Intentional Oversizing of Valve in Transcatheter Aortic Valve Replacement: Is Bigger Better? A Large, Single-Center Experience.

Background: The current clinical practice standard is 10% to 20% oversizing of self-expanding valves in transcatheter aortic valve replacement. We aimed to determine whether >20% oversizing of self-expanding valves (Medtronic Evolut) would lead to better valve performance with similar or better outcomes. Methods: From October 2011 to December 2016, we approached all transcatheter aortic valve replacement patients with a conscious attempt at large oversizing (>20%). The most common valve used, excluding those used in valve-in-valve patients, was the 29-mm Evolut R (29%). We used a retrospective chart review to compare moderate oversizing (group 1; 10% to 20%) with large oversizing (group 2; >20%). Results: Of 556 patients, 45% were male; the overall mean Society of Thoracic Surgeons risk score was 5.8 ± 3.8. Eighty-five (15%) patients needed a pacemaker, and 21 (3.8%) developed significant paravalvular leak. Mean oversizing was 20.3% ± 6.0%, with 41.4% of patients included in group 1 and 54.5% in group 2. Incidences of complications in group 2 vs. group 1 were as follows: a) paravalvular leak (2.0 vs. 6.1%; odds ratio = 0.31, p = 0.01), b) pacemaker (15 vs. 14%), c) gastrointestinal bleed (n = 4 vs. 0; 1.3 vs. 0.0%; p = 0.03), d) annular dissection (n = 1 vs. 0; 0.3 vs. 0%; p = 0.29), e) mortality (n = 5 vs. 4; 1.6 vs. 1.7%). Incidence of paravalvular leak was higher in those who died than survivors (13 vs. 1.3%; p ≤ 0.0001). Conclusions: These data suggest that, in current self-expanding valves, >20% oversizing delivers a significantly lower prevalence of paravalvular leak without an increase in other complications. Since paravalvular leak is associated with increased mortality, >20% oversizing may represent a superior prosthesis choice.

Reinterventions After CoreValve/Evolut Transcatheter or Surgical Aortic Valve Replacement for Treatment of Severe Aortic Stenosis.

BACKGROUND: Data on valve reintervention after transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) are limited. OBJECTIVES: The authors compared the 5-year incidence of valve reintervention after self-expanding CoreValve/Evolut TAVR vs SAVR. METHODS: Pooled data from CoreValve and Evolut R/PRO (Medtronic) randomized trials and single-arm studies encompassed 5,925 TAVR (4,478 CoreValve and 1,447 Evolut R/PRO) and 1,832 SAVR patients. Reinterventions were categorized by indication, timing, and treatment. The cumulative incidence of reintervention was compared between TAVR vs SAVR, Evolut vs CoreValve, and Evolut vs SAVR. RESULTS: There were 99 reinterventions (80 TAVR and 19 SAVR). The cumulative incidence of reintervention through 5 years was higher with TAVR vs SAVR (2.2% vs 1.5%; P = 0.017), with differences observed early (≤1 year; adjusted subdistribution HR: 3.50; 95% CI: 1.53-8.02) but not from >1 to 5 years (adjusted subdistribution HR: 1.05; 95% CI: 0.48-2.28). The most common reason for reintervention was paravalvular regurgitation after TAVR and endocarditis after SAVR. Evolut had a significantly lower incidence of reintervention than CoreValve (0.9% vs 1.6%; P = 0.006) at 5 years with differences observed early (adjusted subdistribution HR: 0.30; 95% CI: 0.12-0.73) but not from >1 to 5 years (adjusted subdistribution HR: 0.61; 95% CI: 0.21-1.74). The 5-year incidence of reintervention was similar for Evolut vs SAVR (0.9% vs 1.5%; P = 0.41). CONCLUSIONS: A low incidence of reintervention was observed for CoreValve/Evolut R/PRO and SAVR through 5 years. Reintervention occurred most often at ≤1 year for TAVR and >1 year for SAVR. Most early reinterventions were with the first-generation CoreValve and managed percutaneously. Reinterventions were more common following CoreValve TAVR compared with Evolut TAVR or SAVR.

Structural Valve Deterioration After Self-Expanding Transcatheter or Surgical Aortic Valve Implantation in Patients at Intermediate or High Risk.

