Comparison of balloon-expandable vs. self-expandable valves in patients undergoing transfemoral transcatheter aortic valve implantation: from the CENTER-collaboration.

Aims: The aim of this study was to compare clinical outcomes of patients undergoing transfemoral transcatheter aortic valve implantation (TAVI) with balloon-expandable (BE) valves vs. self-expandable (SE) valves. Transcatheter aortic valve implantation is a minimally invasive and lifesaving treatment in patients with aortic valve stenosis. Even though BE-valves and SE-valves are both commonly used on a large scale, adequately sized trials comparing clinical outcomes in patients with severe aortic valve stenosis treated with BE-valves compared with SE-valves are lacking. Methods and results: In this CENTER-collaboration, data from 10 registries or clinical trials, selected through a systematic search, were pooled and analysed. Propensity score methodology was used to reduce treatment selection bias and potential confounding. The primary endpoints were mortality and stroke at 30 days follow-up in patients treated with BE-valves compared with SE-valves. Secondary endpoints included clinical outcomes, e.g. bleeding during hospital admission. All outcomes were split for early-generation BE-valves compared with early-generation SE-valves and new-generation BE-valves with new-generation SE-valves. The overall patient population (N = 12 381) included 6239 patients undergoing TAVI with BE-valves and 6142 patients with SE-valves. The propensity matched population had a mean age of 81 ± 7 years and a median STS-PROM score or 6.5% [interquartile range (IQR) 4.0-13.0%]. At 30-day follow-up, the mortality rate was not statistically different in patients undergoing TAVI with BE-valves compared with SE-valves [BE: 5.3% vs. SE: 6.2%, relative risk (RR) 0.9; 95% confidence interval (CI) 0.7-1.0, P = 0.10]. Stroke occurred less frequently in patients treated with BE-valves (BE: 1.9% vs. SE: 2.6%, RR 0.7; 95% CI 0.5-1.0, P = 0.03). Also, patients treated with BE-valves had a three-fold lower risk of requiring pacemaker implantation (BE: 7.8% vs. SE: 20.3%, RR 0.4; 95% CI 0.3-0.4, P < 0.001). In contrast, patients treated with new-generation BE-valves more frequently experienced major and life-threatening bleedings compared with new-generation SE-valves (BE: 4.8% vs. SE: 2.1%, RR 2.3; 95% CI 1.6-3.3, P < 0.001). Conclusion: In this study, which is the largest study to compare valve types in TAVI, we demonstrated that the incidence of stroke and pacemaker implantation was lower in patients undergoing transfemoral TAVI with BE-valves compared with SE-valves. In contrast, patients treated with new-generation BE-valves more often suffered from major or life-threatening bleedings than patients with new-generation SE-valves. Mortality at 30-days was not statistically different in patients treated with BE-valves compared with SE-valves. This study was a propensity-matched analysis generated from observational data, accordingly current outcomes will have to be confirmed in a large scale randomized controlled trial.

Infective endocarditis after transcatheter aortic valve implantation: results from a large multicenter registry.

BACKGROUND: We aimed to determine the incidence, predictors, clinical characteristics, management, and outcomes of infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: This multicenter registry included 53 patients (mean age, 79±8 years; men, 57%) who suffered IE after TAVI of 7944 patients after a mean follow-up of 1.1±1.2 years (incidence, 0.67%, 0.50% within the first year after TAVI). Mean time from TAVI was 6 months (interquartile range, 1-14 months). Orotracheal intubation (hazard ratio, 3.87; 95% confidence interval, 1.55-9.64; P=0.004) and the self-expandable CoreValve system (hazard ratio, 3.12; 95% confidence interval, 1.37-7.14; P=0.007) were associated with IE (multivariate analysis including 3067 patients with individual data). The most frequent causal microorganisms were coagulase-negative staphylococci (24%), followed by Staphylococcus aureus (21%) and enterococci (21%). Vegetations were present in 77% of patients (transcatheter valve leaflets, 39%; stent frame, 17%; mitral valve, 21%). At least 1 complication of IE occurred in 87% of patients (heart failure in 68%). However, only 11% of patients underwent valve intervention (valve explantation and valve-in-valve procedure in 4 and 2 patients, respectively). The mortality rate in hospital was 47.2% and increased to 66% at the 1-year follow-up. IE complications such as heart failure (P=0.037) and septic shock (P=0.002) were associated with increased in-hospital mortality. CONCLUSIONS: The incidence of IE at 1 year after TAVI was 0.50%, and the risk increased with the use of orotracheal intubation and a self-expandable valve system. Staphylococci and enterococci were the most common agents. Although most patients presented at least 1 complication of IE, valve intervention was performed in a minority of patients, and nearly half of the patients died during the hospitalization period.

Permanent pacemaker implantation after transcatheter aortic valve implantation: impact on late clinical outcomes and left ventricular function.

