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Sample records for myc-mediated hypertrophic cardiomyopathy

  1. 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

  2. Hypertrophic cardiomyopathy: a review.

    PubMed

    Hensley, Nadia; Dietrich, Jennifer; Nyhan, Daniel; Mitter, Nanhi; Yee, May-Sann; Brady, MaryBeth

    2015-03-01

    Hypertrophic cardiomyopathy (HCM) is a relatively common disorder that anesthesiologists encounter among patients in the perioperative period. Fifty years ago, HCM was thought to be an obscure disease. Today, however, our understanding and ability to diagnose patients with HCM have improved dramatically. Patients with HCM have genotypic and phenotypic variability. Indeed, a subgroup of these patients exhibits the HCM genotype but not the phenotype (left ventricular hypertrophy). There are a number of treatment modalities for these patients, including pharmacotherapy to control symptoms, implantable cardiac defibrillators to manage malignant arrhythmias, and surgical myectomy and septal ablation to decrease the left ventricular outflow obstruction. Accurate diagnosis is vital for the perioperative management of these patients. Diagnosis is most often made using echocardiographic assessment of left ventricular hypertrophy, left ventricular outflow tract gradients, systolic and diastolic function, and mitral valve anatomy and function. Cardiac magnetic resonance imaging also has a diagnostic role by determining the extent and location of left ventricular hypertrophy and the anatomic abnormalities of the mitral valve and papillary muscles. In this review on hypertrophic cardiomyopathy for the noncardiac anesthesiologist, we discuss the clinical presentation and genetic mutations associated with HCM, the critical role of echocardiography in the diagnosis and the assessment of surgical interventions, and the perioperative management of patients with HCM undergoing noncardiac surgery and management of the parturient with HCM. PMID:25695573

  3. Misconceptions and Facts About Hypertrophic Cardiomyopathy.

    PubMed

    Argulian, Edgar; Sherrid, Mark V; Messerli, Franz H

    2016-02-01

    Hypertrophic cardiomyopathy is the most common genetic heart disease. Once considered relentless, untreatable, and deadly, it has become a highly treatable disease with contemporary management. Hypertrophic cardiomyopathy is one of cardiology's "great masqueraders." Mistakes and delays in diagnosis abound. Hypertrophic cardiomyopathy commonly "masquerades" as asthma, anxiety, mitral prolapse, and coronary artery disease. However, once properly diagnosed, patients with hypertrophic cardiomyopathy can be effectively managed to improve both symptoms and survival. This review highlights some of the misconceptions about hypertrophic cardiomyopathy. Providers at all levels should have awareness of hypertrophic cardiomyopathy to promptly diagnose and properly manage these individuals. PMID:26299316

  4. Cardiac arrhythmias in hypertrophic cardiomyopathy.

    PubMed Central

    Bjarnason, I; Hardarson, T; Jonsson, S

    1982-01-01

    This study was designed to assess the prevalence of cardiac arrhythmias in a group of relatives of patients who had come to necropsy with hypertrophic cardiomyopathy. Another aim of the study was to assess the validity of an interventricular septal thickness of 1.3 cm or more, measured by echocardiography, as a diagnostic criterion of hypertrophic cardiomyopathy among relatives of cases proven at necropsy. Fifty close relatives of eight deceased patients were examined. By the above definition 22 relatives had hypertrophic cardiomyopathy and 28 did not. A comparison of the prevalence and types of cardiac arrhythmias, as shown by 24 hour ambulatory electrocardiographic monitoring, was made between the two groups and a third apparently healthy group of 40 people. The patients with hypertrophic cardiomyopathy showed a significant increase in supraventricular extrasystoles/24 hours, supraventricular arrhythmias, high grade ventricular arrhythmia, and the number of patients with more than 10 ventricular extrasystoles every 24 hours when compared with the other groups. There was no significant difference between normal relatives and controls. The prevalence and types of arrhythmia in these patients were similar to those found by other investigators using different diagnostic criteria. These results support the contention that these patients do indeed have hypertrophic cardiomyopathy and suggest that all close relatives of necropsy proven cases should be examined by echocardiography and subsequently by ambulatory electrocardiographic monitoring if the interventricular septal thickness is 1.3 more. PMID:7201843

  5. Hypertrophic cardiomyopathy in a college athlete.

    PubMed

    Simons, S M; Moriarity, J

    1992-12-01

    The greatest catastrophy in sports is an athlete's unexpected sudden death. Identifying those athletes at risk remains a great challenge to physicians performing preseason examinations. Hypertrophic cardiomyopathy is the most common cause of nontraumatic sudden death in athletes. Most cases of this diseased heart are diagnosed easily by echocardiography. The case presented exemplifies the attention to detail required to differentiate the borderline diseased heart from the conditioned athletic heart. Once a diagnosis of hypertrophic cardiomyopathy is made, further participation in intense physical exercise is discouraged. This recommendation is necessary despite the unknown relative sudden death risk for the minimal criteria cases.

  6. Contractile Dysfunction in Sarcomeric Hypertrophic Cardiomyopathy.

    PubMed

    MacIver, David H; Clark, Andrew L

    2016-09-01

    The pathophysiological mechanisms underlying the clinical phenotype of sarcomeric hypertrophic cardiomyopathy are controversial. The development of cardiac hypertrophy in hypertension and aortic stenosis is usually described as a compensatory mechanism that normalizes wall stress. We suggest that an important abnormality in hypertrophic cardiomyopathy is reduced contractile stress (the force per unit area) generated by myocardial tissue secondary to abnormalities such as cardiomyocyte disarray. In turn, a progressive deterioration in contractile stress provokes worsening hypertrophy and disarray. A maintained or even exaggerated ejection fraction is explained by the increased end-diastolic wall thickness producing augmented thickening. We propose that the nature of the hemodynamic load in an individual with hypertrophic cardiomyopathy could determine its phenotype. Hypertensive patients with hypertrophic cardiomyopathy are more likely to develop exaggerated concentric hypertrophy; athletic individuals an asymmetric pattern; and inactive individuals a more apical hypertrophy. The development of a left ventricular outflow tract gradient and mitral regurgitation may be explained by differential regional strain resulting in mitral annular rotation.

  7. Hypertrophic Cardiomyopathy in Athletes: Catching a Killer.

    ERIC Educational Resources Information Center

    Maron, Barry J.

    1993-01-01

    A leading cause of sudden death among young athletes, hypertrophic cardiomyopathy (HCM) does not always present cardiac signs and symptoms. Echocardiography offers the most effective means for diagnosis. Some patients require pharmaceutical or surgical intervention. Patients with HCM should not engage in organized competitive sports or…

  8. Infective endocarditis in hypertrophic cardiomyopathy

    PubMed Central

    Dominguez, Fernando; Ramos, Antonio; Bouza, Emilio; Muñoz, Patricia; Valerio, Maricela C.; Fariñas, M. Carmen; de Berrazueta, José Ramón; Zarauza, Jesús; Pericás Pulido, Juan Manuel; Paré, Juan Carlos; de Alarcón, Arístides; Sousa, Dolores; Rodriguez Bailón, Isabel; Montejo-Baranda, Miguel; Noureddine, Mariam; García Vázquez, Elisa; Garcia-Pavia, Pablo

    2016-01-01

    Abstract Infective endocarditis (IE) complicating hypertrophic cardiomyopathy (HCM) is a poorly known entity. Although current guidelines do not recommend IE antibiotic prophylaxis (IEAP) in HCM, controversy remains. This study sought to describe the clinical course of a large series of IE HCM and to compare IE in HCM patients with IE patients with and without an indication for IEAP. Data from the GAMES IE registry involving 27 Spanish hospitals were analyzed. From January 2008 to December 2013, 2000 consecutive IE patients were prospectively included in the registry. Eleven IE HCM additional cases from before 2008 were also studied. Clinical, microbiological, and echocardiographic characteristics were analyzed in IE HCM patients (n = 34) and in IE HCM reported in literature (n = 84). Patients with nondevice IE (n = 1807) were classified into 3 groups: group 1, HCM with native-valve IE (n = 26); group 2, patients with IEAP indication (n = 696); group 3, patients with no IEAP indication (n = 1085). IE episode and 1-year follow-up data were gathered. One-year mortality in IE HCM was 42% in our study and 22% in the literature. IE was more frequent, although not exclusive, in obstructive HCM (59% and 74%, respectively). Group 1 exhibited more IE predisposing factors than groups 2 and 3 (62% vs 40% vs 50%, P < 0.01), and more previous dental procedures (23% vs 6% vs 8%, P < 0.01). Furthermore, Group 1 experienced a higher incidence of Streptococcus infections than Group 2 (39% vs 22%, P < 0.01) and similar to Group 3 (39% vs 30%, P = 0.34). Overall mortality was similar among groups (42% vs 36% vs 35%, P = 0.64). IE occurs in HCM patients with and without obstruction. Mortality of IE HCM is high but similar to patients with and without IEAP indication. Predisposing factors, previous dental procedures, and streptococcal infection are higher in IE HCM, suggesting that HCM patients could benefit from IEAP. PMID:27368014

  9. Aortic biomechanics in hypertrophic cardiomyopathy

    PubMed Central

    Badran, Hala Mahfouz; Soltan, Ghada; Faheem, Nagla; Elnoamany, Mohamed Fahmy; Tawfik, Mohamed; Yacoub, Magdi

    2015-01-01

    Background: Ventricular-vascular coupling is an important phenomenon in many cardiovascular diseases. The association between aortic mechanical dysfunction and left ventricular (LV) dysfunction is well characterized in many disease entities, but no data are available on how these changes are related in hypertrophic cardiomyopathy (HCM). Aim of the work: This study examined whether HCM alone is associated with an impaired aortic mechanical function in patients without cardiovascular risk factors and the relation of these changes, if any, to LV deformation and cardiac phenotype. Methods: 141 patients with HCM were recruited and compared to 66 age- and sex-matched healthy subjects as control group. Pulse pressure, aortic strain, stiffness and distensibility were calculated from the aortic diameters measured by M-mode echocardiography and blood pressure obtained by sphygmomanometer. Aortic wall systolic and diastolic velocities were measured using pulsed wave Doppler tissue imaging (DTI). Cardiac assessment included geometric parameters and myocardial deformation (strain and strain rate) and mechanical dyssynchrony. Results: The pulsatile change in the aortic diameter, distensibility and aortic wall systolic velocity (AWS') were significantly decreased and aortic stiffness index was increased in HCM compared to control (P < .001) In HCM AWS' was inversely correlated to age(r = − .32, P < .0001), MWT (r = − .22, P < .008), LVMI (r = − .20, P < .02), E/Ea (r = − .16, P < .03) LVOT gradient (r = − 19, P < .02) and severity of mitral regurg (r = − .18, P < .03) but not to the concealed LV deformation abnormalities or mechanical dyssynchrony. On multivariate analysis, the key determinant of aortic stiffness was LV mass index and LVOT obstruction while the role LV dysfunction in aortic stiffness is not evident in this population. Conclusion: HCM is associated with abnormal aortic mechanical properties. The severity of cardiac

  10. An unusual ST-segment elevation: apical hypertrophic cardiomyopathy shows the ace up its sleeve.

    PubMed

    de Santis, Francesco; Pergolini, Amedeo; Zampi, Giordano; Pero, Gaetano; Pino, Paolo Giuseppe; Minardi, Giovanni

    2013-01-01

    Apical hypertrophic cardiomyopathy is part of the broad clinical and morphologic spectrum of hypertrophic cardiomyopathy. We report a patient with electrocardiographic abnormalities in whom acute coronary syndrome was excluded and apical hypertrophic cardiomyopathy was demonstrated by careful differential diagnosis.

  11. Hypertrophic cardiomyopathy in a neonate associated with nemaline myopathy.

    PubMed

    Mir, Arshid; Lemler, Matthew; Ramaciotti, Claudio; Blalock, Shannon; Ikemba, Catherine

    2012-01-01

    Nemaline myopathy is a congenital nonprogressive skeletal muscle disorder with a characteristic rod body formation in the skeletal muscle fibers. Cardiac involvement in nemaline myopathy is rare, although both dilated and hypertrophic cardiomyopathy have been reported. We describe an infant diagnosed with hypertrophic cardiomyopathy and hypotonia on the first day of life. Muscle biopsy confirmed nemaline myopathy at 3 weeks of age. The diagnosis of nemaline myopathy precluded consideration of heart transplantation, thus shifting the focus to comfort care. This is the earliest presentation of hypertrophic cardiomyopathy reported in the literature in the setting of nemaline myopathy. The approach to determining an etiology for hypertrophic cardiomyopathy in an infant is reviewed. PMID:22067214

  12. Hypertrophic cardiomyopathy in owl monkeys (Aotus spp.).

    PubMed

    Knowlen, Grant G; Weller, Richard E; Perry, Ruby L; Baer, Janet F; Gozalo, Alfonso S

    2013-06-01

    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.

  13. Screening for hypertrophic cardiomyopathy in cats.

    PubMed

    Häggström, Jens; Luis Fuentes, Virginia; Wess, Gerhard

    2015-12-01

    Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats, and it can lead to increased morbidity and mortality. Cats are often screened for HCM because of the presence of a heart murmur, but screening for breeding purposes has also become common. These cats are usually purebred cats of breeding age, and generally do not present with severe disease or with any clinical signs. This type of screening is particularly challenging because mild disease may be difficult to differentiate from a normal phenotype, and the margin for error is small, with potentially major consequences for the breeder. This article reviews HCM screening methods, with particular emphasis on echocardiography.

  14. The embryological basis of subclinical hypertrophic cardiomyopathy.

    PubMed

    Captur, Gabriella; Ho, Carolyn Y; Schlossarek, Saskia; Kerwin, Janet; Mirabel, Mariana; Wilson, Robert; Rosmini, Stefania; Obianyo, Chinwe; Reant, Patricia; Bassett, Paul; Cook, Andrew C; Lindsay, Susan; McKenna, William J; Mills, Kevin; Elliott, Perry M; Mohun, Timothy J; Carrier, Lucie; Moon, James C

    2016-06-21

    Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomeric proteins, the commonest being MYBPC3 encoding myosin-binding protein C. It is characterised by left ventricular hypertrophy but there is an important pre-hypertrophic phenotype with features including crypts, abnormal mitral leaflets and trabeculae. We investigated these during mouse cardiac development using high-resolution episcopic microscopy. In embryonic hearts from wildtype, homozygous (HO) and heterozygous (HET) Mybpc3-targeted knock-out (KO) mice we show that crypts (one or two) are a normal part of wildtype development but they almost all resolve by birth. By contrast, HO and HET embryos had increased crypt presence, abnormal mitral valve formation and alterations in the compaction process. In scarce normal human embryos, crypts were sometimes present. This study shows that features of the human pre-hypertrophic HCM phenotype occur in the mouse. In an animal model we demonstrate that there is an embryological HCM phenotype. Crypts are a normal part of cardiac development but, along with the mitral valve and trabeculae, their developmental trajectory is altered by the presence of HCM truncating Mybpc3 gene mutation.

  15. The embryological basis of subclinical hypertrophic cardiomyopathy

    PubMed Central

    Captur, Gabriella; Ho, Carolyn Y.; Schlossarek, Saskia; Kerwin, Janet; Mirabel, Mariana; Wilson, Robert; Rosmini, Stefania; Obianyo, Chinwe; Reant, Patricia; Bassett, Paul; Cook, Andrew C.; Lindsay, Susan; McKenna, William J.; Mills, Kevin; Elliott, Perry M.; Mohun, Timothy J.; Carrier, Lucie; Moon, James C.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomeric proteins, the commonest being MYBPC3 encoding myosin-binding protein C. It is characterised by left ventricular hypertrophy but there is an important pre-hypertrophic phenotype with features including crypts, abnormal mitral leaflets and trabeculae. We investigated these during mouse cardiac development using high-resolution episcopic microscopy. In embryonic hearts from wildtype, homozygous (HO) and heterozygous (HET) Mybpc3-targeted knock-out (KO) mice we show that crypts (one or two) are a normal part of wildtype development but they almost all resolve by birth. By contrast, HO and HET embryos had increased crypt presence, abnormal mitral valve formation and alterations in the compaction process. In scarce normal human embryos, crypts were sometimes present. This study shows that features of the human pre-hypertrophic HCM phenotype occur in the mouse. In an animal model we demonstrate that there is an embryological HCM phenotype. Crypts are a normal part of cardiac development but, along with the mitral valve and trabeculae, their developmental trajectory is altered by the presence of HCM truncating Mybpc3 gene mutation. PMID:27323879

  16. The embryological basis of subclinical hypertrophic cardiomyopathy.

    PubMed

    Captur, Gabriella; Ho, Carolyn Y; Schlossarek, Saskia; Kerwin, Janet; Mirabel, Mariana; Wilson, Robert; Rosmini, Stefania; Obianyo, Chinwe; Reant, Patricia; Bassett, Paul; Cook, Andrew C; Lindsay, Susan; McKenna, William J; Mills, Kevin; Elliott, Perry M; Mohun, Timothy J; Carrier, Lucie; Moon, James C

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomeric proteins, the commonest being MYBPC3 encoding myosin-binding protein C. It is characterised by left ventricular hypertrophy but there is an important pre-hypertrophic phenotype with features including crypts, abnormal mitral leaflets and trabeculae. We investigated these during mouse cardiac development using high-resolution episcopic microscopy. In embryonic hearts from wildtype, homozygous (HO) and heterozygous (HET) Mybpc3-targeted knock-out (KO) mice we show that crypts (one or two) are a normal part of wildtype development but they almost all resolve by birth. By contrast, HO and HET embryos had increased crypt presence, abnormal mitral valve formation and alterations in the compaction process. In scarce normal human embryos, crypts were sometimes present. This study shows that features of the human pre-hypertrophic HCM phenotype occur in the mouse. In an animal model we demonstrate that there is an embryological HCM phenotype. Crypts are a normal part of cardiac development but, along with the mitral valve and trabeculae, their developmental trajectory is altered by the presence of HCM truncating Mybpc3 gene mutation. PMID:27323879

  17. Cushing's syndrome in pregnancy and neonatal hypertrophic obstructive cardiomyopathy.

    PubMed

    Fayol, L; Masson, P; Millet, V; Simeoni, U

    2004-10-01

    Cushing's syndrome is rare in pregnancy but can cause spontaneous abortion, stillbirth or premature birth. We report a case of transient hypertrophic obstructive cardiomyopathy in a newborn whose mother had hypercortisolism due to a primary adrenal lesion. There was no family history of hypertrophic obstructive cardiomyopathy. Follow-up revealed complete resolution of the cardiac abnormalities in the infant. Cushing's syndrome in the mother resolved after delivery. Although maternal hypercortisolism seldom results in symptomatic hypercortisolism in the newborn, hypertrophic obstructive cardiomyopathy can occur. PMID:15499965

  18. [Left ventricular hypertrophy in the cat - "when hypertrophic cardiomyopathy is not hypertrophic cardiomyopathy"].

    PubMed

    Glaus, T; Wess, G

    2010-07-01

    According to WHO classification hypertrophic cardiomyopathy (HCM) is a primary genetic cardiomyopathy. Echocardiographically HCM is characterized by symmetric, asymmetric or focal left ventricular hypertrophy (LVH) without recognizable underlying physical cause. However, echocardiographically HCM in cats may not be distinguishable from other causes of a thick appearing left ventricle. Hypovolemia can look like a hypertrophied ventricle but is basically only pseudohypertrophic. Well recognized and logical physical causes of LVH include systemic hypertension and outflow obstruction. LVH similar to HCM may also be found in feline hyperthyroidism. The context of the disease helps to differentiate these physical / physiological causes of LVH. Difficult to distinguish from HCM, particularly when based on a snapshot of a single echocardiographic exam, are myocarditis and . Only the clinical and echocardiographic course allow a reasonably confident etiological diagnosis and the differentiation between HCM and secondary LVH. PMID:20582898

  19. Echocardiography in the treatment of hypertrophic cardiomyopathy.

    PubMed

    Musat, Dan; Sherrid, Mark V

    2006-12-01

    Echocardiography is the best technique to diagnose, evaluate, follow-up and guide the treatment of hypertrophic cardiomyopathy (HCM). Diagnosis of HCM depends on left ventricular wall thickness >/=15 mm. Also noted are mitral valve systolic anterior motion, anteriorly positioned mitral valve leaflet coaptation, anomalous anterior insertion of papillary muscles, and diastolic dysfunction. Resting left ventricular outflow tract (LVOT) gradient occurs in 25% of patients and provocable gradients may be demonstrated in more than half of patients. Echocardiography is important for sudden death risk assessment; patients with a wall thickness more than 30 mm have a higher risk of sudden cardiac death, as often as 2%/year. Two thirds of the symptomatic obstructed patients can be successfully managed long term with medical treatment alone (beta-blockers, disopyramide, verapamil) guided by transthoracic echocardiography (TTE) response and follow-up. Obstructed patients, who fail medical therapy, are usually offered invasive treatment: surgical septal myectomy, alcohol septal ablation, or DDD pacemaker. Preoperative TTE is a necessary guide for the surgeon in planning the operation. It gives the surgeon precise measurements of septal thickness, mitral valve leaflets length and floppiness and papillary muscle anomalies. Intraoperative transesophageal echocardiography is a very important tool for evaluating surgical results. Persistent SAM, resting outflow gradient more than 30 mm Hg or more than 50 mmHg with provocation, moderate to severe mitral regurgitation are indications for immediate revision. For patients >40 years old, and also not suitable for surgery because of comorbidities, alcohol septal ablation is viable alternative therapy for relief of obstruction and improvement of symptoms. Echocardiography is a valuable tool to choose the site of ablation (using myocardial contrast echocardiography), as well as for evaluation of results.

  20. Surviving competitive athletics with hypertrophic cardiomyopathy.

    PubMed

    Maron, B J; Klues, H G

    1994-06-01

    Hypertrophic cardiomyopathy (HC) is probably the most common cause of sudden cardiac death in youthful athletes, and this diagnosis has represented a contraindication to continued participation in competitive sports. Less well appreciated is the fact that within the clinical spectrum of HC are patients who, despite having this disease, have been able to undertake particularly intensive and often extraordinary levels of training for sports competition over many years without dying suddenly. Fourteen such patients (13 men and 1 woman, aged 30 to 66 years [mean 43]) form the present study group. HC was initially identified at 24 to 57 years of age (mean 34), usually under fortuitous circumstances. Patients most often competed in distance running (including the marathon, 7), but also in swimming, triathalon, basketball, and football. The duration of training ranged from 6 to 22 years (mean 15) and 5 continue to train and compete actively. The magnitude of training, competition, and achievement was considerable in most patients; 12 of the 14 performed either at the national, collegiate or professional level in their sport, completed numerous marathon and triathalon events, or sustained particularly rigorous training regimens of > or = 50 miles/week. Echocardiographic studies demonstrated a left ventricular wall thickness of 18 to 28 mm (mean 20) in most patients (12 of 14) having a relatively localized pattern of ventricular septal hypertrophy. It is possible for some patients with HC to tolerate particularly intense athletic training and competition for many years, and even maintain high levels of achievement without incurring symptoms and disease progression or dying suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Hypertrophic cardiomyopathy. Tools for identifying risk and alleviating symptoms.

    PubMed

    DeLuca, M; Tak, T

    2000-06-01

    Hypertrophic cardiomyopathy is characterized by left or right ventricular hypertrophy that is usually asymmetric and involves the interventricular septum. The condition has numerous genetic, anatomic, and clinical variations and continues to stimulate interest and investigation into causes and treatment options. New genetic forms of the disorder are being identified because of the rapid growth of molecular genetics. However, even with technological advances and a large database of information, risk stratification and treatment of hypertrophic cardiomyopathy remain difficult and controversial. Because of the high risk of sudden death, it is imperative that patients be advised against participation in competitive sports.

  2. Hypertrophic Cardiomyopathy: Practical Steps for Preventing Sudden Death.

    ERIC Educational Resources Information Center

    Maron, Barry J.

    2002-01-01

    Hypertrophic cardiomyopathy (HCM) is a rare cause of death among athletes, with deaths occurring in young, apparently healthy people. Differentiating HCM from conditioning hypertrophy is challenging. Routine detection involves family history, physical examination, electrocardiography, and echocardiography. Keys to differential diagnosis include…

  3. 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.

  4. Genetics Home Reference: familial hypertrophic cardiomyopathy

    MedlinePlus

    ... cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of the heart (cardiac) muscle . Thickening usually occurs ... also lead to symptoms of the condition. Cardiac hypertrophy often begins in adolescence or young adulthood, although ...

  5. Hypertrophic Cardiomyopathy Registry (HCMR): The rationale and design of an international, observational study of hypertrophic cardiomyopathy

    PubMed Central

    Kramer, Christopher M.; Appelbaum, Evan; Desai, Milind Y.; Desvigne-Nickens, Patrice; DiMarco, John P.; Friedrich, Matthias G.; Geller, Nancy; Heckler, Sarahfaye; Ho, Carolyn Y.; Jerosch-Herold, Michael; Ivey, Elizabeth A.; Keleti, Julianna; Kim, Dong-Yun; Kolm, Paul; Kwong, Raymond Y.; Maron, Martin S.; Schulz-Menger, Jeanette; Piechnik, Stefan; Watkins, Hugh; Weintraub, William S.; Wu, Pan; Neubauer, Stefan

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease with a frequency as high as 1 in 200. In many cases, HCM is caused by mutations in genes encoding the different components of the sarcomere apparatus. HCM is characterized by unexplained left ventricular hypertrophy (LVH), myofibrillar disarray, and myocardial fibrosis. The phenotypic expression is quite variable. While the majority of patients with HCM are asymptomatic, serious consequences are experienced in a subset of affected individuals who present initially with sudden cardiac death (SCD) or progress to refractory heart failure (HF). The HCMR study is a National Heart Lung and Blood Institute (NHLBI)-sponsored 2750 patient, 41 site, international registry and natural history study designed to address limitations in extant evidence to improve prognostication in HCM (NCT01915615). In addition to collection of standard demographic, clinical, and echocardiographic variables, patients will undergo state-of-the-art cardiac magnetic resonance (CMR) for assessment of left ventricular (LV) mass and volumes as well as replacement scarring and interstitial fibrosis. In addition, genetic and biomarker analysis will be performed. HCMR has the potential to change the paradigm of risk stratification in HCM, using novel markers to identify those at higher risk. PMID:26299218

  6. Familial hypertrophic cardiomyopathy: vectorcardiographic findings in echocardiographically unaffected relative.

    PubMed Central

    Loperfido, F; Fiorilli, R; Digaetano, A; Di Gennaro, M; Santarelli, P; Bellocci, F; Coppola, E; Zecchi, P

    1982-01-01

    The electrocardiographic and vectorcardiographic (Frank system) features of the first degree relatives of subjects with documented familial hypertrophic cardiomyopathy were analysed. A total of nine affected members and 29 relatives were examined in four families. THe subjects were considered to be affected when the septal to free posterior wall thickness ratio exceeded 1.3 at M-mode echocardiography. Four relatives had asymmetric septal hypertrophy. Among 25 relatives without evidence of asymmetric septal hypertrophy, two over 20 years and 10 under 20 years of age showed increased voltage of QRS anterior forces (Qz amplitude greater than 0.80 mV) on the orthogonal electrocardiogram. The vectorcardiographic data of the relatives under 20 years of age without evidence of asymmetric septal hypertrophy (18 subjects) were compared with those of 38 normal control subjects of comparable age range. The young relatives without disproportionate septal hypertrophy had significantly greater Qz amplitude and Q/Rz ratio than the normal control subjects. In contrast, the echocardiographic data were not significantly different. We suggest that the electrocardiographic finding of abnormal anterior forces in one or more first degree relatives of subjects with documented hypertrophic cardiomyopathy may constitute a valuable aid in ascertaining the genetic transmission of the disease and in recognising affected members without echocardiographic evidence of hypertrophic cardiomyopathy. Images PMID:7200794

  7. Reversible transition from a hypertrophic to a dilated cardiomyopathy

    PubMed Central

    Spillmann, Frank; Kühl, Uwe; Van Linthout, Sophie; Dominguez, Fernando; Escher, Felicitas; Schultheiss, Heinz‐Peter; Pieske, Burkert

    2015-01-01

    Abstract We report the case of a 17‐year‐old female patient with known hypertrophic cardiomyopathy and a Wolff‐Parkinson‐White syndrome. She came to our department for further evaluation of a new diagnosed dilated cardiomyopathy characterized by an enlargement of the left ventricle and a fall in ejection fraction. Clinically, she complained about atypical chest pain, arrhythmic episodes with presyncopal events, and dyspnea (NYHA III) during the last 6 months. Non‐invasive and invasive examinations including magnetic resonance imaging, electrophysiological examinations, and angiography did not lead to a conclusive diagnosis. Therefore, endomyocardial biopsies (EMBs) were taken to investigate whether a specific myocardial disease caused the impairment of the left ventricular function. EMB analysis resulted in the diagnosis of a virus‐negative, active myocarditis. Based on this diagnosis, an immunosuppressive treatment with prednisolone and azathioprine was started, which led to an improvement of cardiac function and symptoms within 3 months after initiating therapy. In conclusion, we show that external stress triggered by myocarditis can induce a reversible transition from a hypertrophic cardiomyopathy to a dilated cardiomyopathy phenotype. This case strongly underlines the need for a thorough and invasive examination of heart failure of unknown causes, including EMB investigations as recommend by the actual ESC position statement.

  8. 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

  9. Ehlers-Danlos Syndrome associated with cardiomyopathy hypertrophic obstructive.

    PubMed

    Pinto, Raimundo José Almeida de Oliveira; Santos, Adaílton Araújo dos; Azevedo, Mablo de Castro; Meira, Saulo Sacramento

    2015-01-01

    Ehlers-Danlos syndrome is a rare clinical condition caused by a genetic change that results in the formation of structurally or functionally altered collagen. The clinical manifestations are varied, being the most obvious skin hypermotility and increased joint flexibility, although other systems - such as cardiovascular, respiratory and neurological - may also be affected. This paper presents the report of a patient who sought medical attention with complaints of atypical chest pain. Clinical evaluation enabled hypothetical diagnosis of hypertrophic obstructive cardiomyopathy and Ehlers-Danlos syndrome. Initial electrocardiogram, echocardiogram and 24 hours holter allowed the confirmation of the first hypothesis. A skin biopsy performed later associated clinical data and confirmed the second hypothesis.

  10. Spiral hypertrophic cardiomyopathy as detected by cardiac magnetic resonance.

    PubMed

    Amin, Nessim; Williams, Ronald B; Yarmozik, June A; Biederman, Robert W W

    2014-03-01

    Hypertrophic cardiomyopathy (HCM) is a genetically determined heart muscle disease; characterized by left ventricular hypertrophy (LVH). Spiral HCM is described as having a counterclockwise rotation pattern of hypertrophy along with variable degrees of fibrosis. A 34-year-old female presented with symptoms suggestive of heart failure. Echocardiography showed concentric LVH with normal contractility. Cardiac MRI showed asymmetric septal hypertrophy with mid-cavity obliteration and a spiral pattern of variably increasing wall thickness. Late gadolinium enhancement (LGE) demonstrated several areas of abnormal postgadolinium uptake. We report a case of spiral HCM. We should consider cardiovascular magnetic resonance (CMR) as the reference standard for diagnosing HCM. PMID:24749165

  11. Hypertrophic cardiomyopathy in a mixed breed cat family.

    PubMed

    Nakagawa, Kiyoshi; Takemura, Naoyuki; Machida, Noboru; Kawamura, Masamichi; Amasaki, Hajime; Hirose, Hisashi

    2002-07-01

    A spayed female mixed cat (case 1) and its female offspring, the result of a pairing between case 1 and its male sibling, were diagnosed with hypertrophic cardiomyopathy (HCM). A pedigree survey revealed that the prevalence of HCM was at least 12.5% in the family, which was considered to be significantly higher than that in a hospital-based population (approximately 1.6%). Thus, this finding seems to support the suspected occurrence of familial HCM in this group of related cats.

  12. Family communication in a population at risk for hypertrophic cardiomyopathy.

    PubMed

    Batte, Brittany; Sheldon, Jane P; Arscott, Patricia; Huismann, Darcy J; Salberg, Lisa; Day, Sharlene M; Yashar, Beverly M

    2015-04-01

    Encouraging family communication is an integral component of genetic counseling; therefore, we sought to identify factors impacting communication to family members at risk for Hypertrophic Cardiomyopathy (HCM). Participants (N = 383) completed an online survey assessing: 1) demographics (gender, genetic test results, HCM family history, and disease severity); 2) illness representations; 3) family functioning and cohesiveness; 4) coping styles; 5) comprehension of HCM autosomal dominant inheritance; and 6) communication of HCM risk information to at-risk relatives. Participants were a national sample of individuals with HCM, recruited through the Hypertrophic Cardiomyopathy Association. Data from 183 participants were analyzed using a logistic regression analysis, with family communication as a dichotomous dependent variable. We found that female gender and higher comprehension of autosomal dominant inheritance were significant predictors of participants' communication of HCM risk information to all their siblings and children. Our results suggest that utilizing interventions that promote patient comprehension (e.g., a teaching-focused model of genetic counseling) are important and may positively impact family communication within families with HCM.

  13. [A clinical study of hypertrophic obstructive cardiomyopathy in the elderly].

    PubMed

    Chida, K; Ohkawa, S; Maeda, S; Kuboki, K; Imai, T; Sakai, M; Watanabe, C; Matsushita, S; Ueda, K; Kuramoto, K

    1990-09-01

    Seven elderly patients with hypertrophic obstructive cardiomyopathy (HOCM), who had the three following characteristics on echocardiograms 1) extremely thickened septum, 2) systolic anterior motion of the mitral valve, 3) mid systolic semi-closure of the aortic valve, were clinically evaluated. Ages ranged from 73 to 86 years old (average 78.9% yr.) and all were women. None had not a family history of hypertrophic cardiomyopathy but they had mild hypertension. Six patients showed a significant high voltage on the ST-segment and T-wave abnormalities ("strain" pattern). The left ventricular posterior wall as well as the septum was thickened in 5 and the remaining 2 showed asymmetrical septal hypertrophy (ASH) on echocardiograms. The left ventricular cavity was narrowed due to left ventricular hypertrophy and the shape of the left ventricular cavity was ovoid in all patients. The aorto-septal angles in these 7 patients were 80 degrees to 120 degrees. In addition, proximal septal bulge in all and anterior displacement of the mitral posterior leaflet due to the mitral ring calcification (MRC) in some patients contributed to the narrowing of the left ventricular outflow tract, and the mitral valve was pulled up toward the septum because of the good left ventricular systolic function (ejection fraction: 70 to 94% by echocardiography) and blood was ejected at a high velocity through a narrowed outflow tract (Venturi effect). Pressure gradients in the left ventricular outflow tract was 38 to 146 mmHg in 5 examined by cardiac catheterization. Biopsy specimens were obtained from 2 patients, showing hypertrophic myocytes (diameter: 20 to 30 micron) in 2 and mild disarray in 1.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Down Syndrome with Complete Atrioventricular Septal Defect, Hypertrophic Cardiomyopathy, and Pulmonary Vein Stenosis.

    PubMed

    Mahadevaiah, Guruprasad; Gupta, Manoj; Ashwath, Ravi

    2015-10-01

    The prevalence of congenital heart disease in infants with Down syndrome is 40%, compared with 0.3% in children who have normal chromosomes. Atrioventricular and ventricular septal defects are often associated with chromosomal aberrations, such as in trisomy 21, whereas hypertrophic cardiomyopathy is chiefly thought to be secondary to specific gene mutations. We found only one reported case of congenital hypertrophic cardiomyopathy and atrioventricular septal defect in an infant with Down syndrome. Here, we report atrioventricular septal defect, hypertrophic cardiomyopathy, and pulmonary vein stenosis in a neonate with Down syndrome-an apparently unique combination. In addition, we discuss the relevant medical literature.

  15. Down Syndrome with Complete Atrioventricular Septal Defect, Hypertrophic Cardiomyopathy, and Pulmonary Vein Stenosis

    PubMed Central

    Mahadevaiah, Guruprasad; Gupta, Manoj

    2015-01-01

    The prevalence of congenital heart disease in infants with Down syndrome is 40%, compared with 0.3% in children who have normal chromosomes. Atrioventricular and ventricular septal defects are often associated with chromosomal aberrations, such as in trisomy 21, whereas hypertrophic cardiomyopathy is chiefly thought to be secondary to specific gene mutations. We found only one reported case of congenital hypertrophic cardiomyopathy and atrioventricular septal defect in an infant with Down syndrome. Here, we report atrioventricular septal defect, hypertrophic cardiomyopathy, and pulmonary vein stenosis in a neonate with Down syndrome—an apparently unique combination. In addition, we discuss the relevant medical literature. PMID:26504441

  16. Coexistence of familial hypertrophic cardiomyopathy and vasospastic angina pectoris in two brothers.

    PubMed

    Suzuki, Nobuaki; Seto, Shinji; Koide, Yuji; Sato, Osami; Hirano, Hisataka; Kawano, Hiroaki; Yano, Katsusuke

    2003-09-01

    Two brothers had familial hypertrophic cardiomyopathy and vasospastic angina pectoris concurrently. Their family history showed that one of their sisters had hypertrophic cardiomyopathy and another brother died suddenly at age 52. The clinical diagnosis of hypertrophic cardiomyopathy was confirmed by an echocardiogram and left ventriculography. They had typical chest pain at rest, and a significant vasospasm of coronary arteries with chest pain and obvious ST-T changes in the electrocardiograms was provoked by intracoronary injection of acetylcholine in both patients. The administration of a calcium antagonist and nitrate was effective for ameliorating chest pain with no cardiovascular events during the follow up period of more than 3 years. Although underlying pathophysiologic abnormalities of familial hypertrophic cardiomyopathy and vasospastic angina pectoris are considered to be transmitted genetically, the genetic backgrounds of these cases remain to be clarified.

  17. Hypertrophic cardiomyopathy with Jeune syndrome: The first reported case.

    PubMed

    Güvenç, Osman; Sündüs Uygun, Saime; Çimen, Derya; Aslan, Eyüp; Annagür, Ali

    2016-09-01

    Jeune syndrome (Asphyxiating thoracic dysplasia) is a rare dystrophy of the skeleton, inherited as an autosomal recessive condition. Patients develop a narrowed thorax, rhizomelic dwarfism, and hepatic, renal, and pancreatic abnormalities. High rates of pulmonary hypoplasia and pulmonary hypertension have been reported. Some patients die in early stages of life due to respiratory failure. The case of a patient referred with a history of severe asphyxiating birth, who had been diagnosed with Jeune syndrome and later hypertrophic cardiomyopathy (HCM) upon echocardiographic examination is described in the present report. This rare disease is discussed with respect to the current literature, as the present is the first reported case to be accompanied by HCM. PMID:27665332

  18. Clinical utility of natriuretic peptides and troponins in hypertrophic cardiomyopathy.

    PubMed

    Kehl, Devin W; Buttan, Anshu; Siegel, Robert J; Rader, Florian

    2016-09-01

    The diagnosis of hypertrophic cardiomyopathy (HCM) is based on clinical, echocardiographic and in some cases genetic findings. However, prognostication remains limited except in the subset of patients with high-risk indicators for sudden cardiac death. Additional methods are needed for risk stratification and to guide clinical management in HCM. We reviewed the available data regarding natriuretic peptides and troponins in HCM. Plasma levels of natriuretic peptides, and to a lesser extent serum levels of troponins, correlate with established disease markers, including left ventricular thickness, symptom status, and left ventricular hemodynamics by Doppler measurements. As a reflection of left ventricular filling pressure, natriuretic peptides may provide an objective measure of the efficacy of a specific therapy. Both natriuretic peptides and troponins predict clinical risk in HCM independently of established risk factors, and their prognostic power is additive. Routine measurement of biomarker levels therefore may be useful in the clinical evaluation and management of patients with HCM.

  19. Ehlers-Danlos Syndrome associated with cardiomyopathy hypertrophic obstructive.

    PubMed

    Pinto, Raimundo José Almeida de Oliveira; Santos, Adaílton Araújo dos; Azevedo, Mablo de Castro; Meira, Saulo Sacramento

    2015-01-01

    Ehlers-Danlos syndrome is a rare clinical condition caused by a genetic change that results in the formation of structurally or functionally altered collagen. The clinical manifestations are varied, being the most obvious skin hypermotility and increased joint flexibility, although other systems - such as cardiovascular, respiratory and neurological - may also be affected. This paper presents the report of a patient who sought medical attention with complaints of atypical chest pain. Clinical evaluation enabled hypothetical diagnosis of hypertrophic obstructive cardiomyopathy and Ehlers-Danlos syndrome. Initial electrocardiogram, echocardiogram and 24 hours holter allowed the confirmation of the first hypothesis. A skin biopsy performed later associated clinical data and confirmed the second hypothesis. PMID:26312722

  20. Hypertrophic cardiomyopathy and ultra-endurance running - two incompatible entities?

    PubMed

    Wilson, Mathew G; Chandra, Navin; Papadakis, Michael; O'Hanlon, Rory; Prasad, Sanjay K; Sharma, Sanjay

    2011-01-01

    Regular and prolonged exercise is associated with increased left ventricular wall thickness that can overlap with hypertrophic cardiomyopathy (HCM). Differentiating physiological from pathological hypertrophy has important implications, since HCM is the commonest cause of exercise-related sudden cardiac death in young individuals. Most deaths have been reported in intermittent 'start-stop' sports such as football (soccer) and basketball. The theory is that individuals with HCM are unable to augment stroke volume sufficiently to meet the demands of endurance sports and are accordingly 'selected-out' of participation in such events. We report the case of an ultra-endurance athlete with 25 years of > 50 km competitive running experience, with genetically confirmed HCM; thereby demonstrating that these can be two compatible entities.

  1. A new era in clinical genetic testing for hypertrophic cardiomyopathy.

    PubMed

    Wheeler, Matthew; Pavlovic, Aleksandra; DeGoma, Emil; Salisbury, Heidi; Brown, Colleen; Ashley, Euan A

    2009-12-01

    Building on seminal studies of the last 20 years, genetic testing for hypertrophic cardiomyopathy (HCM) has become a clinical reality in the form of targeted exonic sequencing of known disease-causing genes. This has been driven primarily by the decreasing cost of sequencing, but the high profile of genome-wide association studies, the launch of direct-to-consumer genetic testing, and new legislative protection have also played important roles. In the clinical management of hypertrophic cardiomyopathy, genetic testing is primarily used for family screening. An increasing role is recognized, however, in diagnostic settings: in the differential diagnosis of HCM; in the differentiation of HCM from hypertensive or athlete's heart; and more rarely in preimplantation genetic diagnosis. Aside from diagnostic clarification and family screening, use of the genetic test for guiding therapy remains controversial, with data currently too limited to derive a reliable mutation risk prediction from within the phenotypic noise of different modifying genomes. Meanwhile, the power of genetic testing derives from the confidence with which a mutation can be called present or absent in a given individual. This confidence contrasts with our more limited ability to judge the significance of mutations for which co-segregation has not been demonstrated. These variants of "unknown" significance represent the greatest challenge to the wider adoption of genetic testing in HCM. Looking forward, next-generation sequencing technologies promise to revolutionize the current approach as whole genome sequencing will soon be available for the cost of today's targeted panel. In summary, our future will be characterized not by lack of genetic information but by our ability to effectively parse it.

  2. Mid-ventricular obstructive hypertrophic cardiomyopathy with an apical aneurysm caused by vasospastic angina.

    PubMed

    Kiyooka, Takahiko; Satoh, Yasuhiro

    2014-03-20

    Mid-ventricular obstructive hypertrophic cardiomyopathy (MVOHCM) is a rare form of cardiomyopathy, characterized by the presence of a pressure gradient between the left ventricular basal and apical chambers and is frequently associated with an apical aneurysm. However, the exact cause of this aneurysm remains unknown. We here describe a patient with MVOHCM in whom the apical aneurysm may be caused by vasospastic angina.

  3. Progress with genetic cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular dysplasia/cardiomyopathy.

    PubMed

    Hershberger, Ray E; Cowan, Jason; Morales, Ana; Siegfried, Jill D

    2009-05-01

    This review focuses on the genetic cardiomyopathies: principally dilated cardiomyopathy, with salient features of hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia/cardiomyopathy, regarding genetic etiology, genetic testing, and genetic counseling. Enormous progress has recently been made in identifying genetic causes for each cardiomyopathy, and key phenotype and genotype information is reviewed. Clinical genetic testing is rapidly emerging with a principal rationale of identifying at-risk asymptomatic or disease-free relatives. Knowledge of a disease-causing mutation can guide clinical surveillance for disease onset, thereby enhancing preventive and treatment interventions. Genetic counseling is also indicated for patients and their family members regarding the symptoms of their cardiomyopathy, its inheritance pattern, family screening recommendations, and genetic testing options and possible results.

  4. Radiofrequency catheter septal ablation for hypertrophic obstructive cardiomyopathy in children

    PubMed Central

    Emmel, M.; Sreeram, N.

    2005-01-01

    Background The definitive therapeutic options for symptomatic obstructive cardiomyopathy in childhood are restricted. At present, extensive surgical myectomy is the only procedure that is of proven benefit. Patients and Methods Three patients, aged 5, 11 and 17 years, respectively, with progressive hypertrophic obstructive cardiomyopathy and increasing symptoms were considered for radiofrequency catheter septal ablation. The peak Doppler gradient recorded on several occasions ranged between 50 to 90mmHg. Via a femoral arterial approach, the His bundle was initially plotted and marked using the LocaLisa navigation system. Subsequently, using a cooled tip catheter a series of lesions were placed in the hypertrophied septum, taking care to stay away from the His bundle. A total of 17, 50 and 45 lesions were applied in the three patients. In one case, the procedure was complicated by two episodes of ventricular fibrillation requiring DC cardioversion but without any neurological sequelae. Results The preablation peak-to-peak gradient between left ventricle and aorta was 50 mmHg, 60 mmHg and 60 mmHg, respectively, and remained unchanged immediately after the procedure. All patients were discharged from hospital 48 hours later. Serial measurement of serum troponin T and CK-MB isoenzyme confirmed significant myocardial necrosis. Follow-up echocardiography both at seven days and at six weeks postablation confirmed a beneficial haemodynamic result, with reduction of left ventricular outflow obstruction and relief of symptoms. Conclusion In young children, in whom alcohol-induced septal ablation is not an option, radiofrequency catheter ablation offers an alternative to surgery, with the benefits of repeatability and a lower risk of procedure-related permanent AV block. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:25696442

  5. Pharmacological treatment of hypertrophic cardiomyopathy: current practice and novel perspectives.

    PubMed

    Ammirati, Enrico; Contri, Rachele; Coppini, Raffaele; Cecchi, Franco; Frigerio, Maria; Olivotto, Iacopo

    2016-09-01

    Hypertrophic cardiomyopathy (HCM) is entering a phase of intense translational research that holds promise for major advances in disease-specific pharmacological therapy. For over 50 years, however, HCM has largely remained an orphan disease, and patients are still treated with old drugs developed for other conditions. While judicious use of the available armamentarium may control the clinical manifestations of HCM in most patients, specific experience is required in challenging situations, including deciding when not to treat. The present review revisits the time-honoured therapies available for HCM, in a practical perspective reflecting real-world scenarios. Specific agents are presented with doses, titration strategies, pros and cons. Peculiar HCM dilemmas such as treatment of dynamic outflow obstruction, heart failure caused by end-stage progression and prevention of atrial fibrillation and ventricular arrhythmias are assessed. In the near future, the field of HCM drug therapy will rapidly expand, based on ongoing efforts. Approaches such as myocardial metabolic modulation, late sodium current inhibition and allosteric myosin inhibition have moved from pre-clinical to clinical research, and reflect a surge of scientific as well as economic interest by academia and industry alike. These exciting developments, and their implications for future research, are discussed. PMID:27109894

  6. Diastolic filling in a physical model of obstructive hypertrophic cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Schovanec, Joseph; Samaee, Milad; Lai, Hong Kuan; Santhanakrishnan, Arvind

    2015-11-01

    Hypertrophic Cardiomyopathy (HCM) is an inherited heart disease that affects as much as one in 500 individuals, and is the most common cause of sudden death in young athletes. The myocardium becomes abnormally thick in HCM and deforms the internal geometry of the left ventricle (LV). Previous studies have shown that a vortex is formed during diastolic filling, and further that the dilated LV morphology seen in systolic heart failure results in altering the filling vortex from elliptical to spherical shape. We have also previously shown that increasing LV wall stiffness decreases the filling vortex circulation. However, alterations to intraventricular filling fluid dynamics due to an obstructive LV morphology and locally elevated wall stiffness (in the hypertrophied region) have not been previously examined from a mechanistic standpoint. We conducted an experimental study using an idealized HCM physical model and compared the intraventricular flow fields obtained from 2D PIV to a baseline LV physical model with lower wall stiffness and anatomical geometry. The obstruction in the HCM model leads to earlier breakdown of the filling vortex as compared to the anatomical LV. Intraventricular filling in both models under increased heart rates will be discussed.

  7. Factors Associated with Uptake of Genetics Services for Hypertrophic Cardiomyopathy.

    PubMed

    Khouzam, Amirah; Kwan, Andrea; Baxter, Samantha; Bernstein, Jonathan A

    2015-10-01

    Hypertrophic cardiomyopathy (HCM) is a common cardiovascular disorder with variable expressivity and incomplete penetrance. Clinical guidelines recommend consultation with a genetics professional as part of an initial assessment for HCM, yet there remains an underutilization of genetics services. We conducted a study to assess factors associated with this underutilization within the framework of the Health Belief Model (HBM). An online survey was completed by 306 affected individuals and at risk family members. Thirty-seven percent of individuals (113/306) had visited a genetics professional for reasons related to HCM. Genetic testing was performed on 53 % (162/306). Individuals who had undergone testing were more likely to have seen a genetics professional (p < 0.001), had relatives with an HCM diagnosis (p = 0.002), and have a known familial mutation (p < 0.001). They were also more likely to agree that genetic testing would satisfy their curiosity (p < 0.001), provide reassurance (p < 0.001), aid family members in making healthcare decisions (p < 0.001), and encourage them to engage in a healthier lifestyle (p = 0.002). The HBM components of cues to action and perceived benefits and barriers had the greatest impact on uptake of genetic testing. In order to ensure optimal counseling and care for individuals and families with HCM, awareness and education around HCM and genetic services should be promoted in both physicians and patients alike.

  8. Echocardiographic diagnosis of the different phenotypes of hypertrophic cardiomyopathy.

    PubMed

    Parato, Vito Maurizio; Antoncecchi, Valeria; Sozzi, Fabiola; Marazia, Stefania; Zito, Annapaola; Maiello, Maria; Palmiero, Pasquale

    2016-01-01

    Hypertrophic Cardiomyopathy (HCM) is an inherited cardiovascular disorder of great genetic heterogeneity and has a prevalence of 0.1 - 0.2 % in the general population. Several hundred mutations in more than 27 genes, most of which encode sarcomeric structures, are associated with the HCM phenotype. Then, HCM is an extremely heterogeneous disease and several phenotypes have been described over the years. Originally only two phenotypes were considered, a more common, obstructive type (HOCM, 70 %) and a less common, non-obstructive type (HNCM, 30 %) (Maron BJ, et al. Am J Cardiol 48:418 -28, 1981). Wigle et al. (Circ 92:1680-92, 1995) considered three types of functional phenotypes: subaortic obstruction, midventricular obstruction and cavity obliteration. A leader american working group suggested that HCM should be defined genetically and not morphologically (Maron BJ, et al. Circ 113:1807-16, 2006). The European Society of Cardiology Working Group on Myocardial and Pericardial Diseases recommended otherwise a morphological classification (Elliott P, et al. Eur Heart J 29:270-6, 2008). Echocardiography is still the principal tool for the diagnosis, prognosis and clinical management of HCM. It is well known that the echocardiographic picture may have a clinical and prognostic impact. For this reason, in this article, we summarize the state of the art regarding the echocardiographic pattern of the HCM phenotypes and its impact on clinical course and prognosis. PMID:27519172

  9. Staphylococcus hominis native mitral valve bacterial endocarditis (SBE) in a patient with hypertrophic obstructive cardiomyopathy.

    PubMed

    Cunha, Burke A; Esrick, Michael D; Larusso, Melissa

    2007-01-01

    There are several species of coagulase-negative Staphylococci (CoNS) that are part of the normal skin flora and are relatively noninvasive/low virulence organisms. CoNS are important pathogens in patients with prosthetic devices and are the most common pathogen associated with prosthetic valve endocarditis. CoNS native valve infective endocarditis (IE) is rare. Patients with hypertrophic obstructive cardiomyopathy and an outflow pressure gradient greater than 30 mm Hg are predisposed to IE. There has been only one reported case of non-mitral valve IE due to CoNS in a patient with hypertrophic obstructive cardiomyopathy. To the best of our knowledge, we report the first case of Staphylococcal hominis mitral valve endocarditis in a patient with hypertrophic obstructive cardiomyopathy.

  10. Successful management of hypertrophic cardiomyopathy in a Matschie's tree kangaroo (Dendrolagus matschiei).

    PubMed

    Fredholm, Daniel V; Jones, Ashley E; Hall, Natalie H; Russell, Kathleen; Heard, Darryl J

    2015-03-01

    A 3-yr-old, intact male Matschie's tree kangaroo (Dendrolagus matschiei) was examined for a 1-wk history of intermittent lethargy and tachypnea. An echocardiogram revealed concentric hypertrophy of the left ventricular free wall and interventricular septum. These findings were compared to measurements from healthy Matschie's tree kangaroos, supporting a diagnosis of hypertrophic cardiomyopathy. At the time of publication, the patient has been managed for over 11.5 yr, using a combination of enalapril, furosemide, diltiazem, and diet modifications. Hypertrophic cardiomyopathy should be considered as a differential diagnosis in tree kangaroos exhibiting signs of cardiovascular or respiratory distress. This case represents the first report of antemortem diagnosis and successful management of hypertrophic cardiomyopathy in a Matschie's tree kangaroo.

  11. Altered patterns of cardiac intercellular junction distribution in hypertrophic cardiomyopathy.

    PubMed Central

    Sepp, R.; Severs, N. J.; Gourdie, R. G.

    1996-01-01

    OBJECTIVE: To examine the distribution pattern of intercellular junctions (the mechanically coupling desmosomes and the electrically coupling gap junctions) in hypertrophic cardiomyopathy (HCM) hearts showing myofibre disarray. DESIGN: Samples from six necropsied hearts were studied, representing the interventricular septum and the free walls of the left and right ventricles. Immunohistochemical labelling of desmoplakin was used as a marker for desmosomes, and of connexin43 as a marker for gap junctions, in single and double stainings. The slides were examined by confocal laser scanning microscopy. RESULTS: Marked disorganisation of intercalated discs was observed in areas featuring myofibre disarray. Besides overall derangement, localised abnormalities in desmosome organisation were evident, which included: (1) the formation of abnormally enlarged megadiscs; (2) the presence of intersecting disc structures; and (3) aberrant side to side desmosomal connections. Gap junctional abnormalities included: (1) random distribution of gap junctions over the surface of myocytes, rather than localisation to intercalated discs; (2) abundant side to side gap junction connections between adjacent myocytes; and (3) formation of abnormally shaped gap junctions. Circles of myocytes continuously interconnected by gap junctions were also observed. Regions of the diseased hearts lacking myofibre disarray, and control hearts of normal patients and patients with other cardiac diseases, did not show these alterations. CONCLUSIONS: The disorganisation of the intercellular junctions associated with myofibre disarray in HCM may play an important role in the pathophysiological manifestations of the disease. The remodelling of gap junction distribution may underlie the formation of an arrhythmogenic substrate, thereby contributing to the generation and maintenance of cardiac arrhythmias associated with HCM. Images PMID:8944586

  12. A Murine Hypertrophic Cardiomyopathy Model: The DBA/2J Strain.

    PubMed

    Zhao, Wenyuan; Zhao, Tieqiang; Chen, Yuanjian; Zhao, Fengbo; Gu, Qingqing; Williams, Robert W; Bhattacharya, Syamal K; Lu, Lu; Sun, Yao

    2015-01-01

    Familial hypertrophic cardiomyopathy (HCM) is attributed to mutations in genes that encode for the sarcomere proteins, especially Mybpc3 and Myh7. Genotype-phenotype correlation studies show significant variability in HCM phenotypes among affected individuals with identical causal mutations. Morphological changes and clinical expression of HCM are the result of interactions with modifier genes. With the exceptions of angiotensin converting enzyme, these modifiers have not been identified. Although mouse models have been used to investigate the genetics of many complex diseases, natural murine models for HCM are still lacking. In this study we show that the DBA/2J (D2) strain of mouse has sequence variants in Mybpc3 and Myh7, relative to widely used C57BL/6J (B6) reference strain and the key features of human HCM. Four-month-old of male D2 mice exhibit hallmarks of HCM including increased heart weight and cardiomyocyte size relative to B6 mice, as well as elevated markers for cardiac hypertrophy including β-myosin heavy chain (MHC), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and skeletal muscle alpha actin (α1-actin). Furthermore, cardiac interstitial fibrosis, another feature of HCM, is also evident in the D2 strain, and is accompanied by up-regulation of type I collagen and α-smooth muscle actin (SMA)-markers of fibrosis. Of great interest, blood pressure and cardiac function are within the normal range in the D2 strain, demonstrating that cardiac hypertrophy and fibrosis are not secondary to hypertension, myocardial infarction, or heart failure. Because D2 and B6 strains have been used to generate a large family of recombinant inbred strains, the BXD cohort, the D2 model can be effectively exploited for in-depth genetic analysis of HCM susceptibility and modifier screens.

  13. Angiotensin converting enzyme gene polymorphism in familial hypertrophic cardiomyopathy patients

    SciTech Connect

    Yu, B; Peric, S.; Ross, D.

    1994-09-01

    An insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene is a useful predictor of human plasma ACE levels. ACE levels tend to be lowest in subjects with ACE genotype DD and intermediate in subjects with ACE genotype ID. Angiotensin II (Ang II) as a product of ACE is a cardiac growth factor and produces a marked hypertrophy of the chick myocyte in cell culture. Rat experiments also suggest that a small dose of ACE inhibitor that does not affect the afterload results in prevention or regression of cardiac hypertrophy. In order to study the relationship of ACE and the severity of hypertrophy, the ACE genotype has been determined in 28 patients with a clinical diagnosis of familial hypertrophic cardiomyopathy (FHC) and 51 normal subjects. The respective frequencies of I and D alleles were: 0.52 and 0.48 (in FHC patients) and 0.44 and 0.56 (in the normal controls). There was no significant difference in the allele frequencies between FHC and normal subjects ({chi}{sup 2}=0.023, p>0.05). The II, ID, and DD genotypes were present in 7, 15, and 6 FHC patients, respectively. The averages of maximal thickness of the interventricular septum measured by echocardiography or at autopsy were 18 {plus_minus}3, 19{plus_minus}4, and 19{plus_minus}3 mm in II, ID and DD genotypes, respectively. The ACE gene polymorphism did not correlate with the severity of left ventricular hypertrophy in FHC patients (r{sub s}=0.231, p>0.05). These results do not necessarily exclude the possible effect of Ang II on the hypertrophy since the latter may be produced through the action of chymase in the human ventricles. However, ACE gene polymorphism is not a useful predictor of the severity of myocardial hypertrophy in FHC patients.

  14. Clinical significance of giant negative T waves in hypertrophic cardiomyopathy

    SciTech Connect

    Alfonso, F.; Nihoyannopoulos, P.; Stewart, J.; Dickie, S.; Lemery, R.; McKenna, W.J. )

    1990-04-01

    To assess the clinical significance of giant negative T waves in patients with hypertrophic cardiomyopathy from Western nations, clinical, echocardiographic, radionuclide and 48 h electrocardiographic (ECG) monitoring findings were compared in 27 patients with and 56 patients without giant negative T waves. Patients with giant negative T waves were older at diagnosis (43 +/- 15 versus 32 +/- 14 years, p less than 0.005), had greater ECG voltage (SV1 + RV5 = 57 +/- 20 versus 37 +/- 18 mm, p less than 0.001) and had a more vertical frontal plane axis (38.4 +/- 34 versus 13.4 +/- 45 degrees, p less than 0.05). Left ventricular wall thickness on two-dimensional echocardiography was similar at the mitral valve level (mean 16.5 +/- 4 versus 16.6 +/- 3 cm), but was greater at the papillary muscle level (mean 20.7 +/- 5 versus 17.6 +/- 3 mm, p less than 0.01) and apex (mean 23.3 +/- 5 versus 17.3 +/- 3 mm, p less than 0.001) in patients with giant negative T waves. Fewer patients with giant negative T waves had asymmetric septal hypertrophy (12 (44%) of 27 versus 36 (64%) of 56, p = 0.08) or systolic anterior motion of the mitral valve (4 (14%) of 27 versus 25 (45%) of 56, p less than 0.01), whereas left ventricular end-diastolic (44.1 +/- 6 versus 39.6 +/- 5 mm, p = 0.01) and end-systolic dimensions (27.8 +/- 4 versus 24 +/- 6 mm, p less than 0.05) were greater in this group. Nonsustained ventricular tachycardia was seen on ECG monitoring in 21% of patients in both groups.

  15. Anaesthetic management of severe hypertrophic obstructive cardiomyopathy with bronchial asthma for emergency caesarean section.

    PubMed

    Rajesh, M C; Varma, Ravi; Lima, P; Ramdas, E K

    2012-10-01

    A 39-year-old primi and a known case of hypertrophic obstructive cardiomyopathy presented for emergency lower segment caesarean section. She was also an asthmatic with a recent exacerbation. She underwent uneventful lower segment caesarean section under general anaesthesia with lumbar epidural analgesia for postoperative pain relief. Anaesthetic agents and techniques were selected to suit the haemodynamic profile of severe hypertrophic obstructive cardiomyopathy in pregnancy. The case has been reported because of successful outcome in an emergency scenario with such high intraventricular gradients and omissions in the case so that it will be of benefit to readers who may happen to land up in similar situations. PMID:23738413

  16. Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sustained pressure overload causes cardiac hypertrophy and the transition to heart failure. We show here that dietary supplementation with physiologically relevant levels of copper (Cu) reverses pre-established hypertrophic cardiomyopathy in the presence of pressure overload induced by ascending aor...

  17. Missense mutation of the {beta}-cardiac myosin heavy-chain gene in hypertrophic cardiomyopathy

    SciTech Connect

    Arai, Shoichi; Matsuoka, Rumiko; Hirayama, Kenji; Sakurai, Hisanao

    1995-09-11

    Hypertrophic cardiomyopathy occurs as an autosomal dominant familial disorder or as a sporadic disease without familial involvement. We describe a missense mutation of the {beta}-cardiac myosin heavy chain (MHC) gene, a G to T transversion (741 Gly{r_arrow}Trp) identified by direct sequencing of exon 20 in four individuals affected with familial hypertrophic cardiomyopathy. Three individuals with sporadic hypertrophic cardiomyopathy, whose parents are clinically and genetically unaffected, had sequence variations of exon 34 of the {alpha}-cardiac MHC gene (a C to T transversion, 1658 Asp{r_arrow}Asp, resulting in FokI site polymorphism), of intron 33 of the {alpha}-cardiac MHC gene (a G to A and an A to T transversion), and also of intron 14 of the {beta}-cardiac MHC gene (a C to T transversion in a patient with Noonan syndrome). Including our case, 30 missense mutations of the {beta}-cardiac MHC gene in 49 families have been reported thus far worldwide. Almost all are located in the region of the gene coding for the globular head of the molecule, and only one mutation was found in both Caucasian and Japanese families. Missense mutations of the {Beta}-cardiac MHC gene in hypertrophic cardiomyopathy may therefore differ according to race. 29 refs., 6 figs., 3 tabs.

  18. Relationship between Regional Fat Distribution and Hypertrophic Cardiomyopathy Phenotype

    PubMed Central

    Guglielmi, Valeria; Maresca, Luciano; Lanzillo, Chiara; Marinoni, Giorgia Michela; D’Adamo, Monica; Di Roma, Mauro; Preziosi, Paolo; Bellia, Alfonso; Calò, Leonardo; Sbraccia, Paolo

    2016-01-01

    Background Hypertrophic cardiomyopathy (HCM), the most common genetic heart disease, is characterized by heterogeneous phenotypic expression. Body mass index has been associated with LV mass and heart failure symptoms in HCM. The aim of our study was to investigate whether regional (trunk, appendicular, epicardial) fat distribution and extent could be related to hypertrophy severity and pattern in HCM. Methods Cardiovascular magnetic resonance was performed in 32 subjects with echocardiography-based diagnosis of HCM (22M/10F, 57.2±12.6 years) characterized by predominant hypertrophy at the interventricular septum (IVS). Regional fat distribution was assessed by dual-energy X-ray absorptiometry. Results Gender differences were detected in maximum IVS thickness (M: 18.3±3.8 mm vs. F: 14.3±4 mm, p = 0.012), right ventricle (RV) systolic function (M: 61.3±6.7%; F: 67.5±6.3%, p = 0.048), indexed RV end-diastolic (M: 64.8±16.3 ml/m2; F: 50.7±15.5 ml/m2, p = 0.04) and end-systolic volumes (M: 24.3±8.3 ml/m2; F: 16.7±7.4 ml/m2, p = 0.04). After adjusting for age and gender, maximum IVS thickness was associated with truncal fat (Tr-FAT) (β = 0.43, p = 0.02), but not with either appendicular or epicardial fat. Epicardial fat resulted independently associated with NT-proBNP levels (β = 0.63, p = 0.04). Late Gadolinium Enhancement-positive subjects displayed greater maximum IVS thickness (p = 0.02), LV mass index (p = 0.015) and NT-proBNP levels (p = 0.04), but no associations with fat amount or distribution were observed. Conclusion Truncal, but not appendicular or epicardial fat amount, seems to be related with maximum IVS thickness, the hallmark feature in our cohort of HCM patients. Further prospective researches are needed to assess a potential causative effect of central adiposity on HCM phenotype. PMID:27388274

  19. Clinical Utility of Cardiovascular Magnetic Resonance in Hypertrophic Cardiomyopathy

    PubMed Central

    2012-01-01

    Hypertrophic cardiomyopathy (HCM) is characterized by substantial genetic and phenotypic heterogeneity, leading to considerable diversity in clinical course including the most common cause of sudden death in young people and a determinant of heart failure symptoms in patients of any age. Traditionally, two-dimensional echocardiography has been the most reliable method for establishing a clinical diagnosis of HCM. However, cardiovascular magnetic resonance (CMR), with its high spatial resolution and tomographic imaging capability, has emerged as a technique particularly well suited to characterize the diverse phenotypic expression of this complex disease. For example, CMR is often superior to echocardiography for HCM diagnosis, by identifying areas of segmental hypertrophy (ie., anterolateral wall or apex) not reliably visualized by echocardiography (or underestimated in terms of extent). High-risk HCM patient subgroups identified with CMR include those with thin-walled scarred LV apical aneurysms (which prior to CMR imaging in HCM remained largely undetected), end-stage systolic dysfunction, and massive LV hypertrophy. CMR observations also suggest that the cardiomyopathic process in HCM is more diffuse than previously regarded, extending beyond the LV myocardium to include thickening of the right ventricular wall as well as substantial morphologic diversity with regard to papillary muscles and mitral valve. These findings have implications for management strategies in patients undergoing invasive septal reduction therapy. Among HCM family members, CMR has identified unique phenotypic markers of affected genetic status in the absence of LV hypertrophy including: myocardial crypts, elongated mitral valve leaflets and late gadolinium enhancement. The unique capability of contrast-enhanced CMR with late gadolinium enhancement to identify myocardial fibrosis has raised the expectation that this may represent a novel marker, which may enhance risk stratification. At

  20. Myocardial Native T1 Time in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Kato, Shingo; Nakamori, Shiro; Bellm, Steven; Jang, Jihye; Basha, Tamer; Maron, Martin; Manning, Warren J; Nezafat, Reza

    2016-10-01

    In hypertrophic cardiomyopathy (HC), there are significant variations in left ventricular (LV) wall thickness and fibrosis, which necessitates a volumetric coverage. Slice-interleaved T1 (STONE) mapping sequence allows for the assessment of native T1 time with complete coverage of LV myocardium. The aims of this study were to evaluate spatial heterogeneity of native T1 time in patients with HC. Twenty-nine patients with HC (55 ± 16 years) and 15 healthy adult control subjects (46 ± 19 years) were studied. Native T1 mapping was performed using STONE sequence which enables acquisition of 5 slices in the short-axis plane within a 90 seconds free-breathing scan. We measured LV native T1 time and maximum LV wall thickness in each 16 segments from 3 slices (basal, midventricular and apical slice). Late gadolinium enhanced (LGE) magnetic resonance imaging was acquired to assess the presence of myocardial enhancement. In patients with HC, LV native T1 time was significantly elevated compared with healthy controls, regardless of the presence or absence of LGE (mean native T1 time; LGE positive segments from HC, 1,141 ± 46 ms; LGE negative segments from HC, 1,114 ± 56 ms; segments from healthy controls, 1,065 ± 35 ms, p <0.001). Elevation of native T1 time was defined as >1,135 ms, which was +2SD of native T1 time by STONE sequence in healthy controls. A total of 120 of 405 (30%) LGE negative segments from patients with HC showed elevated native T1 time. Prevalence of segments with elevated native T1 time for basal, midventricular, and apical slice was 29%, 25%, 38%, respectively. Significant correlation was found between LV wall thickness and LV native T1 time (y = 0.029 × -22.6, p <0.001 by Spearman's correlation coefficient). In conclusion, substantial number of segments without LGE showed elevation of native T1 time, and whole-heart T1 mapping revealed heterogeneity of myocardial native T1 time in patients with HC. PMID:27567135

  1. Left Atrial Mechanical Function and Global Strain in Hypertrophic Cardiomyopathy

    PubMed Central

    Yoon, Yeonyee E.; Kim, Hack-Lyoung; Lee, Seung-Pyo; Kim, Hyung-Kwan; Kim, Yong-Jin; Cho, Goo-Yeong; Zo, Joo-Hee; Sohn, Dae-Won

    2016-01-01

    Background Atrial fibrillation is the most common arrhythmia and is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM). Although left atrial (LA) remodeling and dysfunction are known to associate with the development of atrial fibrillation in HCM, the changes of the LA in HCM patients remain unclear. This study aimed to evaluate the changes in LA size and mechanical function in HCM patients compared to control subjects and to determine the characteristics of HCM associated with LA remodeling and dysfunction. Methods Seventy-nine HCM patients (mean age, 54 ± 11 years; 76% were men) were compared to 79 age- and sex-matched controls (mean age, 54 ± 11 years; 76% were men) and 20 young healthy controls (mean age, 33 ± 5 years; 45% were men). The LA diameter, volume, and mechanical function, including global strain (ε), were evaluated by 2D-speckle tracking echocardiography. The phenotype of HCM, maximal left ventricular (LV) wall thickness, LV mass, and presence and extent of late gadolinium enhancement (LGE) were evaluated with cardiac magnetic resonance imaging. Results HCM patients showed increased LA volume index, impaired reservoir function, and decreased LA ε compared to the control subjects. When we divided the HCM group according to a maximal LA volume index (LAVImax) of 38.7 ml/m2 or LA ε of 21%, no significant differences in the HCM phenotype and maximal LV wall thickness were observed for patients with LAVImax >38.7 ml/m2 or LA ε ≤21%. Conversely, the LV mass index was significantly higher both in patients with maximal LA volume index >38.7 ml/m2 and with LA ε ≤21% and was independently associated with LAVImax and LA ε. Although the LGE extent was increased in patients with LA ε ≤21%, it was not independently associated with either LAVImax or LA ε. Conclusions HCM patients showed progressed LA remodeling and dysfunction; the determinant of LA remodeling and dysfunction was LV mass index rather than LV myocardial fibrosis

  2. Prediction of Sarcomere Mutations in Subclinical Hypertrophic Cardiomyopathy

    PubMed Central

    Captur, Gabriella; Lopes, Luis R.; Mohun, Timothy J.; Patel, Vimal; Li, Chunming; Bassett, Paul; Finocchiaro, Gherardo; Ferreira, Vanessa M.; Esteban, Maite Tome; Muthurangu, Vivek; Sherrid, Mark V.; Day, Sharlene M.; Canter, Charles E.; McKenna, William J.; Seidman, Christine E.; Bluemke, David A.; Elliott, Perry M.; Ho, Carolyn Y.; Moon, James C.

