Hypertrophic Cardiomyopathy Population Research Articles

Clinical Profile and Health Disparities in a Multiethnic Cohort of Patients With Hypertrophic Cardiomyopathy.

Clinical studies of hypertrophic cardiomyopathy are over-represented by individuals of European ethnicity, with less known about other ethnic groups. We investigated differences between patients in a multiethnic Australian hypertrophic cardiomyopathy population. We performed a retrospective cohort study of 836 unrelated hypertrophic cardiomyopathy probands attending a specialized clinic between 2002 and 2020. Major ethnic groups were European (n=611), East Asian (n=75), South Asian (n=58), and Middle Eastern and North African (n=68). The minor ethnicity groups were Oceanian (n=9), People of the Americas (n=7), and African (n=8). One-way ANOVA with Dunnett post hoc test and Bonferroni adjustment were performed. Mean age of the major ethnic groups was 54.9±16.9 years, and 527 (65%) were male. Using the European group as the control, East Asian patients had a lower body mass index (29 versus 25 kg/m2, P<0.0001). South Asians had a lower prevalence of atrial fibrillation (10% versus 31%, P=0.024). East Asians were more likely to have apical hypertrophy (23% versus 6%, P<0.0001) and Middle Eastern and North African patients more likely to present with left ventricular outflow tract obstruction (46% versus 34%, P=0.0003). East Asians were less likely to undergo genetic testing (55% versus 85%, P<0.0001) or have an implantable cardioverter-defibrillator implanted (19% versus 36%, P=0.037). East Asians were more likely to have a causative variant in a gene other than MYBPC3 or MYH7, whereas Middle Eastern and North African and South Asians had the highest rates of variants of uncertain significance (27% and 21%, P<0.0001). There are few clinical differences based on ethnicity, but importantly, we identify health disparities relating to access to genetic testing and implantable cardioverter-defibrillator use. Unless addressed, these gaps will likely widen as we move towards precision-medicine-based care of individuals with hypertrophic cardiomyopathy.

Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.

Thromboembolism in Patients with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease, which has a marked heterogeneity in clinical expression, natural history, and prognosis. HCM is associated with a high prevalence of thromboembolic events (stroke and systemic embolic events), even if taking no account of atrial fibrillation (AF), leading to unexpected disability and death in patients of all ages. Several risk factors of thromboembolism such as AF, greater age, left atrial diameter, heart failure and others have been confirmed in patients with HCM. Conventional thromboembolic predictive models were estimated by several trials in HCM population but it turned out to be unsatisfactory. Based on those previous explorations, researchers tried to modify or develop novel models suitable for HCM population in thromboembolism prediction. In consideration of catastrophic advent events of thromboembolism, current guidelines have recommended life-long anticoagulant therapy after a single short AF.Therefore, early identification of risk factors for thromboembolism, accurate risk stratification, timely preventive measures and aggressive management may help to avoid serious adverse thromboembolic events in HCM population.

Post-Mortem Cardiac Magnetic Resonance for the Diagnosis of Hypertrophic Cardiomyopathy.

Background: Post-mortem cardiac magnetic resonance (PMCMR) is an emerging tool supporting forensic medicine for the identification of the causes of cardiac death, such as hypertrophic cardiomyopathy (HCM). We proposed a new method of PMCMR to diagnose HCM despite myocardial rigor mortis. Methods: We performed CMR in 49 HCM patients, 30 non-HCM hypertrophy, and 32 healthy controls. In cine images, rigor mortis was simulated by the analysis of the cardiac phase corresponding to 25% of diastole. Left ventricular mass, mean, and standard deviation (SD) of WT, maximal WT, minimal WT, and their difference were compared for the identification of HCM. These parameters were validated at PMCMR, evaluating eight hearts with HCM, 10 with coronary artery disease, and 10 with non-cardiac death. Results: The SD of WT with a cut-off of > 2.4 had the highest accuracy to identify HCM (AUC 0.95, 95% CI = 0.89–0.98). This was particularly evident in the female population of HCM (AUC=0.998), with 100% specificity (95% CI = 85–100%) and 96% sensitivity (95% CI = 79–99%). Using this parameter, at PMCMR, all of the eight patients with HCM were correctly identified with no false positives. Conclusions: PMCMR allows identification of HCM as the cause of sudden death using the SD of WT > 2.4 as the diagnostic parameter.

