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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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163 hot topic(s) found with the query "Cardiomyopathy"

Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry.
Elizabeth Jordan et al. JAMA 2023 8 (5) 432-441 (Posted: Aug 03, 2023 6PM)

Does the rare variant genetic architecture of dilated cardiomyopathy differ between patients of African and European ancestry? In this cross-sectional study of 1198 patients with dilated cardiomyopathy, significantly fewer patients of African ancestry (8.2%) than those European ancestry (25.5%) had variants classified as pathogenic or likely pathogenic, a difference due in part to fewer predicted loss-of-function variants and less case-based evidence to support pathogenicity for variants found only in patients of African ancestry.

Transthyretin Cardiac Amyloidosis: Underrecognized in the Underrepresented.
Douglas J Leedy et al. J Am Heart Assoc 2023 7 e030802 (Posted: Jul 25, 2023 8AM)

Over the past decade, transthyretin cardiac amyloidosis (ATTR-CM) has rapidly emerged as an increasingly diagnosed cause of heart failure (HF) among older adults, predominantly those with HF with preserved ejection fraction. Although still frequently classified as a rare disease, there is mounting evidence that ATTR-CM is not as “rare” as it has been historically described. Because of the development of effective disease-modifying therapies, such as transthyretin stabilizers, early and accurate identification of ATTR-CM is essential.

Clinical Penetrance of the Transthyretin V122I Variant in Older Black Patients With Heart Failure: The SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study.
Avni Madhani et al. J Am Heart Assoc 2023 7 e028973 (Posted: Jul 25, 2023 8AM)

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF) among patients =60?years of age. Although the V122I (valine to isoleucine substitution at position 122 of the transthyretin protein) variant associated with hereditary ATTR-CM is present in 3.4% of self-identified Black individuals in the United States (or 1.5?million people), the phenotypic penetrance is not known. In this study, among older Black individuals with HF and increased left ventricular wall thickness, of those with ATTR-CM, 63% had wild-type, and of those with V122I, the phenotypic penetrance of ATTR-CM was 39% (95% CI, 17–64), suggesting that genotype alone is insufficient for diagnosis.

EMQN: Recommendations for genetic testing in inherited cardiomyopathies and arrhythmias
JB Hayesmoore et al. EJHG July 13, 2023 (Posted: Jul 14, 2023 1PM)

Inherited cardiomyopathies and arrhythmias (ICAs) are a prevalent and clinically heterogeneous group of genetic disorders that are associated with increased risk of sudden cardiac death and heart failure. Making a genetic diagnosis can inform the management of patients and their at-risk relatives and, as such, molecular genetic testing is now considered an integral component of the clinical care pathway. However, ICAs are characterised by high genetic and allelic heterogeneity, incomplete / age-related penetrance, and variable expressivity.

The next step toward personalized recommendations for genetic cardiomyopathies
SLVM Stroeks et al, EJHG, June 6, 2023 (Posted: Jun 06, 2023 8AM)

The genetic basis of dilated cardiomyopathy (DCM) is very heterogeneous, with over 65 genes described in association with its development. The most prevalent genetic etiology are truncating variants in TTN (TTNtv), that comprise around 50% of all genetic cases. Truncating variants in FLNC (FLNCtv) are the latest discovery to the genetic landscape of DCM, and the gene is now included in every cardiomyopathy gene panel.

Diagnostic and prognostic relevance of using large gene panels in the genetic testing of patients with dilated cardiomyopathy.
Sophie L V M Stroeks et al. Eur J Hum Genet 2023 5 (Posted: May 19, 2023 10AM)

It was previously suggested that increasing the number of genes on diagnostic gene panels could increase the genetic yield in patient with dilated cardiomyopathy (DCM). We explored the diagnostic and prognostic relevance of testing DCM patients with an expanded gene panel. The current study included 225 consecutive DCM patients who had no genetic diagnosis after a 48-gene cardiomyopathy-panel. Overall, the use of large gene panels for genetic testing in DCM does not increase the diagnostic yield. Current diagnostic gene panels should be limited to the robust DCM-associated genes.

Prevalence and Clinical Consequences of Multiple Pathogenic Variants in Dilated Cardiomyopathy
SLVM Stroeks et al, Circ Genomics & Prec Med, March 27, 2023 (Posted: Mar 27, 2023 7AM)

One hundred thirty-one likely pathogenic/pathogenic (LP/P) variants in robust DCM-associated genes were found in 685 patients with DCM (19.1%) genotyped for the robust genes. Three of the 131 patients had a second LP/P variant (2.3%). These 3 patients had a comparable disease onset, disease severity, and clinical course to patients with DCM with one LP/P.

Detection of subclinical hypertrophic cardiomyopathy.
George Joy et al. Nature reviews. Cardiology 2023 3 (Posted: Mar 09, 2023 1PM)

Hypertrophic cardiomyopathy (HCM) is defined by ventricular hypertrophy. However, the broader phenotype includes abnormal cardiomyocyte orientation (disarray), myocardial ischaemia and electrical abnormalities, which seem to manifest before overt hypertrophy. With advances in cascade genetic testing and novel therapeutic agents, the detection of subclinical HCM is a rapidly emerging priority. In this context, we outline the role of novel biomarkers, particularly quantitative perfusion and diffusion tensor MRI.

