Makkar, Raj

BACKGROUND: The EARLY TAVR trial (Evaluation of TAVR Compared to Surveillance for Patients with Asymptomatic Severe Aortic Stenosis) demonstrated that early transcatheter aortic valve replacement (TAVR) was superior to clinical surveillance (CS) in asymptomatic severe aortic stenosis. The relative impact of early TAVR versus CS strategy by age is unknown. METHODS: The study population of the EARLY TAVR trial was stratified into 4 age groups: 65 to 69 years (n=141), 70 to 74 years (n=263), 75 to 79 years (n=250), and ≥80 years (n=247). Associations between age and the trial primary end point of death, stroke, or unplanned cardiovascular hospitalization; the composite end point of death, stroke, or heart failure hospitalization; and its individual components were examined. Interaction tests evaluated whether the treatment effect of early TAVR versus CS differed by age. RESULTS: No interaction was detected between age and the treatment effect of early TAVR versus CS for the composites or individual outcomes. We observed lower stroke rates with early TAVR compared with CS in the youngest (65–69 years, absolute risk reduction, 13%; P =0.008) and oldest (≥80 years; absolute risk reduction, 12.3%; P =0.029) age groups. The absolute difference in heart failure hospitalization rates between the early TAVR and CS arms at 2 years was greatest in the oldest patients (≥80 years, 9.1%; 75–79 years, 5.9%; 70–74 years, 5.1%; 65–69 years, 4.4%). In the CS group, time to conversion to AVR was similar across all age groups (median, 11 months; P =0.73). Approximately one-third of younger patients (65–69 years) in the CS arm presented with acute valve syndrome at the time of conversion, the frequency of which tended to increase with age ( P =0.06). CONCLUSIONS: In the EARLY TAVR trial, the relative benefit of early TAVR over CS was consistent among all age groups. The greatest absolute reduction in stroke rate with early TAVR compared with CS appeared in the youngest and oldest groups, whereas reduction in heart failure hospitalization was most pronounced in the oldest patients. These data suggest that early TAVR should be considered in all age groups above 65 years. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03042104.

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.

Importance Transcatheter tricuspid valve replacement (TTVR) demonstrated superior outcomes over medical therapy in patients with severe tricuspid regurgitation (TR) in the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device II (TRISCEND II) randomized clinical trial, and received regulatory approval in the US in 2024. Contemporary real-world data on its effectiveness and safety remain limited. Objective To evaluate 30-day clinical, echocardiographic, and health status outcomes of TTVR in real-world use. Design, Setting, and Population Retrospective cohort study of all consecutive patients who underwent TTVR in the US from February 2024 through March 2025 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients had symptomatic, severe TR despite optimal medical therapy and TTVR was deemed appropriate by a heart team. Statistical analysis was conducted from September 2025 to February 2026. Exposure Device-enabled TTVR. Main Outcomes and Measures Thirty-day event rates (all-cause death, stroke, bleeding, new cardiac implantable electronic device [CIED] implantation, heart failure hospitalizations), TR reduction, and changes in health status (New York Heart Association [NYHA] functional class and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) are reported. Subgroup analyses examined the impact of baseline CIED status on outcomes. Results Among 1034 attempted procedures at 82 centers (mean [SD] age, 77.1 [10.6] years; 69.1% female; 73.2% NYHA functional class III/IV), a valve was successfully implanted in 1017 patients (98.4%). Mild or less TR was achieved in 98.4% of patients post procedure and in 97.7% at 30 days. At 30 days, all-cause mortality was 3.1%; stroke, 0.2%; bleeding, 7.9%; new CIED, 15.9% in CIED-naive patients; and heart failure hospitalization, 3.1%. There were significant improvements in NYHA functional class (class I/II, 82.7%; P < .001) and mean KCCQ-OS score (22.4 points; P < .001) from baseline to 30 days. There were no significant differences in 30-day mortality ( P = .47), heart failure hospitalization ( P > .99), and functional outcomes ( P = .55) when patients were stratified by baseline CIED status. Conclusions and Relevance Early US real-world experience with TTVR confirms safety and effectiveness in patients with severe TR. Thirty-day outcomes are consistent with the TRISCEND II pivotal trial, demonstrating acceptable safety, near-complete TR elimination, and significant health status improvements in an older, comorbid population. Rates of new CIED implantation and bleeding were lower than randomized clinical trial experience.

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.