Safety and outcomes of a structured exercise programme in young patients with hypertrophic cardiomyopathy: the SAFE-HCM trial

Abstract Background Contemporary studies in hypertrophic cardiomyopathy (HCM) suggest that moderate intensity exercise can improve cardiorespiratory fitness without raising significant safety concerns. Although low/moderate intensity exercise may be appropriate for older HCM patients, it is unlikely to attract younger, often asymptomatic patients, who wish to engage in higher intensity regimes. Purpose To assess the feasibility, safety and outcomes of an individually tailored, high intensity exercise programme in young patients with HCM. Methods In this RCT, 80 patients with HCM, aged 16–60 (mean 45.7, [SD8.6]) underwent baseline testing with ECG, echocardiography, blood testing, exercise testing, 48-hour ECG and psychological assessment. Individuals were randomised to a 12-week supervised exercise programme (HRR increased from 70–85%) (n=40) or usual activity (n=40). Baseline investigations were repeated at 12 weeks. Feasibility was assessed by a) recruitment, adherence and retention rates; b) staffing ratios and logistics; c) acceptability of the intervention/educational materials. Safety was assessed as a composite of 1) cardiovascular death, 2) cardiac arrest, 3) device therapy, 4) exercise induced syncope, 5) sustained/non-sustained (NS) ventricular tachycardia (VT) or 6) sustained atrial arrhythmias. Secondary outcomes included health and psychological benefits. Results 67 individuals (82.5%) completed the study. Reasons for refusal included travel, work and family commitments. The majority (64.7%) of exercising individuals progressed to 85%HRR. Resource requirements were similar to other programmes. All individuals felt supported, more confident to exercise, and found educational materials clear and informative. There was no significant difference between groups for the composite safety outcome. One individual experienced exercise induced syncope due to ventricular standstill (exercise) and another sustained VT (control). Both required device implantation. There was no significant difference between groups in episodes of NSVT (p=0.573) or ectopic burden (p=0.729). At 12 weeks, exercise group participants demonstrated greater activity levels (+1.1 hours [CI 0.2–2.1], p=0.024). The change in peak aerobic capacity (+255.2ml/min [CI 93.2–417.1], p=0.003), time to anaerobic threshold (AT) (+115s [CI 54.2–176.0], p&amp;lt;0.001), total exercise time (+108.1s [CI 33.1–183.0], p=0.005) and oxygen uptake at AT (+2.44ml/kg/min [CI 0.6–4.2], p=0.009) were all significantly greater in the exercise group. HADS anxiety (p&amp;lt;0.001) and depression (p=0.017) scores demonstrated the greatest reduction in the exercise group. Conclusions A high intensity exercise programme is feasible in young patients with HCM, with considerable gains in cardiorespiratory fitness and psychological outcomes. Importantly, arrhythmia burden was not increased in the exercise group. Further research is still required to assess the long-term safety of high intensity exercise in the HCM population. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Cardiac Risk in the Young

Prevalence and Impact of Atrial Fibrillation in a Cohort of Patients with Hypertrophic Cardiomyopathy in Ireland.

Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with hypertrophic cardiomyopathy (HCM), and is associated with deterioration in clinical status and outcome. To date, no data have been published pertaining to AF in an Irish HCM population. 159 patients with HCM attending St Vincent's University Hospital and Blackrock Clinic, Dublin, were identified. Detailed review of medical notes, Holter monitor, echocardiogram, cardiac MRI (CMR) and implantable cardioverter-defibrillator (ICD) records was performed.Prevalence of AF was 38.4%. HCM patients with AF (HCM-AF) were older (60.6±14.8 v 54.9±17.3 years, P=0.016) and more symptomatic (NYHA II: 29.7% v 16.9%, NYHA III: 4.3% v 1.2%) than HCM patients without AF. History of stroke was recorded in 16.4% of HCM-AF patients, compared with 1% in those without AF.HCM-AF patients had lower left ventricular ejection fraction (echo: 59.5±11.8v68±8, P<0.001; CMR: 62.3%v70.5%, P<0.01) and higher left atrial diameter (echo: 49.8±9.5v40.9±7.4, p<0.001; CMR 62.3±11.3v70.4±9, p<0.001), compared with those without AF. Myocardial fibrosis was detected on CMR in 74% of HCM-AF patients and 62% of those without AF.34% of patients had an ICD in situ, of whom 61% had AF. 24% of these HCM-AF patients received inappropriate shocks, all triggered by AF. AF is common in the Irish HCM population. It is associated with increased risk of stroke, deterioration in symptom status and is a common trigger for inappropriate ICD discharge. We have shown, in-keeping with previous studies, that AF is associated with reduced EF, increased LA diameter and mitral regurgitation in this HCM population.

Trabeculated Myocardium in Hypertrophic Cardiomyopathy: Clinical Consequences.

Aims: Hypertrophic cardiomyopathy (HCM) is often accompanied by increased trabeculated myocardium (TM)—which clinical relevance is unknown. We aim to measure the left ventricular (LV) mass and proportion of trabeculation in an HCM population and to analyze its clinical implication. Methods and Results: We evaluated 211 patients with HCM (mean age 47.8 ± 16.3 years, 73.0% males) with cardiac magnetic resonance (CMR) studies. LV trabecular and compacted mass were measured using dedicated software for automatic delineation of borders. Mean compacted myocardium (CM) was 160.0 ± 62.0 g and trabecular myocardium (TM) 55.5 ± 18.7 g. The percentage of trabeculated myocardium (TM%) was 26.7% ± 6.4%. Females had significantly increased TM% compared to males (29.7 ± 7.2 vs. 25.6 ± 5.8, p < 0.0001). Patients with LVEF < 50% had significantly higher values of TM% (30.2% ± 6.0% vs. 26.6% ± 6.4%, p = 0.02). Multivariable analysis showed that female gender and neutral pattern of hypertrophy were directly associated with TM%, while dynamic obstruction, maximal wall thickness and LVEF% were inversely associated with TM%. There was no association between TM% with arterial hypertension, physical activity, or symptoms. Atrial fibrillation and severity of hypertrophy were the only variables associated with cardiovascular death. Multivariable analysis failed to demonstrate any correlation between TM% and arrhythmias. Conclusions: Approximately 25% of myocardium appears non-compacted and can automatically be measured in HCM series. Proportion of non-compacted myocardium is increased in female, non-obstructives, and in those with lower contractility. The amount of trabeculation might help to identify HCM patients prone to systolic heart failure.

Temporal Trend of Age at Diagnosis in Hypertrophic Cardiomyopathy: An Analysis of the International Sarcomeric Human Cardiomyopathy Registry.

Background:Over the last 50 years, the epidemiology of hypertrophic cardiomyopathy (HCM) has changed because of increased awareness and availability of advanced diagnostic tools. We aim to describe the temporal trends in age, sex, and clinical characteristics at HCM diagnosis over >4 decades.Methods:We retrospectively analyzed records from the ongoing multinational Sarcomeric Human Cardiomyopathy Registry. Overall, 7286 patients with HCM diagnosed at an age ≥18 years between 1961 and 2019 were included in the analysis and divided into 3 eras of diagnosis (<2000, 2000–2010, >2010).Results:Age at diagnosis increased markedly over time (40±14 versus 47±15 versus 51±16 years, P<0.001), both in US and non-US sites, with a stable male-to-female ratio of about 3:2. Frequency of familial HCM declined over time (38.8% versus 34.3% versus 32.7%, P<0.001), as well as heart failure symptoms at presentation (New York Heart Association III/IV: 18.1% versus 15.8% versus 12.6%, P<0.001). Left ventricular hypertrophy became less marked over time (maximum wall thickness: 20±6 versus 18±5 versus 17±5 mm, P<0.001), while prevalence of obstructive HCM was greater in recent cohorts (peak gradient >30 mm Hg: 31.9% versus 39.3% versus 39.0%, P=0.001). Consistent with decreasing phenotypic severity, yield of pathogenic/likely pathogenic variants at genetic testing decreased over time (57.7% versus 45.6% versus 38.4%, P<0.001).Conclusions:Evolving HCM populations include progressively greater representation of older patients with sporadic disease, mild phenotypes, and genotype-negative status. Such trend suggests a prominent role of imaging over genetic testing in promoting HCM diagnoses and urges efforts to understand genotype-negative disease eluding the classic monogenic paradigm.

