Early Regression of Left Ventricular Wall Thickness following Percutaneous Aortic Valve Replacement (Full title below)

From the *Department of Cardiology and the §Department of Cardiothoracic Surgery, Glenfield Hospital, Leicester, United Kingdom. The authors report no conflicts of interest regarding the content herein. Manuscript submitted November 17, 2008, provisional acceptance given December 2, 2008 and final version accepted December 31, 2009. Corresponding author: Jan Kovac, MD, Department of Cardiology, Glenfield Hospital, Leicester United Kingdom LE3 9QP. E-mail: jankovac2@hotmail.com ________________________________

Early Regression of Left Ventricular Wall Thickness following Percutaneous Aortic Valve Replacement with the CoreValve Bioprosthesis

ABSTRACT: Background/Aims. Severe aortic stenosis (AS) is associated with hypertrophy of the left ventricle (LVH), which is linked to adverse clinical outcomes. To date, the effects of the novel technology of percutaneous aortic valve replacement (PAVR) on LVH in severe AS have not been described. We sought to test the hypothesis that PAVR would result in regression of LVH associated with severe AS. Methods. Patients were recruited as part of a single-arm, prospective, safety, feasibility and clinical outcome study of the third-generation CoreValve percutaneous aortic bioprosthesis. To assess hypertrophy at baseline and at 1 month, the parasternal long-axis view in end-diastole was used to assess interventricular septal dimension and left ventricular posterior wall dimension. Results. 15 patients were studied. There were significant periprocedural reductions in peak (76.6 ± 28.1 mmHg to 16.3 ± 7.5 mmHg; p Methods The study cohort comprises patients with AS and LVH undergoing PAVR within a single-arm, prospective multicenter international safety, feasibility and clinical outcome study of the 18 Fr third-generation CoreValve aortic revalving system. Baseline operative risk was estimated by the logistic Euroscore.8 Inclusion criteria for the study were severe symptomatic AS (aortic valve area Results Baseline characteristics. The characteristics at baseline are summarized in Table 1. Fifteen patients with severe AS and LVH underwent PAVR between the 30th of January 2007 and the 17th of July 2007. Patients had a mean (SD) age of 85.8 (4.5) years and were predominantly female. All patients were symptomatic, with the majority (66.7%) having New York Heart Association (NYHA) Class II symptoms and the remainder Class III symptoms. Peak transvalvular gradient at baseline was 76.6 ± 28.1 mmHg and mean 45.3 ± 18.4 mmHg. Calculated aortic valve area at baseline was 0.73 ± 0.19 cm2. At 1-month follow up there were no case fatalities. Hemodynamic results. A complete study dataset was available in 14 of the 15 patients. One patient with previous total pneumonectomy had unsuitable transthoracic echocardiographic windows, with poor endocardial definition preventing accurate measurement of wall thickness and chamber dimensions. In this patient, valve hemodynamic measurements were recorded. Significant periprocedural reductions were observed in peak (76.6 ± 28.1 mmHg to 16.3 ± 7.5 mmHg; p 55%). There was no change in EF from baseline to 1 month (54.8 ± 8.0 % to 57.5 ± 5.9 %; n = 14; p = 0.415). However, in patients with some degree of LV systolic impairment at baseline (EF 0.001). Data were available for 11 patients at the latest available follow up of 6–12 months; 3 died within this timeframe. IVSd dimension was 1.39 ± 0.21 cm (p = 0.02 for reduction relative to baseline). There was a nonsignificant trend toward a reduced LVPWd of 1.24 ± 0.19 cm at this later timepoint (p = NS relative to baseline). Changes in C-reactive protein (CRP). CRP was minimally elevated at baseline at 7.8 mg/L (1.3). It increased dramatically to 96 mg/L (64.3) (p = 0.03) predischarge and partially recovered to 26.1 mg/L (28.4) at a median follow up of 30 days. Discussion In our study, significant regression of septal hypertrophy was observed as early as 1 month following PAVR. While we observed a reduction in LV mass at this early timepoint, this was not statistically significant. No overall change in PWd was observed. A degree of asymmetric hypertrophy was observed at baseline, which has previously been reported in severe AS.13 LVH is an independent predictor of cardiovascular morbidity and mortality.16,21 In isolated aortic stenosis, LV mass predicts the presence of heart failure and systolic dysfunction independent of the severity of valvular obstruction.17 After open aortic valve replacement, hypertrophy fails to regress in around a third or more18 of patients and is difficult to predict with clinical parameters;19 moreover, lower regression is associated with a higher incidence of heart failure and death.19 While the effects of open AVR on hypertrophy have been studied, this is the first documentation of changes in this important clinical variable following PAVR with the CoreValve. Our findings approximate to those seen at medium-term follow up of open AVR with different prostheses. De Paulis et al evaluated patients undergoing open AVR with three different prostheses. In their cohort (10 patients in each group) a comparable reduction in septal wall thickness at a mean of 12–15 months was observed regardless of prosthesis (15% reduction with the Sorin stentless bioprosthesis, 13% with the Hancock stented bioprosthesis and 15% with the Carbomedics bileaflet mechanical valve13). Christakis et al observed a significant reduction in LV mass regardless of prosthesis used in 54 patients undergoing open AVR before and 1 week post surgery. The authors speculated that this early regression in LV mass was due to a reduction in transvalvular gradients and wall stress. We have demonstrated comparable reductions in transvalvular gradients, and a nonsignificant trend toward reduction in LV wall mass at this timepoint. The reasons for asymmetric regression in LVH at this timepoint are unclear. The base of the CoreValve stent is deployed in a position adjacent to the basal septum. One explanation may be that contact between the CoreValve stent and local septal tissue (which does not occur in the posterior wall) induces early changes in the tissue constitution, with inflammation leading to fibrosis or necrosis replacing hypertrophied tissue. Although we noted changes in inflammatory indices in our population, it is impossible to ascertain whether these changes reflect this process or are simply a reflection of the complex healing process that occurs with implantation and embedding of this valve. (It is important to note that none of these patients demonstrated signs of infection and serial blood cultures were negative in all patients; likewise, no patients developed endocarditis at follow up.) The limited spatial resolution of two-dimensional echocardiography impairs the efficacy of this tool in evaluating this issue. Although these findings may better be assessed using magnetic resonance imaging (MRI), concerns regarding MRI compromise of prosthesis stability in the very early post-implantation phase were initially raised at the time of the trial. However, this has now been performed safely at a few institutions, including our own, in isolated cases without adverse sequelae. Ten-year follow-up studies on open AVR have indicated that the greatest rate of LV mass regression occurs in the first year.22,23 It is equally feasible that changes in posterior wall thickness and LV mass occur several months after PAVR. Conclusion We demonstrate an early regression of septal hypertrophy after percutaneous aortic valve replacement for severe calcific AS which is comparable to that seen at 1 year following conventional surgical aortic valve replacement. Direct comparisons between changes seen following percutaneous and conventional aortic valve replacement will be of interest. Longer follow up employing MRI may help determine later changes and evaluate the reasons for asymmetric patterns of hypertrophic regression and its longer-term significance. Acknowledgements. We thank Dr. Jean-Claude Laborde, lead proctor for Corevalve, for his training in the procedure and ongoing significant input and advice in challenging cases.

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