Survival analysis and gender differences in hypertrophic cardiomyopathy proband patients referred for genetic testing.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is believed to have low overall mortality rate, that could be influenced by gender, particularly among probands. We aimed to evaluate the survival rates and possible gender differences in a homogeneous cohort of HCM proband patients, referred for genetic testing, from the same geographical area, without differences in medical care access nor clinical referral pathways. METHODS: we compared the mortality rates of a cohort of consecutive HCM probands referred for genetic testing (2000-2022), from a Spanish region (xxx1) with a centralized genetic testing pathway, with its control reference population by Ederer II method. Gender differences were analyzed. RESULTS: Among the 649 HCM probands included in this study, there were significantly more men than women (61.3% vs 38.7, p < 0.05), with an earlier diagnosis (53.5 vs 61.1 years old, p < 0.05). Clinical evolution or arrhythmogenic HCM profile did no show no significant gender differences. Mean follow up was 9,8 years ±6,6 SD (9,9 ± 7 vs 9,6 ± 6,1, p = 0.59). No statistically significant differences in observed mortality, expected survival and excess mortality were found in the general HCM proband cohort. However, we found a significant excess mortality in female probands with HCM. No additional differences in analysis by genetic status were identified. CONCLUSION: Expected survival in our HCM probands did not differ from its reference population. However, despite no gender differences in phenotype severity were identified, proband HCM women did present a diagnosis delay and worse mortality outcomes.

[Sudden death in adults : Data from 305 consecutive autopsy cases in Algeria]. / Mort subite de l'adulte : données de 305 cas d'autopsies consécutives en Algérie.

BACKGROUND-AIMS: Sudden death in a young adult who showed no prodrome or complaint during his lifetime is a tragedy. The death often remains unexplained by doctors and is often the subject of a judicial investigation following which an autopsy is ordered. Our study joins several studies around the world, where the results have linked sudden death in adults to a cardiac origin. METHODS: Through a series of 305 autopsies carried out in the forensic medicine department of the Frantz Fanon hospital in the city of Bejaia in Algeria over a period of two years, 57 cases corresponded to unexplained sudden deaths, i.e. an incidence of 3 cases per 100,000 inhabitants per year. RESULTS: Sudden death was of cardiac origin in 50.8% of cases (N=28). Two epidemiologic profiles emerge in our study: the first is that of a man aged between 50 and 60 years of age, with several deleterious lifestyle habits (in particular smoking) with a cardiovascular history, previously followed by a cardiologist, who died suddenly out-of-hospital, from ischemic heart disease. The second is that of a young adult under 40 years of age, of average build, with no particular medical history, having not previously consulted a cardiologist, who died suddenly of hypertrophic cardiomyopathy. CONCLUSIONS: In many instances, we observed major anatomical lesion, which had not motivated any prior medical consultation either with a general practitioner or with a cardiologist.

Sex-Related Differences in Patients With Hypertrophic Cardiomyopathy Undergoing Alcohol Septal Ablation.

BACKGROUND: Previous studies have shown that women with hypertrophic obstructive cardiomyopathy (HCM) have worse long-term outcomes irrespective of intervention. However, the outcomes of patients undergoing alcohol septal ablation (ASA) based on sex have not been described. Hence, this study aimed to evaluate pressure changes and long-term mortality in patients with HCM undergoing ASA based on sex. METHODS AND RESULTS: This is a single-center retrospective study evaluating hemodynamic changes and long-term mortality in patients with HCM treated with ASA according to sex. A total of 259 patients were included (aged 68.4±11.9 years, 62.2% women). Women had higher age and baseline pressures at the time of ASA, with a greater percent reduction in mean left atrial pressure (men versus women: 2.2% versus 15.9%, respectively; P=0.02). Women had better survival (median survival rate of men versus women: 8.6 versus 12.5 years, respectively; P=0.011). On Cox multivariable regression, predictors of mortality were age (per group change <60 years, 61-70 years, 71-80 years, and >80 years; hazard ratio [HR], 1.45 [95% CI, 1.10-1.91], P=0.008), female sex (HR, 0.59 [95% CI, 0.35-0.99], P=0.048), chronic kidney disease (HR, 1.88 [95% CI, 1.06-3.33], P=0.031), and left ventricular outflow tract gradient reduction ≤86% (HR, 1.91 [95% CI, 1.14-3.19], P=0.014). CONCLUSIONS: Women with HCM undergoing ASA are older and have higher left-sided baseline pressures compared with men yet have better survival. Further studies exploring the mechanisms of differential outcomes according to sex in patients with HCM undergoing ASA are needed.

