Summary Intercellular signaling by extracellular vesicles (EVs) is a route of cell-cell crosstalk that allows cells to deliver biological messages to specific recipient cells. EVs convey these ...messages through their distinct cargoes consisting of cytokines, proteins, nucleic acids, and lipids, which they transport from the donor cell to the recipient cell. In cardiovascular disease (CVD), endothelial- and immune cell-derived EVs are emerging as key players in different stages of disease development. EVs can contribute to atherosclerosis development and progression by promoting endothelial dysfunction, intravascular calcification, unstable plaque progression, and thrombus formation after rupture. In contrast, an increasing body of evidence highlights the beneficial effects of certain EVs on vascular function and endothelial regeneration. However, the effects of EVs in CVD are extremely complex and depend on the cellular origin, the functional state of the releasing cells, the biological content, and the diverse recipient cells. This paper summarizes recent progress in our understanding of EV signaling in cardiovascular health and disease and its emerging potential as a therapeutic agent.
Objectives The aim of this study was to provide a simple, reproducible, and point-of-care assessment of peri-prosthetic aortic regurgitation (periAR) during transcatheter aortic valve implantation ...(TAVI) and to decipher the impact of this peri-procedural parameter on outcome. Background Because periAR after TAVI might be associated with adverse outcome, precise quantification of periAR is of paramount importance but remains technically challenging. Methods The severity of periAR was prospectively evaluated in 146 patients treated with the Medtronic CoreValve (Minneapolis, Minnesota) prosthesis by echocardiography, angiography, and measurement of the aortic regurgitation (AR) index, which is calculated as ratio of the gradient between diastolic blood pressure (DBP) and left ventricular end-diastolic pressure (LVEDP) to systolic blood pressure (SBP): (DBP − LVEDP)/SBP × 100. Results After TAVI, 53 patients (36.3%) showed no signs of periAR and 71 patients (48.6%) showed only mild periAR, whereas 18 patients (12.3%) and 4 patients (2.7%) suffered from moderate and severe periAR, respectively. The AR index decreased stepwise from 31.7 ± 10.4 in patients without periAR, to 28.0 ± 8.5 with mild periAR, 19.6 ± 7.6 with moderate periAR, and 7.6 ± 2.6 with severe periAR (p < 0.001), respectively. Patients with AR index <25 had a significantly increased 1-year mortality risk compared with patients with AR index ≥25 (46.0% vs. 16.7%; p < 0.001). The AR index provided additional prognostic information beyond the echocardiographically assessed severity of periAR and independently predicted 1-year mortality (hazard ratio: 2.9, 95% confidence interval: 1.3 to 6.4; p = 0.009). Conclusions The assessment of the AR index allows a precise judgment of periAR, independently predicts 1-year mortality after TAVI, and provides additional prognostic information that is complementary to the echocardiographically assessed severity of periAR.
Paravalvular aortic regurgitation (PAR) negatively affects the prognosis after transcatheter aortic valve replacement (TAVR) with dramatically increased morbidity and mortality in patients with more ...than mild PAR. Because transcatheter heart valves are implanted in a sutureless fashion using oversizing to anchor the prosthesis stent frame at the level of the virtual aortic annulus, stent frame underexpansion due to heavily calcified cusps, suboptimal placement of the prosthesis, and/or annulus-prosthesis-size mismatch due to malsizing can contribute to paravalvular leakage. In contrast to open heart surgery, TAVR does not offer the opportunity to measure the aortic annulus under direct vision during the procedure. Therefore, the dilemma before each TAVR procedure is the appropriate sizing of the dimensions of the aortic annulus and to choose not only the size but also the transcatheter heart valve type (self-expanding vs. balloon-expandable) that fits the given anatomy best. Because precise echocardiographic quantification of PAR in patients with TAVR remains challenging especially in the acute implantation situation, a multimodal approach for the evaluation of PAR with the use of hemodynamic measurements and imaging modalities is imperative to precisely quantify the severity of aortic regurgitation immediately after valve implantation and to identify patients who will benefit from corrective measures such as post-dilation or valve-in-valve implantation. Every measure has to be taken to prevent or reduce PAR to provide a satisfying long-term clinical outcome.
