Prevalence Of Hypertrophic Cardiomyopathy Research Articles

Reported physical symptoms during screening echocardiography are not associated with presence of suspected hypertrophic cardiomyopathy.

The prevalence of hypertrophic cardiomyopathy (HCM) can be silent and can present with sudden death as the first manifestation of this disease. The goal of this study was to evaluate any association between reported physical symptoms with the presence of suspected HCM. The Anthony Bates Foundation has been performing screening echocardiography across the United States for the prevention of sudden death since 2001. A total of 4,120 subjects between the ages of 6 and 79 underwent echocardiographic screening. We evaluated any association between any symptoms and suspected HCM defined as any left ventricular wall thickness ³ 15 mm. The total prevalence of suspected HCM in the entire study population was 1.1%. The presence of physical symptoms was not associated with HCM (chest pain in 4.3% of participants with HCM vs. 9.9% of the control, p=0.19, palpitation in 4.3% of participants with HCM vs. 7.3% of the control., p=0.41, shortness of breath in 6.4% of participant with HCM vs. 11.7% of the control., p=0.26, lightheadedness in 4.3% of participant with HCM vs. 13.1% of the control., p=0.07, ankle swelling in 2.1% of participant with HCM vs. 4.0% of the control., p=0.52, dizziness in 8.5% of participant with HCM vs. 12.2% of the control., p=0.44). Echocardiographic presence of suspected HCM is not associated with a higher prevalence of physical symptoms in the participants undergoing screening echocardiography.

Re-evaluating the Incidence and Prevalence of Clinical Hypertrophic Cardiomyopathy: An Epidemiological Study of Olmsted County, Minnesota

ObjectiveTo contemporaneously reappraise the incidence-rate, prevalence, and natural history of hypertrophic cardiomyopathy (HCM) in Olmsted County, Minnesota, from 1984 to 2015. Patients and MethodsA validated medical-record linkage system collecting information for residents of Olmsted County was used to identify all cases of HCM between January 1, 1984, and December 31, 2015. After adjudication of records from Mayo Clinic and Olmsted Medical Center, data relating to diagnoses and outcomes were abstracted. The calculated incidence rate and prevalence were standardized to the US 1980 White population (age- and sex-adjusted) and compared with a prior study examining the years 1975-1984. ResultsTwo hundred seventy subjects with HCM were identified. The age- and sex-adjusted incidence rate was 6.6 per 100,000 person-years, and the point prevalence of HCM on January 1, 2016, was 89 per 100,000 population. The incidence rate and point prevalence of HCM on January 1, 2016, standardized to the US 1980 White population (age- and sex-adjusted), were 6.7 (95% CI, 7.1 to 8.8) per 100,000 person-years and 81.5 per 100,000 population, respectively. The incidence rate of HCM increased each decade since the index study. Individuals with HCM had a higher overall standardized mortality rate than the general population with an observed to expected HR of 1.44 (95% CI, 1.21 to 1.71; P<.001) which improved by each decade. ConclusionThe incidence and prevalence of HCM are higher than rates reported from a prior study in the same community examining the years 1975-1984, but lower than other study cohorts. The risk of mortality in HCM remains higher than expected, albeit with improvement in rates of mortality observed each decade during the study period.

Abstract 12668: Prevalence of Phenotypic Hypertrophic Cardiomyopathy Among Students Referred for Sport Pre-Participation Cardiovascular Screening

Background: Although rare, sudden cardiac death (SCD) is a tragic event for young sports participants and has catastrophic impact on the community. Hypertrophic cardiomyopathy (HCM) is a leading cause of SCD in sports. Comprehensive initial pre-participation physical evaluation (CIPPE) is mandated for middle school, and junior and senior high school students by Pennsylvania Interscholastic Athletic Association (PIAA) primarily for reducing potential sports-related injuries and SCD. Prospective data has been limited in this age group in regard to the prevalence of HCM. Methods: Between 2015 and 2023, we prospectively screened 424 students [age 10-21 (15±2) years, 60% male, 64% Caucasian) referred for cardiovascular disease pre-participation screening based on at least one positive response on the 14-point AHA questionnaire during CIPPE. Evaluation included 12-lead ECG and rhythm strip (100%), transthoracic echo (96.4%), ambulatory heart rhythm monitor (3.8%), treadmill exercise ECG (14.5%), stress echo (2.1%), and cardiac MRI (0.9%). Results: Overall, 1 (0.24%) student was diagnosed with definitive and two were diagnosed with probable HCM [Table-1]. Conclusion: In this prospective cohort of middle school and junior and senior high school students with at least one positive response to the 14-point AHA questionnaire, 1 (0.24%) had definitive and 2 (0.47%) had probable phenotypic HCM.

