Cross-Validation of Risk Scores for Patients Undergoing Transcatheter Edge-to-Edge Repair for Mitral Regurgitation.

Background: Risk scores may identify patients with mitral regurgitation (MR) who are at risk for adverse events, but who may still benefit from transcatheter edge-to-edge repair (TEER). We sought to cross-validate the MitraScore and COAPT risk score to predict adverse events in patients undergoing TEER. Methods: MitraScore validation was carried out in the COAPT population which included 614 patients with FMR who were randomized 1:1 to guideline-directed medical therapy (GDMT) with or without TEER and were followed for 2 years. Validation of the COAPT risk score was carried out in 1007 patients from the MIVNUT registry of TEER-treated patients with both FMR and degenerative MR who were followed for a mean of 2.1 years. The predictive value was assessed using the area under the receiver operating characteristic curve (AUC) plots. The primary outcome was all-cause mortality. Results: The MitraScore had fair to good predictive accuracy for mortality in the overall COAPT trial population (AUC, 0.67); its accuracy was higher in patients treated with TEER (AUC, 0.74) than GDMT alone (AUC, 0.65). The COAPT risk score had fair predictive accuracy for death in the overall MitraScore cohort (AUC, 0.64), which was similar in patients with FMR and degenerative MR (AUC, 0.64 and 0.66, respectively). There was a consistent benefit of treatment with TEER plus GDMT compared with GDMT alone in the COAPT trial population across all MitraScore risk strata. Conclusions: The COAPT risk score and MitraScore are simple tools that are useful for the prediction of 2-year mortality in patients eligible for or undergoing treatment with TEER.

Changes in Left Ventricular Function and Outcomes After Trancatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

Background: Transcatheter edge-to-edge repair (TEER) improved outcomes in patients with heart failure (HF) and severe secondary mitral regurgitation (SMR) compared with guideline-directed medical therapy (GDMT) alone regardless of the severity of baseline left ventricular ejection fraction (LVEF). The study aimed to evaluate the effect of early changes in LVEF after TEER and GDMT alone in patients with HF and severe SMR. Methods: Within the COAPT trial, we evaluated outcomes according to changes in LVEF from baseline to 30 days. The primary outcome was all-cause death or HF hospitalization (HFH) between 30 days and 2 years. Results: Among 432 patients with paired echocardiographic data, 182 (42.1%) had increased LVEF (LVEF change 6.0% ± 4.9%) and 250 (57.9%) had a decrease or no change in LVEF (LVEF change -6.6% ± 5.6%) from baseline to 30 days. LVEF at 30 days increased more frequently with GDMT alone compared with TEER plus GDMT (51.4% vs 33.0%; P = .0001). Between 30 days and 2 years, there were no significant differences in death or HFH in the increase LVEF and the decrease LVEF groups (58.8% vs 51.4%; multivariable-adjusted HR, 0.97; 95% CI, 0.87-1.08; P = .59). TEER plus GDMT reduced the 30-day to 2-year rate of death or HFH compared with GDMT alone consistently in patients with increase LVEF and decrease LVEF (Pint = 0.75). Conclusions: Among patients with HF and severe SMR, early improvements in LVEF were more frequent with GDMT alone compared with TEER plus GDMT but were not associated with subsequent outcomes at 2 years. TEER reduced death or HFH during 2-year follow-up irrespective of early LVEF changes.

TRISCEND II: Novel Randomized Trial Design for Transcatheter Tricuspid Valve Replacement.

