Placement Of Aortic Transcatheter Valves Research Articles

Effect of Sex and Flow Status on Outcomes After Surgical or Transcatheter Aortic Valve Replacement

BackgroundLow stroke volume index <35 ml/m2 despite preserved ejection fraction (paradoxical low flow [PLF]) is associated with adverse outcomes in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). However, whether the risk associated with PLF is similar in both sexes is unknown. ObjectivesThe purpose of this study was to analyze the risk associated with PLF in severe aortic stenosis for men and women randomized to TAVR or SAVR. MethodsPatients with ejection fraction ≥50% from the PARTNER (Placement of Aortic Transcatheter Valves) 2 and 3 trials were stratified by sex and treatment arm. The impact of PLF on the 2-year occurrence of the composite of death or heart failure hospitalization (primary endpoint) and of all-cause mortality alone (secondary endpoint) was analyzed. Analysis of variance was used to assess baseline differences between groups. Multivariate Cox regression analysis was used to identify predictors of the endpoint. ResultsOut of 2,242 patients, PLF was present in 390 men and 239 women (30% vs 26%, P = 0.06). PLF was associated with a higher rate of NYHA functional class III to IV dyspnea (60% vs 54%, P < 0.001) and a higher prevalence of atrial fibrillation (39% vs 24%, P < 0.001). PLF was a significant predictor of the primary endpoint among women undergoing SAVR in multivariate analysis (adjusted HR: 2.25 [95% CI: 1.14-4.43], P = 0.02) but was not associated with a worse outcome in any of the other groups (all P > 0.05). ConclusionsIn women with PLF, TAVR may improve outcomes compared to SAVR. PLF appears to have less impact on outcomes in men.

Patient-Prosthesis Mismatch After Surgical Aortic Valve Replacement: Analysis of the PARTNER Trials

BackgroundOur objective was to compare the impact of patient-prosthesis mismatch (PPM) for 2 years after surgical aortic valve replacement within the prospective, randomized Placement of Aortic Transcatheter Valves (PARTNER) trials. MethodsSurgical aortic valve replacement patients from the PARTNER 1, 2, and 3 trials were included. PPM was classified as moderate (indexed effective orifice area ≤0.85 cm2/m2) or severe (indexed effective orifice area ≤0.65 cm2/m2). The primary endpoint was the composite of all-cause death and heart failure rehospitalization at 2 years. ResultsBy the predicted PPM method (PPMP), 59.1% had no PPM, 38.8% moderate PPM, and 2.1% severe PPM; whereas by the measured PPM method (PPMM), 42.4% had no PPM, 36.0% moderate, and 21.6% severe. Patients with no PPMP (23.6%) had a lower rate of the primary endpoint compared with patients with moderate (28.2%, P = .03) or severe PPMP (38.8%, P = .02). Using the PPMM method, there was no difference between the no (17.7%) and moderate PPMM groups (21.1%) in the primary outcome (P = .16). However, those with no PPMM or moderate PPMM were improved compared with severe PPMM (27.4%, P < .001 and P = .02, respectively). ConclusionsSevere PPM analyzed by PPMP was only 2.1% for surgical aortic valve replacement patients. The PPMM method overestimated the incidence of severe PPM relative to PPMP, but was also associated with worse outcome. There was higher all-cause mortality in patients with severe PPM, thus surgical techniques to minimize PPM remain critical.

Abstract 14928: Coronary Artery Disease Impacts Cardiac Remodeling in Patients Treated for Severe Aortic Stenosis in the PARTNER Trials

Introduction: Coronary artery disease (CAD) is common in patients with severe aortic stenosis (AS), but the impact on cardiac remodeling and outcomes after AS treatment is unknown. Hypothesis: We hypothesize that greater CAD burden will be associated with less beneficial remodeling and increased adverse events. Methods: Patients with severe AS in the PARTNER (Placement of Aortic Transcatheter Valves) 1, 2 or 3 trials, with baseline and 1 year echoes, were categorized as: 1. Obstructive CAD (coronary stenosis ≥50% on invasive angiography, prior myocardial infarction (MI) or previous revascularization); or 2. Non-obstructive or no CAD (all stenosis &lt;50% and no prior MI or revasc). Clinical and imaging characteristics were compared and changes in cardiac structure and function were assessed at 1 year. Associations between CAD, cardiac remodeling and cardiovascular (CV) events at 2 years were examined. Results: Among 5552 patients with severe AS, 1598 (28.8%) had non-obstructive or no CAD and were more likely to be female (67.1%), have fewer CAD risk factors, and receive SAVR (28% vs. 19%) compared to those with obstructive CAD (all p&lt;0.0001). Despite lower LV mass index (LVMi), patients with non-obstructive or no CAD had higher aortic valve velocities, gradients, ejection fraction (EF) and stroke volume index compared to those with obstructive CAD. After 1 year, the decrease in LVMi was similar between groups (p=0.91), but patients with obstructive CAD were more likely to increase EF by ≥5% (p=0.006), reduce LV dimensions (p=0.04), or decrease mitral regurgitation (p=0.01). After adjustment for baseline factors and AS treatment, CV death or heart failure (HF) hospitalization was higher among patients with obstructive CAD (HR 1.16, 95% CI: 1.03-1.30, p=0.01). When LV remodeling at 1 year was also adjusted for, the point estimate was similar but there was no significant difference in the landmarked rate of CV death or HF hospitalization between year 1 and 2 (HR 1.22, 95% CI: 0.95-1.56, p=0.12). Conclusions: Nearly a third of patients with severe AS did not have obstructive CAD and had a better prognosis after treatment for AS. However, patients with obstructive CAD and LV remodeling were not at greater risk for CV events compared to those with non-obstructive or no CAD.