Electrocardiographic voltage criteria in patients with hypertrophic cardiomyopathy.

Several ECG voltage criteria have been proposed for the diagnosis of left ventricular hypertrophy (LVH). Notably, ECG criteria have been historically validated in concentric LVH but not in hypertrophic cardiomyopathy (HCM), wherein the hypertrophy pattern is typically asymmetric. The aim of our study was to evaluate the performance of ECG voltage criteria for LVH diagnosis in the HCM population. The electrocardiograms of 92 HCM patients and 41 sex- and age-matched controls were evaluated with the most frequently used ECG voltage criteria for LVH diagnosis. Cardiac magnetic resonance (MRI) was performed in HCM and controls in order to quantify LVH and its distribution. In the HCM population, the maximal diagnostic accuracy was achieved by Amplitude total and Amplitude total product criteria (58% for both), while the Cornell Voltage best performed in septal HCM (62%), the Sokolov in aVL and Gubner criteria in apical HCM (79% for both) and the Cornell Voltage and Product in anterior HCM (86% for both). All the ECG voltage criteria showed a poor correlation with left ventricular mass and maximal thickness measured by cardiac MRI. In our study, only a few ECG voltage criteria used for the detection of LVH in clinical practice showed an acceptable performance in the HCM population. Further studies are needed to clarify the role of ECG for LVH detection in HCM patients.

Sudden Cardiac Death-Relevant Events of Hypertrophic Cardiomyopathy in a Regional Japanese Cohort - Results From the Kochi RYOMA Study.

Background: Sudden cardiac death (SCD) is a most devastating complication of hypertrophic cardiomyopathy (HCM). The aim of this study was to clarify the clinical features of HCM in patients who experienced SCD-relevant events in an aged Japanese community.Methods and Results: In 2004, we established a cardiomyopathy registration network in Kochi Prefecture, and herein report on 293 patients with HCM who are followed as part of the registry. The mean (±SD) age at registration and diagnosis was 63±14 and 56±16 years, respectively. SCD-relevant events occurred in 19 patients during a mean follow-up period of 6.1±3.2 years (incidence rate 1.0%/year): sudden death in 9 patients, successful recovery from cardiopulmonary arrest in 4 patients, and appropriate implantable cardioverter–defibrillator discharge in 6 patients. At registration, 13 patients were in the dilated phase of HCM (D-HCM). During the follow-up period, HCM developed to D-HCM in 21 patients; thus, 34 patients in total had D-HCM. Multivariate analysis revealed that D-HCM at registration or during follow-up and detection of non-sustained ventricular tachycardia (NSVT) during follow-up were significant predictors of SCD-relevant events.Conclusions: In this HCM population in an aged Japanese community, the annual rate of SCD-relevant events was 1.0%. HCM developed to D-HCM in a considerable number of patients, and D-HCM and NSVT were shown to be independently associated with an increased risk of SCD-relevant events.

Telehealth monitoring for hypertrophic cardiomyopathy and amyloid cardiomyopathy patients: lessons from the coronavirus disease 2019 lockdown in Italy.

