Mavacamten for HOCM

 FDA approved Mavacamten (Camzyos from Bristol-Myers Squibb) for HOCM for children (May 2022).

Mavacamten is allosteric inhibitor of Myosin

Explorer-HCM trial data showed 

    (i) improved in peak VO2 and 

    (ii) stabilization or improvement in NYHA function class

compared to placebo.

Long-term extension study showed that benefits lasted at 1-year follow up. There was improvement in QoL reported by patients.

Valor-HCM - addition of Mavacamten to maximally-tolerated medical management, reduced the need for surgical or cath intervention for septal reduction.

News from TCTMD dt. 4/29/22

Spectrum and outcome of primary cardiomyopathies diagnosed during fetal life

R Weber, ..., E. Jaeggi.
From Toronto group
JACC Heart Failure 2014;2(4):403-411

Pediatric Dilated Cardiomyopathy - Recovery

Recovery of echocardiographic function in children with idiopathic cardiomyopathy. Results from Pediatric Cardiomyopathy Registry.

Melanie D. Everitt, et al. JACC 2014; 63(14): 1405-13.

Editorial: Alan Lewis. JACC 2014; 63(14): 1414-15.

MRI: Delayed enhancement in LVNC

Figure 1 Comparison of In Vivo CE-MRI and Histological Sections in LVNC
(A) Contrast-enhanced magnetic resonance imaging (CE-MRI) in short-axis view demonstrated that diffuse delayed enhancement occurred in the interventricular septum, left ventricular free wall, and the trabecular meshwork region of the left ventricle. (B) The histological section in isolated left ventricular noncompaction (LVNC) from the apical segment of the left ventricle demonstrated that fibrosis presented within trabeculations (arrow) as well as in compacted myocardium (arrowhead). In addition, mucoid degeneration (asterisk) was identified in endocardium. (Masson's Trichrome stain, original magnification x1).

J Am Coll Cardiol, 2011; 58:311-312,
© 2011 by the American College of Cardiology Foundation

RESEARCH CORRESPONDENCE

Histopathological Features of Delayed Enhancement Cardiovascular Magnetic Resonance in Isolated Left Ventricular Noncompaction

Yan Chaowu, PhD, MD*, Li Li, PhD and Zhao Shihua, PhD, MD

Contrast-enhanced magnetic resonance imaging (CE-MRI) is an important imaging modality for the evaluation of isolated left ventricular noncompaction (LVNC). The delayed gadolinium enhancement has been identified in both compacted and noncompacted myocardium, and it may correlate with the clinical severity of LVNC (1–3). However, little is known about the histological basis of myocardial delayed enhancement in LVNC patients, especially in the noncompacted myocardium. In this study, we made a comparison between the myocardial delayed enhancement and histological findings in a patient with LVNC who underwent heart transplantation.

A 27-year-old man was admitted with exertional dyspnea. Chest roentgenogram showed cardiomegaly with pulmonary venous congestion, and the cardiothoracic ratio was 72%. The LVNC was diagnosed by echocardiography, and the ratio of the noncompacted to compacted myocardium was 3.2. The left ventricular end-diastolic dimension was 63 mm, and left ventricular ejection fraction was 18%. Contrast-enhanced MRI was performed, and deep intertrabecular recesses presented in the apical and lateral wall of the left ventricle. The near-transmural delayed enhancement occurred in the interventricular septum, and diffuse enhancement presented in the free wall and the trabecular meshwork region of the left ventricle. In addition, CE-MRI detected the left ventricular thrombus and pericardial and pleural effusions. One week later, informed consent was obtained, and heart transplantation was carried out. The pathological findings of the explanted heart were compared with the previous in vivo CE-MRI (Fig. 1 ). In the compacted myocardium with delayed enhancement, extensive fibrosis was identified and predominantly localized in the mid-myocardial wall. The collagen volume fraction was 27.9% in the histological section, which came from the region of near-transmural delayed enhancement in the interventricular septum. In the noncompacted myocardium with delayed enhancement (the trabecular meshwork region of left ventricle), however, 2 types of pathological findings presented: mucoid degeneration in the endocardium and fibrosis within the trabeculations. The collagen volume fraction of trabeculations was 37.4% in the left ventricular apex and 32.8% in the lateral wall of the left ventricle. In the myocardial regions without delayed enhancement, there was no significant increase in the amount of fibrosis. The epicardial coronary arteries were normal in the patient.

