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Sample records for dilated congestive cardiomyopathy

  1. Diagnosis and treatment of congestive heart failure secondary to dilated cardiomyopathy in a hedgehog.

    PubMed

    Delk, K W; Eshar, D; Garcia, E; Harkin, K

    2014-03-01

    A one-year-old African pygmy hedgehog (Atelerix albiventris) was evaluated for severe respiratory distress. Physical examination findings included marked dyspnoea, cyanosis and tachypnoea. Radiographic findings included an enlarged heart and pulmonary oedema, and dilated cardiomyopathy was confirmed via echocardiogram. The patient was treated for congestive heart failure because of dilated cardiomyopathy with furosemide, enalapril, pimobendan and l-carnitine. Within 24 hours of treatment, the pulmonary oedema and cyanosis had resolved. Following discharge, clinical improvement was noted by the owner and echocardiogram confirmed improved fractional shortening. Cardiomyopathy has been reported at post-mortem examination in hedgehogs, but there are no reports of ante-mortem diagnosis and treatment. Performing baseline cardiac assessment in hedgehogs is recommended, and treatment with l-carnitine and pimobendan may improve outcome, as carnitine deficiency is a possible cause of cardiomyopathy in hedgehogs. Successful emergency treatment of congestive heart failure in the hedgehog of this report may be effective for other hedgehogs presented with similar clinical signs. PMID:24372164

  2. Dilated cardiomyopathy

    MedlinePlus

    Hare JM. The dilated, restrictive, and infiltrative cardiomyopathies. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine . 9th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 68.

  3. Current Treatment of Dilated Cardiomyopathy

    PubMed Central

    Massin, Edward K.

    1991-01-01

    Within the last decade, the treatment for patients with dilated cardiomyopathy has changed. Clinical management of these patients is aimed at controlling congestive heart failure, treating arrhythmias, preventing pulmonary and systemic emboli, and managing chest pain. The goals of treatment for patients with dilated cardiomyopathy are to make the patient feel better and live longer. To achieve this, we direct treatment to improving left ventricular function and cardiac output and controlling arrhythmias and thromboemboli. Basic treatment begins with inotropic therapy, preload reduction, and afterload reduction. For patients with symptomatic disease, we recommend diuretics, digoxin, and converting enzyme inhibitors for first-line therapy. Patients with arrhythmias may be treated by the addition of amiodarone, a pacemaker, or an automatic implantable cardioverter-defibrillator; and most such patients need to be anticoagulated. All patients need close follow-up for possible drug toxicity associated with their regimens. Heart transplantation can be considered for patients refractory to medical treatment. Although the incidence of dilated cardiomyopathy continues to increase, we are learning better ways to treat it. In the future, new drugs with fewer side effects should be available to treat, and perhaps impede, the development of dilated cardiomyopathy. (Texas Heart Institute Journal 1991;18:41-9) PMID:15227507

  4. A surprising cause of reversible dilated cardiomyopathy

    PubMed Central

    Vlot, Mariska; de Jong, Margriet; de Ronde, Pim; Tukkie, Raymond

    2014-01-01

    This case report describes two cases of dilated cardiomyopathy due to hypocalcaemia as a result of hypoparathyroidism. Patient A suffered from dilated cardiomyopathy due to secondary hypoparathyroidism as a result of previous neck surgery. Patient B suffered from dilated cardiomyopathy with congestive heart failure due to primary hypoparathyroidism. Hypoparathyroidism can exist for years before being recognised, especially after neck surgery. Besides standard treatment of heart failure, restoration of serum calcium levels with calcium and vitamin D supplementation can lead to rapid improvement of cardiac function and should be continued lifelong. Both patients were responding very well to heart failure therapy and calcium supplementation as ejection fraction improved after restoration of plasma calcium levels. This case report emphasises that hypocalcaemia should be in the differential diagnosis of heart failure. PMID:24879729

  5. Cardiomyopathy, familial dilated

    PubMed Central

    Taylor, Matthew RG; Carniel, Elisa; Mestroni, Luisa

    2006-01-01

    Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by ventricular dilatation and impaired systolic function. Patients with DCM suffer from heart failure, arrhythmia, and are at risk of premature death. DCM has a prevalence of one case out of 2500 individuals with an incidence of 7/100,000/year (but may be under diagnosed). In many cases the disease is inherited and is termed familial DCM (FDC). FDC may account for 20–48% of DCM. FDC is principally caused by genetic mutations in FDC genes that encode for cytoskeletal and sarcomeric proteins in the cardiac myocyte. Family history analysis is an important tool for identifying families affected by FDC. Standard criteria for evaluating FDC families have been published and the use of such criteria is increasing. Clinical genetic testing has been developed for some FDC genes and will be increasingly utilized for evaluating FDC families. Through the use of family screening by pedigree analysis and/or genetic testing, it is possible to identify patients at earlier, or even presymptomatic stages of their disease. This presents an opportunity to invoke lifestyle changes and to provide pharmacological therapy earlier in the course of disease. Genetic counseling is used to identify additional asymptomatic family members who are at risk of developing symptoms, allowing for regular screening of these individuals. The management of FDC focuses on limiting the progression of heart failure and controlling arrhythmia, and is based on currently accepted treatment guidelines for DCM. It includes general measures (salt and fluid restriction, treatment of hypertension, limitation of alcohol intake, control of body weight, moderate exercise) and pharmacotherapy. Cardiac resynchronization, implantable cardioverter defibrillators and left ventricular assist devices have progressively expanding usage. Patients with severe heart failure, severe reduction of the functional capacity and depressed left ventricular ejection

  6. Intramyocardial VEGF-B167 Gene Delivery Delays the Progression Towards Congestive Failure in Dogs With Pacing-Induced Dilated Cardiomyopathy

    PubMed Central

    Pepe, Martino; Mamdani, Mohammed; Zentilin, Lorena; Csiszar, Anna; Qanud, Khaled; Zacchigna, Serena; Ungvari, Zoltan; Puligadda, Uday; Moimas, Silvia; Xu, Xiaobin; Edwards, John G.; Hintze, Thomas H.; Giacca, Mauro; Recchia, Fabio A.

    2016-01-01

    Rationale Vascular endothelial growth factor (VEGF)-B selectively binds VEGF receptor (VEGFR)-1, a receptor that does not mediate angiogenesis, and is emerging as a major cytoprotective factor. Objective To test the hypothesis that VEGF-B exerts non–angiogenesis-related cardioprotective effects in nonischemic dilated cardiomyopathy. Methods and Results AAV-9–carried VEGF-B167 cDNA (1012 genome copies) was injected into the myocardium of chronically instrumented dogs developing tachypacing-induced dilated cardiomyopathy. After 4 weeks of pacing, green fluorescent protein–transduced dogs (AAV-control, n=8) were in overt congestive heart failure, whereas the VEGF-B–transduced (AAV-VEGF-B, n=8) were still in a well-compensated state, with physiological arterial PO2. Left ventricular (LV) end-diastolic pressure in AAV-VEGF-B and AAV-control was, respectively, 15.0±1.5 versus 26.7±1.8 mm Hg and LV regional fractional shortening was 9.4±1.6% versus 3.0±0.6% (all P<0.05). VEGF-B prevented LV wall thinning but did not induce cardiac hypertrophy and did not affect the density of α-smooth muscle actin–positive microvessels, whereas it normalized TUNEL-positive cardiomyocytes and caspase-9 and -3 activation. Consistently, activated Akt, a major negative regulator of apoptosis, was superphysiological in AAV-VEGF-B, whereas the proapoptotic intracellular mediators glycogen synthase kinase (GSK)-3β and FoxO3a (Akt targets) were activated in AAV-control, but not in AAV-VEGF-B. Cardiac VEGFR-1 expression was reduced 4-fold in all paced dogs, suggesting that exogenous VEGF-B167 exerted a compensatory receptor stimulation. The cytoprotective effects of VEGF-B167 were further elucidated in cultured rat neonatal cardiomyocytes exposed to 10−8 mol/L angiotensin II: VEGF-B167 prevented oxidative stress, loss of mitochondrial membrane potential, and, consequently, apoptosis. Conclusions We determined a novel, angiogenesis-unrelated cardioprotective effect of VEGF-B167 in

  7. Genetics Home Reference: familial dilated cardiomyopathy

    MedlinePlus

    ... Related Dilated Cardiomyopathy Genetic Testing Registry (1 link) Primary dilated cardiomyopathy ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific articles on PubMed (1 link) PubMed OMIM (36 links) ...

  8. A predictive model for canine dilated cardiomyopathy-a meta-analysis of Doberman Pinscher data.

    PubMed

    Simpson, Siobhan; Edwards, Jennifer; Emes, Richard D; Cobb, Malcolm A; Mongan, Nigel P; Rutland, Catrin S

    2015-01-01

    Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic dysfunction which often leads to congestive heart failure. Although multiple human loci have been implicated in the pathogenesis of dilated cardiomyopathy, the identified variants are typically associated with rare monogenic forms of dilated cardiomyopathy. The potential for multigenic interactions contributing to human dilated cardiomyopathy remains poorly understood. Consistent with this, several known human dilated cardiomyopathy loci have been excluded as common causes of canine dilated cardiomyopathy, although canine dilated cardiomyopathy resembles the human disease functionally. This suggests additional genetic factors contribute to the dilated cardiomyopathy phenotype.This study represents a meta-analysis of available canine dilated cardiomyopathy genetic datasets with the goal of determining potential multigenic interactions relating the sex chromosome genotype (XX vs. XY) with known dilated cardiomyopathy associated loci on chromosome 5 and the PDK4 gene in the incidence and progression of dilated cardiomyopathy. The results show an interaction between known canine dilated cardiomyopathy loci and an unknown X-linked locus. Our study is the first to test a multigenic contribution to dilated cardiomyopathy and suggest a genetic basis for the known sex-disparity in dilated cardiomyopathy outcomes. PMID:25834770

  9. Genetics Home Reference: dilated cardiomyopathy with ataxia syndrome

    MedlinePlus

    ... dilated cardiomyopathy with ataxia syndrome dilated cardiomyopathy with ataxia syndrome Enable Javascript to view the expand/collapse ... Open All Close All Description Dilated cardiomyopathy with ataxia (DCMA) syndrome is an inherited condition characterized by ...

  10. GENETIC CAUSES OF DILATED CARDIOMYOPATHY

    PubMed Central

    Mestroni, Luisa; Brun, Francesca; Spezzacatene, Anita; Sinagra, Gianfranco; Taylor, Matthew RG

    2014-01-01

    Dilated cardiomyopathy is a disease of the myocardium characterized by left ventricular dilatation and/or dysfunction, affecting both adult and pediatric populations. Almost half of cases are genetically determined with an autosomal pattern of inheritance. Up to 40 genes have been identified affecting proteins of a wide variety of cellular structures such as the sarcomere, the nuclear envelope, the cytoskeleton, the sarcolemma and the intercellular junction. Novel gene mutations have been recently identified thanks to advances in next-generation sequencing technologies. Genetic screening is an essential tool for early diagnosis, risk assessment, prognostic stratification and, possibly, adoption of primary preventive measures in affected patients and their asymptomatic relatives. The purpose of this article is to review the genetic basis of DCM, the known genotype-phenotype correlations, the role of current genetic sequencing techniques in the discovery of novel pathogenic gene mutations and new therapeutic perspectives. PMID:25584016

  11. Stem Cell Therapy for Pediatric Dilated Cardiomyopathy

    PubMed Central

    Selem, Sarah M.; Kaushal, Sunjay; Hare, Joshua M.

    2014-01-01

    Dilated cardiomyopathy is a serious and life-threatening disorder in children. It is the most common form of pediatric cardiomyopathy. Therapy for this condition has varied little over the last several decades and mortality continues to be high. Currently, children with dilated cardiomyopathy are treated with pharmacological agents and mechanical support, but most require heart transplantation and survival rates are not optimal. The lack of common treatment guidelines and inadequate survival rates after transplantation necessitates more therapeutic clinical trials. Stem cell and cell-based therapies offer an innovative approach to restore cardiac structure and function towards normal, possibly reducing the need for aggressive therapies and cardiac transplantation. Mesenchymal stem cells and cardiac stem cells may be the most promising cell types for treating children with dilated cardiomyopathy. The medical community must begin a systematic investigation of the benefits of current and novel treatments such as stem cell therapies for treating pediatric dilated cardiomyopathy. PMID:23666883

  12. Cushing's Disease Presented by Reversible Dilated Cardiomyopathy.

    PubMed

    Aydoğan, Berna İmge; Gerede, Demet Menekşe; Canpolat, Asena Gökçay; Erdoğan, Murat Faik

    2015-01-01

    Introduction. Dilated cardiomyopathy is rarely reported among CS patients especially without hypertension and left ventricular hypertrophy. Materials and Methods. We hereby report a Cushing's syndrome case presenting with dilated cardiomyopathy. Results. A 48-year-old female patient was admitted to our clinic with severe proximal myopathy and dilated cardiomyopathy without ventricular hypertrophy. Cushing's disease was diagnosed and magnetic-resonance imaging of the pituitary gland revealed a microadenoma. Under diuretic and ketoconazole treatments, she underwent a successful transnasal/transsphenoidal adenomectomy procedure. Full recovery of symptoms and echocardiographic features was achieved after six months of surgery. Conclusion. Cushing's syndrome must be kept in mind as a reversible cause of dilated cardiomyopathy. Recovery of cardiomyopathy is achieved with successful surgery. PMID:26649206

  13. Cushing's Disease Presented by Reversible Dilated Cardiomyopathy

    PubMed Central

    Aydoğan, Berna İmge; Gerede, Demet Menekşe; Canpolat, Asena Gökçay; Erdoğan, Murat Faik

    2015-01-01

    Introduction. Dilated cardiomyopathy is rarely reported among CS patients especially without hypertension and left ventricular hypertrophy. Materials and Methods. We hereby report a Cushing's syndrome case presenting with dilated cardiomyopathy. Results. A 48-year-old female patient was admitted to our clinic with severe proximal myopathy and dilated cardiomyopathy without ventricular hypertrophy. Cushing's disease was diagnosed and magnetic-resonance imaging of the pituitary gland revealed a microadenoma. Under diuretic and ketoconazole treatments, she underwent a successful transnasal/transsphenoidal adenomectomy procedure. Full recovery of symptoms and echocardiographic features was achieved after six months of surgery. Conclusion. Cushing's syndrome must be kept in mind as a reversible cause of dilated cardiomyopathy. Recovery of cardiomyopathy is achieved with successful surgery. PMID:26649206

  14. Myocardial gallium-67 imaging in dilated cardiomyopathy

    PubMed Central

    O'Connell, John B.; Henkin, Robert E.

    1985-01-01

    The use of gallium-67, an isotope that is avid for areas of inflammation in patients with dilated cardiomyopathy, is described and compared with endomyocardial biopsy in 68 consecutive patients with dilated cardiomyopathy. Myocarditis was diagnosed in 8% on biopsy and the likelihood of a positive biopsy when the gallium scan was positive for inflammation, rose to 36%. It is concluded that gallium scanning is a useful adjunct to biopsy in detecting myocarditis in patients with dilated cardiomyopathy and in following patients with evidence of myocarditis on biopsy. Disadvantages of gallium-67 imaging include the radiation dose accumulated with multiple scans and 72h delay from initial injection of the isotope to imaging. It is suggested that definitive conclusions regarding the technique should await the results of a large multicentre trial evaluating gallium in comparison with endomyocardial biopsy in the diagnosis of myocarditis. ImagesFigure 1Figure 2

  15. Efficacy of Pimobendan in the Prevention of Congestive Heart Failure or Sudden Death in Doberman Pinschers with Preclinical Dilated Cardiomyopathy (The PROTECT Study)

    PubMed Central

    Summerfield, NJ; Boswood, A; O'Grady, MR; Gordon, SG; Dukes-McEwan, J; Oyama, MA; Smith, S; Patteson, M; French, AT; Culshaw, GJ; Braz-Ruivo, L; Estrada, A; O'Sullivan, ML; Loureiro, J; Willis, R; Watson, P

    2012-01-01

    Background The benefit of pimobendan in delaying the progression of preclinical dilated cardiomyopathy (DCM) in Dobermans is not reported. Hypothesis That chronic oral administration of pimobendan to Dobermans with preclinical DCM will delay the onset of CHF or sudden death and improve survival. Animals Seventy-six client-owned Dobermans recruited at 10 centers in the UK and North America. Methods The trial was a randomized, blinded, placebo-controlled, parallel group multicenter study. Dogs were allocated in a 1:1 ratio to receive pimobendan (Vetmedin capsules) or visually identical placebo. The composite primary endpoint was prospectively defined as either onset of CHF or sudden death. Time to death from all causes was a secondary endpoint. Results The proportion of dogs reaching the primary endpoint was not significantly different between groups (P = .1). The median time to the primary endpoint (onset of CHF or sudden death) was significantly longer in the pimobendan (718 days, IQR 441–1152 days) versus the placebo group (441 days, IQR 151–641 days) (log-rank P = 0.0088). The median survival time was significantly longer in the pimobendan (623 days, IQR 491–1531 days) versus the placebo group (466 days, IQR 236–710 days) (log-rank P = .034). Conclusion and Clinical Importance The administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome. PMID:23078651

  16. Peripartum cardiomyopathy and dilated cardiomyopathy: different at heart

    PubMed Central

    Bollen, Ilse A. E.; Van Deel, Elza D.; Kuster, Diederik W. D.; Van Der Velden, Jolanda

    2015-01-01

    Peripartum cardiomyopathy (PPCM) is a severe cardiac disease occurring in the last month of pregnancy or in the first 5 months after delivery and shows many similar clinical characteristics as dilated cardiomyopathy (DCM) such as ventricle dilation and systolic dysfunction. While PPCM was believed to be DCM triggered by pregnancy, more and more studies show important differences between these diseases. While it is likely they share part of their pathogenesis such as increased oxidative stress and an impaired microvasculature, discrepancies seen in disease progression and outcome indicate there must be differences in pathogenesis as well. In this review, we compared studies in DCM and PPCM to search for overlapping and deviating disease etiology, pathogenesis and outcome in order to understand why these cardiomyopathies share similar clinical features but have different underlying pathologies. PMID:25642195

  17. Familial occurrence of bovine dilated cardiomyopathy in Denmark.

    PubMed

    Leifsson, P S; Agerholm, J S

    2004-01-01

    Bovine dilated cardiomyopathy (BDCM) is a hereditary disease genetically related to the Canadian Holstein sire Montwick Red Apple Sovereign (MRAS). The occurrence of this disorder in the Red Danish Dairy breed, Holsteins, and Red Holsteins in Denmark is reported. Fourteen cases were diagnosed during a 13-year period. All suffered from congestive heart failure because of progressive myocardial fibrosis. Pedigree information was available in 12 cases revealing both maternal and paternal relationship to MRAS. Several sires were identified as carriers of BDCM. These sires originated from breeding lines used to upgrade Danish cattle populations. The findings indicate that BDCM is a potential health problem for Danish cattle. PMID:15533113

  18. Dilated cardiomyopathy associated with chronic overuse of an adrenaline inhaler

    PubMed Central

    Stewart, M J; Fraser, D M; Boon, N

    1992-01-01

    Endogenous catecholamines in excess are known to cause dilated cardiomyopathy. A patient presented with dilated cardiomyopathy after many years of overusing an adrenaline inhaler. Pathological features and a considerable improvement in myocardial function after withdrawal implicated the exogenous catecholamine excess in the pathogenesis of the cardiomyopathy. PMID:1389744

  19. The use of radiofrequency catheter ablation to cure dilated cardiomyopathy.

    PubMed

    Schmidt, S B; Lobban, J H; Reddy, S; Hoelper, M; Palmer, D L

    1997-01-01

    Incessant supraventricular tachycardia can cause a dilated cardiomyopathy. This article discusses the case of a 55-year-old woman whose cardiomyopathy was reversed when she underwent successful radiofrequency catheter ablation of a unifocal atrial tachycardia. PMID:9197188

  20. A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Familial dilated cardiomyopathy is a primary myocardial disease that can result in the development of congestive heart failure and sudden cardiac death. Spontaneous animal models of familial dilated cardiomyopathy exist and the Doberman pinscher dog is one of the most commonly reported canine breeds...

  1. Dilated cardiomyopathy following use of xenadrine EFX.

    PubMed

    Riccioni, Graziano; Speziale, Giuseppe; Scotti, Luca; Bucciarelli, Valentina; Cappetti, Silvia; Nasso, Giuseppe; Gallina, Sabina; Bucciarelli, Tonino

    2016-03-01

    We describe a case of a 35-year-old man presented at the emergency room of our institution with acute onset of dyspnea and dizziness. He was a body builder and had been using Xenadrine EFX for weight loss reduction. The laboratory analyses were normal. A chest radiograph showed an enlarged cardiac silhouette with clear lung fields. Transtoracic two-dimensional color Doppler echocardiography revealed a diffuse hypokinesia with a marked decreased in systolic function and a high teledyastolic diameter. This case document the possible relation to use of Xenadrine EFX for weight loss and the recurrence of dilated cardiomyopathy. PMID:26680256

  2. Dilated cardiomyopathy associated with toluene abuse.

    PubMed

    Vural, Mutlu; Ogel, Kultegin

    2006-01-01

    The use of paint thinner and glue to achieve an euphoric state has been associated with serious social and health problems in children and young adults. We present the case of a 21-year-old man with dilated cardiomyopathy occurring following abuse of paint thinner and glue containing toluene as main compound. After cessation of toluene abuse, the patient recovered rapidly and completely. Because of the increasing prevalence of toluene abuse, harmful effects of this volatile agent on the heart are also discussed. PMID:16479101

  3. The Diagnosis and Evaluation of Dilated Cardiomyopathy.

    PubMed

    Japp, Alan G; Gulati, Ankur; Cook, Stuart A; Cowie, Martin R; Prasad, Sanjay K

    2016-06-28

    Dilated cardiomyopathy (DCM) is best understood as the final common response of myocardium to diverse genetic and environmental insults. A rigorous work-up can exclude alternative causes of left ventricular (LV) dilation and dysfunction, identify etiologies that may respond to specific treatments, and guide family screening. A significant proportion of DCM cases have an underlying genetic or inflammatory basis. Measurement of LV size and ejection fraction remain central to diagnosis, risk stratification, and treatment, but other aspects of cardiac remodeling inform prognosis and carry therapeutic implications. Assessment of myocardial fibrosis predicts both risk of sudden cardiac death and likelihood of LV functional recovery, and has significant potential to guide patient selection for cardioverter-defibrillator implantation. Detailed mitral valve assessment is likely to assume increasing importance with the emergence of percutaneous interventions for functional mitral regurgitation. Detection of pre-clinical DCM could substantially reduce morbidity and mortality by allowing early instigation of cardioprotective therapy. PMID:27339497

  4. Genetics Home Reference: DMD-associated dilated cardiomyopathy

    MedlinePlus

    ... 2344-7. Review. Citation on PubMed Berko BA, Swift M. X-linked dilated cardiomyopathy. N Engl J ... Gelb B, Zhu XM, Chamberlain JS, McCabe ER, Swift M. X-linked dilated cardiomyopathy. Molecular genetic evidence ...

  5. Spontaneous Dilated Cardiomyopathy and Right-Sided Heart Failure as a Differential Diagnosis for Hepatosis Dietetica in a Production Pig

    PubMed Central

    Collins, Dalis E; Eaton, Kathryn A; Hoenerhoff, Mark J

    2015-01-01

    An experimentally naïve 37.7-kg Yorkshire-crossbred gilt died unexpectedly 2 d after arrival. Necropsy revealed severe dilated cardiomyopathy characterized grossly by markedly dilated ventricles and thinned ventricular walls and interventricular septum. Histologically there was multifocal myofiber attenuation and patchy loss of myofiber cross striations. The liver contained submassive to massive, diffuse hepatic centrilobular hemorrhage and degeneration. These lesions supported a diagnosis of dilated cardiomyopathy with right heart failure and secondary hepatic degeneration due to marked acute passive congestion. To our knowledge, this case is the first report of spontaneous dilated cardiomyopathy in swine and represents a potential diagnostic challenge regarding the differentiation of the cardiac-associated liver lesion from hepatosis dietetica. The diagnosis of dilated cardiomyopathy and right-sided heart failure was supported by the character of the hepatic lesion, absence of typical gross or histologic lesions of mulberry heart disease, and normal selenium levels. PMID:26310462

  6. An adult with a sinus venosus atrial septal defect and dilated cardiomyopathy

    PubMed Central

    Oakley, Luke; Foley, Sean; Cox, Justin; Seidensticker, Daniel

    2014-01-01

    Dilated cardiomyopathy, heart failure and atrial septal defects are well-recognised entities in isolation, but are rarely seen together. Now that 90% of children with congenital heart disease survive into adulthood, such combinations of disease are increasingly seen in adult cardiology. While most young patients with dilated cardiomyopathy respond well to medical therapy, some do not, and require more invasive management. We describe a 32 year-old man with dilated cardiomyopathy and a sinus venosus-type atrial septal defect associated with a remarkable pulmonary to systemic flow ratio of 5:1. We propose that the atrial septal defect blunted his heart failure symptoms by serving as a ‘pop-off’ valve and limiting pulmonary congestion. The patient ultimately failed medical management and received a left ventricular assist device. The case is presented along with a discussion of this unique pathophysiology and a brief review of the literature in this rapidly evolving field. PMID:24855073

  7. An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy

    PubMed Central

    Talavera, Jesús; Fernández-Del-Palacio, María Josefa; García-Nicolás, Obdulio; Seva, Juan; Brooks, Gavin; Moraleda, Jose M.

    2015-01-01

    Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality. PMID:26788502

  8. Genetics of Human and Canine Dilated Cardiomyopathy

    PubMed Central

    Simpson, Siobhan; Edwards, Jennifer; Ferguson-Mignan, Thomas F. N.; Cobb, Malcolm; Mongan, Nigel P.; Rutland, Catrin S.

    2015-01-01

    Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed. PMID:26266250

  9. Chronic respiratory illness as a predictor of survival in idiopathic dilated cardiomyopathy: the Washington, DC, Dilated Cardiomyopathy Study.

    PubMed Central

    Martin, S. A.; Coughlin, S. S.; Metayer, C.; René, A. A.; Hammond, I. W.

    1996-01-01

    Although bronchial asthma and emphysema have been associated with idiopathic dilated cardiomyopathy in case-control studies, little is known about the prognostic importance of chronic respiratory disease in idiopathic dilated cardiomyopathy. To study this, we examined history of bronchial asthma, emphysema and chronic bronchitis, and respiratory medication use as possible predictors of survival in idiopathic dilated cardiomyopathy using data from a Washington, DC, population-based study (n = 129). The cumulative survival rates among patients with a history of emphysema or chronic bronchitis were 60% and 48% at 12 and 36 months, respectively, compared with 81.8% and 67.2% among patients without emphysema or chronic bronchitis. The survival rates of idiopathic dilated cardiomyopathy patients with and without a history of bronchial asthma at the time of idiopathic dilated cardiomyopathy diagnosis were similar. In multivariate analysis using the proportional hazards model, only ventricular arrhythmias and ejection fraction were found to be statistically significant predictors of survival in idiopathic dilated cardiomyopathy. The adjusted relative risk estimate for emphysema and chronic bronchitis was close to one. Thus, the results of this population-based study do not suggest that history of chronic respiratory illness is an independent predictor of survival in idiopathic dilated cardiomyopathy. PMID:8961693

  10. Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.

    PubMed

    Ware, James S; Li, Jian; Mazaika, Erica; Yasso, Christopher M; DeSouza, Tiffany; Cappola, Thomas P; Tsai, Emily J; Hilfiker-Kleiner, Denise; Kamiya, Chizuko A; Mazzarotto, Francesco; Cook, Stuart A; Halder, Indrani; Prasad, Sanjay K; Pisarcik, Jessica; Hanley-Yanez, Karen; Alharethi, Rami; Damp, Julie; Hsich, Eileen; Elkayam, Uri; Sheppard, Richard; Kealey, Angela; Alexis, Jeffrey; Ramani, Gautam; Safirstein, Jordan; Boehmer, John; Pauly, Daniel F; Wittstein, Ilan S; Thohan, Vinay; Zucker, Mark J; Liu, Peter; Gorcsan, John; McNamara, Dennis M; Seidman, Christine E; Seidman, Jonathan G; Arany, Zoltan

    2016-01-21

    Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder. PMID:26735901

  11. Patient with Eating Disorder, Carnitine Deficiency and Dilated Cardiomyopathy.

    PubMed

    Fotino, A Domnica; Sherma, A

    2015-01-01

    Dilated cardiomyopathy is characterized by a dilated and poorly functioning left ventricle and can result from several different etiologies including ischemic, infectious, metabolic, toxins, autoimmune processes or nutritional deficiencies. Carnitine deficiency-induced cardiomyopathy (CDIM) is an uncommon cause of dilated cardiomyopathy that can go untreated if not considered. Here, we describe a 30-year-old woman with an eating disorder and recent percutaneous endoscopic gastrotomy (PEG) tube placement for weight loss admitted to the hospital for possible PEG tube infection. Carnitine level was found to be low. Transthoracic echocardiogram (TTE) revealed ejection fraction 15%. Her hospital course was complicated by sepsis from a peripherally inserted central catheter (PICC). She was discharged on a beta-blocker and carnitine supplementation. One month later her cardiac function had normalized. Carnitine deficiency-induced myopathy is an unusual cause of cardiomyopathy and should be considered in adults with decreased oral intake or malabsorption who present with cardiomyopathy. PMID:27159507

  12. Intraventricular vortex properties in nonischemic dilated cardiomyopathy

    PubMed Central

    Benito, Yolanda; Alhama, Marta; Yotti, Raquel; Martínez-Legazpi, Pablo; del Villar, Candelas Pérez; Pérez-David, Esther; González-Mansilla, Ana; Santa-Marta, Cristina; Barrio, Alicia; Fernández-Avilés, Francisco; del Álamo, Juan C.

    2014-01-01

    Vortices may have a role in optimizing the mechanical efficiency and blood mixing of the left ventricle (LV). We aimed to characterize the size, position, circulation, and kinetic energy (KE) of LV main vortex cores in patients with nonischemic dilated cardiomyopathy (NIDCM) and analyze their physiological correlates. We used digital processing of color-Doppler images to study flow evolution in 61 patients with NIDCM and 61 age-matched control subjects. Vortex features showed a characteristic biphasic temporal course during diastole. Because late filling contributed significantly to flow entrainment, vortex KE reached its maximum at the time of the peak A wave, storing 26 ± 20% of total KE delivered by inflow (range: 1–74%). Patients with NIDCM showed larger and stronger vortices than control subjects (circulation: 0.008 ± 0.007 vs. 0.006 ± 0.005 m2/s, respectively, P = 0.02; KE: 7 ± 8 vs. 5 ± 5 mJ/m, P = 0.04), even when corrected for LV size. This helped confining the filling jet in the dilated ventricle. The vortex Reynolds number was also higher in the NIDCM group. By multivariate analysis, vortex KE was related to the KE generated by inflow and to chamber short-axis diameter. In 21 patients studied head to head, Doppler measurements of circulation and KE closely correlated with phase-contract magnetic resonance values (intraclass correlation coefficient = 0.82 and 0.76, respectively). Thus, the biphasic nature of filling determines normal vortex physiology. Vortex formation is exaggerated in patients with NIDCM due to chamber remodeling, and enlarged vortices are helpful for ameliorating convective pressure losses and facilitating transport. These findings can be accurately studied using ultrasound. PMID:24414062

  13. Isolated Right Ventricular Dilated Cardiomyopathy: An Early Diagnosis

    PubMed Central

    Briongos Figuero, Sem; Acena Navarro, Alvaro

    2015-01-01

    Because of an incomplete right bundle branch block, a severe right ventricular dilatation with no left ventricular cardiomyopathy was found in a 44-year-old man. Magnetic resonance and transesophageal echocardiography confirmed the finding and these tests also failed to find any potential cause. A pulmonary hemodynamic study and a coronary angiography were strictly normal. Lastly pulmonary function tests and a pulmonary angiography were performed, which did not find any lung disease causing the right ventricular dilatation. The patient was catalogued as an early stage of an idiopathic form of right ventricular dilated cardiomyopathy. PMID:26346826

  14. X-Linked Dilated Cardiomyopathy: A Cardiospecific Phenotype of Dystrophinopathy

    PubMed Central

    Nakamura, Akinori

    2015-01-01

    X-linked dilated cardiomyopathy (XLDCM) is a distinct phenotype of dystrophinopathy characterized by preferential cardiac involvement without any overt skeletal myopathy. XLDCM is caused by mutations of the Duchenne muscular dystrophy (DMD) gene and results in lethal heart failure in individuals between 10 and 20 years. Patients with Becker muscular dystrophy, an allelic disorder, have a milder phenotype of skeletal muscle involvement compared to Duchenne muscular dystrophy (DMD) and sometimes present with dilated cardiomyopathy. The precise relationship between mutations in the DMD gene and cardiomyopathy remain unclear. However, some hypothetical mechanisms are being considered to be associated with the presence of some several dystrophin isoforms, certain reported mutations, and an unknown dystrophin-related pathophysiological mechanism. Recent therapy for Duchenne muscular dystrophy, the severe dystrophinopathy phenotype, appears promising, but the presence of XLDCM highlights the importance of focusing on cardiomyopathy while elucidating the pathomechanism and developing treatment. PMID:26066469

  15. A case of pregnancy complicated with dilated cardiomyopathy 1X

    PubMed Central

    Oki, Shinya; Nagamatsu, Takeshi; Iriyama, Takayuki; Komatsu, Atsushi; Osuga, Yutaka; Fujii, Tomoyuki

    2015-01-01

    Dilated cardiomyopathy 1X (CMD1X) is characterized by dilated cardiomyopathy (DCM) with mildest limb-girdle muscle symptoms and normal intelligence. Compound heterozygous mutation in fukutin gene is known as its genetic cause. Here, we report a pregnancy case complicated with CMD1X. A 25-year-old primiparous woman, who had been diagnosed as CMD1X at the age of 19, was referred to our hospital at 6 weeks of gestation. In early pregnancy, the evaluation of her cardiac function showed ejection fraction 47% and NYHA class II. Worsening of cardiac function was observed from 30 weeks, manifesting reduced cardiac load with left ventricular dilatation and in-hospital bed rest was necessary. Elective cesarean section was performed at 35 weeks to prevent deterioration of cardiac function. The parameters of her cardiac function returned to the pre-pregnancy status in a month after delivery, whereas she realized persistent worsening of muscular weakness at postpartum. PMID:26566449

  16. Cardiomyopathy and right-sided congestive heart failure in a red-tailed hawk (Buteo jamaicensis).

    PubMed

    Knafo, S Emmanuelle; Rapoport, Gregg; Williams, Jamie; Brainard, Benjamin; Driskell, Elizabeth; Uhl, Elizabeth; Crochik, Sonia; Divers, Stephen J

    2011-03-01

    A 15-year-old female red-tailed hawk (Buteo jamaicensis) was evaluated because of dyspnea, anorexia, and coelomic distension. Diagnostic imaging results confirmed severe coelomic effusion and revealed a markedly dilated right ventricle. The diagnosis was right-sided congestive heart failure. Results of measurements of vitamin E, selenium, lead, zinc, and cardiac troponin levels were normal or nondiagnostic. The hawk was treated with furosemide, antifungal and antimicrobial agents, and supplemental fluids and oxygen, but euthanasia was elected because of the poor prognosis and the practical difficulties associated with intensive case management. To our knowledge, this is the first described case of cardiomyopathy and congestive heart failure in a captive red-tailed hawk. PMID:21657185

  17. Linkage of familial dilated cardiomyopathy with conduction defect and muscular dystrophy to chromosome 6q23.

    PubMed Central

    Messina, D N; Speer, M C; Pericak-Vance, M A; McNally, E M

    1997-01-01

    Inherited cardiomyopathies may arise from mutations in genes that are normally expressed in both heart and skeletal muscle and therefore may be accompanied by skeletal muscle weakness. Phenotypically, patients with familial dilated cardiomyopathy (FDC) show enlargement of all four chambers of the heart and develop symptoms of congestive heart failure. Inherited cardiomyopathies may also be accompanied by cardiac conduction-system defects that affect the atrioventricular node, resulting in bradycardia. Several different chromosomal regions have been linked with the development of autosomal dominant FDC, but the gene defects in these disorders remain unknown. We now characterize an autosomal dominant disorder involving dilated cardiomyopathy, cardiac conduction-system disease, and adult-onset limb-girdle muscular dystrophy (FDC, conduction disease, and myopathy [FDC-CDM]). Genetic linkage was used to exclude regions of the genome known to be linked to dilated cardiomyopathy and muscular dystrophy phenotypes and to confirm genetic heterogeneity of these disorders. A genomewide scan identified a region on the long arm of chromosome 6 that is significantly associated with the presence of myopathy (D6S262; maximum LOD score [Z(max)] 4.99 at maximum recombination fraction [theta(max)] .00), identifying FDC-CDM as a genetically distinct disease. Haplotype analysis refined the interval containing the genetic defect, to a 3-cM interval between D6S1705 and D6S1656. This haplotype analysis excludes a number of striated muscle-expressed genes present in this region, including laminin alpha2, laminin alpha4, triadin, and phospholamban. Images Figure 2 PMID:9382102

  18. Dilated cardiomyopathy secondary to chronic cocaine abuse: a case report

    PubMed Central

    2013-01-01

    Background Cocaine is a potent sympathomimetic agent associated with the development of possible fatal cardiovascular complications. Dysrhythmias, acute myocardial infarction, hypertension and dilated cardiomyopathy are just some of many cardiovascular effects related to the abuse of cocaine. Case presentation A 38-year-old Hispanic male with a past medical history of hypertension presented with a chief complaint of progressive shortness of breath. The patient confessed to the use of cocaine for almost 18 years once per week. On examination he was hypertensive and tachycardic with a systolic murmur over the 5th intercostal space at the level of the left mid-clavicular line. Laboratory workup revealed an elevated Brain natriuretic peptide; urine toxicology was positive for cocaine. 2D-echocardiogram showed dilated cardiomyopathy. Cardiac catheterization excluded angioischemic cause. He was managed medically and subsequently discharged with drug rehabilitation. On follow-up diagnostic evaluation after 5 months of cocaine cessation, his ejection function improved significantly. Conclusion The exact incidence of cocaine related cardiomyopathy is unknown and likely underreported. The clinical course is abrupt and comparatively similar to other types of cardiomyopathy. The management is like other forms of cardiomyopathy; however β-blockers should be avoided. The myocardial dysfunction is reversible with abstaining from additional cocaine ingestion. Non-invasive testing should be performed after several months to re-evaluate the treatment response. PMID:24341463

  19. Update 2011: Clinical and Genetic Issues in Familial Dilated Cardiomyopathy

    PubMed Central

    Hershberger, Ray E.; Siegfried, Jill D.

    2011-01-01

    A great deal of progress has recently been made in the discovery and understanding of the genetics of familial dilated cardiomyopathy (FDC). A consensus has emerged that with a new diagnosis of idiopathic dilated cardiomyopathy (IDC), the clinical screening of 1st degree family members will reveal FDC in at least 20-35% of cases. Point mutations in 31 autosomal and 2 X-linked genes representing diverse gene ontogeny have been implicated in causing FDC, but account for only 30-35% of genetic cause. Next generation sequencing (NGS) methods have dramatically decreased sequencing costs, making clinical genetic testing feasible for extensive panels of DCM genes. NGS also provides opportunities to discover additional genetic cause of FDC and IDC. Guidelines for evaluation and testing of FDC and IDC are now available, and when combined with FDC genetic testing and counseling will bring FDC/IDC genetics to the forefront of cardiovascular genetic medicine. PMID:21492761

  20. Noncompaction and Dilated Cardiomyopathy in a Patient with Schizophrenia

    PubMed Central

    Stöllberger, Claudia

    2016-01-01

    Objectives. Psychosis and left ventricular hypertrabeculation (or noncompaction) (LVHT) have not been described in the same patient. Here we report a patient with a long-term history of schizophrenia who was later diagnosed with dilated cardiomyopathy (dCMP) and LVHT. Case Report. A 47-year-old Caucasian male developed nondifferentiated schizophrenia at the age of 26 y. Since the age of 33 y he was regularly drinking alcohol. At the age of 47 y he developed heart failure. Transthoracic echocardiography showed an enlarged left ventricle, reduced systolic function, and surprisingly LVHT in the apical segment. Additionally, the left atrium was enlarged, the right ventricular cavities were mildly enlarged, and there were pulmonary hypertension and a small pericardial effusion. Cardiac MRI confirmed the echocardiographic findings. Since coronary angiography was normal, dilated cardiomyopathy was additionally diagnosed. Since he was taking clozapine during years, dilated cardiomyopathy could be due to not only alcohol consumption but also the long-term neuroleptic medication. Conclusions. LVHT may be associated with nondifferentiated psychosis. Management of LVHT is challenging in patients with psychosis due to poor compliance and adherence of these patients. Patients with LVHT and psychosis need particular attention since they usually take cardiotoxic drugs for a long time, which may further deteriorate the prognosis of LVHT. PMID:27547471

  1. Four chamber pacing in dilated cardiomyopathy.

    PubMed

    Cazeau, S; Ritter, P; Bakdach, S; Lazarus, A; Limousin, M; Henao, L; Mundler, O; Daubert, J C; Mugica, J

    1994-11-01

    A 54-year-old man received a four chamber pacing system for severe congestive heart failure (NYHA functional Class IV). His ECG showed a left bundle branch block (200-msec QRS duration) with 200-msec PR interval, normal QRS axis, and 90-msec interatrial interval. An acute hemodynamic study with insertion of four temporary leads was performed prior to the implant, which demonstrated a significant increase in cardiac output and decrease of pulmonary capillary wedge pressure. A permanent pacemaker was implanted based on the encouraging results of the acute study. The right chamber leads were introduced by cephalic and subclavian approaches. The left atrium was paced with a coronary sinus lead, Medtronic SP 2188-58 model. An epicardial Medtronic 5071 lead was placed on the LV free wall. The four leads were connected to a standard bipolar DDD pacemaker, Chorus 6234. The two atrial leads were connected via a Y-connector to the atrial channel of the pacemaker with a bipolar pacing configuration. The two ventricular leads were connected in a similar fashion to the ventricular channel of the device. The right chamber leads were connected to the distal poles. The left chamber leads were connected to the proximal poles of the pacemaker. Six weeks later, the patient's clinical status improved markedly with a weight loss of 17 kg and disappearance of peripheral edema. His functional class was reduced to NYHA II. Four chamber pacing is technically feasible. In patients with evidence of interventricular dyssynchrony, this original pacing mode probably provides a mechanical activation sequence closer to the natural one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7845801

  2. Hearing Profile in Patients with Dilated and Hypertrophic Cardiomyopathies

    PubMed Central

    El-Zarea, Gehan Abd El-Rahman; Hassan, Yasser Elsayed Mohamed; Mahmoud, Ahmed Mohamed Ahmed

    2016-01-01

    Introduction Cardiomyopathy may cause disruptions in the micro-vascular system of the stria vascularis in the cochlea, and, subsequently, may result in cochlear degeneration. Degeneration in the stria vascularis affects the physical and chemical processes in the organ of Corti, thereby causing a possible hearing impairment. The objective of this study was to assess the hearing profiles of patients with dilated and hypertrophic cardiomyopathies to determine the relationship between the degree of hearing loss and the degree and duration of the disease and to compare the dilated and hypertrophic cardiomyopathies as regards hearing profile. Methods In this case control study, we studied 21 patients (cases/study group/group 1) and 15 healthy individuals (controls/group 2). Six patients (group 1a) had hypertrophic cardiomyopathy (HCM), and 15 patients (group 1b) had dilated cardiomyopathy (DCM). The data were analyzed using the t-test, chi-squared test, Kruskal-Wallis test, and the Multiple Mann-Whitney test. Results The results of this study showed that 80% of those patients with DCM (group 1b) had bilateral sensorineural hearing loss (SNHL), and 100% of the patients with HCM (group 1a) had mild to severe bilateral sloping SNHL. Distortion Product Otoacoustic Emissions (DPOAEs) were present in 14% of the study group and in 100 % of the control group. The results of the measurements of auditory brainstem response (ABR) showed that 50% of the study group had abnormal latencies compared to the control group, and there was no correlation between the duration of the disease and the degree of hearing loss or DPOAE. Fifty percent of the patients with HCM and 35% of the patients with DCM had positive family histories of similar conditions, and 35% of those with HCM had a positive family history of sudden death. Conclusion The results of this study suggested that the link between heart disease and hearing loss and early identification of hearing loss in patients with

  3. Imaging Phenotype vs. Genotype in Non-Hypertrophic Heritable Cardiomyopathies: Dilated Cardiomyopathy and Arrhythmogenic Right Ventricular Cardiomyopathy

    PubMed Central

    Raman, Subha V.; Basso, Cristina; Tandri, Harikrishna; Taylor, Matthew R. G.

    2011-01-01

    Advances in cardiovascular imaging increasingly afford unique insights into heritable myocardial disease. As clinical presentation of genetic cardiomyopathies may range from nonspecific symptoms to sudden cardiac death, accurate diagnosis has implications for individual patients as well as related family members. The initial consideration of genetic cardiomyopathy may occur in the imaging laboratory, where one must recognize the patient with arrhythmogenic right ventricular cardiomyopathy (ARVC) among the many with ventricular arrhythmia referred to define myocardial substrate. Accurate diagnosis of the patient presenting with dyspnea and palpitations whose first-degree relatives have lamin A/C cardiomyopathy may warrant genetic testing1, 2 plus imaging of diastolic function and myocardial fibrosis3. As advances in cardiac imaging afford detection of subclinical structural and functional changes, the imaging specialist must be attuned to signatures of specific genetic disorders. With increased availability of both advanced imaging as well as genotyping techniques, this review seeks to provide cardiovascular imaging specialists and clinicians with the contemporary information needed for more precise diagnosis and treatment of heritable myocardial disease. A companion paper in this series covers imaging phenotype and genotype considerations in hypertrophic cardiomyopathy (HCM). This review details clinical features, imaging phenotype and current genetic understanding for two of the most common non-HCM conditions that prompt myocardial imaging - dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). While all modalities are considered herein, considerable focus is given to CMR with its unique capabilities for myocardial tissue characterization. PMID:21081743

  4. Becker Muscular Dystrophy (BMD) caused by duplication of exons 3-6 of the dystrophin gene presenting as dilated cardiomyopathy

    SciTech Connect

    Tsai, A.C.; Allingham-Hawkins, D.J.; Becker, L.

    1994-09-01

    X-linked dilated cardiomyopathy (XLCM) is a progressive myocardial disease presenting with congestive heart failure in teenage males without clinical signs of skeletal myopathy. Tight linkage of XLCM to the DMD locus has been demonstrated; it has been suggested that, at least in some families, XLCM is a {open_quotes}dystrophinopathy.{close_quotes} We report a 14-year-old boy who presented with acute heart failure due to dilated cardiomyopathy. He had no history of muscle weakness, but physical examination revealed pseudohypertrophy of the calf muscles. He subsequently received a heart transplantation. Family history was negative. Serum CK level at the time of diagnosis was 10,416. Myocardial biopsy showed no evidence of carditis. Dystrophin staining of cardiac and skeletal muscle with anti-sera to COOH and NH{sub 2}termini showed a patchy distribution of positivity suggestive of Becker muscular dystrophy. Analysis of 18 of the 79 dystrophin exons detected a duplication that included exons 3-6. The proband`s mother has an elevated serum CK and was confirmed to be a carrier of the same duplication. A mutation in the muscle promotor region of the dystrophin gene has been implicated in the etiology of SLCM. However, Towbin et al. (1991) argued that other 5{prime} mutations in the dystrophin gene could cause selective cardiomyopathy. The findings in our patient support the latter hypothesis. This suggests that there are multiple regions in the dystrophin gene which, when disrupted, can cause isolated dilated cardiomyopathy.

  5. Clinical management of dilated cardiomyopathy: current knowledge and future perspectives.

    PubMed

    Merlo, Marco; Cannatá, Antonio; Vitagliano, Alice; Zambon, Elena; Lardieri, Gerardina; Sinagra, Gianfranco

    2016-01-01

    Dilated cardiomyopathy (DCM) is a primary heart muscle disease characterized by a progressive dilation and dysfunction of either the left or both ventricles. The management of DCM is currently challenging for clinicians. The persistent lack of knowledge about the etiology and pathophysiology of this disease continues to determine important fields of uncertainty in managing this condition. Molecular cardiology and genetics currently represent the most crucial horizon of increasing knowledge. Understanding the mechanisms underlying the disease allows clinicians to treat this disease more effectively and to further improve outcomes of DCM patients through advancements in etiologic characterization, prognostic stratification and individualized therapy. Left ventricular reverse remodeling predicts a lower rate of major cardiac adverse events independently from other factors. Optimized medical treatment and device implantation are pivotal in inducing left ventricular reverse remodeling. Newly identified targets, such as angiotensin-neprilysin inhibition, phosphodiesterase inhibition and calcium sensitizing are important in improving prognosis in patients affected by DCM. PMID:26606394

  6. Characteristic adaptations of the extracellular matrix in dilated cardiomyopathy.

    PubMed

    Louzao-Martinez, Laura; Vink, Aryan; Harakalova, Magdalena; Asselbergs, Folkert W; Verhaar, Marianne C; Cheng, Caroline

    2016-10-01

    Dilated cardiomyopathy (DCM) is a relatively common heart muscle disease characterized by the dilation and thinning of the left ventricle accompanied with left ventricular systolic dysfunction. Myocardial fibrosis is a major feature in DCM and therefore it is inevitable that corresponding extracellular matrix (ECM) changes are involved in DCM onset and progression. Increasing our understanding of how ECM adaptations are involved in DCM could be important for the development of future interventions. This review article discusses the molecular adaptations in ECM composition and structure that have been reported in both animal and human studies of DCM. Furthermore, we provide a transcriptome-based catalogue of ECM genes that are associated with DCM, generated by using NCBI Gene Expression Omnibus database sets for DCM. Based on this in silico analysis, many novel ECM components involved in DCM are identified and discussed in this review. With the information gathered, we propose putative pathways of ECM adaptations in onset and progression of DCM. PMID:27391006

  7. Therapeutic Role of Mobilized Bone Marrow Cells in Children with Nonischemic Dilated Cardiomyopathy

    PubMed Central

    Habeeb, Nevin M.; Youssef, Omneya I.; El Hadidi, Eman S.

    2012-01-01

    Dilated cardiomyopathy is an important cause of congestive cardiac failure in infants and children. Mobilizing hematopoietic progenitor cells is a promising intervention to this deadly disease. Aim. Evaluate granulocyte colony stimulating factor (GCSF) as therapeutic modality in children with idiopathic dilated cardiomyopathy (IDCM). Subjects and Methods. This case-control prospective study was conducted on 20 children with IDCM following up at Cardiology Clinic Children's Hospital, Ain Shams University (group 1) who were compared to another 10 age-, sex-, duration-of-illness-, and systolic-function-matched children with IDCM as control (group 2). They were subjected to history taking, clinical examination, echocardiography, and peripheral blood CD34+ cell assessment before and one week after GCSF intake for 5 consecutive days (by group 1 but not group 2). Results. A significant improvement in echocardiographic data and CD34+-T-cell increase was found in group 1 one week after GCSF intake and for the next 6 months CD34+ T cells percentage of change showed no significant correlation with the that of the left ventricular dimensions and systolic function. Conclusion. Administration of GCSF to children with IDCM resulted in clinical and echocardiographic improvement not correlated to mobilized CD34+ T cells, implying involvement of additional mechanisms over simple stem cell mobilization. PMID:23150834

  8. Viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management

    PubMed Central

    Kearney, M; Cotton, J; Richardson, P; Shah, A

    2001-01-01

    Viral infection of the heart is relatively common and usually of little consequence. It can, however, lead to substantial cardiac damage and severe acute heart failure. It can also evolve into the progressive syndrome of chronic heart failure. Recent studies have gone some way towards unravelling the complex mechanisms underlying the heart muscle damage that occurs after viral infection. These studies have lent support to both immune and viral mediated (independent of an immune response) cardiac damage. Acute myocarditis can present in various ways, and it may be a cause of sudden death in an otherwise healthy young adult. New treatments for viral heart disease are awaited. In the meanwhile, the haemodynamic support of patients with acute left ventricular failure caused by myocarditis should be aggressive, to allow for the possibility of spontaneous recovery. Contemporary trials of treatment in chronic heart failure secondary to dilated cardiomyopathy support the use of angiotensin converting enzyme inhibitors, β adrenoceptor blockers, and spironolactone in such patients.


Keywords: myocarditis; heart failure; coxsackie B virus; dilated cardiomyopathy PMID:11123385

  9. Severe heart failure, dilated cardiomyopathy and pulmonary haemosiderosis in coeliac disease: report of two cases.

    PubMed

    Poddar, Banani; Shava, Upender; Srivastava, Anshu; Kapoor, Aditya

    2014-05-01

    Coeliac disease (CD) is a chronic inflammatory, multi-system disorder with protean manifestations which has been linked to various auto-immune-mediated disorders. Dilated cardiomyopathy (DCM) is a rare extra-intestinal manifestation that is being recognised increasingly in patients with CD. Two cases of CD are described, an 18-year-old boy and a 13-year-old girl, both of whom presented with rapid onset of congestive heart failure and severe left ventricular systolic dysfunction. Upper limb venous thrombosis and recurrent haemoptysis secondary to pulmonary haemosiderosis in the second case were the other unusual features. The importance of CD screening of patients with DCM and pulmonary haemosiderosis is emphasised. PMID:24090525

  10. Molecular profiling of dilated cardiomyopathy that progresses to heart failure

    PubMed Central

    Wakimoto, Hiroko; Gorham, Joshua M.; Conner, David A.; Christodoulou, Danos C.; Parfenov, Michael G.; DePalma, Steve R.; Eminaga, Seda; Konno, Tetsuo; Seidman, Jonathan G.; Seidman, Christine E.

    2016-01-01

    Dilated cardiomyopathy (DCM) is defined by progressive functional and structural changes. We performed RNA-seq at different stages of disease to define molecular signaling in the progression from pre-DCM hearts to DCM and overt heart failure (HF) using a genetic model of DCM (phospholamban missense mutation, PLNR9C/+). Pre-DCM hearts were phenotypically normal yet displayed proliferation of nonmyocytes (59% relative increase vs. WT, P = 8 × 10−4) and activation of proinflammatory signaling with notable cardiomyocyte-specific induction of a subset of profibrotic cytokines including TGFβ2 and TGFβ3. These changes progressed through DCM and HF, resulting in substantial fibrosis (17.6% of left ventricle [LV] vs. WT, P = 6 × 10−33). Cardiomyocytes displayed a marked shift in metabolic gene transcription: downregulation of aerobic respiration and subsequent upregulation of glucose utilization, changes coincident with attenuated expression of PPARα and PPARγ coactivators -1α (PGC1α) and -1β, and increased expression of the metabolic regulator T-box transcription factor 15 (Tbx15). Comparing DCM transcriptional profiles with those in hypertrophic cardiomyopathy (HCM) revealed similar and distinct molecular mechanisms. Our data suggest that cardiomyocyte-specific cytokine expression, early fibroblast activation, and the shift in metabolic gene expression are hallmarks of cardiomyopathy progression. Notably, key components of these profibrotic and metabolic networks were disease specific and distinguish DCM from HCM. PMID:27239561

  11. Absence of viral nucleic acids in early and late dilated cardiomyopathy

    PubMed Central

    Mahon, N; Zal, B; Arno, G; Risley, P; Pinto-Basto, J; McKenna, W; Davies, M; Baboonian, C

    2001-01-01

    OBJECTIVE—To investigate whether viral infection acts as a trigger factor for the development of dilated cardiomyopathy in genetically predisposed individuals with a family history of disease.
SETTING—Patients attending the cardiomyopathy unit in a cardiac tertiary referral centre.
DESIGN—Nested polymerase chain reaction (nPCR) was used to determine whether enteroviral, adenoviral, or cytomegaloviral nucleic acids were detectable in the myocardium of 19 asymptomatic relatives of patients with dilated cardiomyopathy; all these relatives had echocardiographic abnormalities thought to represent early disease. Explanted hearts from patients with end stage dilated cardiomyopathy were also studied and were compared with 25 controls (ischaemic heart disease (21), valvar heart disease (2), hypertrophic cardiomyopathy (1), restrictive cardiomyopathy (1)). Myocardial tissue from two fatal cases of culture positive coxsackie myocarditis was used as a positive control.
RESULTS—No viral nucleic acid was detected in any group other than in those with myocarditis. Spiking of random wells with purified recombinant viral nucleic acids confirmed the sensitivity and reproducibility of the assays.
CONCLUSIONS—Myocardial viral infection is not detectable in relatives of patients with dilated cardiomyopathy who are suspected of having early disease. There is no evidence that viruses act as a trigger factor for initiating the dilated cardiomyopathy in these patients.


Keywords: viral infection; dilated cardiomyopathy PMID:11711469

  12. [Right ventricular dysplasia and dilated cardiomyopathy observed by radionuclide images].

    PubMed

    Takamura, I; Ando, J; Miyamoto, A; Kobayashi, T; Sakamoto, S; Yasuda, H

    1985-12-01

    Four cases of right ventricular dysplasia (RVD) and 28 cases of dilated cardiomyopathy (DCM) were studied. RVD was characterized clinically by syncope, sustained recurrent ventricular tachycardia with left bundle branch block patterns on the surface electrocardiogram, and right heart failure. Furthermore, moderate to severe dilatation of the right ventricle and depressed right ventricular function were apparent on radionuclide angiography. However, left ventricular dilatation and depressed left ventricular function were documented in DCM. Right ventricular volume was proportional to left ventricular volume in DCM, however, right ventricular volume was disproportionately greater in RVD. On the T1-201 perfusion image, left ventricular perfusion defects were delineated in 10 of 26 patients with DCM, and in one of four RVD patients. During two to eight year follow-up periods, six patients died suddenly five of whom had left ventricular perfusion defects. However, in 19 patients without left ventricular perfusion defects, only one sudden death was observed. A connecting link between sudden death and left ventricular perfusion defect is suggested. PMID:3841888

  13. [Microvolt T-wave alternans. Ischemic vs. nonischemic dilated cardiomyopathy].

    PubMed

    Klingenheben, Thomas

    2015-03-01

    The use of implantable cardioverter defibrillators (ICD) for primary preventive therapy of sudden arrhythmogenic death has become a mainstay in selected patients with systolic congestive heart failure, particularly in the setting of ischemic and nonischemic cardiomyopathy (Moss et al., N Engl J Med 346:877–883, 2002; Bardy et al., N Engl J Med 352:225–237, 2005). However, more accurate identification of high-risk patients is desirable in order to avoid unnecessary ICD implants. Since currently available risk stratification methods have limited predictive accuracy, development of new techniques is important in order to noninvasively assess arrhythmogenic risk in patients prone to sudden death.Microvolt level T-wave alternans (mTWA) has recently been proposed to assess abnormalities in ventricular repolarization favoring the occurrence of reentrant arrhythmias (Adam et al., J Electrocardiol 17:209–218, 1984; Pastore et al., Circulation 99:1385–1394, 1999). In 1994, a preliminary clinical study by Rosenbaum et al. convincingly demonstrated that mTWA is closely related to arrhythmia induction in the electrophysiology laboratory as well as to the occurrence of spontaneous ventricular tachyarrhythmias during follow-up (Rosenbaum et al., N Engl J Med 330:235–241,1994). More recently, a number of clinical studies have examined its clinical applicability in ischemic and nonischemic cardiomyopathy. PMID:25693483

  14. Dilated aortic root and severe aortic regurgitation causing dilated cardiomyopathy in classic Ehlers-Danlos syndrome.

    PubMed

    Zainal, Abir; Hamad, Mahmoud Nidal; Naqvi, Syed Yaseen

    2016-01-01

    Ehlers-Danlos syndrome (EDS) is a group of heritable disorders characterised by vast clinical heterogeneity ranging from the classic constellation of symptoms including skin hyperextensibility, joint hypermobility and skin fragility to the exceedingly critical consequences of arterial rupture and visceral perforation. We describe the case of a 65-year-old male with a history of classic EDS who reported of dyspnoea on exertion, orthopnoea, fatigue and palpitations. He was found to have dilated cardiomyopathy with an ejection fraction of 35%, aortic root dilation and severe aortic valve regurgitation. The authors intend to draw attention to the rare cardiac manifestations of this condition and the therapeutic challenges involved in managing such patients. PMID:27413024

  15. Hypothyroid heart: myxoedema as a cause of reversible dilated cardiomyopathy.

    PubMed

    Madan, Nidhi; Tiwari, Nidhish; Stampfer, Morris; Schubart, Ulrich

    2015-01-01

    Hypothyroidism may cause several cardiac manifestations including conduction abnormalities, pericardial effusion, decreased myocardial contractility and accelerated coronary atherosclerosis. Although cardiac output is reduced in hypothyroidism, frank heart failure (HF) is relatively rare because of the low peripheral oxygen demand. Several mechanisms have been postulated in hypothyroid-induced HF, including genomic as well as non-genomic actions of thyroid hormone. Dilated cardiomyopathy (DCM) of other aetiologies is usually progressive, and is associated with significant morbidity and mortality. We report a case of DCM associated with severe hypothyroidism with marked improvement on restoration of euthyroid state. Our case is unique in that the patient had no known risk factors for cardiac disease and experienced marked improvement despite being on minimal doses of HF medications, illustrating the relationship between hypothyroidism and development of left ventricular dysfunction, and its reversible nature with restoration of euthyroid status. PMID:26468223

  16. Diagnosis, prevalence, and screening of familial dilated cardiomyopathy

    PubMed Central

    Sweet, Mary; Taylor, Matthew R.G.; Mestroni, Luisa

    2016-01-01

    Introduction Dilated cardiomyopathy (DCM) is the most common cardiomyopathy and occurs often in families. As an inherited disease, understanding the significance of diagnostic procedures and genetic screening within families is of utmost importance. Areas covered Genetic studies have shown that in 30–40% of familial DCM (FDC) cases a causative genetic mutation can be identified. Successful genetic analysis is highly dependent on close examination of patient and family history, and clinical guidelines exist recommending genetic testing to aid in the evaluation of family members at risk of developing FDC. Clinical genetic testing offers a resource for families to identify the etiology of their disease, and in some cases may provide clinical prognostic insight. Expert Opinion As an inherited disease, future FCD studies will focus on elucidating the remaining 60–70% of genetic causes in inherited cases and the pathogenic mechanisms leading to the phenotype. Specifically, a focus on regulatory regions, copy number variation, genetic and environmental modifiers and functional confirmatory investigations will be essential.

  17. Relevance of truncating titin mutations in dilated cardiomyopathy.

    PubMed

    Akinrinade, O; Alastalo, T-P; Koskenvuo, J W

    2016-07-01

    Dilated cardiomyopathy (DCM), a genetically heterogeneous cardiac disease characterized by left ventricular dilatation and systolic dysfunction, is caused majorly by truncations of titin (TTN), especially in A-band region. Clinical interpretation of TTN-truncating variants (TTNtv) has been challenged by the existing inaccurate variant assessment strategies and uncertainty in the true frequency of TTNtv across the general population. We aggregated TTNtv identified in 1788 DCM patients and compared the variants with those reported in over 60,000 Exome Aggregation Consortium reference population. We implemented our current variant assessment strategy that prioritizes TTNtv affecting all transcripts of the gene, and observed a decline in the prevalence of TTNtv in DCM. Despite this decline, TTNtv are more prevalent in DCM patients compared with reference population (p = 4.1 × 10(-295) ). Moreover, our extended analyses confirmed the enrichment of TTNtv not only in the A-band but also in the I/A-band junction of TTN. We estimated the probability of pathogenicity of TTNtv affecting all transcripts of TTN, identified in unselected DCM patients to be 97.8% (likelihood ratio (LR) = 42.2). We emphasize that identifying a TTNtv, especially in the A-band region, has a higher risk of being disease-causing than previously anticipated, and recommend prioritizing TTNtv affecting at least five transcripts of the gene. PMID:26777568

  18. Dilated cardiomyopathy with Graves disease in a young child.

    PubMed

    Choi, Yu Jung; Jang, Jun Ho; Park, So Hyun; Oh, Jin-Hee; Koh, Dae Kyun

    2016-06-01

    Graves disease (GD) can lead to complications such as cardiac arrhythmia and heart failure. Although dilated cardiomyopathy (DCMP) has been occasionally reported in adults with GD, it is rare in children. We present the case of a 32-month-old boy with DCMP due to GD. He presented with irritability, vomiting, and diarrhea. He also had a history of weight loss over the past few months. On physical examination, he had tachycardia without fever, a mild diffuse goiter, and hepatomegaly. The chest radiograph showed cardiomegaly with pulmonary edema, while the echocardiography revealed a dilated left ventricle with an ejection fraction (EF) of 28%. The thyroid function test (TFT) showed elevated serum T3 and decreased thyroid stimulating hormone (TSH) levels. The TSH receptor autoantibody titer was elevated. He was diagnosed with DCMP with GD; treatment with methylprednisolone, diuretics, inotropics, and methimazole was initiated. The EF improved after the TFT normalized. At follow-up several months later, although the TFT results again showed evidence of hyperthyroidism, his EF had not deteriorated. His cardiac function continues to remain normal 1.5 months after treatment was started, although he still has elevated T3 and high TSH receptor antibody titer levels due to poor compliance with drug therapy. To summarize, we report a young child with GD-induced DCMP who recovered completely with medical therapy and, even though the hyperthyroidism recurred several months later, there was no relapse of the DCMP. PMID:27462586

  19. Dilated cardiomyopathy with Graves disease in a young child

    PubMed Central

    Choi, Yu Jung; Jang, Jun Ho; Oh, Jin-Hee; Koh, Dae Kyun

    2016-01-01

    Graves disease (GD) can lead to complications such as cardiac arrhythmia and heart failure. Although dilated cardiomyopathy (DCMP) has been occasionally reported in adults with GD, it is rare in children. We present the case of a 32-month-old boy with DCMP due to GD. He presented with irritability, vomiting, and diarrhea. He also had a history of weight loss over the past few months. On physical examination, he had tachycardia without fever, a mild diffuse goiter, and hepatomegaly. The chest radiograph showed cardiomegaly with pulmonary edema, while the echocardiography revealed a dilated left ventricle with an ejection fraction (EF) of 28%. The thyroid function test (TFT) showed elevated serum T3 and decreased thyroid stimulating hormone (TSH) levels. The TSH receptor autoantibody titer was elevated. He was diagnosed with DCMP with GD; treatment with methylprednisolone, diuretics, inotropics, and methimazole was initiated. The EF improved after the TFT normalized. At follow-up several months later, although the TFT results again showed evidence of hyperthyroidism, his EF had not deteriorated. His cardiac function continues to remain normal 1.5 months after treatment was started, although he still has elevated T3 and high TSH receptor antibody titer levels due to poor compliance with drug therapy. To summarize, we report a young child with GD-induced DCMP who recovered completely with medical therapy and, even though the hyperthyroidism recurred several months later, there was no relapse of the DCMP. PMID:27462586

  20. A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher.

    PubMed

    Meurs, Kathryn M; Lahmers, Sunshine; Keene, Bruce W; White, Stephen N; Oyama, Mark A; Mauceli, Evan; Lindblad-Toh, Kerstin

    2012-08-01

    Familial dilated cardiomyopathy is a primary myocardial disease that can result in the development of congestive heart failure and sudden cardiac death. Spontaneous animal models of familial dilated cardiomyopathy exist and the Doberman pinscher dog is one of the most commonly reported canine breeds. The objective of this study was to evaluate familial dilated cardiomyopathy in the Doberman pinscher dog using a genome-wide association study for a genetic alteration(s) associated with the development of this disease in this canine model. Genome-wide association analysis identified an area of statistical significance on canine chromosome 14 (p(raw) = 9.999e-05 corrected for genome-wide significance), fine-mapping of additional SNPs flanking this region localized a signal to 23,774,190-23,781,919 (p = 0.001) and DNA sequencing identified a 16-base pair deletion in the 5' donor splice site of intron 10 of the pyruvate dehydrogenase kinase 4 gene in affected dogs (p < 0.0001). Electron microscopy of myocardium from affected dogs demonstrated disorganization of the Z line, mild to moderate T tubule and sarcoplasmic reticulum dilation, marked pleomorphic mitochondrial alterations with megamitochondria, scattered mitochondria with whorling and vacuolization and mild aggregates of lipofuscin granules. In conclusion, we report the identification of a splice site deletion in the PDK4 gene that is associated with the development of familial dilated cardiomyopathy in the Doberman pinscher dog. PMID:22447147

  1. Beneficial effects of long-term beta-blockade in congestive cardiomyopathy.

    PubMed Central

    Swedberg, K; Hjalmarson, A; Waagstein, F; Wallentin, I

    1980-01-01

    Twenty-eight patients with heart failure caused by congestive cardiomyopathy, which had been diagnosed according to the criteria of Goodwin and Oakley, were treated with beta-blocking agents for six to 62 months, except for four patients who died within two months. Repeated non-invasive investigations were performed before and during treatment as well as exercise tests and chest x-rays. The echocardiographic and pulse curve findings indicated an improvement in systolic and diastolic myocardial function. The ejection fraction increased from 0.32 +/- 0.02 to 0.42 +/- 0.04, and the third heart sound amplitude and rapid filling wave were significantly reduced. The functional classification improved in 15 patients while in 12 patients it remained unchanged and in one it deteriorated. During follow-up, 10 patients died, most of them suddenly. The mortality was lower than expected in this severely ill group of patients. The beneficial effect of chronic beta-blockade in patients with congestive cardiomyopathy suggests that catecholamines are involved in the pathogenesis of congestive cardiomyopathy, and that patients with congestive cardiomyopathy may have inappropriate sympathetic cardiac stimulation which can be reduced by chronic beta-blockade. It is suggested that beta-receptor blockade should be added to conventional treatment with digitalis and diuretics in all patients with severe myocardial failure caused by congestive cardiomyopathy. PMID:6107090

  2. Syncope secondary to transient atrioventricular block in a German shepherd dog with dilated cardiomyopathy and atrial fibrillation.

    PubMed

    Billen, Frédéric; Van Israël, Nicole

    2006-05-01

    This case report describes transient atrioventricular block as the etiology for syncopal events in a 6-year-old male German shepherd dog with atrial fibrillation and dilated cardiomyopathy. The arrhythmia diagnosis was obtained via Holter monitoring. Medical treatment with a sustained-release preparation of theophylline, as an additive to the standard congestive heart failure treatment (benazepril, furosemide and pimobendan) may have contributed to temporary remission of the syncopal events. However, the congestive heart failure progressed and the dog was euthanized. Veterinarians should be aware of the possibility of transient atrioventricular block causing syncope in dogs with DCM and AF and should be careful in empirically lowering the ventricular response rate if these dogs present with syncopal episodes. PMID:19083338

  3. Contemporary Outcome in Patients With Idiopathic Dilated Cardiomyopathy.

    PubMed

    Broch, Kaspar; Murbræch, Klaus; Andreassen, Arne Kristian; Hopp, Einar; Aakhus, Svend; Gullestad, Lars

    2015-09-15

    Outcome is better in patients with idiopathic dilated cardiomyopathy (IDC) than in ischemic heart failure (HF), but morbidity and mortality are nevertheless presumed to be substantial. Most data on the prognosis in IDC stem from research performed before the widespread use of current evidence-based treatment, including implantable devices. We report outcome data from a cohort of patients with IDC treated according to current HF guidelines and compare our results with previous figures: 102 consecutive patients referred to our tertiary care hospital with idiopathic IDC and a left ventricular ejection fraction <40% were included in a prospective cohort study. After extensive baseline work-up, follow-up was performed after 6 and 13 months. Vital status and heart transplantation were recorded. Over the first year of follow-up, the patients were on optimal pharmacological treatment, and 24 patients received implantable devices. Left ventricular ejection fraction increased from 26 ± 10% to 41 ± 11%, peak oxygen consumption increased from 19.5 ± 7.1 to 23.4 ± 7.8 ml/kg/min, and functional class improved substantially (all p values <0.001). After a median follow-up of 3.6 years, 4 patients were dead, and heart transplantation had been performed in 9 patients. According to our literature search, survival in patients with IDC has improved substantially over the last decades. In conclusion, patients with IDC have a better outcome than previously reported when treated according to current guidelines. PMID:26233575

  4. Genetics and genetic testing of dilated cardiomyopathy: a new perspective.

    PubMed

    Mestroni, Luisa; Taylor, Matthew R G

    2013-01-01

    The completion of the Human Genome Project was a landmark achievement, but as clinical genetic testing becomes more mainstream, the extent of remarkable genetic variation is increasingly being appreciated. Newer DNA sequencing technology can now complete the sequencing of an entire human genome several times over in a matter of days, but this will undoubtedly add new challenges to the difficulty of distinguishing true pathogenic variants from benign variants in diagnostic genetics and in the research setting. The recent discovery of the role of titin gene (TTN) mutations in dilated cardiomyopathy (DCM) will make genetic testing in this disease more efficient. Furthermore, better understanding of genotype-phenotype associations will assist clinicians in identifying early stages of disease and providing more appropriate treatments. This high level of complexity requires an expert genetic team to offer counseling and to manage, deliver, and follow-up over time the results of genetic testing, which is particularly important for screening of family members potentially at risk. In DCM, genetic testing may be useful for the identification of non-carriers and asymptomatic carriers, as well as for prevention strategies, sport recommendations, and defibrillator implantation. It can also guide reproductive decision-making including utilization of pre-implantation genetic diagnostic strategies. PMID:23375013

  5. Deception in simplicity: hereditary phospholamban mutations in dilated cardiomyopathy.

    PubMed

    Young, Howard S; Ceholski, Delaine K; Trieber, Catharine A

    2015-02-01

    The sarcoplasmic reticulum (SR) calcium pump (SERCA) and its regulator phospholamban are required for cardiovascular function. Phospholamban alters the apparent calcium affinity of SERCA in a process that is modulated by phosphorylation via the β-adrenergic pathway. This regulatory axis allows for the dynamic control of SR calcium stores and cardiac contractility. Herein we focus on hereditary mutants of phospholamban that are associated with heart failure, such as Arg(9)-Cys, Arg(9)-Leu, Arg(9)-His, and Arg(14)-deletion. Each mutant has a distinct effect on PLN function and SR calcium homeostasis. Arg(9)-Cys and Arg(9)-Leu do not inhibit SERCA, Arg(14)-deletion is a partial inhibitor, and Arg(9)-His is comparable to wild-type. While the mutants have distinct functional effects on SERCA, they have in common that they cannot be phosphorylated by protein kinase A (PKA). Arg(9) and Arg(14) are required for PKA recognition and phosphorylation of PLN. Thus, mutations at these positions eliminate β-adrenergic control and dynamic cardiac contractility. Hydrophobic mutations of Arg(9) cause more complex changes in function, including loss of PLN function and dominant negative interaction with SERCA in heterozygous individuals. In addition, aberrant interaction with PKA may prevent phosphorylation of wild-type PLN and sequester PKA from other local subcellular targets. Herein we consider what is known about each mutant and how the synergistic changes in SR calcium homeostasis lead to impaired cardiac contractility and dilated cardiomyopathy. PMID:25563649

  6. QT variability improves risk stratification in patients with dilated cardiomyopathy.

    PubMed

    Fischer, C; Seeck, A; Schroeder, R; Goernig, M; Schirdewan, A; Figulla, H R; Baumert, M; Voss, A

    2015-04-01

    Recently it could be demonstrated that systolic and diastolic blood pressure variability (BPV) as well as segmented Poincare plot analysis (SPPA) contribute to risk stratification in patients suffering from dilated cardiomyopathy (DCM). The aim of this study was to improve the risk stratification applying a multivariate technique including QT variability (QTV). We enrolled and significantly separated 56 low risk and 13 high risk DCM patients by nearly all applied BPV and QTV methods, but not with traditional heart rate variability analysis. The optimum set of two indices calculating the multivariate discriminate analysis (DA) included one BPV index calculated by symbolic dynamics method (DBP(Shannon)) and one index calculated from QTV (QTV(log)) achieving an area under the receiver operating characteristics curve (AUC) of 92%, sensitivity of 92.3% and specificity of 89.3%. Performing only electrocardiogram analysis, the optimum multivariate approach including indices from segmented Poincaré plot analysis and QTV still achieved a remarkable AUC of 88.3%. Increasing the number of indices for multivariate DA up to three, we achieved an AUC of 95.7%, sensitivity of 100% and specificity of 85.7% including one clinical, one BPV and one QTV index. Summarizing, we identified DCM patients with an increased risk of sudden cardiac death applying QTV analysis in a multivariate approach. PMID:25799313

  7. [Studies on the genetic susceptibility to dilated cardiomyopathy].

