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Indian Heart Journal 2022To assess the safety and efficacy of omecamtiv mecarbil compared with placebo in heart failure (HF) patients. (Meta-Analysis)
Meta-Analysis Review
AIM
To assess the safety and efficacy of omecamtiv mecarbil compared with placebo in heart failure (HF) patients.
METHODS
We searched PubMed, Web of Science, Cochrane Library, and SCOPUS until August 15th, 2021. We included all randomized controlled studies comparing omecamtiv mecarbil with placebo in heart failure patients. The meta-analysis was carried out using Rev Man software V5.4.
RESULTS
A total of eight studies were included in our systematic review. Pooled analysis showed that omecamtiv mecarbil is not associated with increased incidence of death, any adverse events, hypotension, heart failure, ventricular tachyarrhythmia, dyspnea, dizziness, and serious adverse events. Regarding the efficacy, omecamtiv mecarbil significantly reduced heart rate with some studies demonstrating its significant improvement in left ventricular ejection fraction and systolic function.
CONCLUSION
Omecamtiv mecarbil is a well-tolerated drug in heart failure patients. The limited data regarding the efficacy suggested that it may improve ejection fraction and systolic function.
Topics: Cardiac Myosins; Heart Failure; Humans; Stroke Volume; Urea; Ventricular Function, Left
PubMed: 35301008
DOI: 10.1016/j.ihj.2022.03.005 -
Clinical Cardiology Jan 2024Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.
Topics: United States; Humans; Cardiomyopathy, Hypertrophic; Heart; Disease Progression; Heart Failure; Myosins
PubMed: 38269637
DOI: 10.1002/clc.24207 -
International Journal of Molecular... Oct 2022Adult skeletal muscle fibres are classified as type 1, 2A, 2X, and 2B. These classifications are based on the expression of the dominant myosin heavy chain isoform.... (Review)
Review
Adult skeletal muscle fibres are classified as type 1, 2A, 2X, and 2B. These classifications are based on the expression of the dominant myosin heavy chain isoform. Muscle fibre-specific gene expression and proportions of muscle fibre types change during development and in response to exercise, chronic electrical stimulation, or inactivity. To identify genes whose gain or loss-of-function alters type 1, 2A, 2X, or 2B muscle fibre proportions in mice, we conducted a systematic review of transgenic mouse studies. The systematic review was conducted in accordance with the 2009 PRISMA guidelines and the PICO framework. We identified 25 "muscle fibre genes" (, , , , , , , , , , , , , , , , , , , , , , , and ) whose gain or loss-of-function significantly changes type 1, 2A, 2X or 2B muscle fibre proportions in mice. The fact that 15 of the 25 muscle fibre genes are transcriptional regulators suggests that muscle fibre-specific gene expression is primarily regulated transcriptionally. A reanalysis of existing datasets revealed that the expression of and increases and decreases after exercise, respectively. This suggests that these genes help to regulate the muscle fibre adaptation to exercise. Finally, there are many known DNA sequence variants of muscle fibre genes. It seems likely that such DNA sequence variants contribute to the large variation of muscle fibre type proportions in the human population.
Topics: Adult; Mice; Animals; Humans; Muscle Fibers, Skeletal; Myosin Heavy Chains; Protein Isoforms; Electric Stimulation; Muscle, Skeletal; RNA-Binding Proteins; Forkhead Transcription Factors; Nuclear Receptor Co-Repressor 1
PubMed: 36361732
DOI: 10.3390/ijms232112933 -
PloS One 2014Pathological cardiac hypertrophy activates a suite of genes called the fetal gene program (FGP). Pathological hypertrophy occurs in diabetic cardiomyopathy (DCM);... (Review)
Review
Pathological cardiac hypertrophy activates a suite of genes called the fetal gene program (FGP). Pathological hypertrophy occurs in diabetic cardiomyopathy (DCM); therefore, the FGP is widely used as a biomarker of DCM in animal studies. However, it is unknown whether the FGP is a consistent marker of hypertrophy in rodent models of diabetes. Therefore, we analyzed this relationship in 94 systematically selected studies. Results showed that diabetes induced with cytotoxic glucose analogs such as streptozotocin was associated with decreased cardiac weight, but genetic or diet-induced models of diabetes were significantly more likely to show cardiac hypertrophy (P<0.05). Animal strain, sex, age, and duration of diabetes did not moderate this effect. There were no correlations between the heart weight:body weight index and mRNA or protein levels of the fetal genes α-myosin heavy chain (α-MHC) or β-MHC, sarco/endoplasmic reticulum Ca2+-ATPase, atrial natriuretic peptide (ANP), or brain natriuretic peptide. The only correlates of non-indexed heart weight were the protein levels of α-MHC (Spearman's ρ = 1, P<0.05) and ANP (ρ = -0.73, P<0.05). These results indicate that most commonly measured genes in the FGP are confounded by diabetogenic methods, and are not associated with cardiac hypertrophy in rodent models of diabetes.
