Adult Hypertrophic Cardiomyopathy Patients Research Articles

Genotype-phenotype relationship in hypertrophic cardiomyopathy

Abstract Background/Introduction Hypertrophic cardiomyopathy (HCM) is an inherited highly heterogeneous disease with variable penetrance and expression, but the exact relationship between the underlying genetic cause and the clinical course remains elusive. Purpose The aim of our study was to analyse the phenotypic and molecular characteristics of individuals with HCM examined and treated at our University Hospital. Methods Clinical data from adult HCM patients treated at our hospital between 2005 and 2023 were analysed. Informed consents to participate in the study were obtained from all participants. Clinical manifestation, instrumental examination and next generation sequencing (NGS) data of HCM related genes were collected. The Mann–Whitney U for two groups and Kruskal–Wallis tests for more than two groups were used to compare continuous variables. Univariate logistic regression was used to analyze categorical variables. Results The study involved 191 unrelated individuals, 58.6% males, the median age at HCM diagnosis was 50, interquartile range 37 – 60 years. A median follow-up was 3.9 [1.6-6.4] years. Pathogenic and likely pathogenic (P/LP) variants were identified in 45.5% (N=87) of affected individuals. Truncating variants were observed in 31 individuals. MYBPC3 P/LP variants were the most common (N=47), following by MYH7 (N=22) and other (N=18). Individuals with MYBPC3 P/LP truncating variants had higher HCM estimated 5-year risk of sudden cardiac death (SCD) during primary evaluation (3.1 [2.5-4.6]) compared to individuals with P/LP variants in other genes (2.4 [1.9-3.7]) and individuals with negative NGS results (1.8 [1.5-2.7], p<0,001). Patients with MYBPC3 P/LP variants experienced the earliest onset of symptoms (median age 37.0 [30.5-50.0] years) and HCM diagnosis (median age 38.0 [31.0-51.5] years) compared to individuals with other genes P/LP variants (median age 46.0 [31.0-56.2] years and 47.5 [31.5 – 59.5] years, respectively) and genotype negative individuals (median age 51.5 [44.0-61.0] years and 52.0 [45.0-63.2] years, respectively), p>0,001). The presence of P/LP variant was associated with significantly thicker left ventricular wall (maximal thickness) on cardiac imaging in comparison with negative NGS results (18.0 [15.0-21.0] mm vs. 16.0 [14.0-18.0] mm, p=0.002 on transthoracic echocardiography and 20.0 [17.0-22.5] mm vs. 18.0 [16.0-20.0] mm, p<0,001 on cardiac magnetic resonance). The presence of MYBPC3 truncating variants were associated with the greatest risk of ventricular tachycardia in comparison with negative NGS results (OR 3.05, 95% CI:1.3, 8.0, p=0.025). Conclusion More severe HCM phenotype is associated with detection of P/LP variants in HCM related genes. The presence of the MYBPC3 P/LP variant is associated with an earlier onset of the disease and truncating variants of this gene are related to a higher risk for ventricular tachycardia and an estimated 5-year risk of SCD.

Association between hospital volume, clinical events, resource utilization, and costs of septal myectomy and alcohol septal ablation procedures in US patients with hypertrophic cardiomyopathy

Abstract Background Prior studies have evaluated the relationship between hospital procedural volumes of septal reduction therapies (SRT) for obstructive hypertrophic cardiomyopathy (HCM) and outcomes. Other analyses, including economic outcomes, are needed to support clinical decisions among adult patients diagnosed with HCM. Objective The objective of this study was to reconfirm the relationship between higher SRT procedural volume, including septal myectomy (SM) -with and without mitral valve repair or replacement (MVRR)- and alcohol septal ablation (ASA), and clinical events, healthcare resource utilization, and hospitalization costs using more contemporary hospitalization data. Data & Methods This cross-sectional study utilizes retrospective observational data from the PINC AI™ Healthcare Database (PHD), a US hospital administrative database. The study population consists of adult patients with HCM undergoing ASA or SM procedures between January 1, 2012, and March 31, 2022. Hospital volume was determined by tertiles of total SRT performed for ASA, SM separately during the study period. We compare clinical events (including death, stroke, acute renal failure, and pacemaker implantation), readmission, index length of stay, and hospitalization costs across tertiles. We present p-values between tertiles and within procedure types. Results A total of 3,068 adult HCM patients in 315 US hospitals underwent SRT during the study period, including 1,400 with ASA and 1,668 with SM. Table 1 shows the patient and hospital characteristics by tertiles of hospital volume. The median age of patients was 66 years for ASA and 62 years for SM. Medicare coverage accounted for 59.9% of ASA and 44.9% of SM, followed by commercial coverage (28.5% of ASA and 39% of SM). Most hospitals in the study were teaching hospitals (74% for ASA and 67% for SM). In the highest SRT volume tertile (5% of hospitals performing SRT) the average annual number of procedures was 3.5 ASA and 4.9 SM. Table 2 presents the outcomes by hospital volume (low-, mid-, and high-volume). Recorded in-hospital death rates for ASA were 1.4%, 1.4%, and 1.1%, respectively (not statistically different); for SM, 5.1%, 3.4% and 2.9%, respectively (not statistically different). For ASA and SM, index hospital costs, and 30-day readmission rates had an inverse relationship to hospital volume, with statistically significant differences for both procedures between the low- and high-volume hospitals (p<0.05). Conclusion The annual number of SRT procedures for obstructive HCM remains low, even for higher volume hospitals. This study shows high variability in clinical events, resource utilization, and in-hospital costs by hospital procedure volume and type of SRT. We reconfirmed that higher hospital procedure volume is associated with fewer adverse clinical events and lower costs.