    2014-01-01

    Background Sarcomere protein mutations in hypertrophic cardiomyopathy (HCM) induce subtle cardiac structural changes prior to the development of left ventricular hypertrophy (LVH). We have proposed that myocardial crypts are part of this phenotype and independently associated with the presence of sarcomere gene mutations. We tested this hypothesis in genetic HCM pre-LVH (G+LVH−). Methods and Results A multi-centre case-control study investigated crypts and 22 other cardiovascular magnetic resonance (CMR) parameters in subclinical HCM to determine their strength of association with sarcomere gene mutation carriage. The G+LVH− sample (n=73) was 29±13 years old and 51% male. Crypts were related to the presence of sarcomere mutations (for ≥1 crypt, β=2.5, 95% confidence interval [CI] 0.5-4.4, p=0.014; for ≥2 crypts, β=3.0, 95%CI 0.8-7.9, p=0.004). In combination with 3 other parameters: anterior mitral valve leaflet (AMVL) elongation (β=2.1, 95%CI 1.7-3.1, p<0.001), abnormal LV apical trabeculae (β=1.6, 95%CI 0.8-2.5, p<0.001), and smaller LV end-systolic volumes (β=1.4, 95%CI 0.5-2.3, p=0.001), multiple crypts indicated the presence of sarcomere gene mutations with 80% accuracy and an area under the curve of 0.85 (95%CI 0.8-0.9). In this G+LVH− population cardiac myosin-binding protein C mutation carriers had twice the prevalence of crypts when compared to the other combined mutations (47 vs. 23%; odds ratio, 2.9; 95%CI 1.1–7.9; p=0.045). Conclusions The subclinical HCM phenotype measured by CMR in a multi-center environment and consisting of crypts (particularly multiple), AMVL elongation, abnormal trabeculae and smaller LV systolic cavity, is indicative of the presence of sarcomere gene mutations and highlights the need for further study. PMID:25228707

  3. A New 4D Trajectory-Based Approach Unveils Abnormal LV Revolution Dynamics in Hypertrophic Cardiomyopathy

    PubMed Central

    Madeo, Andrea; Piras, Paolo; Re, Federica; Gabriele, Stefano; Nardinocchi, Paola; Teresi, Luciano; Torromeo, Concetta; Chialastri, Claudia; Schiariti, Michele; Giura, Geltrude; Evangelista, Antonietta; Dominici, Tania; Varano, Valerio; Zachara, Elisabetta; Puddu, Paolo Emilio

    2015-01-01

    The assessment of left ventricular shape changes during cardiac revolution may be a new step in clinical cardiology to ease early diagnosis and treatment. To quantify these changes, only point registration was adopted and neither Generalized Procrustes Analysis nor Principal Component Analysis were applied as we did previously to study a group of healthy subjects. Here, we extend to patients affected by hypertrophic cardiomyopathy the original approach and preliminarily include genotype positive/phenotype negative individuals to explore the potential that incumbent pathology might also be detected. Using 3D Speckle Tracking Echocardiography, we recorded left ventricular shape of 48 healthy subjects, 24 patients affected by hypertrophic cardiomyopathy and 3 genotype positive/phenotype negative individuals. We then applied Generalized Procrustes Analysis and Principal Component Analysis and inter-individual differences were cleaned by Parallel Transport performed on the tangent space, along the horizontal geodesic, between the per-subject consensuses and the grand mean. Endocardial and epicardial layers were evaluated separately, different from many ecocardiographic applications. Under a common Principal Component Analysis, we then evaluated left ventricle morphological changes (at both layers) explained by first Principal Component scores. Trajectories’ shape and orientation were investigated and contrasted. Logistic regression and Receiver Operating Characteristic curves were used to compare these morphometric indicators with traditional 3D Speckle Tracking Echocardiography global parameters. Geometric morphometrics indicators performed better than 3D Speckle Tracking Echocardiography global parameters in recognizing pathology both in systole and diastole. Genotype positive/phenotype negative individuals clustered with patients affected by hypertrophic cardiomyopathy during diastole, suggesting that incumbent pathology may indeed be foreseen by these methods

  4. A new 4D trajectory-based approach unveils abnormal LV revolution dynamics in hypertrophic cardiomyopathy.

    PubMed

    Madeo, Andrea; Piras, Paolo; Re, Federica; Gabriele, Stefano; Nardinocchi, Paola; Teresi, Luciano; Torromeo, Concetta; Chialastri, Claudia; Schiariti, Michele; Giura, Geltrude; Evangelista, Antonietta; Dominici, Tania; Varano, Valerio; Zachara, Elisabetta; Puddu, Paolo Emilio

    2015-01-01

    The assessment of left ventricular shape changes during cardiac revolution may be a new step in clinical cardiology to ease early diagnosis and treatment. To quantify these changes, only point registration was adopted and neither Generalized Procrustes Analysis nor Principal Component Analysis were applied as we did previously to study a group of healthy subjects. Here, we extend to patients affected by hypertrophic cardiomyopathy the original approach and preliminarily include genotype positive/phenotype negative individuals to explore the potential that incumbent pathology might also be detected. Using 3D Speckle Tracking Echocardiography, we recorded left ventricular shape of 48 healthy subjects, 24 patients affected by hypertrophic cardiomyopathy and 3 genotype positive/phenotype negative individuals. We then applied Generalized Procrustes Analysis and Principal Component Analysis and inter-individual differences were cleaned by Parallel Transport performed on the tangent space, along the horizontal geodesic, between the per-subject consensuses and the grand mean. Endocardial and epicardial layers were evaluated separately, different from many ecocardiographic applications. Under a common Principal Component Analysis, we then evaluated left ventricle morphological changes (at both layers) explained by first Principal Component scores. Trajectories' shape and orientation were investigated and contrasted. Logistic regression and Receiver Operating Characteristic curves were used to compare these morphometric indicators with traditional 3D Speckle Tracking Echocardiography global parameters. Geometric morphometrics indicators performed better than 3D Speckle Tracking Echocardiography global parameters in recognizing pathology both in systole and diastole. Genotype positive/phenotype negative individuals clustered with patients affected by hypertrophic cardiomyopathy during diastole, suggesting that incumbent pathology may indeed be foreseen by these methods. Left

  5. Echocardiography Differences Between Athlete’s Heart Hearth and Hypertrophic Cardiomyopathy

    PubMed Central

    Kreso, Amir; Barakovic, Fahir; Medjedovic, Senad; Halilbasic, Amila; Klepic, Muhamed

    2015-01-01

    Introduction: Among long term athletes there is always present hypertrophy of the left ventricle walls as well as increased cardiac mass. These changes are the result of the heart muscle adaptation to load during the years of training, which should not be considered as pathology. In people suffering from hypertrophic cardiomyopathy (HCM), there is also present hypertrophy of the left ventricle walls and increased mass of the heart, but these changes are the result of pathological changes in the heart caused by a genetic predisposition for the development HCM of. Differences between myocardial hypertrophy in athletes and HCM are not clearly differentiated and there are always dilemmas between pathological and physiological hypertrophy. The goal of the study is to determine and compare the echocardiographic cardiac parameters of longtime athletes to patients with hypertrophic cardiomyopathy. Material and methods: The study included 60 subjects divided into two groups: active athletes and people with hypertrophic cardiomyopathy. Results: Mean values of IVSd recorded in GB is IVSd=17.5 mm (n=20, 95% CI, 16.00–19.00 mm), while a significantly smaller mean value is recorded in GA, IVSd=10.0 mm (n=40, 95% CI, 9.00-11.00 mm). The mean value of the left ventricle in diastole (LVDd) recorded in the GA is LVDd=51 mm (n=40; 95% CI, 48.00 to 52.00 mm), while in the group with hypertrophic cardiomyopathy (GB) mean LVDd value is 42 mm (n=20; 95% CI, 40.00 to 48.00 mm). The mean value of the rear wall of the left ventricle (LVPWd) recorded in the GA is LVDd=10 mm (n=40; 95% CI, 9.00-10.00 mm) while in the group with hypertrophic cardiomyopathy (GB) mean LVDd is 14 mm (n=20; 95% CI, 12.00 to 16.00 mm). The mean of the left ventricle during systole (LVSD) observed in GA is LVSD=34 mm (n=40; 95% CI, 32.00 to 36.00 mm), while in the group with hypertrophic cardiomyopathy (GB) mean LVSD is 28 mm (n=20; 95% CI, 24.00 to 28.83 mm). The mean ejection fraction (EF%) observed in GA is EF

  6. Health related quality of life and psychological wellbeing in patients with hypertrophic cardiomyopathy.

    PubMed Central

    Cox, S.; O'Donoghue, A. C.; McKenna, W. J.; Steptoe, A.

    1997-01-01

    OBJECTIVE: To assess the health related quality of life and psychological wellbeing of patients with hypertrophic cardiomyopathy, to correlate these with symptoms, clinical, and psychosocial factors. DESIGN: Questionnaire distributed to 171 hypertrophic cardiomyopathy patients aged at least 14 years, selected at random from a dataset of 480 patients. Assessments included the Short Form 36 (SF-36) Health Survey, the Hospital Anxiety and Depression questionnaire, and measures of adjustment, worry, and patient satisfaction. RESULTS: There was an 80.1% response rate to the questionnaire. Patients had severe limitations in all eight dimensions of quality of life assessed by the SF-36: physical functioning, role limitations owing to physical problems, role limitations owing to emotional problems, social functioning, mental health, general health perceptions, vitality, and bodily pain. Levels of anxiety and depression were also high compared with population norms. Quality of life was particularly impaired in patients with chest pain and dyspnoea, but was less consistently related to clinical cardiological measures. Adjustment to the condition and patient satisfaction were generally good. In multivariate analysis, quality of life was associated with a combination of symptom patterns and psychosocial factors. No differences in quality of life, anxiety or depression were observed between patients with no known family history, those with familial cardiomyopathy, and patients with a family history of premature sudden death. CONCLUSIONS: Hypertrophic cardiomyopathy is associated with substantial restrictions in health related quality of life. Symptoms, adjustment, and quality of interactions with clinical staff contribute to these limitations. Recognition of the problems confronted by patients with hypertrophic cardiomyopathy requires continued efforts at education both of the public and health professionals. PMID:9326995

  7. Is surgery the gold standard in the treatment of obstructive hypertrophic cardiomyopathy?

    PubMed Central

    Knyshov, Gennady; Lazoryshynets, Vasyl; Rudenko, Kostyantyn; Kravchuk, Borys; Beshlyaga, Vyacheslav; Zalevsky, Valery; Rasputnyak, Olga; Batsak, Bogdan

    2013-01-01

    OBJECTIVES Hypertrophic cardiomyopathy is a complex and relatively common genetic cardiac disease and has been the subject of intensive scrutiny and investigation for over 40 years. The aim of this non-randomized cohort study was to compare subjective and objective outcomes in hypertrophic cardiomyopathy patients undergoing drug therapy, surgical myotomy-myectomy, dual-chamber pacing and alcohol septal ablation. METHODS We examined 194 patients: 103 with non-obstructive hypertrophic cardiomyopathy and 91 with obstructive hypertrophic cardiomyopathy. All the patients with a non-obstructive form were on drug therapy. Ninety-one consecutive patients with drug-refractory obstructive hypertrophic cardiomyopathy were treated invasively. Dual-chamber pacemaker implantation was performed for 49 patients with previous positive temporary pacing test (Group 1). In 28 patients with massive left ventricle hypertrophy and obliteration of its cavities, extensive myotomy-myectomy was performed (Group 2). In 14 patients with midventricular obstruction and appropriate coronary anatomy, alcohol septal ablation was performed (Group 3). RESULTS The peak left ventricle outflow tract gradient was 84.1 ± 15.2 mmHg in Group 1, 113.3 ± 14.9 mmHg in Group 2 and 97.5 ± 8.9 mmHg in Group 3. Dual-chamber pacing in Group 1 with optimal atrio-ventricular delay (85–180 ms for atrium pacing and 45–120 ms for atrial sensing) leads to dramatic decreases in left ventricle outflow tract gradient to 17.6 ± 11.8 mmHg and degree of mitral regurgitation. After extensive myectomy in Group 2, we observed a reduction of left ventricle outflow tract gradient to 17.3 ± 10.2 mmHg. Septal alcohol ablation in Group 3 leads to a left ventricle outflow tract gradient decrease from 97.5 ± 8.9 to 25.3 ± 5.8 mmHg. CONCLUSIONS Surgical myectomy, dual-chamber pacing and alcohol septal ablation are equally effective in reducing obstruction in case of correct indications. Dual-chamber pacing is indicated in

  8. Right ventricular cavity near obliteration in neonatal severe biventricular hypertrophic cardiomyopathy

    PubMed Central

    Jivanji, Salim GM; Daubeney, Piers; Franklin, Rodney; Sheppard, Mary

    2014-01-01

    A newborn presenting with cyanosis at day 9 of life was admitted to the local hospital. Initial local echocardiography confirmed a cardiac issue and the patient was transferred to a tertiary cardiac hospital. Further imaging confirmed a rare presentation of cardiomyopathy with severe right ventricular outflow tract obstruction. Surgery was performed but with postoperative haemodynamic instability complicated by incessant ventricular tachycardia. Following discussion with the family, care was withdrawn. Postmortem demonstrated a rare form of hypertrophic cardiomyopathy with right ventricular outflow tract obstruction not previously described in a neonate. PMID:25336549

  9. [Non-pharmacological treatment of hypertrophic obstructive cardiomyopathy guided by echocardiography].

    PubMed

    La Canna, Giovanni; Montorfano, Matteo; Ficarra, Eleonora; Michev, Iassen; Capritti, Elvia; Grimaldi, Antonio; De Cobelli, Francesco; Verzini, Alessandro; Colombo, Antonio; Alfieri, Ottavio

    2006-03-01

    As a relevant cause of symptoms and adverse clinical prognosis, left ventricular obstruction should be regarded as an important therapeutic target in patients with hypertrophic obstructive cardiomyopathy. The surgical approach (including septal myectomy or mitral valve surgery) and percutaneous transluminal septal myocardial ablation offer a non-pharmacological option for the treatment of symptomatic left ventricular obstruction and symptoms unresponsive to medical treatment. The surgical approach is established as an effective strategy for relieving symptoms from dynamic obstruction. Percutaneous septal ablation, on the other hand, has only recently been introduced into clinical practice and, despite its efficacy as an obstructive abolisher, little is known about the prognostic long-term impact of procedural-induced myocardial damage. Due to its accuracy and diagnostic versatility, including intraprocedural use, Doppler echocardiography provides essential information for the planning and monitoring of non-pharmacological therapy in patients with hypertrophic obstructive cardiomyopathy.

  10. An autopsy report of acute myocardial infarction with hypertrophic obstructive cardiomyopathy-like heart.

    PubMed

    Ushikoshi, Hiroaki; Okada, Hideshi; Morishita, Kentaro; Imai, Hajime; Tomita, Hiroyuki; Nawa, Takahide; Suzuki, Kodai; Ikeshoji, Haruka; Kato, Hisaaki; Yoshida, Takahiro; Yoshida, Shozo; Shirai, Kunihiro; Toyoda, Izumi; Hara, Akira; Ogura, Shinji

    2015-01-01

    An 84-year-old woman, who was followed up as hypertrophic obstructive cardiomyopathy (HOCM) in a local hospital, was transferred to our center because of anterior chest pain and diagnosed with acute myocardial infarction (MI). Coronary angiography showed total occlusion of the mid-left anterior descending, and flow was restored after endovascular thrombectomy. An autopsy was performed after she died on hospital day 6. At autopsy, there was no significant stenosis in this vessel and the absence of plaque rupture was confirmed. Likewise, it was unclear asymmetric hypertrophy at autopsy, it could not deny that a sigmoid deformity of the basal septum occurs in elderly patients and can mimic the asymmetric septal hypertrophy of hypertrophic cardiomyopathy. MI was thought to be caused by coronary spasm or squeezing in HOCM-like heart. Therefore, it may be necessary antithrombosis therapy in HOCM-like patients with no history of paroxysmal atrial fibrillation.

  11. Myocardial stunning in hypertrophic cardiomyopathy: recovery predicted by single photon emission computed tomographic thallium-201 scintigraphy

    SciTech Connect

    Fine, D.G.; Clements, I.P.; Callahan, M.J.

    1989-05-01

    A young woman with hypertrophic cardiomyopathy confirmed by echocardiography and cardiac catheterization presented with chest pain and features of a large left ventricular aneurysm. The initial diagnosis was myocardial ischemia with either an evolving or an ancient myocardial infarction. Subsequently, verapamil therapy was associated with complete resolution of the extensive left ventricular wall motion abnormalities, normalization of left ventricular ejection fraction and a minimal myocardial infarction. Normal thallium uptake on single photon emission computed tomographic scintigraphy early in the hospital course predicted myocardial viability in the region of the aneurysm. Thus, orally administered verapamil may reverse spontaneous extensive myocardial ischemia in hypertrophic cardiomyopathy and possibly limit the extent of myocardial infarction in such circumstances.

  12. Left Atrial trajectory impairment in Hypertrophic Cardiomyopathy disclosed by Geometric Morphometrics and Parallel Transport

    PubMed Central

    Piras, Paolo; Torromeo, Concetta; Re, Federica; Evangelista, Antonietta; Gabriele, Stefano; Esposito, Giuseppe; Nardinocchi, Paola; Teresi, Luciano; Madeo, Andrea; Chialastri, Claudia; Schiariti, Michele; Varano, Valerio; Uguccioni, Massimo; Puddu, Paolo E.

    2016-01-01

    The analysis of full Left Atrium (LA) deformation and whole LA deformational trajectory in time has been poorly investigated and, to the best of our knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy. Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and 46 healthy subjects, investigated them by three–dimensional Speckle Tracking Echocardiography, and studied the derived landmark clouds via Geometric Morphometrics with Parallel Transport. Trajectory shape and trajectory size were different in Controls versus HCM and their classification powers had high AUC (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two trajectories were much different at the transition between LA conduit and booster pump functions. Full shape and deformation analyses with trajectory analysis enabled a straightforward perception of pathophysiological consequences of HCM condition on LA functioning. It might be worthwhile to apply these techniques to look for novel pathophysiological approaches that may better define atrio–ventricular interaction. PMID:27713503

  13. Microvascular permeability changes might explain cardiac tamponade after alcohol septal ablation for hypertrophic cardiomyopathy.

    PubMed

    Hsu, Jen-Te; Hsiao, Ju-Feng; Chang, Jung-Jung; Chung, Chang-Min; Chang, Shih-Tai; Pan, Kuo-Li

    2014-04-01

    Various sequelae of alcohol septal ablation for hypertrophic obstructive cardiomyopathy have been reported. Of note, some cases of cardiac tamponade after alcohol septal ablation cannot be well explained. We describe the case of a 78-year-old woman with hypertrophic obstructive cardiomyopathy in whom cardiac tamponade developed one hour after alcohol septal ablation, probably unrelated to mechanical trauma. At that time, we noted a substantial difference in the red blood cell-to-white blood cell ratio between the pericardial effusion (1,957.4) and the peripheral blood (728.3). In addition to presenting the patient's case, we speculate that a possible mechanism for acute tamponade--alcohol-induced changes in microvascular permeability--is a reasonable explanation for cases of alcohol septal ablation that are complicated by otherwise-unexplainable massive pericardial effusions. PMID:24808788

  14. Left Atrial trajectory impairment in Hypertrophic Cardiomyopathy disclosed by Geometric Morphometrics and Parallel Transport

    NASA Astrophysics Data System (ADS)

    Piras, Paolo; Torromeo, Concetta; Re, Federica; Evangelista, Antonietta; Gabriele, Stefano; Esposito, Giuseppe; Nardinocchi, Paola; Teresi, Luciano; Madeo, Andrea; Chialastri, Claudia; Schiariti, Michele; Varano, Valerio; Uguccioni, Massimo; Puddu, Paolo E.

    2016-10-01

    The analysis of full Left Atrium (LA) deformation and whole LA deformational trajectory in time has been poorly investigated and, to the best of our knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy. Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and 46 healthy subjects, investigated them by three–dimensional Speckle Tracking Echocardiography, and studied the derived landmark clouds via Geometric Morphometrics with Parallel Transport. Trajectory shape and trajectory size were different in Controls versus HCM and their classification powers had high AUC (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two trajectories were much different at the transition between LA conduit and booster pump functions. Full shape and deformation analyses with trajectory analysis enabled a straightforward perception of pathophysiological consequences of HCM condition on LA functioning. It might be worthwhile to apply these techniques to look for novel pathophysiological approaches that may better define atrio–ventricular interaction.

  15. Microvascular Permeability Changes Might Explain Cardiac Tamponade after Alcohol Septal Ablation for Hypertrophic Cardiomyopathy

    PubMed Central

    Hsu, Jen-Te; Hsiao, Ju-Feng; Chang, Jung-Jung; Chung, Chang-Min; Chang, Shih-Tai; Pan, Kuo-Li

    2014-01-01

    Various sequelae of alcohol septal ablation for hypertrophic obstructive cardiomyopathy have been reported. Of note, some cases of cardiac tamponade after alcohol septal ablation cannot be well explained. We describe the case of a 78-year-old woman with hypertrophic obstructive cardiomyopathy in whom cardiac tamponade developed one hour after alcohol septal ablation, probably unrelated to mechanical trauma. At that time, we noted a substantial difference in the red blood cell-to-white blood cell ratio between the pericardial effusion (1,957.4) and the peripheral blood (728.3). In addition to presenting the patient's case, we speculate that a possible mechanism for acute tamponade—alcohol-induced changes in microvascular permeability—is a reasonable explanation for cases of alcohol septal ablation that are complicated by otherwise-unexplainable massive pericardial effusions. PMID:24808788

  16. Hypertrophic Cardiomyopathy (HCM): How Flow Analysis May Drive Medical Management and Surgical Approach

    NASA Astrophysics Data System (ADS)

    Abraham, Theodore P.

    2011-11-01

    Hypertrophic Cardiomyopathy (HCM) is the most common inherited heart disease and occurs in 1 in 500 persons worldwide regardless of race, age and gender. It is the most common cause of sudden death in the young and also causes heart failure and cardiac arrhythmias. The primary anatomic abnormality is thickening of certain walls, or sometimes global thickening of the left or right ventricle. The patterns of thickening along with increased ventricular stiffness lead to suboptimal ventricular filling and inefficient ejection of blood from the ventricle. Treatment for HCM can be medical or surgical. The choice of therapy is driven by the presence and severity of outflow obstruction. Flow analysis could provide sophisticated information about outflow and inflow ventricular dynamics. These flow dynamics features may enable better medical choices and provide information that would allow superior surgical planning. Associate Professor of Medicine & Director, Hypertrophic Cardiomyopathy Clinic

  17. Intrauterine Treatment of a Fetus with Familial Hypertrophic Cardiomyopathy Secondary to MYH7 Mutation.

    PubMed

    Hill, Meghan G; Sekhon, Mehtab K; Reed, Kathryn L; Anderson, Caroline F; Borjon, Nydia D; Tardiff, Jil C; Barber, Brent J

    2015-12-01

    There is no clear consensus on optimal management of fetuses affected by familial hypertrophic cardiomyopathy (HCM). Intrauterine treatment of the condition has not been attempted in any standardized fashion. We report the case of a fetus treated by maternal propranolol during the third trimester after septal hypertrophy and diastolic dysfunction was diagnosed on fetal echocardiogram. The pregnancy went successfully to term, and fetal septal hypertrophy was noted to improve prior to delivery. PMID:26337809

  18. Coronary artery ectasia and systolic flow cessation in a patient with hypertrophic cardiomyopathy: a case report.

    PubMed

    Zografos, Theodoros; Kokladi, Maria; Katritsis, Demosthenes

    2010-12-01

    Coronary artery ectasia (CAE) is characterized by diffuse or localized inappropriate dilation of coronary arteries and is often associated with slow coronary blood flow. Although CAE has been described to coexist with several clinical entities there are only three reports of CAE in the presence of hypertrophic cardiomyopathy (HCM). We report a case of CAE and slow coronary flow with systolic flow cessation in a 61-year old male with coronary artery disease and HCM.

  19. Papillary Thyroid Carcinoma Treated with Radiofrequency Ablation in a Patient with Hypertrophic Cardiomyopathy: A Case Report

    PubMed Central

    Sun, Jianyi; Liu, Xiaosun; Zhang, Qing; Hong, Yanyun; Song, Bin; Teng, Xiaodong

    2016-01-01

    Standard therapy has not been established for thyroid cancer when a thyroidectomy is contraindicated due to systemic disease. Herein, we reported a patient who had hypertrophic cardiomyopathy and papillary thyroid carcinoma treated by radiofrequency ablation because of inability to tolerate a thyroidectomy. Radiofrequency ablation can be used to treat thyroid cancer when surgery is not feasible, although the long-term outcome needs further observation. PMID:27390548

  20. Role of endocardial septal ablation in the treatment of hypertrophic obstructive cardiomyopathy.

    PubMed

    Aksu, Tolga; Güler, Tümer Erdem; Yalın, Kıvanç; Gölcük, Şükriye Ebru; Özcan, Kazım Serhan

    2016-09-01

    Septal reduction therapy is accepted as a first therapeutic option for symptomatic drug-resistant hypertrophic obstructive cardiomyopathy (HOCM). Although, surgical septal myectomy is the gold standard method, alcohol septal ablation is a well-studied alternative approach in the patients with suitable anatomy. Endocardial septal ablation (ESA) therapy was relatively new defined modality and outcomes of the procedure were not clearly elucidated yet. We aimed to review the clinical aspects of ESA procedure and provide some historical background. PMID:27609434

  1. Pressure-derived indices of left ventricular isovolumic relaxation in patients with hypertrophic cardiomyopathy.

    PubMed Central

    Thompson, D S; Wilmshurst, P; Juul, S M; Waldron, C B; Jenkins, B S; Coltart, D J; Webb-Peploe, M M

    1983-01-01

    High fidelity measurements of left ventricular pressure were made at increasing pacing rates in 21 patients with hypertrophic cardiomyopathy and a control group of 11 patients investigated for chest pain who proved to have normal hearts. In both groups the fall in pressure during isovolumic relaxation from the point of min dp/dt approximated closely to a monoexponential, and could be described by a time constant and asymptote. The time constant shortened and the asymptote increased as heart rate rose in both groups. The time constant was longer and min dp/dt less in the cardiomyopathy group than controls at all heart rates. In the cardiomyopathy patients min dp/dt, but not the time constant, was related to systolic pressure. During pacing, eight cardiomyopathy patients developed metabolic evidence of myocardial ischaemia, but indices of relaxation did not differ between these eight and the other 13 either at basal heart rate or the highest pacing rate. In 10 cardiomyopathy patients measurements were repeated at comparable pacing rates after propranolol (0.2 mg/kg). Left ventricular end-diastolic pressure and indices of contractility decreased after the drug, but the time constant did not change. Eight patients received verapamil (20 mg) after which there were substantial reductions in systolic pressure and contractility. Min dp/dt decreased in proportion to systolic pressure, but the time constant was unchanged. At the highest pacing rate before drug administration three patients had abnormal lactate extraction which was corrected by either propranolol (one patient) or verapamil (two patients). Despite abolition of metabolic evidence of ischaemia, relaxation did not improve. It is concluded that abnormal isovolumic relaxation is common in patients with hypertrophic cardiomyopathy, but its severity correlates poorly with other features of the disease. Abnormal relaxation is not the result of ischaemia, and pressure derived indices of relaxation do not improve after

  2. Myocardial edema in Takotsubo syndrome mimicking apical hypertrophic cardiomyopathy: An insight into diagnosis by cardiovascular magnetic resonance.

    PubMed

    Izgi, Cemil; Ray, Sanjoy; Nyktari, Evangelia; Alpendurada, Francisco; Lyon, Alexander R; Rathore, Sudhir; Baksi, Arun John

    2015-01-01

    Myocardial edema is one of the characteristic features in the pathogenesis of Takotsubo syndrome. We report a middle aged man who presented with typical clinical and echocardiographic features of apical variant of Takotsubo syndrome. However, a cardiovascular magnetic resonance study performed 10 days after presentation did not show any apical 'ballooning' but revealed features of an apical hypertrophic cardiomyopathy on cine images. Tissue characterization with T2 weighted images proved severe edema as the cause of significantly increased apical wall thickness. A follow-up cardiovascular magnetic resonance study was performed 5 months later which showed that edema, wall thickening and the appearance of apical hypertrophic cardiomyopathy all resolved, confirming Takotsubo syndrome as the cause of the initial appearance. As the affected myocardium most commonly involves the apical segments, an edema induced increase in apical wall thickness may lead to appearances of an apical hypertrophic cardiomyopathy rather than apical ballooning in the acute to subacute phase of Takotsubo syndrome.

  3. The Metabolome in Finnish Carriers of the MYBPC3-Q1061X Mutation for Hypertrophic Cardiomyopathy

    PubMed Central

    Heliö, Tiina; Jääskeläinen, Pertti; Laine, Mika; Hilvo, Mika; Nieminen, Markku S.; Laakso, Markku; Hyötyläinen, Tuulia; Orešič, Matej; Kuusisto, Johanna

    2015-01-01

    Aims Mutations in the cardiac myosin-binding protein C gene (MYBPC3) are the most common genetic cause of hypertrophic cardiomyopathy (HCM) worldwide. The molecular mechanisms leading to HCM are poorly understood. We investigated the metabolic profiles of mutation carriers with the HCM-causing MYBPC3-Q1061X mutation with and without left ventricular hypertrophy (LVH) and non-affected relatives, and the association of the metabolome to the echocardiographic parameters. Methods and Results 34 hypertrophic subjects carrying the MYBPC3-Q1061X mutation, 19 non-hypertrophic mutation carriers and 20 relatives with neither mutation nor hypertrophy were examined using comprehensive echocardiography. Plasma was analyzed for molecular lipids and polar metabolites using two metabolomics platforms. Concentrations of branched chain amino acids, triglycerides and ether phospholipids were increased in mutation carriers with hypertrophy as compared to controls and non-hypertrophic mutation carriers, and correlated with echocardiographic LVH and signs of diastolic and systolic dysfunction in subjects with the MYBPC3-Q1061X mutation. Conclusions Our study implicates the potential role of branched chain amino acids, triglycerides and ether phospholipids in HCM, as well as suggests an association of these metabolites with remodeling and dysfunction of the left ventricle. PMID:26267065

  4. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice

    PubMed Central

    Green, Eric M.; Wakimoto, Hiroko; Anderson, Robert L.; Evanchik, Marc J.; Gorham, Joshua M.; Harrison, Brooke C.; Henze, Marcus; Kawas, Raja; Oslob, Johan D.; Rodriguez, Hector M.; Song, Yonghong; Wan, William; Leinwand, Leslie A.; Spudich, James A.; McDowell, Robert S.; Seidman, J. G.; Seidman, Christine E.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is an inherited disease of heart muscle that can be caused by mutations in sarcomere proteins. Clinical diagnosis depends on an abnormal thickening of the heart, but the earliest signs of disease are hyperdynamic contraction and impaired relaxation. Whereas some in vitro studies of power generation by mutant and wild-type sarcomere proteins are consistent with mutant sarcomeres exhibiting enhanced contractile power, others are not. We identified a small molecule, MYK-461, that reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain. Here we demonstrate that early, chronic administration of MYK-461 suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain. These data indicate that hyperdynamic contraction is essential for HCM pathobiology and that inhibitors of sarcomere contraction may be a valuable therapeutic approach for HCM. PMID:26912705

  5. 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.

  6. Usefulness of MRI to demonstrate the mechanisms of myocardial ischemia in hypertrophic cardiomyopathy with myocardial bridge.

    PubMed

    Thomson, Vivien; Botnar, Rene; Croisille, Pierre

    2007-01-01

    We present a case of symptomatic primary hypertrophic cardiomyopathy (HCM) associated with myocardial bridging of the left anterior descending (LAD) artery and suspected ischemia that could be related either to LAD artery compression or to microvascular perfusion abnormalities. MRI demonstrated the morphological appearance of myocardial hypertrophy, and coronary MR angiography evidenced the myocardial bridge and its functional consequences with stress MR perfusion. In conclusion, as a non-invasive comprehensive imaging technique, MRI should be considered in identifying the mechanisms of myocardial ischemia in HCM with myocardial bridge. PMID:16888385

  7. The role of intraoperative transesophageal echocardiographic monitoring in a patient with hypertrophic cardiomyopathy undergoing laparoscopic surgery.

    PubMed

    Gregory, Stephen H; Fierro, Michael A

    2016-11-01

    Hypertrophic cardiomyopathy (HCM) presents a significant perioperative challenge. Anesthetic drugs, patient positioning, and surgical technique can provoke worsening left ventricular outflow tract obstruction and hemodynamic deterioration. In this case report, we present the perioperative management of a 70-year-old male with a history of HCM who underwent a robotic laparoscopic prostatectomy. Discussion focuses on the utilization of echocardiographic guidance in the care of patients with HCM undergoing noncardiac surgery, as well as the pathophysiology of laparoscopic insufflation and its effects on left ventricular outflow tract obstruction in HCM. PMID:27687358

  8. Trileaflet Mitral Valve with Three Papillary Muscles Associated with Hypertrophic Cardiomyopathy: A Novel Case.

    PubMed

    Rosanio, Salvatore; Simonsen, Cameron J; Starwalt, John; Keylani, Abdul M; Vitarelli, Antonio

    2015-09-01

    Congenital mitral valve (MV) malformations are uncommon, except for MV prolapse. Despite their infrequency, most of them are well-known and defined entities, such as congenital MV stenosis with two papillary muscles, parachute MV, supravalvular mitral ring, hypoplastic MV, isolated cleft in the anterior and/or posterior leaflets, and double-orifice MV. A trileaflet MV with three separate papillary muscles with concordant atrioventricular and ventricle-arterial connections is exceptionally rare. To the best of the authors' knowledge, it has been reported only once in association with subaortic valvular stenosis. We hereby describe a novel case associated with hypertrophic cardiomyopathy. PMID:25809503

  9. Findings of Cardiac Magnetic Resonance Imaging in Hypertrophic Cardiomyopathy after 16 Years

    PubMed Central

    Kim, Gee-Hee; Jang, Bo-Hyun; Lee, Hyeong-Han; Hong, Solim; Eum, Sang-Hoon; Jeon, Howook; Moon, Donggyu

    2016-01-01

    A 58-year-old man had been diagnosed with non-obstructive hypertrophic cardiomyopathy (HCMP) according to echocardiography findings 16 years ago. Echocardiography showed ischemic cardiomyopathy (CMP)-like features with decreased systolic function but a non-dilated chamber. Coronary angiography was performed but showed a normal coronary artery. Cardiac magnetic resonance imaging (MRI) revealed multifocal transmural and subepicardial delayed-enhancing areas at the anteroseptal, septal, and inferoseptal left ventricular (LV) wall, and wall thinning and decreased motion of the anteroseptal LV wall. Findings of ischemic CMP-like features by echocardiography suggested microvascular dysfunction. This late stage of HCMP carries a high risk of sudden death. Cardiac MRI evaluation may be necessary in cases of ischemic CMP-like features in HCMP. In this case, the diagnosis of end-stage HCMP with microvascular dysfunction was confirmed by using cardiac MRI after a follow-up period of more than 16 years. PMID:27721955

  10. Furthering the link between the sarcomere and primary cardiomyopathies: restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy.

    PubMed

    Caleshu, Colleen; Sakhuja, Rahul; Nussbaum, Robert L; Schiller, Nelson B; Ursell, Philip C; Eng, Celeste; De Marco, Teresa; McGlothlin, Dana; Burchard, Esteban González; Rame, J Eduardo

    2011-09-01

    Mutations in genes that encode components of the sarcomere are well established as the cause of hypertrophic and dilated cardiomyopathies. Sarcomere genes, however, are increasingly being associated with other cardiomyopathies. One phenotype more recently recognized as a disease of the sarcomere is restrictive cardiomyopathy (RCM). We report on two patients with RCM associated with multiple mutations in sarcomere genes not previously associated with RCM. Patient 1 presented with NYHA Class III/IV heart failure at 22 years of age. She was diagnosed with RCM and advanced heart failure requiring heart transplantation. Sequencing of sarcomere genes revealed previously reported homozygous p.Glu143Lys mutations in MYL3, and a novel heterozygous p.Gly57Glu mutation in MYL2. The patient's mother is a double heterozygote for these mutations, with no evidence of cardiomyopathy. Patient 2 presented at 35 years of age with volume overload while hospitalized for oophorectomy. She was diagnosed with RCM and is being evaluated for heart transplantation. Sarcomere gene sequencing identified homozygous p.Asn279His mutations in TPM1. The patient's parents are consanguineous and confirmed heterozygotes. Her father was diagnosed with HCM at 42 years of age. This is the first report of mutations in TPM1, MYL3, and MYL2 associated with primary, non-hypertrophied RCM. The association of more sarcomere genes with RCM provides further evidence that mutations in the various sarcomere genes can cause different cardiomyopathy phenotypes. These cases also contribute to the growing body of evidence that multiple mutations have an additive effect on the severity of cardiomyopathies. PMID:21823217

  11. New treatment strategies for hypertrophic obstructive cardiomyopathy: alcohol ablation of the septum: the new gold standard?

    PubMed

    Hess, Otto M; Sigwart, Ulrich

    2004-11-16

    Hypertrophic cardiomyopathy is a primary myocardial disorder with an autosomal pattern of inheritance characterized by inappropriate myocardial hypertrophy. Annual mortality has been reported to be 1% to 2% and sudden death represents the most common cause. Treatment strategies are 1) medical therapy in patients with mild to moderate symptoms, 2) reduction of septal hypertrophy by surgical myectomy or alcohol ablation, and 3) implantation of an automatic cardioverter-defibrillator in the presence of non-sustained ventricular tachyarrhythmias. A debate has been started on whether surgical myectomy or alcohol ablation of the septum is the appropriate treatment for hypertrophic obstructive cardiomyopathy. Surgical (transaortic) myectomy has been the gold standard in the past 20 to 30 years for treatment of symptomatic patients with significant hemodynamic outflow tract obstruction. However, modern interventional technologies allow reduction of the myocardial septum by injection of alcohol into the first or second septal branch under guidance of two-dimensional (2D)-contrast echocardiography. This percutaneous technique not only has a lower morbidity than surgical myectomy but can be guided precisely by 2D echocardiography. One potential complication is transient (<30%) or permanent (<10%) atrioventricular block III; however, this complication is relatively rare. A randomized trial comparing the two treatment modalities is lacking, and the chance is small that such a trial will be performed because alcohol ablation can be done with high success and low complication rates, leaving only complex interventions (with valvular reconstructions and so on) for surgical myectomy.

  12. Percutaneous Septal Ablation in Hypertrophic Obstructive Cardiomyopathy: From Experiment to Standard of Care

    PubMed Central

    Faber, Lothar

    2014-01-01

    Hypertrophic cardiomyopathy (HCM) is one of the more common hereditary cardiac conditions. According to presence or absence of outflow obstruction at rest or with provocation, a more common (about 60–70%) obstructive type of the disease (HOCM) has to be distinguished from the less common (30–40%) nonobstructive phenotype (HNCM). Symptoms include exercise limitation due to dyspnea, angina pectoris, palpitations, or dizziness; occasionally syncope or sudden cardiac death occurs. Correct diagnosis and risk stratification with respect to prophylactic ICD implantation are essential in HCM patient management. Drug therapy in symptomatic patients can be characterized as treatment of heart failure with preserved ejection fraction (HFpEF) in HNCM, while symptoms and the obstructive gradient in HOCM can be addressed with beta-blockers, disopyramide, or verapamil. After a short overview on etiology, natural history, and diagnostics in hypertrophic cardiomyopathy, this paper reviews the current treatment options for HOCM with a special focus on percutaneous septal ablation. Literature data and the own series of about 600 cases are discussed, suggesting a largely comparable outcome with respect to procedural mortality, clinical efficacy, and long-term outcome. PMID:26556411

  13. Influence of verapamil therapy on left ventricular performance at rest and during exercise in hypertrophic cardiomyopathy.

    PubMed

    Hanrath, P; Schlüter, M; Sonntag, F; Diemert, J; Bleifeld, W

    1983-09-01

    To determine the hemodynamic effect of verapamil at rest and during exercise, 18 patients with hypertrophic cardiomyopathy were studied before and after 7 weeks of treatment with oral verapamil (maximal dose, 720 mg/day). At rest and at peak exercise, verapamil produced a significant increase in left ventricular (LV) systolic performance in terms of stroke volume index (rest, from 43 +/- 11 to 53 +/- 11 ml/m2, p less than 0.001; exercise, from 46 +/- 11 to 51 +/- 10 ml/m2, p less than 0.01), whereas heart rate decreased (rest, from 81 +/- 14 to 70 +/- 11 min-1, p less than 0.001; exercise, from 150 +/- 21 to 141 +/- 18 min-1, p less than 0.01). Cardiac index at rest and during exercise remained unchanged. Systolic vascular resistance did not change at rest, but decreased significantly during exercise (974 +/- 243 to 874 +/- 174 dynes s cm-5; p less than 0.05). After verapamil administration, pulmonary artery pressures did not change at rest, but decreased significantly during exercise. This was probably due to a shift in the LV pressure-volume relation. The improvement in LV hemodynamics was associated with a significant increase in exercise capacity. The findings of this study indicate that in patients with hypertrophic cardiomyopathy, hemodynamic improvement at rest and during exercise can be achieved by chronic administration of verapamil.

  14. 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.

  15. Supraventricular tachycardia in a patient with Lown-Ganong-Levine syndrome associated with apical hypertrophic cardiomyopathy.

    PubMed

    Hayano, M; Imamura, Y; Tsuruta, M; Inoue, J; Nakashima, H; Fukuyama, K; Eguchi, Y; Tsuji, S; Matsuo, S; Yano, K

    1988-03-01

    Electrophysiologic study of a 55-year-old patient with Lown-Ganong-Levine syndrome associated with apical hypertrophic cardiomyopathy is reported. The patient had a history of recurrent attacks of tachyarrhythmia and his electrocardiogram showed a short P-R interval (0.10 sec) with narrow QRS complex and left ventricular hypertrophy with giant negative T waves. His cineangiogram showed severe apical hypertrophy. An electrophysiologic study was performed. The results of programmed atrial pacing show the existence of the dual A-V nodal pathways. The A-H interval at rapid atrial pacing increased maximally by 103 msec. Atrial stimulation could depolarize parts of the atrium without altering the supraventricular tachycardia. These findings suggested that preferential rapidly conducting A-V nodal and intranodal reentry are the responsible mechanisms in this reciprocating tachycardia. We conclude that the short P-R interval was due to intranodal reentry through the dual A-V nodal pathways. To our knowledge, a case of Lown-Ganong-Levine syndrome with apical hypertrophic cardiomyopathy has not been previously described in the literature.

  16. 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

  17. Alcohol septal ablation in obstructive acromegalic hypertrophic cardiomyopathy - a first case report.

    PubMed

    Viveiros Monteiro, André; Fiarresga, António; Cacela, Duarte; de Sousa, Lídia; Ramos, Ruben; Galrinho, Ana; Branco, Luísa; Cruz Ferreira, Rui

    2016-09-01

    Acromegaly is a rare disease, mostly caused by a growth hormone (GH)-secreting benign pituitary tumor, with an increased production of GH and insulin-like growth factor 1 (IGF-1). Cardiovascular complications are common and are associated with cardiomyocyte apoptosis and concentric cardiac hypertrophy. Suppression of GH and IGF-1 appears to improve cardiac function only in the short term, with little or no decrease in left ventricular mass or improvement in cardiac function after prolonged treatment. Alcohol septal ablation (ASA) has emerged as a minimally invasive alternative to septal myectomy, with significant improvement in symptoms, gradients and left ventricular remodeling. In this report, we describe the case of a 73-year-old woman with acromegaly due to a pituitary adenoma diagnosed and treated surgically at the age of 38 but with recurrence and reoperation at the age of 50. She was referred to our cardiology department due to a three-month history of progressively worsening exercise-induced dyspnea and orthopnea under optimal medical therapy. Echocardiography and magnetic resonance imaging revealed severe basal hypertrophy of the interventricular septum (19 mm), dynamic left ventricular outflow tract obstruction with a gradient of 70 mmHg at rest and 120 mmHg with Valsalva maneuver, and systolic anterior movement (SAM). Genetic testing excluded the most frequent forms of familial hypertrophic cardiomyopathy. ASA was performed with injection of 2 cc of alcohol in the first septal branch of the left coronary artery, without complications. At one-year reassessment, significant clinical and echocardiographic improvement was noted, with disappearance of SAM. To our knowledge, there have been no previously reported cases of ASA in hypertrophic cardiomyopathy due to acromegaly. We report a case of successful ASA in acromegalic cardiomyopathy. PMID:27503591

  18. Alcohol septal ablation in obstructive acromegalic hypertrophic cardiomyopathy - a first case report.

    PubMed

    Viveiros Monteiro, André; Fiarresga, António; Cacela, Duarte; de Sousa, Lídia; Ramos, Ruben; Galrinho, Ana; Branco, Luísa; Cruz Ferreira, Rui

    2016-09-01

    Acromegaly is a rare disease, mostly caused by a growth hormone (GH)-secreting benign pituitary tumor, with an increased production of GH and insulin-like growth factor 1 (IGF-1). Cardiovascular complications are common and are associated with cardiomyocyte apoptosis and concentric cardiac hypertrophy. Suppression of GH and IGF-1 appears to improve cardiac function only in the short term, with little or no decrease in left ventricular mass or improvement in cardiac function after prolonged treatment. Alcohol septal ablation (ASA) has emerged as a minimally invasive alternative to septal myectomy, with significant improvement in symptoms, gradients and left ventricular remodeling. In this report, we describe the case of a 73-year-old woman with acromegaly due to a pituitary adenoma diagnosed and treated surgically at the age of 38 but with recurrence and reoperation at the age of 50. She was referred to our cardiology department due to a three-month history of progressively worsening exercise-induced dyspnea and orthopnea under optimal medical therapy. Echocardiography and magnetic resonance imaging revealed severe basal hypertrophy of the interventricular septum (19 mm), dynamic left ventricular outflow tract obstruction with a gradient of 70 mmHg at rest and 120 mmHg with Valsalva maneuver, and systolic anterior movement (SAM). Genetic testing excluded the most frequent forms of familial hypertrophic cardiomyopathy. ASA was performed with injection of 2 cc of alcohol in the first septal branch of the left coronary artery, without complications. At one-year reassessment, significant clinical and echocardiographic improvement was noted, with disappearance of SAM. To our knowledge, there have been no previously reported cases of ASA in hypertrophic cardiomyopathy due to acromegaly. We report a case of successful ASA in acromegalic cardiomyopathy.

  19. Ablation of ALCAT1 Mitigates Hypertrophic Cardiomyopathy through Effects on Oxidative Stress and Mitophagy

    PubMed Central

    Liu, Xiaolei; Ye, Benlan; Miller, Shane; Yuan, Huijuan; Zhang, Hongxiu; Tian, Liang; Nie, Jia; Imae, Rieko; Arai, Hiroyuki; Li, Yuanjian; Cheng, Zeneng

    2012-01-01

    Oxidative stress causes mitochondrial dysfunction and heart failure through unknown mechanisms. Cardiolipin (CL), a mitochondrial membrane phospholipid required for oxidative phosphorylation, plays a pivotal role in cardiac function. The onset of age-related heart diseases is characterized by aberrant CL acyl composition that is highly sensitive to oxidative damage, leading to CL peroxidation and mitochondrial dysfunction. Here we report a key role of ALCAT1, a lysocardiolipin acyltransferase that catalyzes the synthesis of CL with a high peroxidation index, in mitochondrial dysfunction associated with hypertrophic cardiomyopathy. We show that ALCAT1 expression was potently upregulated by the onset of hyperthyroid cardiomyopathy, leading to oxidative stress and mitochondrial dysfunction. Accordingly, overexpression of ALCAT1 in H9c2 cardiac cells caused severe oxidative stress, lipid peroxidation, and mitochondrial DNA (mtDNA) depletion. Conversely, ablation of ALCAT1 prevented the onset of T4-induced cardiomyopathy and cardiac dysfunction. ALCAT1 deficiency also mitigated oxidative stress, insulin resistance, and mitochondrial dysfunction by improving mitochondrial quality control through upregulation of PINK1, a mitochondrial GTPase required for mitochondrial autophagy. Together, these findings implicate a key role of ALCAT1 as the missing link between oxidative stress and mitochondrial dysfunction in the etiology of age-related heart diseases. PMID:22949503

  20. Suppression of ventricular fibrillation by electrical modification of the Purkinje system in hypertrophic cardiomyopathy.

    PubMed

    Yokoshiki, Hisashi; Mitsuyama, Hirofumi; Watanabe, Masaya; Mizukami, Kazuya; Tsutsui, Hiroyuki

    2014-09-01

    A 56-year-old man in hypertrophic cardiomyopathy had an electrical storm caused by ventricular fibrillation (VF). Mapping during the initiation of the VF triggered by a premature ventricular contraction (PVC1), with right bundle branch block (RBBB)-like morphology and superior axis, demonstrated a prominent Purkinje-muscle junction (PMJ) delay at the distal portion of the left posterior fascicle. Delivery of radiofrequency (RF) energy to this area abolished the VF triggered by the PVC1. However, VF emerged by triggering another PVC (PVC2) with RBBB-like morphology and inferior axis. Similarly, the initiation of VF was associated with the PMJ delay at the peripheral left anterior fascicle, where RF delivery completely suppressed the VF. The PMJ delay and subsequent Purkinje-muscle reentry-like activity could be essential for the initiation of the Purkinje-related VF.

  1. Cardiac Magnetic Resonance and Computed Tomography in Hypertrophic Cardiomyopathy: an Update

    PubMed Central

    de Oliveira, Diogo Costa Leandro; Assunção, Fernanda Boldrini; dos Santos, Alair Agusto Sarmet Moreira Damas; Nacif, Marcelo Souto

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease and represents the main cause of sudden death in young patients. Cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) are noninvasive imaging methods with high sensitivity and specificity, useful for the establishment of diagnosis and prognosis of HCM, and for the screening of patients with subclinical phenotypes. The improvement of image analysis by CMR and CCT offers the potential to promote interventions aiming at stopping the natural course of the disease. This study aims to describe the role of RCM and CCT in the diagnosis and prognosis of HCM, and how these methods can be used in the management of these patients. PMID:27305111

  2. [New strategies for assessing the risk of sudden cardiac death in hypertrophic cardiomyopathy].

    PubMed

    Jaworski, Krzysztof; Możeńska, Olga; Kosior, Dariusz A

    2016-07-01

    Hypertrophic cardiomyopathy (HCM) is characterized by a primarily increased ventricular wall thickness, usually caused by the mutations in genes encoding sarcomere proteins. Thanks to the growing awareness in the medical community as well as advances in diagnostic techniques HCM can be diagnosed at earlier stages than ever before. However, in some cases the first symptom of this disease is a sudden cardiac death (SCD) and diagnosis remains unknown until post-mortem examination. Implantation of a cardioverterdefibrillator (ICD) provides the most effective method of SCD prevention. Nevertheless, due to a number of risks associated with surgery as well as the possession of such devices, predictive factors of serious ventricular arrhythmia in individual patients have been sought for many years. The aim of this review is to present the current strategies of risk assessment and prevention of SCD in patients with HCM. PMID:27590646

  3. [New strategies for assessing the risk of sudden cardiac death in hypertrophic cardiomyopathy].

    PubMed

    Jaworski, Krzysztof; Możeńska, Olga; Kosior, Dariusz A

    2016-08-01

    Hypertrophic cardiomyopathy (HCM) is characterized by a primarily increased ventricular wall thickness, usually caused by the mutations in genes encoding sarcomere proteins. Thanks to the growing awareness in the medical community as well as advances in diagnostic techniques HCM can be diagnosed at earlier stages than ever before. However, in some cases the first symptom of this disease is a sudden cardiac death (SCD) and diagnosis remains unknown until post-mortem examination. Implantation of a cardioverterdefibrillator (ICD) provides the most effective method of SCD prevention. Nevertheless, due to a number of risks associated with surgery as well as the possession of such devices, predictive factors of serious ventricular arrhythmia in individual patients have been sought for many years. The aim of this review is to present the current strategies of risk assessment and prevention of SCD in patients with HCM. PMID:27591441

  4. Apical Hypertrophic Cardiomyopathy: The Ace-of-Spades as the Disease Card

    PubMed Central

    Diaconu, Camelia C.; Dumitru, Nicoleta; Fruntelata, Ana G.; Lacau, Smarandita; Bartos, Daniela

    2015-01-01

    Apical cardiac hypertrophy (Yamaguchi syndrome) is a relatively rare form of hypertrophic cardiomyopathy. A 67-year-old woman presented with exertional angina and moderate dyspnea. Her electrocardiogram showed sinus rhythm, flattened T waves in the limb leads and a strain pattern in the V2-V6 leads. Echocardiographic examination showed that apical wall thickness of the left ventricle (LV) was 19 mm. Coronary angiography was normal, but left ventriculography revealed a spade-like shaped LV cavity, typical for apical cardiac hypertrophy. The diagnostic criteria for apical cardiac hypertrophy are: 1) asymmetric LV hypertrophy - predominantly at the apex of the ventricle; 2) LV wall thickness of 15 mm or more during diastole; and 3) apical to posterior wall thickness ratio of 1.5 or more determined by 2-dimensional echocardiography or cardiac magnetic resonance imaging. Although relatively rare, Yamaguchi syndrome must enter into the differential diagnosis of patients presenting with exertional angina pectoris. PMID:27122852

  5. Cardiac Magnetic Resonance and Computed Tomography in Hypertrophic Cardiomyopathy: an Update.

    PubMed

    Oliveira, Diogo Costa Leandro de; Assunção, Fernanda Boldrini; Santos, Alair Agusto Sarmet Moreira Damas Dos; Nacif, Marcelo Souto

    2016-08-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease and represents the main cause of sudden death in young patients. Cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) are noninvasive imaging methods with high sensitivity and specificity, useful for the establishment of diagnosis and prognosis of HCM, and for the screening of patients with subclinical phenotypes. The improvement of image analysis by CMR and CCT offers the potential to promote interventions aiming at stopping the natural course of the disease. This study aims to describe the role of RCM and CCT in the diagnosis and prognosis of HCM, and how these methods can be used in the management of these patients. PMID:27305111

  6. What is really a nonobstructive hypertrophic cardiomyopathy? The importance of orthostatic factor in exercise echocardiography.

    PubMed

    Cotrim, Carlos; Almeida, Ana Rita; Lopes, Luís; Fazendas, Paula; João, Isabel; Pereira, Hélder

    2011-01-01

    The authors report the case of a 23-year-old girl with nonobstructive hypertrophic cardiomyopathy evaluated by resting echocardiography. The patient complained of syncope after playing basketball. The patient was submitted to treadmill exercise echocardiogram, and she exercised for 9 minutes in standard Bruce protocol. The left ventricular outflow gradient did not occur at peak workload; however she developed intraventricular gradient greater than 100 mmHg after exercise in orthostatic position. There was fall in arterial pressure, and the patient was then put in supine position. The authors suggest the possible role of exercise stress echo in symptomatic patients with no significant gradient at baseline, as well as maintenance in orthostatic position after exercise, as an important stress factor. This can disclose the occurrence of left ventricular outflow tract obstruction that should not be detected in other way and has potential relevance in the patient's symptoms understanding.

  7. Hypertrophic cardiomyopathy

    MedlinePlus

    ... permanent pacemaker to control the heartbeat An implanted defibrillator that recognizes life-threatening heart rhythms and sends an electrical pulse to stop them. Sometimes a defibrillator is placed, even if the patient has not ...

  8. 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

  9. 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

  10. Virtual Cardiac Surgery Using CFD: Application to Septal Myectomy in Obstructive Hypertrophic Cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Vedula, Vijay; Mittal, Rajat; Abraham, Theodore

    2011-11-01

    Obstructive hypertrophic cardiomyopathy (HOCM) is characterized by ventricular wall thickening, diastolic dysfunction, and dynamic outflow tract obstruction, all of which strongly influence the vortex dynamics and pressure distribution in the left ventricle (LV). Severe cases of HCM are usually managed through septal myectomy where the surgeon resects the hypertrophic mass. Surgeons currently try to remove as much tissue as possible in order to optimize the post surgical result. However, excessive debulking increases the chance of ventricular septal defects, bundle branch block or complete heart block, and aneurysmal septal thinning. On the other hand, insufficient tissue removal also leads to unsatisfactory outcomes in terms of reduction of outflow tract pressure gradient. Knowing how much muscle to remove and where to remove it from could reduce the likelihood of complications and suboptimal outcomes. In the present study, we employ an immersed boundary solver to model the effect of septal myectomy for ventricles with HOCM and demonstrate the potential of such an approach for surgical planning. Computational resources were provided by the National Institute of Computational Science under Tergrid grant number TG-CTS100002.

  11. Expression of proto-oncogenes and gene mutation of sarcomeric proteins in patients with hypertrophic cardiomyopathy.

    PubMed

    Kai, H; Muraishi, A; Sugiu, Y; Nishi, H; Seki, Y; Kuwahara, F; Kimura, A; Kato, H; Imaizumi, T

    1998-09-21

    Several mutations of cardiac beta-myosin heavy chain (beta-MHC) gene were reported in patients with hypertrophic cardiomyopathy (HCM). Involvement of proto-oncogenes has been shown in the mechanism of experimental cardiac hypertrophy. This study sought to examine the effects of c-H-ras and c-myc expression in the steady-state myocardium on hypertrophic changes and to evaluate the possible interaction between beta-MHC mutation and proto-oncogene expression in HCM. Endomyocardial biopsy was performed in 17 HCM patients (5 beta-MHC mutations and 1 troponin T mutation) and 7 control subjects (no mutation). Reverse transcription-polymerase chain reaction analysis revealed c-H-ras expression in all members of both groups. Cardiomyocyte size was correlated with the expression level of c-H-ras (P<0.001), and c-H-ras expression was upregulated in HCM patients (P<0.01). HCM patients with a beta-MHC mutation had the higher c-H-ras expression than did control subjects or patients without a mutation (P<0.01). c-myc mRNA was expressed in 7 of 17 HCM patients but not in control subjects. Myocyte size was greater in c-myc-positive HCM patients than in control subjects and c-myc-negative HCM patients (P<0.001 and P<0.05, respectively). The proto-oncogene expression did not affect clinical findings, myocardial fibrosis, or disarray. In conclusion, c-H-ras and c-myc expression in the steady-state myocardium may play a role in the hypertrophic mechanism in HCM. It is possible that ss-MHC gene mutation has some effect on the regulation of proto-oncogene expression in HCM.

  12. Myocarditis caused by Feline Immunodeficiency Virus in Five Cats with Hypertrophic Cardiomyopathy.

    PubMed

    Rolim, V Machado; Casagrande, R Assis; Wouters, A Terezinha Barth; Driemeier, D; Pavarini, S Petinatti

    2016-01-01

    Viral infections have been implicated as the cause of cardiomyopathy in several mammalian species. This study describes hypertrophic cardiomyopathy (HCM) and myocarditis associated with feline immunodeficiency virus (FIV) infection in five cats aged between 1 and 4 years. Clinical manifestations included dyspnoea in four animals, one of which also exhibited restlessness. One animal showed only lethargy, anorexia and vomiting. Necropsy examination revealed marked cardiomegaly, marked left ventricular hypertrophy and pallor of the myocardium and epicardium in all animals. Microscopical and immunohistochemical examination showed multifocal infiltration of the myocardium with T lymphocytes and fewer macrophages, neutrophils and plasma cells. An intense immunoreaction for FIV antigen in the cytoplasm and nucleus of lymphocytes and the cytoplasm of some macrophages was observed via immunohistochemistry (IHC). IHC did not reveal the presence of antigen from feline calicivirus, coronavirus, feline leukaemia virus, feline parvovirus, Chlamydia spp. or Toxoplasma gondii. The results demonstrate the occurrence of FIV infection in inflammatory cells in the myocardium of five cats with myocarditis and HCM. PMID:26797583

  13. [Implantation of a dual chamber pacemaker-defibrillator (DDD-ICD) in a patient with hypertrophic obstructive cardiomyopathy].

    PubMed

    Neuberger, H R; Mewis, C; Dörnberger, V; Bosch, R F; Kühlkamp, V

    1999-07-01

    A 70-year-old woman with severely symptomatic hypertrophic obstructive cardiomyopathy was unresponsive to drug treatment. She had recurrent ventricular tachyarrhythmias and syncope and was at high risk for sudden death; a dual chamber pacemaker defibrillator (DDD-ICD) was implanted. Her initial left ventricular outflow tract gradient was 80 mm Hg and fell to 40 mm Hg during dual-chamber pacing at an atrial ventricular delay of 140 ms. In the follow-up over six months she was asymptomatic with respect to angina pectoris; ventricular tachycardias could be successfully terminated by antitachycardia pacing or by shocks. A dual chamber pacemaker defibrillator is an important therapeutic option for patients with symptomatic hypertrophic obstructive cardiomyopathy and ventricular tachyarrhythmias.

  14. Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype

    PubMed Central

    Marques, Mayra de A.; de Oliveira, Guilherme A. P.

    2016-01-01

    Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM) was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the “disease of the sarcomere.” The most common macroscopic phenotypes are left ventricle and interventricular septal thickening, but because the clinical profile of this disease is quite heterogeneous, these phenotypes are not suitable for an accurate diagnosis. The development of genomic approaches for clinical investigation allows for diagnostic progress and understanding at the molecular level. Meanwhile, the lack of accurate in vivo models to better comprehend the cellular events triggered by this pathology has become a challenge. Notwithstanding, the imbalance of Ca2+ concentrations, altered signaling pathways, induction of apoptotic factors, and heart remodeling leading to abnormal anatomy have already been reported. Of note, a misbalance of signaling biomolecules, such as kinases and tumor suppressors (e.g., Akt and p53), seems to participate in apoptotic and fibrotic events. In HCM, structural and cellular information about defective sarcomeric proteins and their altered interactome is emerging but still represents a bottleneck for developing new concepts in basic research and for future therapeutic interventions. This review focuses on the structural and cellular alterations triggered by HCM-causing mutations in troponin and tropomyosin proteins and how structural biology can aid in the discovery of new platforms for therapeutics. We highlight the

  15. Genetics of hypertrophic cardiomyopathy: advances and pitfalls in molecular diagnosis and therapy

    PubMed Central

    Roma-Rodrigues, Catarina; Fernandes, Alexandra R

    2014-01-01

    Hypertrophic cardiomyopathy (HCM) is a primary disease of the cardiac muscle that occurs mainly due to mutations (>1,400 variants) in genes encoding for the cardiac sarcomere. HCM, the most common familial form of cardiomyopathy, affecting one in every 500 people in the general population, is typically inherited in an autosomal dominant pattern, and presents variable expressivity and age-related penetrance. Due to the morphological and pathological heterogeneity of the disease, the appearance and progression of symptoms is not straightforward. Most HCM patients are asymptomatic, but up to 25% develop significant symptoms, including chest pain and sudden cardiac death. Sudden cardiac death is a dramatic event, since it occurs without warning and mainly in younger people, including trained athletes. Molecular diagnosis of HCM is of the outmost importance, since it may allow detection of subjects carrying mutations on HCM-associated genes before development of clinical symptoms of HCM. However, due to the genetic heterogeneity of HCM, molecular diagnosis is difficult. Currently, there are mainly four techniques used for molecular diagnosis of HCM, including Sanger sequencing, high resolution melting, mutation detection using DNA arrays, and next-generation sequencing techniques. Application of these methods has proven successful for identification of mutations on HCM-related genes. This review summarizes the features of these technologies, highlighting their strengths and weaknesses. Furthermore, current therapeutics for HCM patients are correlated with clinically observed phenotypes and are based on the alleviation of symptoms. This is mainly due to insufficient knowledge on the mechanisms involved in the onset of HCM. Tissue engineering alongside regenerative medicine coupled with nanotherapeutics may allow fulfillment of those gaps, together with screening of novel therapeutic drugs and target delivery systems. PMID:25328416

  16. Novel genotype–phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy

    PubMed Central

    Lopes, Luis R; Syrris, Petros; Guttmann, Oliver P; O'Mahony, Constantinos; Tang, Hak Chiaw; Dalageorgou, Chrysoula; Jenkins, Sharon; Hubank, Mike; Monserrat, Lorenzo; McKenna, William J; Plagnol, Vincent; Elliott, Perry M

    2015-01-01

    Objective A predictable relation between genotype and disease expression is needed in order to use genetic testing for clinical decision-making in hypertrophic cardiomyopathy (HCM). The primary aims of this study were to examine the phenotypes associated with sarcomere protein (SP) gene mutations and test the hypothesis that variation in non-sarcomere genes modifies the phenotype. Methods Unrelated and consecutive patients were clinically evaluated and prospectively followed in a specialist clinic. High-throughput sequencing was used to analyse 41 genes implicated in inherited cardiac conditions. Variants in SP and non-SP genes were tested for associations with phenotype and survival. Results 874 patients (49.6±15.4 years, 67.8% men) were studied; likely disease-causing SP gene variants were detected in 383 (43.8%). Patients with SP variants were characterised by younger age and higher prevalence of family history of HCM, family history of sudden cardiac death, asymmetric septal hypertrophy, greater maximum LV wall thickness (all p values<0.0005) and an increased incidence of cardiovascular death (p=0.012). Similar associations were observed for individual SP genes. Patients with ANK2 variants had greater maximum wall thickness (p=0.0005). Associations at a lower level of significance were demonstrated with variation in other non-SP genes. Conclusions Patients with HCM caused by rare SP variants differ with respect to age at presentation, family history of the disease, morphology and survival from patients without SP variants. Novel associations for SP genes are reported and, for the first time, we demonstrate possible influence of variation in non-SP genes associated with other forms of cardiomyopathy and arrhythmia syndromes on the clinical phenotype of HCM. PMID:25351510

  17. Relation of QRS duration to mortality in a community-based cohort with hypertrophic cardiomyopathy.

    PubMed

    Bongioanni, Sergio; Bianchi, Francesca; Migliardi, Alessandro; Gnavi, Roberto; Pron, Paolo Giay; Casetta, Marzia; Conte, Maria Rosa

    2007-08-01

    A prolonged QRS duration on the standard electrocardiogram is associated with an increased risk of cardiovascular death in cardiomyopathies of different origin. However, the relation between QRS duration and prognosis in hypertrophic cardiomyopathy (HC) remains undefined. We assessed the relation between QRS duration and cardiovascular death in 241 consecutive patients with HC. The study cohort was divided into 2 groups according to QRS duration: <120 and > or =120 ms. Of the 241 patients, 191 (79%) had a QRS duration <120 ms and 50 (21%) a QRS duration > or =120 ms. During a mean follow-up of 7.9 +/- 5.1 years, 35 patients died of cardiovascular causes related to HC. Of these 35 patients, 13 (6%) had a QRS duration <120 ms and 22 (43%) had a QRS duration > or =120 ms (p <0.01). Risk of cardiovascular death was significantly higher in patients with a QRS duration > or =120 ms than in those with a QRS duration <120 ms (relative risk 5.2, p <0.0001). At 8-year follow-up, cumulative risks of HC-related death were 7.1% in patients with a QRS duration <120 ms and 55% in those with a QRS duration > or =120 ms. Multivariate analysis confirmed that a QRS duration > or =120 ms was independently associated with an increased risk of cardiovascular death (hazard ratio 3.2, p = 0.007). New York Heart Association functional class III/IV was the only other clinical variable significantly and independently associated with an increased risk of cardiovascular death. In conclusion, in patients with HC, QRS duration on standard electrocardiogram is directly related to cardiovascular mortality, and a QRS duration > or =120 ms is a strong and independent predictor of prognosis.

  18. Slowed atrial and atrioventricular conduction and depressed HRV in a murine model of hypertrophic cardiomyopathy.

    PubMed

    Lim, Wei-Wen; Baumert, Mathias; Neo, Melissa; Kuklik, Pawel; Ganesan, Anand N; Lau, Dennis H; Tsoutsman, Tatiana; Semsarian, Christopher; Sanders, Prashanthan; Saint, David A

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a common heritable cardiac disorder with diverse clinical outcomes including sudden death, heart failure, and stroke. Depressed heart rate variability (HRV), a measure of cardiac autonomic regulation, has been shown to predict mortality in patients with cardiovascular disease. Cardiac autonomic remodelling in animal models of HCM are not well characterised. This study analysed Gly203Ser cardiac troponin-I transgenic (TG) male mice previously demonstrated to develop hallmarks of HCM by age 21 weeks. 33 mice aged 30 and 50 weeks underwent continuous electrocardiogram (ECG) recording for 30 min under anaesthesia. TG mice demonstrated prolonged P-wave duration (P < 0.001) and PR intervals (P < 0.001) compared to controls. Additionally, TG mice demonstrated depressed standard deviation of RR intervals (SDRR; P < 0.01), coefficient of variation of RR intervals (CVRR; P < 0.001) and standard deviation of heart rate (SDHR; P < 0.001) compared to controls. Additionally, total power was significantly reduced in TG mice (P < 0.05). No significant age-related difference in either strain was observed in ECG or HRV parameters. Mice with HCM developed slowed atrial and atrioventricular conduction and depressed HRV. These changes were conserved with increasing age. This finding may be indicative of atrial and ventricular hypertrophy or dysfunction, and perhaps an indication of worse clinical outcome in heart failure progression in HCM patients.

  19. Constructing "best interests": genetic testing of children in families with hypertrophic cardiomyopathy.

    PubMed

    Geelen, Els; Van Hoyweghen, Ine; Doevendans, Pieter A; Marcelis, Carlo L M; Horstman, Klasien

    2011-08-01

    Professional guidelines on genetic testing of children have recently shifted their focus from protecting the child's autonomous choice to professionals, together with parents, striving to work in the child's "best interest." This notion of "best interest" allows room for therapeutical as well as psychological and social considerations, and gives rise to the question how parents and professionals weigh up the child's best interest in practice. In this qualitative study, we followed six extended families involved in genetic testing for hypertrophic cardiomyopathy in the Netherlands for 3½ years. In total 57 members of these families were interviewed in depth; many of them more than once. Our empirical analysis shows that the best interest of a child is constructed via long-term processes in the broader context of family and kin. In this context, "best interests" are considered and reconsidered. We conclude that a child's best interest should not be framed as the result of an instantaneous agreement between parents and professionals. In dealing with genetic testing of children, parents as well as professionals reflect on and learn from the processes of generating new meanings of "best interest." To enable professionals to deal with the variety in family life, these learning processes should be documented closely. PMID:21739592

  20. Comparison of Modified With Classic Morrow Septal Myectomy in Treating Hypertrophic Obstructive Cardiomyopathy

    PubMed Central

    Song, Bangrong; Dong, Ran

    2016-01-01

    Abstract This study aimed to compare the efficacy and safety of the classic Morrow septal myectomy with the modified procedure in treating hypertrophic obstructive cardiomyopathy (HOCM). A retrospective study was conducted to compare the outcomes of classic with modified Morrow septal myectomy in 42 patients treated from January 2005 to July 2011. Preoperative and postoperative ventricular septal thickness, left ventricular (LV) outflow tract velocity and gradient were measured echocardiographically. In both groups, the ventricular septal thickness, LV outflow tract velocity, and LV outflow tract gradient were significantly decreased after the operation. The modified Morrow procedure group, however, showed significantly greater reduction in these echocardiographic parameters than the classic procedure group. All patients in the modified procedure group were asymptomatic postoperatively with a postoperative transvalvular pressure gradient <30 mm Hg. In the classic procedure group, only 14 (87.5%) patients, however, were asymptomatic postoperatively with a postoperative transvalvular pressure gradient <30 mm Hg, and 2 patients still had severe LV outflow obstruction postoperatively. The modified Morrow septal myectomy is safe and effective in treating HOCM patients, and is superior to the classic procedure in reducing the LV outflow tract gradient and velocity, restoring normal anatomic atrioventricular size, and alleviating symptoms associated with HOCM. PMID:26765408

  1. Outcomes of an extended Morrow procedure without a concomitant mitral valve procedure for hypertrophic obstructive cardiomyopathy

    PubMed Central

    Liu, Yun; Song, Yunhu; Gao, Ge; Ran, Jun; Su, Wenjun; Li, Haojie; Tang, Yajie; Duan, Fujian; Sun, Hansong

    2016-01-01

    The indications for a concomitant mitral valve (MV) procedure remain controversial for patients with hypertrophic obstructive cardiomyopathy (HOCM). According to previous studies, a concomitant MV surgery was required in 11–20% of inpatient operations. Thus, we aimed to study the outcomes of an extended Morrow procedure without a concomitant MV procedure for HOCM patients who had no intrinsic abnormalities of the MV apparatus. We retrospectively reviewed 232 consecutive HOCM patients who underwent extended Morrow procedures from January 2010 to October 2014. Only 10 (4.31%) patients with intrinsic MV diseases underwent concomitant MV procedures. Of the 232 patients, 230 had no to mild mitral regurgitation (MR) postoperatively. We separated the 232 patients into two groups according to preoperative MR degree. One group is mild MR, and the other is moderate or severe MR. The three-month, one-year, and three-year composite end-point event-free survival rates had no difference between two groups (p = 0.820). When we separated the patients to postoperative no or trace MR group and mild MR group, there was also no difference on survival rates (p = 0.830). In conclusion, concomitant mitral valve procedures are not necessary for HOCM patients with MR caused by systolic anterior motion, even moderate to severe extent. PMID:27357867

  2. Fabry disease in patients with hypertrophic cardiomyopathy: a practical approach to diagnosis.

    PubMed

    Seo, Jiwon; Kim, Minji; Hong, Geu-Ru; Kim, Dae-Seong; Son, Jang-Won; Cho, In Jeong; Shim, Chi Young; Chang, Hyuk-Jae; Ha, Jong-Won; Chung, Namsik

    2016-09-01

    This study aimed to develop a new set of screening criteria that is easily applicable and highly sensitive for the detection of patients at high risk of Fabry disease (FD) among hypertrophic cardiomyopathy (HCM) patients. We prospectively studied 273 consecutive unrelated patients who were referred to HCM clinic for unknown left ventricular hypertrophy. Among the 273 patients, we selected 65 high-risk patients who fulfilled at least one of our newly proposed screening criteria. All 273 patients were assayed for plasma α-galactosidase A (α-GAL A) activity. The new screening criteria were: (1) atypical HCM, (2) history or presence of documented arrhythmia, (3) short PR interval defined as <120 ms on electrocardiogram, and (4) symptoms of autonomic dysfunction. From this screening study, three unrelated patients (4.6%; 2 females and 1 male) were newly diagnosed with FD using α-GAL A activity and mutation analysis of the GLA gene. Using the screening method based on the newly proposed criteria, the prevalence of FD in our HCM population was 4.6% if at least one criterion was met and 18.8% if ⩾3 criteria were met. Therefore, our proposed criteria are easily applicable and highly sensitive for classifying patients at high risk of FD from HCM patients. PMID:27225851

  3. Decreased contractility due to energy deprivation in a transgenic rat model of hypertrophic cardiomyopathy.

    PubMed

    Luedde, Mark; Flögel, Ulrich; Knorr, Maike; Grundt, Christina; Hippe, Hans-Joerg; Brors, Benedikt; Frank, Derk; Haselmann, Uta; Antony, Claude; Voelkers, Mirko; Schrader, Juergen; Most, Patrick; Lemmer, Bjoern; Katus, Hugo A; Frey, Norbert

    2009-04-01

    Hypertrophic cardiomyopathy (HCM) is associated with cardiac hypertrophy, diastolic dysfunction, and sudden death. Recently, it has been suggested that inefficient energy utilization could be a common molecular pathway of HCM-related mutations. We have previously generated transgenic Sprague-Dawley rats overexpressing a truncated cardiac troponin T (DEL-TNT) molecule, displaying typical features of HCM such as diastolic dysfunction and an increased susceptibility to ventricular arrhythmias. We now studied these rats using 31P magnetic resonance spectroscopy (MRS). MRS demonstrated that cardiac energy metabolism was markedly impaired, as indicated by a decreased phosphocreatine to ATP ratio (-31%, p < 0.05). In addition, we assessed contractility of isolated cardiomyocytes. While DEL-TNT and control cardiomyocytes showed no difference under baseline conditions, DEL-TNT cardiomyocytes selectively exhibited a decrease in fractional shortening by 28% after 1 h in glucose-deprived medium (p < 0.05). Moreover, significant decreases in contraction velocity and relaxation velocity were observed. To identify the underlying molecular pathways, we performed transcriptional profiling using real-time PCR. DEL-TNT hearts exhibited induction of several genes critical for cardiac energy supply, including CD36, CPT-1/-2, and PGC-1alpha. Finally, DEL-TNT rats and controls were studied by radiotelemetry after being stressed by isoproterenol, revealing a significantly increased frequency of arrhythmias in transgenic animals. In summary, we demonstrate profound energetic alterations in DEL-TNT hearts, supporting the notion that inefficient cellular ATP utilization contributes to the pathogenesis of HCM. PMID:19189074

  4. Stimulation of the renin-angiotensin system in cats with hypertrophic cardiomyopathy.

    PubMed

    Taugner, F M

    2001-01-01

    Feline hypertrophic cardiomyopathy (HCM) is a disease of the ventricular myocardium, which may cause sudden death in cats, but neither the aetiology nor the effect on the circulation are well understood. Fourteen cats of either sex with naturally occurring HCM were studied post mortem. Their ages ranged from 9 months to 10 years with an average age of 4.9 years. Heart weights and heart weight expressed as a percentage of body weight were elevated (27.9 g and 0.65%, respectively) as compared with normal values obtained in previous studies. Myocardial disarray was evident in nine of the 14 cats and moderate to severe fibrosis was present in six animals. To evaluate the renal renin-angiotensin system, semiquantitative morphometric data were obtained by means of renin immunohistochemistry and compared with results from an earlier study of 10 healthy cats by the author. The juxtaglomerular index was 36.8% in the cats with HCM as compared with 30.6% in healthy cats. The renin-positive portion of the afferent arteriole was increased in cats affected by HCM to 86.0 microm as compared with 49.9 microm in normal cats. The increase in kidney renin values in cats with HCM may have been due to decreased blood pressure and reduced renal perfusion resulting from impaired cardiac output. PMID:11578127

  5. Are We Missing Hypertrophic Cardiomyopathy in Pregnancy? Experience of a Tertiary Care Hospital

    PubMed Central

    Suri, Vanita; Aggarwal, Neelam; Chopra, Seema; Bahl, Ajay; Vijayverghia, Rajesh

    2014-01-01

    Background: Controversies persist regarding risks associated with pregnancy and delivery in women with hypertrophic cardiomyopathy (HCM). To date, pregnancy outcome data for these patients is scarce. We report the experience of pregnancies with HCM in a tertiary care hospital. Materials and Methods: Data regarding cardiac illness and obstetric profile of all women attending the cardio-obstetrics clinic from January 1990 to December 2012 were studied. The records of cardiac illness of all women were checked and all patients with HCM were included in the study. Results: Out of total 2016 patients booked in the cardio-obstetrics clinic between 1990 and 2012, only 4 women were found to have a diagnosis of HCM (0.2%). Of these, 2 women with left ventricular outflow tract obstruction and one with non-obstructive HCM had only mild symptoms and tolerated pregnancy and labour well. One patient had HCM with restrictive physiology developed heart failure and intra-uterine fetal death. Conclusion: HCM is underdiagnosed and rarely identified in pregnancy. Most patients with HCM tolerated pregnancy well, howeverone patient with restrictive physiology developed heart failure during her first pregnancy. PMID:25386487

  6. Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing

    PubMed Central

    Xu, Jing; Li, Zhongshan; Ren, Xianguo; Dong, Ming; Li, Jinxin; Shi, Xingjuan; Zhang, Yu; Xie, Wei; Sun, Zhongsheng; Liu, Xiangdong; Dai, Qiming

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with high heterogeneity. Limited knowledge concerning the genetic background of nearly 40% HCM cases indicates there is a clear need for further investigation to explore the genetic pathogenesis of the disease. In this study, we undertook a whole exome sequencing (WES) approach to identify novel candidate genes and mutations associated with HCM. The cohort consisted of 74 unrelated patients with sporadic HCM (sHCM) previously determined to be negative for mutations in eight sarcomere genes. The results showed that 7 of 74 patients (9.5%) had damaging mutations in 43 known HCM disease genes. Furthermore, after analysis combining the Transmission and De novo Association (TADA) program and the ToppGene program, 10 putative genes gained priority. A thorough review of public databases and related literature revealed that there is strong supporting evidence for most of the genes playing roles in various aspects of heart development. Findings from recent studies suggest that the putative and known disease genes converge on three functional pathways: sarcomere function, calcium signaling and metabolism pathway. This study illustrates the benefit of WES, in combination with rare variant analysis tools, in providing valuable insight into the genetic etiology of a heterogeneous sporadic disease. PMID:26573135

  7. Effect of Left Ventricular Outflow Tract Obstruction on Left Atrial Mechanics in Hypertrophic Cardiomyopathy

    PubMed Central

    Williams, Lynne K.; Chan, Raymond H.; Carasso, Shemy; Durand, Miranda; Misurka, Jimmy; Crean, Andrew M.; Ralph-Edwards, Anthony; Gruner, Christiane; Woo, Anna; Lesser, John R.; Maron, Barry J.; Maron, Martin S.; Rakowski, Harry

    2015-01-01

    Left atrial (LA) volumes are known to be increased in hypertrophic cardiomyopathy (HCM) and are a predictor of adverse outcome. In addition, LA function is impaired and is presumed to be due to left ventricular (LV) diastolic dysfunction as a result of hypertrophy and myocardial fibrosis. In the current study, we assess the incremental effect of outflow tract obstruction (and concomitant mitral regurgitation) on LA function as assessed by LA strain. Patients with HCM (50 obstructive, 50 nonobstructive) were compared to 50 normal controls. A subset of obstructive patients who had undergone septal myectomy was also studied. Utilising feature-tracking software applied to cardiovascular magnetic resonance images, LA volumes and functional parameters were calculated. LA volumes were significantly elevated and LA ejection fraction and strain were significantly reduced in patients with HCM compared with controls and were significantly more affected in patients with obstruction. LA volumes and function were significantly improved after septal myectomy. LVOT obstruction and mitral regurgitation appear to further impair LA mechanics. Septal myectomy results in a significant reduction in LA volumes, paralleled by an improvement in function. PMID:26788503

  8. Cardiac sarcoidosis mimicking hypertrophic cardiomyopathy: clinical utility of radionuclide imaging for differential diagnosis.