Echocardiographic predictors of outcomes in hypertrophic cardiomyopathy

The use of echocardiography, a straightforward and widely available technique, allows for a comprehensive assessment of the patient with hypertrophic cardiomyopathy (HCM) under both resting and stress conditions. The true prevalence of HCM has been redefined over time by this imaging approach, which has also made it feasible to pinpoint parameters that clinicians may use to stratify patients at risk for adverse cardiovascular events. The current and emerging prognostic predictors in HCM, assessed with transthoracic echocardiography at rest and during provocation, are discussed in this review.

Isolated discrete upper septal thickening in a non-referral cat population of senior and young cats

Introduction/objectivesDiscrete upper septal thickening (DUST) is a phenotype of elderly people. The cardiac phenotype in senior cats has been incompletely described. We aimed to characterize the echocardiographic phenotype of senior cats, specifically to determine prevalence of DUST and hypertrophic cardiomyopathy (HCM). AnimalsOne hundred and forty-nine healthy, normotensive cats. Materials and methodsProspective cross-sectional study. Senior (≥9 years) and young (<6 years) cats were recruited from non-referral population. We defined DUST as an isolated basilar septal bulge, and HCM as left ventricular wall thickness ≥6 mm. An interventricular septum ratio (basal-to-mid septal thickness ratio) was calculated. We assessed for associations between clinical and echocardiographic variables and DUST. Data are presented as mean (±SD), median (range), or frequency (percentage). ResultsOne-hundred and two senior and 47 young cats were enrolled. Aortoseptal angle (AoSA) was steeper in senior cats (137° (±14.5) vs. 145° (±12.3) in young cats, P=0.002). Eighteen cats had DUST (18/149, 12%), fourteen senior, and four young cats (P=0.4). Cats with DUST had steeper AoSA (125° (±8.3) vs. 142° (±13.7), P<0.0001) and higher interventricular septum ratio (1.4 (1.2–2.0) vs. 1.0 (0.7–1.8)). Univariable analysis showed decreased odds of DUST with greater AoSA (OR 0.9, P<0.0001), age was not associated with DUST. Twenty-nine senior cats had HCM (28.4%). Discussion/conclusionsPrevalence of DUST was 12%. There was no association between age and DUST. Smaller/steeper AoSA was the main factor associated with DUST. There was a high prevalence of HCM in this senior population.

HCM-associated ALMS1 variant: Allele drop-out and frequency in Italian Sphynx cats.

Hypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy in domestic cats, and some inherited variants are available for genetic testing. A variant of the Alstrom syndrome protein 1 gene (ALMS1) was recently reported to be associated with HCM in the Sphynx cat breed (A3: g.92439157G>C). Genetic screening of the variant, promoted by the Osservatorio Veterinario Italiano Cardiopatie and Genefast Laboratory, was offered to Sphynx cat owners and breeders in Italy. Genotype data were initially obtained by Sanger sequencing. In one case where the samples of a trio were available, inconsistency in the vertical transmission of the variant suggested an allele dropout (ADO) of the wt allele. A new external primer pair was designed as an alternative to the original. The larger PCR product obtained was sanger sequenced, and five novel single nucleotide variants (SNVs) not yet annotated in open-access databases were detected. Three of these SNVs were within the original primer-binding regions and were assumed to have caused ADO. The haplotype, including the ADO SNVs, was detected in two cats belonging to different lineages. To accurately genotype ALMS1 g.92439157G>C in the samples, we set up a real-time TaqMan MGB assay while avoiding all surrounding SNVs. At g.92439157G>C, for 136 Sphynx cats, g.92439157 C variant was highly widespread (freq. >0.50). The present study reports five new variants surrounding ALMS1 g.92439157G>C that must be considered when designing the test. The study also indicates the need to verify the correspondence between the g.92439157 C variant frequency and the prevalence of HCM by increasing clinical visits and follow-ups and finally to promote genetic counselling for accurate management of mating plans in Italian Sphynx cats.