Anatomical, functional and prognostic correlates of resting coronary flow velocity in patients with hypertrophic cardiomyopathy

Abstract Background The clinical significance of baseline peak diastolic coronary flow velocity (CFV) in the left anterior descending coronary artery (LAD) has not been investigated yet in patients with hypertrophic cardiomyopathy (HCM). Aim To assess the anatomical, functional and prognostic correlates of baseline LAD CFV in HCM. Methods 384 consecutive adult HCM patients (age=52+15 years, 164 [43%] females) with no known coronary artery disease from 8 centers in 5 countries were prospectively analyzed. All patients underwent comprehensive transthoracic echocardiography including CFV measurement with pulse wave Doppler in the mid-distal LAD. All patients had preserved left ventricular (LV) function. LV force was calculated as (peak instantaneous LV outflow tract gradient+systolic blood pressure)/LV end-systolic volume. Patients were followed for a median of 50 months (IQ range 18-97 months), the outcome measure was a composite endpoint of all-cause death and acute heart failure. Results The mean CFV was 36±11 cm/s. CFV was positively correlated with LV maximal wall thickness (r=0.375, p<0.001), LV maximal septal thickness (r=0.320, p<0.001), resting LV outflow tract gradient (r=0.274, p<0.001), LV force (r=0.227, p<0.001), mean E/e’ (r=0.479, p<0.001) and heart rate (r=0.221, p<0.001). During follow-up, 54 events occurred (33 all-cause deaths and 21 acute heart failures). Receiver operating characteristic analysis was used to determine the best cut-off value of CFV (>31 cm/s) to predict the composite endpoint. Patients with CFV >31 cm/s had a significantly worse 10-year event-free survival compared to those with CFV ≤31 cm/s, see Figure. Conclusion Higher resting LAD CFV is associated with greater LV wall thickness, higher LV outflow tract gradient, faster heart rate and more elevated left ventricular filling pressures in HCM. Elevated resting CFV may indicate a coronary microcirculation dysfunction either primary or secondary to anatomical (septal hypertrophy), functional (increased myocardial oxygen demand), or autonomic (increased sympathetic drive) determinants. Whatever the underlying endotype, high resting CFV is related to worse prognosis in the long term.Figure.

The importance of vasodilator stress echocardiography in predicting all-cause mortality and acute heart failure in hypertrophic cardiomyopathy

Abstract Background Reduced coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) during vasodilator stress echocardiography (VSE) is a marker of poor outcome and is associated with higher baseline coronary flow velocity (CFV) in hypertrophic cardiomyopathy (HCM). However, whether resting CFV has additive predictive value to CFVR during VSE in HCM is unknown. Aim To assess the prognostic value of baseline CFV and CFVR during VSE in HCM. Methods 325 adult HCM patients (age=52+15 years, 147 [45%] females) with preserved left ventricular function and no known coronary artery disease who underwent VSE in 6 certified centers between 1999 and 2021 were prospectively analyzed. VSE modality was adenosine (0.14 mg/kg/min in 2', n=232) or dipyridamole (0.84 mg/kg in 6', n=93). CFVR in the LAD was assessed by transthoracic (n=306) or transoesophageal (n=19) echocardiography. Patients were followed for a median of 67 months (IQ range 31-103 months), the primary endpoint was a composite of all-cause mortality and acute heart failure (HF). Results Receiver operating characteristic analysis was used to determine the best cut-off value of CFV (>31 cm/s, elevated) and CFVR (≤2.0, reduced) to predict the primary endpoint. Patients with reduced CFVR had more frequently elevated baseline CFV (75% vs 49%, p<0.001). Elevated resting CFV was a predictor of composite endpoint at univariable (HR 2.04, 95% CI 11.05-3.97, p=0.035) but not at multivariable analysis. A reduced CFVR was an independent predictor of all-cause mortality (HR 5.50, 95% CI 1.94-15.59, p=0.001), acute HF (HR 5.80, 95% CI 1.60-21.00, p=0.007), and the composite end-point (HR 4.95, 95% CI 2.39-10.25, p<0.001). The 5-year event rate was 6-fold higher in patients with reduced CFVR compared to patients with preserved CFVR (19% vs 3%, p<0.001), with no additional impact of resting CFV (see Figure). Conclusion LAD CFVR ≤2.0 during VSE is a strong and independent predictor of all-cause mortality and acute HF in HCM. Elevated resting CFV is more frequent in patients with reduced CFVR, but has no independent prognostic value when CFVR is considered.Kaplan-Meier event-free survival curves

