Favorable Effects of Vasodilators on Left Ventricular Remodeling in Asymptomatic Patients With Chronic Moderate‐Severe Aortic Regurgitation and Normal Ejection Fraction: A Meta‐Analysis of Clinical Trials

Abstract

Background: The role of vasodilator therapy in asymptomatic patients with chronic moderate to severe aortic regurgitation (AR) and normal left ventricular (LV) function is uncertain. We assessed the effects of vasodilator therapy (hydralazine, calcium channel blockers, and angiotensin-converting enzyme inhibitors) in this subgroup of patient population. Hypothesis: Vasodilators have favorable effects on LV remodelling in asymptomatic patients with chronic moderate to severe aortic regurgitation and normal LV function. Methods: We performed a systematic literature search for randomized clinical trials using long-term vasodilator therapy in asymptomatic patients with chronic severe AR and normal LV function. The magnitude of difference between the vasodilator and nonvasodilator groups was assessed by computing the mean difference (MD). Heterogeneity of the studies was analyzed by Cochran Q statistics. The MD for LV ejection fraction, LV end systolic volume index, and LV end diastolic volume index were computed by random effects model. The MD for LV end-systolic diameter and LV end-diastolic diameter were computed by fixed effects model. A 2-sided alpha error <0.05 was considered to be statistically significant. Results: Seven studies with 460 patients were included. Meta-analysis of the studies revealed a significant increase in LVEF (MD: 5.32, 95% confidence interval [CI]: 0.37 to 10.26, P = 0.035), a significant decrease in LV end diastolic volume index (MD: −16.282, 95% CI: −23.684 to −8.881, P < 0.001), and a significant decrease in LV end diastolic diameter (MD: −2.343, 95% CI: −3.397 to −1.288, P < 0.001) in the vasodilator group compared with the nonvasodilator group. However, there was no significant decrease in LV end systolic volume index (MD: −6.105, 95% CI: −12.478 to 0.267, P = 0.060) or in LV end systolic diameter (MD: 0.00, 95% CI: −0.986 to 0.986, P = 1.0) in the vasodilator group compared with the nonvasodilator group. Conclusions: In asymptomatic patients with chronic severe AR and normal LV function, vasodilators have favorable effects on LV remodeling.

Impact of renin‐angiotensin system inhibitors on long‐term clinical outcomes of patients with rheumatic heart disease

“…First, the left ventricular and atrial remodelling were very advanced at this late stage 34 due to long‐term progression of interstitial fibrosis and thus difficult to reverse by RAASi. In our study, we found that RAASi had no effect on reversing LAD and left ventricular end‐diastolic diameter sizes (Supporting Information, Table ), which was partial similar to previously reported association of RAASi therapy with left heart remodelling in patients with chronic moderate–severe aortic regurgitation 35 . Second, surgical treatment only afforded short‐term easement of mechanical damage from cardiomyocyte hypertrophy caused by reduction of preload or afterload in the early post‐operative period.…”

“…In our study, we found that RAASi had no effect on reversing LAD and left ventricular end‐diastolic diameter sizes (Supporting Information, Table S2 ), which was partial similar to previously reported association of RAASi therapy with left heart remodelling in patients with chronic moderate–severe aortic regurgitation. 35 Second, surgical treatment only afforded short‐term easement of mechanical damage from cardiomyocyte hypertrophy caused by reduction of preload or afterload in the early post‐operative period. In patients with rheumatic MS undergoing percutaneous mitral balloon valvuloplasty, improved ventricular function only lasted ~1 year, and this was also observed for patients undergoing aortic valve replacement.…”

Angiotensin II–Converting Enzyme Inhibition Improves Survival, Ventricular Remodeling, and Myocardial Energetics in Experimental Aortic Regurgitation

“…5,22 The controversy regarding the efficacy of vasodilators, including ACEI in the treatment of AR, is far from resolved. Recently, a meta-analysis of all the randomized clinical trials that evaluated vasodilators in AR 23 showed that the evidence points toward the efficacy of vasodilators although a wide discrepancy exists between the trials' design and results. ACEIs were found almost always favorable in terms of protection against LV dilatation and loss of ejection fraction.…”

Pharmacological interventions for the treatment of aortic root and heart valve disease

“…However, since it is the volume overload of regurgitant blood that leads to myocardial dysfunction in AR, drugs such as vasodilators might reduce the haemodynamic burden on the LV and prevent its remodelling. In a metaanalysis of hydralazine, calcium channel blockers (CCB), and ACE-Is in asymptomatic severe AR with normal LV function, vasodilator therapy showed favourable e ects on LV remodelling (Shah 2012). Although the potential of beta-blockade in AR is controversial, since it prolongs diastole and may worsen the volume overload, preclinical and observational data suggest it may be cardioprotective in AR.…”

“…Alongside the benefits, potential harms of medications need to be identified. Multiple meta-analyses have been carried out in this area, such as on the role of betablockers in Marfan syndrome or vasodilators in AR, and more wideranging reviews have also been published (Mahajerin 2007;Shah 2012;Siontis 2016;Marquis-Gravel 2016). However, an up-to-date systematic review of studies involving populations with aortic valve and root disease, and treated with medication acting directly or indirectly on the cardiovascular system, may support healthcare providers when choosing pharmacologic agents in those patients for whom surgery is not (or not yet) feasible, and would be a significant addition to the literature.…”