Abstract 14894: The Impact of Coronary Artery Disease on Cardiovascular Events Differs Between Men and Women in the PARTNER Trials

Introduction: Among individuals with severe aortic stenosis (AS), there is significant heterogeneity in the burden of coronary artery disease (CAD). Hypothesis: We hypothesize that a greater CAD burden will be associated with increased adverse events after AS treatment. Methods: Patients with severe AS in the PARTNER (Placement of Aortic Transcatheter Valves) 1, 2 and 3 trials and registries were categorized by CAD burden. Clinical characteristics, imaging, treatment, and outcomes were compared between those with obstructive CAD [defined invasively as coronary stenosis ≥50%, prior myocardial infarction (MI) or revascularization] and patients with no or non-obstructive CAD (all stenoses &lt;50% and no prior MI or revascularization). The primary endpoint was cardiovascular (CV) death or heart failure (HF) hospitalization at 2 years. Results: Among 8058 patients with severe AS, 2200 (27.3%) had non-obstructive or no CAD and were more likely to be female (61.2%) with fewer CAD risk factors. Left ventricular (LV) mass index and LV dimensions were smaller and LV ejection fraction was higher among those with non-obstructive or no CAD. TAVR was performed in 72.0% of non-obstructive or no CAD patients and in 81.3% of patients with obstructive CAD (p&lt;0.0001); the remaining patients received SAVR. After adjustment for clinical, imaging, and AS treatment differences, the rate of CV death or HF hospitalization was higher among those with obstructive CAD (HR 1.16, 95% CI: 1.03-1.30, p=0.01). However, there was a significant sex-related difference in the primary outcome particularly between males and females with non-obstructive or no CAD, p interaction =0.003 (Figure). Conclusions: Patients with a greater burden of CAD had worse clinical outcomes after treatment for severe AS. However, there was a significant interaction by sex. Further study is needed to understand the increased CV risk among females compared to males with non-obstructive or no CAD.

Survival After Surgical Aortic Valve Replacement in Low-Risk Patients: A Contemporary Trial Benchmark

BackgroundThe use of transcatheter aortic valve replacement for severe aortic stenosis in low-risk patients necessitates an evaluation of contemporary long-term, real-world outcomes of similar patients undergoing surgical aortic valve replacement (SAVR) in a national cohort. MethodsAll patients undergoing primary, isolated SAVR in The Society of Thoracic Surgeons (STS) database between 2011 and 2019 were examined. The study population of 42,586 adhered to the inclusion/exclusion criteria of the Placement of Aortic Transcatheter Valves (PARTNER) 3 and Evolut Low Risk randomized trials. Patients were further stratified by STS predicted risk of mortality (PROM), age, and left ventricular ejection fraction. The primary end-point was all-cause National Death Index mortality. Unadjusted survival to 8 years was estimated using the Kaplan-Meier method. ResultsMean age was 74.3 ± 5.7 years and mean STS PROM was 1.9% ± 0.8%. The overall Kaplan-Meier time to event analysis for all-cause mortality at 1, 3, 5, and 8 years was 2.6%, 4.5%, 7.1%, and 12.4%, respectively. In subset analyses, survival was significantly better for (1) lower STS PROM (P < .001), (2) younger vs older age (P < .001), and (3) higher vs lower left ventricular ejection fraction (P < .001). When STS PROM was below 1% or the patient age was below age 75 years, the 8-year survival after SAVR was 95%. ConclusionsThe results of this national study confirm that long-term survival after SAVR remains excellent, at 92.9% at 5 years. These contemporary longitudinal data serve to aid in the balanced interpretation of current and future trials comparing SAVR and transcatheter aortic valve replacement and may assist in the clinical decision-making process for patients of lower surgical risk.

