Publications by authors named "Sheila M Hegde"
Background: This study aims to characterize right ventricular dysfunction (RVD) in heart failure (HF) with preserved ejection fraction and understand the cumulative prognostic value of abnormal RV echocardiographic parameters in HF with preserved ejection fraction.
Methods And Results: Data from 809 patients in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in HF With Preserved Ejection Fraction) echocardiographic substudy (55% women, mean age 74±8 years) were analyzed. Correlates of RVD (defined as tricuspid annular plane systolic excursion <1.
Aims: To evaluate clinical outcomes, echocardiographic features, and the efficacy and safety of sacubitril/valsartan compared to valsartan across age groups in the PARAGON-HF trial.
Methods And Results: A total of 4796 participants ≥50 years of age with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) ≥45% were divided into three age groups: <65 years (n = 825), 65-74 years (n = 1772), and ≥75 years (n = 2199). Echocardiograms of 1097 patients were analysed in a standardized fashion at a core imaging laboratory.
Article Synopsis
- Mavacamten, a cardiac myosin inhibitor, showed significant improvements in symptoms and heart function in Japanese patients with obstructive hypertrophic cardiomyopathy (HCM) during the HORIZON-HCM study.
- In a trial involving 38 patients, 36 completed the 30-week treatment, which resulted in a notable reduction in postexercise left ventricular outflow tract (LVOT) gradient and improvements in cardiac biomarkers and quality of life metrics.
- The treatment was well tolerated, with adverse events reported but none leading to discontinuation, and no deaths occurred throughout the study.
Article Synopsis
- The study investigates differences between men and women in heart function after a heart attack (MI) to understand why women have higher rates of hospitalization for heart failure.
- It analyzes echocardiographic data from 544 patients in the PARADISE-MI trial to assess heart function pre and post-MI, focusing on parameters like left ventricular ejection fraction (LVEF) and chamber sizes.
- Although women showed better heart function indicators at the start, the study found that the changes over 8 months and the relationship between heart function metrics and clinical outcomes were similar for both sexes.
Background: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) hypertrophy, LV outflow tract obstruction, and left atrial dilation, which can be associated with progressive heart failure, atrial fibrillation, and stroke. Aficamten is a next-in-class cardiac myosin inhibitor that reduces outflow tract obstruction by modulating cardiac contractility, with the potential to reverse pathological remodeling and, in turn, reduce cardiovascular events.
Objectives: This study sought to investigate the effect of aficamten on cardiac remodeling compared with placebo using cardiovascular magnetic resonance (CMR) and its association with key clinical endpoints in the SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) CMR substudy.
Background: Aficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study.
Objectives: The authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM.
Methods: Serial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF).
Background And Aims: Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten.
Methods: Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion.
Article Synopsis
- The study analyzed the role of biomarkers NT-proBNP and hs-cTnI in managing obstructive hypertrophic cardiomyopathy (oHCM) and how they relate to treatment effects of aficamten.
- Baseline levels of NT-proBNP correlated with the left ventricular outflow tract gradient (LVOT-G) and diastolic function, while hs-cTnI correlated with left ventricular thickness.
- After 8 weeks of aficamten treatment, NT-proBNP decreased by 79% and hs-cTnI by 41%, with these reductions linked to improvements in heart function, health status, and exercise capacity, suggesting that these biomarkers are useful for tracking treatment response.
Article Synopsis
- Renal dysfunction is common in heart failure patients and linked to poor outcomes, but how cardiac structure and function impact kidney health remains unclear.
- This study analyzed data from the PARAGON-HF trial to explore the relationship between echocardiographic measurements of heart structure/function and changes in kidney function over time.
- Results showed that higher left ventricular mass and certain heart parameters are associated with greater declines in kidney function and an increased risk of serious kidney-related events, suggesting that cardiac health plays a crucial role in renal outcomes for these patients.
Article Synopsis
- This study examined the impact of high-dose influenza vaccination on patients with adult congenital heart disease (ACHD) compared to those without ACHD, focusing on all-cause mortality and cardiopulmonary hospitalizations.
- 272 ACHD patients were included, revealing that they were generally younger and had specific health conditions compared to the non-ACHD group of 4,988 individuals.
- Results showed no significant difference in the primary outcomes between ACHD and non-ACHD groups, indicating that both high- and standard-dose vaccines had similar effects on health outcomes.