BACKGROUND: Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. METHODS AND RESULTS: A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74-1.30; P=0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56-1.17; P=0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77-1.30; P=0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11-0.85; P=0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time (P=0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, -2.26; 95% confidence interval, -4.07 to -0.44; P=0.013; R(2)=0.121). CONCLUSIONS: The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time.

Advanced chronic kidney disease in patients undergoing transcatheter aortic valve implantation: insights on clinical outcomes and prognostic markers from a large cohort of patients.

AIM: The aim of this study was to determine the effects of advanced chronic kidney disease (CKD) on early and late outcomes after transcatheter aortic valve implantation (TAVI), and to evaluate the predictive factors of poorer outcomes in such patients. METHODS AND RESULTS: This was a multicentre study including a total of 2075 consecutive patients who had undergone TAVI. Patients were grouped according the estimated glomerular filtration rate as follows: CKD stage 1-2 (≥60 mL/min/1.73 m(2); n = 950), stage 3 (30-59 mL/min/1.73 m(2); n = 924), stage 4 (15-29 mL/min/1.73 m(2); n = 134) and stage 5 (<15 mL/min/1.73 m² or dialysis; n = 67). Clinical outcomes were evaluated at 30-days and at follow-up (median of 15 [6-29] months) and defined according to the VARC criteria. Advanced CKD (stage 4-5) was an independent predictor of 30-day major/life-threatening bleeding (P = 0.001) and mortality (P = 0.027), and late overall, cardiovascular and non-cardiovascular mortality (P < 0.01 for all). Pre-existing atrial fibrillation (HR: 2.29, 95% CI: 1.47-3.58, P = 0.001) and dialysis therapy (HR: 1.86, 95% CI: 1.17-2.97, P = 0.009) were the predictors of mortality in advanced CKD patients, with a mortality rate as high as 71% at 1-year follow-up in those patients with these 2 factors. Advanced CKD patients who had survived at 1-year follow-up exhibited both a significant improvement in NYHA class (P < 0.001) and no deterioration in valve hemodynamics (P = NS for changes in mean gradient and valve area over time). CONCLUSIONS: Advanced CKD was associated with a higher rate of early and late mortality and bleeding events following TAVI, with AF and dialysis therapy determining a higher risk in these patients. The mortality rate of patients with both factors was unacceptably high and this should be taken into account in the clinical decision-making process in this challenging group of patients.

Incidence, predictors, and prognostic significance of impaired functional status early after transcatheter aortic valve replacement.

INTRODUCTION AND OBJECTIVES: There are scarce data on the factors associated with impaired functional status after transcatheter aortic valve replacement (TAVR) and its clinical impact. This study aimed to determine the incidence, predictors, and prognostic implications of impaired functional class (NYHA class III-IV) following TAVR. METHODS: This multicenter study included 3462 transarterial TAVR patients receiving newer generation devices. The patients were compared according to their NYHA class at 1 month of follow-up (NYHA I-II vs NYHA III-IV). A multivariate logistic regression was performed to identify the predictors of 30-day NYHA class III-IV. Patient survival was compared with the Kaplan-Meier method and factors associated with decreased survival were identified with Cox regression analysis. RESULTS: The mean age of the study population was 80.3±7.3 years, with 47% of women, and a median Society of Thoracic Surgeons score of 3.8% [IQR, 2.5-5.8]. A total of 208 patients (6%) were in NYHA class III-IV 1 month after TAVR. Predictors of 30-day NYHA class III-IV were baseline NYHA class III-IV (OR, 1.76; 95%CI, 1.08-2.89; P=.02), chronic pulmonary obstructive disease (OR, 1.80; 95%CI, 1.13-2.83; P=.01), and post-TAVR severe mitral regurgitation (OR, 2.00; 95%CI, 1.21-3.31; P<.01). Patients in NYHA class III-IV 1 month after TAVR were at higher risk of death (HR, 3.68; 95%CI, 2.39-5.70; P<.01) and heart failure-related hospitalization (HR, 6.00; 95%CI, 3.76-9.60; P<.01) at 1-year follow-up. CONCLUSIONS: Up to 6% of contemporary TAVR patients exhibited an impaired functional status following TAVR. Worse baseline NYHA class, chronic pulmonary obstructive disease, and severe mitral regurgitation predicted 30-day NYHA class III/IV, and this determined a higher risk of mortality and heart failure hospitalization at 1-year follow-up. Further studies on the prevention and treatment optimization of patients with impaired functional status after TAVR are needed.

Cardiac Death After Transcatheter Aortic Valve Replacement With Contemporary Devices.