Diastolic Dysfunction and Health Status Outcomes After Transcatheter Aortic Valve Replacement

BackgroundBaseline left ventricular diastolic dysfunction (LVDD) is associated with poor health status in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), but health status improvement after TAVR appears similar across all grades of LVDD. Here, we aim to examine the relationship between changes in LVDD severity and health status outcomes following TAVR. MethodsPatients who underwent TAVR and had evaluable LVDD at both baseline and 1 year in the PARTNER (Placement of Aortic Transcatheter Valves) 2 SAPIEN 3 registries and PARTNER 3 trial were analyzed. LVDD grade was evaluated using echocardiography core lab data and an adapted definition of American Society of Echocardiography guidelines. Health status was assessed using the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score. The association between ΔLVDD severity and ΔKCCQ-OS was examined using linear regression models adjusted for baseline KCCQ-OS. ResultsOf 1100 patients, 724 (65.8%), 283 (25.7%), and 93 (8.5%) had grade 0/1, 2, and 3 LVDD at baseline, respectively. At 1 year, LVDD severity was unchanged in 790 (71.8%) patients, improved in 189 (17.2%), and worsened in 121 (11.0%). Among 376 patients with baseline grade 2 or 3 LVDD, 50.3% had improvement in LVDD. In the overall cohort, KCCQ-OS score improved by 21.9 points at 1 year. There was a statistically significant association between change in LVDD severity (improved, unchanged, and worsened) and ΔKCCQ-OS at 1 year (p = 0.007). ConclusionsChange in LVDD grade was associated with change in health status 1 year following TAVR.

Outcomes of SAPIEN 3 Transcatheter Aortic Valve Replacement Compared With Surgical Valve Replacement in Intermediate-Risk Patients

BackgroundPrevious studies demonstrated transcatheter aortic valve replacement (TAVR) with an earlier generation balloon-expandable valve to be noninferior to surgical aortic valve replacement (SAVR) for death and disabling stroke in intermediate-risk patients with symptomatic, severe aortic stenosis at 5 years. However, limited long-term data are available with the more contemporary SAPIEN 3 (S3) bioprosthesis. ObjectivesThe aim of this study was to compare 5-year risk-adjusted outcomes in intermediate-risk patients undergoing S3 TAVR vs SAVR. MethodsPropensity score matching was performed to account for baseline differences in intermediate-risk patients undergoing S3 TAVR in the PARTNER 2 (Placement of Aortic Transcatheter Valves) S3 single-arm study and SAVR in the PARTNER 2A randomized clinical trial. The primary composite endpoint consisted of 5-year all-cause death and disabling stroke. ResultsA total of 783 matched pairs of intermediate-risk patients with severe aortic stenosis were studied. There were no differences in the primary endpoint between S3 TAVR and SAVR at 5 years (40.2% vs 42.7%; HR: 0.87; 95% CI: 0.74-1.03; P = 0.10). The incidence of mild or greater paravalvular regurgitation was more common after S3 TAVR. There were no differences in structural valve deterioration–related stage 2 and 3 hemodynamic valve deterioration or bioprosthetic valve failure. ConclusionsIn this propensity-matched analysis of intermediate-risk patients, 5-year rates of death and disabling stroke were similar between S3 TAVR and SAVR. Rates of structural valve deterioration–related hemodynamic valve deterioration were similar, but paravalvular regurgitation was more common after S3 TAVR. Longer-term follow-up is needed to further evaluate differences in late adverse clinical events and bioprosthetic valve durability. (PII S3i [PARTNER II Trial: Placement of Aortic Transcatheter Valves II – S3 Intermediate], NCT03222128; PII A (PARTNER II Trial: Placement of Aortic Transcatheter Valves II – XT Intermediate and High Risk], NCT01314313)

Outcomes After Isolated Aortic Valve Replacements in Patients With Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a frequently encountered co-morbidity and is 1 of the main culprits for inoperability in cardiac surgeries among patients with aortic stenosis (AS). 1 Mok M Nombela-Franco L Dumont E Urena M DeLarochellière R Doyle D Villeneuve J Côté M Ribeiro HB Allende R Laflamme J DeLarochellière H Laflamme L Amat-Santos I Pibarot P Maltais F Rodés-Cabau J. Chronic obstructive pulmonary disease in patients undergoing transcatheter aortic valve implantation: insights on clinical outcomes, prognostic markers, and functional status changes. JACC Cardiovasc Interv. 2013; 6: 1072-1084 Crossref PubMed Scopus (82) Google Scholar ,2 Kumbhani DJ Kapadia SR Jneid H. Transcatheter or surgical aortic valve replacement in patients with chronic lung disease? The answer, my friend, is blowin’ in the Wind. J Am Heart Assoc. 2018; 7e008933 Crossref Google Scholar Aortic valve replacement (AVR) through surgical approach (surgical aortic valve replacement [SAVR]) carries a high risk of morbidity and mortality in patients with COPD on home-oxygen (home-O2), 3 Kumar K Morris CC Samhan A Herman T Chau T Lantz G Chadderdon SM Song HK Zahr FE Golwala H. Intermediate-term outcomes following transcatheter aortic valve implantation in patients with a history of supplemental home oxygen use. Am J Cardiol. 2022; 167: 159-160 Abstract Full Text Full Text PDF Scopus (0) Google Scholar ,4 Dvir D Waksman R Barbash IM Kodali SK Svensson LG Tuzcu EM Xu K Minha S Alu MC Szeto WY Thourani VH Makkar R Kapadia S Satler LF Webb JG Leon MB Pichard AD. Outcomes of patients with chronic lung disease and severe aortic stenosis treated with transcatheter versus surgical aortic valve replacement or standard therapy: insights from the PARTNER trial (placement of AoRTic transcatheter Valve). J Am Coll Cardiol. 2014; 63: 269-279 Crossref PubMed Scopus (81) Google Scholar which makes AVR through transcatheter approach (transcatheter aortic valve implantation [TAVI]) an increasingly attractive option in this patient population. 5 Doldi P Steffen J Orban M Theiss H Sadoni S Hagl C Massberg S Hausleiter J Deseive S Braun D. Clinical outcome following transcatheter aortic valve implantation in patients with chronic obstructive pulmonary disease. JACC Cardiovasc Interv. 2022; 15: 1188-1190 Crossref Scopus (1) Google Scholar However, the outcomes of home-O2 users among patients with AS and COPD who undergo different treatment strategies are not well understood. Hence, we compared the outcomes of home-O2 users and nonusers among patients with AS and COPD from a nationwide registry.