Relationship Between Genotype Status and Clinical Outcome in Hypertrophic Cardiomyopathy.

BACKGROUND: The genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and the relationship between genotype status and clinical outcome is incompletely resolved. METHODS AND RESULTS: We assessed a large international HCM cohort to define in contemporary terms natural history and clinical consequences of genotype. Consecutive patients (n=1468) with established HCM diagnosis underwent genetic testing. Patients with pathogenic (or likely pathogenic) variants were considered genotype positive (G+; n=312; 21%); those without definite disease-causing mutations (n=651; 44%) or variants of uncertain significance (n=505; 35%) were considered genotype negative (G-). Patients were followed up for a median of 7.8 years (interquartile range, 3.5-13.4 years); HCM end points were examined by cumulative event incidence. Over follow-up, 135 (9%) patients died, 33 from a variety of HCM-related causes. After adjusting for age, all-cause and HCM-related mortality did not differ between G- versus G+ patients (hazard ratio [HR], 0.78 [95% CI, 0.46-1.31]; P=0.37; HR, 0.93 [95% CI, 0.38-2.30]; P=0.87, respectively). Adverse event rates, including heart failure progression to class III/IV, heart transplant, or heart failure death, did not differ (G- versus G+) when adjusted for age (HR, 1.20 [95% CI, 0.63-2.26]; P=0.58), nor was genotype independently associated with sudden death event risk (HR, 1.39 [95% CI, 0.88-2.21]; P=0.16). In multivariable analysis, age was the only independent predictor of all-cause and HCM-related mortality, heart failure progression, and sudden death events. CONCLUSIONS: In this large consecutive cohort of patients with HCM, genotype (G+ or G-) was not a predictor of clinical course, including all-cause and HCM-related mortality and risk for heart failure progression or sudden death. G+ status should not be used to dictate clinical management or predict outcome in HCM.

Catheter ablation versus antiarrhythmic drug therapy for sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. METHODS: A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. RESULTS: Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029). CONCLUSIONS: In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.

Target population for a selective cardiac myosin inhibitor in hypertrophic obstructive cardiomyopathy: Real-life estimation from the French register of hypertrophic cardiomyopathy (REMY).

BACKGROUND: The efficacy of current pharmacological therapies in hypertrophic cardiomyopathy is limited. A cardiac myosin inhibitor, mavacamten, has recently been approved as a first-in-class treatment for symptomatic hypertrophic obstructive cardiomyopathy. AIMS: To assess the profile and burden of cardiac myosin inhibitor candidates in the hypertrophic cardiomyopathy prospective Register of hypertrophic cardiomyopathy (REMY) held by the French Society of Cardiology. METHODS: Data were collected at baseline and during follow-up from patients with hypertrophic cardiomyopathy enrolled in REMY by the three largest participating centres. RESULTS: Among 1059 adults with hypertrophic cardiomyopathy, 461 (43.5%) had obstruction; 325 (30.7%) of these were also symptomatic, forming the "cardiac myosin inhibitor candidates" group. Baseline features of this group were: age 58±15years; male sex (n=196; 60.3%); diagnosis-to-inclusion delay 5 (1-12)years; maximum wall thickness 20±6mm; left ventricular ejection fraction 69±6%; family history of hypertrophic cardiomyopathy or sudden cardiac death (n=133; 40.9%); presence of a pathogenic sarcomere gene mutation (n=101; 31.1%); beta-blocker or verapamil treatment (n=304; 93.8%), combined with disopyramide (n=28; 8.7%); and eligibility for septal reduction therapy (n=96; 29%). At the end of a median follow-up of 66 (34-106) months, 319 (98.2%) were treated for obstruction (n=43 [13.2%] received disopyramide), 46 (14.2%) underwent septal reduction therapy and the all-cause mortality rate was 1.9/100 person-years (95% confidence interval 1.4-2.6) (46 deaths). Moreover, 41 (8.9%) patients from the initial hypertrophic obstructive cardiomyopathy group became eligible for a cardiac myosin inhibitor. CONCLUSIONS: In this cohort of patients with hypertrophic cardiomyopathy selected from the REMY registry, one third were eligible for a cardiac myosin inhibitor.