BACKGROUND: The burden of cardiac death after transcatheter aortic valve replacement (TAVR), particularly from advanced heart failure (HF) and sudden cardiac death (SCD), remains largely unknown. OBJECTIVES: This study sought to evaluate the incidence and predictors of SCD and HF-related death in TAVR recipients treated with newer-generation devices. METHODS: This study included a total of 5,421 consecutive patients who underwent TAVR with newer-generation devices using balloon (75.7%) or self-expandable (24.3%) valves. RESULTS: After a median follow-up of 2 (IQR: 1-3) years, 976 (18.0%) patients had died, 50.8% from cardiovascular causes. Advanced HF and SCD accounted for 11.6% and 7.5% of deaths, respectively. Independent predictors of HF-related death were atrial fibrillation (HR: 2.17; 95% CI: 1.47-3.22; P < 0.001), prior pacemaker (HR: 1.79; 95% CI: 1.10-2.92; P = 0.01), reduced left ventricular ejection fraction (HR: 1.08 per 5% decrease; 95% CI: 1.01-1.14; P = 0.02), transthoracic approach (HR: 2.50; 95% CI: 1.37-4.55; P = 0.003), and new-onset persistent left bundle branch block (HR: 1.85; 95% CI: 1.14-3.02; P = 0.01). Two baseline characteristics (diabetes, HR: 1.81; 95% CI: 1.13-2.89; P = 0.01; and chronic kidney disease, HR: 1.72; 95% CI: 1.02-2.90; P = 0.04) and 3 procedural findings (valve in valve, HR: 2.17; 95% CI: 1.01-4.64; P = 0.04; transarterial nontransfemoral approach, HR: 2.23; 95% CI: 1.23-4.48; P = 0.01; and periprocedural ventricular arrhythmia, HR: 7.19; 95% CI: 2.61-19.76; P < 0.001) were associated with an increased risk of SCD after TAVR. CONCLUSIONS: Advanced HF and SCD accounted for a fifth of deaths after TAVR in contemporary practice. Potentially treatable factors leading to increased risk of HF deaths and SCD were identified, such as arrhythmia/dyssynchrony factors for HF and valve-in-valve TAVR or periprocedural ventricular arrhythmias for SCD.

Survival and predictive factors of mortality after 30 days in patients treated with percutaneous implantation of the CoreValve aortic prosthesis.

BACKGROUND: Few data exist on the clinical impact of transcatheter aortic valve implantation (TAVI) in patients with symptomatic aortic stenosis and a high surgical risk. The aim of this study was to determine the survival and the factors predicting mortality after 30 days post-TAVI with the CoreValve prosthesis (Medtronic, Minneapolis, MN). METHODS: From April 2008 to October 2010, the CoreValve prosthesis (Medtronic) was implanted in 133 consecutive high-risk surgical patients with symptomatic severe aortic stenosis. RESULTS: The mean age was 79.5 ± 6.7 years. The logistic European System for Cardiac Operative Risk Evaluation was 21.5% ± 14%. The implantation success rate was 97.7%. In-hospital mortality was 4.5%, and the combined end point of death, vascular complications, myocardial infarction, or stroke had a rate of 9%. Survival at 12 and 24 months was 84.5% and 79%, respectively, after a mean follow-up of 11.3 ± 8 months. The New York Heart Association functional class improved from 3.3 ± 0.5 to 1.18 ± 0.4 and remained stable at 1 year. A high Charlson index (hazard ratio [HR] 1.44, 95% CI 1.09-1.89, P < .01) and a worse Karnofsky score before the procedure (HR 0.95, 95% CI 0.92-0.99, P = .021) were predictors of mortality after 30 days. CONCLUSIONS: Transcatheter aortic valve implantation with the CoreValve prosthesis for patients with aortic stenosis and a high surgical risk is a safe, efficient option resulting in a medium-term clinical improvement. Survival during follow-up depends on the associated comorbidities. Early mortality beyond 30 days is predicted by preoperative comorbidity scores and the functional status of the patient.

Impact of Morbid Obesity and Obesity Phenotype on Outcomes After Transcatheter Aortic Valve Replacement.

Background There is a paucity of outcome data on patients who are morbidly obese (MO) undergoing transcatheter aortic valve replacement. We aimed to determine their periprocedural and midterm outcomes and investigate the impact of obesity phenotype. Methods and Results Consecutive patients who are MO (body mass index, ≥40 kg/m2, or ≥35 kg/m2 with obesity-related comorbidities; n=910) with severe aortic stenosis who underwent transcatheter aortic valve replacement in 18 tertiary hospitals were compared with a nonobese cohort (body mass index, 18.5-29.9 kg/m2, n=2264). Propensity-score matching resulted in 770 pairs. Pre-transcatheter aortic valve replacement computed tomography scans were centrally analyzed to assess adipose tissue distribution; epicardial, abdominal visceral and subcutaneous fat. Major vascular complications were more common (6.6% versus 4.3%; P=0.043) and device success was less frequent (84.4% versus 88.1%; P=0.038) in the MO group. Freedom from all-cause and cardiovascular mortality were similar at 2 years (79.4 versus 80.6%, P=0.731; and 88.7 versus 87.4%, P=0.699; MO and nonobese, respectively). Multivariable analysis identified baseline glomerular filtration rate and nontransfemoral access as independent predictors of 2-year mortality in the MO group. An adverse MO phenotype with an abdominal visceral adipose tissue:subcutaneous adipose tissue ratio ≥1 (VAT:SAT) was associated with increased 2-year all-cause (hazard ratio [HR], 3.06; 95% CI, 1.20-7.77; P=0.019) and cardiovascular (hazard ratio, 4.11; 95% CI, 1.06-15.90; P=0.041) mortality, and readmissions (HR, 1.81; 95% CI, 1.07-3.07; P=0.027). After multivariable analysis, a (VAT:SAT) ratio ≥1 remained a strong predictor of 2-year mortality (hazard ratio, 2.78; P=0.035). Conclusions Transcatheter aortic valve replacement in patients who are MO has similar short- and midterm outcomes to nonobese patients, despite higher major vascular complications and lower device success. An abdominal VAT:SAT ratio ≥1 identifies an obesity phenotype at higher risk of adverse clinical outcomes.