Economic Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis and Low Surgical Risk: Results from the PARTNER 3 Trial.

In patients with severe symptomatic aortic stenosis at low surgical risk, transfemoral transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve has been shown to reduce the composite of death, stroke, or rehospitalization at 2-year follow-up compared with surgical aortic valve replacement (SAVR). Whether TAVR is cost-effective compared with SAVR for low-risk patients remains uncertain. Between 2016 and 2017, 1000 low-risk patients with aortic stenosis were randomly assigned to TAVR with the SAPIEN 3 valve or SAVR in the PARTNER 3 trial (Placement of Aortic Transcatheter Valves). Of these patients, 929 underwent valve replacement, were enrolled in the United States, and were included in the economic substudy. Procedural costs were estimated using measured resource use. Other costs were determined by linkage with Medicare claims or by regression models when linkage was not feasible. Health utilities were estimated using the EuroQOL 5-item questionnaire. With the use of a Markov model informed by in-trial data, lifetime cost-effectiveness from the perspective of the US health care system was estimated in terms of cost per quality-adjusted life-year gained. Although procedural costs were nearly $19 000 higher with TAVR, total index hospitalization costs were only $591 more with TAVR compared with SAVR. Follow-up costs were lower with TAVR such that TAVR led to 2-year cost savings of $2030/patient compared with SAVR (95% CI, -$6222 to $1816) and a gain of 0.05 quality-adjusted life-years (95% CI, -0.003 to 0.102). In our base-case analysis, TAVR was projected to be an economically dominant strategy with a 95% probability that the incremental cost-effectiveness ratio for TAVR would be <$50 000/quality-adjusted life-year gained (consistent with high economic value from a US health care perspective). These findings were sensitive to differences in long-term survival, however, such that a modest long-term survival advantage with SAVR would render SAVR cost-effective (although not cost saving) compared with TAVR. For patients with severe aortic stenosis and low surgical risk similar to those enrolled in the PARTNER 3 trial, transfemoral TAVR with the SAPIEN 3 valve is cost saving compared with SAVR at 2 years and is projected to be economically attractive in the long run as long as there are no substantial differences in late death between the 2 strategies. Long-term follow-up will be critical to ultimately determine the preferred treatment strategy for low-risk patients from both a clinical and economic perspective.

Cardiac Damage and Quality of Life After Aortic Valve Replacement in the PARTNER Trials

BackgroundThe extent of extravalvular cardiac damage is associated with increased risk of adverse events among patients with severe aortic stenosis undergoing aortic valve replacement (AVR). ObjectivesThe goal was to describe the association of cardiac damage on health status before and after AVR. MethodsPatients from the PARTNER (Placement of Aortic Transcatheter Valves) 2 and 3 trials were pooled and classified by echocardiographic cardiac damage stage at baseline and 1 year as previously described (stage 0-4). We examined the association between baseline cardiac damage and 1-year health status (assessed by the Kansas City Cardiomyopathy Questionnaire Overall Score [KCCQ-OS]). ResultsAmong 1,974 patients (794 surgical AVR, 1,180 transcatheter AVR), the extent of cardiac damage at baseline was associated with lower KCCQ scores both at baseline and at 1 year after AVR (P < 0.0001) and with increased rates of a poor outcome (death, KCCQ-OS <60, or a decrease in KCCQ-OS of ≥10 points) at 1 year (stages 0-4: 10.6% vs 19.6% vs 29.0% vs 44.7% vs 39.8%; P < 0.0001). In a multivariable model, each 1-stage increase in baseline cardiac damage was associated with a 24% increase in the odds of a poor outcome (95% CI: 9%-41%; P = 0.001). Change in stage of cardiac damage at 1 year after AVR was associated with the extent of improvement in KCCQ-OS over the same period (mean change in 1-year KCCQ-OS: improvement of ≥1 stage +26.8 [95% CI: 24.2-29.4] vs no change +21.4 [95% CI: 20.0-22.7] vs deterioration of ≥1 stage +17.5 [95% CI: 15.4-19.5]; P < 0.0001). ConclusionsThe extent of cardiac damage before AVR has an important impact on health status outcomes, both cross-sectionally and after AVR. (PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - XT Intermediate and High Risk (PII A), NCT01314313; The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves - PII B [PARTNERII B], NCT02184442; PARTNER 3 Trial: Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis [P3], NCT02675114)

