Evaluating the efficacy and safety of mavacamten in hypertrophic cardiomyopathy: A systematic review and meta-analysis focusing on qualitative assessment, biomarkers, and cardiac imaging.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left ventricular outlet tract (LVOT). Mavacamten, a first-in-class cardiac myosin inhibitor, is increasingly being studied in randomized controlled trials. In this meta-analysis, we aimed to analyse the efficacy and safety profile of Mavacamten compared to placebo in patients of HCM. METHOD: We carried out a comprehensive search in PubMed, Cochrane, and clinicaltrials.gov to analyze the efficacy and safety of mavacamten compared to placebo from 2010 to 2023. To calculate pooled odds ratio (OR) or risk ratio (RR) at 95% confidence interval (CI), the Mantel-Haenszel formula with random effect was used and Generic Inverse Variance method assessed pooled mean difference value at a 95% CI. RevMan was used for analysis. P<0.05 was considered significant. RESULTS: We analyzed five phase 3 RCTs including 609 patients to compare mavacamten with a placebo. New York Heart Association (NYHA) grade improvement and KCCQ score showed the odds ratio as 4.94 and 7.93 with p<0.00001 at random effect, respectively. Cardiac imaging which included LAVI, LVOT at rest, LVOT post valsalva, LVOT post-exercise, and reduction in LVEF showed the pooled mean differences for change as -5.29, -49.72, -57.45, -36.11, and -3.00 respectively. Changes in LVEDV and LVMI were not statistically significant. The pooled mean difference for change in NT-proBNP and Cardiac troponin-I showed 0.20 and 0.57 with p<0.00001. The efficacy was evaluated in 1) A composite score, which was defined as either 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction, or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening and 2) changes in pVO2, which was not statistically significant. Similarly, any treatment-associated emergent adverse effects (TEAE), treatment-associated serious adverse effects (TSAE), and cardiac-related adverse effects were not statistically significant. CONCLUSION: Mavacamten influences diverse facets of HCM comprehensively. Notably, our study delved into the drug's impact on the heart's structural and functional aspects, providing insights that complement prior findings. Further large-scale trials are needed to evaluate the safety profile of Mavacamten.

Long-Term Outcomes of Women With Peripartum Cardiomyopathy Having Subsequent Pregnancies.

BACKGROUND: Long-term maternal outcomes of subsequent pregnancies (SSPs) in patients with peripartum cardiomyopathy (PPCM) have not been analyzed. OBJECTIVES: The goal of this study was to evaluate the long-term survival of SSPs in women with PPCM. METHODS: We conducted a retrospective review of 137 PPCMs in the registry. The clinical and echocardiographic findings were compared between the recovery group (RG) and nonrecovery group (NRG), defined as left ventricular ejection fraction ≥50% and <50% after an index of pregnancy, respectively. RESULTS: Forty-five patients with SSPs were included with a mean age of 27.0 ± 6.1 years, 80% were of African American descent, and 75.6% from a low socioeconomic background. Thirty (66.7%) women were in the RG. Overall, SSPs were associated with a decrease in mean left ventricular ejection fraction from 45.1% ± 13.7% to 41.2% ± 14.5% (P = 0.009). At 5 years, adverse outcomes were significantly higher in the NRG compared with the RG (53.3% vs 20%; P = 0.04), driven by relapse PPCM (53.3% vs 20.0%; P = 0.03). Five-year all-cause mortality was 13.33% in the NRG compared with 3.33% in the RG (P = 0.25). At a median follow-up of 8 years, adverse outcomes and all-cause mortality rates were similar in the NRG and RG (53.3% vs 33.3% [P = 0.20] and 20% vs 20%, respectively). CONCLUSIONS: Subsequent pregnancies in women with PPCM are associated with adverse events. The normalization of left ventricular function does not guarantee a favorable outcome in the SSPs.

Decreased availability of nitric oxide and hydrogen sulfide is a hallmark of COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is involved in a global outbreak affecting millions of people who manifest a variety of symptoms. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is increasingly associated with cardiovascular complications requiring hospitalizations; however, the mechanisms underlying these complications remain unknown. Nitric oxide (NO) and hydrogen sulfide (H2S) are gasotransmitters that regulate key cardiovascular functions. METHODS: Blood samples were obtained from 68 COVID-19 patients and 33 controls and NO and H2S metabolites were assessed. H2S and NO levels were compared between cases and controls in the entire study population and subgroups based on race. The availability of gasotransmitters was examined based on severity and outcome of COVID-19 infection. The performance of H2S and NO levels in predicting COVID-19 infection was also analyzed. Multivariable regression analysis was performed to identify the effects of traditional determinants of gasotransmitters on NO and H2S levels in the patients with COVID-19 infection. RESULTS: Significantly reduced NO and H2S levels were observed in both Caucasian and African American COVID-19 patients compared to healthy controls. COVID-19 patients who died had significantly higher NO and H2S levels compared to COVID-19 patients who survived. Receiver-operating characteristic analysis of NO and H2S metabolites in the study population showed free sulfide levels to be highly predictive of COVID-19 infection based on reduced availability. Traditional determinants of gasotransmitters, namely age, race, sex, diabetes, and hypertension had no effect on NO and H2S levels in COVID-19 patients. CONCLUSION: These observations provide the first insight into the role of NO and H2S in COVID-19 infection, where their low availability may be a result of reduced synthesis secondary to endotheliitis, or increased consumption from scavenging of reactive oxygen species.