Mishell, Jacob M.

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.

Introduction: The relationship between aortic stenosis (AS) severity, AS-related symptoms, and clinical outcomes is poorly understood. Research Question: Does a history of AS-related symptoms at the time of diagnosis affect clinical outcomes including death and AS-related hospitalization? Methods: Using a combination of natural language processing algorithms and administrative codes, we ascertained physician-assessed AS, AS severity, and AS-related symptoms (chest pain, acute coronary syndrome, syncope, presyncope, orthopnea, dyspnea, PND, and worsening heart failure) in the year prior or up to 60 days after an initial AS diagnosis among 602,821 adults with echocardiograms in a large, integrated health system from 2010-2019. We examined multivariable associations between AS severity and recent AS-related symptoms for the outcomes of death and AS-related hospitalizations using Cox models. Results: Among 40,333 patients identified with incident AS, the majority had recent AS-related symptoms (mild: 80%, mild-moderate: 77%, moderate: 77%, moderate-severe: 85%, and severe AS: 87%). Patients with recent symptoms were older (mean [SD] age 78 [10] vs 75 [11] years; p<0.01), more likely female (51% vs 47%; p<0.01), and had a higher comorbidity burden. In unadjusted analyses, symptom status was a strong discriminator of risk over a median (IQR) of 2.2 (0.8-4.3) years of follow-up ( Figure ). After multivariable adjustment, AS-related symptoms remained strongly associated with death and AS-related hospitalization across the spectrum of AS severity, with moderate symptomatic patients having risk similar to severe asymptomatic patients. Conclusions: The majority of patients diagnosed with AS have recent and/or active AS-related symptoms, which is associated with a significantly increased risk of adverse outcomes. Incorporating symptom status across the individual grades of AS may improve risk stratification beyond AS severity alone.

Background: In the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation), among 614 patients with heart failure with 3+ or 4+ secondary mitral regurgitation (MR), transcatheter mitral valve repair (TMVr) with the MitraClip reduced MR, heart failure hospitalizations, and mortality and improved quality of life compared with guideline-directed medical therapy (GDMT) alone. We aimed to examine the prognostic relationship between MR reduction and outcomes after TMVr and GDMT alone. Methods: Outcomes in COAPT between 30 days and 2 years were examined on the basis of the severity of residual MR at 30 days. Results: TMVr-treated patients had less severe residual MR at 30 days than GDMT-treated patients (0/1+, 2+, and 3+/4+: 72.9%, 19.9%, and 7.2% versus 8.2%, 26.1%, and 65.8%, respectively [ P <0.0001]). The rate of composite death or heart failure hospitalizations between 30 days and 2 years was lower in patients with 30-day residual MR of 0/1+ and 2+ compared with patients with 30-day residual MR of 3+/4+ (37.7% versus 49.5% versus 72.2%, respectively [ P <0.0001]). This relationship was consistent in the TMVr and GDMT arms ( P interaction =0.92). The improvement in Kansas City Cardiomyopathy Questionnaire score from baseline to 30 days was maintained between 30 days and 2 years in patients with 30-day MR ≤2+ but deteriorated in those with 30-day MR 3+/4+ (–0.3±1.7 versus –9.4±4.6 [ P =0.0008]) consistently in both groups ( P interaction =0.95). Conclusions: In the COAPT trial, reduced MR at 30 days was associated with greater freedom from death or heart failure hospitalizations and improved quality of life through 2-year follow-up whether the MR reduction was achieved by TMVr or GDMT. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01626079.