By Van Selby, MD
Assistant Professor of Medicine, University of California, San Francisco, Cardiology Division, Advanced Heart Failure Section
Dr. Selby reports no financial relationships relevant to this field of study.
SYNOPSIS: Right ventricular dysfunction is common in dilated cardiomyopathy and frequently recovers with medical therapy for heart failure. Recovery of right ventricular function predicts subsequent improvement in left ventricular function and is associated with better outcomes.
SOURCE: Merlo M, Gobbo M, Stolfo D, et al. The prognostic impact of the evolution of RV function in idiopathic DCM. JACC Cardiovasc Imaging 2016;9:1034-1042.
Although dilated cardiomyopathy (DCM) is defined by left ventricular (LV) systolic dysfunction, right ventricular (RV) dysfunction also has been identified as an important prognostic marker. No study to date has evaluated changes in RV function over time and the association with survival in patients being treated for DCM.
Merlo et al retrospectively analyzed RV function at baseline and at least one follow-up assessment in 512 patients with recently diagnosed idiopathic DCM who were enrolled in the Trieste Heart Muscle Disease Registry between 1993 and 2008. All patients featured LV ejection fraction (EF) < 50%, and coronary artery disease was ruled out with angiography in all patients > 35 years of age and those with risk factors. At baseline, 95% of patients were treated with angiotensin-converting enzyme inhibitors and 84% with beta-blockers. RV function was evaluated using the RV fractional area change (RV-FAC: end-diastolic area - end-systolic area/end-diastolic area x 100). The primary outcome was a composite of death or heart transplantation.
At baseline, 20% of the cohort experienced RV dysfunction, defined as RV-FAC < 35%. Subjects with RV dysfunction demonstrated more advanced New York Heart Association functional class, worse LV systolic function, and higher pulmonary artery systolic pressure. Baseline RV dysfunction was associated independently with increased rates of death or heart transplant (hazard ratio, 1.71; P = 0.0413).
During follow-up, 86% of patients with RV dysfunction at baseline recovered RV function, with a median time to recovery of six months. Recovery of RV function was associated with subsequent LV reverse remodeling (LVRR, defined as an improvement in EF ≥ 10%), occurring at a median time of 24 months (odds ratio, 2.49; P = 0.018). Subjects with RV dysfunction at baseline who subsequently recovered RV function on follow-up evaluation demonstrated similar overall survival compared to those with normal RV function (P = 0.205). On the other hand, those with persistent RV dysfunction or those who developed RV dysfunction on subsequent evaluations experienced significantly worse survival (P = 0.003 for the global comparison). The authors concluded that systematic serial evaluation of RV function may assist clinical decision making, and RV reverse remodeling should be considered an important target in the early management of DCM.
COMMENTARY
This is among the first studies to report the natural history of RV function in a large cohort of DCM, with several important findings. RV dysfunction was common, present in 20% of subjects at baseline, and is associated with worse outcomes independent of other clinical or echocardiographic predictors. However, the majority of subjects with baseline RV dysfunction recover function, and this recovery occurs relatively quickly. Those with recovery of RV function demonstrated long-term survival that was similar to those with normal RV function, highlighting the importance of serial echocardiograms when using RV function as a prognostic marker in idiopathic DCM.
Interestingly, recovery of RV function was a strong predictor of subsequent LVRR. When LVRR occurred, it did so after a median follow-up of 24 months. The authors hypothesized the different time to recovery in RV and LV function may be related to the effects of neurohormonal antagonist therapy on each ventricle. Changes in RV function appear to reflect the early hemodynamic benefits of treatment such as lowering vascular resistance and left-sided filling pressures. Among patients with baseline RV dysfunction, those who subsequently recovered experienced a significant reduction in pulmonary artery systolic pressure, whereas those with persistent dysfunction did not. Subjects who recovered function also had a marked reduction in the prevalence of LV diastolic dysfunction on follow-up evaluation, compared to no significant change in those who did not recover. On the other hand, the LV response to neurohormonal blockade therapy depends on structural changes to the LV, which occur at a slower pace. Early after initial diagnosis, assessment of RV function may be more important than LV function when determining prognosis, although this requires validation in further studies.
This was a retrospective study, limited only to patients with idiopathic DCM. Whether the findings extend to patients with ischemic or other cardiomyopathies is unknown. RV function only was evaluated using RV-FAC. Accurate measurement of RV-FAC requires adequate echocardiographic windows. In everyday practice, simpler methods, such as the tricuspid annular plane systolic excursion, often are used. Whether the same prognostic significance holds for alternate measures of RV function is unknown.
The left ventricle, especially systolic function, measured by EF, often is the primary focus of follow-up echocardiograms in patients with systolic heart failure. The findings of Merlo et al emphasize the importance of comprehensive evaluations, including RV function. Future studies will help clarify the role of monitoring changes in RV function when assessing response to therapy for heart failure.
Right ventricular dysfunction is common in dilated cardiomyopathy and frequently recovers with medical therapy for heart failure. Recovery of right ventricular function predicts subsequent improvement in left ventricular function and is associated with better outcomes.
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