newly diagnosed AML patients and in 20 healthy subjects for comparison. The results revealed upregulated miR-181 expression in the total cohort of AML patients, which was correlated with longer survival. However, in a subset of older AML patients treated with azacitidine, low miR-181 expression at diagnosis was a predictor for complete remission and prolonged survival. The findings indicated that miR-181 has an important role in AML and determines response to azacitidine treatment in older AML patients. PMID:27698792

Disc erosion in Models 103 and 104 of Beall mitral valve prostheses

PubMed Central

Gómez, Ricardo; Verduras, María José; Lopez-Quintana, Alfonso; Riera, Luis; Zerolo, Ignacio; Martinez-Bordiu, Cristóbal

1981-01-01

Three cases of severe disc variance and erosion of the Teflon-disc Beall mitral valve prosthesis (Models 103 and 104) are reported. In two patients, the Beall mitral valves were excised and replaced with two Björk-Shiley mitral valves. The remaining patient did not survive, and at autopsy, the lens was found at the aortic bifurcation level. Because of this potentially lethal complication, careful follow-up of patients with Beall mitral valve prostheses (Models 103 and 104) is recommended. Images PMID:15216211

A new cannulation method for isolated mitral valve surgery--"apicoaortic-pa" cannulation.

PubMed

Wada, J; Komatsu, S; Nakae, S; Kazui, T

1976-06-01

The present paper describes experimental and clinical studies of a new method "Apicoaortic-PA" cannulation for mitral valve surgery. Our experimental study showed that this method was more rapid and more physiological for cardiopulmonary bypass. We used this technique in 55 cases of isolated mitral valve surgery with successful results. Our general philosophy of surgical approach to the mitral valve diseases is also discussed. We advocate the utilization of the "Apicoaortic Pulmonary Artery" cannulation method for clinical use in isolated mitral valve surgery through the left thoracotomy.