To the Editor As a result of the coronavirus disease 2019 (COVID-19) lockdown imposed beginning on 9 March 2020, Italian hospitals were required to postpone or even halt outpatient visits deemed as nonurgent. Methods The Hypertrophic Cardiomyopathy (HCM) Outpatient Clinic at the Ospedale Policlinico San Martino, Genova, regularly follows patients affected by HCM and cardiac amyloidosis. At the beginning of the COVID-19 lockdown an already operating service for patients’ communications (via telephone and E-mail) was implemented, and each patient with a scheduled visit in the forthcoming weeks (up to 15 May 2020) was contacted by a medical trainee to assess urgency related to her/his medical evaluation. According to information collected via the telemedical contact, patients were divided into ‘stable’ (group-A) and ‘potentially unstable’ (group-B). Patients were deemed as ‘potentially unstable’ if one or more of the following were present: signs and/or symptoms of heart failure, in particular if worsening relatively to the precontact condition; known end-stage HCM; heart failure hospitalization(s) and/or more than three outpatients evaluations in the prior 6 months. Those in group-B received weekly telemedical contact to monitor their conditions. Results Forty patients (27 males, median age: 62 years) received a telecontact, of whom 28 were HCM and 12 were cardiac amyloidosis patients. Nineteen patients were deemed as ‘potentially unstable’ (10 cardiac amyloidosis and 9 HCM). The main reason for inclusion in group-B was a recent heart failure hospitalization. Characteristics of patients in group-A versus B are shown in Table 1. As of 7 May 2020 no patients in group-A sought medical attention outside the planned telemedical contacts, and none needed an outpatient visit or hospitalization. In group-B, eight patients needed unplanned medical attention. In four instances, their needs were managed via telecontact without the need for in-person evaluations: two cardiac amyloidosis patients needed optimization of diuretic therapy; two obstructive HCM patients needed optimization of therapy for relief of obstruction. In three other instances, a medical outpatient evaluation was required: two cardiac amyloidosis patients presented worsening heart failure symptoms, and one severely obese HCM patient presented a new-onset atrial fibrillation with high ventricular response. Finally, one cardiac amyloidosis patient required hospitalization due to acute decompensated heart failure.Table 1: Characteristics of patients according to group allocationComment In this series of cardiomyopathy patients managed during the COVID-19 lockdown in Italy, a strategy of telehealth monitoring was feasible and effective, at least in the short term, with even a subset of patients contacted via E-mail. Telemedical contact by trained staff was able to stratify patients in higher and lower heart failure risk. No unplanned medical contact was required by patients deemed at low heart failure risk; moreover, half of the unplanned medical contacts among those at high heart failure risk was managed via repeated telemedical evaluations. Though of course not generalizable to the whole HCM and cardiac amyloidosis cardiomyopathy population, our report may offer suggestions for future management of this increasing cohort of patients. Telemedicine interventions have shown a beneficial effect in the management of heart failure patients.1 In current COVID-19 times, telemedicine served as an emergency tool, yet lessons from its impact on healthcare may be exploited for the future.2 In the case of cardiomyopathies such as HCM or cardiac amyloidosis, telehealth monitoring may be useful, in particular for a specific subset of low-risk patients, such as genotype-positive-phenotype-negative relatives. However, strategies of telehealth monitoring have never been specifically assessed in the case of cardiomyopathies. Implementation of telehealth strategies in Cardiomyopathy Units may help adequate followup for all patients and, at the same time, allow a better allocation of resources for in-hospital visits. Many already available tools may be exploited for telehealth strategies, including: telephone-based follow-up, remote monitoring of devices, use of novel portable devices,3 web-based interactive platforms.4 Telehealth monitoring cannot replace in-hospital in-person medical evaluation, but may be a valid practice in the near future. Acknowledgements Conflicts of interest There are no conflicts of interest.

