Sustained Elevation of Vascular Endothelial Growth Factor and Angiopoietin-2 Levels After Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) exposes the systemic vasculature to increased mechanical forces. Endothelial adaptation to mechanical stimuli is associated with angiogenic activation through various growth factors. We studied the potential angiogenic shift evoked by TAVR. METHODS: From a cohort of 69 consecutive patients undergoing TAVR, we excluded patients with conditions known to affect angiogenic factors, and serum vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 were assessed by ELISA. We assessed in vitro the properties of endothelial cells after exposure to serum collected from patients undergoing TAVR using adhesion, migration, and Matrigel angiogenesis assays. The correlation between changes in angiogenic factors and cardiac functions was evaluated on 30- day echocardiograms. RESULTS: The study population consisted of 46 patients (82 ± 5 years). Two days after TAVR the post/pre TAVR ratio of VEGF, Ang-1, and Ang-2 was 5.38 ± 4 (P < 0.001), 1.05 ± 0.49 (P = 0.27), and 4.65 ± 2.01 (P < 0.001), respectively. The increase in VEGF and Ang-2 showed a significant correlation (r = 0.609; P < 0.001), but no correlation was found with hemolysis or tissue injury markers. Patients with relatively low levels of VEGF or an Ang-2 rise had more severe aortic stenosis and coronary disease at baseline. Exposure of endothelial cells to post-TAVR serum induced adhesion, migration, and tube formation compared with pre-TAVR serum. An increase in VEGF levels correlated with improvement in pulmonary systolic pressure and a right ventricular fractional area change at 30 days, (r = 0.54 and r = 0.48, respectively; P < 0.01). CONCLUSIONS: Sustained elevation of VEGF and Ang-2 levels occur after TAVR, reflecting a systemic angiogenic shift. A rise in VEGF levels is associated with a decrease in pulmonary blood pressure in patients undergoing TAVR.

Impact of Diabetes Mellitus and Hemoglobin A1C on Outcome After Transcatheter Aortic Valve Implantation.

Surgical aortic valve replacement (SAVR) is associated with an increased mortality risk in elderly or high-risk patients. Transcatheter aortic valve implantation (TAVI) is an alternative to surgery in patients with symptomatic severe aortic stenosis who are inoperable or at high operative risk. The impact of diabetes mellitus (DM) on patients referred to TAVI merits further investigation. The aim of our study was to evaluate the clinical characteristics and the impact of DM status on the updated Valve Academic Research Consortium 2-defined outcomes of TAVI and to stratify patient outcomes according to their initial glycated hemoglobin (HbA1c) levels. We enrolled and stratified patients who underwent TAVI at our institution according to DM status. A total of 586 patients were enrolled: 348 (59%) without DM and 238 (41%) with DM. There were no significant differences in 30-day mortality patients with diabetes compared to patients without diabetes (3.3% vs 2.9%, p = 0.974). Insulin-treated DM was not associated with adverse outcome in comparison to orally treated DM. To delineate the prognostic power of HbA1C in these patients, the cohort was divided into 3 groups according to HbA1C levels (<5.7%, 5.7% to 6.49%, and ≥6.5%). Patients with HbA1C ≥6.5% were at increased risk for mortality during follow-up (hazard ratio 2.571, 95% confidence interval 1.077 to 6.136, p = 0.033) compared to patients with HbA1C <5.7%. In conclusion, unlike SAVR, DM is not associated with an increased mortality risk after TAVI, nor is it associated with increased complications rates. A more poorly controlled disease, as manifested by elevated HbA1c levels, may be associated with increased mortality during long-term follow-up.