РЕЗУЛЬТАТЫ ЭЛЕКТРОКАРДИОГРАФИЧЕСКОГО ИССЛЕДОВАНИЯ ПРИ ГКМП У РАЗНОВОЗРАСТНЫХ КОШЕК

Cardiomyopathies are a heterogeneous group of myocardial diseases with varying phenotypes and prognosis. Feline cardiomyopathies are common, and cardiovascular disease is among the 10 most common causes of death in cats. Hypertrophic cardiomyopathy (HCM) is a common cause of heart failure, arterial thromboembolism, and sudden death in cats. HCM is a primary myocardial lesion characterized by unexplained left ventricular hypertrophy (LVH) and impaired myocardial relaxation. The cause of primary or idiopathic in cats is unknown, but hereditary pathology probably exists in many cases. The disease is widespread in breeds such as Maine Coon, Persian, Ragdoll, American Shorthair. There are also reports of HCM in littermates and other close relatives of domestic shorthair cats. The method of electrocardiography is quite sensitive in the diagnosis of cardiomyopathies in humans, therefore, the study of ECG signs of HCM in cats, as well as the study of the dynamics of disease progression, the development and improvement of the treatment of this disease is an urgent scientific and practical problem in veterinary medicine, which has not been sufficiently resolved to date. According to the obtained ECG data, it can be concluded that recording in animals of different ages, as well as in animals that have a hereditary predisposition to the development of this disease, can play a key role in diagnosing an early stage of cardiomyopathy. The prevalence of HCM in cats with a predisposition to this disease is much higher than in cats without this genetic predisposition. Further studies involving more cats with HCM, secondary left ventricular hypertrophy, and normal hearts are proposed to better understand the heterogeneity and complexity of this myocardial disease.

Prevalence of Hypertrophic Cardiomyopathy in Neonates of Diabetic Mothers: A Six-month Follow-up Study

Background: Hypertrophic cardiomyopathy (HCM) is known to be the most common cardiac disorder in fetuses of diabetic mothers, especially when diabetes is not controlled in pregnancy. This study aimed as to estimate the prevalence of HCM in neonates born to diabetic mothers and to evaluate therapeutic interventions with follow-up after six months. We also focused on the possible association of neonatal HCM with the maternal type of diabetes.&#x0D; Methods: A cross-sectional study was conducted between October 2016, and September 2017, in the Cardiac Clinic of Yazd, a city in the center of Iran. The subjects were 150 neonates of mothers with diabetes. We determined HCM through fetal echocardiography before treatment and assessed the maternal and fetal factors. Finally, after a 6-month follow-up period, the data were analyzed statistically.&#x0D; Results: According to the results, the prevalence of HCM in neonates of diabetic mothers was 14% (P &lt; 0.0001). The results showed that there is a relationship between maternal uncontrolled diabetes and the incidence of HCM in the infant (P &lt; 0.0001), but there is no relationship between the type of diabetes and the incidence of HCM. Our results also showed that propranolol was effective in improving HCM, and spontaneous recovery of HCM was low in infants.&#x0D; Conclusion: We concluded that controlling maternal diabetes has the greatest effect on the prevention of HCM in neonates. Also, neonates of diabetic mothers need more heart tests and follow-ups. Therefore, more studies on the effects of maternal diabetes-induced HCM in neonates are needed.

Patterns of Left Ventricular Hypertrophy and Late Gadolinium Enhancement onCardiac Magnetic Resonanace in Patients with Hypertrophic Cardiomyopathy