Severity of and Recovery From Anemia After Transcatheter Aortic Valve Replacement: An Analysis of the PARTNER Trials and Registries

<h2>Abstract</h2><h3>Background</h3> Anemia is associated with increased mortality in patients undergoing transcatheter aortic valve replacement (TAVR); however, data on the effect of the severity of and recovery from anemia on clinical outcomes are limited. This study examined the impact of the severity of and recovery from anemia after TAVR. <h3>Methods</h3> Patients with symptomatic, severe aortic stenosis across all surgical risk groups from the Placement of Aortic Transcatheter Valves I, II, and III trials and registries who underwent TAVR were analyzed. Baseline anemia was defined as mild (hemoglobin [Hb] level ≥11.0 g/dL and <13.0 g/dL for men and ≥11.0 g/dL and <12.0 g/dL for women) and moderate-to-severe anemia (Hb level < 11.0 g/dL). Recovery from anemia was defined as an increase of ≥1 g/dL in the Hb level. Patients with missing Hb information and major bleeding within 30 days were excluded. The association of the severity of and recovery from anemia with clinical outcomes was analyzed using multivariable Cox proportional hazards regression models. The primary outcome was 1-year all-cause mortality. <h3>Results</h3> The Kaplan-Meier estimate for 1-year all-cause mortality was 5.4%, 8.2%, and 14.5% in patients with no, mild, and moderate-to-severe anemia, respectively (<i>P</i> < .001). Recovery from anemia at 30 days occurred in 8.4% (229/2730) of all patients. Compared with those without baseline or 30-day anemia, patients with recovery from anemia had similar 1-year mortality (hazard ratio, 1.02; confidence interval, 0.50-2.08; <i>P</i> = .96), whereas those without recovery from anemia had higher 1-year mortality (hazard ratio, 1.82; confidence interval, 1.17-2.85; <i>P</i> = .009). <h3>Conclusions</h3> In patients undergoing TAVR, moderate-to-severe anemia is independently associated with increased 1-year mortality, and recovery from anemia after TAVR is associated with favorable outcomes. Further efforts are needed to determine whether preprocedural correction of anemia improves post-TAVR outcomes.

Impact of Right Ventricle-Pulmonary Artery Coupling on Clinical Outcomes in the PARTNER 3 Trial.

Physiologic right ventricle-pulmonary artery (RV-PA) coupling may be impaired in patients with aortic stenosis (AS). This study aimed to assess the incidence and prognostic significance of impaired RV-PA coupling in low-risk patients with symptomatic severe AS undergoing transcatheter aortic valve replacement or surgical aortic valve replacement. RV-PA coupling was measured by transthoracic echocardiography as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) in patients in the PARTNER (Placement of Aortic Transcatheter Valve) 3 trial. The primary endpoint was the composite of all-cause mortality, stroke, and rehospitalization at the 2-year follow-up. Among 570 low-risk patients included in the analysis, RV-PA uncoupling was defined by a TAPSE/PASP ratio≤ 0.55mm/mmHg. At baseline, 222 of 570 (38.9%) patients had RV-PA uncoupling. At 2 years, patients with baseline RV-PA uncoupling had an increased incidence of the primary endpoint (19.1% vs 9.9%, P = 0.002), all-cause mortality (5.9% vs 0.6%, P< 0.001), cardiovascular mortality (4.1% vs 0.6%, P = 0.003), and rehospitalization (13.5% vs 7.3%, P = 0.018). On multivariable analysis, baseline RV-PA uncoupling remained an independent predictor of the primary endpoint at 2 years (HR: 1.92; 95%CI: 1.04-3.57; P = 0.038). In patients with symptomatic severe AS at low surgical risk undergoing transcatheter aortic valve replacement or surgical aortic valve replacement, baseline RV-PA uncoupling defined by TAPSE/PASP ≤ 0.55mmHg was associated with adverse clinical outcomes at 2 years, including all-cause mortality, cardiovascular mortality, and rehospitalization.