    PubMed

    Li, Y Y; Zhang, J N; Ma, W Z

    1993-01-01

    HLA-DQB1,-DRB1 genes of 27 Chinese patients with dilated cardiomyopathy (DCM), 7 high risk individuals in a DCM kindred and 17 normal control subjects were analysed with the use of restriction fragment length polymorphisms (RFLP) with full length DQB1 and DRB1 cDNA probes according to the standard and nomenclature of the Xth International Histocompatibility Workshop. The resulting restriction patterns allowed genotyping of HLA-DR and HLA-DQw. D-DQw8 frequency increased significantly in patients with DCM as compared with that of the controls (P < 0.05). D-DQw4 also increased in patients although no statistical significance was shown when Chi-square value was corrected with Yate's correction, whereas D-DQw5 overrepresented in controls (P < 0.05). Over half of the high risk individuals (4/7) in the familial DCM kindred carry D-DQw8 and D-DQw4. These results support the hypothesis that HLA class II genes were associated with an increased risk for DCM, HLA-DQB rather than -DRB may confer genetic susceptibility to DCM. PMID:8104770

  8. Celiac disease prevalence in Brazilian dilated cardiomyopathy patients.

    PubMed

    De Bem, Ricardo Schmit T; Da Ro Sa Utiyama, Shirley Ramos; Nisihara, Renato Mitsunori; Fortunato, Jerônimo Antônio; Tondo, Josué Augusto; Carmes, Eliane Ribeiro; Souza, Raquel Almada E; Pisani, Julio César; Amarante, Heda Maria Barska Dos Santos

    2006-05-01

    Celiac disease (CD) is a permanent condition of gluten intolerance and a number of autoimmune diseases have been associated with it. In the past few years, a relation between CD and dilated cardiomyopathy (CM) was described in Europe and United States. The aim of this study was to evaluate the prevalence of CD among south Brazilian precardiac transplant patients with advanced CM. A total of 74 patients on a list for heart transplantation were evaluated for the presence CD. The presence of anti-endomisial antibody (IgA-EmA) was determined by indirect immunofluorescence and for the anti-transglutaminase antibody (IgA anti-h-tTG) by ELISA. Serologically positive patients were submitted to upper endoscopy with intestinal biopsy. Two individuals (2.63%) were positive for IgA-EmA and 5 (6.75%) for IgA anti-h-tTG; 1 (1.35%) had both tests positive. Histologic confirmation of CD occurred only in the IgA-EmA positive patients. In conclusion, data from the present study allows recommend the screening for CD in patients with CM using IgA-EmA test as the method of choice. PMID:16758314

  9. Prevalence of Celiac Disease in Children with Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Zahmatkeshan, Mozhgan; Fallahpoor, Mahsa; Amoozgar, Hamid

    2014-01-01

    Objective: This study aimed to evaluate the prevalence of celiac disease (CD) in the patients with dilated cardiomyopathy (DCM). Simultaneous presentation of these two diseases has been recently reported in some studies; however, few researches have been done on children. The sooner CD is diagnosed, the better the prognosis will be, especially in the patients with a chronic disease like DCM. Methods: In this study, 82 cases were screened for CD by measuring the level of anti-body against transglutaminase (anti tTG). These cases included 41 patients with DCM labeled according to clinical evaluation and echocardiography and 41 healthy children who had been referred for routine checkup. All the patients were between 1 and 18 years old. The expired patients and those with previous diagnosis of CD were excluded from the study. Besides, the patients with positive antibody results underwent intestinal biopsy to match the serology findings with histopathology of CD in the intestine. Finally, the data were analyzed by the SPSS statistical software (v. 16) and through t-test and Pearson correlation coefficient. Findings: According to the findings, 1/41 (2.5%) DCM cases had positive tTG antibody level and negative intestinal biopsy which is classified as potential CD in the children with DCM. In addition, 7/41 (17%) patients had borderline anti body level. A direct correlation was observed between age and anti tTG level. Conclusion: It is beneficial to assess CD in DCM children with unknown cause. PMID:25793066

  10. Dilated cardiomyopathy and acute liver injury associated with combined use of ephedra, gamma-hydroxybutyrate, and anabolic steroids.

    PubMed

    Clark, Brychan M; Schofield, Richard S

    2005-05-01

    Anabolic-androgenic steroids are synthetic derivatives of testosterone that some athletes have used to enhance muscle mass and improve their athletic performance. Ephedrine is a potent sympathomimetic agent that can lead to cardiomyopathy similar to that seen with catecholamine excess. Adverse cardiovascular events attributed to anabolic steroid and ephedra use, such as arrhythmias, myocardial infarction, cardiomyopathy, and sudden death, are rarely reported. Bodybuilders have used gamma-hydroxybutyrate, a potent secretagogue of growth hormone, to promote muscle development. Although dilated cardiomyopathy is a known complication of excess growth hormone levels, it has not been associated with use of gamma-hydroxybutyrate. A healthy 40-year-old man was admitted to our hospital for new-onset congestive heart failure and severe acute hepatitis that developed several months after he began using anabolic-androgenic steroids, ephedra, and gamma-hydroxybutyrate supplements. Analysis with an objective causality assessment scale revealed a probable adverse drug reaction between the patient's use of anabolic steroids, ephedra, and gamma-hydroxybutyrate and the development of his cardiomyopathy and acute liver injury. PMID:15899737

  11. Sustained left ventricular diastolic dysfunction after exercise in patients with dilated cardiomyopathy

    PubMed Central

    Morikawa, M; Sato, H; Sato, H; Koretsune, Y; Ohnishi, Y; Kurotobi, T; Kuzuya, T; Hori, M

    1998-01-01

    Objective—To investigate the recovery process of exercise induced diastolic dysfunction in heart failure, using Doppler echocardiographic techniques.
Design and patients—Transmitral flow velocity profiles and standard non-invasive haemodynamic indices were obtained serially over seven days after symptom limited bicycle exercise tests in 18 patients with dilated cardiomyopathy and eight normal subjects. In three patients with cardiomyopathy we also measured the pulmonary capillary wedge pressure for 24 hours after exercise.
Results—The intensity of exercise, as assessed by respiratory gas analysis, was lower in patients with dilated cardiomyopathy than in normal subjects. Despite the higher exercise level, all haemodynamic variables returned to baseline within one hour after exercise in normal subjects. In contrast, patients with dilated cardiomyopathy showed a sustained decrease in the peak early diastolic filling velocity and a sustained increase in the deceleration time of early filling for 24 hours or more after exercise. Because other haemodynamic variables recovered within one hour after exercise even in patients with dilated cardiomyopathy, the postexercise changes in ventricular filling were not explained by changes in loading conditions.
Conclusions—Exercise induced diastolic left ventricular dysfunction of the failing heart persists for 24 hours or more after exercise. The efficacy of exercise training on a daily basis in dilated cardiomyopathy requires further evaluation.

 Keywords: exercise;  chronic heart failure;  mitral flow velocity;  diastolic stunning PMID:9875086

  12. Taurine for the Treatment of Canine Dilated Cardiomyopathy: A Veterinarian's Personal Experience.

    PubMed

    Vail, Jane

    2006-01-01

    In dogs, dilated cardiomyopathy is a common cardiac disease that is associated with treatment failure, a progressively compromised quality of life, and eventual death from heart failure. Cardiomyopathy in companion animals is treated with a variety of drugs manufactured for the management of cardiac dyfunction in humans, but often those agents do not produce a significantly beneficial response in veterinary patients. In this article, Lara Ivan, DVM, presents her personal experience with the use of a compounded form of the amino acid taurine in the treatment of her Doberman pinscher, whose dilated cardiomyopathy was characteristically sudden in onset. Robert Borger, RPh, a specialist in veterinary compounding, comments on the preparation of taurine for use in dogs with dilated cardiomyopathy. PMID:23974413

  13. Aberrant sialylation causes dilated cardiomyopathy and stress-induced heart failure.

    PubMed

    Deng, Wei; Ednie, Andrew R; Qi, Jianyong; Bennett, Eric S

    2016-09-01

    Dilated cardiomyopathy (DCM), the third most common cause of heart failure, is often associated with arrhythmias and sudden cardiac death if not controlled. The majority of DCM is of unknown etiology. Protein sialylation is altered in human DCM, with responsible mechanisms not yet described. Here we sought to investigate the impact of clinically relevant changes in sialylation on cardiac function using a novel model for altered glycoprotein sialylation that leads to DCM and to chronic stress-induced heart failure (HF), deletion of the sialyltransferase, ST3Gal4. We previously reported that 12- to 20-week-old ST3Gal4 (-/-) mice showed aberrant cardiac voltage-gated ion channel sialylation and gating that contribute to a pro-arrhythmogenic phenotype. Here, echocardiography supported by histology revealed modest dilated and thinner-walled left ventricles without increased fibrosis in ST3Gal4 (-/-) mice starting at 1 year of age. Cardiac calcineurin expression in younger (16-20 weeks old) ST3Gal4 (-/-) hearts was significantly reduced compared to WT. Transverse aortic constriction (TAC) was used as a chronic stressor on the younger mice to determine whether the ability to compensate against a pathologic insult is compromised in the ST3Gal4 (-/-) heart, as suggested by previous reports describing the functional implications of reduced cardiac calcineurin levels. TAC'd ST3Gal4 (-/-) mice presented with significantly reduced systolic function and ventricular dilation that deteriorated into congestive HF within 6 weeks post-surgery, while constricted WT hearts remained well-adapted throughout (ejection fraction, ST3Gal4 (-/-) = 34 ± 5.2 %; WT = 53.8 ± 7.4 %; p < 0.05). Thus, a novel, sialo-dependent model for DCM/HF is described in which clinically relevant reduced sialylation results in increased arrhythmogenicity and reduced cardiac calcineurin levels that precede cardiomyopathy and TAC-induced HF, suggesting a causal link among aberrant sialylation

  14. Rare variant mutations identified in pediatric patients with dilated cardiomyopathy

    PubMed Central

    Rampersaud, Evadnie; Siegfried, Jill D; Norton, Nadine; Li, Duanxiang; Martin, Eden; Hershberger, Ray E

    2010-01-01

    Dilated cardiomyopathy (DCM) in infants and children can be partially explained by genetic cause but the catalogue of known genes is limited. We reviewed our database of 41 cases diagnosed with DCM before 18 years of age who underwent detailed clinical and genetic evaluation, and summarize here the evidence for mutations causing DCM in these cases from 15 genes (PSEN1, PSEN2, CSRP3, LBD3, MYH7, SCN5A, TCAP, TNNT2, LMNA, MYBPC3, MYH6, TNNC1, TNNI3, TPM1, and RBM20). Thirty-five of the 41 pediatric cases had relatives with adult-onset DCM. More males (66%) were found among children diagnosed after 1 year of age with DCM. Nineteen mutations in 9 genes were identified among 15 out of 41 patients; 3 patients (diagnosed at ages 2 weeks, 9 and 13 years) had multiple mutations. Of the 19 mutations identified in 12 families, mutations in TPM1 (32%) and TNNT2 (21%) were the most commonly found. Of the 6 patients diagnosed before 1 year of age, 3 had mutations in TPM1 (including a set of identical twins), 1 in TNNT2, 1 in MYH7, and 1 with multiple mutations (MYH7 and TNNC1). Most DCM was accompanied by advanced heart failure and need for cardiac transplantation. We conclude that in some cases pediatric DCM has a genetic basis, which is complicated by allelic and locus heterogeneity as seen in adult-onset DCM. We suggest that future prospective comprehensive family-based genetic studies of pediatric DCM are indicated to further define mutation frequencies in known genes and to discover novel genetic cause. PMID:21483645

  15. Pediatric idiopathic dilated cardiomyopathy: A single center experience

    PubMed Central

    Azhar, Ahmad S.

    2013-01-01

    Context: Idiopathic dilated cardiomyopathy (IDCM) is a severe illness with high mortality in the pediatric population. AIMS: To highlight our experience about clinical course and outcome of IDCM. Settings and Design: Patients’ files were reviewed retrospectively for diagnosed cases of IDCM in the pediatric cardiology unit of King Abdul Aziz University Hospital, Jeddah, Saudi Arabia, from Jan 2003 to Jun 2011. Materials and Methods: Data about full history, clinical examination and investigations were recorded and grouped according to outcome as alive and well (group 1), alive and symptomatic (group 2) and worsened or dead (group 3). Statistical Analysis: Data was subjected to descriptive analysis. Chi-square and Student's paired t-test techniques were used where appropriate. Spearman rank correlation and survival analysis was done. Results: Eighty three patients were included with presenting age median (range), i.e.,14 (2 months–12 years) with females predominance 53 (63.9%). On presentation; cardiomegaly was noted in 72 (86.7%) with increased lung vascularity in 45 (54%). Sixty-one (74%) patients had ST segment and T-wave changes on electrocardiogram, while the same number had left ventricular hypertrophy, and 15 (18%) had arrhythmias. Echocardiography records on presentation and at last follow-up showed significant difference in several areas. Group 1 had 40 (48.2%), Group 2 had 23 (27.7%) while 20 (24.1%) were in Group 3 including nine cases who died. Survival rate over three years was 78%. Older the age, worse was the outcome (Spearman's rho = 0.3, P = 0.04). Conclusion: Majority of subjects were presented during first year of life; the three year survival rate was 78%. Favorable outcome was correlated with younger age at presentation. PMID:23633851

  16. Rare variant mutations identified in pediatric patients with dilated cardiomyopathy.

    PubMed

    Rampersaud, Evadnie; Siegfried, Jill D; Norton, Nadine; Li, Duanxiang; Martin, Eden; Hershberger, Ray E

    2011-01-01

    Dilated cardiomyopathy (DCM) in infants and children can be partially explained by genetic cause but the catalogue of known genes is limited. We reviewed our database of 41 cases diagnosed with DCM before 18 years of age who underwent detailed clinical and genetic evaluation, and summarize here the evidence for mutations causing DCM in these cases from 15 genes (PSEN1, PSEN2, CSRP3, LBD3, MYH7, SCN5A, TCAP, TNNT2, LMNA, MYBPC3, MYH6, TNNC1, TNNI3, TPM1, and RBM20). Thirty-five of the 41 pediatric cases had relatives with adult-onset DCM. More males (66%) were found among children diagnosed after 1 year of age with DCM. Nineteen mutations in 9 genes were identified among 15 out of 41 patients; 3 patients (diagnosed at ages 2 weeks, 9 and 13 years) had multiple mutations. Of the 19 mutations identified in 12 families, mutations in TPM1 (32%) and TNNT2 (21%) were the most commonly found. Of the 6 patients diagnosed before 1 year of age, 3 had mutations in TPM1 (including a set of identical twins), 1 in TNNT2, 1 in MYH7, and 1 with multiple mutations (MYH7 and TNNC1). Most DCM was accompanied by advanced heart failure and need for cardiac transplantation. We conclude that in some cases pediatric DCM has a genetic basis, which is complicated by allelic and locus heterogeneity as seen in adult-onset DCM. We suggest that future prospective comprehensive family-based genetic studies of pediatric DCM are indicated to further define mutation frequencies in known genes and to discover novel genetic cause. PMID:21483645

  17. Predictors of Disease Progression in Pediatric Dilated Cardiomyopathy

    PubMed Central

    Molina, Kimberly M.; Shrader, Peter; Colan, Steven D.; Mital, Seema; Margossian, Renee; Sleeper, Lynn A.; Shirali, Girish; Barker, Piers; Canter, Charles E.; Altmann, Karen; Radojewski, Elizabeth; Selamet Tierney, Elif Seda; Rychik, Jack; Tani, Lloyd Y.

    2014-01-01

    Background Despite medical advances, children with dilated cardiomyopathy (DCM) remain at high risk of death or need for cardiac transplantation. We sought to identify predictors of disease progression in pediatric DCM. Methods and Results The Pediatric Heart Network evaluated chronic DCM patients with prospective echocardiographic and clinical data collection during an 18-month follow-up. Inclusion criteria were age <22 years and DCM disease duration >2 months. Patients requiring intravenous inotropic/mechanical support or listed status 1A/1B for transplant were excluded. Disease progression was defined as an increase in transplant listing status, hospitalization for heart failure, intravenous inotropes, mechanical support, or death. Predictors of disease progression were identified using Cox proportional hazards modeling and classification and regression tree analysis. Of the 127 patients, 28 (22%) had disease progression during the 18-month follow-up. Multivariable analysis identified older age at diagnosis (hazard ratio=1.14 per year; P<0.001), larger left ventricular (LV) end-diastolic M-mode dimension z-score (hazard ratio=1.49; P<0.001), and lower septal peak systolic tissue Doppler velocity z-score (hazard ratio=0.81; P=0.01) as independent predictors of disease progression. Classification and regression tree analysis stratified patients at risk of disease progression with 89% sensitivity and 94% specificity based on LV end-diastolic M-mode dimension z-score ≥7.7, LV ejection fraction <39%, LV inflow propagation velocity (color M-mode) z-score <-0.28, and age at diagnosis ≥8.5 months. Conclusions In children with chronic stable DCM, a combination of diagnosis after late infancy and echocardiographic parameters of larger LV size and systolic and diastolic function predicted disease progression. PMID:24132734

  18. Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy

    PubMed Central

    Politano, Luisa; Melacini, Paola; Calore, Chiara; Polo, Angela; Vianello, Sara; Sorarù, Gianni; Semplicini, Claudio; Pantic, Boris; Taglia, Antonella; Picillo, Ester; Magri, Francesca; Gorni, Ksenija; Messina, Sonia; Vita, Gian Luca; Vita, Giuseppe; Comi, Giacomo P.; Ermani, Mario; Calvo, Vincenzo; Angelini, Corrado; Hoffman, Eric P.; Pegoraro, Elena

    2015-01-01

    Objective Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset. Methods A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up. Results Patients were followed up to an average age of 15.9 ± 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027). Conclusions We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts. PMID:26513582

  19. The influence of enalapril and spironolactone on electrolyte concentrations in Doberman pinschers with dilated cardiomyopathy.

    PubMed

    Thomason, J D; Rapoport, G; Fallaw, T; Calvert, C A

    2014-12-01

    The combination of an angiotensin-converting enzyme inhibitor (ACEI) with an aldosterone receptor antagonist can increase serum potassium and magnesium and lower serum sodium concentrations. The objective of this study was to retrospectively determine whether an ACEI and spironolactone can be co-administered to Doberman pinschers with occult dilated cardiomyopathy without serious adverse influences on serum electrolyte concentrations. Between 2001 and 2007, 26 client-owned Doberman pinschers were given enalapril, spironolactone, and carvedilol and followed for at least 6 months. Most dogs had been prescribed mexiletine for ventricular tachyarrhythmia suppression. Dogs were treated with pimobendan when congestive heart failure was imminent. Baseline and follow-up (3-10 visits) color-flow Doppler echocardiograms, serum urea nitrogen (SUN), creatinine, sodium, potassium, and magnesium concentration data were tabulated. Compared to baseline data, there were no significant changes in serum sodium or serum creatinine concentrations. Serum magnesium (P = 0.003), serum potassium (P = 0.0001), and SUN (P = 0.0001) concentrations increased significantly with time. Although the combination of ACEI and spironolactone was associated with significant increases in magnesium, potassium, and SUN concentrations, these changes were of no apparent clinical relevance. At the dosages used in this study, this combination of drugs appears safe. PMID:25257351

  20. Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss.

    PubMed

    Schönberger, Jost; Wang, Libin; Shin, Jordan T; Kim, Sang Do; Depreux, Frederic F S; Zhu, Hao; Zon, Leonard; Pizard, Anne; Kim, Jae B; Macrae, Calum A; Mungall, Andy J; Seidman, J G; Seidman, Christine E

    2005-04-01

    We identified a human mutation that causes dilated cardiomyopathy and heart failure preceded by sensorineural hearing loss (SNHL). Unlike previously described mutations causing dilated cardiomyopathy that affect structural proteins, this mutation deletes 4,846 bp of the human transcriptional coactivator gene EYA4. To elucidate the roles of eya4 in heart function, we studied zebrafish embryos injected with antisense morpholino oligonucleotides. Attenuated eya4 transcript levels produced morphologic and hemodynamic features of heart failure. To determine why previously described mutated EYA4 alleles cause SNHL without heart disease, we examined biochemical interactions of mutant Eya4 peptides. Eya4 peptides associated with SNHL, but not the shortened 193-amino acid peptide associated with dilated cardiomyopathy and SNHL, bound wild-type Eya4 and associated with Six proteins. These data define unrecognized and crucial roles for Eya4-Six-mediated transcriptional regulation in normal heart function. PMID:15735644

  1. Elevated Serum Bisphenol A Level in Patients with Dilated Cardiomyopathy

    PubMed Central

    Xiong, Qinmei; Liu, Xiao; Shen, Yang; Yu, Peng; Chen, Sisi; Hu, Jinzhu; Yu, Jianhua; Li, Juxiang; Wang, Hong-Sheng; Cheng, Xiaoshu; Hong, Kui

    2015-01-01

    Background: This study aimed to determine serum Bisphenol A (BPA) concentrations in patients with dilated cardiomyopathy (DCM) as well as the association between serum BPA and several hormonal parameters in DCM patients compared with a healthy control group. Materials and methods: Eighty-eight DCM patients and 88 age- and gender-matched healthy controls were included. Serum BPA levels and several hormonal parameters (including total testosterone (T), sex hormone-binding globulin (SHBG) and estradiol (E2) were measured by using corresponding ELISA Kits. The free androgen index (FAI) was calculated by the formula: total T in nmol/L × 100/SHBG in nmol/L. Results: BPA levels in the total DCM group were significantly higher compared with that in the controls (6.9 ± 2.7 ng/mL vs. 3.8 ± 1.9 ng/mL, p < 0.001). Significant difference was also observed in SHBG and FAI between DCM patients and controls, (76.9 ± 30.9 nM/L vs. 41.0 ± 15.6 nM/L and 2.9 ± 3.5 vs. 5.3 ± 2.6, respectively, both of p < 0.001). Similar trends were observed in the male and female subgroup. Mean T level was lower in DCM group than in control group (540.8 ± 186.0 pg/mL vs. 656.3 ± 112.9 pg/mL, p < 0.001). Linear regression analysis has shown that increasing serum BPA levels were statistically significantly associated with increased SHBG levels. However, no statistical difference was noted for E2. Conclusion: Our findings firstly demonstrated that BPA exposure increased in DCM patients compared with that in healthy controls, while FAI and T levels decreased. SHBG presented a positive association with BPA. It is concluded that hormone disorder induced by BPA exposure might be an environmental factor in the pathology of DCM. PMID:25996886

  2. Pathogenesis of dilated cardiomyopathy: molecular, structural, and population analyses in tropomodulin-overexpressing transgenic mice.

    PubMed

    Sussman, M A; Welch, S; Gude, N; Khoury, P R; Daniels, S R; Kirkpatrick, D; Walsh, R A; Price, R L; Lim, H W; Molkentin, J D

    1999-12-01

    Dilated cardiomyopathy is characterized by decreased contractile function and loss of myofibril organization. Previously unexplored structural and molecular events that precede and initiate dilation can now be studied in tropomodulin-overexpressing transgenic (TOT) mice exhibiting progressive dilated cardiomyopathy. Onset of dilation did not correspond to a change in transgene expression levels, which were more than threefold above normal at birth and remained elevated throughout postnatal life. Similarly, mitogen-activated protein kinase activation (p38, ERK1/ERK2, JNK1/JNK2) was not associated with dilation. In contrast, calcineurin was activated before dilation, presumably due to doubling of intracellular diastolic calcium levels in TOT cardiomyocytes. Amplitude of systolic calcium transients was greatly increased as well, demonstrating the novel and unique calcium handling profile of TOT cardiomyocytes. Loss of myofibril organization was not apparent by confocal microscopy until over 1 week after birth, although neonatal sarcomeric abnormalities were revealed by ultrastructural analysis. Rapid postnatal increases in heart:body weight ratio at 1.5 weeks were followed by two waves of mortality between 2 and 3 weeks after birth coincident with maturational stress. Ultimately, TOT pathogenesis is a compensatory response to altered sarcomeric structure driven by calcineurin activation within days after birth, making TOTs an excellent paradigm for studying the role of calcium overload in dilated cardiomyopathy. PMID:10595939

  3. Non-invasive evaluation of arrhythmic risk in dilated cardiomyopathy: From imaging to electrocardiographic measures

    PubMed Central

    Iacoviello, Massimo; Monitillo, Francesco

    2014-01-01

    Malignant ventricular arrhythmias are a major adverse event and worsen the prognosis of patients affected by ischemic and non-ischemic dilated cardiomyopathy. The main parameter currently used to stratify arrhythmic risk and guide decision making towards the implantation of a cardioverter defibrillator is the evaluation of the left ventricular ejection fraction. However, this strategy is characterized by several limitations and consequently additional parameters have been suggested in order to improve arrhythmic risk stratification. The aim of this review is to critically revise the prognostic significance of non-invasive diagnostic tools in order to better stratify the arrhythmic risk prognosis of dilated cardiomyopathy patients. PMID:25068017

  4. Usefulness of sugammadex in a patient with Becker muscular dystrophy and dilated cardiomyopathy.

    PubMed

    Shimauchi, Tsukasa; Yamaura, Ken; Sugibe, Sayaka; Hoka, Sumio

    2014-09-01

    A 54-year-old patient with Becker muscular dystrophy and dilated cardiomyopathy underwent laparoscopic cholecystectomy under total intravenous anesthesia. Muscle relaxation was induced by rocuronium (0.4 mg/kg body weight) under train-of-four (TOF) ratio monitoring. The TOF ratio was 0 at intubation, and 0.2 at the end of surgery. Residual muscle relaxant activity was successfully reversed by sugammadex (2 mg/kg body weight) without any hemodynamic adverse effects (TOF ratio 1.0 at extubation). The clinical and hemodynamic findings suggest that sugammadex can be safely used in patients with Becker muscular dystrophy and dilated cardiomyopathy. PMID:25199695

  5. Ventricular arrhythmias in dilated cardiomyopathy as an independent prognostic hallmark. Italian Multicenter Cardiomyopathy Study (SPIC) Group.

    PubMed

    De Maria, R; Gavazzi, A; Caroli, A; Ometto, R; Biagini, A; Camerini, F

    1992-06-01

    Prevalence and characteristics of ventricular arrhythmias (VA) on Holter monitoring were evaluated in 218 patients with invasively documented idiopathic dilated cardiomyopathy to clarify their relation to pump dysfunction, and their prognostic role. VA were observed in 205 patients (94%) and were high grade (ventricular pairs or tachycardia) in 130 (60%). No simple or multiform ventricular premature complexes were present in 88 patients (group 1; 41%), ventricular pairs in 63 (group 2; 32%), and ventricular tachycardia in 67 (group 3; 27%). Only echocardiographic right ventricular dimensions (p less than 0.05) and prevalence of VA during effort (8% in group 1, 15% in group 2, and 14% in group 3; p = 0.0005) differed significantly between groups. VA severity, and number of ventricular premature beats and tachycardia episodes were not correlated to right/left ventricular dimensions and pump function indexes. During a mean follow-up of 29 +/- 16 months, 27 patients died from cardiac events, and 16 received transplants. Three-year survival probability was lower in groups 2 (0.82) and 3 (0.81) than in group 1 (0.94). By Cox multivariate analysis, VA severity (p less than 0.01) was a major independent predictor of prognosis after markers of ventricular dysfunction such as left ventricular ejection fraction (p less than 0.001) and stroke work index (p less than 0.001). PMID:1590236

  6. Idiopathic dilated cardiomyopathy: computerized anatomic study of relashionship between septal and free left ventricle wall

    PubMed Central

    Juliani, Paulo Sérgio; da Costa, Éder França; Correia, Aristides Tadeu; Monteiro, Rosangela; Jatene, Fabio Biscegli

    2014-01-01

    Introduction A feature of dilated cardiomyopathy is the deformation of ventricular cavity, which contributes to systolic dysfunction. Few studies have evaluated this deformation bearing in mind ventricular regions and segments of the ventricle, which could reveal important details of the remodeling process, supporting a better understanding of its role in functional impairment and the development of new therapeutic strategies. Objective To evaluate if, in basal, equatorial and apical regions, increased internal transverse perimeter of left ventricle in idiopathic dilated cardiomyopathy occurs proportionally between the septal and non-septal segment. Methods We performed an anatomical study with 28 adult hearts from human cadavers. One group consisted of 18 hearts with idiopathic dilated cardiomyopathy and another group with 10 normal hearts. After lamination and left ventricle digital image capture, in three different regions (base, equator and apex), the transversal internal perimeter of left ventricle was divided into two segments: septal and not septal. These segments were measured by proper software. It was established an index of proportionality between these segments, called septal and non-septal segment index. Then we determined whether this index was the same in both groups. Results Among patients with normal hearts and idiopathic dilated cardiomyopathy, the index of proportionality between the two segments (septal and non-septal) showed no significant difference in the three regions analyzed. The comparison results of the indices NSS/SS among normal and enlarged hearts were respectively: in base 1.99 versus 1.86 (P=0.46), in equator 2.22 versus 2.18 (P=0.79) and in apex 2.96 versus 3.56 (P=0.11). Conclusion In the idiopathic dilated cardiomyopathy, the transversal dilatation of left ventricular internal perimeter occurs proportionally between the segments corresponding to the septum and free wall at the basal, equatorial and apical regions of this chamber

  7. Knock-in mouse model of dilated cardiomyopathy caused by troponin mutation.

    PubMed

    Du, Cheng-Kun; Morimoto, Sachio; Nishii, Kiyomasa; Minakami, Reiko; Ohta, Mika; Tadano, Naoto; Lu, Qun-Wei; Wang, Yuan-Yuan; Zhan, Dong-Yun; Mochizuki, Misato; Kita, Satomi; Miwa, Yoshikazu; Takahashi-Yanaga, Fumi; Iwamoto, Takahiro; Ohtsuki, Iwao; Sasaguri, Toshiyuki

    2007-07-20

    We created knock-in mice in which a deletion of 3 base pairs coding for K210 in cardiac troponin (cTn)T found in familial dilated cardiomyopathy patients was introduced into endogenous genes. Membrane-permeabilized cardiac muscle fibers from mutant mice showed significantly lower Ca(2+) sensitivity in force generation than those from wild-type mice. Peak amplitude of Ca(2+) transient in cardiomyocytes was increased in mutant mice, and maximum isometric force produced by intact cardiac muscle fibers of mutant mice was not significantly different from that of wild-type mice, suggesting that Ca(2+) transient was augmented to compensate for decreased myofilament Ca(2+) sensitivity. Nevertheless, mutant mice developed marked cardiac enlargement, heart failure, and frequent sudden death recapitulating the phenotypes of dilated cardiomyopathy patients, indicating that global functional defect of the heart attributable to decreased myofilament Ca(2+) sensitivity could not be fully compensated by only increasing the intracellular Ca(2+) transient. We found that a positive inotropic agent, pimobendan, which directly increases myofilament Ca(2+) sensitivity, had profound effects of preventing cardiac enlargement, heart failure, and sudden death. These results verify the hypothesis that Ca(2+) desensitization of cardiac myofilament is the absolute cause of the pathogenesis of dilated cardiomyopathy associated with this mutation and strongly suggest that Ca(2+) sensitizers are beneficial for the treatment of dilated cardiomyopathy patients affected by sarcomeric regulatory protein mutations. PMID:17556660

  8. A predictive model for canine dilated cardiomyopathy—a meta-analysis of Doberman Pinscher data

    PubMed Central

    Simpson, Siobhan; Edwards, Jennifer; Emes, Richard D.; Cobb, Malcolm A.; Rutland, Catrin S.

    2015-01-01

    Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic dysfunction which often leads to congestive heart failure. Although multiple human loci have been implicated in the pathogenesis of dilated cardiomyopathy, the identified variants are typically associated with rare monogenic forms of dilated cardiomyopathy. The potential for multigenic interactions contributing to human dilated cardiomyopathy remains poorly understood. Consistent with this, several known human dilated cardiomyopathy loci have been excluded as common causes of canine dilated cardiomyopathy, although canine dilated cardiomyopathy resembles the human disease functionally. This suggests additional genetic factors contribute to the dilated cardiomyopathy phenotype.This study represents a meta-analysis of available canine dilated cardiomyopathy genetic datasets with the goal of determining potential multigenic interactions relating the sex chromosome genotype (XX vs. XY) with known dilated cardiomyopathy associated loci on chromosome 5 and the PDK4 gene in the incidence and progression of dilated cardiomyopathy. The results show an interaction between known canine dilated cardiomyopathy loci and an unknown X-linked locus. Our study is the first to test a multigenic contribution to dilated cardiomyopathy and suggest a genetic basis for the known sex-disparity in dilated cardiomyopathy outcomes. PMID:25834770

  9. Hereditary dilated cardiomyopathy in Holstein-Friesian cattle in Japan: association with hereditary myopathy of the diaphragmatic muscles.

    PubMed

    Furuoka, H; Yagi, S; Murakami, A; Honma, A; Kobayashi, Y; Matsui, T; Miyahara, K; Taniyama, H

    2001-01-01

    This report deals with the pathology and genetic basis of dilated cardiomyopathy in 10 Holstein-Friesian cows aged 3-6 years, a disease similar to that reported in Simmental-Red Holstein and Holstein-Friesian cattle in several other countries. The main clinical signs were associated with systemic circulatory failure, and at necropsy the animals showed cardiomegaly, severe congestion and fibrosis of the liver, and systemic cardiac oedema. Histologically, hypertrophy and vacuolation of the cardiac muscle fibres and severe fibrosis were noted. Electron microscopically, the sarcoplasm of the hypertrophic fibres was seen to be filled with fine structures of low electron-density, together with thin filamentous material, suggesting myofibrillar lysis. The mitochondria showed increased size, an abnormal cristae pattern and vacuolation due to partial loss of cristae. Pedigree analysis of the affected cattle indicated an autosomal recessive mode of inheritance. The family line of this cardiomyopathy overlapped with that of hereditary myopathy of the diaphragmatic muscles in Holstein-Friesian cattle, the pathological aspects and inheritance mode of which were reported previously. The available evidence suggested a genetic association between these two pathologically distinct diseases. PMID:11578132

  10. Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene

    PubMed Central

    Moncayo-Arlandi, Javier; Allegue, Catarina; Iglesias, Anna; Mangas, Alipio; Brugada, Ramon

    2016-01-01

    Background Dilated cardiomyopathy, a major cause of chronic heart failure and cardiac transplantation, is characterized by left ventricular or biventricular heart dilatation. In nearly 50% of cases the pathology is inherited, and more than 60 genes have been reported as disease-causing. However, in 30% of familial cases the mutation remains unidentified even after comprehensive genetic analysis. This study clinically and genetically assessed a large Spanish family affected by dilated cardiomyopathy to search for novel variations. Methods and Results Our study included a total of 100 family members. Clinical assessment was performed in alive, and genetic analysis was also performed in alive and 1 deceased relative. Genetic screening included resequencing of 55 genes associated with sudden cardiac death, and Sanger sequencing of main disease-associated genes. Genetic analysis identified a frame-shift variation in BAG3 (p.H243Tfr*64) in 32 patients. Genotype-phenotype correlation identified substantial heterogeneity in disease expression. Of 32 genetic carriers (one deceased), 21 relatives were clinically affected, and 10 were asymptomatic. Seventeen of the symptomatic genetic carriers exhibited proto-diastolic septal knock by echocardiographic assessment. Conclusions We report p.H243Tfr*64_BAG3 as a novel pathogenic variation responsible for familial dilated cardiomyopathy. This variation correlates with a more severe phenotype of the disease, mainly in younger individuals. Genetic analysis in families, even asymptomatic individuals, enables early identification of individuals at risk and allows implementation of preventive measures. PMID:27391596

  11. Multi-Detector Row Computed Tomography Findings of Pelvic Congestion Syndrome Caused by Dilated Ovarian Veins

    PubMed Central

    Eren, Suat

    2010-01-01

    Objective: To evaluate the efficacy of multi-detector row CT (MDCT) on pelvic congestion syndrome (PCS), which is often overlooked or poorly visualized with routine imaging examination. Materials and Methods: We evaluated the MDCT features of 40 patients with PCS (mean age, 45 years; range, 29–60 years) using axial, coronal, sagittal, 3D volume-rendered, and Maximum Intensity Projection MIP images. Results: MDCT revealed pelvic varices and ovarian vein dilatations in all patients. Bilateral ovarian vein dilatation was present in 25 patients, and 15 patients had unilateral dilatation. While 12 cases of secondary pelvic varices occurred simultaneously with a retroaortic left renal vein, 10 cases were due solely to a mass obstruction or stenosis of venous structures. Conclusion: MDCT is an effective tool in the evaluation of PCS, and it has more advantages than other imaging modalities. PMID:25610142

  12. Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants

    SciTech Connect

    Glowniak, J.V.; Turner, F.E.; Gray, L.L.; Palac, R.T.; Lagunas-Solar, M.C.; Woodward, W.R.

    1989-07-01

    Iodine-123 metaiodobenzylguanidine ((/sup 123/I)MIBG) is a norepinephrine analog which can be used to image the sympathetic innervation of the heart. In this study, cardiac imaging with (/sup 123/I)MIBG was performed in patients with idiopathic congestive cardiomyopathy and compared to normal controls. Initial uptake, half-time of tracer within the heart, and heart to lung ratios were all significantly reduced in patients compared to normals. Uptake in lungs, liver, salivary glands, and spleen was similar in controls and patients with cardiomyopathy indicating that decreased MIBG uptake was not a generalized abnormality in these patients. Iodine-123 MIBG imaging was also performed in cardiac transplant patients to determine cardiac nonneuronal uptake. Uptake in transplants was less than 10% of normals in the first 2 hr and nearly undetectable after 16 hr. The decreased uptake of MIBG suggests cardiac sympathetic nerve dysfunction while the rapid washout of MIBG from the heart suggests increased cardiac sympathetic nerve activity in idiopathic congestive cardiomyopathy.

  13. Acute dilated cardiomyopathy in a patient with beriberi and cryoglobulinaemic vasculitis: an unusual potential complication of two rare disorders.

    PubMed

    Tejedor, Ana; Solé, Manel; Prieto-González, Sergio; Alba, Marco Antonio; Grau, Josep Maria; Cid, Maria Cinta; Hernández-Rodríguez, José

    2014-01-01

    We report the case of a 45-year-old patient who presented with acute dilated cardiomyopathy. During admission the patient was consecutively diagnosed with cryoglobulinaemic vasculitis and beriberi. In both diseases, cardiac involvement may occur as dilated cardiomyopathy. Thiamin deficiency was the final cause for the severe cardiac manifestations (cardiac acute beriberi or Shoshin syndrome), which returned to normal after thiamin supplementation. PMID:24429381

  14. Risk Stratification for Sudden Cardiac Death In Patients With Non-ischemic Dilated Cardiomyopathy

    PubMed Central

    Shekha, Karthik; Ghosh, Joydeep; Thekkoott, Deepak; Greenberg, Yisachar

    2005-01-01

    Non ischemic dilated cardiomyopathy (NIDCM) is a disorder of myocardium. It has varying etiologies. Albeit the varying etiologies of this heart muscle disorder, it presents with symptoms of heart failure, and rarely as sudden cardiac death (SCD). Manifestations of this disorder are in many ways similar to its counterpart, ischemic dilated cardiomyopathy (IDCM). A proportion of patients with NIDCM carries a grave prognosis and is prone to sudden cardiac death from sustained ventricular arrhythmias. Identification of this subgroup of patients who carry the risk of sudden cardiac death despite adequate medical management is a challenge .Yet another method is a blanket treatment of patients with this disorder with anti arrhythmic medications or anti tachyarrhythmia devices like implantable cardioverter defibrillators (ICD). However this modality of treatment could be a costly exercise even for affluent economies. In this review we try to analyze the existing data of risk stratification of NIDCM and its clinical implications in practice. PMID:16943952

  15. Sheehan's syndrome with reversible dilated cardiomyopathy: A case report and brief overview.

    PubMed

    Islam, A K M Monwarul; Hasnat, Mohammad A; Doza, Fatema; Jesmin, Humayra

    2014-04-01

    Sheehan's syndrome is a rare condition characterized by post-partal panhypopituitarism due to necrosis of adenohypophysis resulting from severe post-partum hemorrhage. Lethargy, amenorrhea and failure of lactation are the usual presenting features. Cardiac involvement in Sheehan's syndrome is rare. The case presented here describes dilated cardiomyopathy in a 36-year-old lady who failed to respond adequately to the standard anti-failure treatment. Further investigation revealed the diagnosis of Sheehan's syndrome. Besides other manifestations, cardiac function reverted to normal after giving replacement therapy with glucocorticoid, levothyroxine and sex hormone. Physicians, specially those in developing countries, should have high index of suspicion for the diagnosis of Sheehan's syndrome while dealing with a case of 'peripartal dilated cardiomyopathy'. Persistent amenorrhea and failure of lactation may be important clues in this context. Timely diagnosis and appropriate treatment can lessen the sufferings of the patients. PMID:24719543

  16. [Dilated cardiomyopathy and visceral anomalies in myotonic dystrophy].

    PubMed

    Pentimone, F; Del Corso, L; Vannini, A; Mori, L; Moruzzo, D

    1990-05-01

    In dystrophia myotonica clinical evidence of cardiac involvement usually appears several years after the onset of neuromuscular symptoms. In more than 90% of cases there is damage to the specialized cardiac tissues and in about 7% of cases there are alterations to the myocardium. We report a case characterized by early and spread deterioration of the pump function developing into refractory congestive heart failure. The contemporary involvement of the smooth muscle of gallbladder and colon confirms the hypothesis that dystrophia myotonica is a pan-muscle disease. PMID:2234457

  17. Autoimmunity to alpha myosin in a subset of patients with idiopathic dilated cardiomyopathy.

    PubMed Central

    Goldman, J. H.; Keeling, P. J.; Warraich, R. S.; Baig, M. K.; Redwood, S. R.; Dalla Libera, L.; Sanderson, J. E.; Caforio, A. L.; McKenna, W. J.

    1995-01-01

    OBJECTIVE--To use an enzyme linked immunoassay (ELISA) technique to assess frequency and disease specificity of anti-alpha-myosin antibodies in patients with dilated cardiomyopathy and their relatives. METHODS--Evaluation was performed on sera (dilution 1/320) from 123 consecutive patients with dilated cardiomyopathy (WHO criteria) (age 42 (SD 14) years), 252 of their relatives (35 (17) years), 203 healthy controls (45 (16) years), and 92 patients with ischaemic heart disease (63 (11) years). RESULTS--Abnormal antibody levels were commoner in patients with dilated cardiomyopathy (25, 20%) than in ischaemic heart disease (4, 4%), or normal controls (4, 2%, P = 0.001). Forty one (16%) of the relatives had abnormal results compared to the controls (4, 2%, P < 0.001) and antibodies were detected in 20 (38%) of pedigrees. Relatives from non-familial kindreds had higher antibody levels than those with familial disease (P << 0.001), and higher antibody levels were identified in 53 relatives of probands who had abnormal results compared to 116 relatives for whom the proband had a normal result (0.37 (SEM 0.02) v 0.22 (0.01); P < 0.001). CONCLUSIONS--The finding of anti-alpha-myosin antibodies in 20% of patients with dilated cardiomyopathy, in 16% of their asymptomatic relatives, and in 38% of families (particularly those with non-familial disease and where proband also had an abnormal result) provides additional evidence for autoimmunity against alpha myosin in a subset of patients. PMID:8541162

  18. Familial aggregation of idiopathic dilated cardiomyopathy: clinical features and pedigree analysis in 14 families.

    PubMed Central

    Zachara, E; Caforio, A L; Carboni, G P; Pellegrini, A; Pompili, A; Del Porto, G; Sciarra, A; Bosman, C; Boldrini, R; Prati, P L

    1993-01-01

    OBJECTIVE--A recent prospective study in patients with dilated cardiomyopathy has reported that the disease is familial in at least 20% of cases, but the pattern of inheritance could not be ascertained. The presence of an autosomal dominant pattern, such as seen in hypertrophic cardiomyopathy, could make it possible to search for single gene defects with linkage analysis, whereas polygenic inheritance would be consistent with the autoimmune hypothesis. To assess the pattern of inheritance, we retrospectively identified patients with familial disease and assessed their first degree relatives (parents, siblings and children) for dilated cardiomyopathy. DESIGN AND PATIENTS--The family history of 105 consecutive patients with dilated cardiomyopathy was reviewed and 14 who had at least one first degree relative with documented disease were identified as probands. Their healthy relatives (109) were studied by physical examination, electrocardiography, M mode and cross sectional echocardiography, and were classified as unequivocally normal or as potential carriers. The potential carriers had abnormal electrocardiography with either at least one echocardiographic measurement of left ventricular cavity dimension or percentage fractional shortening outside 2 SDs of normal values (based on age and body surface area). The potential carriers underwent 24 hour Holter monitoring and maximal treadmill exercise. RESULTS AND CONCLUSION--Twenty three relatives (21%) were classified as potential carriers: 12 had an increased left ventricular end diastolic dimension, with reduced percentage fractional shortening in three; 11 had an abnormal electrocardiogram and increased end diastolic dimension, with reduced percentage fractional shortening in five. Such abnormalities were very mild and follow up is necessary to find whether such changes represent early disease. Pedigree analysis was most consistent with polygenic inheritance. PMID:8435238

  19. Histology of the explanted hearts of children transplanted for dilated cardiomyopathy.

    PubMed

    Crossland, David S; Edmonds, Katy; Rassl, Doris; Black, Fiona; Dark, John H; Smith, Jon; O'Sullivan, John J

    2008-02-01

    There is little information as to the histology of the explanted hearts of children transplanted for presumed dilated cardiomyopathy. We therefore aimed to describe the histology of these explants. Thirty-six children [mean age 7.4 years (range 0.1-17)] transplanted for dilated cardiomyopathy were identified. Based on histological examination of the explanted hearts patients were classified into three groups: severe inflammation, mild to moderate inflammation, and minimal or no inflammation. Cell death/damage and fibrosis were also scored. Duration of symptoms and degree of support at transplant were ascertained from the case notes. Two patients had severe confluent inflammation, nine mild or moderate focal inflammation, and 25 minimal or no inflammation. The degree of inflammation and fibrosis did not correlate with the interval between presentation and transplant (p = 0.37 and p = 0.78). Patients requiring inotropes or ventricular assist had a shorter time interval between presentation and transplant (p = 0.017) although these levels of support were not associated with the degree of inflammation or fibrosis (p = 0.90 and 0.5). We conclude that the explanted hearts of one-third of children transplanted for presumed cardiomyopathy have some degree of inflammation. Histological findings are not associated with symptom duration or support required. PMID:18186893

  20. [Nuclear changes and p62 expression in ischemic and dilated cardiomyopathy].

    PubMed

    Cortés, Raquel; Portolés, Manuel; Roselló-Lletí, Esther; Martínez-Dolz, Luis; Almenar, Luis; Salvador, Antonio; Rivera, Miguel

    2007-12-01

    The study's objectives were to investigate nuclear stereology and to determine the level of p62, a protein involved in nuclear transport, in human cardiomyocytes from patients with heart failure due to ischemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM). We studied 23 human hearts: 10 had ICM, 10 had DCM, and three were from control subjects. The size of the nucleus was significantly increased in ICM and DCM hearts compared with those from controls (by 60% and 66%, respectively, P=.03), as was the size of the nucleolus (by 59%, P=.02 and 75%, P=.03, respectively). In addition, the p62 level was significantly increased in both forms of cardiomyopathy compared with controls (ICM 110%, P=.01; and DCM 145%, P=.04). In the ICM group, there were correlations between the p62 level and nuclear size (r=0.615, P=.05) and between the p62 level and the heterochromatin percentage (r=-0.707; P=.02). In conclusion, cardiomyocytes from hearts affected by ICM and DCM showed changes in nuclear and nucleolar morphology. The p62 level had doubled in both forms of cardiomyopathy and, in ICM hearts, there was a correlation with nuclear changes. PMID:18082099

  1. Late gadolinium enhanced cardiovascular magnetic resonance of lamin A/C gene mutation related dilated cardiomyopathy

    PubMed Central

    2011-01-01

    Background The purpose of this study was to identify early features of lamin A/C gene mutation related dilated cardiomyopathy (DCM) with cardiovascular magnetic resonance (CMR). We characterise myocardial and functional findings in carriers of lamin A/C mutation to facilitate the recognition of these patients using this method. We also investigated the connection between myocardial fibrosis and conduction abnormalities. Methods Seventeen lamin A/C mutation carriers underwent CMR. Late gadolinium enhancement (LGE) and cine images were performed to evaluate myocardial fibrosis, regional wall motion, longitudinal myocardial function, global function and volumetry of both ventricles. The location, pattern and extent of enhancement in the left ventricle (LV) myocardium were visually estimated. Results Patients had LV myocardial fibrosis in 88% of cases. Segmental wall motion abnormalities correlated strongly with the degree of enhancement. Myocardial enhancement was associated with conduction abnormalities. Sixty-nine percent of our asymptomatic or mildly symptomatic patients showed mild ventricular dilatation, systolic failure or both in global ventricular analysis. Decreased longitudinal systolic LV function was observed in 53% of patients. Conclusions Cardiac conduction abnormalities, mildly dilated LV and depressed systolic dysfunction are common in DCM caused by a lamin A/C gene mutation. However, other cardiac diseases may produce similar symptoms. CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM. PMID:21689390

  2. New contribution to the study of ventricular remodeling and valve rings in dilated cardiomyopathy: anatomical and histological evaluation

    PubMed Central

    Dalva, Moise; Correia, Aristides Tadeu; Jatene, Natalia de Freitas; Saldiva, Paulo Hilário Nascimento; Jatene, Fabio Biscegli

    2014-01-01

    Introduction Idiopathic dilated cardiomyopathy causes great impact but many aspects of its pathophysiology remain unknown. Objective To evaluate anatomical and histological aspects of hearts with idiopathic dilated cardiomyopathy and compare them to a control group, evaluating the behavior of the perimeters of the atrioventricular rings and ventricles and to compare the percentage of collagen and elastic fibers of the atrioventricular rings. Methods Thirteen hearts with cardiomyopathy and 13 normal hearts were analysed. They were dissected keeping the ventricular mass and atrioventricular rings, with lamination of segments 20%, 50% and 80% of the distance between the atrioventricular groove and the ventricular apex. The sections were subjected to photo scanning, with measurement of perimeters. The atrioventricular rings were dissected and measured digitally to evaluate their perimeters, later being sent to the pathology laboratory, and stained by hematoxylin-eosin, picrosirius and oxidized resorcin fuccin. Results Regarding to ventricles, dilation occurs in all segments in the pathological group, and the right atrioventricular ring measurement was higher in idiopathic dilated cardiomyopathy group, with no difference in the left side. With respect to collagen, both sides had lower percentage of fibers in the pathological group. With respect to the elastic fibers, there was no difference between the groups. Conclusion There is a change in ventricular geometry in cardiomyopathy group. The left atrioventricular ring does not dilate, in spite of the fact that in both ventricles there is lowering of collagen. PMID:25714199

  3. Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Westphal, Ricardo João; Bueno, Ronaldo Rocha Loures; Galvão, Paulo Bezerra de Araújo; Zanis Neto, José; Souza, Juliano Mendes; Guérios, Ênio Eduardo; Senegaglia, Alexandra Cristina; Brofman, Paulo Roberto; Pasquini, Ricardo; da Cunha, Claudio Leinig Pereira

    2014-01-01

    Background Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. PMID:25590932

  4. Knock-out of nexilin in mice leads to dilated cardiomyopathy and endomyocardial fibroelastosis.

    PubMed

    Aherrahrou, Zouhair; Schlossarek, Saskia; Stoelting, Stephanie; Klinger, Matthias; Geertz, Birgit; Weinberger, Florian; Kessler, Thorsten; Aherrahrou, Redouane; Moreth, Kristin; Bekeredjian, Raffi; Hrabě de Angelis, Martin; Just, Steffen; Rottbauer, Wolfgang; Eschenhagen, Thomas; Schunkert, Heribert; Carrier, Lucie; Erdmann, Jeanette

    2016-01-01

    Cardiomyopathy is one of the most common causes of chronic heart failure worldwide. Mutations in the gene encoding nexilin (NEXN) occur in patients with both hypertrophic and dilated cardiomyopathy (DCM); however, little is known about the pathophysiological mechanisms and relevance of NEXN to these disorders. Here, we evaluated the functional role of NEXN using a constitutive Nexn knock-out (KO) mouse model. Heterozygous (Het) mice were inter-crossed to produce wild-type (WT), Het, and homozygous KO mice. At birth, 32, 46, and 22 % of the mice were WT, Het, and KO, respectively, which is close to the expected Mendelian ratio. After postnatal day 6, the survival of the Nexn KO mice decreased dramatically and all of the animals died by day 8. Phenotypic characterizations of the WT and KO mice were performed at postnatal days 1, 2, 4, and 6. At birth, the relative heart weights of the WT and KO mice were similar; however, at day 4, the relative heart weight of the KO group was 2.3-fold higher than of the WT group. In addition, the KO mice developed rapidly progressive cardiomyopathy with left ventricular dilation and wall thinning and decreased cardiac function. At day 6, the KO mice developed a fulminant DCM phenotype characterized by dilated ventricular chambers and systolic dysfunction. At this stage, collagen deposits and some elastin deposits were observed within the left ventricle cavity, which resembles the features of endomyocardial fibroelastosis (EFE). Overall, these results further emphasize the role of NEXN in DCM and suggest a novel role in EFE. PMID:26659360

  5. Fragmented narrow QRS complex: Predictor of left ventricular dyssynchrony in non-ischemic dilated cardiomyopathy

    PubMed Central

    Yusuf, Jamal; Agrawal, Devendra Kumar; Mukhopadhyay, Saibal; Mehta, Vimal; Trehan, Vijay; Tyagi, Sanjay

    2013-01-01

    Background Cardiac resynchronization therapy is an important therapeutic modality in drug refractory symptomatic patients of heart failure with wide QRS (≥120 ms) on electrocardiogram. However, wide QRS (considered as a marker of electrical dyssynchrony) occurs in only 30% of heart failure patients, making majority of drug refractory heart failure patients ineligible for resynchronization therapy. Significant numbers of patients with narrow QRS have echocardiographic evidence of left ventricular dyssynchrony. However, there is sparse data about additional features on the surface ECG which can predict intraventricular dyssynchrony. This study was undertaken to assess the utility of fragmented narrow QRS complex to predict significant intraventricular dyssynchrony in symptomatic patients of non-ischemic dilated cardiomyopathy. Method 100 symptomatic patients of non-ischemic dilated cardiomyopathy with narrow QRS complexes (50 each with fragmented and normal QRS) were recruited. Tissue Doppler imaging was used to assess intraventricular dyssynchrony as per ‘Yu index’. Results 78% patients (n = 39) in fQRS complex group and 14% (n = 7) in normal QRS complex group had significant intraventricular dyssynchrony (χ2 = 20.61; p < 0.000005). fQRS complexes had 84.78% sensitivity, 79.62% specificity, a positive predictive value of 78% and negative predictive value of 86% to detect intraventricular dyssynchrony. fQRS also had sensitivity and specificity of 93% and 90% respectively to localize the dyssynchronous segment. Conclusion fQRS is a marker of electrical dyssynchrony, which results in significant intraventricular dyssynchrony in patients of non-ischemic dilated cardiomyopathy and a narrow QRS interval. fQRS localizes the dyssynchronous segment and might be useful in identifying patients who can benefit from cardiac resynchronization therapy. PMID:23647897

  6. D117N in Cypher/ZASP may not be a causative mutation for dilated cardiomyopathy and ventricular arrhythmias.

    PubMed

    Levitas, Aviva; Konstantino, Yuval; Muhammad, Emad; Afawi, Zaid; Marc Weinstein, Jean; Amit, Guy; Etzion, Yoram; Parvari, Ruti

    2016-05-01

    Dilated cardiomyopathy (DCM) and malignant ventricular arrhythmias are important causes of congestive heart failure, heart transplantation, and sudden cardiac death in young patients. Cypher/ZASP is a cytoskeletal protein localized in the sarcomeric Z-line that has a pivotal role in maintaining adult cardiac structure and function. The putative mutation p.(D117N) in Cypher/ZASP has been suggested to cause systolic dysfunction, dilated left ventricle with hypertrabeculated myocardium, and intraventricular conduction disturbance, based on two reported sporadic cases. In two unrelated Bedouin families, one with pediatric DCM and the other with DCM and ventricular arrhythmias at young adulthood searching for the causative mutation by exome sequencing we identified the p.(D117N) variant in Cypher/ZASP. However, p.(D117N) did not segregate as the causative mutation in these families, i.e. it was not present in some patients and was found in several individuals who had no clinical manifestations. Furthermore, the carrier frequency in the Bedouin population of origin is estimated to be 5.2%, which is much higher than the incidence of idiopathic DCM in this population. Thus, our data support the notion that the p.(D117N) variant in Cypher/ZASP is not a causative mutation in the families tested by us. The results also indicates that at least in some cases, the p.(D117N) in Cypher/ZASP is not a causative mutation and the role of D117N in Cypher/ZASP in cardiac pathologies should be further clarified and re-evaluated. PMID:26419279

  7. Dilated cardiomyopathy (DCM) associated with SSA antibody in primary Sjögren syndrome.

    PubMed

    Nishinarita, M; Nakagawa, M; Tanaka, E

    2000-06-01

    Abstract A 33-year-old Japanese woman was diagnosed with primary Sjögren syndrome (SS) in 1995. At this time, SSA antibody had not been detected by the Oucterlony or EIA methods. Two years later, the patient developed dyspnea. A chest X-ray showed cardiomegaly. An echocardiogram indicated severe diffuse hypokynesis of the cardiac wall with a left ventricular ejection fraction of 32%. Positive SSA antibody (over 500 u/ml) was noted in her serum as measured by the EIA method. We considered her cardiac manifestation to be dilated cardiomyopathy associated with primary SS. PMID:24383566

  8. Role of Cardiac Magnetic Resonance in the Evaluation of Dilated Cardiomyopathy: Diagnostic Contribution and Prognostic Significance

    PubMed Central

    2014-01-01

    Dilated cardiomyopathy (DCM) represents the final common morphofunctional pathway of various pathological conditions in which a combination of myocyte injury and necrosis associated with tissue fibrosis results in impaired mechanical function. Recognition of the underlying aetiology of disease and accurate disease monitoring may be crucial to individually optimize therapeutic strategies and stratify patient's prognosis. In this regard, CMR has emerged as a new reference gold standard providing important information for differential diagnosis and new insight about individual risk stratification. The present review article will focus on the role of CMR in the evaluation of present condition, analysing respective strengths and limitations in the light of current literature and technological developments. PMID:24967294

  9. Normalization of left ventricular function following cardiac resynchronization therapy: left bundle branch block as a potential etiology of dilated cardiomyopathy.

    PubMed

    Fujii, Banyo; Takami, Mistuaki

    2008-06-01

    Patients with chronic heart failure (HF) not infrequently present conduction disturbances, which are most commonly exhibited as a left bundle branch block (LBBB). LBBB is associated with intraventricular conduction delay, paradoxical septal motion, and hemodynamic deterioration, indicating an impairment of left ventricular (LV) function. However, there is controversy as to whether dilated cardiomyopathy leading to HF could develop just as a result of conduction disturbances without apparent pre-existing heart disease. We report here 2 cases of patients with non-ischemic dilated cardiomyopathy and LBBB who had complete reversal of their LV dysfunction and enlargement after cardiac resynchronization therapy, which corrects the LV activation sequence. These cases might support the idea that conduction disturbances themselves can be a principal etiology in the development of dilated cardiomyopathy. PMID:18503236

  10. Gastrointestinal Congestion Dilates the Hepatic Artery Through the P38 MAPK Signal Transduction Pathway During Liver Transplantation.

    PubMed

    Cao, Zhongping; Tang, Xiaowen; Hou, Shike

    2016-01-01

    During the neohepatic stage of liver transplantation, hemodynamics change markedly. The current study aimed to investigate whether gastrointestinal congestion caused by inferior vena cava and hepatic portal vein clamping can dilate the hepatic artery and to determine the associated mechanisms. Ring segments of the hepatic artery were treated with the plasma from gastrointestinal congestion or the superior vena cava. The fractions in gastrointestinal congestion and the superior vena cava plasma were tested, and the effect of these fractions on the tone of the hepatic artery ring was examined. Different signal transduction blockers and different inhibitors were then used to determine the exact signal transduction pathway involved. In addition, endothelial cell structure was observed by transmission electron microscopy after treatment with the gastrointestinal congestion plasma or the superior vena cava plasma. Gastrointestinal congestion plasma contained more inflammatory cytokines than superior vena cava plasma, and these cytokines could cause hepatic artery ring dilatation. A P38 mitogen-activated protein kinase (P38 MAPK) signal transduction pathway blocker and nitric oxide (NO), prostaglandin (PGI2), nuclear factor-κB (NF-κB), and adenosine triphosphate (ATP)-sensitive K (KATP) channel inhibitors were able to significantly reverse the ring tension caused by gastrointestinal congestion plasma. The normal endothelium was also injured by treatment with gastrointestinal congestion plasma. The inflammatory cytokines in gastrointestinal congestion can cause hepatic artery ring dilatation through the P38 MAPK signal transduction pathway, and this phenomenon is also associated with NO, PGI2, NF-κB, and the KATP channel. These inflammatory cytokines can injure endothelial cells in the hepatic artery. PMID:26955003

  11. Myocardial Infarction-Associated Transcript, a Long Noncoding RNA, Is Overexpressed During Dilated Cardiomyopathy Due to Chronic Chagas Disease.

    PubMed

    Frade, Amanda Farage; Laugier, Laurie; Ferreira, Ludmila Rodrigues Pinto; Baron, Monique Andrade; Benvenuti, Luiz Alberto; Teixeira, Priscila Camillo; Navarro, Isabela Cunha; Cabantous, Sandrine; Ferreira, Frederico Moraes; da Silva Cândido, Darlan; Gaiotto, Fabio Antônio; Bacal, Fernando; Pomerantzeff, Pablo; Santos, Ronaldo Honorato Barros; Kalil, Jorge; Cunha-Neto, Edecio; Chevillard, Christophe

    2016-07-01

    Long noncoding RNAs (lncRNAs) modulate gene expression at the epigenetic, transcriptional, and posttranscriptional levels. Dysregulation of the lncRNA known as myocardial infarction-associated transcript (MIAT) has been associated with myocardial infarction. Chagas disease causes a severe inflammatory dilated chronic cardiomyopathy (CCC). We investigated the role of MIAT in CCC. A whole-transcriptome analysis of heart biopsy specimens and formalin-fixed, paraffin-embedded samples revealed that MIAT was overexpressed in patients with CCC, compared with subjects with noninflammatory dilated cardiomyopathy and controls. These results were confirmed in a mouse model. Results suggest that MIAT is a specific biomarker of CCC. PMID:26951817

  12. Results of comprehensive diagnostic work-up in ‘idiopathic’ dilated cardiomyopathy

    PubMed Central

    Broch, Kaspar; Andreassen, Arne K; Hopp, Einar; Leren, Trond P; Scott, Helge; Müller, Fredrik; Aakhus, Svend; Gullestad, Lars

    2015-01-01

    Objective Dilated cardiomyopathy (DCM) is characterised by left ventricular dilation and dysfunction not caused by coronary disease, valvular disease or hypertension. Owing to the considerable aetiological and prognostic heterogeneity in DCM, an extensive diagnostic work-up is recommended. We aimed to assess the value of diagnostic testing beyond careful physical examination, blood tests, echocardiography and coronary angiography. Methods From October 2008 to November 2012, we prospectively recruited 102 patients referred to our tertiary care hospital with a diagnosis of ‘idiopathic’ DCM based on patient history, physical examination, routine blood tests, echocardiography and coronary angiography. Extended work-up included cardiac MRI, exercise testing, right-sided catheterisation with biopsies, 24 h ECG and genetic testing. Results In 15 patients (15%), a diagnosis other than ‘idiopathic’ DCM was made based on additional tests. In 10 patients (10%), a possibly disease-causing mutation was detected. 2 patients were found to have non-compaction cardiomyopathy based on MRI findings; 2 patients had systemic inflammatory disease with cardiac involvement; and in 1 patient, cardiac amyloidosis was diagnosed by endomyocardial biopsy. Only in 5 cases did the results of the extended work-up have direct therapeutic consequences. Conclusions In patients with DCM, in whom patient history and routine work-up carry no clues to the aetiology, the diagnostic and therapeutic yield of extensive additional testing is modest. PMID:26468400

  13. Oral Chinese Herbal Medicine for Treatment of Dilated Cardiomyopathy: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhu, Yu-Shuo; Ju, Jian-Qing; Du, Feng; Zang, Yan-Ping; Wang, Xiao-Bing; Sheng, Jie

    2016-01-01

    Dilated cardiomyopathy (DCM) is one of the main causes of heart failure and could increase death, hospitalization, and rehospitalization rate. The effect of conventional medicine treatment (CMT) is limited; meanwhile, the combination of CMT and Oral Chinese Herbal Medicine (OCHM) represents exciting adjunctive therapies. In this study, we ascertained the therapeutic effect of OCHM in combination with CMT for dilated cardiomyopathy by using meta-analysis methods for controlled clinical trials. We searched studies from five databases and extracted data from these studies. We also assessed the methodological quality of the included studies. We evaluated the following outcome measures to estimate the prognosis in patients with DCM: left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), stroke volume (SV), brain natriuretic peptide (BNP), 6-minute walk test (6MWT), and overall efficacy. The result showed that OCHM combined with CMT for the improvement of therapeutic effect in DCM patients. However, the evidence remains weak due to the small sample size, high clinical heterogeneity, and poor methodological quality of the included trials. Further, large sample size and well-designed trials are needed.

  14. Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.

    PubMed

    Sun, Ning; Yazawa, Masayuki; Liu, Jianwei; Han, Leng; Sanchez-Freire, Veronica; Abilez, Oscar J; Navarrete, Enrique G; Hu, Shijun; Wang, Li; Lee, Andrew; Pavlovic, Aleksandra; Lin, Shin; Chen, Rui; Hajjar, Roger J; Snyder, Michael P; Dolmetsch, Ricardo E; Butte, Manish J; Ashley, Euan A; Longaker, Michael T; Robbins, Robert C; Wu, Joseph C

    2012-04-18

    Characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure, dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy in patients. DCM is the most common diagnosis leading to heart transplantation and places a significant burden on healthcare worldwide. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for creating disease-specific cellular models, investigating underlying mechanisms, and optimizing therapy. Here, we generated cardiomyocytes from iPSCs derived from patients in a DCM family carrying a point mutation (R173W) in the gene encoding sarcomeric protein cardiac troponin T. Compared to control healthy individuals in the same family cohort, cardiomyocytes derived from iPSCs from DCM patients exhibited altered regulation of calcium ion (Ca(2+)), decreased contractility, and abnormal distribution of sarcomeric α-actinin. When stimulated with a β-adrenergic agonist, DCM iPSC-derived cardiomyocytes showed characteristics of cellular stress such as reduced beating rates, compromised contraction, and a greater number of cells with abnormal sarcomeric α-actinin distribution. Treatment with β-adrenergic blockers or overexpression of sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (Serca2a) improved the function of iPSC-derived cardiomyocytes from DCM patients. Thus, iPSC-derived cardiomyocytes from DCM patients recapitulate to some extent the morphological and functional phenotypes of DCM and may serve as a useful platform for exploring disease mechanisms and for drug screening. PMID:22517884

  15. Successful treatment of cardiac electrical storm in dilated cardiomyopathy using esmolol: A case report

    PubMed Central

    LI, LI; ZHOU, YUAN-LI; ZHANG, XUE-JING; WANG, HUA-TING

    2016-01-01

    The present study reports a case of electrical storm occurring in a 43-year-old woman with dilated cardiomyopathy. The patient suffered from a cardiac electrical storm, with 98 episodes of ventricular tachycardia rapidly degenerating to ventricular fibrillation in hospital. The patient was converted with a total of 120 defibrillations. Recurrent ventricular tachycardia/fibrillation was initiated by premature ventricular beats. The patient did not respond to the use of amiodaronum. However, the administration of esmolol stabilized the patient's heart rhythm. A moderate dose of the β-blocker esmolol, administered as an 0.5-mg intravenous bolus injection followed by an infusion at a rate of 0.15 mg/kg/min, inhibited the recurrence of ventricular fibrillation and normalized the electrocardiographic pattern. The results suggest that esmolol may be able to improve the survival rate of patients with electrical storm in dilated cardiomyopathy and should be considered as a primary therapy in the management of cardiac electrical storms. PMID:27347024

  16. De novo RRAGC mutation activates mTORC1 signaling in syndromic fetal dilated cardiomyopathy.

    PubMed

    Long, Pamela A; Zimmermann, Michael T; Kim, Maengjo; Evans, Jared M; Xu, Xiaolei; Olson, Timothy M

    2016-08-01

    Idiopathic dilated cardiomyopathy (DCM) is a heritable, genetically heterogeneous disorder with variable age-dependent penetrance. We sought to identify the genetic underpinnings of syndromic, sporadic DCM in a newborn female diagnosed in utero. Postnatal evaluation revealed ventricular dilation and systolic dysfunction, bilateral cataracts, and mild facial dysmorphisms. Comprehensive metabolic and genetic testing, including chromosomal microarray, mitochondrial DNA and targeted RASopathy gene sequencing, and clinical whole exome sequencing for known cardiomyopathy genes was non-diagnostic. Following exclusion of asymptomatic DCM in the parents, trio-based whole exome sequencing was carried out on a research basis, filtering for rare, predicted deleterious de novo and recessive variants. An unreported de novo S75Y mutation was discovered in RRAGC, encoding Ras-related GTP binding C, an essential GTPase in nutrient-activated mechanistic target of rapamycin complex 1 (mTORC1) signaling. In silico protein modeling and molecular dynamics simulation predicted the mutation to disrupt ligand interactions and increase the GDP-bound state. Overexpression of RagC(S75Y) rendered AD293 cells partially insensitive to amino acid deprivation, resulting in increased mTORC1 signaling compared to wild-type RagC. These findings implicate mTORC1 dysregulation through a gain-of-function mutation in RagC as a novel molecular basis for syndromic forms of pediatric heart failure, and expand genotype-phenotype correlation in RASopathy-related syndromes. PMID:27234373

  17. Comparison of Immune Profiles in Fetal Hearts with Idiopathic Dilated Cardiomyopathy, Maternal Autoimmune-Associated Dilated Cardiomyopathy and the Normal Fetus.

    PubMed

    Nield, Lynne E; von Both, Ingo; Popel, Najla; Strachan, Kate; Manlhiot, Cedric; Shannon, Patrick; McCrindle, Brian W; Atkinson, Adelle; Miner, Steven E S; Jaeggi, Edgar T; Taylor, Glenn P

    2016-02-01

    The etiology of idiopathic dilated cardiomyopathy (iDCM) remains unknown. Immune therapies have improved outcome in fetuses with DCM born to mothers with autoimmune disease (aDCM). The purpose of this retrospective study was to compare the myocardial B and T cell profiles in fetuses and neonates with idiopathic DCM (iDCM) versus autoimmune-mediated DCM (aDCM) and to describe the normal cell maturation within the human fetal myocardium. Of 60 fetal autopsy cases identified from institutional databases, 10 had aDCM (18-38 weeks), 12 iDCM (19-37 weeks) and 38 had normal hearts (11-40 weeks). Paraffin-embedded myocardium sections were stained for all lymphocyte (CD45), B cells (CD20, CD79a), T cells (CD3, CD4, CD7, CD8) and monocyte (CD68) surface markers. Two independent, blinded cell counts were performed. Normal hearts expressed all B and T cell markers in a bimodal fashion, with peaks at 22 and 37 weeks of gestation. The aDCM cohort was most distinct from normal hearts, with less overall T cell markers [EST -9.1 (2.6) cells/mm(2), p = 0.001], CD4 [EST -2.0 (0.6), p = 0.001], CD3 [EST -3.9 (1.0), p < 0.001], CD7 [EST -3.0 (1.1), p = 0.01] overall B cell markers [EST -4.9 (1.8), p = 0.01] and CD79a counts [EST -2.3 (0.9), p = 0.01]. The iDCM group had less overall B cell markers [EST -4.0 (1.8), p = 0.03] and CD79a [EST -1.7 (0.9), p = 0.05], but no difference in T cell markers. Autoimmune-mediated DCM fetuses have less B and T cell markers, whereas iDCM fetuses have less B cell markers compared with normal fetal hearts. The fetal immune system may play a role in the normal development of the heart and evolution of dilated cardiomyopathy. PMID:26481221

  18. Investigation of MMP-2 and MMP-9 activities in canine sera with dilated cardiomyopathy.

    PubMed

    Chegeni, S; Khaki, Z; Shirani, D; Vajhi, A; Taheri, M; Tamrchi, Y; Rostami, A

    2015-01-01

    Dilated cardiomyopathy (DCM) is accompanied by myocytes and connective tissue changes. Matrix metalloproteinases (MMPs) play important roles in cardiac remodeling. It seems that the gelatinases (MMP-2 and MMP-9) are effective enzymes in cardiomyopathy. Dilated cardiomyopathy was confirmed in 22 dogs (patient group) including 11 female and 11 male by clinical examination, auscultation, thoracic radiography and echocardiography. 17 healthy dogs (control group) with similar weight and breed to patients were also selected from referred cases to Small Animal Hospital of the Veterinary Faculty of Tehran University and the same diagnostic procedures were performed on them. After that, serum MMP-2 and MMP-9 of control and patient groups were measured by semi-quantitative zymography. Semiquantitative analysis of zymograms from canine serums with DCM showed that total MMP-9 in patients is more than control group, while there was no significant difference in total MMP-2 between the two groups. Pro-MMP-2 was not detected in patient group but its active form was present in both groups, of course MMP-2 activity in patients was significantly more than control. Active form of MMP-9 was detected only in patients. Although pro-MMP-9 was present in both groups, its level in control group was significantly higher than patients. The heart enlargement was observed in the left, right or both parts. Statistically significant differences in active form of MMP-2 and MMP-9 levels were observed between different groups of heart enlargement (right, left and both parts) compared to control but this difference was not significant considering chambers affected and VHS (vertebral heart score) groups. In conclusion, although there are some changes in serum MMP-2 and MMP-9 levels in canine DCM, it seems that increase of MMP-9 is more prominent than MMP-2 and neither of them were affected by heart enlargement or VHS grade. PMID:27175173

  19. Dilated cardiomyopathy

    MedlinePlus

    ... to identify infections such as Lyme disease and HIV Iron tests of the blood Serum TSH and T4 test to identify thyroid problems Tests for amyloidosis Heart enlargement or other problems with the structure and function of the heart (such as weak ...

  20. Changes in myocardial cytoskeletal intermediate filaments and myocyte contractile dysfunction in dilated cardiomyopathy: an in vivo study in humans

    PubMed Central

    Di, S; Marotta, M; Salvatore, G; Cudemo, G; Cuda, G; De Vivo, F; Di, B; Ciaramella, F; Caputo, G; de Divitiis, O

    2000-01-01

    AIM—To investigate in vivo the intermediate cytoskeletal filaments desmin and vimentin in myocardial tissues from patients with dilated cardiomyopathy, and to determine whether alterations in these proteins are associated with impaired contractility.
METHODS—Endomyocardial biopsies were performed in 12 patients with dilated cardiomyopathy and in 12 controls (six women with breast cancer before anthracycline chemotherapy and six male donors for heart transplantation). Biopsy specimens were analysed by light microscopy and immunochemistry (desmin, vimentin). Myocyte contractile protein function was evaluated by the actin-myosin in vitro motility assay. Left ventricular ejection fraction was assessed by echocardiography and radionuclide ventriculography.
RESULTS—Patients with dilated cardiomyopathy had a greater cardiomyocyte diameter than controls (p < 0.01). The increase in cell size was associated with a reduction in contractile function, as assessed by actin-myosin motility (r = −0.643; p < 0.01). Quantitative immunochemistry showed increased desmin and vimentin contents (p < 0.01), and the desmin distribution was disturbed in cardiomyopathy. There was a linear relation between desmin distribution and actin-myosin sliding in vitro (r = 0.853; p < 0.01) and an inverse correlation between desmin content and ejection fraction (r = −0.773; p < 0.02). Negative correlations were also found between myocardial vimentin content and the actin-myosin sliding rate (r = −0.74; p < 0.02) and left ventricular ejection fraction (r = −0.68; p < 0.01).
CONCLUSIONS—Compared with normal individuals, the myocardial tissue of patients with dilated cardiomyopathy shows alterations of cytoskeletal intermediate filament distribution and content associated with reduced myocyte contraction.


Keywords: dilated cardiomyopathy; desmin; vimentin; cardiac biopsy; actin-myosin PMID:11083750

  1. Mutation analysis of the phospholamban gene in 315 South Africans with dilated, hypertrophic, peripartum and arrhythmogenic right ventricular cardiomyopathies.

    PubMed

    Fish, Maryam; Shaboodien, Gasnat; Kraus, Sarah; Sliwa, Karen; Seidman, Christine E; Burke, Michael A; Crotti, Lia; Schwartz, Peter J; Mayosi, Bongani M

    2016-01-01

    Cardiomyopathy is an important cause of heart failure in Sub-Saharan Africa, accounting for up to 30% of adult heart failure hospitalisations. This high prevalence poses a challenge in societies without access to resources and interventions essential for disease management. Over 80 genes have been implicated as a cause of cardiomyopathy. Mutations in the phospholamban (PLN) gene are associated with dilated cardiomyopathy (DCM) and severe heart failure. In Africa, the prevalence of PLN mutations in cardiomyopathy patients is unknown. Our aim was to screen 315 patients with arrhythmogenic right ventricular cardiomyopathy (n = 111), DCM (n = 95), hypertrophic cardiomyopathy (n = 40) and peripartum cardiomyopathy (n = 69) for disease-causing PLN mutations by high resolution melt analysis and DNA sequencing. We detected the previously reported PLN c.25C > T (p.R9C) mutation in a South African family with severe autosomal dominant DCM. Haplotype analysis revealed that this mutation occurred against a different haplotype background to that of the original North American family and was therefore unlikely to have been inherited from a common ancestor. No other mutations in PLN were detected (mutation prevalence = 0.2%). We conclude that PLN is a rare cause of cardiomyopathy in African patients. The PLN p.R9C mutation is not well-tolerated, emphasising the importance of this gene in cardiac function. PMID:26917049

  2. Mutation analysis of the phospholamban gene in 315 South Africans with dilated, hypertrophic, peripartum and arrhythmogenic right ventricular cardiomyopathies

    PubMed Central

    Fish, Maryam; Shaboodien, Gasnat; Kraus, Sarah; Sliwa, Karen; Seidman, Christine E.; Burke, Michael A.; Crotti, Lia; Schwartz, Peter J.; Mayosi, Bongani M.