Transcatheter Aortic Valve Replacement for Residual Lesion of the Aortic Valve Following "Healed" Infective Endocarditis.

OBJECTIVES: This study aimed to evaluate the safety and mid-term efficacy of transcatheter aortic valve replacement (TAVR) in the setting of aortic valve (AV) infective endocarditis (IE) with residual lesion despite successful antibiotic treatment. BACKGROUND: Patients with AV-IE presenting residual lesion despite successful antibiotic treatment are often rejected for cardiac surgery due to high-risk. The use of TAVR following IE is not recommended. METHODS: This was a multicenter retrospective study across 10 centers, gathering baseline, in-hospital, and 1-year follow-up characteristics of patients with healed AV-IE treated with TAVR. Matched comparison according to sex, EuroSCORE, chronic kidney disease, left ventricular function, prosthesis type, and valve-in-valve procedure was performed with a cohort of patients free of prior IE treated with TAVR (46 pairs). RESULTS: Among 2,920 patients treated with TAVR, 54 (1.8%) presented with prior AV-IE with residual valvular lesion and healed infection. They had a higher rate of multivalvular disease and greater surgical risk scores. A previous valvular prosthesis was more frequent than a native valve (50% vs. 7.5%; p < 0.001). The in-hospital and 1-year mortality rates were 5.6% and 11.1%, respectively, comparable to the control cohort. After matching, the 1-year III to IV aortic regurgitation rate was 27.9% (vs. 10%; p = 0.08) and was independently associated with higher mortality. There was only 1 case of IE relapse (1.8%); however, 18% of patients were complicated with sepsis, and 43% were readmitted due to heart failure. CONCLUSIONS: TAVR is a safe therapeutic alternative for residual valvular lesion after successfully healed AV-IE. At 1-year follow-up, the risk of IE relapse was low and mortality rate did not differ from TAVR patients free of prior IE, but one-fourth presented with significant aortic regurgitation and >50% required re-admission.

Third-Generation Balloon and Self-Expandable Valves for Aortic Stenosis in Large and Extra-Large Aortic Annuli From the TAVR-LARGE Registry.

BACKGROUND: Currently, 2 third-generation transcatheter valves, 29-mm Sapien-3 and 34-mm Evolut-R (ER), are indicated for large sized aortic annuli. We analyzed short and 1-year performance of these valves in patients with large (area ≥575 mm2 or perimeter ≥85 mm) and extra-large (≥683 mm2 or ≥94.2 mm) aortic annuli undergoing transcatheter aortic valve replacement. METHODS: A total of 833 patients across 12 centers with symptomatic aortic stenosis and large aortic annuli underwent transcatheter aortic valve replacement with 29-mm Sapien-3 (n=640) or 34-mm ER (n=193). Clinical, anatomic, and procedural characteristics were collected, and Valve Academic Research Consortium-2 outcomes were reported. RESULTS: Median aortic annulus area and perimeter were 617 mm2 (591-657) and 89.1 mm (87.0-92.1), respectively (704 mm2 [689-743] and 96.0 mm [94.5-97.9] in the subgroup of 124 patients with extra-large annuli). Overall device success was 94.3% (Sapien-3, 95.8% and ER, 89.3%; P=0.001), with a higher rate of significant paravalvular leak (P=0.004), second valve implantation (P=0.013), and valve embolization (P=0.009) in the ER group. Thirty-day and 1-year mortality was 2.4% and 9.2%, respectively, without differences between groups. Valve hemodynamics were excellent (mean gradient, 8.8±3.6 mm Hg; 3.3% rate of moderate-severe paravalvular leak) in the extra-large annulus, without differences compared with the large annulus group. CONCLUSIONS: In patients with large and extra-large aortic annuli, transcatheter aortic valve replacement using 29-mm Sapien-3 and 34-mm ER is safe and feasible. Observed differences in clinical outcomes and hemodynamic performance may guide valve choice in this cohort of patients undergoing transcatheter aortic valve replacement.

