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In aortic stenosis (AS), narrowing of the valve results in an increased pressure gradient between the left ventricle and aorta.1 The related chronic elevation in the afterload leads to a rise in the systolic wall stress of the left ventricle, causing concentric hypertrophy, which is considered a mechanism to maintain cardiac output despite the increased narrowing of the aortic valve. In the long term, however, left ventricular hypertrophy is a two-edged sword that is connected with unfavourable changes in myocardial function. The myocardium in AS is characterised by an increased myocardial cell mass and myocardial fibrosis. This remodelling results in elevated myocardial stiffness, impaired relaxation and increased left ventricular filling pressures, with the development of diastolic heart failure. In addition, patients with AS often have concomitant arterial hypertension—particularly among elderly patients with calcific AS. This means a double loading of the left ventricle with additive unfavourable changes in the myocardial function. The question arises whether there is a drug therapy that can favourably affect this double burden on the left ventricle.
In patients with arterial hypertension, the pathophysiological changes of the increased afterload can be partly reversed by effective drug therapy. The extent of left ventricular hypertrophy and its regression under therapy has a prognostic significance.2 Previous studies suggest, in particular, the use of a renin-angiotensin system (RAS) blockade, which may have direct cardiac positive effects besides the effect on blood pressure.2 Therefore, drugs for RAS blockade may be an interesting option for treating patients with AS.
Nadir et al have recently demonstrated in a retrospective epidemiological study that RAS blockade is associated with improved survival and reduced cardiovascular events in patients with varying degrees of AS. Interestingly, the peripheral blood pressure under therapy was not different in the two study groups with and without RAS blockade.3 It is therefore suspected that there is a positive effect of RAS blockade on myocardial remodelling beyond the effects on blood pressure.
Regardless of a possible positive effect of RAS blockade, aortic valve replacement is the only effective therapy for symptomatic severe AS. Aortic valve replacement causes a dramatic reduction in the chronically increased afterload of the left ventricle. This treatment induces regression of the left ventricular hypertrophy over the first few months and years, especially in patients with initially severe hypertrophy.4 Since the postoperative regression of left ventricular hypertrophy may have prognostic significance, it is conceivable that RAS blockade also yields benefits after aortic valve replacement.
Recently, Goel et al investigated the effect of RAS blockade in patients with severe AS undergoing surgical aortic valve replacement. In their monocentric, retrospective examination, they were able to demonstrate a prognostic advantage of RAS blockade.5 However, in this study, there was no association between the RAS blockade and the extent of regression of left ventricular hypertrophy. The authors therefore suspected a positive effect of RAS blockade on left ventricular fibrosis, which explains the improved prognosis. This assumption, however, is not supported by data from the study.
With the development of transcatheter valves 15 years ago, an interventional treatment of AS is available. In recent years, this therapy has undergone rapid development of an experimental method for inoperable patients that has become a routine procedure. In the last 2 years, prospective, randomised multicentre studies have shown that transcatheter aortic valve implantation (TAVI) is equivalent in patients with intermediate risk compared with surgical valve replacement.6 7 This means that, currently, healthier patients with longer life expectancies are treated with TAVI compared with just a few years ago. The great successes of transcatheter valves have shifted the focus from short-term survival to the long-term outcomes of patients. However, there are still no studies and no recommendations for drug therapy after TAVI to favourably influence the prognosis.
In their Heart paper Ochiai et al examined for the first time the effects of therapy with RAS inhibitors after successful TAVI.8 In the prospective Optimized Catheter Valvular Intervention (OCEAN)-TAVI registry, 1215 patients were enrolled between 2013 and 2016 and treated with TAVI. In this subanalysis, 560 patients were retrospectively examined. The patients were divided into two groups based on the prescription of ACE inhibitors or angiotensin receptor blockers (ARBs) within the first 180 days after TAVI.
On the one hand, there were 371 patients with an at least a two-time prescription of ACE inhibitors or ARB (RAS blockade group), and on the other hand 189 patients without any prescription of ACE inhibitors or ARBs (no RAS blockade group). The authors observed a significantly stronger regression of left ventricular hypertrophy after 6 months in patients in the RAS blockade group than in patients in the no RAS blockade group. This result should be interpreted with caution, however, as the left ventricular mass varied in the different groups at the baseline and this might have led to considerable bias. The significantly more pronounced left ventricular hypertrophy in the RAS blockade group exhibited a significant regression so that the left ventricular mass was similar in both groups after 6 months (p=0.13).
Of particular clinical interest is that the present study by Ochiai et al suggests a prognostic benefit of RAS blockade after TAVI. The 2-year mortality of patients treated with RAS blockade was significantly lower than that of patients who were never treated with RAS blockade (7.5% vs 12.5%, p=0.031). The RAS blockade was an independent predictor of all-cause mortality (HR 0.45, 95% CI 0.22 to 0.91, p=0.025). In addition, the prognostic effect was also observed in patients with paravalvular regurgitation. This point is of particular interest because paravalvular regurgitation is a substantial problem of the transcatheter valves that lacks a completely convincing solution. However, the authors did not further differentiate the extent of paravalvular regurgitation in their study. This would be interesting because moderate and severe paravalvular regurgitation has considerable prognostic implications. Another interesting group of patients are those with prosthesis–patient mismatch. In this study, RAS blockade also yielded an advantage. In conclusion, the study by Ochiai et al is the first to demonstrate the utility of drug therapy after TAVI.
The present study confirms previous investigations, which showed a prognostic impact of RAS blockade in patients with AS.3 5 The investigation of Ochiai et al is of clinical interest because they suspected an effect even in patients who were undergoing TAVI. In particular, the drug therapy of patients with paravalvular regurgitation might be important.
However, there are some limitations. All of the studies to date have been retrospective studies. In addition, the link between the RAS blockade, regression of left ventricular hypertrophy and prognosis is uncertain. The prognostic benefit of RAS blockade in patients with AS is therefore possibly explained by other mechanisms. The encouraging results, as well as the limitations of previous retrospective studies, should prompt us to begin a prospective study to investigate the importance of RAS blockade in patients with AS.
Handling editor Catherine M Otto
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.