Approaches to Genetic Screening in Cardiomyopathies: Practical Guidance for Clinicians.
Amy R Kontorovich et al. JACC. Heart failure 2023 2 (2) 133-142 (Posted: Mar 01, 2023 0PM)

Patients and families benefit when the genetic etiology of cardiomyopathy is elucidated through a multidisciplinary approach including genetic counseling and judicious use of genetic testing. The yield of genetic testing is optimized when performed on a proband with a clear phenotype, and interrogates genes that are validated in association with that specific form of cardiomyopathy. Variants of uncertain significance are frequently uncovered and should not be overinterpreted.

CRISPR gene-editing therapies for hypertrophic cardiomyopathy.
Alanna Strong et al. Nature medicine 2023 2 (Posted: Feb 17, 2023 6AM)

Hypertrophic cardiomyopathy (HCM) is a primary cardiac disorder characterized by abnormal heart muscle thickening and caused by heterozygous pathogenic variants in genes encoding sarcomeric proteins. HCM often presents during young adulthood and can progress to heart failure, arrhythmia and sudden cardiac death. Pre-symptomatic gene editing in preclinical models of hypertrophic cardiomyopathy shows therapeutic promise; clinical studies are now needed to assess safety and efficacy in humans.

Benefits, Harms and Costs of Newborn Genetic Screening for Hypertrophic Cardiomyopathy: Estimates from the PreEMPT Model
KD Chrisiensen et al, Genetics in Medicine, January 31, 2023 (Posted: Feb 01, 2023 6AM)

In a cohort of 3.7 million newborns, newborn genetic screening would reduce HCM-related deaths through age 20 by 44 (95% uncertainty interval (95% UI): 10 to 103) but increase the numbers of children undergoing surveillance by 8,127 (95% UI, 6,308 to 9,664). Compared to usual care, newborn genetic screening costs $267,000 per life-year saved (95% UI, $106,000 to $919,000 per life-year saved). Newborn genetic screening for HCM could prevent deaths but at a high cost and would require many healthy children to undergo surveillance.

Cardiomyopathy prevalence exceeds 30% in individuals with TTN variants and early atrial fibrillation.
Schiabor Barrett Kelly M et al. Genetics in medicine : official journal of the American College of Medical Genetics 2023 1 100012 (Posted: Jan 16, 2023 6AM)

Truncating variants in TTN (TTNtvs) represent the largest known genetic cause of dilated cardiomyopathies (DCM), but their penetrance for DCM in general populations is low. More broadly, patients with cardiomyopathies (CM) often exhibit other cardiac conditions, such as atrial fibrillation (Afib), which has also been linked to TTNtvs. This retrospective analysis aims to characterize the relationship between different cardiac conditions in those with TTNtvs and identify individuals with the highest risk of DCM.

The Use of Cell-free DNA in Clinical Practice: Work in Progress
M Clyne et al, CDC Blog Post, December 14, 2022 Brand (Posted: Dec 14, 2022 5PM)

Since its discovery in 1948, the utility of cfDNA has been studied extensively in screening, diagnosis, prognosis, therapy and monitoring disease progression. Although effort has focused on cancer, and mostly in NSCLC, other areas of research are ongoing, including autoimmune disease, metabolic disorders, Alzheimer’s disease, and other neurologic conditions, COVID-19, myocarditis and dilated cardiomyopathy, and refractory epilepsy. In addition to circulating cfDNA, potential clinical applications exist for other omics, including epigenetics and exosomal miRNAs, as well as use of cfDNA in other body fluids (e.g. urine).

Hypertrophic Cardiomyopathy (HCM) and Family Health History of Sudden Death
CDC, December 2022 (Posted: Dec 08, 2022 9AM)

If you have a family member, especially a parent, sibling, or child, who died suddenly before age 40, let your doctor know. You might need to be screened for HCM, a genetic condition that causes the heart muscle to become thick and can lead to sudden death. While some people with HCM are very sick, many people, especially children, teens, and young adults, have no or few symptoms and may not know they have a heart problem. Sharing your family history with your doctor can help you and other relatives find HCM early.

Equitable and Informed Consent in Genetic Studies.
Navar Ann Marie et al. JAMA cardiology 2022 11 (Posted: Nov 18, 2022 6AM)

As costs of genetic sequencing have declined and access to testing has become more widespread, genetic epidemiology studies are increasingly conducted to identify new pathogenic variants and understand the prevalence and implications of known pathogenic variants. Ensuring diversity in these studies is critical to ensure the generalizability of their results. Unfortunately, people of African and Latin American ancestry and Indigenous populations are underrepresented in clinical research and even more so in genetic studies. This is a particular concern in nonischemic dilated cardiomyopathy (DCM), a disease that disproportionately affects Black persons in the United States.

Knowledge of Genome Sequencing and Trust in Medical Researchers Among Patients of Different Racial and Ethnic Groups With Idiopathic Dilated Cardiomyopathy.
Ni Hanyu et al. JAMA cardiology 2022 11 (Posted: Nov 18, 2022 6AM)

What is the level of genetic knowledge and trust in medical researchers among Hispanic participants, non-Hispanic Black participants, and non-Hispanic White participants in a cardiovascular genetic study? In this cross-sectional study of 1121 patients with dilated cardiomyopathy, the genome-sequencing knowledge level was lower in Hispanic and non-Hispanic Black patients than non-Hispanic White patients. Trust in medical researchers was lowest in non-Hispanic Black patients; a higher trust level was associated with a higher level of genome-sequencing knowledge within racial and ethnic groups.