    PubMed

    Yazaki, Y; Isobe, M; Hayasaka, M; Tanaka, M; Fujii, T; Sekiguchi, M

    1998-06-01

    A 62-year-old woman with skin sarcoidosis was admitted to our hospital to ascertain whether she had cardiac involvement. Although she displayed no cardiac signs or symptoms, the electrocardiogram showed first-degree atrioventricular block, right bundle branch block with left anterior fascicular block, and giant negative T waves in the V3 lead. Echocardiography revealed marked hypertrophy localized in the basal portion of the interventricular septum (IVS) without systolic dysfunction, mimicking hypertrophic cardiomyopathy (HCM). Exercise thallium-201 myocardial imaging revealed redistribution in the anteroseptal region. Both gallium-67 (67Ga) and technetium-99m pyrophosphate (99mTc-PYP) scintigraphy revealed abnormal uptake in the myocardium. These findings disappeared after 2 months of steroid treatment. Reports of cardiac sarcoidosis mimicking HCM are rare. However, hypertrophy in the basal portion of the IVS is an important sign of early cardiac involvement in sarcoidosis. 67Ga and 99mTc-PYP scintigraphy were useful and necessary to differentiate this type of cardiac sarcoidosis from HCM.

  9. A Delta-Sarcoglycan Gene Polymorphism as a Risk Factor for Hypertrophic Cardiomyopathy

    PubMed Central

    Garrido-Garduño, Martín H.; Pérez-Martínez, Ramón A.; Ruiz, Victor M.; Herrera-Tepatlán, Esteban; Rodríguez-Cruz, Maricela; Jiménez-Vaca, Ana L.; Minauro-Sanmiguel, Fernando; Salamanca-Gómez, Fabio A.

    2012-01-01

    Background: The C allele of c.−94C>G polymorphism of the delta-sarcoglycan gene was associated as a risk factor for coronary spasm in Japanese patients with hypertrophic cardiomyopathy (HCM). Aim: We evaluated whether the c.−94C>G polymorphism can be a risk factor for HCM in Mexican patients. Methods: The polymorphism was genotyped and the risk was estimated in 35 HCM patients and 145 healthy unrelated individuals. Data of this polymorphism reported in Mexican Amerindian populations were included. Results: The C allele frequency in HCM patients was higher with an odds ratio (OR) of 2.37, and the risk for the CC genotype increased to 5.0. The analysis with Mexican Amerindian populations showed that the C allele frequency was significantly higher in HCM patients with an OR of 2.96 and for CC genotype the risk increased to 7.60. Conclusions: The C allele of the c.−94C>G polymorphism is a risk factor for HCM, which is increased by the Amerindian component and can play an important role in the etiology and progression of disease in Mexican patients. PMID:22524166

  10. Decreased contractility due to energy deprivation in a transgenic rat model of hypertrophic cardiomyopathy.

    PubMed

    Luedde, Mark; Flögel, Ulrich; Knorr, Maike; Grundt, Christina; Hippe, Hans-Joerg; Brors, Benedikt; Frank, Derk; Haselmann, Uta; Antony, Claude; Voelkers, Mirko; Schrader, Juergen; Most, Patrick; Lemmer, Bjoern; Katus, Hugo A; Frey, Norbert

    2009-04-01

    Hypertrophic cardiomyopathy (HCM) is associated with cardiac hypertrophy, diastolic dysfunction, and sudden death. Recently, it has been suggested that inefficient energy utilization could be a common molecular pathway of HCM-related mutations. We have previously generated transgenic Sprague-Dawley rats overexpressing a truncated cardiac troponin T (DEL-TNT) molecule, displaying typical features of HCM such as diastolic dysfunction and an increased susceptibility to ventricular arrhythmias. We now studied these rats using 31P magnetic resonance spectroscopy (MRS). MRS demonstrated that cardiac energy metabolism was markedly impaired, as indicated by a decreased phosphocreatine to ATP ratio (-31%, p < 0.05). In addition, we assessed contractility of isolated cardiomyocytes. While DEL-TNT and control cardiomyocytes showed no difference under baseline conditions, DEL-TNT cardiomyocytes selectively exhibited a decrease in fractional shortening by 28% after 1 h in glucose-deprived medium (p < 0.05). Moreover, significant decreases in contraction velocity and relaxation velocity were observed. To identify the underlying molecular pathways, we performed transcriptional profiling using real-time PCR. DEL-TNT hearts exhibited induction of several genes critical for cardiac energy supply, including CD36, CPT-1/-2, and PGC-1alpha. Finally, DEL-TNT rats and controls were studied by radiotelemetry after being stressed by isoproterenol, revealing a significantly increased frequency of arrhythmias in transgenic animals. In summary, we demonstrate profound energetic alterations in DEL-TNT hearts, supporting the notion that inefficient cellular ATP utilization contributes to the pathogenesis of HCM.

  11. Fabry disease in patients with hypertrophic cardiomyopathy: a practical approach to diagnosis.

    PubMed

    Seo, Jiwon; Kim, Minji; Hong, Geu-Ru; Kim, Dae-Seong; Son, Jang-Won; Cho, In Jeong; Shim, Chi Young; Chang, Hyuk-Jae; Ha, Jong-Won; Chung, Namsik

    2016-09-01

    This study aimed to develop a new set of screening criteria that is easily applicable and highly sensitive for the detection of patients at high risk of Fabry disease (FD) among hypertrophic cardiomyopathy (HCM) patients. We prospectively studied 273 consecutive unrelated patients who were referred to HCM clinic for unknown left ventricular hypertrophy. Among the 273 patients, we selected 65 high-risk patients who fulfilled at least one of our newly proposed screening criteria. All 273 patients were assayed for plasma α-galactosidase A (α-GAL A) activity. The new screening criteria were: (1) atypical HCM, (2) history or presence of documented arrhythmia, (3) short PR interval defined as <120 ms on electrocardiogram, and (4) symptoms of autonomic dysfunction. From this screening study, three unrelated patients (4.6%; 2 females and 1 male) were newly diagnosed with FD using α-GAL A activity and mutation analysis of the GLA gene. Using the screening method based on the newly proposed criteria, the prevalence of FD in our HCM population was 4.6% if at least one criterion was met and 18.8% if ⩾3 criteria were met. Therefore, our proposed criteria are easily applicable and highly sensitive for classifying patients at high risk of FD from HCM patients.

  12. Obtaining insurance after DNA diagnostics: a survey among hypertrophic cardiomyopathy mutation carriers.

    PubMed

    Christiaans, Imke; Kok, Tjitske M; van Langen, Irene M; Birnie, Erwin; Bonsel, Gouke J; Wilde, Arthur A M; Smets, Ellen M A

    2010-02-01

    Hypertrophic cardiomyopathy (HCM) is a common hereditary heart disease associated with increased mortality. Disclosure of DNA test results may have social implications such as low access to insurance. In The Netherlands, insurance companies are restricted in the use of genetic information of their clients by the Medical Examination Act. A cross-sectional survey was used to assess the frequency and type of problems encountered by HCM mutation carriers applying for insurance, and associations with carriers' characteristics. The response rate was 86% (228/264). A total of 66 carriers (29%) applied for insurance of whom 39 reported problems (59%) during an average follow-up of 3 years since the DNA test result. More problems were encountered by carriers with manifest disease (P<0.001) and carriers with symptoms of HCM (P=0.049). Carriers identified after predictive DNA testing less frequently experienced problems (P=0.002). Three carriers without manifest HCM reported problems (5% of applicants). Frequently reported problems were higher premium (72%), grant access to medical records (62%), and complete rejection (33%). In conclusion, HCM mutation carriers frequently encounter problems when applying for insurances, often in the case of manifest disease, but the risk assessment of insurance companies is largely justified. Still, 5% of carriers encounter potentially unjustified problems, indicating the necessity to monitor the application of the existing laws and regulations by insurance companies and to educate counselees on the implications of these laws and regulations.

  13. Mid-Term Results of Dual-Chamber Pacing in Children with Hypertrophic Obstructive Cardiomyopathy.

    PubMed

    Alday, Luis E.; Bruno, Eva; Moreyra, Eduardo; Amuchastegui, Luis M.; Juaneda, Ernesto; Maisuls, Hector

    1998-04-01

    BACKGROUND: Permanent dual-chambered pacing (DDD) is an alternative to surgical treatment in patients with severe hypertrophic obstructive cardiomyopathy (HOCM) who do not have a satisfactory response to medical treatment. METHODS: Five children with severe HOCM still symptomatic despite medical treatment underwent permanent DDD pacing and were followed for 21 +/- 9.7 months. RESULTS: All patients improved their functional class. Doppler echocardiographic studies showed an early reduction of the left ventricular outflow tract gradient from 66 +/- 40 to 40 +/- 20 mmHg (P < 0.05) and to 30 +/- 11 mmHg (P < 0.05 and NS for comparison with the baseline and the early post-DDD pacing gradients, respectively) at mid-term follow-up. There was no evidence of left ventricular systolic dysfunction, and the results of left ventricular filling studies ruled out deleterious effects on diastolic function. Doppler echocardiography played a key role in the initial and subsequent assessment of these patients. CONCLUSIONS: Permanent DDD pacing is a reasonable alternative to surgery in children with HOCM who are still symptomatic despite medical therapy.

  14. Comparison of surgical septal myectomy to medical therapy alone in patients with hypertrophic cardiomyopathy and syncope.

    PubMed

    Orme, Nicholas M; Sorajja, Paul; Dearani, Joseph A; Schaff, Hartzell V; Gersh, Bernard J; Ommen, Steve R

    2013-02-01

    The presence of syncope despite medical therapy in patients with hypertrophic cardiomyopathy (HC) is considered an indication for surgical myectomy; however, no study has examined the long-term effects on recurrent syncope and survival after surgery in these patients. We examined 239 patients with HC and a history of syncope who had undergone surgical myectomy (mean age 48 ± 17 years; 56% men). The patients were age- and gender-matched to patients with HC and syncope who were treated medically without myectomy (mean age 51 ± 16 years; 59% men). The median follow-up period was 4.7 years (0.8, 11.3). The recurrence rate of syncope was 11% in the myectomy patients and 40% in the medical group (p <0.0001). Multiple episodes of syncope, left ventricular outflow tract obstruction, and recent syncope were identified as baseline predictors of recurrent syncope. Survival free of all-cause mortality was greater for patients who had undergone surgical myectomy than for the medically treated patients (10-year estimate 82 ± 4% vs 69 ± 4%; p = 0.01). In conclusion, surgical myectomy in patients with HC and a history of syncope was associated with a reduction in recurrent syncope and increased survival.

  15. Myocardial deformation from tagged MRI in hypertrophic cardiomyopathy using an efficient registration strategy

    NASA Astrophysics Data System (ADS)

    Piella, G.; De Craene, M.; Oubel, E.; Larrabide, I.; Huguet, M.; Bijnens, B. H.; Frangi, A. F.

    2009-02-01

    This paper combines different parallelization strategies for speeding up motion and deformation computation by non-rigid registration of a sequence of images. The registration is performed in a two-level acceleration approach: (1) parallelization of each registration process using MPI and/or threads, and (2) distribution of the sequential registrations over a cluster. On a 24-node double quad-core Intel Xeon (2.66 GHz CPU, 16 GB RAM) cluster, the method is demonstrated to efficiently compute the deformation of a cardiac sequence reducing the computation time from more than 3 hours to a couple of minutes (for low downsampled images). It is shown that the distribution of the sequential registrations over the cluster together with the parallelization of each pairwise registration by multithreading lowers the computation time towards values compatible with clinical requirements (a few minutes per patient). The combination of MPI and multithreading is only advantageous for large input data sizes. Performances are assessed for the specific scenario of aligning cardiac sequences of taggedMagnetic Resonance (tMR) images, with the aim of comparing strain in healthy subjects and hypertrophic cardiomyopathy (HCM) patients. In particular, we compared the distribution of systolic strain in both populations. On average, HCM patients showed lower average values of strain with larger deviation due to the coexistence of regions with impaired deformation and regions with normal deformation.

  16. [Hypertrophic cardiomyopathy: a rare cause of vascular dementia. A case report].

    PubMed

    Ben Hamouda, Ibtissem; Tougourti, Mohamed Néjib; Hamza, Mohsen

    2002-07-01

    Herein, we report a case of a 51 year old man who experienced three ischemic cerebral infarcts in a time of few months. The patient consulted after the third accident. Neurological presentation included pseudobulbar syndrome with a mild cognitive deficit, aphasia, left hemiparesia, hemiasomatognosia and homonymous lateral hemianopsia. Cerebral tomodensitometry and magnetic resonance imaging evidenced large infarcts images involving right middle cerebral artery territory and bilateral borderline zones in the junction of the territories of the middle and posterior cerebral arteries. Ambulatory 24 hours ECG recording (Holter) revealed two hits of non-sustained ventricular tachycardia. Transoesophageal echocardiography conveyed to the diagnosis of hypertrophic cardiomyopathy and displayed the presence of a left auricular thrombus. Anticoagulant therapy and rehabilitation allowed a substantial recovering of the patient's cognitive functions and wasting of the intracardiac thrombus. The clinical features observed in our patient meet the recommended DSM IV diagnosis criteria of vascular dementia, an exceptional complication of HCM. The clinical findings, neuroimagery investigation results, and the chronological link between cerebral attacks and cognitive function deterioration argue for a demential syndrome of vascular origin resulting from multiple embolic infarcts involving medium sized arteries (multi-infarct dementia). The authors emphasize the rarity of such observation. HCM must be considered as a potential cause of embolic stroke and likewise a multi-infarct dementia. PMID:12611354

  17. Bilateral brachial plexus blocks in a patient of hypertrophic obstructive cardiomyopathy with hypertensive crisis.

    PubMed

    Pai, Rohini V Bhat; Hegde, Harihar V; Santhosh, McB; Roopa, S; Deshpande, Shrinivas S; Rao, P Raghavendra

    2013-01-01

    Hypertrophic obstructive cardiomyopathy (HOCM) is a challenge to anesthesiologists due to the complex pathophysiology involved and various perioperative complications associated with it. We present a 50-year-old man, a known case of HOCM, who successfully underwent emergency haemostasis, and debridement of the traumatically amputated right upper limb and the contused lacerated wound on the left forearm under bilateral brachial plexus blocks. His co-morbidities included hypertension (in hypertensive crisis) and diabetes mellitus. He was full stomach and also had an anticipated difficult airway. The management included invasive pressure monitoring and labetalol infusion for emergent control of blood pressure. The regional anaesthesia technique required careful consideration to the dosage of local anaesthetics and staggered performance of brachial plexus blocks on each of the upper limbs to avoid local anaesthetic toxicity. Even though bilateral brachial plexus blocks are rarely indicated, it seemed to be the most appropriate anaesthetic technique in our patient. With careful consideration of the local anaesthetic toxicity and meticulous technique, bilateral brachial plexus blocks can be successfully performed in those patients where general anaesthesia is deemed to be associated with higher risk.

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

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

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

  19. Potential mechanisms of improvement after various treatments for hypertrophic obstructive cardiomyopathy.

    PubMed Central

    Leachman, R D

    1995-01-01

    In sum, systolic dysfunction of the ventricle associated with left ventricular outlet obstruction and often with mitral valve regurgitation may be improved by myotomy, myomectomy, mitral valve replacement, and perhaps by the creation of left bundle branch block via DDD right ventricular pacing. Diastolic dysfunction of the ventricle may be improved by prolonging the diastolic filling period, shortening the isovolumic relaxation period with calcium channel blocking drugs, or perhaps by altering the atrioventricular activation time with a DDD pacemaker. The symptoms and complications of associated arrhythmias may be improved by medication, particularly with beta-blockers, which tend to stabilize the atrial rhythm and perhaps the ventricular rhythms. In treating patients with demonstrated ventricular arrhythmias, other antiarrhythmic agents may be helpful. (Table II summarizes the abnormalities, causes, and treatments of hypertrophic obstructive cardiomyopathy.) Epicardial coronary atherosclerosis is not rare in these patients, and arteriographic confirmation may lead to improvement by surgical bypass treatment. Since stroke volume is nearly fixed, cardiac output depends very much on heart rate. For this reason, each patient needs to receive the appropriate dosage of medications to achieve the optimal heart rate for his or her own physiologic state. Images PMID:7647595

  20. Hypertrophic cardiomyopathy and sudden cardiac death due to physical exercise in Croatia in a 27-year period.

    PubMed

    Duraković, Zijad; Duraković, Marjeta Misigoj; Skavić, Josip

    2011-12-01

    The paper deals with the sudden cardiac death during physical exercise in males in Croatia. The data are a part of a retrospective study dealing with 69 sudden death due to physical activity in men in Croatia during 27 years: from January 1, 1984 to December 31, 2010. Three of them suddenly died during training and two of them died during recreational physical exercise, probably because of malignant ventricular arrhythmia due to hyperthrophic cardiomyopathy. One had an obstructive form of hypertrophic cardiomyopathy with i.v. septum of 40 mm and four had a non-obstructive forms of hyperthrophic cardiomyopathy with left ventricular wall of 18-20-22-25 mm. First athlete was a short trails runner, aged 24, with no any previous physical discomforts, who suddenly collapsed and died during training. The second athlete was a soccer player aged 18, with no any previous physical discomfort, who suddenly collapsed and died during training. The third aged 15, was a school boy, basketball player, with no any previous physical discomfort, who collapsed and died during training. Two aged 25 and 34, were with no physical discomfort during exercise and died suddenly during recreational soccer games. A sudden cardiac death due to physical exercise in young athletes in Croatia suffered of hyperthropic cardiomyopathy reached 0.06/100 000 yearly (p = 0.00000) in 27 years, in teenagers 0.26/100 000 (p = 0.00226), in teenagers suffered of hypertrophic cardiomyopathy reached 0.10/100 000 (p = 0.00000), in all young athletes suffered of other heart diseases reached 0.19/100 000 (p = 0.00005), and in the total male population aged 15 or more, engaged in sports and recreational physical exercise: 0.71/100.0000 (p = 0.00001).

  1. Complex I deficiency due to selective loss of Ndufs4 in the mouse heart results in severe hypertrophic cardiomyopathy.

    PubMed

    Chouchani, Edward T; Methner, Carmen; Buonincontri, Guido; Hu, Chou-Hui; Logan, Angela; Sawiak, Stephen J; Murphy, Michael P; Krieg, Thomas

    2014-01-01

    Mitochondrial complex I, the primary entry point for electrons into the mitochondrial respiratory chain, is both critical for aerobic respiration and a major source of reactive oxygen species. In the heart, chronic dysfunction driving cardiomyopathy is frequently associated with decreased complex I activity, from both genetic and environmental causes. To examine the functional relationship between complex I disruption and cardiac dysfunction we used an established mouse model of mild and chronic complex I inhibition through heart-specific Ndufs4 gene ablation. Heart-specific Ndufs4-null mice had a decrease of ∼ 50% in complex I activity within the heart, and developed severe hypertrophic cardiomyopathy as assessed by magnetic resonance imaging. The decrease in complex I activity, and associated cardiac dysfunction, occurred absent an increase in mitochondrial hydrogen peroxide levels in vivo, accumulation of markers of oxidative damage, induction of apoptosis, or tissue fibrosis. Taken together, these results indicate that diminished complex I activity in the heart alone is sufficient to drive hypertrophic cardiomyopathy independently of alterations in levels of mitochondrial hydrogen peroxide or oxidative damage.

  2. 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 ...

  3. Morphologic evidence for "small vessel disease" in patients with hypertrophic cardiomyopathy.

    PubMed

    Maron, B J; Wolfson, J K; Epstein, S E; Roberts, W C

    1987-01-01

    Many patients with hypertrophic cardiomyopathy (HCM) have signs and symptoms or metabolic and hemodynamic evidence of myocardial ischemia and dysfunction in the absence of extramural coronary atherosclerosis. To investigate the possibility that a form of "small vessel disease" could account for these findings, a histologic analysis of left ventricular myocardium obtained at necropsy was carried out in 48 patients with hypertophic cardiomyopathy and in 68 controls with either normal hearts or acquired heart disease. In HCM, abnormal intramural coronary arteries (IMCA) were characterized by thickening of the vessel wall and an apparent decrease in luminal size (external arterial diameter less than 1500 micron; average 300 micron). The wall thickening was due to proliferation of medial and/or intimal components, particularly smooth muscle cells and collagen. Of the 48 patients with HCM,40 (83%) had abnormal IMCAs located in the ventricular septum (33 patients), anterior left ventricular free wall (20 patients) or posterior free wall (nine patients); an average of 3.0 +/- 0.7 IMCA were identified per tissue section. Altered IMCAs were also significantly more common in tissue sections having considerable myocardial fibrosis (31 out of 42, 74%) than in those with no or mild fibrosis (31 or 102, 30%; p less than 0.001). Abnormal IMCA wera also identified in 3 out of 8 infants who died of HCM before 1 year of age. In contrast, only rare altered IMCA were identified in six (9%) of the 69 control patients, and those arteries showed only mild thickening of the wall and minimal luminal narrowing (abnormal IMCA per section: 0.1 +/- 0.05: p less than 0.001). Moreover, of those patients who did show abnormal IMCA, such vessels were about twenty times more frequent in patients with HCM (0.9 +/- 0.2/cm2 myocardium) than in controls (0.04 +/- 0.02/cm2 myocardium). Hence, abnormal IMCA with markedly thickened walls and narrowed lumens are present in increased numbers in most patients

  4. Apical aneurysm and myocardial bridging in a patient with hypertrophic cardiomyopathy: association or consequence of the myocardial bridging?

    PubMed

    Foucault, Anthony; Hilpert, Loic; Hédoire, Francois; Saloux, Eric; Gomes, Sophie; Pellissier, Arnaud; Scanu, Patrice; Champ-Rigot, Laure; Milliez, Paul

    2012-01-01

    The identification of high-risk patients with hypertrophic cardiomyopathy (HC) for primary prevention of sudden cardiac death (SCD) remains a challenging issue, since major risk factors sometimes lack specificity. We report the case of a patient with HC and association of apical aneurysm and myocardial bridging who had been initially not implanted because she had only one major risk factor. She subsequently experienced a sustained ventricular tachycardia that finally motivated the implantation. We conclude that it is never an easy decision to implant a preventive implantable cardioverter-defibrillator (ICD). Nevertheless, additional criteria for a better selection of patients who would benefit from an ICD implant are certainly useful.

  5. Relation Between Temperature Extremes and Symptom Exacerbation in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Bois, John P; Adams, Jonathon C; Kumar, Gautam; Ommen, Steve R; Nishimura, Rick A; Klarich, Kyle W

    2016-03-15

    Warm temperatures induce peripheral vasodilation, decrease afterload, and may concurrently increase the left ventricular outflow tract (LVOT) gradient. We aimed to assess the impact of subjective ambient temperature on hypertrophic cardiomyopathy (HC) symptoms and determine whether they were associated with LVOT gradient, patient quality of life (QOL), and risk of sudden cardiac death (SCD). We identified consecutive patients with HC presenting to a tertiary referral center. Of the 173 patients in the study, 143 (83%) had HC symptoms, with ambient temperature change worsening symptoms for 72 patients (50%). Symptom exacerbation occurred only with heat for 57 (79%), whereas symptoms were exacerbated with cold only or with cold and heat equally for 15 (21%). Patients affected by any temperature exacerbation more commonly were women (p = 0.009), had a lower QOL (p = 0.04), had a family history of HC (p = 0.007), or underwent myectomy (p = 0.01). A greater proportion of patients with heat-only exacerbation had a family history of HC (p = 0.005) and SCD (p = 0.05). The presence of an LVOT gradient either at rest or with provocation was similar in all groups. In conclusion, although no appreciable difference in LVOT gradients were observed between patient groups, approximately half of the patients with HC reporting symptoms at baseline noted worsening of symptoms with temperature changes, with >75% describing heat-induced symptom exacerbation. Furthermore, affected patients more frequently were women, underwent surgical intervention and device implantation, and had an overall lower QOL.

  6. Formin Homology 2 Domain Containing 3 (FHOD3) Variants Associated with Hypertrophic Cardiomyopathy

    PubMed Central

    Wooten, Eric C.; Hebl, Virginia Bartleson; Wolf, Matthew J.; Greytak, Sarah R.; Orr, Nicole; Draper, Isabelle; Calvino, Jenna E.; Kapur, Navin K.; Maron, Martin S.; Kullo, Iftikhar J.; Ommen, Steve R.; Bos, J. Martijn; Ackerman, Michael J.; Huggins, Gordon S.

    2013-01-01

    Background Incomplete penetrance and variable expression of Hypertrophic Cardiomyopathy (HCM) is well appreciated. Common genetic polymorphisms variants that may affect HCM penetrance and expression have been predicted but are not well established. Methods and Results We performed a case-control genome wide association (GWA) study to identify common HCM-associated genetic polymorphisms and then asked whether such common variants were more represented in HCM or could explain the heterogeneity of HCM phenotypes. We identified an intronic FHOD3 variant (rs516514) associated with HCM (OR = 2.45 (95% CI 1.76–3.41), p=1.25 × 10−7) and validated this finding in an independent cohort. Next, we tested FHOD3-V1151I (rs2303510), a non-synonymous variant in partial linkage disequilibrium (LD) with rs516514, and we detected an even stronger association with HCM (p=1.76 × 10−9). While HCM patients were more likely to carry these FHOD3 alleles subjects homozygous for FHOD3-1151I had similar HCM phenotypes as carriers of the V1151 allele. FHOD3 expression is increased in the setting of HCM and both alleles of FHOD3-V1151I were detected in HCM myectomy tissue. Previously FHOD3 was found to be required for formation of the sarcomere and here we demonstrate that its fly homolog fhos is required for normal adult heart systolic contraction. Conclusions Here we demonstrate the association of a common non-synonymous FHOD3 genetic variant with HCM. This discovery further strengthens the potential role of gene mutations and polymorphisms that alter the amino acid sequence of sarcomere proteins and HCM. PMID:23255317

  7. Reproducibility of Gadolinium Enhancement Patterns and Wall Thickness in Hypertrophic Cardiomyopathy

    PubMed Central

    Rodriguez-Granillo, Gaston A.; Deviggiano, Alejandro; Capunay, Carlos; Zan, Macarena C. De; Carrascosa, Patricia

    2016-01-01

    Background Reproducibility data of the extent and patterns of late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) is limited. Objective To explore the reproducibility of regional wall thickness (WT), LGE extent, and LGE patterns in patients with HCM assessed with cardiac magnetic resonance (CMR). Methods The extent of LGE was assessed by the number of segments with LGE, and by the total LV mass with LGE (% LGE); and the pattern of LGE-CMR was defined for each segment. Results A total of 42 patients (672 segments) with HCM constituted the study population. The mean WT measurements showed a mean difference between observers of -0.62 ± 1.0 mm (6.1%), with limits of agreement of 1.36 mm; -2.60 mm and intraclass correlation coefficient (ICC) of 0.95 (95% CI 0.93-0.96). Maximum WT measurements showed a mean difference between observers of -0.19 ± 0.8 mm (0.9%), with limits of agreement of 1.32 mm; -1.70 mm, and an ICC of 0.95 (95% CI 0.91-0.98). The % LGE showed a mean difference between observers of -1.17 ± 1.2 % (21%), with limits of agreement of 1.16%; -3.49%, and an ICC of 0.94 (95% CI 0.88-0.97). The mean difference between observers regarding the number of segments with LGE was -0.40 ± 0.45 segments (11%), with limits of agreement of 0.50 segments; -1.31 segments, and an ICC of 0.97 (95% CI 0.94-0.99). Conclusions The number of segments with LGE might be more reproducible than the percent of the LV mass with LGE. PMID:27305110

  8. Physical activity in hypertrophic cardiomyopathy: prevalence of inactivity and perceived barriers

    PubMed Central

    Sweeting, Joanna; Ingles, Jodie; Timperio, Anna; Patterson, Jillian; Ball, Kylie; Semsarian, Christopher

    2016-01-01

    Objectives This study aimed to determine the prevalence of physical inactivity and perceived barriers to physical activity among individuals with hypertrophic cardiomyopathy (HCM), and to determine potential demographic, clinical and health-related factors influencing likelihood of meeting physical activity guidelines. Methods This was a cross-sectional study of consecutive patients (n=198) with HCM attending a specialist HCM centre from July 2014 to November 2015. The primary outcome measure was physical activity (minutes per day), as measured by self-report (International Physical Activity Questionnaire (IPAQ)) and objective means (ActiGraph accelerometer). For both, participants were classified as meeting guidelines if they did at least 150 min per week of physical activity. Quality of life (Short Form-36 V.2, SF-36v2), barriers to exercise and clinical–demographic data were also collected. Results In total, 54.8% of participants did not meet physical activity recommendations based on IPAQ, and 12.7% did not meet guidelines based on accelerometer data. The most commonly identified barriers to exercise were ‘pain interferes with my exercise’ (33%) and ‘I have an injury/disability that stops me’ (29%). Independent factors associated with meeting guidelines included older age (OR 0.66, 95% CI 0.51 to 0.85, p=0.002), higher education level (OR 2.31, 95% CI 1.08 to 4.93, p=0.03), better physical quality of life (OR 1.05, 95% CI 1.0 to 1.09, p=0.05) and more reported barriers (OR 0.71, 95% CI 0.56 to 0.91, p=0.01). Conclusions More than half of the patients with HCM did not meet minimum physical activity recommendations. Several barriers to exercise among individuals with HCM exist, and provide the basis for targeted interventions to promote physical activity and improve overall health in patients with HCM. PMID:27547438

  9. Relation of left ventricular thickness to age and gender in hypertrophic cardiomyopathy.

    PubMed

    Maron, Barry J; Casey, Susan A; Hurrell, David G; Aeppli, Dorothee M

    2003-05-15

    Left ventricular (LV) wall thickening is the most consistent clinical marker of hypertrophic cardiomyopathy (HC), and characteristically increases substantially during adolescence. In this study, we used 2-dimensional echocardiography to develop a cross-sectional profile of LV wall thicknesses in adult patients with HC. We studied a regional community-based cohort of 239 consecutively enrolled patients (aged 18 to 91 years). On average, maximum LV wall thickness decreased relative to increasing age (p = 0.007) within 4 age groups: 22.8 +/- 5.1 mm (18 to 39 years) to 22.1 +/- 5.1 mm (40 to 59 years) to 21.1 +/- 3.7 mm (60 to 74 years) to 20.8 +/- 3.6 mm (>or=75 years). The LV thickness index (summation of wall thicknesses in all 4 segments) also decreased with age (p = 0.017): 63.0 +/- 12.2 mm to 59.8 +/- 11.9 mm to 58.3 +/- 10.4 mm to 57.9 +/- 9.8 mm. Decreasing magnitude of LV hypertrophy was independently associated with increasing age, but not with other relevant disease variables, such as symptoms and outflow obstruction. However, when separated by gender, this inverse relation between age and LV wall thickness was statistically significant only for women (p = 0.007). In conclusion, in an unselected HC cohort, cross-sectional analysis showed a modest but statistically significant inverse relation between age and LV hypertrophy that was largely gender-specific for women. This association constitutes another facet of the natural history of this complex and heterogenous disease and may reflect disproportionate occurrence of premature death in young patients with HC with marked hypertrophy or possibly gradual LV remodeling.

  10. Prognostic significance of radionuclide-assessed diastolic function in hypertrophic cardiomyopathy

    SciTech Connect

    Chikamori, T.; Dickie, S.; Poloniecki, J.D.; Myers, M.J.; Lavender, J.P.; McKenna, W.J. )

    1990-02-15

    To evaluate the prognostic significance of diastolic function in hypertrophic cardiomyopathy (HC), technetium-99m gated equilibrium radionuclide angiography, acquired in list mode, was performed in 161 patients. Five diastolic indexes were calculated. During 3.0 +/- 1.9 years, 13 patients had disease-related deaths. With univariate analysis, these patients were younger (29 +/- 20 vs 42 +/- 16 years; p less than 0.05), had a higher incidence of syncope (p less than 0.025), dyspnea (p less than 0.001), reduced peak filling rate (2.9 +/- 0.9 vs 3.4 +/- 1.0 end-diastolic volume/s; p = 0.09) with increased relative filling volume during the rapid filling period (80 +/- 7 vs 75 +/- 12%; p = 0.06) and decreased atrial contribution (17 +/- 7 vs 22 +/- 11%; p = 0.07). Stepwise discriminant analysis revealed that young age at diagnosis, syncope at diagnosis, reduced peak ejection rate, positive family history, reduced peak filling rate, increased relative filling volume by peak filling rate and concentric left ventricular hypertrophy were the most statistically significant (p = 0.0001) predictors of disease-related death (sensitivity 92%, specificity 76%, accuracy 77%, positive predictive value 25%). Discriminant analysis excluding the diastolic indexes, however, showed similar predictability (sensitivity 92%, specificity 76%, accuracy 78%, positive predictive value 26%). To obtain more homogeneous groups for analysis, patients were classified as survivors or electrically unstable, including sudden death, out-of-hospital ventricular fibrillation and nonsustained ventricular tachycardia during 48-hour ambulatory electrocardiography, and heart failure death or cardiac transplant.

  11. An in silico analysis of troponin I mutations in hypertrophic cardiomyopathy of Indian origin.

    PubMed

    Ramachandran, Gayatri; Kumar, Manoj; Selvi Rani, Deepa; Annanthapur, Venkateshwari; Calambur, Narasimhan; Nallari, Pratibha; Kaur, Punit

    2013-01-01

    Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder of the myocardium which is hypertrophied resulting in arrhythmias and heart failure leading to sudden cardiac death (SCD). Several sarcomeric proteins and modifier genes have been implicated in this disease. Troponin I, being a part of the Troponin complex (troponin I, troponin C, troponin T), is an important gene for sarcomeric function. Four mutations (1 novel) were identified in Indian HCM cases, namely, Pro82Ser, Arg98Gln, Arg141Gln and Arg162Gln in Troponin I protein, which are in functionally significant domains. In order to analyse the effect of the mutations on protein stability and protein-protein interactions within the Troponin complex, an in silico study was carried out. The freely available X-ray crystal structure (PDB ID: 1JIE) was used as the template to model the protein followed by loop generation and development of troponin complex for both the troponin I wild type and four mutants (NCBI ID: PRJNA194382). The structural study was carried out to determine the effect of mutation on the structural stability and protein-protein interactions between three subunits in the complex. These mutations, especially the arginine to glutamine substitutions were found to result in local perturbations within the troponin complex by creating/removing inter/intra molecular hydrogen bonds with troponin T and troponin C. This has led to a decrease in the protein stability and loss of important interactions between the three subunits. It could have a significant impact on the disease progression when coupled with allelic heterogeneity which was observed in the cases carrying these mutations. However, this can be further confirmed by functional studies on protein levels in the identified cases. PMID:23967088

  12. Significance of positive or negative thallium-201 scintigraphy in hypertrophic cardiomyopathy

    SciTech Connect

    von Dohlen, T.W.; Prisant, L.M.; Frank, M.J. )

    1989-09-01

    Myocardial ischemia, fibrosis and infarction may occur in patients with hypertrophic cardiomyopathy (HC) in the absence of epicardial coronary artery disease. To determine their prevalence and relation with common characteristics, stress thallium-201 scintigraphy was performed in 28 patients. Eleven (39%) had positive scans despite normal epicardial coronary arteries (7 patients) or a pretest risk of coronary disease less than or equal to 5% (4 patients). There was no relation between thallium defects and age, sex, chest pain or outflow tract gradients at rest. However, the mean left ventricular ejection fraction was significantly lower in those with perfusion abnormalities compared with those without (64 +/- 15 vs 75 +/- 11%, respectively, p less than 0.05). Also, the mean ventricular septal thickness was greater in patients with positive scans (27 +/- 7 vs 21 +/- 6 mm, p less than 0.05), and there was a nonparametric relation between increasing septal thickness and the frequency of positive scans (p less than 0.025). Seven of 11 patients with positive scans had ventricular tachycardia compared with none among those who had negative scans (p less than 0.001), and 5 of these 11 patients had conduction system disease requiring permanent pacemaker insertion compared with 1 of 17 with negative scans (p less than 0.025). It is concluded that thallium perfusion abnormalities are common in patients with HC in the absence of epicardial coronary disease, and are strongly associated with potentially lethal arrhythmias. Thallium scintigraphy appears to identify a subset of patients with HC at increased risk for sudden death, who therefore require closer follow-up.

  13. Physical activity and other health behaviors in adults with hypertrophic cardiomyopathy.

    PubMed

    Reineck, Elizabeth; Rolston, Brice; Bragg-Gresham, Jennifer L; Salberg, Lisa; Baty, Linda; Kumar, Suwen; Wheeler, Matthew T; Ashley, Euan; Saberi, Sara; Day, Sharlene M

    2013-04-01

    The clinical expression of hypertrophic cardiomyopathy (HC) is undoubtedly influenced by modifying genetic and environmental factors. Lifestyle practices such as tobacco and alcohol use, poor nutritional intake, and physical inactivity are strongly associated with adverse cardiovascular outcomes and increased mortality in the general population. Before addressing the direct effect of such modifiable factors on the natural history of HC, it is critical to define their prevalence in this population. A voluntary survey, drawing questions in part from the 2007 to 2008 National Health and Nutrition Examination Survey (NHANES), was posted on the HC Association website and administered to patients with HC at the University of Michigan. Propensity score matching to NHANES participants was used. Dichotomous and continuous health behaviors were analyzed using logistic and linear regression, respectively, and adjusted for body mass index and propensity score quintile. Compared to the matched NHANES participants, the patients with HC reported significantly less alcohol and tobacco use but also less time engaged in physical activity at work and for leisure. Time spent participating in vigorous or moderate activity was a strong predictor of self-reported exercise capacity. The body mass index was greater in the HC cohort than in the NHANES cohort. Exercise restrictions negatively affected emotional well-being in most surveyed subjects. In conclusion, patients with HC are less active than the general United States population. The well-established relation of inactivity, obesity, and cardiovascular mortality might be exaggerated in patients with HC. More data are needed on exercise in those with HC to strike a balance between acute risks and the long-term health benefits of exercise. PMID:23340032

  14. Differentiating hypertrophic cardiomyopathy from athlete's heart: An electrocardiographic and echocardiographic approach.

    PubMed

    Grazioli, Gonzalo; Usín, Domingo; Trucco, Emilce; Sanz, Maria; Montserrat, Silvia; Vidal, Bàrbara; Gutierrez, Josep; Canal, Ramon; Brugada, Josep; Mont, Lluis; Sitges, Marta

    2016-01-01

    Differential diagnosis of hypertrophic cardiomyopathy (HCM) vs athlete's heart is challenging in individuals with mild-moderate left-ventricular hypertrophy. This study aimed to assess ECG and echocardiographic parameters proposed for the differential diagnosis of HCM. The study included 75 men in three groups: control (n=30), "gray zone" athletes with interventricular septum (IVS) measuring 13-15mm (n=25) and HCM patients with IVS of 13-18mm (n=20). The most significant differences were found in relative septal thickness (RST), calculated as the ratio of 2 x IVS to left ventricle end-diastolic diameter (LV-EDD) (0.37, 0.51, 0.71, respectively; p<0.01) and in spatial QRS-T angle as visually estimated (9.8, 33.6, 66.2, respectively; p<0.01). The capacity for differential HCM diagnosis of each of the 5 criteria was assessed using the area under the curve (AUC), as follows: LV-EDD<54 (0.60), family history (0.61), T-wave inversion (TWI) (0.67), spatial QRS-T angle>45 (0.75) and RST>0.54 (0.92). Pearson correlation between spatial QRS-T angle>45 and TWI was 0.76 (p 0.01). The combination of spatial QRS-T angle>45 and RST>0.54 for diagnosis of HCM had an AUC of 0.79. The best diagnostic criteria for HCM was RST>0.54. The spatial QRS-T angle>45 did not add sensitivity if TWI was present. No additional improvement in differential diagnosis was obtained by combining parameters.

  15. Creatine Kinase ATP and Phosphocreatine Energy Supply in a Single Kindred of Patients with Hypertrophic Cardiomyopathy

    PubMed Central

    Abraham, M. Roselle; Bottomley, Paul A.; Dimaano, Veronica Lea; Pinheiro, Aurelio; Steinberg, Angela; Traill, Thomas A.; Abraham, Theodore P.; Weiss, Robert G

    2013-01-01

    A lethal and extensively characterized familial form of hypertrophic cardiomyopathy (HC) is due to a point mutation (Arg403Gln) in the cardiac β-myosin heavy-chain (MHC) gene. Although this is associated with abnormal energy metabolism and progression to heart failure in an animal model, in vivo cardiac energetic shave not been characterized in patients with this mutation. Noninvasive phosphorus saturation transfer magnetic resonance spectroscopy was used to measure the adenosine triphosphate (ATP)supplied by the creatine kinase (CK) reaction and phosphocreatine (PCr), the heart’s primary energy reserve, in 9 of 10 patients from a single kindred with HC caused by Arg403GIn mutation, and 17 age-matched healthy controls. Systolic and diastolic function was assessed by echocardiography in all 10 HC patients. HC patients had impairment of diastolic function as well as mild systolic dysfunction, when assessed using global systolic longitudinal strain. Myocardial [PCr] was significantly decreased by 24% in patients (7.1±2.3μmol/g) compared to controls (9.4±1.2μmol/g; p=0.003). The pseudo-first-order CK rate-constant was 26% lower (0.28±0.15 vs. 0.38±0.07s−1, p=0.035) and the forward CK flux was 44% lower (2.0±1.4 vs3.6±0.9 μmol/g/s, p=0.001) than controls. The contractile abnormalities did not correlate with metabolic indices. In conclusion, myocardial PCr and CK ATP delivery are significantly reduced in patients with HC due to Arg403Gln mutation, akin to prior results from mice with the same mutation. Lack of a relation between energetic and contractile abnormalities suggests the former are due to the sarcomeric mutation and not a late consequence of mechanical dysfunction. PMID:23751935

  16. Right Ventricular and Right Atrial Involvement Can Predict Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy?

    PubMed Central

    Doesch, Christina; Lossnitzer, Dirk; Rudic, Boris; Tueluemen, Erol; Budjan, Johannes; Haubenreisser, Holger; Henzler, Thomas; Schoenberg, Stefan O.; Borggrefe, Martin; Papavassiliu, Theano

    2016-01-01

    Objectives and Background: Atrial fibrillation (AF) is associated with clinical deterioration, stroke and disability in patients with hypertrophic cardiomyopathy (HCM). Therefore, the objective of this study was to evaluated cardiac magnetic resonance (CMR)-derived determinants for the occurrence of AF in patients with HCM. Methods: 98 Patients with HCM and 30 healthy controls underwent CMR and were followed-up for 6±3 years. Results: 19 (19.4%) patients presented with AF at initial diagnosis, 19 (19.4%) developed AF during follow-up and 60 (61.2%) remained in sinus rhythm (SR). Compared to healthy controls, patients with HCM who remained in SR presented with significantly increased left ventricular mass, an elevated left ventricular remodeling index, enlarged left atrial volumes and reduced septal mitral annular plane systolic excursion (MAPSE) compared to healthy controls. Whereas HCM patients who presented with AF at initial diagnosis and those who developed AF during follow-up additionally presented with reduced tricuspid annular plane systolic excursion (TAPSE) and right atrial (RA) dilatation. Receiver-operator curve analysis indicated good predictive performance of TAPSE, RA diameter and septal MAPSE (AUC 0.73, 0.69 and 0.71, respectively) to detect patients at risk of developing AF. Conclusion: Reduced MAPSE measurements and enlarged LA volumes seems to be a common feature in patients with HCM, whereas reduced TAPSE and RA dilatation only seem to be altered in patients with history of AF and those developing AF. Therefore, they could serve as easy determinable markers of AF in patients with HCM. PMID:26812947

  17. Diltiazem Treatment for Preclinical Hypertrophic Cardiomyopathy Mutation Carriers: A Pilot Randomized Trial to Modify Disease Expression

    PubMed Central

    Ho, Carolyn Y.; Lakdawala, Neal K.; Cirino, Allison L.; Lipshultz, Steven E.; Sparks, Elizabeth; Abbasi, Siddique A.; Kwong, Raymond Y.; Antman, Elliott M.; Semsarian, Christopher; González, Arantxa; López, Begoña; Diez, Javier; Orav, E. John; Colan, Steven D.; Seidman, Christine E.

    2014-01-01

    Background Hypertrophic cardiomyopathy (HCM) is caused by sarcomere mutations and characterized by left ventricular hypertrophy (LVH) with increased risk of heart failure and sudden death. HCM typically cannot be diagnosed early in life, although subtle phenotypes are present. Animal studies indicate alterations in intracellular calcium handling before LVH develops. Furthermore, early treatment with diltiazem appeared to attenuate disease emergence. Objectives To assess the safety, feasibility, and effect of diltiazem as disease-modifying therapy for at-risk HCM mutation carriers. Methods In a pilot, double-blind trial, we randomly assigned 38 sarcomere mutation carriers without LVH (mean age 15.8 years) to therapy with diltiazem 360 mg/day (or 5 mg/kg/day) or placebo. Treatment duration ranged from 12 to 42 months (median 25 months). Study procedures included electrocardiography, echocardiography, cardiac magnetic resonance imaging, and serum biomarker measurement. Results Diltiazem was not associated with serious adverse events. Heart rate and blood pressure did not differ significantly between groups. However, mean left ventricular end diastolic diameter improved towards normal in the diltiazem group but decreased further in controls (change in z-scores, +0.6 vs. −0.5; P<0.001). Mean LV thickness-to-dimension ratio was stable in the diltiazem group, but increased in controls (−0.02 vs. +0.15; P=0.04). Among MYBPC3 mutation carriers, LV wall thickness and mass, diastolic filling, and cardiac troponin I levels improved in those taking diltiazem compared with controls. Four participants developed overt HCM, two in each treatment group. Conclusions Preclinical administration of diltiazem is safe and may improve early LV remodeling in HCM. This novel strategy merits further exploration. PMID:25543971

  18. Differentiating hypertrophic cardiomyopathy from athlete's heart: An electrocardiographic and echocardiographic approach.

    PubMed

    Grazioli, Gonzalo; Usín, Domingo; Trucco, Emilce; Sanz, Maria; Montserrat, Silvia; Vidal, Bàrbara; Gutierrez, Josep; Canal, Ramon; Brugada, Josep; Mont, Lluis; Sitges, Marta

    2016-01-01

    Differential diagnosis of hypertrophic cardiomyopathy (HCM) vs athlete's heart is challenging in individuals with mild-moderate left-ventricular hypertrophy. This study aimed to assess ECG and echocardiographic parameters proposed for the differential diagnosis of HCM. The study included 75 men in three groups: control (n=30), "gray zone" athletes with interventricular septum (IVS) measuring 13-15mm (n=25) and HCM patients with IVS of 13-18mm (n=20). The most significant differences were found in relative septal thickness (RST), calculated as the ratio of 2 x IVS to left ventricle end-diastolic diameter (LV-EDD) (0.37, 0.51, 0.71, respectively; p<0.01) and in spatial QRS-T angle as visually estimated (9.8, 33.6, 66.2, respectively; p<0.01). The capacity for differential HCM diagnosis of each of the 5 criteria was assessed using the area under the curve (AUC), as follows: LV-EDD<54 (0.60), family history (0.61), T-wave inversion (TWI) (0.67), spatial QRS-T angle>45 (0.75) and RST>0.54 (0.92). Pearson correlation between spatial QRS-T angle>45 and TWI was 0.76 (p 0.01). The combination of spatial QRS-T angle>45 and RST>0.54 for diagnosis of HCM had an AUC of 0.79. The best diagnostic criteria for HCM was RST>0.54. The spatial QRS-T angle>45 did not add sensitivity if TWI was present. No additional improvement in differential diagnosis was obtained by combining parameters. PMID:27016258

  19. Comparison of Outcomes in Patients With Nonobstructive, Labile-Obstructive, and Chronically Obstructive Hypertrophic Cardiomyopathy.

    PubMed

    Pozios, Iraklis; Corona-Villalobos, Celia; Sorensen, Lars L; Bravo, Paco E; Canepa, Marco; Pisanello, Chiara; Pinheiro, Aurelio; Dimaano, Veronica L; Luo, Hongchang; Dardari, Zeina; Zhou, Xun; Kamel, Ihab; Zimmerman, Stefan L; Bluemke, David A; Abraham, M Roselle; Abraham, Theodore P

    2015-09-15

    Patients with nonobstructive hypertrophic cardiomyopathy (HC) are considered low risk, generally not requiring aggressive intervention. However, nonobstructive and labile-obstructive HC have been traditionally classified together, and it is unknown if these 2 subgroups have distinct risk profiles. We compared cardiovascular outcomes in 293 patients HC (96 nonobstructive, 114 labile-obstructive, and 83 obstructive) referred for exercise echocardiography and magnetic resonance imaging and followed for 3.3 ± 3.6 years. A subgroup (34 nonobstructive, 28 labile-obstructive, 21 obstructive) underwent positron emission tomography. The mean number of sudden cardiac death risk factors was similar among groups (nonobstructive: 1.4 vs labile-obstructive: 1.2 vs obstructive: 1.4 risk factors, p = 0.2). Prevalence of late gadolinium enhancement (LGE) was similar across groups but more non-obstructive patients had late gadolinium enhancement ≥20% of myocardial mass (23 [30%] vs 19 [18%] labile-obstructive and 8 [11%] obstructive, p = 0.01]. Fewer labile-obstructive patients had regional positron emission tomography perfusion abnormalities (12 [46%] vs nonobstructive 30 [81%] and obstructive 17 [85%], p = 0.003]. During follow-up, 60 events were recorded (36 ventricular tachycardia/ventricular fibrillation, including 30 defibrillator discharges, 12 heart failure worsening, and 2 deaths). Nonobstructive patients were at greater risk of VT/VF at follow-up, compared to labile obstructive (hazed ratio 0.18, 95% confidence interval 0.04 to 0.84, p = 0.03) and the risk persisted after adjusting for age, gender, syncope, family history of sudden cardiac death, abnormal blood pressure response, and septum ≥3 cm (p = 0.04). Appropriate defibrillator discharges were more frequent in nonobstructive (8 [18%]) compared to labile-obstructive (0 [0%], p = 0.02) patients. In conclusion, nonobstructive hemodynamics is associated with more pronounced fibrosis and ischemia than labile

  20. Atrial Fibrillation in Hypertrophic Cardiomyopathy: Is the Extent of Septal Hypertrophy Important?

    PubMed Central

    Kim, Eun Kyoung; Lee, Sang-chol; Park, Seung-jung; Kim, June Soo; On, Young Keun

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a cardiac disease associated with a high incidence of atrial fibrillation (AF). Recent studies have suggested that interventricular septum thickness may influence the risk stratification of patients with AF. We evaluated the effects of septal hypertrophy on morbidity and mortality in patients with HCM. Patients were followed for a median of 6.1 years and were divided into two groups according to the extent of septal hypertrophy. A total of 1,360 HCM patients were enrolled: 482 (33%) apical or apicoseptal, 415 (28%) asymmetric septal, 388 (27%) basal septal, 38 (2.6%) concentric, and 37 (2.5%) diffuse and mixed type. Ninety-two all-cause deaths and 21 cardiac deaths occurred. The total event rates were significantly higher for patients with HCM with more extensive septal hypertrophy (group A) compared to those with HCM ± focal septal hypertrophy (group B), regardless of type (p<0.001). Arrhythmias occurred in 502 patients, with a significantly higher incidence in group A than in group B (p<0.001). Among patients with arrhythmias, the incidence of AF was significantly higher in group A than group B (p<0.001). In univariate Cox analysis, a greater extent of septal hypertrophy (p<0.001), E/E´ ratio (p = 0.011), and mitral regurgitation grade (p = 0.003) were significantly associated with developing AF. In multivariate Cox analyses, a greater extent of septal hypertrophy [odds ratio (OR) 5.44 (2.29–12.92), p<0.001] in patients with HCM was significantly associated with developing AF. In conclusion, a greater extent of septal hypertrophy is an independent predictor of progression to AF in patients with HCM. PMID:27258035

  1. Verapamil prevents silent myocardial perfusion abnormalities during exercise in asymptomatic patients with hypertrophic cardiomyopathy

    SciTech Connect

    Udelson, J.E.; Bonow, R.O.; O'Gara, P.T.; Maron, B.J.; Van Lingen, A.; Bacharach, S.L.; Epstein, S.E.

    1989-05-01

    Recent studies indicate that reversible 201Tl perfusion defects, compatible with silent myocardial ischemia, commonly develop during exercise in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy (HCM). To determine whether this represents a dynamic process that may be modified favorably by medical therapy, we studied 29 asymptomatic or minimally symptomatic patients with HCM, aged 12-55 years (mean, 28), with exercise 201Tl emission computed tomography under control conditions and again after 1 week of oral verapamil (mean dosage, 453 mg/day). Treadmill time increased slightly during verapamil (21.0 +/- 3.6 to 21.9 +/- 2.7 minutes, p less than 0.005), but peak heart rate-blood pressure product was unchanged (26.3 +/- 6.0 X 10(3)) compared with 25.0 +/- 6.4 X 10(3). Two midventricular short-axis images per study were divided into five regions each, and each of these 10 regions was then analyzed on a 0-2 scale by three observers blinded with regard to the patients' therapy. Average regional scores of 1.5 or less were considered to represent perfusion defects, and a change in regional score of 0.5 or more was considered to constitute a significant change. During control studies, 15 patients (52%) developed perfusion defects with exercise (average, 3.7 regions per patient). In 14 of these patients, all perfusion defects completely reversed after 3 hours of rest; one patient had fixed defects. After administration of verapamil, exercise perfusion scores improved in 10 of the 14 patients (71%) with reversible defects; there was overall improvement in 34 of 50 (68%) regions with initially reversible perfusion defects.

  2. Autonomous and Non-autonomous Defects Underlie Hypertrophic Cardiomyopathy in BRAF-Mutant hiPSC-Derived Cardiomyocytes.

    PubMed

    Josowitz, Rebecca; Mulero-Navarro, Sonia; Rodriguez, Nelson A; Falce, Christine; Cohen, Ninette; Ullian, Erik M; Weiss, Lauren A; Rauen, Katherine A; Sobie, Eric A; Gelb, Bruce D

    2016-09-13

    Germline mutations in BRAF cause cardio-facio-cutaneous syndrome (CFCS), whereby 40% of patients develop hypertrophic cardiomyopathy (HCM). As the role of the RAS/MAPK pathway in HCM pathogenesis is unclear, we generated a human induced pluripotent stem cell (hiPSC) model for CFCS from three patients with activating BRAF mutations. By cell sorting for SIRPα and CD90, we generated a method to examine hiPSC-derived cell type-specific phenotypes and cellular interactions underpinning HCM. BRAF-mutant SIRPα(+)/CD90(-) cardiomyocytes displayed cellular hypertrophy, pro-hypertrophic gene expression, and intrinsic calcium-handling defects. BRAF-mutant SIRPα(-)/CD90(+) cells, which were fibroblast-like, exhibited a pro-fibrotic phenotype and partially modulated cardiomyocyte hypertrophy through transforming growth factor β (TGFβ) paracrine signaling. Inhibition of TGFβ or RAS/MAPK signaling rescued the hypertrophic phenotype. Thus, cell autonomous and non-autonomous defects underlie HCM due to BRAF mutations. TGFβ inhibition may be a useful therapeutic option for patients with HCM due to RASopathies or other etiologies. PMID:27569062

  3. Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy

    PubMed Central

    Sasagawa, Shota; Nishimura, Yuhei; Okabe, Shiko; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Okamoto, Ryuji; Ito, Masaaki; Tanaka, Toshio

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and is associated with a number of potential outcomes, including impaired diastolic function, heart failure, and sudden cardiac death. Various etiologies have been described for HCM, including pressure overload and mutations in sarcomeric and non-sarcomeric genes. However, the molecular pathogenesis of HCM remains incompletely understood. In this study, we performed comparative transcriptome analysis to identify dysregulated genes common to five mouse HCM models of differing etiology: (i) mutation of myosin heavy chain 6, (ii) mutation of tropomyosin 1, (iii) expressing human phospholamban on a null background, (iv) knockout of frataxin, and (v) transverse aortic constriction. Gene-by-gene comparison identified five genes dysregulated in all five HCM models. Glutathione S-transferase kappa 1 (Gstk1) was significantly downregulated in the five models, whereas myosin heavy chain 7 (Myh7), connective tissue growth factor (Ctgf), periostin (Postn), and reticulon 4 (Rtn4) were significantly upregulated. Gene ontology comparison revealed that 51 cellular processes were significantly enriched in genes dysregulated in each transcriptome dataset. Among them, six processes (oxidative stress, aging, contraction, developmental process, cell differentiation, and cell proliferation) were related to four of the five genes dysregulated in all HCM models. GSTK1 was related to oxidative stress only, whereas the other four genes were related to all six cell processes except MYH7 for oxidative stress. Gene–gene functional interaction network analysis suggested correlative expression of GSTK1, MYH7, and actin alpha 2 (ACTA2). To investigate the implications of Gstk1 downregulation for cardiac function, we knocked out gstk1 in zebrafish using the clustered regularly interspaced short palindromic repeats/Cas9 system. We found that expression of the zebrafish homologs of MYH7, ACTA2, and actin alpha 1

  4. How does morphology impact on diastolic function in hypertrophic cardiomyopathy? A single centre experience

    PubMed Central

    Finocchiaro, Gherardo; Haddad, Francois; Pavlovic, Aleksandra; Magavern, Emma; Sinagra, Gianfranco; Knowles, Joshua W; Myers, Jonathan; Ashley, Euan A

    2014-01-01

    Objectives It is unclear if morphology impacts on diastole in hypertrophic cardiomyopathy (HCM). We sought to determine the relationship between various parameters of diastolic function and morphology in a large HCM cohort. Setting Tertiary referral centre from Stanford, California, USA. Partecipants 383 patients with HCM and normal systolic function between 1999 and 2011. A group of 100 prospectively recruited age-matched and sex-matched healthy participants were used as controls. Primary and secondary outcome measures Echocardiograms were assessed by two blinded board-certified cardiologists. HCM morphology was classified as described in the literature (reverse, sigmoid, symmetric, apical and undefined). Results Reverse curvature morphology was most commonly observed (218 (57%). Lateral mitral annular E′<12 cm/s was present in 86% of reverse, 88% of sigmoid, 79% of symmetric, 86% of apical and 81% of undefined morphology, p=0.65. E/E′ was similarly elevated (E/E′: 12.3±7.9 in reverse curvature, 12.1±6.1 in sigmoid, 12.7±9.5 in symmetric, 9.4±4.0 in apical, 12.7±7.9 in undefined morphology, p=0.71) and indexed left atrial volume (LAVi)>40 mL/m2 was present in 47% in reverse curvature, 33% in sigmoid, 32% in symmetric, 37% in apical and 32% in undefined, p=0.09. Each morphology showed altered parameters of diastolic function when compared with the control population. Left ventricular (LV) obstruction was independently associated with all three diastolic parameters considered, in particular with LAVi>40 mL/m2 (OR 2.04 (95% CI 1.23 to 3.39), p=0.005), E/E′>15 (OR 4.66 (95% CI 2.51 to 8.64), p<0.001) and E′<8 (OR 2.55 (95% CI 1.42 to 4.53), p=0.001). Other correlates of diastolic dysfunction were age, LV wall thickness and moderate-to-severe mitral regurgitation. Conclusions In HCM, diastolic dysfunction is present to similar degrees independently from the morphological pattern. The main correlates of diastolic dysfunction are LV obstruction, age

  5. Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy.

    PubMed

    Sasagawa, Shota; Nishimura, Yuhei; Okabe, Shiko; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Okamoto, Ryuji; Ito, Masaaki; Tanaka, Toshio

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and is associated with a number of potential outcomes, including impaired diastolic function, heart failure, and sudden cardiac death. Various etiologies have been described for HCM, including pressure overload and mutations in sarcomeric and non-sarcomeric genes. However, the molecular pathogenesis of HCM remains incompletely understood. In this study, we performed comparative transcriptome analysis to identify dysregulated genes common to five mouse HCM models of differing etiology: (i) mutation of myosin heavy chain 6, (ii) mutation of tropomyosin 1, (iii) expressing human phospholamban on a null background, (iv) knockout of frataxin, and (v) transverse aortic constriction. Gene-by-gene comparison identified five genes dysregulated in all five HCM models. Glutathione S-transferase kappa 1 (Gstk1) was significantly downregulated in the five models, whereas myosin heavy chain 7 (Myh7), connective tissue growth factor (Ctgf), periostin (Postn), and reticulon 4 (Rtn4) were significantly upregulated. Gene ontology comparison revealed that 51 cellular processes were significantly enriched in genes dysregulated in each transcriptome dataset. Among them, six processes (oxidative stress, aging, contraction, developmental process, cell differentiation, and cell proliferation) were related to four of the five genes dysregulated in all HCM models. GSTK1 was related to oxidative stress only, whereas the other four genes were related to all six cell processes except MYH7 for oxidative stress. Gene-gene functional interaction network analysis suggested correlative expression of GSTK1, MYH7, and actin alpha 2 (ACTA2). To investigate the implications of Gstk1 downregulation for cardiac function, we knocked out gstk1 in zebrafish using the clustered regularly interspaced short palindromic repeats/Cas9 system. We found that expression of the zebrafish homologs of MYH7, ACTA2, and actin alpha 1 were

  6. Transcoronary ablation of septal hypertrophy (TASH): a new treatment option for hypertrophic obstructive cardiomyopathy.

    PubMed

    Kuhn, H; Gietzen, F H; Leuner, C; Schäfers, M; Schober, O; Strunk-Müller, C; Obergassel, L; Freick, M; Gockel, B; Lieder, F; Raute-Kreinsen, U

    2000-01-01

    In 1991, our group started to develop a catheter interventional therapy for hypertrophic obstructive cardiomyopathy (HOCM). The new concept was proposed in 1994. It is based on the conventional PTCA technique with the aim of inducing an artificial myocardial infarction by instillation of 96% ethanol into the most proximally situated septal branch of the left anterior descending coronary artery. This leads to a subaortic contraction disorder with subsequent decrease of the intraventricular pressure gradient, shrinkage of the hypertrophied septal bulge and widening of the outflow tract ("therapeutic remodeling"). The subaortic defect is small and well demarcated as assessed by left ventricular angiography, transesophageal echocardiography and 18 F-glucose positron emission tomography. The term transcoronary ablation of septum hypertrophy (TASH) was suggested. Our patient cohort that now comprises 215 therapeutic procedures in 187 patients underwent a large variety of prospective studies (maximum follow-up 4.5 years) including invasive controls at regular intervals, investigation of hemodynamics at rest and at exercise, transesophageal and transthoracic echocardiography, Doppler echocardiography during bicycle exercise, electrophysiologic testing, Holter monitoring and measurement of myocardial metabolism and perfusion, assessment of microembolic events by transcranial Doppler sonography and histological examinations. This article gives an overview and reports our increasing experience in applying TASH. The following post-TASH findings were obtained: significant hemodynamic and clinical improvement at rest and at exercise, decrease of septum thickness, increase of outflow tract area and decrease of induced ventricular tachycardia. There were well-demarcated, histologically atypical subaortic myocardial defects, no microembolic events, abnormal early peak of infarct related enzymes, and no change of baroreflex sensitivity. Pre-/post-TASH evaluations of the patients

  7. Preserved cross-bridge kinetics in human hypertrophic cardiomyopathy patients with MYBPC3 mutations.

    PubMed

    van Dijk, Sabine J; Boontje, Nicky M; Heymans, Martijn W; Ten Cate, Folkert J; Michels, Michelle; Dos Remedios, Cris; Dooijes, Dennis; van Slegtenhorst, Marjon A; van der Velden, Jolanda; Stienen, Ger J M

    2014-08-01

    Mutations in the MYBPC3 gene, encoding cardiac myosin binding protein C (cMyBP-C) are frequent causes of hypertrophic cardiomyopathy (HCM). Previously, we have presented evidence for reduced cMyBP-C expression (haploinsufficiency), in patients with a truncation mutation in MYBPC3. In mice, lacking cMyBP-C cross-bridge kinetics was accelerated. In this study, we investigated whether cross-bridge kinetics was altered in myectomy samples from HCM patients harboring heterozygous MYBPC3 mutations (MYBPC3mut). Isometric force and the rate of force redevelopment (k tr) at different activating Ca(2+) concentrations were measured in mechanically isolated Triton-permeabilized cardiomyocytes from MYBPC3mut (n = 18) and donor (n = 7) tissue. Furthermore, the stretch activation response of cardiomyocytes was measured in tissue from eight MYBPC3mut patients and five donors to assess the rate of initial force relaxation (k 1) and the rate and magnitude of the transient increase in force (k 2 and P 3, respectively) after a rapid stretch. Maximal force development of the cardiomyocytes was reduced in MYBPC3mut (24.5 ± 2.3 kN/m(2)) compared to donor (34.9 ± 1.6 kN/m(2)). The rates of force redevelopment in MYBPC3mut and donor over a range of Ca(2+) concentrations were similar (k tr at maximal activation: 0.63 ± 0.03 and 0.75 ± 0.09 s(-1), respectively). Moreover, the stretch activation parameters did not differ significantly between MYBPC3mut and donor (k 1: 8.5±0.5 and 8.8 ± 0.4 s(-1); k 2: 0.77 ± 0.06 and 0.74 ± 0.09 s(-1); P 3: 0.08 ± 0.01 and 0.09 ± 0.01, respectively). Incubation with protein kinase A accelerated k 1 in MYBPC3mut and donor to a similar extent. Our experiments indicate that, at the cMyBP-C expression levels in this patient group (63 ± 6 % relative to donors), cross-bridge kinetics are preserved and that the depressed maximal force development is not explained by perturbation of cross-bridge kinetics.

  8. Targeted next-generation sequencing helps to decipher the genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy.

    PubMed

    Cecconi, Massimiliano; Parodi, Maria I; Formisano, Francesco; Spirito, Paolo; Autore, Camillo; Musumeci, Maria B; Favale, Stefano; Forleo, Cinzia; Rapezzi, Claudio; Biagini, Elena; Davì, Sabrina; Canepa, Elisabetta; Pennese, Loredana; Castagnetta, Mauro; Degiorgio, Dario; Coviello, Domenico A

    2016-10-01

    Hypertrophic cardiomyopathy (HCM) is mainly associated with myosin, heavy chain 7 (MYH7) and myosin binding protein C, cardiac (MYBPC3) mutations. In order to better explain the clinical and genetic heterogeneity in HCM patients, in this study, we implemented a target-next generation sequencing (NGS) assay. An Ion AmpliSeq™ Custom Panel for the enrichment of 19 genes, of which 9 of these did not encode thick/intermediate and thin myofilament (TTm) proteins and, among them, 3 responsible of HCM phenocopy, was created. Ninety-two DNA samples were analyzed by the Ion Personal Genome Machine: 73 DNA samples (training set), previously genotyped in some of the genes by Sanger sequencing, were used to optimize the NGS strategy, whereas 19 DNA samples (discovery set) allowed the evaluation of NGS performance. In the training set, we identified 72 out of 73 expected mutations and 15 additional mutations: the molecular diagnosis was achieved in one patient with a previously wild-type status and the pre-excitation syndrome was explained in another. In the discovery set, we identified 20 mutations, 5 of which were in genes encoding non-TTm proteins, increasing the diagnostic yield by approximately 20%: a single mutation in genes encoding non-TTm proteins was identified in 2 out of 3 borderline HCM patients, whereas co-occuring mutations in genes encoding TTm and galactosidase alpha (GLA) altered proteins were characterized in a male with HCM and multiorgan dysfunction. Our combined targeted NGS-Sanger sequencing-based strategy allowed the molecular diagnosis of HCM with greater efficiency than using the conventional (Sanger) sequencing alone. Mutant alleles encoding non-TTm proteins may aid in the complete understanding of the genetic and phenotypic heterogeneity of HCM: co-occuring mutations of genes encoding TTm and non-TTm proteins could explain the wide variability of the HCM phenotype, whereas mutations in genes encoding only the non

  9. Heart rate turbulence and clinical prognosis in hypertrophic cardiomyopathy and myocardial infarction.

    PubMed

    Kawasaki, Tatsuya; Azuma, Akihiro; Asada, Satoshi; Hadase, Mitsuyoshi; Kamitani, Tadaaki; Kawasaki, Shingo; Kuribayashi, Toshiro; Sugihara, Hiroki

    2003-07-01

    Short-term fluctuations in sinus cycle length after a single ventricular premature complex (VPC) have attracted considerable interest and has been termed heart rate turbulence (HRT). The onset and slope of HRT have each been reported to be independent and powerful predictors of clinical prognosis in patients with myocardial infarction (MI), but there are no data available for patients with hypertrophic cardiomyopathy (HCM). Thus the present study analyzed the 2 HRT variables to determine their prognostic value in HCM patients. Holter monitoring data were obtained from 104 HCM patients, 44 MI patients and 56 normal controls, from which singular VPCs followed by >or=20 normal sinus beats were isolated and the HRT onset and slope were automatically calculated. HRT onset and slope were abnormal in MI patients, but not in HCM patients, as compared with normal control subjects (onset -1.1+/-2.9, -2.1+/-3.4, -1.4+/-5.1%; slope 10.6 +/-8.6, 18.0+/-13.9, 16.6+/-9.7 ms/beat, respectively). During the follow-up period of 27+/-10 months, 7 HCM patients and 10 MI patients either died from cardiac death or were hospitalized for congestive heart failure. In MI patients, HRT onset was higher and the HRT slope was lower in patients with cardiac events than in patients without (onset 1.1+/-2.7 vs -1.7+/-2.7%, p=0.011; slope 5.7+/-4.3 vs 12.0+/-9.0 ms/beat, p=0.028). In HCM patients, however, the HRT onset and slope were similar between patients with and without cardiac events (onset -2.0+/-2.0 vs -2.1 +/-3.5%, p=0.98; slope 18.1+/-10.9 vs 18.0+/-14.0 ms/beat, p=0.68). In conclusion, unlike MI patients, the HRT variables in selected HCM patients were not abnormal and failed to predict the clinical prognosis.