Comparing indices of systemic inflammation and cardiac phenotype between hypertensive and non-hypertensive hypertrophic cardiomyopathy

Abstract Background Arterial hypertension (HTN) is associated with excess mortality in hypertrophic cardiomyopathy (HCM), but underlying mechanisms are largely elusive. Purpose The purpose of this study was to investigate the association between HTN and indices of systemic inflammation and cardiac function in a HCM cohort. Methods This was a single-center cross-sectional case-control study comparing 30 adult HCM patients with HTN (HTN+) and 30 sex- and age-matched HCM patients without HTN (HTN-). Echocardiographic measures were assessed using post-processing analyses by a blinded investigator. Results Mean age of the total sample was 54.6±10.1 years, 30% were women. Mean end-diastolic interventricular septum (IVSd) thickness was 2.1±0.4 cm, 18% previously underwent septal reduction therapy, and 47% had left ventricular outflow tract obstruction. HTN+ portrayed more severe IVSd thickness than HTN- [2.2±0.3 cm vs. 2.0±0.4 cm; p = 0.017], while echocardiographic measures of systolic and diastolic function, including speckle-tracking derived parameters, did not differ between groups. Moreover, levels of N-terminal pro B-type natriuretic peptide were balanced between groups. Compared with HTN-, HTN+ patients exhibited higher circulating plasma levels of interleukin-6 [2.8 pg/ml (2.0, 5.4) vs. 2.1 pg/ml (1.5, 3.4); p = 0.008] and high-sensitivity C-reactive protein [2.6 mg/l (1.4, 6.5) vs. 1.1 mg/l (0.9, 2.4); p = 0.004] Conclusion This study demonstrates that HTN is associated with low-grade systemic inflammation among HCM patients. Moreover, this analysis indicates that HTN+ do not exhibit an altered systolic and diastolic function compared to HTN-. Accordingly, the adverse impact of HTN in HCM patients may be a consequence of systemic effects rather than alterations of cardiac function.TableFigure

Abstract 14514: Hypertrophic Cardiomyopathy - Genotype Distribution and Genotype-Phenotype Correlations - A Unique Perspective From a Single Center Study

Background: The role of genotype in risk stratification of hypertrophic cardiomyopathy (HCM) is unclear. Hypothesis: Genotype status affects phenotype and associated outcomes. Aims: To evaluate genotype-phenotype correlations in all adult HCM patients seen at our Cardiac Specialty Center over 13 years and associated outcomes. Methods: We evaluated genotype-phenotype correlations, all-cause mortality, and a composite outcome, including mortality, stroke, implantable cardioverter-defibrillator placement, heart failure hospitalization, LV assist device implantation, heart transplant, septal myectomy, and alcohol septal ablation. Results: Of 827 HCM patients, genotyping was completed in 754 (91.2%), which included 27% genotype-positive (Gen-P), 22% variants of unknown significance (VUS), and 51% genotype-negative (Gen-N) patients with a mean age of 47, 57, and 58 years, respectively. The most common gene implicated was MYBPC3 (63%). LV hypertrophy on electrocardiogram was more frequent in Gen-N than Gen-P patients. Gen-P patients had more frequent non-sustained ventricular tachycardia on Holter monitoring (25% vs 10%), grade III diastolic dysfunction (12% vs 7%), elevated ProBNP (71% vs 61%), and lower ejection fraction (66% vs 69%) than Gen-N patients (P <.05 for all comparisons). All heart transplantations (N=5) were performed in Gen-P patients. LVOT obstruction was more frequent in Gen-N than Gen-P patients (48% vs 26%, P <.01). Distribution of outcomes is shown in Panels A-H. The composite outcome was worse in Gen-P vs Gen-N patients (HR 1.84, P <.01). The other independent predictors of poor composite outcome were old age, male sex, obesity, and atrial fibrillation. A separate analysis of mortality showed similar survival in all groups. Conclusion: Differences exist in phenotype and outcomes based on the genotype status, with more severe phenotype and poorer outcomes in Gen-P patients in our single-state single-center experience.

Association between clinical phenotypes of hypertrophic cardiomyopathy and Ca2+ gene variation gene variation

