Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4.

BACKGROUND: This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy (nHCM). METHODS: Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤ 30 mmHg, left ventricular ejection fraction [LVEF] ≥ 60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] > 300 pg/mL) received aficamten 5-15 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. RESULTS: We enrolled 41 patients (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥ 1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP levels (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of -5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF < 50% (range: 41%-48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study. CONCLUSIONS: Aficamten administration for symptomatic nHCM was generally safe and was associated with improvements in heart failure symptoms and cardiac biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04219826.

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.

Mortality After Alcohol Septal Ablation vs. Septal Myectomy in Patients With Obstructive Hypertrophic Cardiomyopathy.

Background: Alcohol septal ablation (ASA) and septal myectomy (SM) are 2 options for septal reduction therapy (SRT) to treat medication-resistant symptomatic obstructive hypertrophic cardiomyopathy (HCM). Because differences in mortality rates after these different SRT methods have not been extensively investigated in real-world settings, in this study compared the 1-year mortality rates after ASA and SM using population-based database. Methods and Results: Utilizing New York Statewide Planning and Research Cooperative System (SPARCS) data from 2005 to 2016, we performed a comparative effectiveness study of ASA vs. SM in patients with HCM. The outcome was all-cause death up to 360 days after SRT. We constructed a multivariable logistic regression model and performed sensitivity analysis with propensity score (PS)-matching and inverse probability of treatment weighting (IPTW) methods. We identified 755 patients with HCM who underwent SRT: 348 with ASA and 407 with SM. The multivariable analysis showed that all-cause deaths were significantly fewer in the ASA group at 360 days after SRT (adjusted odds ratio=0.34; 95% confidence interval [CI] 0.13-0.84; P=0.02). The PS-matching and IPTW methods also supported a lower mortality rate in the ASA group at 360 days post-SRT. Conclusions: In this population-based study of patients with HCM who underwent SRT in a real-world setting, the 1-year all-cause mortality rate was significantly lower in patients who underwent ASA compared with SM.