Severe tricuspid regurgitation remains largely undertreated given limited treatment options. Transcatheter tricuspid valve interventions have emerged as a promising therapy for these patients, and the TRISCEND II pivotal trial is the first randomized controlled trial to evaluate transcatheter tricuspid valve replacement (TTVR). The TRISCEND II pivotal trial studies the transcatheter EVOQUE (Edwards Lifesciences, Irvine, California) tricuspid valve replacement system using a United States Food and Drug Administration Breakthrough Device Designation-a program intended to provide timely access to medical devices by speeding up development, assessment, and review. The TRISCEND II trial is a prospective, multicenter trial that randomizes patients with symptomatic severe tricuspid regurgitation to treatment with either TTVR in conjunction with optimal medical therapy or optimal medical therapy alone. The trial's novel 2-phase design evaluates 30-day safety and 6-month effectiveness end points for the first 150 patients in the initial phase and a 1-year safety and effectiveness end point for the full cohort of 400 patients in the second phase. The TRISCEND II trial's 2-phase trial design provided an opportunity for early review and led to the first commercial approval of a TTVR system. In conclusion, the design of the TRISCEND II trial will likely inform future transcatheter tricuspid device trials.

Left Atrial Improvement in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial.

BACKGROUND: Functional mitral regurgitation induces adverse effects on the left ventricle and the left atrium. Left atrial (LA) dilatation and reduced LA strain are associated with poor outcomes in heart failure (HF). Transcatheter edge-to-edge repair (TEER) of the mitral valve reduces heart failure hospitalization (HFH) and all-cause death in selected HF patients. OBJECTIVES: The aim of this study was to evaluate the impact of LA strain improvement 6 months after TEER on the outcomes of patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. METHODS: The difference in LA strain between baseline and the 6-month follow-up was calculated. Patients with at least a 15% improvement in LA strain were labeled as "LA strain improvers." All-cause death and HFH were assessed between the 6 and 24-month follow-up. RESULTS: Among 347 patients (mean age 71 ± 12 years, 63% male), 106 (30.5%) showed improvement of LA strain at the 6-month follow-up (64 [60.4%] from the TEER + guideline-directed medical therapy [GDMT] group and 42 [39.6%] from the GDMT alone group). An improvement in LA strain was significantly associated with a reduction in the composite of death or HFH between the 6-month and 24-month follow-up, with a similar risk reduction in both treatment arms (Pinteraction = 0.27). In multivariable analyses, LA strain improvement remained independently associated with a lower risk of the primary composite endpoint both as a continuous variable (adjusted HR: 0.94 [95% CI: 0.89-1.00]; P = 0.03) and as a dichotomous variable (adjusted HR: 0.49 [95% CI: 0.27-0.89]; P = 0.02). The best outcomes were observed in patients treated with TEER in whom LA strain improved. CONCLUSIONS: In symptomatic HF patients with severe mitral regurgitation, improved LA strain at the 6-month follow-up is associated with subsequently lower rates of the composite endpoint of all-cause mortality or HFH, both after TEER and GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079).

Prevalence of Cardiovascular Disease and Risk Factors Among Former National Football League Players.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide, but prevalence estimates in former professional athletes are limited. OBJECTIVES: HUDDLE (Heart Health: Understanding and Diagnosing Disease by Leveraging Echocardiograms) aimed to raise awareness and estimate the prevalence of CVD and associated risk factors among members of the National Football League (NFL) Alumni Association and their families through education and screening events. METHODS: HUDDLE was a multicity, cross-sectional study of NFL alumni and family members aged 50 years and older. Subjects reported their health history and participated in CVD education and screening (blood pressure, electrocardiogram, and transthoracic echocardiogram [TTE] assessments). Phone follow-up by investigators occurred 30 days postscreening to review results and recommendations. This analysis focuses on former NFL athletes. RESULTS: Of 498 participants screened, 57.2% (N = 285) were former NFL players, the majority of whom were African American (67.6%). The prevalence of hypertension among NFL alumni was estimated to be 89.8%, though only 37.5% reported a history of hypertension. Of 285 evaluable participants, 61.8% had structural cardiac abnormalities by TTE. Multivariable analysis showed that hypertension was a significant predictor of clinically relevant structural abnormalities on TTE. CONCLUSIONS: HUDDLE identified a large discrepancy between participant self-awareness and actual prevalence of CVD and risk factors, highlighting a significant opportunity for population health interventions. Structural cardiac abnormalities were observed in most participants and were independently predicted by hypertension, affirming the role of TTE for CVD screening in this population aged older than 50 years. (Heart Health: Understanding and Diagnosing Disease by Leveraging Echocardiograms [HUDDLE]; NCT05009589).