Objective: To evaluate the patterns of left ventricular hypertrophy (LVH) and late gadolinium enhancement (LGE) inhypertrophic cardiomyopathy.&#x0D; Study Design: Analytical cross-Sectional Study.&#x0D; Place and Duration of Study: Tertiary Cardiac Care Center, Rawalpindi Pakistan from 01 June 2020 to 30 Dec 2021.&#x0D; Methodology: This study was carried out at a tertiary cardiac care center retrospectively from 1 June 2020 to 31 December 2021. Patients having LV hypertrophy due to aortic stenosis, hypertension, athlete’s heart, and infiltrative disorders were excluded from study. Cases were included using nonprobability consecutive sampling. Sample size estimated by taking 0.2- 0.5 % (1 in 200-500) prevalence of hypertrophic cardiomyopathy using open epi sample size calculator was (n=38) taking 99.99% confidence interval. For the purpose of study all patients with confirmed HCM undergoing CMR during given period were included in study.Approval from the ethical review committee with IERB (IERB letter # 9/2/R&amp;D/2022/179) was sought. CMR was performed using MRI 3 Tesla. Data analysis was done on SPSS version-26. Quantitative variables were expressed as Mean±SD. Qualitative variables were expressed as frequencies and percentages. ANOVA and student t-test (95% CI and 5% margin of error) was applied to compare the study variables. p-vale &lt;0.05 was considered statistically significant.&#x0D; Results: Majority 77(86.7%) of patients were males. Most common pattern of involvement for LV hypertrophy was asymmetrical septal hypertrophy in 47 (52.8%) followed by apical HCM in 29(32.6%). LVOT obstruction was observed in 30(33.7%) of patients. Mean maximum LV wall thickness was 22mm±5.47.&#x0D; Conclusion: Our study shows association, between the extent of Late Gadolinium Enhancement and LV wall thickness, myocardial mass index in HCM patients.

Population estimates of obstructive and non-obstructive hypertrophic cardiomyopathy in the UK and Germany

Abstract Background While numerous publications have estimated the prevalence of diagnosed hypertrophic cardiomyopathy (HCM), none have quantified the real-world proportion of obstructive and non-obstructive HCM using nationally representative data sources in any European countries. Purpose To estimate the prevalence of diagnosed HCM and its subtypes in the UK and Germany. Methods Patients with HCM were identified in the UK from 01 Apr 2009 to 30 Oct 2020 and Germany from 2011 to 2019. UK patients with HCM were identified using electronic health records from the Clinical Practice Research Datalink (CPRD) primary care data linked with Hospital Episode Statistics (HES) secondary care data using ICD-10 (I42.1, I42.2), Read, Medcode, SNOMED, and OPCS codes. German patients with HCM were identified using a nationally representative administrative claims data pool (WIG2 Benchmark database) from several German Statutory Health Insurance (SHI)-insurances using ICD-10 and OPS codes. Obstructive HCM was identified as any obstructive HCM diagnosis, any HCM diagnosis with septal reduction therapy, and any HCM diagnosis and left ventricular outflow tract obstruction (LVOTO; not in German claims data). Non-obstructive HCM was any non-obstructive or unspecified HCM diagnosis without evidence of any obstructive HCM. Annual prevalence was calculated for each year in the respective study periods and average annual prevalence across the study period. Results The average annual prevalence rate of HCM was 4.15/10,000 in the UK and 8.61/10,000 in Germany, while the average annual prevalence rate of obstructive HCM was 2.84/10,000 in the UK and 4.18/10,000 in Germany (Table). The proportion of HCM that was obstructive HCM was 68% in the UK and 49% in Germany. The prevalence rates of diagnosed HCM and obstructive HCM tended to increase over time (Figure). Conclusion The prevalence of HCM, obstructive HCM and the proportion of HCM that is obstructive varied between the UK and Germany. The prevalence of HCM was generally consistent with previously published estimates. Although there are limitations with coding in administrative data, it is important to differentiate obstructive HCM from non-obstructive HCM given their unique treatments and disease progression and management, especially since at least 49–68% of HCM is obstructive. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol Myers-Squibb

Should we be screening cats for cardiomyopathy? If so, how?

Occult feline hypertrophic cardiomyopathy (HCM) can result in unexpected sudden death or congestive heart failure (CHF) following routine interventions such as anesthesia, fluid administration, or, potentially, administration of corticosteroids. Consequently, clinicians would like to be able to screen at-risk cats to detect occult HCM and either avoid the risky intervention or attempt to reduce the risk of death or CHF. Currently, the feline N-terminal-proBrain natriuretic peptide test is the only potential screening test for detecting occult HCM. However, some cardiologists have pointed out the poor sensitivity of the test precludes its use as a screening test. This interpretation appears somewhat flawed. Using the current rapid test will allow clinicians to correctly identify half of the cats with moderate-to-severe occult HCM. A small number of cats without HCM will also test positive, necessitating an ultimately needless echocardiographic evaluation to demonstrate their disease-free status. However, the low prevalence of HCM in the general cat population and the apparently much lower rate of adverse events than would be predicted brings into question whether clinicians should bother screening. Therefore, until a more sensitive and accurate screening test becomes available, clinicians will have to decide for themselves whether identifying half of the at-risk cats of sudden death and CHF with this test is better than identifying none of them.

Systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy: a narrative review.

Background and ObjectiveThe prevalence of hypertrophic cardiomyopathy (HCM) is estimated to be 1 in 200 to 500 individuals, with systolic anterior motion (SAM) of the mitral valve (MV) and left ventricular outflow tract (LVOT) obstruction present in 60% to 70%. In this narrative review, we aim to elucidate the pathophysiology of SAM-septal contact and LVOT obstruction in HCM by presenting a detailed review on the anatomy of the MV apparatus in HCM, examining the various existing theories pertaining to the SAM phenomenon as supported by cardiac imaging, and providing a critical assessment of management strategies for SAM in HCM.MethodsA literature review was performed using PubMed, EMBASE, Ovid, and the Cochrane Library, of all scientific articles published through December 2021. A focus was placed on descriptive studies, reports correlating echocardiographic findings with pathologic diagnosis, and outcomes studies.Key Content and FindingsThe pathophysiology of SAM involves the complex interplay between HCM morphology, MV apparatus anatomic abnormalities, and labile hemodynamic derangements. Echocardiography and cardiac magnetic resonance (CMR) vector flow mapping have identified drag forces, as opposed to the “Venturi effect”, as the main hydraulic forces responsible for SAM. The degree of mitral regurgitation with SAM is variable, and its severity is correlated with degree of LVOT obstruction and outcomes. First line therapy for the amelioration of SAM and LVOT obstruction is medical therapy with beta-blockers, non-dihydropyridine calcium-channel blockers, and disopyramide, in conjunction with lifestyle modifications. In refractory cases septal reduction therapy is performed, which may be combined with a ‘resect-plicate-release’ procedure, anterior mitral leaflet extension, surgical edge-to-edge MV repair, anterior mitral leaflet retention plasty, or secondary chordal cutting.ConclusionsRecent scientific advances in the field of HCM have allowed for a maturation of our understanding of the SAM phenomenon. Cardiac imaging plays a critical role in its diagnosis, treatment, and surveillance, and in our ability to apply the appropriate therapeutic regimens. The increasing prevalence of HCM places an emphasis on continued basic and clinical research to further improve outcomes for this challenging population.

Identification of Novel Genetic Variants and Comorbidities Associated With ICD-10-Based Diagnosis of Hypertrophic Cardiomyopathy Using the UK Biobank Cohort.

Objectives: To identify previously unrecognized genetic variants and clinical variables associated with the ICD-10 (International Classification of Diseases 10)-based diagnosis of hypertrophic cardiomyopathy in the UK Biobank cohort. Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder with more than 2000 known mutations in one of eight genes encoding sarcomeric proteins. However, there is considerable variation in disease manifestation, suggesting the role of additional unrecognized contributors, genetic and otherwise. There is substantial interest in the use of real-world data, such as electronic health records to better understand disease mechanisms and discover new treatment strategies, but whether ICD-10-based diagnosis can be used to study HCM genetics is unknown. Methods: In a genome-wide association study (GWAS) using the UK Biobank, we analyzed the genomes of 363 individuals diagnosed with HCM based on ICD-10 coding compared to 7,260 age, ancestry, and sex-matched controls in a 1:20 case:control design. Genetic variants were analyzed by Plink’s firth logistic regression and assessed for association with HCM. We also examined 61 biomarkers and other diagnoses in the 363 HCM cases and matched controls. Results: The prevalence of ICD-10-based diagnosis of HCM in the UK Biobank cohort was 1 in 1,342, suggesting disease assignment based on the two ICD-10 codes underestimates HCM prevalence. In addition, common cardiovascular comorbidities were more prevalent in ICD-10-based HCM cases in comparison to controls. We identified two novel, non-sarcomeric genetic variants in KMT2C rs78630626, and PARD3B rs188937806 that were associated with ICD-10 codes for HCM with genome-wide significance (p < 5 x 10−8). These are associated with an increased odds ratio (OR) of ∼3.8 for being diagnosed with HCM. Minor allele frequency (MAF) of each variant was >1%. Discussion: Disease assignment based strictly on ICD-10 codes may underestimate HCM prevalence. Individuals with HCM were more frequently diagnosed with several comorbid conditions, such as hypertension, atherosclerotic heart disease, diabetes, and kidney failure, suggesting they may contribute to disease manifestation. This UK Biobank database-based GWAS identified common variants in KMT2C and PARD3B that are associated with HCM diagnosis, which may represent novel modifier genes. Our study demonstrates the feasibility and limitations of conducting phenotypic and genotypic characterization of HCM based on ICD-10 diagnosis in a large population-based cohort.

Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy in Adult Solid Organ Transplant Recipients.

Background.Hypertrophic cardiomyopathy (HCM) in pediatric solid organ transplant recipients has been reported in association with use of calcineurin inhibitors. However, data on the incidence and prevalence of HCM in adult posttransplant patients are limited. We sought to describe the clinical characteristics of solid organ transplant recipients who were diagnosed with HCM from 2011 to 2021 at a single center.Methods.Patients who had undergone solid organ transplant and exhibited left ventricular hypertrophy with left ventricular wall thickness ≥13 mm on transthoracic echocardiography were included. Clinical history, pedigree analysis, clinical genetic testing, transthoracic echocardiography, cardiac magnetic resonance imaging, treatment, and follow-up testing results were collected. Categorical variables were described as n (%). Continuous variables were described with medians and interquartile ranges and compared using the Wilcoxon rank-sum and Kruskal-Wallis tests. A 2-sided P < 0.05 was considered statistically significant.Results.Three lung, 5 kidney, and 4 liver transplant recipients from 12 different families were included. Seven patients (58%) did not carry a preexisting diagnosis of hypertension, and none had a history of aortic or subaortic stenosis. A majority of patients exhibited asymmetric septal hypertrophy (67%; medial septal thickness versus left ventricular posterior wall thickness 17 versus 13 mm; P < 0.001) and dynamic left ventricular outflow tract (LVOT) obstruction (58%). All patients were managed long term with calcineurin inhibitors. Clinical genetic testing in 6 patients identified 2 with disease-causing variants in 2 sarcomere genes, myosin binding protein-C and myosin heavy chain 7. Four patients (33%) underwent successful septal reduction therapy for treatment of symptomatic LVOT obstruction.Conclusions.Symptomatic HCM with dynamic LVOT obstruction can develop in solid organ transplant recipients, and genetic testing can identify individuals with sarcomeric HCM. Medical management and septal reduction therapies are treatment options for severe symptomatic disease.

An overview of the current genetic and phenotypical selection strategies to reduce the prevalence of feline hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a common and potentially lethal heart disease in cats. To reduce its prevalence, breeding cats are frequently screened on the basis of their phenotype or genotype. Although echocardiography is the most reliable phenotypical method, its efficacy is limited by the incomplete penetrance of HCM and by difficulties in distinguishing primary HCM from other causes of left ventricular hypertrophy. On the other hand, genetic testing is hampered by the genetic heterogeneity of the disease. Genetic tests are currently only available for Maine Coons and Ragdolls. Because of the high prevalence of HCM, stringent selection may have a negative impact on the genetic diversity of a breed. A more optimal selection would therefore be a slow and careful exclusion of phenotypically and/or genetically positive cats.

Diagnostic yield of hypertrophic cardiomyopathy in first-degree relatives of decedents with idiopathic left ventricular hypertrophy.