Objectives The aim of this study was to determine the influence of baseline renal function and periprocedural acute kidney injury (AKI) on prognosis after transcatheter aortic valve implantation ...(TAVI). Background Evidence is growing that renal function is a major predictor of mortality in patients after TAVI. Methods TAVI was performed with the 18-F CoreValve prosthesis via transfemoral access. All-cause mortality was determined 30 days and 1 year after TAVI in 77 patients with a mean Society of Thoracic Surgeons mortality score of 9.3 ± 6.1% and a mean logistic European System for Cardiac Operative Risk Evaluation of 31.2 ± 17.6%. Results Overall procedural success rate was 98% with 1 periprocedural death. The 30-day mortality was 10%, and 1-year mortality was 26%. The mortality risk increased stepwise across quartiles of baseline serum creatinine. An AKI occurred in 20 of 77 patients: 12 patients (60%) with AKI died during follow-up. The incidence of AKI was related to peripheral arterial disease (65% vs. 39%; p = 0.04), the occurrence of a systemic inflammatory response syndrome (60% vs. 21%, p = 0.002), and post-procedural peri-prosthetic regurgitation ≥2+ (35% vs. 9%, p = 0.02). Impaired renal function at baseline reflected by serum creatinine ≥1.58 mg/dl (hazard ratio: 3.9, 95% confidence interval: 1.6 to 9.5; p = 0.002) and the occurrence of AKI (hazard ratio: 5.9, 95% confidence interval: 2.4 to 14.5, p < 0.001) that was not related to the amount of contrast dye were strong predictors of 1-year mortality after TAVI. Conclusions Impaired renal function at baseline and the occurrence of periprocedural AKI, independent whether renal function returns to baseline or not, are strong predictors of 30-day and 1-year mortality after TAVI.
Abstract Objectives The purpose of this study was to investigate the persistence rates of iatrogenic atrial septal defect (iASD) after interventional edge-to-edge repair with serial transesophageal ...echocardiography examinations and close clinical follow-up (FU). Background Transcatheter mitral valve repair (TMVR) with the MitraClip system (Abbott Vascular, Abbott Park, Illinois) is a therapeutic alternative to surgery in selected high-risk patients. Clip placement requires interatrial transseptal puncture and meticulous manipulation of the steerable sheath. The persistence of iASD after MitraClip procedures and its clinical relevance is unknown. Methods A total of 66 patients (76.7% male, mean age 77.1 ± 7.9 years) with symptomatic mitral regurgitation (MR) at prohibitive surgical risk (EuroSCORE II 10.1 ± 6.1%) underwent MitraClip procedures and completed 6 months of FU. Results Transesophageal echocardiography after FU showed persistent iASD in 50% of cases. Patients with iASD did not significantly differ from patients without ASD concerning baseline characteristics, New York Heart Association functional class, severity of MR, and acute procedural success rates (p > 0.05). When comparing procedural details and hemodynamic measures between groups, MitraClip procedures took longer in patients without iASD (82.4 ± 39.7 min vs. 68.9 ± 45.5 min; p = 0.05), and echocardiography after FU showed less decrease of systolic pulmonary artery pressures in the iASD group (−1.6 ± 14.1 mm Hg vs. 9.3 ± 17.4 mm Hg; p = 0.02). Clinically, patients with iASD presented more often with New York Heart Association functional classes >II after FU (57% vs. 30%; p = 0.04), showed higher levels of N-terminal pro-brain natriuretic peptide (6,667.3 ± 7,363.9 ng/dl vs. 4,835.9 ± 6,681.7 ng/dl; p = 0.05), and had less improvement in 6-min walking distances (20.8 ± 107.4 m vs. 114.6 ± 116.4 m; p = 0.001). Patients with iASD showed higher death rates during 6 months (16.6% vs. 3.3%; p = 0.05). Cox regression analysis found that only persistence of iASD (p = 0.04) was associated with 6-month survival. Conclusions The persistence rate of 50% iASD after MitraClip procedures is considerably high. Persistent interatrial shunting was associated with worse clinical outcomes and increased mortality. Further studies are warranted to investigate if persistent interatrial shunting is the mediator or marker of advanced disease in these patients.
