Previous dogma held that vasodilators and heart rate reducing agents should be avoided in severe AS to avoid catastrophic hypotension. However, no major adverse effects of ACEI or beta-blocker therapy were observed in a series of 453 medically managed patients with severe AS.13,14 A number of studies have shown the haemodynamic safety of using ACEIs in patients with AS and preserved systolic function, and no serious adverse events were seen in the ramipril arm of RIAS.12,15,16 For these reasons, cautious use of ACEIs, ARBs, and beta blockade is appropriate in AS if indicated for other reasons.
Patients with AS who are not candidates for definitive treatment in the form of aortic valve replacement (AVR) on account of left ventricular systolic dysfunction (LVSD) may benefit from cautious supportive treatment with diuretics, ACEIs, ARBs, and aldosterone antagonists. A haemodynamic study has shown short term beneficial effects of sildenafil in patients with severe AS17 and nitroprusside can be used as a bridge to definitive treatment in compromised patients with severe AS and LVSD.18
Atrial fibrillation (AF) can be highly symptomatic in patients with AS on account of associated impairment in diastolic function. An aggressive rhythm control strategy is therefore essential.
Aortic regurgitation
Systemic vasodilators reduce the diastolic pressure gradient between the aorta and LV and are thought to reduce regurgitant volume in aortic regurgitation (AR) (see figure 3) and potentially delay the need for AVR. Two small randomised trials have examined this hypothesis in patients with aortic regurgitation and normal left ventricular systolic function, with mixed results.19,20 The earlier trial randomised 143 patients to either nifedipine or digoxin and showed a reduced rate of progression to AVR over six years, while the more recent trial randomised 95 patients to either nifedipine, enalapril or no treatment and found no difference.
Courtesy of John Chambers
There are many criticisms of both trials, including the use of digoxin as the comparator in the first trial and the lack of statistical power of the second. A meta-analysis has concluded that vasodilators have a favourable impact on LV remodelling,21 but given the lack of definite clinical benefit and potential risks (including coronary hypoperfusion due to inadequate diastolic pressure), current European Society of Cardiology (ESC) guidelines only recommend their use in patients with hypertension, a contraindication to surgery or with persisting LVSD after surgery.22
Beta blockers (see figure 4) and other negatively chronotropic agents are relatively contraindicated in AR, due to the possible increase in regurgitant volume as a result of prolonged diastole. However, beta blockers were associated with improved mortality in a large cohort of 756 patients with severe AR, even after adjusting for the presence of coronary artery disease, LVSD and hypertension.23
Interestingly, the association with improved mortality was seen in those with higher heart rates, where the duration of diastole would be most expected to lengthen with beta blockade. Although we do not have strong evidence, beta blockers can be considered for cautious introduction in patients with AR, particularly if there is another indication for their use.