Genetic Basis of Childhood Cardiomyopathy
RD Bagnall et al, Circ Genomics Prec Medicine, October 12, 2022 (Posted: Oct 12, 2022 8AM)

We recruited children from a pediatric cardiology service or genetic heart diseases clinic. We performed Sanger, gene panel, exome or genome sequencing and classified variants for pathogenicity using American College of Molecular Genetics and Genomics guidelines. The highest genetic testing diagnostic yields were in restrictive cardiomyopathy (n=16, 80%) and hypertrophic cardiomyopathy (n=65, 66%), and lowest in dilated cardiomyopathy (n=26, 29%) and left ventricular noncompaction (n=3, 25%). Pathogenic variants were primarily found in genes encoding sarcomere proteins, with TNNT2 and TNNI3 variants associated with more severe clinical outcomes.

Assessment of the Diagnostic Yield of Combined Cardiomyopathy and Arrhythmia Genetic Testing.
Dellefave-Castillo Lisa M et al. JAMA cardiology 2022 8 (Posted: Aug 15, 2022 7PM)

In this cohort study of 4782 patients with a suspected genetic cardiomyopathy or arrhythmia, combined cardiomyopathy and arrhythmia testing revealed clinically relevant variants in 1 in 5 patients, and 66.0% of patients with positive findings had potential clinical management implications. The combined testing approach captured 10.9% of patients who would have been missed if genetic testing had been restricted to a specific suspected disease subtype.

Global reports of takotsubo (stress) cardiomyopathy following COVID-19 vaccination: a systematic review and meta-analysis
SK Ahmed et al, MEDRXIV, June 7, 2022 (Posted: Jun 08, 2022 6AM)

Rare and Common Genetic Variation Underlying the Risk of Hypertrophic Cardiomyopathy in a National Biobank.
Biddinger Kiran J et al. JAMA cardiology 2022 5 (Posted: May 19, 2022 10AM)

What are the contributions of rare and common genetic variation to risk of hypertrophic cardiomyopathy (HCM)? In this cohort study, rare variants in 14 genes prioritized by the American College of Medical Genetics and Genomics conferred the greatest risk of HCM, while a common variant (polygenic) score accounted for the greatest proportion of HCM susceptibility. Together, rare variants and the polygenic score enhanced the prediction of incident HCM when added to clinical factors.

Mortality Among Patients With Early-Onset Atrial Fibrillation and Rare Variants in Cardiomyopathy and Arrhythmia Genes.
Yoneda Zachary T et al. JAMA cardiology 2022 5 (Posted: May 13, 2022 8AM)

In this cohort study of 1293 participants diagnosed with AF before 66 years of age, time to death was significantly associated with a disease-associated variant, age at AF diagnosis, and the interaction between age at AF diagnosis and variant status. The findings suggest that among patients with early-onset AF, the presence of a disease-associated rare variant for an inherited cardiomyopathy or arrhythmia syndrome may be associated with an increased risk of mortality.

Association of Pathogenic DNA Variants Predisposing to Cardiomyopathy With Cardiovascular Disease Outcomes and All-Cause Mortality.
Patel Aniruddh P et al. JAMA cardiology 2022 5 (Posted: May 13, 2022 8AM)

In this genetic association study of 9667 participants in the US (Atherosclerosis in Risk Communities [ARIC]) and 49?744 participants in the UK (UK Biobank), a pathogenic or likely pathogenic variant for inherited cardiomyopathy was identified in 0.61% of ARIC participants and 0.73% of UK Biobank participants. These individuals were at 1.7- to 2.1-fold increased risk of heart failure, 2.1- to 2.9-fold increased risk of atrial fibrillation, and 1.5- to 1.7-fold increased risk of all-cause mortality, and they were not reliably identified by imaging. These results suggest that 0.7% of participants harbor a pathogenic variant related to inherited cardiomyopathy and are at increased risk of cardiovascular morbidity and all-cause mortality.

Genetic Testing for Early-Onset Atrial Fibrillation-Is It Time to Personalize Care?
McNally Elizabeth M et al. JAMA cardiology 2022 5 (Posted: May 13, 2022 8AM)

New studies recognize that AF may be the first clinical presentation of carrying a P/LP variant in cardiomyopathic genes. These studies also distinguish that carriers of P/LP cardiomyopathy gene variants have worse long-term outcomes compared with noncarriers. In light of these data, is it time to personalize care for EOAF and incorporate panel-based rare-variant genetic testing into the clinical management framework as is currently recommended for cardiomyopathy? Even with incomplete penetrance, can these genetic variants be incorporated as key risk-enhancing factors to inform a precision approach to screening, prevention, and management of a variety of cardiovascular diseases, including AF?

Heart Failure, Precision Medicine, and Incremental Equity- The Case of Hereditary Amyloid Cardiomyopathy
MR Echols et al, JAMA, April 4, 2022 (Posted: Apr 05, 2022 11AM)

An important consideration is whether a genome-guided precision approach could have beneficial effects on health equity among patients with heart failure. It is well established that poor heart failure outcomes occur disproportionately among Black individuals. Furthermore, as with other major health disparities, even though huge investments in research and development have produced greater mechanistic insight and an ever-widening therapeutic armamentarium, thereby improving outcomes for patients with heart failure in general, they have not produced a substantial reduction in race-related disparities

Association of Transthyretin Val122Ile Variant With Incident Heart Failure Among Black Individuals
V Parcha et al, JAMA, April 4, 2022 (Posted: Apr 05, 2022 11AM)

In this retrospective cohort study that included 7514 Black participants in the US with a median 11.1 years of follow-up, the incidence of heart failure was 15.6 per 1000 person-years among Val122Ile variant carriers compared with 7.2 per 1000 person-years among noncarriers, with an adjusted hazard ratio of 2.43.