Objective: To observe the association between clinical phenotypes of hypertrophic cardiomyopathy (HCM) patients and a rare calcium channel and regulatory gene variation (Ca2+ gene variation) and to compare clinical phenotypes of HCM patients with Ca2+ gene variation, a single sarcomere gene variation and without gene variation and to explore the influence of rare Ca2+ gene variation on the clinical phenotypes of HCM. Methods: Eight hundred forty-two non-related adult HCM patients diagnosed for the first time in Xijing Hospital from 2013 to 2019 were enrolled in this study. All patients underwent exon analyses of 96 hereditary cardiac disease-related genes. Patients with diabetes mellitus, coronary artery disease, post alcohol septal ablation or septal myectomy, and patients who carried sarcomere gene variation of uncertain significance or carried>1 sarcomere gene variation or carried>1 Ca2+ gene variation, with HCM pseudophenotype or carrier of ion channel gene variations other than Ca2+ based on the genetic test results were excluded. Patients were divided into gene negative group (no sarcomere or Ca2+ gene variants), sarcomere gene variation group (only 1 sarcomere gene variant) and Ca2+ gene variant group (only 1 Ca2+ gene variant). Baseline data, echocardiography and electrocardiogram data were collected for analysis. Results: A total of 346 patients were enrolled, including 170 patients without gene variation (gene negative group), 154 patients with a single sarcomere gene variation (sarcomere gene variation group) and 22 patients with a single rare Ca2+ gene variation (Ca2+ gene variation group). Compared with gene negative group, patients in Ca2+ gene variation group had higher blood pressure and higher percentage of family history of HCM and sudden cardiac death (P<0.05); echocardiographic results showed that patients in Ca2+ gene variation group had thicker ventricular septum ((23.5±5.8) mm vs. (22.3±5.7) mm, P<0.05); electrocardiographic results showed that patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (400.6±47.2) ms, P<0.05) and higher RV5+SV1 ((4.51±2.26) mv vs. (3.50±1.65) mv, P<0.05). Compared with sarcomere gene variation group, patients in Ca2+ gene variation group had later onset age and higher blood pressure (P<0.05); echocardiographic results showed that there was no significant difference in ventricular septal thickness between two groups; patients in Ca2+ gene variation group had lower percentage of left ventricular outflow tract pressure gradient>30 mmHg (1 mmHg=0.133 kPa, 22.8% vs. 48.1%, P<0.05) and the lower early diastolic peak velocity of the mitral valve inflow/early diastolic peak velocity of the mitral valve annulus (E/e') ratio ((13.0±2.5) vs. (15.9±4.2), P<0.05); patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (399.0±43.0) ms, P<0.05) and lower percentage of ST segment depression (9.1% vs. 40.3%, P<0.05). Conclusion: Compared with gene negative group, the clinical phenotype of HCM is more severe in patients with rare Ca2+ gene variation; compared with patients with sarcomere gene variation, the clinical phenotype of HCM is milder in patients with rare Ca2+ gene variation.

Extended Myectomy for Hypertrophic Cardiomyopathy: Early Outcomes From a Nascent Centre of Excellence in Canada

Hypertrophic cardiomyopathy (HCM) is one of the commonest inherited cardiac abnormalities. The disorder is clinically and genetically heterogeneous and is characterized by left ventricular wall thickening that is not explained by abnormal loading conditions. HCM is estimated to affect between 1 in 200 and 1 in 500 people in the general population. In the majority of cases, HCM patients have a relatively benign course; however, if left untreated, this abnormality can lead to sudden cardiac death, especially in young adults and athletes. Therefore, early diagnosis is crucial to help implement the proper management for patients with HCM. In response to the growing need for more HCM centres of excellence in Canada, we developed one such centre at the University of Ottawa Heart Institute from the start of 2018. This centre will help in the early diagnosis and management of HCM patients, especially those with left ventricular outflow tract obstruction who might benefit from myectomy surgery. This paper describes our early experience with surgical myectomy in adult HCM patients between January 2018 and December 2020. We report the results of 27 patients with HCM who underwent myectomy surgery during the study period. All 27 patients survived to discharge, and all were still alive at 6 months postdischarge. Our experience highlights the crucial role that preoperative and perioperative imaging play in the management of this condition, in addition to the vital role of having a committed “heart team” of cardiologists, surgeons, and anesthesiologists.

Prognostic significance of serum alkaline phosphatase for all-cause mortality in patients with hypertrophic cardiomyopathy: A cohort of the hospitalized population.

Higher levels of serum alkaline phosphatase (ALP) as a novel risk factor was recently found associated with mortality in different population, whereas, the relationship remains unknown in hypertrophic cardiomyopathy (HCM) population. In this study, we hypothesized that increased ALP could predict all-cause mortality in the adult HCM population. In this cohort study, retrospective data from 538 HCM patients consecutively recruited in West China Hospital were collected. Patients were divided into two groups by baseline ALP with 80IU/L as the cutoff. All-cause mortality was set as the endpoint. Subgroup analysis was conducted in patients with normal liver function. In total, 461 adult HCM patients were included. After a median follow-up of 4.7 years, 91 patients died. Alkaline phosphatase was an independent predictor of all-cause mortality since patients in the higher ALP group had an increased risk (adjusted HR 2.0, 95% CI: 1.3-3.3, P < 0.01) compared with those in the lower ALP group. In subgroup analysis, the relationship was consistent with the overall (adjusted HR: 3.0, 95% CI: 1.7-5.3, P < 0.01 for the higher ALP group). In the Chinese cohort study of HCM patients, serum ALP is independently associated with all-cause mortality. Patients with a measured value above 80IU/L had an increased risk of all-cause mortality and this cutoff might help with risk stratification in HCM population.

