Left Ventricular Hypertrophy Regression after Percutaneous Aortic Valve Replacement – A Sign of More Good Things to Come?

From the VA Boston Healthcare System and Brigham and Women’s Hospital, Boston, Massachusetts. Disclosure: Dr. Bhatt has served as a consultant for the following: Arena, Astellas, Astra Zeneca, Bayer, Bristol Myers Squibb, Cardax, Centocor, Cogentus, Daiichi-Sankyo, Eisai, Eli Lilly, Glaxo Smith Kline, Johnson & Johnson, McNeil, Medtronic, Millennium, Molecular Insights, Otsuka, Paringenix, PDL, Philips, Portola, Sanofi Aventis, Schering Plough, Takeda, The Medicines Company, and Vertex. Address for correspondence: Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC, Chief of Cardiology, VA Boston Healthcare System, Director, Integrated Interventional Cardiovascular Program, Brigham and Women's Hospital and the VA Boston Healthcare System. E-mail: dlbhattmd@alum.mit.edu ___________________________________ Individuals aged greater than or equal to 65 years constitute 22% of the total population of the United States, of whom, people aged greater than or equal to 85 years are the fastest growing cohort.1 With the aging population, the prevalence of aortic valve disease is on the rise. It is estimated that approximately 2% of people > 65 years, 3% of people > 75 years, and 4% percent of people > 85 years of age have aortic stenosis.2 Surgery is the mainstay of treatment for symptomatic patients, as medical therapy does not provide significant advantages for these patients. Without surgery, progressive disability due to symptoms of angina, syncope or heart failure ensues, and survival rarely exceeds 2–3 years. Currently, surgical aortic valve replacement is the only treatment that offers both symptomatic and prognostic benefit. However, one-third of elderly patients with severe symptomatic aortic stenosis are denied valve surgery because of advanced age and comorbidities.3,4 Percutaneous aortic valve replacement potentially offers an excellent solution to symptomatic patients with high surgical risk. In this issue of the Journal, Jilaihawi et al evaluated 15 patients with severe and symptomatic aortic stenosis who underwent percutaneous aortic valve replacement using the third-generation CoreValve percutaneous aortic bioprosthesis.5 The patients were a high-risk cohort, with a mean age of 85.8 years. Of the total, 13 patients had ischemic heart disease and, where appropriate, revascularization was performed prior to percutaneous aortic valve replacement. Remarkably, there were no periprocedural deaths. The procedure resulted in significant improvement in hemodynamics. There was a large reduction in gradients, with a 79% reduction in the peak transaortic gradient (from 77 mmHg to 14 mmHg) and an 82% reduction in mean transaortic gradient (from 46 mmHg to 7 mmHg). This resulted in a near-doubling of aortic valve area from 0.7 cm2 to 1.7 cm2 — an increase of 1 cm2! In those patients with some degree of left ventricular dysfunction at baseline, the ejection fraction increased by an average of 10%. The hemodynamic improvements seen in this study were associated with a 13% reduction in septal wall thickness as early as 1 month post procedure — comparable to long-term results obtained after surgery. This impressive regression, as early as 1 month post procedure, begs the question if percutaneous aortic valve implantation might provide an even more efficient and effective way to treat aortic stenosis than conventional surgery. In patients with aortic stenosis, left ventricular hypertrophy (LVH) is secondary to changes in the ventricular wall due to increased afterload. It has been shown that in patients with isolated aortic stenosis, increased LV mass predicted the presence of systolic dysfunction and heart failure independently of the severity of valvular obstruction and that LVH may be maladaptive rather than beneficial in these patients.6 Aortic valve replacement with a prosthetic valve in patients with aortic stenosis greatly reduces the afterload of the left ventricle, with consequent better hemodynamic performance. Regression of LVH is a more direct parameter to quantify the reduced work of the left ventricle and therefore to judge the hemodynamic efficiency of the aortic valve substitute. Furthermore, it has become more widely accepted that incomplete regression of LVH may lead to poor long-term survival following aortic valve replacement. Therefore, the extent and rate of regression in LVH after aortic valve replacement has been considered an important, though somewhat controversial, determinant of long-term survival. However, regression of LVH is incomplete in > 50% of patients studied at 1–2 years after aortic valve replacement.7 In a systematic review of 27 articles published evaluating the outcome of valve replacement in 1,546 aortic stenosis patients, it was determined that ventricles regress rapidly and reach their approximate final size within the first 6 months of surgery.8 Others have shown that this is a continuing process in the early postoperative phase, with reduction in left ventricular mass index from 10 days to 3 months and 3 months to 1.5 years post surgery,9 and that the regression of myocardial hypertrophy is a process that occurs over many years after correction of the primary hemodynamic abnormality.10 The early regression is thought to be due to regression of myocyte contractile elements after relief of the pressure load, and the late regression as a consequence of remodeling of the interstitial collagen matrix, which may take place over years.11 The commonly evaluated factors associated with left ventricular mass regression after aortic valve replacement surgeries are valve size, valve gradients and patient-prosthesis mismatch. After aortic valve replacement surgery, prosthesis-patient mismatch has been reported to be a predictor of postoperative elevated transvalvular gradients and residual LVH that affects long-term survival.12,13 However, other studies have shown that the prosthesis-patient mismatch does not affect LV mass regression and survival.14–16 Studies have shown that in patients post surgical aortic valve replacement, blood pressure control, rather than the type or size of prosthesis, was a major determinant of the degree of LV remodeling. These observations underscore the important role of strict control of blood pressure to improve survival in these patients.17 The effect of LV mass regression on mid- to long-term survival after aortic valve replacement surgery has also been questioned, with some studies showing no effect of the degree of LV mass regression on survival.10,18 The hemodynamic changes that occur post percutaneous aortic valve replacement are similar to the changes post aortic valve surgery. Consequently, many of the factors which contribute to LVH regression in this cohort should be similar to the ones in the surgical cohort. In the study published in this issue of the Journal, the authors showed a 13% decrease in septal wall thickness within 1 month of the procedure. The surgical literature seems to suggest that early regression occurs as early as 10 days post surgery. However, in the present series of patients, no changes were observed in posterior wall thickness or in LV in the early stages. The more important measure of hypertrophy, the overall LV mass, presumably did not change in the cohort of patients followed up for 6–12 months. The role of blood pressure control, which in some studies has been shown to be a better predictor of LV mass regression post aortic valve surgery, was not discussed by the authors. More studies are needed to further elucidate the effects of percutaneous valve replacement on these parameters and the exact time course of any changes. Conclusion. It is encouraging to see that none of the patients died and all of them had a significant decrease in post-procedure mean and peak gradients, as well as a large and significant increase in aortic valve area. The effects on hemodynamics and myocardial structure seem comparable with surgery, with the benefits obtained early — though without the early risks of surgery. Percutaneous aortic valve replacement thus appears to be the “light at the end of the tunnel” for patients with severe debilitating aortic stenosis who are not good surgical candidates. The initial experience with percutaneous aortic valve replacement has been encouraging, and if results of ongoing trials of percutaneous aortic valve replacement (Table) are as promising as what was seen in the study by Jilaihawi et al, the use of this technology may expand to include patients at lower surgical risk as well.

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