    2016-01-01

    Cardiomyopathy is an important cause of heart failure in Sub-Saharan Africa, accounting for up to 30% of adult heart failure hospitalisations. This high prevalence poses a challenge in societies without access to resources and interventions essential for disease management. Over 80 genes have been implicated as a cause of cardiomyopathy. Mutations in the phospholamban (PLN) gene are associated with dilated cardiomyopathy (DCM) and severe heart failure. In Africa, the prevalence of PLN mutations in cardiomyopathy patients is unknown. Our aim was to screen 315 patients with arrhythmogenic right ventricular cardiomyopathy (n = 111), DCM (n = 95), hypertrophic cardiomyopathy (n = 40) and peripartum cardiomyopathy (n = 69) for disease-causing PLN mutations by high resolution melt analysis and DNA sequencing. We detected the previously reported PLN c.25C > T (p.R9C) mutation in a South African family with severe autosomal dominant DCM. Haplotype analysis revealed that this mutation occurred against a different haplotype background to that of the original North American family and was therefore unlikely to have been inherited from a common ancestor. No other mutations in PLN were detected (mutation prevalence = 0.2%). We conclude that PLN is a rare cause of cardiomyopathy in African patients. The PLN p.R9C mutation is not well-tolerated, emphasising the importance of this gene in cardiac function. PMID:26917049

  3. Norwood Stage 1 With Surgical Ventricular Reconstruction and Mitral Valve Repair for Neonatal Idiopathic Left Ventricular Dilated Cardiomyopathy.

    PubMed

    Myers, Patrick O; Sologashvili, Tornike; Beghetti, Maurice; Tissot, Cécile

    2016-07-01

    A newborn girl presented with a prenatal diagnosis of dilated left ventricular cardiomyopathy, mitral valve regurgitation, and ductal-dependent circulation. The left ventricle was severely dilated and hypokinetic. The patient underwent Norwood stage 1 single ventricle palliation with a Damus-Kaye-Stansel anastomosis, atrioseptectomy, and a modified Blalock-Taussig shunt. The left ventricle was managed with Batista surgical ventricular reconstruction, with resection of the dilated and thinned ventricular myocardium, along with periventricular Alfieri repair of the mitral valve. The patient had an uneventful postoperative recovery, followed by stage 2 bidirectional Glenn and tricuspid valvuloplasty at 2.75 months of age. PMID:27343520

  4. Titin Mutations in iPS cells Define Sarcomere Insufficiency as a Cause of Dilated Cardiomyopathy

    PubMed Central

    Hinson, John T.; Chopra, Anant; Nafissi, Navid; Polacheck, William J.; Benson, Craig C.; Swist, Sandra; Gorham, Joshua; Yang, Luhan; Schafer, Sebastian; Sheng, Calvin C.; Haghighi, Alireza; Homsy, Jason; Hubner, Norbert; Church, George; Cook, Stuart A.; Linke, Wolfgang A.; Chen, Christopher S.; Seidman, J. G.; Seidman, Christine E.

    2015-01-01

    Human mutations that truncate the massive sarcomere protein titin (TTNtv) are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtv, diminish contractile performance and are pathogenic. By combining functional analyses with RNAseq, we explain why truncations in the A-band domain of TTN cause DCM while truncations in the I-band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS-cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and β-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodelling. PMID:26315439

  5. MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy.

    PubMed

    Lange, Stephan; Gehmlich, Katja; Lun, Alexander S; Blondelle, Jordan; Hooper, Charlotte; Dalton, Nancy D; Alvarez, Erika A; Zhang, Xiaoyu; Bang, Marie-Louise; Abassi, Yama A; Dos Remedios, Cristobal G; Peterson, Kirk L; Chen, Ju; Ehler, Elisabeth

    2016-01-01

    MLP (muscle LIM protein)-deficient mice count among the first mouse models for dilated cardiomyopathy (DCM), yet the exact role of MLP in cardiac signalling processes is still enigmatic. Elevated PKCα signalling activity is known to be an important contributor to heart failure. Here we show that MLP directly inhibits the activity of PKCα. In end-stage DCM, PKCα is concentrated at the intercalated disc of cardiomyocytes, where it is sequestered by the adaptor protein CARP in a multiprotein complex together with PLCβ1. In mice deficient for both MLP and CARP the chronic PKCα signalling chain at the intercalated disc is broken and they remain healthy. Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCα and that chronic uninhibited PKCα activity at the intercalated disc in the absence of functional MLP leads to heart failure. PMID:27353086

  6. MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy

    PubMed Central

    Lange, Stephan; Gehmlich, Katja; Lun, Alexander S.; Blondelle, Jordan; Hooper, Charlotte; Dalton, Nancy D.; Alvarez, Erika A.; Zhang, Xiaoyu; Bang, Marie-Louise; Abassi, Yama A.; dos Remedios, Cristobal G.; Peterson, Kirk L.; Chen, Ju; Ehler, Elisabeth

    2016-01-01

    MLP (muscle LIM protein)-deficient mice count among the first mouse models for dilated cardiomyopathy (DCM), yet the exact role of MLP in cardiac signalling processes is still enigmatic. Elevated PKCα signalling activity is known to be an important contributor to heart failure. Here we show that MLP directly inhibits the activity of PKCα. In end-stage DCM, PKCα is concentrated at the intercalated disc of cardiomyocytes, where it is sequestered by the adaptor protein CARP in a multiprotein complex together with PLCβ1. In mice deficient for both MLP and CARP the chronic PKCα signalling chain at the intercalated disc is broken and they remain healthy. Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCα and that chronic uninhibited PKCα activity at the intercalated disc in the absence of functional MLP leads to heart failure. PMID:27353086

  7. Radiofrequency catheter ablation for dyssynchrony-induced dilated cardiomyopathy in an infant.

    PubMed

    Kwon, Elena N; Carter, Kerri A; Kanter, Ronald J

    2014-01-01

    The relationship between accessory pathway-mediated ventricular preexcitation and left ventricular dyssynchrony-induced dysfunction has been described in patients with Wolff-Parkinson-White (WPW) syndrome in the absence of sustained supraventricular tachycardia (SVT). Supraventricular tachycardia in infants is usually successfully suppressed with antiarrhythmic medications, but catheter ablation has ultimately been required as definitive treatment in medically resistant cases. Catheter ablation has not been described in young infants for dyssynchrony-related dilated cardiomyopathy in the absence of SVT. We describe a case of an infant with WPW who did not have sustained supraventricular tachycardia, but who developed rapid progression of ventricular dysfunction after birth. Preexcitation could not be medically suppressed but was successfully ablated. This was followed by complete resolution of ventricular dysfunction within 2 months. PMID:23902593

  8. A locus on chromosome 5 is associated with dilated cardiomyopathy in Doberman Pinschers.

    PubMed

    Mausberg, Theresa-Bernadette; Wess, Gerhard; Simak, Julia; Keller, Lisa; Drögemüller, Michaela; Drögemüller, Cord; Webster, Matthew T; Stephenson, Hannah; Dukes-McEwan, Joanna; Leeb, Tosso

    2011-01-01

    Dilated cardiomyopathy (DCM) is a heterogeneous group of heart diseases with a strong genetic background. Currently, many human DCM cases exist where no causative mutation can be identified. DCM also occurs with high prevalence in several large dog breeds. In the Doberman Pinscher a specific DCM form characterized by arrhythmias and/or echocardiographic changes has been intensively studied by veterinary cardiologists. We performed a genome-wide association study in Doberman Pinschers. Using 71 cases and 70 controls collected in Germany we identified a genome-wide significant association to DCM on chromosome 5. We validated the association in an independent cohort collected in the United Kingdom. There is no known DCM candidate gene under the association signal. Therefore, DCM in Doberman Pinschers offers the chance of identifying a novel DCM gene that might also be relevant for human health. PMID:21625443

  9. Review on CFD simulation in heart with dilated cardiomyopathy and myocardial infarction.

    PubMed

    Chan, Bee Ting; Lim, Einly; Chee, Kok Han; Abu Osman, Noor Azuan

    2013-05-01

    The heart is a sophisticated functional organ that plays a crucial role in the blood circulatory system. Hemodynamics within the heart chamber can be indicative of exert cardiac health. Due to the limitations of current cardiac imaging modalities, computational fluid dynamics (CFD) have been widely used for the purposes of cardiac function assessment and heart disease diagnosis, as they provide detailed insights into the cardiac flow field. An understanding of ventricular hemodynamics and pathological severities can be gained through studies that employ the CFD method. In this research the hemodynamics of two common myocardial diseases, dilated cardiomyopathy (DCM) and myocardial infarction (MI) were investigated, during both the filling phase and the whole cardiac cycle, through a prescribed geometry and fluid structure interaction (FSI) approach. The results of the research indicated that early stage disease identification and the improvement of cardiac assisting devices and therapeutic procedures can be facilitated through the use of the CFD method. PMID:23428371

  10. Variants of resistin gene and the risk of idiopathic dilated cardiomyopathy in Pakistan

    PubMed Central

    Hussain, Sabir; Haroon, Javeria; Ejaz, Shagufta; Javed, Qamar

    2016-01-01

    Background In cardiovascular disease phenotypes, a genetic factor is an important determinant of both familial and non-familial dilated cardiomyopathies. Resistin is a novel adipocyte derived peptide, associated with inflammation and suggested to be involved in contractile abnormalities of cardiomyocytes. Methods In this study, we examined the association of the RETN SNPs in − 420 and + 299 in patients with idiopathic dilated cardiomyopathy (IDCM). Patients with IDCM (n = 250) and healthy controls (n = 250) were enrolled in this study. RETN genotyping was performed by using PCR-RFLP method. Results RETN − 420C > G and + 299G > A polymorphisms were significantly more prevalent in patient group vs. controls (P < 0.0001 and P = 0.0007, respectively). GG genotype at − 420 and AA genotype at + 299 were higher in the patient group compared with healthy controls (OR = 11.4, P < 0.0001, and OR = 2.3, P = 0.030, respectively). We found that the − 420G allele increased the risk of developing IDCM in patients (P < 0.0001). Moreover, there was a significant difference between G and A alleles at RETN + 299 from IDCM cases and controls (P = 0.0032). The RETN − 420G and + 299A haplotypes were more prevalent in the patient vs. control group (P < 0.0001). Conclusion The results suggest that the RETN − 420C > G and + 299G > A polymorphisms may have a role in the pathogenesis of IDCM. PMID:27114921

  11. The Role of Leucine-Rich Repeat Containing Protein 10 (LRRC10) in Dilated Cardiomyopathy

    PubMed Central

    Brody, Matthew J.; Lee, Youngsook

    2016-01-01

    Leucine-rich repeat containing protein 10 (LRRC10) is a cardiomyocyte-specific member of the Leucine-rich repeat containing (LRRC) protein superfamily with critical roles in cardiac function and disease pathogenesis. Recent studies have identified LRRC10 mutations in human idiopathic dilated cardiomyopathy (DCM) and Lrrc10 homozygous knockout mice develop DCM, strongly linking LRRC10 to the molecular etiology of DCM. LRRC10 localizes to the dyad region in cardiomyocytes where it can interact with actin and α-actinin at the Z-disc and associate with T-tubule components. Indeed, this region is becoming increasingly recognized as a signaling center in cardiomyocytes, not only for calcium cycling, excitation-contraction coupling, and calcium-sensitive hypertrophic signaling, but also as a nodal signaling hub where the myocyte can sense and respond to mechanical stress. Disruption of a wide range of critical structural and signaling molecules in cardiomyocytes confers susceptibility to cardiomyopathies in addition to the more classically studied mutations in sarcomeric proteins. However, the molecular mechanisms underlying DCM remain unclear. Here, we review what is known about the cardiomyocyte functions of LRRC10, lessons learned about LRRC10 and DCM from the Lrrc10 knockout mouse model, and discuss ongoing efforts to elucidate molecular mechanisms whereby mutation or absence of LRRC10 mediates cardiac disease. PMID:27536250

  12. A Heterozygous ZMPSTE24 Mutation Associated with Severe Metabolic Syndrome, Ectopic Fat Accumulation, and Dilated Cardiomyopathy

    PubMed Central

    Galant, Damien; Gaborit, Bénédicte; Desgrouas, Camille; Abdesselam, Ines; Bernard, Monique; Levy, Nicolas; Merono, Françoise; Coirault, Catherine; Roll, Patrice; Lagarde, Arnaud; Bonello-Palot, Nathalie; Bourgeois, Patrice; Dutour, Anne; Badens, Catherine

    2016-01-01

    ZMPSTE24 encodes the only metalloprotease, which transforms prelamin into mature lamin A. Up to now, mutations in ZMPSTE24 have been linked to Restrictive Dermopathy (RD), Progeria or Mandibulo-Acral Dysplasia (MAD). We report here the phenotype of a patient referred for severe metabolic syndrome and cardiomyopathy, carrying a mutation in ZMPSTE24. The patient presented with a partial lipodystrophic syndrome associating hypertriglyceridemia, early onset type 2 diabetes, and android obesity with truncal and abdominal fat accumulation but without subcutaneous lipoatrophy. Other clinical features included acanthosis nigricans, liver steatosis, dilated cardiomyopathy, and high myocardial and hepatic triglycerides content. Mutated fibroblasts from the patient showed increased nuclear shape abnormalities and premature senescence as demonstrated by a decreased Population Doubling Level, an increased beta-galactosidase activity and a decreased BrdU incorporation rate. Reduced prelamin A expression by siRNA targeted toward LMNA transcripts resulted in decreased nuclear anomalies. We show here that a central obesity without subcutaneous lipoatrophy is associated with a laminopathy due to a heterozygous missense mutation in ZMPSTE24. Given the high prevalence of metabolic syndrome and android obesity in the general population, and in the absence of familial study, the causative link between mutation and phenotype cannot be formally established. Nevertheless, altered lamina architecture observed in mutated fibroblasts are responsible for premature cellular senescence and could contribute to the phenotype observed in this patient. PMID:27120622

  13. Arginylation regulates myofibrils to maintain heart function and prevent dilated cardiomyopathy

    PubMed Central

    Kurosaka, Satoshi; Leu, N. Adrian; Pavlov, Ivan; Han, Xuemei; Ribeiro, Paula Aver Bretanha; Xu, Tao; Bunte, Ralph; Saha, Sougata; Wang, Junling; Cornachione, Anabelle; Mai, Wilfried; Yates, John R; Rassier, Dilson E.; Kashina, Anna

    2012-01-01

    Protein arginylation mediated by arginyltransferase (ATE1) is essential for heart formation during embryogenesis, however its cell-autonomous role in cardiomyocytes and the differentiated heart muscle has never been investigated. To address this question, we generated cardiac muscle-specific Ate1 knockout mice, in which Ate1 deletion was driven by α-myosin heavy chain promoter (αMHC-Ate1 mouse). These mice were initially viable, but developed severe cardiac contractility defects, dilated cardiomyopathy, and thrombosis over time, resulting in high rates of lethality after 6 months of age. These symptoms were accompanied by severe ultrastructural defects in cardiac myofibrils, seen in the newborns and far preceding the onset of cardiomyopathy, suggesting that these defects were primary and likely underlay the development of the future heart defects. Several major sarcomeric proteins were arginylated in vivo. Moreover, Ate1 deletion in the hearts resulted in a significant reduction of active and passive myofibril forces, suggesting that arginylation is critical for both myofibril structural integrity and contractility. Thus, arginylation is essential for maintaining the heart function by regulation of the major myofibril proteins and myofibril forces, and its absence in the heart muscle leads to progressive heart failure through cardiomyocyte-specific defects. PMID:22626847

  14. The Role of Leucine-Rich Repeat Containing Protein 10 (LRRC10) in Dilated Cardiomyopathy.

    PubMed

    Brody, Matthew J; Lee, Youngsook

    2016-01-01

    Leucine-rich repeat containing protein 10 (LRRC10) is a cardiomyocyte-specific member of the Leucine-rich repeat containing (LRRC) protein superfamily with critical roles in cardiac function and disease pathogenesis. Recent studies have identified LRRC10 mutations in human idiopathic dilated cardiomyopathy (DCM) and Lrrc10 homozygous knockout mice develop DCM, strongly linking LRRC10 to the molecular etiology of DCM. LRRC10 localizes to the dyad region in cardiomyocytes where it can interact with actin and α-actinin at the Z-disc and associate with T-tubule components. Indeed, this region is becoming increasingly recognized as a signaling center in cardiomyocytes, not only for calcium cycling, excitation-contraction coupling, and calcium-sensitive hypertrophic signaling, but also as a nodal signaling hub where the myocyte can sense and respond to mechanical stress. Disruption of a wide range of critical structural and signaling molecules in cardiomyocytes confers susceptibility to cardiomyopathies in addition to the more classically studied mutations in sarcomeric proteins. However, the molecular mechanisms underlying DCM remain unclear. Here, we review what is known about the cardiomyocyte functions of LRRC10, lessons learned about LRRC10 and DCM from the Lrrc10 knockout mouse model, and discuss ongoing efforts to elucidate molecular mechanisms whereby mutation or absence of LRRC10 mediates cardiac disease. PMID:27536250

  15. A young man with hemoptysis: Rare association of idiopathic pulmonary hemosiderosis, celiac disease and dilated cardiomyopathy.

    PubMed

    Khilnani, Gopi C; Jain, Neetu; Tiwari, Pavan; Hadda, Vijay; Singh, Lavleen

    2015-01-01

    Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of recurrent diffuse alveolar hemorrhage (DAH) with no specific treatment. Herein, we discuss a case of hemoptysis, who had IPH and other rare associations. A 19-year-old man presented with recurrent hemoptysis, generalized weakness and progressive dyspnea for 3 years. Earlier, he was diagnosed with anemia and was treated with blood transfusions and hematinics. On examination he had pallor, tachycardia and was underweight. Investigations revealed low level of hemoglobin (7.8 g/dl) and iron deficiency. An electrocardiography (ECG) showed sinus tachycardia, interventricular conduction delay and T-wave inversion. Echocardiography revealed dilated cardiomyopathy with left ventricular dysfunction. Computed tomography of the chest demonstrated bilateral diffuse ground glass opacity suggestive of pulmonary hemorrhage. Pulmonary function tests showed restrictive pattern with increased carbon monoxide diffusion. Bronchoalveolar lavage and transbronchial lung biopsy showed hemosiderin-laden macrophages. Patient could recall recurrent episodes of diarrhea in childhood. Serum antitissue transglutamase antibodies were raised (291.66 IU/ml, normal <30 IU/ml). Duodenal biopsy showed subtotal villous atrophy consistent with celiac disease. He was started on gluten-free diet, beta blockers and diuretics. After two years of treatment, he has been showing consistent improvement. Screening for CD is important in patients with IPH. Cardiomyopathy forms rare third association. All three show improvement with gluten-free diet. PMID:25624603

  16. A Heterozygous ZMPSTE24 Mutation Associated with Severe Metabolic Syndrome, Ectopic Fat Accumulation, and Dilated Cardiomyopathy.

    PubMed

    Galant, Damien; Gaborit, Bénédicte; Desgrouas, Camille; Abdesselam, Ines; Bernard, Monique; Levy, Nicolas; Merono, Françoise; Coirault, Catherine; Roll, Patrice; Lagarde, Arnaud; Bonello-Palot, Nathalie; Bourgeois, Patrice; Dutour, Anne; Badens, Catherine

    2016-01-01

    ZMPSTE24 encodes the only metalloprotease, which transforms prelamin into mature lamin A. Up to now, mutations in ZMPSTE24 have been linked to Restrictive Dermopathy (RD), Progeria or Mandibulo-Acral Dysplasia (MAD). We report here the phenotype of a patient referred for severe metabolic syndrome and cardiomyopathy, carrying a mutation in ZMPSTE24. The patient presented with a partial lipodystrophic syndrome associating hypertriglyceridemia, early onset type 2 diabetes, and android obesity with truncal and abdominal fat accumulation but without subcutaneous lipoatrophy. Other clinical features included acanthosis nigricans, liver steatosis, dilated cardiomyopathy, and high myocardial and hepatic triglycerides content. Mutated fibroblasts from the patient showed increased nuclear shape abnormalities and premature senescence as demonstrated by a decreased Population Doubling Level, an increased beta-galactosidase activity and a decreased BrdU incorporation rate. Reduced prelamin A expression by siRNA targeted toward LMNA transcripts resulted in decreased nuclear anomalies. We show here that a central obesity without subcutaneous lipoatrophy is associated with a laminopathy due to a heterozygous missense mutation in ZMPSTE24. Given the high prevalence of metabolic syndrome and android obesity in the general population, and in the absence of familial study, the causative link between mutation and phenotype cannot be formally established. Nevertheless, altered lamina architecture observed in mutated fibroblasts are responsible for premature cellular senescence and could contribute to the phenotype observed in this patient. PMID:27120622

  17. A young man with hemoptysis: Rare association of idiopathic pulmonary hemosiderosis, celiac disease and dilated cardiomyopathy

    PubMed Central

    Khilnani, Gopi C; Jain, Neetu; Tiwari, Pavan; Hadda, Vijay; Singh, Lavleen

    2015-01-01

    Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of recurrent diffuse alveolar hemorrhage (DAH) with no specific treatment. Herein, we discuss a case of hemoptysis, who had IPH and other rare associations. A 19-year-old man presented with recurrent hemoptysis, generalized weakness and progressive dyspnea for 3 years. Earlier, he was diagnosed with anemia and was treated with blood transfusions and hematinics. On examination he had pallor, tachycardia and was underweight. Investigations revealed low level of hemoglobin (7.8 g/dl) and iron deficiency. An electrocardiography (ECG) showed sinus tachycardia, interventricular conduction delay and T-wave inversion. Echocardiography revealed dilated cardiomyopathy with left ventricular dysfunction. Computed tomography of the chest demonstrated bilateral diffuse ground glass opacity suggestive of pulmonary hemorrhage. Pulmonary function tests showed restrictive pattern with increased carbon monoxide diffusion. Bronchoalveolar lavage and transbronchial lung biopsy showed hemosiderin-laden macrophages. Patient could recall recurrent episodes of diarrhea in childhood. Serum antitissue transglutamase antibodies were raised (291.66 IU/ml, normal <30 IU/ml). Duodenal biopsy showed subtotal villous atrophy consistent with celiac disease. He was started on gluten-free diet, beta blockers and diuretics. After two years of treatment, he has been showing consistent improvement. Screening for CD is important in patients with IPH. Cardiomyopathy forms rare third association. All three show improvement with gluten-free diet. PMID:25624603

  18. Multiomics approach to identify novel biomarkers for dilated cardiomyopathy: Proteome and transcriptome analyses of 4C30 dilated cardiomyopathy mouse model.

    PubMed

    Nishigori, Mitsuhiro; Yagi, Hiroaki; Mochiduki, Akikazu; Minamino, Naoto

    2016-11-01

    Dilated cardiomyopathy (DCM) is an intractable disease, without any radical treatment option other than cardiac transplantation. Additionally, biomarkers to determine progressive staging are not yet available. Irrespective of the diversity of causative gene mutations, the phenotype of DCM is rather common. Therefore, it is plausible to determine DCM staging in terms of variations in protein and mRNA levels. In this study, we performed proteome and transcriptome analysis of the left ventricle of 4C30 DCM model mice showing mild and severe phenotypes at 12 and 24 weeks (wk) after birth, respectively. Proteomic analyses results showed 109 proteins that increased and 133 others that decreased among 1874 detected proteins. We selected biomarker candidates by confirming consistent alterations in protein levels at 12 and 24 wk, and mRNA levels at 12 wk, and narrowed these down based on the requirement that they should be detectable in blood. Finally, we selected six biomarker candidates based on sustained or augmented alteration at 24 wk and confirmed their definite alterations in the left ventricle by quantitative polymerase chain reaction, western blot analysis, and multiple reaction monitoring (MRM). To assess the validity of this strategy, we measured plasma concentrations of the six candidates by MRM method and identified two proteins (FTL1 and GRP78) that demonstrated significant elevation in the 4C30 mice plasma. Taken together, a multiomics strategy comparing tissue expression levels of proteins and mRNAs between diseased and control groups, with appropriate confirmation, is a promising approach for the discovery of new biomarkers. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 491-502, 2016. PMID:26799926

  19. Antisense-mediated exon skipping: a therapeutic strategy for titin-based dilated cardiomyopathy

    PubMed Central

    Gramlich, Michael; Pane, Luna Simona; Zhou, Qifeng; Chen, Zhifen; Murgia, Marta; Schötterl, Sonja; Goedel, Alexander; Metzger, Katja; Brade, Thomas; Parrotta, Elvira; Schaller, Martin; Gerull, Brenda; Thierfelder, Ludwig; Aartsma-Rus, Annemieke; Labeit, Siegfried; Atherton, John J; McGaughran, Julie; Harvey, Richard P; Sinnecker, Daniel; Mann, Matthias; Laugwitz, Karl-Ludwig; Gawaz, Meinrad Paul; Moretti, Alessandra

    2015-01-01

    Frameshift mutations in the TTN gene encoding titin are a major cause for inherited forms of dilated cardiomyopathy (DCM), a heart disease characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure. To date, there are no specific treatment options for DCM patients but heart transplantation. Here, we show the beneficial potential of reframing titin transcripts by antisense oligonucleotide (AON)-mediated exon skipping in human and murine models of DCM carrying a previously identified autosomal-dominant frameshift mutation in titin exon 326. Correction of TTN reading frame in patient-specific cardiomyocytes derived from induced pluripotent stem cells rescued defective myofibril assembly and stability and normalized the sarcomeric protein expression. AON treatment in Ttn knock-in mice improved sarcomere formation and contractile performance in homozygous embryos and prevented the development of the DCM phenotype in heterozygous animals. These results demonstrate that disruption of the titin reading frame due to a truncating DCM mutation can be restored by exon skipping in both patient cardiomyocytes in vitro and mouse heart in vivo, indicating RNA-based strategies as a potential treatment option for DCM. PMID:25759365

  20. Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C–deficient mice

    PubMed Central

    Nikolova, Vesna; Leimena, Christiana; McMahon, Aisling C.; Tan, Ju Chiat; Chandar, Suchitra; Jogia, Dilesh; Kesteven, Scott H.; Michalicek, Jan; Otway, Robyn; Verheyen, Fons; Rainer, Stephen; Stewart, Colin L.; Martin, David; Feneley, Michael P.; Fatkin, Diane

    2004-01-01

    Laminopathies are a group of disorders caused by mutations in the LMNA gene that encodes the nuclear lamina proteins, lamin A and lamin C; their pathophysiological basis is unknown. We report that lamin A/C–deficient (Lmna–/–) mice develop rapidly progressive dilated cardiomyopathy (DCM) characterized by left ventricular (LV) dilation and reduced systolic contraction. Isolated Lmna–/– myocytes show reduced shortening with normal baseline and peak amplitude of Ca2+ transients. Lmna–/– LV myocyte nuclei have marked alterations of shape and size with central displacement and fragmentation of heterochromatin; these changes are present but less severe in left atrial nuclei. Electron microscopy of Lmna–/– cardiomyocytes shows disorganization and detachment of desmin filaments from the nuclear surface with progressive disruption of the cytoskeletal desmin network. Alterations in nuclear architecture are associated with defective nuclear function evidenced by decreased SREBP1 import, reduced PPARγ expression, and a lack of hypertrophic gene activation. These findings suggest a model in which the primary pathophysiological mechanism in Lmna–/– mice is defective force transmission resulting from disruption of lamin interactions with the muscle-specific desmin network and loss of cytoskeletal tension. Despite severe DCM, defects in nuclear function prevent Lmna–/– cardiomyocytes from developing compensatory hypertrophy and accelerate disease progression. PMID:14755333

  1. Postpartum dilated cardiomyopathy in a patient with systemic lupus erythematosus, nephritis and lupus anticoagulant: a diagnostic dilemma

    PubMed Central

    Hall, Daniel; New, David; Kelly, Teresa

    2011-01-01

    A 32-year-old Caucasian woman presented with shortness of breath four weeks postpartum. She was known to suffer from systemic lupus erythematosus with cutaneous, joint and minor renal involvement. During pregnancy, the patient had developed nephrotic syndrome for which she was managed with prophylactic anticoagulation and corticosteroid therapy. A leg deep vein thrombosis had arisen following caesarean section following antepartum haemorrhage. Examination revealed a heart murmur, and pulmonary signs. Computed tomography pulmonary angiogram showed cardiomegaly and bilateral pleural effusions but no pulmonary embolus. Echocardiogram demonstrated dilated cardiomyopathy. An initial diagnosis of peripartum cardiomyopathy was considered, with lupus myocarditis and coronary in situ thrombosis among the differential diagnoses.

  2. Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

    PubMed

    Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

    2014-03-01

    Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment. PMID:24684896

  3. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases.

    PubMed

    Pinto, Yigal M; Elliott, Perry M; Arbustini, Eloisa; Adler, Yehuda; Anastasakis, Aris; Böhm, Michael; Duboc, Denis; Gimeno, Juan; de Groote, Pascal; Imazio, Massimo; Heymans, Stephane; Klingel, Karin; Komajda, Michel; Limongelli, Giuseppe; Linhart, Ales; Mogensen, Jens; Moon, James; Pieper, Petronella G; Seferovic, Petar M; Schueler, Stephan; Zamorano, Jose L; Caforio, Alida L P; Charron, Philippe

    2016-06-14

    In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance. PMID:26792875

  4. Cofilin-2 Phosphorylation and Sequestration In Myocardial Aggregates: Novel Pathogenetic Mechanisms For Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Subramanian, Khaushik; Gianni, Davide; Balla, Cristina; Assenza, Gabriele Egidy; Joshi, Mugdha; Semigran, Marc J.; Macgillivray, Thomas E.; Van Eyk, Jennifer E.; Agnetti, Giulio; Paolocci, Nazareno; Bamburg, James R.; Agrawal, Pankaj B.; del Monte, Federica

    2015-01-01

    BACKGROUND Recently, tangles and plaque-like aggregates have been identified in certain cases of dilated cardiomyopathy (DCM). This suggests a potential underlying cause for the one-third of cases, traditionally labeled idiopathic (iDCM), where there is no specific diagnostic test or targeted therapy. OBJECTIVE We sought to identify the make-up of myocardial aggregates to understand the molecular mechanisms of these cases of DCM; this strategy has been central to understanding Alzheimer’s disease. METHODS Aggregates were extracted from human iDCM samples with high congophilic reactivity (an indication of plaque presence) and the findings validated in a larger cohort of samples. We tested the expression, distribution, and activity of cofilin in human tissue and generated a cardiac-specific knockout mouse model to investigate the functional impact of the human findings. We also modeled cofilin inactivity in vitro using pharmacological and genetic gain and loss of function approaches. RESULTS Aggregates in the human myocardium were enriched for cofilin-2, an actin-depolymerizing protein known to participate in neurodegenerative diseases and nemaline myopathy. Cofilin-2 was predominantly phosphorylated, rendering it inactive. Cardiac-specific haploinsufficiency of cofilin-2 in mice recapitulated the human disease’s morphological, functional, and structural phenotype. Pharmacological stimulation of cofilin-2 phosphorylation and genetic overexpression of the phosphomimetic protein promoted the accumulation of “stress-like” fibers and severely impaired cardiomyocyte contractility. CONCLUSIONS Our study provides the first biochemical characterization of prefibrillar myocardial aggregates in humans and the first report to link cofilin-2 to cardiomyopathy. The findings suggest a common pathogenetic mechanism between certain iDCMs and other chronic degenerative diseases, laying the groundwork for new therapeutic strategies. PMID:25814227

  5. Modulation of Serotonin Transporter Function during Fetal Development Causes Dilated Heart Cardiomyopathy and Lifelong Behavioral Abnormalities

    PubMed Central

    Noorlander, Cornelle W.; Ververs, Frederique F. T.; Nikkels, Peter G. J.; van Echteld, Cees J. A.; Visser, Gerard H. A.; Smidt, Marten P.

    2008-01-01

    Background Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI. Methodology/Principal Findings In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. Conclusions These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy and a higher

  6. Regional mapping of myocardial hibernation phenotype in idiopathic end-stage dilated cardiomyopathy

    PubMed Central

    Lionetti, Vincenzo; Matteucci, Marco; Ribezzo, Marco; Di Silvestre, Dario; Brambilla, Francesca; Agostini, Silvia; Mauri, Pierluigi; Padeletti, Luigi; Pingitore, Alessandro; Delsedime, Luisa; Rinaldi, Mauro; Recchia, Fabio A; Pucci, Angela

    2014-01-01

    Myocardial hibernation (MH) is a well-known feature of human ischaemic cardiomyopathy (ICM), whereas its presence in human idiopathic dilated cardiomyopathy (DCM) is still controversial. We investigated the histological and molecular features of MH in left ventricle (LV) regions of failing DCM or ICM hearts. We examined failing hearts from DCM (n = 11; 41.9 ± 5.45 years; left ventricle-ejection fraction (LV-EF), 18 ± 3.16%) and ICM patients (n = 12; 58.08 ± 1.7 years; LVEF, 21.5 ± 6.08%) undergoing cardiac transplantation, and normal donor hearts (N, n = 8). LV inter-ventricular septum (IVS) and antero-lateral free wall (FW) were transmurally (i.e. sub-epicardial, mesocardial and sub-endocardial layers) analysed. LV glycogen content was shown to be increased in both DCM and ICM as compared with N hearts (P < 0.001), with a U-shaped transmural distribution (lower values in mesocardium). Capillary density was homogenously reduced in both DCM and ICM as compared with N (P < 0.05 versus N), with a lower decrease independent of the extent of fibrosis in sub-endocardial and sub-epicardial layers of DCM as compared with ICM. HIF1-α and nestin, recognized ischaemic molecular hallmarks, were similarly expressed in DCM-LV and ICM-LV myocardium. The proteomic profile was overlapping by ˜50% in DCM and ICM groups. Morphological and molecular features of MH were detected in end-stage ICM as well as in end-stage DCM LV, despite epicardial coronary artery patency and lower fibrosis in DCM hearts. Unravelling the presence of MH in the absence of coronary stenosis may be helpful to design a novel approach in the clinical management of DCM. PMID:24444256

  7. Coronary microcirculation changes in non-ischemic dilated cardiomyopathy identified by novel perfusion CT

    PubMed Central

    Miller, Wayne L.; Behrenbeck, Thomas R.; McCollough, Cynthia H.; Williamson, Eric E.; Leng, Shuai; Kline, Timothy L.

    2015-01-01

    Intramyocardial microvessels demonstrate functional changes in cardiomyopathies. However, clinical computed tomography (CT) does not have adequate spatial resolution to assess the microvessels. Our hypothesis is that these functional changes manifest as altered heterogeneity of the spatial distribution of arteriolar perfusion territories. Our goal was to determine whether the spatial analysis of perfusion CT could clinically detect changes in the function and structure of the intramyocardial microcirculation in a non-ischemic dilated cardiomyopathy (DCM). Two groups were studied: (1) a Control group (12 male plus 12 female) with no risk factors nor evidence of coronary artery disease, and (2) a DCM group (12 male plus 12 female)with left ventricular ejection fraction ≤40 %and no evidence of coronary artery disease. Using the CT scan, the LV free wall thickness and its radius of curvature were measured. The DCM group was sub divided into those with LV free wall thickness <11.5 mm and those with thickness≥11.5 mm. In themyocardial opacification phase of the CT scan sequence, myocardial perfusion (F) and intramyocardial blood volume (Bv) for multiple intramyocardial regions were computed. No significant differences between the groups were demonstrable in overall myocardial F or Bv. However, the myocardial regional data showed significantly increased spatial heterogeneity in the DCM group when compared to the Control group. The findings demonstrate that altered function of the subresolution intramyocardial microcirculation can be quantified with myocardial perfusion CT and that significant changes in these parameters occur in the DCM subjects with LV wall thickness greater than 11.5 mm. PMID:25712168

  8. Anomalous origin of the left coronary artery from the pulmonary artery presenting as dilated cardiomyopathy: a case report

    PubMed Central

    2014-01-01

    Introduction Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital anomaly and one of the causes of myocardial ischemia. The usual clinical course is severe left-sided heart failure and mitral valve insufficiency presenting during the first months of life. Case presentation We report the case of a 6-month-old Tunisian girl who presented with dilated cardiomyopathy. Echocardiography suspected anomalous origin of the left coronary artery. The definitive diagnosis of anomalous origin of the left coronary artery from the pulmonary artery was reached by multislice computed tomography and coronary angiography. Conclusion In cases of dilated cardiomyopathy, anomalous origin of the left coronary artery from the pulmonary artery syndrome has to be kept in mind as a surgically correctable cause. PMID:24885797

  9. Cardiomyopathy

    MedlinePlus

    ... or surgeries may also be used, including: A defibrillator that sends an electrical pulse to stop life- ... failure - overview Heart transplant Hypertrophic cardiomyopathy Implantable cardioverter-defibrillator Peripartum cardiomyopathy Restrictive cardiomyopathy Patient Instructions Heart failure - ...

  10. Cardiomyopathy

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Cardiomyopathy? Cardiomyopathy refers to diseases of the heart muscle. These ... many causes, signs and symptoms, and treatments. In cardiomyopathy, the heart muscle becomes enlarged, thick, or rigid. ...

  11. Low dose dobutamine stress echocardiography predicts the improvement of left ventricular systolic function in dilated cardiomyopathy

    PubMed Central

    Kitaoka, H; Takata, J; Yabe, T; Hitomi, N; Furuno, T; Doi, Y

    1999-01-01

    OBJECTIVE—To determine whether dobutamine stress echocardiography can predict the improvement of left ventricular systolic function in patients with dilated cardiomyopathy (DCM).
METHODS—Myocardial contractile reserve, as assessed by dobutamine stress echocardiography, was determined in 18 patients with DCM (mean (SD) age 53 (13) years, left ventricular ejection fraction (LVEF) 28 (10)%) and compared with changes in LVEF during a follow up period of 15 (8) months. The LVEF and regional left ventricular wall motion score (0, normal to 4, dyskinesis) of 12 segments in short axis and four chamber views were analysed before and after dobutamine infusion (5-20 µg/kg/min).
RESULTS—During a follow up period of 15 (8) months, a significant improvement in LVEF (> 20%) was found in seven patients but not in the remaining 11. Baseline haemodynamic findings were similar in both groups. Patients with an improvement in follow up LVEF showed a greater change in wall motion score from baseline during dobutamine infusion than patients with no improvement (at rest, 1.7 (0.4) v 1.9 (0.2), NS; dobutamine 10 µg/kg/min, 0.6 (0.4) v 1.2 (0.4), p < 0.05). The percentage change in LVEF during dobutamine infusion was also significantly greater in patients who showed improvement than in those who did not. The change in LVEF during the follow up period (follow up LVEF/baseline LVEF) correlated well with the change in LVEF during dobutamine stress (LVEF at rest/LVEF at dobutamine 10 µg/kg/min; r = 0.74, p < 0.001).
CONCLUSIONS—Changes in left ventricular systolic performance during low dose dobutamine stress echocardiography are a useful marker to predict the outcome of left ventricular systolic function in patients with DCM.


Keywords: dilated cardiomyopathy; dobutamine stress echocardiography; contractile reserve PMID:10212172

  12. Autoantibodies in dilated cardiomyopathy induce vascular endothelial growth factor expression in cardiomyocytes

    SciTech Connect

    Saygili, Erol; Noor-Ebad, Fawad; Schröder, Jörg W.; Mischke, Karl; Saygili, Esra; Rackauskas, Gediminas; Marx, Nikolaus; Kelm, Malte; Rana, Obaida R.

    2015-09-11

    Background: Autoantibodies have been identified as major predisposing factors for dilated cardiomyopathy (DCM). Patients with DCM show elevated serum levels of vascular endothelial growth factor (VEGF) whose source is unknown. Besides its well-investigated effects on angiogenesis, evidence is present that VEGF signaling is additionally involved in fibroblast proliferation and cardiomyocyte hypertrophy, hence in cardiac remodeling. Whether autoimmune effects in DCM impact cardiac VEGF signaling needs to be elucidated. Methods: Five DCM patients were treated by the immunoadsorption (IA) therapy on five consecutive days. The eluents from the IA columns were collected and prepared for cell culture. Cardiomyocytes from neonatal rats (NRCM) were incubated with increasing DCM-immunoglobulin-G (IgG) concentrations for 48 h. Polyclonal IgG (Venimmun N), which was used to restore IgG plasma levels in DCM patients after the IA therapy was additionally used for control cell culture purposes. Results: Elevated serum levels of VEGF decreased significantly after IA (Serum VEGF (ng/ml); DCM pre-IA: 45 ± 9.1 vs. DCM post–IA: 29 ± 6.7; P < 0.05). In cell culture, pretreatment of NRCM by DCM-IgG induced VEGF expression in a time and dose dependent manner. Biologically active VEGF that was secreted by NRCM significantly increased BNP mRNA levels in control cardiomyocytes and induced cell-proliferation of cultured cardiac fibroblast (Fibroblast proliferation; NRCM medium/HC-IgG: 1 ± 0.0 vs. NRCM medium/DCM-IgG 100 ng/ml: 5.6 ± 0.9; P < 0.05). Conclusion: The present study extends the knowledge about the possible link between autoimmune signaling in DCM and VEGF induction. Whether this observation plays a considerable role in cardiac remodeling during DCM development needs to be further elucidated. - Highlights: • Mechanisms of remodeling in dilated cardiomyopathy (DCM) are not fully understood. • Autoantibodies have been identified as major predisposing factors

  13. Anaesthetic management of laparoscopic surgery for rectal cancer in patients of dilated cardiomyopathy with poor ejection fraction: a case report

    PubMed Central

    Wu, Yao-Hua; Hu, Liang; Xia, Jin; Hao, Quan-Shui; Feng, Li; Xiang, Hong-Bing

    2015-01-01

    A patient with dilated cardiomyopathy with poor ejection fraction posted for laparoscopic surgery for rectal cancer which was successfully performed under general anesthesia with endotracheal intubation and mechanical ventilation was reported. Our observations strongly indicate that detailed preoperative assessment, watchful intraoperative monitoring, and skillful optimization of fluid status and hemodynamic play important role in the high risk patient under general anesthesia with endotracheal intubation and mechanical ventilation. PMID:26309623

  14. Serum lipidomics meets cardiac magnetic resonance imaging: profiling of subjects at risk of dilated cardiomyopathy.

    PubMed

    Sysi-Aho, Marko; Koikkalainen, Juha; Seppänen-Laakso, Tuulikki; Kaartinen, Maija; Kuusisto, Johanna; Peuhkurinen, Keijo; Kärkkäinen, Satu; Antila, Margareta; Lauerma, Kirsi; Reissell, Eeva; Jurkko, Raija; Lötjönen, Jyrki; Heliö, Tiina; Orešič, Matej

    2011-01-01

    Dilated cardiomyopathy (DCM), characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure, sudden cardiac death or need for heart transplantation. Lamin A/C gene (LMNA) on chromosome 1p12 is the most significant disease gene causing DCM and has been reported to cause 7-9% of DCM leading to cardiac transplantation. We have previously performed cardiac magnetic resonance imaging (MRI) to LMNA carriers to describe the early phenotype. Clinically, early recognition of subjects at risk of developing DCM would be important but is often difficult. Thus we have earlier used the MRI findings of these LMNA carriers for creating a model by which LMNA carriers could be identified from the controls at an asymptomatic stage. Some LMNA mutations may cause lipodystrophy. To characterize possible effects of LMNA mutations on lipid profile, we set out to apply global serum lipidomics using Ultra Performance Liquid Chromatography coupled to mass spectrometry in the same LMNA carriers, DCM patients without LMNA mutation and controls. All DCM patients, with or without LMNA mutation, differed from controls in regard to distinct serum lipidomic profile dominated by diminished odd-chain triglycerides and lipid ratios related to desaturation. Furthermore, we introduce a novel approach to identify associations between the molecular lipids from serum and the MR images from the LMNA carriers. The association analysis using dependency network and regression approaches also helped us to obtain novel insights into how the affected lipids might relate to cardiac shape and volume changes. Our study provides a framework for linking serum derived molecular markers not only with clinical endpoints, but also with the more subtle intermediate phenotypes, as derived from medical imaging, of potential pathophysiological relevance. PMID:21283746

  15. Sensitivity Analysis of Left Ventricle with Dilated Cardiomyopathy in Fluid Structure Simulation

    PubMed Central

    Chan, Bee Ting; Abu Osman, Noor Azuan; Lim, Einly; Chee, Kok Han; Abdul Aziz, Yang Faridah; Abed, Amr Al; Lovell, Nigel H.; Dokos, Socrates

    2013-01-01

    Dilated cardiomyopathy (DCM) is the most common myocardial disease. It not only leads to systolic dysfunction but also diastolic deficiency. We sought to investigate the effect of idiopathic and ischemic DCM on the intraventricular fluid dynamics and myocardial wall mechanics using a 2D axisymmetrical fluid structure interaction model. In addition, we also studied the individual effect of parameters related to DCM, i.e. peak E-wave velocity, end systolic volume, wall compliance and sphericity index on several important fluid dynamics and myocardial wall mechanics variables during ventricular filling. Intraventricular fluid dynamics and myocardial wall deformation are significantly impaired under DCM conditions, being demonstrated by low vortex intensity, low flow propagation velocity, low intraventricular pressure difference (IVPD) and strain rates, and high-end diastolic pressure and wall stress. Our sensitivity analysis results showed that flow propagation velocity substantially decreases with an increase in wall stiffness, and is relatively independent of preload at low-peak E-wave velocity. Early IVPD is mainly affected by the rate of change of the early filling velocity and end systolic volume which changes the ventriculo:annular ratio. Regional strain rate, on the other hand, is significantly correlated with regional stiffness, and therefore forms a useful indicator for myocardial regional ischemia. The sensitivity analysis results enhance our understanding of the mechanisms leading to clinically observable changes in patients with DCM. PMID:23825628

  16. Sensitivity analysis of left ventricle with dilated cardiomyopathy in fluid structure simulation.

    PubMed

    Chan, Bee Ting; Abu Osman, Noor Azuan; Lim, Einly; Chee, Kok Han; Abdul Aziz, Yang Faridah; Abed, Amr Al; Lovell, Nigel H; Dokos, Socrates

    2013-01-01

    Dilated cardiomyopathy (DCM) is the most common myocardial disease. It not only leads to systolic dysfunction but also diastolic deficiency. We sought to investigate the effect of idiopathic and ischemic DCM on the intraventricular fluid dynamics and myocardial wall mechanics using a 2D axisymmetrical fluid structure interaction model. In addition, we also studied the individual effect of parameters related to DCM, i.e. peak E-wave velocity, end systolic volume, wall compliance and sphericity index on several important fluid dynamics and myocardial wall mechanics variables during ventricular filling. Intraventricular fluid dynamics and myocardial wall deformation are significantly impaired under DCM conditions, being demonstrated by low vortex intensity, low flow propagation velocity, low intraventricular pressure difference (IVPD) and strain rates, and high-end diastolic pressure and wall stress. Our sensitivity analysis results showed that flow propagation velocity substantially decreases with an increase in wall stiffness, and is relatively independent of preload at low-peak E-wave velocity. Early IVPD is mainly affected by the rate of change of the early filling velocity and end systolic volume which changes the ventriculo:annular ratio. Regional strain rate, on the other hand, is significantly correlated with regional stiffness, and therefore forms a useful indicator for myocardial regional ischemia. The sensitivity analysis results enhance our understanding of the mechanisms leading to clinically observable changes in patients with DCM. PMID:23825628

  17. Induction of Ankrd1 in Dilated Cardiomyopathy Correlates with the Heart Failure Progression

    PubMed Central

    Bogomolovas, Julius; Brohm, Kathrin; Čelutkienė, Jelena; Balčiūnaitė, Giedrė; Bironaitė, Daiva; Bukelskienė, Virginija; Daunoravičus, Dainius; Witt, Christian C.; Fielitz, Jens; Grabauskienė, Virginija; Labeit, Siegfried

    2015-01-01

    Progression of idiopathic dilated cardiomyopathy (IDCM) is marked with extensive left ventricular remodeling whose clinical manifestations and molecular basis are poorly understood. We aimed to evaluate the clinical potential of titin ligands in monitoring progression of cardiac remodeling associated with end-stage IDCM. Expression patterns of 8 mechanoptotic machinery-associated titin ligands (ANKRD1, ANKRD2, TRIM63, TRIM55, NBR1, MLP, FHL2, and TCAP) were quantitated in endomyocardial biopsies from 25 patients with advanced IDCM. When comparing NYHA disease stages, elevated ANKRD1 expression levels marked transition from NYHA < IV to NYHA IV. ANKRD1 expression levels closely correlated with systolic strain depression and short E wave deceleration time, as determined by echocardiography. On molecular level, myocardial ANKRD1 and serum adiponectin correlated with low BAX/BCL-2 ratios, indicative of antiapoptotic tissue propensity observed during the worsening of heart failure. ANKRD1 is a potential marker for cardiac remodeling and disease progression in IDCM. ANKRD1 expression correlated with reduced cardiac contractility and compliance. The association of ANKRD1 with antiapoptotic response suggests its role as myocyte survival factor during late stage heart disease, warranting further studies on ANKRD1 during end-stage heart failure. PMID:25961010

  18. Gating pore currents, a new pathological mechanism underlying cardiac arrhythmias associated with dilated cardiomyopathy

    PubMed Central

    Moreau, Adrien; Gosselin-Badaroudine, Pascal; Chahine, Mohamed

    2015-01-01

    Voltage-gated ion channels (VGIC) are transmembrane proteins responsible for the generation of electrical signals in excitable cells. VGIC were first described in 1952 by Hodgkin and Huxley,1 and have since been associated with various physiological functions such as propagating nerve impulses, locomotion, and cardiac excitability. VGIC include channels specialized in the selective passage of K+, Ca2+ Na+, or H+. They are composed of 2 main structures: the pore domain (PD) and the voltage sensor domain (VSD). The PD ensures the physiological flow of ions and is typically composed of 8 transmembrane segments (TM). The VSD detects voltage variations and is composed of 4 TM (S1-S4). Given their crucial physiological role, VGIC dysfunctions are associated with diverse pathologies known as ion channelopathies. These dysfunctions usually affect the membrane expression of ion channels or voltage-dependent conformational changes of the pore. However, an increasing number of ion channelopathies, including periodic paralysis, dilated cardiomyopathy (DCM) associated with cardiac arrhythmias, and peripheral nerve hyperexcitability (PNH), have been linked to the appearance of a new pathological mechanism involving the creation of an alternative permeation pathway through the normally non-conductive VSD of VGIC. This permeation pathway is called the gating pore or omega pore. PMID:26046592

  19. Study of peripheral stem cells mobilization as a treatment line of pediatric dilated cardiomyopathy

    PubMed Central

    El-Shehaby, Waled; Hables, Nahed; Hamad, Said; Attia, Mohamed; El-Said, Ayman

    2015-01-01

    Background Mobilizing hematopoietic stem cells may be a promising intervention for the treatment of idiopathic dilated cardiomyopathy (IDCM) in infant and children. So the aim of the work is to evaluate the efficacy of granulocyte-colony stimulating factor (G-CSF) as a therapeutic modality in pediatric IDCM. Methods A randomized clinical trial was conducted on 40 pediatric patients with IDCM. They were subjected to history taking, clinical examination, serum lactate dehydrogenase (LDH), total creatinine phosphokinase (CPK), creatinine phosphokinase isoenzyme B (CK-MB) isoenzyme, and peripheral blood CD34+ cell assessment before and at day 7 after subcutaneous G-CSF injection for 5 consecutive days. Echocardiography was done before and 1, 3 and 6 months after therapy. Results Clinical improvement in the form of regression of patients Modified Ross heart failure (MRHC) classification classes. Increased percentage of CD34+ mobilized cells from the bone marrow, and significant increase in blood counts especially white blood cells 7 days after G-CSF injection. Significant improvement was found in echocardiographic data evaluating systolic function of the heart [Ejection fraction, Fractional shortening and systolic velocity at mitral annulus (Sm)]. Conclusions Administration of G-CSF may be beneficial in improving systolic functions of the heart in pediatric IDCM and more studies with a large number of patients are needed. PMID:27358889

  20. HLA-DR3 antigen in the resistance to idiopathic dilated cardiomyopathy

    PubMed Central

    Jin, B.; Wu, B.W.; Wen, Z.C.; Shi, H.M.; Zhu, J.

    2016-01-01

    Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR3 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies were identified by searching the PUBMED and Embase database (starting from June 2015). A total of 19 case-control studies including 1378 cases and 10383 controls provided data on the association between HLA-DR3 antigen and genetic susceptibility to IDC. Overall, significantly decreased frequency of HLA-DR3 allele (OR=0.72; 95%CI=0.58-0.90; P=0.004) was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically decreased risk was found for IDC in myocardial biopsy cases (OR=0.69; 95%CI=0.57-0.84; P=0.0003). In the subgroup analysis by ethnicity, borderline statistically significantly decreased risk was found among Europeans from 12 case-control studies (OR=0.76; 95%CI=0.58-1.00; P=0.05). In conclusion, our results suggest that individuals with HLA-DR3 antigen may have a protective effect against IDC. PMID:27007655

  1. Dilated Cardiomyopathy Revealing Cushing Disease: A Case Report and Literature Review.

    PubMed

    Marchand, Lucien; Segrestin, Bérénice; Lapoirie, Marion; Favrel, Véronique; Dementhon, Julie; Jouanneau, Emmanuel; Raverot, Gérald

    2015-11-01

    Cardiovascular impairments are frequent in Cushing's syndrome and the hypercortisolism can result in cardiac structural and functional changes that lead in rare cases to dilated cardiomyopathy (DCM). Such cardiac impairment may be reversible in response to a eucortisolaemic state.A 43-year-old man with a medical past of hypertension and history of smoking presented to the emergency department with global heart failure. Coronary angiography showed a significant stenosis of a marginal branch and cardiac MRI revealed a nonischemic DCM. The left ventricular ejection fraction (LVEF) was estimated as 28% to 30%. Clinicobiological features and pituitary imaging pointed toward Cushing's disease and administration of adrenolytic drugs (metyrapone and ketoconazole) was initiated. Despite the normalization of cortisol which had been achieved 2 months later, the patient presented an acute heart failure. A massive mitral regurgitation secondary to posterior papillary muscle rupture was diagnosed as a complication of the occlusion of the marginal branch. After 6 months of optimal pharmacological treatment for systolic heart failure, as well as treatment with inhibitors of steroidogenesis, there was no improvement of LVEF. The percutaneous mitral valve was therefore repaired and a defibrillator implanted. The severity of heart failure contraindicated pituitary surgery and the patient was instead treated by stereotaxic radiotherapy.This is the first case reporting a Cushing's syndrome DCM without improvement of LVEF despite normalization of serum cortisol levels. PMID:26579807

  2. Dilated cardiomyopathy and impaired cardiac hypertrophic response to angiotensin II in mice lacking FGF-2

    PubMed Central

    Pellieux, Corinne; Foletti, Alessandro; Peduto, Giovanni; Aubert, Jean-François; Nussberger, Jürg; Beermann, Friedrich; Brunner, Hans-R.; Pedrazzini, Thierry

    2001-01-01

    FGF-2 has been implicated in the cardiac response to hypertrophic stimuli. Angiotensin II (Ang II) contributes to maintain elevated blood pressure in hypertensive individuals and exerts direct trophic effects on cardiac cells. However, the role of FGF-2 in Ang II–induced cardiac hypertrophy has not been established. Therefore, mice deficient in FGF-2 expression were studied using a model of Ang II–dependent hypertension and cardiac hypertrophy. Echocardiographic measurements show the presence of dilated cardiomyopathy in normotensive mice lacking FGF-2. Moreover, hypertensive mice without FGF-2 developed no compensatory cardiac hypertrophy. In wild-type mice, hypertrophy was associated with a stimulation of the c-Jun N-terminal kinase, the extracellular signal regulated kinase, and the p38 kinase pathways. In contrast, mitogen-activated protein kinase (MAPK) activation was markedly attenuated in FGF-2–deficient mice. In vitro, FGF-2 of fibroblast origin was demonstrated to be essential in the paracrine stimulation of MAPK activation in cardiomyocytes. Indeed, fibroblasts lacking FGF-2 expression have a defective capacity for releasing growth factors to induce hypertrophic responses in cardiomyocytes. Therefore, these results identify the cardiac fibroblast population as a primary integrator of hypertrophic stimuli in the heart, and suggest that FGF-2 is a crucial mediator of cardiac hypertrophy via autocrine/paracrine actions on cardiac cells. PMID:11748268

  3. Elevated levels of antibodies against sulphatide are present in all chronic chagasic and dilated cardiomyopathy sera.

    PubMed Central

    Avila, J L; Rojas, M; Carrasco, H

    1993-01-01

    A natural anti-sulphatide antibody was found to be present in the serum of every normal individual studied. The reactivity of the antibody was assessed by its interaction with galactosylceramide-I3-sulphate. Antigen-antibody binding was strongly blocked by 1 mM heparin, dextran sulphate and chondroitin sulphate A, and by 5 mM chondroitin sulphate B. Antibodies avidly absorb to rabbit erythrocytes, but discretely to rat erythrocytes, suggesting that they are different from galactocerebroside antibodies. Elevated levels of sulphatide antibodies were present in all of 102 chronic Trypanosoma cruzi-infected patients studied, but not in other patients having cutaneous or visceral leishmaniasis, T. rangeli infection or several other protozoal, helminthic or mycotic infections. Interestingly, 100% of 40 dilated cardiomyopathy patients also have elevated levels of sulphatide antibodies. As T. cruzi is rich in galactocerebroside sulphate, it is proposed that in chagasic patients this glycolipid could act as an immunogen, inducing elevated titres of sulphatide antibodies, which could be important in the pathogenesis of cardiac or peripheral nerve symptoms. PMID:8513577

  4. Respiratory chain defect of myocardial mitochondria in idiopathic dilated cardiomyopathy of Doberman pinscher dogs.

    PubMed

    McCutcheon, L J; Cory, C R; Nowack, L; Shen, H; Mirsalami, M; Lahucky, R; Kovac, L; O'Grady, M; Horne, R; O'Brien, P J

    1992-11-01

    Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of unknown cause. We tested the hypothesis that IDCM was associated with a myocardial metabolic defect by determining a comprehensive biochemical profile of metabolite concentrations and enzyme activities for the major metabolic pathways of the myocardium. We used the Doberman pinscher breed as a naturally occurring canine model of IDCM and compared its myocardial profile with that of healthy adult mongrels. Compared with controls, myocardium in IDCM had markedly reduced mitochondrial electron transport activity and myoglobin concentration, in association with acidosis and energy depletion following anoxic challenge: 60% decreased NADH dehydrogenase and 50% decreased ATP synthetase activities; 90% decreased myoglobin concentration; and 30% reduced ATP and 50% increased lactate and proton concentrations. Sarcoplasmic reticulum Ca(2+)-transport ATPase was decreased by 42%. There was a 15% compensatory increase in fatty acid oxidation and Krebs cycle activity. Other biochemical changes were mild by comparison with the mitochondrial defects. We conclude that IDCM is associated with a marked impairment of mitochondrial production of ATP, arising from decreased activity of the mitochondrial electron transport system, including myoglobin. These changes may be secondary to an underlying genetic defect or may indicate a deficiency of the mitochondrial respiratory chain that predisposes this breed to heart failure. PMID:1338376

  5. [Dilated cardiomyopathy (DCM) in dogs--pathological, clinical, diagnosis and genetic aspects].

    PubMed

    Broschk, C; Distl, O

    2005-10-01

    Dilated cardiomyopathy (DCM) is a heart disease which is often found in humans and animals. The age of onset of this progressive disease varies between 3 and 7 years of age. A juvenile form of DCM has been found in Portuguese Water Dogs and Doberman Pinscher Dogs. Some breeds such as Doberman pinscher, Newfoundland, Portuguese Water dog, Boxer, Great Dane, Cocker Spaniel and Irish Wolfhound exhibit a higher prevalence to DCM. There also seems to be a sex predisposition as male dogs are affected more often than female dogs and in Great Danes an X-linked recessive inheritance is likely. In Newfoundland and Boxer an autosomal dominant inheritance was found whereas an autosomal recessive inheritance was described in Portuguese Water Dogs. Atrial fibrillation as a cause or consequence of DCM is assumed for certain breeds. The causes of DCM are widely unknown in dogs. A genetic basis for this heart disease seems to exist. Apart from a few exceptions the mode of inheritance and the possible underlying gene mutations are not known for DCM in dogs. In humans mutations in several genes responsible for DCM have been identified. Comparative genetic analyses in dogs using genes causing DCM in men and a genome-wide scan with anonymus markers were not able to detect causative mutations or genomic regions harboring gene loci linked to DCM. The investigation of the genetic basis of canine DCM may lead to new insights into the pathogenesis of DCM and may result in new therapeutic approaches and breeding strategies. PMID:16320572

  6. Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy

    PubMed Central

    Wu, Lei; Ong, SuFey; Talor, Monica V.; Barin, Jobert G.; Baldeviano, G. Christian; Kass, David A.; Bedja, Djahida; Zhang, Hao; Sheikh, Asfandyar; Margolick, Joseph B.; Iwakura, Yoichiro; Rose, Noel R.; Čiháková, Daniela

    2014-01-01

    Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in individuals below the age of 40. We recently reported that IL-17A is required for the development of DCMi. We show a novel pathway connecting IL-17A, cardiac fibroblasts (CFs), GM-CSF, and heart-infiltrating myeloid cells with the pathogenesis of DCMi. Il17ra−/− mice were protected from DCMi, and this was associated with significantly diminished neutrophil and Ly6Chi monocyte/macrophage (MO/MΦ) cardiac infiltrates. Depletion of Ly6Chi MO/MΦ also protected mice from DCMi. Mechanistically, IL-17A stimulated CFs to produce key chemokines and cytokines that are critical downstream effectors in the recruitment and differentiation of myeloid cells. Moreover, IL-17A directs Ly6Chi MO/MΦ in trans toward a more proinflammatory phenotype via CF-derived GM-CSF. Collectively, this IL-17A–fibroblast–GM-CSF–MO/MΦ axis could provide a novel target for the treatment of DCMi and related inflammatory cardiac diseases. PMID:24935258

  7. Functional Class in Children with Idiopathic Dilated Cardiomyopathy. A pilot Study

    PubMed Central

    Tavares, Aline Cristina; Bocchi, Edimar Alcides; Guimarães, Guilherme Veiga

    2016-01-01

    Background Idiopathic dilated cardiomyopathy (IDCM), most common cardiac cause of pediatric deaths, mortality descriptor: a low left ventricular ejection fraction (LVEF) and low functional capacity (FC). FC is never self reported by children. Objective The aims of this study were (i) To evaluate whether functional classifications according to the children, parents and medical staff were associated. (iv) To evaluate whether there was correlation between VO2 max and Weber's classification. Method Prepubertal children with IDCM and HF (by previous IDCM and preserved LVEF) were selected, evaluated and compared. All children were assessed by testing, CPET and functional class classification. Results Chi-square test showed association between a CFm and CFp (1, n = 31) = 20.6; p = 0.002. There was no significant association between CFp and CFc (1, n = 31) = 6.7; p = 0.4. CFm and CFc were not associated as well (1, n = 31) = 1.7; p = 0.8. Weber's classification was associated to CFm (1, n = 19) = 11.8; p = 0.003, to CFp (1, n = 19) = 20.4; p = 0.0001and CFc (1, n = 19) = 6.4; p = 0.04). Conclusion Drawing were helpful for children's self NYHA classification, which were associated to Weber's stratification. PMID:27168472

  8. Involvement of mast cells in the development of fibrosis in rats with postmyocarditis dilated cardiomyopathy.

    PubMed

    Palaniyandi Selvaraj, Suresh; Watanabe, Kenichi; Ma, Meilei; Tachikawa, Hitoshi; Kodama, Makoto; Aizawa, Yoshifusa

    2005-11-01

    Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality. Occurrence of myocardial fibrosis is an important event in the ventricular remodeling process, which takes place during DCM. Mast cells are well known inflammatory cells implicated in various biological phenomena. The involvement of mast cells in the development of myocardial fibrosis of DCM in rats after autoimmune myocarditis remains unknown. Nine-week-old male Lewis rats were immunized with cardiac myosin and divided into vehicle treated (group V) and disodium cromoglycate (DSCG), a mast cell stabilizer (24 mg/kg i.p.) treated (group DSCG) groups. The animals were sacrificed after 60 d of immunization. The myocardium was excised and preserved for histopathology and protein analysis. Myocardial levels of transforming growth factor (TGF) beta1 and collagen-III were quantified. Staining of mast cells was performed by toluidine blue. A significant correlation was obtained between myocardial fibrosis and cardiac mast cell density. DSCG reduced myocardial fibrosis besides preventing infiltration and degranulation of mast cells. Our findings confirm the active participation of mast cells in the progression of myocardial fibrosis in rats with postmyocarditis DCM. PMID:16272703

  9. Knockout of Lmod2 results in shorter thin filaments followed by dilated cardiomyopathy and juvenile lethality

    PubMed Central

    Pappas, Christopher T.; Mayfield, Rachel M.; Henderson, Christine; Jamilpour, Nima; Cover, Cathleen; Hernandez, Zachary; Hutchinson, Kirk R.; Chu, Miensheng; Nam, Ki-Hwan; Valdez, Jose M.; Wong, Pak Kin; Granzier, Henk L.; Gregorio, Carol C.

    2015-01-01

    Leiomodin 2 (Lmod2) is an actin-binding protein that has been implicated in the regulation of striated muscle thin filament assembly; its physiological function has yet to be studied. We found that knockout of Lmod2 in mice results in abnormally short thin filaments in the heart. We also discovered that Lmod2 functions to elongate thin filaments by promoting actin assembly and dynamics at thin filament pointed ends. Lmod2-KO mice die as juveniles with hearts displaying contractile dysfunction and ventricular chamber enlargement consistent with dilated cardiomyopathy. Lmod2-null cardiomyocytes produce less contractile force than wild type when plated on micropillar arrays. Introduction of GFP-Lmod2 via adeno-associated viral transduction elongates thin filaments and rescues structural and functional defects observed in Lmod2-KO mice, extending their lifespan to adulthood. Thus, to our knowledge, Lmod2 is the first identified mammalian protein that functions to elongate actin filaments in the heart; it is essential for cardiac thin filaments to reach a mature length and is required for efficient contractile force and proper heart function during development. PMID:26487682

  10. Risk of Idiopathic Dilated Cardiomyopathy in 29 000 Patients With Celiac Disease

    PubMed Central

    Emilsson, Louise; Andersson, Bert; Elfström, Peter; Green, Peter H.R.; Ludvigsson, Jonas F.

    2012-01-01

    Background Dilated cardiomyopathy (DCM) is a rare disease of largely unknown origin. Previous studies have suggested an increased prevalence of celiac disease (CD) in patients with DCM. These studies, however, were based on a maximum of 5 patients with both CD and DCM. In the present large Swedish population-based cohort study, we examined the risk of idiopathic DCM in patients with CD determined by small-intestinal histopathology. Methods and Results From 2006 to 2008, we collected duodenal/jejunal biopsy data on CD (equal to villous atrophy, Marsh stage 3, n=29 071 unique individuals) from (all) 28 pathology departments in Sweden. These individuals were compared with 144 429 reference individuals matched for age, sex, calendar year, and county. Data on DCM were obtained through the National Patient Register and confirmed by patient charts and echocardiography data. During follow-up, 17 patients with CD and 52 reference individuals developed idiopathic DCM. Thus, patients with CD were at an increased risk of idiopathic DCM (hazard ratio, 1.73; 95% confidence interval, 1.00 to 3.00), although the risk estimate failed to attain statistical significance (P=0.052). Conclusion This nationwide study found a moderately but not statistically significantly increased risk of idiopathic DCM in patients with biopsy-verified CD. (J Am Heart Assoc. 2012;1:e001594 doi: 10.1161/JAHA.112.001594.) PMID:23130142

  11. Initial clinical experience of real-time three-dimensional echocardiography in patients with ischemic and idiopathic dilated cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Shiota, T.; McCarthy, P. M.; White, R. D.; Qin, J. X.; Greenberg, N. L.; Flamm, S. D.; Wong, J.; Thomas, J. D.

    1999-01-01

    The geometry of the left ventricle in patients with cardiomyopathy is often sub-optimal for 2-dimensional ultrasound when assessing left ventricular (LV) function and localized abnormalities such as a ventricular aneurysm. The aim of this study was to report the initial experience of real-time 3-D echocardiography for evaluating patients with cardiomyopathy. A total of 34 patients were evaluated with the real-time 3D method in the operating room (n = 15) and in the echocardiographic laboratory (n = 19). Thirteen of 28 patients with cardiomyopathy and 6 other subjects with normal LV function were evaluated by both real-time 3-D echocardiography and magnetic resonance imaging (MRI) for obtaining LV volumes and ejection fractions for comparison. There were close relations and agreements for LV volumes (r = 0.98, p <0.0001, mean difference = -15 +/- 81 ml) and ejection fractions (r = 0.97, p <0.0001, mean difference = 0.001 +/- 0.04) between the real-time 3D method and MRI when 3 cardiomyopathy cases with marked LV dilatation (LV end-diastolic volume >450 ml by MRI) were excluded. In these 3 patients, 3D echocardiography significantly underestimated the LV volumes due to difficulties with imaging the entire LV in a 60 degrees x 60 degrees pyramidal volume. The new real-time 3D echocardiography is feasible in patients with cardiomyopathy and may provide a faster and lower cost alternative to MRI for evaluating cardiac function in patients.

  12. Antifailure Therapy Including Spironolactone Improves Left Ventricular Energy Supply‐Demand Relations in Nonischemic Dilated Cardiomyopathy

    PubMed Central

    Bell, Susan P.; Adkisson, Douglas W.; Lawson, Mark A.; Wang, Li; Ooi, Henry; Sawyer, Douglas B.; Kronenberg, Marvin W.

    2014-01-01

    Background Left ventricular (LV) energy supply‐demand imbalance is postulated to cause “energy starvation” and contribute to heart failure (HF) in nonischemic dilated cardiomyopathy (NIDCM). Using cardiac magnetic resonance (CMR) and [11C] acetate positron emission tomography (PET), we evaluated LV perfusion and oxidative metabolism in NIDCM and the effects of spironolactone on LV supply‐demand relations. Methods and Results Twelve patients with NIDCM underwent CMR and PET at baseline and after ≥6 months of spironolactone therapy added to a standard HF regimen. The myocardial perfusion reserve index (MPRI) was calculated after gadolinium injection during adenosine, as compared to rest. The monoexponential clearance rate of [11C] acetate (kmono) was used to calculate the work metabolic index (WMI), an index of LV mechanical efficiency, and kmono/RPP (rate‐pressure product), an index of energy supply/demand. At baseline, the subendocardium was hypoperfused versus the subepicardium (median MPRI, 1.63 vs. 1.80; P<0.001), but improved to 1.80 (P<0.001) after spironolactone. The WMI increased (P=0.001), as did kmono/RPP (P=0.003). These improvements were associated with reverse remodeling, increased LV ejection fraction, and decreases in LV mass and systolic wall stress (all P<0.002). Conclusions NIDCM is associated with subendocardial hypoperfusion and impaired myocardial oxidative metabolism, consistent with energy starvation. Antifailure therapy improves parameters of energy starvation and is associated with augmented LV performance. Clinical Trial Registration URL: http://www.clinicaltrials.gov/ Unique identifier: ID NCT00574119. PMID:25164945

  13. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy.

    PubMed

    Tricò, Domenico; Baldi, Simona; Frascerra, Silvia; Venturi, Elena; Marraccini, Paolo; Neglia, Danilo; Natali, Andrea

    2016-01-01

    Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p < 0.05), did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2 equivalents, p < 0.05), while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217. PMID:26798650

  14. Targeted next-generation sequencing of candidate genes reveals novel mutations in patients with dilated cardiomyopathy

    PubMed Central

    ZHAO, YUE; FENG, YUE; ZHANG, YUN-MEI; DING, XIAO-XUE; SONG, YU-ZHU; ZHANG, A-MEI; LIU, LI; ZHANG, HONG; DING, JIA-HUAN; XIA, XUE-SHAN

    2015-01-01

    Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure, and it is characterized by genetic and clinical heterogeneity, even for some patients with a very poor clinical prognosis; in the majority of cases, DCM necessitates a heart transplant. Genetic mutations have long been considered to be associated with this disease. At present, mutations in over 50 genes related to DCM have been documented. This study was carried out to elucidate the characteristics of gene mutations in patients with DCM. The candidate genes that may cause DCM include MYBPC3, MYH6, MYH7, LMNA, TNNT2, TNNI3, MYPN, MYL3, TPM1, SCN5A, DES, ACTC1 and RBM20. Using next-generation sequencing (NGS) and subsequent mutation confirmation with traditional capillary Sanger sequencing analysis, possible causative non-synonymous mutations were identified in ~57% (12/21) of patients with DCM. As a result, 7 novel mutations (MYPN, p.E630K; TNNT2, p.G180A; MYH6, p.R1047C; TNNC1, p.D3V; DES, p.R386H; MYBPC3, p.C1124F; and MYL3, p.D126G), 3 variants of uncertain significance (RBM20, p.R1182H; MYH6, p.T1253M; and VCL, p.M209L), and 2 known mutations (MYH7, p.A26V and MYBPC3, p.R160W) were revealed to be associated with DCM. The mutations were most frequently found in the sarcomere (MYH6, MYBPC3, MYH7, TNNC1, TNNT2 and MYL3) and cytoskeletal (MYPN, DES and VCL) genes. As genetic testing is a useful tool in the clinical management of disease, testing for pathogenic mutations is beneficial to the treatment of patients with DCM and may assist in predicting disease risk for their family members before the onset of symptoms. PMID:26458567

  15. The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy.

    PubMed

    Fonfara, Sonja; Hetzel, Udo; Oyama, Mark A; Kipar, Anja

    2014-03-01

    Serotonin signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). A contribution of serotonin to valvular disease has been reported, but myocardial expression of 5-HTR2B and its role in canine dilated cardiomyopathy (DCM) is not known. The aim of the present study was to investigate myocardial 5-HTR2B mRNA expression in dogs with DCM and to correlate results with expression of markers for inflammation and remodelling. Myocardial samples from eight healthy dogs, four dogs with DCM, five with cardiac diseases other than DCM and six with systemic non-cardiac diseases were investigated for 5-HTR2B mRNA expression using quantitative PCR (qPCR). The results were compared to mRNA expression of selected cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP). Laser microdissection with subsequent qPCR and immunohistochemistry were employed to identify the cells expressing 5-HTR2B. The myocardium of control dogs showed constitutive 5-HTR2B mRNA expression. In dogs with DCM, 5-HTR2B mRNA values were significantly greater than in all other groups, with highest levels of expression in the left ventricle and right atrium. Myocytes were identified as the source of 5-HTR2B mRNA and protein. A significant positive correlation of 5-HTR2B mRNA with expression of several cytokines, MMPs and TIMPs was observed. The findings suggest that serotonin might play a role in normal cardiac structure and function and could contribute to myocardial remodelling and functional impairment in dogs with DCM. PMID:24440442

  16. Computer-based assessment of left ventricular wall stiffness in patients with ischemic dilated cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Su, Y.; Teo, S. K.; Tan, R. S.; Lim, C. W.; Zhong, L.

    2013-02-01

    Ischemic dilated cardiomyopathy (IDCM) is a degenerative disease of the myocardial tissue accompanied by left ventricular (LV) structural changes such as interstitial fibrosis. This can induce increased passive stiffness of the LV wall. However, quantification of LV passive wall stiffness in vivo is extremely difficult, particularly in ventricles with complex geometry. Therefore, we sought to (i) develop a computer-based assessment of LV passive wall stiffness from cardiac magnetic resonance (CMR) imaging in terms of a nominal stiffness index (E*); and (ii) investigate whether E* can offer an insight into cardiac mechanics in IDCM. CMR scans were performed in 5 normal subjects and 5 patients with IDCM. For each data sample, an in-house software was used to generate a 1-to-1 corresponding mesh pair of the LV from the ED and ES phases. The E* values are then computed as a function of local ventricular wall strain. We found that E* in the IDCM group (40.66 - 215.12) was at least one order of magnitude larger than the normal control group (1.00 - 6.14). In addition, the IDCM group revealed much higher inhomogeneity of E* values manifested by a greater spread of E* values throughout the LV. In conclusion, there is a substantial elevated ventricular stiffness index in IDCM. This would suggest that E* could be used as discriminator for early detection of disease state. The computational performance per data sample took approximately 25 seconds, which demonstrates its clinical potential as a real-time cardiac assessment tool.

