Cardiac Myosins – ABC CARDIOL

IJCS

Editorial

Cardiac Myosin Inhibitors in Patients with Hypertrophic Cardiomyopathy

Marcelo Imbroinise Bittencourt et al. Ricardo Mourilhe-Rocha

In recent years, we have witnessed a significant shift in the management of symptomatic Hypertrophic Cardiomyopathy (HCM). For decades, treatment relied on medications that provided hemodynamic support without directly addressing sarcomeric hypercontractility, the primary pathophysiological driver of the disease. The emergence of Cardiac Myosin Inhibitors (CMIs), particularly mavacamten and aficamten, has transformed this landscape.^, In an article published in this issue of the International Journal of Cardiovascular Sciences, Fogaça PHT et al. present an updated systematic review and meta-analysis that reinforces the efficacy of this class of medications while providing important insights into their effects in both obstructive and non-obstructive HCM.

The study pooled data from six randomized controlled trials. Five included patients with obstructive HCM, whereas one – the MAVERICK-HCM trial – included patients with non-obstructive HCM.^,,- The inclusion of non-obstructive patients represents a distinctive aspect of this analysis, as the benefits of CMIs in the absence of left ventricular outflow tract (LVOT) obstruction remain less well established.

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IJCS

Original Article

Efficacy of Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Cardiomyopathy: An Updated Meta-Analysis and Systematic Review

Pedro Henrique Tavares Fogaça et al. Gabriel Grando Alves Camila Sales Sales Fagundes Fernanda Lavarda Scheinpflug … João Candido Tavares Fogaça Mateus Diniz Marques

Abstract

Background:

This study evaluates the efficacy of cardiac myosin inhibitors (CMI), which appear to be an innovative alternative for hypertrophic cardiomyopathy (HCM), a disease lacking highly effective pharmacologic treatments.

Objective:

To provide updated efficacy data on CMI (aficamten or mavacamten) in symptomatic HCM.

Materials and methods:

We searched PubMed, Embase, and Cochrane databases for randomized controlled trials comparing CMI to placebo in symptomatic HCM, reporting: (1) New York Heart Association (NYHA) functional class improvement; (2) change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS); (3) percent change from baseline in left ventricular outflow tract (LVOT) gradient at rest and after Valsalva maneuver; and (4) serious adverse events. Heterogeneity was examined with I² statistics, and p values < 0.05 indicated sta tistical significance. Continuous endpoints were analyzed using pooled mean difference (MD), and binary endpoints were analyzed using odds ratios (OR), both with 95% confidence intervals (CI).

Results:

We included six RCTs with 826 patients, 443 of whom received CMI. Compared to placebo, NYHA class improvement was more frequent in patients receiving CMI (OR: 4.10; 95% CI: 2.79 to 6.02; p < 0.00001), with significant differences in KCCQ-CSS change (MD: 7.15; 95% CI: 4.21 to 10.10; p < 0.00001), as well as in LVOT gradient change at rest (MD: −38.25; 95% CI: −46.76 to −29.74; p < 0.00001) and after Valsalva maneuver (MD: −46.49; 95% CI: −54.70 to −38.27; p < 0.00001). There were no significant differences in serious adverse events (OR: 0.64; 95% CI: 0.31 to 1.31; p = 0.22).

Conclusion:

CMI shows greater efficacy than placebo in treating symptomatic HCM.

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ABC

Original Article

Effect of Fetal Hypothyroidism on Cardiac Myosin Heavy Chain Expression in Male Rats

Nasibeh Yousefzadeh et al. Sajad Jeddi Mohammad Reza Alipour

Abstract

Background:

Thyroid hormone deficiency during fetal life could affect the cardiac function in later life. The mechanism underlying this action in fetal hypothyroidism (FH) in rats has not been elucidated thus far.

Objective:

The aim of this study is to evaluation the effect of FH on cardiac function in male rats and to determine the contribution of α-myosin heavy chain (MHC) and β-MHC isoforms.

Methods:

Six pregnant female rats were randomly divided into two groups: The hypothyroid group received water containing 6-propyl-2-thiouracil during gestation and the controls consumed tap water. The offspring of the rats were tested in adulthood. Hearts from the FH and control rats were isolated and perfused with langendroff setup for measuring hemodynamic parameters; also, the heart mRNA expressions of α- MHC and β-MHC were measured by qPCR.

Results:

Baseline LVDP (74.0 ± 3.1 vs. 92.5 ± 3.2 mmHg, p < 0.05) and heart rate (217 ± 11 vs. 273 ± 6 beat/min, p < 0.05) were lower in the FH rats than controls. Also, these results showed the same significance in ±dp/dt. In the FH rats, β-MHC expression was higher (201%) and α- MHC expression was lower (47%) than control.

Conclusion:

Thyroid hormone deficiency during fetal life could attenuate normal cardiac functions in adult rats, an effect at least in part due to the increased expression of β-MHC to α- MHC ratio in the heart.

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Cardiac Myosin Inhibitors in Patients with Hypertrophic Cardiomyopathy

Efficacy of Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Cardiomyopathy: An Updated Meta-Analysis and Systematic Review

Abstract

Background:

Objective:

Materials and methods:

Results:

Conclusion:

Effect of Fetal Hypothyroidism on Cardiac Myosin Heavy Chain Expression in Male Rats

Abstract

Background:

Objective:

Methods:

Results:

Conclusion:

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