  10. Targeted next-generation sequencing helps to decipher the genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy

    PubMed Central

    Cecconi, Massimiliano; Parodi, Maria I.; Formisano, Francesco; Spirito, Paolo; Autore, Camillo; Musumeci, Maria B.; Favale, Stefano; Forleo, Cinzia; Rapezzi, Claudio; Biagini, Elena; Davì, Sabrina; Canepa, Elisabetta; Pennese, Loredana; Castagnetta, Mauro; Degiorgio, Dario; Coviello, Domenico A.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is mainly associated with myosin, heavy chain 7 (MYH7) and myosin binding protein C, cardiac (MYBPC3) mutations. In order to better explain the clinical and genetic heterogeneity in HCM patients, in this study, we implemented a target-next generation sequencing (NGS) assay. An Ion AmpliSeq™ Custom Panel for the enrichment of 19 genes, of which 9 of these did not encode thick/intermediate and thin myofilament (TTm) proteins and, among them, 3 responsible of HCM phenocopy, was created. Ninety-two DNA samples were analyzed by the Ion Personal Genome Machine: 73 DNA samples (training set), previously genotyped in some of the genes by Sanger sequencing, were used to optimize the NGS strategy, whereas 19 DNA samples (discovery set) allowed the evaluation of NGS performance. In the training set, we identified 72 out of 73 expected mutations and 15 additional mutations: the molecular diagnosis was achieved in one patient with a previously wild-type status and the pre-excitation syndrome was explained in another. In the discovery set, we identified 20 mutations, 5 of which were in genes encoding non-TTm proteins, increasing the diagnostic yield by approximately 20%: a single mutation in genes encoding non-TTm proteins was identified in 2 out of 3 borderline HCM patients, whereas co-occuring mutations in genes encoding TTm and galactosidase alpha (GLA) altered proteins were characterized in a male with HCM and multiorgan dysfunction. Our combined targeted NGS-Sanger sequencing-based strategy allowed the molecular diagnosis of HCM with greater efficiency than using the conventional (Sanger) sequencing alone. Mutant alleles encoding non-TTm proteins may aid in the complete understanding of the genetic and phenotypic heterogeneity of HCM: co-occuring mutations of genes encoding TTm and non-TTm proteins could explain the wide variability of the HCM phenotype, whereas mutations in genes encoding only the non-TTm proteins are identifiable in

  11. Familial Hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3.

    PubMed Central

    MacRae, C A; Ghaisas, N; Kass, S; Donnelly, S; Basson, C T; Watkins, H C; Anan, R; Thierfelder, L H; McGarry, K; Rowland, E

    1995-01-01

    We have mapped a disease locus for Wolff-Parkinson-White syndrome (WPW) and familial hypertrophic cardiomyopathy (FHC) segregating in a large kindred to chromosome 7 band q3. Although WPW syndrome and FHC have been observed in members of the same family in prior studies, the relationship between these two diseases has remained enigmatic. A large family with 25 surviving individuals who are affected by one or both of these conditions was studied. The disease locus is closely linked to loci D7S688, D7S505, and D7S483 (maximum two point LOD score at D7S505 was 7.80 at theta = 0). While four different FHC loci have been described this is the first locus that can be mutated to cause both WPW and/or FHC. PMID:7657794

  12. Nemaline myopathy and non-fatal hypertrophic cardiomyopathy caused by a novel ACTA1 E239K mutation.

    PubMed

    Kim, Sun-Young; Park, Young-Eun; Kim, Hyang-Sook; Lee, Chang-Hoon; Yang, Dong Heon; Kim, Dae-Seong

    2011-08-15

    A twenty-year old male presented with diffuse limb muscle weakness and exertional dyspnea since childhood. The diagnosis of nemaline myopathy was given based on the muscle pathology findings that revealed nemaline rods on light and electron microscopy and discovery of a novel mutation, E239K, in ACTA1. Incidentally, the patient had hypertrophic cardiomyopathy (HCM) as shown by echocardiography. In nemaline myopathy, a few cases of HCM have been reported, albeit rarely and always fatal, but only one patient had ACTA1 mutation. This present report describes an infantile onset of nemaline myopathy with a milder clinical course and non-fatal HCM as compared with previous cases, showing clinical diversity in skeletal and cardiac manifestations of conditions associated with ACTA1 mutations. PMID:21570694

  13. Reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy

    PubMed Central

    2012-01-01

    Background Myocardial disarray is an important histological feature of hypertrophic cardiomyopathy (HCM) which has been studied post-mortem, but its in-vivo prevalence and extent is unknown. Cardiac Diffusion Tensor Imaging (cDTI) provides information on mean intravoxel myocyte orientation and potentially myocardial disarray. Recent technical advances have improved in-vivo cDTI, and the aim of this study was to assess the interstudy reproducibility of quantitative in-vivo cDTI in patients with HCM. Methods and results A stimulated-echo single-shot-EPI sequence with zonal excitation and parallel imaging was implemented. Ten patients with HCM were each scanned on 2 different days. For each scan 3 short axis mid-ventricular slices were acquired with cDTI at end systole. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) maps were created using a cDTI post-processing platform developed in-house. The mean ± SD global FA was 0.613 ± 0.044, MD was 0.750 ± 0.154 × 10-3 mm2/s and HA was epicardium −34.3 ± 7.6°, mesocardium 3.5 ± 6.9° and endocardium 38.9 ± 8.1°. Comparison of initial and repeat studies showed global interstudy reproducibility for FA (SD = ± 0.045, Coefficient of Variation (CoV) = 7.2%), MD (SD = ± 0.135 × 10-3 mm2/s, CoV = 18.6%) and HA (epicardium SD = ± 4.8°; mesocardium SD = ± 3.4°; endocardium SD = ± 2.9°). Reproducibility of FA was superior to MD (p = 0.003). Global MD was significantly higher in the septum than the reference lateral wall (0.784 ± 0.188 vs 0.750 ± 0.154 x10-3 mm2/s, p < 0.001). Septal HA was significantly lower than the reference lateral wall in all 3 transmural layers (from −8.3° to −10.4°, all p < 0.001). Conclusions To the best of our knowledge, this is the first study to assess the interstudy reproducibility of DTI in the human HCM heart in-vivo and the largest cDTI study in HCM to date. Our results show good reproducibility of FA

  14. Loss of the AE3 Anion Exchanger in a Hypertrophic Cardiomyopathy Model Causes Rapid Decompensation and Heart Failure

    PubMed Central

    Al Moamen, Nabeel J.; Prasad, Vikram; Bodi, Ilona; Miller, Marian L.; Neiman, Michelle L.; Lasko, Valerie M.; Alper, Seth L.; Wieczorek, David F.; Lorenz, John N.; Shull, Gary E.

    2010-01-01

    The AE3 Cl−/HCO3− exchanger is abundantly expressed in the sarcolemma of cardiomyocytes, where it mediates Cl−-uptake and HCO3−-extrusion. Inhibition of AE3-mediated Cl−/HCO3− exchange has been suggested to protect against cardiac hypertrophy; however, other studies indicate that AE3 might be necessary for optimal cardiac function. To test these hypotheses we crossed AE3-null mice, which appear phenotypically normal, with a hypertrophic cardiomyopathy mouse model carrying a Glu180Gly mutation in α–tropomyosin (TM180). Loss of AE3 had no effect on hypertrophy; however, survival of TM180/AE3 double mutants was sharply reduced compared with TM180 single mutants. Analysis of cardiac performance revealed impaired cardiac function in TM180 and TM180/AE3 mutants. TM180/AE3 double mutants were more severely affected and exhibited little response to β-adrenergic stimulation, a likely consequence of their more rapid progression to heart failure. Increased expression of calmodulin-dependent kinase II and protein phosphatase 1 and differences in methylation and localization of protein phosphatase 2A were observed, but were similar in single and double mutants. Phosphorylation of phospholamban on Ser16 was sharply increased in both single and double mutants relative to wild-type hearts under basal conditions, leading to reduced reserve capacity for β-adrenergic stimulation of phospholamban phosphorylation. Imaging analysis of isolated myocytes revealed reductions in amplitude and decay of Ca2+ transients in both mutants, with greater reductions in TM180/AE3 mutants, consistent with the greater severity of their heart failure phenotype. Thus, in the TM180 cardiomyopathy model, loss of AE3 had no apparent anti-hypertrophic effect and led to more rapid decompensation and heart failure. PMID:21056571

  15. Non-invasive assessment of diastolic function in hypertrophic cardiomyopathy on and off beta adrenergic blocking drugs.

    PubMed Central

    Alvares, R F; Goodwin, J F

    1982-01-01

    Beta adrenergic blocking drugs in hypertrophic cardiomyopathy provide symptomatic relief but their effect on long-term prognosis is uncertain. Thirty patients were studied non-invasively by simultaneous recordings of echocardiogram, apex-cardiogram, phonocardiogram, and electrocardiogram in order to assess diastolic abnormalities on and off oral beta adrenergic blocking drugs. While on treatment these patients had a mean dose of propranolol 200 mg/day. The treatment was stopped for one week and then non-invasive assessment was repeated. The following diastolic time intervals were studied: isovolumic relaxation period (A2-mitral valve opening); rapid relaxation period (A2-O point of the apexcardiogram), and the period from mitral valve opening to the O point of the apexcardiogram (Mo-O) when most of the filling of the left ventricle occurs. The prolongation of the rapid relaxation period reflects a reduced rate of fall of the left ventricular pressure when the pressure differential does not change between A2 and the O point of the apexcardiogram, and in this study this period was prolonged in 19, shortened in eight, and remained the same in three patients after beta blockade. The Mo-O point was prolonged in 22, shortened in seven, and was unchanged in one patient after beta adrenergic blocking drugs. All these results were independent of heart rate. In conclusion the response of diastolic time intervals to beta blocking drugs in hypertrophic cardiomyopathy was variable but there was a significant number of patients in whom the time available for filling of the left ventricle was prolonged, suggesting better filling possibly because of improved distensibility of the left ventricle after beta adrenergic blocking drugs. PMID:6125160

  16. Microarray analysis of active cardiac remodeling genes in a familial hypertrophic cardiomyopathy mouse model rescued by a phospholamban knockout

    PubMed Central

    Rajan, Sudarsan; Pena, James R.; Jegga, Anil G.; Aronow, Bruce J.; Wolska, Beata M.

    2013-01-01

    Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed two mouse models that affect cardiac performance. One mouse model encodes an FHC-associated mutation in α-tropomyosin: Glu → Gly at amino acid 180, designated as Tm180. These mice display a phenotype that is characteristic of FHC, including severe cardiac hypertrophy with fibrosis and impaired physiological performance. The other model was a gene knockout of phospholamban (PLN KO), a regulator of calcium uptake in the sarcoplasmic reticulum of cardiomyocytes; these hearts exhibit hypercontractility with no pathological abnormalities. Previous work in our laboratories shows that when mice were genetically crossed between the PLN KO and Tm180, the progeny (PLN KO/Tm180) display a rescued hypertrophic phenotype with improved morphology and cardiac function. To understand the changes in gene expression that occur in these models undergoing cardiac remodeling (Tm180, PLN KO, PLN KO/Tm180, and nontransgenic control mice), we conducted microarray analyses of left ventricular tissue at 4 and 12 mo of age. Expression profiling reveals that 1,187 genes changed expression in direct response to the three genetic models. With these 1,187 genes, 11 clusters emerged showing normalization of transcript expression in the PLN KO/Tm180 hearts. In addition, 62 transcripts are highly involved in suppression of the hypertrophic phenotype. Confirmation of the microarray analysis was conducted by quantitative RT-PCR. These results provide insight into genes that alter expression during cardiac remodeling and are active during modulation of the cardiomyopathic phenotype. PMID:23800848

  17. Coexistence of Digenic Mutations in Both Thin (TPM1) and Thick (MYH7) Filaments of Sarcomeric Genes Leads to Severe Hypertrophic Cardiomyopathy in a South Indian FHCM.

    PubMed

    Selvi Rani, Deepa; Nallari, Pratibha; Dhandapany, Perundurai S; Rani, Jhansi; Meraj, Khunza; Ganesan, Mala; Narasimhan, Calambur; Thangaraj, Kumarasamy

    2015-05-01

    Mutations in sarcomeric genes are the leading cause for cardiomyopathies. However, not many genetic studies have been carried out on Indian cardiomyopathy patients. We performed sequence analyses of a thin filament sarcomeric gene, α-tropomyosin (TPM1), in 101 hypertrophic cardiomyopathy (HCM) patients and 147 dilated cardiomyopathy (DCM) patients against 207 ethnically matched healthy controls, revealing 13 single nucleotide polymorphisms (SNPs). Of these, one mutant, S215L, was identified in two unrelated HCM cases-patient #1, aged 44, and patient #2, aged 65-and was cosegregating with disease in these families as an autosomal dominant trait. In contrast, S215L was completely absent in 147 DCM and 207 controls. Patient #1 showed a more severe disease phenotype, with poor prognosis and a family history of sudden cardiac death, than patient #2. Therefore, these two patients and the family members positive for S215L were further screened for variations in MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, and ACTC. Interestingly, two novel thick filaments, D896N (homozygous) and I524K (heterozygous) mutations, in the MYH7 gene were identified exclusively in patient #1 and his family members. Thus, we strongly suggest that the coexistence of these digenic mutations is rare, but leads to severe hypertrophy in a South Indian familial hypertrophic cardiomyopathy (FHCM). PMID:25607779

  18. A 13-year-old girl with proximal weakness and hypertrophic cardiomyopathy with Danon disease.

    PubMed

    Kim, Hunmin; Cho, Anna; Lim, Byung Chan; Kim, Min Jung; Kim, Ki Joong; Nishino, Ichizo; Hwang, Yong Seung; Chae, Jong-Hee

    2010-06-01

    Danon disease is caused by deficiency of lysosome-associated membrane protein-2 (LAMP-2). It is characterized clinically by cardiomyopathy, myopathy, and mental retardation in boys. Herein we report a 13-year-old female patient with Danon disease who presented with early-onset skeletal myopathy and cardiomyopathy. She had a de novo novel mutation in the LAMP2 gene, and her muscles showed many autophagic vacuoles with sarcolemmal features and complete absence of LAMP-2 expression. To the best of our knowledge, this girl is one of the earliest-onset manifesting carriers of Danon disease with typical muscle pathology.

  19. Post systolic shortening in nonobstructive hypertrophic cardiomyopathy with delayed emptying of the apex: a Doppler flow, tissue Doppler and strain rate imaging case study.

    PubMed

    Støylen, Asbjørn; Sletvold, Olav; Skjaerpe, Terje

    2003-02-01

    We report a case of a 92-year-old woman with syncope and exertional dyspnea, who on echocardiographic examination proved to have hypertrophic cardiomyopathy. Doppler flow revealed delayed emptying of the apex, extending into the early filling phase. Tissue Doppler and strain rate imaging illustrated postsystolic shortening corresponding to the apical ejection, demonstrating that the apical flow was due to wall thickening resulting in active ejection. The imaging methods and mechanics of post-systolic shortening are discussed.

  20. Enhanced Transmural Fiber Rotation and Connexin 43 Heterogeneity Are Associated With an Increased Upper Limit of Vulnerability in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy

    PubMed Central

    Ripplinger, Crystal M.; Li, Wenwen; Hadley, Jennifer; Chen, Junjie; Rothenberg, Florence; Lombardi, Raffaella; Wickline, Samuel A.; Marian, Ali J.; Efimov, Igor R.

    2008-01-01

    Human hypertrophic cardiomyopathy, characterized by cardiac hypertrophy and myocyte disarray, is the most common cause of sudden cardiac death in the young. Hypertrophic cardiomyopathy is often caused by mutations in sarcomeric genes. We sought to determine arrhythmia propensity and underlying mechanisms contributing to arrhythmia in a transgenic (TG) rabbit model (β-myosin heavy chain–Q403) of human hypertrophic cardiomyopathy. Langendorff-perfused hearts from TG (n = 6) and wild-type (WT) rabbits (n = 6) were optically mapped. The upper and lower limits of vulnerability, action potential duration (APD) restitution, and conduction velocity were measured. The transmural fiber angle shift was determined using diffusion tensor MRI. The transmural distribution of connexin 43 was quantified with immunohistochemistry. The upper limit of vulnerability was significantly increased in TG versus WT hearts (13.3 ± 2.1 versus 7.4 ± 2.3 V/cm; P = 3.2e−5), whereas the lower limits of vulnerability were similar. APD restitution, conduction velocities, and anisotropy were also similar. Left ventricular transmural fiber rotation was significantly higher in TG versus WT hearts (95.6 ± 10.9° versus 79.2 ± 7.8°; P = 0.039). The connexin 43 density was significantly increased in the mid-myocardium of TG hearts compared with WT (5.46 ± 2.44% versus 2.68 ± 0.77%; P = 0.024), and similar densities were observed in the endo- and epicardium. Because a nearly 2-fold increase in upper limit of vulnerability was observed in the TG hearts without significant changes in APD restitution, conduction velocity, or the anisotropy ratio, we conclude that structural remodeling may underlie the elevated upper limit of vulnerability in human hypertrophic cardiomyopathy. PMID:17885214

  1. Human Engineered Cardiac Tissues Created Using Induced Pluripotent Stem Cells Reveal Functional Characteristics of BRAF-Mediated Hypertrophic Cardiomyopathy.

    PubMed

    Cashman, Timothy J; Josowitz, Rebecca; Johnson, Bryce V; Gelb, Bruce D; Costa, Kevin D

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death that often goes undetected in the general population. HCM is also prevalent in patients with cardio-facio-cutaneous syndrome (CFCS), which is a genetic disorder characterized by aberrant signaling in the RAS/MAPK signaling cascade. Understanding the mechanisms of HCM development in such RASopathies may lead to novel therapeutic strategies, but relevant experimental models of the human condition are lacking. Therefore, the objective of this study was to develop the first 3D human engineered cardiac tissue (hECT) model of HCM. The hECTs were created using human cardiomyocytes obtained by directed differentiation of induced pluripotent stem cells derived from a patient with CFCS due to an activating BRAF mutation. The mutant myocytes were directly conjugated at a 3:1 ratio with a stromal cell population to create a tissue of defined composition. Compared to healthy patient control hECTs, BRAF-hECTs displayed a hypertrophic phenotype by culture day 6, with significantly increased tissue size, twitch force, and atrial natriuretic peptide (ANP) gene expression. Twitch characteristics reflected increased contraction and relaxation rates and shorter twitch duration in BRAF-hECTs, which also had a significantly higher maximum capture rate and lower excitation threshold during electrical pacing, consistent with a more arrhythmogenic substrate. By culture day 11, twitch force was no longer different between BRAF and wild-type hECTs, revealing a temporal aspect of disease modeling with tissue engineering. Principal component analysis identified diastolic force as a key factor that changed from day 6 to day 11, supported by a higher passive stiffness in day 11 BRAF-hECTs. In summary, human engineered cardiac tissues created from BRAF mutant cells recapitulated, for the first time, key aspects of the HCM phenotype, offering a new in vitro model for studying intrinsic mechanisms and screening new

  2. Ablation of plasma membrane Ca(2+)-ATPase isoform 4 prevents development of hypertrophy in a model of hypertrophic cardiomyopathy.

    PubMed

    Prasad, Vikram; Lorenz, John N; Lasko, Valerie M; Nieman, Michelle L; Jiang, Min; Gao, Xu; Rubinstein, Jack; Wieczorek, David F; Shull, Gary E

    2014-12-01

    The mechanisms linking the expression of sarcomeric mutant proteins to the development of pathological hypertrophy in hypertrophic cardiomyopathy (HCM) remain poorly understood. We investigated the role of the plasma membrane Ca(2+)-ATPase PMCA4 in the HCM phenotype using a transgenic model that expresses mutant (Glu180Gly) α-tropomyosin (Tm180) in heart. Immunoblot analysis revealed that cardiac PMCA4 expression was upregulated early in Tm180 disease pathogenesis. This was accompanied by an increase in levels of the L-type Ca(2+)-channel, which is implicated in pathological hypertrophy. When Tm180 mice were crossed with a PMCA4-null line, loss of PMCA4 caused the abrogation of hypertrophy in Tm180/PMCA4-null double mutant mice. RT-PCR analysis of Tm180/PMCA4-null hearts revealed blunting of the fetal program and reversion of pro-fibrotic Col1a1 and Col3a1 gene expression to wild-type levels. This was accompanied by evidence of reduced L-type Ca(2+)-channel expression, and diminished calcineurin activity. Expression of the metabolic substrate transporters glucose transporter 4 and carnitine palmitoyltransferase 1b was preserved and Tm180-related changes in mRNA levels of various contractile stress-related proteins including the cardiac ankyrin protein CARP and the N2B isoform of titin were reversed in Tm180/PMCA4-null hearts. cGMP levels were increased and phosphorylation of vasodilator-stimulated phosphoprotein was elevated in Tm180/PMCA4-null hearts. These changes were associated with a sharp reduction in left ventricular end-diastolic pressure in Tm180/PMCA4-null hearts, which occurred despite persistence of Tm180-related impairment of relaxation dynamics. These results reveal a novel and specific role for PMCA4 in the Tm180 hypertrophic phenotype, with the "protective" effects of PMCA4 deficiency encompassing multiple determinants of HCM-related hypertrophy. PMID:25280781

  3. Human Engineered Cardiac Tissues Created Using Induced Pluripotent Stem Cells Reveal Functional Characteristics of BRAF-Mediated Hypertrophic Cardiomyopathy

    PubMed Central

    Johnson, Bryce V.; Gelb, Bruce D.; Costa, Kevin D.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death that often goes undetected in the general population. HCM is also prevalent in patients with cardio-facio-cutaneous syndrome (CFCS), which is a genetic disorder characterized by aberrant signaling in the RAS/MAPK signaling cascade. Understanding the mechanisms of HCM development in such RASopathies may lead to novel therapeutic strategies, but relevant experimental models of the human condition are lacking. Therefore, the objective of this study was to develop the first 3D human engineered cardiac tissue (hECT) model of HCM. The hECTs were created using human cardiomyocytes obtained by directed differentiation of induced pluripotent stem cells derived from a patient with CFCS due to an activating BRAF mutation. The mutant myocytes were directly conjugated at a 3:1 ratio with a stromal cell population to create a tissue of defined composition. Compared to healthy patient control hECTs, BRAF-hECTs displayed a hypertrophic phenotype by culture day 6, with significantly increased tissue size, twitch force, and atrial natriuretic peptide (ANP) gene expression. Twitch characteristics reflected increased contraction and relaxation rates and shorter twitch duration in BRAF-hECTs, which also had a significantly higher maximum capture rate and lower excitation threshold during electrical pacing, consistent with a more arrhythmogenic substrate. By culture day 11, twitch force was no longer different between BRAF and wild-type hECTs, revealing a temporal aspect of disease modeling with tissue engineering. Principal component analysis identified diastolic force as a key factor that changed from day 6 to day 11, supported by a higher passive stiffness in day 11 BRAF-hECTs. In summary, human engineered cardiac tissues created from BRAF mutant cells recapitulated, for the first time, key aspects of the HCM phenotype, offering a new in vitro model for studying intrinsic mechanisms and screening new

  4. The flexibility of two tropomyosin mutants, D175N and E180G, that cause hypertrophic cardiomyopathy

    SciTech Connect

    Li, Xiaochuan; Suphamungmee, Worawit; Janco, Miro; Geeves, Michael A.; Marston, Steven B.; Fischer, Stefan; Lehman, William

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Well-known tropomyosin mutants, D175N and E180G are linked to cardiomyopathies. Black-Right-Pointing-Pointer The structural mechanics of D175N and E180G tropomyosins have been investigated. Black-Right-Pointing-Pointer D175N and E180G mutations increase both local and global tropomyosin flexibility. Black-Right-Pointing-Pointer In muscle, this increased flexibility will enhance myosin interactions on actin. Black-Right-Pointing-Pointer Extra myosin interaction can alter cardiac Ca{sup 2+}-switching, leading to dysfunction. -- Abstract: Point mutations targeting muscle thin filament proteins are the cause of a number of cardiomyopathies. In many cases, biological effects of the mutations are well-documented, whereas their structural and mechanical impact on filament assembly and regulatory function is lacking. In order to elucidate molecular defects leading to cardiac dysfunction, we have examined the structural mechanics of two tropomyosin mutants, E180G and D175N, which are associated with hypertrophic cardiomyopathy (HCM). Tropomyosin is an {alpha}-helical coiled-coil dimer which polymerizes end-to-end to create an elongated superhelix that wraps around F-actin filaments of muscle and non-muscle cells, thus modulating the binding of other actin-binding proteins. Here, we study how flexibility changes in the E180G and D175N mutants might affect tropomyosin binding and regulatory motion on F-actin. Electron microscopy and Molecular Dynamics simulations show that E180G and D175N mutations cause an increase in bending flexibility of tropomyosin both locally and globally. This excess flexibility is likely to increase accessibility of the myosin-binding sites on F-actin, thus destabilizing the low-Ca{sup 2+} relaxed-state of cardiac muscle. The resulting imbalance in the on-off switching mechanism of the mutants will shift the regulatory equilibrium towards Ca{sup 2+}-activation of cardiac muscle, as is observed in affected

  5. Impact of Cryoballoon Ablation in Hypertrophic Cardiomyopathy-related Heart Failure due to Paroxysmal Atrial Fibrillation. A Comparative Case Series

    PubMed Central

    Maagh, Petra; Plehn, Gunnar; Christoph, Arnd; Oernek, Ahmet; Meissner, Axel

    2016-01-01

    Background: Atrial fibrillation (AF) represents a turning point in hypertrophic cardiomyopathy (HCM). Pulmonary Vein Isolation (PVI) with Radiofrequency Catheter Ablation (RFCA) is accepted to be successful in restoring sinus rhythm (SR) in HCM patients. The efficacy of cryoballoon (CB) therapy in HCM patients has not been studied so far. Methods: 166 patients with AF underwent PVI with CB technology in our single center between 1/2012 and 12/2015. To evaluate the efficacy of the CB therapy in HCM patients, we compared their clinical outcome with those in “Non-HCM” AF patients in a 3 and 6 months follow-up. Results: Out of 166 AF patients (65.7% paroxysmal AF, PAF), 4 patients had HCM and PAF (young males < 50 years). During the blanking period, 26 patients (15.8%) suffered from AF recurrence (11.0% PAF), including all HCM patients. The 6 months follow up of “Non-HCM” AF patients showed acceptable results (80% stable SR), whereas the HCM patients remained AF. In Conclusion: Even if the CB provides advantages, the single device cannot be recommended in HCM patients because of early AF recurrences. Anyway, because of the specific hemodynamic changes in HCM patients with AF, ablation should be sought in an early state of its occurrence, then, however, preferably with RFCA.

  6. Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy.

    PubMed

    Kopajtich, Robert; Nicholls, Thomas J; Rorbach, Joanna; Metodiev, Metodi D; Freisinger, Peter; Mandel, Hanna; Vanlander, Arnaud; Ghezzi, Daniele; Carrozzo, Rosalba; Taylor, Robert W; Marquard, Klaus; Murayama, Kei; Wieland, Thomas; Schwarzmayr, Thomas; Mayr, Johannes A; Pearce, Sarah F; Powell, Christopher A; Saada, Ann; Ohtake, Akira; Invernizzi, Federica; Lamantea, Eleonora; Sommerville, Ewen W; Pyle, Angela; Chinnery, Patrick F; Crushell, Ellen; Okazaki, Yasushi; Kohda, Masakazu; Kishita, Yoshihito; Tokuzawa, Yoshimi; Assouline, Zahra; Rio, Marlène; Feillet, François; Mousson de Camaret, Bénédict; Chretien, Dominique; Munnich, Arnold; Menten, Björn; Sante, Tom; Smet, Joél; Régal, Luc; Lorber, Abraham; Khoury, Asaad; Zeviani, Massimo; Strom, Tim M; Meitinger, Thomas; Bertini, Enrico S; Van Coster, Rudy; Klopstock, Thomas; Rötig, Agnès; Haack, Tobias B; Minczuk, Michal; Prokisch, Holger

    2014-12-01

    Respiratory chain deficiencies exhibit a wide variety of clinical phenotypes resulting from defective mitochondrial energy production through oxidative phosphorylation. These defects can be caused by either mutations in the mtDNA or mutations in nuclear genes coding for mitochondrial proteins. The underlying pathomechanisms can affect numerous pathways involved in mitochondrial physiology. By whole-exome and candidate gene sequencing, we identified 11 individuals from 9 families carrying compound heterozygous or homozygous mutations in GTPBP3, encoding the mitochondrial GTP-binding protein 3. Affected individuals from eight out of nine families presented with combined respiratory chain complex deficiencies in skeletal muscle. Mutations in GTPBP3 are associated with a severe mitochondrial translation defect, consistent with the predicted function of the protein in catalyzing the formation of 5-taurinomethyluridine (τm(5)U) in the anticodon wobble position of five mitochondrial tRNAs. All case subjects presented with lactic acidosis and nine developed hypertrophic cardiomyopathy. In contrast to individuals with mutations in MTO1, the protein product of which is predicted to participate in the generation of the same modification, most individuals with GTPBP3 mutations developed neurological symptoms and MRI involvement of thalamus, putamen, and brainstem resembling Leigh syndrome. Our study of a mitochondrial translation disorder points toward the importance of posttranscriptional modification of mitochondrial tRNAs for proper mitochondrial function.

  7. Mutations in GTPBP3 Cause a Mitochondrial Translation Defect Associated with Hypertrophic Cardiomyopathy, Lactic Acidosis, and Encephalopathy

    PubMed Central

    Kopajtich, Robert; Nicholls, Thomas J.; Rorbach, Joanna; Metodiev, Metodi D.; Freisinger, Peter; Mandel, Hanna; Vanlander, Arnaud; Ghezzi, Daniele; Carrozzo, Rosalba; Taylor, Robert W.; Marquard, Klaus; Murayama, Kei; Wieland, Thomas; Schwarzmayr, Thomas; Mayr, Johannes A.; Pearce, Sarah F.; Powell, Christopher A.; Saada, Ann; Ohtake, Akira; Invernizzi, Federica; Lamantea, Eleonora; Sommerville, Ewen W.; Pyle, Angela; Chinnery, Patrick F.; Crushell, Ellen; Okazaki, Yasushi; Kohda, Masakazu; Kishita, Yoshihito; Tokuzawa, Yoshimi; Assouline, Zahra; Rio, Marlène; Feillet, François; Mousson de Camaret, Bénédict; Chretien, Dominique; Munnich, Arnold; Menten, Björn; Sante, Tom; Smet, Joél; Régal, Luc; Lorber, Abraham; Khoury, Asaad; Zeviani, Massimo; Strom, Tim M.; Meitinger, Thomas; Bertini, Enrico S.; Van Coster, Rudy; Klopstock, Thomas; Rötig, Agnès; Haack, Tobias B.; Minczuk, Michal; Prokisch, Holger

    2014-01-01

    Respiratory chain deficiencies exhibit a wide variety of clinical phenotypes resulting from defective mitochondrial energy production through oxidative phosphorylation. These defects can be caused by either mutations in the mtDNA or mutations in nuclear genes coding for mitochondrial proteins. The underlying pathomechanisms can affect numerous pathways involved in mitochondrial physiology. By whole-exome and candidate gene sequencing, we identified 11 individuals from 9 families carrying compound heterozygous or homozygous mutations in GTPBP3, encoding the mitochondrial GTP-binding protein 3. Affected individuals from eight out of nine families presented with combined respiratory chain complex deficiencies in skeletal muscle. Mutations in GTPBP3 are associated with a severe mitochondrial translation defect, consistent with the predicted function of the protein in catalyzing the formation of 5-taurinomethyluridine (τm5U) in the anticodon wobble position of five mitochondrial tRNAs. All case subjects presented with lactic acidosis and nine developed hypertrophic cardiomyopathy. In contrast to individuals with mutations in MTO1, the protein product of which is predicted to participate in the generation of the same modification, most individuals with GTPBP3 mutations developed neurological symptoms and MRI involvement of thalamus, putamen, and brainstem resembling Leigh syndrome. Our study of a mitochondrial translation disorder points toward the importance of posttranscriptional modification of mitochondrial tRNAs for proper mitochondrial function. PMID:25434004

  8. Impact of Cryoballoon Ablation in Hypertrophic Cardiomyopathy-related Heart Failure due to Paroxysmal Atrial Fibrillation. A Comparative Case Series

    PubMed Central

    Maagh, Petra; Plehn, Gunnar; Christoph, Arnd; Oernek, Ahmet; Meissner, Axel

    2016-01-01

    Background: Atrial fibrillation (AF) represents a turning point in hypertrophic cardiomyopathy (HCM). Pulmonary Vein Isolation (PVI) with Radiofrequency Catheter Ablation (RFCA) is accepted to be successful in restoring sinus rhythm (SR) in HCM patients. The efficacy of cryoballoon (CB) therapy in HCM patients has not been studied so far. Methods: 166 patients with AF underwent PVI with CB technology in our single center between 1/2012 and 12/2015. To evaluate the efficacy of the CB therapy in HCM patients, we compared their clinical outcome with those in “Non-HCM” AF patients in a 3 and 6 months follow-up. Results: Out of 166 AF patients (65.7% paroxysmal AF, PAF), 4 patients had HCM and PAF (young males < 50 years). During the blanking period, 26 patients (15.8%) suffered from AF recurrence (11.0% PAF), including all HCM patients. The 6 months follow up of “Non-HCM” AF patients showed acceptable results (80% stable SR), whereas the HCM patients remained AF. In Conclusion: Even if the CB provides advantages, the single device cannot be recommended in HCM patients because of early AF recurrences. Anyway, because of the specific hemodynamic changes in HCM patients with AF, ablation should be sought in an early state of its occurrence, then, however, preferably with RFCA. PMID:27647995

  9. Evaluation of the Mayo Clinic Phenotype-Based Genotype Predictor Score in Patients with Clinically Diagnosed Hypertrophic Cardiomyopathy.

    PubMed

    Murphy, Sinead L; Anderson, Jason H; Kapplinger, Jamie D; Kruisselbrink, Teresa M; Gersh, Bernard J; Ommen, Steve R; Ackerman, Michael J; Bos, J Martijn

    2016-04-01

    Genetic testing for hypertrophic cardiomyopathy (HCM) can provide an important clinical marker for disease outcome and family screening. This study set out to validate our recently developed phenotype-based HCM genotype predictor score. Patients clinically diagnosed with HCM and evaluated by genetic counselors comprised the study cohort. Genotype score was derived based on clinical and echocardiographic variables. Total score was correlated with the yield of genetic testing. Of 564 HCM patients, 198 sought genetic testing (35 %; 55 % male; mean age at diagnosis, 50 ± 20 years). Of these, 101 patients (51 %) were genotype positive for a HCM-associated genetic mutation (55 % male; mean age at diagnosis, 42 ± 18 years). Cochran-Armitage analysis showed similar, statistically significant trends of increased yields for higher genotype scores for both the original and study cohort. Validated by the current study, this scoring system provides an easy-to-use, clinical tool to aid in determining the likelihood of a positive HCM genetic test. PMID:26914223

  10. Rapidly Progressive Hypertrophic Cardiomyopathy in an Infant with Noonan syndrome with multiple Lentigines. Palliative Treatment with a Rapamycin Analog

    PubMed Central

    Hahn, Andreas; Lauriol, Jessica; Thul, Josef; Behnke-Hall, Kachina; Logeswaran, Tushiha; Schänzer, Anne; Böğürcü, Nuray; Garvalov, Boyan K.; Zenker, Martin; Gelb, Bruce D.; von Gerlach, Susanne; Kandolf, Reinhard; Kontaridis, Maria I.; Schranz, Dietmar

    2015-01-01

    Noonan syndrome with multiple lentigines (NSML) frequently manifests with hypertrophic cardiomyopathy (HCM). Recently, it was demonstrated that mTOR inhibition reverses HCM in NSML mice. We report for the first time on the effects of treatment with a rapamycin analog in an infant with LS and a malignant form of HCM. In the boy, progressive HCM was diagnosed during the first week of life and diagnosis of NSML was established at age 20 weeks by showing a heterozygous Q510E mutation in the PTPN11 gene. Immunoblotting with antibodies against pERK, pAkt, and pS6RP in fibroblasts demonstrated reduced RAS/MAPK and enhanced Akt/mTOR pathway activities. Because of the patient’s critical condition, everolimus therapy was started at age 24 weeks and continued until heart transplantation at age 36 weeks. Prior to surgery, heart failure improved from NYHA stage IV to II and brain natriuretic peptide values decreased from 9600 to <1000 pg/ml, but no reversal of cardiac hypertrophy was observed. Examination of the explanted heart revealed severe hypertrophy and myofiber disarray with extensive perivascular fibrosis. These findings provide evidence that Akt/mTOR activity is enhanced in NSML with HCM and suggest that rapamycin treatment could be principally feasible for infantile NSML. But the preliminary experiences made in this single patient indicate that therapy should start early to prevent irreversible cardiac remodelling. PMID:25708222

  11. Familial hypertrophic cardiomyopathy mutations in troponin I (K183D, G203S, K206Q) enhance filament sliding.

    PubMed

    Köhler, Jan; Chen, Ying; Brenner, Bernhard; Gordon, Albert M; Kraft, Theresia; Martyn, Donald A; Regnier, Michael; Rivera, Anthony J; Wang, Chien-Kao; Chase, P Bryant

    2003-07-01

    A major cause of familial hypertrophic cardiomyopathy (FHC) is dominant mutations in cardiac sarcomeric genes. Linkage studies identified FHC-related mutations in the COOH terminus of cardiac troponin I (cTnI), a region with unknown function in Ca(2+) regulation of the heart. Using in vitro assays with recombinant rat troponin subunits, we tested the hypothesis that mutations K183Delta, G203S, and K206Q in cTnI affect Ca(2+) regulation. All three mutants enhanced Ca(2+) sensitivity and maximum speed (s(max)) of filament sliding of in vitro motility assays. Enhanced s(max) (pCa 5) was observed with rabbit skeletal and rat cardiac (alpha-MHC or beta-MHC) heavy meromyosin (HMM). We developed a passive exchange method for replacing endogenous cTn in permeabilized rat cardiac trabeculae. Ca(2+) sensitivity and maximum isometric force did not differ between preparations exchanged with cTn(cTnI,K206Q) or wild-type cTn. In both trabeculae and motility assays, there was no loss of inhibition at pCa 9. These results are consistent with COOH terminus of TnI modulating actomyosin kinetics during unloaded sliding, but not during isometric force generation, and implicate enhanced cross-bridge cycling in the cTnI-related pathway(s) to hypertrophy. PMID:12759477

  12. Evaluation of the Mayo Clinic Phenotype-Based Genotype Predictor Score in Patients with Clinically Diagnosed Hypertrophic Cardiomyopathy

    PubMed Central

    Murphy, Sinead L.; Anderson, Jason H.; Kapplinger, Jamie D.; Kruisselbrink, Teresa M.; Gersh, Bernard J.; Ommen, Steve R.; Ackerman, Michael J.; Bos, J. Martijn

    2016-01-01

    Genetic testing for hypertrophic cardiomyopathy (HCM) can provide an important clinical marker for disease outcome and family screening. This study set out to validate our recently developed phenotype-based HCM genotype predictor score. Patients clinically diagnosed with HCM and evaluated by genetic counselors comprised the study cohort. Genotype score was derived based on clinical and echocardio-graphic variables. Total score was correlated with the yield of genetic testing. Of 564 HCM patients, 198 sought genetic testing (35 %; 55 % male; mean age at diagnosis, 50 ±20 years). Of these, 101 patients (51 %) were genotype positive for a HCM-associated genetic mutation (55 % male; mean age at diagnosis, 42 ± 18 years). Cochran-Armitage analysis showed similar, statistically significant trends of increased yields for higher genotype scores for both the original and study cohort. Validated by the current study, this scoring system provides an easy-to-use, clinical tool to aid in determining the likelihood of a positive HCM genetic test. PMID:26914223

  13. A mutation in the {beta}-myosin rod associated with hypertrophic cardiomyopathy has an unexpected molecular phenotype

    SciTech Connect

    Armel, Thomas Z.; Leinwand, Leslie A.

    2010-01-01

    Hypertrophic cardiomyopathy (HCM) is a common, autosomal dominant disorder primarily characterized by left ventricular hypertrophy and is the leading cause of sudden cardiac death in youth. HCM is caused by mutations in several sarcomeric proteins, with mutations in MYH7, encoding {beta}-MyHC, being the most common. While many mutations in the globular head region of the protein have been reported and studied, analysis of HCM-causing mutations in the {beta}-MyHC rod domain has not yet been reported. To address this question, we performed an array of biochemical and biophysical assays to determine how the HCM-causing E1356K mutation affects the structure, stability, and function of the {beta}-MyHC rod. Surprisingly, the E1356K mutation appears to thermodynamically destabilize the protein, rather than alter the charge profile know to be essential for muscle filament assembly. This thermodynamic instability appears to be responsible for the decreased ability of the protein to form filaments and may be responsible for the HCM phenotype seen in patients.

  14. Short-limb dwarfism and hypertrophic cardiomyopathy in a patient with paternal isodisomy 14: 45,XYidic(14)(p11)

    SciTech Connect

    Walter, C.A.; Moore, C.M.; Kaye, C.I.

    1996-11-11

    Uniparental disomy (UPD) has been shown to result in specific disorders either due to imprinting and/or homozygosity of mutant alleles. Here we present the findings in a child with paternal UPD14. Ultrasound evaluation was performed at 30 weeks of gestation because of abnormally large uterine size. Pertinent ultrasound findings included polyhydramnios, short limbs, abnormal position of hands, small thorax, and nonvisualization of the fetal stomach. Postnatally the infant was found to have a low birth weight, short birth length, contractures, short limbs, and a small thorax with upslanting ribs. Assisted ventilation and gastrostomy were required. At age 6 months, the infant required hospitalization for hypertrophic cardiomyopathy which responded to Atenolol{reg_sign}. Initial cytogenetic studies demonstrated an apparently balanced de novo Robertsonian translocation involving chromosomes 14 and a karyotype designation of 45,XY,t(14q14q). No indication of mosaicism for trisomy 14 was observed in metaphase spreads prepared from peripheral blood lymphocytes or skin-derived fibroblasts. C-band and fluorescence in situ hybridization results demonstrated that the chromosome was dicentric. DNA analyses showed paternal uniparental isodisomy for chromosome 14. Based on the cytogenetic and DNA results a final karyotype designation of 45,XY,idic(14)(p11) was assigned to this infant with paternal isodisomy of chromosome 14. 41 refs., 5 figs., 2 tabs.

  15. Sudden Cardiac Arrest in a Patient With Apical Hypertrophic Cardiomyopathy: Case Report and a Brief Review of Literature.

    PubMed

    Gupta, Tanush; Paul, Neha; Palaniswamy, Chandrasekar; Balasubramaniyam, Nivas; Aronow, Wilbert S; Kolte, Dhaval; Khera, Sahil; Shah, Amar B; Gass, Alan

    2016-01-01

    Apical hypertrophic cardiomyopathy (HCM) is a phenotypic variant of nonobstructive HCM, in which hypertrophy of the myocardium predominantly involves the left ventricular apex. It is common in Japanese and other Asian populations but is rare in the United States. Apical HCM has a relatively benign prognosis in terms of cardiovascular mortality; however, morbid events such as ventricular aneurysms, apical thrombi, diastolic dysfunction, atrial fibrillation, and myocardial infarction are not uncommon. We report a case of an 18-year-old white man who presented to our hospital after an out-of-hospital cardiac arrest. The patient had a witnessed collapse while playing basketball in the field. He was found to be pulseless and unresponsive by his coach, and cardiopulmonary resuscitation was immediately started. Upon arrival of emergency medical services, an automated external defibrillator advised shock and he was defibrillated thrice. Return of spontaneous circulation was achieved in 15 minutes. He was intubated for airway protection and was brought to the hospital. Therapeutic hypothermia was initiated. He demonstrated good neurological status after active rewarming. Subsequent cardiac magnetic resonance imaging was suggestive of apical HCM with right ventricular involvement. The patient underwent an implantable cardioverter defibrillator placement for secondary prevention and was subsequently discharged. In conclusion, apical HCM can rarely be associated with adverse cardiovascular events. The diagnosis may be missed on transthoracic 2-dimensional cardiac echocardiogram, and cardiac magnetic resonance imaging should be considered to exclude apical HCM in young patients who present after sudden cardiac arrest. PMID:25923227

  16. Effect of propranolol and disopyramide on left ventricular function at rest and during exercise in hypertrophic cardiomyopathy.

    PubMed

    Hartmann, A; Kühn, J; Hopf, R; Klepzig, H; Standke, R; Kober, G; Maul, F D; Hör, G; Kaltenbach, M

    1992-01-01

    In 19 patients with hypertrophic cardiomyopathy (15 males, 4 females, mean age 49.2 +/- 10.8 years) left ventricular function was studied with radionuclide ventriculography at rest and during exercise in a crossover design without intervention and after disopyramide and propranolol treatment. 15 of the 19 patients had a resting or latent intraventricular gradient of more than 30 mm Hg. Left ventricular function at rest and during exercise was evaluated before medication, 90 min after oral administration of 200 mg disopyramide or 160 mg propranolol and after 3 weeks of oral therapy with disopyramide 200 mg 2 times a day or propranolol 80 mg 4 times a day. After long-term treatment with disopyramide, resting ejection fraction decreased from 72 +/- 12 to 69 +/- 14% (p less than 0.01) and peak ejection rate (PER) decreased from 3.46 +/- 135 to 3.24 +/- 65 end-diastolic volume (EDV).s-1 (p less than 0.01). Peak filling rate (PFR) at rest decreased from 3.01 +/- 0.8 to 2.77 +/- 0.63 EDV.s-1 (p less than 0.05). Time to peak filling rate (TPFR) at rest and during exercise after acute and chronic therapy did not change compared to control values. Acute and long-term administration of propranolol lead to a significant reduction in heart rate at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Assessment of left ventricular longitudinal function in cats with subclinical hypertrophic cardiomyopathy using tissue Doppler imaging and speckle tracking echocardiography.

    PubMed

    Sugimoto, Keisuke; Fujii, Yoko; Sunahara, Hiroshi; Aoki, Takuma

    2015-09-01

    Hypertrophic cardiomyopathy (HCM) in cats is characterized by concentric left ventricular (LV) hypertrophy and both diastolic and systolic dysfunction. Although impaired cardiac function detected by tissue Doppler imaging (TDI) in cats with HCM was previously reported, reference ranges of TDI in normal cats and cats with HCM have been reported as widely variable. Two-dimensional speckle tracking echocardiography (STE) was useful for assessment of cardiac function in human patients with HCM, but clinical utility was not known in cats. The aim of this study was to assess global and segmental LV myocardial function using STE in cats with HCM whose TDI variables were within the reference range. A total of 35 cats of different breeds were enrolled in this study. The HCM group (n=22) was cats diagnosed as HCM without left atrial enlargement and with normal TDI measurements. HCM cats were further divided into a segmental hypertrophy (S-HCM) group and a diffuse hypertrophy (D-HCM) group. The control group consisted of 13 clinically healthy cats. No cats in any group showed any clinical symptoms. Conventional echocardiography, TDI, and global and segmental STE indices were evaluated and compared between groups. Only the longitudinal strain rate during early diastole was significantly decreased in both HCM groups, even in all segments including those without hypertrophy in S-HCM group. This study suggests that STE parameters are the more sensitive variables compared with conventional TDI parameters to detect early myocardial diastolic dysfunction in cats with HCM.

  18. Sudden Cardiac Arrest in a Patient With Apical Hypertrophic Cardiomyopathy: Case Report and a Brief Review of Literature.

    PubMed

    Gupta, Tanush; Paul, Neha; Palaniswamy, Chandrasekar; Balasubramaniyam, Nivas; Aronow, Wilbert S; Kolte, Dhaval; Khera, Sahil; Shah, Amar B; Gass, Alan

    2016-01-01

    Apical hypertrophic cardiomyopathy (HCM) is a phenotypic variant of nonobstructive HCM, in which hypertrophy of the myocardium predominantly involves the left ventricular apex. It is common in Japanese and other Asian populations but is rare in the United States. Apical HCM has a relatively benign prognosis in terms of cardiovascular mortality; however, morbid events such as ventricular aneurysms, apical thrombi, diastolic dysfunction, atrial fibrillation, and myocardial infarction are not uncommon. We report a case of an 18-year-old white man who presented to our hospital after an out-of-hospital cardiac arrest. The patient had a witnessed collapse while playing basketball in the field. He was found to be pulseless and unresponsive by his coach, and cardiopulmonary resuscitation was immediately started. Upon arrival of emergency medical services, an automated external defibrillator advised shock and he was defibrillated thrice. Return of spontaneous circulation was achieved in 15 minutes. He was intubated for airway protection and was brought to the hospital. Therapeutic hypothermia was initiated. He demonstrated good neurological status after active rewarming. Subsequent cardiac magnetic resonance imaging was suggestive of apical HCM with right ventricular involvement. The patient underwent an implantable cardioverter defibrillator placement for secondary prevention and was subsequently discharged. In conclusion, apical HCM can rarely be associated with adverse cardiovascular events. The diagnosis may be missed on transthoracic 2-dimensional cardiac echocardiogram, and cardiac magnetic resonance imaging should be considered to exclude apical HCM in young patients who present after sudden cardiac arrest.

  19. Coexistence of mitochondrial DNA and β myosin heavy chain mutations in hypertrophic cardiomyopathy with late congestive heart failure

    PubMed Central

    Arbustini, E; Fasani, R; Morbini, P; Diegoli, M; Grasso, M; Dal, B; Marangoni, E; Banfi, P; Banchieri, N; Bellini, O; Comi, G; Narula, J; Campana, C; Gavazzi, A; Danesino, C; Vigano, M

    1998-01-01

    Objective—To investigate the possible coexistence of mitochondrial DNA (mtDNA) mutations in patients with β myosin heavy chain (βMHC) linked hypertrophic cardiomyopathy (HCM) who develop congestive heart failure.
Design—Molecular analysis of βMHC and mtDNA gene defects in patients with HCM.
Setting—Cardiovascular molecular diagnostic and heart transplantation reference centre in north Italy.
Patients—Four patients with HCM who underwent heart transplantation for end stage heart failure, and after pedigree analysis of 60 relatives, eight additional affected patients and 27 unaffected relatives. A total of 111 unrelated healthy adult volunteers served as controls. Disease controls included an additional 27 patients with HCM and 102 with dilated cardiomyopathy.
Intervention—Molecular analysis of DNA from myocardial and skeletal muscle tissue and from peripheral blood specimens.
Main outcome measures—Screening for mutations in βMHC (exons 3-23) and mtDNA tRNA (n = 22) genes with denaturing gradient gel electrophoresis or single strand conformational polymorphism followed by automated DNA sequencing.
Results—One proband (kindred A) (plus seven affected relatives) had arginine 249 glutamine (Arg249Gln) βMHC and heteroplasmic mtDNA tRNAIle A4300G mutations. Another unrelated patient (kindred B) with sporadic HCM had identical mutations. The remaining two patients (kindred C), a mother and son, had a novel βMHC mutation (lysine 450 glutamic acid) (Lys450Glu) and a heteroplasmic missense (T9957C, phenylalanine (Phe)->leucine (Leu)) mtDNA mutation in subunit III of the cytochrome C oxidase gene. The amount of mutant mtDNA was higher in the myocardium than in skeletal muscle or peripheral blood and in affected patients than in asymptomatic relatives. Mutations were absent in the controls. Pathological and biochemical characteristics of patients with mutations Arg249Gln plus A4300G (kindreds A and B) were identical, but different from

  20. Utility of continuous wave Doppler echocardiography in the noninvasive assessment of left ventricular outflow tract pressure gradient in patients with hypertrophic cardiomyopathy.

    PubMed

    Panza, J A; Petrone, R K; Fananapazir, L; Maron, B J

    1992-01-01

    Subaortic obstruction is an important determinant of the clinical presentation of and therapeutic approach to patients with hypertrophic cardiomyopathy. Therefore, assessment of the presence and magnitude of the intraventricular pressure gradient is paramount in the clinical evaluation of these patients. To establish the utility of continuous wave Doppler echocardiography in assessing the pressure gradient in hypertrophic cardiomyopathy, 28 patients representing the wide hemodynamic spectrum of this disease underwent simultaneous determination of the subaortic gradient by continuous wave Doppler ultrasound and cardiac catheterization. With use of the modified Bernoulli equation, the Doppler-estimated gradient showed a strong correlation with the maximal instantaneous pressure difference measured at catheterization, both under basal conditions (r = 0.93; p less than 0.0001) and during provocative maneuvers (r = 0.89; p less than 0.0001). In 26 of the 28 patients, all assessments of the subaortic gradient were in agreement within 15 mm Hg (average difference 5 +/- 3 mm Hg). In the other two patients there were substantial differences between these measurements (under basal conditions in one patient and after provocation in another), although the Doppler technique predicted the presence of marked subaortic obstruction in each. In both patients the erroneous interpretation was due to superimposition of the mitral regurgitation signal on that of left ventricular outflow. Doppler waveforms from the left ventricular outflow tract showed variability in contour among different patients and in individual patients. Hence, continuous wave Doppler echocardiography is a useful noninvasive method for estimating the subaortic gradient in patients with hypertrophic cardiomyopathy. However, technical factors such as contamination of the outflow tract jet with that of mitral regurgitation and variability in waveform configuration may importantly influence such assessments of the

  1. Usefulness of Electrocardiographic Patterns at Presentation to Predict Long-term Risk of Cardiac Death in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Biagini, Elena; Pazzi, Chiara; Olivotto, Iacopo; Musumeci, Beatrice; Limongelli, Giuseppe; Boriani, Giuseppe; Pacileo, Giuseppe; Mastromarino, Vittoria; Bacchi Reggiani, Maria Letizia; Lorenzini, Massimiliano; Lai, Francesco; Berardini, Alessandra; Mingardi, Francesca; Rosmini, Stefania; Resciniti, Elvira; Borghi, Claudia; Autore, Camillo; Cecchi, Franco; Rapezzi, Claudio

    2016-08-01

    The objective of this study was to investigate the prognostic significance of 12-lead electrocardiogram (ECG) patterns in a large multicenter cohort of patients with hypertrophic cardiomyopathy; 1,004 consecutive patients with hypertrophic cardiomyopathy and a recorded standard ECG (64% men, mean age 50 ± 16 years) were evaluated at 4 Italian centers. The study end points were sudden cardiac death (SCD) or surrogates, including appropriate implanted cardiac defibrillator discharge and resuscitated cardiac arrest and major cardiovascular events (including SCD or surrogates and death due to heart failure, cardioembolic stroke, or heart transplantation). Prevalence of baseline electrocardiographic characteristics was: normal ECG 4%, ST-segment depression 56%, pseudonecrosis waves 33%, "pseudo-ST-segment elevation myocardial infarction (STEMI)" pattern 17%, QRS duration ≥120 ms 17%, giant inverted T waves 6%, and low QRS voltages 3%. During a mean follow-up of 7.4 ± 6.8 years, 77 patients experienced SCD or surrogates and 154 patients experienced major cardiovascular events. Independent predictors of SCD or surrogates were unexplained syncope (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.4 to 4.5, p = 0.003), left ventricular ejection fraction <50% (HR 3.5, 95% CI 1.9 to 6.7, p = 0.0001), nonsustained ventricular tachycardia (HR 1.7, 95% CI 1.1 to 2.6, p = 0.027), pseudo-STEMI pattern (HR 2.3, 95% CI 1.4 to 3.8, p = 0.001), QRS duration ≥120 ms (HR 1.8, 95% CI 1.1 to 3.0, p = 0.033), and low QRS voltages (HR 2.3, 95% CI 1.01 to 5.1, p = 0.048). Independent predictors of major cardiovascular events were age (HR 1.02, 95% CI 1.01 to 1.03, p = 0.0001), LV ejection fraction <50% (HR 3.73, 95% CI 2.39 to 5.83, p = 0.0001), pseudo-STEMI pattern (HR 1.66, 95% CI 1.13 to 2.45, p = 0.010), QRS duration ≥120 ms (HR 1.69, 95% CI 1.16 to 2.47, p = 0.007), and prolonged QTc interval (HR 1.68, 95% CI 1.21 to 2.34, p = 0.002). In conclusion, a detailed

  2. Echocardiography and cardiac MRI in mutation-negative hypertrophic cardiomyopathy in an older patient: a case defining the need for ICD.

    PubMed

    Rodriguez, Fatima; Degnan, Kathleen O; Seidman, Christine E; Mangion, Judy R

    2014-08-01

    We report the case of a 67-year-old man with hypertrophic cardiomyopathy who presented for a second opinion about implantable cardio-defibrillator (ICD) placement after a witnessed syncopal episode. Despite his older age, being mutation-negative, and having a maximal septal thickness of 2.2 cm on echocardiography, he demonstrated rapid progression of myocardial fibrosis on cardiac MRI, correlating to ventricular tachyarrhythmias and syncope. We review the role of echocardiography and cardiac MRI in optimizing medical care for such patients who may not otherwise meet criteria for an ICD placement or further interventions. PMID:24816179

  3. CCN2 plays a key role in extracellular matrix gene expression in severe hypertrophic cardiomyopathy and heart failure.

    PubMed

    Tsoutsman, Tatiana; Wang, Xiaoyu; Garchow, Kendra; Riser, Bruce; Twigg, Stephen; Semsarian, Christopher

    2013-09-01

    Hypertrophic cardiomyopathy (HCM) is the most common inherited primary myocardial disorder. HCM is characterized by interstitial fibrosis and excessive accumulation of extracellular matrix (ECM) proteins. Fibrosis in HCM has been associated with impaired cardiac function and heart failure, and has been considered a key substrate for ventricular arrhythmias and sudden death. The molecular triggers underpinning ECM production are not well established. We have previously developed a double-mutant mouse model of HCM that recapitulates the phenotype seen in humans with multiple mutations, including earlier onset of the disease, progression to a dilated phenotype, severe heart failure and premature mortality. The present study investigated the expression of ECM-encoding genes in severe HCM and heart failure. Significant upregulation of structural Fn1, regulatory Mmp14, Timp1, Serpin3A, SerpinE1, SerpineE2, Tgfβ1, and Tgfβ2; and matricellular Ccn2, Postn, Spp1, Thbs1, Thbs4, and Tnc was evident from the early, pre-phenotype stage. Non-myocytes expressed ECM genes at higher levels than cardiomyocytes in normal and diseased hearts. Synchronous increase of secreted CCN2 and TIMP1 plasma levels and decrease of MMP3 levels were observed in end-stage disease. CCN2 protein expression was increased from early disease in double-mutant hearts and played an important role in ECM responses. It was a powerful modulator of ECM regulatory (Timp1 and SerpinE1) and matricellular protein-encoding (Spp1, Thbs1, Thbs4 and Tnc) gene expression in cardiomyocytes when added exogenously in vitro. Modulation of CCN2 (CTGF, connective tissue growth factor) and associated early ECM changes may represent a new therapeutic target in the treatment and prevention of heart failure in HCM. PMID:23756156

  4. Association Between Genetic Variation in the SCN10A Gene and Cardiac Conduction Abnormalities in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Iio, Chiharuko; Ogimoto, Akiyoshi; Nagai, Takayuki; Suzuki, Jun; Inoue, Katsuji; Nishimura, Kazuhisa; Uetani, Teruyoshi; Okayama, Hideki; Okura, Takafumi; Shigematsu, Yuji; Tabara, Yasuharu; Kohara, Katsuhiko; Miki, Tetsuro; Hamada, Mareomi; Higaki, Jitsuo

    2015-01-01

    Arrhythmias are associated with reduced quality of life and poor prognosis in patients with hypertrophic cardiomyopathy (HCM). Recent genome-wide association studies revealed that a nonsynonymous single nucleotide polymorphism, rs6795970, in the SCN10A gene was associated with the PR interval. We examined whether the PR prolonging allele (A allele) in the SCN10A gene may be associated with cardiac conduction abnormalities in HCM patients.We genotyped the polymorphism in 149 HCM patients. Conduction abnormalities were defined as first-degree heart block, bundle-branch block, and bifascicular heart block. Patients were divided into two groups: group A consisted of 122 patients (82%) without a conduction abnormality; and group B consisted of 27 patients (18%) with one or more cardiac conduction abnormalities. The frequency distribution of the SCN10A genotypes (G/G, G/A, and A/A) among the patients with HCM was 71%, 26%, and 3%, respectively. A cardiac conduction abnormality was documented in 9% with G/G and 40% with G/A or A/A. There was a significant difference in the genotype distribution between the two groups (P = 0.0002). In the dominant A allele model, there was a significant difference in genotypes between the two groups (P < 0.0001). In addition, the A allele remained significant after adjusting for other covariates in a multivariate model (odds ratio = 6.30 [95% confidence interval: 2.24 to 19.09], P = 0.0005).The rs6795970 in the SCN10A gene, which is reported to carry a high risk of heart block, might be associated with cardiac conduction abnormalities in HCM patients. PMID:26104176

  5. Registration of dynamic multiview 2D ultrasound and late gadolinium enhanced images of the heart: Application to hypertrophic cardiomyopathy characterization.

    PubMed

    Betancur, Julián; Simon, Antoine; Halbert, Edgar; Tavard, François; Carré, François; Hernández, Alfredo; Donal, Erwan; Schnell, Frédéric; Garreau, Mireille

    2016-02-01

    Describing and analyzing heart multiphysics requires the acquisition and fusion of multisensor cardiac images. Multisensor image fusion enables a combined analysis of these heterogeneous modalities. We propose to register intra-patient multiview 2D+t ultrasound (US) images with multiview late gadolinium-enhanced (LGE) images acquired during cardiac magnetic resonance imaging (MRI), in order to fuse mechanical and tissue state information. The proposed procedure registers both US and LGE to cine MRI. The correction of slice misalignment and the rigid registration of multiview LGE and cine MRI are studied, to select the most appropriate similarity measure. It showed that mutual information performs the best for LGE slice misalignment correction and for LGE and cine registration. Concerning US registration, dynamic endocardial contours resulting from speckle tracking echocardiography were exploited in a geometry-based dynamic registration. We propose the use of an adapted dynamic time warping procedure to synchronize cardiac dynamics in multiview US and cine MRI. The registration of US and LGE MRI was evaluated on a dataset of patients with hypertrophic cardiomyopathy. A visual assessment of 330 left ventricular regions from US images of 28 patients resulted in 92.7% of regions successfully aligned with cardiac structures in LGE. Successfully-aligned regions were then used to evaluate the abilities of strain indicators to predict the presence of fibrosis. Longitudinal peak-strain and peak-delay of aligned left ventricular regions were computed from corresponding regional strain curves from US. The Mann-Withney test proved that the expected values of these indicators change between the populations of regions with and without fibrosis (p < 0.01). ROC curves otherwise proved that the presence of fibrosis is one factor amongst others which modifies longitudinal peak-strain and peak-delay. PMID:26619189

  6. Survival and Clinical Behavior of Hypertrophic Cardiomyopathy in a Latin American Cohort in Contrast to Cohorts from the Developed World

    PubMed Central

    Espinola-Zavaleta, Nilda; Vega, Antonio; Basto, Diego Martínez; Alcantar-Fernández, Ana Cecilia; Guarner Lans, Veronica

    2015-01-01

    Background Hypertrophic cardiomyopathy (HCM) is the most common hereditary heart disease with diverse phenotipyc, genetic expession and clinical presentations. The evolution of patients with HCM in Latin America has not been properly described being the frequency, the long-term prognosis as well as the predominant phenotypic expression still unknown. The aim of this study was to determine the survival rate of HCM patients having different phenotypes in a Mexican cohort of patients. Methods Clinical and echocardiographic data obtained from 77 Mexican patients with recently diagnosed HCM were analyzed. The follow-up was of 12.5 years. Results 96.1% of patients were in functional class I/II according to the New York Heart Association, 2.6% in class III and 1.3% in class IV. Only 3.9% of them went to surgery for myectomy. During the follow-up, 17 patients (22%) died: 4/9 (44%) had apical HCM, 5/20 (25%) had obstructive septal asymmetric HCM, 6/35 (17%) had nonobstructive septal asymmetric HCM and 2/3 (15%) had concentric HCM. The survival rate was worse for patients with apical HCM, followed by those with obstructive and nonobstructive septal asymmetric HCM and patients showing concentric HCM had the best survival rates. There is significant difference in survival rates which declined in 65% in a 9 years-period. Log rank test showed significant differences (p < 0.002). Conclusion The survival rate of patients with HCM was worse in those with apical variety. The majority of patients received medical treatment. The indication for myectomy was below that observed in other international centers. PMID:25883752

  7. Novel insights on the relationship between T-tubular defects and contractile dysfunction in a mouse model of hypertrophic cardiomyopathy.

    PubMed

    Crocini, C; Ferrantini, C; Scardigli, M; Coppini, R; Mazzoni, L; Lazzeri, E; Pioner, J M; Scellini, B; Guo, A; Song, L S; Yan, P; Loew, L M; Tardiff, J; Tesi, C; Vanzi, F; Cerbai, E; Pavone, F S; Sacconi, L; Poggesi, C

    2016-02-01

    Abnormalities of cardiomyocyte Ca(2+) homeostasis and excitation-contraction (E-C) coupling are early events in the pathogenesis of hypertrophic cardiomyopathy (HCM) and concomitant determinants of the diastolic dysfunction and arrhythmias typical of the disease. T-tubule remodelling has been reported to occur in HCM but little is known about its role in the E-C coupling alterations of HCM. Here, the role of T-tubule remodelling in the electro-mechanical dysfunction associated to HCM is investigated in the Δ160E cTnT mouse model that expresses a clinically-relevant HCM mutation. Contractile function of intact ventricular trabeculae is assessed in Δ160E mice and wild-type siblings. As compared with wild-type, Δ160E trabeculae show prolonged kinetics of force development and relaxation, blunted force-frequency response with reduced active tension at high stimulation frequency, and increased occurrence of spontaneous contractions. Consistently, prolonged Ca(2+) transient in terms of rise and duration are also observed in Δ160E trabeculae and isolated cardiomyocytes. Confocal imaging in cells isolated from Δ160E mice reveals significant, though modest, remodelling of T-tubular architecture. A two-photon random access microscope is employed to dissect the spatio-temporal relationship between T-tubular electrical activity and local Ca(2+) release in isolated cardiomyocytes. In Δ160E cardiomyocytes, a significant number of T-tubules (>20%) fails to propagate action potentials, with consequent delay of local Ca(2+) release. At variance with wild-type, we also observe significantly increased variability of local Ca(2+) transient rise as well as higher Ca(2+)-spark frequency. Although T-tubule structural remodelling in Δ160E myocytes is modest, T-tubule functional defects determine non-homogeneous Ca(2+) release and delayed myofilament activation that significantly contribute to mechanical dysfunction. PMID:26714042

  8. Novel insights on the relationship between T-tubular defects and contractile dysfunction in a mouse model of hypertrophic cardiomyopathy

    PubMed Central

    Crocini, C.; Ferrantini, C.; Scardigli, M.; Coppini, R.; Mazzoni, L.; Lazzeri, E.; Pioner, J.M.; Scellini, B.; Guo, A.; Song, L.S.; Yan, P.; Loew, L.M.; Tardiff, J.; Tesi, C.; Vanzi, F.; Cerbai, E.; Pavone, F.S.; Sacconi, L.; Poggesi, C.

    2016-01-01

    Abnormalities of cardiomyocyte Ca2 + homeostasis and excitation–contraction (E–C) coupling are early events in the pathogenesis of hypertrophic cardiomyopathy (HCM) and concomitant determinants of the diastolic dysfunction and arrhythmias typical of the disease. T-tubule remodelling has been reported to occur in HCM but little is known about its role in the E–C coupling alterations of HCM. Here, the role of T-tubule remodelling in the electro-mechanical dysfunction associated to HCM is investigated in the Δ160E cTnT mouse model that expresses a clinically-relevant HCM mutation. Contractile function of intact ventricular trabeculae is assessed in Δ160E mice and wild-type siblings. As compared with wild-type, Δ160E trabeculae show prolonged kinetics of force development and relaxation, blunted force-frequency response with reduced active tension at high stimulation frequency, and increased occurrence of spontaneous contractions. Consistently, prolonged Ca2 + transient in terms of rise and duration are also observed in Δ160E trabeculae and isolated cardiomyocytes. Confocal imaging in cells isolated from Δ160E mice reveals significant, though modest, remodelling of T-tubular architecture. A two-photon random access microscope is employed to dissect the spatio-temporal relationship between T-tubular electrical activity and local Ca2 + release in isolated cardiomyocytes. In Δ160E cardiomyocytes, a significant number of T-tubules (> 20%) fails to propagate action potentials, with consequent delay of local Ca2 + release. At variance with wild-type, we also observe significantly increased variability of local Ca2 + transient rise as well as higher Ca2 +-spark frequency. Although T-tubule structural remodelling in Δ160E myocytes is modest, T-tubule functional defects determine non-homogeneous Ca2 + release and delayed myofilament activation that significantly contribute to mechanical dysfunction. PMID:26714042

  9. The prognostic value of standardized reference values for speckle-tracking global longitudinal strain in hypertrophic cardiomyopathy.

    PubMed

    Hartlage, Gregory R; Kim, Jonathan H; Strickland, Patrick T; Cheng, Alan C; Ghasemzadeh, Nima; Pernetz, Maria A; Clements, Stephen D; Williams, B Robinson

    2015-03-01

    Speckle-tracking left ventricular global longitudinal strain (GLS) assessment may provide substantial prognostic information for hypertrophic cardiomyopathy (HCM) patients. Reference values for GLS have been recently published. We aimed to evaluate the prognostic value of standardized reference values for GLS in HCM patients. An analysis of HCM clinic patients who underwent GLS was performed. GLS was defined as normal (more negative or equal to -16%) and abnormal (less negative than -16%) based on recently published reference values. Patients were followed for a composite of events including heart failure hospitalization, sustained ventricular arrhythmia, and all-cause death. The power of GLS to predict outcomes was assessed relative to traditional clinical and echocardiographic variables present in HCM. 79 HCM patients were followed for a median of 22 months (interquartile range 9-30 months) after imaging. During follow-up, 15 patients (19%) met the primary outcome. Abnormal GLS was the only echocardiographic variable independently predictive of the primary outcome [multivariate Hazard ratio 5.05 (95% confidence interval 1.09-23.4, p = 0.038)]. When combined with traditional clinical variables, abnormal GLS remained independently predictive of the primary outcome [multivariate Hazard ratio 5.31 (95 % confidence interval 1.18-24, p = 0.030)]. In a model including the strongest clinical and echocardiographic predictors of the primary outcome, abnormal GLS demonstrated significant incremental benefit for risk stratification [net reclassification improvement 0.75 (95 % confidence interval 0.21-1.23, p < 0.0001)]. Abnormal GLS is an independent predictor of adverse outcomes in HCM patients. Standardized use of GLS may provide significant incremental value over traditional variables for risk stratification.

  10. Dyssynchronization reduces dynamic obstruction without affecting systolic function in patients with hypertrophic obstructive cardiomyopathy: a pilot study.

    PubMed

    Giraldeau, Geneviève; Duchateau, Nicolas; Bijnens, Bart; Gabrielli, Luigi; Penela, Diego; Evertz, Reinder; Mont, Lluis; Brugada, Josep; Berruezo, Antonio; Sitges, Marta

    2016-08-01

    Dyssynchrony from biventricular pacing (BiV) can reduce dynamic obstruction in hypertrophic obstructive cardiomyopathy (HOCM), but its consequences on the left ventricular (LV) systolic function are unknown. We evaluate changes in LV systolic function and assess the effectiveness of BiV in HOCM. Thirteen patients with HOCM (55 [33/75] years, five males) received a BiV device and underwent 2D transthoracic echocardiography before the implantation and at 12 months follow-up. Global longitudinal and radial strain, and the timing of segmental displacement curves were measured by commercial speckle-tracking software to assess LV systolic function and dyssynchrony. Peak gradient in the LV outflow tract (LVOT) significantly decreased from 80 [51/100] to 30 [5/66] mmHg (p = 0.005). LV global strain was preserved from baseline to follow-up: 35.1 [20.2/43.8] % vs. 32.6 [27.1/44.1] %, p = NS (radial), and -16.6 [-19.1/-14.4] % vs. -15.7 [-17.0/-14.2] %, p = NS (longitudinal). Dyssynchrony analysis using displacement curves showed inversion of wall motion timing with earlier displacement of the lateral wall at follow-up only in patients with reduction in LVOT gradient. BiV reduces LVOT obstruction in patients with HOCM when dyssynchronization of LV motion and inversion of the timing of LV wall activation are reached. Notably, this does not lead to further deterioration of LV systolic function at mid-term follow-up.