Clinical and Echocardiographic Characteristics of Flow-Based Classification Following Balloon-Expandable Transcatheter Heart Valve in PARTNER Trials

BackgroundCurrent expected normal echocardiographic measures of transcatheter heart valve (THV) function were derived from pooled cohorts of the randomized trials; however, THV function by flow state before or following transcatheter aortic valve replacement (TAVR) has not been previously reported. ObjectivesThis study sought to assess the expected normal echocardiographic hemodynamics for the balloon-expandable THV grouped by stroke volume index (SVI). MethodsPatients with severe aortic stenosis enrolled in PARTNER (Placement of Aortic Transcatheter Valves) 1 (high/extreme surgical risk), PARTNER 2 (intermediate surgical risk), or PARTNER 3 (low surgical risk) trials with complete core laboratory echocardiography were included. Patients were grouped by low-flow (SVILOW <35 mL/m2) and normal-flow (SVINORMAL ≥35 mL/m2). Mean gradient, effective orifice area (EOA), and Doppler velocity index (DVI) were collected at baseline and at 30 days post-TAVR. Prosthesis-patient mismatch (PPM) was both calculated and predicted from normative data, using defined criteria. ResultsIn the entire population (N = 4,991), mean age was 81.8 years, 58% of patients were male, and 42% had low flow. Compared with patients with baseline SVINORMAL, those with SVILOW were more likely to be male; have more comorbidities; and lower left ventricular ejection fraction, mean gradient, and EOA. Post-TAVR, SVILOW increased to SVINORMAL in 17.3% and SVINORMAL decreased to SVILOW in 12.3% of patients. Using baseline SVI, follow-up EOA, mean gradient, and DVI for patients with SVILOW tended to be lower than for patients with SVINORMAL. Using the post-TAVR SVI, follow-up EOA, mean gradient, and DVI were significantly lower for patients with SVILOW than for those with SVINORMAL (P < 0.001 for all). The incidence of calculated, but not predicted, severe PPM was higher in patients with low flow than it was in patients with normal flow, suggesting pseudo-PPM in the presence of low flow. ConclusionsThis study demonstrates that flow affects THV hemodynamics and both baseline and follow-up SVI should be considered when predicting THV hemodynamics prior to TAVR, as well as assessing valve function following valve implantation.

Association Between Early Left Ventricular Ejection Fraction Improvement After Transcatheter Aortic Valve Replacement and 5-Year Clinical Outcomes

In patients with severe aortic stenosis and left ventricular ejection fraction (LVEF) less than 50%, early LVEF improvement after transcatheter aortic valve replacement (TAVR) is associated with improved 1-year mortality; however, its association with long-term clinical outcomes is not known. To examine the association between early LVEF improvement after TAVR and 5-year outcomes. This cohort study analyzed patients enrolled in the Placement of Aortic Transcatheter Valves (PARTNER) 1, 2, and S3 trials and registries between July 2007 and April 2015. High- and intermediate-risk patients with baseline LVEF less than 50% who underwent transfemoral TAVR were included in the current study. Data were analyzed from August 2020 to May 2021. Early LVEF improvement, defined as increase of 10 percentage points or more at 30 days and also as a continuous variable (ΔLVEF between baseline and 30 days). All-cause death at 5 years. Among 659 included patients with LVEF less than 50%, 468 (71.0%) were male, and the mean (SD) age was 82.4 (7.7) years. LVEF improvement within 30 days following transfemoral TAVR occurred in 216 patients (32.8%) (mean [SD] ΔLVEF, 16.4 [5.7%]). Prior myocardial infarction, diabetes, cancer, higher baseline LVEF, larger left ventricular end-diastolic diameter, and larger aortic valve area were independently associated with lower likelihood of LVEF improvement. Patients with vs without early LVEF improvement after TAVR had lower 5-year all-cause death (102 [50.0%; 95% CI, 43.3-57.1] vs 246 [58.4%; 95% CI, 53.6-63.2]; P = .04) and cardiac death (52 [29.5%; 95% CI, 23.2-37.1] vs 135 [38.1%; 95% CI, 33.1-43.6]; P = .05). In multivariable analyses, early improvement in LVEF (modeled as a continuous variable) was associated with lower 5-year all-cause death (adjusted hazard ratio per 5% increase in LVEF, 0.94 [95% CI, 0.88-1.00]; P = .04) and cardiac death (adjusted hazard ratio per 5% increase in LVEF, 0.90 [95% CI, 0.82-0.98]; P = .02) after TAVR. Restricted cubic spline analysis demonstrated a visual inflection point at ΔLVEF of 10% beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement. There were no statistically significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire Overall Summary score at 5 years in patients with vs without early LVEF improvement. In subgroup analysis, the association between early LVEF improvement and 5-year all-cause death was consistent regardless of the presence or absence of coronary artery disease or prior myocardial infarction. In patients with severe aortic stenosis and LVEF less than 50%, 1 in 3 experience LVEF improvement within 1 month after TAVR. Early LVEF improvement is associated with lower 5-year all-cause and cardiac death.