ABSTRACTBackgroundComparisons of outcomes after transcatheter aortic valve replacement with balloon‐expandable (BEV) versus self‐expanding (SEV) valves are limited.HypothesisThis study aimed to compare clinical and hemodynamic outcomes of BEV and SEV at short‐term (30 days), midterm (1 year), and long‐term (> 1 year) endpoints.MethodsPubMed, Embase, Scopus, and Cochrane Library databases were searched until July 2024 for randomized controlled trials. Random‐effect model (DerSimonian–Laird method) was used to pool the risk ratios (RR), mean differences, and 95% confidence intervals (CI).ResultsA total of 10 studies comprising 4325 patients (2295 BEV, 2030 SEV) were included. In short‐term, cardiovascular (RR: 0.56, 95% CI: 0.36–0.87) and all‐cause mortality (RR: 0.54, 95% CI: 0.35–0.81) were lower in the BEV group. Risk of moderate to severe paravalvular leak (PVL) was lower among BEV patients in short‐term (RR: 0.28, 95% CI: 0.17–0.49) and long‐term (RR: 0.28, 95% CI: 0.1–0.79). A limited number of studies showed a greater risk of clinical valve thrombosis on BEV in midterm and long‐term. The need for permanent pacemaker implantation was lower in BEV at both short‐term (RR: 0.56, 95% CI: 0.37–0.87), and midterm (RR: 0.78, 95% CI: 0.64–0.94). The SEV group had a larger effective orifice area with lower mean transvalvular pressure gradient at all endpoints.ConclusionsBEV is associated with reduced risk of clinical outcomes in short‐term; however, most differences diminish in longer evaluations, except for moderate to severe PVL, which remains elevated for SEV. SEVs had better hemodynamic results and lower risk of clinical valve thrombosis.

Abstract Worldwide, valvular heart disease (VHD) is a common cause of hospitalization for acute heart failure. In acute heart failure caused by VHD, symptoms result from rapid haemodynamic changes and subsequent decline in cardiac function, and if left untreated, leads to acute decompensation and cardiogenic shock. Current evidence remains scarce and recommendations regarding the management of acute heart failure caused by VHD are lacking in most recent international guidelines. Herein, we review the management of acute heart failure caused by VHD with a focus on transcatheter therapies and describe currently available evidence based on a systematic literature search on the following valve pathologies: (i) aortic stenosis, (ii) aortic regurgitation, (iii) mitral regurgitation, and (iv) mitral stenosis. Articles reporting outcomes following urgent or emergent valve intervention in the setting of cardiogenic shock or acute heart failure were considered. After screening a total of 2234 articles, 76 published between 1994 and 2023 were included in subsequent analysis. Based on available evidence, proposed treatment algorithms to guide optimal management of acute heart failure caused by VHD were created. As the number of patients presenting with acute heart failure caused by VHD continues to rise and outcomes following transcatheter valve interventions continue to improve, it is inevitable that minimally invasive options will play an increasingly important role in the acute setting, especially given these patients are at an increased operative risk. This review aims to present an organized approach to the complex management and interventional treatment of patients with acute heart failure caused by VHD.

Background: The research on the outcomes of transcatheter aortic valve replacement with balloon-expandable valves (BEV) and self-expanding valves (SEV) are limited. Hypothesis: This study aims to compare the clinical and hemodynamic outcomes of BEV and SEV at short-term (30 days), mid-term (1 year), and long-term (>1 year) endpoints. Methods: PubMed, Embase, Scopus, and Cochrane Library databases were searched up to April 25, 2024, for randomized controlled trials (RCTs). Random-effect model (DerSimonian–Laird method) was used to pool the risk ratios (RR), mean differences (MD) and 95% confidence interval (CI) for binary and continuous outcomes, respectively. Results: A total of 11 RCTs comprising 4,325 patients (2,295 BEV, 2,030 SEV) were included. At short-term, the risk of cardiovascular (RR: 0.56, 95% CI: 0.36-0.87) and all-cause mortality (RR: 0.54, 95% CI: 0.35-0.81) were lower in the BEV group. However, no differences were noted between the two treatment modalities in longer follow-ups despite the lower risk of moderate to severe paravalvular leak (PVL) among BEV patients. The risk of stroke was comparable between two groups across all three follow-up endpoints, albeit a limited number of studies suggesting the BEV group showed a greater risk of clinical valve thrombosis in mid-term and long-term assessments. The need for permanent pacemaker implantation was lower in BEV arm in short-term (RR: 0.56, 95% CI: 0.37-0.87) and mid-term (RR: 0.78, 95% CI: 0.64-0.94). Yet, this difference was not observed in long-term follow-ups. Conversely, the SEV group had a larger effective orifice area with lower mean transvalvular pressure gradient from short-term (MD: 0.17, 95% CI: 0.07-0.26 and MD: 3.71, 95% CI: 2.64-4.78, respectively) to long-term (MD: 0.25, 95% CI: 0.17-0.32 and MD: 3.73, 95% CI: 3.19-4.27, respectively) periods. Conclusions: BEV is associated with reduced risk of clinical outcomes at short-term; however, most differences diminish in longer evaluations, except for moderate to severe PVL. Conversely, SEV is linked to better hemodynamic outcomes and a lower risk of clinical valve thrombosis across all follow-up durations.

