The Role of ECG Strain Pattern in Prognosis after TAVI: A Sub-Analysis of the DIRECT Trial.

BACKGROUND: The presence of an electrocardiographic (ECG) strain pattern-among other ECG features-has been shown to be predictive of adverse cardiovascular outcomes in asymptomatic patients with aortic stenosis. However, data evaluating its impact on symptomatic patients undergoing TAVI are scarce. Therefore, we tried to investigate the prognostic impact of baseline ECG strain pattern on clinical outcomes after TAVI. METHODS: A sub-group of patients of the randomized DIRECT (Pre-dilatation in Transcatheter Aortic Valve Implantation Trial) trial with severe aortic stenosis who underwent TAVI with a self-expanding valve in one single center were consecutively enrolled. Patients were categorized into two groups according to the presence of ECG strain. Left ventricular strain was defined as the presence of ≥1 mm convex ST-segment depression with asymmetrical T-wave inversion in leads V5 to V6 on the baseline 12-lead ECG. Patients were excluded if they had paced rhythm or left bundle branch block at baseline. Multivariate Cox proportional hazard regression models were generated to assess the impact on outcomes. The primary clinical endpoint was all-cause mortality at 1 year after TAVI. RESULTS: Of the 119 patients screened, 5 patients were excluded due to left bundle branch block. Among the 114 included patients (mean age: 80.8 ± 7), 37 patients (32.5%) had strain pattern on pre-TAVI ECG, while 77 patients (67.5%) did not exhibit an ECG strain pattern. No differences in baseline characteristics were found between the two groups. At 1 year, seven patients reached the primary clinical endpoint, with patients in the strain group demonstrating significantly higher mortality in Kaplan-Meier plots compared to patients without left ventricular strain (five vs. two, log-rank p = 0.022). There was no difference between the strain and no strain group regarding the performance of pre-dilatation (21 vs. 33, chi-square p = 0.164). In the multivariate analysis, left ventricular strain was found to be an independent predictor of all-cause mortality after TAVI [Exp(B): 12.2, 95% Confidence Intervals (CI): 1.4-101.9]. CONCLUSION: Left ventricular ECG strain is an independent predictor of all-cause mortality after TAVI. Thus, baseline ECG characteristics may aid in risk-stratifying patients scheduled for TAVI.

Long-Term Outcomes and Valve Performance in Patients Undergoing Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) is an established method for treating patients with aortic valve stenosis. We sought to determine the long-term clinical outcomes and performance of a self-expanding bioprosthesis beyond 5 years. Consecutive patients scheduled for TAVI were included in the analysis. Primary end points were all-cause and cardiovascular mortality, structural valve deterioration (SVD) and bioprosthetic valve failure (BVF), based on the VARC-2 criteria and consensus statement by ESC/EAPCI. The study prospectively evaluated 273 patients (80.61 ± 7.00 years old, 47% females) who underwent TAVI with CoreValve/Evolut-R (Medtronic Inc.). The median follow-up duration was 5 years (interquartile range: 2.9 to 6; longest: 8 years). At 1, 5, and 8 years, estimated survival rates were 89.0%, 61.1%, and 56.0%, respectively, while cardiovascular mortality was 8% at the end of follow-up. Regarding valve performance, 5% of patients had early BVF and 1% had late BVF. Concerning SVD, 16 patients (6% of the total population) had moderate SVD (91% had an increase in mean gradient), with no severe SVD cases. Five patients with SVD died during follow-up. Actual analysis of the 8-year cumulative incidence of function of moderate SVD was 5.9% (2.5% to 16.2%). At multivariate analysis, the factor that emerged as an independent predictor for future SVD, was smaller bioprosthetic valve size (HR 0.58, 95% CI 0.41 to 0.82, p = 0.002). Long-term evaluation beyond 5 years after TAVI with a self-expanding bioprosthesis demonstrated low rates of cardiovascular mortality and structural valve deterioration. Valve size was an independent predictor for SVD.

Endothelial dysfunction in conduit arteries and in microcirculation. Novel therapeutic approaches.

The vascular endothelium not only is a single monolayer of cells between the vessel lumen and the intimal wall, but also plays an important role by controlling vascular function and structure mainly via the production of nitric oxide (NO). The so called "cardiovascular risk factors" are associated with endothelial dysfunction, that reduces NO bioavailability, increases oxidative stress, and promotes inflammation contributing therefore to the development of atherosclerosis. The significant role of endothelial dysfunction in the development of atherosclerosis emphasizes the need for efficient therapeutic interventions. During the last years statins, angiotensin-converting enzyme inhibitors, angiotensin-receptor antagonists, antioxidants, beta-blockers and insulin sensitizers have been evaluated for their ability to restore endothelial function (Briasoulis et al., 2012). As there is not a straightforward relationship between therapeutic interventions and improvement of endothelial function but rather a complicated interrelationship between multiple cellular and sub-cellular targets, research has been focused on the understanding of the underlying mechanisms. Moreover, the development of novel diagnostic invasive and non-invasive methods has allowed the early detection of endothelial dysfunction expanding the role of therapeutic interventions and our knowledge. In the current review we present the available data concerning the contribution of endothelial dysfunction to atherogenesis and review the methods that assess endothelial function with a view to understand the multiple targets of therapeutic interventions. Finally we focus on the classic and novel therapeutic approaches aiming to improve endothelial dysfunction and the underlying mechanisms.