A systematic review and meta-analysis of the efficacy and safety of Mavacamten therapy in international cohort of 524 patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.

Physical therapy interventions for the management of hand tremors in patients with Parkinson's disease: a systematic review.

BACKGROUND: Several physical therapy modalities have been used to improve hand tremors in patients with Parkinson's disease (PD). However, little is known about the efficacy of these techniques. Therefore, we conducted this study to synthesize evidence from published studies on the efficacy of physical therapy techniques for hand tremors in PD patients. METHODS: We followed the PRISMA statement and Cochrane handbook guidelines when conducting this study. We conducted an electronic literature search of PubMed, Cochrane Central Register of Clinical Trials, Web of Science, Ovid, and Embase, and then we selected clinical trials assessing the efficacy of any physical therapy intervention for hand tremors in patients with PD. Study outcomes were extracted, and evidence was synthesized narratively. RESULTS: A total of six modalities described in six studies were included in this systematic review. Out of the six interventions, the tremor's glove and electrical stimulation showed significant improvements in root mean square angular velocity (59% and 43.8%, respectively) and UPDRS tremor score (P < 0.05 for both). Also, eccentric exercises were associated with significant reductions in the mean resting tremor amplitude (P < 0.05). These data were dependent on single studies; therefore, a meta-analysis was not feasible. CONCLUSION: Several physical therapy interventions, such as electrical stimulation, exercises, transcranial low voltage pulsed electromagnetic fields, weights, and virtual reality showed promising results in reducing hand tremors. However, this evidence was based on a limited number of included studies, and more RCTs with larger sample sizes are required to confirm the efficacy of these interventions.