Targeting the sarcomere in inherited cardiomyopathies
SJ Lehman, et al, Nat Rev Cardiology, March 18, 2022 (Posted: Mar 20, 2022 0PM)

Variants in >12 genes encoding sarcomeric proteins can cause various cardiomyopathies. The two most common are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Current therapeutics do not target the root causes of these diseases, but attempt to prevent disease progression and/or to manage symptoms. Accordingly, novel approaches are being developed to treat the cardiac muscle dysfunction directly. Challenges to developing therapeutics for these diseases include the diverse mechanisms of pathogenesis, some of which are still being debated and defined. Four small molecules that modulate the myosin motor protein in the cardiac sarcomere have shown great promise in the settings of HCM and DCM, regardless of the underlying genetic pathogenesis, and similar approaches are being developed to target other components of the sarcomere.

Whole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy
R LeSurf et al, NPJ Genomic Medicine, March 14, 2022 (Posted: Mar 14, 2022 8AM)

We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25, p?=?6.70?×?10-7 versus controls).

Real life experience with the wearable cardioverter-defibrillator in an international multicenter Registry.
El-Battrawy Ibrahim et al. Scientific reports 2022 2 (1) 3203 (Posted: Feb 27, 2022 10AM)

Patients at high risk for sudden cardiac death (SCD) may benefit from wearable cardioverter defibrillators (WCD) by avoiding immediate implantable cardioverter defibrillator (ICD) implantation. Different factors play an important role including patient selection, compliance and optimal drug treatment. We aimed to present real world data from 4 centers from Germany and Switzerland. Between 04/2012 and 03/2019, 708 patients were included in this registry. Patients were followed up over a mean time of 28?±?35.5 months. Outcome data including gender differences and different etiologies of cardiomyopathy were analyzed. Out of 708 patients (81.8% males, mean age 61.0?±?14.6), 44.6% of patients had non-ischemic cardiomyopathy, 39.8% ischemic cardiomyopathy, 7.9% myocarditis, 5.4% prior need for ICD explantation and 2.1% channelopathy.

Minor hypertrophic cardiomyopathy genes, major insights into the genetics of cardiomyopathies.
Walsh Roddy et al. Nature reviews. Cardiology 2021 9 (3) 151-167 (Posted: Feb 27, 2022 10AM)

Cardiomyopathies are often inherited diseases, but highly variable penetrance and the lack of Mendelian genetic variants in substantial numbers of patients increasingly suggests a complex genetic etiology. Genome-wide association studies have identified large overlaps in significant loci for cardiomyopathies and left ventricular traits, with opposite effects (risk or protective alleles) observed for hypertrophic and dilated cardiomyopathy. Variants in genes encoding non-sarcomeric proteins account for a small proportion of patients with Mendelian hypertrophic cardiomyopathy but are the presumed causal genes at several genome-wide association study loci, expanding their role in cardiomyopathy genetics.These genes have complex genotype–phenotype correlations.

Association of Titin Variations With Late-Onset Dilated Cardiomyopathy
A Cannata et al, JAMA Cardiology, February 9, 2022 (Posted: Feb 09, 2022 4PM)

Is dilated cardiomyopathy diagnosed in individuals older than 60 years characterized by a specific genetic background and have similar clinical characteristics to the known epidemiology? In this cohort study of 184 patients with late-onset dilated cardiomyopathy, compared with the current epidemiology, a high genetic variation burden was identified, largely due to titin-truncating variants. Patients with a positive genetic test had higher mortality than genotype-negative patients.

Identifying Dilated Cardiomyopathy Through Family-Based Screening
KG Aragam, JAMA, February 1, 2022 (Posted: Feb 01, 2022 4PM)

What might be done to mitigate the onset of DCM in first-degree relatives? Existing trial data support a role for evidence-based neurohormonal agents (such as angiotensin-converting enzyme inhibitors) to prevent the progression of asymptomatic left ventricular systolic dysfunction to overt and symptomatic clinical heart failure. A new study suggests the utility of family-based clinical screening for DCM to more readily identify the individuals with preclinical disease who might benefit from the early initiation of neurohormonal therapies.

Prevalence and Cumulative Risk of Familial Idiopathic Dilated Cardiomyopathy
GS Huggins et al, JAMA< February 1, 2022 (Posted: Feb 01, 2022 4PM)

What is the prevalence of familial disease among patients with idiopathic dilated cardiomyopathy (DCM) and the lifetime risk of DCM for their first-degree family members by race and ethnicity? In this family-based, cross-sectional study of 1220 patients with DCM and their 1693 family members, the estimated familial DCM prevalence was 29.7% and the estimated DCM risk by age 80 years in family members was 19%. These findings suggest substantial prevalence of familial DCM among patients and elevated lifetime risk.

Diagnosis and Evaluation of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review.
Maron Barry J et al. Journal of the American College of Cardiology 2022 79(4) 372-389 (Posted: Feb 01, 2022 8AM)

Hypertrophic cardiomyopathy (HCM) is a relatively common often inherited global heart disease, with complex phenotypic and genetic expression and natural history, affecting both genders and many races and cultures. Prevalence is 1:200-1:500, largely based on the disease phenotype with imaging, inferring that 750,000 Americans may be affected by HCM. However, cross-sectional data show that only a fraction are clinically diagnosed, suggesting under-recognition, with most clinicians exposed to small segments of the broad disease spectrum. Highly effective HCM management strategies have emerged, altering clinical course and substantially lowering mortality and morbidity rates.