Neutrophil‐to‐Lymphocyte Ratios in Patients Undergoing Aortic Valve Replacement: The PARTNER Trials and Registries

BackgroundThe neutrophil‐to‐lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow‐up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis.Methods and ResultsNLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5–24.9) and was evaluated as continuous variable and categorical tertiles (low: NLR ≤2.70, n=1963; intermediate: NLR 2.70–4.20, n=1958; high: NLR ≥4.20, n=1960). No patients had known baseline infection. High baseline NLR was associated with increased risk of death or rehospitalization at 3 years (58.4% versus 41.0%; adjusted hazard ratio [aHR], 1.39; 95% CI, 1.18–1.63; P<0.0001) compared with those with low NLR, irrespective of treatment modality. In both patients treated with TAVR and patients treated with SAVR, NLR decreased between baseline and 2 years. A 1‐unit observed decrease in NLR between baseline and 1 year was associated with lower risk of death or rehospitalization between 1 year and 3 years (aHR, 0.86; 95% CI, 0.82–0.89; P<0.0001).ConclusionsElevated baseline NLR was independently associated with increased subsequent mortality and rehospitalization after TAVR or SAVR. The observed decrease in NLR after TAVR or SAVR was associated with improved outcomes.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT00530894, NCT0134313, NCT02184442, NCT03225001, NCT0322141.

Evolution and Prognostic Impact of Cardiac Damage After Aortic Valve Replacement

BackgroundThe impact of aortic valve replacement (AVR) on progression/regression of extravalvular cardiac damage and its association with subsequent prognosis is unknown. ObjectivesThe purpose of this study was to describe the evolution of cardiac damage post-AVR and its association with outcomes. MethodsPatients undergoing transcatheter or surgical AVR from the PARTNER (Placement of Aortic Transcatheter Valves) 2 and 3 trials were pooled and classified by cardiac damage stage at baseline and 1 year (stage 0, no damage; stage 1, left ventricular damage; stage 2, left atrial or mitral valve damage; stage 3, pulmonary vasculature or tricuspid valve damage; and stage 4, right ventricular damage). Proportional hazards models determined association between change in cardiac damage post-AVR and 2-year outcomes. ResultsAmong 1,974 patients, 121 (6.1%) were stage 0, 287 (14.5%) stage 1, 1,014 (51.4%) stage 2, 412 (20.9%) stage 3, and 140 (7.1%) stage 4 pre-AVR. Two-year mortality was associated with extent of cardiac damage at baseline and 1 year. Compared with baseline, cardiac damage improved in ∼15%, remained unchanged in ∼60%, and worsened in ∼25% of patients at 1 year. The 1-year change in cardiac damage stage was independently associated with mortality (adjusted HR for improvement: 0.49; no change: 1.00; worsening: 1.95; P = 0.023) and composite of death or heart failure hospitalization (adjusted HR for improvement: 0.60; no change: 1.00; worsening: 2.25; P < 0.001) at 2 years. ConclusionsIn patients undergoing AVR, extent of extravalvular cardiac damage at baseline and its change at 1 year have important prognostic implications. These findings suggest that earlier detection of aortic stenosis and intervention before development of irreversible cardiac damage may improve global cardiac function and prognosis. (PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - XT Intermediate and High Risk [PII A], NCT01314313; The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves - PII B [PARTNERII B], NCT02184442; and PARTNER 3 Trial: Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis [P3], NCT02675114)

5-Year Follow-Up From the PARTNER 2 Aortic Valve-in-Valve Registry for Degenerated Aortic SurgicalBioprostheses.

The aim of this study was to report the outcomes of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) at 5 years. TAVR for degenerated surgical bioprostheses in patients at high risk for reoperative surgery is an important treatment option that may delay or obviate the need for surgical intervention; however, long-term outcomes of this procedure are unknown. The PARTNER (Placement of Aortic Transcatheter Valves) 2 ViV and continued access registries prospectively enrolled patients with failed surgical bioprostheses at high risk for reoperation. Five-year clinical and echocardiographic follow-up data were obtained in 95.9% of patients. In 365 (96 registry and 269 continued access) patients, the mean age was 78.9 ± 10.2 years, the mean Society of Thoracic Surgeons predicted risk of surgical mortality score was 9.1 ± 4.7%, and New York Heart Association functional class was III or IV in 90.4%. At 5 years, the Kaplan-Meier rates of all-cause mortality and any stroke were 50.6% and 10.5%, respectively. Using Valve Academic Research Consortium 3 definitions, the incidence of structural valve deterioration, related hemodynamic valve deterioration, or bioprosthetic valve failure at 5 years was 6.6%. Aortic valve re-replacement was performed in 6.3% (n=14), the majority of which was due to stenosis (n=6) and combined aortic insufficiency/paravalvular regurgitation (n=3). The mean gradient, Doppler velocity index, paravalvular regurgitation, and quality of life measured by Kansas City Cardiomyopathy Questionnaire scores in survivors remained stable from 30days postprocedure through 5 years. At the 5-year follow-up, TAVR for bioprosthetic aortic valve failure in high surgical risk patients was associated with sustained improvement in clinical and echocardiographic outcomes.

Characteristics and clinical outcomes in patients with prior chest radiation undergoing TAVR: Observations from PARTNER-2.