Mitral Regurgitation in Low-Flow, Low-Gradient Aortic Stenosis Patients Undergoing TAVR: Insights From the TOPAS-TAVI Registry.

OBJECTIVES: This study sought to determine the incidence, clinical impact, and changes over time of mitral regurgitation (MR) in patients with low-flow, low-gradient aortic stenosis (LFLG-AS) undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Few data exist on the clinical impact and changes in severity over time of MR in patients with LFLG-AS undergoing TAVR. METHODS: A total of 308 TAVR candidates with LFLG-AS were included. Patients were categorized according to MR severity at baseline, and presence of MR improvement at 12-month follow-up. Clinical outcomes were assessed at 1 and 12 months (+ echocardiography), and yearly thereafter. RESULTS: Baseline mild and moderate-to-severe MR were present in 118 (38.3%) and 115 (37.3%) patients, respectively. MR was of functional and mixed etiology in 77.2% and 22.7% of patients, respectively. A total of 131 patients (42.5%) died after a median follow-up of 2 (1 to 3) years. Baseline moderate-or-greater MR had no impact on mortality (hazard ratio [HR]: 1.34; 95% confidence interval [CI]: 0.72 to 2.48) or heart failure hospitalization (HR: 1.02; 95% CI: 0.49 to 2.10). At 1-year follow-up, MR improved in 44.3% of patients and remained unchanged/worsened in 55.7%. The lack of MR improvement was associated with a higher risk of all-cause and cardiac mortality (HR: 2.02; 95% CI: 1.29 to 3.17; HR: 3.03; 95% CI: 1.27 to 7.23, respectively), rehospitalization for cardiac causes (HR: 1.50; 95% CI: 1.04 to 2.15), and an increased overall-mortality/heart failure rehospitalization (HR: 1.94; 95% CI: 1.25 to 3.02). A higher baseline left ventricular end-diastolic diameter and a higher increase in left ventricular ejection fraction were found to be independent predictors of MR improvement at 1-year follow-up (odds ratio: 0.69; 95% CI: 0.51 to 0.94; and odds ratio: 0.81; 95% CI: 0.67 to 0.96, respectively). CONCLUSIONS: Most TAVR candidates with LFLG-AS had some degree of MR, of functional origin in most cases. MR improved in about one-half of patients, with larger left ventricular size and a higher increase in left ventricular ejection fraction post-TAVR determining MR improvement over time. The lack of MR improvement at 1 year was associated with poorer outcomes.

Nutritional risk index predicts survival in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Among patients undergoing transcatheter aortic valve replacement (TAVR), prognosis is impacted by nutritional status, but the influence of the nutritional risk index (NRI) is unknown. Here we calculated the NRI to determine the prevalence and prognostic impact in terms of mortality of malnutrition in TAVR patients. METHODS AND RESULTS: This retrospective multicenter study included 941 patients who underwent TAVR between 2008 and 2016 (mean age, 80.7 ±â€¯6.5 years; 57% female). The NRI was calculated as 1.519 × albumin (g/L) + 41.7 × (real weight [kg] / ideal weight [kg]). The mean NRI was 98.1 ±â€¯7.0%. The patients were stratified into the following groups based on malnutrition risk: severe (NRI < 83.5; n = 83; 8.82%), moderate (83.5 ≥ NRI < 97.5; n = 370; 39.32%), mild (97.5 ≥ NRI < 100; n = 102; 10.84%), and no risk (NRI ≥ 100; n = 386; 41.02%). During the follow-up period (2.1 ±â€¯1.1 years), 186 patients died, representing 19.8% of the total cohort. Cox regression models were used to analyze the relationship between NRI and mortality during follow-up. Compared to patients with no or mild nutritional risk, those with moderate or severe nutritional risk had a 45% greater risk of mortality during follow-up (adjusted HR, 1.45; 95% CI, 1.05-1.99; P = 0.021). CONCLUSION: Malnutrition is common among TAVR patients. Our present data indicated that the NRI was independently associated with increased risk of death during long-term follow-up after TAVR. Based on its potential to improve risk prediction, NRI appears to be a promising tool for the clinical assessment of patients who are candidates for TAVR.

Impact of Percutaneous Coronary Revascularization of Severe Coronary Lesions on Secondary Branches.