Importance: The frequency and clinical importance of structural valve deterioration (SVD) in patients undergoing self-expanding transcatheter aortic valve implantation (TAVI) or surgery is poorly understood. Objective: To evaluate the 5-year incidence, clinical outcomes, and predictors of hemodynamic SVD in patients undergoing self-expanding TAVI or surgery. Design, Setting, and Participants: This post hoc analysis pooled data from the CoreValve US High Risk Pivotal (n = 615) and SURTAVI (n = 1484) randomized clinical trials (RCTs); it was supplemented by the CoreValve Extreme Risk Pivotal trial (n = 485) and CoreValve Continued Access Study (n = 2178). Patients with severe aortic valve stenosis deemed to be at intermediate or increased risk of 30-day surgical mortality were included. Data were collected from December 2010 to June 2016, and data were analyzed from December 2021 to October 2022. Interventions: Patients were randomized to self-expanding TAVI or surgery in the RCTs or underwent self-expanding TAVI for clinical indications in the nonrandomized studies. Main Outcomes and Measures: The primary end point was the incidence of SVD through 5 years (from the RCTs). Factors associated with SVD and its association with clinical outcomes were evaluated for the pooled RCT and non-RCT population. SVD was defined as (1) an increase in mean gradient of 10 mm Hg or greater from discharge or at 30 days to last echocardiography with a final mean gradient of 20 mm Hg or greater or (2) new-onset moderate or severe intraprosthetic aortic regurgitation or an increase of 1 grade or more. Results: Of 4762 included patients, 2605 (54.7%) were male, and the mean (SD) age was 82.1 (7.4) years. A total of 2099 RCT patients, including 1128 who received TAVI and 971 who received surgery, and 2663 non-RCT patients who received TAVI were included. The cumulative incidence of SVD treating death as a competing risk was lower in patients undergoing TAVI than surgery (TAVI, 2.20%; surgery, 4.38%; hazard ratio [HR], 0.46; 95% CI, 0.27-0.78; P = .004). This lower risk was most pronounced in patients with smaller annuli (23 mm diameter or smaller; TAVI, 1.32%; surgery, 5.84%; HR, 0.21; 95% CI, 0.06-0.73; P = .02). SVD was associated with increased 5-year all-cause mortality (HR, 2.03; 95% CI, 1.46-2.82; P < .001), cardiovascular mortality (HR, 1.86; 95% CI, 1.20-2.90; P = .006), and valve disease or worsening heart failure hospitalizations (HR, 2.17; 95% CI, 1.23-3.84; P = .008). Predictors of SVD were developed from multivariate analysis. Conclusions and Relevance: This study found a lower rate of SVD in patients undergoing self-expanding TAVI vs surgery at 5 years. Doppler echocardiography was a valuable tool to detect SVD, which was associated with worse clinical outcomes. Trial Registration: ClinicalTrials.gov Identifiers: NCT01240902, NCT01586910, and NCT01531374.

2-Year Outcomes After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients.

BACKGROUND: The Evolut Low Risk Trial (Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients) showed that transcatheter aortic valve replacement (TAVR) with a supra-annular, self-expanding valve was noninferior to surgery for the primary endpoint of all-cause mortality or disabling stroke at 2 years. This finding was based on a Bayesian analysis performed after 850 patients had reached 1 year of follow-up. OBJECTIVES: The goal of this study was to report the full 2-year clinical and echocardiographic outcomes for patients enrolled in the Evolut Low Risk Trial. METHODS: A total of 1,414 low-surgical risk patients with severe aortic stenosis were randomized to receive TAVR or surgical AVR. An independent clinical events committee adjudicated adverse events, and a central echocardiographic core laboratory assessed hemodynamic endpoints. RESULTS: An attempted implant was performed in 730 TAVR and 684 surgical patients from March 2016 to May 2019. The Kaplan-Meier rates for the complete 2-year primary endpoint of death or disabling stroke were 4.3% in the TAVR group and 6.3% in the surgery group (P = 0.084). These rates were comparable to the interim Bayesian rates of 5.3% with TAVR and 6.7% with surgery (difference: -1.4%; 95% Bayesian credible interval: -4.9% to 2.1%). All-cause mortality rates were 3.5% vs 4.4% (P = 0.366), and disabling stroke rates were 1.5% vs 2.7% (P = 0.119), respectively. Between years 1 and 2, there was no convergence of the primary outcome curves. CONCLUSIONS: The complete 2-year follow-up from the Evolut Low Risk Trial found that TAVR is noninferior to surgery for the primary endpoint of all-cause mortality or disabling stroke, with event rates that were slightly better than those predicted by using the Bayesian analysis. (Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients [Evolut Low Risk Trial]; NCT02701283).

The impact of pulmonary hypertension on outcomes of transcatheter mitral valve replacement in mitral annular calcification.