1266Novel formin homology 2 domain containing 3 (FHOD3) mutations associated with the pathogenesis of hypertrophic cardiomyopathy (HCM) in an Irish population

Abstract Background The genetic cause of hypertrophic cardiomyopathy (HCM) remains unexplained in a substantial proportion of cases. Recent large sequencing studies suggest that, though not previously implicated, FHOD3 (a Formin protein responsible for sarcomere assembly) may have a role in the pathogenesis of HCM, particularly variants affecting a conserved small coil-coiled domain (amino acids 622 to 655). Aim To investigate the relationship between novel FHOD3 mutations, previously classified as variants of uncertain significance (American College of Medical Genetics ACMG Class III), and the development of HCM. Methods A single center review of HCM probands carrying mutations in the FHOD3 gene was conducted. Existing HCM patients from the family heart screening clinic database were retrospectively reviewed. Frequency of FHOD3 mutations, segregation among family members and clinical characteristics of patients were reviewed. All genetic analysis was conducted via the same internationally validated next generation sequencing lab. Results Of 367 HCM probands identified in our center, 9 (2.45%) were found to have ACMG Class III mutations affecting the FHOD3 gene. Five of these 9 probands (56%) displayed the same p.Arg637Gln mutation, while the remaining 4 (44%) carry the same p.Ile648Thr residue alteration. Both of these are rare mutations, found to be present in &amp;lt;1% of controls in previous large sequencing studies and not previously reported. Among probands with the p.Ile648Thr mutation, co-segregation was confirmed in one family, another first-degree relative in the same family having suffered a sudden cardiac death (HCM confirmed on autopsy). In those with the p.Arg367Gln mutation, a strong family history was observed in two separate families, 4 first-degree members having a confirmed HCM diagnosis. Carriers of both mutation types displayed varying degrees of disease severity with rates of non-sustained ventricular tachycardia and device implantation similar to other HCM cohorts (∼40%). Conclusions FHOD3 is a novel gene, recently implicated in the pathogenesis of HCM, though not previously well described in the literature. Carrier frequency of FHOD3 mutations in the HCM population in our center is similar to that described in recent publication (1-2%), and all carry variants affecting the suspected small coil-coiled domain (amino-acids 622-625). Abstract Figure.

Genotype-Related Clinical Characteristics and Myocardial Fibrosis and Their Association with Prognosis in Hypertrophic Cardiomyopathy

Background: The spectrum of genetic variants and their clinical significance of Hypertrophic cardiomyopathy (HCM) have been poorly studied in Asian patients. The objectives of this study were to assess the spectrum of genetic variants and genotype–phenotype relationships within a Korean HCM population. Methods: Eighty-nine consecutive unrelated HCM patients were included. All patients underwent genotypic analysis for 23 HCM-associated genes. Clinical parameters including echocardiographic and cardiac magnetic resonance (CMR) parameters were evaluated. A composite of major adverse cardiac and cerebrovascular events was assessed. Results: Genetic variants were detected in 55 of 89 subjects. Pathogenic variants or likely pathogenic variants were identified in 27 of HCM patients in MYBPC3, TNNI3, MYH7, and MYL7. Variants of uncertain significance were identified in 28 patients. There were significant differences in the presence of non-sustained ventricular tachycardia (p = 0.030) and myocardial fibrosis on CMR (p = 0.029) in the detected compared to the not-detected groups. Event-free survival was superior in the not-detected group (p = 0.006). Conclusion: Genetic variants in patients with HCM are relatively common and are associated with adverse clinical events and myocardial fibrosis on CMR. Genotypic analysis may add important information to clinical variables in the assessment of long-term risk for HCM patients.

The Impact of Syndromic Genetic Disorders on Medical Management and Mortality in Pediatric Hypertrophic Cardiomyopathy Patients.

Hypertrophic cardiomyopathy (HCM) is a prevalent cardiomyopathy in children, with variable etiologies, phenotypes, and associated syndromic genetic disorders (GD). The spectrum of evaluation in this heterogeneous population has not been well described. We aimed to describe mortality and medical management in the pediatric HCM population, and compare HCM pediatric patients with GD to those without GD. Children (< 18years) with HCM from the claims-based Truven Health Analytics MarketScan Research Database for years 2013-2016 were identified. Outcomes, including patient visits, diagnostic tests, procedures, medications, and mortality, were reported across demographic and clinical characteristics. Multivariable negative binomial, logistic, and survival models were utilized to test the association between those with and without GD by outcomes. 4460 patients were included, with a median age of 11years (IQR 3-16), 61.7% male, 17.7% with GD, and 2.1% who died during the study period. There were 0.36 inpatient admissions per patient-year. Patients with GD were younger [8years (IQR 1-14) vs 12years (IQR 3-16) (p < 0.0001)], had more echocardiograms (1.77 vs 0.93) p < 0.0001; and ambulatory cardiac monitoring per year (0.32 vs 0.24); p = 0.0002. Adjusting for potential confounders including age, other chronic medical conditions, procedures, and heart failure, GD had increased risk of mortality [HR 2.46 (95% CI 1.62, 3.74)], myectomy [HR 1.59 (95% CI 1.08, 2.35)], and more annual admissions [OR 1.36 (CI 1.27, 1.45]. Patients with HCM show higher rates of death, admission, testing, and myectomy when concomitant syndromic genetic disorders are present, suggesting that the disease profile and resource utilization are different from HCM patients without GD.