The purpose of this study is to investigate the viability of transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis (AS) in patients with prior chest radiation therapy (cXRT). Since patients with prior cXRT perform poorly with surgical aortic valve replacement, TAVR can be a viable alternative. However, clinical outcomes after TAVR in this patient population have not been well studied. From the pooled registry of the placement of aortic transcatheter valvesII trial, we identified patients with and without prior cXRT who underwent TAVR (n = 64 and 3923, respectively). The primary outcome was a composite of all-cause death and any stroke at 2 years. Time to event analyses were shown as Kaplan-Meier event rates and compared by log-rank testing. Hazard ratios (HRs) were estimated and compared by Cox proportional hazards regression model. There was no significant difference in the primary outcome between the patients with and without prior cXRT (30.7% vs. 27.0%; p = 0.75; HR, 1.08; 95% confidence interval, 0.66-1.77). Rates of myocardial infarction, vascular complications, acute kidney injury, or new pacemaker implant after TAVR were not statistically different between the two groups. The rate of immediate reintervention with a second valve for aortic regurgitation after TAVR was higher among the patients with prior cXRT. However, no further difference was observed during 2 years follow-up after discharge from the index-procedure hospitalization. TAVR is a viable alternative for severe symptomatic AS in patients who had cXRT in the past.

The PARTNER 3 Bicuspid Registry forTranscatheter Aortic Valve Replacement in Low-Surgical-Risk Patients.

The study compared 1-year outcomes between transcatheter aortic valve replacement (TAVR) patientswith bicuspid aortic valve (BAV) morphology and clinically similar patients having tricuspid aortic valve (TAV) morphology. There are limited prospective data on TAVR using the SAPIEN 3 device in low-surgical-risk patientswithsevere, symptomatic aortic stenosis and bicuspid anatomy. Low-risk, severe aortic stenosis patients with BAV were candidates for the PARTNER 3 (Placement ofAorticTranscatheter Valves 3) (P3) bicuspid registry or the P3 bicuspid continued access protocol. Patients treated in these registries were pooled and propensity score matched to TAV patients from the P3 randomized TAVR trial. Outcomes were compared between groups. The primary endpoint was the 1-year composite rate of death, stroke, and cardiovascular rehospitalization. Of 320 total submitted BAV patients, 169 (53%) were treated, and most were Sievers type 1. Theremaining 151 patients were excluded caused by anatomic or clinical criteria. Propensity score matching with the P3 TAVR cohort (496 patients) yielded 148 pairs. There were no differences in baseline clinical characteristics; however, BAV patients had larger annuli and they experienced longer procedure duration. There was no difference in the primary endpoint between BAV and TAV (10.9% vs 10.2%; P = 0.80) or in the rates of the individual components (death: 0.7% vs 1.4%; P = 0.58; stroke: 2.1% vs 2.0%; P = 0.99; cardiovascular rehospitalization: 9.6% vs 9.5%; P= 0.96). Among highly select bicuspid aortic stenosis low-surgical-risk patients without extensive raphe or subannular calcification, TAVR with the SAPIEN 3 valve demonstrated similar outcomes to a matched cohort of patientswith tricuspid aortic stenosis.

Impact of Frailty and Prefrailty on Outcomes of Transcatheter or Surgical Aortic Valve Replacement.

Randomized trials have shown short- and mid-term benefits with transcatheter versus surgical aortic valve replacement (TAVR versus SAVR) for patients at intermediate or low-risk for surgery. Frailty and prefrailty could explain some of this benefit due to an impaired ability to recover fully from a major surgical procedure. We examined 2-year outcomes (survival and Kansas City Cardiomyopathy Questionnaire [KCCQ] scores) among patients at intermediate or low surgical risk treated with transfemoral-TAVR or SAVR within the PARTNER (Placement of Aortic Transcatheter Valves) 2A trial, SAPIEN 3 intermediate-risk registry, and PARTNER 3 trial. Frailty was examined as a continuous variable based on grip strength, gait speed, serum albumin, and activities of daily living. We tested the interaction of frailty markers by treatment (TAVR versus SAVR) in proportional hazards regression models (survival) and piecewise linear regression models (KCCQ), adjusting for patient demographic and clinical factors. Among the 3025 patients in the analytic cohort (2003 TAVR, 1022 SAVR; mean age 79.3 years, 61.6% men), 799 (26.4%) were nonfrail, 2041 (67.5%) were prefrail (1-2 frailty markers), and 185 (6.1%) were frail (3-4 frailty markers). Increasing frailty (none versus prefrail versus frail) was associated with higher 2-year mortality (5.5% versus 11.1% versus 22.8%; log-rank P<0.001) and worse 2-year health status among survivors (KCCQ scores adjusted for baseline: 84.8 versus 79.6 versus 77.4, P<0.001). In multivariable models, there were no significant interactions between frailty markers and treatment group for either survival (interaction P=0.39) or health status (interaction P>0.47 for all time points). In a cohort of older patients with severe aortic stenosis who were at low or intermediate surgical risk, increasing frailty markers were associated with worse 2-year mortality and greater health status impairment after either TAVR or SAVR, but there were no significant interactions between type of valve replacement and frailty with respect to either outcome.