Noncontrast T1ρ dispersion imaging is sensitive to diffuse fibrosis: A cardiovascular magnetic resonance study at 3T in hypertrophic cardiomyopathy

PurposeTo determine the sensitivity of a noncontrast T1 dispersion cardiovascular magnetic resonance technique for detecting diffuse fibrosis in hypertrophic cardiomyopathy (HCM). MethodsThirty-two adult HCM patients and ten age- and gender-matched healthy volunteers were prospectively included in this study. Patients and controls underwent cine, T1ρ-mapping, and pre- and post-contrast T1-mapping imaging using a 3-T magnetic resonance system. Myocardial extracellular volume fraction (ECV) maps were obtained using pre- and post-contrast T1 maps to determine reference values for diffuse fibrosis. Myocardial T1ρ and T1ρ dispersion maps called myocardial fibrosis index (mFI) maps provided 570 myocardial segments for Pearson or Spearman correlation analysis. The left ventricle myocardia of the HCM patients were divided into 16 segments that were further classified as either normal-thickness myocardium (<15 mm) (HCM-N) or hypertrophic myocardium (≥15 mm) (HCM-H). ResultsECV and mFI values increased progressively on a per-segment basis from healthy controls to the HCM-N group and then to the HCM-H group (ECV: 27.4 ± 2.8% vs. 31.1 ± 4.2% vs. 37.6 ± 6.9%, respectively [P < 0.0001]; mFI: 6.1 ± 0.9 ms vs. 8 ± 1.9 ms vs. 11 ± 3.3 ms, respectively [P < 0.0001]). There was a strong positive correlation between the segmented ECV and the mFI (r = 0.878). The mFI was equally or significantly better than the ECV for differentiating fibrosis content in HCM-N and HCM-H according to their receiver operating characteristic curves. ConclusionA T1ρ dispersion imaging mFI can sensitively detect diffuse myocardial fibrosis in HCM, even in HCM-N.

Relation between lymphocyte to monocyte ratio and survival in patients with hypertrophic cardiomyopathy: a retrospective cohort study.

BackgroundThe lymphocyte-to-monocyte ratio (LMR) has been proposed as a novel prognostic factor in malignancies and cardiovascular diseases. Our study aimed to ascertain whether LMR is a useful biomarker in discriminating the hypertrophic cardiomyopathy (HCM) patients at higher risk of all-cause mortality.MethodsThis retrospective study consisted of 354 adult HCM patients. Cox’s proportional hazards regression models were used to analyze the association between LMR and all-cause mortality. Smooth curve fitting was conducted to explore the linear relationship between LMR and all-cause mortality.ResultsDuring the follow-up, 44 patients reached the study endpoint. The all-cause mortality rate was 7.3 per 100 person-years in the first tertile and decreased across the three tertiles of LMR. With the first tertile as reference, adjusted hazard ratios (HR) for all-cause mortality were 0.43 for the second tertile (95% CI [0.20–0.91], p = 0.027) and 0.39 for the third tertile (95% CI [0.17–0.90], p = 0.028), respectively. Smooth curve fitting exhibited a nonlinear relationship between LMR values and all-cause mortality. For LMR < 6.5, per SD increase resulted in a significantly decreased risk of all-cause mortality by 62% (HR: 0.38, 95% CI [0.21–0.68]). For LMR ≥ 6.5, the all-cause mortality risk did not progressively increase. Stratified and subgroup analyses revealed similar results to the main analyses,andE-value analysis suggested robustness to unmeasured confounding.ConclusionsThe study demonstrated that LMR was an independent predictor of all-cause mortality in HCM patients, and LMR may be useful for identifying HCM patients at high mortality risk.

Impact of comorbidities on atrial fibrillation and sudden cardiac death in hypertrophic cardiomyopathy.

The impact of comorbid disease states on the development of atrial and ventricular arrhythmias in patients with hypertrophic cardiomyopathy (HCM) remains unresolved. Evaluate the association of comorbidities linked to arrhythmias in other cardiovascular diseases (e.g., obesity, systemic hypertension, diabetes, obstructive sleep apnea, renal disorders, tobacco, and alcohol use) to atrial fibrillation (AF) and sudden cardiac death (SCD) events in a large cohort of HCM patients. A total of 2269 patients, 54 ± 15 years of age, 1392 males, were evaluated at the Tufts HCM Institute between 2004 and 2018 and followed for an average of 4 ± 3 years for new-onset clinical AF and SCD events (appropriate defibrillation for ventricular tachyarrhythmias, resuscitated cardiac arrest, or SCD). One or more comorbidity was present in 75% of HCM patients, including 50% with ≥2 comorbidities, most commonly obesity (body mass index [BMI] ≥ 30 kg/m2 ) in 43%. New-onset atrial fibrillation developed in 11% of our cohort (2.6%/year). On univariate analysis, obesity was associated with a 1.7-fold increased risk for AF (p = .03) with 12% of obese patients developing AF (3.3%/year) as compared to 7% of patients with BMI < 25 kg/m2 (1.6%/year; p = .006). On multivariate analysis, age and LA transverse dimension emerged as the only variables predictive of AF. Comorbidities, including obesity, were not independently associated with AF development (p > .10 for each). SCD events occurred in 3.3% of patients (0.8%/year) and neither obesity nor other comorbidities were associated with increased risk for SCD (p > .10 for each). In adult HCM patients comorbidities do not appear to impact AF or SCD risk. Therefore, for most patients with HCM, adverse disease related events of AF and SCD appear to be primarily driven by underlying left ventricular and atrial myopathy as opposed to comorbidities.