Evaluation of new predictive scores for sudden cardiac death in childhood hypertrophic cardiomyopathy in a French cohort.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is rare in children, and sudden cardiac death (SCD) is difficult to predict. Two prognostic scores - HCM Risk-Kids and Precision Medicine for Cardiomyopathy (PRIMaCY) - were developed to assess the risk of SCD in the next 5 years in children with HCM. AIMS: To test the ability of these scores to predict SCD in children with HCM. Also, to identify factors associated with a severe cardiac rhythmic event (SCRE) (ventricular fibrillation, sustained ventricular tachycardia, heart transplant for rhythmic reasons or SCD). METHODS: Retrospective, multicentre, observational study at 10 medical centres in the Nord-Pas-de-Calais region, France. RESULTS: This study included 72 paediatric patients with HCM during 2009-2019 who were followed for a median (interquartile range [IQR]) of 8.5 (5.0-16.2) years. Eleven patients (15.3%) presented with SCRE. HCM Risk-Kids was high, with a median (IQR) score of 6.2% (2.1-12.8%; significant threshold≥6.0%) and the PRIMaCY median (IQR) score was 7.1% (2.6-15.0%; significant threshold≥8.3%). The positive predictive value was only 27.1% (95% confidence interval [CI] 21.5-32.5%) for HCM Risk-Kids (with a threshold of≥6.0%) and 33.2% (95% CI 27.1-38.9%) for the PRIMaCY score (with a threshold of≥8.3%). The negative predictive values were 95.4% (95% CI 92.3-97.7%) and 93.0% (95% CI 89.8-96.2%), respectively. Three of 28 patients with an implantable cardioverter defibrillator (ICD) experienced complications (including inappropriate shocks). CONCLUSION: HCM Risk-Kids and the PRIMaCY score have low positive predictive values to predict SCD in paediatric patients. If used alone, they could increase the rate of ICD implantation and thus ICD complications. Therefore, the scores should be used in combination with other data (genetic and magnetic resonance imaging results).

Pregnancy related complications in women with hypertrophic cardiomyopathy: a nationwide population-based cohort study.

BACKGROUND: The impact of hypertrophic cardiomyopathy (HCM) on cardiovascular and obstetrical outcomes in pregnant women remains unclear, particularly in Asian populations. This study aimed to evaluate the maternal cardiovascular and obstetrical outcomes in Korean women with HCM. METHODS: Using data from the Korean National Health Insurance Service database, we identified women who gave birth via cesarean section or vaginal delivery after being diagnosed with HCM between 2006 and 2019. Maternal cardiovascular and obstetrical outcomes were assessed based on the trimester of pregnancy. RESULTS: This study included 122 women and 158 pregnancies. No maternal deaths were noted; however, 21 cardiovascular events, such as hospital admission for cardiac problems, including heart failure and atrial fibrillation (AF), new-onset AF or ventricular tachycardia (VT) occurred in 14 pregnancies (8.8%). Cardiac events occurred throughout pregnancy with a higher occurrence in the third trimester. Cesarean sections were performed in 49.3% of the cases, and all cardiovascular outcomes occurring after delivery were observed in patients who had undergone cesarean sections. Seven cases involved preterm delivery, and two of these cases were accompanied by cardiac events, specifically AF. Pre-existing arrhythmia (AF: odds ratio (OR): 7.44, 95% confidence interval (CI): 2.61-21.21, P < 0.001; VT: OR: 31.61, 95% CI: 5.85-172.77, P < 0.001) was identified as a predictor for composite outcomes of cardiovascular events or preterm delivery. CONCLUSIONS: Most pregnant women with HCM were well-tolerated. However, cardiovascular complications could occur in some patients. Therefore, planned delivery may be necessary for selected patients, especially the women with pre-existing arrhythmias.

