Reversed Reverse Remodeling
Can Biomonitoring Solve the Clinical Conundrum of the 3Rs?
In the course of managing patients with chronic heart failure (HF) because of left ventricular systolic dysfunction (LVSD; typically defined as an LV ejection fraction [EF] ≤40–50%), the goals of care include prescription of guideline-directed medical therapy with the achievement of target doses of angiotensin-converting enzyme inhibitors or angiotensin receptor II blockers, mineralocorticoid receptor antagonists, and β-adrenergic blockers (BBs).1 Each of these guideline-directed medical therapy agents has been associated with reduction in complications of HF, improving event-free survival in a broad range of studies, particularly when titrated to target doses; together with cardiac resynchronization therapy, this represents the best care that can be delivered for our patients with HF.
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Underlying clinical improvement is LV reverse remodeling (LVRR), characterized by decreased LV dimensions, normalization of LV shape, and improvement in systolic function; LVRR may be achieved through the application of guideline-directed medical therapy, in particular higher-dose BB therapy, and LVRR is unmistakably accompanied by improved prognosis. For example, pooled results of 22 studies about the effects of carvedilol suggest an improvement in LVEF of 6.9% during a 30-week follow-up period; in a smaller number of studies, concordant effects on LV volumes from carvedilol were also observed, with −26.7 and −33.9 mL changes in end-diastolic and end-systolic volumes, respectively, during a similar follow-up period.2 Models examining the likelihood for favorable outcome after LVRR suggested that improved LVEF or reduced LV volumes powerfully portend improved outcomes.2
Although LVRR frequently occurs during addition and uptitration of HF therapy (and is among the most powerful benefits of cardiac resynchronization therapy), the precise mechanisms underlying the structural improvement are not well understood. Patients with dilated cardiomyopathy generally experience the greatest structural improvement, raising the possibility of a reversal of inflammatory or other nonischemic processes that led to LV dysfunction …