  17. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy

    PubMed Central

    Tricò, Domenico; Baldi, Simona; Frascerra, Silvia; Venturi, Elena; Marraccini, Paolo; Neglia, Danilo; Natali, Andrea

    2016-01-01

    Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p < 0.05), did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2 equivalents, p < 0.05), while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217. PMID:26798650

  18. Cardiovascular magnetic resonance T2 mapping can detect myocardial edema in idiopathic dilated cardiomyopathy.

    PubMed

    Nishii, Tatsuya; Kono, Atsushi K; Shigeru, Mayumi; Takamine, Sachiko; Fujiwara, Sei; Kyotani, Katsusuke; Aoyama, Nobukazu; Sugimura, Kazuro

    2014-06-01

    Myocardial edema and inflammation play an important role in dilated cardiomyopathy (DCM). This pathologic condition can be identified noninvasively using cardiovascular magnetic resonance imaging (CMR). The purpose of this study was to determine the effectiveness of T2 values obtained with T2 mapping in the detection of edema in DCM patients, compared with that of conventional T2-weighted imaging (T2WI). CMR was used for 15 normal controls (NML) and 26 DCM patients. The DCM patients were classified as having either mild dysfunction with a left ventricular ejection fraction (EF) >35% or severe dysfunction with an EF ≤35%. Myocardial edema was assessed by both T2 mapping and T2WI. The differences between the T2 values determined from T2 mapping and the T2 ratios that were calculated from the T2WI were compared among the NML, mild DCM, and severe DCM patients. The T2 values for the NML, mild DCM, and severe DCM patients were 51.2 ± 1.6, 61.2 ± 0.37, and 67.4 ± 6.8, respectively (P < 0.05 for each pair), and the corresponding T2 ratios were 1.88 ± 0.09, 2.12 ± 0.37, and 2.04 ± 0.34, respectively (P > 0.05). T2 mapping clearly showed that the myocardial water content was larger in DCM patients than in NML controls and that the myocardial water content increased as the disease progressed. Thus, T2 mapping is a useful technique for the diagnosis and quantitation of diffuse myocardial edema. PMID:24715436

  19. Circulating Omentin-1 Levels Are Decreased in Dilated Cardiomyopathy Patients with Overt Heart Failure

    PubMed Central

    Huang, Ying; Lin, Yingzhong; Zhang, Shumin; Wang, Zhijian; Zhang, Jianwei; Chang, Chao; Liu, Ling; Ji, Qingwei; Liu, Xiaofei

    2016-01-01

    Background. Recent evidence demonstrated that the circulating levels of omentin-1 are related to the presence of ischemic heart disease and heart failure. However, omentin-1 plasma levels in patients with nonischemic dilated cardiomyopathy (DCM), which is the most common etiology of heart failure, have yet to be investigated. Methods. Plasma levels of omentin-1 and adiponectin were measured in 100 patients with DCM and 45 healthy controls. Results. Plasma omentin-1 levels significantly decreased in DCM patients compared with the control group, whereas adiponectin levels significantly increased in DCM patients compared with the control group. Plasma omentin-1 levels were negatively correlated with adiponectin (R = −0.376, P = 0.005), C-reactive protein (CRP) (R = −0.320, P = 0.001), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (R = −0.365, P = 0.000) levels as well as left ventricular end-diastolic diameter (LVEDD) (R = −0.200, P = 0.046) but were positively correlated with left ventricular ejection fraction (LVEF) (R = 0.496, P = 0.000). Plasma adiponectin levels were positively correlated with CRP (R = 0.273, P = 0.006) and NT-proBNP (R = 0.329, P = 0.001) levels but were negatively correlated with fasting glucose (R = −0.218, P = 0.029) and LVEF (R = −0.615, P = 0.000) levels. Furthermore, omentin-1 (OR 0.983, 95% CI 0.970 to 0.996; P = 0.008) levels were independently associated with the presence of DCM before NT-proBNP was added. Conclusions. Omentin-1 is a novel biomarker of DCM. PMID:27313334

  20. A dilated cardiomyopathy mutation blunts adrenergic response and induces contractile dysfunction under chronic angiotensin II stress.

    PubMed

    Wilkinson, Ross; Song, Weihua; Smoktunowicz, Natalia; Marston, Steven

    2015-12-01

    We investigated cardiac contractility in the ACTC E361G transgenic mouse model of dilated cardiomyopathy (DCM). No differences in cardiac dimensions or systolic function were observed in young mice, whereas young adult mice exhibited only mild diastolic abnormalities. Dobutamine had an inotropic and lusitropic effect on the mouse heart. In papillary muscle at 37°C, dobutamine increased relaxation rates [∼50% increase of peak rate of force decline normalized to force (dF/dtmin/F), 25% reduction of time to 90% relaxation (t90) in nontransgenic (NTG) mice], but in the ACTC E361G mouse, dF/dtmin/F was increased 20-30%, and t90 was only reduced 10% at 10 Hz. Pressure-volume measurements showed increases in maximum rate of pressure decline and decreases in time constant of left ventricular pressure decay in the ACTC E361G mouse that were 25-30% of the changes in the NTG mouse, consistent with blunting of the lusitropic response. The inotropic effect of dobutamine was also blunted in ACTC E361G mice, and the dobutamine-stimulated increase in cardiac output (CO) was reduced from 2,100 to 900 μl/min. Mice were treated with high doses of ANG II for 4 wk. The chronic stress treatment evoked systolic dysfunction in ACTC E361G mice but not in NTG. There was a significant reduction in rates of pressure increase and decrease, as well as reduced end-systolic pressure and increased volume. Ejection fraction and CO were reduced in the ACTC E361G mouse, indicating DCM. In vitro DCM-causing mutations uncouple the relationship between Ca(2+) sensitivity and troponin I phosphorylation. We conclude that this leads to the observed, reduced response to β1 agonists and reduced cardiac reserve that predisposes the heart to DCM under conditions of chronic stress. PMID:26432839

  1. Variability of M-Mode Versus Two-Dimensional Echocardiography Measurements in Children With Dilated Cardiomyopathy

    PubMed Central

    Margossian, Renee; Sleeper, Lynn A.; Canter, Charles E.; Chen, Shan; Tani, Lloyd Y.; Shirali, Girish; Szwast, Anita; Tierney, Elif Seda Selamet; Campbell, M. Jay; Golding, Fraser; Wang, Yanli; Altmann, Karen; Colan, Steven D.

    2015-01-01

    M-mode and 2-dimensional (2D) echocardio-graphic imaging are routinely used to quantify left-ventricular (LV) size and function in pediatric patients with dilated cardiomyopathy (DCM). The reproducibility of and correlation between these techniques are unknown. This analysis sought to compare interreader, intrareader, and interacquisition reproducibility of M-mode versus 2D measurements in pediatric DCM patients. The Ventricular Volume Variability study of the Pediatric Heart Network is a multicenter, prospective, observational study assessing the course of chronic DCM in children. Two sonographers performed baseline image acquisitions locally, and two readers performed measurements at the echocardiographic core laboratory. One reader repeated measurements 1 month later. These data were used to assess reproducibility and agreement between M-mode and 2D measurements. One hundred sixty-nine subjects were enrolled. M-mode had similar or greater reproducibility in both intrareader and interreader settings for LV dimensions, shortening fraction (SF), and most wall thicknesses. In contrast, 2D reproducibility was similar or better for nearly all variables in the interacquisition setting but not for SF. Interacquisition variability was approximately twice the intrareader variability. LV dimensions by either modality consistently had high reproducibility and had the highest agreement between modalities. In pediatric DCM patients, variability of linear echocardiographic assessment could be minimized by relying on a single reader and using a consistent method (M-mode or 2D) for serial measurements, preferably M-mode when SF is the primary variable of interest. Except for LV dimensions, M-mode and 2D values should not be used interchangeably due to poor agreement. PMID:24265000

  2. Variability of M-mode versus two-dimensional echocardiography measurements in children with dilated cardiomyopathy.

    PubMed

    Lee, Caroline K; Margossian, Renee; Sleeper, Lynn A; Canter, Charles E; Chen, Shan; Tani, Lloyd Y; Shirali, Girish; Szwast, Anita; Tierney, Elif Seda Selamet; Campbell, M Jay; Golding, Fraser; Wang, Yanli; Altmann, Karen; Colan, Steven D

    2014-04-01

    M-mode and 2-dimensional (2D) echocardiographic imaging are routinely used to quantify left-ventricular (LV) size and function in pediatric patients with dilated cardiomyopathy (DCM). The reproducibility of and correlation between these techniques are unknown. This analysis sought to compare interreader, intrareader, and interacquisition reproducibility of M-mode versus 2D measurements in pediatric DCM patients. The Ventricular Volume Variability study of the Pediatric Heart Network is a multicenter, prospective, observational study assessing the course of chronic DCM in children. Two sonographers performed baseline image acquisitions locally, and two readers performed measurements at the echocardiographic core laboratory. One reader repeated measurements 1 month later. These data were used to assess reproducibility and agreement between M-mode and 2D measurements. One hundred sixty-nine subjects were enrolled. M-mode had similar or greater reproducibility in both intrareader and interreader settings for LV dimensions, shortening fraction (SF), and most wall thicknesses. In contrast, 2D reproducibility was similar or better for nearly all variables in the interacquisition setting but not for SF. Interacquisition variability was approximately twice the intrareader variability. LV dimensions by either modality consistently had high reproducibility and had the highest agreement between modalities. In pediatric DCM patients, variability of linear echocardiographic assessment could be minimized by relying on a single reader and using a consistent method (M-mode or 2D) for serial measurements, preferably M-mode when SF is the primary variable of interest. Except for LV dimensions, M-mode and 2D values should not be used interchangeably due to poor agreement. PMID:24265000

  3. Genetic Variation in the Alternative Splicing Regulator, RBM20, is associated with Dilated Cardiomyopathy

    PubMed Central

    Refaat, Marwan M.; Lubitz, Steven A.; Makino, Seiko; Islam, Zahid; Frangiskakis, J. Michael; Mehdi, Haider; Gutmann, Rebecca; Zhang, Michael L.; Bloom, Heather L.; MacRae, Calum A.; Dudley, Samuel C.; Shalaby, Alaa A.; Weiss, Raul; McNamara, Dennis M.; London, Barry; Ellinor, Patrick T.

    2012-01-01

    BACKGROUND Dilated cardiomyopathy (DCM) is a leading cause of heart failure and death. The etiology of DCM is genetically heterogeneous. OBJECTIVES We sought to define the prevalence of mutations in the RNA splicing protein, RBM20, in a large cohort with DCM, and to determine if genetic variation in RBM20 is associated with clinical outcomes. METHODS Subjects included in the GRADE (Genetic Risk Assessment of Defibrillator Events) study were at least 18 years of age, had an ejection fraction of ≤ 30%, and an implantable cardioverter-defibrillator (ICD). The coding region and splice junctions of RBM20 were screened in DCM subjects; two common polymorphisms in RBM20, rs942077 and rs35141404, were genotyped in all GRADE subjects. RESULTS 1465 subjects were enrolled in the GRADE study and 283 with DCM were screened for RBM20 mutations. The mean age of subjects with DCM was 58 ± 13 years, 64% were male and the mean follow up was 24.2 ± 17.1 months after ICD placement. RBM20 mutations were identified in eight subjects with DCM (2.8%). Mutation carriers had a similar survival, transplantation rate, and frequency of ICD therapy compared to non-mutation carriers. Three of eight subjects (37.5%) with RBM20 mutations had atrial fibrillation (AF) whereas 19 (7.4%) subjects without mutations had AF (p= 0.02). Among all GRADE subjects, rs35141404 was associated with AF (minor allele OR 0.62, 95% CI 0.44–0.86, p=0.006). In the subset of GRADE subjects with DCM, rs35141404 was associated with AF (minor allele OR 0.58, p=0.047). CONCLUSIONS Mutations in RBM20 were observed in approximately 3% of subjects with DCM. There were no differences in survival, transplantation rate, and frequency of ICD therapy in mutation carriers. PMID:22004663

  4. Circulating Omentin-1 Levels Are Decreased in Dilated Cardiomyopathy Patients with Overt Heart Failure.

    PubMed

    Huang, Ying; Lin, Yingzhong; Zhang, Shumin; Wang, Zhijian; Zhang, Jianwei; Chang, Chao; Liu, Ling; Ji, Qingwei; Liu, Xiaofei

    2016-01-01

    Background. Recent evidence demonstrated that the circulating levels of omentin-1 are related to the presence of ischemic heart disease and heart failure. However, omentin-1 plasma levels in patients with nonischemic dilated cardiomyopathy (DCM), which is the most common etiology of heart failure, have yet to be investigated. Methods. Plasma levels of omentin-1 and adiponectin were measured in 100 patients with DCM and 45 healthy controls. Results. Plasma omentin-1 levels significantly decreased in DCM patients compared with the control group, whereas adiponectin levels significantly increased in DCM patients compared with the control group. Plasma omentin-1 levels were negatively correlated with adiponectin (R = -0.376, P = 0.005), C-reactive protein (CRP) (R = -0.320, P = 0.001), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (R = -0.365, P = 0.000) levels as well as left ventricular end-diastolic diameter (LVEDD) (R = -0.200, P = 0.046) but were positively correlated with left ventricular ejection fraction (LVEF) (R = 0.496, P = 0.000). Plasma adiponectin levels were positively correlated with CRP (R = 0.273, P = 0.006) and NT-proBNP (R = 0.329, P = 0.001) levels but were negatively correlated with fasting glucose (R = -0.218, P = 0.029) and LVEF (R = -0.615, P = 0.000) levels. Furthermore, omentin-1 (OR 0.983, 95% CI 0.970 to 0.996; P = 0.008) levels were independently associated with the presence of DCM before NT-proBNP was added. Conclusions. Omentin-1 is a novel biomarker of DCM. PMID:27313334

  5. Nanofibrous clinical-grade collagen scaffolds seeded with human cardiomyocytes induces cardiac remodeling in dilated cardiomyopathy.

    PubMed

    Joanne, Pierre; Kitsara, Maria; Boitard, Solène-Emmanuelle; Naemetalla, Hany; Vanneaux, Valérie; Pernot, Mathieu; Larghero, Jérôme; Forest, Patricia; Chen, Yong; Menasché, Philippe; Agbulut, Onnik

    2016-02-01

    Limited data are available on the effects of stem cells in non-ischemic dilated cardiomyopathy (DCM). Since the diffuse nature of the disease calls for a broad distribution of cells, this study investigated the scaffold-based delivery of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) in a mouse model of DCM. Nanofibrous scaffolds were produced using a clinical grade atelocollagen which was electrospun and cross-linked under different conditions. As assessed by scanning electron microscopy and shearwave elastography, the optimum crosslinking conditions for hiPS-CM colonization proved to be a 10% concentration of citric acid crosslinking agent and 150 min of post-electrospinning baking. Acellular collagen scaffolds were first implanted in both healthy mice and those with induced DCM by a cardiac-specific invalidation of serum response factor (SRF). Seven and fourteen days after implantation, the safety of the scaffold was demonstrated by echocardiography and histological assessments. The subsequent step of implantation of the scaffolds seeded with hiPS-CM in DCM induced mice, using cell-free scaffolds as controls, revealed that after fourteen days heart function decreased in controls while it remained stable in the treated mice. This pattern was associated with an increased number of endothelial cells, in line with the greater vascularity of the scaffold. Moreover, a lesser degree of fibrosis consistent with the upregulation of several genes involved in extracellular matrix remodeling was observed. These results support the interest of the proposed hiPS-CM seeded electrospun scaffold for the stabilization of the DCM outcome with potential for its clinical use in the future. PMID:26708641

  6. Cardiomyopathy

    MedlinePlus

    Cardiomyopathy is disease in which the heart muscle becomes weakened, stretched, or has another structural problem. It ... cannot pump or function well. Most people with cardiomyopathy have heart failure .

  7. Cardiomyopathy

    MedlinePlus

    ... and the most common reason for needing a heart transplant. Cardiomyopathy is so dangerous because it often goes ... damaged by ischemic cardiomyopathy, doctors may recommend a heart transplant. Arrhythmogenic Right Ventricular Dysplasia Arrhythmogenic right ventricular dysplasia ( ...

  8. Cardiomyopathy

    MedlinePlus

    Cardiomyopathy is the name for diseases of the heart muscle. These diseases enlarge your heart muscle or ... tissue. Some people live long, healthy lives with cardiomyopathy. Some people don't even realize they have ...

  9. [A case of limb-girdle muscular dystrophy 2M diagnosed by the occurence of dilated cardiomyopathy].

    PubMed

    Matsui, Misa; Endo, Takuyuki; Matsumura, Tsuyoshi; Saito, Toshio; Fujimura, Harutoshi

    2015-01-01

    We report a 24-year-old Japanese man initially suspected to have Becker's muscular dystrophy at the age of 6 years, because of a high level of creatine kinase in serum, though he discontinued visiting the hospital. At the age of 23, he was admitted to the hospital for severe dilated cardiomyopathy, and subsequently diagnosed with limb-girdle muscular dystrophy2M (LGMD2M) based on muscle biopsy and gene analysis. It was recently reported that some patients with fukutinopathy develop LGMD. Most of the cases reported in Japan showed mild skeletal muscle involvement despite serious cardiomyopathy, which may sometimes the initial symptom of the disease. Since muscular dystrophy patients can develop severe cardiac failure, irrespective of the severity of skeletal muscle involvement, regular examinations of cardiopulmonary function are necessary. PMID:26050665

  10. Lack of correlation between intracavitary thrombosis detected by cross sectional echocardiography and systemic emboli in patients with dilated cardiomyopathy.

    PubMed Central

    Ciaccheri, M; Castelli, G; Cecchi, F; Nannini, M; Santoro, G; Troiani, V; Zuppiroli, A; Dolara, A

    1989-01-01

    The correlation between intracavitary thrombosis detected by cross sectional echocardiography and systemic embolism was studied in 126 consecutive patients with idiopathic dilated cardiomyopathy who were examined from January 1980 to September 1987. A total of 1041 serial echocardiograms were obtained with 3.5 and 5 MHz transducers. The mean follow up period was 41.2 months. The survival rate was 88% at two years and 56% at five years. Echocardiography showed intracavitary thrombi in 14 (11.1%) patients; 13 were mural and 11 were localised at the apex of the left ventricle. Twelve patients (8.4%) had systemic emboli; this corresponded to an incidence of new embolic events of 1.4 for 100 patient-years. Patients with intracavitary thrombi or systemic emboli were treated with oral anticoagulants, as were nine in functional class IV of the New York Heart Association, for 61 patient-years. The cumulative observation period for the whole population study was 418 patient-years. None of the patients with intracavitary thrombosis had embolic complications and none of those with embolism had intracavitary thrombi. Rates of intracavitary thrombosis and systemic embolism in this series were low and there was no overlap between the two events. This may have been because the patients did not have severe dilated cardiomyopathy, because echocardiography did not detect all the thrombi, or because patients were treated with oral anticoagulants. The presence of intracardiac thrombosis detected by cross sectional echocardiography is not predictive of systemic embolism in patients with idiopathic dilated cardiomyopathy. Criteria for the use of the anticoagulant treatment remain largely empirical in these cases. Images Fig 1 Fig 2 PMID:2757871

  11. Prediction of the effectiveness of long term β blocker treatment for dilated cardiomyopathy by signal averaged electrocardiography

    PubMed Central

    Yamada, T; Fukunami, M; Shimonagata, T; Kumagai, K; Kim, J; Sanada, S; Ogita, H; Hori, M; Hoki, N

    1998-01-01

    Objective—To determine whether the effectiveness of long term β blocker treatment for idiopathic dilated cardiomyopathy can be predicted by signal averaged electrocardiography (ECG).
Patients—31 patients with dilated cardiomyopathy and without bundle branch block were included in a retrospective study and 16 in a prospective study.
Methods—A signal averaged ECG was recorded before β blocker treatment, and three variables were measured from the vector magnitude: QRS duration, root mean square voltage for the last 40 ms (RMS40), and duration of the terminal low amplitude signals (< 40 µV) (LAS40). In the retrospective study, these variables were compared among good responders (showing ⩾ 0.10 increase in ejection fraction 12 months after start of β blocker treatment) and poor responders without such improvement. The validity of the signal averaged ECG criteria for prediction of the response to β blocker treatment was examined in the prospective study.
Results—In the retrospective study, good responders (n = 16) had a shorter QRS duration (mean (SD): 122.9 (11) v 138 (14.4) ms, p < 0.005) and LAS40 (33.1 (8.9) v 42.5 (7.8) ms, p < 0.005), and a higher RMS40 (31.6 (16.3) v 19.0 (10.3) µV, p < 0.02) than poor responders (n = 15). Signal averaged ECG criteria for good response were defined as two or more of the following: QRS duration < 130 ms, RMS40 > 20 µV, LAS40 < 40 ms (sensitivity 81%, specificity 73%). In the prospective study, six of seven patients who met these criteria showed a good response to the β blocker treatment, while eight of nine who did not showed a poor response (χ2 = 6.1, p < 0.02). The signal averaged ECG criteria gave a sensitivity of 86% and a specificity of 89% for predicting the effectiveness of β blocker treatment.
Conclusions—A signal averaged ECG might be useful in predicting the effectiveness of β blocker treatment for dilated cardiomyopathy.

 Keywords: signal

  12. The Role of Cardiac Troponin T Quantity and Function in Cardiac Development and Dilated Cardiomyopathy

    PubMed Central

    Ahmad, Ferhaan; Banerjee, Sanjay K.; Lage, Michele L.; Huang, Xueyin N.; Smith, Stephen H.; Saba, Samir; Rager, Jennifer; Conner, David A.; Janczewski, Andrzej M.; Tobita, Kimimasa; Tinney, Joseph P.; Moskowitz, Ivan P.; Perez-Atayde, Antonio R.; Keller, Bradley B.; Mathier, Michael A.; Shroff, Sanjeev G.; Seidman, Christine E.; Seidman, J. G.

    2008-01-01

    Background Hypertrophic (HCM) and dilated (DCM) cardiomyopathies result from sarcomeric protein mutations, including cardiac troponin T (cTnT, TNNT2). We determined whether TNNT2 mutations cause cardiomyopathies by altering cTnT function or quantity; whether the severity of DCM is related to the ratio of mutant to wildtype cTnT; whether Ca2+ desensitization occurs in DCM; and whether absence of cTnT impairs early embryonic cardiogenesis. Methods and Findings We ablated Tnnt2 to produce heterozygous Tnnt2+/− mice, and crossbreeding produced homozygous null Tnnt2−/− embryos. We also generated transgenic mice overexpressing wildtype (TGWT) or DCM mutant (TGK210Δ) Tnnt2. Crossbreeding produced mice lacking one allele of Tnnt2, but carrying wildtype (Tnnt2+/−/TGWT) or mutant (Tnnt2+/−/TGK210Δ) transgenes. Tnnt2+/− mice relative to wildtype had significantly reduced transcript (0.82±0.06[SD] vs. 1.00±0.12 arbitrary units; p = 0.025), but not protein (1.01±0.20 vs. 1.00±0.13 arbitrary units; p = 0.44). Tnnt2+/− mice had normal hearts (histology, mass, left ventricular end diastolic diameter [LVEDD], fractional shortening [FS]). Moreover, whereas Tnnt2+/−/TGK210Δ mice had severe DCM, TGK210Δ mice had only mild DCM (FS 18±4 vs. 29±7%; p<0.01). The difference in severity of DCM may be attributable to a greater ratio of mutant to wildtype Tnnt2 transcript in Tnnt2+/−/TGK210Δ relative to TGK210Δ mice (2.42±0.08, p = 0.03). Tnnt2+/−/TGK210Δ muscle showed Ca2+ desensitization (pCa50 = 5.34±0.08 vs. 5.58±0.03 at sarcomere length 1.9 µm, p<0.01), but no difference in maximum force generation. Day 9.5 Tnnt2−/− embryos had normally looped hearts, but thin ventricular walls, large pericardial effusions, noncontractile hearts, and severely disorganized sarcomeres. Conclusions Absence of one Tnnt2 allele leads to a mild deficit in transcript but not protein, leading to a normal cardiac phenotype. DCM results from abnormal

  13. Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy.

    PubMed

    Stark, Klaus; Esslinger, Ulrike B; Reinhard, Wibke; Petrov, George; Winkler, Thomas; Komajda, Michel; Isnard, Richard; Charron, Philippe; Villard, Eric; Cambien, François; Tiret, Laurence; Aumont, Marie-Claude; Dubourg, Olivier; Trochu, Jean-Noël; Fauchier, Laurent; Degroote, Pascal; Richter, Anette; Maisch, Bernhard; Wichter, Thomas; Zollbrecht, Christa; Grassl, Martina; Schunkert, Heribert; Linsel-Nitschke, Patrick; Erdmann, Jeanette; Baumert, Jens; Illig, Thomas; Klopp, Norman; Wichmann, H-Erich; Meisinger, Christa; Koenig, Wolfgang; Lichtner, Peter; Meitinger, Thomas; Schillert, Arne; König, Inke R; Hetzer, Roland; Heid, Iris M; Regitz-Zagrosek, Vera; Hengstenberg, Christian

    2010-10-01

    Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP) were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39%) and idiopathic DCM (p = 1.06 × 10⁻⁶, OR  = 0.67 [95% CI 0.57-0.79] for the minor allele T). Three more SNPs showed p < 2.21 × 10⁻⁵. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n =564, n = 981 controls, p = 2.07 × 10⁻³, OR = 0.79 [95% CI 0.67-0.92]), France 1 (n = 433 cases, n = 395 controls, p =3.73 × 10⁻³, OR  = 0.74 [95% CI 0.60-0.91]), and France 2 (n = 249 cases, n = 380 controls, p = 2.26 × 10⁻⁴, OR  = 0.63 [95% CI 0.50-0.81]). The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28 × 10⁻¹³, OR= 0.72 [95% CI 0.65-0.78]). None of the other three SNPs showed significant results in the replication stage.This finding of the HSPB7 gene from a genetic search for idiopathic DCM using a large SNP

  14. Genetic Association Study Identifies HSPB7 as a Risk Gene for Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Stark, Klaus; Esslinger, Ulrike B.; Reinhard, Wibke; Petrov, George; Winkler, Thomas; Komajda, Michel; Isnard, Richard; Charron, Philippe; Villard, Eric; Cambien, François; Tiret, Laurence; Aumont, Marie-Claude; Dubourg, Olivier; Trochu, Jean-Noël; Fauchier, Laurent; DeGroote, Pascal; Richter, Anette; Maisch, Bernhard; Wichter, Thomas; Zollbrecht, Christa; Grassl, Martina; Schunkert, Heribert; Linsel-Nitschke, Patrick; Erdmann, Jeanette; Baumert, Jens; Illig, Thomas; Klopp, Norman; Wichmann, H.-Erich; Meisinger, Christa; Koenig, Wolfgang; Lichtner, Peter; Meitinger, Thomas; Schillert, Arne; König, Inke R.; Hetzer, Roland; Heid, Iris M.; Regitz-Zagrosek, Vera; Hengstenberg, Christian

    2010-01-01

    Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP) were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39%) and idiopathic DCM (p = 1.06×10−6, OR = 0.67 [95% CI 0.57–0.79] for the minor allele T). Three more SNPs showed p < 2.21×10−5. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n = 564, n = 981 controls, p = 2.07×10−3, OR = 0.79 [95% CI 0.67–0.92]), France 1 (n = 433 cases, n = 395 controls, p = 3.73×10−3, OR = 0.74 [95% CI 0.60–0.91]), and France 2 (n = 249 cases, n = 380 controls, p = 2.26×10−4, OR = 0.63 [95% CI 0.50–0.81]). The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28×10−13, OR = 0.72 [95% CI 0.65–0.78]). None of the other three SNPs showed significant results in the replication stage. This finding of the HSPB7 gene from a

  15. Prognostic Significance of Frontal QRS-T Angle in Patients with Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Li, Sheng-Na; Zhang, Xin-Lin; Cai, Guo-Long; Lin, Ruo-Wei; Jiang, He; Chen, Jian-Zhou; Xu, Biao; Huang, Wei

    2016-01-01

    Background: Current risk stratification of idiopathic dilated cardiomyopathy (IDC) lacks sufficient sensitivity and specificity. The objective of this study was to investigate the predictive role of frontal QRS-T angles in IDC. Methods: A prospective study with 509 IDC patients was performed from February 2008 to December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up was conducted every 6 months. Analyses by Cox Proportional Hazards model were performed to evaluate the association between QRS-T angle and outcomes. The primary outcome of interest was all-cause mortality. Results: During a median follow-up of 34 months, 90 of 316 patients with QRS-T angles >90° died compared to 31 of 193 patients with QRS-T angles ≤90° (hazard ratio [HR] =2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR = 2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05), cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR = 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T angle (100.9 ± 53.4° vs. 107.2 ± 54.4°, P < 0.001). The frontal QRS-T angle correlated well with established risk factors, such as left ventricular ejection fraction, brain natriuretic peptide, and New York Heart Association functional class. Conclusions: The frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation. PMID:27503013

  16. Dilated cardiomyopathy due to type II X-linked 3-methylglutaconic aciduria: successful treatment with pantothenic acid.

    PubMed Central

    Ostman-Smith, I; Brown, G; Johnson, A; Land, J M

    1994-01-01

    A case of dilated cardiomyopathy in a young boy secondary to type II 3-methylglutaconic aciduria is described. A metabolic cause for his dilated cardiomyopathy was suspected because of the development on the electrocardiogram of an unusual "camel's hump" shape of the T waves, and of progressive thickening with increasing echogenicity of the left ventricular wall. He initially improved on digoxin treatment, but did not maintain the response with conventional dietary treatment for this condition. Supplementation with L-carnitine was associated with rapid deterioration in cardiac state, and may be contraindicated in this condition. At a point when the patient was moribund, large doses of pantothenic acid, a precursor of coenzyme A, produced a dramatic and sustained improvement in myocardial function and in growth, neutrophil cell count, hypocholesterolaemia, and hyperuricaemia, which suggests that limitation of availability of coenzyme A is a fundamental pathological process in this condition. The clinical improvement has been maintained for 13 months, and myocardial function is now nearly normal. Oral pantothenol, unlike pantothenic acid, is not efficacious. PMID:7833193

  17. Cardiomyocyte-Specific Ablation of Med1 Subunit of the Mediator Complex Causes Lethal Dilated Cardiomyopathy in Mice

    PubMed Central

    Jia, Yuzhi; Chang, Hsiang-Chun; Schipma, Matthew J.; Liu, Jing; Shete, Varsha; Liu, Ning; Sato, Tatsuya; Thorp, Edward B.; Barger, Philip M.; Zhu, Yi-Jun; Viswakarma, Navin; Kanwar, Yashpal S.; Ardehali, Hossein; Thimmapaya, Bayar; Reddy, Janardan K.

    2016-01-01

    Mediator, an evolutionarily conserved multi-protein complex consisting of about 30 subunits, is a key component of the polymerase II mediated gene transcription. Germline deletion of the Mediator subunit 1 (Med1) of the Mediator in mice results in mid-gestational embryonic lethality with developmental impairment of multiple organs including heart. Here we show that cardiomyocyte-specific deletion of Med1 in mice (csMed1-/-) during late gestational and early postnatal development by intercrossing Med1fl/fl mice to α-MyHC-Cre transgenic mice results in lethality within 10 days after weaning due to dilated cardiomyopathy-related ventricular dilation and heart failure. The csMed1-/- mouse heart manifests mitochondrial damage, increased apoptosis and interstitial fibrosis. Global gene expression analysis revealed that loss of Med1 in heart down-regulates more than 200 genes including Acadm, Cacna1s, Atp2a2, Ryr2, Pde1c, Pln, PGC1α, and PGC1β that are critical for calcium signaling, cardiac muscle contraction, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and peroxisome proliferator-activated receptor regulated energy metabolism. Many genes essential for oxidative phosphorylation and proper mitochondrial function such as genes coding for the succinate dehydrogenase subunits of the mitochondrial complex II are also down-regulated in csMed1-/- heart contributing to myocardial injury. Data also showed up-regulation of about 180 genes including Tgfb2, Ace, Atf3, Ctgf, Angpt14, Col9a2, Wisp2, Nppa, Nppb, and Actn1 that are linked to cardiac muscle contraction, cardiac hypertrophy, cardiac fibrosis and myocardial injury. Furthermore, we demonstrate that cardiac specific deletion of Med1 in adult mice using tamoxifen-inducible Cre approach (TmcsMed1-/-), results in rapid development of cardiomyopathy and death within 4 weeks. We found that the key findings of the csMed1-/- studies described above are highly reproducible in TmcsMed1-/- mouse heart

  18. Cardiac dilatation index as an indicator of terminal central congestion evaluated using postmortem CT and forensic autopsy data.

    PubMed

    Michiue, Tomomi; Sogawa, Nozomi; Ishikawa, Takaki; Maeda, Hitoshi

    2016-06-01

    Previous studies demonstrated possible application of postmortem quantitative CT data analysis of the heart and lung in situ to investigate terminal cardiopulmonary pathophysiology. The present study analyzed virtual CT morphometric and autopsy data of the heart to investigate terminal central congestion in forensic autopsy cases (n=113, within 3 days postmortem); the virtual total heart weight in situ was estimated using CT morphometry, and the difference from and ratio to the measured weight at autopsy were calculated as indicators of heart blood pooling and the cardiac dilatation index (CDI) before dissection, respectively. There were substantial differences between the estimated heart blood pooling in situ and volume recovered at autopsy, including a characteristic decrease in drowning, alcohol/sedative-hypnotic intoxication and sudden cardiac death (SCD), possibly due to blood redistribution after thoracic dissection. The estimated in situ heart blood pool and CDI values were higher in SCD but lower in fatal hemorrhage and hemopericardium, as well as in acute mechanical asphyxiation and hyperthermia (heatstroke). In addition, there was a significant difference in heart blood pooling between mechanical asphyxiation or drowning and SCD. The CDI was significantly lower in fatal hyperthermia (heatstroke) than in drowning, fatal methamphetamine abuse, alcohol/sedative-hypnotic intoxication and SCD. These findings suggest the usefulness of applying the CDI and postmortem heart blood volume in situ as supplementary indicators of terminal central congestion, especially for investigating deaths from hemorrhage, hemopericardium, hyperthermia (heatstroke) and SCD. PMID:27115507

  19. Increased B-Type Natriuretic Peptide Concentration Is Associated with Reduced Coronary Vasoreactivity in Patients with Dilated Cardiomyopathy but Not in Healthy Young Subjects

    PubMed Central

    Sundell, Jan; Engblom, Erik; Koistinen, Juhani; Ylitalo, Antti; Laine, Hanna; Kalliokoski, Riikka; Airaksinen, K. E. Juhani; Bax, Jeroen J.; Knuuti, Juhani

    2011-01-01

    Background/Aims. Natriuretic peptides are associated with the cardiovascular disease risk under a range of different circumstances. However, less is known about whether this association is found also in young healthy subjects. Methods. 9 patients with dilated cardiomyopathy and 26 healthy young subjects were studied. The myocardial blood flow measurements were performed basally and during adenosine infusion using PET. Results. S-proBNP concentrations were significantly higher (2153 ± 1964 versus 28 ± 17 ng/L, P = .000002) and adenosine-stimulated flow lower (1.6 ± 0.8 versus 3.6 ± 1.1 mL·g−1·min−1, P = .00001) in patients with dilated cardiomyopathy when compared to healthy subjects. S-proBNP concentration was inversely associated with adenosine stimulated flow in patients with dilated cardiomyopathy (r = −0.75, P = .019) but not in healthy subjects (r = −0.06, P = .84). Conclusions. Natriuretic peptides are inversely associated with coronary vasoreactivity in patients with dilated cardiomyopathy but not in healthy young subjects. Since reduced coronary vasoreactivity seems to be one of the earliest abnormalities in the development of coronary artery disease, this might indicate that natriuretic peptides are not predictor of cardiovascular disease risk in healthy young subjects. PMID:22347648

  20. Persistent Recovery of Normal Left Ventricular Function and Dimension in Idiopathic Dilated Cardiomyopathy During Long‐Term Follow‐up: Does Real Healing Exist?

    PubMed Central

    Merlo, Marco; Stolfo, Davide; Anzini, Marco; Negri, Francesco; Pinamonti, Bruno; Barbati, Giulia; Ramani, Federica; Di Lenarda, Andrea; Sinagra, Gianfranco

    2015-01-01

    Background An important number of patients with idiopathic dilated cardiomyopathy have dramatically improved left ventricular function with optimal treatment; however, little is known about the evolution and long‐term outcome of this subgroup, which shows apparent healing. This study assesses whether real healing actually exists in dilated cardiomyopathy . Methods and Results Persistent apparent healing was evaluated among 408 patients with dilated cardiomyopathy receiving tailored medical treatment and followed over the very long‐term. Persistent apparent healing was defined as left ventricular ejection fraction ≥50% and indexed left ventricular end‐diastolic diameter ≤33 mm/m2 at both mid‐term (19±4 months) and long‐term (103±9 months) follow‐up. At mid‐term, 63 of 408 patients (15%) were apparently healed; 38 (60%; 9% of the whole population) showed persistent apparent healing at long‐term evaluation. No predictors of persistent apparent healing were found. Patients with persistent apparent healing showed better heart transplant–free survival at very long‐term follow‐up (95% versus 71%; P=0.014) compared with nonpersistently normalized patients. Nevertheless, in the very long term, 37% of this subgroup experienced deterioration of left ventricular systolic function, and 5% died or had heart transplantation. Conclusions Persistent long‐term apparent healing was evident in a remarkable proportion of dilated cardiomyopathy patients receiving optimal medical treatment and was associated with stable normalization of main clinical and laboratory features. This condition can be characterized by a decline of left ventricular function over the very long term, highlighting the relevance of serial and individualized follow‐up in all patients with dilated cardiomyopathy, especially considering the absence of predictors for long‐term apparent healing. PMID:25587018

  1. Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model

    PubMed Central

    Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Kawaguchi, Naomasa; Nakatani, Satoshi; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

    2016-01-01

    Background Improving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart. Methods We generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5). Results Diastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P < 0.001; tau, 47 [6.0] vs 36 [4.4] ms: P = 0.005. Ejection fraction, 22 (6.0) versus 46 (7.5) %, P < 0.001; end-systolic elastance, 2.5 (0.4) versus 8.2 (3.5) mm Hg/ml, P = 0.001). Histological examination revealed that the volume of collagen I and the collagen I/III ratio in the myocardium were significantly higher in the control than that in the SMCST group (collagen I, 6.0 [0.8] vs 2.6 [1.3]; P = 0.006; collagen I/III ratio, 4.8 [1.7] vs 1.2 [0.4]; P = 0.010). Conclusions The potential of SMCST to ameliorate both systolic and diastolic performance was proven. The SMCST may be an alternative therapy of conventional medical treatment in the dilated cardiomyopathy heart. PMID:26636739

  2. Exome sequencing identified mutations in CASK and MYBPC3 as the cause of a complex dilated cardiomyopathy phenotype.

    PubMed

    Reinstein, Eyal; Tzur, Shay; Bormans, Concetta; Behar, Doron M

    2016-01-01

    Whole-exome sequencing for clinical applications is now an integral part of medical genetics practice. Though most studies are performed in order to establish diagnoses in individuals with rare and clinically unrecognizable disorders, due to the constantly decreasing costs and commercial availability, whole-exome sequencing has gradually become the initial tool to study patients with clinically recognized disorders when more than one gene is responsible for the phenotype or in complex phenotypes, when variants in more than one gene can be the cause for the disease. Here we report a patient presenting with a complex phenotype consisting of severe, adult-onset, dilated cardiomyopathy, hearing loss and developmental delay, in which exome sequencing revealed two genetic variants that are inherited from a healthy mother: a novel missense variant in the CASK gene, mutations in which cause a spectrum of neurocognitive manifestations, and a second variant, in MYBPC3, that is associated with hereditary cardiomyopathy. We conclude that although the potential for co-occurrence of rare diseases is higher when analyzing undefined phenotypes in consanguineous families, it should also be given consideration in the genetic evaluation of complex phenotypes in non-consanguineous families. PMID:27173948

  3. Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold intolerance

    PubMed Central

    Xiong, Dingding; He, Huamei; James, Jeanne; Tokunaga, Chonan; Powers, Corey; Huang, Yan; Osinska, Hanna; Towbin, Jeffrey A.; Purevjav, Enkhsaikhan; Balschi, James A.; Javadov, Sabzali; McGowan, Francis X.; Strauss, Arnold W.

    2013-01-01

    The very long-chain acyl-CoA dehydrogenase (VLCAD) enzyme catalyzes the first step of mitochondrial β-oxidation. Patients with VLCAD deficiency present with hypoketotic hypoglycemia and cardiomyopathy, which can be exacerbated by fasting and/or cold stress. Global VLCAD knockout mice recapitulate these phenotypes: mice develop cardiomyopathy, and cold exposure leads to rapid hypothermia and death. However, the contribution of different tissues to development of these phenotypes has not been studied. We generated cardiac-specific VLCAD-deficient (cVLCAD−/−) mice by Cre-mediated ablation of the VLCAD in cardiomyocytes. By 6 mo of age, cVLCAD−/− mice demonstrated increased end-diastolic and end-systolic left ventricular dimensions and decreased fractional shortening. Surprisingly, selective VLCAD gene ablation in cardiomyocytes was sufficient to evoke severe cold intolerance in mice who rapidly developed severe hypothermia, bradycardia, and markedly depressed cardiac function in response to fasting and cold exposure (+5°C). We conclude that cardiac-specific VLCAD deficiency is sufficient to induce cold intolerance and cardiomyopathy and is associated with reduced ATP production. These results provide strong evidence that fatty acid oxidation in myocardium is essential for maintaining normal cardiac function under these stress conditions. PMID:24285112

  4. Graves' thyrotoxicosis-induced reversible cardiomyopathy: a case report.

    PubMed

    Al-Ghamdi, Ahmad S; Aljohani, Naji

    2013-01-01

    The objective of this report is to present a case of Graves' thyrotoxicosis-induced cardiomyopathy. This is a case of a 26 year old woman that presented with severe symptomatic congestive heart failure and was subsequently diagnosed with dilated cardiomyopathy secondary to Graves' disease. Despite an initial left ventricular systolic ejection fraction of 20% on echocardiography, treatment with anti-thyroid agents led to rapid improvement of her clinical status and normalization of her ejection fraction. The proposed mechanisms underlying the development of systolic dysfunction in thyrotoxicosis are discussed and the literature on similar cases previously reported is highlighted. Cardiomyopathy should be considered even in young patients with Graves' thyrotoxicosis. PMID:23645990

  5. The calcium release-activated calcium channel Orai1 represents a crucial component in hypertrophic compensation and the development of dilated cardiomyopathy.

    PubMed

    Horton, Jaime S; Buckley, Cadie L; Alvarez, Ernest M; Schorlemmer, Anita; Stokes, Alexander J

    2014-01-01

    As exceptionally calcium selective store-operated channels, Orai channels play a prominent role in cellular calcium signaling. While most studied in the immune system, we are beginning to recognize that Orai1 provides unique calcium signaling pathways in numerous tissue contexts. To assess the involvement of Orai1 in cardiac hypertrophy we used transverse aortic constriction to model pressure overload cardiac hypertrophy and heart failure in Orai1 deficient mice. We demonstrate that Orai1 deficient mice have significantly decreased survival in this pressure overload model. Transthoracic echocardiography reveals that Orai1 deficient mice develop rapid dilated cardiomyopathy, with greater loss of function, and histological and molecular data indicate that this pathology is associated with significant apoptosis, but not major differences in cellular hypertrophy, fibrosis, and some major hypertrophic makers. Orai1 represents a crucial calcium entry mechanism in the compensation of the heart to pressure overload over-load, and the development of dilated cardiomyopathy. PMID:24135962

  6. The calcium release-activated calcium channel Orai1 represents a crucial component in hypertrophic compensation and the development of dilated cardiomyopathy

    PubMed Central

    Horton, Jaime S; Buckley, Cadie L; Alvarez, Ernest M; Schorlemmer, Anita; Stokes, Alexander J

    2014-01-01

    As exceptionally calcium selective store-operated channels, Orai channels play a prominent role in cellular calcium signaling. While most studied in the immune system, we are beginning to recognize that Orai1 provides unique calcium signaling pathways in numerous tissue contexts. To assess the involvement of Orai1 in cardiac hypertrophy we used transverse aortic constriction to model pressure overload cardiac hypertrophy and heart failure in Orai1 deficient mice. We demonstrate that Orai1 deficient mice have significantly decreased survival in this pressure overload model. Transthoracic echocardiography reveals that Orai1 deficient mice develop rapid dilated cardiomyopathy, with greater loss of function, and histological and molecular data indicate that this pathology is associated with significant apoptosis, but not major differences in cellular hypertrophy, fibrosis, and some major hypertrophic makers. Orai1 represents a crucial calcium entry mechanism in the compensation of the heart to pressure overload over-load, and the development of dilated cardiomyopathy. PMID:24135962

  7. Quantitative genomic and antigenomic enterovirus RNA detection in explanted heart tissue samples from patients with end-stage idiopathic dilated cardiomyopathy.

    PubMed

    Lévêque, Nicolas; Renois, Fanny; Talmud, Déborah; Nguyen, Yohan; Lesaffre, François; Boulagnon, Camille; Bruneval, Patrick; Fornes, Paul; Andréoletti, Laurent

    2012-10-01

    Standardized one-step real-time RT-PCR assay detected enterovirus RNA in cardiac biopsy samples from 4 of 20 patients suffering from idiopathic dilated cardiomyopathy (IDCM). The median viral load was 287 copies per microgram of total extracted nucleic acids, with positive- to negative-strand RNA ratios ranging from 2 to 20. These results demonstrate enterovirus persistence in the heart of IDCM patients, characterized by low viral loads and low positive- to negative-RNA ratios. PMID:22837323

  8. Chronic administration of small nonerythropoietic peptide sequence of erythropoietin effectively ameliorates the progression of postmyocardial infarction-dilated cardiomyopathy.

    PubMed

    Ahmet, Ismayil; Tae, Hyun-Jin; Brines, Michael; Cerami, Anthony; Lakatta, Edward G; Talan, Mark I

    2013-06-01

    The cardioprotective properties of erythropoietin (EPO) in preclinical studies are well documented, but erythropoietic and prothrombotic properties of EPO preclude its use in chronic heart failure (CHF). We tested the effect of long-term treatment with a small peptide sequence within the EPO molecule, helix B surface peptide (HBSP), that possesses tissue-protective, but not erythropoietic properties of EPO, on mortality and cardiac remodeling in postmyocardial infarction-dilated cardiomyopathy in rats. Starting 2 weeks after permanent left coronary artery ligation, rats received i.p. injections of HBSP (60 µg/kg) or saline two times per week for 10 months. Treatment did not elicit an immune response, and did not affect the hematocrit. Compared with untreated rats, HBSP treatment reduced mortality by 50% (P < 0.05). Repeated echocardiography demonstrated remarkable attenuation of left ventricular dilatation (end-diastolic volume: 41 versus 86%; end-systolic volume: 44 versus 135%; P < 0.05), left ventricle functional deterioration (ejection fraction: -4 versus -63%; P < 0.05), and myocardial infarction (MI) expansion (3 versus 38%; P < 0.05). A hemodynamic assessment at study termination demonstrated normal preload independent stroke work (63 ± 5 versus 40 ± 4; P < 0.05) and arterioventricular coupling (1.2 ± 0.2 versus 2.7 ± 0.7; P < 0.05). Histologic analysis revealed reduced apoptosis (P < 0.05) and fibrosis (P < 0.05), increased cardiomyocyte density (P < 0.05), and increased number of cardiomyocytes in myocardium among HBSP-treated rats. The results indicate that HBSP effectively reduces mortality, ameliorates the MI expansion and CHF progression, and preserves systolic reserve in the rat post-MI model. There is also a possibility that HBSP promoted the increase of the myocytes number in the myocardial wall remote from the infarct. Thus, HBSP peptide merits consideration for clinical testing. PMID:23584743

  9. Novel familial dilated cardiomyopathy mutation in MYL2 affects the structure and function of myosin regulatory light chain.

    PubMed

    Huang, Wenrui; Liang, Jingsheng; Yuan, Chen-Ching; Kazmierczak, Katarzyna; Zhou, Zhiqun; Morales, Ana; McBride, Kim L; Fitzgerald-Butt, Sara M; Hershberger, Ray E; Szczesna-Cordary, Danuta

    2015-06-01

    Dilated cardiomyopathy (DCM) is a disease of the myocardium characterized by left ventricular dilatation and diminished contractile function. Here we describe a novel DCM mutation in the myosin regulatory light chain (RLC), in which aspartic acid at position 94 is replaced by alanine (D94A). The mutation was identified by exome sequencing of three adult first-degree relatives who met formal criteria for idiopathic DCM. To obtain insight into the functional significance of this pathogenic MYL2 variant, we cloned and purified the human ventricular RLC wild-type (WT) and D94A mutant proteins, and performed in vitro experiments using RLC-mutant or WT-reconstituted porcine cardiac preparations. The mutation induced a reduction in the α-helical content of the RLC, and imposed intra-molecular rearrangements. The phosphorylation of RLC by Ca²⁺/calmodulin-activated myosin light chain kinase was not affected by D94A. The mutation was seen to impair binding of RLC to the myosin heavy chain, and its incorporation into RLC-depleted porcine myosin. The actin-activated ATPase activity of mutant-reconstituted porcine cardiac myosin was significantly higher compared with ATPase of wild-type. No changes in the myofibrillar ATPase-pCa relationship were observed in wild-type- or D94A-reconstituted preparations. Measurements of contractile force showed a slightly reduced maximal tension per cross-section of muscle, with no change in the calcium sensitivity of force in D94A-reconstituted skinned porcine papillary muscle strips compared with wild-type. Our data indicate that subtle structural rearrangements in the RLC molecule, followed by its impaired interaction with the myosin heavy chain, may trigger functional abnormalities contributing to the DCM phenotype. PMID:25825243

  10. Evaluation of acceleration and deceleration cardiac processes using phase-rectified signal averaging in healthy and idiopathic dilated cardiomyopathy subjects.

    PubMed

    Bas, Rosana; Vallverdú, Montserrat; Valencia, Jose F; Voss, Andreas; de Luna, Antonio Bayés; Caminal, Pere

    2015-02-01

    The aim of the present study was to investigate the suitability of the Phase-Rectified Signal Averaging (PRSA) method for improved risk prediction in cardiac patients. Moreover, this technique, which separately evaluates acceleration and deceleration processes of cardiac rhythm, allows the effect of sympathetic and vagal modulations of beat-to-beat intervals to be characterized. Holter recordings of idiopathic dilated cardiomyopathy (IDC) patients were analyzed: high-risk (HR), who suffered sudden cardiac death (SCD) during the follow-up; and low-risk (LR), without any kind of cardiac-related death. Moreover, a control group of healthy subjects was analyzed. PRSA indexes were analyzed, for different time scales T and wavelet scales s, from RR series of 24 h-ECG recordings, awake periods and sleep periods. Also, the behavior of these indexes from simulated data was analyzed and compared with real data results. Outcomes demonstrated the PRSA capacity to significantly discriminate healthy subjects from IDC patients and HR from LR patients on a higher level than traditional temporal and spectral measures. The behavior of PRSA indexes agrees with experimental evidences related to cardiac autonomic modulations. Also, these parameters reflect more regularity of the autonomic nervous system (ANS) in HR patients. PMID:25585858

  11. An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system.

    PubMed

    Bhattacharya-Ghosh, Benjamin; Bozkurt, Selim; Rutten, Marcel C M; van de Vosse, Frans N; Díaz-Zuccarini, Vanessa

    2014-10-01

    Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view. PMID:25147131

  12. Novel m.15434C>A (p.230L>I) Mitochondrial Cytb Gene Missense Mutation Associated with Dilated Cardiomyopathy

    PubMed Central

    Zarrouk Mahjoub, Sinda; Mehri, Sounira; Ourda, Fatma; Finsterer, Josef; Ben Arab, Saïda

    2012-01-01

    Background. Previously it has been shown that various types of hypertrophic and dilative cardiomyopathy (hCMP, dCMP) can be attributed to disturbed mitochondrial oxidative energy metabolism. Several studies described mutations in mitochondrial DNA-located genes encoding for subunits of respiratory chain complexes, including the cytochrome b gene (MT-CYB), causing CMPs. Methods and Results. In the present study the MT-CYB gene was analysed in 30 patients with hCMP, 40 patients with dCMP, and 50 controls for alterations. Altogether, 27 MT-CYB variants were detected. Twenty-four of them were single nucleotide polymorphisms defining common haplogroups. The variant m.15434C>A was found in a single patient with severe dCMP and assessed as novel mutation, since it was not found in healthy controls or available data sets, and was nonhaplogroup associated with Phylotree. This variant altered an amino acid (L230I) with a high interspecific amino acid conservation index (CI = 97.7%) indicative of the functional importance of the residue. Conclusions. Though the L230I mutation seems to play a causative role for dCMP, prospective studies on yeast or transgenic mice models with defined mutation are warranted to study the pathogenetic impact of this mutation. PMID:22811935

  13. Effect of pimobendan on the clinical outcome and survival of cats with non-taurine responsive dilated cardiomyopathy.

    PubMed

    Hambrook, Lydia E; Bennett, Peter F

    2012-04-01

    This retrospective study was designed to assess the effect of pimobendan on the median survival time (MST) of cats with non-taurine responsive dilated cardiomyopathy (DCM). Thirty-two client-owned cats with a left ventricular internal dimension at end systole (LVIDs) >14 mm, a fractional shortening (FS) <28% and a lack of response to taurine therapy were included over a 9-year period (2001-2010). These cats were divided into pimobendan (n=16) and non-pimobendan (n=16) treatment groups. All cats received standard treatment with frusemide, taurine and benazepril or enalapril. Nine cats in the non-pimobendan group also received digoxin. The MST of the pimobendan group (49 days; range 1 to >502 days) was four times that of the non-pimobendan group (12 days; 1 to 244 days). The difference in survival between the two groups was statistically significant (P = 0.048). Hypothermia and FS <20% were associated with a poor prognosis. No adverse effects to pimobendan were noted. PMID:22412159

  14. Resting and dobutamine stress echocardiographic factors associated with the development of occult dilated cardiomyopathy in healthy Doberman pinscher dogs.

    PubMed

    Minors, S L; O'Grady, M R

    1998-01-01

    In 29 healthy Doberman Pinschers, echocardiographic parameters evaluating systolic and diastolic function were examined prospectively at rest and during dobutamine constant rate infusion (5 micrograms/kg/minute) to determine if any parameters were associated with the development of occult dilated cardiomyopathy (DCM). A resting echocardiogram was repeated 1 year later to determine which dogs had met our criteria for occult DCM. Six dogs developed occult DCM during the follow-up period. Univariate logistic regression analysis showed that at rest, an increased left ventricular internal dimension in systole (LVID-S) (P = .02), preejection period (PEP) (P = .03), ratio of PEP to left ventricular ejection time (P = .02), and isovolumic relaxation time (P = .02) were significantly associated with the development of occult DCM. During dobutamine stress echocardiography (DSE), high LVID-S (P = .02) and systolic wall stress index (P = .04) and reduced fractional shortening (P = .02) and ratio of peak early to late diastolic mitral filling velocity (E/A) (P = .05) were associated with the development of occult DCM. Multiple logistic regression showed that LVID-S (P = .002) and E/A (P = .002) measured during dobutamine infusion also were associated with the development of occult DCM. Reclassification based on the DSE data was not significantly different than reclassification based on the resting echocardiographic data. Resting echocardiography and DSE have the potential to be clinically applicable screening tests for very early systolic and diastolic dysfunction in Doberman Pinschers, heralding the onset of occult DCM as it is currently defined. PMID:9773414

  15. FasL expression in cardiomyocytes activates the ERK1/2 pathway, leading to dilated cardiomyopathy and advanced heart failure.

    PubMed

    Huby, Anne-Cecile; Turdi, Subat; James, Jeanne; Towbin, Jeffrey A; Purevjav, Enkhsaikhan

    2016-02-01

    Increase in the apoptotic molecule Fas ligand (FasL) in serum and cardiomyocytes has been shown to be associated with progressive dilated cardiomyopathy (DCM) and congestive heart failure (CHF) in humans. However, the underlying mechanism(s) of FasL-related deterioration of heart function remain obscure. The aim of the present study is to determine roles of myocardial FasL in the activation of alternative pathways such as extracellular-signal-regulated kinase 1/2 (ERK1/2), inflammation or fibrosis and to identify effective treatments of progressive DCM and advanced CHF. Transgenic mice with cardiomyocyte-specific overexpression of FasL were investigated and treated with an ERK1/2 inhibitor (U-0126), losartan (los), prednisolone (pred) or placebo. Morpho-histological and molecular studies were subsequently performed. FasL mice showed significantly higher mortality compared with wild-type (WT) littermates due to DCM and advanced CHF. Prominent perivascular and interstitial fibrosis, increased interleukin secretion and diffuse CD3-positive cell infiltration were evident in FasL hearts. Up-regulation of the short form of Fas-associated death domain (FADD)-like interleukin 1β-converting enzyme (FLICE) inhibitory protein (s-FLIP), RIP (receptor-interacting protein) and ERK1/2 and down-regulation of transforming growth factor beta 1 (TGFβ1) and nuclear factor-κB (NF-κB) was determined in the myocardium, whereas expression of ERK1/2, periostin (Postn) and osteopontin increased in cardiac fibroblasts. U-0126 and los increased CHF survival by 75% compared with pred and placebo groups. U-0126 had both anti-fibrotic and anti-apoptotic effects, whereas los reduced fibrosis only. Myocardial FasL expression in mice activates differential robust fibrotic, apoptotic and inflammatory responses via ERK1/2 in cardiomyocytes and cardiac fibroblasts inducing DCM and CHF. Blocking the ERK1/2 pathway prevented progression of FasL-induced DCM and CHF by reducing fibrosis, inflammation

  16. An Uncommon Association of Familial Partial Lipodystrophy, Dilated Cardiomyopathy, and Conduction System Disease

    PubMed Central

    Panikkath, Ragesh; Panikkath, Deepa; Sanchez-Iglesias, S.; Araujo-Vilar, D; Lado-Abeal, Joaquin

    2016-01-01

    A 46-year-old African American woman presented with severe respiratory distress requiring intubation and was diagnosed with nonischemic cardiomyopathy. She had the typical phenotype of familial partial lipodystrophy 2 (FPLD2). Sequence analysis of LMNA gene showed a heterozygous missense mutation at exon 8 (c.1444C>T) causing amino acid change, p.R482W. She later developed severe coronary artery disease requiring multiple percutaneous coronary interventions and coronary artery bypass surgery. She was later diagnosed with diabetes, primary hyperparathyroidism, and euthyroid multinodular goiter. She had sinus nodal and atrioventricular nodal disease and had an implantable cardioverter defibrillator implantation due to persistent left ventricular dysfunction. The device eroded through the skin few months after implantation and needed a re-implant on the contralateral side. She had atrial flutter requiring ablation. This patient with FPLD2 had most of the reported cardiac complications of FPLD2. This case is presented to improve the awareness of the presentation of this disease among cardiologists and internists. PMID:27504462

  17. An Uncommon Association of Familial Partial Lipodystrophy, Dilated Cardiomyopathy, and Conduction System Disease.

    PubMed

    Panikkath, Ragesh; Panikkath, Deepa; Sanchez-Iglesias, S; Araujo-Vilar, D; Lado-Abeal, Joaquin

    2016-01-01

    A 46-year-old African American woman presented with severe respiratory distress requiring intubation and was diagnosed with nonischemic cardiomyopathy. She had the typical phenotype of familial partial lipodystrophy 2 (FPLD2). Sequence analysis of LMNA gene showed a heterozygous missense mutation at exon 8 (c.1444C>T) causing amino acid change, p.R482W. She later developed severe coronary artery disease requiring multiple percutaneous coronary interventions and coronary artery bypass surgery. She was later diagnosed with diabetes, primary hyperparathyroidism, and euthyroid multinodular goiter. She had sinus nodal and atrioventricular nodal disease and had an implantable cardioverter defibrillator implantation due to persistent left ventricular dysfunction. The device eroded through the skin few months after implantation and needed a re-implant on the contralateral side. She had atrial flutter requiring ablation. This patient with FPLD2 had most of the reported cardiac complications of FPLD2. This case is presented to improve the awareness of the presentation of this disease among cardiologists and internists. PMID:27504462

  18. Types of Cardiomyopathy

    MedlinePlus

    ... ventricles, making it harder for the heart to pump blood. Hypertrophic cardiomyopathy also can cause stiffness of the ... Over time, the heart loses the ability to pump blood effectively. Dilated cardiomyopathy can lead to heart failure , ...

  19. Endothelial Restoration of Receptor Activity-Modifying Protein 2 Is Sufficient to Rescue Lethality, but Survivors Develop Dilated Cardiomyopathy.

    PubMed

    Kechele, Daniel O; Dunworth, William P; Trincot, Claire E; Wetzel-Strong, Sarah E; Li, Manyu; Ma, Hong; Liu, Jiandong; Caron, Kathleen M

    2016-09-01

    RAMPs (receptor activity-modifying proteins) serve as oligomeric modulators for numerous G-protein-coupled receptors, yet elucidating the physiological relevance of these interactions remains complex. Ramp2 null mice are embryonic lethal, with cardiovascular developmental defects similar to those observed in mice null for canonical adrenomedullin/calcitonin receptor-like receptor signaling. We aimed to genetically rescue the Ramp2(-/-) lethality in order to further delineate the spatiotemporal requirements for RAMP2 function during development and thereby enable the elucidation of an expanded repertoire of RAMP2 functions with family B G-protein-coupled receptors in adult homeostasis. Endothelial-specific expression of Ramp2 under the VE-cadherin promoter resulted in the partial rescue of Ramp2(-/-) mice, demonstrating that endothelial expression of Ramp2 is necessary and sufficient for survival. The surviving Ramp2(-/-) Tg animals lived to adulthood and developed spontaneous hypotension and dilated cardiomyopathy, which was not observed in adult mice lacking calcitonin receptor-like receptor. Yet, the hearts of Ramp2(-/-) Tg animals displayed dysregulation of family B G-protein-coupled receptors, including parathyroid hormone and glucagon receptors, as well as their downstream signaling pathways. These data suggest a functional requirement for RAMP2 in the modulation of additional G-protein-coupled receptor pathways in vivo, which is critical for sustained cardiovascular homeostasis. The cardiovascular importance of RAMP2 extends beyond the endothelium and canonical adrenomedullin/calcitonin receptor-like receptor signaling, in which future studies could elucidate novel and pharmacologically tractable pathways for treating cardiovascular diseases. PMID:27402918

  20. Cardiac myosin light chain phosphorylation and inotropic effects of a biased ligand, TRV120023, in a dilated cardiomyopathy model

    PubMed Central

    Tarigopula, Madhusudhan; Davis, Robert T.; Mungai, Paul T.; Ryba, David M.; Wieczorek, David F.; Cowan, Conrad L.; Violin, Jonathan D.; Wolska, Beata M.; Solaro, R. John

    2015-01-01

    Aims Therapeutic approaches to treat familial dilated cardiomyopathy (DCM), which is characterized by depressed sarcomeric tension and susceptibility to Ca2+-related arrhythmias, have been generally unsuccessful. Our objective in the present work was to determine the effect of the angiotensin II type 1 receptor (AT1R) biased ligand, TRV120023, on contractility of hearts of a transgenic mouse model of familial DCM with mutation in tropomyosin at position 54 (TG-E54K). Our rationale is based on previous studies, which have supported the hypothesis that biased G-protein-coupled receptor ligands, signalling via β-arrestin, increase cardiac contractility with no effect on Ca2+ transients. Our previous work demonstrated that the biased ligand TRV120023 is able to block angiotensin-induced hypertrophy, while promoting an increase in sarcomere Ca2+ response. Methods and results We tested the hypothesis that the depression in cardiac function associated with DCM can be offset by infusion of the AT1R biased ligand, TRV120023. We intravenously infused saline, TRV120023, or the unbiased ligand, losartan, for 15 min in TG-E54K and non-transgenic mice to obtain left ventricular pressure–volume relations. Hearts were analysed for sarcomeric protein phosphorylation. Results showed that the AT1R biased ligand increases cardiac performance in TG-E54K mice in association with increased myosin light chain-2 phosphorylation. Conclusion Treatment of mice with an AT1R biased ligand, acting via β-arrestin signalling, is able to induce an increase in cardiac contractility associated with an increase in ventricular myosin light chain-2 phosphorylation. AT1R biased ligands may prove to be a novel inotropic approach in familial DCM. PMID:26045475

  1. Comparison of the Structure and Function of Phospholamban and the Arginine-14 Deficient Mutant Associated with Dilated Cardiomyopathy

    PubMed Central

    Hughes, Eleri; Middleton, David A.

    2014-01-01

    Phospholamban (PLB) is a pentameric protein that plays an important role in regulating cardiac contractility via a reversible inhibitory association with the sarcoplasmic reticulum Ca2+ATPase (SERCA), the enzyme responsible for maintaining correct calcium homeostasis. Here we study the functional and biophysical characteristics of a PLB mutant associated with human dilated cardiomyopathy (DCM), with a deletion of arginine at position 14 (PLBR14Δ). In agreement with recent findings, we find that PLBR14Δ has a reduced inhibitory effect on SERCA compared to wild type PLB (PLBWT) when reconstituted into lipid membranes. The mutation also leads to a large reduction in the protein kinase A-catalysed phosphorylation of Ser-16 in the cytoplasmic domain of PLBR14Δ. Measurements on SERCA co-reconstituted with an equimolar mixture of PLBWT and PLBR14Δ (representing the lethal heterozygous state associated with DCM) indicates that the loss-of-function mutation has a dominant effect on PLBWT functionality and phosphorylation capacity, suggesting that mixed PLBWT/PLBR14Δ pentamers are formed that have characteristics typical of the mutant protein. Structural and biophysical analysis of PLBR14Δ indicates that the mutation perturbs slightly the helical structure of the PLB cytoplasmic domain and reduces its affinity for the phospholipid bilayer surface, thereby altering the orientation of the cytoplasmic domain relative to the wild-type protein. These results indicate that the structure and function consequences of the R14 deletion have profound effects on the regulation of SERCA which may contribute to the aetiology of DCM. PMID:25225809

  2. Identification of nondiabetic heart failure-associated genes by bioinformatics approaches in patients with dilated ischemic cardiomyopathy

    PubMed Central

    YU, ANZHONG; ZHANG, JINGYAO; LIU, HAIYAN; LIU, BING; MENG, LINGDONG

    2016-01-01

    Heart failure (HF) is a common pathological condition affecting 4% of the worldwide population. However, approaches for predicting or treating nondiabetic HF (ND-HF) progression are insufficient. In the current study, the gene expression profile GSE26887 was analyzed, which contained samples from 5 healthy controls, 7 diabetes mellitus-HF patients and 12 ND-HF patients with dilated ischemic cardiomyopathy. The dataset of 5 healthy controls and 12 ND-HF patients was normalized with robust multichip average analysis and the differentially expressed genes (DEGs) were screened by unequal variance t-test and multiple-testing correction. In addition, the protein-protein interaction (PPI) network of the upregulated and downregulated genes was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database and the Cytoscape software platform. Subsequently, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A total of 122 upregulated and 133 downregulated genes were detected. The most significantly up- and downregulated genes were EIF1AY and SERPINE1, respectively. In addition, 38 and 77 nodes were obtained in the up- and downregulated PPI network. DEGs that owned the highest connectivity degree were USP9Y and UTY in the upregulated network, and CD44 in the downregulated networks, respectively. NPPA and SERPINE1 were also found to be hub genes in the PPI network. Several GO terms and pathways that were enriched by DEGs were identified, and the most significantly enriched KEGG pathways were drug metabolism and extracellular matrix-receptor interaction. In conclusion, the two DEGs, NPPA and SERPINE1, may be important in the pathogenesis of HF and may be used for the diagnosis and treatment of HF. PMID:27284354

  3. A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy

    PubMed Central

    Villard, Eric; Perret, Claire; Gary, Françoise; Proust, Carole; Dilanian, Gilles; Hengstenberg, Christian; Ruppert, Volker; Arbustini, Eloisa; Wichter, Thomas; Germain, Marine; Dubourg, Olivier; Tavazzi, Luigi; Aumont, Marie-Claude; DeGroote, Pascal; Fauchier, Laurent; Trochu, Jean-Noël; Gibelin, Pierre; Aupetit, Jean-François; Stark, Klaus; Erdmann, Jeanette; Hetzer, Roland; Roberts, Angharad M.; Barton, Paul J.R.; Regitz-Zagrosek, Vera; Aslam, Uzma; Duboscq-Bidot, Laëtitia; Meyborg, Matthias; Maisch, Bernhard; Madeira, Hugo; Waldenström, Anders; Galve, Enrique; Cleland, John G.; Dorent, Richard; Roizes, Gerard; Zeller, Tanja; Blankenberg, Stefan; Goodall, Alison H.; Cook, Stuart; Tregouet, David A.; Tiret, Laurence; Isnard, Richard; Komajda, Michel; Charron, Philippe; Cambien, François

    2011-01-01

    Aims Dilated cardiomyopathy (DCM) is a major cause of heart failure with a high familial recurrence risk. So far, the genetics of DCM remains largely unresolved. We conducted the first genome-wide association study (GWAS) to identify loci contributing to sporadic DCM. Methods and results One thousand one hundred and seventy-nine DCM patients and 1108 controls contributed to the discovery phase. Pools of DNA stratified on disease status, population, age, and gender were constituted and used for testing association of DCM with 517 382 single nucleotide polymorphisms (SNPs). Three DCM-associated SNPs were confirmed by individual genotyping (P < 5.0 10−7), and two of them, rs10927875 and rs2234962, were replicated in independent samples (1165 DCM patients and 1302 controls), with P-values of 0.002 and 0.009, respectively. rs10927875 maps to a region on chromosome 1p36.13 which encompasses several genes among which HSPB7 has been formerly suggested to be implicated in DCM. The second identified locus involves rs2234962, a non-synonymous SNP (c.T757C, p. C151R) located within the sequence of BAG3 on chromosome 10q26. To assess whether coding mutations of BAG3 might cause monogenic forms of the disease, we sequenced BAG3 exons in 168 independent index cases diagnosed with familial DCM and identified four truncating and two missense mutations. Each mutation was heterozygous, present in all genotyped relatives affected by the disease and absent in a control group of 347 healthy individuals, strongly suggesting that these mutations are causing the disease. Conclusion This GWAS identified two loci involved in sporadic DCM, one of them probably implicates BAG3. Our results show that rare mutations in BAG3 contribute to monogenic forms of the disease, while common variant(s) in the same gene are implicated in sporadic DCM. PMID:21459883

  4. Rbm20-deficient cardiogenesis reveals early disruption of RNA processing and sarcomere remodeling establishing a developmental etiology for dilated cardiomyopathy

    PubMed Central

    Beraldi, Rosanna; Li, Xing; Martinez Fernandez, Almudena; Reyes, Santiago; Secreto, Frank; Terzic, Andre; Olson, Timothy M.; Nelson, Timothy J.

    2014-01-01

    Dilated cardiomyopathy (DCM) due to mutations in RBM20, a gene encoding an RNA-binding protein, is associated with high familial penetrance, risk of progressive heart failure and sudden death. Although genetic investigations and physiological models have established the linkage of RBM20 with early-onset DCM, the underlying basis of cellular and molecular dysfunction is undetermined. Modeling human genetics using a high-throughput pluripotent stem cell platform was herein designed to pinpoint the initial transcriptome dysfunction and mechanistic corruption in disease pathogenesis. Tnnt2-pGreenZeo pluripotent stem cells were engineered to knockdown Rbm20 (shRbm20) to determine the cardiac-pathogenic phenotype during cardiac differentiation. Intracellular Ca2+ transients revealed Rbm20-dependent alteration in Ca2+ handling, coinciding with known pathological splice variants of Titin and Camk2d genes by Day 24 of cardiogenesis. Ultrastructural analysis demonstrated elongated and thinner sarcomeres in the absence of Rbm20 that is consistent with human cardiac biopsy samples. Furthermore, Rbm20-depleted transcriptional profiling at Day 12 identified Rbm20-dependent dysregulation with 76% of differentially expressed genes linked to known cardiac pathology ranging from primordial Nkx2.5 to mature cardiac Tnnt2 as the initial molecular aberrations. Notably, downstream consequences of Rbm20-depletion at Day 24 of differentiation demonstrated significant dysregulation of extracellular matrix components such as the anomalous overexpression of the Vtn gene. By using the pluripotent stem cell platform to model human cardiac disease according to a stage-specific cardiogenic roadmap, we established a new paradigm of familial DCM pathogenesis as a developmental disorder that is patterned during early cardiogenesis and propagated with cellular mechanisms of pathological cardiac remodeling. PMID:24584570

  5. Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution.

    PubMed

    Ameling, Sabine; Bhardwaj, Gourav; Hammer, Elke; Beug, Daniel; Steil, Leif; Reinke, Yvonne; Weitmann, Kerstin; Grube, Markus; Trimpert, Christiane; Klingel, Karin; Kandolf, Reinhard; Hoffmann, Wolfgang; Nauck, Matthias; Dörr, Marcus; Empen, Klaus; Felix, Stephan B; Völker, Uwe

    2016-09-01

    Immunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment. Transcription profiling of endomyocardial biopsies with Affymetrix whole genome arrays was performed on 33 paired samples of DCM patients collected before and 6 months after IA/IgG. Therapy-related effects on myocardial protein levels were analysed by label-free proteome profiling for a subset of 23 DCM patients. Data were analysed regarding therapy-associated differences in gene expression and protein levels by comparing responders (defined by improvement of left ventricular ejection fraction ≥20 % relative and ≥5 % absolute) and non-responders. Responders to IA/IgG showed a decrease in serum N-terminal proBNP levels in comparison with baseline which was accompanied by a decreased expression of heart failure markers, such as angiotensin converting enzyme 2 or periostin. However, despite clinical improvement even in responders, IA/IgG did not trigger general inversion of DCM-associated molecular alterations in myocardial tissue. Transcriptome profiling revealed reduced gene expression for connective tissue growth factor, fibronectin, and collagen type I in responders. In contrast, in non-responders after IA/IgG, fibrosis-associated genes and proteins showed elevated levels, whereas values were reduced or maintained in responders. Thus, improvement of LV function after IA/IgG seems to be related to a reduced gene expression of heart failure markers and pro-fibrotic molecules as well as reduced fibrosis progression. PMID:27412778

  6. Stage-dependent benefits and risks of pimobendan in mice with genetic dilated cardiomyopathy and progressive heart failure

    PubMed Central

    Nonaka, Miki; Morimoto, Sachio; Murayama, Takashi; Kurebayashi, Nagomi; Li, Lei; Wang, Yuan-Yuan; Arioka, Masaki; Yoshihara, Tatsuya; Takahashi-Yanaga, Fumi; Sasaguri, Toshiyuki

    2015-01-01

    Background and Purpose The Ca2+ sensitizer pimobendan is a unique inotropic agent that improves cardiac contractility with less of an increase in oxygen consumption and potentially fewer adverse effects on myocardial remodelling and arrhythmia, compared with traditional inotropes. However, clinical trials report contradictory effects of pimobendan in patients with heart failure (HF). We provide mechanistic experimental evidence of the efficacy of pimobendan using a novel mouse model of progressive HF. Experimental Approach A knock-in mouse model of human genetic dilated cardiomyopathy, which shows a clear transition from compensatory to end-stage HF at a fixed time during growth, was used to evaluate the efficacy of pimobendan and explore the underlying molecular and cellular mechanisms. Key Results Pimobendan prevented myocardial remodelling in compensated HF and significantly extended life span in both compensated and end-stage HF, but dose-dependently increased sudden death in end-stage HF. In cardiomyocytes isolated from end-stage HF mice, pimobendan induced triggered activity probably because of early or delayed afterdepolarizations. The L-type Ca2+ channel blocker verapamil decreased the incidence of triggered activity, suggesting that this was from over-elevated cytoplasmic Ca2+ through increased Ca2+ entry by PDE3 inhibition under diminished sarcoplasmic reticulum Ca2+ reuptake and increased Ca2+ leakage from sarcoplasmic reticulum in end-stage HF. Conclusions and Implications Pimobendan was beneficial regardless of HF stage, but increased sudden cardiac death in end-stage HF with extensive remodelling of Ca2+ handling. Reduction of cytoplasmic Ca2+ elevated by PDE3 inhibition might decrease this risk of sudden cardiac death. PMID:25560565

  7. Detection and comparison of microRNA expression in the serum of Doberman Pinschers with dilated cardiomyopathy and healthy controls

    PubMed Central

    2013-01-01

    Background Dilated cardiomyopathy (DCM) is the most common heart disease in Doberman Pinschers. MicroRNAs (miRNAs) are short non-coding RNAs playing important roles in gene regulation. Different miRNA expression patterns have been described for DCM in humans and might represent potential diagnostic markers. There are no studies investigating miRNA expression profiles in canine DCM. The aims of this study were to screen the miRNA expression profile of canine serum using miRNA microarray and to compare expression patterns of a group of Doberman Pinschers with DCM and healthy controls. Results Eight Doberman Pinschers were examined by echocardiography and 24-hour-ECG and classified as healthy (n = 4) or suffering from DCM (n = 4). Total RNA was extracted from serum and hybridized on a custom-designed 8x60k miRNA microarray (Agilent) containing probes for 1368 individual miRNAs. Although total RNA concentrations were very low in serum samples, 404 different miRNAs were detectable with sufficient signal intensity on miRNA microarray. 22 miRNAs were differentially expressed in the two groups (p < 0.05 and fold change (FC) > 1.5), but did not reach statistical significance after multiple testing correction (false discovery rate adjusted p > 0.05). Five miRNAs were selected for further analysis using quantitative Real-Time RT-PCR (qPCR) assays. No significant differences were found using specific miRNA qPCR assays (p > 0.05). Conclusions Numerous miRNAs can be detected in canine serum. Between healthy and DCM dogs, miRNA expression changes could be detected, but the results did not reach statistical significance most probably due to the small group size. miRNAs are potential new circulating biomarkers in veterinary medicine and should be investigated in larger patient groups and additional canine diseases. PMID:23327631

  8. Transgenic rescue of neurogenic atrophy in the nmd mouse reveals a role for Ighmbp2 in dilated cardiomyopathy

    PubMed Central

    Maddatu, Terry P.; Garvey, Sean M.; Shroeder, David G.; Hampton, Thomas G.; Cox, Gregory A.