OBJECTIVES: To assess the impact of pulmonary hypertension (PH) on outcomes of patients with severe mitral annular calcification (MAC) undergoing transcatheter mitral valve replacement (TMVR). BACKGROUND: PH is associated with poor outcomes after mitral valve surgery. Whether the presence of PH in patients with MAC undergoing (TMVR) is associated with poor outcomes, is unknown. METHODS: Retrospective evaluation of 116 patients from 51 centers in 11 countries who underwent TMVR with valve in mitral annular calcification (ViMAC) using balloon-expandable aortic transcatheter valves (THVs) from September 2012 to March 2017. Pulmonary artery systolic blood pressure (PASP) by echocardiogram was available in 90 patients. The subjects were stratified based on PASP: No PH = PASP ≤35 mmHg (n = 11); mild to moderate PH = PASP 36-49 mmHg (n = 21) and severe PH = PASP ≥50 mmHg (n = 58). Clinical, procedural, and echocardiographic outcomes were assessed. RESULTS: Mean age was 72.7 (±12.8) years, 59 (65.6%) were female, Society of Thoracic Surgeons score was 15.8 + 11.8% and 90.0% where in New York Heart Association (NYHA) class III-IV. There was no significant difference in all-cause mortality at 30 days (no PH = 27.3%, mild-moderate PH = 19.0%, severe PH = 31.6%; p = 0.55) or at 1 year (no PH = 54.5%, mild-moderate PH = 38.1%, severe PH = 56.1%; p = 0.36). No difference in adverse events, NYHA class or amount of residual mitral regurgitation at 1 year were observed between the groups. CONCLUSION: This study suggests that the presence of PH in patients with predominantly mitral stenosis with MAC undergoing TMVR does not impact mortality or adverse events. Further studies are needed to fully understand the effect of PH in this group of patients.

Enhanced Detection of Heart Valve Disease Using Integrated Artificial Intelligence at Scale.

BACKGROUND: Undertreatment of heart valve disease creates unnecessary patient risk. Poorly integrated healthcare data systems are unequipped to solve this problem. A software program using a rules-based algorithm to search the electronic health record for heart valve disease among patients treated by healthcare systems in the United States may provide a solution. METHODS: A software interface allowed concurrent access to picture archiving communication systems, the electronic health record, and other sources. The software platform was created to programmatically run a rules engine to search structured and unstructured data for identification of moderate or severe heart valve disease using guideline-reported values. Incidence and progression of disease as well as compliance with a care pathway were assessed. RESULTS: In 2 health institutions in the United States 60,145 patients had 77,215 echocardiograms. Moderate or severe aortic stenosis (AS) was identified at a rate of 9.1% of patients (5474 and 6910 echocardiograms) in this population. The precision and accuracy of the algorithm for the detection of moderate or severe AS was 92.9% and 98.6%, respectively. Thirty-five percent of patients (441/1265) with moderate stenosis and a subsequent echocardiogram progressed to severe stenosis (mean interval, 358 days). In 1 sample 70.3% of moderate AS patients lacked a 6-month echocardiogram or appointment. The platform enabled 100% accountability for all patients with severe AS. CONCLUSIONS: A rules-based software program enhances detection of heart valve disease and can be used to measures disease progression and care pathway compliance.

Early clinical and procedural outcomes in large series of 34-mm self-expanding transcatheter aortic valve replacement.

OBJECTIVES: We aimed to evaluate early clinical and procedural outcomes with the 34-mm Evolut R transcatheter aortic valve replacement (TAVR) prosthesis. BACKGROUND: The 34-mm Evolut R (Medtronic, Minneapolis, MN) self-expanding TAVR prosthesis was designed to treat patients with larger annuli. METHODS: Clinical, demographic, procedural, and echocardiographic data on consecutive patients who underwent TAVR with a 34-mm Evolut R prosthesis at our institution were collected and analyzed. RESULTS: One hundred ninety-six patients underwent TAVR with this prosthesis from November 2016 to July 2018, a majority (n = 188, 96%) through transfemoral access and with conscious sedation (n = 182, 93%). Mean age, Society of Thoracic Surgery risk score, and follow-up were 82 ± 8 years, 5.4 ± 5%, and 8.2 ± 5.3 months, respectively. Mean aortic valve (AV) peak velocity was 4.0 ± 0.6 m/s, mean AV gradient was 38 ± 13 mmHg, AV area was 0.79 ± 0.23 cm2 ; calcium score was 3,503 ± 1,970 Agatston units, and perimeter was 85 ± 4.3 mm. Device implantation was successful in all but one patient. Postprocedure mean AV peak velocity, AV mean gradient, and AV area were 1.9 ± 0.4 m/s, 7 ± 3 mmHg, and 2.6 ± 0.7 cm2 , respectively. New pacemaker requirement rate was 16%, and moderate paravalvular leak was present in six patients (3%), which improved to mild in three patients at 6-month follow-up. In-hospital, 30-day, 6-month, and 12-month survival rates were 98%, 96% (hospital discharge), 96% (30-day), 89% (6-month), and 83% (12-month). CONCLUSION: These data demonstrate high success and good procedural, echocardiographic, and clinical outcomes of 34-mm Evolut R in patients with large annuli.

Durability and Clinical Outcomes of Transcatheter Aortic Valve Replacement for Failed Surgical Bioprostheses.

