Despite the rising prevalence of HF, new evidence-based novel therapies for patients with worsening HF remain lacking, e.g., safe inotropic therapies. Traditional inotropes increase contractility by altering intracellular calcium flux, a pathway that may be responsible for the multitude of adverse effects associated with current options. Omecamtiv mecarbil, a direct myosin activator, increases contractility through a distinct pathway by increasing the proportion of myosin heads that are bound to actin in a high-affinity state. Phase II clinical trials in patients with chronic HF with this agent seem promising. A phase III trial investigating this therapy has not yet been pursued to date.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11886-016-0778-xDOI Listing

Publication Analysis

Top Keywords

cardiac myosin
4
myosin activators
4
activators systolic
4
systolic heart
4
heart failure
4
failure friend
4
friend foe?
4
foe? despite
4
despite rising
4
rising prevalence
4

Similar Publications

Background: Hypertrophic cardiomyopathy (HCM) needs careful differentiation from other cardiomyopathies. Current guidelines recommend genetic testing, but genetic data on differential diagnoses and their relation with clinical outcomes in HCM are still lacking. This study aimed to investigate the prevalence of genetic variants and the proportion of other cardiomyopathies in patients with suspected HCM in Korea and compare the outcomes of HCM according to the presence of sarcomere gene mutation.

View Article and Find Full Text PDF

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by structural and functional abnormalities. Current management strategies, such as medications and septal reduction therapies, have significant limitations and risks. Recently, cardiac myosin inhibitors (CMIs) like mavacamten and aficamten have shown promise as noninvasive treatment options.

View Article and Find Full Text PDF

Heart failure with preserved ejection fraction (HFpEF) is a major public health challenge, affecting millions worldwide and placing a significant burden on healthcare systems due to high hospitalization rates and limited treatment options. HFpEF is characterized by impaired cardiac relaxation, or diastolic dysfunction. However, there are no therapies that directly treat the primary feature of the disease.

View Article and Find Full Text PDF

Comparison of Alcohol Septal Ablation with Mavacamten in Obstructive Hypertrophic Cardiomyopathy.

Am J Cardiol

December 2024

Northwestern University, Feinberg School of Medicine, Chicago IL 60611; The Hypertrophic Cardiomyopathy Program at the Bluhm Cardiovascular Institute, Chicago IL 60611; Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Chicago IL 60611.

Background: Obstructive hypertrophic cardiomyopathy (HCM) is associated with significant morbidity due to left ventricular outflow tract (LVOT) obstruction. While alcohol septal ablation (ASA) is an established interventional treatment, mavacamten, a novel cardiac myosin inhibitor, has emerged as a non-invasive pharmacological alternative. Understanding the comparative efficacy of these two treatments is important for optimizing patient care.

View Article and Find Full Text PDF

The polycomb protein complex interacts with GATA-6/PPARα to inhibit α-MHC expression.

Dev Growth Differ

December 2024

Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

Transcription factors collaborate with epigenetic regulatory factors to orchestrate cardiac differentiation for heart development, but the underlying mechanism is not fully understood. Here, we report that GATA-6 induces cardiac differentiation but peroxisome proliferator-activated receptor α (PPARα) reverses GATA-6-induced cardiac differentiation, possibly because GATA-6/PPARα recruits the polycomb protein complex containing EZH2/Ring1b/BMI1 to the promoter of the cardiac-specific α-myosin heavy chain (α-MHC) gene and suppresses α-MHC expression, which ultimately inhibits cardiac differentiation. Furthermore, Ring1b ubiquitylates PPARα and GATA-6.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!