The genetic architecture of pediatric cardiomyopathy.
Ware Stephanie M et al. American journal of human genetics 2022 1 (Posted: Jan 14, 2022 8AM)

To understand the genetic contribution to primary pediatric cardiomyopathy, we performed exome sequencing in a large cohort of 528 children with cardiomyopathy. Using clinical interpretation guidelines and targeting genes implicated in cardiomyopathy, we identified a genetic cause in 32% of affected individuals.

Hypertrophic Cardiomyopathy and Public Health: An Expanding List of Tier 1 Genomic Applications
CDC Seminar Announcement, January 27, 2022 Brand (Posted: Nov 22, 2021 11AM)

This seminar will briefly describe the CDC Tier-Classified Guideline Database, which currently includes three Tier 1 guidelines (the latest published less than one year ago, in December, 2020) addressing hypertrophic cardiomyopathy. The primary focus of the seminar will be on the genetics of hypertrophic cardiomyopathy and the nexus between genetics and clinical traits. A short primer on the disease process for hypertrophic cardiomyopathy will also be included.

New CDC Partnerships to Advance the Development and Validation of Next Generation Sequencing Tests: A Publicly Available List of Expert Curated Variants
L Kalman et al, CDC Blog Post, November 16, 2021 Brand (Posted: Nov 17, 2021 5PM)

CDC has partnered with the Clinical Genome Resource (ClinGen) to develop a publicly available list of expert curated variants. As part of this study, the ClinGen Variant Curation Expert Panels nominated 546 variants found in 84 disease associated genes (link to table of genes ), including common pathogenic and difficult to detect variants. Variant types nominated included 346 SNVs, 104 deletions, 37 CNVs, 25 duplications, 18 deletion-insertions, 5 inversions, 4 insertions, 2 complex rearrangements, 3 in difficult to sequence regions, and 2 fusions. The nominated variants are associated with a wide range of diseases that include heritable cancers, inborn errors of metabolism, cardiomyopathy, diabetes, and immune disorders.

An Expanding List of Tier 1 Genomic Applications: Evidence-based Guidelines for Hypertrophic Cardiomyopathy and Public Health
MA Burke et al, CDC Blog, October 6,2021 Brand (Posted: Oct 07, 2021 6AM)

The CDC Tier-Classified Guideline Database includes three Tier 1 guidelines on hypertrophic cardiomyopathy (HCM). A 2014 guideline from the European Society of Cardiology, a 2017 guideline from the American Heart Association, American College of Cardiology, and Heart Rhythm Society, and a 2020 guideline from the American Heart Association and American College of Cardiology all recommend genetic testing for patients meeting diagnostic criteria for HCM. Each includes recommendations for evaluation of family history, cascade genetic testing in relatives, and genetic counseling of affected individuals.

Valsartan in early-stage hypertrophic cardiomyopathy: a randomized phase 2 trial
CY Ho et al, Nature Medicine, September 23, 2021 (Posted: Sep 24, 2021 6AM)

Valsartan (n?=?88) improved cardiac structure and function compared to placebo (n?=?90), as reflected by an increase in the composite z-score (between-group difference +0.231, 95% confidence interval (+0.098, +0.364); P?=?0.001), which met the primary endpoint of the study. Treatment was well-tolerated. These results indicate a key opportunity to attenuate disease progression in early-stage sarcomeric HCM with an accessible and safe medication.

Cascade health service use in family members following genetic testing in children: a scoping literature review
A Cernat et al, EJHG, August 26, 2021 (Posted: Aug 27, 2021 7AM)

Uptake of cascade testing varied across diseases, from 37% for cystic fibrosis, 39% to 65% for hypertrophic cardiomyopathy, and 90% for rare monogenic conditions. Two studies evaluated costs. It was concluded that cascade testing in the child-to-parent direction has been reported in a variety of diseases, and that understanding the scope of cascade testing will aid in the design and conduct of HTA of emerging genetic technologies to better inform funding and policy decisions.

Genomic Autopsy of Sudden Deaths in Young Individuals
G Webster et al, JAMA Cardiology, August 13, 2021 (Posted: Aug 14, 2021 8AM)

In this cohort study of 103 decedents from a national collaboration of medical examiners, pathogenic/likely pathogenic variants in arrhythmia or cardiomyopathy genes were identified in 13%. In multivariate analysis, rare variants in cardiac genes (pathogenic/likely pathogenic/uncertain significance) were associated with younger age at death.

Clinical impact of re-evaluating genes and variants implicated in dilated cardiomyopathy
SLVM Stroeks et al, Genetics in Medicine, June 30, 2021 (Posted: Jul 01, 2021 8AM)

Stringent gene selection for dilated cardiomyopathy genetic testing reduced the number of variants of unknown significance while retaining ability to detect similar P/LP variants. The number of genes on diagnostic panels should be limited to genes that have the highest signal to noise ratio.

Towards precision medicine in heart failure
CS Weldy et al, Nat Rev Cardiol, June 9, 2021 (Posted: Jun 11, 2021 7AM)

We summarize the biology of heart failure (HF), emphasizing the causal relationships between genetic contributors and traditional structure-based remodelling outcomes, and highlight the mechanisms of action of traditional and novel therapeutics. We discuss the latest advances in our understanding of both the Mendelian genetics of cardiomyopathy and the complex genetics of the clinical syndrome presenting as HF.

Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals
L Guo et al, JAMA Cardiology, June 2, 2021 (Posted: Jun 02, 2021 10PM)

In this genetic association study of 413 adults who had unexplained SCD, nearly one-fifth of individuals had pathogenic or likely pathogenic genetic variants consistent with inherited cardiomyopathies or arrhythmia syndromes, despite having normal cardiac findings. These clinically significant variants were predominantly associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and long QT syndrome.