    2005-01-01

    Immunoglobulin mu binding protein 2 (IGHMBP2) is a DNA/RNA helicase with a putative role in transcriptional regulation and splicing. A recessive mutation of the Ighmbp2 gene in neuromuscular degeneration (nmd) mice causes progressive neurogenic atrophy of limb muscles. Affected mice show significant loss of motor neurons with large caliber axons and a moderate reduction of neurons with small caliber axons in the ventral nerve roots of the spinal cord. To investigate the role of Ighmbp2 in the pathogenesis of neuromuscular degeneration, we generated two independent lines of transgenic mice expressing the full-length Ighmbp2 cDNA specifically in neurons. Histopathological evaluation of L4 ventral nerve roots revealed that transgenic expression of the Ighmbp2 cDNA prevented primary motor neuron degeneration, while restoring the normal axonal morphology and density in nmd mice. A similar neuronal improvement is found in mutant mice carrying the CAST/EiJ-derived modifier of nmd (MnmC). Intriguingly, both the transgenic and modified nmd mice went on to develop a previously unobserved cardiac and skeletal myopathy. Necropsy of nmd mice in end-stage heart failure revealed a primary dilated cardiomyopathy with secondary respiratory failure that was confirmed by in vivo ECG and echocardiographic measures. Our results suggest that reduced levels of IGHMBP2 in nmd mice compromise the integrity and function not only of motor neurons, but also of skeletal and cardiac myocytes. These findings highlight the important role of IGHMBP2 in the maintenance and survival of these terminally differentiated cell types. PMID:15069027

  9. Heart Mitochondrial Proteome Study Elucidates Changes in Cardiac Energy Metabolism and Antioxidant PRDX3 in Human Dilated Cardiomyopathy

    PubMed Central

    Roselló-Lletí, Esther; Tarazón, Estefanía; Barderas, María G.; Ortega, Ana; Otero, Manuel; Molina-Navarro, Maria Micaela; Lago, Francisca; González-Juanatey, Jose Ramón; Salvador, Antonio; Portolés, Manuel; Rivera, Miguel

    2014-01-01

    Background Dilated cardiomyopathy (DCM) is a public health problem with no available curative treatment, and mitochondrial dysfunction plays a critical role in its development. The present study is the first to analyze the mitochondrial proteome in cardiac tissue of patients with DCM to identify potential molecular targets for its therapeutic intervention. Methods and Results 16 left ventricular (LV) samples obtained from explanted human hearts with DCM (n = 8) and control donors (n = 8) were extracted to perform a proteomic approach to investigate the variations in mitochondrial protein expression. The proteome of the samples was analyzed by quantitative differential electrophoresis and Mass Spectrometry. These changes were validated by classical techniques and by novel and precise selected reaction monitoring analysis and RNA sequencing approach increasing the total heart samples up to 25. We found significant alterations in energy metabolism, especially in molecules involved in substrate utilization (ODPA, ETFD, DLDH), energy production (ATPA), other metabolic pathways (AL4A1) and protein synthesis (EFTU), obtaining considerable and specific relationships between the alterations detected in these processes. Importantly, we observed that the antioxidant PRDX3 overexpression is associated with impaired ventricular function. PRDX3 is significantly related to LV end systolic and diastolic diameter (r = 0.73, p value<0.01; r = 0.71, p value<0.01), fractional shortening, and ejection fraction (r = −0.61, p value<0.05; and r = −0.62, p value<0.05, respectively). Conclusion This work could be a pivotal study to gain more knowledge on the cellular mechanisms related to the pathophysiology of this disease and may lead to the development of etiology-specific heart failure therapies. We suggest new molecular targets for therapeutic interventions, something that up to now has been lacking. PMID:25397948

  10. Dilated cardiomyopathy mutations in δ-sarcoglycan exert a dominant-negative effect on cardiac myocyte mechanical stability.

    PubMed

    Campbell, Matthew D; Witcher, Marc; Gopal, Anoop; Michele, Daniel E

    2016-05-01

    Delta-sarcoglycan is a component of the sarcoglycan subcomplex within the dystrophin-glycoprotein complex located at the plasma membrane of muscle cells. While recessive mutations in δ-sarcoglycan cause limb girdle muscular dystrophy 2F, dominant mutations in δ-sarcoglycan have been linked to inherited dilated cardiomyopathy (DCM). The purpose of this study was to investigate functional cellular defects present in adult cardiac myocytes expressing mutant δ-sarcoglycans harboring the dominant inherited DCM mutations R71T or R97Q. This study demonstrates that DCM mutant δ-sarcoglycans can be stably expressed in adult rat cardiac myocytes and traffic similarly to wild-type δ-sarcoglycan to the plasma membrane, without perturbing assembly of the dystrophin-glycoprotein complex. However, expression of DCM mutant δ-sarcoglycan in adult rat cardiac myocytes is sufficient to alter cardiac myocyte plasma membrane stability in the presence of mechanical strain. Upon cyclical cell stretching, cardiac myocytes expressing mutant δ-sarcoglycan R97Q or R71T have increased cell-impermeant dye uptake and undergo contractures at greater frequencies than myocytes expressing normal δ-sarcoglycan. Additionally, the R71T mutation creates an ectopic N-linked glycosylation site that results in aberrant glycosylation of the extracellular domain of δ-sarcoglycan. Therefore, appropriate glycosylation of δ-sarcoglycan may also be necessary for proper δ-sarcoglycan function and overall dystrophin-glycoprotein complex function. These studies demonstrate that DCM mutations in δ-sarcoglycan can exert a dominant negative effect on dystrophin-glycoprotein complex function leading to myocardial mechanical instability that may underlie the pathogenesis of δ-sarcoglycan-associated DCM. PMID:26968544

  11. Heart‐type fatty acid binding protein is a novel prognostic marker in patients with non‐ischaemic dilated cardiomyopathy

    PubMed Central

    Komamura, K; Sasaki, T; Hanatani, A; Kim, J; Hashimura, K; Ishida, Y; Ohkaru, Y; Asayama, K; Tanaka, T; Ogai, A; Nakatani, T; Kitamura, S; Kangawa, K; Miyatake, K; Kitakaze, M

    2006-01-01

    Objective To determine whether concentrations of heart‐type fatty acid binding protein (H‐FABP) measured before hospital discharge predict critical cardiac events in patients with idiopathic dilated cardiomyopathy (DCM). Patients 92 consecutive patients with DCM were enrolled and followed up for four years. Main outcome measures Serum concentrations of H‐FABP, brain natriuretic peptide (BNP), cardiac troponin T before hospital discharge and survival rate. Results 23 patients died of cardiac causes, received a left ventricular assist device or underwent heart transplantation during the four‐year follow up. Univariate analyses showed that New York Heart Association functional class, heart rate, ejection fraction, serum H‐FABP and plasma BNP were significant variables. According to multivariate analysis, serum H‐FABP and plasma BNP concentrations were independent predictors of critical cardiac events. Cardiac troponin T before hospital discharge was not a predictor. The area under the receiver operating characteristic curve for death from critical cardiac events was similar between H‐FABP and BNP. Patients with an H‐FABP concentration at or above the median (⩾ 5.4 ng/ml) had a significantly lower survival rate than those below the median, according to analysis by log rank test (p < 0.0001). When combined with BNP concentration at or above the median (⩾ 138 pg/ml), H‐FABP below the median predicted the worst prognosis among the combinations. Conclusions The concentration of serum H‐FABP before discharge from hospital may be an independent predictor for critical cardiac events in DCM. PMID:16387818

  12. Knock-in mice harboring a Ca2+ desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy

    PubMed Central

    McConnell, Bradley K.; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P.; Reiser, Peter J.; Tikunova, Svetlana B.

    2015-01-01

    The physiological consequences of aberrant Ca2+ binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca2+ sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca2+ sensitivity of reconstituted thin filaments by increasing the rate of Ca2+ dissociation. In addition, the D73N mutation drastically blunted the extent of Ca2+ desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca2+ sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca2+ sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM. PMID:26379556

  13. Systematic permutation testing in GWAS pathway analyses: identification of genetic networks in dilated cardiomyopathy and ulcerative colitis

    PubMed Central

    2014-01-01

    Background Genome wide association studies (GWAS) are applied to identify genetic loci, which are associated with complex traits and human diseases. Analogous to the evolution of gene expression analyses, pathway analyses have emerged as important tools to uncover functional networks of genome-wide association data. Usually, pathway analyses combine statistical methods with a priori available biological knowledge. To determine significance thresholds for associated pathways, correction for multiple testing and over-representation permutation testing is applied. Results We systematically investigated the impact of three different permutation test approaches for over-representation analysis to detect false positive pathway candidates and evaluate them on genome-wide association data of Dilated Cardiomyopathy (DCM) and Ulcerative Colitis (UC). Our results provide evidence that the gold standard - permuting the case–control status – effectively improves specificity of GWAS pathway analysis. Although permutation of SNPs does not maintain linkage disequilibrium (LD), these permutations represent an alternative for GWAS data when case–control permutations are not possible. Gene permutations, however, did not add significantly to the specificity. Finally, we provide estimates on the required number of permutations for the investigated approaches. Conclusions To discover potential false positive functional pathway candidates and to support the results from standard statistical tests such as the Hypergeometric test, permutation tests of case control data should be carried out. The most reasonable alternative was case–control permutation, if this is not possible, SNP permutations may be carried out. Our study also demonstrates that significance values converge rapidly with an increasing number of permutations. By applying the described statistical framework we were able to discover axon guidance, focal adhesion and calcium signaling as important DCM-related pathways

  14. [Severe pulmonary embolism and acute lower limb ischemia complicating peripartum cardiomyopathy successfully treated by streptokinase].

    PubMed

    Yaméogo, N V; Kaboré, E; Seghda, A; Kagambèga, L J; Kaboré, H P; Millogo, G R C; Kologo, K J; Kambiré, Y; Bama, A; Toguyeni, B J Y; Samadoulougou, A K; Zabsonré, P

    2016-02-01

    Peripartum cardiomyopathy is a cardiac disease at high thromboembolism potential. The authors report a case of peripartum cardiomyopathy admitted for congestive heart failure. Echocardiography found a dilated cardiomyopathy with severely impaired left ventricular systolic function and biventricular thrombi. During hospitalization his condition was complicated by severe bilateral pulmonary embolism and left lower limb arterial acute thrombosis. The treatment consisted of thrombolysis with streptokinase associated with dobutamine (in addition to the conventional treatment of heart failure and bromocriptine). The outcome was favorable, marked by pulmonary and lower limb arterial unblocking. PMID:25623958

  15. Association of genetic polymorphisms on BTNL2 with susceptibility to and prognosis of dilated cardiomyopathy in a Chinese population

    PubMed Central

    Cheng, Liang; Zhao, Rong; Jin, ZhenXiao; Ren, Kai; Deng, Chao; Yu, Shiqiang

    2015-01-01

    Background: Dilated cardiomyopathy (DCM) is one type of primary myocardial disease, partly caused by immunity dysfunctions. BTNL2 (butyrophilin-like 2) has already been confirmed to be involved in the etiology of autoimmune disorders and GWAS (genome wide association study) has also identified mutants of a SNP (single nucleotide polymorphism) near BTNL2 could modulate risk of coronary heart disease (also cardiomyopathy). The current study, therefore, was aimed to investigate whether polymorphisms within or around BTNL2 would be correlated with susceptibility to and prognosis of DCM. Material and methods: Peripheral blood samples were gathered from 82 DCM patients and 75 healthy controls. Nine tag-SNPs within or near BTNL2 were obtained from HapMap Database and previously published studies. Eligible haplotypes were gained on the basis of SHesis software. Genotyping of SNPs was implemented with aid of Sequenom MassArray iPLEX platform and subsequently analyzed via MALDI-TOF mass spectrometry. The odd ratios and their 95% confidence interval (95% CI) were utilized to evaluate the correlations between SNPs/haplotypes and DCM risks. Finally, Cox proportional hazard models and Kaplan-Meier curves were performed to assess association of SNPs/haplotypes with prognosis of DCM patients. The statistical analyses were conducted with SPSS 19.0 software. Results: Under the allelic model, rs3763313 (A > C), rs9268494 (C > A), rs9268492 (C > G) and rs9268402 (A > G) were remarkably associated with susceptibility to grade IV of DCM classified by NYHA (New York heart association) (OR = 0.43, 95% CI: 0.22-0.84; P = 0.018; OR = 0.49, 95% CI: 0.27-0.91; P = 0.024; OR = 0.50, 95% CI: 0.27-0.94; P = 0.035; OR = 0.53, 95% CI: 0.28-0.97; P = 0.048). Haplotype C-C-A-T (rs9268492, rs9268494, rs3763313 and rs3763317 synthesized) was also regarded as a protective factor for DCM patients compared with carriers of other haplotypes (OR = 0.50, 95% CI: 0.26-0.97, P = 0.038). Moreover, the

  16. Dilated cardiomyopathy and left bundle branch block associated with ingestion of colloidal gold and silver is reversed by British antiLewisite and vitamin E: The potential toxicity of metals used as health supplements

    PubMed Central

    Archer, Stephen Lawrence

    2008-01-01

    A case of left bundle branch block and a dilated, nonhypertrophic cardiomyopathy associated with ingestion of colloidal gold and silver as an ‘energy tonic’ is described. The cardiac disease was reversed within two months by a course of dimercaprol (Akorn Inc, USA) (British antiLewisite) and vitamin E. This is the first case of gold and silver cardiomyopathy in humans, and highlights the risks of these colloidal metal ‘health supplements’. PMID:18464946

  17. Modeling structural and functional deficiencies of RBM20 familial dilated cardiomyopathy using human induced pluripotent stem cells.

    PubMed

    Wyles, Saranya P; Li, Xing; Hrstka, Sybil C; Reyes, Santiago; Oommen, Saji; Beraldi, Rosanna; Edwards, Jessica; Terzic, Andre; Olson, Timothy M; Nelson, Timothy J

    2016-01-15

    Dilated cardiomyopathy (DCM) is a leading cause of heart failure. In families with autosomal-dominant DCM, heterozygous missense mutations were identified in RNA-binding motif protein 20 (RBM20), a spliceosome protein induced during early cardiogenesis. Dermal fibroblasts from two unrelated patients harboring an RBM20 R636S missense mutation were reprogrammed to human induced pluripotent stem cells (hiPSCs) and differentiated to beating cardiomyocytes (CMs). Stage-specific transcriptome profiling identified differentially expressed genes ranging from angiogenesis regulator to embryonic heart transcription factor as initial molecular aberrations. Furthermore, gene expression analysis for RBM20-dependent splice variants affected sarcomeric (TTN and LDB3) and calcium (Ca(2+)) handling (CAMK2D and CACNA1C) genes. Indeed, RBM20 hiPSC-CMs exhibited increased sarcomeric length (RBM20: 1.747 ± 0.238 µm versus control: 1.404 ± 0.194 µm; P < 0.0001) and decreased sarcomeric width (RBM20: 0.791 ± 0.609 µm versus control: 0.943 ± 0.166 µm; P < 0.0001). Additionally, CMs showed defective Ca(2+) handling machinery with prolonged Ca(2+) levels in the cytoplasm as measured by greater area under the curve (RBM20: 814.718 ± 94.343 AU versus control: 206.941 ± 22.417 AU; P < 0.05) and higher Ca(2+) spike amplitude (RBM20: 35.281 ± 4.060 AU versus control:18.484 ± 1.518 AU; P < 0.05). β-adrenergic stress induced with 10 µm norepinephrine demonstrated increased susceptibility to sarcomeric disorganization (RBM20: 86 ± 10.5% versus control: 40 ± 7%; P < 0.001). This study features the first hiPSC model of RBM20 familial DCM. By monitoring human cardiac disease according to stage-specific cardiogenesis, this study demonstrates RBM20 familial DCM is a developmental disorder initiated by molecular defects that pattern maladaptive cellular mechanisms of pathological cardiac remodeling. Indeed, hiPSC-CMs recapitulate RBM20 familial DCM phenotype in a dish and establish a tool

  18. A Haplotype of Two Novel Polymorphisms in δ-Sarcoglycan Gene Increases Risk of Dilated Cardiomyopathy in Mongoloid Population

    PubMed Central

    Wang, Hong; Wei, Sisi; Chen, Dan; Ying, Li; Zhou, Qing; Li, Gang; Li, Joyce; Gao, Jimin; Kato, Naoya; Hu, Wei; Li, Yigang; Wang, Yuepeng

    2015-01-01

    The role of genetic abnormality of δ-sarcoglycan (δ-SG) gene in dilated (DCM) and hypertrophied (HCM) cardiomyopathy patients is still unfolding. In this study we first defined the promoter region and then searched for polymorphisms/mutations among the promoter, 5'-untranslated region, and the encoding exons in δ-SG gene in 104 Chinese patients with DCM, 145 with HCM, and 790 normal controls. Two novel polymorphisms were found, an 11 base-pair (bp) deletion (c.-100~-110; -) in the promoter region and a missense polymorphism of A848G resulting in p.Q283R in the highly conserved C-terminus. The prevalence of homozygous genotype -/- of c.-100~-110 was slightly higher in DCM (14.42%) and HCM patients (14.48%), as compared with normal controls (11.01%). The prevalence of genotype of 848A/G was significantly higher in DCM (6.73%; OR = 9.43; p = 0.0002), but not in HCM patients (1.38%; OR = 1.37; p = 0.62), as compared with controls (0.76%). Haplotype -_G consisting c.-100~-110 and A848G was associated with increased risk of DCM (OR = 17.27; 95%CI = 3.19–93.56; p = 0.001) but not associated with HCM (OR = 1.90; 95%CI = 0.38–9.55; p = 0.44). Co-occurrence of the genotypes -/- of c.-100~-110 and 848A/G was found in 5 patients with DCM (4.81%; OR = 39.85; p = 0.0001), none of HCM patients, and only 1 of the controls (0.13%). Both polymorphisms were also found in the Japanese population, but not in the Africans and Caucasians. C.-100~-110 resulted in a decrease of δ-SG promoter activity to 64±3% of the control level (p<0.01). Both co-immunoprecipitation and in vitro protein pull-down assays demonstrated that δ-SG-283R interacts normally to β- and γ-SG, but significantly decreased localization of β/δ/γ-SG on the plasma membrane. In conclusion, haplotype -_G composed of c.-100~-110 and A848G confers higher susceptibility to DCM in the Mongoloid population. PMID:26720722

  19. Th17-related cytokines in systemic lupus erythematosus patients with dilated cardiomyopathies: a possible linkage to parvovirus B19 infection.

    PubMed

    Chen, Der-Yuan; Chen, Yi-Ming; Tzang, Bor-Show; Lan, Joung-Liang; Hsu, Tsai-Ching

    2014-01-01

    Dilated cardiomyopathies (DCM) are a major cause of mortality in patients with systemic lupus erythematosus (SLE). Immune responses induced by human parvovirus B19 (B19) are considered an important pathogenic mechanism in myocarditis or DCM. However, little is known about Th17-related cytokines in SLE patients with DCM about the linkage with B19 infection. IgM and IgG against B19 viral protein, and serum levels of Th17-related cytokines were determined using ELISA in eight SLE patients with DCM and six patients with valvular heart disease (VHD). Humoral responses of anti-B19-VP1u and anti-B19-NS1 antibody were assessed using Western blot and B19 DNA was detected by nested Polymerase Chain Reaction (PCR). Levels of interleukin (IL)-17, IL-6, IL-1β, and tumor necrosis factor (TNF)-α were significantly higher in SLE patients with DCM (mean ± SEM, 390.99±125.48 pg/ml, 370.24±114.09 pg/ml, 36.01±16.90 pg/ml, and 183.84±82.94 pg/ml, respectively) compared to healthy controls (51.32±3.04 pg/ml, p<0.001; 36.88±6.64 pg/ml, p<0.001; 5.39±0.62 pg/ml, p<0.005; and 82.13±2.42 pg/ml, p<0.005, respectively). Levels of IL-17 and IL-6 were higher in SLE patients with DCM versus those with VHD (both p<0.01). Five (62.5%) of DCM patients had detectable anti-B19-NS1 IgG and four (50.0%) of them had anti-B19-VP1u IgG, whereas only one (16.7%) of VHD patients had detectable anti-B19-NS1 IgG and anti-B19-VP1u IgG. Serum levels of IL-17, IL-6 and IL-1β were markedly higher in SLE patients with anti-B19-VP1u IgG and anti-B19-NS1 IgG compared to those without anti-B19-VP1u IgG or anti-B19-NS1 IgG, respectively. These suggest a potential association of B19 with DCM and Th17-related cytokines implicated in the pathogenesis of DCM in SLE patients. PMID:25462010

  20. Pathological features of hypertrophic obstructive cardiomyopathy

    PubMed Central

    Davies, M. J.; Pomerance, Ariela; Teare, R. D.

    1974-01-01

    The macroscopic features of hypertrophic obstructive cardiomyopathy are variable. The most easily recognized picture is of disproportionate and asymmetrical left ventricular hypertrophy with a small ventricular volume. Symmetrical ventricular hypertrophy also occurs and dilatation of the ventricular cavity may lead to a configuration more usually associated with congestive cardiomyopathy. Papillary muscle involvement leads to a bullet shape, often retained even when the ventricle dilates. Eighteen of the hearts showed a distinctive band of fibrous thickening below the aortic valve. This was a mirror image of the free edge of the anterior mitral cusp, had the microscopic features of an endocardial friction lesion, and was clearly the morphological expression of the systolic contact between cusp and septum seen on cineangiography. This band is characteristic of hypertrophic obstructive cardiomyopathy; it was more common in older patients and is of particular diagnostic value in cases with symmetrical hypertrophy, including those with dilated ventricular cavities. Sudden death was the commonest presentation in the younger cases but in several cases over 60 years at death hypertrophic obstructive cardiomyopathy was an incidental necropsy finding. Images PMID:4472994

  1. Comparison of nonlinear methods symbolic dynamics, detrended fluctuation, and Poincaré plot analysis in risk stratification in patients with dilated cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Voss, Andreas; Schroeder, Rico; Truebner, Sandra; Goernig, Matthias; Figulla, Hans Reiner; Schirdewan, Alexander

    2007-03-01

    Dilated cardiomyopathy (DCM) has an incidence of about 20/100 000 new cases per annum and accounts for nearly 10 000 deaths per year in the United States. Approximately 36% of patients with dilated cardiomyopathy (DCM) suffer from cardiac death within five years after diagnosis. Currently applied methods for an early risk prediction in DCM patients are rather insufficient. The objective of this study was to investigate the suitability of short-term nonlinear methods symbolic dynamics (STSD), detrended fluctuation (DFA), and Poincaré plot analysis (PPA) for risk stratification in these patients. From 91 DCM patients and 30 healthy subjects (REF), heart rate and blood pressure variability (HRV, BPV), STSD, DFA, and PPA were analyzed. Measures from BPV analysis, DFA, and PPA revealed highly significant differences (p<0.0011) discriminating REF and DCM. For risk stratification in DCM patients, four parameters from BPV analysis, STSD, and PPA revealed significant differences between low and high risk (maximum sensitivity: 90%, specificity: 90%). These results suggest that STSD and PPA are useful nonlinear methods for enhanced risk stratification in DCM patients.

  2. An uncommon clinical presentation of relapsing dilated cardiomyopathy with identification of sequence variations in MYNPC3, KCNH2 and mitochondrial tRNA cysteine

    PubMed Central

    Guillen Sacoto, Maria J.; Chapman, Kimberly A.; Heath, Deneen; Seprish, Mary Beth; Zand, Dina J.

    2015-01-01

    We describe a young girl with dilated cardiomyopathy, long QT syndrome, and possible energy deficiency. Two major sequence changes were identified by whole exome sequencing (WES) and mitochondrial DNA analysis that were interpreted as potentially causative. Changes were identified in the KCNH2 gene and mitochondrial tRNA for cysteine. A variation was also seen in MYPBC3. Since the launch of WES as a clinically available technology in 2010, there has been concern regarding the identification of variants unrelated to the patient's phenotype. However, in cases where targeted sequencing fails to explain the clinical presentation, the underlying etiology could be more complex than anticipated. In this situation, the extensive reach of this tool helped explain both her phenotype and family history. PMID:26937396

  3. Intraventricular vorticity favors conservation of kinetic energy along the cardiac cycle: analysis in patients with dilated cardiomyopathy by post-processing color-doppler images

    NASA Astrophysics Data System (ADS)

    Alhama, Marta; Benito, Yolanda; Bermejo, Javier; Yotti, Raquel; Perez-David, Esther; Barrio, Alicia; Perez Del Villar, Candelas; Gonzalez Mansilla, Ana; Fernandez Aviles, Francisco; Del Alamo, Juan Carlos

    2011-11-01

    Background: This study assesses if the left ventricle (LV) filling vortex developed during diastole may be a mechanism that improves systolic efficiency. 19 patients with dilated cardiomyopathy (DCM) and 37 healthy volunteers were studied. Recently, we have developed and validated a method that derives two-dimensional maps of the LV flow from standard color-Doppler sequences. Two-dimensional maps of instantaneous LV flow were obtained, and circulation, energy and position of the main and secondary vortices were calculated along the cardiac cycle. At aortic valve opening (AVO) the vortex circulation is higher in DCM subjects than healthy volunteers. However, the position of the vortex is farthest form LV outflow tract (LVOT), and this results in lower flow velocity in LVOT at AVO. This phenomenon is altered in patients with DCM. Supported by ISCIII (Spain) and NIH 1 R21 HL108268-01 (US).

  4. Mitochondrial Cardiomyopathies

    PubMed Central

    El-Hattab, Ayman W.; Scaglia, Fernando

    2016-01-01

    Mitochondria are found in all nucleated human cells and perform various essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA), whereas more than 99% of them are encoded by nuclear DNA (nDNA). Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs for various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20–40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular non-compaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain complexes subunits and their assembly factors, mitochondrial transfer RNAs, ribosomal RNAs, ribosomal proteins, translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia. PMID:27504452

  5. Mitochondrial Cardiomyopathies.

    PubMed

    El-Hattab, Ayman W; Scaglia, Fernando

    2016-01-01

    Mitochondria are found in all nucleated human cells and perform various essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA), whereas more than 99% of them are encoded by nuclear DNA (nDNA). Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs for various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular non-compaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain complexes subunits and their assembly factors, mitochondrial transfer RNAs, ribosomal RNAs, ribosomal proteins, translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia. PMID:27504452

  6. [New echocardiographic para-apical technic for determining the size and thickness of the wall of the right ventricle in probands and patients with dilated cardiomyopathy].

    PubMed

    Dyczynski, J; Schweitzer, L

    1987-12-01

    To evaluate the right ventricular size and free wall thickness a new echocardiographic para-apical technique was developed. All cases were examined from the para-apical window in the extreme left lateral decubitus position, on a special mattress that allowed us to investigate the total apical region. The para-apical transducer position makes it possible to cut the right ventricle cross-sectionally in serial bread-loafing fashion from the apex to the base, like the left ventricle. In this way, using the M-mode technique, either diameters and/or right ventricular free wall thickness as well as shortening fraction could be estimated. To estimate the usefulness of the para-apical technique, a study was performed in 50 normal subjects as well as in 16 patients with dilated cardiomyopathy. In all patients, standard views and the new para-apical view were performed. In five cases, contrast echocardiography of the heart was performed to verify the right-heart anatomy. In five patients, computer-tomography of the heart was performed to see the position of the right-heart chambers in the chest and to evaluate the new para-apical ultrasound window. The standard values for the right ventricle in the control group were (in mean values): diastolic diameter, 28.61 +/- 3.19 mm; systolic diameter, 19.10 +/- 2.40 mm; free wall thickness, 4.46 +/- 1.06 mm and shortening fraction, 32.42% +/- 4.02%. The examined parameters in patients with dilated cardiomyopathy were: diastolic diameter, mean value 38.63 +/- 5.80 mm; systolic diameter, mean value 32.48 +/- 4.96 mm; free wall thickness, mean value 8.70 +/- 1.05 mm and shortening fraction, mean value 15.96 +/- 4.02%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3439250

  7. Mutations in the Voltage Sensors of Domains I and II of Nav1.5 that are Associated with Arrhythmias and Dilated Cardiomyopathy Generate Gating Pore Currents

    PubMed Central

    Moreau, Adrien; Gosselin-Badaroudine, Pascal; Boutjdir, Mohamed; Chahine, Mohamed

    2015-01-01

    Voltage gated sodium channels (Nav) are transmembrane proteins responsible for action potential initiation. Mutations mainly located in the voltage sensor domain (VSD) of Nav1.5, the cardiac sodium channel, have been associated with the development of arrhythmias combined with dilated cardiomyopathy. Gating pore currents have been observed with three unrelated mutations associated with similar clinical phenotypes. However, gating pores have never been associated with mutations outside the first domain of Nav1.5. The aim of this study was to explore the possibility that gating pore currents might be caused by the Nav1.5 R225P and R814W mutations (R3, S4 in DI and DII, respectively), which are associated with rhythm disturbances and dilated cardiomyopathy. Nav1.5 WT and mutant channels were transiently expressed in tsA201 cells. The biophysical properties of the alpha pore currents and the presence of gating pore currents were investigated using the patch-clamp technique. We confirmed the previously reported gain of function of the alpha pores of the mutant channels, which mainly consisted of increased window currents mostly caused by shifts in the voltage dependence of activation. We also observed gating pore currents associated with the R225P and R814W mutations. This novel permeation pathway was open under depolarized conditions and remained temporarily open at hyperpolarized potentials after depolarization periods. Gating pore currents could represent a molecular basis for the development of uncommon electrical abnormalities and changes in cardiac morphology. We propose that this biophysical defect be routinely evaluated in the case of Nav1.5 mutations on the VSD. PMID:26733869

  8. Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy

    PubMed Central

    2013-01-01

    Background In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. Results We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Conclusions Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities. PMID:23937664

  9. Antisense modulation of both exonic and intronic splicing motifs induces skipping of a DMD pseudo-exon responsible for x-linked dilated cardiomyopathy.

    PubMed

    Rimessi, Paola; Fabris, Marina; Bovolenta, Matteo; Bassi, Elena; Falzarano, Sofia; Gualandi, Francesca; Rapezzi, Claudio; Coccolo, Fabio; Perrone, Daniela; Medici, Alessandro; Ferlini, Alessandra

    2010-09-01

    Antisense-mediated exon skipping has proven to be efficacious for subsets of Duchenne muscular dystrophy mutations. This approach is based on targeting specific splicing motifs that interfere with the spliceosome assembly by steric hindrance. Proper exon recognition by the splicing machinery is thought to depend on exonic splicing enhancer sequences, often characterized by purine-rich stretches, representing potential targets for antisense-mediated exon skipping. We identified and functionally characterized two purine-rich regions located within dystrophin intron 11 and involved in splicing regulation of a pseudo-exon. A functional role for these sequences was suggested by a pure intronic DMD deletion causing X-linked dilated cardiomyopathy through the prevalent cardiac incorporation of the aberrant pseudo-exon, marked as Alu-exon, into the dystrophin transcript. The first splicing sequence is contained within the pseudo-exon, whereas the second is localized within its 3' intron. We demonstrated that the two sequences actually behave as splicing enhancers in cell-free splicing assays because their deletion strongly interferes with the pseudo-exon inclusion. Cell-free results were then confirmed in myogenic cells derived from the patient with X-linked dilated cardiomyopathy, by targeting the identified motifs with antisense molecules and obtaining a reduction in dystrophin pseudo-exon recognition. The splicing motifs identified could represent target sequences for a personalized molecular therapy in this particular DMD mutation. Our results demonstrated for the first time the role of intronic splicing sequences in antisense modulation with implications in exon skipping-mediated therapeutic approaches. PMID:20486769

  10. Myocardial Ca-sequestration failure and compensatory increase in Ca-ATPase with congestive cardiomyopathy: kinetic characterization by a homogenate microassay using real-time ratiometric indo-1 spectrofluorometry.

    PubMed

    O'Brien, P J; Shen, H; Weiler, J; Mirsalimi, M; Julian, R

    1991-03-27

    A novel, simple, rapid and reproducible microassay is used for kinetic analysis of Ca-sequestration by homogenates of myocardium of turkeys with furazolidone-induced congestive cardiomyopathy. The assay monitors Ca in real-time using dual-emission ratiometric spectrofluorometry and the Ca-indicator dye indo-1. Using this assay and isolated SR studies we make several novel findings regarding the mechanism of SR failure in furazolidone cardiomyopathy. Qualitative differences in Ca-sequestration were not detected between groups. However, compared to controls the furazolidone treatment resulted in: 1) 50% depression in maximal activities (1.54 +/- 0.36 vs 0.73 +/- 0.12 microM/sec); 2) 2-fold increases in post-sequestration concentrations of ionized Ca (79 +/- 23 vs 141 +/- 13 nmol Ca/L homogenate); 3) 2-fold increases in Ca half-life (415 vs 790 msec); and 4) 25% increased passive Ca-binding capacity of homogenates. The Ca-ATPase specific activity of isolated sarcoplasmic reticulum was 60% increased in congestive cardiomyopathy (543 +/- 140 vs 873 +/- 108 nmol ATP hydrolyzed/min/mg membrane protein) although membrane yield was 20% decreased (0.79 +/- 0.09 vs 0.63 +/- 0.03 mg/g heart). The increased ATPase and decreased Ca-uptake activities in combination with the occurrence of 36% cardiac hypertrophy and 19% decreased body weights resulted in estimates of the relative energy cost to the animal for myocardial Ca transport being 5.5-fold increased with cardiomyopathy (20.5 vs 111 nmol ATP hydrolyzed per microM decrease of sarcoplasmic free Ca/kg body weight). These data indicate that congestive cardiomyopathy is associated with markedly increased permeability of sarcoplasmic reticulum to Ca and compensatorily increased Ca-ATPase activity. Accelerated energy consumption due to the increased energy cost of Ca transport and increased time of myocyte activation are predicted to predispose the myocardium to fatigue and irreversible failure. PMID:1828861

  11. Pharmacological Modulation of Calcium Homeostasis in Familial Dilated Cardiomyopathy: An In Vitro Analysis From an RBM20 Patient-Derived iPSC Model.

    PubMed

    Wyles, S P; Hrstka, S C; Reyes, S; Terzic, A; Olson, T M; Nelson, T J

    2016-06-01

    For inherited cardiomyopathies, abnormal sensitivity to intracellular calcium (Ca(2+) ), incurred from genetic mutations, initiates subsequent molecular events leading to pathological remodeling. Here, we characterized the effect of β-adrenergic stress in familial dilated cardiomyopathy (DCM) using human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) from a patient with RBM20 DCM. Our findings suggest that β-adrenergic stimulation accelerated defective Ca(2+) homeostasis, apoptotic changes, and sarcomeric disarray in familial DCM hiPSC-CMs. Furthermore, pharmacological modulation of abnormal Ca(2+) handling by pretreatment with β-blocker, carvedilol, or Ca(2+) -channel blocker, verapamil, significantly decreased the area under curve, reduced percentage of disorganized cells, and decreased terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive apoptotic loci in familial DCM hiPSC-CMs after β-adrenergic stimulation. These translational data provide patient-based in vitro analysis of β-adrenergic stress in RBM20-deficient familial DCM hiPSC-CMs and evaluation of therapeutic interventions to modify heart disease progression, which may be personalized, but more importantly generalized in the clinic. PMID:27105042

  12. Gating pore currents are defects in common with two Nav1.5 mutations in patients with mixed arrhythmias and dilated cardiomyopathy

    PubMed Central

    Moreau, Adrien; Gosselin-Badaroudine, Pascal; Delemotte, Lucie; Klein, Michael L.

    2015-01-01

    The gating pore current, also called omega current, consists of a cation leak through the typically nonconductive voltage-sensor domain (VSD) of voltage-gated ion channels. Although the study of gating pore currents has refined our knowledge of the structure and the function of voltage-gated ion channels, their implication in cardiac disorders has not been established. Two Nav1.5 mutations (R222Q and R225W) located in the VSD are associated with atypical clinical phenotypes involving complex arrhythmias and dilated cardiomyopathy. Using the patch-clamp technique, in silico mutagenesis, and molecular dynamic simulations, we tested the hypothesis that these two mutations may generate gating pore currents, potentially accounting for their clinical phenotypes. Our findings suggest that the gating pore current generated by the R222Q and R225W mutations could constitute the underlying pathological mechanism that links Nav1.5 VSD mutations with human cardiac arrhythmias and dilatation of cardiac chambers. PMID:25624448

  13. Management of mucopolysaccharidosis type IH (Hurler's syndrome) presenting in infancy with severe dilated cardiomyopathy: a single institution's experience.

    PubMed

    Wiseman, Daniel H; Mercer, Jean; Tylee, Karen; Malaiya, Nilima; Bonney, Denise K; Jones, Simon A; Wraith, J Edmond; Wynn, Robert F

    2013-03-01

    Mucopolysaccharidosis type IH (MPSIH) is a lysosomal storage disorder whose untreated course involves progressive multisystem deterioration and death within the first decade of life. Allogeneic haematopoietic stem cell transplantation (HSCT) is an established treatment modality that improves functional outcome and long-term survival. Optimal outcome requires transplantation early in life and with myeloablative conditioning. Severe cardiomyopathy can be present at diagnosis and may seemingly preclude this approach. We performed a retrospective review of those cases transplanted in Manchester since 2000 that initially presented with established cardiomyopathy, with a view to identifying general management principles. Of 44 MPSIH children transplanted in this period, 6 had displayed moderate or severe cardiomyopathy at presentation; symptomatic cardiac failure was the predominant presenting feature in five of these. Echocardiographic and clinical improvement in cardiac function was observed with extended enzyme replacement therapy (ERT) in all cases, with recovery of fractional shortening to ≥25 % achieved in all patients before coming to transplant (after median 19 weeks ERT). All were transplanted successfully, with good functional and cardiologic outcomes. However, cyclophosphamide conditioning was implicated in acute post-transplant cardiac decompensation in several cases. Our experiences highlight three important messages: (1) A diagnosis of MPSIH should be considered in any infant presenting with unexplained severe cardiac failure; (2) ERT pre-transplant can improve cardiac function sufficiently to permit safe HSCT using myeloablative conditioning; and (3) High dose cyclophosphamide should be avoided in conditioning these patients. PMID:22718273

  14. [Peripartum cardiomyopathy].

    PubMed

    Fennira, S; Demiraj, A; Khouaja, A; Boujnah, M R

    2006-10-01

    Peripartum cardiomyopathy is a rare and under recognized form of dilated cardiomyopathy, defined as a heart failure in the last month of pregnancy or in the first five months post-partum with absence of determinable cause for cardiac failure and absence of demonstrable heart disease. The incidence of peripartum cardiomyopathy ranges from 1 in 1300 to 1 in 15,000 pregnancy. Advanced maternal age, multiparity, twin births, preeclampsia and black race are known risk factors. The etiology of peripartum cardiomyopathy remains unknown but viral, autoimmune or idiopathic myocarditis are highly suggested. The clinical presentation on patients with peripartum cardiomyopathy is similar to that of patients with systolic heart failure. The treatment is based on drugs for sympyomatic control. Studies in graeter populations are need to determine the role of immunosupressive treatment. About half patients of peripartum cardiomyopathy recover. The left ventricular ejection fraction and the left ventricular end-diastolic diameter are statistically significant prognostic factors. The risk of developing peripartum cardiomyopathy in subsequent pregnancies remains high. The place of dobutamine stress test in counseling the patients who desire pregnancy must be more studied. PMID:17078264

  15. 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.

  16. The usefulness of age and sex to predict all-cause mortality in patients with dilated cardiomyopathy: a single-center cohort study

    PubMed Central

    Li, Xiaoping; Cai, Chi; Luo, Rong; Jiang, Rongjian; Zeng, Jie; Tang, Yijia; Chen, Yang; Fu, Michael; He, Tao; Hua, Wei

    2015-01-01

    Objective Recent studies have shown that sex and age are associated with outcomes in patients with cardiomyopathy. The purpose of this study was to determine the all-cause mortality of dilated cardiomyopathy (DCM) by age and sex. Methods and results The patients were divided into non-elderly (age <60 years, n=811) and elderly (age ≥60 years, n=331) groups. No difference in the all-cause mortality rate was observed between elderly and non-elderly patients (27.2% vs 22.2%, log-rank χ2=2.604, P=0.107). Furthermore, no significant difference in mortality was observed between the male and female patients (23.3% vs 24.5%, log-rank χ2=0.707, P=0.400). However, subgroup analysis revealed that elderly male patients exhibited a higher mortality rate than non-elderly male patients (29.4% vs 21.3%, log-rank χ2=5.898, P=0.015), while no difference was observed between the elderly female patients and non-elderly female patients. In the Cox analysis, neither age nor sex was a significant independent predictor of all-cause mortality in patients with DCM. Conclusion In conclusion, no significant difference in mortality between male and female patients or between the elderly and non-elderly patients was observed. Only among males was a difference in mortality observed; elderly male patients experienced greater mortality than that of non-elderly male patients. No effect of age or sex on all-cause mortality was observed in patients with DCM. PMID:26396507

  17. Activated nuclear transcription factor {kappa}B in patients with myocarditis and dilated cardiomyopathy-relation to inflammation and cardiac function

    SciTech Connect

    Alter, Peter . E-mail: palter@med.uni-marburg.de; Rupp, Heinz; Maisch, Bernhard

    2006-01-06

    Objectives and background: Myocarditis is caused by various agents and autoimmune processes. It is unknown whether viral genome persistence represents inactive remnants of previous infections or whether it is attributed to ongoing adverse processes. The latter also applies to the course of autoimmune myocarditis. One principal candidate for an adverse remodeling is nuclear factor-{kappa}B (NF{kappa}B). Methods: A total of 93 patients with suspected myocarditis/cardiomyopathy was examined. Hemodynamics were assessed by echocardiography as well as right and left heart catheterization. Endomyocardial biopsies were taken from the left ventricle. Biopsies were examined by immunohistochemistry and PCR for viral genomes. Selective immunostaining of activated NF{kappa}B was performed. Results: NF{kappa}B was increased in patients with myocarditis when compared with controls (11.1 {+-} 7.1% vs. 5.0 {+-} 5.3%, P < 0.005) whereas dilated cardiomyopathy showed no significant increase. Patients with myocarditis and preserved left ventricular function exhibited increased activated NF{kappa}B when compared with reduced function (r {sup 2} = 0.72, P < 0.001). In parallel, inverse correlation of NF{kappa}B and left ventricular enddiasstolic volume was found (r {sup 2} = 0.43, P < 0.02). Increased activated NF{kappa}B was found in adenovirus persistence when compared with controls (P = 0.001). Only a trend of increased NF{kappa}B activation was seen in cytomegalovirus persistence. Parvovirus B19 persistence did not affect NF{kappa}B activation. Conclusions: Increased activation of NF{kappa}B is related to inflammatory processes in myocarditis. Since activated NF{kappa}B correlates with left ventricular function, it could be assumed that NF{kappa}B activation occurs at early stages of inflammation. Potentially, NF{kappa}B could inhibit loss of cardiomyocytes by apoptosis and protect from cardiac dilation. Since NF{kappa}B is a crucial key transcription factor of inflammation, its

  18. Pimobendan and its use in treating canine congestive heart failure.

    PubMed

    Bowles, Danielle; Fry, Darren

    2011-11-01

    Pimobendan, a calcium sensitizer and phosphodiesterase III inhibitor, has positive inotropic and vasodilatory properties. Its use in patients with naturally occurring congestive heart failure (CHF) has been studied in a number of blinded, randomized, multicenter clinical trials. It has been shown to improve quality of life, reduce heart insufficiency scores, and increase median survival times for patients with CHF due to dilated cardiomyopathy and myxomatous valvular disease. Although most studies have reported positive findings, some potential adverse effects have also been described. Studies are under way to further evaluate the effects of this novel positive inotrope and vasodilator in canine cardiac disease. PMID:22101450

  19. Use of RNA-seq to identify cardiac genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy.

    PubMed

    Friedenberg, Steven G; Chdid, Lhoucine; Keene, Bruce; Sherry, Barbara; Motsinger-Reif, Alison; Meurs, Kathryn M

    2016-07-01

    OBJECTIVE To identify cardiac tissue genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy (DCM). ANIMALS 8 dogs with and 5 dogs without DCM. PROCEDURES Following euthanasia, samples of left ventricular myocardium were collected from each dog. Total RNA was extracted from tissue samples, and RNA sequencing was performed on each sample. Samples from dogs with and without DCM were grouped to identify genes that were differentially regulated between the 2 populations. Overrepresentation analysis was performed on upregulated and downregulated gene sets to identify altered molecular pathways in dogs with DCM. RESULTS Genes involved in cellular energy metabolism, especially metabolism of carbohydrates and fats, were significantly downregulated in dogs with DCM. Expression of cardiac structural proteins was also altered in affected dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that RNA sequencing may provide important insights into the pathogenesis of DCM in dogs and highlight pathways that should be explored to identify causative mutations and develop novel therapeutic interventions. PMID:27347821

  20. [Combined therapy with weight loss and amiodarone improved cardiac function in a patient with idiopathic dilated cardiomyopathy complicated with severe obesity: a case report].

    PubMed

    Tanaka, Haruki; Kawano, Shunichi; Kozai, Toshiyuki; Urabe, Yoshitoshi

    2007-08-01

    Obesity is associated with an increased risk of development of chronic heart failure, but recent epidemiological studies indicate that a higher body mass index (BMI) is associated with a better survival rate. This is described as the 'obesity paradox' or 'reverse epidemiology'. A 42-year-old male was admitted because of recurrent episodes of decompensated heart failure, and the diagnosis was idiopathic dilated cardiomyopathy complicated with severe obesity (BMI 46.0), nonsustained ventricular tachycardia, and central type sleep apnea syndrome. Combined therapy with weight loss (BMI 46.0 to 30.8) and amiodarone (200 mg/day) was instituted in addition to the previous regimen including angiotensin converting enzyme inhibitor, beta blocker, diuretics and pimobendan, improved cardiac function, exercise tolerance, and cardiac sympathetic nerve activity evaluated by cardiac 123I-metaiodobenzylguanidine scintigraphy. Furthermore, we succeeded in uptitration of carvedilol(5 to 10mg/day). This case highlights the possible beneficial effect of weight loss in patients with chronic heart failure complicated with obesity, and the resultant improvement of cardiac sympathetic nerve activity suggests that weight loss may partially mimic beta blocker effects in patients with systolic heart failure. PMID:17802698

  1. Early Progressive Dilated Cardiomyopathy in a Family with Becker Muscular Dystrophy Related to a Novel Frameshift Mutation in the Dystrophin Gene Exon 27

    PubMed Central

    Tsuda, Takeshi; Fitzgerald, Kristi; Scavena, Mena; Gidding, Samuel; Cox, Mary O.; Marks, Harold; Flanigan, Kevin M.; Moore, Steven A.

    2014-01-01

    We report a family in which two male siblings with Becker muscular dystrophy (BMD) developed severe dilated cardiomyopathy (DCM) and progressive heart failure (HF) at age 11; one died at age 14 years while awaiting heart transplant and the other underwent left ventricular assist device (LVAD) implantation at the same age. Genetic analysis of one sibling showed a novel frameshift mutation in exon 27 of Duchenne muscular dystrophy (DMD) gene (c.3779_3785delCTTTGGAins GG), in which 7 base pairs are deleted and two are inserted. While this predicts an amino acid substitution and premature termination (p.Thr1260Argfs*8), muscle biopsy dystrophin immunostaining instead indicates that the mutation is more likely to alter splicing. Despite relatively preserved skeletal muscular performance, both siblings developed progressive heart failure secondary to early onset DCM. In addition, their 7 year old nephew with delayed gross motor development, mild proximal muscle weakness, and markedly elevated serum creatine kinase (CK) level (> 13,000 IU/L) at 16 months was recently demonstrated to have the familial DMD mutation. Here we report a novel genotype of BMD with early onset DCM and progressive lethal heart failure during early adolescence. PMID:25537791

  2. A Mitochondrial DNA A8701G Mutation Associated with Maternally Inherited Hypertension and Dilated Cardiomyopathy in a Chinese Pedigree of a Consanguineous Marriage

    PubMed Central

    Zhu, Ye; Gu, Xiang; Xu, Chao

    2016-01-01

    Background: Cardiovascular diseases, including dilated cardiomyopathy (DCM) and hypertension, are the leading cause of death worldwide. The role of mitochondrial DNA (mtDNA) in the pathogenesis of these diseases has not been completely clarified. In this study, we evaluate whether A8701G mutation is associated with maternally inherited hypertension and DCM in a Chinese pedigree of a consanguineous marriage. Methods: Fourteen subjects in a three-generation Han Chinese family with hypertension and DCM, in which consanguineous marriage was present in the parental generation, were interviewed. We divided all the family members into case (7 maternal members) and control group (7 nonmaternal members) for comparison. Clinical evaluations and sequence analysis of mtDNA were obtained from all participants. Frequency differences between maternal and nonmaternal members were tested to locate the disease-associated mutations. Results: The majority of the family members presented with a maternal inheritance of hypertension and DCM. Sequence analysis of mtDNA in this pedigree identified eight mtDNA mutations. Among the mutations identified, there was only one significant mutation: A8701G (P = 0.005), which is a homoplasmic mitochondrial missense mutation in all the matrilineal relatives. There was no clear evidence for any synergistic effects between A8701G and other mutations. Conclusions: A8701G mutation may act as an inherited risk factor for the matrilineal transmission of hypertension and DCM in conjunction with genetic disorders caused by consanguineous marriage. PMID:26831225

  3. Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study

    NASA Technical Reports Server (NTRS)

    Hohnloser, Stefan H.; Klingenheben, Thomas; Bloomfield, Daniel; Dabbous, Omar; Cohen, Richard J.

    2003-01-01

    OBJECTIVES: This study was designed to evaluate the ability of microvolt-level T-wave alternans (MTWA) to identify prospectively patients with idiopathic dilated cardiomyopathy (DCM) at risk of ventricular tachyarrhythmic events and to compare its predictive accuracy with that of conventional risk stratifiers. BACKGROUND: Patients with DCM are at increased risk of sudden death from ventricular tachyarrhythmias. At present, there are no established methods of assessing this risk. METHODS: A total of 137 patients with DCM underwent risk stratification through assessment of MTWA, left ventricular ejection fraction, baroreflex sensitivity (BRS), heart rate variability, presence of nonsustained ventricular tachycardia (VT), signal-averaged electrocardiogram, and presence of intraventricular conduction defect. The study end point was either sudden death, resuscitated ventricular fibrillation, or documented hemodynamically unstable VT. RESULTS: During an average follow-up of 14 +/- 6 months, MTWA and BRS were significant univariate predictors of ventricular tachyarrhythmic events (p < 0.035 and p < 0.015, respectively). Multivariate Cox regression analysis revealed that only MTWA was a significant predictor. CONCLUSIONS: Microvolt-level T-wave alternans is a powerful independent predictor of ventricular tachyarrhythmic events in patients with DCM.

  4. [Peripartum cardiomyopathy].

    PubMed

    Mouquet, Frédéric; Bouabdallaoui, Nadia

    2015-01-01

    The peripartum cardiomyopathy is a rare form of dilated cardiomyopathy resulting from alteration of angiogenesis toward the end of pregnancy. The diagnosis is based on the association of clinical heart failure and systolic dysfunction assessed by echocardiography or magnetic resonance imaging. Diagnoses to rule out are myocardial infarction, amniotic liquid embolism, myocarditis, inherited cardiomyopathy, and history of treatment by anthracycline. Risk factors are advance maternal age (>30), multiparity, twin pregnancy, African origin, obesity, preeclampsia, gestational hypertension, and prolonged tocolytic therapy. Treatment of acute phase is identical to usual treatment of acute systolic heart failure. After delivery, VKA treatment should be discussed in case of systolic function <25% because of higher risk of thrombus. A specific treatment by bromocriptine can be initiated on a case-by-case basis. Complete recovery of systolic function is observed in 50% of cases. The mortality risk is low. Subsequent pregnancy should be discouraged, especially if systolic function did not recover. PMID:26160284

  5. Alcohol use and congestive heart failure: incidence, importance, and approaches to improved history taking.

    PubMed

    Skotzko, Christine E; Vrinceanu, Alina; Krueger, Lynnette; Freudenberger, Ronald

    2009-03-01

    Alcohol use, abuse, and dependence have the potential to result in alcoholic cardiomyopathy (ACM). This distinct form of congestive heart failure (CHF) is responsible for 21-36% of all cases of nonischemic dilated cardiomyopathy in Western society. Without complete abstinence, the 4-year mortality for ACM approaches 50%. Therefore, accurate and detailed assessment of alcohol use in congestive heart failure is essential. The prevalence of problematic alcohol use is unrecognized by many clinicians. Clinical assessment of alcohol intake is often reduced to a simple question such as, "Do you drink?" Denial and minimization are hallmarks of alcohol abuse, with many individuals underreporting their use of alcohol. Clinicians can overcome these hurdles by implementing practical history taking measures to improve the accuracy of self-reported alcohol use. The data regarding the dangers of ongoing alcohol use in individuals with ACM make attempts to engage individuals in treatment to support abstinence essential. Suggestions for detailed and accurate assessment are discussed. PMID:18034302

  6. The number of regulatory T cells correlates with hemodynamic improvement in patients with inflammatory dilated cardiomyopathy after immunoadsorption therapy.

    PubMed

    Bulut, D; Creutzenberg, G; Mügge, A

    2013-01-01

    Inflammatory DCM (iDCM) may be related to autoimmune processes. An immunoadsorption (IA) has been reported to improve cardiac hemodynamics. The benefit of IA is probably related to the removal of autoantibodies. A recent study suggests additional effects of IA on the T cell-mediated immune reactions, especially on regulatory T cells (Tregs). In this prospective study, the correlation between the level of Tregs and improvement of myocardial contractility in response to IA in patients with iDCM was investigated. Patients (n = 18) with iDCM, reduced left ventricular (LV) ejection fraction (<35%), were enrolled for IA. Before and 6 months after IA, LV systolic function was assessed by echocardiography, and blood levels of Tregs were quantified by FACS analysis. Patients (n = 12) with chronic ischaemic heart failure and comparable reduced LV-EF served as controls. IA improved LV-EF in 12 of 18 patients at 6-month follow-up. These patients were classified as 'IA responder'. In 6 patients, LV-EF remained unchanged. At baseline, IA responder and non-responder subgroups showed similar values for C-reactive protein, white blood cells, lymphocytes and T helper cells, but they differ for the number of circulating Tregs (responder: 2.32 ± 1.38% versus non-responder: 4.86 ± 0.28%; P < 0.01). Tregs increased significantly in the IA responders, but remained unchanged in the IA non-responders. In patients with ischaemic cardiomyopathy, none of these values changed over time. A low level of Tregs in patients with chronic iDCM may characterize a subset of patients who do best respond to IA therapy. PMID:22998220

  7. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    SciTech Connect

    Al-Saaidi, Rasha; Rasmussen, Torsten B.; Palmfeldt, Johan; Nissen, Peter H.; Beqqali, Abdelaziz; Hansen, Jakob; Pinto, Yigal M.; Boesen, Thomas; Mogensen, Jens; Bross, Peter

    2013-11-15

    Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems. The LMNA gene generates two major transcripts encoding the nuclear lamina major components lamin A and lamin C by alternative splicing. Both haploinsuffiency and dominant negative effects have been proposed as disease mechanism for premature termination codon (PTC) mutations in LMNA. These mechanisms however are still not clearly established. In this study, we used a representative LMNA nonsense mutation, p.Arg321Ter, to shed light on the molecular disease mechanisms. Cultured fibroblasts from three DCM patients carrying this mutation were analyzed. Quantitative reverse transcriptase PCR and sequencing of these PCR products indicated that transcripts from the mutant allele were degraded by the nonsense-mediated mRNA decay (NMD) mechanism. The fact that no truncated mutant protein was detectable in western blot (WB) analysis strengthens the notion that the mutant transcript is efficiently degraded. Furthermore, WB analysis showed that the expression of lamin C protein was reduced by the expected approximately 50%. Clearly decreased lamin A and lamin C levels were also observed by immunofluorescence microscopy analysis. However, results from both WB and nano-liquid chromatography/mass spectrometry demonstrated that the levels of lamin A protein were more reduced suggesting an effect on expression of lamin A from the wild type allele. PCR analysis of the ratio of lamin A to lamin C transcripts showed unchanged relative amounts of lamin A transcript suggesting that the effect on the wild type allele was operative at the protein level. Immunofluorescence microscopy analysis showed no abnormal nuclear morphology of patient fibroblast cells. Based on these data, we propose that

  8. Symbolic dynamics to discriminate healthy and ischaemic dilated cardiomyopathy populations: an application to the variability of heart period and QT interval

    PubMed Central

    Valencia, José Fernando; Vallverdu, Montserrat; Rivero, Isidre; Voss, Andreas; de Luna, Antonio Bayes; Porta, Alberto; Caminal, Pere

    2015-01-01

    Myocardial ischaemia is hypothesized to stimulate the cardiac sympathetic excitatory afferents and, therefore, the spontaneous changes of heart period (approximated as the RR interval), and the QT interval in ischaemic dilated cardiomyopathy (IDC) patients might reflect this sympathetic activation. Symbolic analysis is a nonlinear and powerful tool for the extraction and classification of patterns in time-series analysis, which implies a transformation of the original series into symbols and the construction of patterns with the symbols. The aim of this work was to investigate whether symbolic transformations of RR and QT cardiac series can provide a better separation between IDC patients and healthy control (HC) subjects compared with traditional linear measures. The variability of these cardiac series was studied during daytime and night-time periods and also during the complete 24 h recording over windows of short data sequences of approximately 5 min. The IDC group was characterized by an increase in the occurrence rate of patterns without variations (0 V%) and a reduction in the occurrence rate of patterns with one variation (1 V%) and two variations (2 V%). Concerning the RR variability during the daytime, the highest number of patterns had 0 V%, whereas the rates of 1 V% and 2 V% were lower. During the night, 1 V% and 2 V% increased at the expense of diminishing 0 V%. Patterns with and without variations between consecutive symbols were able to increase the separation between the IDC and HC groups, allowing accuracies higher than 80%. With regard to entropy measures, an increase in RR regularity was associated with cardiac disease described by accuracy >70% in the RR series and by accuracy >60% in the QTc series. These results could be associated with an increase in the sympathetic tone in IDC patients. PMID:25548268

  9. mTOR inactivation in myocardium from infant mice rapidly leads to dilated cardiomyopathy due to translation defects and p53/JNK-mediated apoptosis.

    PubMed

    Mazelin, Laetitia; Panthu, Baptiste; Nicot, Anne-Sophie; Belotti, Edwige; Tintignac, Lionel; Teixeira, Geoffrey; Zhang, Qing; Risson, Valérie; Baas, Dominique; Delaune, Emilie; Derumeaux, Geneviève; Taillandier, Daniel; Ohlmann, Théophile; Ovize, Michel; Gangloff, Yann-Gaël; Schaeffer, Laurent

    2016-08-01

    Mechanistic target of rapamycin (mTOR) is a central regulator of cell growth, proliferation, survival and metabolism, as part of mTOR complex 1 (mTORC1) and mTORC2. While partial inhibition of mTORC1 using rapamycin was shown to be cardioprotective, genetic studies in mouse models revealed that mTOR is essential for embryonic heart development and cardiac function in adults. However, the physiological role of mTOR during postnatal cardiac maturation is not fully elucidated. We have therefore generated a mouse model in which cardiac mTOR was inactivated at an early postnatal stage. Mutant mTORcmKO mice rapidly developed a dilated cardiomyopathy associated with cardiomyocyte growth defects, apoptosis and fibrosis, and died during their third week. Here, we show that reduced cardiomyocyte growth results from impaired protein translation efficiency through both 4E-BP1-dependent and -independent mechanisms. In addition, infant mTORcmKO hearts displayed markedly increased apoptosis linked to stretch-induced ANKRD1 (Ankyrin repeat-domain containing protein 1) up-regulation, JNK kinase activation and p53 accumulation. Pharmacological inhibition of p53 with pifithrin-α attenuated caspase-3 activation. Cardiomyocyte death did not result from activation of the MST1/Hippo pro-apoptotic pathway as reported in adult rictor/mTORC2 KO hearts. As well, mTORcmKO hearts showed a strong downregulation of myoglobin content, thereby leading to a hypoxic environment. Nevertheless, they lacked a HIF1α-mediated adaptive response, as mTOR is required for hypoxia-induced HIF-1α activation. Altogether, our results demonstrate that mTOR is critically required for cardiomyocyte growth, viability and oxygen supply in early postnatal myocardium and provide insight into the molecular mechanisms involved in apoptosis of mTOR-depleted cardiomyocytes. PMID:27133769

  10. P2×7 purinergic signaling in dilated cardiomyopathy induced by auto-immunity against muscarinic M2 receptors: autoantibody levels, heart functionality and cytokine expression

    PubMed Central

    Martinez, Camila Guerra; Zamith-Miranda, Daniel; da Silva, Marcia Gracindo; Ribeiro, Karla Consort; Brandão, Izaíra Trincani; Silva, Celio Lopes; Diaz, Bruno Lourenço; Bellio, Maria; Persechini, Pedro Muanis; Kurtenbach, Eleonora

    2015-01-01

    Autoantibodies against the M2 receptors (M2AChR) have been associated with Dilated Cardiomyopathy (DCM). In the heart, P2×7 receptors influence electrical conduction, coronary circulation and response to ischemia. They can also trigger pro-inflammatory responses and the development of neurological, cardiac and renal disorders. Here, P2×7−/− mice displayed an increased heart rate and ST segment depression, but similar exercise performance when compared to wild type (WT) animals. After immunization with plasmid containing M2AChR cDNA sequence, WT mice produced anti-M2AChR antibodies, while P2×7−/− mice showed an attenuated production. Despite this, WT and P2×7−/− showed left ventricle cavity enlargement and decreased exercise tolerance. Transfer of serum from M2AChR WT immunized mice to näive recipients led to an alteration in heart shape. P2×7−/− mice displayed a significant increase in the frequency of spleen regulatory T cells population, which is mainly composed by the FoxP3+CD25− subset. M2AChR WT immunized mice showed an increase in IL-1β, IFNγ and IL-17 levels in the heart, while P2×7−/− group produced lower amounts of IL-1β and IL-17 and higher amounts of IFNγ. These results pointed to previously unnoticed roles of P2×7 in cardiovascular and immune systems, and underscored the participation of IL-17 and IFNγ in the progress of autoimmune DCM. PMID:26592184

  11. Does pretreatment of bone marrow mesenchymal stem cells with 5-azacytidine or double intravenous infusion improve their therapeutic potential for dilated cardiomyopathy?

    PubMed Central

    Yang, Sirui; Piao, Jinhua; Jin, Lianhua; Zhou, Yan

    2013-01-01

    Background This study was designed to investigate whether pretreatment of bone marrow mesenchymal stem cells (BMSCs) with 5-azacytidine (5-aza) or double intravenous infusion could enhance their therapeutic potential for dilated cardiomyopathy (DCM). Material/Methods BMSCs were cultured for 2 weeks in the presence or absence of 5-aza and DCM serum. The cultured BMSCs (Groups 1 and 2), 5-aza-induced BMSCs (Groups 3 and 4), and medium alone (model control) were transplanted into 80 female Wistar rats by intravenous tail vein injection. Double infusion of BMSCs with 1-day time-interval was carried out in Groups 2 and 4. Postmortem histological analysis and evaluation of heart function were performed at 4 weeks post-transplantation. Results Some transplanted BMSCs engrafted into myocardial tissue and were positive for cardiac marker troponin T. The hearts containing transplanted BMSCs secreted a larger amount of vascular endothelial growth factor. Cardiac function parameters and serum level of brain natriuretic peptide (BNP) did not differ among Groups 1, 3, and the model control. As compared with model control, BMSC transplantation in Groups 2 and 4 significantly decreased the serum level of BNP and improved cardiac contractile function, as evidenced by reduced left ventricular end-diastolic and end-systolic diameter, elevated ejection fraction, and fractional shortening. Conclusions BMSC transplantation is a promising strategy for the treatment of DCM. Pretreatment of BMSCs with 5-aza and DCM serum does not enhance their therapeutic efficacy, and the double intravenous BMSC infusion method is superior to single infusion for preserving cardiac contractile function in a rat model of DCM. PMID:23314418

  12. PLEKHM2 mutation leads to abnormal localization of lysosomes, impaired autophagy flux and associates with recessive dilated cardiomyopathy and left ventricular noncompaction.

    PubMed

    Muhammad, Emad; Levitas, Aviva; Singh, Sonia R; Braiman, Alex; Ofir, Rivka; Etzion, Sharon; Sheffield, Val C; Etzion, Yoram; Carrier, Lucie; Parvari, Ruti

    2015-12-20

    Gene mutations, mostly segregating with a dominant mode of inheritance, are important causes of dilated cardiomyopathy (DCM), a disease characterized by enlarged ventricular dimensions, impaired cardiac function, heart failure and high risk of death. Another myocardial abnormality often linked to gene mutations is left ventricular noncompaction (LVNC) characterized by a typical diffuse spongy appearance of the left ventricle. Here, we describe a large Bedouin family presenting with a severe recessive DCM and LVNC. Homozygosity mapping and exome sequencing identified a single gene variant that segregated as expected and was neither reported in databases nor in Bedouin population controls. The PLEKHM2 cDNA2156_2157delAG variant causes the frameshift p.Lys645AlafsTer12 and/or the skipping of exon 11 that results in deletion of 30 highly conserved amino acids. PLEKHM2 is known to interact with several Rabs and with kinesin-1, affecting endosomal trafficking. Accordingly, patients' primary fibroblasts exhibited abnormal subcellular distribution of endosomes marked by Rab5, Rab7 and Rab9, as well as the Golgi apparatus. In addition, lysosomes appeared to be concentrated in the perinuclear region, and autophagy flux was impaired. Transfection of wild-type PLEKHM2 cDNA into patient's fibroblasts corrected the subcellular distribution of the lysosomes, supporting the causal effect of PLEKHM2 mutation. PLEKHM2 joins LAMP-2 and BAG3 as a disease gene altering autophagy resulting in an isolated cardiac phenotype. The association of PLEKHM2 mutation with DCM and LVNC supports the importance of autophagy for normal cardiac function. PMID:26464484

  13. The functional effect of dilated cardiomyopathy mutation (R144W) in mouse cardiac troponin T is differently affected by α- and β-myosin heavy chain isoforms

    PubMed Central

    Gollapudi, Sampath K.; Tardiff, Jil C.

    2015-01-01

    Given the differential impact of α- and β-myosin heavy chain (MHC) isoforms on how troponin T (TnT) modulates contractile dynamics, we hypothesized that the effects of dilated cardiomyopathy (DCM) mutations in TnT would be altered differently by α- and β-MHC. We characterized dynamic contractile features of normal (α-MHC) and transgenic (β-MHC) mouse cardiac muscle fibers reconstituted with a mouse TnT analog (TnTR144W) of the human DCM R141W mutation. TnTR144W did not alter maximal tension but attenuated myofilament Ca2+ sensitivity (pCa50) to a similar extent in α- and β-MHC fibers. TnTR144W attenuated the speed of cross-bridge (XB) distortion dynamics (c) by 24% and the speed of XB recruitment dynamics (b) by 17% in α-MHC fibers; however, both b and c remained unaltered in β-MHC fibers. Likewise, TnTR144W attenuated the rates of XB detachment (g) and tension redevelopment (ktr) only in α-MHC fibers. TnTR144W also decreased the impact of strained XBs on the recruitment of new XBs (γ) by 30% only in α-MHC fibers. Because c, b, g, ktr, and γ are strongly influenced by thin filament-based cooperative mechanisms, we conclude that the TnTR144W- and β-MHC-mediated changes in the thin filament interact to produce a less severe functional phenotype, compared with that brought about by TnTR144W and α-MHC. These observations provide a basis for lower mortality rates of humans (β-MHC) harboring the TnTR141W mutant compared with transgenic mouse studies. Our findings strongly suggest that some caution is necessary when extrapolating data from transgenic mouse studies to human hearts. PMID:25681424

  14. Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy

    SciTech Connect

    He, Shu-Lan; Tan, Wu-Hong; Zhang, Zeng-Tie; Zhang, Feng; Qu, Cheng-Juan; Lei, Yan-Xia; Zhu, Yan-He; Yu, Han-Jie; Xiang, You-Zhang; and others

    2013-10-15

    Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios≥2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD. Highlights: • Thirty-four up-regulated genes were detected in KD versus health controls. • Forty pathways and four networks were detected in KD. • PGC-1alpha regulated energy metabolism and anti-apoptosis in KD.

  15. Cirrhotic cardiomyopathy.

    PubMed

    Milani, A; Zaccaria, R; Bombardieri, G; Gasbarrini, A; Pola, P

    2007-06-01

    Decompensated liver cirrhosis is characterized by a peripheral vasodilation with a low-resistance hyperdynamic circulation. The sustained increase of cardiac work load associated with such a condition may result in an inconstant and often subclinical series of heart abnormalities, constituting a new clinical entity known as "cirrhotic cardiomyopathy". Cirrhotic cardiomyopathy is variably associated with baseline increase in cardiac output, defective myocardial contractility and lowered systo-diastolic response to inotropic and chronotropic stimuli, down-regulated beta-adrenergic function, slight histo-morphological changes, and impaired electric "recovery" ability of ventricular myocardium. Cirrhotic cardiomyopathy is usually clinically latent or mild, likely because the peripheral vasodilation significantly reduces the left ventricle after-load, thus actually "auto-treating" the patient and masking any severe manifestation of heart failure. In cirrhotic patients, the presence of cirrhotic cardiomyopathy may become unmasked and clinically evident by certain treatment interventions that increase the effective blood volume and cardiac pre-load, including surgical or transjugular intrahepatic porto-systemic shunts, peritoneo-venous shunts (LeVeen) and orthotopic liver transplantation. Under these circumstances, an often transient overt congestive heart failure may develop, with increased cardiac output as well as right atrial, pulmonary artery and capillary wedge pressures. PMID:17383244

  16. Alcoholic cardiomyopathy

    PubMed Central

    Guzzo-Merello, Gonzalo; Cobo-Marcos, Marta; Gallego-Delgado, Maria; Garcia-Pavia, Pablo

    2014-01-01

    Alcohol is the most frequently consumed toxic substance in the world. Low to moderate daily intake of alcohol has been shown to have beneficial effects on the cardiovascular system. In contrast, exposure to high levels of alcohol for a long period could lead to progressive cardiac dysfunction and heart failure. Cardiac dysfunction associated with chronic and excessive alcohol intake is a specific cardiac disease known as alcoholic cardiomyopathy (ACM). In spite of its clinical importance, data on ACM and how alcohol damages the heart are limited. In this review, we evaluate available evidence linking excessive alcohol consumption with heart failure and dilated cardiomyopathy. Additionally, we discuss the clinical presentation, prognosis and treatment of ACM. PMID:25228956

  17. Infiltrative Cardiomyopathies

    PubMed Central

    Bejar, David; Colombo, Paolo C; Latif, Farhana; Yuzefpolskaya, Melana

    2015-01-01

    Infiltrative cardiomyopathies can result from a wide spectrum of both inherited and acquired conditions with varying systemic manifestations. They portend an adverse prognosis, with only a few exceptions (ie, glycogen storage disease), where early diagnosis can result in potentially curative treatment. The extent of cardiac abnormalities varies based on the degree of infiltration and results in increased ventricular wall thickness, chamber dilatation, and disruption of the conduction system. These changes often lead to the development of heart failure, atrioventricular (AV) block, and ventricular arrhythmia. Because these diseases are relatively rare, a high degree of clinical suspicion is important for diagnosis. Electrocardiography and echocardiography are helpful, but advanced techniques including cardiac magnetic resonance (CMR) and nuclear imaging are increasingly preferred. Treatment is dependent on the etiology and extent of the disease and involves medications, device therapy, and, in some cases, organ transplantation. Cardiac amyloid is the archetype of the infiltrative cardiomyopathies and is discussed in great detail in this review. PMID:26244036

  18. The Dilated Cardiomyopathy-Causing Mutation ACTC E361G in Cardiac Muscle Myofibrils Specifically Abolishes Modulation of Ca2+ Regulation by Phosphorylation of Troponin I

    PubMed Central

    Vikhorev, Petr G.; Song, Weihua; Wilkinson, Ross; Copeland, O’Neal; Messer, Andrew E.; Ferenczi, Michael A.; Marston, Steven B.

    2014-01-01

    Phosphorylation of troponin I by protein kinase A (PKA) reduces Ca2+ sensitivity and increases the rate of Ca2+ release from troponin C and the rate of relaxation in cardiac muscle. In vitro experiments indicate that mutations that cause dilated cardiomyopathy (DCM) uncouple this modulation, but this has not been demonstrated in an intact contractile system. Using a Ca2+-jump protocol, we measured the effect of the DCM-causing mutation ACTC E361G on the equilibrium and kinetic parameters of Ca2+ regulation of contractility in single transgenic mouse heart myofibrils. We used propranolol treatment of mice to reduce the level of troponin I and myosin binding protein C (MyBP-C) phosphorylation in their hearts before isolating the myofibrils. In nontransgenic mouse myofibrils, the Ca2+ sensitivity of force was increased, the fast relaxation phase rate constant, kREL, was reduced, and the length of the slow linear phase, tLIN, was increased when the troponin I phosphorylation level was reduced from 1.02 to 0.3 molPi/TnI (EC50 P/unP = 1.8 ± 0.2, p < 0.001). Native myofibrils from ACTC E361G transgenic mice had a 2.4-fold higher Ca2+ sensitivity than nontransgenic mouse myofibrils. Strikingly, the Ca2+ sensitivity and relaxation parameters of ACTC E361G myofibrils did not depend on the troponin I phosphorylation level (EC50 P/unP = 0.88 ± 0.17, p = 0.39). Nevertheless, modulation of the Ca2+ sensitivity of ACTC E361G myofibrils by sarcomere length or EMD57033 was indistinguishable from that of nontransgenic myofibrils. Overall, EC50 measured in different conditions varied over a 7-fold range. The time course of relaxation, as defined by tLIN and kREL, was correlated with EC50 but varied by just 2.7- and 3.3-fold, respectively. Our results confirm that troponin I phosphorylation specifically alters the Ca2+ sensitivity of isometric tension and the time course of relaxation in cardiac muscle myofibrils. Moreover, the DCM-causing mutation ACTC E361G blunts this

  19. Myocardial Expression Analysis of Osteopontin and Its Splice Variants in Patients Affected by End-Stage Idiopathic or Ischemic Dilated Cardiomyopathy

    PubMed Central

    Cabiati, Manuela; Svezia, Benedetta; Matteucci, Marco; Botta, Luca; Pucci, Angela; Rinaldi, Mauro; Caselli, Chiara; Lionetti, Vincenzo; Del Ry, Silvia

    2016-01-01

    Osteopontin (OPN) is a phosphoglycoprotein of cardiac extracellular matrix and it is still poorly defined whether its expression changes in failing heart of different origin. The full-length OPN-a and its isoforms (OPN-b, OPN-c) transcriptomic profile were evaluated in myocardium of patients with dilated or ischemic cardiomyopathy (DCM n = 8; LVEF% = 17.5±3; ICM n = 8; LVEF% = 19.5±5.2) and in auricle of valvular patients (VLP n = 5; LVEF%≥50), by Real-time PCR analysis. OPN-a and thrombin mRNA levels resulted significantly higher in DCM compared to ICM patients (DCM:31.3±7.4, ICM:2.7±1.1, p = 0.0002; DCM:19.1±4.9, ICM:5.4±2.2, p = 0.007, respectively). Although both genes’ mRNA levels increased in patients with LVEF<50% (DCM+ICM) with respect to VLP with LVEF>50%, a significant increase in OPN (p = 0.0004) and thrombin (p = 0.001) expression was observed only in DCM. In addition, a correlation between OPN-a and thrombin was found in patients with LVEF<50% (r = 0.6; p = 0.003). The mRNA pattern was confirmed by OPN-a cardiac protein concentration (VLP:1.127±0.26; DCM:1.29±0.22; ICM:1.00±0.077 ng/ml). The OPN splice variants expression were detectable only in ICM (OPN-b: 0.357±0.273; OPN-c: 0.091±0.033) and not in DCM patients. A significant correlation was observed between collagen type I, evaluated by immunohistochemistry analysis, and both OPN-a mRNA expression (r = 0.87, p = 0.002) and OPN protein concentrations (r = 0.77, p = 0.016). Concluding, OPN-a and thrombin mRNA resulted dependent on the origin of heart failure while OPN-b and OPN-c highlighted a different expression for DCM and ICM patients, suggesting their correlation with different clinical-pathophysiological setting. PMID:27479215

  20. The influence of atorvastatin on parameters of inflammation left ventricular function, hospitalizations and mortality in patients with dilated cardiomyopathy – 5-year follow-up

    PubMed Central

    2013-01-01

    Background We assessed the influence of atorvastatin on selected indicators of an inflammatory condition, left ventricular function, hospitalizations and mortality in patients with dilated cardiomyopathy (DCM). Methods We included 68 DCM patients with left ventricular ejection fraction (LVEF) ≤40% treated optimally in a prospective, randomized study. They were observed for 5 years. Patients were divided into two groups: patients who were commenced on atorvastatin 40 mg daily for two months followed by an individually matched dose of 10 or 20 mg/day (group A), and patients who were treated according to current recommendations without statin therapy (group B). Results After 5-year follow-up we assessed 45 patients of mean age 59 ± 11 years - 22 patients in group A (77% male) and 23 patients in group B (82% male). Interleukin-6, tumor necrosis factor alpha, and uric acid concentrations were significantly lower in the statin group than in group B (14.96 ± 4.76 vs. 19.02 ± 3.94 pg/ml, p = 0.012; 19.10 ± 6.39 vs. 27.53 ± 7.39 pg/ml, p = 0.001, and 5.28 ± 0.48 vs. 6.53 ± 0.46 mg/dl, p = 0.001, respectively). In patients on statin therapy a reduction of N-terminal pro-brain natriuretic peptide concentration (from 1425.28 ± 1264.48 to 1098.01 ± 1483.86 pg/ml, p = 0.045), decrease in left ventricular diastolic (from 7.15 ± 0.90 to 6.67 ± 0.88 cm, p = 0.001) and systolic diameters (from 5.87 ± 0.92 to 5.17 ± 0.97, p = 0.001) in comparison to initial values were observed. We also showed the significant increase of LVEF in patients after statin therapy (from 32.0 ± 6.4 to 38.8 ± 8.8%, p = 0.016). Based on a comparison of curves using the log-rank test, the probability of survival to 5 years was significantly higher in patients receiving statins (p = 0.005). Conclusions Atorvastatin in a small dose significantly reduce levels of inflammatory cytokines and uric

  1. Kinetic study of atrial natriuretic peptide in patients with idiopathic dilated cardiomyopathy: evidence for resistance to biologic effects of the hormone even in patients with mild myocardial involvement.

