Mack, Michael J.

Importance Sex-related disparities affect diagnosis, referral, and prognosis of aortic valvular diseases. Contemporary US data on transcatheter aortic valve implantation (TAVI) by sex are limited. Objective To characterize 10-year trends in TAVI use, periprocedural complications, and long-term outcomes among Medicare beneficiaries, stratified by sex. Design, Setting, and Participants This nationwide, retrospective, population-based cohort study used US Medicare claims data from fee-for-service beneficiaries discharged after TAVI from January 1, 2013, to December 31, 2022. The median follow-up time was 2.19 (IQR, 0.94-3.79) years. Exclusions included patients who had concomitant valve surgery, infective endocarditis, valve-in-valve TAVI, transapical TAVI, TAVI for pure aortic insufficiency, or later conversion to Medicare Advantage. Analyses were conducted between October 1, 2024, and April 1, 2025. Exposure TAVI. Main Outcomes and Measures The primary outcome was all-cause mortality. Secondary outcomes included periprocedural mortality, vascular complications, acute kidney injury, major or life-threatening bleeding, stroke, acute myocardial infarction (AMI), permanent pacemaker implantation (PPI), and hospitalization for heart failure (HF). Adjusted odds ratios (AORs) and hazard ratios (AHRs) with 95% CIs were estimated. Results The study included 314 123 patients (141 233 women [45.0%] and 172 890 men [55.0%]). Women were older than men (mean [SD] age, female: 80.3 [7.8] years; male: 79.4 [7.7] years; standardized mean difference, 12%). The proportion of female patients who underwent TAVI declined from 47.6% in 2013 to 43.6% in 2022 ( P < .001). Compared with men, women had higher periprocedural mortality (2.5% vs 2.2%; AOR, 1.20 [95% CI, 1.14-1.26]), vascular complications (5.8% vs 3.6%; AOR, 1.65 [95% CI, 1.60-1.71]), and bleeding (10.4% vs 6.8%; AOR, 1.67 [95% CI, 1.62-1.71]) but less PPI (16.9% vs 20.0%; AOR, 0.81 [95% CI, 0.79-0.82]). Long-term mortality was lower in female patients (AHR, 0.92; 95% CI, 0.91-0.93), although their risks of HF hospitalization, AMI, stroke, and bleeding were higher. Conclusions and Relevance Among Medicare beneficiaries, women constituted a progressively declining proportion of patients treated with TAVI, experienced more periprocedural complications, and demonstrated modestly better long-term survival compared with men. Further work is needed to understand factors influencing these trends and to refine sex-specific strategies for optimal outcomes.

Abstract Background and Aims The TRISCEND II trial demonstrated superior clinical benefits for patients with ≥severe tricuspid regurgitation (TR) treated with the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy vs medical therapy alone. This work reports 1-year and 18-month outcomes in patients stratified by baseline TR severity. Methods The multicentre, prospective TRISCEND II trial enrolled 400 patients with symptomatic, ≥severe TR, and randomized 2:1 to TTVR (n = 267) or control (n = 133). In a post hoc analysis, patients were stratified into severe TR (n = 172) and massive/torrential TR (n = 220) cohorts. Clinical and quality-of-life outcomes were reported at 1 year, with Kaplan–Meier estimates for all-cause mortality and heart failure (HF) hospitalization assessed at 18 months. Study oversight included an independent echocardiographic core laboratory, clinical events committee, and data safety monitoring board. Results One year after TTVR, TR was ≤mild in 95.2% of severe TR and 95.3% of massive/torrential TR patients. The primary safety and effectiveness endpoint (win ratio) favoured TTVR over control regardless of baseline TR severity: severe {1.64 [95% confidence interval (CI): 1.11, 2.43]} and massive/torrential [2.20 (1.55, 3.14)]. At 18 months, TTVR patients had similar mortality to controls [rate difference: severe 0.2% (−11.6, 11.9), massive/torrential −5.8% (−17.6, 6.0)], whereas HF hospitalization rates favoured TTVR in the massive/torrential cohort [vs control, severe 9.8% (−3.0, 22.7), massive/torrential -15.2% (−28.9, −1.5)]. Conclusions Patients with ≥severe TR benefit from TTVR, experiencing improvements in TR severity, functional capacity, and quality of life regardless of baseline TR severity, with a signal for greater benefit in patients with more advanced disease.