The results of this study demonstrated that fibrosis was identified histologically in both compacted and noncompacted myocardium. In the compacted myocardium, the regions of delayed enhancement corresponded well with the focally increased fibrosis. Furthermore, CE-MRI may overestimate the degree of fibrosis replacement, as we found in the interventricular septum. In the noncompacted myocardium, delayed enhancement was associated with fibrosis within the trabeculations as well as mucoid degeneration in the endocardium.
Previous studies have showed that myocardial delayed enhancement presented in patients with LVNC, and it has been proposed that the regions of delayed enhancement probably reflected the regions of increased myocardial fibrosis (1,2). Pathological analysis also demonstrated that fibrosis occurred in the left ventricular myocardium of LVNC patients (4,5). However, further research was lacking to assess the histopathological correlation of myocardial delayed enhancement in LVNC. In the present study, our findings show that the fibrosis is the histological basis in the delayed enhancement of compacted myocardium; however, it is still unknown which mechanism plays the leading role in the delayed enhancement of noncompacted myocardium.

Genetic diagnosis of Cardiomyopathies

Circulation: Cardiovascular Genetics.
2011; 4: 110-122

Targeted Next-Generation Sequencing for the Molecular Genetic Diagnostics of Cardiomyopathies

Benjamin Meder, MD*, Jan Haas, MS*, Andreas Keller, PhD, Christiane Heid, MS, Steffen Just, PhD, Anne Borries, MS, Valesca Boisguerin, PhD, Maren Scharfenberger-Schmeer, PhD, Peer Stähler;, Markus Beier, PhD, Dieter Weichenhan, PhD, Tim M. Strom, MD, Arne Pfeufer, MD, PhD, Bernhard Korn, PhD, Hugo A. Katus, MD and Wolfgang Rottbauer, MD
+ Author Affiliations

From the Department of Internal Medicine III (B.M., J.H., C.H., S.J., H.A.K., W.R.), University of Heidelberg; Biomarker Discovery Center (A.K.); febit biomed gmbh (A.B., V.B., P.S., M.B.); and German Cancer Research Center (DKFZ) (M.S.-S., D.W., B.K.), Heidelberg, Germany; Institute of Human Genetics (T.M.S.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Human Genetics (A.P.), Klinikum rechts der Isar, Technische Universität München, Munich, Germany; and Department of Internal Medicine II (W.R.), University of Ulm, Ulm, Germany.

Abstract

Background— Today, mutations in more than 30 different genes have been found to cause inherited cardiomyopathies, some associated with very poor prognosis. However, because of the genetic heterogeneity and limitations in throughput and scalability of current diagnostic tools up until now, it is hardly possible to genetically characterize patients with cardiomyopathy in a fast, comprehensive, and cost-efficient manner.

Methods and Results— We established an array-based subgenomic enrichment followed by next-generation sequencing to detect mutations in patients with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). With this approach, we show that the genomic region of interest can be enriched by a mean factor of 2169 compared with the coverage of the whole genome, resulting in high sequence coverage of selected disease genes and allowing us to define the genetic pathogenesis of cardiomyopathies in a single sequencing run. In 6 patients, we detected disease-causing mutations, 2 microdeletions, and 4 point mutations. Furthermore, we identified several novel nonsynonymous variants, which are predicted to be harmful, and hence, might be potential disease mutations or modifiers for DCM or HCM.

Conclusions— The approach presented here allows for the first time a comprehensive genetic screening in patients with hereditary DCM or HCM in a fast and cost-efficient manner.

Iron Overload Cardiomyopathy - Review

Iron Overload Cardiomyopathy. Better understanding of an increasing disorder.

Pradeep Gujja, Douglas Rosing, Dorothy Tripoli, Yukitaka Shizukuda.