Abstract 9715: Feasibility of Using Machine Learning to Establish a Risk Prediction Model for Sudden Cardiac Death in Patients with Hypertrophic Cardiomyopathy

Introduction: Risk stratification for sudden cardiac death (SCD) is a great challenge in managing hypertrophic cardiomyopathy (HCM). Hypothesis: This study attempted for the first time to build a machine learning (ML) model for SCD risk prediction. Methods: The present study consisted of 1631 consecutive adult HCM patients without a history of SCD events. Extreme gradient boosting (XGBoost) was applied for ML model construction. We compared the predictive performance of the ML model with that of conventional models by calculating C-statistics and interpreted the ML model output using the SHapley Additive exPlanation (SHAP) value. Results: Fifty patients reached SCD endpoints during a median follow-up of 4.6 years. The C-statistic of the ML model was 0.745 [95% confidence interval (CI), 0.723-0.766], which was significantly higher than that of the model recommended in the 2014 European Society of Cardiology guidelines (C-statistics =0.609; 95% CI 0.585-0.623) and the model recommended in the 2020 American College of Cardiology/American Heart Association guidelines (C-statistics =0.628; 95% CI 0.604-0.652). The ML model incorporated 12 features as predictors, including 5 conventional SCD risk markers (NSVT, quantification of LGE, family history of SCD, LVEF 50%, unexplained syncope), WBC, creatine, uric acid, TBIL and cholesterol, NT-proBNP and family history of HCM. Using SHAP values, we quantified the contribution of each feature within the ML model to the final prediction and visualized the relationship between features and SCD risk. Conclusion: Our study constructed an ML model for the prediction of SCD risk in patients with HCM and provided a clinically intuitive interpretation. The ML model showed better discrimination performance than conventional models, demonstrating the feasibility of ML in SCD risk prediction for patients with HCM.

Abstract 10757: Patient-Reported Quality of Life Outcomes in Hypertrophic Cardiomyopathy Patients

Background: Few studies have systematically assessed quality of life (QOL) in hypertrophic cardiomyopathy (HCM) patients not meeting the septal reduction therapy (SRT) threshold, but require avoiding isometric exertion and weightlifting. We prospectively studied a newly developed QOL instrument to examine the associations between patient characteristics and self-reported QOL scores in HCM patients not anticipated to undergo SRT for at least 6 months. Methods: A single-center, prospective sample of 51 adult HCM patients (54±14 years, mean interventricular septum thickness = 1.7±0.4cm, 65% with left ventricular outflow tract (LVOT) obstruction, mean provokable LVOT gradient 65±42 mmHg, 59% men) completed a baseline 70-item QOL instrument, adapted from validated QOL questionnaires. All patients signed informed consent. Results: Mean self-reported QOL scores (on a 5-point Likert scale with higher scores indicating higher QOL) were as follows: physical function (3.5±1), depression (3.7±1), anxiety (3.6±1), post-traumatic stress disorder (PTSD) (3.7±1), social function (4.1±1), spiritual acceptance of diagnosis (3.8±1), self-efficacy (4±1), and resilience (4±1). Men vs. women reported higher physical function (3.9±1 vs. 2.9±1), less depression (4±1 vs. 3.3±1), less anxiety (3.8±1 vs. 3.3±1), and higher social function (4.3±0.7 vs. 3.8±1) (all p&lt;0.05). Patients with obstructive HCM reported lower physical function scores (3.3±0.8) vs. non-obstructive HCM (3.8±0.8), p=0.03. Symptomatic patients reported lower physical function (3.2±0.8 vs. 4.3±0.5), social function (3.8±0.8 vs. 4.5±0.6) and worse depression (3.5±0.7 vs. 4.3±0.6), anxiety (3.4±0.8 vs. 4.1±0.7) and PTSD (3.5±0.8 vs. 4.3±0.9) scores (all p&lt;0.01). Presence of an implantable cardioverter defibrillator (ICD) was associated with lower vs. higher physical (2.9±0.4 vs. 3.5±1) and social function (3.6±1 vs. 4.1±1) (all p&lt;0.05). Conclusion: In HCM patients not requiring SRT, higher physical function scores were significantly associated with a better self-perceived overall health. Being a woman, having LVOT obstruction, presence of a defibrillator and presence of symptoms was significantly associated with worse perceived physical and social function.