Topics: Animals; Biomarkers; Cardiomegaly; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Humans; Mice; Rats
PubMed: 24663494
DOI: 10.1371/journal.pone.0092903 -
Thorax Nov 2007Skeletal muscle dysfunction is a common feature in chronic obstructive pulmonary disease (COPD) which is associated with intrinsic muscular abnormalities. One of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Skeletal muscle dysfunction is a common feature in chronic obstructive pulmonary disease (COPD) which is associated with intrinsic muscular abnormalities. One of the most consistently reported alterations is a shift from fibre type I to II in the vastus lateralis of these patients. Surprisingly, the relationship between this shift and the severity and phenotype of COPD remains unclear. A study was conducted to determine whether vastus lateralis muscle fibre type proportions are associated with COPD disease severity and to provide reference values for the proportions of fibre types in the vastus lateralis in COPD.
METHODS
A systematic review and a meta-analysis were conducted in which muscle fibre type data and markers of disease severity were collected from the literature.
RESULTS
The forced expiratory volume in 1 s (FEV(1)), the ratio of FEV(1) to forced vital capacity (FVC) and body mass index were positively associated with the proportion of type I fibres in COPD. A proportion of 51% for vastus lateralis fibre type I and 13% for fibre type IIX were calculated from the combined data as normal values for patients with typical GOLD stage 3-4 COPD aged 60-70 years. Based on these reference values, a proportion of fibre type I <27% and of fibre type IIX >29% were defined as pathologically abnormal.
CONCLUSIONS
This review sheds new light on the relationship between skeletal muscle abnormalities and important hallmarks of the disease in severe COPD, and identifies absence of data in GOLD stages 1-2. This review also provides reference values on fibre type composition for diagnostic purposes in COPD.
Topics: Biomarkers; Body Mass Index; Carbon Monoxide; Forced Expiratory Volume; Humans; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Myosin Heavy Chains; Oxygen; Prognosis; Pulmonary Disease, Chronic Obstructive; Respiratory Muscles; Vital Capacity
PubMed: 17526675
DOI: 10.1136/thx.2007.078980 -
Journal of Applied Physiology... Aug 2020As studies examining the hypertrophic effects of resistance training (RT) at the cellular level have produced inconsistent results, we performed a systematic review and... (Meta-Analysis)
Meta-Analysis
As studies examining the hypertrophic effects of resistance training (RT) at the cellular level have produced inconsistent results, we performed a systematic review and meta-analysis to investigate muscle fiber size before and after a structured RT intervention in older adults. A random-effects model was used to calculate mean effect size (ES) and 95% confidence intervals (CI). Thirty-five studies were included (age range: 59.0-88.5 yr), and 44 and 30 effects were used to estimate RT impact on myosin heavy chain (MHC) I and II fiber size. RT produced moderate-to-large increases in MHC I (ES = +0.51, 95%CI +0.31 to +0.71; < 0.001) and II (ES = +0.81, 95%CI +0.56 to +1.05; < 0.001) fiber size, with men and women having a similar response. Age was negatively associated with change in muscle fiber size for both fiber types (MHC I: = 0.11, β = -0.33, = 0.002; MHC II: = 0.10, β = -0.32, = 0.04), indicating a less robust hypertrophic response as age increases in older adults. Unexpectedly, a higher training intensity (defined as percentage of one-repetition maximum) was associated with a smaller increase in MHC II fiber size ( = 15.09%, β = -0.39, = 0.01). Notably, MHC II fiber subtypes (IIA, IIX, IIAX) were examined less frequently, but RT improved their size. Overall, our findings indicate that RT induces cellular hypertrophy in older adults, although the effect is attenuated with increasing age. In addition, hypertrophy of MHC II fibers was reduced with higher training intensity, which may suggest a failure of muscle fibers to hypertrophy in response to high loads in older adults.
Topics: Aged; Aged, 80 and over; Female; Humans; Hypertrophy; Male; Middle Aged; Muscle Fibers, Skeletal; Muscle, Skeletal; Myosin Heavy Chains; Resistance Training
PubMed: 32702280
DOI: 10.1152/japplphysiol.00170.2020