  11. Three-dimensional haemodynamics in patients with obstructive and non-obstructive hypertrophic cardiomyopathy assessed by cardiac magnetic resonance

    PubMed Central

    Allen, Bradley D.; Choudhury, Lubna; Barker, Alex J.; van Ooij, Pim; Collins, Jeremy D.; Bonow, Robert O.; Carr, James C.; Markl, Michael

    2015-01-01

    Aims The left ventricular outflow tract (LVOT) peak pressure gradient is an important haemodynamic descriptor in patients with hypertrophic cardiomyopathy (HCM); however, secondary alterations in aortic blood flow have not been well described in these patients. Aortic flow derangement is not easily assessed by traditional imaging methods, but may provide unique characterization of this disease. In this study, we demonstrated how four-dimensional (4D) flow MRI can assess LVOT peak pressure gradients in HCM patients and also evaluated the ascending aorta (AAo) haemodynamic derangement associated with HCM. Methods and results Obstructive (n = 12) and non-obstructive (n = 18) HCM patients were included in the study along with 10 normal volunteers. 4D flow MRI was used to visualize three-dimensional (3D) blood flow patterns within the LVOT and AAo, which were graded for the presence of helical flow as a marker of flow derangement (absent = 0, mild/moderate = 1, and severe = 2). MRI-estimated pressure gradient (ΔPMRI) was calculated from the peak systolic 3D blood velocity profile within the LVOT. There was higher grade helical flow in obstructive HCM patients compared with non-obstructive patients (P = 0.04) and volunteers (P < 0.001). Non-obstructive patients also had higher helix grade than volunteers (P = 0.002). There was a significant correlation between helical grade and increasing ΔPMRI (rS = 0.69, P < 0.001). Systolic anterior motion (SAM) of the mitral valve was associated with both increasing helix grade (P < 0.001) and ΔPMRI (P = 0.006). Conclusions Ascending aorta flow derangement occurs in both obstructive and non-obstructive HCM patients and can be identified using 4D flow MRI. The degree of flow derangement correlates with LVOT gradient, SAM, and outflow tract geometry. PMID:25108915

  12. Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery

    NASA Technical Reports Server (NTRS)

    Qin, J. X.; Shiota, T.; Lever, H. M.; Kapadia, S. R.; Sitges, M.; Rubin, D. N.; Bauer, F.; Greenberg, N. L.; Agler, D. A.; Drinko, J. K.; Martin, M.; Tuzcu, E. M.; Smedira, N. G.; Lytle, B.; Thomas, J. D.

    2001-01-01

    OBJECTIVES: This study was conducted to evaluate follow-up results in patients with hypertrophic obstructive cardiomyopathy (HOCM) who underwent either percutaneous transluminal septal myocardial ablation (PTSMA) or septal myectomy. BACKGROUND: Controversy exists with regard to these two forms of treatment for patients with HOCM. METHODS: Of 51 patients with HOCM treated, 25 were treated by PTSMA and 26 patients via myectomy. Two-dimensional echocardiograms were performed before both procedures, immediately afterwards and at a three-month follow-up. The New York Heart Association (NYHA) functional class was obtained before the procedures and at follow-up. RESULTS: Interventricular septal thickness was significantly reduced at follow-up in both groups (2.3 +/- 0.4 cm vs. 1.9 +/- 0.4 cm for septal ablation and 2.4 +/- 0.6 cm vs. 1.7 +/- 0.2 cm for myectomy, both p < 0.001). Estimated by continuous-wave Doppler, the resting pressure gradient (PG) across the left ventricular outflow tract (LVOT) significantly decreased immediately after the procedures in both groups (64 +/- 39 mm Hg vs. 28 +/- 29 mm Hg for PTSMA, 62 +/- 43 mm Hg vs. 7 +/- 7 mm Hg for myectomy, both p < 0.0001). At three-month follow-up, the resting PG remained lower in the PTSMA and myectomy groups (24 +/- 19 mm Hg and 11 +/- 6 mm Hg, respectively, vs. those before procedures, both p < 0.0001). The NYHA functional class was also significantly improved in both groups (3.5 +/- 0.5 vs. 1.9 +/- 0.7 for PTSMA, 3.3 +/- 0.5 vs. 1.5 +/- 0.7 for myectomy, both p < 0.0001). CONCLUSIONS: Both myectomy and PTSMA reduce LVOT obstruction and significantly improve NYHA functional class in patients with HOCM. However, there are benefits and drawbacks for each therapeutic method that must be counterbalanced when deciding on treatment for LVOT obstruction.

  13. Significance of Late Gadolinium Enhancement at Right Ventricular Attachment to Ventricular Septum in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Chan, Raymond H; Maron, Barry J; Olivotto, Iacopo; Assenza, Gabriele E; Haas, Tammy S; Lesser, John R; Gruner, Christiane; Crean, Andrew M; Rakowski, Harry; Rowin, Ethan; Udelson, James; Lombardi, Massimo; Tomberli, Benedetta; Spirito, Paolo; Formisano, Francesco; Marra, Martina P; Biagini, Elena; Autore, Camillo; Manning, Warren J; Appelbaum, Evan; Roberts, William C; Basso, Cristina; Maron, Martin S

    2015-08-01

    Cardiovascular magnetic resonance (CMR) with extensive late gadolinium enhancement (LGE) is a novel marker for increased risk for sudden death (SD) in patients with hypertrophic cardiomyopathy (HC). Small focal areas of LGE confined to the region of right ventricular (RV) insertion to ventricular septum (VS) have emerged as a frequent and highly visible CMR imaging pattern of uncertain significance. The aim of this study was to evaluate the prognostic significance of LGE confined to the RV insertion area in patients with HC. CMR was performed in 1,293 consecutive patients with HC from 7 HC centers, followed for 3.4 ± 1.7 years. Of 1,293 patients (47 ± 14 years), 134 (10%) had LGE present only in the anterior and/or inferior areas of the RV insertion to VS, occupying 3.7 ± 2.9% of left ventricular myocardium. Neither the presence nor extent of LGE in these isolated areas was a predictor of adverse HC-related risk, including SD (adjusted hazard ratio 0.82, 95% confidence interval 0.45 to 1.50, p = 0.53; adjusted hazard ratio 1.16/10% increase in LGE, 95% confidence interval 0.29 to 4.65, p = 0.83, respectively). Histopathology in 20 HC hearts show the insertion areas of RV attachment to be composed of a greatly expanded extracellular space characterized predominantly by interstitial-type fibrosis and interspersed disorganized myocyte patterns and architecture. In conclusion, LGE confined to the insertion areas of RV to VS was associated with low risk of adverse events (including SD). Gadolinium pooling in this region of the left ventricle does not reflect myocyte death and repair with replacement fibrosis or scarring.

  14. T1 Measurements Identify Extracellular Volume Expansion in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy

    PubMed Central

    Ho, Carolyn Y.; Abbasi, Siddique A.; Neilan, Tomas G.; Shah, Ravi V.; Chen, Yucheng; Heydari, Bobak; Cirino, Allison L.; Lakdawala, Neal K.; Orav, E. John; González, Arantxa; López, Begoña; Díez, Javier; Jerosch-Herold, Michael; Kwong, Raymond Y.

    2013-01-01

    Background Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere mutations appear to induce profibrotic changes before left ventricular hypertrophy (LVH) develops. To further evaluate these processes, we used cardiac magnetic resonance (CMR) with T1 measurements on a genotyped HCM population to quantify myocardial extracellular volume (ECV). Methods and Results Sarcomere mutation carriers with LVH (G+/LVH+, n = 37) and without LVH (G+/LVH−, n = 29); HCM patients without mutations (sarcomere-negative HCM, n = 11); and healthy controls (n = 11) underwent contrast CMR, measuring T1 times pre- and post-gadolinium infusion. Concurrent echocardiography and serum biomarkers of collagen synthesis, hemodynamic stress, and myocardial injury were also available in a subset. Compared to controls, ECV was increased in patients with overt HCM, as well as G+/LVH− mutation carriers (ECV= 0.36±0.01, 0.33±0.01, 0.27±0.01 in G+/LVH+, G+/LVH−, controls, respectively, P≤0.001 for all comparisons). ECV correlated with NT-proBNP levels (r = 0.58, P<0.001) and global E’ velocity (r = −0.48, P<0.001). Late gadolinium enhancement (LGE) was present in >60% of overt HCM patients but absent from G+/LVH− subjects. Both ECV and LGE were more extensive in sarcomeric HCM than sarcomere-negative HCM. Conclusions Myocardial ECV is increased in HCM sarcomere mutation carriers even in the absence of LVH. These data provide additional support that fibrotic remodeling is triggered early in disease pathogenesis. Quantifying ECV may help characterize the development myocardial fibrosis in HCM and ultimately assist in developing novel disease-modifying therapy, targeting interstitial fibrosis. PMID:23549607

  15. Mechanical and energetic properties of papillary muscle from ACTC E99K transgenic mouse models of hypertrophic cardiomyopathy

    PubMed Central

    Song, Weihua; Vikhorev, Petr G.; Kashyap, Mavin N.; Rowlands, Christina; Ferenczi, Michael A.; Woledge, Roger C.; MacLeod, Kenneth; Curtin, Nancy A.

    2013-01-01

    We compared the contractile performance of papillary muscle from a mouse model of hypertrophic cardiomyopathy [α-cardiac actin (ACTC) E99K mutation] with nontransgenic (non-TG) littermates. In isometric twitches, ACTC E99K papillary muscle produced three to four times greater force than non-TG muscle under the same conditions independent of stimulation frequency and temperature, whereas maximum isometric force in myofibrils from these muscles was not significantly different. ACTC E99K muscle relaxed slower than non-TG muscle in both papillary muscle (1.4×) and myofibrils (1.7×), whereas the rate of force development after stimulation was the same as non-TG muscle for both electrical stimulation in intact muscle and after a Ca2+ jump in myofibrils. The EC50 for Ca2+ activation of force in myofibrils was 0.39 ± 0.33 μmol/l in ACTC E99K myofibrils and 0.80 ± 0.11 μmol/l in non-TG myofibrils. There were no significant differences in the amplitude and time course of the Ca2+ transient in myocytes from ACTC E99K and non-TG mice. We conclude that hypercontractility is caused by higher myofibrillar Ca2+ sensitivity in ACTC E99K muscles. Measurement of the energy (work + heat) released in actively cycling heart muscle showed that for both genotypes, the amount of energy turnover increased with work done but with decreasing efficiency as energy turnover increased. Thus, ACTC E99K mouse heart muscle produced on average 3.3-fold more work than non-TG muscle, and the cost in terms of energy turnover was disproportionately higher than in non-TG muscles. Efficiency for ACTC E99K muscle was in the range of 11–16% and for non-TG muscle was 15–18%. PMID:23604709

  16. The structural and functional effects of the familial hypertrophic cardiomyopathy-linked cardiac troponin C mutation, L29Q

    PubMed Central

    Robertson, Ian M.; Sevrieva, Ivanka; Li, Monica X.; Irving, Malcolm; Sun, Yin-Biao; Sykes, Brian D.

    2015-01-01

    Familial hypertrophic cardiomyopathy (FHC) is characterized by severe abnormal cardiac muscle growth. The traditional view of disease progression in FHC is that an increase in the Ca2 +-sensitivity of cardiac muscle contraction ultimately leads to pathogenic myocardial remodeling, though recent studies suggest this may be an oversimplification. For example, FHC may be developed through altered signaling that prevents downstream regulation of contraction. The mutation L29Q, found in the Ca2 +-binding regulatory protein in heart muscle, cardiac troponin C (cTnC), has been linked to cardiac hypertrophy. However, reports on the functional effects of this mutation are conflicting, and our goal was to combine in vitro and in situ structural and functional data to elucidate its mechanism of action. We used nuclear magnetic resonance and circular dichroism to solve the structure and characterize the backbone dynamics and stability of the regulatory domain of cTnC with the L29Q mutation. The overall structure and dynamics of cTnC were unperturbed, although a slight rearrangement of site 1, an increase in backbone flexibility, and a small decrease in protein stability were observed. The structure and function of cTnC was also assessed in demembranated ventricular trabeculae using fluorescence for in situ structure. L29Q reduced the cooperativity of the Ca2 +-dependent structural change in cTnC in trabeculae under basal conditions and abolished the effect of force-generating myosin cross-bridges on this structural change. These effects could contribute to the pathogenesis of this mutation. PMID:26341255

  17. Cardiac-Specific Over-Expression of Epidermal Growth Factor Receptor 2 (ErbB2) Induces Pro-Survival Pathways and Hypertrophic Cardiomyopathy in Mice

    PubMed Central

    Guo, Xin; Belmonte, Frances; Kang, Byunghak; Bedja, Djahida; Pin, Scott; Tsuchiya, Noriko; Gabrielson, Kathleen

    2012-01-01

    Background Emerging evidence shows that ErbB2 signaling has a critical role in cardiomyocyte physiology, based mainly on findings that blocking ErbB2 for cancer therapy is toxic to cardiac cells. However, consequences of high levels of ErbB2 activity in the heart have not been previously explored. Methodology/Principal Findings We investigated consequences of cardiac-restricted over-expression of ErbB2 in two novel lines of transgenic mice. Both lines develop striking concentric cardiac hypertrophy, without heart failure or decreased life span. ErbB2 transgenic mice display electrocardiographic characteristics similar to those found in patients with Hypertrophic Cardiomyopathy, with susceptibility to adrenergic-induced arrhythmias. The hypertrophic hearts, which are 2–3 times larger than those of control littermates, express increased atrial natriuretic peptide and β-myosin heavy chain mRNA, consistent with a hypertrophic phenotype. Cardiomyocytes in these hearts are significantly larger than wild type cardiomyocytes, with enlarged nuclei and distinctive myocardial disarray. Interestingly, the over-expression of ErbB2 induces a concurrent up-regulation of multiple proteins associated with this signaling pathway, including EGFR, ErbB3, ErbB4, PI3K subunits p110 and p85, bcl-2 and multiple protective heat shock proteins. Additionally, ErbB2 up-regulation leads to an anti-apoptotic shift in the ratio of bcl-xS/xL in the heart. Finally, ErbB2 over-expression results in increased activation of the translation machinery involving S6, 4E-BP1 and eIF4E. The dependence of this hypertrophic phenotype on ErbB family signaling is confirmed by reduction in heart mass and cardiomyocyte size, and inactivation of pro-hypertrophic signaling in transgenic animals treated with the ErbB1/2 inhibitor, lapatinib. Conclusions/Significance These studies are the first to demonstrate that increased ErbB2 over-expression in the heart can activate protective signaling pathways and induce a

  18. Obstructive Form of Hypertrophic Cardiomyopathy-Left Ventricular Outflow Tract Gradient: Novel Methods of Provocation, Monitoring of Biomarkers, and Recent Advances in the Treatment

    PubMed Central

    Dimitrow, Pawel Petkow; Rajtar-Salwa, Renata

    2016-01-01

    Dynamic (latent or/and labile) obstruction of left ventricular outflow (LVOT) was recognized from the earliest clinical descriptions of hypertrophic cardiomyopathy (HCM) and has proved to be a complex phenomenon, as well as arguably the most audible (“visible”) pathophysiological hallmark of this heterogeneous disease. The aim of the current review is focused on two novel issues in a subgroup of obstructive HCM. Firstly, the important methodological problem in HCM is the examination of a subgroup of patients with nonobstructive hypertrophy in resting conditions and hard, but possible provoking obstruction. Recently, investigators have proposed physiological stress test (with double combined stimuli) to disclose such type of patients. The upright exercise is described in the ESC guideline on hypertrophic cardiomyopathy from 2014 and may appear as a candidate for gold standard provocation test. The second novel area of interest is associated with elevated level of signaling biomarkers: hypercoagulation, hemolysis, acquired von Willebrand 2A disease, and enhanced oxidative stress. The accelerated and turbulent flow within narrow LVOT may be responsible for these biochemical disturbances. The most recent advances in the treatment of obstructive HCM are related to nonpharmacological methods of LVOT gradient reduction. This report extensively discusses novel methods. PMID:27247935

  19. A Hypertrophic Cardiomyopathy-associated MYBPC3 Mutation Common in Populations of South Asian Descent Causes Contractile Dysfunction*

    PubMed Central

    Kuster, Diederik W. D.; Govindan, Suresh; Springer, Tzvia I.; Martin, Jody L.; Finley, Natosha L.; Sadayappan, Sakthivel

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) results from mutations in genes encoding sarcomeric proteins, most often MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C). A recently discovered HCM-associated 25-base pair deletion in MYBPC3 is inherited in millions worldwide. Although this mutation causes changes in the C10 domain of cMyBP-C (cMyBP-CC10mut), which binds to the light meromyosin (LMM) region of the myosin heavy chain, the underlying molecular mechanism causing HCM is unknown. In this study, adenoviral expression of cMyBP-CC10mut in cultured adult rat cardiomyocytes was used to investigate protein localization and evaluate contractile function and Ca2+ transients, compared with wild-type cMyBP-C expression (cMyBP-CWT) and controls. Forty-eight hours after infection, 44% of cMyBP-CWT and 36% of cMyBP-CC10mut protein levels were determined in total lysates, confirming equal expression. Immunofluorescence experiments showed little or no localization of cMyBP-CC10mut to the C-zone, whereas cMyBP-CWT mostly showed C-zone staining, suggesting that cMyBP-CC10mut could not properly integrate in the C-zone of the sarcomere. Subcellular fractionation confirmed that most cMyBP-CC10mut resided in the soluble fraction, with reduced presence in the myofilament fraction. Also, cMyBP-CC10mut displayed significantly reduced fractional shortening, sarcomere shortening, and relaxation velocities, apparently caused by defects in sarcomere function, because Ca2+ transients were unaffected. Co-sedimentation and protein cross-linking assays confirmed that C10mut causes the loss of C10 domain interaction with myosin LMM. Protein homology modeling studies showed significant structural perturbation in cMyBP-CC10mut, providing a potential structural basis for the alteration in its mode of interaction with myosin LMM. Therefore, expression of cMyBP-CC10mut protein is sufficient to cause contractile dysfunction in vitro. PMID:25583989

  20. A hypertrophic cardiomyopathy-associated MYBPC3 mutation common in populations of South Asian descent causes contractile dysfunction.

    PubMed

    Kuster, Diederik W D; Govindan, Suresh; Springer, Tzvia I; Martin, Jody L; Finley, Natosha L; Sadayappan, Sakthivel

    2015-02-27

    Hypertrophic cardiomyopathy (HCM) results from mutations in genes encoding sarcomeric proteins, most often MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C). A recently discovered HCM-associated 25-base pair deletion in MYBPC3 is inherited in millions worldwide. Although this mutation causes changes in the C10 domain of cMyBP-C (cMyBP-C(C10mut)), which binds to the light meromyosin (LMM) region of the myosin heavy chain, the underlying molecular mechanism causing HCM is unknown. In this study, adenoviral expression of cMyBP-C(C10mut) in cultured adult rat cardiomyocytes was used to investigate protein localization and evaluate contractile function and Ca(2+) transients, compared with wild-type cMyBP-C expression (cMyBP-C(WT)) and controls. Forty-eight hours after infection, 44% of cMyBP-C(WT) and 36% of cMyBP-C(C10mut) protein levels were determined in total lysates, confirming equal expression. Immunofluorescence experiments showed little or no localization of cMyBP-C(C10mut) to the C-zone, whereas cMyBP-C(WT) mostly showed C-zone staining, suggesting that cMyBP-C(C10mut) could not properly integrate in the C-zone of the sarcomere. Subcellular fractionation confirmed that most cMyBP-C(C10mut) resided in the soluble fraction, with reduced presence in the myofilament fraction. Also, cMyBP-C(C10mut) displayed significantly reduced fractional shortening, sarcomere shortening, and relaxation velocities, apparently caused by defects in sarcomere function, because Ca(2+) transients were unaffected. Co-sedimentation and protein cross-linking assays confirmed that C10(mut) causes the loss of C10 domain interaction with myosin LMM. Protein homology modeling studies showed significant structural perturbation in cMyBP-C(C10mut), providing a potential structural basis for the alteration in its mode of interaction with myosin LMM. Therefore, expression of cMyBP-C(C10mut) protein is sufficient to cause contractile dysfunction in vitro.

  1. Relation of strain by feature tracking and clinical outcome in children, adolescents, and young adults with hypertrophic cardiomyopathy.

    PubMed

    Smith, Brandon M; Dorfman, Adam L; Yu, Sunkyung; Russell, Mark W; Agarwal, Prachi P; Ghadimi Mahani, Maryam; Lu, Jimmy C

    2014-10-15

    Evaluation of hypertrophic cardiomyopathy (HC) in young patients is limited by lack of age-specific norms for wall thickness on cardiovascular magnetic resonance (CMR) images. Left ventricular strain may have a role in identifying and risk stratifying patients with HC, but few data exist for strain measurement on CMR images. In 30 patients (14.1 ± 3.2 years) with clinically diagnosed HC and 24 controls (15.6 ± 2.8 years), strain (radial, longitudinal, and circumferential) was evaluated by 2 experienced readers using CMR feature tracking. In patients with HC, hypertrophied segments had decreased radial (28.0 ± 5.2% vs 58.6 ± 3.9%, p = 0.0002), circumferential (-23.7 ± 1.1% vs -28.3 ± 0.8%, p = 0.004), and longitudinal (-11.2 ± 1.2% vs -21.7 ± 0.8%, p <0.0001) strains versus control segments. Hypertrophied segments had decreased longitudinal (basal segments -12.2 ± 1.9% vs -22.6 ± 1.2%, p = 0.0002), radial (basal segments 22.7 ± 10.8% vs 78.8 ± 7.2%, p = 0.0001), and circumferential (basal segments -22.4 ± 1.7% vs -30.6 ± 1%, p = 0.0004) strains versus nonhypertrophied segments in patients with HC. Longitudinal strain had the lowest intraobserver and interobserver variabilities (coefficient of variability -15.7% and -18.5%). After a median follow-up of 28.1 months (interquartile range [IQR] 4.2 to 33.1), 7 patients with HC with an adverse event outcome (5 ventricular tachycardia, 1 appropriate implantable cardioverter-defibrillator discharge, and 1 death) had reduced global radial (median 39.7%, IQR 39.6% to 46.6% vs 65.4%, IQR 46.1% to 83.4%, p = 0.01) and longitudinal strains (median -16.5%, IQR -18.7% to -15.5% vs -19.7%, IQR -23.8% to -17.5%, p = 0.046) compared with patients with HC without an event. In conclusion, CMR feature tracking detects differences in global and segmental strains and may represent a novel method to predict clinical outcome in patients with HC. Further study is necessary to evaluate longitudinal changes in this population.

  2. Tissue Doppler Imaging Combined with Advanced 12-Lead ECG Analysis Might Improve Early Diagnosis of Hypertrophic Cardiomyopathy in Childhood

    NASA Technical Reports Server (NTRS)

    Femlund, E.; Schlegel, T.; Liuba, P.

    2011-01-01

    Optimization of early diagnosis of childhood hypertrophic cardiomyopathy (HCM) is essential in lowering the risk of HCM complications. Standard echocardiography (ECHO) has shown to be less sensitive in this regard. In this study, we sought to assess whether spatial QRS-T angle deviation, which has shown to predict HCM in adults with high sensitivity, and myocardial Tissue Doppler Imaging (TDI) could be additional tools in early diagnosis of HCM in childhood. Methods: Children and adolescents with familial HCM (n=10, median age 16, range 5-27 years), and without obvious hypertrophy but with heredity for HCM (n=12, median age 16, range 4-25 years, HCM or sudden death with autopsy-verified HCM in greater than or equal to 1 first-degree relative, HCM-risk) were additionally investigated with TDI and advanced 12-lead ECG analysis using Cardiax(Registered trademark) (IMED Co Ltd, Budapest, Hungary and Houston). Spatial QRS-T angle (SA) was derived from Kors regression-related transformation. Healthy age-matched controls (n=21) were also studied. All participants underwent thorough clinical examination. Results: Spatial QRS-T angle (Figure/ Panel A) and septal E/Ea ratio (Figure/Panel B) were most increased in HCM group as compared to the HCM-risk and control groups (p less than 0.05). Of note, these 2 variables showed a trend toward higher levels in HCM-risk group than in control group (p=0.05 for E/Ea and 0.06 for QRS/T by ANOVA). In a logistic regression model, increased SA and septal E/Ea ratio appeared to significantly predict both the disease (Chi-square in HCM group: 9 and 5, respectively, p less than 0.05 for both) and the risk for HCM (Chi-square in HCM-risk group: 5 and 4 respectively, p less than 0.05 for both), with further increased predictability level when these 2 variables were combined (Chi-square 10 in HCM group, and 7 in HCM-risk group, p less than 0.01 for both). Conclusions: In this small material, Tissue Doppler Imaging and spatial mean QRS-T angle

  3. Structural kinetics of cardiac troponin C mutants linked to familial hypertrophic and dilated cardiomyopathy in troponin complexes.

    PubMed

    Dong, Wen-Ji; Xing, Jun; Ouyang, Yexin; An, Jianli; Cheung, Herbert C

    2008-02-01

    The key events in regulating cardiac muscle contraction involve Ca(2+) binding to and release from cTnC (troponin C) and structural changes in cTnC and other thin filament proteins triggered by Ca(2+) movement. Single mutations L29Q and G159D in human cTnC have been reported to associate with familial hypertrophic and dilated cardiomyopathy, respectively. We have examined the effects of these individual mutations on structural transitions in the regulatory N-domain of cTnC triggered by Ca(2+) binding and dissociation. This study was carried out with a double mutant or triple mutants of cTnC, reconstituted into troponin with tryptophanless cTnI and cTnT. The double mutant, cTnC(L12W/N51C) labeled with 1,5-IAEDANS at Cys-51, served as a control to monitor Ca(2+)-induced opening and closing of the N-domain by Förster resonance energy transfer (FRET). The triple mutants contained both L12W and N51C labeled with 1,5-IAEDANS, and either L29Q or G159D. Both mutations had minimal effects on the equilibrium distance between Trp-12 and Cys-51-AEDANS in the absence or presence of bound Ca(2+). L29Q had no effect on the closing rate of the N-domain triggered by release of Ca(2+), but reduced the Ca(2+)-induced opening rate. G159D reduced both the closing and opening rates. Previous results showed that the closing rate of cTnC N-domain triggered by Ca(2+) dissociation was substantially enhanced by PKA phosphorylation of cTnI. This rate enhancement was abolished by L29Q or G159D. These mutations alter the kinetics of structural transitions in the regulatory N-domain of cTnC that are involved in either activation (L29Q) or deactivation (G159D). Both mutations appear to be antagonistic toward phosphorylation signaling between cTnI and cTnC.

  4. Value of Genetic Testing for the Prediction of Long-Term Outcome in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    van Velzen, Hannah G; Vriesendorp, Pieter A; Oldenburg, Rogier A; van Slegtenhorst, Marjon A; van der Velden, Jolanda; Schinkel, Arend F L; Michels, Michelle

    2016-09-15

    Pathogenic gene mutations are found in about 50% of patients with hypertrophic cardiomyopathy (HC). Previous studies have shown an association between sarcomere mutations and medium-term outcome. The association with long-term outcome has not been described. The aim of this cohort study was to assess the long-term outcomes of patients with genotype positive (G+) and genotype negative (G-) HC. The study population consisted of 626 patients with HC (512 probands and 114 relatives) who underwent phenotyping and genetic testing from 1985 to 2014. End points were all-cause mortality, cardiovascular (CV) mortality, heart failure (HF)-related mortality, and sudden cardiac death/aborted sudden cardiac death (SCD/aborted SCD). Kaplan-Meier and multivariate Cox regression analyses were performed. A pathogenic mutation was detected in 327 patients (52%). G+ probands were younger than G- probands (46 ± 15 vs 55 ± 15 years, p <0.001), had more non sustained ventricular tachycardia (34% vs 13%; p <0.001), more often a history of syncope (14% vs 7%; p = 0.016), and more extreme hypertrophy (maximal wall thickness ≥30 mm, 7% vs 1%; p <0.001). G- probands were more symptomatic (New York Heart Association ≥II, 73% vs 53%, p <0.001) and had higher left ventricular outflow tract gradients (42 ± 39 vs 29 ± 33 mm Hg, p = 0.001). During 12 ± 9 years of follow-up, G+ status was an independent risk factor for all-cause mortality (hazard ratio [HR] 1.90, 95% CI 1.14 to 3.15; p = 0.014), CV mortality (HR 2.82, 95% CI 1.49 to 5.36; p = 0.002), HF-related mortality (HR 6.33, 95% CI 1.79 to 22.41; p = 0.004), and SCD/aborted SCD (HR 2.88, 95% CI 1.23 to 6.71; p = 0.015). In conclusion, during long-term follow-up, patients with G+ HC are at increased risk of all-cause death, CV death, HF-related death, and SCD/aborted SCD.

  5. Usefulness of noninvasive detection of left ventricular diastolic abnormalities during isometric stress in hypertrophic cardiomyopathy and in athletes.

    PubMed

    Manolas, J; Kyriakidis, M; Anastasakis, A; Pegas, P; Rigopoulos, A; Theopistou, A; Toutouzas, P

    1998-02-01

    We showed previously that the handgrip apexcardiographic test (HAT) is a useful method for detecting left ventricular (LV) diastolic abnormalities in patients with coronary artery disease and systemic hypertension. This study evaluates the use of HAT for assessing the prevalence and types of exercise-induced diastolic abnormalities in patients with obstructive (n = 31) and nonobstructive (n = 35) hypertrophic cardiomyopathy (HC) as well as its potential value for separating healthy subjects and athletes from patients with HC. We obtained a HAT in 66 consecutive patients with HC and in 72 controls (52 healthy volunteers and 20 athletes). A positive HAT was defined by the presence of one of the following: (1) relative A wave to total height (A/H) during or after handgrip > 21% (compliance type), (2) total apexcardiographic relaxation time (TART) > 143 ms or the heart rate corrected TART (TARTI) during handgrip < 0.14, (relaxation type), (3) both types present (mixed type), and (4) diastolic amplitude time index (DATI = TARTI/[A/D]) during handgrip < 0.27. Of the controls, only 1 of 52 healthy subjects and 1 of 20 athletes showed a positive HAT, whereas of the total HC cohort 63 of 66 patients (95%) had a positive result. There was no significant difference in the distribution of these types between obstructive and nonobstructive HC. Further, no LV diastolic abnormalities were present in 10 of 35 patients (29%) with nonobstructive HC at rest and in 3 of 35 patients (9%) during handgrip, whereas of the patients with obstructive HC only 1 of 31 (3%) had no LV diastolic abnormalities at rest and none during handgrip. Based on HAT data, our study demonstrates that in HC (1) LV diastolic abnormalities are very frequent during handgrip; (2) patients with nonobstructive HC show significantly fewer LV diastolic abnormalities at rest than those with obstructive HC; and (3) no significant difference exists between obstructive and nonobstructive HC in the prevalence of types of

  6. [Obstruction of the right ventricular outflow tract on the obstructive hypertrophic cardiomyopathy. Case report and literature review].

    PubMed

    Soriano, Patricia Pérez; Estrada, Catalina Lomelí; Peralta, Martin Rosas; Negrete, J Antonio Lorenzo; González, Celso Mendoza; Ortiz, Arturo Méndez; Attié, Fause

    2008-01-01

    OHC is a disorder with a broad spectrum of morphological, functional and genetics abnormalities. The Obstruction on the Right Ventricular Outflow (OHCRV) is not expected most of the time, that's way it is not usually detected and rarely mentioned in the cardiological literature. Its clinical presentation may include basically systemic venous hypertension symptoms that come with the hypertrophic cardyomiopathy manifestations. The manifestations of an apparent Right Ventricular Hypertrophic (RVH) in the ECG are probably due to the huge septal vector that activates the septum with a major thickness. The clinical confirmation of the obstruction on the OHCRV produced by a considerable asymmetric septal hypertrophic is easily shown with bidimensional an Doppler echocardiography.

  7. [Mitral Valve Replacement with a Low-Profile Bioprosthesis in Combination with Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy;Report of a Case].

    PubMed

    Furukawa, Koji; Sakaguchi, Shuhei; Nakamura, Eisaku; Yano, Mitsuhiro

    2015-06-01

    An 83-year-old woman diagnosed with hypertrophic obstructive cardiomyopathy was referred to our hospital. Her echocardiogram revealed diffuse left ventricular hypertrophy, severe mitral valve regurgitation with systolic anterior motion of the mitral valve, and left ventricular obstruction with a peak outflow gradient of 142 mmHg. Cardiac catheterization revealed a peak pressure gradient of 60 mmHg across the left ventricular outflow tract. Because of the patient's advanced age, as well as uncertainty regarding our ability to resolve her mitral regurgitation, we performed mitral valve replacement with a St. Jude Medical Epic porcine low-profile bioprosthesis in combination with septal myectomy. The patient's postoperative course was uneventful. At 1 year after the operation, her functional status was New York Heart Association class I. The echocardiogram showed the peak outflow gradient markedly decreased to 9 mmHg. PMID:26066877

  8. Sporadic myopathy, myoclonus, leukoencephalopathy, neurosensory deafness, hypertrophic cardiomyopathy and insulin resistance associated with the mitochondrial 8306 T>C MTTK mutation.

    PubMed

    Cardaioli, Elena; Malfatti, Edoardo; Battisti, Carla; Da Pozzo, Paola; Rubegni, Anna; Gallus, Gian Nicola; Malandrini, Alessandro; Federico, Antonio

    2012-10-15

    We report a new T8306C transition in the D-stem of the MTTK gene of a 67-year-old man who manifested severe adult onset myopathy, myoclonus, leukoencephalopathy, neurosensory hypoacusis, hypertrophic cardiomyopathy and insulin resistance. No other family member was affected, suggesting that our patient was a sporadic case. The T8306C mutation was heteroplasmic in several tissues of the proband, while it was absent from his asymptomatic siblings. Single fibre analysis confirmed the segregation of higher mutational load in cytochrome c oxidase-deficient fibres. The mutation T8306C is predicted to disrupt a highly conserved base pair and was not found in more than 120 controls. This finding broadens the phenotypic and molecular spectrum of mitochondrial tRNA(Lys) associated disorders. PMID:22925535

  9. Hypertrophic cardiomyopathy mutations in the calponin-homology domain of ACTN2 affect actin binding and cardiomyocyte Z-disc incorporation

    PubMed Central

    Haywood, Natalie J.; Wolny, Marcin; Rogers, Brendan; Trinh, Chi H.; Shuping, Yu; Edwards, Thomas A.; Peckham, Michelle

    2016-01-01

    α-Actinin-2 (ACTN2) is the only muscle isoform of α-actinin expressed in cardiac muscle. Mutations in this protein have been implicated in mild to moderate forms of hypertrophic cardiomyopathy (HCM). We have investigated the effects of two mutations identified from HCM patients, A119T and G111V, on the secondary and tertiary structure of a purified actin binding domain (ABD) of ACTN2 by circular dichroism and X-ray crystallography, and show small but distinct changes for both mutations. We also find that both mutants have reduced F-actin binding affinity, although the differences are not significant. The full length mEos2 tagged protein expressed in adult cardiomyocytes shows that both mutations additionally affect Z-disc localization and dynamic behaviour. Overall, these two mutations have small effects on structure, function and behaviour, which may contribute to a mild phenotype for this disease. PMID:27287556

  10. [Repeated percutaneous transluminal septal myocardial ablation leads to reduction of left ventricular outflow-tract pressure gradient in hypertrophic obstructive cardiomyopathy: a case report].

    PubMed

    Takeda, Masafumi; Mori, Takao; Ohashi, Yoshitaka; Ichikawa, Shinobu; Terashima, Mitsuyasu; Ejiri, Junya; Awano, Kojiro

    2006-06-01

    A 61-year-old man with hypertrophic obstructive cardiomyopathy was treated twice with percutaneous transluminal septal myocardial ablation (PTSMA). The first procedure improved the left ventricular outflow tract pressure gradient (LVOTG) from 148 to 48 mmHg and the New York Heart Association (NYHA) class from III to II in a week. However, the LVOTG increased to 197 mmHg and the NYHA class worsened to III within 3 months. In spite of medical treatment with beta-blocker, syncope attack occurred suddenly. Repeated PTSMA was performed. Just after the second procedure, the LVOTG did not decrease. However, the LVOTG decreased to 81 mmHg and the NYHA class improved to II with 3 months. The different response of pressure gradient in the acute and chronic phase with repeated PTSMA was interesting. PMID:16800375

  11. MYC-mediated synthetic lethality for treatment of hematological malignancies.

    PubMed

    Li, Xin; Zhang, Xin A; Xie, Wei; Li, Xiaoqing; Huang, Shiang

    2015-01-01

    Deregulated c-MYC expression is found in many human malignancies. MYC activation induces multiple lineages of hematological malignancies in single Myc transgenic mice. MYC inactivation causes tumor regression. MYC is therefore an attractive target for cancer treatment. However, little progress has been made in the development and application of targeted MYC inactivation in clinical practice. In double Myc transgenic mouse models, Myc-driven leukemogenesis and lymphomagenesis can be accelerated by transduction of non-MYC oncogenes, leading to dual addiction to MYC and the non-MYC oncogenes. Wang et al. (2004) first established the concept of MYC-mediated synthetic lethality (MYC-SL). MYC overexpression sensitized cells to TRAILand DR5-agonist-induced apoptosis. This suggests that MYC-dependent tumor cells may be killed by targeting partner oncogenes of MYC. Many small molecule inhibitors (SMIs) have been proven to induce MYC-SL by targeting AUK-B, Brd4, CDK1, CHK1, MCL-1, the mTOR/4E-BP1/eIF4E pathway, and PIM1/2. Compared with conventional treatment approaches, SMI-induced MYC-SL displays highly selective anticancer activity and much lower cytotoxicity to normal cells. SMI-induced MYC-SL can reverse eIF4F- and PIM2-induced multiple chemoresistance. The combination of an SMI with chemotherapeutic agents can elevate chemotherapy efficacy by enhancing chemosensitivity. This combination will be a promising novel approach to treating MYC-dependent tumors by inducing MYC-SL. PMID:25564254

  12. Maternally inherited hypertrophic cardiomyopathy due to a novel T-to-C transition at nucleotide 9997 in the mitochondrial tRNA{sup glycine} gene

    SciTech Connect

    Merante, F.; Tein, I.; Benson, L.; Robinson, B.H.

    1994-09-01

    The authors report a unique heteroplasmic T-to-C transition at nucleotide 9997 in the mitochondrial tRNA{sup glycine} gene in a multiplex family who manifested nonobstructive cardiomyopathy. The degree of mtDNA heteroplasmy generally correlated with the severity of the symptoms. This T-to-C transition disrupts hydrogen bonding in the region adjacent to the acceptor stem of the tRNA molecule. The thymine residue at position 9997 is highly conserved in mammals, as well as in various vertebrates and invertebrates. A PCR diagnostic test for the presence of the 9997 T-to-C transition revealed that the base change was always present in high proportion in affected family members, not present in unaffected family members, and never present in control subjects from various ethnic groups (25 groups sampled, 42 individuals), thus ruling out the possibility that this change represents a polymorphic variant in the general population. The degree of heteroplasmy in lymphoblast cultures also correlated with the level of enzyme activity present for cytochrome c oxidase (complex IV) and succinate cytochrome c oxidoreductase (complexes II and III). The absence of previously reported mtDNA mutations associated with hypertrophic cardiomyopathy was verified by both PCR diagnostic procedures and sequence analysis. All mitochondrial tRNA genes, as well as genes encoding ATPase subunits 6 and 8, were sequenced and found not to possess base changes consistent with the clinical profile. More detailed biochemical and molecular biological investigations are discussed. 51 refs., 6 figs., 4 tabs.

  13. Prognostic value of non-sustained ventricular tachycardia and the potential role of amiodarone treatment in hypertrophic cardiomyopathy: assessment in an unselected non-referral based patient population

    PubMed Central

    Cecchi, F; Olivotto, I; Montereggi, A; Squillatini, G; Dolara, A; Maron, B

    1998-01-01

    Background—Amiodarone has been reported to reduce the likelihood of sudden death in patients with hypertrophic cardiomyopathy (HCM). However, data regarding the clinical course in HCM have traditionally come from selected referral populations biased toward assessment of high risk patients.
Aims—To evaluate antiarrhythmic treatment for sudden death in an HCM population not subject to tertiary referral bias, closely resembling the true disease state present in the community.
Methods—Cardiovascular mortality was assessed in relation to the occurrence of non-sustained ventricular tachycardia (NSVT) on 24 or 48 hour ambulatory Holter recording, a finding previously regarded as a marker for sudden death, particularly when the arrhythmia was frequent, repetitive or prolonged. 167 consecutive patients were analysed by multiple Holter ECG recordings (mean (SD) 157 (129) hours) and followed for a mean of 10 (5) years. Only patients with multiple repetitive NSVT were treated with amiodarone, and in relatively low doses (220 (44) mg/day).
Results—Nine HCM related deaths occurred: 8 were the consequence of congestive heart failure, but only 1 was sudden and unexpected. Three groups of patients were segregated based on their NSVT profile: group 1 (n = 39), multiple (⩾ 2 runs) and repetitive bursts (on ⩾ 2 Holters) of NSVT, or prolonged runs of ventricular tachycardia, included 4 deaths due to heart failure; group 2 (n = 38), isolated infrequent bursts of NSVT, included 1 sudden death; group 3 (n = 90), without NSVT, included 4 heart failure deaths. Kaplan-Meier survival analysis showed no significant differences in survival between the three groups throughout follow up.
Conclusions—In an unselected patient population with HCM, isolated, non-repetitive bursts of NSVT were not associated with adverse prognosis and so this arrhythmia does not appear to justify chronic antiarrhythmic treatment. Amiodarone, administered in relatively low

  14. Predictive Values of N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin I for Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy

    PubMed Central

    Zhang, Changlin; Liu, Rong; Yuan, Jiansong; Cui, Jingang; Hu, Fenghuan; Yang, Weixian; Zhang, Yan; Chen, Youzhou; Qiao, Shubin

    2016-01-01

    Background Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), in patients with non-obstructive hypertrophic cardiomyopathy. However, their values to predict myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and cardiac troponin I (cTnI) to identify LGE-CMR in patients with HOCM. Methods Peripheral concentrations of NT-proBNP and cTnI were determined in patients with HOCM (n = 163; age = 47.2 ± 10.8 years; 38.7% females). Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis. Results LGE was detected in 120 of 163 patients (73.6%). Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6–2340.8] vs. 866.6 [707.2–1875.2] pmol/L, P = 0.003; 0.024 [0.010–0.049] vs. 0.010 [0.005–0.021] ng/ml, P <0.001, respectively). The extent of LGE was positively correlated with log cTnI (r = 0.371, P <0.001) and log NT-proBNP (r = 0.211, P = 0.007). On multivariable analysis, both log cTnI and maximum wall thickness (MWT) were independent predictors of the presence of LGE (OR = 3.193, P = 0.033; OR = 1.410, P < 0.001, respectively), whereas log NT-proBNP was not. According to the ROC curve analysis, combined measurements of MWT ≥21 mm and/or cTnI ≥0.025ng/ml indicated good diagnostic performance for the presence of LGE, with specificity of 95% or sensitivity of 88%. Conclusions Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with HOCM. PMID:26765106

  15. Mutation-Specific Phenotypes in hiPSC-Derived Cardiomyocytes Carrying Either Myosin-Binding Protein C Or α-Tropomyosin Mutation for Hypertrophic Cardiomyopathy

    PubMed Central

    Prajapati, Chandra; Pölönen, Risto-Pekka; Rajala, Kristiina; Pekkanen-Mattila, Mari; Rasku, Jyrki; Larsson, Kim; Aalto-Setälä, Katriina

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease, which affects the structure of heart muscle tissue. The clinical symptoms include arrhythmias, progressive heart failure, and even sudden cardiac death but the mutation carrier can also be totally asymptomatic. To date, over 1400 mutations have been linked to HCM, mostly in genes encoding for sarcomeric proteins. However, the pathophysiological mechanisms of the disease are still largely unknown. Two founder mutations for HCM in Finland are located in myosin-binding protein C (MYBPC3-Gln1061X) and α-tropomyosin (TPM1-Asp175Asn) genes. We studied the properties of HCM cardiomyocytes (CMs) derived from patient-specific human induced pluripotent stem cells (hiPSCs) carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. Both types of HCM-CMs displayed pathological phenotype of HCM but, more importantly, we found differences between CMs carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn gene mutation in their cellular size, Ca2+ handling, and electrophysiological properties, as well as their gene expression profiles. These findings suggest that even though the clinical phenotypes of the patients carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn gene mutation are similar, the genetic background as well as the functional properties on the cellular level might be different, indicating that the pathophysiological mechanisms behind the two mutations would be divergent as well. PMID:27057166

  16. An explicitly solvated full atomistic model of the cardiac thin filament and application on the calcium binding affinity effects from familial hypertrophic cardiomyopathy linked mutations

    NASA Astrophysics Data System (ADS)

    Williams, Michael; Schwartz, Steven

    2015-03-01

    The previous version of our cardiac thin filament (CTF) model consisted of the troponin complex (cTn), two coiled-coil dimers of tropomyosin (Tm), and 29 actin units. We now present the newest revision of the model to include explicit solvation. The model was developed to continue our study of genetic mutations in the CTF proteins which are linked to familial hypertrophic cardiomyopathies. Binding of calcium to the cTnC subunit causes subtle conformational changes to propagate through the cTnC to the cTnI subunit which then detaches from actin. Conformational changes propagate through to the cTnT subunit, which allows Tm to move into the open position along actin, leading to muscle contraction. Calcium disassociation allows for the reverse to occur, which results in muscle relaxation. The inclusion of explicit TIP3 water solvation allows for the model to get better individual local solvent to protein interactions; which are important when observing the N-lobe calcium binding pocket of the cTnC. We are able to compare in silica and in vitro experimental results to better understand the physiological effects from mutants, such as the R92L/W and F110V/I of the cTnT, on the calcium binding affinity compared to the wild type.

  17. [Effect of peptide bioregulator and cobalt ions on the activity of NORs and associations of acrocentric chromosomes in lymphocytes of patients with hypertrophic cardiomyopathy and their relatives].

    PubMed

    2014-09-01

    The influence of peptide bioregulator - Livagen (Lys-Glu-Asp-Ala) separately and combined with cobalt ions, on the activity of nucleolar organizer regions (NORs) and frequency of associations of acrocentric chromosomes in lymphocytes from patients with hypertrophic cardiomyopathy (HCM) and their relatives has been studied. It is shown that combined action of Livagen and cobalt ions increases the frequency of large-sized scoring 2 NORs in both, patients and their relatives. Significant was also the influence of the studied compounds on associative activity of acrocsentric chromosomes that was expressed in sharp increase of this indicator in both studied groups. In this case more effective was the action of Livagen and cobalt ions. As activity of NOR, also the frequency of associations of acrocentric chromosomes is dependent of quality of acrocentric chromosome stalk condensation, we conclude, that by influence of Livagen and cobalt ions on the lymphocytes of HCM patients and their relatives, occurs decondensation of heterochromatinized chromatin. This may be release condition during condensation of inactivated genes in the studied groups of individuals. Our data are important because it provides new information about protective effect of Livagen and Livagen+Cobalt ions on the lymphocytes of HCM patients and their relatives and may lead to the development of a therapeutic treatment.

  18. How Hypertrophic Cardiomyopathy Became a Contemporary Treatable Genetic Disease With Low Mortality: Shaped by 50 Years of Clinical Research and Practice.

    PubMed

    Maron, Barry J; Rowin, Ethan J; Casey, Susan A; Maron, Martin S

    2016-04-01

    Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease encumbered throughout much of its almost 60-year history by a large measure of misunderstanding and the perception of a grim outcome without effective treatment options. However, it is now apparent that the majority of patients affected with HCM can achieve normal or near-normal life expectancy without disability, and usually do not require major treatment interventions. Nevertheless, for those patients with HCM who are at risk for (or experience) disease-related complications, a constellation of comprehensive nonpharmacologic management strategies have evolved over the last 15 years, altering the natural history and disease course for many, including implantable defibrillators, heart transplant, external defibrillation/therapeutic hypothermia, advances in surgical myectomy, and alcohol ablation. In particular, expanded contemporary risk stratification strategies have led to a more reliable selection of patients likely to achieve primary prevention of sudden death with implantable defibrillators. Most recently, large cohort studies using current management strategies and therapeutic measures have shown that it is now possible to achieve significantly improved survival with a low HCM-related mortality of 0.5% per year across all ages, and including children and young adults characteristically with the most aggressive disease course. These clinical management initiatives, instituted by the practicing cardiology community, have succeeded in preserving life and restoring an active lifestyle for thousands of patients with HCM, while providing many with a measure of reassurance and a reasonable expectation for an extended (if not normal) life span. PMID:27437663

  19. Comparison of right ventricular contractile abnormalities in hypertrophic cardiomyopathy versus hypertensive heart disease using two dimensional strain imaging: a cross-sectional study.

    PubMed

    Afonso, Luis; Briasoulis, Alex; Mahajan, Nitin; Kondur, Ashok; Siddiqui, Fayez; Siddiqui, Sabeeh; Alesh, Issa; Cardozo, Shaun; Kottam, Anupama

    2015-12-01

    Hypertrophic cardiomyopathy (HCM) affects the right ventricle (RV) because of the anatomically hypertrophied septum and plausibly by extension of the myopathic process to the RV. We sought to investigate RV strain in patients with left ventricular hypertrophy secondary to either HCM or hypertension (H-LVH). Our cross-sectional study included 32 patients with HCM, 21 patients with H-LVH, and 11 healthy subjects, who were evaluated with transthoracic echocardiography. Using a dedicated software package, bi-dimensional acquisitions were analyzed to measure segmental longitudinal strain in apical views. Right ventricular global longitudinal strain (GLS) was calculated by averaging septal and right free wall strains. The HCM and H-LVH groups were comparable for age and demographic characteristics. Right ventricular tricuspid annular plane systolic excursion was not significantly different between HCM and H-LVH subjects. Moreover, RV GLS, septal and lateral RV myocardial strain were significantly impaired in patients with HCM (all p < 0.001). Regional and global RV strain parameters were not significantly impaired in H-LVH compared to healthy controls An RV GLS cut-off value of >14.9% differentiated HCM and H-LVH with a 90% sensitivity and a 95% specificity (p < 0.001). RV strain parameters are impaired in patients with HCM. Assessment of two-dimensional RV strain parameters could help differentiate between HCM and H-LVH.

  20. Comparison of left ventricular diastolic function in obstructive hypertrophic cardiomyopathy in patients undergoing percutaneous septal alcohol ablation versus surgical myotomy/myectomy

    NASA Technical Reports Server (NTRS)

    Sitges, Marta; Shiota, Takahiro; Lever, Harry M.; Qin, Jian Xin; Bauer, Fabrice; Drinko, Jeannie K.; Agler, Deborah A.; Martin, Maureen G.; Greenberg, Neil L.; Smedira, Nicholas G.; Lytle, Bruce W.; Tuzcu, E. Murat; Garcia, Mario J.; Thomas, James D.

    2003-01-01

    Both percutaneous transcoronary alcohol septal reduction (ASR) and surgical myectomy are effective treatments to relieve left ventricular (LV) outflow tract obstruction in obstructive hypertrophic cardiomyopathy (HC). LV diastolic function was assessed by echocardiography in 57 patients with obstructive HC at baseline and 5 +/- 4 months after ASR (n = 37) or surgical myectomy (n = 20). LV outflow tract pressure gradient decreased from 65 +/- 40 to 23 +/- 21 mm Hg (p <0.01) after treatment. The ratio of the early-to-late peak diastolic LV inflow velocities, and the ratio of the early peak diastolic LV inflow velocity to the lateral mitral annulus early diastolic velocity determined by tissue Doppler imaging significantly decreased after the procedures (1.6 +/- 1.7 vs 1.0 +/- 0.7 and 15 +/- 8 vs 11 +/- 5, respectively), whereas LV inflow propagation velocity significantly increased (60 +/- 24 vs 71 +/- 36 cm/s). Left atrial size decreased from 29 +/- 7 to 25 +/- 6 cm(2) (p <0.05). Patients had a significant improvement in New York Heart Association functional class and in exercise performance. When comparing ASR with myectomy, no difference was found in the degree of change in any parameter of diastolic function. Thus, diastolic function indexes obtained by echocardiography changed after septal reduction interventions in patients with obstructive HC; this change was similar to that after surgical myectomy and ASR.

  1. Familial hypertrophic cardiomyopathy. Microsatellite haplotyping and identification of a hot spot for mutations in the beta-myosin heavy chain gene.

    PubMed Central

    Dausse, E; Komajda, M; Fetler, L; Dubourg, O; Dufour, C; Carrier, L; Wisnewsky, C; Bercovici, J; Hengstenberg, C; al-Mahdawi, S

    1993-01-01

    Familial hypertrophic cardiomyopathy (FHC) is a clinically and genetically heterogeneous disease. The first identified disease gene, located on chromosome 14q11-q12, encodes the beta-myosin heavy chain. We have performed linkage analysis of two French FHC pedigrees, 720 and 730, with two microsatellite markers located in the beta-myosin heavy chain gene (MYO I and MYO II) and with four highly informative markers, recently mapped to chromosome 14q11-q12. Significant linkage was found with MYO I and MYO II in pedigree 720, but results were not conclusive for pedigree 730. Haplotype analysis of the six markers allowed identification of affected individuals and of some unaffected subjects carrying the disease gene. Two novel missense mutations were identified in exon 13 by direct sequencing, 403Arg-->Leu and 403Arg-->Trp in families 720 and 730, respectively. The 403Arg-->Leu mutation was associated with incomplete penetrance, a high incidence of sudden deaths and severe cardiac events, whereas the consequences of the 403Arg-->Trp mutation appeared less severe. Haplotyping of polymorphic markers in close linkage to the beta-myosin heavy chain gene can, thus, provide rapid analysis of non informative pedigrees and rapid detection of carrier status. Our results also indicate that codon 403 of the beta-myosin heavy chain gene is a hot spot for mutations causing FHC. Images PMID:8254035

  2. Quantitative and qualitative changes in the resting electrocardiograph after percutaneous transluminal septal myocardial ablation for the treatment of symptomatic obstructive hypertrophic cardiomyopathy.

    PubMed

    Thai, Wai-ee; Antonis, Paul R; Hope, Sarah A; Meredith, Ian T

    2008-10-01

    Percutaneous Transluminal Septal Myocardial Ablation (PTSMA) may reduce symptoms in patients with obstructive hypertrophic cardiomyopathy. Limited quantitative and qualitative data exists on the effects of PTSMA on the resting electrocardiograph. We report repolarisation and conduction abnormalities and incidence of arrhythmia post-PTSMA. Twelve-lead electrocardiographs from subjects without pre-procedural pacemakers who underwent successful procedures (37 procedures, mean age 61+/-14 years) were analysed for rhythm, heart rate, PR and QTc intervals, QRS duration and left or right bundle branch block (RBBB, LBBB). Four subjects developed permanent complete AV block, 19 subjects developed new RBBB and two subjects developed new LBBB pre-discharge. At a median follow-up of 34 (range 1-84) months, no new AV block, ventricular arrhythmias or deaths occurred. Post-PTSMA PR, QRS and QTc intervals lengthened (PR 180+/-33 ms, 204+/-40 ms, QRS 105+/-20 ms, 132+/-27 ms and QTc 454+/-32 ms, 491+/-37 ms (pre- and post-PTSMA respectively, all p=0.001). Predictors of permanent complete AV block included female gender (p=0.013), older age (p=0.013) and pre-existing LBBB (p<0.001). Atrio-ventricular and intra-ventricular conduction disturbances are common post-PTSMA. A pre-existing LBBB is a risk factor for the development of complete AV block and may merit prophylactic pacemaker insertion.

  3. Next generation sequencing for clinical diagnostics-principles and application to targeted resequencing for hypertrophic cardiomyopathy: a paper from the 2009 William Beaumont Hospital Symposium on Molecular Pathology.

    PubMed

    Voelkerding, Karl V; Dames, Shale; Durtschi, Jacob D

    2010-09-01

    During the past five years, new high-throughput DNA sequencing technologies have emerged; these technologies are collectively referred to as next generation sequencing (NGS). By virtue of sequencing clonally amplified DNA templates or single DNA molecules in a massively parallel fashion in a flow cell, NGS provides both qualitative and quantitative sequence data. This combination of information has made NGS the technology of choice for complex genetic analyses that were previously either technically infeasible or cost prohibitive. As a result, NGS has had a fundamental and broad impact on many facets of biomedical research. In contrast, the dissemination of NGS into the clinical diagnostic realm is in its early stages. Though NGS is powerful and can be envisioned to have multiple applications in clinical diagnostics, the technology is currently complex. Successful adoption of NGS into the clinical laboratory will require expertise in both molecular biology techniques and bioinformatics. The current report presents principles that underlie NGS including sequencing library preparation, sequencing chemistries, and an introduction to NGS data analysis. These concepts are subsequently further illustrated by showing representative results from a case study using NGS for targeted resequencing of genes implicated in hypertrophic cardiomyopathy. PMID:20805560

  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. In vivo Analysis of Troponin C Knock-in (A8V) Mice: Evidence that TNNC1 Is a Hypertrophic Cardiomyopathy Susceptibility Gene

    PubMed Central

    Feng, Han-Zhong; Bos, J. Martijn; Gonzalez-Martinez, David; Vukmirovic, Milica; Turna, Rajdeep S.; Sanchez-Gonzalez, Marcos A.; Badger, Crystal-Dawn; Zorio, Diego A. R.; Singh, Rakesh K.; Wang, Yingcai; Jin, J.-P.; Ackerman, Michael J.; Pinto, Jose R.

    2015-01-01

    Background Mutations in thin-filament proteins have been linked to hypertrophic cardiomyopathy (HCM), but it has never been demonstrated that variants identified in the TNNC1 (gene encoding troponin C) can evoke cardiac remodeling in-vivo. The goal of this study was to determine whether TNNC1 can be categorized as an HCM susceptibility gene, such that a mouse model can recapitulate the clinical presentation of the proband. Methods and Results The TNNC1-A8V proband diagnosed with severe obstructive HCM at 34-years of age exhibited mild-to-moderate thickening in left and right ventricular walls, decreased left-ventricular dimensions, left-atrial enlargement and hyperdynamic left-ventricular systolic function. Genetically-engineered knock-in mice containing the A8V mutation (heterozygote=KI-TnC-A8V+/−; homozygote=KI-TnC-A8V+/+) were characterized by echocardiography and pressure-volume studies. Three-month-old, KI-TnC-A8V+/+ mice displayed decreased ventricular dimensions, mild diastolic dysfunction, and enhanced systolic function, while KI-TnC-A8V+/− mice displayed cardiac restriction at 14-months of age. KI hearts exhibited atrial enlargement, papillary-muscle hypertrophy and fibrosis. Liquid chromatography-mass spectroscopy was used to determine incorporation of mutant cTnC (~21%) into the KI-TnC-A8V+/− cardiac myofilament. Reduced diastolic sarcomeric length, increased shortening and prolonged Ca2+ and contractile transients were recorded in intact KI-TnC-A8V+/− and KI-TnC-A8V+/+ cardiomyocytes. Ca2+-sensitivity of contraction in skinned fibers increased with mutant gene dose: KI-TnC-A8V+/+ > KI-TnC-A8V+/− > WT, while KI-TnC-A8V+/+ relaxed more slowly upon flash-photolysis of diazo-2. Conclusions The TNNC1-A8V mutant increases the Ca2+-binding affinity of the thin filament, and elicits changes in Ca2+ homeostasis and cellular remodeling, which leads to diastolic dysfunction. These in-vivo alterations further implicate the role of TNNC1 mutations in the

  7. A Next-Generation Sequencing Approach to Identify Gene Mutations in Early- and Late-Onset Hypertrophic Cardiomyopathy Patients of an Italian Cohort

    PubMed Central

    Rubattu, Speranza; Bozzao, Cristina; Pennacchini, Ermelinda; Pagannone, Erika; Musumeci, Beatrice Maria; Piane, Maria; Germani, Aldo; Savio, Camilla; Francia, Pietro; Volpe, Massimo; Autore, Camillo; Chessa, Luciana

    2016-01-01

    Sequencing of sarcomere protein genes in patients fulfilling the clinical diagnostic criteria for hypertrophic cardiomyopathy (HCM) identifies a disease-causing mutation in 35% to 60% of cases. Age at diagnosis and family history may increase the yield of mutations screening. In order to assess whether Next-Generation Sequencing (NGS) may fulfil the molecular diagnostic needs in HCM, we included 17 HCM-related genes in a sequencing panel run on PGM IonTorrent. We selected 70 HCM patients, 35 with early (≤25 years) and 35 with late (≥65 years) diagnosis of disease onset. All samples had a 98.6% average of target regions, with coverage higher than 20× (mean coverage 620×). We identified 41 different mutations (seven of them novel) in nine genes: MYBPC3 (17/41 = 41%); MYH7 (10/41 = 24%); TNNT2, CAV3 and MYH6 (3/41 = 7.5% each); TNNI3 (2/41 = 5%); GLA, MYL2, and MYL3 (1/41=2.5% each). Mutation detection rate was 30/35 (85.7%) in early-onset and 8/35 (22.9%) in late-onset HCM patients, respectively (p < 0.0001). The overall detection rate for patients with positive family history was 84%, and 90.5% in patients with early disease onset. In our study NGS revealed higher mutations yield in patients with early onset and with a family history of HCM. Appropriate patient selection can increase the yield of genetic testing and make diagnostic testing cost-effective. PMID:27483260

  8. A Next-Generation Sequencing Approach to Identify Gene Mutations in Early- and Late-Onset Hypertrophic Cardiomyopathy Patients of an Italian Cohort.

    PubMed

    Rubattu, Speranza; Bozzao, Cristina; Pennacchini, Ermelinda; Pagannone, Erika; Musumeci, Beatrice Maria; Piane, Maria; Germani, Aldo; Savio, Camilla; Francia, Pietro; Volpe, Massimo; Autore, Camillo; Chessa, Luciana

    2016-01-01

    Sequencing of sarcomere protein genes in patients fulfilling the clinical diagnostic criteria for hypertrophic cardiomyopathy (HCM) identifies a disease-causing mutation in 35% to 60% of cases. Age at diagnosis and family history may increase the yield of mutations screening. In order to assess whether Next-Generation Sequencing (NGS) may fulfil the molecular diagnostic needs in HCM, we included 17 HCM-related genes in a sequencing panel run on PGM IonTorrent. We selected 70 HCM patients, 35 with early (≤25 years) and 35 with late (≥65 years) diagnosis of disease onset. All samples had a 98.6% average of target regions, with coverage higher than 20× (mean coverage 620×). We identified 41 different mutations (seven of them novel) in nine genes: MYBPC3 (17/41 = 41%); MYH7 (10/41 = 24%); TNNT2, CAV3 and MYH6 (3/41 = 7.5% each); TNNI3 (2/41 = 5%); GLA, MYL2, and MYL3 (1/41=2.5% each). Mutation detection rate was 30/35 (85.7%) in early-onset and 8/35 (22.9%) in late-onset HCM patients, respectively (p < 0.0001). The overall detection rate for patients with positive family history was 84%, and 90.5% in patients with early disease onset. In our study NGS revealed higher mutations yield in patients with early onset and with a family history of HCM. Appropriate patient selection can increase the yield of genetic testing and make diagnostic testing cost-effective. PMID:27483260

  9. Systolic and diastolic myocardial mechanics in hypertrophic cardiomyopathy and their link to the extent of hypertrophy, replacement fibrosis and interstitial fibrosis.

    PubMed

    Nucifora, Gaetano; Muser, Daniele; Gianfagna, Pasquale; Morocutti, Giorgio; Proclemer, Alessandro

    2015-12-01

    Aim of the present study was to investigate the relations between myocardial mechanics and the extent of hypertrophy and fibrosis in hypertrophic cardiomyopathy (HCM). Forty-five consecutive patients with HCM and 15 subjects without structural heart disease were included. Cardiac magnetic resonance with late gadolinium enhancement (LGE) imaging was performed to evaluate biventricular function, LV mass index and presence/extent of LGE, expression of replacement fibrosis. Myocardial T1 relaxation, a surrogate of interstitial fibrosis, was measured from Look-Locker sequence. Feature-tracking analysis was applied to LV basal, mid and apical short-axis images to assess systolic and diastolic global LV circumferential strain (CS) and strain rate (CSr). Peak systolic CS and CSr were significantly higher among HCM patients as compared to control subjects (p = 0.015 and p = 0.007, respectively). The ratio of peak CSr during early filling to peak systolic CSr was significantly lower among HCM patients (p = 0.002). At multivariate linear regression analysis, LV mass index (p < 0.001) and %LV LGE (p = 0.011) were significantly and independently related to peak systolic CS; LV mass index (p < 0.001) and %LV LGE (p = 0.023) were significantly and independently related to peak systolic CSr; %LV LGE (p = 0.021) and T1 ratio (p = 0.006) were significantly and independently related to the ratio of peak CSr during early filling to peak systolic CSr. LV systolic mechanics are enhanced and LV diastolic mechanics are impaired in HCM. Extent of hypertrophy and replacement fibrosis influence the LV systolic mechanics while extent of replacement fibrosis and interstitial fibrosis influence the LV diastolic mechanics.

  10. Evolution of expression of cardiac phenotypes over a 4-year period in the β-myosin heavy chain-Q403 transgenic rabbit model of human hypertrophic cardiomyopathy

    PubMed Central

    Nagueh, Sherif F.; Chen, Suetnee; Patel, Rajnikant; Tsybouleva, Natalia; Lutucuta, Silvia; Kopelen, Helen A.; Zoghbi, William A.; Quiñones, Miguel A.; Roberts, Robert; Marian, A.J.

    2009-01-01

    Hypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death in the young, is characterized by a diverse array of cardiac phenotypes evolving over several decades. We have developed transgenic rabbits that fully recapitulate the phenotype of human HCM and provide for the opportunity to delineate the sequence of evolution of cardiac phenotypes, and thus, the pathogenesis of HCM. We determined evolution of biochemical, molecular, histological, structural and functional phenotypes at 4 age-periods in 47 β-myosin heavy chain-glutamine (MyHC-Q)-403 transgenic rabbits. Ca+2 sensitivity of myofibrillar ATPase activity was reduced very early and in the absence of other discernible phenotypes. Myocyte disarray also occurred early, prior to, and independent of hypertrophy and fibrosis. The latter phenotypes evolved predominantly during puberty in conjunction with activation of stress-related signaling kinases. Myocardial contraction and relaxation velocities were decreased early despite normal global cardiac function and in the absence of histological phenotype. Global cardiac function declined with aging, while left atrial size was increased along with Doppler indices of left ventricular filling pressure. Thus, Ca+2 sensitivity of myofibrillar ATPase activity is a primary phenotype expressed early and independent of the ensuing phenotypes. Pathogenesis of myocyte disarray, which exhibits age-independent penetrance, differs from those of hypertrophy and fibrosis, which show age-dependent expression. Myocardial dysfunction is an early marker that predicts subsequent development of hypertrophy. These findings in an animal model that recapitulates the phenotype of human HCM, implicate involvement of multiple independent mechanisms in the pathogenesis of cardiac phenotypes in HCM. PMID:15135661

  11. Faster cross-bridge detachment and increased tension cost in human hypertrophic cardiomyopathy with the R403Q MYH7 mutation

    PubMed Central

    Witjas-Paalberends, E Rosalie; Ferrara, Claudia; Scellini, Beatrice; Piroddi, Nicoletta; Montag, Judith; Tesi, Chiara; Stienen, Ger J M; Michels, Michelle; Ho, Carolyn Y; Kraft, Theresia; Poggesi, Corrado; van der Velden, Jolanda

    2014-01-01

    The first mutation associated with hypertrophic cardiomyopathy (HCM) is the R403Q mutation in the gene encoding β-myosin heavy chain (β-MyHC). R403Q locates in the globular head of myosin (S1), responsible for interaction with actin, and thus motor function of myosin. Increased cross-bridge relaxation kinetics caused by the R403Q mutation might underlie increased energetic cost of tension generation; however, direct evidence is absent. Here we studied to what extent cross-bridge kinetics and energetics are related in single cardiac myofibrils and multicellular cardiac muscle strips of three HCM patients with the R403Q mutation and nine sarcomere mutation-negative HCM patients (HCMsmn). Expression of R403Q was on average 41 ± 4% of total MYH7 mRNA. Cross-bridge slow relaxation kinetics in single R403Q myofibrils was significantly higher (P < 0.0001) than in HCMsmn myofibrils (0.47 ± 0.02 and 0.30 ± 0.02 s−1, respectively). Moreover, compared to HCMsmn, tension cost was significantly higher in the muscle strips of the three R403Q patients (2.93 ± 0.25 and 1.78 ± 0.10 μmol l–1 s−1 kN−1 m−2, respectively) which showed a positive linear correlation with relaxation kinetics in the corresponding myofibril preparations. This correlation suggests that faster cross-bridge relaxation kinetics results in an increase in energetic cost of tension generation in human HCM with the R403Q mutation compared to HCMsmn. Therefore, increased tension cost might contribute to HCM disease in patients carrying the R403Q mutation. PMID:24928957

  12. Validation of the 2014 European Society of Cardiology Sudden Cardiac Death Risk Prediction Model in Hypertrophic Cardiomyopathy in a Reference Center in South America.

    PubMed

    Fernández, Adrián; Quiroga, Alejandro; Ochoa, Juan Pablo; Mysuta, Mauricio; Casabé, José Horacio; Biagetti, Marcelo; Guevara, Eduardo; Favaloro, Liliana E; Fava, Agostina M; Galizio, Néstor

    2016-07-01

    Sudden cardiac death (SCD) is a common cause of death in hypertrophic cardiomyopathy (HC). Our aim was to conduct an external and independent validation in South America of the 2014 European Society of Cardiology (ESC) SCD risk prediction model to identify patients requiring an implantable cardioverter defibrillator. This study included 502 consecutive patients with HC followed from March, 1993 to December, 2014. A combined end point of SCD or appropriate implantable cardioverter defibrillator therapy was assessed. For the quantitative estimation of individual 5-year SCD risk, we used the formula: 1 - 0.998(exp(Prognostic index)). Our database also included the abnormal blood pressure response to exercise as a risk marker. We analyzed the 3 categories of 5-year risk proposed by the ESC: low risk (LR) <4%; intermediate risk (IR) ≥4% to <6%, and high risk (HR) ≥6%. The LR group included 387 patients (77%); the IR group 39 (8%); and the HR group 76 (15%). Fourteen patients (3%) had SCD/appropriate implantable cardioverter defibrillator therapy (LR: 0%; IR: 2 of 39 [5%]; and HR: 12 of 76 [16%]). In a receiver-operating characteristic curve, the new model proved to be an excellent predictor because the area under the curve for the estimated risk is 0.925 (statistical C: 0.925; 95% CI 0.8884 to 0.9539, p <0.0001). In conclusion, the SCD risk prediction model in HC proposed by the 2014 ESC guidelines was validated in our population and represents an improvement compared with previous approaches. A larger multicenter, independent and external validation of the model with long-term follow-up would be advisable.

  13. A Mutation in TNNC1-encoded Cardiac Troponin C, TNNC1-A31S, Predisposes to Hypertrophic Cardiomyopathy and Ventricular Fibrillation*

    PubMed Central

    Parvatiyar, Michelle S.; Landstrom, Andrew P.; Figueiredo-Freitas, Cicero; Potter, James D.; Ackerman, Michael J.; Pinto, Jose Renato

    2012-01-01

    Defined as clinically unexplained hypertrophy of the left ventricle, hypertrophic cardiomyopathy (HCM) is traditionally understood as a disease of the cardiac sarcomere. Mutations in TNNC1-encoded cardiac troponin C (cTnC) are a relatively rare cause of HCM. Here, we report clinical and functional characterization of a novel TNNC1 mutation, A31S, identified in a pediatric HCM proband with multiple episodes of ventricular fibrillation and aborted sudden cardiac death. Diagnosed at age 5, the proband is family history-negative for HCM or sudden cardiac death, suggesting a de novo mutation. TnC-extracted cardiac skinned fibers were reconstituted with the cTnC-A31S mutant, which increased Ca2+ sensitivity with no effect on the maximal contractile force generation. Reconstituted actomyosin ATPase assays with 50% cTnC-A31S:50% cTnC-WT demonstrated Ca2+ sensitivity that was intermediate between 100% cTnC-A31S and 100% cTnC-WT, whereas the mutant increased the activation of the actomyosin ATPase without affecting the inhibitory qualities of the ATPase. The secondary structure of the cTnC mutant was evaluated by circular dichroism, which did not indicate global changes in structure. Fluorescence studies demonstrated increased Ca2+ affinity in isolated cTnC, the troponin complex, thin filament, and to a lesser degree, thin filament with myosin subfragment 1. These results suggest that this mutation has a direct effect on the Ca2+ sensitivity of the myofilament, which may alter Ca2+ handling and contribute to the arrhythmogenesis observed in the proband. In summary, we report a novel mutation in the TNNC1 gene that is associated with HCM pathogenesis and may predispose to the pathogenesis of a fatal arrhythmogenic subtype of HCM. PMID:22815480

  14. Echocardiographic Characterization of a Murine Model of Hypertrophic Obstructive Cardiomyopathy Induced by Cardiac-specific Overexpression of Epidermal Growth Factor Receptor 2.