Idiopathic left ventricular hypertrophy (LVH) is defined as LVH in the absence of myocyte disarray or secondary causes. It is unclear whether idiopathic LVH represents the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) or whether it is a unique disease entity. We aimed to ascertain the prevalence of HCM in first-degree relatives of decedents from sudden death with idiopathic LVH at autopsy. Decedents also underwent molecular autopsy to identify the presence of pathogenic variants in genes implicated in HCM. Families of 46 decedents with idiopathic LVH (125 first-degree relatives) were investigated with electrocardiogram, echocardiogram exercise tolerance test, cardiovascular magnetic resonance imaging, 24-h Holter, and ajmaline provocation test. Next-generation sequencing molecular autopsy was performed in 14 (30%) cases. Decedents with idiopathic LVH were aged 33 ± 14 years and 40 (87%) were male. Fourteen families (30%) comprising 16 individuals were diagnosed with cardiac disease, including Brugada syndrome (n = 8), long QT syndrome (n = 3), cardiomyopathy (n = 2), and Wolff-Parkinson-White syndrome (n = 1). None of the family members were diagnosed with HCM. Molecular autopsy did not identify any pathogenic or likely pathogenic variants in genes encoding sarcomeric proteins. Two decedents had pathogenic variants associated with long QT syndrome, which were confirmed in relatives with the clinical phenotype. One decedent had a pathogenic variant associated with Danon disease in the absence of any histopathological findings of the condition or clinical phenotype in the family. Idiopathic LVH appears to be a distinct disease entity from HCM and is associated with fatal arrhythmias in individuals with primary arrhythmia syndromes. Family screening in relatives of decedents with idiopathic LVH should be comprehensive and encompass the broader spectrum of inherited cardiac conditions, including channelopathies.

Hypertrophic Cardiomyopathy: Sudden Death After Exercise

Research Article| February 01 2020 Hypertrophic Cardiomyopathy: Sudden Death After Exercise AAP Grand Rounds (2020) 43 (2): 16. https://doi.org/10.1542/gr.43-2-16 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Hypertrophic Cardiomyopathy: Sudden Death After Exercise. AAP Grand Rounds February 2020; 43 (2): 16. https://doi.org/10.1542/gr.43-2-16 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: exercise, hypertrophic cardiomyopathy, sudden death Source: Weissler-Snir A, Allan K, Cunningham K, et al. Hypertrophic cardiomyopathy-related sudden cardiac death in young people in Ontario. Circulation. 2019; 140(21): 1706– 1716; doi: https://doi.org/10.1161/CIRCULATIONAHA.119.040271Google Scholar Investigators from the University of Toronto, Ontario, Canada, conducted a retrospective study to determine the incidence of sudden cardiac death (SCD) in young people with hypertrophic cardiomyopathy (HCM) and evaluate the role of exercise in HCM-SCD. For the study, they identified cases of HCM-SCD in Ontario, Canada, occurring between 2005 and 2011 among individuals 10–45 years old, as confirmed by means of autopsy at the Office of the Chief Coroner for Ontario (OCCO). OCCO maintains a centralized database and includes information about all sudden deaths attended by the coroner in the province. A diagnosis of HCM as the cause of SCD was considered definite when the autopsy findings included marked cardiomyocyte hypertrophy with pleomorphic to bizarre nuclei and myofiber disarray. Cases with other findings consistent with HCM, but no myofiber disarray, were classified as possible HCM-SCD. Sudden deaths in individuals with known HCM, but in whom no autopsy was performed, were categorized as probable HCM-SCD. The incidence of HCM-SCD among the at-risk population was estimated by using Ontario census data and assuming a prevalence of HCM of 1:500.1 To assess the role of exercise in HCM-SCD, the authors reviewed the death investigation review conducted by the coroner in each autopsied case and categorized the activity level at the time of death as being during sleep, at rest, during light activity, or during moderate or vigorous exercise. During the study period, 44 definite, 3 probable, and 6 possible cases of HCM-SCD were identified. Based on an estimate of the population at risk, the incidence of definite HCM-SCD was calculated as 0.31 per 1,000 HCM person years (95% CI, 0.24–0.44). Including probable and possible cases increased the estimated incidence to 0.38 per 1,000 HCM person years (95% CI, 0.28–0.49). The median age of individuals with HCM-SCD confirmed by means of autopsy was 35.5 years (interquartile range, 26–42 years), and 83% were male; 70% of cases occurred in individuals without prior diagnosed HCM. Overall, 34% of cases occurred at rest, 30% during sleep, 17% during light activity, and 17% during or immediately after moderate or vigorous activity. However, among those ≤20 years, 77.4% of cases of HCM-SCD were associated with moderate or vigorous activity versus 4.8% in older victims. The authors conclude that HCM-SCD is uncommon in the population at risk and infrequently related to exercise, at least in older individuals. Dr Chung has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Every summer, general pediatric offices await the influx of sports physical examination forms that document the preparticipation physical examination (PPE) required by most states.2 The pediatrician who signs the bottom of a PPE form, even if only for a fleeting second, bears the burden... You do not currently have access to this content.