INTRODUCTION AND OBJECTIVES: To analyze the percutaneous revascularization strategy for severe lesions in the secondary branches (SB) (diameter ≥ 2mm) of major epicardial arteries compared with conservative treatment. METHODS: This study analyzed patients with severe SB lesions who underwent percutaneous revascularization treatment compared with patients who received pharmacological treatment. The study examined the percentage of branch-related events (cardiovascular death, myocardial infarction attributable to SB, or the need for revascularization of the SB). RESULTS: We analyzed 679 SB lesions (662 patients). After a mean follow-up of 22.2±10.5 months, there were no significant differences between the 2 treatment groups regarding the percentage of death from cardiovascular causes (1.7% vs 0.4%; P=.14), nonfatal acute myocardial infarction (AMI) (1.7% vs 1.7%; P=.96), the need for SB revascularization (4.1% vs 5.4%; P=.45) or in the total percentage of events (5.1% vs 6.3%; P=.54). The variables showing an association with event occurrence on multivariate analysis were diabetes (SHR, 2.87; 95%CI, 1.37-5.47; P=.004), prior AMI (SHR, 3.54; 95%CI, 1.77-7.30; P<.0001), SB reference diameter (SHR, 0.16; 95%CI, 0.03-0.97; P=.047), and lesion length (SHR, 3.77; 95%CI, 1.03-1.13; P<.0001). These results remained the same after the propensity score analysis. CONCLUSIONS: The percentage of SB-related events during follow-up is low, with no significant differences between the 2 treatment strategies. The variables associated with event occurrence in the multivariate analysis were the presence of diabetes mellitus, prior AMI, and greater lesion length.

Renin-Angiotensin System Inhibition Following Transcatheter Aortic Valve Replacement.

BACKGROUND: Several studies have demonstrated the benefits of transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis, but the presence of persistent fibrosis and myocardial hypertrophy has been related to worse prognosis. OBJECTIVES: The aim of this study was to explore the potential benefits of renin-angiotensin system (RAS) inhibitors on left ventricular remodeling and major clinical outcomes following successful transcatheter aortic valve replacement (TAVR). METHODS: Patients from 10 institutions with severe aortic stenosis who underwent TAVR between August 2007 and August 2017 were included. All baseline data were prospectively recorded, and pre-specified follow-up was performed. Doses and types of RAS inhibitors at discharge were recorded, and matched comparison according to their prescription at discharge was performed. RESULTS: A total of 2,785 patients were included. Patients treated with RAS inhibitors (n = 1,622) presented similar surgical risk scores but a higher rate of all cardiovascular risk factors, coronary disease, and myocardial infarction. After adjustment for these baseline differences, reduction of left ventricular volumes and hypertrophy was greater and cardiovascular mortality at 3-year follow-up was lower (odds ratio: 0.59; 95% confidence interval: 0.41 to 0.87; p = 0.007) in patients treated with RAS inhibitors. Moreover, RAS inhibitors demonstrated a global cardiovascular protective effect with significantly lower rates of new-onset atrial fibrillation, cerebrovascular events, and readmissions. CONCLUSIONS: Post-TAVR RAS inhibitors are associated with lower cardiac mortality at 3-year follow-up and offer a global cardiovascular protective effect that might be partially explained by a positive left ventricular remodeling. An ongoing randomized trial will help confirm these hypothesis-generating findings. (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation [RASTAVI]; NCT03201185).

Outcomes From Transcatheter Aortic Valve Replacement in Patients With Low-Flow, Low-Gradient Aortic Stenosis and Left Ventricular Ejection Fraction Less Than 30%: A Substudy From the TOPAS-TAVI Registry.

Importance: In low-flow, low-gradient aortic stenosis (LFLG AS), the severity of left ventricular dysfunction remains a key factor in the evaluation of aortic valve replacement. Objective: To evaluate the clinical outcomes and changes in left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) in patients with LFLG AS and severe left ventricular dysfunction. Design, Setting, and Participants: This multicenter registry is a substudy of the True or Pseudo-Severe Aortic Stenosis-TAVI registry that included patients with classic LFLG AS, defined as a mean transvalvular gradient less than 35 mm Hg, an effective orifice area less than 1.0 cm2, and an LVEF of 40% or less. Patients were divided in groups with very low (<30%) LVEF and low (30%-40%) LVEF. Dobutamine stress echocardiography (DSE) was performed before TAVR in a subset with very low LVEF, and presence of contractile reserve was defined as an increase of 20% or more in stroke volume. Clinical outcomes were assessed at 1 and 12 months and yearly thereafter, and echocardiography was performed at 1-year follow-up. Retrospective data were collected from 2007 to 2013 and prospective data from January 2013 to March 2018. Data were analyzed from March to October 2018. Exposures: Transcatheter aortic valve replacement in patients with LFLG AS. Main Outcomes and Measures: Changes in LVEF over time; periprocedural and late mortality. Results: A total of 293 patients were included, including 128 (43.7%) with very low LVEF and 165 with low LVEF (56.3%). Their mean (SD) age was 80 (7) years, and most (214 [73.0%]) were men. The mean (SD) LVEF in the very low LVEF group was 22% (5%), compared with 37% (7%) in the low LVEF group (P < .001). There were no differences between groups in rates of periprocedural mortality and late mortality (median [interquartile range], 23 [6-38] months). Patients with very low LVEF displayed a greater increase in LVEF at the 1-year follow-up examination (mean absolute increase, 11.9% [95% CI, 8.8%-15.1%]), than the low LVEF group (3.6% [95% CI, 1.1%-6.1%]; P < .001). In 92 patients with very low LVEF who had preprocedural DSE, results showed a lack of contractile reserve in 45 (49%), but this had no effect on clinical outcomes or changes in LVEF over time. Conclusions and Relevance: In patients with LFLG AS and severe left ventricular dysfunction, TAVR was associated with similar clinical outcomes as in counterparts with milder left ventricular dysfunction. The TAVR procedure was associated with a significant increase in LVEF, irrespective of contractile reserve. These results support TAVR for LFLG AS, irrespective of the severity of left ventricular dysfunction and DSE results.