Clinical characteristics and outcomes of alcohol septal ablation in the era of transcatheter valve interventions.

BACKGROUND: The clinical efficacy and safety of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) have been well-established; however, less is known about outcomes in patients undergoing preemptive ASA before transcatheter mitral valve replacement (TMVR). AIMS: The goal of this study is to characterize the procedural characteristics and examine the clinical outcomes of ASA in both HCM and pre-TMVR. METHODS: This retrospective study compared procedural characteristics and outcomes in patient who underwent ASA for HCM and TMVR. RESULTS: In total, 137 patients were included, 86 in the HCM group and 51 in the TMVR group. The intraventricular septal thickness (mean 1.8 vs. 1.2 cm; p < 0.0001) and the pre-ASA LVOT gradient (73.6 vs. 33.8 mmHg; p ≤ 0.001) were higher in the HCM group vs the TMVR group. The mean volume of ethanol injected was higher (mean 2.4 vs. 1.7 cc; p < 0.0001). The average neo-left ventricular outflow tract area increased significantly after ASA in the patients undergoing TMVR (99.2 ± 83.37 mm2 vs. 196.5 ± 114.55 mm2; p = <0.0001). The HCM group had a greater reduction in the LVOT gradient after ASA vs the TMVR group (49.3 vs. 18 mmHg; p = 0.0040). The primary composite endpoint was higher in the TMVR group versus the HCM group (50.9% vs. 25.6%; p = 0.0404) and had a higher incidence of new permanent pacemaker (PPM) (25.5% vs. 18.6%; p = 0.3402). The TMVR group had a higher rate of all-cause mortality (9.8% vs. 1.2%; p = 0.0268). CONCLUSIONS: Preemptive ASA before TMVR was performed in patients with higher degree of clinical comorbidities, and correspondingly is associated with worse short-term clinical outcomes in comparison to ASA for HCM patients. ASA before TMVR enabled percutaneous mitral interventions in a small but significant minority of patients that would have otherwise been excluded. The degree of LVOT and neoLVOT area increase is significant and predictable.

Trends of hypertrophic cardiomyopathy-related mortality in United States young adults: a nationwide 20-year analysis.

AIMS: Data regarding hypertrophic cardiomyopathy (HCM)-related mortality in United States young adults, defined as those aged between 25 and 44 years, are lacking. We sought to assess the trends in HCM-related mortality among US young adults between 1999 and 2019 and determine differences by sex, race, ethnicity, urbanization and census region. METHODS: Mortality data were retrieved by the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) dataset from January 1999 to December 2019. Age-adjusted mortality rates (AAMRs) were assessed using the Joinpoint regression modeling and expressed as estimated average annual percentage change (AAPC) with relative 95% confidence intervals (95% CIs). RESULTS: Over 20-year period, the AAMR from HCM in US young adults linearly decreased, with no differences between sexes [AAPC: -5.3% (95% CI -6.1 to -4.6), P  < 0.001]. The AAMR decrease was more pronounced in Black patients [AAPC: -6.4% (95% CI -7.6 to -5.1), P  < 0.001], Latinx/Hispanic patients [AAPC: -4.8% (95% CI -7.2 to -2.36), P  < 0.001] and residents of urban areas [AAPC: -5.4% (95% CI -6.2 to -4.6), P  < 0.001]. The higher percentages of HCM-related deaths occurred in the South of the country and at the patient's home. CONCLUSION: HCM-related mortality in US young adults has decreased over the last two decades in the United States. Subgroup analyses by race, ethnicity, urbanization and census region showed ethnoracial and regional disparities that will require further investigation.

Prediction of cardiac death in patients with hypertrophic cardiomyopathy using plasma adipokine levels.