Personalizing Risk for Sudden Cardiac Death Among Patients With Dilated Cardiomyopathies: Moving Beyond Ejection Fraction With Genomics.
Khan Sadiya S et al. JAMA cardiology 2021 5 (Posted: May 13, 2021 7AM)

Large-scale genomic sequencing has significantly advanced our understanding of the monogenic causes of DCM, identifying more than 100 genes that are associated with approximately 40% to 50% of cases. These include genes that encode proteins responsible for contractility, extracellular matrix, and ion channels. Yet, data remain limited on the spectrum of phenotypes associated with each rare variant, which may inform diverse clinical presentations, guide clinical management, and improve outcomes for patients with inherited cardiomyopathies.

An Evidence-Based Assessment of Genes in Dilated Cardiomyopathy.
Jordan Elizabeth et al. Circulation 2021 (Posted: May 11, 2021 10AM)

In the curation of 51 genes, 19 had high evidence (12 definitive/strong; seven moderate). Notably, these 19 genes only explain a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed. Clinical genetic testing panels include most high evidence genes, however genes lacking robust evidence are also commonly included. We recommend that high evidence DCM genes be used for clinical practice and to exercise caution when interpreting variants in variable evidence DCM genes.

An Integrated Review of Hypertrophic Cardiomyopathy in Black Populations: Underrecognized and Understudied.
Arabadjian Milla et al. The Journal of cardiovascular nursing 36(2) 104-115 (Posted: Feb 16, 2021 9AM)

Lack of diversity in general genomic databases has resulted in reclassification of several genetic variants identified as more common in blacks.Blacks are underrepresented in HCM research, even those focused on elucidating HCM manifestations, disease course, and outcomes in black populations. This may be due in part to HCM research that is largely generated from specialty centers that can require patients to navigate complex healthcare systems to reach expert HCM care.

Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity.
Harper Andrew R et al. Nature genetics 2021 Jan (Posted: Jan 27, 2021 9AM)

A genome-wide association study of 2,780 cases and 47,486 controls identified 12 genome-wide-significant susceptibility loci for HCM. Single-nucleotide polymorphism heritability indicated a strong polygenic influence, especially for sarcomere-negative HCM. A genetic risk score showed substantial influence on the odds of HCM in a validation study, halving the odds in the lowest quintile and doubling them in the highest quintile, and also influenced phenotypic severity.

Genetic Contribution to Common Heart Failure—Not So Rare?
EM McNally et al, JAMA Cardiology, December 15, 2020 (Posted: Dec 17, 2020 8AM)

Dilated cardiomyopathy and hypertrophic cardiomyopathy underlie heart failure (HF) and often run in families. For these families, genetic testing provides risk stratification, which is especially important because some genes carry higher risk of arrhythmias, and the testing allows family members to be monitored and treated for early-phase disease. Genetic testing identifies the defective gene in 30% to 50% of families.

Assessing the Role of Rare Genetic Variation in Patients With Heart Failure.
Povysil Gundula et al. JAMA cardiology 2020 Dec (Posted: Dec 17, 2020 8AM)

In this analysis of 5942 patients with heart failure and 13 156 controls using whole-exome sequencing, a significant enrichment of rare protein-truncating variants in the TTN gene and in general an increased burden of mendelian cardiomyopathy variants was demonstrated in patients with heart failure compared with controls.

Mining transcriptomics and clinical data reveals ACE2 expression modulators and identifies cardiomyopathy as a risk factor for mortality in COVID-19 patients
N Kau et al, MEDRXIV, October 23, 2020 (Posted: Oct 24, 2020 10AM)

Genetic screening for hypertrophic cardiomyopathy in large, asymptomatic military cohorts.
Brough Joe et al. American journal of medical genetics. Part C, Seminars in medical genetics 2020 Feb (Posted: Feb 12, 2020 10AM)

Machine learning detection of obstructive hypertrophic cardiomyopathy using a wearable biosensor
R Ueno et al, NPJ Digital Medicine, December 2019 (Posted: Dec 11, 2019 7AM)

Green et al. (June 24 issue)1 developed a machine learning classifier of hypertrophic cardiomyopathy (HCM) patients using a noninvasive optical sensor incorporated in commercial smart watches. The study included 83 patients (19 patients with HCM and 64 healthy controls).

Association of Race With Disease Expression and Clinical Outcomes Among Patients With Hypertrophic Cardiomyopathy
LA Eberly et al, JAMA Cardiology, December 4, 2019 (Posted: Dec 05, 2019 7AM)

Compared with white patients, black patients with hypertrophic cardiomyopathy were diagnosed at a younger age, were less likely to have sarcomere mutations, and had worse symptoms. Inequities in health care access and delivery were associated with race, with lower rates of genetic testing and invasive septal reduction therapy.

Genetics of Unexplained Sudden Cardiac Death in Adult Caucasian and African American Individuals Living in the State of Maryland
L Guo et al, MedRXIV, September 24, 2019 (Posted: Sep 26, 2019 8AM)

This study represents the largest examination reported on the association between cardiomyopathy and arrhythmia P/LP genetic variants and unexplained-SCD in adults with no gross abnormality on rigorous pathological examination. Nearly one-third of those with unexplained-SCD were carriers of P/LP variants.