Intracardiac shunts following transcatheter aortic valve implantation: a multicentre study.

AIMS: The aim of this study was to describe the incidence, mechanisms, management and outcomes of intracardiac shunts (ICS) following TAVI. METHODS AND RESULTS: This was a multicentre registry across 10 centres aimed at gathering all cases of ICS (1.1%) including infection-related (IRICS, 0.3%) or aseptic (AICS, 0.8%) shunts. Patients presented porcelain aorta (24% vs. 6.8%, p=0.024) and had been treated with predilation (88% vs. 68.5%, p=0.037) or post-dilation (59.1% vs. 19.3%, p<0.001) more often. Median time from intervention to diagnosis of ICS was 10 days (IQR: 2-108), being longer for IRICS (171 [63-249] vs. 3 [1-12] days, p=0.002). Interventricular septum (55.6%) and anterior mitral leaflet (57.2%) were the most common locations for AICS and IRICS, respectively. Most patients (76%) developed heart failure but 64% were medically managed. Seven patients (38.9%) underwent percutaneous closure of AICS. The in-hospital mortality rate was 44% (IRICS 100%, AICS 27.8%) compared to global TAVI recipients (8.1%, p<0.001). At one-year follow-up, 76% of the patients had died. ICS, logistic EuroSCORE, and moderate-severe residual aortic regurgitation were independent predictors of death. CONCLUSIONS: Post-TAVI ICS are an uncommon complication independently associated with high early mortality. Currently, most therapeutic alternatives yield poor results but percutaneous closure of AICS was feasible and is a promising alternative.

The Learning Curve and Annual Procedure Volume Standards for Optimum Outcomes of Transcatheter Aortic Valve Replacement: Findings From an International Registry.

OBJECTIVES: The authors aimed to determine the procedural learning curve and minimum annual institutional volumes associated with optimum clinical outcomes for transcatheter aortic valve replacement (TAVR). BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a complex procedure requiring significant training and experience for successful outcome. Despite increasing use of TAVR across institutions, limited information is available for its learning curve characteristics and minimum annual volumes required to optimize clinical outcomes. METHODS: The study collected data for patients at 16 centers participating in the international TAVR registry since initiation of the respective TAVR program. All cases were chronologically ordered into initial (1 to 75), early (76 to 150), intermediate (151 to 225), high (226 to 300), and very high (>300) experience operators for TAVR learning curve characterization. In addition, participating institutions were stratified by annual TAVR case volume into low-volume (<50), moderate-volume (50 to 100), and high-volume (>100) groups for comparative analysis. Procedural and 30-day clinical outcomes were collected and multivariate regression analysis performed for 30-day mortality and the early safety endpoint. RESULTS: A total of 3,403 patients comprised the study population. On multivariate analysis, all-cause mortality was significantly higher for initial (odds ratio [OR]: 3.83; 95% confidence interval [CI]: 1.93 to 7.60), early (OR: 2.41; 95% CI: 1.51 to 5.03), and intermediate (OR: 2.53; 95% CI: 1.19 to 5.40) experience groups compared with the very high experience operators. In addition, the early safety endpoint was significantly worse for all experience groups compared with the very high experience operators. Low annual volume (<50) TAVR institutions had significantly higher all-cause 30-day mortality (OR: 2.70; 95% CI: 1.44 to 5.07) and worse early safety endpoint (OR: 1.60; 95% CI: 1.17 to 2.17) compared with the moderate- and high-volume groups. There was no difference in patient outcomes between intermediate and high annual volume groups. CONCLUSIONS: TAVR procedures display important learning curve characteristics with both greater procedural safety and a lower mortality when performed by experienced operators. In addition, TAVR performed at low annual volume (<50 procedures) institutions is associated with decreased procedural safety and higher patient mortality. These findings have important implications for operator training and patient care at centers performing TAVR.

Impact of anticoagulation therapy on valve haemodynamic deterioration following transcatheter aortic valve replacement.

