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Background. Beta-blockers have been the initial treatment for symptomatic obstructive hypertrophic cardiomyopathy (HCM) despite limited evidence of their efficacy. Aficamten is a cardiac myosin inhibitor that reduces left ventricular outflow tract gradients, improves exercise capacity, and decreases HCM symptoms when added to standard medications. Whether aficamten as monotherapy provides greater clinical benefit than beta-blockers as monotherapy remains unknown.
Methods. We conducted an international, double-blind, double-dummy trial in which adults with symptomatic obstructive HCM were randomly assigned in a 1:1 ratio to receive aficamten (at a daily dose of 5 mg to 20 mg) plus placebo or metoprolol (at a daily dose of 50 mg to 200 mg) plus placebo. The primary end point was the change in peak oxygen uptake at week 24; secondary end points were improvement at week 24 in New York Heart Association (NYHA) functional class and changes at week 24 in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), left ventricular outflow tract gradient after the Valsalva maneuver, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, left atrial volume index, and left ventricular mass index.
Results. A total of 88 patients were assigned to the aficamten group and 87 to the metoprolol group. The mean age of the patients was 58 years, 58.3% were men, and the mean left ventricular outflow tract gradient was 47 mm Hg at rest and 74 mm Hg after the Valsalva maneuver. At 24 weeks, the change in the peak oxygen uptake was 1.1 ml per kilogram of body weight per minute (95% confidence interval [CI], 0.5 to 1.7) in the aficamten group and -1.2 ml per kilogram per minute (95% CI, -1.7 to -0.8) in the metoprolol group (least-squares mean between-group difference, 2.3 ml per kilogram per minute; 95% CI, 1.5 to 3.1; P<0.001). Patients who received aficamten had significantly greater improvements in NYHA class, KCCQ-CSS, left ventricular outflow tract gradient, NT-proBNP level, and left atrial volume index than patients who received metoprolol. No significant difference in left ventricular mass index was observed. Adverse events appeared to be similar in the two treatment groups.
Conclusions. Among patients with symptomatic obstructive HCM, aficamten monotherapy was superior to metoprolol monotherapy in improving peak oxygen uptake and hemodynamics and decreasing symptoms. (Funded by Cytokinetics; MAPLE-HCM ClinicalTrials.gov number, NCT05767346.).
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Background. Mavacamten is approved to treat adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). However, its effects in nonobstructive HCM remain uncertain.
Methods. We conducted a phase 3, international, double-blind, placebo-controlled, clinical trial to determine whether mavacamten improves functional capacity and patient-reported health status among adults with symptomatic nonobstructive HCM. Patients were randomly assigned in a 1:1 ratio to receive mavacamten (starting at 5 mg per day and adjusted up to a maximum of 15 mg per day on the basis of left ventricular ejection fraction) or placebo (with sham dose adjustment) for 48 weeks. The two primary end points were the change from baseline to week 48 in peak oxygen uptake and in the 23-item Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating better health status).
Results. We randomly assigned 289 patients to receive mavacamten and 291 to receive placebo. The mean (±SD) age of the patients was 56±15 years, and 46% were women. From baseline to week 48, the least-squares mean change in peak oxygen uptake was 0.52 ml per kilogram of body weight per minute (95% confidence interval [CI], 0.09 to 0.95) in the mavacamten group and 0.05 ml per kilogram per minute (95% CI, -0.38 to 0.47) in the placebo group (between-group difference, 0.47 ml per kilogram per minute; 95% CI, -0.03 to 0.98; P = 0.07). The least-squares mean change in the KCCQ-CSS was 13.1 points (95% CI, 10.7 to 15.5) in the mavacamten group and 10.4 points (95% CI, 8.0 to 12.8) in the placebo group (between-group difference, 2.7 points; 95% CI, -0.1 to 5.6; P = 0.06). Reductions in ejection fraction and interruptions in the trial regimen were more common with mavacamten than with placebo.
Conclusions. Among patients with nonobstructive HCM, mavacamten did not result in a significantly greater improvement in peak oxygen uptake or decrease in symptoms than placebo. (Funded by Bristol Myers Squibb; ODYSSEY-HCM ClinicalTrials.gov number, NCT05582395.).
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Background. The benefit of rehabilitation interventions in patients who are 65 years of age or older with myocardial infarction and impaired physical performance remains unclear.
Methods. In this multicenter, randomized trial conducted in Italy, we assigned older patients with impaired physical performance 1 month after myocardial infarction in a 2:1 ratio to receive either an intervention consisting of control of cardiovascular risk factors, dietary counseling, and exercise training (intervention group) or usual care (control group). The primary outcome was a composite of cardiovascular death or unplanned hospitalization for cardiovascular causes within 1 year.
Results. A total of 512 patients underwent randomization (342 to the intervention group and 170 to the control group). The median age of the patients was 80 years, and 36% were women. A primary-outcome event occurred in 43 patients (12.6%) in the intervention group and in 35 patients (20.6%) in the control group (hazard ratio, 0.57; 95% confidence interval [CI], 0.36 to 0.89; P = 0.01). Cardiovascular death occurred in 14 patients (4.1%) in the intervention group and in 10 patients (5.9%) in the control group (hazard ratio, 0.69; 95% CI, 0.31 to 1.55). Unplanned hospitalization for cardiovascular causes occurred in 31 patients (9.1%) in the intervention group and in 30 patients (17.6%) in the control group (hazard ratio, 0.48; 95% CI, 0.29 to 0.79). There were no serious adverse events associated with the intervention.
Conclusions. Among older patients with impaired physical performance 1 month after myocardial infarction, a multidomain rehabilitation intervention resulted in a lower incidence of cardiovascular death or unplanned cardiovascular hospitalization within 1 year than usual care. (Funded by the Italian Health Ministry; PIpELINe ClinicalTrials.gov number, NCT04183465.).
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Background. On September 27, 2024, Rwanda reported an outbreak of Marburg virus disease (MVD), after a cluster of cases of viral hemorrhagic fever was detected at two urban hospitals.
Methods. We report key aspects of the epidemiology, clinical manifestations, and treatment of MVD during this outbreak, as well as the overall response to the outbreak. We performed a retrospective epidemiologic and clinical analysis of data compiled across all pillars of the outbreak response and a case-series analysis to characterize clinical features, disease progression, and outcomes among patients who received supportive care and investigational therapeutic agents.
Results. Among the 6340 patients with suspected MVD who underwent testing, 66 had laboratory-confirmed MVD, 51 (77%) of whom were health care workers. The median estimated incubation period was 10 days (interquartile range, 8 to 13), and symptom onset occurred a median of 2 days (interquartile range, 1 to 3) before hospital admission. The results of epidemiologic investigations were highly suggestive of a zoonotic origin of the outbreak: an index patient was identified who had been exposed to Egyptian fruit bats at a mining site. The case fatality rate in the outbreak was 23% (15 deaths among 66 patients). Remdesivir and the monoclonal antibody MBP091 were used under expanded access and clinical trial protocols. In addition, 1710 frontline workers and high-risk contacts received the chimpanzee adenovirus 3-vectored vaccine ChAd3-MARV under emergency use authorization in a phase 2 clinical trial.
Conclusions. Implementation of containment measures, advanced supportive care, and access to investigational countermeasures may have contributed to reduced mortality from MVD in this outbreak. Enhancing surveillance, improving infection prevention and control in health care settings, and ensuring timely deployment of medical countermeasures will be critical for mitigating the effects of future filovirus disease outbreaks.
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