    PubMed

    Sørensen, Lars L; Bedja, Djahida; Sysa-Shah, Polina; Liu, Hongyun; Maxwell, Amanda; Yi, Xu; Pozios, Iraklis; Olsen, Niels T; Abraham, Theodore P; Abraham, Roselle; Gabrielson, Kathleen

    2016-01-01

    Although rare, hypertrophic cardiomyopathy (HCM) with midventricular obstruction is often associated with severe symptoms and complications. None of the existing HCM animal models display this particular phenotype. Our group developed a mouse line that overexpresses the ErbB2 receptor (ErbB2(tg)) in cardiomyocytes; we previously showed that the ErbB2 receptor induces cardiomyocyte hypertrophy, myocyte disarray, and fibrosis compatible with HCM. In the current study, we sought to further echocardiographically characterize the ErbB2(tg) mouse line as a model of HCM. Compared with their wild-type littermates, ErbB2(tg) mice show increased left ventricular (LV) mass, concentric LV hypertrophy, and papillary muscle hypertrophy. This hypertrophy was accompanied by diastolic dysfunction, expressed as reduced E:A ratio, prolonged deceleration time, and elevated E:e' ratio. In addition, ErbB2(tg) mice consistently showed midcavity obstruction with elevated LV gradients, and the flow profile revealed a prolonged pressure increase and a delayed peak, indicating dynamic obstruction. The ejection fraction was increased in ErbB2(tg) mice, due to reduced end-diastolic and end-systolic LV volumes. Furthermore, systolic radial strain and systolic radial strain rate but not systolic circumferential strain and longitudinal strain were decreased in ErbB2(tg) compared with wild-type mice. In conclusion, the phenotype of the ErbB2(tg) mouse model is consistent with midventricular HCM in many important aspects, including massive LV hypertrophy, diastolic dysfunction, and midcavity obstruction. This pattern is unique for a small animal model, suggesting that ErbB2(tg) mice may be well suited for research into the hemodynamics and treatment of this rare form of HCM. PMID:27538857

  15. Differences in the diagnostic value of various criteria of negative T waves for hypertrophic cardiomyopathy based on a molecular genetic diagnosis.

    PubMed

    Konno, Tetsuo; Fujino, Noboru; Hayashi, Kenshi; Uchiyama, Katsuharu; Masuta, Eiichi; Katoh, Hiromasa; Sakamoto, Yuichiro; Tsubokawa, Toshinari; Ino, Hidekazu; Yamagishi, Masakazu

    2007-06-01

    Differences in the diagnostic value of a variety of definitions of negative T waves for HCM (hypertrophic cardiomyopathy) have not yet been clarified, resulting in a number of definitions being applied in previous studies. The aim of the present study was to determine the most accurate diagnostic definition of negative T waves for HCM in genotyped populations. Electrocardiographic and echocardiographic findings were analysed in 161 genotyped subjects (97 carriers and 64 non-carriers). We applied three different criteria that have been used in previous studies: Criterion 1, negative T wave >10 mm in depth in any leads; Criterion 2, negative T wave >3 mm in depth in at least two leads; and Criterion 3, negative T wave >1 mm in depth in at least two leads. Of the three criteria, Criterion 3 had the highest sensitivity (43% compared with 5 and 26% in Criterion 1 and Criterion 2 respectively; P<0.0001) and retained a specificity of 95%, resulting in the highest accuracy. In comparison with abnormal Q waves, negative T waves for Criterion 3 had a lower sensitivity in detecting carriers without LVH (left ventricular hypertrophy) (12.9% for negative T waves compared with 22.6% for abnormal Q waves). On the other hand, in detecting carriers with LVH, the sensitivity of negative T waves increased in a stepwise direction with the increasing extent of LVH (P<0.001), whereas there was less association between the sensitivity of abnormal Q waves and the extent of LVH. In conclusion, Criterion 3 for negative T waves may be the most accurate definition of HCM based on genetic diagnoses. Negative T waves may show different diagnostic value according to the different criteria and phenotypes in genotyped populations with HCM.

  16. Mutations in troponin T associated with Hypertrophic Cardiomyopathy increase Ca(2+)-sensitivity and suppress the modulation of Ca(2+)-sensitivity by troponin I phosphorylation.

    PubMed

    Messer, Andrew E; Bayliss, Christopher R; El-Mezgueldi, Mohammed; Redwood, Charles S; Ward, Douglas G; Leung, Man-Ching; Papadaki, Maria; Dos Remedios, Cristobal; Marston, Steven B

    2016-07-01

    We investigated the effect of 7 Hypertrophic Cardiomyopathy (HCM)-causing mutations in troponin T (TnT) on troponin function in thin filaments reconstituted with actin and human cardiac tropomyosin. We used the quantitative in vitro motility assay to study Ca(2+)-regulation of unloaded movement and its modulation by troponin I phosphorylation. Troponin from a patient with the K280N TnT mutation showed no difference in Ca(2+)-sensitivity when compared with donor heart troponin and the Ca(2+)-sensitivity was also independent of the troponin I phosphorylation level (uncoupled). The recombinant K280N TnT mutation increased Ca(2+)-sensitivity 1.7-fold and was also uncoupled. The R92Q TnT mutation in troponin from transgenic mouse increased Ca(2+)-sensitivity and was also completely uncoupled. Five TnT mutations (Δ14, Δ28 + 7, ΔE160, S179F and K273E) studied in recombinant troponin increased Ca(2+)-sensitivity and were all fully uncoupled. Thus, for HCM-causing mutations in TnT, Ca(2+)-sensitisation together with uncoupling in vitro is the usual response and both factors may contribute to the HCM phenotype. We also found that Epigallocatechin-3-gallate (EGCG) can restore coupling to all uncoupled HCM-causing TnT mutations. In fact the combination of Ca(2+)-desensitisation and re-coupling due to EGCG completely reverses both the abnormalities found in troponin with a TnT HCM mutation suggesting it may have therapeutic potential. PMID:27036851

  17. Differences in global and regional left ventricular myocardial mechanics in various morphologic subtypes of patients with obstructive hypertrophic cardiomyopathy referred for ventricular septal myotomy/myectomy.

    PubMed

    Kobayashi, Taisei; Dhillon, Ashwat; Popovic, Zoran; Bhonsale, Aditya; Smedira, Nicholas G; Thamilarasan, Maran; Lytle, Bruce W; Lever, Harry M; Desai, Milind Y

    2014-06-01

    Patients with obstructive hypertrophic cardiomyopathy (HC) have various left ventricular (LV) shapes: reverse septal curvature (RSC, commonly familial), sigmoid septum (SS, common in hypertensives), and concentric hypertrophy (CH). Longitudinal (systolic and early diastolic) strain rate (SR) is sensitive in detecting regional myocardial dysfunction. We sought to determine differences in longitudinal SR of patients with obstructive HC, based on LV shapes. We studied 199 consecutive patients with HC (50% men) referred for surgical myectomy. Clinical and echocardiographic parameters were recorded. LV shapes were classified on echocardiography, using basal septal 1/3 to posterior wall ratio: RSC = ratio >1.3 (extending to mid and distal septum), SS = ratio >1.3 (extending only to basal 1/3), and concentric = ratio ≤1.3. Longitudinal systolic and early diastolic SRs were measured from apical 4- and 2-chamber views (VVI 2.0; Siemens, Erlangen). Distribution of RSC, SS, and CH was 50%, 28%, and 22%, respectively. Patients with RSC were significantly younger (47 ± 12 vs 64 ± 10 and 57 ± 11, respectively) with lower hypertension (40% vs 71% and 67%, respectively) than patients with SS or CH (both p <0.001). Patients with RSC had lower global systolic (-0.99 ± 0.3 vs -1.05 ± 0.3 and -1.17 ± 0.3) and early diastolic SR (0.95 ± 0.4 vs 0.98 ± 0.3 and 1.16 ± 0.4) versus patients with SS and CH (in 1/s, both p <0.01), despite being much younger and less hypertensive. RSC was associated with abnormal global LV systolic (beta 0.16) and early diastolic (beta -0.17) SR (both p <0.01). In conclusion, patients with HC with RCS have significantly abnormal LV mechanics, despite being younger and less hypertensive. A combination of LV mechanics and shapes could help differentiate between genetically mediated and other causes of obstructive HC.

  18. Impact of left ventricular outflow tract area on systolic outflow velocity in hypertrophic cardiomyopathy: a real-time three-dimensional echocardiographic study

    NASA Technical Reports Server (NTRS)

    Qin, Jian Xin; Shiota, Takahiro; Lever, Harry M.; Rubin, David N.; Bauer, Fabrice; Kim, Yong Jin; Sitges, Marta; Greenberg, Neil L.; Drinko, Jeanne K.; Martin, Maureen; Agler, Deborah A.; Thomas, James D.

    2002-01-01

    OBJECTIVES: The aim of this study was to use real-time three-dimensional echocardiography (3DE) to investigate the quantitative relation between minimal left ventricular (LV) outflow tract area (A(LVOT)) and maximal LV outflow tract (LVOT) velocity in patients with hypertrophic obstructive cardiomyopathy (HCM). BACKGROUND: In patients with HCM, LVOT velocity should change inversely with minimal A(LVOT) unless LVOT obstruction reduces the pumping capacity of the ventricle. METHODS: A total of 25 patients with HCM with systolic anterior motion (SAM) of the mitral valve leaflets underwent real-time 3DE. The smallest A(LVOT) during systole was measured using anatomically oriented two-dimensional "C-planes" within the pyramidal 3DE volume. Maximal velocity across LVOT was evaluated by two-dimensional Doppler echocardiography (2DE). For comparison with 3DE A(LVOT), the SAM-septal distance was determined by 2DE. RESULTS: Real-time 3DE provided unique information about the dynamic SAM-septal relation during systole, with A(LVOT) ranging from 0.6 to 5.2 cm(2) (mean: 2.2 +/- 1.4 cm(2)). Maximal velocity (v) correlated inversely with A(LVOT) (v = 496 A(LVOT)(-0.80), r = -0.95, p < 0.001), but the exponent (-0.80) was significantly different from -1.0 (95% confidence interval: -0.67 to -0.92), indicating a significant impact of small A(LVOT) on the peak LVOT flow rate. By comparison, the best correlation between velocity and 2DE SAM-septal distance was significantly (p < 0.01) poorer at -0.83, indicating the superiority of 3DE for assessing A(LVOT). CONCLUSIONS: Three-dimensional echocardiography-measured A(LVOT) provides an assessment of HCM geometry that is superior to 2DE methods. These data indicate that the peak LVOT flow rate appears to be significantly decreased by reduced A(LVOT). Real-time 3DE is a potentially valuable clinical tool for assessing patients with HCM.

  19. High Spatial Resolution Cardiovascular Magnetic Resonance at 7.0 Tesla in Patients with Hypertrophic Cardiomyopathy – First Experiences: Lesson Learned from 7.0 Tesla

    PubMed Central

    Prothmann, Marcel; von Knobelsdorff-Brenkenhoff, Florian; Töpper, Agnieszka; Dieringer, Matthias A.; Shahid, Etham; Graessl, Andreas; Rieger, Jan; Lysiak, Darius; Thalhammer, C.; Huelnhagen, Till; Kellman, Peter; Niendorf, Thoralf; Schulz-Menger, Jeanette

    2016-01-01

    Background Cardiovascular Magnetic Resonance (CMR) provides valuable information in patients with hypertrophic cardiomyopathy (HCM) based on myocardial tissue differentiation and the detection of small morphological details. CMR at 7.0T improves spatial resolution versus today’s clinical protocols. This capability is as yet untapped in HCM patients. We aimed to examine the feasibility of CMR at 7.0T in HCM patients and to demonstrate its capability for the visualization of subtle morphological details. Methods We screened 131 patients with HCM. 13 patients (9 males, 56 ±31 years) and 13 healthy age- and gender-matched subjects (9 males, 55 ±31years) underwent CMR at 7.0T and 3.0T (Siemens, Erlangen, Germany). For the assessment of cardiac function and morphology, 2D CINE imaging was performed (voxel size at 7.0T: (1.4x1.4x2.5) mm3 and (1.4x1.4x4.0) mm3; at 3.0T: (1.8x1.8x6.0) mm3). Late gadolinium enhancement (LGE) was performed at 3.0T for detection of fibrosis. Results All scans were successful and evaluable. At 3.0T, quantification of the left ventricle (LV) showed similar results in short axis view vs. the biplane approach (LVEDV, LVESV, LVMASS, LVEF) (p = 0.286; p = 0.534; p = 0.155; p = 0.131). The LV-parameters obtained at 7.0T where in accordance with the 3.0T data (pLVEDV = 0.110; pLVESV = 0.091; pLVMASS = 0.131; pLVEF = 0.182). LGE was detectable in 12/13 (92%) of the HCM patients. High spatial resolution CINE imaging at 7.0T revealed hyperintense regions, identifying myocardial crypts in 7/13 (54%) of the HCM patients. All crypts were located in the LGE-positive regions. The crypts were not detectable at 3.0T using a clinical protocol. Conclusions CMR at 7.0T is feasible in patients with HCM. High spatial resolution gradient echo 2D CINE imaging at 7.0T allowed the detection of subtle morphological details in regions of extended hypertrophy and LGE. PMID:26863618

  20. Quantitative diffusion-weighted magnetic resonance imaging in the assessment of myocardial fibrosis in hypertrophic cardiomyopathy compared with T1 mapping.

    PubMed

    Wu, Lian-Ming; Chen, Bing-Hua; Yao, Qiu-Ying; Ou, Yang-Rongzheng; Wu, Rui; Jiang, Meng; Hu, Jiani; An, Dong-Aolei; Xu, Jian-Rong

    2016-08-01

    To identify myocardial fibrosis in hypertrophic cardiomyopathy (HCM) subjects using quantitative cardiac diffusion-weighted imaging (DWI) and to compare its performance with native T1 mapping and extracellular volume (ECV). Thirty-eight HCM subjects (mean age, 53 ± 9 years) and 14 normal controls (mean age, 51 ± 8 years) underwent cardiac magnetic resonance imaging (CMRI) on a 3.0T magnetic resonance (MR) machine with DWI, T1 mapping and late gadolinium enhancement (LGE) imaging as the reference standard. The mean apparent diffusion coefficient (ADC), native T1 value and ECV were determined for each subject. Overall, the HCM subjects exhibited an increased native T1 value (1241.04 ± 78.50 ms), ECV (0.31 ± 0.03) and ADC (2.36 ± 0.34 s/mm(2)) compared with the normal controls (1114.60 ± 37.99 ms, 0.24 ± 0.04, and 1.62 ± 0.38 s/mm(2), respectively) (p < 0.05). DWI differentiated healthy and fibrotic myocardia with an area under the curve (AUC) of 0.93, while the AUCs of the native T1 values (0.93), (p > 0.05) and ECV (0.94), (p > 0.05) exhibited an equal differentiation ability. Both HCM LGE+ and HCM LGE- subjects had an increased native T1 value, ECV and ADC compared to the normal controls (p < 0.05). HCM LGE+ subjects exhibited an increased ECV (0.31 ± 0.04) and ADC (2.43 ± 0.36 s/mm(2)) compared to HCM LGE- subjects (p < 0.05). HCM LGE+ and HCM LGE- subjects had similar native T1 values (1250 ± 76.36 ms vs. 1213.98 ± 92.30 ms, respectively) (p > 0.05). ADC values were linearly associated with increased ECV (R(2) = 0.36) and native T1 values (R(2) = 0.40) among all subjects. DWI is a feasible alternative to native T1 mapping and ECV for the identification of myocardial fibrosis in patients with HCM. DWI and ECV can quantitatively characterize the extent of fibrosis in HCM LGE+ and HCM LGE- patients. PMID:27198892

  1. Mechanical aberrations in hypetrophic cardiomyopathy: emerging concepts

    PubMed Central

    Ntelios, Dimitrios; Tzimagiorgis, Georgios; Efthimiadis, Georgios K.; Karvounis, Haralambos

    2015-01-01

    Hypertrophic cardiomyopathy is the most common monogenic disorder in cardiology. Despite important advances in understanding disease pathogenesis, it is not clear how flaws in individual sarcomere components are responsible for the observed phenotype. The aim of this article is to provide a brief interpretative analysis of some currently proposed pathophysiological mechanisms of hypertrophic cardiomyopathy, with a special emphasis on alterations in the cardiac mechanical properties. PMID:26347658

  2. De novo unbalanced translocation resulting in monosomy for proximal 14q and distal 4p in a fetus with intrauterine growth retardation, Wolf-Hirschhorn syndrome, hypertrophic cardiomyopathy, and partial hemihypoplasia.

    PubMed Central

    Chen, C P; Chern, S R; Lee, C C; Chen, W L; Chen, M H; Chang, K M

    1998-01-01

    We present the perinatal findings of a fetus with a de novo unbalanced chromosome translocation that resulted in monosomy for proximal 14q and monosomy for distal 4p. Prenatal sonographic examination at 27 weeks of gestation showed intrauterine growth retardation, microcephaly, cardiomegaly with arrhythmia, and asymmetry of the upper limbs. Genetic amniocentesis showed an abnormal karyotype of 45,XX,der(4)t(4;14)(p16.3;q12),-14. Linkage analysis of the family confirmed the maternal origin of the deletions. Molecular refinement of the deletion breakpoints indicated that the breakpoints at 4p16.3 and 14q12 were located between loci D4S403 (present) and D4S394 (absent), and between loci D14S252 (present) and D14S64 (absent), respectively. Necropsy showed dysmorphic features compatible with Wolf-Hirschhorn syndrome, hypertrophic cardiomyopathy, partial hemihypoplasia, and a normal brain without evidence of holoprosencephaly. Our case adds to the list of clinical phenotypes associated with the proximal regions of 14q. Images PMID:9863609

  3. Human junctophilin-2 undergoes a structural rearrangement upon binding PtdIns(3,4,5)P3 and the S101R mutation identified in hypertrophic cardiomyopathy obviates this response

    PubMed Central

    Bennett, Hayley J.; Davenport, John Bernard; Collins, Richard F.; Trafford, Andrew W.; Pinali, Christian; Kitmitto, Ashraf

    2013-01-01

    JP2 (junctophilin-2) is believed to hold the transverse tubular and jSR (junctional sarcoplasmic reticulum) membranes in a precise geometry that facilitates excitation–contraction coupling in cardiomyocytes. We have expressed and purified human JP2 and shown using electron microscopy that the protein forms elongated structures ~15 nm long and 2 nm wide. Employing lipid-binding assays and quartz crystal microbalance with dissipation we have determined that JP2 is selective for PS (phosphatidylserine), with a Kd value of ~0.5 μM, with the N-terminal domain mediating this interaction. JP2 also binds PtdIns(3,4,5)P3 at a different site than PS, resulting in the protein adopting a more flexible conformation; this interaction is modulated by both Ca2+ and Mg2+ ions. We show that the S101R mutation identified in patients with hypertrophic cardiomyopathy leads to modification of the protein secondary structure, forming a more flexible molecule with an increased affinity for PS, but does not undergo a structural transition in response to binding PtdIns(3,4,5)P3. In conclusion, the present study provides new insights into the structural and lipid-binding properties of JP2 and how the S101R mutation may have an effect upon the stability of the dyad organization with the potential to alter JP2–protein interactions regulating Ca2+ cycling. PMID:24001019

  4. Significant reduction of left atrial volume concomitant with clinical improvement after percutaneous transluminal septal myocardial ablation for drug-refractory hypertrophic obstructive cardiomyopathy, and its precise detection with multidetector CT

    PubMed Central

    Maekawa, Yuichiro; Akita, Keitaro; Tsuruta, Hikaru; Yamada, Yoshitake; Hayashida, Kentaro; Yuasa, Shinsuke; Murata, Mitsushige; Jinzaki, Masahiro; Fukuda, Keiichi

    2016-01-01

    Objective In patients with hypertrophic obstructive cardiomyopathy (HOCM), left atrial (LA) volume measurement is very important to provide prognostic information. Recent studies demonstrated that multidetector CT (MDCT) is useful to assess the changes in LA volume. Our aim was to examine the utility of a follow-up cardiac MDCT for long-term evaluation of the effect of percutaneous transluminal septal myocardial ablation (PTSMA) on LA volume. Methods We studied a consecutive cohort of 20 patients with drug-refractory symptomatic HOCM after PTSMA. We evaluated LA volume analyses with cardiac MDCT on patients who underwent PTSMA as compared to echocardiography. Results Before PTSMA, 75% of all patients had heart failure-associated symptoms in the New York Heart Association functional class III/IV. All patients experienced relief from heart failure-associated symptoms after PTSMA. Cardiac MDCT showed significant reduction in the index of maximum LA volume during follow-up compared to before PTSMA in the same way as in echocardiography (93.6±34.1 mL/m2 vs 82.6±35.3 mL/m2, p=0.035). A Bland-Altman plot showed small mean differences and limits of agreement in the measurements of the index of maximum LA volume before and after PTSMA between echocardiography and MDCT. Conclusions The follow-up cardiac MDCT was a useful tool to evaluate the effectiveness of PTSMA on reduction of LA volume. Cardiac MDCT might provide comparable measurements of the LA volume in patients with drug-refractory symptomatic HOCM before and after PTSMA compared to echocardiography. PMID:27307994

  5. Prevalence and Phenotypic Expression of Mutations in the MYH7, MYBPC3 and TNNT2 Genes in Families with Hypertrophic Cardiomyopathy in the South of Brazil: A Cross-Sectional Study

    PubMed Central

    Mattos, Beatriz Piva e; Scolari, Fernando Luís; Torres, Marco Antonio Rodrigues; Simon, Laura; de Freitas, Valéria Centeno; Giugliani, Roberto; Matte, Úrsula

    2016-01-01

    Background: Mutations in sarcomeric genes are found in 60-70% of individuals with familial forms of hypertrophic cardiomyopathy (HCM). However, this estimate refers to northern hemisphere populations. The molecular-genetic profile of HCM has been subject of few investigations in Brazil, particularly in the south of the country. Objective: To investigate mutations in the sarcomeric genes MYH7, MYBPC3 and TNNT2 in a cohort of HCM patients living in the extreme south of Brazil, and to evaluate genotype-phenotype associations. Methods: Direct DNA sequencing of all encoding regions of three sarcomeric genes was conducted in 43 consecutive individuals of ten unrelated families. Results: Mutations for CMH have been found in 25 (58%) patients of seven (70%) of the ten study families. Fourteen (56%) individuals were phenotype-positive. All mutations were missense, four (66%) in MYH7 and two (33%) in MYBPC3. We have not found mutations in the TNNT2 gene. Mutations in MYH7 were identified in 20 (47%) patients of six (60%) families. Two of them had not been previously described. Mutations in MYBPC3 were found in seven (16%) members of two (20%) families. Two (5%) patients showed double heterozygosis for both genes. The mutations affected different domains of encoded proteins and led to variable phenotypic expression. A family history of HCM was identified in all genotype-positive individuals. Conclusions: In this first genetic-molecular analysis carried out in the south of Brazil, we found mutations in the sarcomeric genes MYH7 and MYBPC3 in 58% of individuals. MYH7-related disease was identified in the majority of cases with mutation. PMID:27737317

  6. Long Term Ablation of Protein Kinase A (PKA)-mediated Cardiac Troponin I Phosphorylation Leads to Excitation-Contraction Uncoupling and Diastolic Dysfunction in a Knock-in Mouse Model of Hypertrophic Cardiomyopathy*

    PubMed Central

    Dweck, David; Sanchez-Gonzalez, Marcos A.; Chang, Audrey N.; Dulce, Raul A.; Badger, Crystal-Dawn; Koutnik, Andrew P.; Ruiz, Edda L.; Griffin, Brittany; Liang, Jingsheng; Kabbaj, Mohamed; Fincham, Frank D.; Hare, Joshua M.; Overton, J. Michael; Pinto, Jose R.

    2014-01-01

    The cardiac troponin I (cTnI) R21C (cTnI-R21C) mutation has been linked to hypertrophic cardiomyopathy and renders cTnI incapable of phosphorylation by PKA in vivo. Echocardiographic imaging of homozygous knock-in mice expressing the cTnI-R21C mutation shows that they develop hypertrophy after 12 months of age and have abnormal diastolic function that is characterized by longer filling times and impaired relaxation. Electrocardiographic analyses show that older R21C mice have elevated heart rates and reduced cardiovagal tone. Cardiac myocytes isolated from older R21C mice demonstrate that in the presence of isoproterenol, significant delays in Ca2+ decay and sarcomere relaxation occur that are not present at 6 months of age. Although isoproterenol and stepwise increases in stimulation frequency accelerate Ca2+-transient and sarcomere shortening kinetics in R21C myocytes from older mice, they are unable to attain the corresponding WT values. When R21C myocytes from older mice are treated with isoproterenol, evidence of excitation-contraction uncoupling is indicated by an elevation in diastolic calcium that is frequency-dissociated and not coupled to shorter diastolic sarcomere lengths. Myocytes from older mice have smaller Ca2+ transient amplitudes (2.3-fold) that are associated with reductions (2.9-fold) in sarcoplasmic reticulum Ca2+ content. This abnormal Ca2+ handling within the cell may be attributed to a reduction (2.4-fold) in calsequestrin expression in conjunction with an up-regulation (1.5-fold) of Na+-Ca2+ exchanger. Incubation of permeabilized cardiac fibers from R21C mice with PKA confirmed that the mutation prevents facilitation of mechanical relaxation. Altogether, these results indicate that the inability to enhance myofilament relaxation through cTnI phosphorylation predisposes the heart to abnormal diastolic function, reduced accessibility of cardiac reserves, dysautonomia, and hypertrophy. PMID:24973218

  7. Identification and Functional Characterization of a Novel CACNA1C-Mediated Cardiac Disorder Characterized by Prolonged QT Intervals with Hypertrophic Cardiomyopathy, Congenital Heart Defects, and Sudden Cardiac Death

    PubMed Central

    Boczek, Nicole J.; Ye, Dan; Jin, Fang; Tester, David J.; Huseby, April; Bos, J. Martijn; Johnson, Aaron J.; Kanter, Ronald; Ackerman, Michael J.

    2016-01-01

    Background A portion of sudden cardiac deaths (SCD) can be attributed to structural heart diseases such as hypertrophic cardiomyopathy (HCM) or cardiac channelopathies such as long QT syndrome (LQTS); however, the underlying molecular mechanisms are quite distinct. Here, we identify a novel CACNA1C missense mutation with mixed loss-of-function/gain-of-function responsible for a complex phenotype of LQTS, HCM, SCD, and congenital heart defects (CHDs). Methods and Results Whole exome sequencing (WES) in combination with Ingenuity Variant Analysis was completed on three affected individuals and one unaffected individual from a large pedigree with concomitant LQTS, HCM, and CHDs and identified a novel CACNA1C mutation, p.Arg518Cys, as the most likely candidate mutation. Mutational analysis of exon 12 of CACNA1C was completed on 5 additional patients with a similar phenotype of LQTS plus a personal or family history of HCM-like phenotypes, and identified two additional pedigrees with mutations at the same position, p.Arg518Cys/His. Whole cell patch clamp technique was used to assess the electrophysiological effects of the identified mutations in CaV1.2, and revealed a complex phenotype, including loss of current density and inactivation in combination with increased window and late current. Conclusions Through WES and expanded cohort screening, we identified a novel genetic substrate p.Arg518Cys/His-CACNA1C, in patients with a complex phenotype including LQTS, HCM, and CHDs annotated as cardiac-only Timothy syndrome. Our electrophysiological studies, identification of mutations at the same amino acid position in multiple pedigrees, and co-segregation with disease in these pedigrees provides evidence that p.Arg518Cys/His is the pathogenic substrate for the observed phenotype. PMID:26253506

  8. Restrictive cardiomyopathy

    MedlinePlus

    Cardiomyopathy - restrictive; Infiltrative cardiomyopathy; Idiopathic myocardial fibrosis ... of the heart lining (endocardium), such as endomyocardial fibrosis and Loeffler syndrome (rare) Iron overload (hemochromatosis) Sarcoidosis ...

  9. 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

  10. Effects of calcium binding and the hypertrophic cardiomyopathy A8V mutation on the dynamic equilibrium between closed and open conformations of the regulatory N-domain of isolated cardiac troponin C.

    PubMed

    Cordina, Nicole M; Liew, Chu K; Gell, David A; Fajer, Piotr G; Mackay, Joel P; Brown, Louise J

    2013-03-19

    Troponin C (TnC) is the calcium-binding subunit of the troponin complex responsible for initiating striated muscle contraction in response to calcium influx. In the skeletal TnC isoform, calcium binding induces a structural change in the regulatory N-domain of TnC that involves a transition from a closed to open structural state and accompanying exposure of a large hydrophobic patch for troponin I (TnI) to subsequently bind. However, little is understood about how calcium primes the N-domain of the cardiac isoform (cTnC) for interaction with the TnI subunit as the open conformation of the regulatory domain of cTnC has been observed only in the presence of bound TnI. Here we use paramagnetic relaxation enhancement (PRE) to characterize the closed to open transition of isolated cTnC in solution, a process that cannot be observed by traditional nuclear magnetic resonance methods. Our PRE data from four spin-labeled monocysteine constructs of isolated cTnC reveal that calcium binding triggers movement of the N-domain helices toward an open state. Fitting of the PRE data to a closed to open transition model reveals the presence of a small population of cTnC molecules in the absence of calcium that possess an open conformation, the level of which increases substantially upon Ca(2+) binding. These data support a model in which calcium binding creates a dynamic equilibrium between the closed and open structural states to prime cTnC for interaction with its target peptide. We also used PRE data to assess the structural effects of a familial hypertrophic cardiomyopathy point mutation located within the N-domain of cTnC (A8V). The PRE data show that the Ca(2+) switch mechanism is perturbed by the A8V mutation, resulting in a more open N-domain conformation in both the apo and holo states.

  11. 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

  12. 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

  13. [Mitochondrial cardiomyopathy in an adult: a case history].

    PubMed

    Tafanelli, L; Avierinos, J-F; Thuny, F; Pelissier, J-F; Jacquier, A; Renard, S; Amabile, N; Gaubert, J-Y; Habib, G

    2007-12-01

    We report an original case of mitochondrial cardiomyopathy discovered in a young woman during an episode of cardiac decompensation. The diagnosis was suspected from the echocardiographic appearances of granite-like heterogeneous hypertrophic cardiomyopathy. It was confirmed by endomyocardial biopsies. The clinical evolution was favourable with classical treatment. Mitochondrial cardiomyopathy is a rare cause of cardiomyopathy, generally observed in children, with multisystemic localisation. The pathophysiology and genetics are complex. Cardiac involvement is observed in 25% of cases, with the principal manifestation being hypertrophic cardiomyopathy. In the absence of any specific clinical or paraclinical signs, echocardiography and MRI are the techniques of choice for morphological evaluation. Diagnosis relies upon myocardial biopsy, which should be readily advocated in every unexplained case of cardiomyopathy in a young subject. The prognosis is poor and no specific treatment is available.

  14. Enzymic analysis of endomyocardial biopsy specimens from patients with cardiomyopathies.

    PubMed Central

    Peters, T J; Wells, G; Oakley, C M; Brooksby, I A; Jenkins, B S; Webb-Peploe, M M; Coltart, D J

    1977-01-01

    Myocardial biopsies have been obtained from patients with hypertrophic or congestive cardiomyopathies. Marker enzymes for the principal subcellular organelles of the myocardium were estimated using highly sensitive assay procedures. The results were compared with those obtained in tissue from patients with valvular heart disease with good or poor left ventricular function. Left ventricular myocardial tissue from patients with hypertrophic cardiomyopathy showed essentially normal levels of enzymic activities. In congestive cardiomyopathy, right ventricular tissue showed reduced levels of mitochondrial enzymes with increased levels of lactate dehydrogenase. Left ventricular tissue from patients with congestive cardiomyopathy showed reduced levels of mitochondrial and myofibril enzymes but high levels of lactate dehydrogenase. The reduced levels of myofibril Ca++-activated ATP in congestive cardiomyopathy is similar to that found in patients with impaired left ventricular function secondary to valvular disease. It is suggested that defective mitochondrial function is a characteristic feature of congestive cardiomyopathy and that the increased levels of lactate dehydrogenase reflect a compensatory response. PMID:564201

  15. Myocardial mechanics in cardiomyopathies.

    PubMed

    Modesto, Karen; Sengupta, Partho P

    2014-01-01

    Cardiomyopathies are a heterogeneous group of diseases that can be phenotypically recognized by specific patterns of ventricular morphology and function. The authors summarize recent clinical observations that mechanistically link the multidirectional components of left ventricular (LV) deformation with morphological phenotypes of cardiomyopathies for offering key insights into the transmural heterogeneity of myocardial function. Subendocardial dysfunction predominantly alters LV longitudinal shortening, lengthening and suction performance and contributes to the phenotypic patterns of heart failure (HF) with preserved ejection fraction (EF) seen with hypertrophic and restrictive patterns of cardiomyopathy. On the other hand, a more progressive transmural disease results in reduction of LV circumferential and twist mechanics leading to the phenotypic pattern of dilated cardiomyopathy and the clinical syndrome of HF with reduced (EF). A proper characterization of LV transmural mechanics, energetics, and space-time distributions of pressure and shear stress may allow recognition of early functional changes that can forecast progression or reversal of LV remodeling. Furthermore, the interactions between LV muscle and fluid mechanics hold the promise for offering newer mechanistic insights and tracking impact of novel therapies.

  16. 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

  17. Psychological disorders in adults with inherited cardiomyopathies and Takotsubo syndrome.

    PubMed

    Suárez Bagnasco, Mariana; Núñez-Gil, Iván J

    2016-06-03

    We performed a narrative review about psychological disorders in adults with Takotsubo syndrome and inherited cardiomyopathies. Through the electronic database PubMed and PsycINFO we searched all relevant related manuscripts published between 2000 and 2015. We found twelve studies that explore psychological disorders in Takotsubo syndrome and eight about inherited cardiomyopathies: five enrolled patients with hypertrophic cardiomyopathy, two dilated cardiomyopathy, and one arrhythmogenic right ventricular cardiomyopathy. All papers reported the presence of psychological disorders. In Takotsubo syndrome, depression fluctuates between 20.5 and 48% and anxiety was present among 26 and 56%. A study reported that anxiety increases the probability of developing Takotsubo syndrome. In dilated cardiomyopathy, anxiety was present in 50% and depression in 22%. In arrhythmogenic right ventricular cardiomyopathy, younger age, poorer functional capacity and having experienced at least one implantable cardioverter defibrillator shock, were significant independent predictors of both device-specific and generalized anxiety. In hypertrophic cardiomyopathy, anxiety and depression were present in 45.2% and 17.9%, respectively. Thirty seven percent met diagnostic criteria for anxiety disorders and 21% for mood disorders. Nearby half hypertrophic cardiomyopathy patients report triggering of chest pain, dyspnea, and dizziness by emotional stress. Due to the small number of studies, conclusions are limited. However, we discuss some results.

  18. Hypertrophic scar.

    PubMed

    Gabriel, Vincent

    2011-05-01

    Hypertrophic scars are common complications of burn injury and other soft tissue injuries. Excessive extracellular matrix combined with inadequate remodeling of scar tissue results in an aesthetically and functionally unsatisfactory, painful, pruritic scar that can impair function. Treatment options are available to rehabilitation practitioners, but none are entirely satisfactory. An interdisciplinary clinical program is necessary for best outcomes. Challenges to be met by the rehabilitation community include research into the quantification of burn scar measurement, the effects of mechanical forces on wound healing and scar management, and the best combination of surgical, pharmacologic, and therapy interventions to maximize outcome from reconstructive procedures. PMID:21624722

  19. Genetic evaluation of cardiomyopathy--a Heart Failure Society of America practice guideline.

    PubMed

    Hershberger, Ray E; Lindenfeld, Joann; Mestroni, Luisa; Seidman, Christine E; Taylor, Matthew R G; Towbin, Jeffrey A

    2009-03-01

    Substantial progress has been made recently in understanding the genetic basis of cardiomyopathy. Cardiomyopathies with known genetic cause include hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and left ventricular noncompaction (LVNC). HCM, DCM, and RCM have been recognized as distinct clinical entities for decades, whereas ARVD/C and LVNC are relative newcomers to the field. Hence the clinical and genetic knowledge for each cardiomyopathy varies, as do the recommendations and strength of evidence.

  20. Doxorubicin Cardiomyopathy

    PubMed Central

    Chatterjee, Kanu; Zhang, Jianqing; Honbo, Norman; Karliner, Joel S.

    2010-01-01

    Established doxorubicin cardiomyopathy is a lethal disease. When congestive heart failure develops, mortality is approximately 50%. Extensive research has been done to understand the mechanism and pathophysiology of doxorubicin cardiomyopathy, and considerable knowledge and experience has been gained. Unfortunately, no effective treatment for established doxorubicin cardiomyopathy is presently available. Extensive research has been done and is being done to discover preventive treatments. However an effective and clinically applicable preventive treatment is yet to be discovered. PMID:20016174

  1. Clinical Characteristics and Treatment of Cardiomyopathies in Children.

    PubMed

    Price, Jack F; Jeewa, Aamir; Denfield, Susan W

    2016-01-01

    Cardiomyopathies are diseases of the heart muscle, a term introduced in 1957 to identify a group of myocardial diseases not attributable to coronary artery disease. The definition has since been modified to refer to structural and or functional abnormalities of the myocardium where other known causes of myocardial dysfunction, such as systemic hypertension, valvular disease and ischemic heart disease, have been excluded. In this review, we discuss the pathophysiology, clinical assessment and therapeutic strategies for hypertrophic, dilated and hypertrophic cardiomyopathies, with a particular focus on aspects unique to children.

  2. The genetics of dilated cardiomyopathy

    PubMed Central

    Dellefave, Lisa; McNally, Elizabeth M.

    2010-01-01

    Purpose of review More than forty different individual genes have been implicated in the inheritance of dilated cardiomyopathy. For a subset of these genes, mutations can lead to a spectrum of cardiomyopathy that extends to hypertrophic cardiomyopathy and left ventricular noncompaction. In nearly all cases, there is an increased risk of arrhythmias. With some genetic mutations, extracardiac manifestations are likely to be present. The precise genetic etiology can usually not be discerned from the cardiac and/or extracardiac manifestations and requires molecular genetic diagnosis for prognostic determination and cardiac care. Recent findings Newer technologies are influencing genetic testing, especially cardiomyopathy genetic testing, where an increased number of genes are now routinely being tested simultaneously. While this approach to testing multiple genes is increasing the diagnostic yield, the analysis of multiple genes in one test is also resulting in a large amount of genetic information of unclear significance. Summary Genetic testing is highly useful in the care of patients and families, since it guides diagnosis, influences care and aids in prognosis. However, the large amount of benign human genetic variation may complicate genetic results, and often requires a skilled team to accurately interpret the findings. PMID:20186049

  3. Cardiomyopathy in congenital and acquired generalized lipodystrophy: a clinical assessment.

    PubMed

    Lupsa, Beatrice C; Sachdev, Vandana; Lungu, Andreea O; Rosing, Douglas R; Gorden, Phillip

    2010-07-01

    Lipodystrophy is a rare disorder characterized by loss of adipose tissue and low leptin levels. This condition is characterized by severe dyslipidemia, insulin resistance, diabetes mellitus, and steatohepatitis. Another phenotypic feature that occurs with considerable frequency in generalized lipodystrophy is cardiomyopathy. We report here the cardiac findings in a cohort of patients with generalized congenital and acquired lipodystrophy, and present a literature review of the cardiac findings in patients with generalized lipodystrophy. We studied 44 patients with generalized congenital and acquired lipodystrophy, most of them enrolled in a clinical trial of leptin therapy. Patients underwent electrocardiograms and transthoracic echocardiograms to evaluate their cardiac status. We followed these patients for an extended time period, some of them up to 8 years. Evaluation of our cohort of patients with generalized lipodystrophy shows that cardiomyopathy is a frequent finding in this population. Most of our patients had hypertrophic cardiomyopathy, and only a small number had features of dilated cardiomyopathy. Hypertrophic cardiomyopathy was more frequent in patients with seipin mutation, a finding consistent with the literature. The underlying mechanism for cardiomyopathy in lipodystrophy is not clear. Extreme insulin resistance and the possibility of a "lipotoxic cardiomyopathy" should be entertained as possible explanations.

  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.

  5. [Peripartum cardiomyopathy].

    PubMed

    Bouabdallaoui, Nadia; de Groote, Pascal; Mouquet, Frédéric

    2009-06-01

    The peripartum cardiomyopathy is a rare form of dilated cardiomyopathy. Its etiology remains unclear and is likely multifactorial. The diagnosis is based on the association of clinical heart failure and systolic dysfunction assessed by echocardiography or magnetic resonance imaging. Diagnosis to rule out are myocardial infarction, myocarditis, inherited cardiomyopathy, history of treatment by anthracycline. Risk factors are advance maternal age (> 30), multiparity, twin pregnancy, african origin, obesity, pre-eclampsia, gestational hypertension, and prolonged tocolytic therapy. Treatment of acute phase is identical to usual treatment of acute systolic heart failure. Angiotensin converting enzyme inhibitor and VKA are contra indicated during pregnancy. After delivery, VKA treatment should be discussed in case of systolic function < 25 % because of higher risk of thrombus. Complete recovery of systolic function is observed in 50 % of the case. The mortality risk is low. Subsequent pregnancy should be discouraged, especially if systolic function did not recover.

  6. 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

  7. 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.

  8. 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

  9. Cardiomyopathies in Noonan syndrome and the other RASopathies

    PubMed Central

    Gelb, Bruce D.; Roberts, Amy E.; Tartaglia, Marco

    2015-01-01

    Noonan syndrome and related disorders (Noonan syndrome with multiple lentigines, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with loose anagen hair, and other related traits) are autosomal dominant traits. Mutations causing these disorders alter proteins relevant for signaling through RAS. Thus, these traits are now collectively called the RASopathies. While the RASopathies have pleiomorphic features, this review will focus on the hypertrophic cardiomyopathy observed in varying percentages of all of these traits. In addition, inherited abnormalities in one pathway gene, RAF1, cause pediatric-onset dilated cardiomyopathy. The pathogeneses for the RASopathy-associated cardiomyopathies are being elucidated, principally using animal models, leading to genotype-specific insights into how signal transduction is perturbed. Based on those findings, small molecule therapies seem possible for RASopathy-associated cardiomyopathies. PMID:26380542

  10. Positron emission tomography for the evaluation and treatment of cardiomyopathy.

    PubMed

    Shah, Palak; Choi, Brian G; Mazhari, Ramesh

    2011-06-01

    Congestive heart failure accounts for tremendous morbidity and mortality worldwide. There are numerous causes of cardiomyopathy, the most common of which is coronary artery disease. Positron emission tomography (PET) has an established and expanding role in the evaluation of patients with cardiomyopathy. The specific application of PET to hypertrophic cardiomyopathy, cardiac sarcoidosis, and diabetic cardiomyopathy has been studied extensively and promises to be a useful tool for managing these patients. Furthermore, evaluating the efficacy of standard treatments for congestive heart failure is important as health care costs continue to rise. Recently, there have been significant developments in the field of cardiovascular stem cell research. Familiarity with the mechanisms by which stem cells benefit patients with cardiovascular disease is the key to understanding these advances. Molecular imaging techniques including PET/CT imaging play an important role in monitoring stem cell therapy in both animals and humans. These noninvasive imaging techniques will be highlighted in this paper.

  11. 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.

  12. Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay

    PubMed Central

    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

  13. Hypertrophic discoid lupus erythematosus.

    PubMed

    Farley-Loftus, Rachel; Elmariah, Sarina B; Ralston, Jonathan; Kamino, Hideko; Franks, Andrew G

    2010-11-15

    Hypertrophic discoid lupus erythematosus is a distinct form of chronic cutaneous (discoid) lupus, which is characterized by hyperkeratotic plaques that typically are observed over the face, arms, and upper trunk. We present the case of a 43-year-old man with verrucous plaques that were distributed symmetrically over the face, who initially was treated with oral antibiotics and topical glucocorticoids for acne vulgaris. A biopsy specimen confirmed the diagnosis of hypertrophic discoid lupus erythematosus. The clinical and histopathologic features of this clinical variant are reviewed.

  14. Genetic advances in sarcomeric cardiomyopathies: state of the art.

    PubMed

    Ho, Carolyn Y; Charron, Philippe; Richard, Pascale; Girolami, Francesca; Van Spaendonck-Zwarts, Karin Y; Pinto, Yigal

    2015-04-01

    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.

  15. [Cardiomyopathies and pregnancy--how often, when to decide to terminate?].

    PubMed

    Nowalany-Kozielska, Ewa

    2015-01-01

    Cardiomyopathies are a small percentage of heart disease in pregnant women, but usually cause severe complications. It is not know the exact incidence of cardiomyopathy associated with pregnancy in Europe. In these patients, there is a higher probability of death due to changes in hemodynamic, metabolic and hemostatic that occur in pregnancy. Pregnant mortality is 2.4% vs. 0.007%--in the normal population. The most common cause of severe maternal complications is peripartum cardiomyopathy (PPCM). In dilated cardiomyopathy (DCM) and restrictive (RCM) is usually observed significant clinical deterioration during pregnancy. On the other hand, in patients with hypertrophic cardiomyopathy (HCM), pregnancy and childbirth are often associated with a low risk of complications. There is a greater risk in women presenting symptoms before and on pregnancy and in women with large inrtaventricular and subaortic pressure gradient. There are only a few case reports of pregnancy in patients with rare storage diseases and infiltrative phenotype of hypertrophic cardiomyopathy. For these patients the pregnancy is contraindicated. In patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is sometimes the severity of arrhythmia in the third trimester of pregnancy, and childbirth (natural or cesarean section) is usually safe. Remember to informing women with various cardiomyopathies both the risks of pregnancy and about the possibility of transferring the disease to offspring. Contraception should be advised in many cases. PMID:26455023

  16. Targets for therapy in sarcomeric cardiomyopathies

    PubMed Central

    Tardiff, Jil C.; Carrier, Lucie; Bers, Donald M.; Poggesi, Corrado; Ferrantini, Cecilia; Coppini, Raffaele; Maier, Lars S.; Ashrafian, Houman; Huke, Sabine; van der Velden, Jolanda

    2015-01-01

    To date, no compounds or interventions exist that treat or prevent sarcomeric cardiomyopathies. Established therapies currently improve the outcome, but novel therapies may be able to more fundamentally affect the disease process and course. Investigations of the pathomechanisms are generating molecular insights that can be useful for the design of novel specific drugs suitable for clinical use. As perturbations in the heart are stage-specific, proper timing of drug treatment is essential to prevent initiation and progression of cardiac disease in mutation carrier individuals. In this review, we emphasize potential novel therapies which may prevent, delay, or even reverse hypertrophic cardiomyopathy caused by sarcomeric gene mutations. These include corrections of genetic defects, altered sarcomere function, perturbations in intracellular ion homeostasis, and impaired myocardial energetics. PMID:25634554

  17. 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

  18. X-linked cardiomyopathy is heterogeneous

    SciTech Connect

    Wilson, M.J.; Sillence, D.O.; Mulley, J.C.

    1994-09-01

    Two major loci of X-linked cardiomyopathy have been mapped by linkage analysis. The gene for X-linked dilated cardiomyopathy (XLCM) is mapped to the dystrophin locus at Xp21, while Barth syndrome has been localised to distal Xq28. XLCM usually presents in juvenile males with no skeletal disease but decreased dystrophin in cardiac muscle. Barth syndrome most often presents in infants and is characterized by skeletal myopathy, short stature and neutropenia in association with cardiomyopathy of variable severity. Prior to carrier or prenatal diagnosis in a family, delineation of the cardiomyopathy locus involved is essential. We report the linkage mapping of a large kindred in which several male infants have died with hypertrophic cardiomyopathy. There is a family history of unexplained death of infant males less than 6 months old over 4 generations. Features of Barth syndrome such as short stature, skeletal myopathy and neutropenia have not been observed. Genotyping at 10 marker loci in Xq28 has revealed significant pairwise lod scores with the cardiomyopathy phenotype at DXS52 (Z=2.21 at {theta}=0.0), at markers p26 and p39 near DXS15 (Z=2.30 at {theta}=0.0) and at F8C (Z=2.24 at {theta}=0.0). A recombinant detected with DXS296 defines the proximal limit to the localization. No recombinants were detected at any of the loci distal to DXS296. The most distal marker in Xq28, DXS1108, is within 500 kb of the telomere. As the gene in this family is localized to Xq28, it is possible that this disorder is an allelic variant at the Barth syndrome locus.

  19. Incidence of dilated cardiomyopathy

    PubMed Central

    Abelmann, Walter H.

    1985-01-01

    Full reliable data on the incidence and prevalence of dilated cardiomyopathy are not available. In the United States, at least 0.7% of cardiac deaths are attributable to cardiomyopathy. Dilated cardiomyopathy probably contributes the great majority of these cases. The mortality rate for cardiomyopathy in males is twice that of females, and for blacks it is 2.4 times that of whites. Cardiomyopathy was diagnosed in 0.67% of patients discharged from hospitals in 1979 with diagnoses of disease of the circulatory system. Cardiomyopathy accounted for 1% of general cardiologists' and for 7% of academic cardiologists' patient encounters. In Scandinavia, population surveys suggested an annual incidence of dilated cardiomyopathy ranging from 0.73 to 7.5 cases per 100,000 population; for Tokyo this figure is 2.6. The prevalence of cardiomyopathy in underdeveloped and in tropical countries is considerably higher than in developed countries.

  20. [Septal alcohol ablation in patients with hypertrophic cardiomyopathy].

    PubMed

    López-Aburto, Gustavo; Palacios-Rodríguez, Juan Manuel; Cantú-Ramírez, Samuel; Galván-García, Eduardo; Tolosa-Dzul, Gonzalo; Morán-Benavente, Armando; Ontiveros-Martínez, Raúl

    2013-01-01

    Objetivo: conocer características demográficas, clínicas y hemodinámicas de los pacientes con ablación con alcohol para tratar la miocardiopatía hipertrófica septal obstructiva (MHSO). Métodos: estudio observacional, longitudinal, descriptivo de 21 pacientes con MHSO resistente a tratamiento o con gradiente = 30 mm Hg en reposo o = 60 mm Hg provocado y con movimiento sistólico anterior o insuficiencia mitral > grado II. Resultados: edad de 50 ± 16 años; hombres 38.1 % y mujeres 61.9 %. Los síntomas fueron angor 42.9 %, disnea 85.7 % y síncope 23.8 %. La clase funcional NYHA preablación fue grados III y IV en 61.9 %; al año todos tenían grados I y II. Preablación y al año, el espesor del septo interventricular fue de 22.7 ± 4.9 y 20.7 ± 3.1 mm. Preablación, después y al año, la fracción de eyección fue de 65.5 ± 7, 62.2 ± 6.5 y 68.7 ± 6.2 %. Preablación, después y al año, el gradiente del tracto de salida del ventrículo izquierdo fue de 106.9 ± 29.9, 44.6 ± 24.3 y 22.0 ± 5.7 mm Hg. Preablación, la insuficiencia mitral fue grados III y IV en 33.3 y 47.6 % y al año fue grados 0 en 52.4 %, I en 28.6 % y II en 19 %. No hubo defunciones intrahospitalarias. Conclusiones: la ablación septal con alcohol en pacientes con MHSO fue exitosa.

  1. 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.

  2. Mitochondrial cardiomyopathy: pathophysiology, diagnosis, and management.

    PubMed

    Meyers, Deborah E; Basha, Haseeb Ilias; Koenig, Mary Kay

    2013-01-01

    Mitochondrial disease is a heterogeneous group of multisystemic diseases that develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence of inherited mitochondrial disease has been estimated to be greater than 1 in 5,000 births; however, the diagnosis and treatment of this disease are not taught in most adult-cardiology curricula. Because mitochondrial diseases often occur as a syndrome with resultant multiorgan dysfunction, they might not immediately appear to be specific to the cardiovascular system. Mitochondrial cardiomyopathy can be described as a myocardial condition characterized by abnormal heart-muscle structure, function, or both, secondary to genetic defects involving the mitochondrial respiratory chain, in the absence of concomitant coronary artery disease, hypertension, valvular disease, or congenital heart disease. The typical cardiac manifestations of mitochondrial disease--hypertrophic and dilated cardiomyopathy, arrhythmias, left ventricular myocardial noncompaction, and heart failure--can worsen acutely during a metabolic crisis. The optimal management of mitochondrial disease necessitates the involvement of a multidisciplinary team, careful evaluations of patients, and the anticipation of iatrogenic and noniatrogenic complications. In this review, we describe the complex pathophysiology of mitochondrial disease and its clinical features. We focus on current practice in the diagnosis and treatment of patients with mitochondrial cardiomyopathy, including optimal therapeutic management and long-term monitoring. We hope that this information will serve as a guide for practicing cardiologists who treat patients thus affected.

  3. hiPSC MODELING OF INHERITED CARDIOMYOPATHIES

    PubMed Central

    Jung, Gwanghyun; Bernstein, Daniel

    2014-01-01

    Opinion Statement Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a powerful new model system to study the basic mechanisms of inherited cardiomyopathies. hiPSC-CMs have been utilized to model several cardiovascular diseases, achieving the most success in the inherited arrhythmias, including long QT and Timothy syndromes (1,2) and arrhythmogenic right ventricular dysplasia (ARVD) (3). Recently, studies have applied hiPSC-CMs to the study of both dilated (DCM) (4) and hypertrophic (HCM) cardiomyopathies (5,6), providing new insights into basic mechanisms of disease. However, hiPSC-CMs do not recapitulate many of the structural and functional aspects of mature human cardiomyocytes, instead mirroring an immature, embryonic or fetal, phenotype. Thus, much work remains to better understand these differences as well as to develop methods to induce hiPSC-CMs into a fully mature phenotype. Despite these limitations, hiPSC-CMs represent the best current in vitro correlate of the human heart and an invaluable tool in the search for mechanisms underlying cardiomyopathy and for screening new pharmacologic therapies. PMID:24838688

  4. Mitochondrial cardiomyopathy: pathophysiology, diagnosis, and management.

    PubMed

    Meyers, Deborah E; Basha, Haseeb Ilias; Koenig, Mary Kay

    2013-01-01

    Mitochondrial disease is a heterogeneous group of multisystemic diseases that develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence of inherited mitochondrial disease has been estimated to be greater than 1 in 5,000 births; however, the diagnosis and treatment of this disease are not taught in most adult-cardiology curricula. Because mitochondrial diseases often occur as a syndrome with resultant multiorgan dysfunction, they might not immediately appear to be specific to the cardiovascular system. Mitochondrial cardiomyopathy can be described as a myocardial condition characterized by abnormal heart-muscle structure, function, or both, secondary to genetic defects involving the mitochondrial respiratory chain, in the absence of concomitant coronary artery disease, hypertension, valvular disease, or congenital heart disease. The typical cardiac manifestations of mitochondrial disease--hypertrophic and dilated cardiomyopathy, arrhythmias, left ventricular myocardial noncompaction, and heart failure--can worsen acutely during a metabolic crisis. The optimal management of mitochondrial disease necessitates the involvement of a multidisciplinary team, careful evaluations of patients, and the anticipation of iatrogenic and noniatrogenic complications. In this review, we describe the complex pathophysiology of mitochondrial disease and its clinical features. We focus on current practice in the diagnosis and treatment of patients with mitochondrial cardiomyopathy, including optimal therapeutic management and long-term monitoring. We hope that this information will serve as a guide for practicing cardiologists who treat patients thus affected. PMID:24082366

  5. [Arrhythmic cardiomyopathy. Case report].

    PubMed

    Streangă, Violeta; Dimitriu, A G; Iordache, C; Georgescu, G; Grecu, Mihaela

    2004-01-01

    An 11 year-old boy was admitted with incessant sinus node reentrant tachycardia and secondary dilated arrhythmic cardiomyopathy, treated by radiofrequency ablation. Two years later he was admitted with incessant automatic atrial tachycardia and arrhythmic cardiomyopathy; a second catheter ablation procedure failed, but the third one, performed four month later, was successfully and resulted in a restoration of a normal sinus rhythm and a complete regression of arrhythmic cardiomyopathy.

  6. Update on hypertrophic scar treatment

    PubMed Central

    Rabello, Felipe Bettini; Souza, Cleyton Dias; Júnior, Jayme Adriano Farina

    2014-01-01

    Scar formation is a consequence of the wound healing process that occurs when body tissues are damaged by a physical injury. Hypertrophic scars and keloids are pathological scars resulting from abnormal responses to trauma and can be itchy and painful, causing serious functional and cosmetic disability. The current review will focus on the definition of hypertrophic scars, distinguishing them from keloids and on the various methods for treating hypertrophic scarring that have been described in the literature, including treatments with clearly proven efficiency and therapies with doubtful benefits. Numerous methods have been described for the treatment of abnormal scars, but to date, the optimal treatment method has not been established. This review will explore the differences between different types of nonsurgical management of hypertrophic scars, focusing on the indications, uses, mechanisms of action, associations and efficacies of the following therapies: silicone, pressure garments, onion extract, intralesional corticoid injections and bleomycin. PMID:25141117

  7. Update on hypertrophic scar treatment.

    PubMed

    Rabello, Felipe Bettini; Souza, Cleyton Dias; Farina Júnior, Jayme Adriano

    2014-08-01

    Scar formation is a consequence of the wound healing process that occurs when body tissues are damaged by a physical injury. Hypertrophic scars and keloids are pathological scars resulting from abnormal responses to trauma and can be itchy and painful, causing serious functional and cosmetic disability. The current review will focus on the definition of hypertrophic scars, distinguishing them from keloids and on the various methods for treating hypertrophic scarring that have been described in the literature, including treatments with clearly proven efficiency and therapies with doubtful benefits. Numerous methods have been described for the treatment of abnormal scars, but to date, the optimal treatment method has not been established. This review will explore the differences between different types of nonsurgical management of hypertrophic scars, focusing on the indications, uses, mechanisms of action, associations and efficacies of the following therapies: silicone, pressure garments, onion extract, intralesional corticoid injections and bleomycin. PMID:25141117

  8. Animal Models of Congenital Cardiomyopathies Associated With Mutations in Z-Line Proteins.

    PubMed

    Bang, Marie-Louise

    2017-01-01

    The cardiac Z-line at the boundary between sarcomeres is a multiprotein complex connecting the contractile apparatus with the cytoskeleton and the extracellular matrix. The Z-line is important for efficient force generation and transmission as well as the maintenance of structural stability and integrity. Furthermore, it is a nodal point for intracellular signaling, in particular mechanosensing and mechanotransduction. Mutations in various genes encoding Z-line proteins have been associated with different cardiomyopathies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, and left ventricular noncompaction, and mutations even within the same gene can cause widely different pathologies. Animal models have contributed to a great advancement in the understanding of the physiological function of Z-line proteins and the pathways leading from mutations in Z-line proteins to cardiomyopathy, although genotype-phenotype prediction remains a great challenge. This review presents an overview of the currently available animal models for Z-line and Z-line associated proteins involved in human cardiomyopathies with special emphasis on knock-in and transgenic mouse models recapitulating the clinical phenotypes of human cardiomyopathy patients carrying mutations in Z-line proteins. Pros and cons of mouse models will be discussed and a future outlook will be given. J. Cell. Physiol. 232: 38-52, 2017. © 2016 Wiley Periodicals, Inc. PMID:27171814

  9. 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

  10. Repeated radiofrequency ablation of atrial tachycardia in restrictive cardiomyopathy secondary to myofibrillar myopathy.

    PubMed

    Stöllberger, Claudia; Gatterer, Edmund; Finsterer, Josef; Kuck, Karl-Heinz; Tilz, Roland Richard

    2014-08-01

    Myofibrillar myopathy is characterized by nonhyaline and hyaline lesions due to mutations in nuclear genes encoding for extra-myofibrillar or myofibrillar proteins. Cardiac involvement in myofibrillar myopathy may be phenotypically expressed as dilated, hypertrophic, or restrictive cardiomyopathy. Radiofrequency ablation of atrial fibrillation and flutter has so far not been reported in myofibrillar myopathy. We report the case of a young female with myofibrillar myopathy and deteriorating heart failure due to restrictive cardiomyopathy and recurrent atrial fibrillation and atrial tachycardias intolerant to pharmacotherapy. Cardiac arrhythmias were successfully treated with repeat radiofrequency ablations and resulted in regression of heart failure, thus postponing the necessity for cardiac transplantation.

  11. [The characteristics of cardiomyopathy in different geographical regions].

    PubMed

    Faez, H V; Korovina, E A; Shatkovskiĭ, N P; Shelepin, A A; Moiseev, V S

    1992-01-01

    Region-specific characteristics of hypertrophic cardiomyopathy (HC) and dilated cardiomyopathy (DC) were compared for 108 relevant patients living in Dubai (United Arab Emirates) and Moscow (Russia). Out of 49 citizens of Dubai 17 had HC, 32 DC, and 59 Moscow patients had HC in 23, DC in 36 cases. It was found that HC in Dubai tends to run a silent latent course, involving mainly basal septum and right ventricle. Apical lesions were more typical for Moscow citizens who also display more severe myocardial impairment. DC in Dubai produces weaker cardiac insufficiency and arrhythmia. Incidence of idiopathic and periportal DC proved higher in Dubai, while alcohol and virus infection underlie DC more frequently in Moscow.

  12. Cardiomyopathy in Friedreich ataxia: clinical findings and research.

    PubMed

    Payne, R Mark; Wagner, Gregory R

    2012-09-01

    Friedreich ataxia is the most common human ataxia and results from inadequate production of the frataxin protein, most often the result of a triplet expansion in the nuclear FXN gene. The gene cannot be transcribed to generate the messenger ribonucleic acid for frataxin. Frataxin is an iron-binding protein targeted to the mitochondrial matrix. In its absence, multiple iron-sulfur-dependent proteins in mitochondria and the cytosol lack proper assembly, destroying mitochondrial and nuclear function. Mitochondrial oxidant stress may also participate in ongoing cellular injury. Although progressive and debilitative ataxia is the most prominent clinical finding, hypertrophic cardiomyopathy with heart failure is the most common cause of early death in this disease. There is no cure. In this review the authors cover recent basic and clinical findings regarding the heart in Friedreich ataxia, offer recommendations for clinical management of the cardiomyopathy in this disease, and point out new research directions to advance the field.

  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. 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

  15. Phidippides cardiomyopathy: a review and case illustration.

    PubMed

    Trivax, Justin E; McCullough, Peter A

    2012-02-01

    Phidippides was a Greek messenger who experienced sudden death after running more than 175 miles in two days. In today's world, marathon running and other endurance sports are becoming more popular and raising concern about sudden deaths at these events. Once etiologies such has hypertrophic cardiomyopathy, anomalous coronary arteries, and coronary atherosclerosis have been excluded, there is now an additional consideration termed Phidippides cardiomyopathy. Because endurance sports call for a sustained increase in cardiac output for several hours, the heart is put into a state of volume overload. It has been shown that approximately one-third of marathon runners experience dilation of the right atrium and ventricle, have elevations of cardiac troponin and natriuretic peptides, and in a smaller fraction later develop small patches of cardiac fibrosis that are the likely substrate for ventricular tachyarrhythmias and sudden death. Cardiac magnetic resonance imaging is emerging as the diagnostic test of choice for this condition. This review and case report summarizes the key features of this newly appreciated disorder.

  16. Genetic Variation in Cardiomyopathy and Cardiovascular Disorders.

    PubMed

    McNally, Elizabeth M; Puckelwartz, Megan J

    2015-01-01

    With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and practical issues. Genetic variation is a rich source of knowledge for cardiovascular disease because many, if not all, cardiovascular disorders are highly heritable. The role of rare genetic variation in predicting risk and complications of cardiovascular diseases has been well established for hypertrophic and dilated cardiomyopathy, where the number of genes that are linked to these disorders is growing. Bolstered by family data, where genetic variants segregate with disease, rare variation can be linked to specific genetic variation that offers profound diagnostic information. Understanding genetic variation in cardiomyopathy is likely to help stratify forms of heart failure and guide therapy. Ultimately, genetic variation may be amenable to gene correction and gene editing strategies.

  17. Topical treatments for hypertrophic scars.

    PubMed

    Zurada, Joanna M; Kriegel, David; Davis, Ira C

    2006-12-01

    Hypertrophic scars represent an abnormal, exaggerated healing response after skin injury. In addition to cosmetic concern, scars may cause pain, pruritus, contractures, and other functional impairments. Therapeutic modalities include topical medications, intralesional corticosteroids, laser therapy, and cryosurgery. Topical therapies, in particular, have become increasingly popular because of their ease of use, comfort, noninvasiveness, and relatively low cost. This review will discuss the properties and effectiveness of these agents, including pressure therapy, silicone gel sheeting and ointment, polyurethane dressing, onion extract, imiquimod 5% cream, and vitamins A and E in the prevention and treatment of hypertrophic scars. PMID:17097399

  18. 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 ...

  19. Biventricular Takotsubo Cardiomyopathy

    PubMed Central

    Daoko, Joseph; Rajachandran, Manu; Savarese, Ronald; Orme, Joseph

    2013-01-01

    Biventricular takotsubo cardiomyopathy is associated with more hemodynamic instability than is isolated left ventricular takotsubo cardiomyopathy; medical management is more invasive and the course of hospitalization is longer. In March 2011, a 62-year-old woman presented at our emergency department with abdominal pain, nausea, and vomiting. On hospital day 2, she experienced chest pain. An electrocardiogram and cardiac enzyme levels suggested an acute myocardial infarction. She underwent cardiac angiography and was found to have severe left ventricular systolic dysfunction involving the mid and apical segments, which resulted in a left ventricular ejection fraction of 0.10 to 0.15 in the absence of obstructive coronary artery disease. Her hospital course was complicated by cardiogenic shock that required hemodynamic support with an intra-aortic balloon pump and dobutamine. A transthoracic echocardiogram revealed akinesis of the mid-to-distal segments of the left ventricle and mid-to-apical dyskinesis of the right ventricular free wall characteristic of biventricular takotsubo cardiomyopathy. After several days of medical management, the patient was discharged from the hospital in stable condition. To the best of our knowledge, this is the first review of the literature on biventricular takotsubo cardiomyopathy that compares its hemodynamic instability and medical management requirements with those of isolated left ventricular takotsubo cardiomyopathy. Herein, we discuss the case of our patient, review the pertinent medical literature, and convey the prevalence and importance of right ventricular involvement in patients with takotsubo cardiomyopathy. PMID:23914028

  20. [Molecular targets and novel pharmacological options to prevent myocardial hypertrophic remodeling].

    PubMed

    Coppini, Raffaele; Ferrantini, Cecilia; Poggesi, Corrado; Mugelli, Alessandro; Olivotto, Iacopo

    2016-03-01

    Myocardial hypertrophic remodeling is a pathophysiological feature of several cardiac conditions and is the hallmark of hypertrophic cardiomyopathy (HCM), the most common monogenic inherited disease of the heart. In recent years, preclinical and clinical studies investigated the underlying molecular mechanisms and intracellular signaling pathways involved in pathologic cardiomyocyte hypertrophy and highlighted a number of possible molecular targets of therapy aimed at preventing its development. Early prevention of myocardial hypertrophic remodeling is particularly sought after in HCM, as current therapeutic strategies are unable to remove the primary cause of disease, i.e. the disease-causing gene mutation. Studies on transgenic animal models or human myocardial samples from patients with HCM identified intracellular calcium overload as a central mechanism driving pathological hypertrophy. In this review, we analyze recent preclinical and clinical studies on animal models and patients with HCM aimed at preventing or modifying hypertrophic myocardial remodeling. Mounting evidence shows that prevention of pathological hypertrophy is a feasible strategy in HCM and will enter the clinical practice in the near future. Considering the close mechanistic similarities between HCM and secondary hypertrophy, these studies are also relevant for the common forms of cardiac hypertrophy, such as hypertensive or valvular heart disease. PMID:27029877

  1. An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice

    PubMed Central

    Sheikh, Farah; Raskin, Anna; Chu, Pao-Hsien; Lange, Stephan; Domenighetti, Andrea A.; Zheng, Ming; Liang, Xingqun; Zhang, Tong; Yajima, Toshitaka; Gu, Yusu; Dalton, Nancy D.; Mahata, Sushil K.; Dorn, Gerald W.; Heller-Brown, Joan; Peterson, Kirk L.; Omens, Jeffrey H.; McCulloch, Andrew D.; Chen, Ju

    2008-01-01

    The response of cardiomyocytes to biomechanical stress can determine the pathophysiology of hypertrophic cardiac disease, and targeting the pathways regulating these responses is a therapeutic goal. However, little is known about how biomechanical stress is sensed by the cardiomyocyte sarcomere to transduce intracellular hypertrophic signals or how the dysfunction of these pathways may lead to disease. Here, we found that four-and-a-half LIM domains 1 (FHL1) is part of a complex within the cardiomyocyte sarcomere that senses the biomechanical stress–induced responses important for cardiac hypertrophy. Mice lacking Fhl1 displayed a blunted hypertrophic response and a beneficial functional response to pressure overload induced by transverse aortic constriction. A link to the Gαq (Gq) signaling pathway was also observed, as Fhl1 deficiency prevented the cardiomyopathy observed in Gq transgenic mice. Mechanistic studies demonstrated that FHL1 plays an important role in the mechanism of pathological hypertrophy by sensing biomechanical stress responses via the N2B stretch sensor domain of titin and initiating changes in the titin- and MAPK-mediated responses important for sarcomere extensibility and intracellular signaling. These studies shed light on the physiological regulation of the sarcomere in response to hypertrophic stress. PMID:19033658

  2. [Molecular targets and novel pharmacological options to prevent myocardial hypertrophic remodeling].

    PubMed

    Coppini, Raffaele; Ferrantini, Cecilia; Poggesi, Corrado; Mugelli, Alessandro; Olivotto, Iacopo

    2016-03-01

    Myocardial hypertrophic remodeling is a pathophysiological feature of several cardiac conditions and is the hallmark of hypertrophic cardiomyopathy (HCM), the most common monogenic inherited disease of the heart. In recent years, preclinical and clinical studies investigated the underlying molecular mechanisms and intracellular signaling pathways involved in pathologic cardiomyocyte hypertrophy and highlighted a number of possible molecular targets of therapy aimed at preventing its development. Early prevention of myocardial hypertrophic remodeling is particularly sought after in HCM, as current therapeutic strategies are unable to remove the primary cause of disease, i.e. the disease-causing gene mutation. Studies on transgenic animal models or human myocardial samples from patients with HCM identified intracellular calcium overload as a central mechanism driving pathological hypertrophy. In this review, we analyze recent preclinical and clinical studies on animal models and patients with HCM aimed at preventing or modifying hypertrophic myocardial remodeling. Mounting evidence shows that prevention of pathological hypertrophy is a feasible strategy in HCM and will enter the clinical practice in the near future. Considering the close mechanistic similarities between HCM and secondary hypertrophy, these studies are also relevant for the common forms of cardiac hypertrophy, such as hypertensive or valvular heart disease.

  3. Recommendations for participation in competitive sport and leisure-time physical activity in individuals with cardiomyopathies, myocarditis and pericarditis.

    PubMed

    Pelliccia, Antonio; Corrado, Domenico; Bjørnstad, Hans Halvor; Panhuyzen-Goedkoop, Nicole; Urhausen, Axel; Carre, Francois; Anastasakis, Aris; Vanhees, Luc; Arbustini, Eloisa; Priori, Silvia

    2006-12-01

    Several relatively uncommon, but important cardiovascular diseases are associated with increased risk for acute cardiac events during exercise (including sudden death), such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and myo-pericarditis. Practising cardiologists are frequently asked to advise on exercise programmes and sport participation in young individuals with these cardiovascular diseases. Indeed, many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to a physically active lifestyle to take advantage of the many documented benefits of exercise. While recommendations dictating the participation in competitive sport for athletes with cardiomyopathies and myo-pericarditis have recently been published as a consensus document of the European Society of Cardiology, no European guidelines have addressed the possible participation of patients with cardiomyopathies in recreational and amateur sport activities. The present document is intended to offer a comprehensive overview to practising cardiologists and sport physicians of the recommendations governing safe participation in different types of competitive sport, as well as the participation in a variety of recreational physical activities and amateur sports in individuals with cardiomyopathies and myo-pericarditis. These recommendations, based largely on the experience and insights of the expert panel appointed by the European Society of Cardiology, include the most up-to-date information concerning regular exercise and sports activity in patients with cardiomyopathies and myo-pericarditis. PMID:17143118

  4. 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

  5. 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

  6. Acromegaly-induced cardiomyopathy with dobutamine-induced outflow tract obstruction.

    PubMed

    Abdelsalam, Mahmoud A; Nippoldt, Todd B; Geske, Jeffrey B

    2016-01-01

    A 50-year-old man with a history of acromegaly was referred for preoperative cardiac evaluation preceding trans-sphenoidal resection of a pituitary macroadenoma. Dobutamine stress echocardiography was negative for myocardial ischaemia. Resting left ventricular (LV) LV ejection fraction (LVEF) was 64% and there was hypertrophy of ventricular septum (18 mm) without resting LV outflow tract obstruction. With 40 µg/kg/min of dobutamine, the LVEF became hyperdynamic at 80%, and there was a maximal instantaneous LV outflow tract gradient of 77 mm Hg. There was no delayed myocardial enhancement on cardiac MRI and the pattern of hypertrophy was concentric. Acromegaly-induced cardiomyopathy can mimic hypertrophic cardiomyopathy in the setting of dobutamine provocation. Because cardiomyopathy is an important cause of mortality in acromegaly, diagnosis and appropriate management are critical to improve survival. PMID:26961727

  7. Treatment of Chagas Cardiomyopathy

    PubMed Central

    Botoni, Fernando A.; Ribeiro, Antonio Luiz P.; Marinho, Carolina Coimbra; Lima, Marcia Maria Oliveira; Nunes, Maria do Carmo Pereira; Rocha, Manoel Otávio C.

    2013-01-01

    Chagas' disease (ChD), caused by the protozoa Trypanosoma cruzi (T. cruzi), was discovered and described by the Brazilian physician Carlos Chagas in 1909. After a century of original description, trypanosomiasis still brings much misery to humanity and is classified as a neglected tropical disease prevalent in underdeveloped countries, particularly in South America. It is an increasing worldwide problem due to the number of cases in endemic areas and the migration of infected subjects to more developed regions, mainly North America and Europe. Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is yet poorly understood, and independently of its social, clinical, and epidemiological importance, the therapeutic approach of CCC is still transposed from the knowledge acquired from other cardiomyopathies. Therefore, the objective of this review is to describe the treatment of Chagas cardiomyopathy with emphasis on its peculiarities. PMID:24350293

  8. 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

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

    PubMed Central

    Burke, Michael A.; Chang, Stephen; 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

  10. 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

  11. Children's Cardiomyopathy Foundation

    MedlinePlus

    ... on pediatric cardiomyopathy. The hope is that one day every affected child can be cured to live a full and active life. “A Cause for Today… A Cure for Tomorrow” CCF News & Updates Make this holiday season extra sweet and give from the heart to ...