Prognostic value of red blood cell distribution width for mortality in patients with hypertrophic cardiomyopathy

BackgroundRed blood cell distribution width (RDW) has emerged as a useful indicator for adverse outcomes in several cardiovascular diseases. The relation between RDW and the prognosis of hypertrophic cardiomyopathy (HCM) remains to be evaluated. We examined the relation between RDW and all-cause mortality and HCM-related death in a population of adult HCM patients. MethodsWe performed clinical evaluation in 414 consecutive adult HCM patients (median age, 57.5 years; male, 54.8%). ResultsDuring a median follow-up of 3.7 years, all-cause mortality and HCM-related death occurred in 75 (18.1%) and 50 (12.1%) patients, respectively. Based on the tertiles of baseline RDW, mortality increased with higher tertile. With the tertile 1 as reference, adjusted all-cause mortality hazard ratios (HRs) were 3.9 for the tertile 2 (95% confidence interval [CI]: 1.5–10.3) and 3.1 for the tertile 3 (95% CI: 1.1–8.2). Adjusted HCM-related death HRs were higher in the tertile 2 (HR: 5.5; 95% CI: 1.2–24.4) and tertile 3 (HR: 6.6; 95% CI: 1.5–29.0) compared with the tertile 1. Further smooth curve fitting exhibited a saturation effect after adjusting for confounders, and there were a two-stage change and an inflection point. Two-piecewise Cox model suggested mortality significantly increased with RDW level up to the inflection point (about 14.0% for both all-cause mortality and HCM-related death), and RDW was not associated with mortality after the point. ConclusionIn adult HCM patients, we found increased RDW was a significant risk predictor for all-cause mortality and HCM-related death, and a saturation effect was observed.

Hypertrophic cardiomyopathies requiring more monitoring for less atrial fibrillation-related complications: a clustering analysis based on the French registry on hypertrophic cardiomyopathy (REMY).

Defining the risk of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients is an important clinical and prognostic challenge. The aim of this study is to determine HCM phenogroups with different risk of AF occurrence at 5years. We applied retrospectively the Bayesian method, which can analyze a large number of variables, to differentiate phenogroups of patients with different risks of AF and prognoses across a French prospective on-going hospital-based registry of adult HCM patients (REMY). Clinical and imaging data were prospectively recorded, and patients were followed for 5years. A total of 1431 HCM patients were recruited, including 1275 analyzed in the present study after exclusion criteria. The population included 412 women, 369 patients with obstructive HCM, and 252 implanted with an ICD. AF occurred in 167 (11.6%) patients during the 5year follow-up. Three phenogroups were defined according to their common clinical and echocardiographic characteristics. Patients at the highest risk were oldest, more often female, with more frequent comorbidities, anteroposterior diameter of the left atrium was significantly greater, with diastolic dysfunction, outflow-tract obstruction, and mitral valve abnormality, and presented higher pulmonary artery pressure and/or right-ventricular dysfunction. These also had a higher risk of all-cause hospitalizations and death. Based on a clustering analysis, three phenogroups of HCM according to the risk of AF occurrence can be identified. It can indicate which patients should be more monitored and/or treated, particular to prevent the risk of stroke.

Dimensional Assessment of the Heart in Hypertrophic Cardiomyopathy Patients in Tertiary Care Hospitals

Hypertrophic cardiomyopathy (HCM) is one of the most prevalent disorders responsible for sudden cardiac death. Presentation of the symptoms varies due to the degree of thickening, and functional ability of the cardiomyocytes. The aims of the current study were to assess the clinical features, and cardiac morphology. This was a descriptive study with some analytical components. Thirty-four adult HCM patients were included within a duration of four months by patient selection checklist. After informed written consent, relevant information was noted and analyzed. Frequency distribution of phenotypes were, 56% asymmetric septal hypertrophy, 29% concentric hypertrophy, and 15% apical hypertrophy. Breathlessness and chest discomfort were present in 56% and 62% patients respectively, and higher in asymmetric septal HCM. Palpitation was very frequent in concentric HCM (90%). ECG revealed left ventricular hypertrophy in 85% of patients, and 79% of them had ST change. The interventricular septal thickness was narrower in apical type (14.80mm). The posterior wall thickness was higher in concentric HCM (19.20mm). The left atrial size was smaller in Concentric type(34.60mm).

Risk of atrial fibrillation in hypertrophic cardiomyopathy: A clustering analysis based on the French registry on hypertrophic cardiomyopathy (REMY)

Paroxysmal or chronic atrial fibrillation (AF) is frequent in hypertrophic cardiomyopathy (HCM), occurring in more than 20%-25% of patients, and is often considered as an important turning point for the quality of life of these patients. Defining the risk of atrial fibrillation in hypertrophic cardiomyopathy patients is an important clinical and prognostic challenge. The aim of this study is to determine HCM-phenogroups with different risk of AF-occurrence at 5-year. We applied retrospectively the Bayesian method, which can analyze a large number of variables, to differentiate phenogroups of patients with different risks of AF and prognoses across a French prospective on-going hospital-based registry of adult HCM patients (REMY). Clinical and imaging data were prospectively recorded, and patients were followed for 5 years. A total of 1431 HCM patients were recruited, including 1275 analyzed in the present study after exclusion criteria. The population included 412 women, and 369 patients with obstructive HCM. AF-occurred in 167 (11.6 %) patients during the 5-year follow-up. Three phenogroups were defined according to their common clinical and echocardiographic-characteristics. Patients at the highest risk were oldest, more often female, with more frequent comorbidities, anteroposterior diameter of the left atrium was significantly greater, with diastolic dysfunction, outflow-tract obstruction and mitral valve abnormality, and presented higher pulmonary artery pressure and/or right ventricular dysfunction. These also had a higher risk of all-cause hospitalizations and death. Based on a clustering analysis, three phenogroups of HCM according to the risk of AF occurrence can be identified. It can indicate which patients should be more monitored and/or treated, particular to prevent the risk of stroke.