JACC 2010;56(13):1001-12.

Adult oriented. But, summarizes the current state and future directions in dealing with this disease. Useful read.

Ventricular remodeling after Myocarditis vs. Dilated Cardiomyopathy in Children

Circulatation: Heart Failure 2010

Published online Sep 10, 2010

Ventricular Remodeling and Survival are More Favorable for Myocarditis Than For Idiopathic Dilated Cardiomyopathy in Childhood: An Outcomes Study from the Pediatric Cardiomyopathy Registry

Susan R. Foerster; Charles E. Canter; Amy Cinar; Lynn A. Sleeper; Steven A. Webber; Elfriede Pahl;Paul F. Kantor; Jorge A. Alvarez; Steven D. Colan; John L. Jefferies; Jacqueline M. Lamour;Renee Margossian; Jane E. Messere;Paolo G. Rusconi; Robert E. Shaddy; Jeffrey A. Towbin;James D. Wilkinson and Steven E. Lipshultz

Background—Myocarditis is one cause of a new-onset dilated cardiomyopathy phenotype in children, with small studies reporting high rates of recovery of left ventricular (LV) function.

Methods and Results—The presenting characteristics and outcomes of children with myocarditis diagnosed clinically and with biopsy confirmation (BCM, n=119) or with probable myocarditis diagnosed clinically or by biopsy alone (PM, n=253) were compared to children with idiopathic dilated cardiomyopathy (IDCM, n=1123). Characteristics at presentation were assessed as possible predictors of outcomes. The distributions of time to death, transplantation, and echocardiographic normalization in the BCM and PM groups did not differ (P0.5), but both groups differed significantly from the IDCM group (all P0.003). In children with myocarditis,lower LVFS z-score at presentation predicted greater mortality (hazard ratio [HR]=0.85, 95% CI 0.73-0.98, P=0.03) and greater LV posterior wall thickness predicted transplantation (HR=1.17, 95% CI 1.02-1.35, P=0.03). In those with decreased LVFS at presentation, independent predictors of echocardiographic normalization were presentation with an LVEDD z-score >2 (HR=0.36, 95% CI 0.22-0.58, P <0.001)> (HR=1.16, 95% CI 1.01-1.34, P=0.04).

Conclusions—Children with biopsy-confirmed or probable myocarditis had similar proportions of death, transplant, and echocardiographic normalization 3 years after presentation and better outcomes than those of children with IDCM. In children with myocarditis who had impaired LV ejection at presentation, rates of echocardiographic normalization were greater in those without LV dilation and in those with greater septal wall thickness at presentation.

Dilated Cardiomyopathy - Treatment and Outcome

The impact of changing medical treatment on transplant-free survival in pediatric dilated cardiomyopathy. Paul F Kantor, Jonathan R. Abraham, Anne I. Dipchand, Lee N. Benson, Andrew N. Redington. JACC 2010;55:1377-84.

Single institution. Retrospective review of all patients over 30 years (1976-2005).
n-189, 44 died. 24 had transplant. 10 were lost to follow up. So, the study cohort n=111.
2-yr & 5-yr transplant-free survival = 63.6% and 56.3% respectively.

5-yr survival:
Digoxin only - 67.5%
Digoxin & ACEi - 57.2%
ACEi & BB - 58.5%

Multivariate analysis:
Low LVEF at presentation is associated with increased risk of death or transplantation.
End point was not influenced by time era or treatment strategy.

MRI: Early detection of Doxorubincin-induced cardiomyopathy

Early Detection of Doxorubicin Cardiotoxicity Using Gadolinium EnhancedCardiovascular Magnetic Resonance ImagingJames C. Lightfoot, Ralph B. D'Agostino, Jr, Craig A. Hamilton, JenniferJordan, Frank M. Torti, Nancy D. Kock, James Jordan, Susan Workman, and W.Gregory HundleyCirc Cardiovasc Imaging published 9 July 2010,10.1161/CIRCIMAGING.109.918540
http://circimaging.ahajournals.org/cgi/content/abstract/CIRCIMAGING.109.918540v1?papetoc