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Heartbeat: Beta-blockers for aortic regurgitation
  1. Catherine M Otto

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The current paradigm for the pathophysiology of chronic severe aortic regurgitation (AR) is that chronic volume overload results in progressive left ventricular (LV) dilation with eventual symptom onset or asymptomatic LV systolic dysfunction. Clinical management focuses on periodic monitoring of LV size and ejection fraction, as well as symptoms, to ensure aortic valve replacement is performed just before the onset of irreversible LV contractile dysfunction. This paradigm suggests that medical therapy to reduce volume overload or block LV dilation would slow disease progression. Disappointingly, previous studies of medical therapy in adults with chronic severe AR have failed to show a significant effect on clinical outcomes.

In this issue of Heart, Broch and colleagues (see page 191) hypothesized that beta-blocker therapy would reverse LV dilation in patients with chronic AR, similar to the effects of beta-blockers in patients with heart failure with reduced ejection fraction. To test this hypothesis, they performed a double blind clinical trial of metoprolol versus placebo in 75 asymptomatic adults (mean age 44 years, 89% male) with chronic moderate-severe AR using both echocardiographic and cardiac magnetic resonance (CMR) imaging measures of AR severity and LV geometry. Although, there were no serious adverse effects of metoprolol therapy, after 6 months there was no difference between groups in LV end-diastolic volume, exercise capacity or peak oxygen consumption. The only significant differences were a 2.7 (95% CI 0.1 to 5.3) percentage points higher LV ejection fraction and 138 (95% CI 71 to 205) pg/mL higher (p<0.001) N-terminal pro-B-type natriuretic peptide serum level in those randomized to metoprolol compared to the placebo group (figure 1).

Figure 1

Changes in main outcome variables from baseline to follow-up. Panels show the mean (whiskers 5–95% interval) changes in (A) left ventricular end diastolic volume (LVEDV), (B) left ventricular end systolic volume (LVESV), (C) left ventricular ejection …

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