BACKGROUND: Valve-in-valve transcatheter aortic valve replacement (TAVR) is an option when a surgical valve demonstrates deterioration and dysfunction. This study reports 3-year results following valve-in-valve with self-expanding TAVR. METHODS: The CoreValve US Expanded Use Study is a prospective, nonrandomized, single-arm study that evaluates safety and effectiveness of TAVR in extreme risk patients with symptomatic failed surgical biologic aortic valves. Study end points include all-cause mortality, need for valve reintervention, hemodynamic changes over time, and quality of life through 3 years. Patients were stratified by presence of preexisting surgical valve prosthesis-patient mismatch. RESULTS: From March 2013 to May 2015, 226 patients deemed extreme risk (STS-PROM [Society of Thoracic Surgeons Predicted Risk of Mortality] 9.0±7%) had attempted valve-in-valve TAVR. Preexisting surgical valve prosthesis-patient mismatch was present in 47.2% of the cohort. At 3 years, all-cause mortality or major stroke was 28.6%, and 93% of patients were in New York Heart Association I or II heart failure. Valve performance was maintained over 3 years with low valve reintervention rates (4.4%), an improvement in effective orifice area over time and a 2.7% rate of severe structural valve deterioration. Preexisting severe prosthesis-patient mismatch was not associated with 3-year mortality but was associated with significantly less improvement in quality of life at 3-year follow-up (P=0.01). CONCLUSIONS: Self-expanding TAVR in patients with failed surgical bioprostheses at extreme risk for surgery was associated with durable hemodynamics and excellent clinical outcomes. Preexisting surgical valve prosthesis-patient mismatch was not associated with mortality but did limit patient improvement in quality of life over 3-year follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01675440.

Pacemaker Implantation and Dependency After Transcatheter Aortic Valve Replacement in the REPRISE III Trial.

Background As transcatheter aortic valve replacement expands to younger and/or lower risk patients, the long-term consequences of permanent pacemaker implantation are a concern. Pacemaker dependency and impact have not been methodically assessed in transcatheter aortic valve replacement trials. We report the incidence and predictors of pacemaker implantation and pacemaker dependency after transcatheter aortic valve replacement with the Lotus valve. Methods and Results A total of 912 patients with high/extreme surgical risk and symptomatic aortic stenosis were randomized 2:1 (Lotus:CoreValve) in REPRISE III (The Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System-Randomized Clinical Evaluation) trial. Systematic assessment of pacemaker dependency was pre-specified in the trial design. Pacemaker implantation within 30 days was more frequent with Lotus than CoreValve. By multivariable analysis, predictors of pacemaker implantation included baseline right bundle branch block and depth of implantation; diabetes mellitus was also a predictor with Lotus. No association between new pacemaker implantation and clinical outcomes was found. Pacemaker dependency was dynamic (30 days: 43%; 1 year: 50%) and not consistent for individual patients over time. Predictors of pacemaker dependency at 30 days included baseline right bundle branch block, female sex, and depth of implantation. No differences in mortality or stroke were found between patients who were pacemaker dependent or not at 30 days. Rehospitalization was higher in patients who were not pacemaker dependent versus patients without a pacemaker or those who were dependent. Conclusions Pacemaker implantation was not associated with adverse clinical outcomes. Most patients with a new pacemaker at 30 days were not dependent at 1 year. Mortality and stroke were similar between patients with or without pacemaker dependency and patients without a pacemaker. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier NCT02202434.

Novel Multiphase Assessment for Predicting Left Ventricular Outflow Tract Obstruction Before Transcatheter Mitral Valve Replacement.

OBJECTIVES: This study proposes a physiologic assessment of left ventricular outflow tract obstruction (LVOTO) that accommodates changes in systolic flow and accounts for the dynamic neo-left ventricular outflow tract (LVOT). BACKGROUND: Patients considered for transcatheter mitral valve replacement trials often screen-fail because of the perceived risk of LVOTO. In the Intrepid Global Pilot Study, assumed risk of LVOTO was based on computed tomography estimates of the neo-LVOT area computed at end-systole. However, this may overestimate actual risk. METHODS: Retrospective analyses were performed for screen-failed patients for potential LVOTO (n = 33) and treated patients (n = 29) with available dynamic computed tomography. A multiphase assessment of the neo-LVOT area was performed and represented as: 1) multiphase average; and 2) early systolic value. Prospective evaluation was performed in 9 patients approved for enrollment with multiphase and early systole methods that would have previously screen-failed with the end-systolic approach. RESULTS: Of 166 patients screened for possible inclusion; 32 were screen-failed for nonanatomical reasons. Screen failure for assumed LVOTO risk occurred in 37 of 134 (27.6%) patients. Retrospective analysis indicated a potential enrollment increase of 11 of 33 (33.3%) and 18 of 33 (54.5%) patients using multiphase and early systolic assessment methods. In the prospective cohort, there were no clinical observations of LVOTO 30 days post-procedure, despite assumed risk based on end-systolic estimates. CONCLUSIONS: Multiphase, and specifically early systolic, assessment of the neo-LVOT may better determine risk of LVOTO with transcatheter mitral valve replacement compared with end-systolic estimates. This novel approach has the potential to significantly increase patient eligibility, with over one-half of patients previously screen-failed now eligible for treatment.

Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis who are at increased risk for death from surgery; less is known about TAVR in low-risk patients. METHODS: We performed a randomized noninferiority trial in which TAVR with a self-expanding supraannular bioprosthesis was compared with surgical aortic-valve replacement in patients who had severe aortic stenosis and were at low surgical risk. When 850 patients had reached 12-month follow-up, we analyzed data regarding the primary end point, a composite of death or disabling stroke at 24 months, using Bayesian methods. RESULTS: Of the 1468 patients who underwent randomization, an attempted TAVR or surgical procedure was performed in 1403. The patients' mean age was 74 years. The 24-month estimated incidence of the primary end point was 5.3% in the TAVR group and 6.7% in the surgery group (difference, -1.4 percentage points; 95% Bayesian credible interval for difference, -4.9 to 2.1; posterior probability of noninferiority >0.999). At 30 days, patients who had undergone TAVR, as compared with surgery, had a lower incidence of disabling stroke (0.5% vs. 1.7%), bleeding complications (2.4% vs. 7.5%), acute kidney injury (0.9% vs. 2.8%), and atrial fibrillation (7.7% vs. 35.4%) and a higher incidence of moderate or severe aortic regurgitation (3.5% vs. 0.5%) and pacemaker implantation (17.4% vs. 6.1%). At 12 months, patients in the TAVR group had lower aortic-valve gradients than those in the surgery group (8.6 mm Hg vs. 11.2 mm Hg) and larger effective orifice areas (2.3 cm2 vs. 2.0 cm2). CONCLUSIONS: In patients with severe aortic stenosis who were at low surgical risk, TAVR with a self-expanding supraannular bioprosthesis was noninferior to surgery with respect to the composite end point of death or disabling stroke at 24 months. (Funded by Medtronic; ClinicalTrials.gov number, NCT02701283.).

Two-Year Outcomes After Transcatheter Aortic Valve Replacement With Mechanical vs Self-expanding Valves: The REPRISE III Randomized Clinical Trial.

Importance: To our knowledge, REPRISE III is the first large randomized comparison of 2 different transcatheter aortic valve replacement platforms: the mechanically expanded Lotus valve (Boston Scientific) and self-expanding CoreValve (Medtronic). Objective: To evaluate outcomes of Lotus vs CoreValve after 2 years. Design, Setting, and Participants: A total of 912 patients with high/extreme risk and severe, symptomatic aortic stenosis enrolled between September 22, 2014, and December 24, 2015, were randomized 2:1 to receive Lotus (607 [66.6%]) or CoreValve (305 [33.4%] at 55 centers in North America, Europe, and Australia. The first 2-year visit occurred on October 17, 2016, and the last was conducted on April 12, 2018. Clinical and echocardiographic assessments are complete through 2 years and will continue annually through 5 years. Main Outcomes and Measures: All-cause mortality and all-cause mortality or disabling stroke at 2 years. Other clinical factors included overall stroke, disabling stroke, repeated procedures, rehospitalization, valve thrombosis, and pacemaker implantation. Echocardiographic analyses included effective orifice area, mean gradient, and paravalvular leaks (PVLs). Results: Of 912 participants, the mean (SD) age was 82.8 (7.3) years, 465 (51%) were women, and the mean (SD) Society of Thoracic Surgeons predicted risk of mortality was 6.8% (4.0%). At 2 years, all-cause death was 21.3% with Lotus vs 22.5% with CoreValve (hazard ratio [HR], 0.94; 95% CI, 0.69-1.26; P = .67) and all-cause mortality or disabling stroke was 22.8% with Lotus and 27.0% with CoreValve (HR, 0.81; 95% CI, 0.61-1.07; P = .14). Overall stroke was 8.4% vs 11.4% (HR, 0.75; 95% CI, 0.48-1.17; P = .21); disabling stroke was more frequent with CoreValve vs Lotus (4.7% Lotus vs 8.6% CoreValve; HR, 0.53; 95% CI, 0.31-0.93; P = .02). More Lotus patients received a new permanent pacemaker (41.7% vs 26.1%; HR, 1.87; 95% CI, 1.41-2.49; P < .01) or had a valve thrombosis (3.0% vs 0.0%; P < .01) compared with CoreValve. More patients who received CoreValve experienced a repeated procedure (0.6% Lotus vs 2.9% CoreValve; HR, 0.19; 95% CI, 0.05-0.70; P < .01), valve migration (0.0% vs 0.7%; P = .05), or embolization (0.0% vs 2.0%; P < .01) than Lotus. Valve areas remained significantly larger and the mean gradient was lower with CoreValve than Lotus (valve area, mean [SD]: Lotus, 1.53 [0.49] cm2 vs CoreValve, 1.76 [0.51] cm2; P < .01; valve gradient, mean [SD]: Lotus, 13.0 [6.7] mm Hg vs 8.1 [3.7] mm Hg; P < .01). Moderate or greater PVL was more frequent with CoreValve (0.3% Lotus vs 3.8% CoreValve; P < .01) at 2 years. Larger improvements in New York Heart Association (NYHA) functional class were observed with Lotus compared with CoreValve (improved by ≥1 NYHA class: Lotus, 338 of 402 [84.1%] vs CoreValve, 143 of 189 [75.7%]; P = .01; improved by ≥2 NYHA classes: 122 of 402 [37.3%] vs 65 of 305 [21.3%]). Conclusions and Relevance: After 2 years, all-cause mortality rates, mortality or disabling stroke were similar between Lotus and CoreValve. Disabling stroke, functional class, valve migration, and PVL favored the Lotus arm whereas valve hemodynamics, thrombosis, and new pacemaker implantation favored the CoreValve arm. Trial Registration: clinicaltrials.gov Identifier: NCT02202434.