    PubMed

    Iervasi, G; Clerico, A; Pilo, A; Berti, S; Vitek, F; Biagini, A; Bianchi, R; Donato, L

    1994-10-01

    Atrial natriuretic peptide (ANP) kinetics was studied in 12 patients with idiopathic dilated cardiomyopathy at different sodium excretion (30-175 mmol/day) and variable degrees of hemodynamic dysfunction [New York Heart Association (NYHA) class range I-III] to investigate whether differences in renewal and distribution of this hormone (as compared with those of a control group) play a role in pathogenesis and evolution of heart failure. [125I]Labeled ANP was injected as a bolus, and a high-performance liquid chromatography (HPLC) procedure was used to purify the labeled hormone in venous plasma samples collected for < or = 50 min after injection; the main ANP kinetic parameters were then derived from the disappearance curve of the labeled hormone. As in controls, a positive linear regression between ANP metabolic clearance rate (MCR, ml/min/m2) values and daily urinary excretion of sodium (NaUE, mmol/day) was noted in patients. The different linear regression coefficients between normal subjects (MCR = 365 +/- 8.08 NaUE, r = 0.986, p < 0.0001) and patients (MCR = 497 + 18.5 NaUE, r = 0.867, p = 0.001) indicate that in patients a higher peptide clearance rate is needed to obtain the same biologic effect (sodium excretion) and suggest that resistance to biologic effects of the hormone exists in patients at an early stage of disease (NYHA class I). When the efficiency of the ANP system in excreting sodium was expressed as the ratio of NaUE to ANP production rate (PR = MCR x ANP plasma concentration, microgram/day/m2) patients showed significantly lower values (p = 0.0126) than normal volunteers, thus confirming resistance to the hormone effects. Significantly lower values for ANP total distribution volume (16.5 +/- 8.4 L/m2), mean residence time in the sampling space (4.04 +/- 1.14 min), mean residence time in the body (7.25 +/- 2.13 min), and fewer recycles through the initial (sampling) space (0.27 +/- 0.16) were noted in patients, indicating an altered mechanism

  2. Prevalence of Isolated Atrial Amyloidosis in Young Patients Affected by Congestive Heart Failure

    PubMed Central

    Millucci, Lia; Ghezzi, Lorenzo; Bernardini, Giulia; Braconi, Daniela; Tanganelli, Piero; Santucci, Annalisa

    2012-01-01

    Atrial natriuretic peptide (ANP), whose amyloid is responsible of isolated atrial amyloidosis (IAA), is known to play an important role in the pathophysiology of congestive heart failure (CHF). We provide here the microscopic examination of atrial biopsies from 36 young (mean 40 years) CHF patients distinguished in idiopathic dilated cardiomyopathy (DC) affected and hypertrophic Cardiomyopathy (HC) affected, endorsing the presumptive association of early CHF with IAA. We utilized a multiple method, using Congo red (CR) staining, CR fluorescence (CRF), and immunohistochemistry to assess the presence of IAA in CHF. Immunostaining showed a moderate deposition of IAA in the atrium surrounding working myocardium with small intracellular deposits. Our findings suggest a monitoring of young CHF cases for the development of IAA. Our study also demonstrated how the concurrent use of immunohistochemistry, CR, and CRF may greatly enhance the detection of low-grade amyloid deposits. PMID:22536133

  3. Prevalence of isolated atrial amyloidosis in young patients affected by congestive heart failure.

    PubMed

    Millucci, Lia; Ghezzi, Lorenzo; Bernardini, Giulia; Braconi, Daniela; Tanganelli, Piero; Santucci, Annalisa

    2012-01-01

    Atrial natriuretic peptide (ANP), whose amyloid is responsible of isolated atrial amyloidosis (IAA), is known to play an important role in the pathophysiology of congestive heart failure (CHF). We provide here the microscopic examination of atrial biopsies from 36 young (mean 40 years) CHF patients distinguished in idiopathic dilated cardiomyopathy (DC) affected and hypertrophic Cardiomyopathy (HC) affected, endorsing the presumptive association of early CHF with IAA. We utilized a multiple method, using Congo red (CR) staining, CR fluorescence (CRF), and immunohistochemistry to assess the presence of IAA in CHF. Immunostaining showed a moderate deposition of IAA in the atrium surrounding working myocardium with small intracellular deposits. Our findings suggest a monitoring of young CHF cases for the development of IAA. Our study also demonstrated how the concurrent use of immunohistochemistry, CR, and CRF may greatly enhance the detection of low-grade amyloid deposits. PMID:22536133

  4. Sex differences in cardiomyopathies.

    PubMed

    Meyer, Sven; van der Meer, Peter; van Tintelen, J Peter; van den Berg, Maarten P

    2014-03-01

    Cardiomyopathies are a heterogeneous group of heart muscle diseases with a variety of specific phenotypes. According to the contemporary European Society of Cardiology classification, they are classified into hypertrophic (HCM), dilated (DCM), arrhythmogenic right ventricular (ARVC), restrictive (RCM), and unclassified cardiomyopathies. Each class is aetiologically further categorized into inherited (familial) and non-inherited (non-familial) forms. There is substantial evidence that biological sex is a strong modulator of the clinical manifestation of these cardiomyopathies, and sex-specific characteristics are detectable in all classes. For the clinician, it is important to know the sex-specific aspects of clinical disease expression and the potential modes of inheritance or the hereditary influences underlying the development of cardiomyopathies, since these may aid in diagnosing such diseases in both sexes. PMID:24464619

  5. Heart antibodies in cardiomyopathies.

    PubMed Central

    Trueman, T; Thompson, R A; Cummins, P; Littler, W A

    1981-01-01

    The reported frequency of circulating heart reactive antibodies in cardiomyopathies has varied and their significance is unknown. In this study such antibodies were sought in patients with primary congestive and hypertrophic cardiomyopathies and other heart diseases. Standard "single sandwich" and the more sensitive "double sandwich" indirect immunofluorescence techniques failed to disclose a significant difference between any cardiomyopathic group and controls in repeated experiments. With both techniques results were subject to considerable method-specific artefacts and observer variation. No published work associating heart antibodies detected by immunofluorescence methods with cariomyopathies adequately takes these into account. PMID:7028058

  6. Peripartum cardiomyopathy.

    PubMed

    Okeke, Tc; Ezenyeaku, Cct; Ikeako, Lc

    2013-07-01

    Peripartum cardiomyopathy (PPCM) is a rare form of unexplained cardiac failure of unknown origin, unique to the pregnant woman with highly variable outcome associated with high morbidity and mortality. PPCM is fraught with controversies in its definition, epidemiology, pathophysiology, diagnosis and management. PPCM is frequently under diagnosed, inadequately treated and without a laid down follow-up regimen, thus, the aim of this review. Publications on PPCM were accessed using Medline, Google scholar and Pubmed databases. Relevant materials on PPCM, selected references from internet services, journals, textbooks, and lecture notes on PPCM were also accessed and critically reviewed. PPCM is multifactorial in origin. It is a diagnosis of exclusion and should be based on classic echocardiographic criteria. The outcome of PPCM is also highly variable with high morbidity and mortality rates. Future pregnancies are not recommended in women with persistent ventricular dysfunction because the heart cannot tolerate increased cardiovascular workload associated with the pregnancy. Although, multiparity is associated with PPCM, there is an increased risk of fetal prematurity and fetal loss. PPCM is a rare form of dilated cardiomyopathy of unknown origin, unique to pregnant women. The pathophysiology is poorly understood. Echocardiography is central to diagnosis of PPCM and effective treatment monitoring in patients of PPCM. The outcome is highly variable and related to reversal of ventricular dysfunction. PMID:24116305

  7. Atrophic nerve fibers in regions of reduced MIBG uptake in doxorubicin cardiomyopathy

    SciTech Connect

    Takano, Hajime; Ozawa Hideyuki; Kobayashi, Isao

    1995-11-01

    A myocardial MIBG-SPECT examination was conducted 2 wk after doxorubicin chemotherapy on a 52-yr-old woman without cardiac symptoms. Despite normal {sup 201}Tl scintigraphy, reduced MIBG uptake was detected in the apical anterior, inferior and lateral segments of the left ventricle. The patient died of congestive heart failure due to doxorubicin-induced cardiomyopathy 10 mo later. At necropsy, the left ventricle was markedly dilated and the apical anterior, inferior and lateral walls were thin, stiff and whitish. Nerve fibers in the apical inferior wall were atrophic and markedly fibrotic where MIBG uptake was most reduced. Nerve fibers in the septum were normal where MIBG uptake had remained normal. The histologic findings correspond with the findings on the MIBG image. MIBG imaging may detect cardiac sympathetic denervation in doxorubicin-induced cardiomyopathy before cardiac symptoms are manifest and cardiac function deteriorates. 5 refs., 2 figs.

  8. Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder

    PubMed Central

    Bispo, Miguel; Valente, Ana; Maldonado, Rosário; Palma, Rui; Glória, Helena; Nóbrega, João; Alexandrino, Paula

    2009-01-01

    Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure. PMID:19533818

  9. Rationale and Design of The PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis in Dilated CardioMyopathy (The POSEIDON- DCM Study)

    PubMed Central

    Mushtaq, Muzammil; DiFede, Darcy L.; Golpanian, Samuel; Khan, Aisha; Gomes, Samirah; Mendizabal, Adam; Heldman, Alan W.; Hare, Joshua M.

    2014-01-01

    Background While accumulating clinical trials have focused on the impact of cell-therapy in patients with acute MI and ischemic cardiomyopathy, there are fewer efforts to examine cell-based therapy in patients with non-ischemic cardiomyopathy (NICM). We hypothesized that cell-therapy could have a similar impact in NICM. Methods/Results The POSIDEON-DCM trial is a phase I/II trial designed to address autologous vs. allogeneic bone marrow derived MSCs in patients with NICM. In this study, cells will be administered transendocardially with the NOGA injection-catheter system to patients (n=36) randomly allocated to two treatments groups: Group 1 (n=18 auto-hMSCs) and Group 2 (n=18 allo-hMSCs). The primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCS vs. auto-hMSCs in patients with NICM. Conclusions This study will establish safety of transendocardial injection of stem cells (TESI), compare phenotypic outcomes, and offer promising advances in the field of cell-based therapy in patients with NICM. PMID:25354998

  10. Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy: detection of mutations in MT-ND2 and MT-TL1 genes.

    PubMed

    Alila, Olfa Fersi; Rebai, Emna Mkaouar; Tabebi, Mouna; Tej, Amel; Chamkha, Imen; Tlili, Abdelaziz; Bouguila, Jihene; Tilouche, Samia; Soyah, Nejla; Boughamoura, Lamia; Fakhfakh, Faiza

    2016-07-01

    Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. These mutations were described in the mt-tRNA genes and in the mitochondrial protein-coding genes. The aim of this study was to identify the genetic defect in two patients belonging to two families with cardiac dysfunction associated to a wide spectrum of clinical phenotypes. The sequencing analysis of the whole mitochondrial DNA in the two patients and their parents revealed the presence of known polymorphisms associated to cardiomyopathy and two pathogenic mutations in DNA extracted from blood leucocytes: the heteroplasmic m.3243A > G mutation in the MT-TL1 gene in patient A; and the homoplasmic m.5182C > T mutation in the ND2 gene in patient B. Secondary structure analysis of the ND2 protein further supported the deleterious role of the m.5182C > T mutation, as it was found to be involved an extended imbalance in its hydrophobicity and affect its function. In addition, the mitochondrial variants identified in patients A and B classify both of them in the same haplogroup H2a2a1. PMID:26258512

  11. Histological and ultrastructural evaluation of cardiac lesions in idiopathic cardiomyopathy in dogs.

    PubMed Central

    Sandusky, G E; Capen, C C; Kerr, K M

    1984-01-01

    Described are pathological studies of eight dogs which died in congestive heart failure, with a clinical diagnosis of congestive cardiomyopathy. Examination revealed marked dilatation and enlargement of all four chambers of the heart. The ventricular walls were thin with small atrophic papillary muscles. Histological studies on the myocardium revealed scattered areas of myocardial necrosis, especially around the papillary muscles of the left ventricle and random scattered areas of fibrosis. Electron microscopic studies revealed fewer and disoriented myofibrils, myocytolysis, increased numbers of mitochondria with swelling and inclusions, increased glycogen granules and increased numbers of lysosomes, lipofuscin granules and lipid droplets. Mild Z-band abnormalities were found throughout the myofibers. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:6713261

  12. Anthracycline-induced cardiomyopathy in a dog treated with epirubicin

    PubMed Central

    Lee, Ye-Rin; Kang, Min-Hee; Park, Hee-Myung

    2015-01-01

    An 8-year-old American cocker spaniel dog was diagnosed with dilated cardiomyopathy. Four years earlier, the dog had been diagnosed with multicentric lymphoma and had received 4 cycles of multi-agent chemotherapy, including doxorubicin and epirubicin. The total cumulative dose of epirubicin was 168 mg/m2. Dilated cardiomyopathy was considered a consequence of epirubicin toxicity. PMID:26028676

  13. Dystrophin-Deficient Cardiomyopathy.

    PubMed

    Kamdar, Forum; Garry, Daniel J

    2016-05-31

    Dystrophinopathies are a group of distinct neuromuscular diseases that result from mutations in the structural cytoskeletal Dystrophin gene. Dystrophinopathies include Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy, as well as DMD and BMD female carriers. The primary presenting symptom in most dystrophinopathies is skeletal muscle weakness. However, cardiac muscle is also a subtype of striated muscle and is similarly affected in many of the muscular dystrophies. Cardiomyopathies associated with dystrophinopathies are an increasingly recognized manifestation of these neuromuscular disorders and contribute significantly to their morbidity and mortality. Recent studies suggest that these patient populations would benefit from cardiovascular therapies, annual cardiovascular imaging studies, and close follow-up with cardiovascular specialists. Moreover, patients with DMD and BMD who develop end-stage heart failure may benefit from the use of advanced therapies. This review focuses on the pathophysiology, cardiac involvement, and treatment of cardiomyopathy in the dystrophic patient. PMID:27230049

  14. Arrhythmogenic cardiomyopathy.

    PubMed

    Pilichou, Kalliopi; Thiene, Gaetano; Bauce, Barbara; Rigato, Ilaria; Lazzarini, Elisabetta; Migliore, Federico; Perazzolo Marra, Martina; Rizzo, Stefania; Zorzi, Alessandro; Daliento, Luciano; Corrado, Domenico; Basso, Cristina

    2016-01-01

    -functional abnormalities. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, sarcoidosis, dilated cardiomyopathy, right ventricular infarction, congenital heart diseases with right ventricular overload and athlete heart. A positive genetic test in the affected AC proband allows early identification of asymptomatic carriers by cascade genetic screening of family members. Risk stratification remains a major clinical challenge and antiarrhythmic drugs, catheter ablation and implantable cardioverter defibrillator are the currently available therapeutic tools. Sport disqualification is life-saving, since effort is a major trigger not only of electrical instability but also of disease onset and progression. We review the current knowledge of this rare cardiomyopathy, suggesting a flowchart for primary care clinicians and geneticists. PMID:27038780

  15. Pediatric Cardiomyopathies

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Pediatric Cardiomyopathies Updated:Oct 22,2015 Patient education material ... oxygen or high blood pressure. According to the Pediatric Cardiomyopathy Registry, one in every 100,000 children ...

  16. In vitro evaluation of mitochondrial dysfunction and treatment with adeno-associated virus vector in fibroblasts from Doberman Pinschers with dilated cardiomyopathy and a pyruvate dehydrogenase kinase 4 mutation.

    PubMed

    Sosa, Ivan; Estrada, Amara H; Winter, Brandy D; Erger, Kirsten E; Conlon, Thomas J

    2016-02-01

    OBJECTIVE To compare mitochondrial oxygen consumption rate (OCR) of fibroblasts from Doberman Pinschers with and without dilated cardiomyopathy (DCM) and mutation of the gene for pyruvate dehydrogenase kinase isozyme 4 (PDK4) and to evaluate in vitro whether treatment with adeno-associated virus (AAV) vector (ie, gene therapy) would alter metabolic efficiency. ANIMALS 10 Doberman Pinschers screened for DCM and PDK4 mutation. PROCEDURES Fibroblasts were harvested from skin biopsy specimens obtained from Doberman Pinschers, and dogs were classified as without DCM or PDK4 mutation (n = 3) or with occult DCM and heterozygous (4) or homozygous (3) for PDK4 mutation. Fibroblasts were or were not treated with tyrosine mutant AAV type 2 vector containing PDK4 at multiplicities of infection of 1,000. Mitochondrial OCR was measured to evaluate mitochondrial metabolism. The OCR was compared among dog groups and between untreated and treated fibroblasts within groups. RESULTS Mean ± SD basal OCR of fibroblasts from heterozygous (74 ± 8 pmol of O2/min) and homozygous (58 ± 12 pmol of O2/min) dogs was significantly lower than that for dogs without PDK4 mutation (115 ± 9 pmol of O2/min). After AAV transduction, OCR did not increase significantly in any group (mutation-free group, 121 ± 26 pmol of O2/min; heterozygous group, 88 ± 6 pmol of O2/min; homozygous group, 59 ± 3 pmol of O2/min). CONCLUSIONS AND CLINICAL RELEVANCE Mitochondrial function was altered in skin fibroblasts of Doberman Pinschers with DCM and PDK4 mutation. Change in mitochondrial function after in vitro gene therapy at the multiplicities of infection used in this study was not significant. (Am J Vet Res 2016;77:156-161). PMID:27027709

  17. Evolving Approaches to Genetic Evaluation of Specific Cardiomyopathies.

    PubMed

    Teo, Loon Yee Louis; Moran, Rocio T; Tang, W H Wilson

    2015-12-01

    The understanding of the genetic basis of cardiomyopathy has expanded significantly over the past 2 decades. The increasing availability, shortening diagnostic time, and lowering costs of genetic testing have provided researchers and physicians with the opportunity to identify the underlying genetic determinants for thousands of genetic disorders, including inherited cardiomyopathies, in effort to improve patient morbidities and mortality. As such, genetic testing has advanced from basic scientific research to clinical application and has been incorporated as part of patient evaluations for suspected inherited cardiomyopathies. Genetic evaluation framework of inherited cardiomyopathies typically encompasses careful evaluation of family history, genetic counseling, clinical screening of family members, and if appropriate, molecular genetic testing. This review summarizes the genetics, current guideline recommendations, and evidence supporting the genetic evaluation framework of five hereditary forms of cardiomyopathy: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy (RCM), and left ventricular noncompaction (LVNC). PMID:26472190

  18. Importance of genetic evaluation and testing in pediatric cardiomyopathy.

    PubMed

    Tariq, Muhammad; Ware, Stephanie M

    2014-11-26

    Pediatric cardiomyopathies are clinically heterogeneous heart muscle disorders that are responsible for significant morbidity and mortality. Phenotypes include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, left ventricular noncompaction and arrhythmogenic right ventricular cardiomyopathy. There is substantial evidence for a genetic contribution to pediatric cardiomyopathy. To date, more than 100 genes have been implicated in cardiomyopathy, but comprehensive genetic diagnosis has been problematic because of the large number of genes, the private nature of mutations, and difficulties in interpreting novel rare variants. This review will focus on current knowledge on the genetic etiologies of pediatric cardiomyopathy and their diagnostic relevance in clinical settings. Recent developments in sequencing technologies are greatly impacting the pace of gene discovery and clinical diagnosis. Understanding the genetic basis for pediatric cardiomyopathy and establishing genotype-phenotype correlations may help delineate the molecular and cellular events necessary to identify potential novel therapeutic targets for heart muscle dysfunction in children. PMID:25429328

  19. Rationale and design of the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy (the POSEIDON-DCM study): a phase I/II, randomized pilot study of the comparative safety and efficacy of transendocardial injection of autologous mesenchymal stem cell vs. allogeneic mesenchymal stem cells in patients with non-ischemic dilated cardiomyopathy.

    PubMed

    Mushtaq, Muzammil; DiFede, Darcy L; Golpanian, Samuel; Khan, Aisha; Gomes, Samirah A; Mendizabal, Adam; Heldman, Alan W; Hare, Joshua M

    2014-12-01

    While accumulating clinical trials have focused on the impact of cell therapy in patients with acute myocardial infarction (MI) and ischemic cardiomyopathy, there are fewer efforts to examine cell-based therapy in patients with non-ischemic cardiomyopathy (NICM). We hypothesized that cell therapy could have a similar impact in NICM. The POSEIDON-DCM trial is a phase I/II trial designed to address autologous vs. allogeneic bone marrow-derived mesenchymal stem cells (MSCs) in patients with NICM. In this study, cells will be administered transendocardially with the NOGA injection-catheter system to patients (n = 36) randomly allocated to two treatment groups: group 1 (n = 18 auto-human mesenchymal stem cells (hMSC)) and group 2 (n = 18 allo-hMSCs). The primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCS vs. auto-hMSCs in patients with NICM. This study will establish safety of transendocardial injection of stem cells (TESI), compare phenotypic outcomes, and offer promising advances in the field of cell-based therapy in patients with NICM. PMID:25354998

  20. Dietary Salt Exacerbates Isoproterenol-induced Cardiomyopathy in Rats

    EPA Science Inventory

    Spontaneously Hypertensive Heart Failure rats (SHHFs) take far longer to develop compensated heart failure and congestive decompensation than common surgical models of heart failure. Isoproterenol (ISO) infusion can accelerate cardiomyopathy in young SHHFs, while dietary salt loa...

  1. Calcium Ions in Inherited Cardiomyopathies.

    PubMed

    Deftereos, Spyridon; Papoutsidakis, Nikolaos; Giannopoulos, Georgios; Angelidis, Christos; Raisakis, Konstantinos; Bouras, Georgios; Davlouros, Periklis; Panagopoulou, Vasiliki; Goudevenos, John; Cleman, Michael W; Lekakis, John

    2016-01-01

    Inherited cardiomyopathies are a known cause of heart failure, although the pathways and mechanisms leading from mutation to the heart failure phenotype have not been elucidated. There is strong evidence that this transition is mediated, at least in part, by abnormal intracellular Ca(2+) handling, a key ion in ventricular excitation, contraction and relaxation. Studies in human myocytes, animal models and in vitro reconstituted contractile protein complexes have shown consistent correlations between Ca(2+) sensitivity and cardiomyopathy phenotype, irrespective of the causal mutation. In this review we present the available data about the connection between mutations linked to familial hypertrophic (HCM), dilated (DCM) and restrictive (RCM) cardiomyopathy, right ventricular arrhythmogenic cardiomyopathy/dysplasia (ARVC/D) as well as left ventricular non-compaction and the increase or decrease in Ca(2+) sensitivity, together with the results of attempts to reverse the manifestation of heart failure by manipulating Ca(2+) homeostasis. PMID:26411603

  2. Molecular etiology of idiopathic cardiomyopathy

    PubMed Central

    Arimura, T; Hayashi, T; Kimura, A

    2007-01-01

    Summary Idiopathic cardiomyopathy (ICM) is a primary cardiac disorder associated with abnormalities of ventricular wall thickness, size of ventricular cavity, contraction, relaxation, conduction and rhythm. Over the past two decades, molecular genetic analyses have revealed that mutations in the various genes cause ICM and such information concerning the genetic basis of ICM enables us to speculate the pathogenesis of this heterogeous cardiac disease. This review focuses on the molecular pathogenesis, i.e., genetic abnormalities and functional alterations due to the mutations especially in sarcomere/cytoskeletal components, in three characteristic features of ICM, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM). Understanding the functional abnormalities of the sarcomere/cytoskeletal components, in ICM, has unraveled the function of these components not only as a contractile unit but also as a pivot for transduction of biochemical signals. PMID:18646564

  3. Morphometric Documentation of a High Prevalence of Left Ventricular Dilated Cardiomyopathy in Both Clinically Normal and Cyanotic Mature Commercial Broiler Breeder Roosters with Comparisons to Market-Age Broilers.

    PubMed

    Wilson, Floyd D; Magee, Danny L; Jones, Kelli H; Baravik-Munsell, Erica; Cummings, Timothy S; Wills, Robert W; Pace, Lanny W

    2016-09-01

    Previous studies documented the common occurrence of transitory cyanosis and echocardiographic aortic insufficiency in mature commercial broiler breeder roosters. During further investigations, we observed a high prevalence of hearts exhibiting extensive dilation of the left ventricle chamber compatible with dilated left ventricular cardiomyopathy present in both cyanotic and normal subpopulations. We conducted quantitative studies focused on documentation of cardiac ventricle parameters by using simple gross morphometric methods performed on formalin-fixed hearts obtained from both clinically normal roosters and those exhibiting variable transitory cyanosis, echocardiographic aortic insufficiency, or both. A high prevalence of often dramatic left ventricular dilation reflected in enlarged left ventricular chamber areas and elevated left ventricle-to-total ventricle area ratios was morphometrically documented. However, no statistically significant differences in the occurrence of ventricular abnormalities were observed between normal and cyanotic roosters. Age-associated changes were also demonstrated by comparative morphometric studies on hearts from normal market-age broilers (average age of 7 wk) and those of mature roosters (average age of 42 wk). Elevation in both left and right ventricular weight-to-total heart weight ratios dramatically increased with aging. In addition, values (average ± SD) for the left ventricle chamber area-to-total ventricle area ratios increased from 3.2 ± 2.0% in broilers up to 10.0 ± 8.8% in roosters. None of the normal broilers studied demonstrated left ventricular volume ratios above 10%, whereas 33% of the roosters had left ventricular volume ratios above 10%, including 13% with ratios of 20% or higher. However, the left ventricle wall area-to-body weight ratios were much closer for the two age groups (0.85 ± 0.18 cm(2)/kg in broilers and 0.79 ± 0.13 cm(2)/kg in roosters). Also, the standard right ventricle-to-total ventricle

  4. End-stage hypertrophic cardiomyopathy in a cat

    PubMed Central

    White, Andrew J.M.

    2015-01-01

    A 14-year-old Persian cat was referred for evaluation of the progression of hypertrophic cardiomyopathy (HCM) after an acute episode of congestive heart failure. The diagnosis of HCM had been made almost 13 years ago. Echocardiography and electrocardiography revealed end-stage hypertrophic cardiomyopathy and multifocal atrial tachycardia. The patient was discharged on medical management with a grave prognosis. PMID:25969586

  5. End-stage hypertrophic cardiomyopathy in a cat.

    PubMed

    White, Andrew J M

    2015-05-01

    A 14-year-old Persian cat was referred for evaluation of the progression of hypertrophic cardiomyopathy (HCM) after an acute episode of congestive heart failure. The diagnosis of HCM had been made almost 13 years ago. Echocardiography and electrocardiography revealed end-stage hypertrophic cardiomyopathy and multifocal atrial tachycardia. The patient was discharged on medical management with a grave prognosis. PMID:25969586

  6. Evolving molecular diagnostics for familial cardiomyopathies: at the heart of it all

    PubMed Central

    Callis, Thomas E; Jensen, Brian C; Weck, Karen E; Willis, Monte S

    2016-01-01

    Cardiomyopathies are an important and heterogeneous group of common cardiac diseases. An increasing number of cardiomyopathies are now recognized to have familial forms, which result from single-gene mutations that render a Mendelian inheritance pattern, including hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and left ventricular noncompaction cardiomyopathy. Recently, clinical genetic tests for familial cardiomyopathies have become available for clinicians evaluating and treating patients with these diseases, making it necessary to understand the current progress and challenges in cardiomyopathy genetics and diagnostics. In this review, we summarize the genetic basis of selected cardiomyopathies, describe the clinical utility of genetic testing for cardiomyopathies and outline the current challenges and emerging developments. PMID:20370590

  7. Cardiomyopathy in captive African hedgehogs (Atelerix albiventris).

    PubMed

    Raymond, J T; Garner, M M

    2000-09-01

    From 1994 to 1999, 16 captive African hedgehogs (Atelerix albiventris), from among 42 necropsy cases, were diagnosed with cardiomyopathy. The incidence of cardiomyopathy in this study population was 38%. Fourteen of 16 hedgehogs with cardiomyopathy were males and all hedgehogs were adult (>1 year old). Nine hedgehogs exhibited 1 or more of the following clinical signs before death: heart murmur, lethargy, icterus, moist rales, anorexia, dyspnea, dehydration, and weight loss. The remaining 7 hedgehogs died without premonitory clinical signs. Gross findings were cardiomegaly (6 cases), hepatomegaly (5 cases), pulmonary edema (5 cases), pulmonary congestion (4 cases), hydrothorax (3 cases), pulmonary infarct (1 case), renal infarcts (1 case), ascites (1 case), and 5 cases showed no changes. Histologic lesions were found mainly within the left ventricular myocardium and consisted primarily of myodegeneration, myonecrosis, atrophy, hypertrophy, and disarray of myofibers. All hedgehogs with cardiomyopathy had myocardial fibrosis, myocardial edema, or both. Other common histopathologic findings were acute and chronic passive congestion of the lungs, acute passive congestion of the liver, renal tubular necrosis, vascular thrombosis, splenic extramedullary hematopoiesis, and hepatic lipidosis. This is the first report of cardiomyopathy in African hedgehogs. PMID:11021439

  8. Restrictive cardiomyopathy

    MedlinePlus

    ... blood returns from the body (diastole). When the disease progresses, the heart may not pump blood strongly. The abnormal heart function can affect the lungs, liver, and other body systems. Restrictive cardiomyopathy may affect either or both of the ...

  9. What's Cardiomyopathy

    MedlinePlus

    ... or more chambers of the heart. Usually, the enlargement begins in one of the two lower pumping ... idiopathic hypertrophic subaortic stenosis (IHSS) and asymmetrical septal hypertrophy (ASH), non-obstructive hypertrophic cardiomyopathy (HCM) The second ...

  10. Restrictive cardiomyopathy

    MedlinePlus

    ... blood returns from the body (diastole). When the disease progresses, the heart may not pump blood strongly. The abnormal heart function can affect the lungs, liver, and other body systems. Restrictive cardiomyopathy may affect ...

  11. Molecular genetics and pathogenesis of cardiomyopathy.

    PubMed

    Kimura, Akinori

    2016-01-01

    Cardiomyopathy is defined as a disease of functional impairment in the cardiac muscle and its etiology includes both extrinsic and intrinsic factors. Cardiomyopathy caused by the intrinsic factors is called as primary cardiomyopathy of which two major clinical phenotypes are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Genetic approaches have revealed the disease genes for hereditary primary cardiomyopathy and functional studies have demonstrated that characteristic functional alterations induced by the disease-associated mutations are closely related to the clinical types, such that increased and decreased Ca(2+) sensitivities of muscle contraction are associated with HCM and DCM, respectively. In addition, recent studies have suggested that mutations in the Z-disc components found in HCM and DCM may result in increased and decreased stiffness of sarcomere, respectively. Moreover, functional analysis of mutations in the other components of cardiac muscle have suggested that the altered response to metabolic stresses is associated with cardiomyopathy, further indicating the heterogeneity in the etiology and pathogenesis of cardiomyopathy. PMID:26178429

  12. Insights into the hereditability of canine cardiomyopathy.

    PubMed

    Meurs, K M

    1998-11-01

    There is evidence for a genetic etiology of dilated cardiomyopathy in at least two breeds, the Doberman pinscher and the Boxer dog. Significant effort toward determining a genetic etiology in these breeds will depend on careful characterization of the disease, determination of criteria for diagnosing asymptomatic affected individuals, determination of a pattern of inheritance, and, eventually, molecular evaluation of the specific gene. PMID:10098247

  13. Peripartum cardiomyopathy

    MedlinePlus

    ... cancer or prevent rejection of a transplanted organ) Heart transplant if severe congestive heart failure persists For most ... very quickly and may be candidates for a heart transplant. The death rate may be as high as ...

  14. Diabetic cardiomyopathy

    PubMed Central

    Asghar, Omar; Al-Sunni, Ahmed; Khavandi, Kaivan; Khavandi, Ali; Withers, Sarah; Greenstein, Adam; Heagerty, Anthony M.; Malik, Rayaz A.

    2009-01-01

    Diabetic cardiomyopathy is a distinct primary disease process, independent of coronary artery disease, which leads to heart failure in diabetic patients. Epidemiological and clinical trial data have confirmed the greater incidence and prevalence of heart failure in diabetes. Novel echocardiographic and MR (magnetic resonance) techniques have enabled a more accurate means of phenotyping diabetic cardiomyopathy. Experimental models of diabetes have provided a range of novel molecular targets for this condition, but none have been substantiated in humans. Similarly, although ultrastructural pathology of the microvessels and cardiomyocytes is well described in animal models, studies in humans are small and limited to light microscopy. With regard to treatment, recent data with thiazoledinediones has generated much controversy in terms of the cardiac safety of both these and other drugs currently in use and under development. Clinical trials are urgently required to establish the efficacy of currently available agents for heart failure, as well as novel therapies in patients specifically with diabetic cardiomyopathy. PMID:19364331

  15. Left Ventricular Noncompaction: A Distinct Genetic Cardiomyopathy?

    PubMed

    Arbustini, Eloisa; Favalli, Valentina; Narula, Nupoor; Serio, Alessandra; Grasso, Maurizia

    2016-08-30

    Left ventricular noncompaction (LVNC) describes a ventricular wall anatomy characterized by prominent left ventricular (LV) trabeculae, a thin compacted layer, and deep intertrabecular recesses. Individual variability is extreme, and trabeculae represent a sort of individual "cardioprinting." By itself, the diagnosis of LVNC does not coincide with that of a "cardiomyopathy" because it can be observed in healthy subjects with normal LV size and function, and it can be acquired and is reversible. Rarely, LVNC is intrinsically part of a cardiomyopathy; the paradigmatic examples are infantile tafazzinopathies. When associated with LV dilation and dysfunction, hypertrophy, or congenital heart disease, the genetic cause may overlap. The prevalence of LVNC in healthy athletes, its possible reversibility, and increasing diagnosis in healthy subjects suggests cautious use of the term LVNC cardiomyopathy, which describes the morphology but not the functional profile of the cardiomyopathy. PMID:27561770

  16. The Pediatric Cardiomyopathy Registry: 1995–2007

    PubMed Central

    Wilkinson, James D.; Sleeper, Lynn A.; Alvarez, Jorge A.; Bublik, Natalya; Lipshultz, Steven E.

    2008-01-01

    Cardiomyopathy is a serious disorder of the heart muscle and, although rare, it is potentially devastating in children. Funded by the National Heart Lung and Blood Institute since 1994, the Pediatric Cardiomyopathy Registry (PCMR) was designed to describe the epidemiology and clinical course of selected CMs in patients 18 years old or younger and to promote the development of etiology-specific prevention and treatment strategies. Currently, data from more than 3,000 children with cardiomyopathy have been entered in the PCMR database with annual follow-up continuing until death, heart transplant, or loss-to-follow up. Using PCMR data, the incidence of cardiomyopathy in two large regions of the United States is estimated to be 1.13 cases per 100,000 children. Only 1/3 of children had a known etiology at the time of cardiomyopathy diagnosis. Diagnosis was associated with certain patient characteristics, family history, echocardiographic findings, laboratory testing, and biopsy. Greater incidence was found in boys and infants (<1 yr) for both dilated and hypertrophic cardiomyopathy (DCM, HCM) and black race for only DCM. In DCM, prognosis is worse in older children (>1yr), heart failure (HF) at diagnosis or idiopathic etiology. For HCM, worse prognosis is associated with inborn errors of metabolism or combination of HCM and another cardiomyopathy functional type. The best outcomes were observed in children presenting at age >1 yr with idiopathic HCM. PCMR data have enabled analysis of patients with cardiomyopathy and muscular dystrophy, as well as Noonan Syndrome. Currently, collaborations with the Pediatric Heart Transplant Study group and a newly established Pediatric Cardiomyopathy Biologic Specimen Repository at Texas Children’s Hospital will continue to yield important results. The PCMR is the largest and most complete multi-center prospective data resource regarding the etiology, clinical course and outcomes for children with cardiomyopathy. PMID:19343086

  17. Cirrhotic cardiomyopathy

    PubMed Central

    Ruiz-del-Árbol, Luis; Serradilla, Regina

    2015-01-01

    During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function. PMID:26556983

  18. Sex dimorphisms of crossbridge cycling kinetics in transgenic hypertrophic cardiomyopathy mice.

    PubMed

    Birch, Camille L; Behunin, Samantha M; Lopez-Pier, Marissa A; Danilo, Christiane; Lipovka, Yulia; Saripalli, Chandra; Granzier, Henk; Konhilas, John P

    2016-07-01

    Familial hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere and may lead to hypertrophic, dilated, restrictive, and/or arrhythmogenic cardiomyopathy, congestive heart failure, or sudden cardiac death. We hypothesized that hearts from transgenic HCM mice harboring a mutant myosin heavy chain increase the energetic cost of contraction in a sex-specific manner. To do this, we assessed Ca(2+) sensitivity of tension and crossbridge kinetics in demembranated cardiac trabeculas from male and female wild-type (WT) and HCM hearts at an early time point (2 mo of age). We found a significant effect of sex on Ca(2+) sensitivity such that male, but not female, HCM mice displayed a decrease in Ca(2+) sensitivity compared with WT counterparts. The HCM transgene and sex significantly impacted the rate of force redevelopment by a rapid release-restretch protocol and tension cost by the ATPase-tension relationship. In each of these measures, HCM male trabeculas displayed a gain-of-function when compared with WT counterparts. In addition, cardiac remodeling measured by echocardiography, histology, morphometry, and posttranslational modifications demonstrated sex- and HCM-specific effects. In conclusion, female and male HCM mice display sex dimorphic crossbridge kinetics accompanied by sex- and HCM-dependent cardiac remodeling at the morphometric, histological, and cellular level. PMID:27199124

  19. Lactic acidosis associated with cerebellar vermal atrophy and cardiomyopathy.

    PubMed

    Challa, V R; Markesbery, W R; Baumann, R J; Noonan, J A

    1978-08-01

    The association of fluctuating neurological signs and congestive cardiomyopathy with chronic lactic acidosis is described in a 5 1/2 year-old-boy who ultimately succumbed to congestive heart failure. The autopsy findings included severe atrophy of the anterior cerebellar vermis and a hypertrophied heart with left sided endocardial fibroelastosis. Skeletal and cardial muscle calcification was prominent and probably due to the effect of intracellular metabolic alterations associated with lactic acidosis. A review of the literature shows that the combination of cardiomyopathy, isolated atrophy of cerebellar vermis and muscle fiber calcification have not been reported in association with idiopathic lactic acidosis previously. PMID:152418

  20. Bronchovascular role in pulmonary congestion.

    PubMed

    McIlveen, S A

    2000-12-01

    1. A postulated role for the bronchial circulation in the development of pulmonary congestion may be based on recent studies of bronchovascular control. 2. The bronchial circulation is the nutrient blood supply of the conducting airways and, therefore, plays an important role in the function of the bronchial mucosa. Mucosal swelling secondary to elevation of mucosal capillary hydrostatic pressure may decrease airway calibre, increase resistance to airflow and precipitate symptoms of pulmonary congestion. 3. Resting mucosal capillary hydrostatic pressure is relatively constant due to autoregulation of bronchial blood flow and is maintained low by nett bronchovascular constriction due to the dominance of autonomic vasoconstriction over nitric oxidedependent vasodilatation. 4. Bronchial blood flow is also regulated by cardiac afferent reflexes. Stimulation of cardiac vagal and spinal afferents produces vasodilatation and vasoconstriction, respectively. Tonic activity of cardiac spinal afferents probably contributes to the resting autonomic vasoconstriction. 5. Therefore, mild heart failure, which is associated with abnormal cardiovascular reflex function, may decrease cardiac spinal afferent-mediated bronchial vasoconstriction and produce active dilatation due to stimulation of cardiac vagal afferents by excessive myocardial stretch, leading to bronchial mucosal swelling and pulmonary congestion. PMID:11117228

  1. Exome Sequencing Identifies a Novel LMNA Splice-Site Mutation and Multigenic Heterozygosity of Potential Modifiers in a Family with Sick Sinus Syndrome, Dilated Cardiomyopathy, and Sudden Cardiac Death.

    PubMed

    Zaragoza, Michael V; Fung, Lianna; Jensen, Ember; Oh, Frances; Cung, Katherine; McCarthy, Linda A; Tran, Christine K; Hoang, Van; Hakim, Simin A; Grosberg, Anna

    2016-01-01

    The goals are to understand the primary genetic mechanisms that cause Sick Sinus Syndrome and to identify potential modifiers that may result in intrafamilial variability within a multigenerational family. The proband is a 63-year-old male with a family history of individuals (>10) with sinus node dysfunction, ventricular arrhythmia, cardiomyopathy, heart failure, and sudden death. We used exome sequencing of a single individual to identify a novel LMNA mutation and demonstrated the importance of Sanger validation and family studies when evaluating candidates. After initial single-gene studies were negative, we conducted exome sequencing for the proband which produced 9 gigabases of sequencing data. Bioinformatics analysis showed 94% of the reads mapped to the reference and identified 128,563 unique variants with 108,795 (85%) located in 16,319 genes of 19,056 target genes. We discovered multiple variants in known arrhythmia, cardiomyopathy, or ion channel associated genes that may serve as potential modifiers in disease expression. To identify candidate mutations, we focused on ~2,000 variants located in 237 genes of 283 known arrhythmia, cardiomyopathy, or ion channel associated genes. We filtered the candidates to 41 variants in 33 genes using zygosity, protein impact, database searches, and clinical association. Only 21 of 41 (51%) variants were validated by Sanger sequencing. We selected nine confirmed variants with minor allele frequencies <1% for family studies. The results identified LMNA c.357-2A>G, a novel heterozygous splice-site mutation as the primary mutation with rare or novel variants in HCN4, MYBPC3, PKP4, TMPO, TTN, DMPK and KCNJ10 as potential modifiers and a mechanism consistent with haploinsufficiency. PMID:27182706

  2. Exome Sequencing Identifies a Novel LMNA Splice-Site Mutation and Multigenic Heterozygosity of Potential Modifiers in a Family with Sick Sinus Syndrome, Dilated Cardiomyopathy, and Sudden Cardiac Death

    PubMed Central

    Zaragoza, Michael V.; Fung, Lianna; Jensen, Ember; Oh, Frances; Cung, Katherine; McCarthy, Linda A.; Tran, Christine K.; Hoang, Van; Hakim, Simin A.; Grosberg, Anna

    2016-01-01

    The goals are to understand the primary genetic mechanisms that cause Sick Sinus Syndrome and to identify potential modifiers that may result in intrafamilial variability within a multigenerational family. The proband is a 63-year-old male with a family history of individuals (>10) with sinus node dysfunction, ventricular arrhythmia, cardiomyopathy, heart failure, and sudden death. We used exome sequencing of a single individual to identify a novel LMNA mutation and demonstrated the importance of Sanger validation and family studies when evaluating candidates. After initial single-gene studies were negative, we conducted exome sequencing for the proband which produced 9 gigabases of sequencing data. Bioinformatics analysis showed 94% of the reads mapped to the reference and identified 128,563 unique variants with 108,795 (85%) located in 16,319 genes of 19,056 target genes. We discovered multiple variants in known arrhythmia, cardiomyopathy, or ion channel associated genes that may serve as potential modifiers in disease expression. To identify candidate mutations, we focused on ~2,000 variants located in 237 genes of 283 known arrhythmia, cardiomyopathy, or ion channel associated genes. We filtered the candidates to 41 variants in 33 genes using zygosity, protein impact, database searches, and clinical association. Only 21 of 41 (51%) variants were validated by Sanger sequencing. We selected nine confirmed variants with minor allele frequencies <1% for family studies. The results identified LMNA c.357-2A>G, a novel heterozygous splice-site mutation as the primary mutation with rare or novel variants in HCN4, MYBPC3, PKP4, TMPO, TTN, DMPK and KCNJ10 as potential modifiers and a mechanism consistent with haploinsufficiency. PMID:27182706

  3. Celiac disease with pulmonary haemosiderosis and cardiomyopathy.

    PubMed

    Işikay, Sedat; Yilmaz, Kutluhan; Kilinç, Metin

    2012-01-01

    Celiac disease or pulmonary haemosiderosis can be associated with several distinguished conditions. Pulmonary haemosiderosis is a rare, severe and fatal disease characterised by recurrent episodes of alveolar haemorrhage, haemoptysis and anaemia. Association of pulmonary haemosiderosis and celiac disease is extremely rare. We describe a case of celiac disease presented with dilated cardiomyopathy and pulmonary haemosiderosis without gastrointestinal symptoms of celiac disease. In addition, vitamin A deficiency was detected. This case suggests that celiac disease should be considered in patients with cardiomyopathy and/or pulmonary haemosiderosis regardless of the intestinal symptoms of celiac disease. PMID:23169927

  4. Reversible Cardiomyopathies

    PubMed Central

    Patel, Harsh; Madanieh, Raef; Kosmas, Constantine E; Vatti, Satya K; Vittorio, Timothy J

    2015-01-01

    Cardiomyopathies (CMs) have many etiological factors that can result in severe structural and functional dysregulation. Fortunately, there are several potentially reversible CMs that are known to improve when the root etiological factor is addressed. In this article, we discuss several of these reversible CMs, including tachycardia-induced, peripartum, inflammatory, hyperthyroidism, Takotsubo, and chronic illness–induced CMs. Our discussion also includes a review on their respective pathophysiology, as well as possible management solutions. PMID:26052233

  5. Arrhythmogenic Noncompaction Cardiomyopathy: Is There an Echocardiographic Phenotypic Overlap of Two Distinct Cardiomyopathies?

    PubMed Central

    Aras, Dursun; Cay, Serkan; Ozcan, Firat; Baser, Kazım; Dogan, Umuttan; Unlu, Murat; Demirkan, Burcu; Tufekcioglu, Omac; Topaloglu, Serkan

    2015-01-01

    The clinical diagnosis of right ventricular (RV) cardiomyopathies is often challenging. It is difficult to differentiate the isolated left ventricular (LV) noncompaction cardiomyopathy (NC) from biventricular NC or from coexisting arrhythmogenic ventricular cardiomyopathy (AC). There are currently few established morphologic criteria for the diagnosis other than RV dilation and presence of excessive regional trabeculation. The gross and microscopic changes suggest pathological similarities between, or coexistence of, RV-NC and AC. Therefore, the term arrhythmogenic right ventricular cardiomyopathy is somewhat misleading as isolated LV or biventricular involvement may be present and thus a broader term such as AC should be preferred. We describe an unusual case of AC associated with a NC in a 27-year-old man who had a history of permanent pacemaker 7 years ago due to second-degree atrioventricular block. PMID:26448828

  6. Lack of efficacy of low-dose spironolactone as adjunct treatment to conventional congestive heart failure treatment in dogs.

    PubMed

    Schuller, S; Van Israël, N; Vanbelle, S; Clercx, C; McEntee, K

    2011-08-01

    Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone receptor blockade has been shown to reduce morbidity and mortality in human patients with advanced congestive left ventricular heart failure. This study was designed to assess the efficacy and tolerance of long-term low-dose spironolactone when added to conventional heart failure treatment in dogs with advanced heart failure. Eighteen client-owned dogs with advanced congestive heart failure due to either degenerative valve disease (n=11) or dilated cardiomyopathy (n=7) were included in this prospective, placebo-controlled, double-blinded, randomized clinical study. After initial stabilization including furosemide, angiotensin-converting enzyme inhibitors, pimobendan and digoxin, spironolactone at a median dose of 0.52 mg/kg (range 0.49-0.8 mg/kg) once daily (n=9) or placebo (n=9) was added to the treatment, and the dogs were reassessed 3 and 6 months later. Clinical scoring, echocardiography, electrocardiogram, systolic blood pressure measurement, thoracic radiography, sodium, potassium, urea, creatinine, alanine aminotransferase, aldosterone and aminoterminal atrial natriuretic propeptide were assessed at baseline, 3 and 6 months. Survival times were not significantly different between the two treatment groups. Spironolactone was well tolerated when combined with conventional heart failure treatment. PMID:20950346

  7. Primary antiphospholipid syndrome, hypertrophic non-obstructive cardiomyopathy and hypotelorism.

    PubMed

    Kellermair, Joerg; Kammler, Juergen; Laubichler, Peter; Steinwender, Clemens

    2016-01-01

    Antiphospholipid syndrome (APS) is an autoimmune disorder associated with arterial/venous thrombosis. Cardiac manifestations of APS include valve stenosis/insufficiency, coronary artery disease and myocardial dysfunction presenting as dilated cardiomyopathy. In the following report, we present the case of a man with primary APS, hypertrophic non-obstructive cardiomyopathy and hypotelorism-a combination that has not yet been reported in the literature. PMID:27048398

  8. Takotsubo Cardiomyopathy Occurring in the Postoperative Period.

    PubMed

    Deniz, Süleyman; Bakal, Ömer; İnangil, Gökhan; Şen, Hüseyin; Özkan, Sezai

    2015-02-01

    Takotsubo cardiomyopathy simulates acute myocardial infarction, and it is characterised by reversible left ventricular failure. A case of Takotsubo cardiomyopathy diagnosed after emergency angiography performed in a patient with evidence of acute myocardial infarction in the postoperative period will be described in this report. Transurethral resection of a bladder tumour (TUR-BT) was performed in a 92-year-old male patient by the urology clinic. The patient was transferred to the post-anaesthesia care unit after the operation. An echocardiography was performed because of the sudden onset of dyspnoea, tachycardia (140-150 beats per minute, rhythm-atrial fibrillation) and ST-segment elevation on electrocardiography (ECG) at the first postoperative hour, and midapical dyskinesia was detected at the patient. An immediate angiography was performed due to suspicion of acute coronary syndrome. Patent coronary arteries and temporary aneurysmatic dilatation of the apex of the heart were revealed by angiography. As a result of these findings, the patient was diagnosed with Takotsubo cardiomyopathy by the cardiology service. The patient was discharged uneventfully following 10 days in the intensive care unit. Aneurysm of the apex of the left ventricle and normal anatomy of the coronary arteries in the angiography have diagnostic value for Takotsubo cardiomyopathy. Diuretics (furosemide) and beta-blockers (metoprolol) are commonly used for the treatment of Takotsubo cardiomyopathy. Even though Takotsubo cardiomyopathy is a rare and benign disease, it should be kept in mind in patients suspected for acute myocardial infarction in the postoperative period. PMID:27366464

  9. The genetic landscape of cardiomyopathy and its role in heart failure

    PubMed Central

    McNally, Elizabeth M; Barefield, David Y; Puckelwartz, Megan J

    2015-01-01

    Heart failure is highly influenced by heritability, and nearly 100 genes link to familial cardiomyopathy. Despite the marked genetic diversity that underlies these complex cardiovascular phenotypes, several key genes and pathways have emerged. Hypertrophic cardiomyopathy is characterized by increased contractility and a greater energetic cost of cardiac output. Dilated cardiomyopathy is often triggered by mutations that disrupt the giant protein titin. The energetic consequences of these mutations offer molecular targets and opportunities for new drug development and gene correction therapies. PMID:25651172

  10. Arrhythmogenic Cardiomyopathy in a Patient With a Rare Loss‐of‐Function KCNQ1 Mutation

    PubMed Central

    Xiong, Qinmei; Cao, Qing; Zhou, Qiongqiong; Xie, Jinyan; Shen, Yang; Wan, Rong; Yu, Jianhua; Yan, Sujuan; Marian, Ali J.; Hong, Kui

    2015-01-01

    Background Ventricular tachycardia (VT) is a common manifestation of advanced cardiomyopathies. In a subset of patients with dilated cardiomyopathy, VT is the initial and the cardinal manifestation of the disease. The molecular genetic basis of this subset of dilated cardiomyopathy is largely unknown. Methods and Results We identified 10 patients with dilated cardiomyopathy who presented with VT and sequenced 14 common causal genes for cardiomyopathies and arrhythmias. Functional studies included cellular patch clamp, confocal microscopy, and immunoblotting. We identified nonsynonymous variants in 4 patients, including a rare missense p.R397Q mutation in the KCNQ1 gene in a 60‐year‐old man who presented with incessant VT and had mild cardiac dysfunction. The p.R397Q mutation was absent in an ethnically matched control group, affected a conserved amino acid, and was predicted by multiple algorithms to be pathogenic. Co‐expression of the mutant KCNQ1 with its partner unit KCNE1 was associated with reduced tail current density of slowly activating delayed rectifier K+ current (IKs). The mutation reduced membrane localization of the protein. Conclusions Dilated cardiomyopathy with an initial presentation of VT may be a forme fruste of arrhythmogenic cardiomyopathy caused by mutations in genes encoding the ion channels. The findings implicate KCNQ1 as a possible causal gene for arrhythmogenic cardiomyopathy. PMID:25616976

  11. Peri-partum cardiomyopathy in a pregnant woman at term revealed by acute pulmonary edema: what to do in front this catastrophic situation?

    PubMed Central

    Abdedaim, Hatim El ghadbane; Benali, Zine el abidine; Omari, Driss; Mohammed, Drissi; Hicham, Balkhi; Charki, Haimeur

    2014-01-01

    Peripartum Cardiomyopathy is insufficient congestive heart occurring in the last month of pregnancy and 5 months after delivery, in the absence of preexisting heart disease and identified etiology. This heart disease is associated with echocardiography systolic dysfunction and left ventricular dilatation. Its incidence ranges from 1/3000 to 1/15000, depending on the region, including much higher in some African countries, it particularly concern women over 30 years, multiparous and multiple pregnancies. The pathogenesis remains unclear, the prognosis is closely related to the complete recovery of cardiac function. We report through the clinical case of a woman aged 33 years admitted to the ICU for acute pulmonary edema of sudden onset of a term pregnancy and what to do before this critical situation PMID:25368718

  12. Dilating Eye Drops

    MedlinePlus

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Dilating Eye Drops En Español Read in Chinese What are dilating eye drops? Dilating eye drops contain medication to enlarge ( ...

  13. Hypertrophic cardiomyopathy in infants: clinical features and natural history

    SciTech Connect

    Maron, B.J.; Tajik, A.J.; Ruttenberg, H.D.; Graham, T.P.; Atwood, G.F.; Victorica, B.E.; Lie, J.T.; Roberts, W.C.

    1982-01-01

    The clinical and morphologic features of hypertrophic cardiomyopathy in 20 patients recognized as having cardiac disease in the first year of life are described. Fourteen of these 20 infants were initially suspected of having heart disease solely because a heart murmur was identified. However, the infants showed a variety of clinical findings, including signs of marked congestive heart failure (in the presence of nondilated ventricular cavities and normal or increased left ventricular contractility) and substantial cardiac enlargement on chest radiograph. Other findings were markedly different from those usually present in older children and adults with hypertrophic cardiomyopathy (e.g., right ventricular hypertrophy on the ECG and cyanosis). Consequently, in 14 infants, the initial clinical diagnosis was congenital cardiac malformation other than hypertrophic cardiomyopathy. The clinical course was variable in these patients, but the onset of marked congestive heart failure in the first year of life appeared to be an unfavorable prognostic sign; nine of the 11 infants with congestive heart failure died within the first year of life. In infants with hypertrophic cardiomyopathy, unlike older children and adults with this condition, sudden death was less common (two patients) than death due to progressive congestive heart failure.

  14. Troponins, intrinsic disorder, and cardiomyopathy.

    PubMed

    Na, Insung; Kong, Min J; Straight, Shelby; Pinto, Jose R; Uversky, Vladimir N

    2016-08-01

    Cardiac troponin is a dynamic complex of troponin C, troponin I, and troponin T (TnC, TnI, and TnT, respectively) found in the myocyte thin filament where it plays an essential role in cardiac muscle contraction. Mutations in troponin subunits are found in inherited cardiomyopathies, such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The highly dynamic nature of human cardiac troponin and presence of numerous flexible linkers in its subunits suggest that understanding of structural and functional properties of this important complex can benefit from the consideration of the protein intrinsic disorder phenomenon. We show here that mutations causing decrease in the disorder score in TnI and TnT are significantly more abundant in HCM and DCM than mutations leading to the increase in the disorder score. Identification and annotation of intrinsically disordered regions in each of the troponin subunits conducted in this study can help in better understanding of the roles of intrinsic disorder in regulation of interactomes and posttranslational modifications of these proteins. These observations suggest that disease-causing mutations leading to a decrease in the local flexibility of troponins can trigger a whole plethora of functional changes in the heart. PMID:27074551

  15. Imaging Findings of Congestive Hepatopathy.

    PubMed

    Wells, Michael L; Fenstad, Eric R; Poterucha, Joseph T; Hough, David M; Young, Phillip M; Araoz, Philip A; Ehman, Richard L; Venkatesh, Sudhakar K

    2016-01-01

    Congestive hepatopathy (CH) refers to hepatic abnormalities that result from passive hepatic venous congestion. Prolonged exposure to elevated hepatic venous pressure may lead to liver fibrosis and cirrhosis. Liver dysfunction and corresponding clinical signs and symptoms typically manifest late in the disease process. Recognition of CH at imaging is critical because advanced liver fibrosis may develop before the condition is suspected clinically. Characteristic findings of CH on conventional images include dilatation of the inferior vena cava and hepatic veins; retrograde hepatic venous opacification during the early bolus phase of intravenous contrast material injection; and a predominantly peripheral heterogeneous pattern of hepatic enhancement due to stagnant blood flow. Extensive fibrosis can be seen in chronic or severe cases. Hyperenhancing regenerative nodules that may retain hepatobiliary contrast agents are often present. Magnetic resonance (MR) elastography can show elevated liver stiffness and may be useful in evaluation of fibrosis in CH because it can be incorporated easily into routine cardiac MR imaging. Preliminary experience with MR elastography suggests its future use in initial evaluation of patients suspected of having CH, for monitoring of disease, and for assessment after therapy. To facilitate appropriate workup and treatment, radiologists should be familiar with findings suggestive of CH at radiography, ultrasonography, computed tomography, MR imaging, and MR elastography. In addition, knowledge of underlying pathophysiology, comparative histologic abnormalities, and extrahepatic manifestations is useful to avoid diagnostic pitfalls and suggest appropriate additional diagnostic testing. (©)RSNA, 2016. PMID:27284758

  16. Peripartum cardiomyopathy

    PubMed Central

    Blauwet, Lori A; Sliwa, Karen

    2011-01-01

    Peripartum cardiomyopathy (PPCM) is a potentially devastating disease that affects women during the last months of pregnancy or the first months after delivery. The aetiology and pathogenesis of this disease remain unclear, but oxidative stress and the generation of a cardiotoxic fragment of prolactin may play key roles. Diagnosing PPCM remains a challenge, as symptoms may mimic those women experience during normal pregnancy and the peripartum period. A high index of suspicion is thus necessary to make the diagnosis. Patients with PPCM have a varied clinical course, as some patients achieve full recovery while others progress to end-stage heart failure and even death. Standard heart failure treatment is indicated, although special provisions are necessary in pregnant and lactating women. Additional research into the pathophysiology of this disease, including possible genetic contributions, may lead to novel treatment strategies that can improve outcomes.

  17. Lymphocyte subpopulations and hematologic variables in dogs with congestive heart failure.

    PubMed

    Farabaugh, Andrew E; Freeman, Lisa M; Rush, John E; George, Katherine L

    2004-01-01

    Alterations in lymphocyte subpopulations and in other hematologic variables have been documented in people with heart failure. The purpose of the current study was to compare flow cytometric and hematologic variables in dogs with congestive heart failure (CHF) to healthy controls. CD4+ peripheral blood mononuclear cells (PBMC) and CD8+ lymphocytes were analyzed by flow cytometry, and white blood cell count, platelet count, hematocrit, and hemoglobin were determined by a complete blood count. Twenty-five dogs with CHF (International Small Animal Cardiac Health Council [ISACHC] class 2 [n = 12] and ISACHC class 3a [n = 13]) and 13 healthy controls were enrolled in the study. Compared with the controls, dogs with CHF had markedly lower percentages of CD4+ PBMC, CD8+ lymphocytes, hematocrit, and hemoglobin, but markedly higher leukocytes, neutrophils, and platelets. There were no differences in these variables between dogs with dilated cardiomyopathy (n = 6) and those with chronic valvular disease (n = 19). Dogs in ISACHC class 3a had a markedly lower total lymphocyte number, CD4+ and CD8+ cells, and hematocrit, but markedly higher leukocyte and neutrophil numbers relative to the control group. CD4+ and CD8+ subpopulations and other blood cell variables are altered in dogs with CHF. Future studies to determine possible clinical implications of these changes are warranted. PMID:15320588

  18. Metabolic imaging of patients with cardiomyopathy

    SciTech Connect

    Geltman, E.M. )

    1991-09-01

    The cardiomyopathies comprise a diverse group of illnesses that can be characterized functionally by several techniques. However, the delineation of derangements of regional perfusion and metabolism have been accomplished only relatively recently with positron emission tomography (PET). Regional myocardial accumulation and clearance of 11C-palmitate, the primary myocardial substrate under most conditions, demonstrate marked spatial heterogeneity when studied under fasting conditions or with glucose loading. PET with 11C-palmitate permits the noninvasive differentiation of patients with nonischemic from ischemic dilated cardiomyopathy, since patients with ischemic cardiomyopathy demonstrate large zones of intensely depressed accumulation of 11C-palmitate, probably reflecting prior infarction. Patients with hypertrophic cardiomyopathy and Duchenne's muscular dystrophy demonstrate relatively unique patterns of myocardial abnormalities of perfusion and metabolism. The availability of new tracers and techniques for the evaluation of myocardial metabolism (11C-acetate), perfusion (H2(15)O), and autonomic tone (11-C-hydroxyephedrine) should facilitate further understanding of the pathogenesis of the cardiomyopathies.

  19. Inherited cardiomyopathies caused by troponin mutations

    PubMed Central

    Lu, Qun-Wei; Wu, Xiao-Yan; Morimoto, Sachio

    2013-01-01

    Genetic investigations of cardiomyopathy in the recent two decades have revealed a large number of mutations in the genes encoding sarcomeric proteins as a cause of inherited hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive cardiomyopathy (RCM). Most functional analyses of the effects of mutations on cardiac muscle contraction have revealed significant changes in the Ca2+-regulatory mechanism, in which cardiac troponin (cTn) plays important structural and functional roles as a key regulatory protein. Over a hundred mutations have been identified in all three subunits of cTn, i.e., cardiac troponins T, I, and C. Recent studies on cTn mutations have provided plenty of evidence that HCM- and RCM-linked mutations increase cardiac myofilament Ca2+ sensitivity, while DCM-linked mutations decrease it. This review focuses on the functional consequences of mutations found in cTn in terms of cardiac myofilament Ca2+ sensitivity, ATPase activity, force generation, and cardiac troponin I phosphorylation, to understand potential molecular and cellular pathogenic mechanisms of the three types of inherited cardiomyopathy. PMID:23610579

  20. Cardiomyopathies in children

    PubMed Central

    2013-01-01

    Cardiomyopathy (CMP) is a heterogeneous disease caused by a functional abnormality of the cardiac muscle. CMP is of 2 major types, dilated and hypertrophic, and is further classified as either primary or secondary. Secondary CMP is caused by extrinsic factors, including infection, ischemia, hypertension, and metabolic disorders. Primary CMP is diagnosed when the extrinsic factors of secondary CMP are absent. Furthermore, the World Health Organization, American Heart Association, and European Cardiology Association have different systems for clinically classifying primary CMP. Primary CMP is rare and associated with a family history of the disease, implying that genetic factors might affect its incidence. In addition, the incidence of CMP varies widely according to patient ethnicity. Genetic testing plays an important role in the care of patients with CMP and their families because it confirms diagnosis, determines the appropriate care for the patient, and possibly affects patient prognosis. The diagnosis and genetic identification of CMP in patients' families allow the possibility to identify novel genes that may lead to new treatments. This review focuses on the epidemiology, pathophysiology, diagnosis, and treatment of CMP, with the aim of providing pediatricians with insights that may be helpful in the early identification and management of idiopathic CMP in children. PMID:23482511

  1. Children's Cardiomyopathy Foundation

    MedlinePlus

    Search The Children's Cardiomyopathy Foundation (CCF) is a national, non-profit organization focused on pediatric cardiomyopathy, a chronic disease of the heart muscle. CCF is dedicated to accelerating the search for ...

  2. Dilating Eye Drops

    MedlinePlus

    ... Conditions Most Common Searches Adult Strabismus Amblyopia Cataract Conjunctivitis Corneal Abrasions Dilating Eye Drops Lazy eye (defined) ... Loading... Most Common Searches Adult Strabismus Amblyopia Cataract Conjunctivitis Corneal Abrasions Dilating Eye Drops Lazy eye (defined) ...

  3. Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay.

    PubMed

    Olivas-Chacon, Cristina I; Mullins, Carola; Stewart, Kevan; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Non-ischemic cardiomyopathies are defined as either primary or secondary diseases of the myocardium resulting in cardiac dysfunction. While primary cardiomyopathies are confined to the heart and can be genetic or acquired, secondary cardiomyopathies show involvement of the heart as a manifestation of an underlying systemic disease including metabolic, inflammatory, granulomatous, infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently classified as hypertrophic, dilated, restrictive, or unclassifiable, including left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI) not only has the capability to assess cardiac morphology and function, but also the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits, providing a valuable imaging tool in the characterization of non-ischemic cardiomyopathies. This pictorial essay shows some of the most important non-ischemic cardiomyopathies with an emphasis on magnetic resonance imaging features. PMID:26199786

  4. Genetic advances in sarcomeric cardiomyopathies: state of the art

    PubMed Central

    Ho, Carolyn Y.; Charron, Philippe; Richard, Pascale; Girolami, Francesca; Van Spaendonck-Zwarts, Karin Y.; Pinto, Yigal

    2015-01-01

    Genetic studies in the 1980s and 1990s led to landmark discoveries that sarcomere mutations cause both hypertrophic and dilated cardiomyopathies. Sarcomere mutations also likely play a role in more complex phenotypes and overlap cardiomyopathies with features of hypertrophy, dilation, diastolic abnormalities, and non-compaction. Identification of the genetic cause of these important conditions provides unique opportunities to interrogate and characterize disease pathogenesis and pathophysiology, starting from the molecular level and expanding from there. With such insights, there is potential for clinical translation that may transform management of patients and families with inherited cardiomyopathies. If key pathways for disease development can be identified, they could potentially serve as targets for novel disease-modifying or disease-preventing therapies. By utilizing gene-based diagnostic testing, we can identify at-risk individuals prior to the onset of clinical disease, allowing for disease-modifying therapy to be initiated early in life, at a time that such treatment may be most successful. In this section, we review the current application of genetics in clinical management, focusing on hypertrophic cardiomyopathy as a paradigm; discuss state-of-the-art genetic testing technology; review emerging knowledge of gene expression in sarcomeric cardiomyopathies; and discuss both the prospects, as well as the challenges, of bringing genetics to medicine. PMID:25634555

  5. Cardiomyopathy Induced by Pulmonary Sequestration in a 50-Year-Old Man

    PubMed Central

    Chatelain, Shaun; Comp, Robert A.; Grace, R. Randal

    2015-01-01

    A 50-year-old black man presented at the emergency department with midsternal, nonradiating chest pressure and chronic dyspnea on exertion. Four years before the current admission, he had been diagnosed with nonischemic cardiomyopathy at another facility. After our complete evaluation, we suspected that his symptoms arose from left-to-left shunting in association with pulmonary sequestration, a congenital malformation. Our preliminary diagnosis of secondary dilated cardiomyopathy was confirmed by normalization of the patient's ventricular size and function after lobectomy. To our knowledge, this patient is the oldest on record to present with cardiomyopathy consequent to pulmonary sequestration. His case is highly unusual because of his age and the rapid resolution of his symptoms after lobectomy. We believe that pulmonary sequestration should be included in the differential diagnosis of dilated cardiomyopathy. PMID:25873803

  6. Unclassifiable arrhythmic cardiomyopathy associated with Emery-Dreifuss caused by a mutation in FHL1.

    PubMed

    San Román, I; Navarro, M; Martínez, F; Albert, L; Polo, L; Guardiola, J; García-Molina, E; Muñoz-Esparza, C; López-Ayala, J M; Sabater-Molina, M; Gimeno, J R

    2016-08-01

    Emery-Dreifuss muscular dystrophy (EDMD) is a heterogeneous genetic disorder characterized by peripheral muscular weakness often associated with dilated cardiomyopathy. We characterize clinically a large family with a mutation in FHL1 gene (p.Cys255Ser). Penetrance was 44%, 100% for males and 18% for females. The heart was the main organ involved. Affected adult males had mild hypertrophy, systolic dysfunction and restriction with non-dilated ventricles. Carriers had significant QTc prolongation. The proband presented with resuscitated cardiac arrest. There were two transplants. Pathological study of explanted heart showed fibrofatty replacement and scarring consistent with arrhythmogenic cardiomyopathy and prominent left ventricular trabeculations. Myopathic involvement was evident in all males. Females had no significant neuromuscular disease. Mutations in FHL1 cause unclassifiable cardiomyopathy with coexisting EDMD. Prognosis is poor and systolic impairment and arrhythmias are frequent. Thrombopenia and raised creatine phosphokinase should raise suspicion of an FHL-1 disorder in X-linked cardiomyopathy. PMID:26857240

  7. Interplay between the effects of a Protein Kinase C phosphomimic (T204E) and a dilated cardiomyopathy mutation (K211Δ or R206W) in rat cardiac troponin T blunts the magnitude of muscle length-mediated crossbridge recruitment against the β-myosin heavy chain background.

    PubMed

    Michael, John Jeshurun; Gollapudi, Sampath K; Chandra, Murali

    2016-06-01

    Failing hearts of dilated cardiomyopathy (DCM)-patients reveal systolic dysfunction and upregulation of several Protein Kinase C (PKC) isoforms. Recently, we demonstrated that the functional effects of T204E, a PKC phosphomimic of cardiac troponin T (TnT), were differently modulated by α- and β-myosin heavy chain (MHC) isoforms. Therefore, we hypothesized that the interplay between the effects of T204E and a DCM-linked mutation (K211Δ or R206W) in TnT would modulate contractile parameters linked-to systolic function in an MHC-dependent manner. To test our hypothesis, five TnT variants (wildtype, K211Δ, K211Δ + T204E, R206W, and R206W + T204E) were generated and individually reconstituted into demembranated cardiac muscle fibers from normal (α-MHC) and propylthiouracil-treated (β-MHC) rats. Steady-state and mechano-dynamic measurements were performed on reconstituted fibers. Myofilament Ca(2+) sensitivity (pCa50) was decreased by both K211Δ and R206W to a greater extent in α-MHC fibers (~0.15 pCa units) than in β-MHC fibers (~0.06 pCa units). However, T204E exacerbated the attenuating influence of both mutants on pCa50 only in β-MHC fibers. Moreover, the magnitude of muscle length (ML)-mediated crossbridge (XB) recruitment was decreased by K211Δ + T204E (~47 %), R206W (~34 %), and R206W + T204E (~36 %) only in β-MHC fibers. In relevance to human hearts, which predominantly express β-MHC, our data suggest that the interplay between the effects of DCM mutations, PKC phosphomimic in TnT, and β-MHC lead to systolic dysfunction by attenuating pCa50 and the magnitude of ML-mediated XB recruitment. PMID:27411801

  8. Isolated cardiomyopathy caused by a DMD nonsense mutation in somatic mosaicism: genetic normalization in skeletal muscle.

    PubMed

    Juan-Mateu, J; Paradas, C; Olivé, M; Verdura, E; Rivas, E; González-Quereda, L; Rodríguez, M J; Baiget, M; Gallano, P

    2012-12-01

    X-linked dilated cardiomyopathy is a pure cardiac dystrophinopathy phenotype mainly caused by DMD mutations that present a specific transcription effect in cardiac tissue. We report a 26-year-old male who presented with severe dilated cardiomyopathy and high creatine kinase. The patient did not complain of skeletal muscle weakness. A muscle biopsy showed mild dystrophic changes and a low proportion of dystrophin-negative fibres. A molecular study identified a nonsense DMD mutation (p.Arg2098X) in somatic mosaicism. The ratio of mutant versus normal allele in blood and skeletal muscle suggests selective pressure against mutant muscle cells, a process known as genetic normalization. We hypothesize that this process may have mitigated skeletal muscle symptoms in this patient. This is the second report of a DMD somatic mosaic with evidence of genetic normalization in muscle. Somatic DMD mutations should be considered in patients presenting with idiopathic dilated cardiomyopathy. PMID:22092019

  9. A rare form of cardiomyopathy: left ventricular non-compaction cardiomyopathy

    PubMed Central

    Goud, Aditya; Padmanabhan, Sriram

    2016-01-01

    Left ventricular non-compaction is a recently recognized, rare form of cardiomyopathy. It is based on the arrest of endomyocardial morphogenesis during embryogenesis. It was first described in 1984 by Engberding who described it as isolated ‘sinusoids’ within the LV. Right now its prevalence is estimated at 0.014 to 1.3 and 3–4% in heart failure patients. Its clinical manifestations are highly variable, ranging from no symptoms to disabling congestive heart failure, arrhythmias, and systemic thromboemboli. Doppler Echocardiogram is considered the diagnostic procedure of choice and treatment is symptomatic management of its symptoms and complications. PMID:26908378

  10. Cardiomyopathy responsive to gluten withdrawal in a patient with coeliac disease.

    PubMed

    McGrath, Samuel; Thomas, Angharad; Gorard, David Angelo

    2016-01-01

    A 57-year-old man with iron deficiency anaemia developed general malaise, exertional dyspnoea and features of cardiac failure out of proportion to his anaemia (haemoglobin 120 g/L). Investigations showed a severely dilated left ventricle with an ejection fraction of 15%, due to dilated cardiomyopathy. He was treated with high-dose diuretics, ACE inhibitors and β-blocker therapy. Subsequent investigation into his iron deficiency anaemia revealed a new diagnosis of coeliac disease. After starting a gluten-free diet, his cardiac function improved markedly, with ejection fraction reaching 70%, allowing his cardiac medications to be withdrawn. This case suggests a link between coeliac disease and cardiomyopathy. PMID:26976850

  11. Is a red umbilical cord a sign of umbilical venous congestion?: a case report.

    PubMed

    Miyake, Hidehiko; Igarashi, Miwa; Inde, Yusuke; Nakai, Akihito; Suzuki, Shunji; Takeshita, Toshiyuki

    2011-01-01

    Postnatal examination of fetal appendages is important because this information may help predict perinatal outcome. We present a case of a red streak along the entire umbilical vein after a cesarean section due to non-reassuring fetal status. The pathological findings revealed an umbilical cord with dilated vascular changes and mild funisitis. Because the dilated change was intense in the umbilical vein, the red streak of the umbilical cord was caused by venous congestion. Moreover, we considered that the umbilical venous congestion was due to increased resistance in the fetal intra-abdominal umbilical vein, which was associated with the non-reassuring fetal status. PMID:21389648

  12. Nutrition in Pediatric Cardiomyopathy

    PubMed Central

    Miller, Tracie L.; Neri, Daniela; Extein, Jason; Somarriba, Gabriel; Strickman-Stein, Nancy

    2007-01-01

    Pediatric cardiomyopathies are heterogeneous groups of serious disorders of the heart muscle and are responsible for significant morbidity and mortality among children who have the disease. While enormous improvements have been made in the treatment and survival of children with congenital heart disease, parallel strides have not been made in the outcomes for cardiomyopathies. Thus, ancillary therapies, such as nutrition and nutritional interventions, that may not cure but may potentially improve cardiac function and quality of life, are imperative to consider in children with all types of cardiomyopathy. Growth failure is one of the most significant clinical problems of children with cardiomyopathy with nearly one-third of children with this disorder manifesting some degree of growth failure during the course of their illness. Optimal intake of macronutrients can help improve cardiac function. In addition, several specific nutrients have been shown to correct myocardial abnormalities that often occur with cardiomyopathy and heart failure. In particular, antioxidants that can protect against free radical damage that often occurs in heart failure and nutrients that augment myocardial energy production are important therapies that have been explored more in adults with cardiomyopathy than in the pediatric population. Future research directions should pay particular attention to the effect of overall nutrition and specific nutritional therapies on clinical outcomes and quality of life in children with pediatric cardiomyopathy. PMID:18159216

  13. Hypertrophic Cardiomyopathy in Owl Monkeys (Aotus spp.)

    PubMed Central

    Knowlen, Grant G; Weller, Richard E; Perry, Ruby L; Baer, Janet F; Gozalo, Alfonso S

    2013-01-01

    Cardiac hypertrophy is a common postmortem finding in owl monkeys. In most cases the animals do not exhibit clinical signs until the disease is advanced, making antemortem diagnosis of subclinical disease difficult and treatment unrewarding. We obtained echocardiograms, electrocardiograms, and thoracic radiographs from members of a colony of owl monkeys that previously was identified as showing a 40% incidence of gross myocardial hypertrophy at necropsy, to assess the usefulness of these modalities for antemortem diagnosis. No single modality was sufficiently sensitive and specific to detect all monkeys with cardiac hypertrophy. Electrocardiography was the least sensitive method for detecting owl monkeys with hypertrophic cardiomyopathy. Thoracic radiographs were more sensitive than was electrocardiography in this context but cannot detect animals with concentric hypertrophy without an enlarged cardiac silhouette. Echocardiography was the most sensitive method for identifying cardiac hypertrophy in owl monkeys. The most useful parameters suggestive of left ventricular hypertrophy in our owl monkeys were an increased average left ventricular wall thickness to chamber radius ratio and an increased calculated left ventricular myocardial mass. Parameters suggestive of dilative cardiomyopathy were an increased average left ventricular myocardial mass and a decreased average ratio of left ventricular free wall thickness to left ventricular chamber radius. When all 4 noninvasive diagnostic modalities (physical examination, echocardiography, electrocardiography, and thoracic radiography) were used concurrently, the probability of detecting hypertrophic cardiomyopathy in owl monkeys was increased greatly. PMID:23759531

  14. Rapidly Progressing Chagas Cardiomyopathy.

    PubMed

    Hollowed, John; McCullough, Matthew; Sanchez, Daniel; Traina, Mahmoud; Hernandez, Salvador; Murillo, Efrain

    2016-04-01

    Chagas disease, caused by the parasiteTrypanosoma cruzi, can cause a potentially life-threatening cardiomyopathy in approximately 10-40% of afflicted individuals. The decline in cardiac function characteristically progresses over the course of many years. We report a case of Chagas disease in which the patient experienced an atypical rapid deterioration to severe cardiomyopathy over the course of 16 months. This case argues the need for increased routine surveillance for patients with confirmedT. cruziinfection, who are determined to be at high-risk for worsening cardiomyopathy. PMID:26856912

  15. Analysis of shape and motion of the mitral annulus in subjects with and without cardiomyopathy by echocardiographic 3-dimensional reconstruction

    NASA Technical Reports Server (NTRS)

    Flachskampf, F. A.; Chandra, S.; Gaddipatti, A.; Levine, R. A.; Weyman, A. E.; Ameling, W.; Hanrath, P.; Thomas, J. D.