BACKGROUNDS AND AIMS: Hypertrophic cardiomyopathy (HCM) causes cardiac death through both sudden cardiac death (SCD) and death due to heart failure (HF). Although adipokines lead to adverse cardiac remodeling in HCM, the prognostic value of plasma adipokines in HCM remains unknown. We aimed to predict cardiac death in patients with HCM using plasma adipokines. METHODS AND RESULTS: We performed a multicenter prospective cohort study of patients with HCM. The outcome was cardiac death including heart transplant, death due to HF, and SCD. With data from 1 institution (training set), a prediction model was developed using random forest classification algorithm based on 10 plasma adipokines. The performance of the prediction model adjusted for 8 clinical parameters was examined in samples from another institution (test set). Time-to-event analysis was performed in the test set to compare the rate of outcome events between the low-risk and high-risk groups determined by the prediction model. In total, 389 (267 in the training set; 122 in the test set) patients with HCM were included. During the median follow-up of 2.7 years, 21 patients experienced the outcome event. The area under the covariates-adjusted receiver-operating characteristics curve was 0.89 (95 % confidence interval [CI] 0.71-0.99) in the test set. revealed the high-risk group had a significantly higher risk of cardiac death (hazard ratio 17.8, 95 % CI 2.1-148.3, P = 0.008). CONCLUSION: The present multicenter prospective study demonstrated that a panel of plasma adipokines predicts cardiac death in patients with HCM.

Demographics and Trends of Hypertrophic Cardiomyopathy-Related Mortality in the United States, 1999-2020.

There are limited data on the mortality trends of HCM in the United States. To study the demographics and trends of mortality in patients with HCM, a retrospective cohort analysis was done with mortality data of patients with HCM listed as an underlying cause of death in the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database (CDC-WONDER) from January 1999 to December 2020. The analysis took place in February 2022. First, we measured HCM-related age-adjusted mortality rate (AAMR) per 100,000 US population stratified by sex, race, ethnicity, and geographic area. We then calculated the Annual Percentage Change (APC) for AAMR for each. A total of 24,655 HCM-related deaths occurred between 1999 and 2020. The AAMR for HCM-related deaths declined from 0.5/100,000 patients in 1999 to 0.2 in 2020. The APC changes are as follows: -6.8 (95% CI: -11.8 to -1.5) from 2002 to 2009, -1.23 (95% CI -13.8 to 13.2) from 2009 to 2014, -6.71 (95% CI -46.2 to 61.7) from 2014 to 2017 and remained at 2.07 (95% CI -26.1 to 41.1) from 2017 to 2020. Men had consistently higher AAMR than women. Overall, AAMR in men was 0.4 (95% CI: 0.4-0.5), and in women was 0.3 (95% CI: 0.3-0.3). A similar trend was noticed in men and women over the years, starting from 1999 (AAMR men: 0.7 and women: 0.4) to 2020 (AAMR men: 0.3 and women: 0.2). AAMRs were highest among black or African American patients 0.6 (95% CI: 0.5-0.6), followed by non-Hispanic and Hispanic white 0.3 (95% CI 0.3-0.3) and Asian or Pacific Islander 0.2 (95% CI 0.2-0.2). There was substantial variation in each region in the US. States such as California, Ohio, Michigan, Oregon, and Wyoming had the highest AAMR. Large metropolitan cities had higher AAMR than non-metropolitan cities. During the study period from 1999 to 2020, HCM-related mortality steadily decreased. The highest AAMR was observed among men, black patients, and residents of metropolitan areas. States such as California, Ohio, Michigan, Oregon, and Wyoming had the highest AAMR.

Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review.

Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited primary cardiac disease, has now transformed into a contemporary highly treatable condition with effective options that alter natural history along specific personalized adverse pathways at all ages. HCM patients with disease-related complications benefit from: matured risk stratification in which major markers reliably select patients for prophylactic defibrillators and prevention of arrhythmic sudden death; low risk to high benefit surgical myectomy (with percutaneous alcohol ablation a selective alternative) that reverses progressive heart failure caused by outflow obstruction; anticoagulation prophylaxis that prevents atrial fibrillation-related embolic stroke and ablation techniques that decrease the frequency of paroxysmal episodes; and occasionally, heart transplant for end-stage nonobstructive patients. Those innovations have substantially improved outcomes by significantly reducing morbidity and HCM-related mortality to 0.5%/y. Palliative pharmacological strategies with currently available negative inotropic drugs can control symptoms over the short-term in some patients, but generally do not alter long-term clinical course. Notably, a substantial proportion of HCM patients (largely those identified without outflow obstruction) experience a stable/benign course without major interventions. The expert panel has critically appraised all available data and presented management insights and recommendations with concise principles for clinical decision-making.