Myocardial tissue characterization by gadolinium-enhanced cardiac magnetic resonance imaging for risk stratification of adverse events in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy with a wide spectrum of clinical manifestations. Patients can be asymptomatic or suffer major adverse events including sudden cardiac death, ventricular arrhythmias, and heart failure. Identification of individuals with HCM who are at risk for these complications remains challenging. While echocardiography remains the mainstay of diagnostic evaluation, cardiac magnetic resonance imaging (CMR) is an important adjunctive diagnostic modality with emerging applications for risk-stratification of adverse events in the HCM population. Although not included in current guidelines for HCM management, there is increasing evidence to support the use of CMR for routine prognostic assessment of HCM patients. In this review we discuss the use of CMR techniques, including late gadolinium enhancement, T1 mapping, and quantification of extracellular volume fraction, for the risk stratification of three major adverse events in HCM: sudden cardiac death, ventricular arrhythmias, and congestive heart failure.

Scleraxis as a prognostic marker of myocardial fibrosis in hypertrophic cardiomyopathy (SPARC) study.

Interstitial fibrosis is a histopathological hallmark of hypertrophic cardiomyopathy (HCM). Although extracellular matrix (ECM) biomarkers, including matrix metalloproteinases, are overexpressed in HCM patients, they do not correlate with sudden cardiac death (SCD) risk. The objective of this study was to determine whether scleraxis, a transcription factor that regulates collagen gene expression, is detectable in HCM patients and correlates with disease burden. Between 2017 and 2018, a total of 46 HCM patients were enrolled (58 ± 14 years (31 males, 15 females)) with a mean 5 year SCD risk of 2.3% ± 1.3%. Cardiac MRI confirmed HCM in all patients with a mean interventricular septal thickness of 20 ± 2 mm. Late gadolinium enhancement (LGE) was present in 32 (70%) study participants occupying 18% ± 7% of the left ventricular (LV) myocardium. Serum scleraxis levels were significantly higher in the HCM patients by approximately twofold as compared to controls (0.76 ± 0.06 versus 0.32 ± 0.02 ng/mL, p < 0.05). No correlation was demonstrated between serum scleraxis levels and markers of disease severity in HCM patients, including maximum LV wall thickness, %LGE, and SCD risk factors. Serum scleraxis is elevated in the HCM population. Future studies are warranted to evaluate the prognostic value of scleraxis in identifying high-risk HCM patients who require aggressive management for prevention of SCD.

Three-dimensional Deep Convolutional Neural Networks for Automated Myocardial Scar Quantification in Hypertrophic Cardiomyopathy: A Multicenter Multivendor Study.