    2000-01-01

    The shape and dynamics of the mitral annulus of 10 patients without heart disease (controls), 3 patients with dilated cardiomyopathy, and 5 patients with hypertrophic obstructive cardiomyopathy and normal systolic function were analyzed by transesophageal echocardiography and 3-dimensional reconstruction. Mitral annular orifice area, apico-basal motion of the annulus, and nonplanarity were calculated over time. Annular area was largest in end diastole and smallest in end systole. Mean areas were 11.8 +/- 2.5 cm(2) (controls), 15.2 +/- 4.2 cm(2) (dilated cardiomyopathy), and 10.2 +/- 2.4 cm(2) (hypertrophic cardiomyopathy) (P = not significant). After correction for body surface, annuli from patients with normal left ventricular function were smaller than annuli from patients with dilated cardiomyopathy (5.9 +/- 1.2 cm(2)/m(2) vs 7.7 +/- 1.0 cm(2)/m(2); P <.02). The change in area during the cardiac cycle showed significant differences: 23.8% +/- 5.1% (controls), 13.2% +/- 2.3% (dilated cardiomyopathy), and 32.4% +/- 7.6% (hypertrophic cardiomyopathy) (P <.001). Apico-basal motion was highest in controls, followed by those with hypertrophic obstructive and dilated cardiomyopathy (1.0 +/- 0.3 cm, 0.8 +/- 0.2 cm, 0.3 +/- 0.2 cm, respectively; P <.01). Visual inspection and Fourier analysis showed a consistent pattern of anteroseptal and posterolateral elevations of the annulus toward the left atrium. In conclusion, although area changes and apico-basal motion of the mitral annulus strongly depend on left ventricular systolic function, nonplanarity is a structural feature preserved throughout the cardiac cycle in all three groups.

  16. Thiotepa-associated cardiomyopathy during blood or marrow transplantation: association with the female sex and cardiac risk factors.

    PubMed

    Alidina, A; Lawrence, D; Ford, L A; Baer, M R; Bambach, B; Bernstein, S H; Czuczman, M S; Slack, J L; Spangenthal, E; Wetzler, M; Barcos, M P; Proulx, G M; Anderson, B; McCarthy, P L

    1999-01-01

    Thiotepa (TT) has not been reported to cause cardiomyopathy, whereas cyclophosphamide (Cy)-related cardiomyopathy is well characterized. To search for cases of acute onset cardiomyopathy associated with TT, we retrospectively reviewed 171 patients who received TT-containing conditioning regimens for blood or marrow transplantation (BMT). Nine of 171 patients (5.3%) developed clinical congestive heart failure in the post-BMT period. The median time to onset of heart failure was 15 days after BMT (range 5-30). The median pre-BMT left ventricular ejection fraction (LVEF) was 50% (range 42-65%) as determined by two-dimensional echocardiogram, or gated blood pool scan. At the time of cardiomyopathy onset, LVEF was 30%. Six patients died of causes unrelated to heart failure. All affected patients who developed congestive heart failure following administration of TT had some evidence of cardiac dysfunction prior to transplantation. Significant risk factors for the development of cardiomyopathy included low pre-BMT-LVEF and female sex--particularly in females receiving allogeneic transplantation. The incidence of congestive heart failure with TT-containing regimens was similar to the incidence using other regimens with and without Cy. The mean time to clinical evidence of TT-associated cardiomyopathy was longer than the mean time reported with Cy. We recommend caution in using high-dose TT-containing regimens for patients with histories of cardiac dysfunction. PMID:10534063

  17. How Is Cardiomyopathy Treated?

    MedlinePlus

    ... arrest Stopping the disease from getting worse Heart-Healthy Lifestyle Changes Your doctor may suggest lifestyle changes to manage a condition that’s causing your cardiomyopathy including: Heart-healthy eating Aiming for a healthy weight Managing stress ...

  18. Sinuplasty (Balloon Catheter Dilation)

    MedlinePlus

    ... development of the balloon dilating catheter and its adaptation to sinus surgery. In the 1980s, the field ... used in endoscopic sinus surgery. It is the adaptation or application of minimally-invasive balloon technology to ...

  19. Mutation Glu82Lys in lamin A/C gene is associated with cardiomyopathy and conduction defect

    SciTech Connect

    Wang Hu; Wang Jizheng; Zheng Weiyue; Wang Xiaojian; Wang Shuxia; Song Lei; Zou Yubao; Yao Yan; Hui Rutai . E-mail: huirutai@sglab.org

    2006-05-26

    Dilated cardiomyopathy is a form of heart muscle disease characterized by impaired systolic function and ventricular dilation. The mutations in lamin A/C gene have been linked to dilated cardiomyopathy. We screened genetic mutations in a large Chinese family of 50 members including members with dilated cardiomyopathy and found a Glu82Lys substitution mutation in the rod domain of the lamin A/C protein in eight family members, three of them have been diagnosed as dilated cardiomyopathy, one presented with heart dilation. The pathogenic mechanism of lamin A/C gene defect is poorly understood. Glu82Lys mutated lamin A/C and wild type protein was transfected into HEK293 cells. The mutated protein was not properly localized at the inner nuclear membrane and the emerin protein, which interacts with lamin A/C, was also aberrantly distributed. The nuclear membrane structure was disrupted and heterochromatin was aggregated aberrantly in the nucleus of the HEK293 cells stably transfected with mutated lamin A/C gene as determined by transmission electron microscopy.

  20. [Hypertrophic cardiomyopathy. Arrhythmia in hypertrophic cardiomyopathy].

    PubMed

    Colín Lizalde, Luis de Jesús

    2003-01-01

    Hypertrophic cardiomyopathy is a relatively common genetic disorder with heterogeneity in mutations, forms of presentation, prognosis and treatment strategies. Hypertrophic cardiomyopathy is recognized as the most common cause of sudden cardiac death that occurs in young people, including athletes. The clinical diagnosis is complemented with the ecocardiographic study, in which an abnormal myocardial hypertrophy of the septum can be observed in the absence of a cardiac or systemic disease (arterial systemic hypertension, aortic stenosis). The annual sudden mortality rate is 1% and, in selected populations, it ranges between 3 and 6%. The therapeutic strategies depend on the different subsets of patients according to the morbidity and mortality, sudden cardiac death, obstructive symptoms, heart failure or atrial fibrillation and stroke. High risk patients for sudden death may effectively be treated with the automatic implantable cardioverter-defibrillator. PMID:12966640

  1. [Gallium-67 myocardial imaging for the detection of adriamycin cardiomyopathy].

    PubMed

    Morozumi, T; Ishida, Y; Tani, A; Inui, M; Hori, M; Kitabatake, A; Kamada, T; Kondo, H; Kozuka, T; Kimura, K

    1990-05-01

    To detect Adriamycin cardiomyopathy, radionuclide myocardial imagings with Tl-201, Tc-99m pyrophosphate, I-123 metaiodobenzylguanidine and Ga-67 were performed in a 49 year-old-woman receiving Adriamycin (a total dose of 230 mg/m2) for the treatment of breast cancer. This patient demonstrated symptoms of congestive heart failure 2 months after the last intravenous administration. At the period of performing the radionuclide studies, echocardiographic LV ejection fraction (EF) was 22%. Despite severe deterioration of cardiac function, Tl-201 SPECT demonstrated no defect and Tc-99m pyrophosphate (PYP) SPECT demonstrated no positive finding. I-123 metaiodobenzylguanidine (MIBG) scintigraphy demonstrated no regional defect. However, I-123 MIBG washout rate during 4 hours was markedly enhanced, probably reflecting abnormalities of norepinephrine kinetics due to the progression of heart failure. Compared to these pharmaceuticals, Ga-67 was diffusely accumulated in the heart. Then, 5 months after the first study, when LV EF improved to 30% and congestive symptoms disappeared probably owing to beta-blockade therapy, myocardial accumulation of Ga-67 markedly reduced. It has been reported that Ga-67 accumulates in malignant tumor cells and leukocytes. Since, in Adriamycin cardiomyopathy, myocardial accumulation of leukocytes with myocardial fibrotic changes have been histologically demonstrated, the results of Ga-67 scintigraphy may reflect the accumulation of leukocytes. Thus, this case indicates that Ga-67 scintigraphy is advantageous for detecting Adriamycin cardiomyopathy and may be more useful than Tl-201 and Tc-99m PYP scintigraphies. PMID:2395231

  2. Constrictive Pericarditis Versus Restrictive Cardiomyopathy?

    PubMed

    Garcia, Mario J

    2016-05-01

    About one-half of the patients with congestive heart failure have preserved left ventricular ejection fraction (HFpEF). Although the etiology of HFpEF is most commonly related to long-standing hypertension and atherosclerosis, a significant number of suspected HFpEF patients have a restrictive cardiomyopathy or chronic pericardial disease. Recognizing these syndromes is important because early diagnosis may lead to instituting specific therapy that may prolong survival, improve quality of life, and/or recognize and treat an underlying systemic disorder. Advances in diagnostic imaging, biomarkers, and genetic testing today allow identification of the specific etiology in most cases. Novel pharmacological, immunologic, and surgical therapies are leading to improved quality of life and survival. PMID:27126534

  3. Alcoholic cardiomyopathy: Pathophysiologic insights

    PubMed Central

    Piano, Mariann R.; Phillips, Shane A.

    2014-01-01

    Alcoholic cardiomyopathy is a specific heart muscle disease found in individuals with a history of long-term heavy alcohol consumption. Alcoholic cardiomyopathy is associated with a number of adverse histological, cellular, and structural changes within the myocardium. Several mechanisms are implicated in mediating the adverse effects of ethanol, including the generation of oxidative stress, apoptotic cell death, impaired mitochondrial bioenergetics/stress, derangements in fatty acid metabolism and transport, and accelerated protein catabolism. In this review, we discuss the evidence for such mechanisms and present the potential importance of drinking patterns, genetic susceptibility, nutritional factors, race, and sex. The purpose of this review is to provide a mechanistic paradigm for future research in the area of alcoholic cardiomyopathy. PMID:24671642

  4. Dysferlin deficiency confers increased susceptibility to coxsackievirus-induced cardiomyopathy.

    PubMed

    Wang, Chen; Wong, Jerry; Fung, Gabriel; Shi, Junyan; Deng, Haoyu; Zhang, Jingchun; Bernatchez, Pascal; Luo, Honglin

    2015-10-01

    Coxsackievirus infection can lead to viral myocarditis and its sequela, dilated cardiomyopathy, which represent major causes of cardiovascular mortality worldwide in children. Yet, the host genetic susceptible factors and the underlying mechanisms by which viral infection damages cardiac function remain to be fully resolved. Dysferlin is a transmembrane protein highly expressed in skeletal and cardiac muscles. In humans, mutations in the dysferlin gene can cause limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Dysferlin deficiency has also been linked to cardiomyopathy. Defective muscle membrane repair has been suggested to be an important mechanism responsible for muscle degeneration in dysferlin-deficient patients and animals. Using both naturally occurring and genetically engineered dysferlin-deficient mice, we demonstrated that loss of dysferlin confers increased susceptibility to coxsackievirus infection and myocardial damage. More interestingly, we found that dysferlin is cleaved following coxsackieviral infection through the proteolytic activity of virally encoded proteinases, suggesting an important mechanism underlying virus-induced cardiac dysfunction. Our results in this study not only identify dysferlin deficiency as a novel host risk factor for viral myocarditis but also reveal a key mechanism by which coxsackievirus infection impairs cardiac function, leading to the development of dilated cardiomyopathy. PMID:26073173

  5. Cardiomyopathy Following Latrodectus Envenomation

    PubMed Central

    Levine, Michael; Canning, Josh; Chase, Robyn; Ruha, Anne-Michelle

    2010-01-01

    Latrodectus envenomations are common throughout the United States and the world. While many envenomations can result in catecholamine release with resultant hypertension and tachycardia, myocarditis is very rare. We describe a case of a 22-year-old male who sustained a Latrodectus envenomation complicated by cardiomyopathy. PMID:21293781

  6. Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes

    PubMed Central

    Akdis, Deniz; Brunckhorst, Corinna; Duru, Firat

    2016-01-01

    This overview gives an update on the molecular mechanisms, clinical manifestations, diagnosis and therapy of arrhythmogenic cardiomyopathy (ACM). ACM is mostly hereditary and associated with mutations in genes encoding proteins of the intercalated disc. Three subtypes have been proposed: the classical right-dominant subtype generally referred to as ARVC/D, biventricular forms with early biventricular involvement and left-dominant subtypes with predominant LV involvement. Typical symptoms include palpitations, arrhythmic (pre)syncope and sudden cardiac arrest due to ventricular arrhythmias, which typically occur in athletes. At later stages, heart failure may occur. Diagnosis is established with the 2010 Task Force Criteria (TFC). Modern imaging tools are crucial for ACM diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting functional and structural alternations. Of note, structural findings often become visible after electrical alterations, such as premature ventricular beats, ventricular fibrillation (VF) and ventricular tachycardia (VT). 12-lead ECG is important to assess for depolarisation and repolarisation abnormalities, including T-wave inversions as the most common ECG abnormality. Family history and the detection of causative mutations, mostly affecting the desmosome, have been incorporated in the TFC, and stress the importance of cascade family screening. Differential diagnoses include idiopathic right ventricular outflow tract (RVOT) VT, sarcoidosis, congenital heart disease, myocarditis, dilated cardiomyopathy, athlete’s heart, Brugada syndrome and RV infarction. Therapeutic strategies include restriction from endurance and competitive sports, β-blockers, antiarrhythmic drugs, heart failure medication, implantable cardioverter-defibrillators and endocardial/epicardial catheter ablation. PMID:27617087

  7. Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes.

    PubMed

    Akdis, Deniz; Brunckhorst, Corinna; Duru, Firat; Saguner, Ardan M

    2016-08-01

    This overview gives an update on the molecular mechanisms, clinical manifestations, diagnosis and therapy of arrhythmogenic cardiomyopathy (ACM). ACM is mostly hereditary and associated with mutations in genes encoding proteins of the intercalated disc. Three subtypes have been proposed: the classical right-dominant subtype generally referred to as ARVC/D, biventricular forms with early biventricular involvement and left-dominant subtypes with predominant LV involvement. Typical symptoms include palpitations, arrhythmic (pre)syncope and sudden cardiac arrest due to ventricular arrhythmias, which typically occur in athletes. At later stages, heart failure may occur. Diagnosis is established with the 2010 Task Force Criteria (TFC). Modern imaging tools are crucial for ACM diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting functional and structural alternations. Of note, structural findings often become visible after electrical alterations, such as premature ventricular beats, ventricular fibrillation (VF) and ventricular tachycardia (VT). 12-lead ECG is important to assess for depolarisation and repolarisation abnormalities, including T-wave inversions as the most common ECG abnormality. Family history and the detection of causative mutations, mostly affecting the desmosome, have been incorporated in the TFC, and stress the importance of cascade family screening. Differential diagnoses include idiopathic right ventricular outflow tract (RVOT) VT, sarcoidosis, congenital heart disease, myocarditis, dilated cardiomyopathy, athlete's heart, Brugada syndrome and RV infarction. Therapeutic strategies include restriction from endurance and competitive sports, β-blockers, antiarrhythmic drugs, heart failure medication, implantable cardioverter-defibrillators and endocardial/epicardial catheter ablation. PMID:27617087

  8. Angiogenesis and antifibrotic action by hepatocyte growth factor in cardiomyopathy.

    PubMed

    Taniyama, Yoshiaki; Morishita, Ryuichi; Aoki, Motokuni; Hiraoka, Kazuya; Yamasaki, Keita; Hashiya, Naotaka; Matsumoto, Kunio; Nakamura, Toshikazu; Kaneda, Yasufumi; Ogihara, Toshio

    2002-07-01

    Impairment of cardiac function in cardiomyopathy has been postulated to be related to decreased blood blow and increased collagen synthesis. Therefore, a therapeutic approach to alter the blood flow or fibrosis directly by means of growth factors may open a new therapeutic concept in dilated cardiomyopathy. From this viewpoint, hepatocyte growth factor (HGF) is a unique growth factor with antifibrosis and angiogenesis effects. Using the hereditary cardiomyopathic Syrian hamster as a model of genetically determined cardiomyopathy and heart failure, the effects of overexpression of HGF on fibrosis and microvascular dysfunction were examined. HGF gene or control vector was injected by the Hemagglutinating Virus of Japan-liposome method into the anterior heart of cardiomyopathic hamsters (Bio 14.6) under echocardiography once a week, from 12 to 20 weeks of age (total, 8 times). Blood flow, as assessed by a laser Doppler imager score, and the capillary density in hearts, as assessed by alkaline phosphatase staining, were significantly increased in hamsters transfected with HGF gene compared with control-vector-transfected hamsters (P<0.01). In contrast, the fibrotic area was significantly decreased in hamsters transfected with HGF gene compared with control (P<0.01). Overall, in vivo experiments demonstrated that transfection of HGF gene into the myocardium of cardiomyopathic hamsters stimulated blood flow through the induction of angiogenesis and reduction of fibrosis. These results suggest that HGF gene transfer may be useful to protect against myocardial injury in cardiomyopathy through its cardioprotective effects such as antifibrosis and angiogenesis actions. PMID:12105137

  9. Experimental models of inherited cardiomyopathy and its therapeutics

    PubMed Central

    Nonaka, Miki; Morimoto, Sachio

    2014-01-01

    Cardiomyopathy is a disease of myocardium categorized into three major forms, hypertrophic (HCM), dilated (DCM) and restrictive cardiomyopathy (RCM), which has recently been demonstrated to be a monogenic disease due to mutations in various proteins expressed in cardiomyocytes. Mutations in HCM and RCM typically increase the myofilament sensitivity to cytoplasmic Ca2+, leading to systolic hyperfunction and diastolic dysfunction. In contrast, mutations in DCM typically decrease the myofilament sensitivity to cytoplasmic Ca2+ and/or force generation/transmission, leading to systolic dysfunction. Creation of genetically-manipulated transgenic and knock-in animals expressing mutant proteins exogenously and endogenously, respectively, in their hearts provides valuable animal models to discover the molecular and cellular mechanisms for pathogenesis and promising therapeutic strategy in vivo. Recently, cardiomyocytes have been differentiated from patient’s induced pluripotent stem cells as a model of inherited cardiomyopathies in vitro. In this review, we provide overview of experimental models of cardiomyopathies with a focus on revealed molecular and cellular pathogenic mechanisms and potential therapeutics. PMID:25548614

  10. Decreased Levels of BAG3 in a Family with a Rare Variant and in Idiopathic Dilated Cardiomyopathy†

    PubMed Central

    Feldman, Arthur M.; Begay, Rene L.; Knezevic, Tijana; Myers, Valerie D.; Slavov, Dobromir B.; Zhu, Weizhong; Gowan, Katherine; Graw, Sharon L.; Jones, Kenneth L.; Tilley, Douglas G.; Coleman, Ryan C.; Walinsky, Paul; Cheung, Joseph Y.; Mestroni, Luisa; Khalili, Kamel; Taylor, Mathew R.G.

    2015-01-01

    The most common cause of dilated cardiomyopathy and heart failure (HF) is ischemic heart disease; however, in a third of all patients the cause remains undefined and patients are diagnosed as having idiopathic dilated cardiomyopathy (IDC). Recent studies suggest that many patients with IDC have a family history of HF and rare genetic variants in over 35 genes have been shown to be causative of disease. We employed whole-exome sequencing to identify the causative variant in a large family with autosomal dominant transmission of dilated cardiomyopathy. Sequencing and subsequent informatics revealed a novel 10-nucleotide deletion in the BCL2-associated athanogene 3 (BAG3) gene ((Ch10:del 121436332_12143641: del. 1266_1275 [NM 004281]) that segregated with all affected individuals. The deletion predicted a shift in the reading frame with the resultant deletion of 135 amino acids from the C-terminal end of the protein. Consistent with genetic variants in genes encoding other sarcomeric proteins there was a considerable amount of genetic heterogeneity in the affected family members. Interestingly, we also found that the levels of BAG3 protein were significantly reduced in the hearts from unrelated patients with end-stage HF undergoing cardiac transplantation when compared with non-failing controls. Diminished levels of BAG3 protein may be associated with both familial and non-familial forms of dilated cardiomyopathy. PMID:24623017

  11. Dilation and Curettage (D&C)

    MedlinePlus

    ... Advocacy For Patients About ACOG Dilation and Curettage (D&C) Home For Patients Search FAQs Dilation and ... FAQ062, February 2016 PDF Format Dilation and Curettage (D&C) Special Procedures What is dilation and curettage ( ...

  12. RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing

    PubMed Central

    Guo, Wei; Schafer, Sebastian; Greaser, Marion L.; Radke, Michael H.; Liss, Martin; Govindarajan, Thirupugal; Maatz, Henrike; Schulz, Herbert; Li, Shijun; Parrish, Amanda M.; Dauksaite, Vita; Vakeel, Padmanabhan; Klaassen, Sabine; Gerull, Brenda; Thierfelder, Ludwig; Regitz-Zagrosek, Vera; Hacker, Timothy A.; Saupe, Kurt W.; Dec, G. William; Ellinor, Patrick T.; MacRae, Calum A.; Spallek, Bastian; Fischer, Robert; Perrot, Andreas; Özcelik, Cemil; Saar, Kathrin; Hubner, Norbert; Gotthardt, Michael

    2013-01-01

    Alternative splicing plays a major role in the adaptation of cardiac function exemplified by the isoform switch of titin, which adjusts ventricular filling. We previously identified a rat strain deficient in titin splicing. Using genetic mapping, we found a loss-of-function mutation in RBM20 as the underlying cause for the pathological titin isoform expression. Mutations in human RBM20 have previously been shown to cause dilated cardiomyopathy. We showed that the phenotype of Rbm20 deficient rats resembles the human pathology. Deep sequencing of the human and rat cardiac transcriptome revealed an RBM20 dependent regulation of alternative splicing. Additionally to titin we identified a set of 30 genes with conserved regulation between human and rat. This network is enriched for genes previously linked to cardiomyopathy, ion-homeostasis, and sarcomere biology. Our studies emphasize the importance of posttranscriptional regulation in cardiac function and provide mechanistic insights into the pathogenesis of human heart failure. PMID:22466703

  13. An 'Omics' Perspective on Cardiomyopathies and Heart Failure.

    PubMed

    Raghow, Rajendra

    2016-09-01

    Pathological enlargement of the heart, represented by hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), occurs in response to many genetic and non-genetic factors. The clinical course of cardiac hypertrophy is remarkably variable, ranging from lifelong absence of symptoms to rapidly declining heart function and sudden cardiac death (SCD). Unbiased omics studies have begun to provide a glimpse into the molecular framework underpinning altered mechanotransduction, mitochondrial energetics, oxidative stress, and extracellular matrix in the heart undergoing physiological and pathological hypertrophy. Omics analyses indicate that post-transcriptional regulation of gene expression plays an overriding role in the normal and diseased heart. Studies to date highlight a need for more effective bioinformatics to better integrate patient omics data with their comprehensive clinical histories. PMID:27499035

  14. Pelvic Congestion Syndrome

    PubMed Central

    Durham, Janette D.; Machan, Lindsay

    2013-01-01

    Patients with pelvic congestion syndrome present with otherwise unexplained chronic pelvic pain that has been present for greater than 6 months, and anatomic findings that include pelvic venous insufficiency and pelvic varicosities. It remains an underdiagnosed explanation for pelvic pain in young, premenopausal, usually multiparous females. Symptoms include noncyclical, positional lower back, pelvic and upper thigh pain, dyspareunia, and prolonged postcoital discomfort. Symptoms worsen throughout the day and are exacerbated by activity or prolonged standing. Examination may reveal ovarian tenderness and unusual varicosities—vulvoperineal, posterior thigh, and gluteal. Diagnosis is suspected by clinical history and imaging that demonstrates pelvic varicosities. Venography is usually necessary to confirm ovarian vein reflux, although transvaginal ultrasound may be useful in documenting this finding. Endovascular therapy has been validated by several large patient series with long-term follow-up using standardized pain assessment surveys. Embolization has been shown to be significantly more effective than surgical therapy in improving symptoms in patients who fail hormonal therapy. Although there has been variation in approaches between investigators, the goal is elimination of ovarian vein reflux with or without direct sclerosis of enlarged pelvic varicosities. Symptom reduction is seen in 70 to 90% of the treated females despite technical variation. PMID:24436564

  15. Mechanistic Heterogeneity in Contractile Properties of α-Tropomyosin (TPM1) Mutants Associated with Inherited Cardiomyopathies*

    PubMed Central

    Gupte, Tejas M.; Haque, Farah; Gangadharan, Binnu; Sunitha, Margaret S.; Mukherjee, Souhrid; Anandhan, Swetha; Rani, Deepa Selvi; Mukundan, Namita; Jambekar, Amruta; Thangaraj, Kumarasamy; Sowdhamini, Ramanathan; Sommese, Ruth F.; Nag, Suman; Spudich, James A.; Mercer, John A.

    2015-01-01

    The most frequent known causes of primary cardiomyopathies are mutations in the genes encoding sarcomeric proteins. Among those are 30 single-residue mutations in TPM1, the gene encoding α-tropomyosin. We examined seven mutant tropomyosins, E62Q, D84N, I172T, L185R, S215L, D230N, and M281T, that were chosen based on their clinical severity and locations along the molecule. The goal of our study was to determine how the biochemical characteristics of each of these mutant proteins are altered, which in turn could provide a structural rationale for treatment of the cardiomyopathies they produce. Measurements of Ca2+ sensitivity of human β-cardiac myosin ATPase activity are consistent with the hypothesis that hypertrophic cardiomyopathies are hypersensitive to Ca2+ activation, and dilated cardiomyopathies are hyposensitive. We also report correlations between ATPase activity at maximum Ca2+ concentrations and conformational changes in TnC measured using a fluorescent probe, which provide evidence that different substitutions perturb the structure of the regulatory complex in different ways. Moreover, we observed changes in protein stability and protein-protein interactions in these mutants. Our results suggest multiple mechanistic pathways to hypertrophic and dilated cardiomyopathies. Finally, we examined a computationally designed mutant, E181K, that is hypersensitive, confirming predictions derived from in silico structural analysis. PMID:25548289

  16. Privacy-Sensitive Congestion Charging

    NASA Astrophysics Data System (ADS)

    Beresford, Alastair R.; Davies, Jonathan J.; Harle, Robert K.

    National-scale congestion charging schemes are increasingly viewed as the most viable long-term strategy for controlling congestion and maintaining the viability of the road network. In this paper we challenge the widely held belief that enforceable and economically viable congestion charging schemes require drivers to give up their location privacy to the government. Instead we explore an alternative scheme where privately-owned cars enforce congestion charge payments by using an on-board vehicle unit containing a camera and wireless communications. Our solution prevents centralised tracking of vehicle movements but raises an important issue: should we trust our neighbours with a little personal information in preference to entrusting it all to the government?

  17. Mutations in NEBL encoding the cardiac Z-disk protein nebulette are associated with various cardiomyopathies

    PubMed Central

    Tomasov, Pavol; Villard, Eric; Faludi, Reka; Melacini, Paola; Lossie, Janine; Lohmann, Nadine; Richard, Pascale; De Bortoli, Marzia; Angelini, Annalisa; Varga-Szemes, Akos; Sperling, Silke R.; Simor, Tamás; Veselka, Josef; Özcelik, Cemil; Charron, Philippe

    2016-01-01

    Introduction Transgenic mice overexpressing mutated NEBL, encoding the cardiac-specific Z-disk protein nebulette, develop severe cardiac phenotypes. Since cardiomyopathies are commonly familial and because mutations in a single gene may result in variable phenotypes, we tested the hypothesis that NEBL mutations are associated with cardiomyopathy. Material and methods We analyzed 389 patients, including cohorts of patients with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and left ventricular non-compaction cardiomyopathy (LVNC). The 28 coding exons of the NEBL gene were sequenced. Further bioinformatic analysis was used to distinguish variants. Results In total, we identified six very rare heterozygous missense mutations in NEBL in 7 different patients (frequency 1.8%) in highly conserved codons. The mutations were not detectable in 320 Caucasian sex-matched unrelated individuals without cardiomyopathy and 192 Caucasian sex-matched blood donors without heart disease. Known cardiomyopathy genes were excluded in these patients. The mutations p.H171R and p.I652L were found in 2 HCM patients. Further, p.Q581R and p.S747L were detected in 2 DCM patients, while the mutation p.A175T was identified independently in two unrelated patients with DCM. One LVNC patient carried the mutation p.P916L. All HCM and DCM related mutations were located in the nebulin-like repeats, domains responsible for actin binding. Interestingly, the mutation associated with LVNC was located in the C-terminal serine-rich linker region. Conclusions Our data suggest that NEBL mutations may cause various cardiomyopathies. We herein describe the first NEBL mutations in HCM and LVNC. Our findings underline the notion that the cardiomyopathies are true allelic diseases. PMID:27186169

  18. Oral amrinone for the treatment of chronic congestive heart failure: results of a multicenter randomized double-blind and placebo-controlled withdrawal study.

    PubMed

    DiBianco, R; Shabetai, R; Silverman, B D; Leier, C V; Benotti, J R

    1984-11-01

    A placebo-controlled study was employed to evaluate the effects of oral amrinone in patients with congestive heart failure. After a baseline period of at least 4 weeks of standard treatment for refractory congestive heart failure, oral amrinone was added to the treatment regimen of 173 patients. Patients were predominantly male (89%), aged 24 to 76 years (mean 54), with ischemic (52%) or idiopathic (37%) dilated cardiomyopathy, in New York Heart Association functional class II (40%), III (59%) and IV (1%) and having a mean (+/- standard deviation) left ventricular ejection fraction of 25 +/- 15%. Phase 1: After the addition of amrinone (113 +/- 33 mg three times daily), 52 patients (30%) showed a maximal increase in treadmill exercise time exceeding 2 minutes (Naughton protocol), 72 (42%) had a lesser increase, 24 (14%) developed limiting adverse reactions, 20 (12%) died and 5 dropped out of the study. Fifty-two "responders" (30%) who were free of limiting side effects and had a greater than 2 minute increase in exercise time were randomized in double-blind fashion to continued amrinone or switched to placebo (each plus standard treatment) for an additional 12 weeks. Phase 2: Comparison of 31 of these 52 responders who continued to receive amrinone with the remaining 21 randomized to placebo revealed no significant differences in vital signs, indexes of left ventricular size and function, systolic time intervals or maximal exercise time. Continued follow-up study of patients receiving either amrinone or placebo revealed decreases in exercise times of 7 and 10%, respectively (both p less than 0.05 compared with before randomization). Episodes of worsened congestive heart failure severe enough to mandate termination of double-blind treatment were as frequent in patients taking placebo (4[18%] of 21) as in those taking amrinone (4[13%] of 31; p = NS). The average symptom score and functional class of each treatment group remained comparable. Adverse effects such as

  19. Peripartum Cardiomyopathy: Current State of Knowledge, New Developments and Future Directions

    PubMed Central

    Biteker, Murat; Kayataş, Kadir; Duman, Dursun; Turkmen, Muhsin; Bozkurt, Biykem

    2014-01-01

    Peripartum cardiomyopathy (PPCM) is a form of idiopathic dilated cardiomyopathy affecting women in late pregnancy or early puerperium. Although initially described in the late 1800s, it has only recently been recognized as a distinct cardiac condition. The reported incidence and prognosis varies according to geography. The clinical course varies between complete recovery to rapid progression to chronic heart failure, heart transplantation or death. In spite of significant improvements in understanding the pathophysiology and management of the PPCM many features of this unique disease are poorly understood, including incidence, etiology, epidemiology, pathophysiology, predictors of prognosis and optimal therapy. The present article revisits these concepts and recent advances in PPCM. PMID:24646160

  20. The Emerging Role of Cardiovascular Magnetic Resonance Imaging in the Evaluation of Metabolic Cardiomyopathies.

    PubMed

    Mavrogeni, S; Markousis-Mavrogenis, G; Markussis, V; Kolovou, G

    2015-08-01

    The aim of this review is to discuss the role of Cardiovascular Magnetic Resonance (CMR) in the diagnosis, risk stratification, and follow-up of metabolic cardiomyopathies. The classification of myocardial diseases, proposed by WHO/ISFC task force, distinguished specific cardiomyopathies, caused by metabolic disorders, into 4 types: 1) endocrine disorders, 2) storage or infiltration disorders (amyloidosis, hemochromatosis and familial storage disorders), 3) nutritional disorders (Kwashiorkor, beri-beri, obesity, and alcohol), and 4) diabetic heart. Thyroid disease, pheochromocytoma, and growth hormone excess or deficiency may contribute to usually reversible dilated cardiomyopathy. Glucogen storage diseases can be presented with myopathy, liver, and heart failure. Lysosomal storage diseases can provoke cardiac hypertrophy, mimicking hypertrophic cardiomyopathy and arrhythmias. Hereditary hemochromatosis, an inherited disorder of iron metabolism, leads to tissue iron overload in different organs, including the heart. Cardiac amyloidosis is the result of amyloid deposition in the heart, formed from breakdown of normal or abnormal proteins that leads to increased heart stiffness, restrictive cardiomyopathy, and heart failure. Finally, nutritional disturbances and metabolic diseases, such as Kwashiorkor, beri-beri, obesity, alcohol consumption, and diabetes mellitus may also lead to severe cardiac dysfunction. CMR, through its capability to reliably assess anatomy, function, inflammation, rest-stress myocardial perfusion, myocardial fibrosis, aortic distensibility, iron and/or fat deposition can serve as an excellent tool for early diagnosis of heart involvement, risk stratification, treatment evaluation, and long term follow-up of patients with metabolic cardiomyopathies. PMID:26197853

  1. Role of left ventricular twist mechanics in cardiomyopathies, dance of the helices

    PubMed Central

    Kauer, Floris; Geleijnse, Marcel Leonard; van Dalen, Bastiaan Martijn

    2015-01-01

    Left ventricular twist is an essential part of left ventricular function. Nevertheless, knowledge is limited in “the cardiology community” as it comes to twist mechanics. Fortunately the development of speckle tracking echocardiography, allowing accurate, reproducible and rapid bedside assessment of left ventricular twist, has boosted the interest in this important mechanical aspect of left ventricular deformation. Although the fundamental physiological role of left ventricular twist is undisputable, the clinical relevance of assessment of left ventricular twist in cardiomyopathies still needs to be established. The fact remains; analysis of left ventricular twist mechanics has already provided substantial pathophysiological understanding on a comprehensive variety of cardiomyopathies. It has become clear that increased left ventricular twist in for example hypertrophic cardiomyopathy may be an early sign of subendocardial (microvascular) dysfunction. Furthermore, decreased left ventricular twist may be caused by left ventricular dilatation or an extensive myocardial scar. Finally, the detection of left ventricular rigid body rotation in noncompaction cardiomyopathy may provide an indispensible method to objectively confirm this difficult diagnosis. All this endorses the value of left ventricular twist in the field of cardiomyopathies and may further encourage the implementation of left ventricular twist parameters in the “diagnostic toolbox” for cardiomyopathies. PMID:26322187

  2. Bootstrapping Time Dilation Decoherence

    NASA Astrophysics Data System (ADS)

    Gooding, Cisco; Unruh, William G.

    2015-10-01

    We present a general relativistic model of a spherical shell of matter with a perfect fluid on its surface coupled to an internal oscillator, which generalizes a model recently introduced by the authors to construct a self-gravitating interferometer (Gooding and Unruh in Phys Rev D 90:044071, 2014). The internal oscillator evolution is defined with respect to the local proper time of the shell, allowing the oscillator to serve as a local clock that ticks differently depending on the shell's position and momentum. A Hamiltonian reduction is performed on the system, and an approximate quantum description is given to the reduced phase space. If we focus only on the external dynamics, we must trace out the clock degree of freedom, and this results in a form of intrinsic decoherence that shares some features with a proposed "universal" decoherence mechanism attributed to gravitational time dilation (Pikovski et al in Nat Phys, 2015). We note that the proposed decoherence remains present in the (gravity-free) limit of flat spacetime, emphasizing that the effect can be attributed entirely to proper time differences, and thus is not necessarily related to gravity. Whereas the effect described in (Pikovski et al in Nat Phys, 2015) vanishes in the absence of an external gravitational field, our approach bootstraps the gravitational contribution to the time dilation decoherence by including self-interaction, yielding a fundamentally gravitational intrinsic decoherence effect.

  3. Depression and congestive heart failure.

    PubMed

    Guck, Thomas P; Elsasser, Gary N; Kavan, Michael G; Barone, Eugene J

    2003-01-01

    The prevalence rates of depression in congestive heart failure patients range from 24%-42%. Depression is a graded, independent risk factor for readmission to the hospital, functional decline, and mortality in patients with congestive heart failure. Physicians can assess depression by using the SIG E CAPS + mood mnemonic, or any of a number of easily administered and scored self-report inventories. Cognitive-behavior therapy is the preferred psychological treatment. Cognitive-behavior therapy emphasizes the reciprocal interactions among physiology, environmental events, thoughts, and behaviors, and how these may be altered to produce changes in mood and behavior. Pharmacologically, the selective serotonin reuptake inhibitors are recommended, whereas the tricyclic antidepressants are not recommended for depression in congestive heart failure patients. The combination of a selective serotonin reuptake inhibitor with cognitive-behavior therapy is often the most effective treatment. PMID:12826775

  4. Fixed and dilated: the history of a classic pupil abnormality.

    PubMed

    Koehler, Peter J; Wijdicks, Eelco F M

    2015-02-01

    ) understood the relationship between increased ICP with pupil dilation and decreased pulse frequency and blood pressure, warning not to decrease the latter. Concentrating on experimental traumatic effects, Duret (1878) investigated compression and commotion, in which he distinguished two phases, notably pupil constriction by bulbar lesions, due to CSF shock, followed by dilation from congestion and inflammation, due to blood around the oculomotor nerve. The key observation of a fixed dilated pupil as a sign of acute mass effect came gradually and after some localization stumbles. Following the period of extensive experimental research in ICP, the results of which were translated to clinical observations, the prognostic significance was gradually acknowledged by authors of neurological textbooks. It is well known that Cushing did similar experiments in Berne (1900-1901), and later suggested he would not have done so if he had studied the literature. PMID:25415062

  5. Hypertrophic Cardiomyopathy: A Review

    PubMed Central

    Houston, Brian A; Stevens, Gerin R

    2014-01-01

    Hypertrophic cardiomyopathy (HCM) is a global disease with cases reported in all continents, affecting people of both genders and of various racial and ethnic origins. Widely accepted as a monogenic disease caused by a mutation in 1 of 13 or more sarcomeric genes, HCM can present catastrophically with sudden cardiac death (SCD) or ventricular arrhythmias or insidiously with symptoms of heart failure. Given the velocity of progress in both the fields of heart failure and HCM, we present a review of the approach to patients with HCM, with particular attention to those with HCM and the clinical syndrome of heart failure. PMID:25657602

  6. Cardiorespiratory and cardiovascular interactions in cardiomyopathy patients using joint symbolic dynamic analysis.

    PubMed

    Giraldo, Beatriz F; Rodriguez, Javier; Caminal, Pere; Bayes-Genis, Antonio; Voss, Andreas

    2015-01-01

    Cardiovascular diseases are the first cause of death in developed countries. Using electrocardiographic (ECG), blood pressure (BP) and respiratory flow signals, we obtained parameters for classifying cardiomyopathy patients. 42 patients with ischemic (ICM) and dilated (DCM) cardiomyopathies were studied. The left ventricular ejection fraction (LVEF) was used to stratify patients with low risk (LR: LVEF>35%, 14 patients) and high risk (HR: LVEF≤ 35%, 28 patients) of heart attack. RR, SBP and TTot time series were extracted from the ECG, BP and respiratory flow signals, respectively. The time series were transformed to a binary space and then analyzed using Joint Symbolic Dynamic with a word length of three, characterizing them by the probability of occurrence of the words. Extracted parameters were then reduced using correlation and statistical analysis. Principal component analysis and support vector machines methods were applied to characterize the cardiorespiratory and cardiovascular interactions in ICM and DCM cardiomyopathies, obtaining an accuracy of 85.7%. PMID:26736261

  7. Genetics of inherited cardiomyopathy

    PubMed Central

    Jacoby, Daniel; McKenna, William J.

    2012-01-01

    During the past two decades, numerous disease-causing genes for different cardiomyopathies have been identified. These discoveries have led to better understanding of disease pathogenesis and initial steps in the application of mutation analysis in the evaluation of affected individuals and their family members. As knowledge of the genetic abnormalities, and insight into cellular and organ biology has grown, so has appreciation of the level of complexity of interaction between genotype and phenotype across disease states. What were initially thought to be one-to-one gene-disease correlates have turned out to display important relational plasticity dependent in large part on the genetic and environmental backgrounds into which the genes of interest express. The current state of knowledge with regard to genetics of cardiomyopathy represents a starting point to address the biology of disease, but is not yet developed sufficiently to supplant clinically based classification systems or, in most cases, to guide therapy to any significant extent. Future work will of necessity be directed towards elucidation of the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype–phenotype relationship with the ultimate goal of furthering our ability to identify, diagnose, risk stratify, and treat this group of disorders which cause heart failure and sudden death in the young. PMID:21810862

  8. Limited Distribution of a Cardiomyopathy-Associated Variant in India

    PubMed Central

    Simonson, Tatum S.; Zhang, Yuhua; Huff, Chad D.; Xing, Jinchuan; Watkins, W. Scott; Witherspoon, David J.; Woodward, Scott R.; Jorde, Lynn B.

    2010-01-01

    Heart failure is a leading cause of death of people in South Asia, and cardiomyopathy is a major cause of heart failure. Myosin binding protein C (MYBPC3) is expressed in the heart muscle, where it regulates the cardiac response to adrenergic stimulation and is important for the structural integrity of the sarcomere. Mutations in the MYBPC3 gene are associated with hypertrophic or dilated cardiomyopathies. A 25-base-pair deletion in intron 32 causes skipping of the downstream exon and is associated with familial cardiomyopathy. To date, this deletion is found primarily in India and South Asia, although it is also found at low frequency in Southeast Asia. In order to better characterize the distribution of this variant, we determined its frequency in 447 individuals from 19 populations, including 10 populations from India and neighboring populations from Pakistan and Nepal. The deletion frequency is over 8% in some of our Indian samples, and it is not present in any of the populations we sampled outside of India. The differences in the deletion frequencies among populations in India are consistent with patterns of variation previously reported and with patterns we observed among Indian populations based on high-density SNP chip data. Our results indicate the MYBPC3 deletion is primarily found among Indian populations, and that its distribution is consistent with genome-wide patterns of variation in India. PMID:20201939

  9. Update on Myocarditis and Inflammatory Cardiomyopathy: Reemergence of Endomyocardial Biopsy.

    PubMed

    Dominguez, Fernando; Kühl, Uwe; Pieske, Burkert; Garcia-Pavia, Pablo; Tschöpe, Carsten

    2016-02-01

    Myocarditis is defined as an inflammatory disease of the heart muscle and is an important cause of acute heart failure, sudden death, and dilated cardiomyopathy. Viruses account for most cases of myocarditis or inflammatory cardiomyopathy, which could induce an immune response causing inflammation even when the pathogen has been cleared. Other etiologic agents responsible for myocarditis include drugs, toxic substances, or autoimmune conditions. In the last few years, advances in noninvasive techniques such as cardiac magnetic resonance have been very useful in supporting diagnosis of myocarditis, but toxic, infectious-inflammatory, infiltrative, or autoimmune processes occur at a cellular level and only endomyocardial biopsy can establish the nature of the etiological agent. Furthermore, after the generalization of immunohistochemical and viral genome detection techniques, endomyocardial biopsy provides a definitive etiological diagnosis that can lead to specific treatments such as antiviral or immunosuppressive therapy. Endomyocardial biopsy is not commonly performed for the diagnosis of myocarditis due to safety reasons, but both right- and left endomyocardial biopsies have very low complication rates when performed by experienced operators. This document provides a state-of-the-art review of myocarditis and inflammatory cardiomyopathy, with special focus on the role of endomyocardial biopsy to establish specific treatments. PMID:26795929

  10. Arrhythmogenic right ventricular cardiomyopathy, clinical manifestations, and diagnosis.

    PubMed

    Haugaa, Kristina H; Haland, Trine F; Leren, Ida S; Saberniak, Jørg; Edvardsen, Thor

    2016-07-01

    This review aims to give an update on the pathogenesis, clinical manifestations, and diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Arrhythmogenic right ventricular cardiomyopathy is mainly an autosomal dominant inherited disease linked to mutations in genes encoding desmosomes or desmosome-related proteins. Classic symptoms include palpitations, cardiac syncope, and aborted cardiac arrest due to ventricular arrhythmias. Heart failure may develop in later stages. Diagnosis is based on the presence of major and minor criteria from the Task Force Criteria revised in 2010 (TFC 2010), which includes evaluation of findings from six different diagnostic categories. Based on this, patients are classified as having possible, borderline, or definite ARVC. Imaging is important in ARVC diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting structural and functional abnormalities, but importantly these findings may occur after electrical alterations and ventricular arrhythmias. Electrocardiograms (ECGs) and signal-averaged ECGs are analysed for depolarization and repolarization abnormalities, including T-wave inversions as the most common ECG alteration. Ventricular arrhythmias are common in ARVC and are considered a major diagnostic criterion if originating from the RV inferior wall or apex. Family history of ARVC and detection of an ARVC-related mutation are included in the TFC 2010 and emphasize the importance of family screening. Electrophysiological studies are not included in the diagnostic criteria, but may be important for differential diagnosis including RV outflow tract tachycardia. Further differential diagnoses include sarcoidosis, congenital abnormalities, myocarditis, pulmonary hypertension, dilated cardiomyopathy, and athletic cardiac adaptation, which may mimic ARVC. PMID:26498164

  11. Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

    PubMed

    Armenian, Saro H; Hudson, Melissa M; Mulder, Renee L; Chen, Ming Hui; Constine, Louis S; Dwyer, Mary; Nathan, Paul C; Tissing, Wim J E; Shankar, Sadhna; Sieswerda, Elske; Skinner, Rod; Steinberger, Julia; van Dalen, Elvira C; van der Pal, Helena; Wallace, W Hamish; Levitt, Gill; Kremer, Leontien C M

    2015-03-01

    Survivors of childhood cancer treated with anthracycline chemotherapy or chest radiation are at an increased risk of developing congestive heart failure. In this population, congestive heart failure is well recognised as a progressive disorder, with a variable period of asymptomatic cardiomyopathy that precedes signs and symptoms. As a result, several clinical practice guidelines have been developed independently to help with detection and treatment of asymptomatic cardiomyopathy. These guidelines differ with regards to definitions of at-risk populations, surveillance modality and frequency, and recommendations for interventions. Differences between these guidelines could hinder the effective implementation of these recommendations. We report on the results of an international collaboration to harmonise existing cardiomyopathy surveillance recommendations using an evidence-based approach that relied on standardised definitions for outcomes of interest and transparent presentation of the quality of the evidence. The resultant recommendations were graded according to the quality of the evidence and the potential benefit gained from early detection and intervention. PMID:25752563

  12. "Playboy bunny" sign of congestive heart failure.

    PubMed

    Hokama, Akira; Arakaki, Shingo; Shibata, Daisuke; Maeshiro, Tatsuji; Kinjo, Fukunori; Fujita, Jiro

    2011-11-01

    In emergency, ultrasound has been widely used as a noninvasive and effective examination to evaluate congestive heart failure. We highlight "Playboy Bunny" sign as a reliable marker and an important clue to the diagnosis of passive hepatic congestion, caused by congestive heart failure. PMID:22224133

  13. A Review of the Giant Protein Titin in Clinical Molecular Diagnostics of Cardiomyopathies

    PubMed Central

    Gigli, Marta; Begay, Rene L.; Morea, Gaetano; Graw, Sharon L.; Sinagra, Gianfranco; Taylor, Matthew R. G.; Granzier, Henk; Mestroni, Luisa

    2016-01-01

    Titin (TTN) is known as the largest sarcomeric protein that resides within the heart muscle. Due to alternative splicing of TTN, the heart expresses two major isoforms (N2B and N2BA) that incorporate four distinct regions termed the Z-line, I-band, A-band, and M-line. Next-generation sequencing allows a large number of genes to be sequenced simultaneously and provides the opportunity to easily analyze giant genes such as TTN. Mutations in the TTN gene can cause cardiomyopathies, in particular dilated cardiomyopathy (DCM). DCM is the most common form of cardiomyopathy, and it is characterized by systolic dysfunction and dilation of the left ventricle. TTN truncating variants have been described as the most common cause of DCM, while the real impact of TTN missense variants in the pathogenesis of DCM is still unclear. In a recent population screening study, rare missense variants potentially pathogenic based on bioinformatic filtering represented only 12.6% of the several hundred rare TTN missense variants found, suggesting that missense variants are very common in TTN and are frequently benign. The aim of this review is to understand the clinical role of TTN mutations in DCM and in other cardiomyopathies. Whereas TTN truncations are common in DCM, there is evidence that TTN truncations are rare in the hypertrophic cardiomyopathy (HCM) phenotype. Furthermore, TTN mutations can also cause arrhythmogenic right ventricular cardiomyopathy (ARVC) with distinct clinical features and outcomes. Finally, the identification of a rare TTN missense variant cosegregating with the restrictive cardiomyopathy (RCM) phenotype suggests that TTN is a novel disease-causing gene in this disease. Clinical diagnostic testing is currently able to analyze over 100 cardiomyopathy genes, including TTN; however, the size and presence of extensive genetic variation in TTN presents clinical challenges in determining significant disease-causing mutations. This review discusses the current

  14. Treatment of feline asthma with ciclosporin in a cat with diabetes mellitus and congestive heart failure.

    PubMed

    Nafe, Laura A; Leach, Stacey B

    2015-12-01

    A 5-year-old domestic shorthair cat that had been previously diagnosed with diabetes mellitus was presented for episodes of coughing and respiratory distress. Diagnostic testing revealed congestive heart failure secondary to hypertrophic cardiomyopathy and concurrent asthma. All clinical signs and eosinophilic airway inflammation resolved with oral ciclosporin while the cat was concurrently receiving medications for treatment of heart failure (furosemide and enalapril). Ciclosporin should be considered for treatment of feline asthma in patients with concurrent diseases (eg, diabetes mellitus, severe heart disease) that may contraindicate use of oral glucocorticoid therapy. PMID:25527351

  15. Signalling and obfuscation for congestion control

    NASA Astrophysics Data System (ADS)

    Mareček, Jakub; Shorten, Robert; Yu, Jia Yuan

    2015-10-01

    We aim to reduce the social cost of congestion in many smart city applications. In our model of congestion, agents interact over limited resources after receiving signals from a central agent that observes the state of congestion in real time. Under natural models of agent populations, we develop new signalling schemes and show that by introducing a non-trivial amount of uncertainty in the signals, we reduce the social cost of congestion, i.e., improve social welfare. The signalling schemes are efficient in terms of both communication and computation, and are consistent with past observations of the congestion. Moreover, the resulting population dynamics converge under reasonable assumptions.

  16. Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model

    PubMed Central

    Martínez-Morentin, Leticia; Martínez, Lidia; Piloto, Sarah; Yang, Hua; Schon, Eric A.; Garesse, Rafael; Bodmer, Rolf; Ocorr, Karen; Cervera, Margarita; Arredondo, Juan J.

    2015-01-01

    The heart is a muscle with high energy demands. Hence, most patients with mitochondrial disease produced by defects in the oxidative phosphorylation (OXPHOS) system are susceptible to cardiac involvement. The presentation of mitochondrial cardiomyopathy includes hypertrophic, dilated and left ventricular noncompaction, but the molecular mechanisms involved in cardiac impairment are unknown. One of the most frequent OXPHOS defects in humans frequently associated with cardiomyopathy is cytochrome c oxidase (COX) deficiency caused by mutations in COX assembly factors such as Sco1 and Sco2. To investigate the molecular mechanisms that underlie the cardiomyopathy associated with Sco deficiency, we have heart specifically interfered scox expression, the single Drosophila Sco orthologue. Cardiac-specific knockdown of scox reduces fly lifespan, and it severely compromises heart function and structure, producing dilated cardiomyopathy. Cardiomyocytes with low levels of scox have a significant reduction in COX activity and they undergo a metabolic switch from OXPHOS to glycolysis, mimicking the clinical features found in patients harbouring Sco mutations. The major cardiac defects observed are produced by a significant increase in apoptosis, which is dp53-dependent. Genetic and molecular evidence strongly suggest that dp53 is directly involved in the development of the cardiomyopathy induced by scox deficiency. Remarkably, apoptosis is enhanced in the muscle and liver of Sco2 knock-out mice, clearly suggesting that cell death is a key feature of the COX deficiencies produced by mutations in Sco genes in humans. PMID:25792727

  17. Reversion of Severe Mitral Insufficiency in Peripartum Cardiomyopathy Using Levosimendan

    PubMed Central

    Nieto Estrada, Victor H.; Molano Franco, Daniel L.; Valencia Moreno, Albert Alexander; Rojas Gambasica, Jose A.; Jaller Bornacelli, Yamil E.; Martinez Del Valle, Anacaona

    2015-01-01

    Idiopathic peripartum cardiomyopathy presenting with heart failure is a true diagnostic and treatment challenge. Goal oriented clinical management aims at the relapse of left ventricular systolic dysfunction. A 35-year-old patient on her 12th day post-delivery presents progressive signs of heart failure. Transthoracic echocardiography showed severe mitral insufficiency, mild left ventricular dysfunction, mild tricuspid insufficiency, severe pulmonary hypertension, and right atrial enlargement. With wet and cold heart failure signs, the patient was a candidate for inodilator cardiovascular support and volume depletion therapy. As the patient presented a persistent tachycardia at rest, levosimendan was chosen over dobutamine. Levosimendan was administered at a dose of 0.2 µg/kg/min during a period of 24 hours. After inodilator therapy, the patient’s signs and symptoms of heart failure began to decrease, showing improvement of dyspnea, mitral murmur grade went from IV/IV to II/IV, filling pressures and systemic and pulmonary resistance indexes decreased, arterial blood gases improved, and an echocardiography performed 72 h later showed non-dilated cardiomyopathy, mild cardiac contractile dysfunction, mild mitral insufficiency, type I diastolic dysfunction and improvement of pulmonary hypertension. Cardiovascular function in peripartum cardiomyopathy tends to go back to normality in 23-41% of the cases, but in a large group of patients, severe ventricle dysfunction remains months after initial symptoms. This article describes the diagnostic process of a patient with peripartum cardiomyopathy and a successful reversion of a severe case of mitral insufficiency using levosimendan as a new therapeutic strategy in this clinical context. PMID:26566415

  18. MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

    PubMed

    Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

    2016-01-01

    Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders. PMID:26712328

  19. Atrial Remodeling and Atrial Tachyarrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy.

    PubMed

    Wu, Lingmin; Guo, Jinrui; Zheng, Lihui; Chen, Gang; Ding, Ligang; Qiao, Yu; Sun, Wei; Yao, Yan; Zhang, Shu

    2016-09-01

    Less is known about atrial remodeling and atrial tachyarrhythmias (ATa) in arrhythmogenic right ventricular cardiomyopathy (ARVC); this cross-sectional study aimed to determine the prevalence, characterization, and predictors of atrial remodeling and ATa in a large series of patients with ARVC. From February 2004 to September 2014, 294 consecutive patients who met the task force criteria for ARVC were enrolled. The prevalence, characterization, and predictors of atrial dilation and ATa were investigated. Right atrium (RA) dilation was identified in 160 patients (54.4%) and left atrium dilation in 66 patients (22.4%). Both RA and left atrium dilation were found in 44 patients (15.0%). Twenty-five patients (8.5%) had atrial fibrillation (AF), whereas 19 patients (6.5%) had atrial flutter (AFL). Of which, 7 patients (2.4%) had both AF and AFL. Multivariate analysis showed that AFL (odds ratio [OR] 10.309; 95% confidence interval [CI] 2.770 to 38.462; p <0.001), hypertension (OR 9.174; 95% CI 2.364 to 35.714; p = 0.001), and RA dilation (OR 6.993; 95% CI 1.623 to 30.303; p = 0.009) were associated with increased risk for AF. AF (OR 10.526; 95% CI 2.786 to 40.000; p = 0.001) increased the risk of AFL. In conclusion, atrial remodeling and ATa were common in patients with ARVC. PMID:27378141

  20. Dilatancy in Slow Granular Flows

    NASA Astrophysics Data System (ADS)

    Kabla, Alexandre J.; Senden, Tim J.

    2009-06-01

    When walking on wet sand, each footstep leaves behind a temporarily dry impression. This counterintuitive observation is the most common illustration of the Reynolds principle of dilatancy: that is, a granular packing tends to expand as it is deformed, therefore increasing the amount of porous space. Although widely called upon in areas such as soil mechanics and geotechnics, a deeper understanding of this principle is constrained by the lack of analytical tools to study this behavior. Using x-ray radiography, we track a broad variety of granular flow profiles and quantify their intrinsic dilatancy behavior. These measurements frame Reynolds dilatancy as a kinematic process. Closer inspection demonstrates, however, the practical importance of flow induced compaction which competes with dilatancy, leading more complex flow properties than expected.

  1. Dilatancy in slow granular flows.

    PubMed

    Kabla, Alexandre J; Senden, Tim J

    2009-06-01

    When walking on wet sand, each footstep leaves behind a temporarily dry impression. This counterintuitive observation is the most common illustration of the Reynolds principle of dilatancy: that is, a granular packing tends to expand as it is deformed, therefore increasing the amount of porous space. Although widely called upon in areas such as soil mechanics and geotechnics, a deeper understanding of this principle is constrained by the lack of analytical tools to study this behavior. Using x-ray radiography, we track a broad variety of granular flow profiles and quantify their intrinsic dilatancy behavior. These measurements frame Reynolds dilatancy as a kinematic process. Closer inspection demonstrates, however, the practical importance of flow induced compaction which competes with dilatancy, leading more complex flow properties than expected. PMID:19658906

  2. Myocardial Recovery in Peripartum Cardiomyopathy: Prospective Comparison with Recent Onset Cardiomyopathy in Men and Non-Peripartum Women

    PubMed Central

    Cooper, Leslie T.; Mather, Paul J.; Alexis, Jeffrey D.; Pauly, Daniel F.; Torre-Amione, Guillermo; Wittstein, Ilan S.; Dec, G. William; Zucker, Mark; Narula, Jagat; Kip, Kevin; McNamara, Dennis M.

    2011-01-01

    Background Whether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM), than in recent onset cardiomyopathies in men and non-peripartum women has not been prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry. Methods and Results IMAC 2 enrolled 373 subjects with recent onset non-ischemic dilated cardiomyopathy. LVEF was assessed at entry and six months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group1), non-peripartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23±0.08, 0.24±0.08, and 0.27±0.07 (p=0.04), and at six months was 0.39±0.12, 0.42±0.11, and 0.45±0.14 (p=0.007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, p=0.002). Conclusions Prospective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in non-peripartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by six months. PMID:22196838

  3. Molecular screening by polymerase chain reaction detects panleukopenia virus DNA in formalin-fixed hearts from cats with idiopathic cardiomyopathy and myocarditis.

    PubMed

    Meurs, K M; Fox, P R; Magnon, A L; Liu, S; Towbin, J A

    2000-01-01

    Viral myocarditis has been suggested as an etiology for cardiomyopathy in several mammalian species. Myocarditis and idiopathic cardiomyopathy have been reported in the domestic cat, although a viral etiology has not been demonstrated. Because of the continuing interest in the potential relationship between viral myocarditis and cardiomyopathy, we evaluated hearts from cats with spontaneous, idiopathic cardiomyopathy for viral genomic material within myocytes by polymerase chain reaction, and for the presence of myocarditis by light microscopy. Thirty-one (31) formalin-fixed hearts from domestic cats who died of idiopathic cardiomyopathy were randomly selected from pathology archives. Seventeen (17) formalin-fixed hearts from healthy cats were similarly selected as normal controls. The polymerase chain reaction (PCR) was used to evaluate myocardial tissue for the presence of viral genome from feline panleukopenia virus, herpes virus, calici virus, and corona virus. Hearts were examined using light microscopy for histologic evidence of myocarditis according to the Dallas criteria. Panleukopenia virus was identified by PCR in 10 of 31 cats with cardiomyopathy but in none of the controls. Neither cardiomyopathic or control cats tested positive by PCR for herpes virus, calici virus, and corona virus. Myocarditis was detected by histologic examination in 18 of 31 cardiomyopathic cats and in none of 17 control cats. Myocarditis and or feline panleukopenia virus genome was detected in felines with idiopathic hypertrophic, dilated, and restrictive cardiomyopathy, suggesting a possible role of viral infection and inflammation in the pathogenesis of cardiomyopathy in this species. PMID:10867362

  4. Cardiac Magnetic Resonance Imaging Might Complement Two-Dimensional Echocardiography in the Detection of a Reversible Nonischemic Cardiomyopathy

    PubMed Central

    Madanieh, Raef; Mathew, Shawn; Shah, Pratik; Vatti, Satya K.; Madanieh, Abed; Kosmas, Constantine E.; Vittorio, Timothy J.

    2015-01-01

    We report a case of reversible nonischemic dilated cardiomyopathy in a male in his 60s who presented with an acute heart failure syndrome. Both conventional two-dimensional echocardiography and cardiac magnetic resonance imaging (cMRI) demonstrated severe left ventricular systolic dysfunction; however, both modalities were devoid of significant valvular heart disease as well as the presence of fibrosis, infiltration, inflammation, and scar. After six months of aggressive neurohumoral modulation, there was complete reverse remodeling and normalization of left ventricular function, which highlights the role of cMRI as an adjunct to two-dimensional echocardiography in the detection of a potentially reversible nonischemic cardiomyopathy. PMID:26740746

  5. Dilatational band formation in bone

    PubMed Central

    Poundarik, Atharva A.; Diab, Tamim; Sroga, Grazyna E.; Ural, Ani; Boskey, Adele L.; Gundberg, Caren M.; Vashishth, Deepak

    2012-01-01

    Toughening in hierarchically structured materials like bone arises from the arrangement of constituent material elements and their interactions. Unlike microcracking, which entails micrometer-level separation, there is no known evidence of fracture at the level of bone’s nanostructure. Here, we show that the initiation of fracture occurs in bone at the nanometer scale by dilatational bands. Through fatigue and indentation tests and laser confocal, scanning electron, and atomic force microscopies on human and bovine bone specimens, we established that dilatational bands of the order of 100 nm form as ellipsoidal voids in between fused mineral aggregates and two adjacent proteins, osteocalcin (OC) and osteopontin (OPN). Laser microdissection and ELISA of bone microdamage support our claim that OC and OPN colocalize with dilatational bands. Fracture tests on bones from OC and/or OPN knockout mice (OC−/−, OPN−/−, OC-OPN−/−;−/−) confirm that these two proteins regulate dilatational band formation and bone matrix toughness. On the basis of these observations, we propose molecular deformation and fracture mechanics models, illustrating the role of OC and OPN in dilatational band formation, and predict that the nanometer scale of tissue organization, associated with dilatational bands, affects fracture at higher scales and determines fracture toughness of bone. PMID:23129653

  6. Reversible cardiomyopathy after radiofrequency ablation of 30-year persistent atrial tachycardia

    PubMed Central

    Suzuki, Atsushi; Shiga, Tsuyoshi; Arai, Kotaro; Shoda, Morio

    2013-01-01

    Tachycardia-induced cardiomyopathy (TIC) is a reversible form of the left ventricular (LV) systolic dysfunction and is believed to be a relatively acute process. We report a TIC case with a 30-year history of long-lasting persistent atrial tachycardia involving a 44-year-old man previously diagnosed with dilated cardiomyopathy and a low LV ejection fraction (LVEF) of 20%. ECG revealed atrial tachycardia at 110–120 bpm. He was hospitalised with a worsening heart failure. His clinical status was New York Heart Association functional class III, and echocardiography revealed LV dilation and an LVEF of 9%. A two-dimensional speckle-tracking strain measurement revealed LV mechanical dyssynchrony. He underwent radiofrequency ablation for atrial tachycardia. After restoring sinus rhythm, his cardiac symptoms improved immediately. The LV mechanical dyssynchrony decreased a week after ablation, without changes in the LV dilation or LVEF. Thereafter, the LV dilation and systolic function gradually improved, and atrial tachycardia and heart failure remained absent. PMID:24326427

  7. Genetics Home Reference: familial restrictive cardiomyopathy

    MedlinePlus

    ... CARDIOMYOPATHY, FAMILIAL RESTRICTIVE, 3 Sources for This Page Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi ... Sebire N, Ashworth M, Deanfield JE, McKenna WJ, Elliott PM. Idiopathic restrictive cardiomyopathy in children is caused ...

  8. Mitochondrial 12S ribosomal RNA A1555G mutation associated with cardiomyopathy and hearing loss following high-dose chemotherapy and repeated aminoglycoside exposure.

    PubMed

    Skou, Anne-Sofie; Tranebjærg, Lisbeth; Jensen, Tim; Hasle, Henrik

    2014-02-01

    A 19-month-old girl with the A1555G mitochondrial mutation in the 12S ribosomal RNA gene and acute myelogenous leukemia developed dilated cardiomyopathy and bilateral sensorineural hearing loss before undergoing allogeneic stem cell transplantation. She had received gentamicin during episodes of febrile neutropenia. Testing for the A1555G mutation is recommended in patients frequently treated with aminoglycosides. PMID:24252789

  9. Apoptosis in Heart Failure: Release of Cytochrome c from Mitochondria and Activation of Caspase-3 in Human Cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Narula, Jagat; Pandey, Pramod; Arbustini, Eloisa; Haider, Nezam; Narula, Navneet; Kolodgie, Frank D.; dal Bello, Barbara; Semigran, Marc J.; Bielsa-Masdeu, Anna; Dec, G. William; Israels, Sara; Ballester, Manel; Virmani, Renu; Saxena, Satya; Kharbanda, Surender

    1999-07-01

    Apoptosis has been shown to contribute to loss of cardiomyocytes in cardiomyopathy, progressive decline in left ventricular function, and congestive heart failure. Because the molecular mechanisms involved in apoptosis of cardiocytes are not completely understood, we studied the biochemical and ultrastructural characteristics of upstream regulators of apoptosis in hearts explanted from patients undergoing transplantation. Sixteen explanted hearts from patients undergoing heart transplantation were studied by electron microscopy or immunoblotting to detect release of mitochondrial cytochrome c and activation of caspase-3. The hearts explanted from five victims of motor vehicle accidents or myocardial ventricular tissues from three donor hearts were used as controls. Evidence of apoptosis was observed only in endstage cardiomyopathy. There was significant accumulation of cytochrome c in the cytosol, over myofibrils, and near intercalated discs of cardiomyocytes in failing hearts. The release of mitochondrial cytochrome c was associated with activation of caspase-3 and cleavage of its substrate protein kinase C δ but not poly(ADP-ribose) polymerase. By contrast, there was no apparent accumulation of cytosolic cytochrome c or caspase-3 activation in the hearts used as controls. The present study provides in vivo evidence of cytochrome c-dependent activation of cysteine proteases in human cardiomyopathy. Activation of proteases supports the phenomenon of apoptosis in myopathic process. Because loss of myocytes contributes to myocardial dysfunction and is a predictor of adverse outcomes in the patients with congestive heart failure, the present demonstration of an activated apoptotic cascade in cardiomyopathy could provide the basis for novel interventional strategies.

  10. Nitrendipine binding in congestive heart failure due to myocardial infarction

    SciTech Connect

    Dixon, I.M.; Lee, S.L.; Dhalla, N.S. )

    1990-03-01

    Depressed cardiac pump function is the hallmark of congestive heart failure, and it is suspected that decreased influx of Ca2+ into the cardiac cell is responsible for depressed contractile function. Since Ca2+ channels in the sarcolemmal membrane are considered to be an important route for the entry of Ca2+, we examined the status of Ca2+ receptors/channels in failing rat hearts after myocardial infarction of the left ventricular free wall. For this purpose, the left coronary artery was ligated and hearts were examined 4, 8, and 16 weeks later; sham-operated animals served as controls. Hemodynamic assessment revealed decreased total mechanical energy (left ventricular systolic pressure x heart rate), increased left ventricular diastolic pressure, and decreased positive and negative dP/dt in experimental animals at 4, 8, and 16 weeks. Although accumulation of ascites in the abdominal cavity was evident at 4 weeks, other clinical signs of congestive heart failure in experimental rats were evident from the presence of lung congestion and cardiac dilatation at 8 and 16 weeks after induction of myocardial infarction. The density of Ca2+ receptors/channels in crude membranes, as assessed by (3H)nitrendipine binding assay, was found to be decreased in the uninfarcted experimental left ventricle at 8 and 16 weeks; however, no change in the affinity of nitrendipine was evident. A similar depression in the specific binding of another dihydropyridine compound, (3H)PN200-110, was also evident in failing hearts. Brain and skeletal muscle crude membrane preparations, unlike those of the right ventricle and liver, revealed a decrease in Ca2+ receptors/channels density in experimental animals at 16 weeks.

  11. Targeted Next-Generation Sequencing Reveals Hot Spots and Doubly Heterozygous Mutations in Chinese Patients with Familial Cardiomyopathy

    PubMed Central

    Zhao, Yue; Feng, Yue; Zhang, Yun-Mei; Ding, Xiao-Xue; Song, Yu-Zhu; Zhang, A-Mei; Liu, Li; Zhang, Hong; Ding, Jia-Huan; Xia, Xue-Shan

    2015-01-01

    As a common cardiac disease mainly caused by gene mutations in sarcomeric cytoskeletal, calcium-handling, nuclear envelope, desmosomal, and transcription factor genes, inherited cardiomyopathy is becoming one of the major etiological factors of sudden cardiac death (SCD) and heart failure (HF). This disease is characterized by remarkable genetic heterogeneity, which makes it difficult to screen for pathogenic mutations using Sanger sequencing. In the present study, three probands, one with familial hypertrophic cardiomyopathy (FHCM) and two with familial dilated cardiomyopathy (FDCM), were recruited together with their respective family members. Using next-generation sequencing technology (NGS), 24 genes frequently known to be related to inherited cardiomyopathy were screened. Two hot spots (TNNI3-p.Arg145Gly, and LMNA-p.Arg190Trp) and double (LMNA-p.Arg190Trp plus MYH7-p.Arg1045His) heterozygous mutations were found to be highly correlated with familial cardiomyopathy. FDCM patients with doubly heterozygous mutations show a notably severe phenotype as we could confirm in our study; this indicates that the double mutations had a dose effect. In addition, it is proposed that genetic testing using NGS technology can be used as a cost-effective screening tool and help guide the treatment of patients with familial cardiomyopathy particularly regarding the risk of family members who are clinically asymptomatic. PMID:26199943

  12. Endothelial function in pre-pubertal children at risk of developing cardiomyopathy: a new frontier

    PubMed Central

    Tavares, Aline Cristina; Bocchi, Edimar Alcides; Guimarães, Guilherme Veiga

    2012-01-01

    Although it is known that obesity, diabetes, and Kawasaki's disease play important roles in systemic inflammation and in the development of both endothelial dysfunction and cardiomyopathy, there is a lack of data regarding the endothelial function of pre-pubertal children suffering from cardiomyopathy. In this study, we performed a systematic review of the literature on pre-pubertal children at risk of developing cardiomyopathy to assess the endothelial function of pre-pubertal children at risk of developing cardiomyopathy. We searched the published literature indexed in PubMed, Bireme and SciELO using the keywords ‘endothelial', ‘children', ‘pediatric' and ‘infant' and then compiled a systematic review. The end points were age, the pubertal stage, sex differences, the method used for the endothelial evaluation and the endothelial values themselves. No studies on children with cardiomyopathy were found. Only 11 papers were selected for our complete analysis, where these included reports on the flow-mediated percentage dilatation, the values of which were 9.80±1.80, 5.90±1.29, 4.50±0.70, and 7.10±1.27 for healthy, obese, diabetic and pre-pubertal children with Kawasaki's disease, respectively. There was no significant difference in the dilatation, independent of the endothelium, either among the groups or between the genders for both of the measurements in children; similar results have been found in adolescents and adults. The endothelial function in cardiomyopathic children remains unclear because of the lack of data; nevertheless, the known dysfunctions in children with obesity, type 1 diabetes and Kawasaki's disease may influence the severity of the cardiovascular symptoms, the prognosis, and the mortality rate. The results of this study encourage future research into the consequences of endothelial dysfunction in pre-pubertal children. PMID:22473410

  13. Congestion and cascades in payment systems.

    SciTech Connect

    Glass, Robert John, Jr.; Beyeler, Walter Eugene; Soramaki, Kimmo; Bech, Morten Linnemann

    2006-06-01

    We develop a parsimonious model of the interbank payment system to study congestion and the role of liquidity markets in alleviating congestion. The model incorporates an endogenous instruction arrival process, scale-free topology of payments between banks, fixed total liquidity that limits banks' capacity to process arriving instructions, and a global market that distributes liquidity. We find that at low liquidity, the system becomes congested and payment settlement loses correlation with payment instruction arrival, becoming coupled across the network. The onset of congestion is evidently related to the relative values of three characteristic times: the time for banks' net position to return to zero, the time for banks to exhaust their liquidity endowments, and the liquidity market relaxation time. In the congested regime, settlement takes place in cascades having a characteristic size. A global liquidity market substantially diminishes congestion, requiring only a small fraction of the payment-induced liquidity flow to achieve strong beneficial effects.

  14. Traffic congestion and dispersion in Hurricane evacuation

    NASA Astrophysics Data System (ADS)

    Tanaka, Katsunori; Nagatani, Takashi; Hanaura, Hirotoshi

    2007-03-01

    We study the traffic congestion and dispersion of vehicles occurring on a single lane highway in Hurricane evacuation. The traffic congestion depends on both sensitivity and speed of the leading vehicle. When the leading vehicle moves with low speed, the vehicular traffic exhibits the stop and go-wave (oscillating congested traffic) for low sensitivity, while the traffic results in the homogeneous congested traffic for high sensitivity. The traffic dispersion is measured by the time difference between the leading and rear vehicles. The time difference fluctuates highly for the oscillating congestion traffic, while it keeps a constant value for the homogeneous congested traffic. The traffic states in Hurricane evacuation is connected to the phase diagram of conventional traffic.