Concomitant Cox-Maze IV and Septal Myectomy in Patients With Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: In patients with hypertrophic obstructive cardiomyopathy, atrial fibrillation is associated with heart failure and increased late mortality. However, the role of surgical ablation in these patients is not well defined. The aim of this study was to evaluate the efficacy of the concomitant Cox-Maze IV procedure in patients undergoing septal myectomy for hypertrophic obstructive cardiomyopathy. METHODS: Between 2005 and 2019, 347 patients who underwent septal myectomy at a single institution (Washington University School of Medicine, Barnes-Jewish Hospital, St Louis, MO) were retrospectively reviewed. For patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation who underwent a concomitant Cox-Maze IV procedure, freedom from atrial tachyarrhythmias (ATAs) on or off antiarrhythmic drugs (AADs) was evaluated annually. Predictors of ATA recurrence were identified using Fine-Gray regression, with death as a competing risk. RESULTS: A total of 42 patients underwent concomitant septal myectomy and Cox-Maze IV procedures. The majority of patients, 69% (29 of 42), had paroxysmal atrial fibrillation with a 2.5-year median duration. Operative mortality was 7% (3 of 42). New York Heart Association functional class was reduced after surgery (P < .01). Rates of freedom from recurrent ATAs at 1- and 5-year intervals were 93% (27 of 29) and 100% (14 of 14), respectively. Rates of freedom from ATAs and AADs were 83% (24 of 29) and 100% (14 of 14) at the same time points, respectively. Increased left atrial diameter predicted first ATA recurrence (P < .01). Cerebrovascular accident risk was lower in patients with atrial fibrillation who underwent concomitant Cox-Maze IV and septal myectomy relative to myectomy only (P = .02). CONCLUSIONS: Late freedom from ATAs on or off AADs was excellent after Cox-Maze IV and septal myectomy. Although there was a higher than expected rate of perioperative complications, the study results suggest that concomitant surgical ablation should be considered in selected patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation.

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

AIMS: 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 5 years. METHODS AND RESULTS: 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, 369 patients with obstructive HCM, and 252 implanted with an ICD. 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. CONCLUSION: 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.

Early post-septal myectomy outcomes for hypertrophic obstructive cardiomyopathy.

BACKGROUND: We aimed to evaluate early outcomes of septal myectomy in patients with hypertrophic cardiomyopathy. METHODS: We retrospectively analyzed data collected over a 9-year period from 583 patients who underwent septal myectomy for hypertrophic cardiomyopathy at our institution. RESULTS: The mean age was 55.7 ± 13.1 years, and 338 (58%) patients were in New York Heart Association class III or IV. There were 11 (1.9%) early deaths, including 3 (0.5%) intraoperative deaths. Early mortality was lowest after isolated septal myectomy (0.8%) and highest after concomitant mitral valve replacement (6.1%). There were 4 (0.7%) and 9 (1.5%) patients with left ventricular wall rupture and ventricular septal defect, respectively, after myectomy. New pacemaker implantation caused by atrioventricular disturbances was required in 29 (5.0%) patients, and was associated with previous alcohol septal ablation (odds ratio 3.34, 95% confidence interval 1.02-11.0, P = 0.047). Left ventricular wall rupture, intraoperative residual (15.5% moderate, 0.3% severe) mitral regurgitation, and pre-discharge residual outflow tract gradient >30 mm Hg (4.6%) occurrences were surgeon-dependent. CONCLUSIONS: The early results are consistent with example targets reported in the 2020 American College of Cardiology/American Heart Association guidelines for septal reduction therapy outcomes. Septal myectomy safety and efficacy are surgeon-dependent. Previous alcohol septal ablation increases the risk of permanent pacemaker implantation due to postoperative complete atrioventricular block. Therefore, continuous education, mentoring, and learning by doing may play an important role in achieving reasonable septal myectomy safety and efficacy.

Projecting the Long-term Clinical Value of Mavacamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy in the United States: An Assessment of Net Health Benefit.

