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The Role for Cardiovascular Remodeling in Cardiovascular Outcomes
Nishant Krishna Sekaran1, Anna Lisa Crowley1, Fernanda Rodrigues de Souza2
1Durham Veterans Affairs Health System, Duke University Medical Center, Durham, NC, 27710, USA.
Insights
Guideline-directed medical therapies improve heart remodeling in heart failure with reduced ejection fraction (HFrEF). Non-invasive measures like LVEF are key to assessing treatment effectiveness and guiding future research.
Area of Science:
- Cardiology
- Heart Failure Research
- Cardiovascular Imaging
Background:
- Heart injury causes adverse ventricular remodeling, impacting size, shape, and function.
- Non-invasive measures like left ventricular ejection fraction (LVEF) reflect these changes and predict outcomes.
- These metrics are crucial surrogate endpoints for heart failure with reduced ejection fraction (HFrEF) therapies.
Purpose of the Study:
- To critically evaluate recent data (2015-2016) on HFrEF therapies.
- To assess the role of ventricular remodeling in cardiovascular outcomes.
- To review randomized clinical trials (RCTs) and observational studies.
Main Methods:
- Review of published randomized clinical trials (RCTs) and observational studies from 2015-2016.
- Analysis of data on guideline-directed medical therapies (GDMT) for HFrEF.
- Evaluation of non-invasive measures of ventricular remodeling (LVEF, LVESV, LVEDV).
Main Results:
- Certain GDMTs (cardiac resynchronization, revascularization, mechanical support) benefit remodeling.
- Limitations identified for routine mitral valve repair and certain PCI adjuncts.
- New therapies like sacubitril/valsartan show clinical benefits; omecamtiv mecarbil shows remodeling improvement without early clinical benefit.
Conclusions:
- Non-invasive remodeling measures (LVEF, LVESV, LVEDV) are valuable metrics for cardiovascular therapies.
- Reverse remodeling in HFrEF with GDMT supports ongoing research in diagnostics and therapeutics.
- Continued research in implementation science, imaging, and gene-based therapeutics is motivated by these findings.
Purpose Of Review:
Ischemic and non-ischemic injury to the heart causes deleterious changes in ventricular size, shape, and function. This adverse remodeling is mediated by neurohormonal and hemodynamic alterations and is reflected in non-invasive measures of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV). These measures are closely linked to cardiovascular outcomes and have become key surrogate endpoints for evaluating the therapeutic efficacy of contemporary treatments for heart failure with reduced ejection fraction (HFrEF). In this review, we critically evaluate recent published data (2015-2016) from randomized clinical trials (RCTs) and observational studies of HFrEF therapies to assess the role of ventricular remodeling on outcomes.
Recent Findings:
These data highlight the benefits of certain guideline-directed medical therapies (GDMT) such as cardiac resynchronization therapy, surgical revascularization, and mechanical circulatory support on remodeling, while revealing the limitations of other therapies-routine mitral valve repair for patients with moderate ischemic mitral regurgitation and adjuncts to percutaneous coronary intervention in patients with ST elevation myocardial infarction (cyclosporine A and bioabsorbable cardiac matrix). The new angiotensin receptor blocker/neprilysn inhibitor, sacubitril/valsartan, demonstrates convincing improvements in clinical outcomes with a study of remodeling parameters to follow; the new cardiac myosin activator, omecamtiv mecarbil, demonstrates improvement in remodeling parameters without a clear early clinical benefit. The concepts and contemporary trials reviewed in this paper reinforce the value of non-invasive measures of ventricular remodeling (LVEF, LVESV, and LVEDV) as important metrics across a range of cardiovascular therapies. Global non-invasive measures of cardiovascular remodeling have roughly paralleled or preceded hard clinical outcomes. Additionally, the capacity for reverse remodeling in HFrEF with GDMT motivates continued research in the fields of implementation science, diagnostic imaging, and gene-based therapeutics.