BACKGROUND: Transcatheter mitral valve-in-valve replacement offers a less-invasive alternative for high-risk patients with bioprosthetic valve failure. Limited experience exists in intermediate-risk patients. We aim to evaluate 1-year outcomes of the PARTNER 3 mitral valve-in-valve study. METHODS: This prospective, single-arm, multicenter study enrolled symptomatic patients with a failing mitral bioprosthesis demonstrating greater than or equal to moderate stenosis and regurgitation and Society of Thoracic Surgeons score ≥3% and <8%. A balloon-expandable transcatheter heart valve (SAPIEN 3, Edwards Lifesciences) was used via a transeptal approach. The primary end point was the composite of all-cause mortality and stroke at 1 year. RESULTS: A total of 50 patients from 12 sites underwent mitral valve-in-valve from 2018 to 2021. The mean age was 70.1±9.7 years, mean Society of Thoracic Surgeons score was 4.1%±1.6%, and 54% were female. There were no primary end point events (mortality or stroke) through 1 year, and no left-ventricular outflow tract obstruction, endocarditis, or mitral valve reintervention was reported. Six patients (12%) required rehospitalization, including heart failure (n=2), minor procedural side effects (n=2), and valve thrombosis (n=2; both resolved with anticoagulation). An additional valve thrombosis was associated with no significant clinical sequelae. From baseline to 1 year, all subjects with available data had none/trace or mild (grade 1+) mitral regurgitation and the New York Heart Association class improved in 87.2% (41/47) of patients. CONCLUSIONS: Mitral valve-in-valve with a balloon-expandable valve via transseptal approach in intermediate-risk patients was associated with improved symptoms and quality of life, adequate transcatheter valve performance, and no mortality or stroke at 1-year follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03193801.

Background Recently, machine learning algorithms have identified preprocedural γ‐glutamyl transferase (GGT) as a significant predictor of long‐term mortality after coronary revascularization in the SYNTAX (Synergy Between PCI [Percutaneous Coronary Intervention] With Taxus and Cardiac Surgery) trial. The aim of the present study is to investigate the impact of preprocedural GGT on 10‐year all‐cause mortality in patients with complex coronary artery disease after revascularization. Methods and Results The SYNTAX trial was a randomized trial comparing PCI with coronary artery bypass grafting in 1800 patients with complex coronary artery disease. The present report is a post hoc subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) trial, an investigator‐driven extended 10‐year follow‐up of the SYNTAX trial. The association between preprocedural GGT and 10‐year all‐cause mortality was investigated. The mean values of GGT for men and women were 43.5 (SD, 48.5) and 36.4 (SD, 46.1) U/L, respectively. In multivariable Cox regression models adjusted by traditional risk factors, GGT was an independent predictor for all‐cause death at 10‐year follow‐up, and each SD increase in log‐GGT was associated with a 1.24‐fold risk of all cause death at 10‐year follow‐up (95% CI, 1.10–1.40). According to previously reported sex‐related GGT thresholds, patients with higher GGT level had a 1.74‐fold risk of all‐cause death at 10‐year follow‐up (95% CI, 1.32–2.29) compared with patients with lower GGT level. Conclusions Preprocedural GGT is an independent predictor of 10‐year mortality after coronary revascularization in patients with complex coronary artery disease. In patients with elevated GGT, strong secondary prevention may be required after revascularization and must be studied prospectively. Registration URL: https://clinicaltrials.gov/study/NCT03417050 .

Background: Clinical and anatomical characteristics are often considered key factors in deciding between percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD) such as left-main CAD or 3-vessel disease. However, little is known about the interaction between self-reported preprocedural physical/mental health and clinical outcomes after revascularization. Methods: This subgroup analysis of the SYNTAXES trial (SYNTAX Extended Survival), which is the extended follow-up of the randomized SYNTAX trial (Synergy Between PCI With Taxus and Cardiac Surgery) comparing PCI with CABG in patients with left-main CAD or 3-vessel disease, stratified patients by terciles of Physical (PCS) or Mental Component Summary (MCS) scores derived from the preprocedural 36-Item Short Form Health Survey, with higher PCS and MCS scores representing better physical and mental health, respectively. The primary end point was all-cause death at 10 years. Results: A total of 1656 patients with preprocedural 36-Item Short Form Health Survey data were included in the present study. Both higher PCS and MCS were independently associated with lower 10-year mortality (10-point increase in PCS adjusted hazard ratio, 0.84 [95% CI, 0.73–0.97]; P =0.021; in MCS adjusted hazard ratio, 0.85 [95% CI, 0.76–0.95]; P =0.005). A significant survival benefit with CABG over PCI was observed in the highest PCS (>45.5) and MCS (>52.3) terciles with significant treatment-by-subgroup interactions (PCS P interaction =0.033, MCS P interaction =0.015). In patients with both high PCS (>45.5) and MCS (>52.3), 10-year mortality was significantly higher with PCI compared with CABG (30.5% versus 12.2%; hazard ratio, 2.87 [95% CI, 1.55–5.30]; P =0.001), whereas among those with low PCS (≤45.5) or low MCS (≤52.3), there were no significant differences in 10-year mortality between PCI and CABG, resulting in a significant treatment-by-subgroup interaction ( P interaction =0.002). Conclusions: Among patients with left-main CAD or 3-vessel disease, patient-reported preprocedural physical and mental health status was strongly associated with long-term mortality and modified the relative treatment effects of PCI versus CABG. Patients with the best physical and mental health had better 10-year survival with CABG compared with PCI. Assessment of self-reported physical and mental health is important when selecting the optimal revascularization strategy. Registration: URL: https://www.clinicaltrials.gov ; SYNTAXES Unique identifier: NCT03417050. URL: https://www.clinicaltrials.gov ; SYNTAX Unique identifier: NCT00114972.