Abstract 17341: Obesity is Associated With Progressive Heart Failure in Hypertrophic Cardiomyopathy

Background: The impact of comorbid disease states and lifestyle on the natural history of patients with hypertrophic cardiomyopathy (HCM) remains unknown. Objective: Evaluate the association of non-HCM comorbidities including obesity, hypertension, diabetes, obstructive sleep apnea, kidney disease, tobacco use, alcohol use, and lung disease with disease progression in a large cohort of HCM patients. Methods: 2269 patients evaluated at the Tufts HCM Institute between 2004 to 2019, ≥ 18 years of age (54 ± 15 years; 1392 male), and followed for an average of 4 ± 3.4 years for disease progression including progressive heart failure (HF) symptoms (from NYHA class I/II to NYHA class III/IV), new-onset atrial fibrillation (AF), or sudden death (SD) event (including appropriate defibrillation for ventricular arrhythmias, resuscitated cardiac arrest, or SD). Results: Of 1376 patients with NYHA class I/II symptoms at initial clinical evaluation, 252 (18%) developed progressive HF symptoms to NYHA class III/IV over follow-up (5%/year). Obesity (BMI ≥ 30) was significantly more prevalent in patients who had progressive HF during follow-up (43%) compared to those who remained without HF (34%, p = 0.014). In contrast, other comorbidities were not significantly associated with progressive HF symptoms (p &gt; 0.10 for all other comorbidities). Of the 1823 patients without AF history at initial clinical visit, 198 (11%) developed new-onset AF over follow-up (3%/year). No comorbidities were significantly associated with new-onset AF in HCM (p &gt; 0.10), although obesity was more common in patients who developed new-onset AF (48%) compared to those who had no AF (41%, p = 0.08). Notably, SD events were not associated with non-HCM comorbidities (p &gt; 0.10 for all comorbidities), and patients with SD events were less likely to have comorbidities than patients without SD events. Conclusions: In adult HCM patients, obesity is associated with progressive symptoms and outcomes supporting weight loss as an important modifier in obese HCM patients to potentially help prevent HCM complications. In contrast, other non-HCM comorbidities do not appear to impact disease course, and SD events are not associated with comorbidities in HCM.

Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy: The Utility of Myocardial Strain Based on Cardiac MR Tissue Tracking

Myocardial strain for assessment of hypertrophic cardiomyopathy (HCM) is of importance and may play a role in identifying obstruction in HCM patients. To evaluate the utility of myocardial strain for detecting left ventricular (LV) outflow tract (LVOT) obstruction in HCM patients based on magnetic resonance tissue tracking. Retrospective. In all, 44 adult HCM patients with LVOT obstruction and 108 adult HCM patients without LVOT obstruction. 1.5 T; Steady-state free-precession cine sequence; phase-sensitive inversion-prepared segmented gradient echo sequence for late gadolinium enhancement (LGE) imaging. Strain parameters including the local and global levels of LV myocardium and the subtraction (Sub) of myocardial strain variables between interventricular septal segments (IVSS) and noninterventricular septal segments (NIVSS) were measured for differentiating HCM with obstruction from nonobstruction. Average and maximum LV wall thickness (Average and Maximum LVWT) were also analyzed. Univariate and multivariate logistic regression analysis, area under the receiver operating characteristic (ROC) curve (AUC), intraclass correlation coefficient. In multivariate analysis, Average LVWT, Maximum LVWT, and the subtraction of radial peak strain (Sub Radial PS) between NIVSS and IVSS were independently associated with LVOT obstruction. The AUCs were 0.731, 0.840, and 0.890 for Average LVWT, Maximum LVWT, and Sub Radial PS, respectively. Sub Radial PS (cutoff value: 8.1%) demonstrated the highest sensitivity of 75.0% and a high specificity of 87.9% for identifying LVOT; Maximum LVWT (cutoff value: 22.9 mm) showed good sensitivity (72.7%) and specificity (83.3%). Combining Maximum LVWT >22.9 mm and Sub Radial PS > 8.1% achieved a better diagnostic performance (specificity 95.4%, sensitivity 70.5%). Combining Maximum LVWT >22.9 mm and Sub Radial PS >8.1% holds promise for objectively evaluating LVOT obstruction in HCM patients with very high specificity and acceptable sensitivity. 3 TECHNICAL EFFICACY STAGE: 2.