Clinical utility of exome sequencing in infantile heart failure
A Ritter et al, Genetics in Medicine, September 16, 2019 (Posted: Sep 17, 2019 7AM)

Dilated cardiomyopathy was the predominant cardiac diagnosis, seen in 60% of patients. A molecular diagnosis was identified in 66.7% of patients (10/15). Of those diagnoses, 70% would not have been detected using multigene next-generation sequencing panels.

Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy
M Gigli et al. JACC, September 2019 (Posted: Sep 11, 2019 9AM)

Genotype-phenotype correlations in dilated cardiomyopathy are poorly understood. The purpose of this study was to investigate the prognostic role of genetic variant carrier status in a large cohort of DCM patients. Desmosomal and LMNA gene variants identify the subset of DCM patients who are at greatest risk for life-threatening ventricular arrhythmias.

Lessons learned from testing cardiac channelopathy and cardiomyopathy genes in individuals who died suddenly: A two-year prospective study in a large medical examiner's office with an in-house molecular genetics laboratory and genetic counseling services.
Williams Nori et al. Journal of genetic counseling 2019 Aug (Posted: Aug 24, 2019 4PM)

This is a comprehensive review and analysis of 254 cases tested consecutively in the in-house College of American Pathologist-accredited molecular genetics laboratory within the New York City Office of Chief Medical Examiner between October 2015 and February 2018, using a multigene cardiac panel composed of 95 genes.

Prevalence and clinical importance of titin truncating variants in adults without known congestive heart failure
JP Pirruccello et al, MedRXIV, August 2019 (Posted: Aug 23, 2019 8AM)

Cross-sectional studies of various forms of dilated cardiomyopathy have noted a truncating mutation in the gene encoding titin ('TTNtv') in 7-30% of patients, but the clinical importance of identifying a TTNtv in an asymptomatic adult is largely unknown.

Risk Prediction Model in Children With Hypertrophic Cardiomyopathy: A Work in Progress.
Bonow Robert O et al. JAMA cardiology 2019 Aug (Posted: Aug 15, 2019 8AM)

Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids).
Norrish Gabrielle et al. JAMA cardiology 2019 Aug (Posted: Aug 15, 2019 8AM)

Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk. The study provides a new, validated risk stratification model for SCD in childhood HCM that can provide individualized estimates of risk at 5 years using available clinical risk factors.

Prevalence and clinical significance of red flags in patients with hypertrophic cardiomyopathy.
Limongelli Giuseppe et al. International journal of cardiology 2019 Jul (Posted: Jul 17, 2019 8AM)

Genetic Testing and Cascade Screening in Pediatric Long QT Syndrome and Hypertrophic Cardiomyopathy.
Knight Linda M et al. Heart rhythm 2019 Jun (Posted: Jun 26, 2019 8AM)

The efficacy of cascade screening for the inherited heart conditions long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM) is incompletely characterized. This study examined the use of genetic testing and yield of cascade screening across diverse regions in the US, and evaluated obstacles to screening in multipayor systems.

Machine learning detection of obstructive hypertrophic cardiomyopathy using a wearable biosensor
EM Green et al, NPJ Digital Medicine, June 24, 2019 (Posted: Jun 24, 2019 10AM)

Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing?
Sousa Alexandra et al. Cardiology research and practice 2019 20192743650 (Posted: Jun 12, 2019 8AM)

Family screening for hypertrophic cardiomyopathy: Is it time to change practical guidelines?
Lafreniere-Roula Myriam et al. European heart journal 2019 Jun (Posted: Jun 12, 2019 7AM)

A validation study of the European Society of Cardiology guidelines for risk stratification of sudden cardiac death in childhood hypertrophic cardiomyopathy.
Norrish Gabrielle et al. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2019 Jun (Posted: Jun 05, 2019 10AM)

Genetic basis of hypertrophic cardiomyopathy in children.
Rupp Stefan et al. Clinical research in cardiology : official journal of the German Cardiac Society 2019 Mar 108(3) 282-289 (Posted: Jun 05, 2019 10AM)

UNRAVEL: big data analytics research data platform to improve care of patients with cardiomyopathies using routine electronic health records and standardised biobanking.
Sammani A et al. Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 2019 May (Posted: May 29, 2019 8AM)

Dilated Cardiomyopathy - From Epidemiologic to Genetic Phenotypes A Translational Review of Current Literature.
Reichart Daniel et al. Journal of internal medicine 2019 May (Posted: May 29, 2019 8AM)

Sudden Cardiac Death Risk in Hypertrophic Cardiomyopathy: Wither Our Cognitive Miser.
Ommen Steve R et al. JAMA cardiology 2019 May (Posted: May 27, 2019 5PM)

Enhanced American College of Cardiology/American Heart Association Strategy for Prevention of Sudden Cardiac Death in High-Risk Patients With Hypertrophic Cardiomyopathy.
Maron Martin S et al. JAMA cardiology 2019 May (Posted: May 27, 2019 5PM)

Inherited cardiomyopathies.
Miles Chris et al. BMJ (Clinical research ed.) 2019 05 l1570 (Posted: May 08, 2019 3PM)

Evaluating the Clinical Validity of Hypertrophic Cardiomyopathy Genes.
Ingles Jodie et al. Circulation. Genomic and precision medicine 2019 Jan (Posted: Jan 30, 2019 9AM)

Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: the case of hypertrophic cardiomyopathy
R Walsh et al, Genome Medicine, January 29, 2019 (Posted: Jan 30, 2019 9AM)

Analysis of 51 proposed hypertrophic cardiomyopathy genes from genome sequencing data in sarcomere negative cases has negligible diagnostic yield.
Thomson Kate L et al. Genetics in medicine : official journal of the American College of Medical Genetics 2018 Dec (Posted: Dec 12, 2018 9AM)