Abstract Background Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with higher rates of adverse events, and currently it is unclear whether PCI or coronary artery bypass grafting (CABG) is the safer treatment for these patients at very long-term follow up. Objectives To investigate the impact of bifurcation lesions on observed all-cause 10-year mortality in the SYNTAX trial. Methods In the SYNTAX Extended Survival study, 10-year observed mortality was compared among four groups: (a) presence of ≥1 bifurcation lesion and treatment with PCI (n=649), (b) no bifurcation lesion and treatment with PCI (n=248), (c) presence of ≥1 bifurcation lesion and treatment with CABG (n=651), and (d) no bifurcation lesion and treatment with CABG (n=239). Results Compared to patients without bifurcations, those with bifurcation lesion(s) treated with PCI had a significantly higher risk of all-cause death (19.8% vs 30.1%; HR: 1.55, 95% CI: 1.12 to 2.14; p=0.007), whereas following CABG, mortality was similar in patients with or without bifurcation lesion(s) (23.3% vs 23.0%; HR: 0.81, 95% CI: 0.59 to 1.12; p=0.207). (Figure1) There was a significant interaction between bifurcation lesion(s) and treatment arm (p for interaction=0.006). In PCI patients, at 5-years there was no significant difference in mortality between 1- vs 2-stent techniques, whereas at 10-years, a 2-stent technique was associated with higher mortality (33.3% vs 25.9%; HR: 1.51, 95% CI: 1.06 to 2.14; p=0.021, Figure2). Conclusions Bifurcation lesion(s) require special attention from the heart team discussion, considering the higher 10-year all-cause mortality associated with PCI. Careful evaluation of bifurcation lesion complexity may be helpful in decision-making. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research (Frankfurt am Main, Germany). The SYNTAX trial, during 0-5 years follow-up, was funded by Boston Scientific Corporation (Marlborough, MA, USA). Both sponsors had no role in the study design, data collection, data analyses, and interpretation of the study data, nor were involved in the decision to publish the final manuscript. The principal investigators and authors had complete scientific freedom.

Abstract Aims The aim of this study was to investigate the impact on 10-year survival of patient-reported anginal status at 1 year following percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in patients with left main coronary artery disease (LMCAD) and/or three-vessel CAD (3VD). Methods and results In this post hoc analysis of the randomized SYNTAX Extended Survival study, patients were classified as having residual angina (RA) if their self-reported Seattle Angina Questionnaire angina frequency (SAQ-AF) scale was ≤90 at the 1-year follow-up post-revascularization with PCI or CABG. The primary endpoint of all-cause death at 10 years was compared between the RA and no-RA groups. A sensitivity analysis was performed using a 6-month SAQ-AF. At 1 year, 373 (26.1%) out of 1428 patients reported RA. Whilst RA at 1 year was an independent correlate of repeat revascularization at 5 years [18.3 vs. 11.5%; adjusted hazard ratio (HR): 1.54; 95% confidence interval (CI): 1.10–2.15], it was not associated with all-cause death at 10 years (22.1 vs. 21.6%; adjusted HR: 1.11; 95% CI: 0.83–1.47). These results were consistent when stratified by the modality of revascularization (PCI or CABG) or by anginal frequency. The sensitivity analysis replicating the analyses based on 6-month angina status resulted in similar findings. Conclusion Among patients with LMCAD and/or 3VD, patient-reported RA at 1 year post-revascularization was independently associated with repeat revascularization at 5 years; however, it did not significantly increase 10-year mortality, irrespective of the primary modality of revascularization or severity of RA.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Objective We sought to investigate whether long-term clinical outcomes differ following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with three-vessel disease (3VD) and lesions in the proximal left anterior descending artery (P-LAD). Methods This post-hoc analysis of the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) Extended Survival study included patients with 3VD who were classified according to the presence or absence of lesions located in the P-LAD. Ten-year all-cause death and 5-year major adverse cardiac or cerebrovascular events (MACCE) were assessed. Results Among 1088 patients with 3VD, 559 (51.4%) had involvement of P-LAD and their 10-year mortality was numerically higher following PCI versus CABG (28.9% vs 21.9%; HR: 1.39, 95% CI 0.99 to 1.95). Although patients without P-LAD lesions had significantly higher 10-year mortality following PCI compared with CABG, there was no evidence of a treatment-by-subgroup interaction (28.8% vs 20.2%; HR: 1.47, 95% CI 1.03 to 2.09, pinteraction=0.837). The incidence of MACCE at 5 years was significantly higher with PCI than CABG, irrespective of involvement of P-LAD (with P-LAD: HR: 1.86, 95% CI 1.36 to 2.55; without P-LAD: HR: 1.54, 95% CI 1.11 to 2.12; pinteraction=0.408). Individualised assessment using the SYNTAX Score II 2020 established that a quarter of patients with P-LAD lesions had significantly higher mortality with PCI than CABG, whereas in the remaining three-quarters CABG had similar mortality. Conclusions Among patients with 3VD, the presence or absence of a P-LAD lesion was not associated with any treatment effect on long-term outcomes following PCI or CABG. Trial registration number SYNTAXES: NCT03417050; SYNTAX: NCT00114972.