Clinical impact of baseline chronic kidney disease in patients undergoing transcatheter or surgical aortic valve replacement.

OBJECTIVES: To assess the treatment effect of TAVR versus SAVR on clinical outcomes to 3 years in patients stratified by chronic kidney disease (CKD) by retrospectively studying patients randomized to TAVR or SAVR. BACKGROUND: The impact of CKD on mid-term outcomes of patients undergoing TAVR versus SAVR is unclear. METHODS: Patients randomized to TAVR or SAVR in the CoreValve US Pivotal High Risk Trial were retrospectively stratified by eGFR: none/mild or moderate/severe CKD. To evaluate the impact of baseline CKD in TAVR patients only, all patients undergoing an attempted TAVR implant in the US Pivotal Trial and CAS were stratified by baseline eGFR into none/mild, moderate, and severe CKD. The primary endpoint was major adverse cardiovascular and renal events (MACRE), a composite of all-cause mortality, myocardial infarction, stroke/TIA, and new requirement of dialysis. RESULTS: Moderate/severe CKD was present in 62.7% and 60.7% of high-risk patients randomized to TAVR or SAVR, respectively. Baseline characteristics were similar between TAVR and SAVR patients in both CKD subgroups, except for higher rates of diabetes and higher serum creatinine in SAVR patients. Among high-risk patients with moderate/severe CKD, TAVR provided a lower 3-year MACRE rate compared with SAVR: 42.1% vs. 51.0, P = .04. Of 3,733 extreme- and high-risk TAVR patients, 39.9% had none/mild, 53.8% moderate, and 6.4% severe CKD. Worsening baseline CKD was associated with increased 3-year MACRE rates [none/mild 51.5%, moderate 54.5%, severe 63.1%, P = .001]. CONCLUSIONS: TAVR results in lower 3-year MACRE versus SAVR in high-risk patients with moderate/severe CKD. In patients undergoing TAVR, worsening CKD increases mid-term mortality and MACRE. Randomized trials of TAVR vs. SAVR in patients with moderate-severe CKD would help elucidate the best treatment for these complex patients. TRIAL REGISTRATION: CoreValve US Pivotal Trial: NCT01240902. CoreValve Continued Access Study: NCT01531374.

Neurological Complications After Transcatheter Versus Surgical Aortic Valve Replacement in Intermediate-Risk Patients.

BACKGROUND: Neurological events after aortic valve interventions are associated with increased mortality and morbidity. Transcatheter aortic valve replacement (TAVR) is increasingly offered for lower-risk patients with severe aortic stenosis, previously considered candidates for surgical aortic valve replacement (SAVR). Differences in post-procedural neurological events have important implications in treatment allocation. OBJECTIVES: The authors sought to analyze the neurological events in the randomized SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial. METHODS: Patients with severe, symptomatic aortic stenosis at intermediate surgical risk were randomized 1:1 to TAVR or SAVR. The rates of neurological events and quality of life were analyzed at 30 days, and 6 and 12 months post-procedure in a modified intention-to-treat population (mean age 79.8 ± 6.2 years; N = 1,660). RESULTS: The rates of early (30-day) stroke and post-procedural encephalopathy were higher after SAVR versus TAVR (5.4% vs. 3.3%; p = 0.031; and 7.8% vs. 1.6%; p < 0.001, respectively). At 12 months, the rate of stroke was not different between SAVR and TAVR (6.9% vs. 5.2%; p = 0.136). Early stroke and early encephalopathy resulted in an elevated mortality at 12 months in both treatment groups. Quality of life after an early stroke was significantly lower in SAVR versus TAVR patients at 30 days and was similar at 6 and 12 months. CONCLUSIONS: The early stroke rate was lower after TAVR than SAVR. In patients with early strokes, QOL improved earlier after TAVR. At 12-month follow-up, stroke rates and QOL were not different between TAVR and SAVR patients. (Surgical Replacement and Transcatheter Aortic Valve Implantation [SURTAVI]; NCT01586910).

Impact of annular and supra-annular CoreValve deployment locations on aortic and coronary artery hemodynamics.