OBJECTIVE: To evaluate the changes in transvalvular gradients and the incidence of valve haemodynamic deterioration (VHD) following transcatheter aortic valve replacement (TAVR), according to use of anticoagulation therapy. METHODS AND RESULTS: This multicentre study included 2466 patients (46% men; mean age 81±7 years) who underwent TAVR with echocardiography performed at 12-month follow-up. Anticoagulation therapy was used in 707 patients (28.7%) following TAVR (AC group). A total of 663 patients received vitamin K antagonists, and 44 patients received direct oral anticoagulants. A propensity score matching analysis was performed to adjust for intergroup (AC vs non-AC post-TAVR) differences. A total of 622 patients per group were included in the propensity-matched analysis. VHD was defined as a ≥10 mm Hg increase in the mean transprosthetic gradient at follow-up (vs hospital discharge). The mean clinical follow-up was 29±18 months. The mean transvalvular gradient significantly increased at follow-up in the non-AC group within the global cohort (P=0.003), whereas it remained stable over time in the AC group (P=0.323). The incidence of VHD was significantly lower in the AC group (0.6%) compared with the non-AC group (3.7%, P<0.001), and these significant differences remained within the propensity-matched populations (0.6% vs 3.9% in the AC and non-AC groups, respectively, P<0.001). The occurrence of VHD did not associate with an increased risk of all-cause death (P=0.468), cardiovascular death (P=0.539) or stroke (P=0.170) at follow-up. CONCLUSIONS: The lack of anticoagulation therapy post-TAVR was associated with significant increments in transvalvular gradients and a greater risk of VHD. VHD was subclinical in most cases and did not associate with major adverse clinical events. Future randomised trials are needed to determine if systematic anticoagulation therapy post-TAVR would reduce the incidence of VHD.

Impact of renin-angiotensin system inhibitors on clinical outcomes and ventricular remodelling after transcatheter aortic valve implantation: rationale and design of the RASTAVI randomised multicentre study.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) as a treatment in severe aortic stenosis (AS) is an excellent alternative to conventional surgical replacement. However, long-term outcomes are not benign. Renin-angiotensin system (RAS) blockade has shown benefit in terms of adverse remodelling in severe AS and after surgical replacement. METHODS AND ANALYSIS: The RAS blockade after TAVI (RASTAVI) trial aims to detect if there is a benefit in clinical outcomes and ventricular remodelling with this therapeutic strategy following the TAVI procedure. The study has been designed as a randomised 1:1 open-label study that will be undertaken in 8 centres including 336 TAVI recipients. All patients will receive the standard treatment. The active treatment group will receive ramipril as well. Randomisation will be done before discharge, after signing informed consent. All patients will be followed up for 3 years. A cardiac magnetic resonance will be performed initially and at 1 year to assess ventricular remodelling, defined as ventricular dimensions, ejection fraction, ventricular mass and fibrosis. Recorded events will include cardiac death, admission due to heart failure and stroke. The RASTAVI Study will improve the management of patients after TAVI and may help to increase their quality of life, reduce readmissions and improve long-term survival in this scenario. ETHICS AND DISSEMINATION: All authors and local ethics committees have approved the study design. All patients will provide informed consent. Results will be published irrespective of whether the findings are positive or negative. TRIAL REGISTRATION NUMBER: NCT03201185.

Tricuspid but not Mitral Regurgitation Determines Mortality After TAVI in Patients With Nonsevere Mitral Regurgitation.

INTRODUCTION AND OBJECTIVES: Many patients undergoing transcatheter aortic valve implantation (TAVI) have concomitant mitral regurgitation (MR) of moderate grade or less. The impact of coexistent tricuspid regurgitation (TR) remains to be determined. We sought to analyze the impact of moderate vs none-to-mild MR and its trend after TAVI, as well as the impact of concomitant TR and its interaction with MR. METHODS: Multicenter retrospective study of 813 TAVI patients treated through the transfemoral approach with MR ≤ 2 between 2007 and 2015. RESULTS: The mean age was 81 ± 7 years and the mean Society of Thoracic Surgeons score was 6.9% ± 5.1%. Moderate MR was present in 37.3% of the patients, with similar in-hospital outcomes and 6-month follow-up mortality to those with MR < 2 (11.9% vs 9.4%; P = .257). However, they experienced more rehospitalizations and worse New York Heart Association class (P = .008 and .001, respectively). Few patients (3.8%) showed an increase in the MR grade to > 2 post-TAVI. The presence of concomitant moderate/severe TR was associated with in-hospital and follow-up mortality rates of 13% and 34.1%, respectively, regardless of MR grade. Moderate-severe TR was independently associated with mortality (HR, 18.4; 95%CI, 10.2-33.3; P < .001). CONCLUSIONS: The presence of moderate MR seemed not to impact short- and mid-term mortality post-TAVI, but was associated with more rehospitalizations. The presence of moderate or severe TR was associated with higher mortality. This suggests that a thorough evaluation of the mechanisms underlying concomitant mitral and tricuspid valve regurgitation should be performed to determine the best strategy for avoiding TAVI-related futility.