Objectives The aim of this study was to evaluate the performance of the aortic regurgitation (AR) index as a new hemodynamic parameter in an independent transcatheter aortic valve implantation (TAVI) ...cohort and validate its application. Background Increasing evidence associates more-than-mild periprosthetic aortic regurgitation (periAR) with increased mortality and morbidity; therefore precise evaluation of periAR after TAVI is essential. The AR index has been proposed recently as a simple and reproducible indicator for the severity of periAR and predictor of associated mortality. Methods The severity of periAR was evaluated by echocardiography, angiography, and periprocedural measurement of the dimensionless AR index = (diastolic blood pressure − left ventricular end-diastolic pressure/systolic blood pressure) × 100. A cutoff value of 25 was used to identify patients at risk. Results One hundred twenty-two patients underwent TAVI by use of either the Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) (79.5%) or the Edwards-SAPIEN bioprosthesis (Edwards Lifesciences, Irvine, California) (20.5%). The AR index decreased stepwise from 29.4 ± 6.3 in patients without periAR (n = 26) to 28.0 ± 8.5 with mild periAR (n = 76), 19.6 ± 7.6 with moderate periAR (n = 18), and 7.6 ± 2.6 with severe periAR (n = 2) (p < 0.001). Patients with AR index <25 had a significantly increased 1-year mortality rate compared with patients with AR index ≥25 (42.3% vs. 14.3%; p < 0.001). Even in patients with none/mild periAR, the 1-year mortality risk could be further stratified by an AR index <25 (31.3% vs. 14.3%; p = 0.04). Conclusions The validity of the AR index could be confirmed in this independent TAVI cohort and provided prognostic information that was complementary to the severity of AR.
Background Up to 50% of the patients still die or have to be rehospitalized during the first year after transcatheter aortic valve replacement (TAVR). This emphasizes the need for more strategic ...patient selection. The aim of this prospective observational cohort study was to compare the prognostic value of risk scores and circulating biomarkers to predict all-cause mortality and rehospitalization in patients undergoing TAVR. Methods We calculated the hazard ratios and C-statistics (area under the curve AUC) of 4 risk scores (logistic European System for Cardiac Operative Risk Evaluation EuroSCORE, EuroSCORE II, Society of Thoracic Surgeons predicted risk of mortality, and German aortic valve score) and 5 biomarkers of inflammation and/or myocardial dysfunction (high-sensitivity C-reactive protein, growth differentiation factor (GDF)–15, interleukin-6, interleukin-8, and N-terminal pro–B-type natriuretic peptide) for the risk of death (n = 80) and the combination of death or rehospitalization (n = 132) during the first year after TAVR in 310 consecutive TAVR patients. Results The EuroSCORE II and GDF-15 had the strongest predictive value for 1-year mortality (EuroSCORE II, AUC 0.711; GDF-15, AUC 0.686) and for the composite end point (EuroSCORE II, AUC 0.690; GDF-15, AUC 0.682). When added to the logistic EuroSCORE and EuroSCORE II, GDF-15 enhanced the prognostic performance of the score and enabled substantial reclassification of patients. Combinations of increasing tertiles of the logistic EuroSCORE or EuroSCORE II and GDF-15 allowed the stratification of the patients into subgroups with mortality rates ranging from 4.0% to 49.1% and death/rehospitalization rates ranging from 15.3% to 68.4%. Conclusions Our study identified GDF-15 in addition to the logistic EuroSCORE and the EuroSCORE II as the most promising predictors of a poor outcome after TAVR.