CoreValve is widely used in transcatheter aortic valve replacement, but the impact of its deployment location on hemodynamics is unexplored despite a potential role in subsequent aortic and coronary artery pathologies. The objectives of this investigation were to perform fluid-structure interaction (FSI) simulations for a 29 mm CoreValve deployed in annular vs supra-annular locations, and characterize resulting hemodynamics including velocity and wall shear stress (WSS). Patient-specific geometry was reconstructed from computed tomography scans and CoreValve was deployed using a finite element approach. FSI simulations were then performed using a boundary conforming method and realistic boundary conditions. Results showed that CoreValve deployment location impacts hemodynamics in the ascending aorta and flow patterns in the coronary arteries. During peak-systole, annularly deployed CoreValve produced a jet-like flow structure impinging on the outer-curvature of the ascending aorta. Supra-annularly deployed CoreValve having a lateral tilt of 10° led to a more centered jet impinging further downstream. At mid-systole, valve leaflets of the annularly deployed CoreValve closed asymmetrically leading to disorganized flow patterns in the ascending aorta vs those from the supra-annular position. Supra-annularly deployed CoreValve also led to high-velocity para-valvular flow supplying the coronary arteries. CoreValve in the supra-annular position significantly (P < 0.05) elevated WSS within the first few diameters of both coronary arteries as compared to the annular position for many time points quantified. These results afforded by the advanced simulation methods may have important clinical implications given the role of aortic hemodynamics in dilation and the pro-atherogenic nature of WSS alterations in the coronary arteries.

1-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Severe Mitral Annular Calcification.

BACKGROUND: The risk of surgical mitral valve replacement in patients with severe mitral annular calcification (MAC) is high. Several patients worldwide with severe MAC have been treated successfully with transcatheter mitral valve replacement (TMVR) using balloon-expandable aortic transcatheter valves. The TMVR in MAC Global Registry is a multicenter registry that collects data on outcomes of these procedures. OBJECTIVES: The goal of this study was to evaluate 1-year outcomes in this registry. METHODS: This study was a multicenter retrospective review of clinical outcomes. RESULTS: A total of 116 extreme surgical risk patients with severe MAC underwent TMVR; 106 had a procedure date >1 year before data-lock and were included in the analysis. Their mean age was 73 ± 12 years, and 68% were female. The mean Society of Thoracic Surgeons score was 15.3 ± 11.6%, and 90% were in New York Heart Association functional class III or IV. Thirty-day and 1-year all-cause mortality was 25% and 53.7%, respectively. Most patients who survived 30 days were alive at 1 year (49 of 77 [63.6%]), and the majority (71.8%) were in New York Heart Association functional class I or II. Echocardiography data at 1 year were available in 34 patients. Mean left ventricular ejection fraction was 58.6 ± 11.2%, mean mitral valve area was 1.9 ± 0.5 cm2, mean mitral gradient was 5.8 ± 2.2 mm Hg, and 75% had zero or trace mitral regurgitation. CONCLUSIONS: TMVR with balloon-expandable aortic valves in extreme surgical risk patients with severe MAC is feasible but associated with high 30-day and 1-year mortality. Most patients who survive the 30-day post-procedural period are alive at 1 year and have sustained improvement of symptoms and transcatheter valve performance. The role of TMVR in patients with MAC requires further evaluation in clinical trials.

Transcatheter aortic valve replacement in patients with severe mitral or tricuspid regurgitation at extreme risk for surgery.

OBJECTIVES: Patients with symptomatic severe aortic stenosis and severe mitral regurgitation or severe tricuspid regurgitation were excluded from the major transcatheter aortic valve replacement trials. We studied these 2 subgroups in patients at extreme risk for surgery in the prospective, nonrandomized, single-arm CoreValve US Expanded Use Study. METHODS: The primary end point was all-cause mortality or major stroke at 1 year. A favorable medical benefit was defined as a Kansas City Cardiomyopathy Questionnaire overall summary score greater than 45 at 6 months and greater than 60 at 1 year and with a less than 10-point decrease from baseline. RESULTS: There were 53 patients in each group. Baseline characteristics for the severe mitral regurgitation and severe tricuspid regurgitation cohorts were age 84.2 ± 6.4 years and 84.9 ± 6.5 years; male, 29 (54.7%) and 22 (41.5%), and mean Society of Thoracic Surgeons score 9.9% ± 5.0% and 9.2% ± 4.0%, respectively. Improvement in valve regurgitation from baseline to 1 year occurred in 72.7% of the patients with severe mitral regurgitation and in 61.8% of patients with severe tricuspid regurgitation. A favorable medical benefit occurred in 31 of 47 patients (66.0%) with severe mitral regurgitation and 33 of 47 patients (70.2%) with severe tricuspid regurgitation at 6 months, and in 25 of 44 patients (56.8%) with severe mitral regurgitation and 24 of 45 patients (53.3%) with severe tricuspid regurgitation at 1 year. All-cause mortality or major stroke for the severe mitral regurgitation and severe tricuspid regurgitation cohorts were 11.3% and 3.8% at 30 days and 21.0% and 19.2% at 1 year, respectively. There were no major strokes in either group at 1 year. CONCLUSIONS: Transcatheter aortic valve replacement in patients with severe mitral regurgitation or severe tricuspid regurgitation is reasonable and safe and leads to improvement in atrioventricular valve regurgitation.