PURPOSE: The aim of the study was to project the long-term net health benefits of mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the United States. METHODS: A Markov model with 4 mutually exclusive health states (New York Heart Association [NYHA] functional classes I, II, and III/IV and death) was developed to project the life-years (LYs) and quality-adjusted life-years (QALYs) over a lifetime horizon for patients with symptomatic obstructive HCM receiving mavacamten with or without ß-blocker (BB) or calcium channel blocker (CCB) monotherapy or placebo with or without BB or CCB monotherapy. The model simulated a patient cohort with a starting age of 59 years and 41% women. Transition probabilities across NYHA functional classes were estimated using data from the Phase III Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM) and the EXPLORER long-term extension (EXPLORER-LTE) cohort from the Long-term Safety Extension Study of Mavacamten in Adults who Have Completed MAVERICK-HCM or EXPLORER-HCM (MAVA-LTE) trial and were extrapolated after week 30. The mortality risks of NYHA functional class I were assumed to be the age- and sex-specific mortality risks of the US general population. The mortality risks for NYHA class II and III/IV were estimated using those for class I in conjunction with the relative mortality risks derived using patients with obstructive HCM from a large real-world registry. Health state utilities for each treatment were estimated from EXPLORER-HCM. Both LYs and QALYs were aggregated over a lifetime for each treatment arm, discounted at 3% annually, and compared between the 2 arms. Sensitivity analyses were conducted to evaluate the robustness of the model findings. FINDINGS: Over a lifetime, treatment with mavacamten with or without BB or CCB monotherapy was associated with 3.67 incremental LYs compared with placebo with or without BB or CCB monotherapy (13.00 vs 9.33 LYs). Compared with individuals in the placebo group, patients in the mavacamten group were projected to spend 6.17 additional LYs in NYHA functional class I and 0.04 and 2.46 fewer LYs in NYHA functional classes II and III/IV, respectively. With utilities incorporated, mavacamten with or without BB or CCB monotherapy was associated with 4.17 additional QALYs compared with placebo with or without BB or CCB monotherapy (11.74 vs 7.57 QALYs). In the sensitivity analyses, incremental benefits ranged from 1.55 to 6.21 LYs and from 2.48 to 6.19 QALYs across the scenarios. IMPLICATIONS: This model projected substantial net health benefits associated with mavacamten for symptomatic obstructive HCM owing to improved patient survival and quality of life. The projected QALY gain underscored the likely long-term clinical value of mavacamten in symptomatic obstructive HCM.

N-terminal pro-brain natriuretic peptide and adverse outcomes in Chinese patients with hypertrophic cardiomyopathy.

BACKGROUND: Although numerous studies have suggested that elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) is positively correlated with cardiovascular events, especially the heart failure and heart failure-related death (HFRD), evidence of the association between NT-proBNP and the adverse outcomes of hypertrophic cardiomyopathy (HCM) is still relatively limited. The present study was performed to evaluate the relationship between NT-proBNP and outcomes in patients with HCM. METHODS: Observational cohort methodology was used in the present study, and a total of 227 patients were included. And the patients were followed for 44.97 ± 16.37 months. Patients were categorized into three groups according to these NT-proBNP tertiles: first tertile (≤910 pg/ml, n=68), second tertile (913-2141 pg/ml, n=68), and third tertile (≥2151 pg/ml, n=69). The adverse outcomes of the present study were all-cause death (ACD) and cardiac death (CD). RESULTS: According to the risk category of NT-proBNP, the incidence of ACD (P=0.005) and CD (P=0.032) among the three groups showed significant differences. Multivariate Cox regression analysis suggested that the ACD and CD in the third tertile have 7.022 folds (hazard risk [HR] = 7.022 [95% confidence interval [CI]: 1.397-35.282], P=0.018) and 7.129 folds (HR = 7.129 [95% CI: 1.329-38.237], P=0.022) increased risks as compared with those in the first tertile. Kaplan-Meier survival analyses showed that the cumulative risks of ACD and CD in patients with HCM tended to increase. CONCLUSION: The present study indicated NT-proBNP was a novel biomarker suitable for predicting adverse prognosis in patients with HCM, which may be used for early recognition and risk stratification.