BACKGROUND: Previous transcatheter valve therapy registry analyses of transcatheter mitral valve in valve (MViV) replacement of degenerated bioprosthesis reported early experience in the United States. Given recent increases in transseptal MViV volumes and introduction of the SAPIEN 3 Ultra valve, it is important to determine contemporary outcomes for patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV replacement. METHODS: The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry was used to extract data for all patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV from 2015 to September 2022. Primary efficacy outcome was 1-year all-cause mortality. Secondary end points included 30-day mortality, functional class, quality of life, and mitral valve performance. Primary safety outcomes were device success and in-hospital complications. RESULTS: A total of 4243 patients with a mean±SD STS score of 9.2±7.7 underwent transseptal MViV at 455 sites. The rate of Mitral Valve Academic Research Consortium technical (96.6%) success was high, and procedural complications were low. All-cause in-hospital, 30-day, and 1-year mortality rates were 3.2%, 4.3%, and 13.4%, respectively. Significant improvements in New York Heart Association class (New York Heart Association I/II, 18% to 87%) and quality of life (Kansas City Cardiomyopathy Questionnaire score, 38 to 78) were noted at 1 year ( P <0.0001 for both) after MViV. Upon stratifying by STS scores, it was observed that the low-risk group (STS<4) had a significantly lower in-hospital mortality rate of 0.4%, whereas the intermediate-risk group (STS, 4–8) had an in-hospital mortality rate of 1.9%. From 2015 to 2022, the number of transseptal MViV cases/year increased significantly, whereas procedure times, length of stay, and intensive care unit hours shortened significantly. At the same time, there was a significant trend toward reduced in-hospital ( P =0.0005), 30-day ( P =0.004), and 1-year mortality rates ( P =0.01). CONCLUSIONS: This multicenter, prospective study reports excellent procedural outcomes, acceptable 1-year mortality rates, and a significant improvement in quality of life for patients undergoing transseptal MViV in the contemporary era. Patients in the low-risk and intermediate-risk STS score categories had significantly better outcomes compared with those in the high-risk category. MViV is a reasonable therapy for the majority of patients with degenerated bioprosthetic mitral valves, who are anatomical candidates.

Background: Left ventricular (LV) mass regression after aortic valve replacement (AVR) for aortic stenosis (AS) is a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. We examined the effect on clinical outcomes after transcatheter AVR (TAVR) of: 1) amount of LV mass index (LVMi) regression; and 2) persistent severe LV hypertrophy (LVH). Methods: Of 2115 patients with symptomatic AS at high surgical risk receiving TAVR in the PARTNER randomized trial or continued access registry, 462 (55% women) who had severe LVH (LVMi ≥149 g/m 2 men, ≥122 g/m 2 women, by ASE criteria) at baseline (BL) and LVMi measured 6 mo post-TAVR were included in our analysis. The effect of LVMi regression was evaluated by comparing outcomes in patients with greater vs. lesser decrease (dichotomized by median % change) in LVMi between BL and 6 mo, and in those without vs. with persistent severe LVH 6 mo post-TAVR. Cox PH models evaluated rates of all-cause mortality (6-12 mo), rehospitalizations (through 1 yr), and the composite of these two outcomes. Results: LVMi decreased from 173±32 (BL) to 121±25 g/m 2 (6 mo) (p<0.001) in those with greater LVMi regression, and from 164±30 (BL) to 158±34 g/m 2 (6 mo) (p<0.001) in those with lesser LVMi regression. Patients with greater vs. lesser LVMi regression had similar baseline clinical characteristics, a lower rate of rehospitalization (10.5% vs. 19.9%, p=0.006) and lower rate of the composite endpoint of death or rehospitalization (13.2% vs. 21.4%, p=0.02), but a similar rate of death (4.9% vs. 4.8%, p=0.86). Persistent severe LVH at 6 mo post-TAVR was present in 54% (58% of whom were women). Patients without vs. with persistent severe LVH had similar baseline clinical characteristics, a lower rate of rehospitalization (11.9% vs. 18.1%, p=0.053) and lower rate of the composite endpoint of death or rehospitalization (13.3% vs. 20.7%, p=0.03), but a similar rate of death (3.9% vs. 5.7%, p=0.42). Similar results were obtained when including patients with moderate or severe LVH. Conclusions: In high-risk patients with severe AS and severe LVH undergoing TAVR, greater LV mass regression and resolution of initially severe LVH at 6 months are associated with a lower rate of death or repeat hospitalization.