Background Cardiac MRI late gadolinium enhancement (LGE) scar volume is an important marker for outcome prediction in patients with hypertrophic cardiomyopathy (HCM); however, its clinical application is hindered by a lack of measurement standardization. Purpose To develop and evaluate a three-dimensional (3D) convolutional neural network (CNN)-based method for automated LGE scar quantification in patients with HCM. Materials and Methods We retrospectively identified LGE MRI data in a multicenter (n = 7) and multivendor (n = 3) HCM study obtained between November 2001 and November 2011. A deep 3D CNN based on U-Net architecture was used for LGE scar quantification. Independent CNN training and testing data sets were maintained with a 4:1 ratio. Stacks of short-axis MRI slices were split into overlapping substacks that were segmented and then merged into one volume. The 3D CNN per-site and per-vendor performances were evaluated with respect to manual scar quantification performed in a core laboratory setting using Dice similarity coefficient (DSC), Pearson correlation, and Bland-Altman analyses. Furthermore, the performance of 3D CNN was compared with that of two-dimensional (2D) CNN. Results This study included 1073 patients with HCM (733 men; mean age, 49 years ± 17 [standard deviation]). The 3D CNN-based quantification was fast (0.15 second per image) and demonstrated excellent correlation with manual scar volume quantification (r = 0.88, P < .001) and ratio of scar volume to total left ventricle myocardial volume (%LGE) (r = 0.91, P < .001). The 3D CNN-based quantification strongly correlated with manual quantification of scar volume (r = 0.82-0.99, P < .001) and %LGE (r = 0.90-0.97, P < .001) for all sites and vendors. The 3D CNN identified patients with a large scar burden (>15%) with 98% accuracy (202 of 207) (95% confidence interval [CI]: 95%, 99%). When compared with 3D CNN, 2D CNN underestimated scar volume (r = 0.85, P < .001) and %LGE (r = 0.83, P < .001). The DSC of 3D CNN segmentation was comparable among different vendors (P = .07) and higher than that of 2D CNN (DSC, 0.54 ± 0.26 vs 0.48 ± 0.29; P = .02). Conclusion In the hypertrophic cardiomyopathy population, a three-dimensional convolutional neural network enables fast and accurate quantification of myocardial scar volume, outperforms a two-dimensional convolutional neural network, and demonstrates comparable performance across different vendors. © RSNA, 2019 Online supplemental material is available for this article.

Carotid arterial stiffness is increased and related to left ventricular function in patients with hypertrophic cardiomyopathy.

To assess the carotid mechanical properties in patients with hypertrophic cardiomyopathy and the relation between arterial stiffness and left ventricular function in this setting. We have prospectively enrolled 71 patients (52 ± 16 years, 34 men) with hypertrophic cardiomyopathy, divided into two groups depending on the presence (46 patients) or absence (25 patients) of cardiovascular risk factors associated with increased arterial stiffness. Twenty-five normal subjects similar by age and gender with hypertrophic cardiomyopathy patients without risk factors formed the control group. A comprehensive echocardiography was performed in all subjects. Carotid arterial stiffness index (β index), pressure-strain elastic modulus, arterial compliance, and pulse wave velocity were also obtained using an echo-tracking system. β index, pulse wave velocity, and pressure-strain elastic modulus were significantly higher in hypertrophic cardiomyopathy patients without risk factors compared to controls. After linear regression analysis, the increase in carotid β index was independently correlated with the presence of hypertrophic cardiomyopathy [beta = 0.49, 95% confidence interval (CI) = 1.04-3.02; P < 0.001]. In the entire hypertrophic cardiomyopathy population arterial stiffness parameters correlated with age, gender, hypertension degree, presence of hypercholesterolaemia, and the E/e' ratio. In multivariable analysis, β index (beta = 0.36, 95% CI = 0.32-1.25; P = 0.001), global left ventricular longitudinal strain, and the presence of left ventricular outflow tract obstruction were independently correlated with the E/e' ratio. In patients with hypertrophic cardiomyopathy arterial stiffness is increased independently of age or presence of cardiovascular risk factors. Carotid artery stiffness is independently related to left ventricular filling pressure, increased arterial stiffness representing a possible marker of a more severe phenotype.

Validation of the hypertrophic cardiomyopathy risk-sudden cardiac death calculator in Asians

ObjectiveThe hypertrophic cardiomyopathy (HCM) risk-sudden cardiac death (SCD) calculator endorsed by the 2014 European Society of Cardiology has not been independently validated in the Asians. We aimed to investigate whether...

Exercising caution: is there a role for exercise testing in the hypertrophic cardiomyopathy population?

Exercising caution: is there a role for exercise testing in the hypertrophic cardiomyopathy population?