Abstract Objectives The aims of this study were to increase the discriminatory value of the aortic regurgitation index (ARI) for the assessment of paravalvular regurgitation (PVR) and to further ...elucidate the association between aortic regurgitation severity and mortality after transcatheter aortic valve replacement (TAVR). Background Hemodynamic parameters such as the ARI complement predominantly angiographically guided TAVR. However, the ARI depends on several baseline and periprocedural characteristics. Methods The ARI was prospectively calculated before and after TAVR in 600 patients. The severity of PVR was assessed in all patients by angiography and echocardiography according to a 3-class scheme. To account for pre-procedural hemodynamic status, the ARI ratio was calculated as post- over pre-procedural ARI. Results Apart from the degree of PVR (β = −0.396, p < 0.001), pre-procedural hemodynamic status in the form of the ARI before TAVR (β = 0.227, p < 0.001) was associated with post-procedural ARI in multivariate regression analysis. The ARI ratio increased the specificity of post-procedural ARI alone for the prediction of both more than mild PVR and 1-year mortality from 75.1% to 93.2% and from 75.0% to 93.3%, respectively. Patients with post-procedural ARI values <25 after TAVR had significantly increased 1-year mortality only when the ARI ratio was <0.60 (50.0% vs. 26.3%, p = 0.001). Conclusions The ARI ratio integrating pre- and post-procedural hemodynamic status increases the discriminatory value of post-procedural ARI. The ARI ratio, which reflects acute hemodynamic changes after TAVR, is useful to identify patients with negative outcomes.
The acute and long-term effects of transcatheter aortic valve implantation (TAVI) in patients with aortic valve stenosis on left ventricular (LV) function are controversial. The aim of this study was ...to determine the effect of TAVI on LV function with two-dimensional (2D) and three-dimensional (3D) speckle-tracking analysis of LV deformation capability.
Patients underwent standardized 2D and 3D transthoracic echocardiography before TAVI and after 6 months of follow-up, including 3D and 2D LV deformation imaging.
Forty-four patients (mean age, 81.7 ± 5.5 years; 21 men 47.7%; mean body mass index, 26.3 ± 5.1 kg/m(2); mean logistic European System for Cardiac Operative Risk Evaluation score, 24.4 ± 13.7%) undergoing TAVI were prospectively included. After follow-up, mean 3D LV ejection fraction (LVEF) (35.4 ± 13.1% vs 40.6 ± 12.6%, P = .004), 3D LV volumes (end-systolic volume, 85.9 ± 41.8 vs 65.9 ± 33.7 mL, P < .001; end-diastolic volume, 127.6 ± 40.7 vs 106.4 ± 40.9 mL, P = .001), 3D global longitudinal strain (-9.9 ± 3.7% vs -12.6 ± 4.2%, P < .001), and 3D LV twist (6.1 ± 4.3° vs 8.5 ± 6.9°, P = .025) were relevantly improved. LV improvement was pronounced in patients with decreased baseline LV function (area under the curve, 0.78; P < .001), with a cutoff value for 3D LVEF of ≤37% to identify functional responders to TAVI. After follow-up, patients with 3D LVEFs ≤ 37% showed a significant improvements in 3D LVEF (26.0 ± 7.6% vs 35.9 ± 11.7%, P < .001), 3D LV volumes (end-diastolic volume, 147.4 ± 40.6 vs 117.1 ± 45.5 mL, P = .001; end-systolic volume, 110.9 ± 39.2 vs 77.5 ± 37.2 mL, P < .001), 3D global longitudinal strain (-7.8 ± 2.7% vs -11.3 ± 4.2%, P < .001), and 3D LV twist (5.6 ± 4.2° vs 8.0 ± 5.6°, P = .047), whereas in patients with 3D LVEFs > 37%, only 3D global longitudinal strain was relevantly altered (-12.5 ± 3.1% vs -14.2 ± 3.8%, P = .04). Compared with 2D transthoracic echocardiography, 3D LV functional imaging allowed significantly faster image acquisition and data analysis (P < .0001). New York Heart Association functional class improved significantly in both groups (3D LVEF ≤ 37%, from 3.1 ± 0.5 to 2.0 ± 0.6, P < .001; 3D LVEF > 37%, from 2.7 ± 6.7 to 1.5 ± 0.7, P < .001), whereas a significant amelioration of N-terminal pro-brain natriuretic peptide was observed only in patients with baseline 3D LVEFs ≤ 37% (10,314.64 ± 11,682.2 vs 3,398.7 ± 3,598.9 pg/mL, P = .02; 3D LVEF > 37%, 10,306.4 ± 32,000.5 vs 2,868.0 ± 3,816.7 pg/mL, P = .12).
Our results indicate significant improvements of LV global and longitudinal function and clinical parameters 6 months after TAVI that are pronounced in patients with impaired baseline LV function. Compared with 2D LV functional imaging, 3D speckle-tracking imaging allowed significantly faster image acquisition and data analysis.
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