  15. Apoptosis in Anthracycline Cardiomyopathy

    PubMed Central

    Shi, Jianjian; Abdelwahid, Eltyeb; Wei, Lei

    2011-01-01

    Apoptosis is a tightly regulated physiologic process of programmed cell death that occurs in both normal and pathologic tissues. Numerous in vitro or in vivo studies have indicated that cardiomyocyte death through apoptosis and necrosis is a primary contributor to the progression of anthracycline-induced cardiomyopathy. There are now several pieces of evidence to suggest that activation of intrinsic and extrinsic apoptotic pathways contribute to anthracycline-induced apoptosis in the heart. Novel strategies were developed to address a wide variety of cardiotoxic mechanisms and apoptotic pathways by which anthracycline influences cardiac structure and function. Anthracycline-induced apoptosis provides a very valid representation of cardiotoxicity in the heart, an argument which has implications for the most appropriate animal models of damaged heart plus diverse pharmacological effects. In this review we describe various aspects of the current understanding of apoptotic cell death triggered by anthracycline. Differences in the sensitivity to anthracycline-induced apoptosis between young and adult hearts are also discussed. PMID:22212952

  16. Pathogenesis of Arrhythmogenic Cardiomyopathy.

    PubMed

    Asimaki, Angeliki; Kleber, Andre G; Saffitz, Jeffrey E

    2015-11-01

    Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease. It is characterized by frequent ventricular arrhythmias and increased risk of sudden cardiac death typically arising as an early manifestation before the onset of significant myocardial remodelling. Myocardial degeneration, often confined to the right ventricular free wall, with replacement by fibrofatty scar tissue, develops in many patients. ACM is a familial disease but genetic penetrance can be low and disease expression is highly variable. Inflammation might promote disease progression. It also appears that exercise increases disease penetrance and accelerates its development. More than 60% of probands harbour mutations in genes that encode desmosomal proteins, which has raised the possibility that defective cell-cell adhesion might play a role in disease pathogenesis. Recent advances have implicated changes in the canonical wingless-type mouse mammary tumour virus integration site (Wnt)/β-catenin and Hippo signalling pathways and defects in forwarding trafficking of ion channels and other proteins to the intercalated disk in cardiac myocytes. In this review we summarize the current understanding of the pathogenesis of ACM and highlight future research directions. PMID:26199027

  17. Sepsis-induced Cardiomyopathy

    PubMed Central

    Romero-Bermejo, Francisco J; Ruiz-Bailen, Manuel; Gil-Cebrian, Julián; Huertos-Ranchal, María J

    2011-01-01

    Myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to 70%. During the sepsis-induced myocardial dysfunction, both ventricles can dilate and diminish its ejection fraction, having less response to fluid resuscitation and catecholamines, but typically is assumed to be reversible within 7-10 days. In the last 30 years, It´s being subject of substantial research; however no explanation of its etiopathogenesis or effective treatment have been proved yet. The aim of this manuscript is to review on the most relevant aspects of the sepsis-induced myocardial dysfunction, discuss its clinical presentation, pathophysiology, etiopathogenesis, diagnostic tools and therapeutic strategies proposed in recent years. PMID:22758615

  18. High Resolution Systematic Digital Histological Quantification of Cardiac Fibrosis and Adipose Tissue in Phospholamban p.Arg14del Mutation Associated Cardiomyopathy

    PubMed Central

    Gho, Johannes M. I. H.; van Es, René; Stathonikos, Nikolas; Harakalova, Magdalena; te Rijdt, Wouter P.; Suurmeijer, Albert J. H.; van der Heijden, Jeroen F.; de Jonge, Nicolaas; Chamuleau, Steven A. J.; de Weger, Roel A.; Asselbergs, Folkert W.; Vink, Aryan

    2014-01-01

    Myocardial fibrosis can lead to heart failure and act as a substrate for cardiac arrhythmias. In dilated cardiomyopathy diffuse interstitial reactive fibrosis can be observed, whereas arrhythmogenic cardiomyopathy is characterized by fibrofatty replacement in predominantly the right ventricle. The p.Arg14del mutation in the phospholamban (PLN) gene has been associated with dilated cardiomyopathy and recently also with arrhythmogenic cardiomyopathy. Aim of the present study is to determine the exact pattern of fibrosis and fatty replacement in PLN p.Arg14del mutation positive patients, with a novel method for high resolution systematic digital histological quantification of fibrosis and fatty tissue in cardiac tissue. Transversal mid-ventricular slices (n = 8) from whole hearts were collected from patients with the PLN p.Arg14del mutation (age 48±16 years; 4 (50%) male). An in-house developed open source MATLAB script was used for digital analysis of Masson's trichrome stained slides (http://sourceforge.net/projects/fibroquant/). Slides were divided into trabecular, inner and outer compact myocardium. Per region the percentage of connective tissue, cardiomyocytes and fatty tissue was quantified. In PLN p.Arg14del mutation associated cardiomyopathy, myocardial fibrosis is predominantly present in the left posterolateral wall and to a lesser extent in the right ventricular wall, whereas fatty changes are more pronounced in the right ventricular wall. No difference in distribution pattern of fibrosis and adipocytes was observed between patients with a clinical predominantly dilated and arrhythmogenic cardiomyopathy phenotype. In the future, this novel method for quantifying fibrosis and fatty tissue can be used to assess cardiac fibrosis and fatty tissue in animal models and a broad range of human cardiomyopathies. PMID:24732829

  19. External nasal dilators: definition, background, and current uses

    PubMed Central

    Dinardi, Ricardo Reis; de Andrade, Cláudia Ribeiro; Ibiapina, Cássio da Cunha

    2014-01-01

    Our goal was to revise the literature about external nasal dilators (ENDs) as to their definition, history, and current uses. We reviewed journals in the PubMed and MEDLINE databases. The current uses hereby presented and discussed are physical exercise, nasal congestion and sleep, snoring, pregnancy, cancer, and healthy individuals. Numerous studies have shown that ENDs increase the cross-sectional area of the nasal valve, reducing nasal resistance and transnasal inspiratory pressure and stabilizing the lateral nasal vestibule, avoiding its collapse during final inspiration. These effects also facilitate breathing and are beneficial to patients with nasal obstruction. Furthermore, END use is simple, noninvasive, painless, affordable, and bears minimum risk to the user. Most studies have limited sample size and are mainly focused on physical exercise. In conclusion, ENDs seem useful, so further studies involving potential effects on the performance of physical tests and improvements in sleep quality are necessary, especially in children and teenagers. PMID:25419156

  20. Focal nodular hyperplasia with major sinusoidal dilatation: a misleading entity

    PubMed Central

    Laumonier, Hervé; Frulio, Nora; Laurent, Christophe; Balabaud, Charles; Zucman-Rossi, Jessica; Bioulac-Sage, Paulette

    2010-01-01

    Focal nodular hyperplasia (FNH) is a benign liver lesion thought to be a non-specific response to locally increased blood flow. Although the diagnosis of FNH and hepatocellular adenoma (HCA) has made great progress over the last few years using modern imaging techniques, there are still in daily practice some difficulties concerning some atypical nodules. Here, the authors report the case of a 47-year-old woman with a single liver lesion thought to be, by imaging, an inflammatory HCA with major sinusoidal congestion. This nodule was revealed to be, at the microscopical level and after specific immunostaining and molecular analysis, an FNH with sinusoidal dilatation (so-called telangiectatic focal nodular hyperplasia). PMID:22798311

  1. Late systolic click in non-obstructive cardiomyopathy

    PubMed Central

    Mercer, Edward N.; Frye, Robert L.; Giuliani, Emilio R.

    1970-01-01

    Two patients with seriously impaired left ventricular function, abnormal left ventricular conduction on the electrocardiogram, mitral regurgitation, and a very late systolic click are reported. Idiopathic non-obstructive cardiomyopathy seemed to be the cause of the left ventricular dysfunction in both cases. The mitral valve was anatomically normal at the time of operation in one patient, except for dilatation of the annulus, and the mitral regurgitation appeared to be secondary to left ventricular failure. The very late timing of the mitral systolic clicks in these two patients may be related to a large left ventricular end-diastolic volume and impaired left ventricular function, or to an abnormal sequence of excitation of the left ventricle. The timing of the late systolic click in these patients is in contrast to that in patients with mid systolic clicks, hearts of normal size, and little cardiac disability. Images PMID:5470052

  2. Recent advances in diagnosis and management of hypertrophic cardiomyopathy

    PubMed Central

    Siswanto, B B; Aryani, R

    2009-01-01

    Hypertrophic cardiomyopathy (HCM) is characterised by a thickened but non-dilated left ventricle in the absence of another cardiac or systemic condition capable of producing the magnitude of hypertrophy evident. It is the most common familial genetic disease of the heart (1/500 to 1/1000), as well as the most common cause of sudden cardiac death in young people and athletes. Survival rates of patients with HCM have improved from the 1960s onwards. Natural history in patients with HCM might vary from developing severe heart failure or atrial fibrillation, some die suddenly, often at a young age and in the absence of previous symptoms. Because of its heterogeneous clinical course and expression, HCM frequently presents uncertainty and represents a management dilemma to cardiovascular specialists and other practitioners.

  3. Renin-angiotensin-aldosterone-kinin system influences on diabetic vascular disease and cardiomyopathy.

    PubMed

    Flack, J M; Hamaty, M; Staffileno, B A

    1998-01-01

    Diabetes mellitus is associated with an inordinately high risk of virtually all manifestations of cardiovascular-renal disease including atherosclerotic coronary and peripheral vascular disease, congestive heart failure, stroke, nephropathy, and cardiomyopathy unassociated with coronary heart disease. Abnormalities in the renin-angiotensin-aldosterone-kinin (RAAK) cascade have been implicated in the pathogenesis and clinical expression of these cardiovascular-renal sequelae. Thus, pharmacological modulation of the RAAK system is an attractive therapeutic target in diabetes mellitus. Indeed, emerging data from human clinical studies appear to confirm this thesis. PMID:9930381

  4. Congestion in different topologies of traffic networks

    NASA Astrophysics Data System (ADS)

    Wu, J. J.; Gao, Z. Y.; Sun, H. J.; Huang, H. J.

    2006-05-01

    In the present paper, we consider three different types of networks (random, small-world, and scale-free) with dynamic weights and focus on how the characteristic parameters (degree distribution exponent, rewiring probability, and clustering coefficient) affect the degree of congestion and the efficiency. Experiment simulation shows that the scale-free and small-world networks are more prone to suffering from congestion than random ones at low traffic flows, but the scale-free network is more sensitive than the small-world one. Compared with other two topologies, the scale-free network, while its congestion factor rises slowly, can support much more volume of traffic as the traffic flow increases. Results also indicate that for the same value of congestion factor, there may be a different efficiency, which shows that only congestion or efficiency alone cannot evaluate the performance of networks effectively.

  5. Simultaneous interstitial pneumonitis and cardiomyopathy induced by venlafaxine* **

    PubMed Central

    Ferreira, Pedro Gonçalo; Costa, Susana; Dias, Nuno; Ferreira, António Jorge; Franco, Fátima

    2014-01-01

    Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used as an antidepressant. Interindividual variability and herb-drug interactions can lead to drug-induced toxicity. We report the case of a 35-year-old female patient diagnosed with synchronous pneumonitis and acute cardiomyopathy attributed to venlafaxine. The patient sought medical attention due to dyspnea and dry cough that started three months after initiating treatment with venlafaxine for depression. The patient was concomitantly taking Centella asiatica and Fucus vesiculosus as phytotherapeutic agents. Chest CT angiography and chest X-ray revealed parenchymal lung disease (diffuse micronodules and focal ground-glass opacities) and simultaneous dilated cardiomyopathy. Ecocardiography revealed a left ventricular ejection fraction (LVEF) of 21%. A thorough investigation was carried out, including BAL, imaging studies, autoimmune testing, right heart catheterization, and myocardial biopsy. After excluding other etiologies and applying the Naranjo Adverse Drug Reaction Probability Scale, a diagnosis of synchronous pneumonitis/cardiomyopathy associated with venlafaxine was assumed. The herbal supplements taken by the patient have a known potential to inhibit cytochrome P450 enzyme complex, which is responsible for the metabolization of venlafaxine. After venlafaxine discontinuation, there was rapid improvement, with regression of the radiological abnormalities and normalization of the LVEF. This was an important case of drug-induced cardiopulmonary toxicity. The circumstantial intake of inhibitors of the CYP2D6 isoenzyme and the presence of a CYP2D6 slow metabolism phenotype might have resulted in the toxic accumulation of venlafaxine and the subsequent clinical manifestations. Here, we also discuss why macrophage-dominant phospholipidosis was the most likely mechanism of toxicity in this case. PMID:25029655

  6. Physiological growth synergizes with pathological genes in experimental cardiomyopathy.

    PubMed

    Syed, Faisal; Odley, Amy; Hahn, Harvey S; Brunskill, Eric W; Lynch, Roy A; Marreez, Yehia; Sanbe, Atsushi; Robbins, Jeffrey; Dorn, Gerald W

    2004-12-10

    Hundreds of signaling molecules have been assigned critical roles in the pathogenesis of myocardial hypertrophy and heart failure based on cardiac phenotypes from alpha-myosin heavy chain-directed overexpression mice. Because permanent ventricular transgene expression in this system begins during a period of rapid physiological neonatal growth, resulting phenotypes are the combined consequences of transgene effects and normal trophic influences. We used temporally-defined forced gene expression to investigate synergy between postnatal physiological cardiac growth and two functionally divergent cardiomyopathic genes. Phenotype development was compared various times after neonatal (age 2 to 3 days) and adult (age 8 weeks) expression. Proapoptotic Nix caused ventricular dilation and severe contractile depression in neonates, but not adults. Myocardial apoptosis was minimal in adults, but was widespread in neonates, until it spontaneously resolved in adulthood. Unlike normal postnatal cardiac growth, concurrent left ventricular pressure overload hypertrophy did not synergize with Nix expression to cause cardiomyopathy or myocardial apoptosis. Prohypertrophic Galphaq likewise caused eccentric hypertrophy, systolic dysfunction, and pathological gene expression in neonates, but not adults. Thus, normal postnatal cardiac growth can be an essential cofactor in development of genetic cardiomyopathies, and may confound the interpretation of conventional alpha-MHC transgenic phenotypes. PMID:15539635

  7. [Congestive heart failure in patients with chronic kidney disease].

    PubMed

    Poskurica, Mileta; Petrović, Dejan

    2014-01-01

    Cardiovascular disorders are the most frequent cause of death (46-60%) among patients with advanced chronic renal failure (CRF), and on dialysis treatment. Uremic cardiomyopathy is the basic pathophysiologic substrate, whereas ischemic heart disease (IHD) and anemia are the most important contributing factors. Associated with well-know risk factors and specific disorders for terminal kidney failure and dialysis, the aforementioned factors instigate congestive heart failure (CHF). Suspected CHF is based on the anamnesis, clinical examination and ECG, while it is confirmed and defined more precisely on the basis of echocardiography and radiology examination. Biohumoral data (BNP, NT-proBNP) are not sufficiently reliable because of specific volemic fluctuation and reduced natural clearance. Therapy approach is similar to the one for the general population: ACEI, ARBs, β-blockers, inotropic drugs and diuretics. Hypervolemia and most of the related symptoms can be kept under control effectively by the isolated or ultrafiltation, in conjunction with dialysis, during the standard bicarbonate hemodialysis or hemodiafiltration. In the same respect peritoneal dialysis is efficient for the control of hypervolemia symptoms, mainly during the first years of its application and in case of the lower NYHA class (II°/III°). In general, heart support therapy, surgical interventions of the myocardium and valve replacement are rarely used in patients on dialysis, whereas revascularization procedures are beneficial for associated IHD. In selected cases the application of cardiac resynchronization and/or implantation of a cardioverter defibrillator are advisable. PMID:25731010

  8. What Is a Comprehensive Dilated Eye Exam?

    MedlinePlus

    ... su oculista What is a comprehensive dilated eye exam? You may think your eyes are healthy, but ... eye care professional for a comprehensive dilated eye exam is the only way to really be sure. ...

  9. Assessing a murmur, saving a life: current trends in the management of hypertrophic cardiomyopathy.

    PubMed

    Katz, J R; Krafft, P; Fox, K

    1996-11-01

    Hypertrophic cardiomyopathy, formerly called idiopathic hypertrophic subaortic stenosis (IHSS), is the leading cause of sudden cardiac death in young people. Hypertrophic cardiomyopathy is a non-dilated cardiomyopathy primarily affecting the left ventricle, left atria, intraventricular septum, and mitral valve. It is an autosomal dominant genetic disorder that impairs diastolic and systolic function. Diagnosis is complex due to the heterogeneity of the disease. Symptoms and morphology are not always related and clinical signs may be absent or limited to a soft systolic murmur. The first symptom of hypertrophic cardiomyopathy is frequently sudden cardiac death. Echocardiogram is an accurate diagnostic tool. Asymptomatic patients are generally not treated. Treatment for symptomatic patients begins with beta or calcium channel blockers. Antiarrhythmics may be added to protect against sudden cardiac death. Surgical intervention is done if other treatments fall and involves removal of a portion of the obstructive septum. Operative mortality is 5% with a 60% reduction in symptoms. A promising alternative to surgery is dual-chamber pacemakers. Patient and family teaching is the emphasis of long-term management. PMID:8933537

  10. Dimethyl α-ketoglutarate inhibits maladaptive autophagy in pressure overload-induced cardiomyopathy.

    PubMed

    Mariño, Guillermo; Pietrocola, Federico; Kong, Yongli; Eisenberg, Tobias; Hill, Joseph A; Madeo, Frank; Kroemer, Guido

    2014-05-01

    It has been a longstanding problem to identify specific and efficient pharmacological modulators of autophagy. Recently, we found that depletion of acetyl-coenzyme A (AcCoA) induced autophagic flux, while manipulations designed to increase cytosolic AcCoA efficiently inhibited autophagy. Thus, the cell permeant ester dimethyl α-ketoglutarate (DMKG) increased the cytosolic concentration of α-ketoglutarate, which was converted into AcCoA through a pathway relying on either of the 2 isocitrate dehydrogenase isoforms (IDH1 or IDH2), as well as on ACLY (ATP citrate lyase). DMKG inhibited autophagy in an IDH1-, IDH2- and ACLY-dependent fashion in vitro, in cultured human cells. Moreover, DMKG efficiently prevented autophagy induced by starvation in vivo, in mice. Autophagy plays a maladaptive role in the dilated cardiomyopathy induced by pressure overload, meaning that genetic inhibition of autophagy by heterozygous knockout of Becn1 suppresses the pathological remodeling of heart muscle responding to hemodynamic stress. Repeated administration of DMKG prevents autophagy in heart muscle responding to thoracic aortic constriction (TAC) and simultaneously abolishes all pathological and functional correlates of dilated cardiomyopathy: hypertrophy of cardiomyocytes, fibrosis, dilation of the left ventricle, and reduced contractile performance. These findings indicate that DMKG may be used for therapeutic autophagy inhibition. PMID:24675140

  11. Divergent Mitochondrial Biogenesis Responses in Human Cardiomyopathy

    PubMed Central

    Ahuja, Preeti; Wanagat, Jonathan; Wang, Zhihua; Wang, Yibin; Liem, David A.; Ping, Peipei; Antoshechkin, Igor A.; Margulies, Kenneth B.; MacLellan, W. Robb

    2014-01-01

    Background Mitochondria are key players in the development and progression of heart failure (HF). Mitochondrial (mt) dysfunction leads to diminished energy production and increased cell death contributing to the progression of left ventricular (LV) failure. The fundamental mechanisms that underlie mt dysfunction in HF have not been fully elucidated. Methods and Results To characterize mt morphology, biogenesis and genomic integrity in human HF, we investigated LV tissue from non-failing (NF) hearts and end-stage ischemic (ICM) or dilated (DCM) cardiomyopathic hearts. Although mt dysfunction was present in both types of cardiomyopathy, mt were smaller and increased in number in DCM compared to ICM or NF hearts. Mt volume density and mtDNA copy number was increased by ~2-fold (P<0.001) in DCM hearts in comparison to ICM hearts. These changes were accompanied by an increase in the expression of mtDNA-encoded genes in DCM versus no change in ICM. mtDNA repair and antioxidant genes were reduced in failing hearts suggestive of a defective repair and protection system, which may account for the 4.1-fold increase in mtDNA deletion mutations in DCM (P<0.05 vs NF hearts, P<0.05 vs ICM). Conclusions In DCM, mt dysfunction is associated with mtDNA damage and deletions, which could be a consequence of mutating stress coupled with a PGC-1α-dependent stimulus for mt biogenesis. However, this maladaptive compensatory response contributes to additional oxidative damage. Thus, our findings support further investigations into novel mechanisms and therapeutic strategies for mt dysfunction in DCM. PMID:23589024

  12. Network congestion analysis of gravity generated models

    NASA Astrophysics Data System (ADS)

    Maniadakis, Dimitris; Varoutas, Dimitris

    2014-07-01

    The network topology has lately proved to be critical to the appearance of traffic congestion, with scale-free networks being the less affected at high volumes of traffic. Here, the congestion dynamics are investigated for a class of networks that has experienced a resurgence of interest, the networks based on the gravity model. In addition, supplementary to the standard paradigm of uniform traffic volumes between randomly interacting node pairs, more realistic gravity traffic patterns are used to simulate the flows in the network. Results indicate that depending on the traffic pattern, the networks have different tolerance to congestion. Experiment simulation shows that the topologies created on the basis of the gravity model suffer less from congestion than the random, the scale-free or the Jackson-Rogers ones under both random and gravity traffic patterns. The congestion level is found to be approximately correlated with the network clustering coefficient in the case of random traffic, whereas in the case of gravity traffic such a correlation is not a trivial one. Other basic network properties such as the average shortest path and the diameter are seen to correlate fairly well with the congestion level. Further investigation on the adjustment of the gravity model parameters indicates particular sensitivity to network congestion. This work may have practical implications for designing traffic networks with both reasonable budget and good performance.

  13. Treatment of congestion in upper respiratory diseases

    PubMed Central

    Meltzer, Eli O; Caballero, Fernan; Fromer, Leonard M; Krouse, John H; Scadding, Glenis

    2010-01-01

    Congestion, as a symptom of upper respiratory tract diseases including seasonal and perennial allergic rhinitis, acute and chronic rhinosinusitis, and nasal polyposis, is principally caused by mucosal inflammation. Though effective pharmacotherapy options exist, no agent is universally efficacious; therapeutic decisions must account for individual patient preferences. Oral H1-antihistamines, though effective for the common symptoms of allergic rhinitis, have modest decongestant action, as do leukotriene receptor antagonists. Intranasal antihistamines appear to improve congestion better than oral forms. Topical decongestants reduce congestion associated with allergic rhinitis, but local adverse effects make them unsuitable for long-term use. Oral decongestants show some efficacy against congestion in allergic rhinitis and the common cold, and can be combined with oral antihistamines. Intranasal corticosteroids have broad anti-inflammatory activities, are the most potent long-term pharmacologic treatment of congestion associated with allergic rhinitis, and show some congestion relief in rhinosinusitis and nasal polyposis. Immunotherapy and surgery may be used in some cases refractory to pharmacotherapy. Steps in congestion management include (1) diagnosis of the cause(s), (2) patient education and monitoring, (3) avoidance of environmental triggers where possible, (4) pharmacotherapy, and (5) immunotherapy (for patients with allergic rhinitis) or surgery for patients whose condition is otherwise uncontrolled. PMID:20463825

  14. Stress cardiomyopathy: yet another type of neurocardiogenic injury: 'stress cardiomyopathy'.

    PubMed

    Wybraniec, Maciej; Mizia-Stec, Katarzyna; Krzych, Lukasz

    2014-01-01

    Tako-tsubo syndrome pertains to rare acquired cardiomyopathies, characterized by left ventricular dyskinesia and symptomatology typical for acute myocardial infarction (AMI). Despite its low incidence and relatively benign course, stress cardiomyopathy should be thoroughly differentiated from AMI. The importance of tako-tsubo consists of the fact that its manifestation initially resembles AMI. Despite seemingly low incidence of tako-tsubo, acute coronary syndromes globally constitute a major epidemiological issue and both clinical entities should be accurately differentiated. Many patients present with only mild troponin release, certain extent of regional wall motion abnormalities (RWMA) and absence of hemodynamically significant coronary artery stenosis. In such instances, a careful interview aimed at preceding emotional or physical traumatic event should be undertaken. The subsequent verification of the diagnosis is based upon prompt recovery of contractile function. Although precise diagnostic criteria were formulated, symptomatology of tako-tsubo might be clinically misleading due to the possibility of concomitant coronary vasospasm, atypical pattern of RWMA and presence of non-significant coronary disease. For this reason, its exact rate might be underestimated. Stress cardiomyopathy reflects merely a single aspect of a much wider range of neurocardiogenic injury, which encompasses cardiac dysfunction associated with subarachnoid hemorrhage, intracranial hypertension and cerebral ischemia. Both psychological and physical insult to central nervous system may trigger a disastrous response of sympathetic nervous system, eventually leading to end-organ catecholamine-mediated damage. This review sought to delineate the phenomenon of tako-tsubo cardiomyopathy and deliver evidence for common pathophysiology of the broad spectrum of neurocardiogenic injury. PMID:24462197

  15. Multisensory signalling enhances pupil dilation.

    PubMed

    Rigato, Silvia; Rieger, Gerulf; Romei, Vincenzo

    2016-01-01

    Detecting and integrating information across the senses is an advantageous mechanism to efficiently respond to the environment. In this study, a simple auditory-visual detection task was employed to test whether pupil dilation, generally associated with successful target detection, could be used as a reliable measure for studying multisensory integration processing in humans. We recorded reaction times and pupil dilation in response to a series of visual and auditory stimuli, which were presented either alone or in combination. The results indicated faster reaction times and larger pupil diameter to the presentation of combined auditory and visual stimuli than the same stimuli when presented in isolation. Moreover, the responses to the multisensory condition exceeded the linear summation of the responses obtained in each unimodal condition. Importantly, faster reaction times corresponded to larger pupil dilation, suggesting that also the latter can be a reliable measure of multisensory processes. This study will serve as a foundation for the investigation of auditory-visual integration in populations where simple reaction times cannot be collected, such as developmental and clinical populations. PMID:27189316

  16. Multisensory signalling enhances pupil dilation

    PubMed Central

    Rigato, Silvia; Rieger, Gerulf; Romei, Vincenzo

    2016-01-01

    Detecting and integrating information across the senses is an advantageous mechanism to efficiently respond to the environment. In this study, a simple auditory-visual detection task was employed to test whether pupil dilation, generally associated with successful target detection, could be used as a reliable measure for studying multisensory integration processing in humans. We recorded reaction times and pupil dilation in response to a series of visual and auditory stimuli, which were presented either alone or in combination. The results indicated faster reaction times and larger pupil diameter to the presentation of combined auditory and visual stimuli than the same stimuli when presented in isolation. Moreover, the responses to the multisensory condition exceeded the linear summation of the responses obtained in each unimodal condition. Importantly, faster reaction times corresponded to larger pupil dilation, suggesting that also the latter can be a reliable measure of multisensory processes. This study will serve as a foundation for the investigation of auditory-visual integration in populations where simple reaction times cannot be collected, such as developmental and clinical populations. PMID:27189316

  17. Identification of the Syrian hamster cardiomyopathy gene.

    PubMed

    Nigro, V; Okazaki, Y; Belsito, A; Piluso, G; Matsuda, Y; Politano, L; Nigro, G; Ventura, C; Abbondanza, C; Molinari, A M; Acampora, D; Nishimura, M; Hayashizaki, Y; Puca, G A

    1997-04-01

    The BIO14.6 hamster is a widely used model for autosomal recessive cardiomyopathy. These animals die prematurely from progressive myocardial necrosis and heart failure. The primary genetic defect leading to the cardiomyopathy is still unknown. Recently, a genetic linkage map localized the cardiomyopathy locus on hamster chromosome 9qa2.1-b1, excluding several candidate genes. We now demonstrate that the cardiomyopathy results from a mutation in the delta-sarcoglycan gene that maps to the disease locus. This mutation was completely coincident with the disease in backcross and F2 pedigrees. This constitutes the first animal model identified for human sarcoglycan disorders. PMID:9097966

  18. Modeling the pressure-dilatation correlation

    NASA Technical Reports Server (NTRS)

    Sarkar, S.

    1991-01-01

    It is generally accepted that pressure dilatation, which is an additional compressibility term in turbulence transport equations, may be important for high speed flows. Recent direct simulations of homogeneous shear turbulence have given concrete evidence that the pressure dilatation is important insofar that it contributes to the reduced growth of turbulent kinetic energy due to compressibility effects. The problem of modeling pressure dilatation is addressed. A component of the pressure dilatation is isolated which exhibits temporal oscillations and, using direct numerical simulations of homogeneous shear turbulence and isotropic turbulence, show that it has a negligible contribution to the evolution of turbulent kinetic energy. Then, an analysis for the case of homogeneous turbulence is performed to obtain a model for the nonoscillatory pressure dilatation. This model algebraically relates the pressure dilatation to quantities traditionally obtained in incompressible turbulence closures. The model is validated by direct comparison with the pressure dilatation data obtained from the simulations.

  19. Primary Carnitine Deficiency and Cardiomyopathy

    PubMed Central

    Fu, Lijun; Huang, Meirong

    2013-01-01

    Carnitine is essential for the transfer of long-chain fatty acids from the cytosol into mitochondria for subsequent β-oxidation. A lack of carnitine results in impaired energy production from long-chain fatty acids, especially during periods of fasting or stress. Primary carnitine deficiency (PCD) is an autosomal recessive disorder of mitochondrial β-oxidation resulting from defective carnitine transport and is one of the rare treatable etiologies of metabolic cardiomyopathies. Patients affected with the disease may present with acute metabolic decompensation during infancy or with severe cardiomyopathy in childhood. Early recognition of the disease and treatment with L-carnitine may be life-saving. In this review article, the pathophysiology, clinical presentation, diagnosis, treatment and prognosis of PCD are discussed, with a focus on cardiac involvements. PMID:24385988

  20. Atomoxetine-related Takotsubo Cardiomyopathy.

    PubMed

    Naguy, Ahmed; Al-Mutairi, Haya; Al-Tajali, Ali

    2016-05-01

    Many psychotropic medications target norepinephrine receptors, which can have serious cardiovascular implications, especially in the context of overdoses, polypharmacy, and high-risk populations. This article presents the case of a patient with adult attention-deficit/hyperactivity disorder who developed takotsubo cardiomyopathy subsequent to pharmacokinetic and pharmacodynamic interactions between atomoxetine, a selective norepinephrine reuptake inhibitor, and fluoxetine. Clinicians should be mindful of the potential for cardiovascular adverse effects when prescribing agents that target noradrenergic receptors. PMID:27123802

  1. Balloon dilator versus telescopic metal dilators for tract dilatation during percutaneous nephrolithotomy for staghorn stones and calyceal stones

    PubMed Central

    El-Shazly, Mohamed; Salem, Shady; Allam, Adel; Hathout, Badawy

    2015-01-01

    Objective To compare the results of balloon dilatation (BD) vs. telescopic metal dilators (TMDs) in establishing the tract for percutaneous nephrolithotomy (PCNL) in patients with calyceal stones or staghorn stones, but with no hydronephrosis. Patients and methods Data from selected patients over 4 years were recorded retrospectively. Patients with complex staghorn stones, an undilated targeted calyx, or the stone filling the targeted calyx, were included in the study. In all, 97 patients were included, of 235 undergoing PCNL between March 2010 and March 2014, and were divided into two groups according to the technique of primary tract dilatation. Group A included patients who had BD and group B those treated using TMDs. Results In group A (BD, 55 patients) dilatation was successful in 34 (62%). The dilatation failed or there was a need for re-dilatation using TMD in 21 patients (38%). In one of these 21 patients the dilatation failed due to extravasation. In group B (TMD, 42 patients) dilatation was successful in 38 (90%) patients, with incomplete dilatation and a need for re-dilatation in four (10%) patients, and no failed procedures. Group A had a significantly higher failure rate than group B (P < 0.001). Differences in operative duration, blood loss, stone-removal success rate and complication rate were statistically insignificant. Conclusion BD has a higher failure rate than TMD when establishing access for calyceal stones or staghorn stones that have little space around them. PMID:26413325

  2. Traffic congestion in interconnected complex networks

    NASA Astrophysics Data System (ADS)

    Tan, Fei; Wu, Jiajing; Xia, Yongxiang; Tse, Chi K.

    2014-06-01

    Traffic congestion in isolated complex networks has been investigated extensively over the last decade. Coupled network models have recently been developed to facilitate further understanding of real complex systems. Analysis of traffic congestion in coupled complex networks, however, is still relatively unexplored. In this paper, we try to explore the effect of interconnections on traffic congestion in interconnected Barabási-Albert scale-free networks. We find that assortative coupling can alleviate traffic congestion more readily than disassortative and random coupling when the node processing capacity is allocated based on node usage probability. Furthermore, the optimal coupling probability can be found for assortative coupling. However, three types of coupling preferences achieve similar traffic performance if all nodes share the same processing capacity. We analyze interconnected Internet autonomous-system-level graphs of South Korea and Japan and obtain similar results. Some practical suggestions are presented to optimize such real-world interconnected networks accordingly.

  3. Understanding congested travel in urban areas.

    PubMed

    Çolak, Serdar; Lima, Antonio; González, Marta C

    2016-01-01

    Rapid urbanization and increasing demand for transportation burdens urban road infrastructures. The interplay of number of vehicles and available road capacity on their routes determines the level of congestion. Although approaches to modify demand and capacity exist, the possible limits of congestion alleviation by only modifying route choices have not been systematically studied. Here we couple the road networks of five diverse cities with the travel demand profiles in the morning peak hour obtained from billions of mobile phone traces to comprehensively analyse urban traffic. We present that a dimensionless ratio of the road supply to the travel demand explains the percentage of time lost in congestion. Finally, we examine congestion relief under a centralized routing scheme with varying levels of awareness of social good and quantify the benefits to show that moderate levels are enough to achieve significant collective travel time savings. PMID:26978719

  4. Understanding congested travel in urban areas

    PubMed Central

    Çolak, Serdar; Lima, Antonio; González, Marta C.

    2016-01-01

    Rapid urbanization and increasing demand for transportation burdens urban road infrastructures. The interplay of number of vehicles and available road capacity on their routes determines the level of congestion. Although approaches to modify demand and capacity exist, the possible limits of congestion alleviation by only modifying route choices have not been systematically studied. Here we couple the road networks of five diverse cities with the travel demand profiles in the morning peak hour obtained from billions of mobile phone traces to comprehensively analyse urban traffic. We present that a dimensionless ratio of the road supply to the travel demand explains the percentage of time lost in congestion. Finally, we examine congestion relief under a centralized routing scheme with varying levels of awareness of social good and quantify the benefits to show that moderate levels are enough to achieve significant collective travel time savings. PMID:26978719

  5. Understanding congested travel in urban areas

    NASA Astrophysics Data System (ADS)

    Çolak, Serdar; Lima, Antonio; González, Marta C.

    2016-03-01

    Rapid urbanization and increasing demand for transportation burdens urban road infrastructures. The interplay of number of vehicles and available road capacity on their routes determines the level of congestion. Although approaches to modify demand and capacity exist, the possible limits of congestion alleviation by only modifying route choices have not been systematically studied. Here we couple the road networks of five diverse cities with the travel demand profiles in the morning peak hour obtained from billions of mobile phone traces to comprehensively analyse urban traffic. We present that a dimensionless ratio of the road supply to the travel demand explains the percentage of time lost in congestion. Finally, we examine congestion relief under a centralized routing scheme with varying levels of awareness of social good and quantify the benefits to show that moderate levels are enough to achieve significant collective travel time savings.

  6. Mitochondrial myopathy, cardiomyopathy, and pontine signal changes in an adult patient with isolated complex II deficiency.

    PubMed

    Sonam, Kothari; Bindu, Parayil Sankaran; Taly, Arun B; Nalini, Atchayaram; Govindaraju, Chikkanna; Aravinda, Hanumanthapura R; Khan, Nahid Akthar; Thangaraj, Kumaraswamy; Gayathri, Narayanappa

    2014-12-01

    Mitochondrial disorders resulting from an isolated deficiency of complex II of the respiratory chain is rarely reported. The phenotypic spectrum associated with these disorders is heterogeneous and still expanding. This report describes a patient who presented with myopathy, dilated cardiomyopathy, and pontine signal changes on magnetic resonance imaging. Muscle biopsy showed total absence of succinate dehydrogenase on enzyme histochemistry, negative succinate dehydrogenase subunit A (SDHA) activity on immunohistochemistry, and ultrastructural evidence of mitochondrial aggregates of varying sizes confirming the diagnosis of complex II deficiency. A unique phenotype with complex II deficiency is reported. PMID:25415517

  7. Acute cardiomyopathy and multiorgan failure in a patient with pheochromocytoma and neurofibromatosis type 1.

    PubMed

    Ahmed, Rezwan; Darrat, Yousef; Hamoudeh, Eyad; Elhamdani, Mehair Omar; Yaqub, Abid

    2014-02-01

    Pheochromocytomas are catecholamine secreting tumours of the adrenal gland, discovered in 0.1% of patients with hypertension. Our case highlights an atypical presentation of pheochromocytoma in a patient with Neurofibromatosis type 1 who developed cardiogenic shock with multi-organ failure. The patient demonstrated reversible dilated cardiomyopathy during her hospital stay, and her blood pressure fluctuated widely. Discovery of right adrenal mass followed by biochemical testing facilitated the diagnosis. Judicious medical management led to an uneventful surgical removal of the tumour followed by marked stabilization of her blood pressure. We discuss the characteristics of pheochromocytoma associated with Neurofibromatosis type 1 via reversible cardiac dysfunction. PMID:24640818

  8. Skeletal muscle involvement in cardiomyopathies.

    PubMed

    Limongelli, Giuseppe; D'Alessandro, Raffaella; Maddaloni, Valeria; Rea, Alessandra; Sarkozy, Anna; McKenna, William J

    2013-12-01

    The link between heart and skeletal muscle disorders is based on similar molecular, anatomical and clinical features, which are shared by the 'primary' cardiomyopathies and 'primary' neuromuscular disorders. There are, however, some peculiarities that are typical of cardiac and skeletal muscle disorders. Skeletal muscle weakness presenting at any age may indicate a primary neuromuscular disorder (associated with creatine kinase elevation as in dystrophinopathies), a mitochondrial disease (particularly if encephalopathy, ocular myopathy, retinitis, neurosensorineural deafness, lactic acidosis are present), a storage disorder (progressive exercise intolerance, cognitive impairment and retinitis pigmentosa, as in Danon disease), or metabolic disorders (hypoglycaemia, metabolic acidosis, hyperammonaemia or other specific biochemical abnormalities). In such patients, skeletal muscle weakness usually precedes the cardiomyopathy and dominates the clinical picture. Nevertheless, skeletal involvement may be subtle, and the first clinical manifestation of a neuromuscular disorder may be the occurrence of heart failure, conduction disorders or ventricular arrhythmias due to cardiomyopathy. ECG and echocardiogram, and eventually, a more detailed cardiovascular evaluation may be required to identify early cardiac involvement. Paediatric and adult cardiologists should be proactive in screening for neuromuscular and related disorders to enable diagnosis in probands and evaluation of families with a focus on the identification of those at risk of cardiac arrhythmia and emboli who may require specific prophylactic treatments, for example, pacemaker, implantable cardioverter-defibrillator and anticoagulation. PMID:24149064

  9. [Cirrhotic cardiomyopathy: a specific entity].

    PubMed

    Brondex, A; Arlès, F; Lipovac, A-S; Richecoeur, M; Bronstein, J-A

    2012-04-01

    Cirrhosis is a frequent and severe condition, which is the late stage of numerous chronic liver diseases. It is associated with major hemodynamic alterations characteristic of hyperdynamic circulation and with a series of structural, functional, electrophysiological and biological heart abnormalities termed cirrhotic cardiomyopathy. The pathogenesis of this syndrome is multifactorial. It is usually clinically latent or mild, likely because the peripheral vasodilatation significantly reduces the left ventricle afterload. However, sudden changes of hemodynamic state (vascular filling, surgical or transjugular intrahepatic porto-systemic shunts, peritoneo-venous shunts and orthotopic liver transplantation) or myocardial contractility (introduction of beta-blocker therapy) can unmask its presence, and sometimes convert latent to overt heart failure. Cirrhotic cardiomyopathy may also contribute to the pathogenesis of hepatorenal syndrome. This entity has been described recently, and its diagnostic criteria are still under debate. To date, current management recommendations are empirical, nonspecific measures. Recognition of cirrhotic cardiomyopathy depends on a high level of awareness for the presence of this syndrome, particularly in patients with advanced cirrhosis who undergo significant surgical, pharmacological or physiological stresses. PMID:22115174

  10. Cardiomyopathies and the Armed Forces.

    PubMed

    Holdsworth, D A; Cox, A T; Boos, C; Hardman, R; Sharma, S

    2015-09-01

    Cardiomyopathies are a group of heterogeneous myocardial diseases that are frequently inherited and are a recognised cause of premature sudden cardiac death in young individuals. Incomplete expressions of disease and the overlap with the physiological cardiac manifestations of regular intensive exercise create diagnostic challenges in young athletes and military recruits. Early identification is important because sudden death in the absence of prodromal symptoms is a common presentation, and there are several therapeutic strategies to minimise this risk. This paper examines the classification and clinical features of cardiomyopathies with specific reference to a military population and provides a detailed account of the optimum strategy for diagnosis, indications for specialist referral and specific guidance on the occupational significance of cardiomyopathy. A 27-year-old Lance Corporal Signaller presents to his Regimental medical officer (RMO) after feeling 'light-headed' following an 8 mile unloaded run. While waiting to see the RMO, the medical sergeant records a 12-lead ECG. The ECG is reviewed by the RMO immediately prior to the consultation and shows voltage criteria for left ventricular (LV) hypertrophy and inverted T-waves in II, III, aVF and V1-V3 (Figure 1). This Lance Corporal is a unit physical training instructor and engages in >10 h of aerobic exercise per week. He is a non-smoker and does not have any significant medical history. PMID:26246349

  11. Recommendations for Cardiomyopathy Surveillance for Survivors of Childhood Cancer: A Report from the International Late Effects of Childhood Cancer Guideline Harmonization Group

    PubMed Central

    Armenian, Saro H.; Hudson, Melissa M.; Mulder, Renee L.; Chen, Ming Hui; Constine, Louis S.; Dwyer, Mary; Nathan, Paul C.; Tissing, Wim J.E.; Shankar, Sadhna; Sieswerda, Elske; Skinner, Rod; Steinberger, Julia; van Dalen, Elvira C.; van der Pal, Helena; Wallace, W. Hamish; Levitt, Gill; Kremer, Leontien C.M.

    2015-01-01

    Childhood cancer survivors treated with anthracycline chemotherapy or chest radiation are at an increased risk of developing congestive heart failure (CHF). In this population, CHF is well-recognized as a progressive disorder, with a variable period of asymptomatic cardiomyopathy which precedes signs and symptoms. As a result, a number of practice guidelines have been developed to facilitate detection and treatment of asymptomatic cardiomyopathy. These guidelines differ with regards to definitions of at risk populations, surveillance modality and frequency, and recommendations for interventions. These differences may hinder the effective implementation of these recommendations. We report on the results of an international collaboration to harmonize existing cardiomyopathy surveillance recommendations, using an evidence-based approach that relied on standardized definitions for outcomes of interest and transparent presentation of the quality of the evidence. The resultant recommendations were graded according to the quality of the evidence and the potential benefit gained from early detection and intervention. PMID:25752563

  12. Focus on renal congestion in heart failure

    PubMed Central

    Afsar, Baris; Ortiz, Alberto; Covic, Adrian; Solak, Yalcin; Goldsmith, David; Kanbay, Mehmet

    2016-01-01

    Hospitalizations due to heart failure are increasing steadily despite advances in medicine. Patients hospitalized for worsening heart failure have high mortality in hospital and within the months following discharge. Kidney dysfunction is associated with adverse outcomes in heart failure patients. Recent evidence suggests that both deterioration in kidney function and renal congestion are important prognostic factors in heart failure. Kidney congestion in heart failure results from low cardiac output (forward failure), tubuloglomerular feedback, increased intra-abdominal pressure or increased venous pressure. Regardless of the cause, renal congestion is associated with increased morbidity and mortality in heart failure. The impact on outcomes of renal decongestion strategies that do not compromise renal function should be explored in heart failure. These studies require novel diagnostic markers that identify early renal damage and renal congestion and allow monitoring of treatment responses in order to avoid severe worsening of renal function. In addition, there is an unmet need regarding evidence-based therapeutic management of renal congestion and worsening renal function. In the present review, we summarize the mechanisms, diagnosis, outcomes, prognostic markers and treatment options of renal congestion in heart failure. PMID:26798459

  13. Antarctic analog for dilational bands on Europa

    NASA Astrophysics Data System (ADS)

    Hurford, T. A.; Brunt, K. M.

    2014-09-01

    Europa's surface shows signs of extension, which is revealed as lithospheric dilation expressed along ridges, dilational bands and ridged bands. Ridges, the most common tectonic feature on Europa, comprise a central crack flanked by two raised banks a few hundred meters high on each side. Together these three classes may represent a continuum of formation. In Tufts' Dilational Model ridge formation is dominated by daily tidal cycling of a crack, which can be superimposed with regional secular dilation. The two sources of dilation can combine to form the various band morphologies observed. New GPS data along a rift on the Ross Ice Shelf, Antarctica is a suitable Earth analog to test the framework of Tufts' Dilational Model. As predicted by Tufts' Dilational Model, tensile failures in the Ross Ice Shelf exhibit secular dilation, upon which a tidal signal can be seen. From this analog we conclude that Tufts' Dilational Model for Europan ridges and bands may be credible and that the secular dilation is most likely from a regional source and not tidally driven.

  14. Antarctic Analog for Dilational Bands on Europa

    NASA Technical Reports Server (NTRS)

    Hurford, T. A.; Brunt, K. M.

    2014-01-01

    Europa's surface shows signs of extension, which is revealed as lithospheric dilation expressed along ridges, dilational bands and ridged bands. Ridges, the most common tectonic feature on Europa, comprise a central crack flanked by two raised banks a few hundred meters high on each side. Together these three classes may represent a continuum of formation. In Tufts' Dilational Model ridge formation is dominated by daily tidal cycling of a crack, which can be superimposed with regional secular dilation. The two sources of dilation can combine to form the various band morphologies observed. New GPS data along a rift on the Ross Ice Shelf, Antarctica is a suitable Earth analog to test the framework of Tufts' Dilational Model. As predicted by Tufts' Dilational Model, tensile failures in the Ross Ice Shelf exhibit secular dilation, upon which a tidal signal can be seen. From this analog we conclude that Tufts' Dilational Model for Europan ridges and bands may be credible and that the secular dilation is most likely from a regional source and not tidally driven.

  15. Cardiomyopathy in becker muscular dystrophy: Overview.

    PubMed

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-06-26

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed. PMID:27354892

  16. Arrhythmogenic right ventricular cardiomyopathy in a weimaraner

    PubMed Central

    Eason, Bryan D.; Leach, Stacey B.; Kuroki, Keiichi

    2015-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed postmortem in a weimaraner dog. Syncope, ventricular arrhythmias, and sudden death in this patient combined with the histopathological fatty tissue infiltration affecting the right ventricular myocardium are consistent with previous reports of ARVC in non-boxer dogs. Arrhythmogenic right ventricular cardiomyopathy has not been previously reported in weimaraners. PMID:26483577

  17. Cardiomyopathy in becker muscular dystrophy: Overview

    PubMed Central

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-01-01

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed. PMID:27354892

  18. Endocardiosis and congestive heart failure in a captive ostrich (Struthio camelus).

    PubMed

    Kubba, M A G; Al-Azreg, S A

    2013-01-01

    A seven-year-old blue-necked male ostrich was found dead after a few days of illness. The animal was living in an open yard of 25 square meters along with three other females. They were given concentrate-rich ration with free access to green leaves and water. Autopsy revealed cardiac enlargement due to left ventricular hypertrophy and right ventricular dilatation. The left aterioventricular valves were irregularly thickened and contracted. The lungs were engorged with blood and the liver had nutmeg appearance. The small intestine showed segmental sub-serosal petechial hemorrhages. Histological examination revealed myxomatous degeneration of the left aterioventricular valves, pulmonary congestion and edema, congestion of periacinar hepatic zone and fatty degeneration of outer zones, renal glomerulosclerosis and arteriosclerosis. The affected parts of the small intestine showed villous atrophy with lacteal distention. The venules in the affected intestinal segment were severely dilated while the arterioles had narrow lumen and irregular wall thickening with hyaline deposition. The current article reports an endocardiosis in ostrich and discusses other vascular disorders. PMID:26623324

  19. Takotsubo Cardiomyopathy Associated with Severe Hypothyroidism in an Elderly Female.

    PubMed

    Brenes-Salazar, Jorge A

    2016-01-01

    Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is a syndrome that affects predominantly postmenopausal women. Despite multiple described mechanisms, intense, neuroadrenergic myocardial stimulation appears to be the main trigger. Hyperthyroidism, but rarely hypothyroidism, has been described in association with Takotsubo cardiomyopathy. Herein, we present a case of stress cardiomyopathy in the setting of symptomatic hypothyroidism. PMID:27512537

  20. [Monitoring cervical dilatation by impedance].

    PubMed

    Salvat, J; Lassen, M; Sauze, C; Baud, S; Salvat, F

    1992-01-01

    Several different physics procedures have been tried to mechanize the recording of partograms. Can a measure of impedance of tissue Z using potential difference V, according to Ohm's law V = Z1, and 1 is a constant, be correlated with a measure of cervical dilatation using vaginal examination? This was our hypothesis. The tissue impedance meter was made to our design and applied according to a bipolar procedure. Our work was carried out on 28 patients. 10 patients were registered before labour started in order to test the apparatus and to record the impedance variations without labour taking place, and 18 patients were registered in labour to see whether there was any correlation. The level of impedance in the cervix without labour was 302.7 Ohms with a deviation of 8.2. Using student's t tests it was found that there was a significant correlation (p less than 0.001) in four measurements between the impedance measure and measures obtained by extrapolating the degrees of dilatation calculated from vaginal examination. This is a preliminary study in which we have defined the conditions that are necessary to confirm these first results and to further develop the method. PMID:1401774

  1. Technique of percutaneous laser-assisted valve dilatation for valvar atresia in congenital heart disease.

    PubMed Central

    Rosenthal, E; Qureshi, S A; Kakadekar, A P; Anjos, R; Baker, E J; Tynan, M

    1993-01-01

    OBJECTIVE--To investigate the efficacy and safety of transcatheter laser-assisted valve dilatation for atretic valves in children with congenital heart disease. DESIGN--Prospective clinical study. SETTING--Supraregional paediatric cardiology centre. SUBJECTS--Eleven children (aged 1 day-11 years; weight 2.1-35.7 kg) with atresia of pulmonary (10) or tricuspid (one) valve underwent attempted laser-assisted valve dilatation as part of the staged treatment of their cyanotic heart disease. INTERVENTION--After delineating the atretic valve by angiography and/or echocardiography a 0.018 inch "hot tip" laser wire was used to perforate the atretic valve. Subsequently the valve was dilated with conventional balloon dilatation catheters up to the valve annulus diameter. RESULTS--Laser-assisted valve dilatation was successfully accomplished in nine children. In two neonates with pulmonary valve atresia, intact ventricular septum, and coexistent infundibular atresia the procedure resulted in cardiac tamponade: one died immediately and one later at surgery. During a follow up of 1-17 months (mean 11) two infants with pulmonary valve atresia and intact ventricular septum died (one with congestive cardiac failure). The remainder are either well palliated and do not require further procedures (three), or are awaiting further transcatheter or surgical procedures because of associated defects (four). CONCLUSIONS--Laser-assisted valve dilatation is a promising adjunct to surgery in this high risk group of patients. It may avoid surgery in some patients, and may reduce the number of surgical procedures in those requiring staged operations. Images PMID:8343325

  2. Cervical dilation in second-trimester abortion.

    PubMed

    Hayes, Jennifer L; Fox, Michelle C

    2009-06-01

    Dilation and evacuation, the most common method performed for second-trimester abortion in the United States, requires sufficient cervical dilation to reduce the risk of complications such as cervical laceration or uterine perforation. The cervix may be prepared with osmotic dilators such as laminaria, Lamicel, or Dilapan-S, or with pharmacologic agents such as misoprostol. Dilapan-S and Lamicel achieve their maximum dilation faster than laminaria, making same-day procedures possible. Misoprostol has limited data supporting its use in this setting. Decisions regarding which method is best are clinician-dependent, and factors such as gestational age and time allowed for preparation should be considered. PMID:19407523

  3. Evaluation of TCP congestion control algorithms.

    SciTech Connect

    Long, Robert Michael

    2003-12-01

    Sandia, Los Alamos, and Lawrence Livermore National Laboratories currently deploy high speed, Wide Area Network links to permit remote access to their Supercomputer systems. The current TCP congestion algorithm does not take full advantage of high delay, large bandwidth environments. This report involves evaluating alternative TCP congestion algorithms and comparing them with the currently used congestion algorithm. The goal was to find if an alternative algorithm could provide higher throughput with minimal impact on existing network traffic. The alternative congestion algorithms used were Scalable TCP and High-Speed TCP. Network lab experiments were run to record the performance of each algorithm under different network configurations. The network configurations used were back-to-back with no delay, back-to-back with a 30ms delay, and two-to-one with a 30ms delay. The performance of each algorithm was then compared to the existing TCP congestion algorithm to determine if an acceptable alternative had been found. Comparisons were made based on throughput, stability, and fairness.

  4. Ergotamine-Induced Takotsubo Cardiomyopathy.

    PubMed

    Ozpelit, Ebru; Ozpelit, Mehmet E; Akdeniz, Bahri; Göldeli, Özhan

    2016-01-01

    Takotsubo cardiomyopathy (TC) is a recently increasing diagnosed disease showed by transient apical or mid-apical left ventricular dysfunction. It is known as a disease of postmenopausal women, which is usually triggered by emotional or physical stress. Although the trigger is mostly endogenous, some drugs have also been reported as the cause. Published case reports of TC associated with drug usage consist of sympathomimetic drugs, inotropic agents, thyroid hormone, cocaine, and 5-fluorouracil. We present an unusual case of TC in which the possible trigger is ergotamine toxicity. PMID:25099482

  5. Making the Traffic Operations Case for Congestion Pricing: Operational Impacts of Congestion Pricing

    SciTech Connect

    Chin, Shih-Miao; Hu, Patricia S; Davidson, Diane

    2011-02-01

    Congestion begins when an excess of vehicles on a segment of roadway at a given time, resulting in speeds that are significantly slower than normal or 'free flow' speeds. Congestion often means stop-and-go traffic. The transition occurs when vehicle density (the number of vehicles per mile in a lane) exceeds a critical level. Once traffic enters a state of congestion, recovery or time to return to a free-flow state is lengthy; and during the recovery process, delay continues to accumulate. The breakdown in speed and flow greatly impedes the efficient operation of the freeway system, resulting in economic, mobility, environmental and safety problems. Freeways are designed to function as access-controlled highways characterized by uninterrupted traffic flow so references to freeway performance relate primarily to the quality of traffic flow or traffic conditions as experienced by users of the freeway. The maximum flow or capacity of a freeway segment is reached while traffic is moving freely. As a result, freeways are most productive when they carry capacity flows at 60 mph, whereas lower speeds impose freeway delay, resulting in bottlenecks. Bottlenecks may be caused by physical disruptions, such as a reduced number of lanes, a change in grade, or an on-ramp with a short merge lane. This type of bottleneck occurs on a predictable or 'recurrent' basis at the same time of day and same day of week. Recurrent congestion totals 45% of congestion and is primarily from bottlenecks (40%) as well as inadequate signal timing (5%). Nonrecurring bottlenecks result from crashes, work zone disruptions, adverse weather conditions, and special events that create surges in demand and that account for over 55% of experienced congestion. Figure 1.1 shows that nonrecurring congestion is composed of traffic incidents (25%), severe weather (15%), work zones, (10%), and special events (5%). Between 1995 and 2005, the average percentage change in increased peak traveler delay, based on

  6. Successful reversal of propionic acidaemia associated cardiomyopathy: evidence for low myocardial coenzyme Q10 status and secondary mitochondrial dysfunction as an underlying pathophysiological mechanism.

    PubMed

    Baruteau, J; Hargreaves, I; Krywawych, S; Chalasani, A; Land, J M; Davison, J E; Kwok, M K; Christov, G; Karimova, A; Ashworth, M; Anderson, G; Prunty, H; Rahman, S; Grünewald, S

    2014-07-01

    Dilated cardiomyopathy is a rare complication in propionic acidaemia (PA). Underlying pathophysiological mechanisms are poorly understood. We present a child of Pakistani consanguineous parents, diagnosed with late-onset PA at 18months of age. He presented a mild phenotype, showed no severe further decompensations, normal growth and psychomotor development on a low protein diet and carnitine supplementation. At 15years, a mildly dilated left ventricle was noticed. At 17years he presented after a 2-3month history of lethargy and weight loss with severe decompensated dilated cardiomyopathy. He was stabilised on inotropic support and continuous haemofiltration; a Berlin Heart biventricular assist device was implanted. He received d,l-hydroxybutyrate 200mg/kg/day, riboflavin and thiamine 200mg/day each and coenzyme Q10 (CoQ10). Myocardial biopsy showed endocardial fibrosis, enlarged mitochondria, with atypical cristae and slightly low respiratory chain (RC) complex IV activity relative to citrate synthase (0.012, reference range 0.014-0.034). Myocardial CoQ10 was markedly decreased (224pmol/mg, reference range 942-2738), with a marginally decreased white blood cell level (34pmol/mg reference range 37-133). The dose of CoQ10 was increased from 1.5 to 25mg/kg/day. Cardiomyopathy slowly improved allowing removal of the external mechanical cardiac support after 67days. We demonstrate for the first time low myocardial CoQ10 in cardiomyopathy in PA, highlighting secondary mitochondrial impairment as a relevant causative mechanism. According to these findings, a high-dose CoQ10 supplementation could be a potential adjuvant therapeutic to be considered in PA-related cardiomyopathy. PMID:25010387

  7. Dystrophin deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

    PubMed Central

    Spurney, Christopher F.; Knoblach, Susan; Pistilli, Emidio E.; Nagaraju, Kanneboyina; Martin, Gerard R.; Hoffman, Eric P.

    2008-01-01

    Duchenne muscular dystrophy (DMD; dystrophin-deficiency) causes dilated cardiomyopathy in the second decade of life in affected males. We studied the dystrophin-deficient mouse heart (mdx) using high frequency echocardiography, histomorphometry, and gene expression profiling. Heart dysfunction was prominent at 9-10 months of age and showed significantly increased LV internal diameter (end systole) and decreased posterior wall thickness. This cardiomyopathy was associated with a 30% decrease in shortening fraction. Histologically, there was a 10-fold increase in connective tissue volume (fibrosis). mRNA profiling with RT-PCR validation showed activation of key pro-fibrotic genes, including Nox4 and Lox. The Nox gene family expression differed in mdx heart and skeletal muscle, where Nox2 was specifically induced in skeletal muscle while Nox4 was specifically induced in heart. This is the first report of an altered profibrotic gene expression profile in cardiac tissue of dystrophic mice showing echocardiographic evidence of cardiomyopathy. PMID:18440230

  8. Implantable Cardioverter-Defibrillator Discharge in a Patient with Dilated Cardiomyopathy: What Is the Mechanism?

    PubMed

    Docekal, Jermey; Singh, David K

    2016-03-01

    The response to antitachycardia pacing can sometimes reveal clues about tachycardia mechanisms. This article discusses a case in which the diagnosis of typical atrioventricular nodal reciprocating tachycardia could be firmly established from the implantable cardioverter-defibrillator interrogation alone. PMID:26920189

  9. Congestive heart failure in the elderly.

    PubMed

    Rengo, F; Acanfora, D; Trojano, L; Furgi, G; Picone, C; Iannuzzi, G L; Vitale, D F; Rengo, C; Ferrara, N

    1996-01-01

    Several aspects of congestive heart failure are discussed in the light of international literature and of recent findings of our group. The annual incidence of heart failure in elderly subjects, aged >or=75y, is 13 to 50/1000, while it is 1.6/1000 in people aged 45-54 y. The prevalence of heart failure is about 3% in subjects aged 45-64% in subjects aged more than 65 y and 10% in subjects aged more than 75 y. These data are confirmed by our population based study in elderly subjects. The etiology of congestive heart failure is similar in elderly and middle-aged patients. However, several anatomo-functional, hormonal and autonomic nervous system changes, typical of congestive heart failure, occur during physiologic ageing processes also. These findings may explain the dramatic evolution of congestive heart failure in elderly patients. Moreover, some features of the elderly - e.g. comorbidity, atypical clinical presentations, loss of autonomy, increased iatrogen risk should be considered. No specific drugs exist for the pharmacologic treatment of heart failure in the elderly, so that the geriatric specificity in the treatment of heart failure can be recognized in the art of drug choice and dosage, to obtain the best results with the least side effects. The multiple etiology of congestive heart failure, the comorbidity, the loss of autonomy and the deterioration of cognitive functions suggest the need for multidimensional approach and continuative intervention in elderly patients with heart disease, and in particular with congestive heart failure. Further studies on disease- and age-related changes are necessary to develop new and more potent strategies to secure 'successful ageing'. PMID:15374141

  10. On turbulence in dilatant dispersions

    NASA Astrophysics Data System (ADS)

    Baumert, Helmut Z.; Wessling, Bernhard

    2016-07-01

    This paper presents a new theory on the behaviour of shear-thickening (dilatant) fluids under turbulent conditions. The structure of a dilatant colloidal fluid in turbulent motion may be characterized by (at least) four characteristic length scales: (i) the ‘statistically largest’ turbulent scale, {λ }0, labeling the begin of the inertial part of the wavenumber spectrum; (ii) the energy-containing scale, { L }; (iii) Kolmogorov’s micro-scale, {λ }{ K }, related with the size of the smallest vortices existing for a given kinematic viscosity and forcing; (iv) the inner (‘colloidal’) micro-scale, {λ }i, typically representing a major stable material property of the colloidal fluid. In particular, for small ratios r={λ }i/{λ }{ K }∼ { O }(1), various interactions between colloidal structures and smallest turbulent eddies can be expected. In the present paper we discuss particularly that for ρ ={λ }0/{λ }{ K }\\to { O }(1) turbulence (in the narrow, inertial sense) is strangled and chaotic but less mixing fluid motions remain. We start from a new stochastic, micro-mechanical turbulence theory without empirical parameters valid for inviscid fluids as seen in publications by Baumert in 2013 and 2015. It predicts e.g. von Karman’s constant correctly as 1/\\sqrt{2 π }=0.399. In its generalized version for non-zero viscosity and shear-thickening behavior presented in this contribution, it predicts two solution branches for the steady state: The first characterizes a family of states with swift (inertial) turbulent mixing and small {λ }{ K }, potentially approaching {λ }i. The second branch characterizes a state family with ρ \\to { O }(1) and thus strangled turbulence, ρ ≈ { O }(1). Stability properties and a potential dynamic commuting between the two solution branches had to be left for future research.

  11. Inherited cardiomyopathies--Novel therapies.

    PubMed

    Leviner, Dror B; Hochhauser, Edith; Arad, Michael

    2015-11-01

    Cardiomyopathies arising due to a single gene defect represent various pathways that evoke adverse remodeling and cardiac dysfunction. While the gene therapy approach is slowly evolving and has not yet reached clinical "prime time" and gene correction approaches are applicable at the bench but not at the bedside, major advances are being made with molecular and drug therapies. This review summarizes the contemporary drugs introduced or being tested to help manage these unique disorders bearing a major impact on the quality of life and survival of the affected individuals. The restoration of the RNA reading frame facilitates the expression of partly functional protein to salvage or alleviate the disease phenotype. Chaperones are used to prevent the degradation of abnormal but still functional proteins, while other molecules are given for pathogen silencing, to prevent aggregation or to enhance clearance of protein deposits. The absence of protein may be managed by viral gene delivery or protein therapy. Enzyme replacement therapy is already a clinical reality for a series of metabolic diseases. The progress in molecular biology, based on the knowledge of the gene defect, helps generate small molecules and pharmaceuticals targeting the key events occurring in the malfunctioning element of the sick organ. Cumulatively, these tools augment the existing armamentarium of phenotype oriented symptomatic and evidence-based therapies for patients with inherited cardiomyopathies. PMID:26297672

  12. [Takotsubo cardiomyopathy: origin and variants].

    PubMed

    Aronov, D M

    2008-01-01

    This literature review is devoted to the " tako-tsubo " cardiomyopathy - rare type of cardiomyopathy characterized by transient myocardial stunning. In acute phase the disease resembles myocardial infarction. However no involvement of coronary arteries is found at angiography. Echocardiography and ventriculography reveal a- or - hypokinesia of various parts of the left ventricle. Classic (initial) variant of the disease is associated with concomitant apical akinesia and hyperkinesis of basal segments. The heart acquires a distinctive configuration with ballooning apex which resembles device used to trap octopus. The author refers to described by him 11 cases of myocardial damage with infarct-like clinic without changes of coronary arteries in healthy men younger than 35 years (D.M.Aronow, 1968, 1974). These cases occurred during severe physical stress and had in their basis hypercatecholaminemia which led to reversible myocardial damage of the myocardium which corresponded to modern concept of myocardial stunning. During exercise tests these patients had 3 times greater increase of urinal epinephrine excretion compared with 61 patients of the same age with atherosclerotic heart disease. PMID:18991836

  13. A Mutation in the Mitochondrial Fission Gene Dnm1l Leads to Cardiomyopathy

    PubMed Central

    Ashrafian, Houman; Docherty, Louise; Leo, Vincenzo; Towlson, Christopher; Neilan, Monica; Steeples, Violetta; Lygate, Craig A.; Hough, Tertius; Townsend, Stuart; Williams, Debbie; Wells, Sara; Norris, Dominic; Glyn-Jones, Sarah; Land, John; Barbaric, Ivana; Lalanne, Zuzanne; Denny, Paul; Szumska, Dorota; Bhattacharya, Shoumo; Griffin, Julian L.; Hargreaves, Iain; Fernandez-Fuentes, Narcis; Cheeseman, Michael; Watkins, Hugh; Dear, T. Neil

    2010-01-01

    Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l) gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease. PMID:20585624

  14. The role of mutations in the SCN5A gene in cardiomyopathies.

    PubMed

    Zaklyazminskaya, Elena; Dzemeshkevich, Sergei

    2016-07-01

    The SCN5A gene encodes the alpha-subunit of the Nav1.5 ion channel protein, which is responsible for the sodium inward current (INa). Since 1995 several hundred mutations in this gene have been found to be causative for inherited arrhythmias including Long QT syndrome, Brugada syndrome, cardiac conduction disease, sudden infant death syndrome, etc. As expected these syndromes are primarily electrical heart diseases leading to life-threatening arrhythmias with an "apparently normal heart". In 2003 a new form of dilated cardiomyopathy was identified associated with mutations in the SCN5A gene. Recently mutations have been also found in patients with arrhythmogenic right ventricular cardiomyopathy and atrial standstill. The purpose of this review is to outline and analyze the following four topics: 1) SCN5A genetic variants linked to different cardiomyopathies; 2) clinical manifestations of the known mutations; 3) possible molecular mechanisms of myocardial remodeling; and 4) the potential implications of gene-specific treatment for those disorders. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26916278

  15. Congestive Heart Failure and Central Sleep Apnea.

    PubMed

    Sands, Scott A; Owens, Robert L

    2016-03-01

    Congestive heart failure (CHF) is among the most common causes of admission to hospitals in the United States, especially in those over age 65. Few data exist regarding the prevalence CHF of Cheyne-Stokes respiration (CSR) owing to congestive heart failure in the intensive care unit (ICU). Nevertheless, CSR is expected to be highly prevalent among those with CHF. Treatment should focus on the underlying mechanisms by which CHF increases loop gain and promotes unstable breathing. Few data are available to determine prevalence of CSR in the ICU, or how CSR might affect clinical management and weaning from mechanical ventilation. PMID:26972039

  16. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  17. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  18. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  19. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  20. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  1. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rectal dilator. 876.5450 Section 876.5450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5450 Rectal dilator. (a) Identification. A...

  2. 21 CFR 876.5470 - Ureteral dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ureteral dilator. 876.5470 Section 876.5470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5470 Ureteral dilator....

  3. 21 CFR 876.5520 - Urethral dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urethral dilator. 876.5520 Section 876.5520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5520 Urethral dilator....

  4. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Esophageal dilator. 876.5365 Section 876.5365 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5365 Esophageal dilator....

  5. 21 CFR 876.5470 - Ureteral dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ureteral dilator. 876.5470 Section 876.5470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5470 Ureteral dilator....

  6. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rectal dilator. 876.5450 Section 876.5450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5450 Rectal dilator. (a) Identification. A...

  7. BNP, NTproBNP, CMBK, and MMP-2 predict mortality in severe Chagas cardiomyopathy

    PubMed Central

    Sherbuk, Jacqueline E.; Okamoto, Emi E.; Marks, Morgan A.; Fortuny, Enzo; Clark, Eva H.; Galdos-Cardenas, Gerson; Vasquez-Villar, Angel; Fernandez, Antonio B.; Crawford, Thomas C.; Do, Rose Q.; Flores-Franco, Jorge Luis; Colanzi, Rony; Gilman, Robert H.; Bern, Caryn

    2015-01-01

    Background Chagas cardiomyopathy is a chronic sequela of infection by the parasite, Trypanosoma cruzi. Advanced cardiomyopathy is associated with a high mortality rate, and clinical characteristics have been used to predict mortality risk. Though multiple biomarkers have been associated with Chagas cardiomyopathy, it is unknown how these are related to survival. Objectives Our study aimed to identify biomarkers associated with mortality in individuals with severe Chagas cardiomyopathy in an urban Bolivian hospital. Methods The population included individuals with and without T. cruzi infection recruited in an urban hospital in Santa Cruz, Bolivia. Baseline characteristics, ECG findings, medications, and serum cardiac biomarker levels (BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2) were ascertained. Echocardiograms were preferentially performed on those with cardiac symptoms or electrocardiogram abnormalities. Participants were contacted by phone approximately 1 year after initial evaluation; deaths were reported by family members. Receiver operating characteristic curves were used to optimize cut-off values for each marker. For markers with area under curve > 0.55, Cox proportional hazards models were performed to determine the hazards ratio (HR) and 95% confidence interval (CI) for the association of each marker with mortality. Results The median follow-up time was 14.1 months (interquartile range 12.5- 16.7 months). Of 254 individuals with complete cardiac data, 220 (87%) had follow-up data. Of 50 patients with severe Chagas cardiomyopathy, 20 (40%) had died. Higher baseline levels of BNP (HR[95% CI]:3.1 [1.2, 8.4]), NTproBNP (4.4[1.8,11.0]), CKMB (3.3[1.3, 8.0]), and MMP-2 (4.2[1.5, 11.8]) were significantly associated with subsequent mortality. Conclusions Severe Chagas cardiomyopathy is associated with high short-term mortality. BNP, NTproBNP, CKMB and MMP2 have added predictive value for mortality, even in the presence of

  8. Myocardial metabolic, hemodynamic, and electrocardiographic significance of reversible thallium-201 abnormalities in hypertrophic cardiomyopathy

    SciTech Connect

    Cannon, R.O. 3d.; Dilsizian, V.; O'Gara, P.T.; Udelson, J.E.; Schenke, W.H.; Quyyumi, A.; Fananapazir, L.; Bonow, R.O. )

    1991-05-01

    Exercise-induced abnormalities during thallium-201 scintigraphy that normalize at rest frequently occur in patients with hypertrophic cardiomyopathy. However, it is not known whether these abnormalities are indicative of myocardial ischemia. Fifty patients with hypertrophic cardiomyopathy underwent exercise {sup 201}Tl scintigraphy and, during the same week, measurement of myocardial lactate metabolism and hemodynamics during pacing stress. Thirty-seven patients (74%) had one or more {sup 201}Tl abnormalities that completely normalized after 3 hours of rest; 26 had regional myocardial {sup 201}Tl defects, and 26 had apparent left ventricular cavity dilatation with exercise, with 15 having coexistence of these abnormal findings. Of the 37 patients with reversible {sup 201}Tl abnormalities, 27 (73%) had metabolic evidence of myocardial ischemia during rapid atrial pacing compared with four of 13 patients (31%) with normal {sup 201}Tl scans (p less than 0.01). Eleven patients had apparent cavity dilatation as their only {sup 201}Tl abnormality; their mean postpacing left ventricular end-diastolic pressure was significantly higher than that of the 13 patients with normal {sup 201}Tl studies (33 +/- 5 versus 21 +/- 10 mm Hg, p less than 0.001). There was no correlation between the angiographic presence of systolic septal or epicardial coronary arterial compression and the presence or distribution of {sup 201}Tl abnormalities. Patients with ischemic ST segment responses to exercise had an 80% prevalence rate of reversible {sup 201}Tl abnormalities and a 70% prevalence rate of pacing-induced ischemia. However, 69% of patients with nonischemic ST segment responses had reversible {sup 201}Tl abnormalities, and 55% had pacing-induced ischemia. Reversible {sup 201}Tl abnormalities during exercise stress are markers of myocardial ischemia in hypertrophic cardiomyopathy and most likely identify relatively underperfused myocardium.

  9. A case of asymmetrical apical hypertrophy which is a form of hypertrophic nonobstructive cardiomyopathy with giant negative T-waves.

    PubMed

    Sheikhzadeh, A; Ghabussi, P

    1982-09-01

    Clinical, hemodynamic, electrocardiographic (ECG), echocardiographic, left ventricular (LV), and coronary angiographic (CA) findings are reported in a case with apical hypertrophy (AH), a form of hypertrophic nonobstructive cardiomyopathy (HNCM). The most striking symptom was chest pain and the most conspicuous electrocardiographic finding consisted of giant negative T waves, reaching an amplitude of 4.0 mV. Echocardiography revealed an apical thickness of the septum and posterior wall of 40 mm; this was significantly greater than septal and posterior free wall thickening in the LV outflow area. The anterior motion (SAM) of the anterior mitral leaflet, was present, and, in hemodymic investigation, the isoproterenol test was negative. The left ventricular end-diastolic pressure (LVEDP) and the EF were elevated. In the LV angiogram from the right anterior oblique position (RAO), the LV free wall thickness at the apex was significantly thicker than at the outflow tract level. The patient had dilated coronary arteries. We conclude that these findings are typical for AH (HNCM) and it seems that hypertrophic obstructive cardiomyopathy (IHSS, MO), and hypertrophic non-obstructive cardiomyopathy (ASH, AH) are different manifestations of a wide spectrum of hypertrophic cardiomyopathy. PMID:6217360

  10. Aptamer binding and neutralization of β1-adrenoceptor autoantibodies: basics and a vision of its future in cardiomyopathy treatment.

    PubMed

    Haberland, Annekathrin; Wallukat, Gerd; Schimke, Ingolf

    2011-08-01

    Autoantibodies directed against the second extracellular receptor loop of the β(1) receptor (β(1)-ECII-AABs) that belong to the superfamily of G protein-coupled receptors have been frequently found in patients with idiopathic dilated cardiomyopathy, Chagas' cardiomyopathy, and peripartum cardiomyopathy and have been clearly evidenced to be related to disease pathogenesis. Consequently, specific proteins or peptides used as binders in immunoapheresis or as in vivo neutralizers of β(1)-ECII-AABs have been suggested for patient treatment. Aptamers, which are target specifically selected short single- or double-stranded RNA or DNA sequences, are a recently introduced new molecule class applicable to bind and neutralize diverse molecule species, including antibodies. This article reviews selection technologies and characteristics of aptamers with respect to a single-stranded DNA aptamer recently identified as having a very high affinity against β(1)-ECII-AABs. The potential of this aptamer for the elimination of β(1)-ECII-AABs and in vivo neutralization is critically analyzed in view of its potential for future use in cardiomyopathy treatment. PMID:22814426

  11. Extracardiac medical and neuromuscular implications in restrictive cardiomyopathy.

    PubMed

    Stöllberger, Claudia; Finsterer, Josef

    2007-08-01

    Restrictive cardiomyopathy (RCMP) is characterized by restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness. It may occur idiopathically or as a cardiac manifestation of systemic diseases such as scleroderma, amyloidosis, Churg-Strauss syndrome, cystinosis, sarcoidosis, lymphoma, Gaucher's disease, hemochromatosis, Fabry's disease, pseudoxanthoma elasticum, hypereosinophilic syndrome, carcinoid, Noonan's syndrome, reactive arthritis, or Werner's syndrome and various neuromuscular disorders. Whereas in idiopathic RCMP the therapeutic options are only treatment of cardiac congestion, in cases with an underlying disorder, a causal therapy may be available. Patients with RCMP should be investigated as soon as the cardiac diagnosis is established for extracardiac diseases to detect a possibly treatable cause of RCMP before the disease becomes intractable. These investigations include a diligent clinical history and examination, blood tests, and ophthalmologic, otologic, dermatologic, gastroenterologic, nephrologic, hematologic, and neurologic examinations. If extracardiac examinations do not reveal a plausible cause for RCMP, endomyocardial biopsy is indicated. PMID:17680617

  12. Delivering Faster Congestion Feedback with the Mark-Front Strategy

    NASA Technical Reports Server (NTRS)

    Liu, Chunlei; Jain, Raj

    2001-01-01

    Computer networks use congestion feedback from the routers and destinations to control the transmission load. Delivering timely congestion feedback is essential to the performance of networks. Reaction to the congestion can be more effective if faster feedback is provided. Current TCP/IP networks use timeout, duplicate Acknowledgement Packets (ACKs) and explicit congestion notification (ECN) to deliver the congestion feedback, each provides a faster feedback than the previous method. In this paper, we propose a markfront strategy that delivers an even faster congestion feedback. With analytical and simulation results, we show that mark-front strategy reduces buffer size requirement, improves link efficiency and provides better fairness among users. Keywords: Explicit Congestion Notification, mark-front, congestion control, buffer size requirement, fairness.

  13. Managing congestive heart failure using home telehealth.

    PubMed

    Schneider, Nina M

    2004-10-01

    Congestive heart failure (CHF) is the leading cause of rehospitalization and loss of revenue for home care agencies and hospitals. This article outlines how an agency used telehealth to provide CHF patients quality care and improved outcomes while decreasing the number of skilled home nursing visits and reducing rehospitalization rates to 1.2%. PMID:15486513

  14. Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis

    PubMed Central

    Patel, Keval; Griffing, George T.; Hauptman, Paul J.

    2016-01-01

    Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy. PMID:27127432

  15. Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis.

    PubMed

    Patel, Keval; Griffing, George T; Hauptman, Paul J; Stolker, Joshua M

    2016-04-01

    Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy. PMID:27127432

  16. Unveiling nonischemic cardiomyopathies with cardiac magnetic resonance.

    PubMed

    Aggarwal, Niti R; Peterson, Tyler J; Young, Phillip M; Araoz, Philip A; Glockner, James; Mankad, Sunil V; Williamson, Eric E

    2014-02-01

    Cardiomyopathy is defined as a heterogeneous group of myocardial disorders with mechanical or electrical dysfunction. Identification of the etiology is important for accurate diagnosis, treatment and prognosis, but continues to be challenging. The ability of cardiac MRI to non-invasively obtain 3D-images of unparalleled resolution without radiation exposure and to provide tissue characterization gives it a distinct advantage over any other diagnostic tool used f