Allele-Selective Knockdown of MYH7 Using Antisense Oligonucleotides

Hundreds of dominant-negative myosin mutations have been identified that lead to hypertrophic cardiomyopathy, and the biomechanical link between mutation and disease is heterogeneous across this patient population. To increase the therapeutic feasibility of treating this diverse genetic population, we investigated the ability of locked nucleic acid (LNA)-modified antisense oligonucleotides (ASOs) to selectively knock down mutant myosin transcripts by targeting single-nucleotide polymorphisms (SNPs) that were found to be common in the myosin heavy chain 7 (MYH7) gene. We identified three SNPs in MYH7 and designed ASO libraries to selectively target either the reference or alternate MYH7 sequence. We identified ASOs that selectively knocked down either the reference or alternate allele at all three SNP regions. We also show allele-selective knockdown in a mouse model that was humanized on one allele. These results suggest that SNP-targeting ASOs are a promising therapeutic modality for treating cardiac pathology.

Trends of the prevalence and incidence of hypertrophic cardiomyopathy in Korea: A nationwide population-based cohort study.

Temporal trends of the prevalence and incidence of hypertrophic cardiomyopathy (HCM) have not been well established in Asian populations. Using the Korean National Health Insurance Services database, we identified patients with a confirmed diagnosis of HCM between 2010 and 2016. The annual prevalence and incidence of HCM, and their clinical characteristics were investigated. The prevalence of HCM has increased from 0.016% (n = 6313) in 2010 to 0.031% (n = 13,035) in 2016. During a 7-year period, 13,229 patients were newly diagnosed with HCM. The incidence rate increased from 4.15 (per 100,000 person-years) in 2010 to 5.6 in 2016. The prevalence and incidence of HCM increased with age and peaked during the 70s, with male predominance in all age groups. Chest pain is the most frequent clinical presentation followed by shortness of breath and syncope. Hypertension and dyslipidemia were the two most common comorbidities. Heart failure and atrial fibrillation was diagnosed in about 1/3 and 1/4 of patients with HCM, respectively. The prevalence and incidence of HCM gradually increased from 2010 to 2016, possibly due to heightened recognition of the disease. Given the progressively high incidence of HCM with age and high prevalence of coexisting modifiable risk factors, continued efforts are required to increase awareness regarding HCM-related symptoms and potential complications.

Effect of body surface area and gender on wall thickness thresholds in hypertrophic cardiomyopathy.

BackgroundFamily screening for hypertrophic cardiomyopathy (HCM) is based on genetic testing and clinical evaluation (maximal left ventricular wall thickness (MWT) ≥15 mm, or ≥13 mm in first-degree relatives of HCM patients). The aim of this study was to assess the effect of gender and body size on diagnosis of HCM and prediction of clinical outcome.MethodsThis study includes 199 genotype-positive subjects (age 44 ± 15 years, 50% men) referred for cardiac screening. Gender-specific reference values for MWT indexed by body surface area (BSA), height and weight were derived from 147 healthy controls. Predictive accuracy of each method for HCM-related events was assessed by comparing areas under the receiver operating characteristic curves (AUC).ResultsMen had a higher absolute, but similar BSA- and weight-indexed MWT compared with women (14.0 ± 3.9 mm vs 11.5 ± 3.8 mm, p < 0.05; 6.8 ± 2.1 mm/m2 vs 6.6 ± 2.4 mm/m2; 0.17 ± 0.06 mm/kg vs 0.17 ± 0.06 mm/kg, both p > 0.05). Applying BSA- and weight-indexed cut-off values decreased HCM diagnoses in the study group (48% vs 42%; 48% vs 39%, both p < 0.05), reclassified subjects in the largest, lightest and heaviest tertiles (≥2.03 m2: 58% vs 45%; ≤70 kg: 37% vs 46%; ≥85 kg: 53% vs 25%, all p < 0.05) and improved predictive accuracy (AUC 0.76 [95% CI 0.69–0.82] vs 0.78 [0.72–0.85]; and vs 0.80 [0.74–0.87]; both p < 0.05).ConclusionsIn genotype-positive subjects referred for family screening, differences in MWT across gender are mitigated after indexation by BSA or weight. Indexation decreases the prevalence of HCM, particularly in larger men, and improves the predictive accuracy for HCM-related events.