Genetic Testing and Counseling for Hypertrophic Cardiomyopathy.
Cirino Allison L et al. Cardiology clinics 2019 Feb 37(1) 35-43 (Posted: Nov 19, 2018 9AM)

Modeling Hypertrophic Cardiomyopathy in a Dish
NIH Director's Blog, November 8, 2018 Brand (Posted: Nov 08, 2018 11AM)

Clinical predictors of informative genetic testing in hypertrophic cardiomyopathy.
Naraen Akriti et al. European journal of preventive cardiology 2018 Oct 2047487318808044 (Posted: Oct 24, 2018 9AM)

Effect of Gender and Genetic Mutations on Outcomes in Patients With Hypertrophic Cardiomyopathy.
van Velzen Hannah G et al. The American journal of cardiology 2018 Sep (Posted: Oct 10, 2018 7AM)

Exercise Training for Patients With Hypertrophic Cardiomyopathy: JACC Review Topic of the Week.
Dias Katrin A et al. Journal of the American College of Cardiology 2018 Sep 72(10) 1157-1165 (Posted: Sep 05, 2018 9AM)

When to Offer Predictive Genetic Testing to Children at Risk of an Inherited Arrhythmia or Cardiomyopathy The Family Perspective
S Christian et al, CIrc Genomics Prec Medicine, August 2018 (Posted: Aug 27, 2018 8AM)

Association of Variants in BAG3 With Cardiomyopathy Outcomes in African American Individuals
VD Myers, et al. JAMA Cardiology, August 22, 2018 (Posted: Aug 22, 2018 0PM)

Disclosure of diagnosis to at-risk relatives by individuals diagnosed with hypertrophic cardiomyopathy (HCM).
Hudson Janella et al. Journal of community genetics 2018 Aug (Posted: Aug 22, 2018 11AM)

Translating emerging molecular genetic insights into clinical practice in inherited cardiomyopathies.
Asatryan Babken et al. Journal of molecular medicine (Berlin, Germany) 2018 Aug (Posted: Aug 22, 2018 11AM)

Clinical Course and Management of Hypertrophic Cardiomyopathy.
Maron Barry J et al. The New England journal of medicine 2018 Aug (7) 655-668 (Posted: Aug 16, 2018 8AM)

Physical activity restriction for children and adolescents diagnosed with an inherited arrhythmia or cardiomyopathy and its impact on body mass index.
Christian Susan et al. Journal of cardiovascular electrophysiology 2018 Aug (Posted: Aug 15, 2018 10AM)

Whole Genome Sequencing in Hypertrophic Cardiomyopathy
American College Cardiology, July 17, 2018 (Posted: Jul 18, 2018 1PM)

Health behaviors among unaffected participants following receipt of variants of uncertain significance in cardiomyopathy-associated genes.
Miller Ilana M et al. Genetics in medicine : official journal of the American College of Medical Genetics 2018 Jul (Posted: Jul 18, 2018 9AM)

Whole Genome Sequencing Improves Outcomes of Genetic Testing in Patients With Hypertrophic Cardiomyopathy
RD Bagnall et al, JACC, July 2018 (Posted: Jul 17, 2018 9AM)

Additional Genetic Variants in Inherited Dilated Cardiomyopathy- Just Another Brick in the Wall?
JP can Tintelen et al, Circ: Genomics and Precision Medicine, July 16, 2018 (Posted: Jul 16, 2018 2PM)

Genome sequencing as a first-line genetic test in familial dilated cardiomyopathy
AE Minoche et al, Genetics in Medicine, July 2, 2018 (Posted: Jul 02, 2018 8AM)

Genetic evaluation of cardiomyopathy: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).
Hershberger Ray E et al. Genetics in medicine : official journal of the American College of Medical Genetics 2018 Jun (Posted: Jun 20, 2018 9AM)

[Genetic tests in hypertrophic cardiomyopathy: Benefits, limitations, and applications in clinical practice].
Gómez Arraiz I et al. Semergen 2018 May (Posted: Jun 11, 2018 11AM)

Defining the diagnostic effectiveness of genes for inclusion in panels: the experience of two decades of genetic testing for hypertrophic cardiomyopathy at a single center
F. Mazzaratto et al, Genetics in Medicine, June 6, 2018 (Posted: Jun 06, 2018 8AM)

Outcomes of Contemporary Family Screening in Hypertrophic Cardiomyopathy.
van Velzen Hannah G et al. Circulation. Genomic and precision medicine 2018 Apr 11(4) e001896 (Posted: Apr 18, 2018 10AM)

Hypertrophic Cardiomyopathy: Clinical Update.
Geske Jeffrey B et al. JACC. Heart failure 2018 Apr (Posted: Apr 18, 2018 10AM)

Genetic cardiomyopathies.
Wilcox Jane E et al. Current opinion in cardiology 2018 Mar (Posted: Mar 27, 2018 1PM)

Genetic Evaluation of Cardiomyopathy - a Heart Failure Society of America Practice Guideline.
Hershberger Ray E et al. Journal of cardiac failure 2018 Mar (Posted: Mar 27, 2018 1PM)

Familial hypertrophic cardiomyopathy - Identification of cause and risk stratification through exome sequencing.
Biswas Amitabh et al. Gene 2018 Mar (Posted: Mar 27, 2018 1PM)

Genetic Testing for Cardiomyopathies in Clinical Practice.
Ingles Jodie et al. Heart failure clinics 2018 Apr 14(2) 129-137 (Posted: Mar 14, 2018 10AM)

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Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
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