Effect of Aging on Mitochondrial Energetics in the Human Atria.

Energy production in myocardial cells occurs mainly in the mitochondrion. Although alterations in mitochondrial functions in the senescent heart have been documented, the molecular bases for the aging-associated decline in energy metabolism in the human heart are not fully understood. In this study, we examined transcription profiles of genes coding for mitochondrial proteins in atrial tissue from aged (≥65 years old) and comorbidities-matched adult (<65 years old) patients with preserved left ventricular function. We also correlated changes in functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes with gene expression changes. There was significant alteration in the expression of 10% (101/1,008) of genes coding for mitochondrial proteins, with 86% downregulated (87/101). Forty-nine percent of the altered genes were confined to mitochondrial energetic pathways. These changes were associated with a significant decrease in respiratory capacity of mitochondria oxidizing glutamate and malate and functional activity of complex I activity that correlated with the downregulation of NDUFA6, NDUFA9, NDUFB5, NDUFB8, and NDUFS2 genes coding for NADH dehydrogenase subunits. Thus, aging is associated with a decline in activity of OXPHOS within the broader transcriptional downregulation of genes regulating mitochondrial energetics, providing a substrate for reduced energetic efficiency in the senescent human atria.

Direct Aortic Access for Transcatheter Aortic Valve Replacement Using a Self-Expanding Device.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) using a self-expanding valve has been shown to be superior to an open operation in high-risk patients. Extensive iliofemoral peripheral vascular disease can prohibit femoral access. In these cases, direct aortic (DA) implantation may be a suitable option. METHODS: The current analysis compared outcomes in patients undergoing TAVR with the self-expanding CoreValve prosthesis (Medtronic, Minneapolis, MN) by direct aortic (DA) access vs iliofemoral (IF) access. Patients treated in the CoreValve US High Risk and Extreme Risk Pivotal Trials and Continued Access Study were included. Propensity score matching was used to account for differences in baseline characteristics between groups. Clinical outcomes were compared at 30 days and 1 year. RESULTS: We identified 394 matched pairs of IF and DA patients. The all-cause mortality rate was significantly higher in the DA group than in the IF group at 30 days (10.9% vs 4.1%, p < 0.001), but this difference was reduced at 1 year (28.1% vs 23.2%, p = 0.063). All-cause mortality or major stroke was significantly higher for DA vs IF access at 30 days (13.5% vs 5.3%, p < 0.001) and at 1 year (30.4% vs 24.2%, p = 0.025). Major/life-threatening bleeding and acute kidney injury were significantly greater in the DA group at 30 days (66.7% vs 35.4% and 19.7% vs 10.0%, respectively, both p < 0.001). CONCLUSIONS: When femoral access is not feasible, DA access allows effective delivery of the valve but incurs an increased risk of death and adverse events, potentially the result of procedural differences.

Transthoracic echocardiography is adequate for intraprocedural guidance of transcatheter aortic valve implantation.

BACKGROUND: While transcatheter aortic valve implantation (TAVI) has traditionally been supported intraprocedurally by transoesophageal echocardiography (TOE), transthoracic echocardiography (TTE) is increasingly being used. We evaluated echocardiographic imaging characteristics and clinical outcomes in patients who underwent TTE during TAVI (TTE-TAVI). METHODS AND RESULTS: A select team of dedicated sonographers and interventional echocardiographers performed TTE-TAVI in 278 patients, all of whom underwent TAVI through transfemoral access. We implanted the Medtronic EVOLUT R valve in 258 patients (92.8%). TTE images were acquired immediately pre-procedure by a dedicated sonographer in the cardiac catheterization laboratory with the patient in the supine position. TTE was then performed post deployment of TAVI. In the procedure, TTE image quality was fair or better in 249 (89.6%) cases. Color-flow Doppler was adequate or better in 275 (98.9%) cases. In 2 cases, paravalvular regurgitation (PVL) could not be assessed confidently by echocardiography due to poor image quality; in those cases, PVL was assessed by fluoroscopy, aortic root injection and invasive hemodynamics. Both TTE and invasive hemodynamics were used in the assessment of need for post-deployment stent ballooning (n = 23, 8.3%). TTE adequately recognized new pericardial effusion in 3 cases. No case required TOE conversion for image quality. There was only 1 case of intraprocedural TTE failing to recognize moderate PVL, without clinical implication. In 99% of patients, TTE-TAVI adequately assessed PVL compared with 24-h and 1-month follow-up TTE. CONCLUSIONS: With the current generation of TAVI, TTE-TAVI is adequate intraprocedurally when performed by specialized sonographers and dedicated cardiologists in a highly experienced TAVI center.