  12. 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

  13. 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.

  14. Epidemiologic and clinical characteristics of cardiomyopathies in Japan: results from nationwide surveys.

    PubMed

    Matsumori, Akira; Furukawa, Yutaka; Hasegawa, Koji; Sato, Yukihito; Nakagawa, Hideaki; Morikawa, Yuko; Miura, Katsuyuki; Ohno, Yoshiyuki; Tamakoshi, Akiko; Inaba, Yutaka; Sasayama, Shigetake

    2002-04-01

    Nationwide clinico-epidemiological surveys of cardiomyopathies in Japan were carried out. Disorders surveyed included idiopathic dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular dysplasia (ARVD), mitochondrial disease, Fabry's disease of the heart and prolonged Q-T interval syndrome. The total number of patients was estimated at 17,700 for DCM, 21,900 for HCM, 300 for RCM, 520 for ARVD, 640 for mitochondrial disease, 150 for Fabry's disease of the heart, and 1,000 for prolonged Q-T interval syndrome. The prevalence of both DCM and HCM was higher in men than women: the male-to-female ratios were 2.6 and 2.3 for DCM and HCM, respectively. Detailed data on patients with DCM or HCM were collected by a follow-up survey. In 1 year more patients with DCM (5.6%) died than with HCM (2.8%): congestive heart failure (CHF) and arrhythmias were the leading causes of death for DCM and HCM, respectively. Angiotensin converting enzyme inhibitors (64.6%) and beta-adrenergic blockers (40.9%) are commonly used to treat the CHF complicating DCM and may be associated with the clinical improvement in a significant number of DCM patients. Thus, the nationwide surveys of Japanese patients have yielded important current epidemiological and clinical information on the characteristics of cardiomyopathies in Japan.

  15. Hypertrophic lupus vulgaris: an unusual presentation.

    PubMed

    Jain, Vijay K; Aggarwal, Kamal; Jain, Sarika; Singh, Sunita

    2009-07-01

    Lupus vulgaris is the most common form of cutaneous tuberculosis occurring in previously sensitized individuals with a high degree of tuberculin sensitivity. Various forms including plaque, ulcerative, hypertrophic, vegetative, papular, and nodular forms have been described. A 30-year-old male patient presented with a very large hypertrophic lupus vulgaris lesion over left side of chest since 22 years. Histopathological examination showed granulomatous infiltration without caseation necrosis. The Mantoux reaction was strongly positive. Hypertrophic lupus vulgaris of such a giant size and that too at an unusual site is extremely rare and hence is being reported.

  16. [The clinical practice guidelines of the Sociedad Española de Cardiología on cardiomyopathies and myocarditis].

    PubMed

    Galve Basilio, E; Alfonso Manterola, F; Ballester Rodés, M; Castro Beiras, A; Fernández de Soria Pantoja, R; Penas Lado, M; Sánchez Domínguez, J

    2000-03-01

    Myocardial diseases are a extraordinarily heterogeneous group of processes that only have in common the fact that they involve heart muscle and that they cause a wide spectrum of myocardial dysfunction. The approach of the management and treatment of the cardiomyopathies is a continuous matter of discussion because the vast majority of alternatives in this field have not been based on the best scientific possible evidence and, since except for the case of heart failure associated with dilated cardiomyopathy. The majority of different options have not been studied by means of large (or even small) randomized trials. Nevertheless, this chapter has tried to provide the reader with different approaches on how to deal with important clinical problems in dilated, hypertrophic and restrictive cardiomyopathies, and in myocarditis as well. For this, we have utilized the most relevant information found coupled with our best clinical judgment, although we admit that many of the clinical recommendations can be controversial.

  17. Laser application for hypertrophic rhinitis

    NASA Astrophysics Data System (ADS)

    Inouye, Tetsuzo; Tanabe, Tetsuya; Nakanoboh, Manabu; Ogura, Masami

    1995-05-01

    The CO2 and KTP/532 lasers have been used in the treatment of an allergic and hypertrophic rhinitis for the past several years. As we know, the laser enables a surgeon to perform the operation with minimum hemorrhage and minimized pain, during and after the procedure. Additionally many of these operations can be performed under local anesthesia instead of general anesthesia, on an outpatient basis. The laser is used to irradiate the mucous membranes of the inferior turbinates. Vaporization and cutting is easily done. Post operative management of the local operated area is easy. The advantages of laser surgery over regular surgical techniques are supreme for intranasal operations when performed under local anesthesia.

  18. Role of neuropeptides in cardiomyopathies.

    PubMed

    Dvorakova, Magdalena Chottova; Kruzliak, Peter; Rabkin, Simon W

    2014-11-01

    The role of neuropeptides in cardiomyopathy-associated heart failure has been garnering more attention. Several neuropeptides--Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP) and their receptors have been studied in the various types of cardiomyopathies. The data indicate associations with the strength of the association varying depending on the kind of neuropeptide and the nature of the cardiomyopathy--diabetic, ischemic, inflammatory, stress-induced or restrictive cardiomyopathy. Several neuropeptides appear to alter regulation of genes involved in heart failure. Demonstration of an association is an essential first step in proving causality or establishing a role for a factor in a disease. Understanding the complexity of neuropeptide function should be helpful in establishing new or optimal therapeutic strategies for the treatment of heart failure in cardiomyopathies.

  19. A common factor in hypertrophic osteoarthropathy

    PubMed Central

    Carroll, K. B.; Doyle, L.

    1974-01-01

    Carroll, K. B. and Doyle, L. (1974).Thorax, 29, 262-264. A common factor in hypertrophic osteoarthropathy. Two cases of oesophageal disease with hypertrophic osteoarthropathy are presented. The unusual site of the primary lesion has prompted a review of the literature and led to the conclusion that there is a common innervation accounting for a common afferent arc which is an integral and basic part of the mechanism in this disorder. Images PMID:4831530

  20. MTO1-deficient mouse model mirrors the human phenotype showing complex I defect and cardiomyopathy.

    PubMed

    Becker, Lore; Kling, Eva; Schiller, Evelyn; Zeh, Ramona; Schrewe, Anja; Hölter, Sabine M; Mossbrugger, Ilona; Calzada-Wack, Julia; Strecker, Valentina; Wittig, Ilka; Dumitru, Iulia; Wenz, Tina; Bender, Andreas; Aichler, Michaela; Janik, Dirk; Neff, Frauke; Walch, Axel; Quintanilla-Fend, Leticia; Floss, Thomas; Bekeredjian, Raffi; Gailus-Durner, Valérie; Fuchs, Helmut; Wurst, Wolfgang; Meitinger, Thomas; Prokisch, Holger; de Angelis, Martin Hrabě; Klopstock, Thomas

    2014-01-01

    Recently, mutations in the mitochondrial translation optimization factor 1 gene (MTO1) were identified as causative in children with hypertrophic cardiomyopathy, lactic acidosis and respiratory chain defect. Here, we describe an MTO1-deficient mouse model generated by gene trap mutagenesis that mirrors the human phenotype remarkably well. As in patients, the most prominent signs and symptoms were cardiovascular and included bradycardia and cardiomyopathy. In addition, the mutant mice showed a marked worsening of arrhythmias during induction and reversal of anaesthesia. The detailed morphological and biochemical workup of murine hearts indicated that the myocardial damage was due to complex I deficiency and mitochondrial dysfunction. In contrast, neurological examination was largely normal in Mto1-deficient mice. A translational consequence of this mouse model may be to caution against anaesthesia-related cardiac arrhythmias which may be fatal in patients.

  1. E101K and M123V alpha-cardiac actin gene mutations are not associated with cardiomyopathy in Iranian population

    PubMed Central

    Jebelli, Asiyeh; Beyranvand, Eshrat; Sadeghian, Hakimeh; Boroumand, Mohammad Ali; Behmanesh, Mehrdad

    2015-01-01

    BACKGROUND Cardiomyopathies are myocardial disorders in which the heart muscle is structurally and functionally abnormal. Several mutations in sarcomere protein coding genes are responsible for different types of cardiomyopathies. ACTC1 is one of the main sarcomere components in heart muscle. Two mutations of E101K and M123V in this gene are shown to be associated with cardiomyopathies. METHODS In this case and control study, a sample of contains 30 hypertrophic cardiomyopathy and 100 dilated cardiomyopathy patients, as well as 130 healthy individuals were screened for two mutations of E101K and M123V. The genotypes of samples were determined in whole blood genomic DNA by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and mismatched-PCR-RLFP techniques. RESULTS All patients and healthy peoples had wild type genotype for both locations and even no heterozygous was detected. CONCLUSION Despite previous reports, no association was observed between both mutations with cardiomyopathy. Our results indicated that two mutations of E101K and M123V of ACTC1 gene may are not associated with cardiomyopathy in Iranian population. PMID:26715934

  2. 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

  3. Exome Sequencing Identifies Mitochondrial Alanyl-tRNA Synthetase Mutations in Infantile Mitochondrial Cardiomyopathy

    PubMed Central

    Götz, Alexandra; Tyynismaa, Henna; Euro, Liliya; Ellonen, Pekka; Hyötyläinen, Tuulia; Ojala, Tiina; Hämäläinen, Riikka H.; Tommiska, Johanna; Raivio, Taneli; Oresic, Matej; Karikoski, Riitta; Tammela, Outi; Simola, Kalle O.J.; Paetau, Anders; Tyni, Tiina; Suomalainen, Anu

    2011-01-01

    Infantile cardiomyopathies are devastating fatal disorders of the neonatal period or the first year of life. Mitochondrial dysfunction is a common cause of this group of diseases, but the underlying gene defects have been characterized in only a minority of cases, because tissue specificity of the manifestation hampers functional cloning and the heterogeneity of causative factors hinders collection of informative family materials. We sequenced the exome of a patient who died at the age of 10 months of hypertrophic mitochondrial cardiomyopathy with combined cardiac respiratory chain complex I and IV deficiency. Rigorous data analysis allowed us to identify a homozygous missense mutation in AARS2, which we showed to encode the mitochondrial alanyl-tRNA synthetase (mtAlaRS). Two siblings from another family, both of whom died perinatally of hypertrophic cardiomyopathy, had the same mutation, compound heterozygous with another missense mutation. Protein structure modeling of mtAlaRS suggested that one of the mutations affected a unique tRNA recognition site in the editing domain, leading to incorrect tRNA aminoacylation, whereas the second mutation severely disturbed the catalytic function, preventing tRNA aminoacylation. We show here that mutations in AARS2 cause perinatal or infantile cardiomyopathy with near-total combined mitochondrial respiratory chain deficiency in the heart. Our results indicate that exome sequencing is a powerful tool for identifying mutations in single patients and allows recognition of the genetic background in single-gene disorders of variable clinical manifestation and tissue-specific disease. Furthermore, we show that mitochondrial disorders extend to prenatal life and are an important cause of early infantile cardiac failure. PMID:21549344

  4. Diabetic cardiomyopathy, causes and effects

    PubMed Central

    Boudina, Sihem

    2010-01-01

    Diabetes is associated with increased incidence of heart failure even after controlling for coronary artery disease and hypertension. Thus, as diabetic cardiomyopathy has become an increasingly recognized entity among clinicians, a better understanding of its pathophysiology is necessary for early diagnosis and the development of treatment strategies for diabetes-associated cardiovascular dysfunction. We will review recent basic and clinical research into the manifestations and the pathophysiological mechanisms of diabetic cardiomyopathy. The discussion will be focused on the structural, functional and metabolic changes that occur in the myocardium in diabetes and how these changes may contribute to the development of diabetic cardiomyopathy in affected humans and relevant animal models. PMID:20180026

  5. Takotsubo cardiomyopathy (Broken heart syndrome).

    PubMed

    Javed, Aqib; Chitkara, Kamal; Mahmood, Arslan; Kainat, Aleesha

    2015-11-01

    Takotsubo cardiomyopathy is an acute reversible cardiomyopathy characterised by transient regional left ventricular (LV) motion abnormalities. It is diagnosed on a coronary angiography and left ventriculography. We report the case of a 50-year-old lady who presented with sudden onset of chest pain, with no history of cardiac disease and no risk factors. Remarkably though, she had lost her husband the previous night. Coronary and LV angiography was done which revealed findings typical of takotsubo cardiomyopathy. We report this case for its rarity. Informed consent was taken from the patient before undertaking and reporting this study. PMID:26564308

  6. Echocardiographic manifestations of infiltrative cardiomyopathy. A report of seven cases due to amyloid.

    PubMed

    Child, J S; Levisman, J A; Abbasi, A S; MacAlpin, R N

    1976-12-01

    Echocardiography has been useful in the evaluation of congestive and hypertrophic cardiomyopathies. We present echocardiographic findings in seven patients with infiltrative cardiomyopathy due to amyloid. Cardiac amyloidosis was documented at autopsy in two patients, and the diagnosis was suggested by clinical, echocardiographic, tissue, or hemodynamic findings in the other five. Hemodynamic findings in three patients mimicked constrictive pericarditis; and autopsy was performed on one of the three and showed a normal pericardium. Underlying disorders were multiple myeloma (five patients), ankylosing spondylitis (one patient), and an unknown disorder (one patient). The basic echocardiographic findings in infiltrative cardiomyopathy due to amyloid were (1) symmetrically increased left ventricular wall thickness (in the absence of hypertension or aortic valvular disease), (2) hypokinesia and decreased systolic thickening of the interventricular septum and left ventricular posterior wall, and (3) small to normal size of the left ventricular cavity. Two patients also had small pericardial effusions. Thus, in a patient with congestive heart failure, these echocardiographic findings should suggest infiltrative cardiomyopathy.

  7. 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

  8. A Review of the Giant Protein Titin in Clinical Molecular Diagnostics of Cardiomyopathies.

    PubMed

    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

  9. Hypertrophic pachymeningitis accompanying neuromyelitis optica spectrum disorder: A case report.

    PubMed

    Kon, Tomoya; Nishijima, Haruo; Haga, Rie; Funamizu, Yukihisa; Ueno, Tatsuya; Arai, Akira; Suzuki, Chieko; Nunomura, Jin-ichi; Baba, Masayuki; Takahashi, Toshiyuki; Tomiyama, Masahiko

    2015-10-15

    We report a case of idiopathic cerebral hypertrophic pachymeningitis accompanying neuromyelitis optica spectrum disorder. No other identifiable cause of pachymeningitis was detected. Corticosteroid therapy was effective for both diseases. Hypertrophic pachymeningitis is closely related to autoimmune inflammatory disease of the central nervous system. This case supports the hypothesis that hypertrophic pachymeningitis can be a rare comorbidity of neuromyelitis optica spectrum disorder.

  10. Alcoholic cardiomyopathy: pathophysiologic insights.

    PubMed

    Piano, Mariann R; Phillips, Shane A

    2014-12-01

    Alcoholic cardiomyopathy (ACM) is a specific heart muscle disease found in individuals with a history of long-term heavy alcohol consumption. ACM 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 ACM.

  11. 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

  12. Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model.

    PubMed

    Martínez-Morentin, Leticia; Martínez, Lidia; Piloto, Sarah; Yang, Hua; Schon, Eric A; Garesse, Rafael; Bodmer, Rolf; Ocorr, Karen; Cervera, Margarita; Arredondo, Juan J

    2015-07-01

    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.

  13. Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia.

    PubMed

    Perdomini, Morgane; Belbellaa, Brahim; Monassier, Laurent; Reutenauer, Laurence; Messaddeq, Nadia; Cartier, Nathalie; Crystal, Ronald G; Aubourg, Patrick; Puccio, Hélène

    2014-05-01

    Cardiac failure is the most common cause of mortality in Friedreich's ataxia (FRDA), a mitochondrial disease characterized by neurodegeneration, hypertrophic cardiomyopathy and diabetes. FRDA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Impaired mitochondrial oxidative phosphorylation, bioenergetics imbalance, deficit of Fe-S cluster enzymes and mitochondrial iron overload occur in the myocardium of individuals with FRDA. No treatment exists as yet for FRDA cardiomyopathy. A conditional mouse model with complete frataxin deletion in cardiac and skeletal muscle (Mck-Cre-Fxn(L3/L-) mice) recapitulates most features of FRDA cardiomyopathy, albeit with a more rapid and severe course. Here we show that adeno-associated virus rh10 vector expressing human FXN injected intravenously in these mice fully prevented the onset of cardiac disease. Moreover, later administration of the frataxin-expressing vector, after the onset of heart failure, was able to completely reverse the cardiomyopathy of these mice at the functional, cellular and molecular levels within a few days. Our results demonstrate that cardiomyocytes with severe energy failure and ultrastructure disorganization can be rapidly rescued and remodeled by gene therapy and establish the preclinical proof of concept for the potential of gene therapy in treating FRDA cardiomyopathy.

  14. Exercise Rehabilitation in Pediatric Cardiomyopathy

    PubMed Central

    Somarriba, Gabriel; Extein, Jason; Miller, Tracie L.

    2008-01-01

    Children with cardiomyopathy carry significant risk of morbidity and mortality. New research and technology have brought about significant advancements to the diagnosis and clinical management of children with cardiomyopathy. However, currently heart transplantation remains the standard of care for children with symptomatic and progressive cardiomyopathy. Cardiovascular rehabilitation programs have yielded success in improving cardiac function, overall physical activity, and quality of life in adults with congestive heart failure from a variety of conditions. There is encouraging and emerging data on its effects in children with chronic illness and with its proven benefits in other pediatric disorders, the implementation of a program for with cardiomyopathy should be considered. Exercise rehabilitation programs may improve specific endpoints such quality of life, cardiovascular function and fitness, strength, flexibility, and metabolic risk. With the rapid rise in pediatric obesity, children with cardiomyopathy may be at similar risk for developing these modifiable risk factors. However, there are potentially more detrimental effects of inactivity in this population of children. Future research should focus on the physical and social effects of a medically supervised cardiac rehabilitation program with correct determination of the dosage and intensity of exercise for optimal benefits in this special population of children. It is imperative that more detailed recommendations for children with cardiomyopathy be made available with evidence-based research. PMID:18496603

  15. Primary hypertrophic osteoarthropathy (pachydermoperiostosis): a case report.

    PubMed

    Karkucak, Murat; Erturk, Engin; Capkin, Erhan; Akyazi, Hikmet; Ozden, Gonca; Tosun, Mehmet

    2007-02-01

    Hypertrophic osteoarthropathy is characterized by digital clubbing and periosteal reaction of long bones. Most cases are associated with malignancy or other conditions such as congenital heart disease, liver cirrhosis, pulmonary fibrosis, biliary atresia, and gastrointestinal polyps. We report a 19-year-old man presenting with arthritis, broadening of the fingers and clubbing of the fingers and toes for the previous 3 years. The ankles and knees were swollen. X-rays showed periosteal apposition. The search for a secondary cause remained negative. In cases of arthralgia/arthritis together with clubbed fingers, consideration must be given to hypertrophic osteoarthropathy. The primary or idiopathic form is rare and has a good prognosis.

  16. Hypoxia-driven glycolytic and fructolytic metabolic programs: Pivotal to hypertrophic heart disease.

    PubMed

    Mirtschink, Peter; Krek, Wilhelm

    2016-07-01

    Pathologic cardiac growth is an adaptive response of the myocardium to various forms of systemic (e.g. pressure overload) or genetically-based (e. g. mutations in genes encoding sarcomeric proteins) stress. It represents a key aspect of different types of heart disease including aortic stenosis (AS) and hypertrophic cardiomyopathy (HCM). While many of the pathophysiological and hemodynamical aspects of pathologic cardiac hypertrophy have been uncovered during the last decades, its underlying metabolic determinants are only beginning to come into focus. Here, we review the epidemiological evidence and pathological features of hypertrophic heart disease in AS and HCM and consider in this context the development of microenvironmental tissue hypoxia as a key component of the heart's growth response to pathologic stress. We particularly reflect on recent evidence illustrating how activation of hypoxia-inducible factor (HIF) drives glycolytic and fructolytic metabolic programs to maintain ATP generation and support anabolic growth of the pathologically-stressed heart. Finally we discuss how this metabolic programs, when protracted, deprive the heart of energy leading ultimately to heart failure. 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.

  17. Hypoxia-driven glycolytic and fructolytic metabolic programs: Pivotal to hypertrophic heart disease.

    PubMed

    Mirtschink, Peter; Krek, Wilhelm

    2016-07-01

    Pathologic cardiac growth is an adaptive response of the myocardium to various forms of systemic (e.g. pressure overload) or genetically-based (e. g. mutations in genes encoding sarcomeric proteins) stress. It represents a key aspect of different types of heart disease including aortic stenosis (AS) and hypertrophic cardiomyopathy (HCM). While many of the pathophysiological and hemodynamical aspects of pathologic cardiac hypertrophy have been uncovered during the last decades, its underlying metabolic determinants are only beginning to come into focus. Here, we review the epidemiological evidence and pathological features of hypertrophic heart disease in AS and HCM and consider in this context the development of microenvironmental tissue hypoxia as a key component of the heart's growth response to pathologic stress. We particularly reflect on recent evidence illustrating how activation of hypoxia-inducible factor (HIF) drives glycolytic and fructolytic metabolic programs to maintain ATP generation and support anabolic growth of the pathologically-stressed heart. Finally we discuss how this metabolic programs, when protracted, deprive the heart of energy leading ultimately to heart failure. 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:26896647

  18. 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) ...

  19. [Levosimendan for septic shock with takotsubo cardiomyopathy].

    PubMed

    Schlürmann, C-N; Reinöhl, J; Kalbhenn, J

    2016-01-01

    As a stress-induced disease, takotsubo cardiomyopathy can also occur in septic syndromes; however, the hemodynamic management is fundamentally different from the treatment approaches for classical septic cardiomyopathy, as beta mimetics can increase the heart failure symptoms in takotsubo cardiomyopathy. This article reports the case of an 82-year-old female patient who presented with acute abdomen due to adhesion ileus and takotsubo cardiomyopathy, developed severe septic shock with peritonitis and could be successfully hemodynamically stabilized with levosimendan.

  20. 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

  1. Peripartum cardiomyopathy and dilated cardiomyopathy: different at heart.

    PubMed

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

    2014-01-01

    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

  2. Dilated cardiomyopathy: an anaesthetic challenge.

    PubMed

    Kaur, Haramritpal; Khetarpal, Ranjana; Aggarwal, Shobha

    2013-06-01

    Idiopathic dilated cardiomyopathy is a primary myocardial disease of unknown etiology characterized by left ventricular or biventricular dilation and impaired contractility. Depending upon diagnostic criteria used, the reported annual incidence varies between 5 and 8 cases per 100,000 populations. Dilated cardiomyopathy is defined by presence of: a) fractional myocardial shortening less than 25% (>2SD) and/or ejection fraction less than 45% (>2SD) and b) Left Ventricular End Diastolic Diameter (LVEDD) greater than 117% excluding any known cause of myocardial disease. Such cases are always a challenge to the anesthesiologist as they are most commonly complicated by progressive cardiac failure. We report the anesthetic management of a patient with dilated cardiomyopathy undergoing surgery for carcinoma breast. PMID:23905133

  3. Percutaneous cardioscopy of the cardiac chambers in patients with hypertrophic cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Fujimori, Yoshiharu; Uchida, Yasumi; Nakamura, Fumitaka; Tomaru, Takanobu; Miwa, Atsuko; Hirose, Junichi; Sasaki, Michihiko; Oshima, Tomomitsu; Tsubouchi, Hiroyuki

    1993-05-01

    Recent advances in fiberoptic technology enables us to observe the cardiac chambers percutaneously in various categories of heart disease. We applied cardioscopy in 4 patients with HCM. Two of them presented excessive or good left ventricular function and no history of congestive heart failure (CHF). The other two patients showed reduced left ventricular function with a history of CHF. Cardioscopy was successfully performed in all patients. In patients with excessive or good left ventricular function, the color of the endocardial surface was light brown mixed with white. The trabeculae were significantly thick and contracted vigorously. In patients with reduced left ventricular function, the color was whiter, and the thickness and contraction of the trabeculae were reduced obviously. Myocardial biopsy revealed that interstitial fibrosis was prominent in the latters. These results indicate that (1) cardioscopy is safe and useful for evaluation of the internal surface of the ventricle in patients with HCM, and (2) cardioscopic characteristics of the ventricle are closely related to histopathological features.

  4. Capnocytophaga ochracea-related Bacterium Bacteremia in a Hypertrophic Cardiomyopathy Patient without Neutropenia.

    PubMed

    Ito, Shimpei; Hagiya, Hideharu; Kimura, Keigo; Nishi, Isao; Yoshida, Hisao; Kioka, Hidetaka; Ohtani, Tomohito; Yamaguchi, Osamu; Tanabe, Kazuaki; Tomono, Kazunori; Sakata, Yasushi

    2016-01-01

    Gram-negative fusiform rods were detected in a blood culture obtained from a 63-year-old man who had been hospitalized for a long duration for severe heart failure. Although the organism could not be identified using a conventional method, it was finally identified as a bacterium of the Capnocytophaga ochracea group based on the results of biochemical testing, 16S rRNA sequencing and a matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis. Although neutropenic patients with poor oral hygiene are exclusively vulnerable to Capnocytophaga bacteremia, this case was unique because such predisposing conditions were not noted. A multi-centered investigation is warranted for a better understanding of this clinically rare, but potentially pathogenic organism. PMID:27629977

  5. Severe, early onset hypertrophic cardiomyopathy in a family with LEOPARD syndrome

    PubMed Central

    Limongelli, Giuseppe; Pacileo, Giuseppe; Russo, Maria Giovanna; Sarkozy, Anna; Felicetti, Maria; Di Salvo, Giovanni; Morelli, Carmela; Calabrò, Paolo; Paladini, Dario; Marino, Bruno; Dallapiccola, Bruno; Calabrò, Raffaele

    2008-01-01

    Objective: Leopard syndrome is an acronym (multiple Lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness) describing an autosomal dominant disease due to mutations in the raS-MapK pathway. Methods: Here, we describe a family (mother and daughter) with clinical and molecular diagnosis of Leopard syndrome 1 and HCM, and we report the prenatal diagnosis of HCM in a fetus at risk for Leopard syndrome. Results: An echocardiography was conducted showing a significant hypertrophy of both ventricles (left and right ventricular wall thickness 9mm and 3 mm). After a multidisciplinary counseling the couple opted for the termination of pregnancy Conclusion: Further genotype-phenotype studies are warranted to fully elucidate the impact of the genotype on the natural history of patients with LS and LVH PMID:22439023

  6. Post-mortem genetic testing in a family with long-QT syndrome and hypertrophic cardiomyopathy.

    PubMed

    Kane, David A; Triedman, John

    2014-01-01

    Pediatric sudden unexplained deaths are rare and tragic events that should be evaluated with all the tools available to the medical community. The current state of genetic testing is an excellent resource that improves our ability to diagnose cardiovascular disorders that can lead to sudden cardiac arrest. Post-mortem genetic testing is not typically a covered benefit of health insurance and may not be offered to families in the setting of a negative autopsy. This unusual case includes two separate cardiovascular disorders that highlight the use of genetic testing and its role in diagnosis, screening, and risk stratification. The insurance company's decision to cover post-mortem testing demonstrated both compassion as well as an understanding of the long-term cost effectiveness.

  7. Calcification of in vitro developed hypertrophic cartilage

    SciTech Connect

    Tacchetti, C.; Quarto, R.; Campanile, G.; Cancedda, R.

    1989-04-01

    We have recently reported that dedifferentiated cells derived from stage 28-30 chick embryo tibiae, when transferred in suspension culture in the presence of ascorbic acid, develop in a tissue closely resembling hypertrophic cartilage. Ultrastructural examination of this in vitro formed cartilage showed numerous matrix vesicles associated with the extracellular matrix. In the present article we report that the in vitro developed hypertrophic cartilage undergoes calcification. We indicate a correlation between the levels of alkaline phosphatase activity and calcium deposition at different times of development. Following the transfer of cells into suspension culture and an initial lag phase, the level of alkaline phosphatase activity rapidly increased. In most experiments the maximum of activity was reached after 5 days of culture. When alkaline phosphatase activity and /sup 45/Ca deposition were measured in the same experiment, we observed that the increase in alkaline phosphatase preceded the deposition of nonwashable calcium deposits in the cartilage.

  8. Ablation of the Cardiac-Specific Gene Leucine-Rich Repeat Containing 10 (Lrrc10) Results in Dilated Cardiomyopathy

    PubMed Central

    Brody, Matthew J.; Hacker, Timothy A.; Patel, Jitandrakumar R.; Feng, Li; Sadoshima, Junichi; Tevosian, Sergei G.; Balijepalli, Ravi C.; Moss, Richard L.; Lee, Youngsook

    2012-01-01

    Leucine-rich repeat containing 10 (LRRC10) is a cardiac-specific protein exclusively expressed in embryonic and adult cardiomyocytes. However, the role of LRRC10 in mammalian cardiac physiology remains unknown. To determine if LRRC10 is critical for cardiac function, Lrrc10-null (Lrrc10−/−) mice were analyzed. Lrrc10−/− mice exhibit prenatal systolic dysfunction and dilated cardiomyopathy in postnatal life. Importantly, Lrrc10−/− mice have diminished cardiac performance in utero, prior to ventricular dilation observed in young adults. We demonstrate that LRRC10 endogenously interacts with α-actinin and α-actin in the heart and all actin isoforms in vitro. Gene expression profiling of embryonic Lrrc10−/− hearts identified pathways and transcripts involved in regulation of the actin cytoskeleton to be significantly upregulated, implicating dysregulation of the actin cytoskeleton as an early defective molecular signal in the absence of LRRC10. In contrast, microarray analyses of adult Lrrc10−/− hearts identified upregulation of oxidative phosphorylation and cardiac muscle contraction pathways during the progression of dilated cardiomyopathy. Analyses of hypertrophic signal transduction pathways indicate increased active forms of Akt and PKCε in adult Lrrc10−/− hearts. Taken together, our data demonstrate that LRRC10 is essential for proper mammalian cardiac function. We identify Lrrc10 as a novel dilated cardiomyopathy candidate gene and the Lrrc10−/− mouse model as a unique system to investigate pediatric cardiomyopathy. PMID:23236519

  9. Development and pathomechanisms of cardiomyopathy in very long-chain acyl-CoA dehydrogenase deficient (VLCAD(-/-)) mice.

    PubMed

    Tucci, Sara; Flögel, Ulrich; Hermann, Sven; Sturm, Marga; Schäfers, Michael; Spiekerkoetter, Ute

    2014-05-01

    Hypertrophic cardiomyopathy is a typical manifestation of very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), the most common long-chain β-oxidation defects in humans; however in some patients cardiac function is fully compensated. Cardiomyopathy may also be reversed by supplementation of medium-chain triglycerides (MCT). We here characterize cardiac function of VLCAD-deficient (VLCAD(-/-)) mice over one year. Furthermore, we investigate the long-term effect of a continuous MCT diet on the cardiac phenotype. We assessed cardiac morphology and function in VLCAD(-/-) mice by in vivo MRI. Cardiac energetics were measured by (31)P-MRS and myocardial glucose uptake was quantified by positron-emission-tomography (PET). Metabolic adaptations were identified by the expression of genes regulating glucose and lipid metabolism using real-time-PCR. VLCAD(-/-) mice showed a progressive decrease in heart function over 12 months accompanied by a reduced phosphocreatine-to-ATP-ratio indicative of chronic energy deficiency. Long-term MCT supplementation aggravated the cardiac phenotype into dilated cardiomyopathy with features similar to diabetic heart disease. Cardiac energy production and function in mice with a β-oxidation defect cannot be maintained with age. Compensatory mechanisms are insufficient to preserve the cardiac energy state over time. However, energy deficiency by impaired β-oxidation and long-term MCT induce cardiomyopathy by different mechanisms. Cardiac MRI and MRS may be excellent tools to assess minor changes in cardiac function and energetics in patients with β-oxidation defects for preventive therapy.

  10. Inflammation and cutaneous nervous system involvement in hypertrophic scarring

    PubMed Central

    Li, Shao-hua; Yang, Heng-lian; Xiao, Hu; Wang, Yi-bing; Wang, De-chang; Huo, Ran

    2015-01-01

    This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation. PMID:26692869

  11. 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 ...

  12. Genetic engineering and therapy for inherited and acquired cardiomyopathies.

    PubMed

    Day, Sharlene; Davis, Jennifer; Westfall, Margaret; Metzger, Joseph

    2006-10-01

    The cardiac myofilaments consist of a highly ordered assembly of proteins that collectively generate force in a calcium-dependent manner. Defects in myofilament function and its regulation have been implicated in various forms of acquired and inherited human heart disease. For example, during cardiac ischemia, cardiac myocyte contractile performance is dramatically downregulated due in part to a reduced sensitivity of the myofilaments to calcium under acidic pH conditions. Over the last several years, the thin filament regulatory protein, troponin I, has been identified as an important mediator of this response. Mutations in troponin I and other sarcomere genes are also linked to several distinct inherited cardiomyopathic phenotypes, including hypertrophic, dilated, and restrictive cardiomyopathies. With the cardiac sarcomere emerging as a central player for such a diverse array of human heart diseases, genetic-based strategies that target the myofilament will likely have broad therapeutic potential. The development of safe vector systems for efficient gene delivery will be a critical hurdle to overcome before these types of therapies can be successfully applied. Nonetheless, studies focusing on the principles of acute genetic engineering of the sarcomere hold value as they lay the essential foundation on which to build potential gene-based therapies for heart disease.

  13. Periostin induces fibroblast proliferation and myofibroblast persistence in hypertrophic scarring.

    PubMed

    Crawford, Justin; Nygard, Karen; Gan, Bing Siang; O'Gorman, David Brian

    2015-02-01

    Hypertrophic scarring is characterized by the excessive development and persistence of myofibroblasts. These cells contract the surrounding extracellular matrix resulting in the increased tissue density characteristic of scar tissue. Periostin is a matricellular protein that is abnormally abundant in fibrotic dermis, however, its roles in hypertrophic scarring are largely unknown. In this report, we assessed the ability of matrix-associated periostin to promote the proliferation and myofibroblast differentiation of dermal fibroblasts isolated from the dermis of hypertrophic scars or healthy skin. Supplementation of a thin type-I collagen cell culture substrate with recombinant periostin induced a significant increase in the proliferation of hypertrophic scar fibroblasts but not normal dermal fibroblasts. Periostin induced significant increases in supermature focal adhesion formation, α smooth muscle actin levels and collagen contraction in fibroblasts cultured from hypertrophic scars under conditions of increased matrix tension in three-dimensional type-I collagen lattices. Inhibition of Rho-associated protein kinase activity significantly attenuated the effects of matrix-associated periostin on hypertrophic scar fibroblasts and myofibroblasts. Depletion of endogenous periostin expression in hypertrophic scar myofibroblasts resulted in a sustained decrease in α smooth muscle actin levels under conditions of reducing matrix tension, while matrix-associated periostin levels caused the cells to retain high levels of a smooth muscle actin under these conditions. These findings indicate that periostin promotes Rho-associated protein kinase-dependent proliferation and myofibroblast persistence of hypertrophic scar fibroblasts and implicate periostin as a potential therapeutic target to enhance the resolution of scars.

  14. Topical modalities for treatment and prevention of postsurgical hypertrophic scars.

    PubMed

    Foo, Chong Wee; Tristani-Firouzi, Payam

    2011-08-01

    There is no universally accepted treatment regimen and no evidence-based literature to guide management of hypertrophic scars. This article summarizes the existing literature regarding topical treatments such as silicone gel sheeting and ointment, onion extract, vitamin E, pressure garment therapy, massage therapy, and topical imiquimod 5% cream in the management of hypertrophic scars.

  15. Topical modalities for treatment and prevention of postsurgical hypertrophic scars.

    PubMed

    Foo, Chong Wee; Tristani-Firouzi, Payam

    2011-08-01

    There is no universally accepted treatment regimen and no evidence-based literature to guide management of hypertrophic scars. This article summarizes the existing literature regarding topical treatments such as silicone gel sheeting and ointment, onion extract, vitamin E, pressure garment therapy, massage therapy, and topical imiquimod 5% cream in the management of hypertrophic scars. PMID:21856542

  16. 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

  17. [Stress-induced Takotsubo cardiomyopathy].

    PubMed

    Høst, Ulla; Søgaard, Peter; Hansen, Peter Riis

    2009-09-14

    A case of Takotsubo cardiomyopathy is described in a postmenopausal woman admitted for suspected recent myocardial infarction, triggered by significant social stress during a family Christmas dinner. Coronary angiography showed no significant lesions. Acute echocardiography demonstrated apical ballooning and an ejection fraction of 30%. The clinical course was uneventful and after one month, echocardiography showed complete resolution of the apical ballooning and recovery of left ventricular systolic function.

  18. 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

  19. Takotsubo cardiomyopathy a short review.

    PubMed

    Roshanzamir, Shahbaz; Showkathali, Refai

    2013-08-01

    Takotsubo cardiomyopathy (TCM), otherwise cardiomyopathy,apical ballooning syndrome or broken heart syndrome is a reversible cardiomyopathy, predominantly occurs in post-menopausal women and commonly due to emotional or physical stress. Typically, patients present with chest pain and ST elevation or T wave inversion on their electrocardiogram mimicking acute coronary syndrome, but with normal or non-flow limiting coronary artery disease. Acute dyspnoea, hypotension and even cardiogenic shock may be the presenting feature of this condition. The wall motion abnormalities typically involve akinesia of the apex of the left ventricle with hyperkinesia of the base of the heart. Atypical forms of TCM have also recently been described. An urgent left ventriculogram or echocardiogram is the key investigation to identify this syndrome. Characteristically, there is only a limited release of cardiac enzymes disproportionate to the extent of regional wall motion abnormality. Transient right ventricular dysfunction may occur and is associated with more complications, longer hospitalisation and worse left ventricular systolic dysfunction. Recently, cardiac MRI has been increasingly used to diagnose this condition and to differentiate from acute coronary syndrome in those who have abnormal coronary arteries. Treatment is often supportive, however beta-blocker and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocking agent are being used in routine clinical practice. The syndrome is usually spontaneously reversible and cardiovascular function returns to normal after a few weeks. This review article will elaborate on the pathophysiology, clinical features including the variant forms, latest diagnostic tools, management and prognosis of this condition. PMID:23642025

  20. Blepharoptosis and hypertrophic osteoarthropathy: A case report.

    PubMed

    Dogan, Aysun Sanal; Acaroglu, Gölge; Dikmetas, Ozlem

    2016-04-01

    A 52-year-old male patient presented to our hospital with a history of secondary hypertrophic osteoarthropathy (HOA) associated with an abdominal neoplasia and blepharoptosis. He had finger clubbing, hyperhidrosis, and hypertrichosis. He also had a recent history of extensive abdominal surgery with a pathology report of myelolipoma. Routine blood work was unremarkable. Upper eyelid reconstruction with blepharoplasty, upper eyelid wedge resection, and brow suspension was performed to address his eyelid concerns. By this case report, we would like to attract notice that the eyelid involvement may be a part of HOA and to emphasize the importance of systemic and pathologic evaluation in failed blepharoptosis surgery. PMID:27221686

  1. Idiopathic Hypertrophic Pachymeningitis in the Craniocervical Junction

    PubMed Central

    Bang, Jin Hyuk; Kim, Eo Jin

    2015-01-01

    Idiopathic hypertrophic pachymeningitis (IHP) is a rare disease, and it is characterized by chronic progressive inflammatory fibrosis and thickening of the dura mater with resultant compression of the spinal cord or neural structure without any identifiable cause. It can occur in the intracranial or spinal dura mater alone or as a craniospinal form. The spinal form is rarer than the cranial form and the craniospinal form is extremely rare. We report a rare case of IHP in the craniocervical junction involving both the cranial and spinal dura mater and discuss the diagnosis and management of the disease. PMID:26512276

  2. Blepharoptosis and hypertrophic osteoarthropathy: A case report

    PubMed Central

    Doğan, Aysun Şanal; Acaroğlu, Gölge; Dikmetas, Ozlem

    2016-01-01

    A 52-year-old male patient presented to our hospital with a history of secondary hypertrophic osteoarthropathy (HOA) associated with an abdominal neoplasia and blepharoptosis. He had finger clubbing, hyperhidrosis, and hypertrichosis. He also had a recent history of extensive abdominal surgery with a pathology report of myelolipoma. Routine blood work was unremarkable. Upper eyelid reconstruction with blepharoplasty, upper eyelid wedge resection, and brow suspension was performed to address his eyelid concerns. By this case report, we would like to attract notice that the eyelid involvement may be a part of HOA and to emphasize the importance of systemic and pathologic evaluation in failed blepharoptosis surgery. PMID:27221686

  3. Twice malignant transformation of hypertrophic lichen planus.

    PubMed

    Krasowska, Dorota; Kozłowicz, Katarzyna; Kowal, Małgorzata; Kurylcio, Andrzej; Budzyńska-Włodarczyk, Jolanta; Polkowski, Wojciech; Chodorowska, Grażyna

    2012-01-01

    Lichen planus is a chronic mucocutaneous T-cell-mediated disease, the cause of which remains unknown. The first case of lichen planus that transformed into squamous cell carcinoma was reported in 1903. The presented study concerns the case of a 62-year-old woman in whom twice malignant transformation of hypertrophic lichen planus in the dorsal part of the left foot developed. Several studies have pointed out the malignant transformation potential of lichen planus. Epidemiological studies from the last 20 years have revealed a malignant transformation rate of 0.27% per year, emphasizing the importance of the clinical follow-up of lichen planus patients.

  4. 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

  5. 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

  6. Nemaline myopathy with dilated cardiomyopathy in childhood.

    PubMed

    Gatayama, Ryohei; Ueno, Kentaro; Nakamura, Hideaki; Yanagi, Sadamitsu; Ueda, Hideaki; Yamagishi, Hiroyuki; Yasui, Seiyo

    2013-06-01

    We present a case of a 9-year-old boy with nemaline myopathy and dilated cardiomyopathy. The combination of nemaline myopathy and cardiomyopathy is rare, and this is the first reported case of dilated cardiomyopathy associated with childhood-onset nemaline myopathy. A novel mutation, p.W358C, in ACTA1 was detected in this patient. An unusual feature of this case was that the patient's cardiac failure developed during early childhood with no delay of gross motor milestones. The use of a β-blocker did not improve his clinical course, and the patient died 6 months after diagnosis of dilated cardiomyopathy. Congenital nonprogressive nemaline myopathy is not necessarily a benign disorder: deterioration can occur early in the course of dilated cardiomyopathy with neuromuscular disease, and careful clinical evaluation is therefore necessary. PMID:23650303

  7. 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

  8. Modeling Dilated Cardiomyopathies in Drosophila

    PubMed Central

    Wolf, Matthew J.

    2013-01-01

    Over the past hundred years, the fruit fly, Drosophila melanogaster, has provided tremendous insights into genetics and human biology. Drosophila-based research utilizes powerful, genetically-tractable approaches to identify new genes and pathways that potentially contribute to human diseases. New resources available in the fly research community have advanced the ability to examine genome-wide effects on cardiac function and facilitate the identification of structural, contractile, and signaling molecules that contribute to cardiomyopathies. This powerful model system continues to provide discoveries of novel genes and signaling pathways that are conserved among species and translatable to human pathophysiology. PMID:22863366

  9. Early onset cardiomyopathy associated with the mitochondrial tRNALeu((UUR)) 3271T>C MELAS mutation.

    PubMed

    Brisca, Giacomo; Fiorillo, Chiara; Nesti, Claudia; Trucco, Federica; Derchi, Maria; Andaloro, Antonio; Assereto, Stefania; Morcaldi, Guido; Pedemonte, Marina; Minetti, Carlo; Santorelli, Filippo M; Bruno, Claudio

    2015-03-13

    Mitochondrial disorders are a heterogeneous group of diseases sharing a defect of the oxidative phosphorylation system. Point mutations in the mitochondrial DNA are a common cause of mitochondrial disorders and frequently affect the sequences encoding mitochondrial transfer RNAs. The m.3271T>C mutation in the mitochondrial tRNA(Leu(UUR)) is traditionally reported in patients with clinical features of the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome and in mitochondrial diabetes. Here we describe the clinical, pathological, and molecular features of an Italian child and his asymptomatic mother, carrying the m.3271T>C mutation in the mitochondrial tRNA(Leu(UUR)) gene, in association with an unusual clinical phenotype dominated by hypertrophic cardiomyopathy and provide review literature of cases with this mutation. To the best of our knowledge, there are no reports describing the association of this mutation with cardiomyopathy, and our cases suggest that the m.3271T>C mutation has to be taken into account in the diagnostic approach of maternally inherited cardiomyopathies.

  10. The molecular basis of hypertrophic scars.

    PubMed

    Zhu, Zhensen; Ding, Jie; Tredget, Edward E

    2016-01-01

    Hypertrophic scars (HTS) are caused by dermal injuries such as trauma and burns to the deep dermis, which are red, raised, itchy and painful. They can cause cosmetic disfigurement or contractures if craniofacial areas or mobile region of the skin are affected. Abnormal wound healing with more extracellular matrix deposition than degradation will result in HTS formation. This review will introduce the physiology of wound healing, dermal HTS formation, treatment and difference with keloids in the skin, and it also review the current advance of molecular basis of HTS including the involvement of cytokines, growth factors, and macrophages via chemokine pathway, to bring insights for future prevention and treatment of HTS. PMID:27574672

  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. Diabetic Cardiomyopathy: Mechanisms and Therapeutic Targets

    PubMed Central

    Battiprolu, Pavan K.; Gillette, Thomas G.; Wang, Zhao V.; Lavandero, Sergio; Hill, Joseph A.

    2010-01-01

    The incidence and prevalence of diabetes mellitus are each increasing rapidly in our society. The majority of patients with diabetes succumb ultimately to heart disease, much of which stems from atherosclerotic disease and hypertension. However, cardiomyopathy can develop independent of elevated blood pressure or coronary artery disease, a process termed diabetic cardiomyopathy. This disorder is a complex diabetes-associated process characterized by significant changes in the physiology, structure, and mechanical function of the heart. Here, we review recently derived insights into mechanisms and molecular events involved in the pathogenesis of diabetic cardiomyopathy. PMID:21274425

  13. The MEF2A gene is excluded as a candidate in 3 families with cardiomyopathies that are not linked to myosin

    SciTech Connect

    Bachinski, L.L.; Abchee, A.; Krahe, R.

    1994-09-01

    Inherited cardiomyopathies, as exemplified by hypertrophic cardiomyopathy (HCM) and idiopathic dilated cardiomyopathy (DCM), are genetically heterogeneous disorders of the myocardium which serve as paradigms for the growth response of the heart to most stimuli. HCM is an autosomal dominant disease shown to be caused by at least 5 different genes, but {beta}-myosin heavy chain (MYH7) is the only one of these genes to be identified to date. No loci have as yet been identified for DCM. MEF2A is one of at least 4 known MEF2 genes which are members of the MADS box family of transcription factors. MEF2A is expressed in cardiac tissue; thus MEF2A is a logical candidate gene for these disorders of the cardiac growth response. We have investigated the possibility of linkage between a trinucleotide repeat polymorphism in the MEF2A gene and these cardiomyopathies is a DCM family and 2 HCM families not linked to MYH7. MEF2A was excluded as a candidate for DCM (LOD of -9.03) and HCM (LODs of-5.43 and -2.44) in these families. No expansion of this trinucleotide repeat was seen in 100 unrelated HCM probands or in the DCM family, which appears to exhibit anticipation.

  14. Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy.

    PubMed

    Chen, Yung-Lung; Chung, Sheng-Ying; Chai, Han-Tan; Chen, Chih-Hung; Liu, Chu-Feng; Chen, Yi-Ling; Huang, Tien-Hung; Zhen, Yen-Yi; Sung, Pei-Hsun; Sun, Cheuk-Kwan; Chua, Sarah; Lu, Hung-I; Lee, Fan-Yen; Sheu, Jiunn-Jye; Yip, Hon-Kan

    2015-12-01

    This study tested for the benefits of early administration of carvedilol as protection against doxorubicin (DOX)-induced cardiomyopathy. Thirty male, adult B6 mice were categorized into group 1 (untreated control), group 2 [DOX treatment (15 mg/every other day for 2 weeks, i.p.], and group 3 [carvedilol (15 mg/kg/d, from day 7 after DOX treatment for 28 days)], and euthanized by day 35 after DOX treatment. By day 35, the left ventricular ejection fraction (LVEF) was significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the left ventricular (LV) end-diastolic and LV end-systolic dimensions showed an opposite pattern to the LVEF among the three groups. The protein expressions of fibrotic (Smad3, TGF-β), apoptotic (BAX, cleaved caspase 3, PARP), DNA damage (γ-H2AX), oxidative stress (oxidized protein), mitochondrial damage (cytosolic cytochrome-C), heart failure (brain natriuretic peptide), and hypertrophic (β-MHC) biomarkers of the LV myocardium showed an opposite pattern to the LVEF among the three groups. The protein expressions of antifibrotic (BMP-2, Smad1/5), α-MHC, and phosphorylated-Akt showed an identical pattern to the LVEF among the three groups. The microscopic findings of fibrotic and collagen-deposition areas and the numbers of γ-H2AX(+) and 53BP1(+) cells in the LV myocardium exhibited an opposite pattern, whereas the numbers of endothelial cell (CD31(+), vWF(+)) markers showed an identical pattern to the LVEF among the three groups. Cardiac stem cell markers (C-kit(+) and Sca-1(+) cells) were significantly and progressively increased from group 1 to group 3. Additionally, the in vitro study showed carvedilol treatment significantly inhibited DOX-induced cardiomyoblast DNA (CD90/XRCC1(+), CD90/53BP1(+), and r-H2AX(+) cells) damage. Early carvedilol therapy protected against DOX-induced DNA damage and cardiomyopathy.

  15. Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy.

    PubMed

    Chen, Yung-Lung; Chung, Sheng-Ying; Chai, Han-Tan; Chen, Chih-Hung; Liu, Chu-Feng; Chen, Yi-Ling; Huang, Tien-Hung; Zhen, Yen-Yi; Sung, Pei-Hsun; Sun, Cheuk-Kwan; Chua, Sarah; Lu, Hung-I; Lee, Fan-Yen; Sheu, Jiunn-Jye; Yip, Hon-Kan

    2015-12-01

    This study tested for the benefits of early administration of carvedilol as protection against doxorubicin (DOX)-induced cardiomyopathy. Thirty male, adult B6 mice were categorized into group 1 (untreated control), group 2 [DOX treatment (15 mg/every other day for 2 weeks, i.p.], and group 3 [carvedilol (15 mg/kg/d, from day 7 after DOX treatment for 28 days)], and euthanized by day 35 after DOX treatment. By day 35, the left ventricular ejection fraction (LVEF) was significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the left ventricular (LV) end-diastolic and LV end-systolic dimensions showed an opposite pattern to the LVEF among the three groups. The protein expressions of fibrotic (Smad3, TGF-β), apoptotic (BAX, cleaved caspase 3, PARP), DNA damage (γ-H2AX), oxidative stress (oxidized protein), mitochondrial damage (cytosolic cytochrome-C), heart failure (brain natriuretic peptide), and hypertrophic (β-MHC) biomarkers of the LV myocardium showed an opposite pattern to the LVEF among the three groups. The protein expressions of antifibrotic (BMP-2, Smad1/5), α-MHC, and phosphorylated-Akt showed an identical pattern to the LVEF among the three groups. The microscopic findings of fibrotic and collagen-deposition areas and the numbers of γ-H2AX(+) and 53BP1(+) cells in the LV myocardium exhibited an opposite pattern, whereas the numbers of endothelial cell (CD31(+), vWF(+)) markers showed an identical pattern to the LVEF among the three groups. Cardiac stem cell markers (C-kit(+) and Sca-1(+) cells) were significantly and progressively increased from group 1 to group 3. Additionally, the in vitro study showed carvedilol treatment significantly inhibited DOX-induced cardiomyoblast DNA (CD90/XRCC1(+), CD90/53BP1(+), and r-H2AX(+) cells) damage. Early carvedilol therapy protected against DOX-induced DNA damage and cardiomyopathy. PMID:26511374

  16. 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.

  17. 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

  18. 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

  19. 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

  20. [Echocardiography methods in the diagnosis of cardiomyopathies in children].

    PubMed

    First, T; Skovránek, J

    1988-12-16

    We investigated 59 children with cardiomyopathy (CMP) by echocardiographic methods (ECHO). 29 children with dilated CMP showed typical enlargement of the left ventricle 159 +/- 31%, xxx; (% of normal value +/- SD) and of the left atrium (143 +/- 27%, xxx). Systolic and diastolic function of the left ventricle were decreased, systolic change in size of the left ventricle % delta D = 16 +/- 7%; xxx; systolic change in area of the left ventricle % delta A = 20 +/- 8%; xxx; maximum filling rate of the left ventricle in the phase of quick filling E max = 0.37 +/- 0.09 m. sec-1, xxx; the percentage of filling in the first third of diastole 0.33 DA = 37 +/- 9%, xx. Mitral insufficiency was found by us in 81% of children. In 25 children with hypertrophic CMP the size of left ventricle was decreased (81 +/- 13%, xxx). Asymmetric septal hypertrophy was found by us in 69% of children, symmetric hypertrophy in 27%, local hypertrophy of the apex in 4%. Systolic function of the left ventricle was increased (% delta D = 47 +/- 10%, xxx; % delta A = 70 +/- 10%, xxx). Diastolic dysfunction manifested itself by reduced E max (0.71 +/- 0.19 m.sec-1, xx) and 0.33 DA (45 +/- 12%, x). Mitral insufficiency was found in 54% of the children. In the case of the 5 children with restrictive CMP an extreme enlargement of left atrium (195 +/- 41%, xxx) was typical, as well as diastolic dysfunction of the left ventricle (0.33 DA = 67 +/- 6%, x).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3239073

  1. Dilated cardiomyopathy due to a phospholamban duplication.

    PubMed

    Lee, Teresa M; Addonizio, Linda J; Chung, Wendy K

    2014-10-01

    Dilated cardiomyopathy is characterised by dilation and impaired systolic function. We present the case of a child with dilated cardiomyopathy caused by a 624 kb duplication of 6q22.31, which includes the phospholamban gene. The patient also has failure to thrive and developmental delay due to complex cytogenetic abnormalities including a 5p15 deletion associated with Cri du Chat and an 11p15 duplication associated with Russell-Silver syndrome. PMID:24451198

  2. Takotsubo Cardiomyopathy: A New Perspective in Asthma

    PubMed Central

    Marmoush, Fady Y.; Barbour, Mohamad F.; Noonan, Thomas E.; Al-Qadi, Mazen O.

    2015-01-01

    Takotsubo cardiomyopathy (TCM) is an entity of reversible cardiomyopathy known for its association with physical or emotional stress and may mimic myocardial infarction. We report an exceedingly rare case of albuterol-induced TCM with moderate asthma exacerbation. An interesting association that may help in understanding the etiology of TCM in the asthmatic population. Although the prognosis of TCM is excellent, it is crucial to recognize beta agonists as a potential stressor. PMID:26246918

  3. Obesity Cardiomyopathy: Pathophysiologic Factors and Nosologic Reevaluation.

    PubMed

    Bhatheja, Samit; Panchal, Hemang B; Ventura, Hector; Paul, Timir K

    2016-08-01

    Cardiovascular disease in populations with obesity is a major concern because of its epidemic proportion. Obesity leads to the development of cardiomyopathy directly via inflammatory mediators and indirectly by obesity-induced hypertension, diabetes and coronary artery diseases. The aim of this review article is to re-visit the available knowledge and the evidence on pathophysiologic mechanisms of obesity-related cardiomyopathy and to propose its placement into a specific category of myocardial disease. PMID:27524223

  4. [Lipoprotein lipase and diabetic cardiomyopathy].

    PubMed

    Liu, Xiang-Yu; Yin, Wei-Dong; Tang, Chao-Ke

    2014-02-01

    Lipoprotein lipase (LPL) hydrolyzes plasma triglyceride-rich lipoproteins into free fatty acids (FFA) to provide energy for cardiac tissue. During diabetes, cardiac energy supply is insufficient due to defected utilization of glucose. As a compensation of cardiac energy supply, FFAs are released through the hydrolysis of very low density lipoprotein (VLDL) and chylomicrons (CM) due to activation of LPL activity. In diabetic patients, activated LPL activity and elevated FFAs result in the intracellular accumulation of reactive oxygen species and lipids in myocardium and potentially induce the diabetic cardiomyopathy (DCM). The present review summarizes the regulatory mechanisms of myocardial LPL and the pathogenesis of DCM induced by LPL and provides novel therapeutic targets and pathways for DCM. PMID:24873138

  5. Stimulant-related Takotsubo cardiomyopathy.

    PubMed

    Butterfield, Mike; Riguzzi, Christine; Frenkel, Oron; Nagdev, Arun

    2015-03-01

    Takotsubo cardiomyopathy (TC) is a rare but increasingly recognized mimic of acute coronary syndrome. Patients present with angina,ST-segment changes on electrocardiogram (both elevations and depressions),and rapid rises in cardiac biomarkers. Many kinds of stressful events have been associated with TC, but only a handful of drug-related cases have previously been reported. We describe the case of a 58-year-old woman who developed TC 2 days after crack cocaine use, a diagnosis first suggested as bedside echocardiography in the emergency department.Recognition of the classic echocardiographic appearance of TC—apical hypokinesis causing “ballooning” of the left ventricle during systole—may greatly assist providers in the early identification of this condition.

  6. Molecular Pathology of Dilated Cardiomyopathies.

    PubMed

    Pathak, S K; Kukreja, R C; Hess, M

    1996-02-01

    The term idiopathic, defined as being of unknown etiology or mechanism, is no longer applicable to the dilated cardiomyopathies. The tools of molecular biology and clinical investigation have made significant progress, and it is now to the rare and exceptional case that one is forced to apply the term idiopathic. Further, having arrived at more precise cause, direct therapeutic intervention will become possible. The concept of gene insertion and "genetic therapy" is under active investigation. Unfortunately, the significant advances in the cause and disease mechanisms of DCM have not been matched in therapeutics. With few exceptions, we indirectly treat the DCMs by managing the CHF syndrome. However, several important points have emerged. The concept of LV afterload reduction is valid and efficacious. The use of vasodilator therapy has significantly reduced both mortality and morbidity and, in certain forms of cardiomyopathy (e.g., hypertensive, alcoholic, and doxorubicin-related), have significantly altered hemodynamics and permitted the injured heart to heal and return to a near normal functional state. However, as much as we want to congratulate ourselves on the progress bought with the use of vasodilators and ACE inhibitors, one must keep in mind that under the best of circumstances, the DCMs still carry an unacceptably high morbidity and mortality. A 40% to 50% 4- to 5-year mortality rate is depressing. Herein lies the challenge. With the significant progress in pathogenesis and etiology, we now stand at the threshold of new, innovative advances in therapeutics. These new concepts in both therapeutics and prevention will require courage, dedication, and hard work. But bit by bit, these seemingly insolvable problems will yield to the discipline and imagination of the investigator. The DCMs will continue to be a challenging problem for future investigators. Progress has been dramatic, and it should continue even at an accelerated pace as we approach the twenty

  7. Takotsubo cardiomyopathy following lightning strike.

    PubMed

    Dundon, B K; Puri, R; Leong, D P; Worthley, M I

    2008-07-01

    Lightning strike is the most common environmental cause of sudden cardiac death, but may also be associated with a myriad of injuries to various organ systems. Direct myocardial injury may be manifest as electrocardiographic alterations or elevation in cardiac-specific isoenzymes; however, significant electrical cardiac trauma appears uncommon. A case is presented of severe acute cardiomyopathy in a "Takotsubo" distribution causing cardiogenic shock following lightning strike in a previously healthy 37-year-old woman. Although rarely identified in this context, Takotsubo cardiomyopathy (also known as "transient left ventricular apical ballooning syndrome") is characterised by transient cardiac dysfunction, electrocardiographic changes that may mimic acute myocardial infarction and minimal release of cardiac-specific enzymes in the absence of obstructive coronary artery disease. The condition is associated with a substantial female bias (up to 90% of cases) in reported series, and despite occasionally dramatic presentations recovery of left ventricular function is almost universal over days to weeks. In rare instances, however, the syndrome has been associated with more catastrophic complications such as papillary muscle or cardiac free wall rupture, necessitating emergency surgical intervention to preserve life. In clinical practice, non-lethal lightning strike-induced cardiac injury is frequently associated with small elevations of cardiac isoenzymes without overt clinical sequelae; however, the incidence of silent myocardial mechanical dysfunction remains unknown. Cases such as the one presented highlight the potential for serious, albeit usually transient, cardiac sequelae from lightning strike injury and remind us that our mothers' advice to remain indoors during thunderstorms is probably worth heeding. PMID:18573973

  8. Takotsubo cardiomyopathy following lightning strike.

    PubMed

    Dundon, Benjamin K; Puri, Rishi; Leong, Darryl P; Worthley, Matthew Ian

    2009-01-01

    Lightning strike is the most common environmental cause of sudden cardiac death, but it may also be associated with a myriad of injuries to various organ systems. Direct myocardial injury may be manifest as electrocardiographic alterations or elevation in cardiac-specific isoenzymes; however, significant electrical cardiac trauma appears uncommon. A case is presented of severe acute cardiomyopathy in a "Takotsubo" distribution causing cardiogenic shock following lightning strike in a previously healthy 37-year-old woman. Although rarely identified in this context, Takotsubo cardiomyopathy (also known as "transient left ventricular apical ballooning syndrome") is characterised by transient cardiac dysfunction, electrocardiographic changes that may mimic acute myocardial infarction and minimal release of cardiac-specific enzymes in the absence of obstructive coronary artery disease. The condition is associated with a substantial female bias (up to 90% of cases) in reported series, and despite occasionally dramatic presentations recovery of left ventricular function is almost universal over days to weeks. In rare instances, however, the syndrome has been associated with more catastrophic complications such as papillary muscle or cardiac free wall rupture, necessitating emergency surgical intervention to preserve life. In clinical practice, non-lethal lightning strike-induced cardiac injury is frequently associated with small elevations of cardiac isoenzymes without overt clinical sequelae; however, the incidence of silent myocardial mechanical dysfunction remains unknown. Cases such as the one presented highlight the potential for serious, albeit usually transient, cardiac sequelae from lightning strike injury and remind us that our mothers' advice to remain indoors during thunderstorms is probably worth heeding. PMID:21686980

  9. Cardiomyopathy

    MedlinePlus

    ... Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 65. McKenna WJ, Elliott P. ... eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 60. McMurray JJV, Pfeffer MA. ...

  10. Development and pathomechanisms of cardiomyopathy in very long-chain acyl-CoA dehydrogenase deficient (VLCAD(-/-)) mice.

    PubMed

    Tucci, Sara; Flögel, Ulrich; Hermann, Sven; Sturm, Marga; Schäfers, Michael; Spiekerkoetter, Ute

    2014-05-01

    Hypertrophic cardiomyopathy is a typical manifestation of very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), the most common long-chain β-oxidation defects in humans; however in some patients cardiac function is fully compensated. Cardiomyopathy may also be reversed by supplementation of medium-chain triglycerides (MCT). We here characterize cardiac function of VLCAD-deficient (VLCAD(-/-)) mice over one year. Furthermore, we investigate the long-term effect of a continuous MCT diet on the cardiac phenotype. We assessed cardiac morphology and function in VLCAD(-/-) mice by in vivo MRI. Cardiac energetics were measured by (31)P-MRS and myocardial glucose uptake was quantified by positron-emission-tomography (PET). Metabolic adaptations were identified by the expression of genes regulating glucose and lipid metabolism using real-time-PCR. VLCAD(-/-) mice showed a progressive decrease in heart function over 12 months accompanied by a reduced phosphocreatine-to-ATP-ratio indicative of chronic energy deficiency. Long-term MCT supplementation aggravated the cardiac phenotype into dilated cardiomyopathy with features similar to diabetic heart disease. Cardiac energy production and function in mice with a β-oxidation defect cannot be maintained with age. Compensatory mechanisms are insufficient to preserve the cardiac energy state over time. However, energy deficiency by impaired β-oxidation and long-term MCT induce cardiomyopathy by different mechanisms. Cardiac MRI and MRS may be excellent tools to assess minor changes in cardiac function and energetics in patients with β-oxidation defects for preventive therapy. PMID:24530811

  11. Inhibited early immunologic response is associated with hypertrophic scarring.

    PubMed

    Butzelaar, Liselotte; Schooneman, Dennis P M; Soykan, Ezgi A; Talhout, Wendy; Ulrich, Magda M W; van den Broek, Lenie J; Gibbs, Susan; Beelen, Robert H J; Mink van der Molen, Aebele B; Niessen, Frank B

    2016-10-01

    This study aimed to examine changes in the inflammatory response in early hypertrophic compared to normal wound healing. The immune system is thought to be involved in hypertrophic scar formation. However, the exact mechanism and time of onset of the derailment remain unknown. In a prospective observational study, skin biopsies were taken directly postwounding and 3 hours later from patients who had elective cardiothoracic surgery. The skin biopsies were analysed for mRNA, proteins and cells involved in the early inflammatory phase of wound healing. The endpoint was scar outcome (hypertrophic (HTS) or normal (NTS)) at one year after surgery. There were significant differences between the NTS and HTS groups regarding the fold changes of mRNA expression of P-selectin during surgery. Postoperative skin concentrations of inflammatory proteins IL-6, IL-8 and CCL2 were significantly lower in the HTS compared to the NTS group. Also, a trend of higher pre-operative M2 macrophage numbers was observed in the HTS group. Neutrophil numbers increased equally during surgery in both groups. The increase of P-selectin mRNA in hypertrophic wound healing could affect leucocyte migration. The decreased concentrations of inflammatory proteins in hypertrophic wound healing indicate a reduced inflammatory response, which has consequences for the treatment of hypertrophic scarring during the early inflammatory phase. In a conclusion, alterations of wound healing associated with hypertrophic scarring are visible as early as 3 hours postwounding and include a reduced rather than increased inflammatory protein response. PMID:27249786

  12. Paraneoplastic hypertrophic osteopathy in 30 dogs

    PubMed Central

    Withers, S. S.; Johnson, E. G.; Culp, W. T. N.; Rodriguez, C. O.; Skorupski, K. A.; Rebhun, R. B.

    2016-01-01

    Paraneoplastic hypertrophic osteopathy (pHO) is known to occur in both canine and human cancer patients. While the pathology of pHO is well-described in the dog, very little information exists regarding the true clinical presentation of dogs affected with pHO. The primary objective of this study was to provide a more comprehensive clinical picture of pHO. To this end, we retrospectively identified 30 dogs and recorded data regarding presenting complaints and physical examination (PE) findings on the date of pHO diagnosis. As a secondary objective, any blood test results were also collected from the computerized records. The most common clinical signs included leg swelling, ocular discharge and/or episcleral injection, lameness, and lethargy. The most common haematological and serum biochemical abnormalities included anaemia, neutrophilia and elevated alkaline phosphatase. In addition to presenting a more detailed clinical description of pHO in the dog, these data support the previously described haematological, serum biochemical and PE abnormalities published in individual case reports. PMID:23489591

  13. Hypertrophic olivary degeneration secondary to pontine haemorrhage.

    PubMed

    Wein, Sara; Yan, Bernard; Gaillard, Frank

    2015-07-01

    We report a 58-year-old man who developed hyptertrophic olivary degeneration (HOD) after haemorrhage of a cavernous malformation in the pons. Lesions of the triangle of Guillain and Mollaret (the dentatorubro-olivary pathway) may lead to HOD, a secondary transsynaptic degeneration of the inferior olivary nucleus. HOD is considered unique because the degenerating olive initially becomes hypertrophic rather than atrophic. The primary lesion causing pathway interruption is often haemorrhage, either due to hypertension, trauma, surgery or, as in our patient, a vascular malformation such as a cavernoma. Ischaemia and demyelination can also occasionally be the inciting events. The classic clinical presentation of HOD is palatal myoclonus, although not all patients with HOD develop this symptom. The imaging features of HOD evolve through characteristic phases. The clue to the diagnosis of HOD is recognition of the distinct imaging stages and identification of a remote primary lesion in the triangle of Guillain and Mollaret. Familiarity with the classic imaging findings of this rare phenomenon is necessary in order to avoid misdiagnosis and prevent unnecessary intervention.

  14. Interplay between the E2F pathway and β-adrenergic signaling in the pathological hypertrophic response of myocardium.

    PubMed

    Major, Jennifer L; Salih, Maysoon; Tuana, Balwant S

    2015-07-01

    The E2F/Pocket protein (Rb) pathway regulates cell growth, differentiation, and death by modulating gene expression. We previously examined this pathway in the myocardium via manipulation of the unique E2F repressor, E2F6, which is believed to repress gene activity independently of Rb. Mice with targeted expression of E2F6 in postnatal myocardium developed dilated cardiomyopathy (DCM) without hypertrophic growth. We assessed the mechanisms of the apparent failure of compensatory hypertrophic growth as well as their response to the β-adrenergic agonist isoproterenol. As early as 2 weeks, E2F6 transgenic (Tg) mice present with dilated thinner left ventricles and significantly reduced ejection fraction and fractional shortening which persists at 6 weeks of age, but with no apparent increase in left ventricle weight: body weight (LVW:BW). E2F6-Tg mice treated with isoproterenol (6.1 mg/kg/day) show double the increase in LVW:BW than their Wt counterparts (32% vs 16%, p-value: 0.007). Western blot analysis revealed the activation of the adrenergic pathway in Tg heart tissue under basal conditions with ~2-fold increase in the level of β2-adrenergic receptors (p-value: 8.9E-05), protein kinase A catalytic subunit (PKA-C) (p-value: 0.0176), activated c-Src tyrosine-protein kinase (p-value: 0.0002), extracellular receptor kinase 2 (ERK2) (p-value: 0.0005), and induction of the anti-apoptotic protein Bcl2 (p-value 0. 0.00001). In contrast, a ~60% decrease in the cardiac growth regulator: AKT1 (p-value 0.0001) and a ~four fold increase in cyclic AMP dependent phosphodiesterase 4D (PDE4D), the negative regulator of PKA activity, were evident in the myocardium of E2F6-Tg mice. The expression of E2F3 was down-regulated by E2F6, but was restored by isoproterenol. Further, Rb expression was down-regulated in Tg mice in response to isoproterenol implying a net activation of the E2F pathway. Thus the unique regulation of E2F activity by E2F6 renders the myocardium hypersensitive

  15. 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

  16. Medicinal Plants for the Treatment of Hypertrophic Scars

    PubMed Central

    Ye, Qi; Wang, Su-Juan; Chen, Jian-Yu; Xin, Hai-Liang; Zhang, Hong

    2015-01-01

    Hypertrophic scar is a complication of wound healing and has a high recurrence rate which can lead to significant abnormity in aesthetics and functions. To date, no ideal treatment method has been established. Meanwhile, the underlying mechanism of hypertrophic scarring has not been clearly defined. Although a large amount of scientific research has been reported on the use of medicinal plants as a natural source of treatment for hypertrophic scarring, it is currently scattered across a wide range of publications. Therefore, a systematic summary and knowledge for future prospects are necessary to facilitate further medicinal plant research for their potential use as antihypertrophic scar agents. A bibliographic investigation was accomplished by focusing on medicinal plants which have been scientifically tested in vitro and/or in vivo and proved as potential agents for the treatment of hypertrophic scars. Although the chemical components and mechanisms of action of medicinal plants with antihypertrophic scarring potential have been investigated, many others remain unknown. More investigations and clinical trials are necessary to make use of these medical plants reasonably and phytotherapy is a promising therapeutic approach against hypertrophic scars. PMID:25861351

  17. Identification of novel mutations including a double mutation in patients with inherited cardiomyopathy by a targeted sequencing approach using the Ion Torrent PGM system

    PubMed Central

    ZHAO, YUE; CAO, HONG; SONG, YINDI; FENG, YUE; DING, XIAOXUE; PANG, MINGJIE; ZHANG, YUNMEI; ZHANG, HONG; DING, JIAHUAN; XIA, XUESHAN

    2016-01-01

    Inherited cardiomyopathy is the major cause of sudden cardiac death (SCD) and heart failure (HF). The disease is associated with extensive genetic heterogeneity; pathogenic mutations in cardiac sarcomere protein genes, cytoskeletal protein genes and nuclear envelope protein genes have been linked to its etiology. Early diagnosis is conducive to clinical monitoring and allows for presymptomatic interventions as needed. In the present study, the entire coding sequences and flanking regions of 12 major disease (cardiomyopathy)-related genes [namely myosin, heavy chain 7, cardiac muscle, β (MYH7); myosin binding protein C, cardiac (MYBPC3); lamin A/C (LMNA); troponin I type 3 (cardiac) (TNNI3); troponin T type 2 (cardiac) (TNNT2); actin, α, cardiac muscle 1 (ACTC1); tropomyosin 1 (α) (TPM1); sodium channel, voltage gated, type V alpha subunit (SCN5A); myosin, light chain 2, regulatory, cardiac, slow (MYL2); myosin, heavy chain 6, cardiac muscle, α (MYH6); myosin, light chain 3, alkali, ventricular, skeletal, slow (MYL3); and protein kinase, AMP-activated, gamma 2 non-catalytic subunit (PRKAG2)] in 8 patients with dilated cardiomyopathy (DCM) and in 8 patients with hypertrophic cardiomyopathy (HCM) were amplified and then sequenced using the Ion Torrent Personal Genome Machine (PGM) system. As a result, a novel heterozygous mutation (MYH7, p.Asn885Thr) and a variant of uncertain significance (TNNT2, p.Arg296His) were identified in 2 patients with HCM. These 2 missense mutations, which were absent in the samples obtained from the 200 healthy control subjects, altered the amino acid that was evolutionarily conserved among a number of vertebrate species; this illustrates that these 2 non-synonymous mutations play a role in the pathogenesis of HCM. Moreover, a double heterozygous mutation (PRKAG2, p.Gly100Ser plus MYH7, p.Arg719Trp) was identified in a patient with severe familial HCM, for the first time to the best of our knowledge. This patient provided us with more

  18. Could it be Quetiapine-induced Peripartum Cardiomyopathy?

    PubMed Central

    Kaler, Mandeep; Shakur, Rameen; Learner, Hazel I; Deaner, Andrew; Howard, Richard J

    2013-01-01

    Peri-partum Cardiomyopathy (PPCM) is a rare and life threatening complication of pregnancy. There are only two cases registered with the World Health Organization of cases of cardiomyopathy in patients taking Quetiapine. Here we discuss an interesting case of potential Quetiapine induced cardiomyopathy.