Article Synopsis
- * In the PARAGON-HF study, having multiple CKM conditions significantly increased the risk of heart failure hospitalizations and cardiovascular death, especially among those with three conditions.
- * Despite these complications, the treatment effects of sacubitril/valsartan were effective across different levels of CKM multimorbidity, indicating its consistent benefit regardless of the number of related health issues.
Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated atherosclerosis. The only approved treatment is the farnesyltransferase inhibitor lonafarnib, which improves vascular structure and function, extending average untreated lifespan of 14.5 years by 4.
View Article and Find Full Text PDFBackground: The phase 2 PIONEER-HCM (Phase 2 Open-label Pilot Study Evaluating Mavacamten in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction) study showed that mavacamten improved left ventricular outflow tract gradients, exercise capacity, and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), but the results of longer-term treatment are less well described. We report interim results from the PIONEER-OLE (PIONEER Open-Label Extension) study, the longest-term study of mavacamten in patients with symptomatic obstructive HCM.
Methods And Results: Patients who previously completed PIONEER-HCM (n=20) were eligible to enroll in PIONEER-OLE.
Article Synopsis
- A secondary analysis of the INVESTED trial found that high-dose trivalent influenza vaccines didn't significantly lower mortality or hospitalizations for patients with high-risk cardiovascular disease compared to standard-dose quadrivalent vaccines.
- The study focused on the antibody response to these vaccines and how it relates to clinical outcomes among patients who had recent heart issues.
- Results showed that high-dose vaccines produced a stronger antibody response for various influenza strains, indicating a better immune response despite no clear impact on health outcomes.
Background: Data assessing the long-term safety and efficacy of mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy are needed.
Objectives: The authors sought to evaluate interim results from the EXPLORER-Long Term Extension (LTE) cohort of MAVA-LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM; NCT03723655).
Methods: After mavacamten or placebo withdrawal at the end of the parent EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545), patients could enroll in MAVA-LTE.
Background: Compared with men, women with hypertrophic cardiomyopathy (HCM) have a higher incidence of heart failure and worse outcomes. We investigated baseline clinical and echocardiographic characteristics and response to mavacamten among women compared with men in the EXPLORER-HCM study (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy).
Methods: A prespecified post hoc analysis of sex from the blinded, randomized EXPLORER-HCM trial of mavacamten versus placebo in symptomatic patients with obstructive HCM was performed.
Article Synopsis
- - The study explored whether high-dose trivalent influenza vaccines provide better protection against serious heart and lung events compared to standard-dose quadrivalent vaccines in high-risk cardiovascular patients during flu season.
- - Conducted as a secondary analysis of the INVESTED trial from 2016 to 2019, involving 3,094 patients, the research tracked weekly flu activity and its impact on health outcomes.
- - Results indicated that increasing influenza-like illness (ILI) activity correlated with a higher risk of serious health events, but high-dose vaccines did not show a significant advantage over standard doses in preventing these issues.
Monitoring treatment with cardiac myosin inhibitors in symptomatic obstructive hypertrophic cardiomyopathy.
Curr Opin Cardiol
September 2023
Purpose Of Review: Cardiac myosin inhibitors (CMIs) represent a major milestone in the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy. The objective of this review is to discuss the mechanisms of action, clinical trial evidence, safety profile and monitoring of CMIs, which are important to the implementation of these drugs in clinical practice.
Recent Findings: Mavacamten and aficamten have both been shown to substantially improve left ventricular outflow tract gradients, biomarkers and symptoms in patients with obstructive hypertrophic cardiomyopathy.
Aims: In the EXPLORER-HCM trial, mavacamten improved exercise capacity and symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten effects on the primary endpoint, a composite of peak oxygen consumption (VO ) and New York Heart Association (NYHA) class, were greater in patients not receiving background beta-blockers than in those receiving beta-blockers. We sought to determine if the effect of background treatment was consistent across other clinically meaningful parameters.
View Article and Find Full Text PDFArticle Synopsis
- Sodium-glucose cotransporter-2 inhibitors like dapagliflozin show potential benefits for heart failure patients, and the study explores how sex affects these outcomes.
- In a large analysis of heart failure patients, women showed different health profiles compared to men but experienced significant health benefits from dapagliflozin, including lower rates of cardiovascular events and deaths.
- Both men and women responded similarly to dapagliflozin in reducing primary outcomes, indicating that the drug is equally effective across sexes without notable differences in safety or efficacy.