  19. High Frequency QRS ECG Accurately Detects Cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Arenare, Brian; Poulin, Gregory; Moser, Daniel R.; Delgado, Reynolds

    2005-01-01

    High frequency (HF, 150-250 Hz) analysis over the entire QRS interval of the ECG is more sensitive than conventional ECG for detecting myocardial ischemia. However, the accuracy of HF QRS ECG for detecting cardiomyopathy is unknown. We obtained simultaneous resting conventional and HF QRS 12-lead ECGs in 66 patients with cardiomyopathy (EF = 23.2 plus or minus 6.l%, mean plus or minus SD) and in 66 age- and gender-matched healthy controls using PC-based ECG software recently developed at NASA. The single most accurate ECG parameter for detecting cardiomyopathy was an HF QRS morphological score that takes into consideration the total number and severity of reduced amplitude zones (RAZs) present plus the clustering of RAZs together in contiguous leads. This RAZ score had an area under the receiver operator curve (ROC) of 0.91, and was 88% sensitive, 82% specific and 85% accurate for identifying cardiomyopathy at optimum score cut-off of 140 points. Although conventional ECG parameters such as the QRS and QTc intervals were also significantly longer in patients than controls (P less than 0.001, BBBs excluded), these conventional parameters were less accurate (area under the ROC = 0.77 and 0.77, respectively) than HF QRS morphological parameters for identifying underlying cardiomyopathy. The total amplitude of the HF QRS complexes, as measured by summed root mean square voltages (RMSVs), also differed between patients and controls (33.8 plus or minus 11.5 vs. 41.5 plus or minus 13.6 mV, respectively, P less than 0.003), but this parameter was even less accurate in distinguishing the two groups (area under ROC = 0.67) than the HF QRS morphologic and conventional ECG parameters. Diagnostic accuracy was optimal (86%) when the RAZ score from the HF QRS ECG and the QTc interval from the conventional ECG were used simultaneously with cut-offs of greater than or equal to 40 points and greater than or equal to 445 ms, respectively. In conclusion 12-lead HF QRS ECG employing

  20. Hypertrophic scarring: the greatest unmet challenge after burn injury.

    PubMed

    Finnerty, Celeste C; Jeschke, Marc G; Branski, Ludwik K; Barret, Juan P; Dziewulski, Peter; Herndon, David N

    2016-10-01

    Improvements in acute burn care have enabled patients to survive massive burns that would have once been fatal. Now up to 70% of patients develop hypertrophic scars after burns. The functional and psychosocial sequelae remain a major rehabilitative challenge, decreasing quality of life and delaying reintegration into society. Approaches to optimise healing potential of burn wounds use targeted wound care and surgery to minimise the development of hypertrophic scarring. Such approaches often fail, and modulation of the established scar is continued although the optimal indication, timing, and combination of therapies have yet to be established. The need for novel treatments is paramount, and future efforts to improve outcomes and quality of life should include optimisation of wound healing to attenuate or prevent hypertrophic scarring, well-designed trials to confirm treatment efficacy, and further elucidation of molecular mechanisms to allow development of new preventive and therapeutic strategies.

  1. Hypertrophic olivary degeneration and cerebrovascular disease: movement in a triangle.

    PubMed

    Santos, Ana Filipa; Rocha, Sofia; Varanda, Sara; Pinho, João; Rodrigues, Margarida; Ramalho Fontes, João; Soares-Fernandes, João; Ferreira, Carla

    2015-02-01

    Hypertrophic olivary degeneration is a rare kind of trans-synaptic degeneration that occurs after lesions of the dentatorubro-olivary pathway. The lesions, commonly unilateral, may result from hemorrhage due to vascular malformation, trauma, surgical intervention or hypertension, tumor, or ischemia. Bilateral cases are extremely rare. This condition is classically associated with development of palatal tremor, but clinical manifestations can include other involuntary movements. We describe 2 cases: unilateral hypertrophic olivary degeneration in a 60-year-old man with contralateral athetosis and neurologic worsening developing several years after a pontine hemorrhage and bilateral hypertrophic olivary degeneration in a 77-year-old woman with development of palatal tremor, probably secondary to pontine ischemic lesions (small vessel disease).

  2. [Scarlet fever with multisystem organ failure and hypertrophic gastritis].

    PubMed

    Sandrini, J; Beucher, A-B; Kouatchet, A; Lavigne, C

    2009-05-01

    Scarlet fever is a rare disease in adult patients. We report a patient in whom scarlet fever was associated with hypertrophic gastritis and multiple organ failure. A 62-year-old woman presented with septic shock and multiple organ failure. Bacteriological survey was negative. Abdominal tomodensitometry showed an hypertrophic gastritis. Histological analysis demonstrated a non specific gastritis without any tumoral sign. Cefotaxime and amoxicillin led to improvement and hypertrophic gastritis progressively resolved. A sandpaper rash over the body with finger desquamation, elevation of antistreptolysin O and a recent contact with an infected grandson led to the diagnosis of scarlet fever. Due to antibiotic prescription, scarlet fever is now uncommon. Although classical, ENT or gastroenteritis presentations may be puzzling for the diagnosis of scarlet fever. As 150 years ago, diagnosis of scarlet fever is still a clinical challenge.

  3. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy

    PubMed Central

    Jia, Guanghong; DeMarco, Vincent G.; Sowers, James R.

    2016-01-01

    Insulin resistance, type 2 diabetes mellitus and associated hyperinsulinaemia can promote the development of a specific form of cardiomyopathy that is independent of coronary artery disease and hypertension. Termed diabetic cardiomyopathy, this form of cardiomyopathy is a major cause of morbidity and mortality in developed nations, and the prevalence of this condition is rising in parallel with increases in the incidence of obesity and type 2 diabetes mellitus. Of note, female patients seem to be particularly susceptible to the development of this complication of metabolic disease. The diabetic cardiomyopathy observed in insulin-resistant or hyperinsulinaemic states is characterized by impaired myocardial insulin signalling, mitochondrial dysfunction, endoplasmic reticulum stress, impaired calcium homeostasis, abnormal coronary microcirculation, activation of the sympathetic nervous system, activation of the renin–angiotensin–aldosterone system and maladaptive immune responses. These pathophysiological changes result in oxidative stress, fibrosis, hypertrophy, cardiac diastolic dysfunction and eventually systolic heart failure. This Review highlights a surge in diabetic cardiomyopathy research, summarizes current understanding of the molecular mechanisms underpinning this condition and explores potential preventive and therapeutic strategies. PMID:26678809

  4. Diabetic Cardiomyopathy; Summary of 41 Years

    PubMed Central

    Canpolat, Ugur; Aydogdu, Sinan; Abboud, Hanna Emily

    2015-01-01

    Patients with diabetes have an increased risk for development of cardiomyopathy, even in the absence of well known risk factors like coronary artery disease and hypertension. Diabetic cardiomyopathy was first recognized approximately four decades ago. To date, several pathophysiological mechanisms thought to be responsible for this new entity have also been recognized. In the presence of hyperglycemia, non-enzymatic glycosylation of several proteins, reactive oxygen species formation, and fibrosis lead to impairment of cardiac contractile functions. Impaired calcium handling, increased fatty acid oxidation, and increased neurohormonal activation also contribute to this process. Demonstration of left ventricular hypertrophy, early diastolic and late systolic dysfunction by sensitive techniques, help us to diagnose diabetic cardiomyopathy. Traditional treatment of heart failure is beneficial in diabetic cardiomyopathy, but specific strategies for prevention or treatment of cardiac dysfunction in diabetic patients has not been clarified yet. In this review we will discuss clinical and experimental studies focused on pathophysiology of diabetic cardiomyopathy, and summarize diagnostic and therapeutic approaches developed towards this entity. PMID:26240579

  5. Histochemical and enzymehistochemical alterations during experimental cardiomyopathy.

    PubMed

    Kirvalidze, I; Khetsuriani, R; Jorbenadze, T; Shukakidze, A; Kipiani, T

    2006-05-01

    Investigation of ethiology, pathogenesis, morphogenesis, pathokinesis, treatment and prevention of cardiomyopathy is one of the most important problems of cardiology. Last years many scientific forums have been devoted to cardiomyopathy problems and still many issues remain disputable and needs further investigation and definition. In particular, investigation of metabolic processes in cardiac muscle seems of great importance. Obtained data will promote elaboration of adequate means toward the correction of cardiac decompensation during cardiomyopathy. The main goal of present study was the investigation of oxidation-reduction and electron transport associated protein activity in myocardium during experimental cardiomyopathy. Experiments were carried out on 30 male rats (180 - 200 g weight). Based on histological, histochemical, enzymehistological investigations conclusion has been made that during experimental autoimmune cardiomyopathy activity of oxidation-reduction and electron transport enzymes is sharply decreased along with the decrease of ascorbic acid and tiny granule glycogen amount (with altered topographic distribution) determining energy deficiency and weakening of cardiac muscle contractile function. It is possible to consider that the present study will open the way for future research and prompt us to select optimal therapeutic agents. PMID:16783088

  6. The epidemiology of infantile hypertrophic pyloric stenosis.

    PubMed

    Schechter, R; Torfs, C P; Bateson, T F

    1997-10-01

    Infants with infantile hypertrophic pyloric stenosis (IHPS) born from 1983 to 1988 and recorded in the California Birth Defects Monitoring Program (CBDMP) database were compared with their birth cohort by demographic characteristics and selected associated birth defects. We identified 1963 cases of IHPS for a cumulative incidence of 1.9 per 1000 livebirths. The cumulative incidence per 1000 livebirths was 2.4 in White, 1.8 in Hispanic, 0.7 in Black, and 0.6 in Asian infants. Between weeks 3-12 after birth, 1871 (95%) IHPS cases were diagnosed. Premature infants were diagnosed with IHPS later than term or post-term infants. The incidence of IHPS declined for those born to maternal age groups of > or = 25 years and, independently, for successive birth ranks. The probandwise concordance rate for IHPS in monozygous twins was less than unity (0.25-0.44), although higher than the concordance for dizygous twins (0.05-0.10). The incidence of Smith-Lemli-Opitz syndrome (SLO) diagnosed in infants with IHPS (3 of 1963) was 157-fold higher than the incidence of SLO diagnosed in the CBDMP population. IHPS occurs in all of the largest racial and ethnic groups in California, most frequently in White and Hispanic infants. Pyloric stenosis presents only within a brief phase of development, which may be delayed in premature infants. A predominant discordance of disease state in monozygous twins implies an aetiological role for undetermined environmental factors. The association between SLO, caused by deficient cholesterol synthesis, and IHPS deserves additional study. Infants with suspected SLO require close observation for the onset of IHPS.

  7. Peripartum cardiomyopathy – case series

    PubMed Central

    Prasad, Gowri Sayi; Bhupali, Ashok; Prasad, Sayi; Patil, Ajit N.; Deka, Yashodhan

    2014-01-01

    Objectives To study the pattern of presentation, course of disease and outcome of pregnancy in Peripartum Cardiomyopathy. Methods A prospective study of sixteen cases of PPCM was conducted at Apple Saraswati Multispecialty Hospital and Dr. D.Y. Patil Medical College and Hospital, Kolhapur, Maharashtra, India from January 2006 to December 2012. Data included age distribution, parity, gestational age, symptoms and risk factors. Medical management and pregnancy outcome were documented. Serial echocardiography data was compiled for a period of one year. Results In our study 9/16 (56%) were primigravidae, 4/16 (25%) had pre-eclamsia and 6/16 (35%) had co-existing hypertension. The difference in Echocardiography parameters observed between recovered and non-recovered patients was significant: Left Ventricular End diastolic dimension (5.6 cm vs 6.06 cm), Left Ventricular Ejection Fraction (28.7% vs 22.4%) and Left Ventricular fractional shortening (17.5% vs 13.4%). Thirteen out of sixteen patients were followed up for a period of one year out of which 61% (8/13) patients recovered completely. There was one mortality. Conclusion PPCM is a diagnosis of exclusion. Majority were young primigravidae presenting postnatally. Pre-eclampsia and hypertension were risk factors. ECHO parameters were reliable predictors of recovery. Future pregnancies are better avoided. PMID:24814122

  8. Electrocardiographic predictors of peripartum cardiomyopathy

    PubMed Central

    Karaye, Kamilu M; Karaye, Kamilu M; Lindmark, Krister; Henein, Michael Y; Lindmark, Krister; Henein, Michael Y

    2016-01-01

    Summary Objective To identify potential electrocardiographic predictors of peripartum cardiomyopathy (PPCM). Methods: This was a case–control study carried out in three hospitals in Kano, Nigeria. Logistic regression models and a risk score were developed to determine electrocardiographic predictors of PPCM. Results: A total of 54 PPCM and 77 controls were consecutively recruited after satisfying the inclusion criteria. After controlling for confounding variables, a rise in heart rate of one beat/minute increased the risk of PPCM by 6.4% (p = 0.001), while the presence of ST–T-wave changes increased the odds of PPCM 12.06-fold (p < 0.001). In the patients, QRS duration modestly correlated (r = 0.4; p < 0.003) with left ventricular dimensions and end-systolic volume index, and was responsible for 19.9% of the variability of the latter (R2 = 0.199; p = 0.003). A risk score of ≥ 2, developed by scoring 1 for each of the three ECG disturbances (tachycardia, ST–T-wave abnormalities and QRS duration), had a sensitivity of 85.2%, specificity of 64.9%, negative predictive value of 86.2% and area under the curve of 83.8% (p < 0.0001) for potentially predicting PPCM. Conclusion In postpartum women, using the risk score could help to streamline the diagnosis of PPCM with significant accuracy, prior to confirmatory investigations PMID:27213852

  9. [Hypertrophic scars and keloids: which therapeutic options today?].

    PubMed

    Gailloud-Matthieu, M C; Raffoul, W; Egloff, D V

    1999-09-01

    Hypertrophic scars and keloids are a hyperproliferative response of connective tissue to trauma. Histologically the difference between the two is that keloids invade normal tissue whereas hypertrophic scars remain confined within the original wound. A variety of treatments have been proposed, which we will review according to their efficiency. Prevention of pathological scarring will also be discussed, and we will present our current attitude to treat these scars. As a surgical treatment for keloids, we have been using the intralesional technique which we think gives better results.

  10. Familial idiopathic hypertrophic osteoarthropathy and cranial suture defects in children

    SciTech Connect

    Reginato, A.J.; Schiapachasse, V.; Guerrero, R.

    1982-05-01

    Three children with idiopathic hypertrophic osteoarthropathy and cranial suture defects are reported. The syndrome was recognized after birth and in the two oldest siblings, the cranial defects and subperiosteal bone formation resolved almost completely by age 4 and 6 years. The joint swelling and clubbing persisted and mild bone reabsorption of the distal phalanges became apparent at an older age. Two siblings and both parents had normal bone X-rays and no clubbing. This study confirms the association of cranial sutural defects and familial idopathic hypertrophic osteoarthropathy.

  11. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    PubMed

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

  12. Primary cardiac lymphoma mimicking infiltrative cardiomyopathy.

    PubMed

    Lee, Ga Yeon; Kim, Won Seog; Ko, Young-Hyeh; Choi, Jin-Oh; Jeon, Eun-Seok

    2013-05-01

    Primary cardiac lymphoma is a rare malignancy which has been described as thickened myocardium due to the infiltration of atypical lymphocytes and accompanying intracardiac masses. Here, we report a case of a primary cardiac lymphoma without demonstrable intracardiac masses, mimicking infiltrative cardiomyopathy. A 40-year-old male presented with exertional dyspnoea and was diagnosed as having restrictive cardiomyopathy with severely decreased LV systolic function. Endomyocardial biopsy was performed and the diagnosis of primary cardiac lymphoma was confirmed. After appropriate chemotherapy, he recovered his systolic function fully. PMID:23248217

  13. Takotsubo cardiomyopathy: can hearts really break?

    PubMed

    Farris, Cindy; McEnroe-Petitte, Denise; Kanayama, Tiffanie

    2014-01-01

    Takotsubo cardiomyopathy (TCM), or broken-heart syndrome, is a form of cardiomyopathy (CM) that is significantly different from other common types. This form of CM occurs spontaneously and can be easily reversed. TCM is seen primarily in postmenopausal women with a recent stressful event. Patients with TCM often present with symptoms suggestive of a myocardial infarction. Home health-care and hospice clinicians interact frequently with caregivers and other family members who are living under stressful circumstances. It is important that home care clinicians be familiar with TCM and understand the relationship that may exist between stress, stressful events, triggers, and TCM. PMID:24978575

  14. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    PubMed

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity. PMID:26613951

  15. Process of Hypertrophic Scar Formation: Expression of Eukaryotic Initiation Factor 6

    PubMed Central

    Yang, Qing-Qing; Yang, Si-Si; Tan, Jiang-Lin; Luo, Gao-Xing; He, Wei-Feng; Wu, Jun

    2015-01-01

    Background: Hypertrophic scar is one of the most common complications and often causes the disfigurement or deformity in burn or trauma patients. Therapeutic methods on hypertrophic scar treatment have limitations due to the poor understanding of mechanisms of hypertrophic scar formation. To throw light on the molecular mechanism of hypertrophic scar formation will definitely improve the outcome of the treatment. This study aimed to illustrate the negative role of eukaryotic initiation factor 6 (eIF6) in the process of human hypertrophic scar formation, and provide a possible indicator of hypertrophic scar treatment and a potential target molecule for hypertrophic scar. Methods: In the present study, we investigated the protein expression of eIF6 in the human hypertrophic scar of different periods by immunohistochemistry and Western blot analysis. Results: In the hypertrophic scar tissue, eIF6 expression was significantly decreased and absent in the basal layer of epidermis in the early period, and increased slowly and began to appear in the basal layer of epidermis by the scar formation time. Conclusions: This study confirmed that eIF6 expression was significantly related to the development of hypertrophic scar, and the eIF6 may be a target molecule for hypertrophic scar control or could be an indicator of the outcomes for other treatment modalities. PMID:26481747

  16. Hypertrophic Osteoarthropathy Presenting as Unilateral Cellulitis with Successful Treatment Using Pamidronate Disodium

    PubMed Central

    Bernardo, Sebastian G.; Burnett, Mark E.; Gordon, Marsha

    2012-01-01

    Hypertrophic pulmonary osteoarthropathy is a paraneoplastic syndrome seen in patients with lung cancer. This condition is characterized by the presence of digital clubbing, periosteal thickening, synovial thickening, and severe pain of the affected joints. Other syndromes exhibiting clubbing may or may not have underlying diseases causing their manifestation. An example is primary hypertrophic osteoarthropathy, or pachydermoperiostosis. While clubbing makes up part of the clinical picture in both hypertrophic pulmonary osteoarthropathy and hypertrophic osteoarthropathy, the latter has no underlying disease associations. Rather, primary hypertrophic osteoarthropathy is familial, idiopathic, and has a chronic course often beginning during puberty in males. Secondary hypertrophic osteoarthropathy is an acquired form of clubbing that is classically associated with lung disease. However, it has also been associated with diseases of the heart, liver, and intestines. In the setting of pulmonary malignancy, secondary hypertrophic osteoarthropathy is known as hypertrophic pulmonary osteoarthropathy. Hypertrophic pulmonary osteoarthropathy has a distinct constellation of clinical findings that includes intractable pain often refractory to treatments other than resolution of the underlying disease process. The authors herein report a case of hypertrophic pulmonary osteoarthropathy masquerading as recurrent lower extremity cellulitis with chronic hand and foot pain in the setting of pulmonary malignancy that responded dramatically to intravenous pamidronate disodium (a bisphosphonate). Given the rarity of hypertrophic osteoarthropathy associated with lung cancer and the difficulty with pain management in such circumstances, the authors present the following case in which pain was mitigated by treatment with bisphosphonate therapy. PMID:23050033

  17. Mitochondrial dysfunction in uremic cardiomyopathy

    PubMed Central

    Taylor, David; Bhandari, Sunil

    2015-01-01

    Uremic cardiomyopathy (UCM) is characterized by metabolic remodelling, compromised energetics, and loss of insulin-mediated cardioprotection, which result in unsustainable adaptations and heart failure. However, the role of mitochondria and the susceptibility of mitochondrial permeability transition pore (mPTP) formation in ischemia-reperfusion injury (IRI) in UCM are unknown. Using a rat model of chronic uremia, we investigated the oxidative capacity of mitochondria in UCM and their sensitivity to ischemia-reperfusion mimetic oxidant and calcium stressors to assess the susceptibility to mPTP formation. Uremic animals exhibited a 45% reduction in creatinine clearance (P < 0.01), and cardiac mitochondria demonstrated uncoupling with increased state 4 respiration. Following IRI, uremic mitochondria exhibited a 58% increase in state 4 respiration (P < 0.05), with an overall reduction in respiratory control ratio (P < 0.01). Cardiomyocytes from uremic animals displayed a 30% greater vulnerability to oxidant-induced cell death determined by FAD autofluorescence (P < 0.05) and reduced mitochondrial redox state on exposure to 200 μM H2O2 (P < 0.01). The susceptibility to calcium-induced permeability transition showed that maximum rates of depolarization were enhanced in uremia by 79%. These results demonstrate that mitochondrial respiration in the uremic heart is chronically uncoupled. Cardiomyocytes in UCM are characterized by a more oxidized mitochondrial network, with greater susceptibility to oxidant-induced cell death and enhanced vulnerability to calcium-induced mPTP formation. Collectively, these findings indicate that mitochondrial function is compromised in UCM with increased vulnerability to calcium and oxidant-induced stressors, which may underpin the enhanced predisposition to IRI in the uremic heart. PMID:25587120

  18. Regulation of Cardiac Hypertrophic Signaling by Prolyl Isomerase Pin1

    PubMed Central

    Toko, Haruhiro; Konstandin, Mathias H.; Doroudgar, Shirin; Ormachea, Lucia; Joyo, Eri; Joyo, Anya Y.; Din, Shabana; Gude, Natalie A.; Collins, Brett; Völkers, Mirko; Thuerauf, Donna J.; Glembotski, Christopher C.; Chen, Chun-Hau; Lu, Kun Ping; Müller, Oliver J.; Uchida, Takafumi; Sussman, Mark A.

    2013-01-01

    Rationale Cardiac hypertrophy results from the complex interplay of differentially regulated cascades based upon the phosphorylation status of involved signaling molecules. While numerous critical regulatory kinases and phosphatases have been identified in the myocardium, the intracellular mechanism for temporal regulation of signaling duration and intensity remains obscure. In the non-myocyte context, control of folding, activity, and stability of proteins is mediated by the prolyl isomerase Pin1, but the role of Pin1 in the heart is unknown. Objective To establish the role of Pin1 in the heart. Methods and Results Here we show that either genetic deletion or cardiac over-expression of Pin1 blunts hypertrophic responses induced by transaortic constriction and consequent cardiac failure in vivo. Mechanistically, we find that Pin1 directly binds to Akt, MEK and Raf-1 in cultured cardiomyocytes following hypertrophic stimulation. Furthermore, loss of Pin1 leads to diminished hypertrophic signaling of Akt and MEK, while over-expression of Pin1 increases Raf-1 phosphorylation on the auto-inhibitory site Ser259 leading to reduced MEK activation. Conclusions Collectively, these data support a role for Pin1 as a central modulator of the intensity and duration of two major hypertrophic signaling pathways, thereby providing a novel target for regulation and control of cardiac hypertrophy. PMID:23487407

  19. Difficulty of diagnosing infected hypertrophic pseudarthrosis by radionuclide imaging

    SciTech Connect

    Hadjipavlou, A.; Lisbona, R.; Rosenthall, L.

    1983-02-01

    Hypertrophic pseudarthrosis was studied with /sup 99m/Tc MDP and /sup 67/Ga citrate in 11 patients. Two of the 11 pseudarthroses were complicated by infection. A high concentration of both radiopharmaceuticals was obtained at all 11 sites and their distribution patterns were identical. It was therefore impossible to distinguish the infected from the noninfected pseudarthroses by using /sup 67/Ga.

  20. Hypertrophic osteopathy associated with a renal adenoma in a cat.

    PubMed

    Johnson, Robert L; Lenz, Stephen D

    2011-01-01

    Hypertrophic osteopathy is a hyperostotic syndrome of the appendicular skeleton that is most commonly associated with intrathoracic neoplasia or inflammation. The condition is rarely associated with intra-abdominal lesions. The majority of cases have occurred in dogs and human beings, with fewer cases reported in cats, horses, and other species. A 15-year-old male neutered Domestic Shorthair cat presented for swollen limbs and difficulty in ambulation. Radiographs and gross postmortem revealed severe periosteal hyperostosis of the diaphysis and metaphysis of all 4 limbs, including the humerus, radius, ulna, carpi, metacarpi, femur, tibia, tarsi, metatarsi, and phalanges. The axial skeleton was spared. Hyperostotic lesions were characterized microscopically by lamellar bony trabeculae separated by adipocytes and scant hematopoietic tissue. In several areas, fibrovascular connective tissue, woven bone, and islands of cartilage were also present. A 2.5 cm × 2.5 cm perirenal neoplasm compressed the left kidney and adrenal gland. This mass consisted of well-differentiated tubules of cuboidal epithelial cells and was most consistent with a renal tubular adenoma, because mitotic figures were rare, and no distant metastases were found. Thoracic pathology was absent. Hyperostosis was consistent with hypertrophic osteopathy secondary to the renal adenoma. The pathogenesis of hypertrophic osteopathy is uncertain, but predominant theories point to increased peripheral circulation and angiogenesis as a key initiating event. Recent literature highlights the potential role of vascular endothelial growth factor and platelet-derived growth factor in the human condition. The mechanism by which this renal adenoma caused hypertrophic osteopathy is unknown.

  1. Inflammation and impaired adipogenesis in hypertrophic obesity in man.

    PubMed

    Gustafson, Birgit; Gogg, Silvia; Hedjazifar, Shahram; Jenndahl, Lachmi; Hammarstedt, Ann; Smith, Ulf

    2009-11-01

    Obesity is associated mainly with adipose cell enlargement in adult man (hypertrophic obesity), whereas the formation of new fat cells (hyperplastic obesity) predominates in the prepubertal age. Adipose cell size, independent of body mass index, is negatively correlated with whole body insulin sensitivity. Here, we review recent findings linking hypertrophic obesity with inflammation and a dysregulated adipose tissue, including local cellular insulin resistance with reduced IRS-1 and GLUT4 protein content. In addition, the number of preadipocytes in the abdominal subcutaneous adipose tissue capable of undergoing differentiation to adipose cells is reduced in hypertrophic obesity. This is likely to promote ectopic lipid accumulation, a well-known finding in these individuals and one that promotes insulin resistance and cardiometabolic risk. We also review recent results showing that TNFα, but not MCP-1, resistin, or IL-6, completely prevents normal adipogenesis in preadipocytes, activates Wnt signaling, and induces a macrophage-like phenotype in the preadipocytes. In fact, activated preadipocytes, rather than macrophages, may completely account for the increased release of chemokines and cytokines by the adipose tissue in obesity. Understanding the molecular mechanisms for the impaired preadipocyte differentiation in the subcutaneous adipose tissue in hypertrophic obesity is a priority since it may lead to new ways of treating obesity and its associated metabolic complications.

  2. Hypertrophic osteoarthropathy as a clinical manifestation of lung cancer.

    PubMed

    Davis, Melissa C; Sherry, Victoria

    2011-10-01

    Hypertrophic osteoarthropathy is a paraneoplastic syndrome most often found in non-small cell lung cancer. Diagnosis is confirmed by the presence of clubbing on physical examination and periostitis on bone scintigram, and the syndrome generally resolves with treatment of the underlying malignancy. This article presents a case study and describes symptom management options, including nonsteroidal anti-inflammatory agents, octreotide, and bisphosphonates.

  3. A case of hypertrophic osteoarthropathy in a Belgian blue cow

    PubMed Central

    Guyot, Hugues; Sandersen, Charlotte; Rollin, Frédéric

    2011-01-01

    A 12-year-old cow was presented with chronic respiratory disease and lameness. Chronic pleuritis, pneumonia, and bronchial carcinoma were found as well as periosteal proliferation on limb bones. Ancillary tests and necropsy confirmed a combined pathology of pulmonary inflammation and neoplasm, and hypertrophic pulmonary osteopathy. PMID:22654134

  4. Multicenter study on hepatitis C virus infection in patients with dilated cardiomyopathy. North Italy Transplant Program (NITP).

    PubMed

    Prati, D; Poli, F; Farma, E; Picone, A; Porta, E; De Mattei, C; Zanella, A; Scalamogna, M; Gamba, A; Gronda, E; Faggian, G; Livi, U; Puricelli, C; Viganò, M; Sirchia, G

    1999-06-01

    Preliminary epidemiological and histological studies from Japan suggested that hepatitis C virus (HCV) infection has a role in the development of dilated cardiomyopathy (DCM). This multicenter study was conducted to verify this hypothesis on a large cohort of Italian patients with end-stage heart failure. Antibodies to HCV were determined in the 752 consecutive patients (608 males and 144 females; age, 53 +/- 13 years) who entered the waiting list for cardiac transplantation from 1995 to 1997 at the six cardiac surgery centers participating in the North Italy Transplant program. Three hundred and nine patients (41%) had dilated, 9 (1%) restrictive, and 4 (0.5%) hypertrophic cardiomyopathy; 284 patients (38%) had ischemic, 65 (9%) valvular, and 22 (3%) congenital heart disease; 5 patients (0.5%) had primary pulmonary hypertension; 54 patients (7%) had other or nonspecified heart disease. Overall, 41 of 752 patients (5.4%) resulted anti-HCV-reactive. Serological evidence of HCV infection was found in 12 of 309 patients with DCM (3.9%; 95% CI, 1.7-6.0), and in 29 of 443 without DCM (6.5%; 95% CI, 4.2-8.8), without statistical difference (difference of prevalence rate: 2.6%; 95% CI, -4.9 to 5.8). In conclusion, HCV does not seem to have a primary role in the pathogenesis of DCM. However, since our findings are in disagreement with those obtained in smaller series of patients of other ethnicity, large studies from different countries should be conducted.

  5. 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

  6. Secondary coronary artery vasospasm promotes cardiomyopathy progression.

    PubMed

    Wheeler, Matthew T; Korcarz, Claudia E; Collins, Keith A; Lapidos, Karen A; Hack, Andrew A; Lyons, Matthew R; Zarnegar, Sara; Earley, Judy U; Lang, Roberto M; McNally, Elizabeth M

    2004-03-01

    Genetic defects in the plasma membrane-associated sarcoglycan complex produce cardiomyopathy characterized by focal degeneration. The infarct-like pattern of cardiac degeneration has led to the hypothesis that coronary artery vasospasm underlies cardiomyopathy in this disorder. We evaluated the coronary vasculature of gamma-sarcoglycan mutant mice and found microvascular filling defects consistent with arterial vasospasm. However, the vascular smooth muscle sarcoglycan complex was intact in the coronary arteries of gamma-sarcoglycan hearts with perturbation of the sarcoglycan complex only within the adjacent myocytes. Thus, in this model, coronary artery vasospasm derives from a vascular smooth muscle-cell extrinsic process. To reduce this secondary vasospasm, we treated gamma-sarcoglycan-deficient mice with the calcium channel antagonist verapamil. Verapamil treatment eliminated evidence of vasospasm and ameliorated histological and functional evidence of cardiomyopathic progression. Echocardiography of verapamil-treated, gamma-sarcoglycan-null mice showed an improvement in left ventricular fractional shortening (44.3 +/- 13.3% treated versus 37.4 +/- 15.3% untreated), maximal velocity at the aortic outflow tract (114.9 +/- 27.9 cm/second versus 92.8 +/- 22.7 cm/second), and cardiac index (1.06 +/- 0.30 ml/minute/g versus 0.67 +/- 0.16 ml/minute/g, P < 0.05). These data indicate that secondary vasospasm contributes to the development of cardiomyopathy and is an important therapeutic target to limit cardiomyopathy progression.

  7. Biventricular Takotsubo Cardiomyopathy Associated with Epilepsy

    PubMed Central

    Koo, Namho; Yoon, Byung Woo; Song, Yonggeon; Lee, Chang Kyun; Lee, Tae Yeon

    2015-01-01

    We describe a case of Takotsubo cardiomyopathy in an elderly woman after status epilepticus. In an emergency echocardiography, not only left ventricular apical ballooning but also right ventricular apical hypokinesia was observed. After a medical management, the patient's condition was improved and a follow-up echocardiography showed substantial recovery of left and right ventricular apical ballooning. PMID:26755936

  8. Emergency management of decompensated peripartum cardiomyopathy.

    PubMed

    Lata, Indu; Gupta, Renu; Sahu, Sandeep; Singh, Harpreet

    2009-05-01

    Peripartum cardiomyopathy (PPCM) is a rare life-threatening cardiomyopathy of unknown cause that occurs in the peripartum period in previously healthy women.[1] the symptomatic patients should receive standard therapy for heart failure, managed by a multidisciplinary team. The diagnosis of PPCM rests on the echocardiographic identification of new left ventricular systolic dysfunction during a limited period surrounding parturition. Diagnostic criteria include an ejection fraction of less than 45%, fractional shortening of less than 30%, or both, and end-diastolic dimension of greater than 2.7 cm/m(2) body surface-area. This entity presents a diagnostic challenge because many women in the last month of a normal pregnancy experience dyspnea, fatigue, and pedal edema, symptoms identical to early congestive heart failure. There are no specific criteria for differentiating subtle symptoms of heart failure from normal late pregnancy. Therefore, it is important that a high index of suspicion be maintained to identify the rare case of PPCM as general examination showing symptoms of heart failure with pulmonary edema. PPCM remains a diagnosis of exclusion. No additional specific criteria have been identified to allow distinction between a peripartum patient with new onset heart failure and left ventricular systolic dysfunction as PPCM and another form of dilated cardiomyopathy. Therefore, all other causes of dilated cardiomyopathy with heart failure must be systematically excluded before accepting the designation of PPCM. Recent observations from Haiti[2] suggest that a latent form of PPCM without clinical symptoms might exist. The investigators identified four clinically normal postpartum women with asymptomatic systolic dysfunction on echocardiography, who subsequently either developed clinically detectable dilated cardiomyopathy or improved and completely recovered heart function. PMID:19561973

  9. Psoriasis and dilated cardiomyopathy: coincidence or associated diseases?

    PubMed

    Eliakim-Raz, Noa; Shuvy, Mony; Lotan, Chaim; Planer, David

    2008-01-01

    Psoriasis is a common immune-mediated disease which affects 1-3% of the population. The etiology of psoriasis is unknown. Idiopathic dilated cardiomyopathy is probably the end result of a variety of toxic, metabolic or infectious agents. During a computerized search for cardiomyopathy among all patients hospitalized with psoriasis in the Hadassah University Hospital since 1980 we found an increased prevalence of cardiomyopathy, and specifically dilated cardiomyopathy. We present 4 patients who suffer from both conditions. In accordance with previous data, an association between preexisting psoriasis and dilated cardiomyopathy is suggested. We suggest that the genetic risk factors of dilated cardiomyopathy are shared by psoriasis, and more specifically psoriatic arthritis. Alternatively, the immune reaction that is triggered in dilated cardiomyopathy leading to the progression of the disease might be enhanced in patients with psoriasis or psoriatic arthritis. Chronic inflammation and persistent secretion of proinflammatory cytokines may be considered a potential pathway, triggering the initiation and progression of dilated cardiomyopathy in psoriatic patients. Further investigation of the genetic and immune risk factors involved in dilated cardiomyopathy and in psoriasis may lead to a better understanding of the pathogenesis and treatment of dilated cardiomyopathy.

  10. Analysis of hypertrophic and normal scar gene expression with cDNA microarrays.

    PubMed

    Tsou, R; Cole, J K; Nathens, A B; Isik, F F; Heimbach, D M; Engrav, L H; Gibran, N S

    2000-01-01

    Hypertrophic scar is one form of abnormal wound healing. Previous studies have suggested that hypertrophic scar formation results from altered gene expression of extracellular matrix molecules. A broadscale evaluation of gene expression in hypertrophic scars has not been reported. To better understand abnormalities in hypertrophic scar gene expression, we compared messenger RNA expression in hypertrophic scars, normal scars, and uninjured skin with the use of complementary (c)DNA microarrays. Total RNA was extracted from freshly excised human hypertrophic scars, normal scars, or uninjured skin and reverse transcribed into cDNA with the incorporation of [33P] deoxycytidine triphosphate. The resulting radioactive cDNA probes were hybridized onto cDNA microarrays of 4000 genes. Hybridization signals were normalized and analyzed. In the comparison of tissue samples, mean intensities were calculated for each gene within each group (hypertrophic scars, normal scars, and uninjured skin). Ratios of the mean intensities of hypertrophic scars to normal scars, hypertrophic scars to uninjured skin, and normal scars to uninjured skin were generated. A ratio that was greater than 1 indicated upregulation of any particular gene and a ratio that was less than 1 indicated downregulation of any particular gene. Our data indicated that 142 genes were overexpressed and 50 genes were underexpressed in normal scars compared with uninjured skin, 107 genes were overexpressed and 71 were underexpressed in hypertrophic scars compared with uninjured skin, and 44 genes were overexpressed and 124 were underexpressed in hypertrophic scars compared with normal scars. Our analysis of collagen, growth factor, and metalloproteinase gene expression confirmed that our molecular data were consistent with published biochemical and clinical observations of normal scars and hypertrophic scars. cDNA microarray analysis provides a powerful tool for the investigation of differential gene expression in

  11. 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.

  12. Effects of Noscarna™ on hypertrophic scarring in the rabbit ear model: histopathological aspects.

    PubMed

    Lee, Dong Won; Ku, Sae Kwang; Cho, Hyuk Jun; Kim, Jeong Hwan; Hiep, Tran Tuan; Han, Sang Duk; Kim, Bo Gyun; Kang, Min Kyung; Do, Eui Seon; Jun, Joon Ho; Jang, Sun Woo; Son, Mi-Won; Sohn, Young Taek; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2012-11-01

    In this study, we evaluated the effects of silicone-based gel on the healing of hypertrophic scars in the rabbit ear model. After 4-week application of silicone-based gel containing allantoin, dexpanthenol and heparin (Noscarna™) to scars in a rabbit ear model of hypertrophic scarring, significant improvements in hypertrophic scar healing and a great loss of skin pigment were observed compared to the non-treated control, base or silicone control-treated scars. Furthermore, histological analysis of Noscarna™-treated scars revealed a significant reduction in scar elevation index (SEI), anterior skin and epithelial thicknesses, inflammatory cells, vessels, collagen disorganization and fibroblasts compared to all control hypertrophic scars. Furthermore, Noscarna™ showed more favorable effects on hypertrophic scars than a commercial product, Contractubex®. Therefore, these results clearly demonstrated that the newly developed silicone-based gel, Noscarna™, could be a promising formulation as an effective therapeutic agent for hypertrophic scars. PMID:23212642

  13. Clinical Genetic Testing for the Cardiomyopathies and Arrhythmias: A Systematic Framework for Establishing Clinical Validity and Addressing Genotypic and Phenotypic Heterogeneity

    PubMed Central

    Garcia, John; Tahiliani, Jackie; Johnson, Nicole Marie; Aguilar, Sienna; Beltran, Daniel; Daly, Amy; Decker, Emily; Haverfield, Eden; Herrera, Blanca; Murillo, Laura; Nykamp, Keith; Topper, Scott

    2016-01-01

    Advances in DNA sequencing have made large, diagnostic gene panels affordable and efficient. Broad adoption of such panels has begun to deliver on the promises of personalized medicine, but has also brought new challenges such as the presence of unexpected results, or results of uncertain clinical significance. Genetic analysis of inherited cardiac conditions is particularly challenging due to the extensive genetic heterogeneity underlying cardiac phenotypes, and the overlapping, variable, and incompletely penetrant nature of their clinical presentations. The design of effective diagnostic tests and the effective use of the results depend on a clear understanding of the relationship between each gene and each considered condition. To address these issues, we developed simple, systematic approaches to three fundamental challenges: (1) evaluating the strength of the evidence suggesting that a particular condition is caused by pathogenic variants in a particular gene, (2) evaluating whether unusual genotype/phenotype observations represent a plausible expansion of clinical phenotype associated with a gene, and (3) establishing a molecular diagnostic strategy to capture overlapping clinical presentations. These approaches focus on the systematic evaluation of the pathogenicity of variants identified in clinically affected individuals, and the natural history of disease in those individuals. Here, we applied these approaches to the evaluation of more than 100 genes reported to be associated with inherited cardiomyopathies and arrhythmias including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia or cardiomyopathy, long QT syndrome, short QT syndrome, Brugada, and catecholaminergic polymorphic ventricular tachycardia, and to a set of related syndromes such as Noonan Syndrome and Fabry disease. These approaches provide a framework for delivering meaningful and accurate genetic test results to individuals with hereditary

  14. Clinical Genetic Testing for the Cardiomyopathies and Arrhythmias: A Systematic Framework for Establishing Clinical Validity and Addressing Genotypic and Phenotypic Heterogeneity.

    PubMed

    Garcia, John; Tahiliani, Jackie; Johnson, Nicole Marie; Aguilar, Sienna; Beltran, Daniel; Daly, Amy; Decker, Emily; Haverfield, Eden; Herrera, Blanca; Murillo, Laura; Nykamp, Keith; Topper, Scott

    2016-01-01

    Advances in DNA sequencing have made large, diagnostic gene panels affordable and efficient. Broad adoption of such panels has begun to deliver on the promises of personalized medicine, but has also brought new challenges such as the presence of unexpected results, or results of uncertain clinical significance. Genetic analysis of inherited cardiac conditions is particularly challenging due to the extensive genetic heterogeneity underlying cardiac phenotypes, and the overlapping, variable, and incompletely penetrant nature of their clinical presentations. The design of effective diagnostic tests and the effective use of the results depend on a clear understanding of the relationship between each gene and each considered condition. To address these issues, we developed simple, systematic approaches to three fundamental challenges: (1) evaluating the strength of the evidence suggesting that a particular condition is caused by pathogenic variants in a particular gene, (2) evaluating whether unusual genotype/phenotype observations represent a plausible expansion of clinical phenotype associated with a gene, and (3) establishing a molecular diagnostic strategy to capture overlapping clinical presentations. These approaches focus on the systematic evaluation of the pathogenicity of variants identified in clinically affected individuals, and the natural history of disease in those individuals. Here, we applied these approaches to the evaluation of more than 100 genes reported to be associated with inherited cardiomyopathies and arrhythmias including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia or cardiomyopathy, long QT syndrome, short QT syndrome, Brugada, and catecholaminergic polymorphic ventricular tachycardia, and to a set of related syndromes such as Noonan Syndrome and Fabry disease. These approaches provide a framework for delivering meaningful and accurate genetic test results to individuals with hereditary

  15. [The morphological changes in the myocardial tissue after sudden cardiac death from alcoholic cardiomyopathy].

    PubMed

    Sokolova, O V

    2016-01-01

    This paper was designed to report the results of the retrospective analysis of the protocols of 180 forensic medical autopsy sections stored in the archives of Sankt-Petersburg Bureau of Forensic Medical Expertise and the data of the histological studies of myocardial tissues obtained after sudden cardiac death from alcoholic cardiomyopathy. The study revealed the following most pathognomonic histological criteria for alcoholic heart lesions: the alternation of hypertrophic and atrophic cardiomyocytes in the state of severe parenchymatous degeneration, pronounced mesenchymal fatty dystrophy in combination with pathological changes of the vascular walls (vascular wall plasmatization), sub-endothelial accumulation of the PAS-positive tissue compounds, microcirculatory disorders in the form of erythrocyte stasis with the manifestations of the blood "sludge" phenomenon, and precapillary fibrosis. The signs of severe parenchymatous and stromal vascular dystrophy of the myocardial histohematic barrier (HHB) are supposed to reflect the toxic effects of ethanol and its metabolites that are directly involved in the mechanisms underlying the disturbances of intracellular metabolism and dyscirculatory events leading to the development of heart muscle hypoxia.

  16. Na(+)-H(+) exchanger inhibitor prevents early death in hereditary cardiomyopathy.

    PubMed

    Bkaily, Ghassan; Chahine, Mirna; Al-Khoury, Johny; Avedanian, Levon; Beier, Norbert; Scholz, Wolfgang; Jacques, Danielle

    2015-11-01

    Using the UM-X7.1 hereditary cardiomyopathic and muscular dystrophy hamsters (HCMH), we tested the effects of lifelong preventive or curative treatments during the heart failure phase with the NHE-1 inhibitor EMD 87580 (EMD) or with the angiotensin-converting enzyme inhibitor cilazapril on the intracellular Na(+) and Ca(2+) overloads, elevated level of NHE-1, necrosis, hypertrophy, heart failure, and early death. Our results showed that 310-day pretreatment of 30-day-old HCMHs with EMD significantly prevented cardiac necrosis, cardiomyocyte hypertrophy, and reduced the heart to body mass ratio. This treatment significantly prevented Na(+) and Ca(2+) overloads and the increase in NHE-1 protein level observed in HCMHs. Importantly, this lifelong preventive treatment significantly decreased the levels of creatine kinase and prevented early death of HCMHs. Curative treatment of hypertrophic 275-day-old HCMHs for 85 days with EMD significantly prevented hypertrophy and early death of HCMHs. However, treatments with cilazapril did not have any significant effects on the cardiac parameters studied or on early death of HCMHs. Our results suggest that the increase in the NHE-1 level and the consequent Na(+) and Ca(2+) overloads are implicated in the pathological process leading to heart failure and early death in HCMHs, and treatment with the NHE-1 inhibitor is promising for preventing early death in hereditary cardiomyopathy.

  17. Regulatory Light Chain Mutations Associated with Cardiomyopathy Affect Myosin Mechanics and Kinetics

    PubMed Central

    Greenberg, Michael J.; Watt, James D.; Jones, Michelle; Kazmierczak, Katarzyna; Szczesna-Cordary, Danuta; Moore, Jeffrey R.

    2009-01-01

    The myosin regulatory light chain (RLC) wraps around the alpha helical neck region of myosin. This neck region has been proposed to act as a lever arm, amplifying small conformational changes in the myosin head to generate motion. The RLC serves an important structural role, supporting the myosin neck region and a modulatory role, tuning the kinetics of the actin myosin interaction. Given the importance of the RLC, it is not surprising that mutations of the RLC can lead to familial hypertrophic cardiomyopathy (FHC), the leading cause of sudden cardiac death in people under 30. Population studies identified two FHC mutations located near the cationic binding site of the RLC, R58Q and N47K. Although these mutations are close in sequence, they differ in clinical presentation and prognosis with R58Q showing a more severe phenotype. We examined the molecular based changes in myosin that are responsible for the disease phenotype by purifying myosin from transgenic mouse hearts expressing mutant myosins and examining actin filament sliding using the in vitro motility assay. We found that both R58Q and N47K showed reductions in force compared to the wild type that could result in compensatory hypertrophy. Furthermore, we observed a higher ATPase rate and an increased activation at submaximal calcium levels for the R58Q myosin that could lead to decreased efficiency and incomplete cardiac relaxation, potentially explaining the more severe phenotype for the R58Q mutation. PMID:18929571

  18. Idiopathic hypertrophic cranial pachymenigitis - A long follow-up needed.

    PubMed

    Hashmi, M A; Gautam, G; Sengupta, P; Singh, H; Haque, N

    2011-07-01

    Idiopathic hypertrophic cranial pachymenigitis is a rare clinical condition caused by localized or diffuse inflammatory thickening of dura matter. Described here is a person having diffuse thickening of dura matter of base of skull and he was on follow-up treatment for 5 years with us. Diagnosis was done by excluding other conditions and with biopsy. The patient responded to steroid and the MRI picture, which is given serially, shows improvement. PMID:22347338

  19. [The sonographic diagnosis of hypertrophic stenosis of the pylorus].

    PubMed

    Rodríguez, R I; Briceño de Rodríguez, J A; Urrutia, M

    1993-09-01

    The clinical records of 18 children were studied, between 15 and 60 days old. They were hospitalized due to vomiting and diagnosis of suspected pyloric hypertrophic stenosis (PHS). The sonography confirmed the diagnosis in 8 children, by the thickening of the muscular layer and enlargement of the pyloric canal. The surgery (pyloromyotomy) ratified the diagnosis in all 8 children. They all were in good health after being operated. PMID:8146343

  20. [The sonographic diagnosis of hypertrophic stenosis of the pylorus].

    PubMed

    Rodríguez, R I; Briceño de Rodríguez, J A; Urrutia, M

    1993-05-01

    The clinical records of 18 children were studied, between 15 and 60 days old. They were hospitalized due to vomiting and diagnosis of suspected pyloric hypertrophic stenosis (PHS). The sonography confirmed the diagnosis in 8 children, by the thickening of the muscular layer and enlargement of the pyloric canal. The surgery (pyloromyotomy) ratified the diagnosis in all 8 children. They all were in good health after being operated. PMID:8327749

  1. Developments in the management of Chagas cardiomyopathy.

    PubMed

    Tanowitz, Herbert B; Machado, Fabiana S; Spray, David C; Friedman, Joel M; Weiss, Oren S; Lora, Jose N; Nagajyothi, Jyothi; Moraes, Diego N; Garg, Nisha Jain; Nunes, Maria Carmo P; Ribeiro, Antonio Luiz P

    2015-12-01

    Over 100 years have elapsed since the discovery of Chagas disease and there is still much to learn regarding pathogenesis and treatment. Although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. A recently released negative clinical trial with benznidazole in patients with chronic Chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. New drugs and new delivery systems, including those based on nanotechnology, are being sought. Although vaccine development is still in its infancy, the reality of a therapeutic vaccine remains a challenge. New ECG methods may help to recognize patients prone to developing malignant ventricular arrhythmias. The management of heart failure, stroke and arrhythmias also remains a challenge. Although animal experiments have suggested that stem cell based therapy may be therapeutic in the management of heart failure in Chagas cardiomyopathy, clinical trials have not been promising.

  2. A case of Takotsubo cardiomyopathy after chemotherapy

    PubMed Central

    Malley, Tamir; Watson, Edmund

    2016-01-01

    Here we present the case of a patient with diffuse large B-cell lymphoma who was admitted to hospital for an elective autologous peripheral blood stem cell transplant after cytotoxic treatment with lomustine, cytarabine, cyclophosphomide and etoposide (LACE). On the final day of chemotherapeutic treatment, she developed sudden onset dyspnoea. Electrocardiography confirmed acute antero-lateral T-wave inversion. She went onto have coronary angiography that demonstrated unobstructed coronary arteries. Left ventriculography demonstrated apical ballooning, consistent with Takotsubo (stress) cardiomyopathy. The link between chemotherapy and Takotsubo cardiomyopathy has become increasingly recognized in recent years, although causality remains to be established and the mechanism of action is not yet fully understood. PMID:27066260

  3. [Takotsubo Cardiomyopathy: Cause of a Cardiogenic Shock].

    PubMed

    Fevereiro, Maria do Carmo; Simões, Maria Inês; Lampreia, Fátima; Marcão, Isabel; Godinho, António; Lopes, Vitor

    2015-01-01

    Takotsubo cardiomyopathy, of unknown etiology, is characterized by sudden and transient systolic dysfunction of the mid-apical segments of the left ventricle without significant coronary disease, and full normalization of segmental changes. More common in middle-aged women, it is cause of differential diagnosis with acute coronary syndrome. We present the case of a 59 year old woman admitted to the emergency room with sudden chest pain and dyspnea. At presentation: acute hypotensive pulmonary edema requiring aminergic support and invasive ventilation. Blood tests showed elevated necrosis myocardial enzymes. Serial electrocardiograms: sinus rhythm with progressive inversion of the T wave through the precordial leads (v2 - v6). Control echocardiograms: overall decreased systolic function with apical akinesia, and full reversal of the changes in 2 weeks. Cardiogenic shock of unknown etiology was admitted and a coronary computed tomography angiography was performed excluding coronary heart disease, supporting the diagnosis of Takotsubo cardiomyopathy.

  4. Developments in the management of Chagas cardiomyopathy.

    PubMed

    Tanowitz, Herbert B; Machado, Fabiana S; Spray, David C; Friedman, Joel M; Weiss, Oren S; Lora, Jose N; Nagajyothi, Jyothi; Moraes, Diego N; Garg, Nisha Jain; Nunes, Maria Carmo P; Ribeiro, Antonio Luiz P

    2015-12-01

    Over 100 years have elapsed since the discovery of Chagas disease and there is still much to learn regarding pathogenesis and treatment. Although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. A recently released negative clinical trial with benznidazole in patients with chronic Chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. New drugs and new delivery systems, including those based on nanotechnology, are being sought. Although vaccine development is still in its infancy, the reality of a therapeutic vaccine remains a challenge. New ECG methods may help to recognize patients prone to developing malignant ventricular arrhythmias. The management of heart failure, stroke and arrhythmias also remains a challenge. Although animal experiments have suggested that stem cell based therapy may be therapeutic in the management of heart failure in Chagas cardiomyopathy, clinical trials have not been promising. PMID:26496376

  5. Takotsubo Cardiomyopathy: Case Series and Literature Review

    PubMed Central

    Cavayero, Chase; Kar, Pran; Kar, Sunny

    2016-01-01

    Although originally considered to be uncommon, Takotsubo cardiomyopathy is becoming increasingly visible, annually comprising an increasing portion of suspected diagnoses of acute coronary syndrome. This condition is characterized by reversible left ventricular akinesis without significant coronary artery obstruction. This case study presents five patients diagnosed with Takotsubo cardiomyopathy, as confirmed by echocardiogram and angiography. All of the patients presented with classic myocardial chest pain and elevated troponins. Following diagnosis, they were treated with supportive measures, particularly angiotensin-converting enzyme inhibitors, and beta-blockers. All patients made a full recovery. Though the mechanism of Takotsubo has not been fully elucidated, hypotheses suggest it may be related to excessive catecholamine levels causing either myocardial stunning or coronary vasospasm. Recognition and understanding of this unusual pathology are essential because it can lead to improved clinical management. PMID:27446769

  6. Targeted 46-gene and clinical exome sequencing for mutations causing cardiomyopathies.

    PubMed

    Waldmüller, Stephan; Schroeder, Christopher; Sturm, Marc; Scheffold, Thomas; Imbrich, Kerstin; Junker, Sandra; Frische, Christian; Hofbeck, Michael; Bauer, Peter; Bonin, Michael; Gawaz, Meinrad; Gramlich, Michael

    2015-10-01

    With the implementation of high-throughput sequencing protocols, the exhaustive scanning of known and candidate disease genes has become a feasible approach to genetic testing of patients with cardiomyopathy. A primary objective of the present study was to assess the performance characteristics of a 46-gene next-generation sequencing (NGS) assay that targets well-established cardiomyopathy genes. A total of 25 samples were analyzed. Twelve of those had previously been sequenced using resequencing arrays and served as reference samples for the assessment of the assay's performance characteristics. The remaining 13 samples were derived from consecutive patients. Both the analytical sensitivity and the specificity of the assay were 100% and the percentage of low-coverage bases was 0.4%, at an average read depth of 210×. In order to assess the diagnostic yield of the test, 13 consecutive samples representing cases of Dilated (n = 7), Hypertrophic (n = 4) and Left Ventricular Non-Compaction Cardiomyopathy (n = 2), were subjected to the 46-gene NGS assay. Including predicted pathogenic variants in the gene TTN, a total of 22 variants (11 novel) were detected in 10 patients, with a clear preponderance of variants of unknown pathogenicity (class 3 variants, 21/22, 95%). Of the seven DCM cases, two were digenic, involving variants in the genes MYH7 and RBM20 in one case and in DSP and TTN in the other case. Three other patients carried single TTN variants predicted to be pathogenic. Of the four HCM patients, one was trigenic (LAMA4, PKP2 and TTN) and three were digenic (DSP and TTN, MYH7 and NEXN, NEXN and TTN, respectively). As to LVNC, one of the two patients had one variant in the gene ABCC9 and two predicted pathogenic variants in the gene TTN. Strikingly, out of the thirteen investigated cases, only a single case exhibited a likely pathogenic or pathogenic variant justifying a positive test report. The percentage of inconclusive cases thus amounted to 69%. Three cases

  7. Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy.

    PubMed

    Uppal, Sandeep; Diggle, Christine P; Carr, Ian M; Fishwick, Colin W G; Ahmed, Mushtaq; Ibrahim, Gamal H; Helliwell, Philip S; Latos-Bieleńska, Anna; Phillips, Simon E V; Markham, Alexander F; Bennett, Christopher P; Bonthron, David T

    2008-06-01

    Digital clubbing, recognized by Hippocrates in the fifth century BC, is the outward hallmark of pulmonary hypertrophic osteoarthropathy, a clinical constellation that develops secondary to various acquired diseases, especially intrathoracic neoplasm. The pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood, but a clinically indistinguishable primary (idiopathic) form of hypertrophic osteoarthropathy (PHO) is recognized. This familial disorder can cause diagnostic confusion, as well as significant disability. By autozygosity methods, we mapped PHO to chromosome 4q33-q34 and identified mutations in HPGD, encoding 15-hydroxyprostaglandin dehydrogenase, the main enzyme of prostaglandin degradation. Homozygous individuals develop PHO secondary to chronically elevated prostaglandin E(2) levels. Heterozygous relatives also show milder biochemical and clinical manifestations. These findings not only suggest therapies for PHO, but also imply that clubbing secondary to other pathologies may be prostaglandin mediated. Testing for HPGD mutations and biochemical testing for HPGD deficiency in patients with unexplained clubbing might help to obviate extensive searches for occult pathology. PMID:18500342

  8. Immersion pulmonary oedema and Takotsubo cardiomyopathy.

    PubMed

    Ng, Andrew; Edmonds, Carl

    2015-12-01

    A 67-year-old female scuba diver developed a typical immersion pulmonary oedema (IPE), but investigations strongly indicated Takotsubo cardiomyopathy (TC). The cardiac abnormalities included increased cardiac enzymes, electrocardiographic anomalies and echocardiographic changes, all reverting to normal within days. This case demonstrates a similarity and association between IPE and TC, and the importance of prompt cardiac investigations both in the investigation of IPE and in making the diagnosis of TC. PMID:26687314

  9. Immersion pulmonary oedema and Takotsubo cardiomyopathy.

    PubMed

    Ng, Andrew; Edmonds, Carl

    2015-12-01

    A 67-year-old female scuba diver developed a typical immersion pulmonary oedema (IPE), but investigations strongly indicated Takotsubo cardiomyopathy (TC). The cardiac abnormalities included increased cardiac enzymes, electrocardiographic anomalies and echocardiographic changes, all reverting to normal within days. This case demonstrates a similarity and association between IPE and TC, and the importance of prompt cardiac investigations both in the investigation of IPE and in making the diagnosis of TC.

  10. The broken heart syndrome: Takotsubo cardiomyopathy.

    PubMed

    Peters, Matthew N; George, Praveen; Irimpen, Anand M

    2015-05-01

    First described in 1990, Takotsubo cardiomyopathy consists of a transient systolic dysfunction of localized segments of the left ventricle. Commonly occurring in postmenopausal women, Takotsubo is often associated with intense physical and/or emotional stress. It is traditionally identified by distinctive wall motion patterns on transthoracic echocardiogram and left ventriculography. Further understanding of the disease mechanisms and recognition of at-risk populations has potentially tremendous therapeutic benefit. PMID:25576036

  11. [Dilated cardiomyopathy induced by ectopic atrial tachycardia].

    PubMed

    Velázquez Rodríguez, E; Martínez Enríquez, A

    2000-01-01

    The deleterious effect of chronic or incessant supraventricular tachycardia on ventricular function is well-known and it has been demonstrated than can ultimately lead to dilated cardiomyopathy if unrecognized. Any variety of supraventricular tachycardia with chronic evolution may lead to left ventricular dysfunction, ectopic atrial tachycardia because of its persistent nature, often incessant and poorly responsive to antiarrhythmic drugs is a frequent cause of reversible congestive heart failure in patients without other demonstrable organic heart disease. Five patients (aged 14 to 52 years) were referred with symptoms of heart failure, NYHA functional class II (one patient), class III (one patient) and class IV (3 patients) associated with an incessant ectopic atrial tachycardia. Four patients underwent radiofrequency catheter ablation of the ectopic focus and one patient was treated with amiodarone. All patients were successfully treated and the echocardiographic assessment of left ventricular function indicated regression of the cardiomyopathy picture with recovery of systolic function, (mean left ventricular ejection fraction 39.2 +/- 6.1% before vs mean 62.4 +/- 4.8% after (p < 0.01). The clinical and echocardiographic picture of cardiomyopathy induced by incessant ectopic atrial tachycardia is reversible after successful treatment. This stresses the necessity of recognizing such arrhythmia as cause of primary heart failure. PMID:10959459

  12. SPARC–Dependent Cardiomyopathy in Drosophila

    PubMed Central

    Motamedchaboki, Khatereh; Bodmer, Rolf

    2016-01-01

    Background— The Drosophila heart is an important model for studying the genetics underpinning mammalian cardiac function. The system comprises contractile cardiomyocytes, adjacent to which are pairs of highly endocytic pericardial nephrocytes that modulate cardiac function by uncharacterized mechanisms. Identifying these mechanisms and the molecules involved is important because they may be relevant to human cardiac physiology. Methods and Results— This work aimed to identify circulating cardiomodulatory factors of potential relevance to humans using the Drosophila nephrocyte–cardiomyocyte system. A Kruppel-like factor 15 (dKlf15) loss-of-function strategy was used to ablate nephrocytes and then heart function and the hemolymph proteome were analyzed. Ablation of nephrocytes led to a severe cardiomyopathy characterized by a lengthening of diastolic interval. Rendering adult nephrocytes dysfunctional by disrupting their endocytic function or temporally conditional knockdown of dKlf15 led to a similar cardiomyopathy. Proteomics revealed that nephrocytes regulate the circulating levels of many secreted proteins, the most notable of which was the evolutionarily conserved matricellular protein Secreted Protein Acidic and Rich in Cysteine (SPARC), a protein involved in mammalian cardiac function. Finally, reducing SPARC gene dosage ameliorated the cardiomyopathy that developed in the absence of nephrocytes. Conclusions— The data implicate SPARC in the noncell autonomous control of cardiac function in Drosophila and suggest that modulation of SPARC gene expression may ameliorate cardiac dysfunction in humans. PMID:26839388

  13. Chagas Disease Cardiomyopathy: Immunopathology and Genetics

    PubMed Central

    Chevillard, Christophe

    2014-01-01

    Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects ca. 10 million people worldwide. About 30% of Chagas disease patients develop chronic Chagas disease cardiomyopathy (CCC), a particularly lethal inflammatory cardiomyopathy that occurs decades after the initial infection, while most patients remain asymptomatic. Mortality rate is higher than that of noninflammatory cardiomyopathy. CCC heart lesions present a Th1 T-cell-rich myocarditis, with cardiomyocyte hypertrophy and prominent fibrosis. Data suggest that the myocarditis plays a major pathogenetic role in disease progression. Major unmet goals include the thorough understanding of disease pathogenesis and therapeutic targets and identification of prognostic genetic factors. Chagas disease thus remains a neglected disease, with no vaccines or antiparasitic drugs proven efficient in chronically infected adults, when most patients are diagnosed. Both familial aggregation of CCC cases and the fact that only 30% of infected patients develop CCC suggest there might be a genetic component to disease susceptibility. Moreover, previous case-control studies have identified some genes associated to human susceptibility to CCC. In this paper, we will review the immunopathogenesis and genetics of Chagas disease, highlighting studies that shed light on the differential progression of Chagas disease patients to CCC. PMID:25210230

  14. 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.

  15. Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies

    PubMed Central

    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

    2016-01-01

    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

  16. 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

  17. Maternally inherited cardiomyopathy and hearing loss associated with a novel mutation in the mitochondrial tRNA{sup Lys} gene (G8363A)

    SciTech Connect

    Santorelli, F.M.; Mak, Suk-Chun; El-Schahawi, M.

    1996-05-01

    A novel G8363A mutation in the mtDNA tRNA{sup Lys} gene was associated, in two unrelated families, with a syndrome consisting of encephalomyopathy, sensorineural hearing loss, and hypertrophic cardiomyopathy. Muscle biopsies from the probands showed mitochondrial proliferation and partial defects of complexes I, III, and IV of the electron-transport chain. The G8363A mutation was very abundant (>95%) in muscle samples from the probands and was less copious in blood from 18 maternal relatives (mean 81.3% {plus_minus} 8.5%). Single-muscle-fiber analysis showed significantly higher levels of mutant genomes in cytochrome c oxidase-negative fibers than in cytochrome c oxidase-positive fibers. The mutation was not found in >200 individuals, including normal controls and patients with other mitochondrial encephalomyopathies, thus fulfilling accepted criteria for pathogenicity. 23 refs., 3 figs., 1 tab.

  18. Takotsubo cardiomyopathy: a case report and literature review.

    PubMed

    Rozema, Tamika; Klein, Lisa R

    2016-02-01

    Takotsubo cardiomyopathy, "broken heart syndrome", is a well-known diagnosis in adults; however, this entity remains rare and is not well represented in the paediatric population. This report illustrates a case of takotsubo cardiomyopathy in a premature neonate with a brief discussion of the condition. PMID:26175107

  19. 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 ...

  20. Lessons learned from the Pediatric Cardiomyopathy Registry (PCMR) Study Group.

    PubMed

    Wilkinson, James D; Westphal, Joslyn A; Bansal, Neha; Czachor, Jason D; Razoky, Hiedy; Lipshultz, Steven E

    2015-08-01

    Cardiomyopathy is a rare disorder of the heart muscle, affecting 1.13 cases per 100,000 children, from birth to 18 years of age. Cardiomyopathy is the leading cause of heart transplantation in children over the age of 1. The Pediatric Cardiomyopathy Registry funded in 1994 by the National Heart, Lung, and Blood Institute was established to examine the epidemiology of the disease in children below 18 years of age. More than 3500 children across the United States and Canada have been enrolled in the Pediatric Cardiomyopathy Registry, which has followed-up these patients until death, heart transplantation, or loss to follow-up. The Pediatric Cardiomyopathy Registry has provided the most in-depth illustration of this disease regarding its aetiology, clinical course, associated risk factors, and patient outcomes. Data from the registry have helped in guiding the clinical management of cardiomyopathy in children under 18 years of age; however, questions still remain regarding the most clinically effective diagnostic and treatment approaches for these patients. Future directions of the registry include the use of next-generation whole-exome sequencing and cardiac biomarkers to identify aetiology-specific treatments and improve diagnostic strategies. This article provides a brief synopsis of the work carried out by the Pediatric Cardiomyopathy Registry since its inception, including the current knowledge on the aetiologies, outcomes, and treatments of cardiomyopathy in children.

  1. 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

  2. Structural differences in epiphyseal and physeal hypertrophic chondrocytes

    PubMed Central

    Shapiro, Frederic; Flynn, Evelyn

    2015-01-01

    We have observed that epiphyseal and physeal hypertrophic chondrocytes in BALB/c mice show considerable differences of light microscopic and ultrastructural appearance, even when the cells are at the same stage of differentiation. In addition, cell structure maintenance improved with tissue preparation controlled for osmolarity and for membrane stabilization using 0.5% ruthenium hexammine trichloride (RHT) for both light microscopy (LM) and electron microscopy (EM) or 0.5% lanthanum nitrate for LM. Physeal hypertrophic chondrocytes showed a gradual increase in size closer to the metaphysis and a change in shape as cells elongated along the long axis. The nucleus remained central, with uniformly dispersed chromatin, and the rough endoplasmic reticulum (RER) was randomly dispersed throughout cytoplasm with little to no presence against the cell membrane. Even the lowermost cells showed thin elongated or dilated cisternae of RER and intact cell membranes. Epiphyseal chondrocytes remained circular to oval with no elongation. Nucleus and RER were positioned as a complete transcellular central nucleocytoplasmic column or as an incomplete bud with RER of the column/bud always continuous with RER peripherally against the intact cell membrane. RER was densely packed with parallel cisternae with adjacent cytoplasm empty of organelles but often filled with circular deposits of moderately electron-dense material consistent with fat. Optimal technique for LM involved fixation using glutaraldehyde (GA) 1.3%, paraformaldehyde (PFA) 1% and RHT 0.5% (mOsm 606) embedded in JB-4 plastic and stained with 0.5% toluidine blue. Optimal technique for EM used fixation with GA 1.3%, PFA 1%, RHT 0.5% and cacodylate buffer 0.03 M (mOsm 511) and post-fixation including 1% osmium tetroxide. These observations lead to the possibility that the same basic cell, the hypertrophic chondrocyte, has differing functional mechanisms at different regions of the developing bone. PMID:25987982

  3. A Novel Triple Medicine Combination Injection for the Resolution of Keloids and Hypertrophic Scars

    PubMed Central

    Gold, Michael H.

    2014-01-01

    Keloids and hypertrophic scars remain one of the more difficult treatment concerns for clinicians. A variety of therapies have been used in the past with moderate success. On occasion, combination therapy has been used to treat these lesion, in an attempt to lessen the symptoms of pain and pruritus that often accompanies keloids and hypertrophic scars, as well as treating the actual lesions themselves. A novel triple combination injection process is introduced here in an attempt to further reduce the signs and symptoms of these lesions. The combination includes 5-fluoruracil, triamcinolone acetonide, and hyaluronidase. All three work in concert to treat keloids and hypertrophic scars, and this is the first work at looking at these medicines given together, at the same time, in a series of recalcitrant keloids and hypertrophic scars. The positive results warrant further investigation and hope for those with keloids and hypertrophic scars. PMID:25489380

  4. Recurrent hypertrophic peroneal tubercle associated with peroneus brevis tendon tear.

    PubMed

    Ochoa, Leah M; Banerjee, Rahul

    2007-01-01

    Stenosing peroneal tenosynovitis resulting from hypertrophy of the peroneal tubercle has been well described. Successful surgical treatment addresses the hypertrophied peroneal tubercle as well as any intrinsic tendon pathology. We report a case of recurrent foot pain caused by stenosing peroneal tenosynovitis in a 16-year-old woman. Four months after excision of a hypertrophic peroneal tubercle, the patient developed a recurrence of symptoms. Imaging studies, repeat operative exploration, and pathologic specimen demonstrated a recurrence of the peroneal tubercle hypertrophy associated with a longitudinal tear of the peroneus brevis tendon. Re-resection of the hypertrophied tubercle and peroneal tendon repair resulted in a resolution of symptoms. PMID:17761327

  5. Cardiomyopathy induced by incessant fascicular ventricular tachycardia.

    PubMed

    Velázquez-Rodríguez, Enrique; Rodríguez-Piña, Horacio; Pacheco-Bouthillier, Alex; Deras-Mejía, Luz María

    2013-01-01

    A 12-year-old girl with symptoms of fatigue, decreased exercise tolerance and progressive dyspnea (New York Heart Association functional class III) with a possible diagnosis of dilated cardiomyopathy secondary to viral myocarditis. Because of incessant wide QRS tachycardia refractory to antiarrhythmic drugs, she was referred for electrophysiological study. The diagnosis was idiopathic left ventricular tachycardia involving the posterior fascicle of the left bundle branch. After successful treatment with radiofrequency catheter ablation guided by a Purkinje potential radiological and echocardiographic evaluation showed complete reversal of left ventricular function in the first 3 months and no recurrence of arrhythmia during 2 years of follow up.

  6. Refractory dilated cardiomyopathy associated with metastatic neuroblastoma.

    PubMed

    Carlson, Peter; Jefferies, John L; Kearney, Debra; Russell, Heidi

    2010-10-01

    A 2-year-old African American male presented with heart failure and an abdominal mass. Computerized tomography (CT) scan revealed a 7 cm adrenal lesion, confirmed as poorly differentiated neuroblastoma (NB). CT and meta-iodobenzoguanidine (MIBG) scans identified multiple metastases, but cardiac MIBG imaging was absent. Cardiac ejection fraction (EF) was 8% with 7% shortening fraction. The patient underwent six cycles of chemotherapy and investigational immunotherapy. Cardiac function improved to 26% EF. However, the tumor proved unresponsive to treatment. The patient died from stage IV congestive heart failure (CHF) and progressive NB. Autopsy confirmed dilated cardiomyopathy with endocardial fibroelastosis.

  7. 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

  8. Clinical and epidemiological aspects of cardiomyopathies: a critical review of current knowledge.

    PubMed

    Sangiorgi, Mario

    2003-02-01

    Five years after the second report of the WHO/ISFC Task Force on the definition and classification of cardiomyopathies (CM), a critical review of the matter appears well-timed. The need for a correct definition of myocardial diseases is emphasized by considering them the result of a 'direct' injury due to different known and unknown causes and not a consequence of ischemic disease or of pressure and/or volume overload. This is in order to eliminate terms like ischemic CM, valvular CM, and hypertensive CM, which are a source of confusion. The concept of myocardial injury is also reviewed. This should not only include the structural/organic macroscopic injury, but also the subcellular, ultrastructural, and molecular damage (mostly of genetic origin) of the contracting element proteins, of citosol, sarcolemma and cell membrane ion channels. As the myocardium is a complex structure, made of common fibers and of specific conduction tissue, injury may be clinically identified either by ventricular function impairment or by bioelectric function defects, i.e. tachyarrhythmias and/or bradyarrhythmias, which sometimes are the unique manifestation of the disease (arrhythmogenic CM, in the strict sense). On the basis of the morpho-functional alterations, CMs may be classified as dilated CM (which could be better identified as hypokinetic CM, referring to the functional aspect, because the morphologic aspect is not always present), hypertrophic CM, restrictive CM, and arrhythmogenic CM (including not only arrhythmogenic right ventricular CM, but also other forms, like the so-called arrhythmias of the 'apparently' healthy heart, due to 'occult' myocardial injury). Moreover, these forms may present in association, like mixed CM (dilated-arrhythmogenic, dilated-hypertrophic, etc.). From an etiologic point of