Paradox of disproportionate atrial functional mitral regurgitation and survival after transcatheter edge-to-edge repair.

AIMS: This study aims to assess the applicability of the mitral regurgitation (MR) proportionality concept in patients with atrial functional mitral regurgitation (aFMR) treated with transcatheter edge-to-edge repair (M-TEER). We hypothesized that patients with disproportionate MR (higher MR relative to left ventricular size) would exhibit different outcomes compared to those with proportionate MR, despite undergoing M-TEER. METHODS AND RESULTS: We retrospectively analysed 98 patients with aFMR from the EuroSMR registry who underwent M-TEER between 2008 and 2019. Patients met criteria for aFMR (normal indexed left ventricular end-diastolic volume [LVEDV], preserved left ventricular ejection fraction [LVEF] ≥ 50% without regional wall motion abnormalities, and structurally normal mitral valves). We excluded patients with missing effective regurgitant orifice area (EROA) or LVEDV data. The primary endpoint was 2-year mortality, with an EROA/LVEDV ratio employed to differentiate disproportionate from proportionate MR. Procedural success and baseline characteristics were analysed, and multivariate Cox proportional hazards models were used to identify mortality predictors. The mean patient age was 79 ± 7.3 years, with 68.8% female, and 79% had a history of atrial fibrillation. The mean EROA was 0.27 ± 0.14 cm2, and LVEDV was 95.6 ± 33.7 mL. Disproportionate MR was identified with an EROA/LVEDV ratio >0.339 cm2/100 mL. While procedural success was similar in both groups, disproportionate MR was associated with a numerically higher estimate of systolic pulmonary artery pressures (sPAP) and rates of NYHA ≥III and TR ≥ 3+. Disproportionate MR had a significant association with increased 2-year mortality (P < 0.001). The EROA/LVEDV ratio and tricuspid annular plane systolic excursion (TAPSE) were independent predictors of 2-year mortality (EROA/LVEDV: HR: 1.35, P = 0.010; TAPSE: HR: 0.85, P = 0.020). CONCLUSIONS: This analysis introduces the MR proportionality concept in aFMR patients and its potential prognostic value. Paradoxically, disproportionate MR in aFMR was linked to a 1.35-fold increase in 2-year mortality post-M-TEER, emphasizing the importance of accurate preprocedural FMR characterization. Our findings in patients with disproportionate MR indicate that a high degree of aFMR with high regurgitant volumes may lead to aggravated symptoms, which is a known contributor to increased mortality following M-TEER. These results underline the need for further research into the pathophysiology of aFMR to inform potential preventative and therapeutic strategies, ensuring optimal patient outcomes.

Right Heart Remodeling and Outcomes in Patients With Tricuspid Regurgitation: A Literature Review and Meta-Analysis.

BACKGROUND: Functional tricuspid regurgitation (TR) can develop either because of right ventricular (RV) remodeling (ventricular functional TR) and/or right atrial dilation (atrial functional TR). OBJECTIVES: This meta-analysis aimed to investigate the association between right heart remodeling and long-term (>1 year) all-cause mortality in patients with significant TR (at least moderate, ≥2+). METHODS: MEDLINE, ISI Web of Science, and SCOPUS databases were searched. Studies reporting data on at least 1 RV functional parameter and long-term all-cause mortality in patients with significant TR were included. This study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements. RESULTS: Out of 8,902 studies, a total of 14 were included, enrolling 4,394 subjects. The duration of follow-up across the studies varied, ranging from a minimum of 15.5 months to a maximum of 73.2 months. Overall, long-term all-cause mortality was 31% (95% CI: 20%-41%; P ≤ 0.001). By means of meta-regression analyses, an inverse relation was found between tricuspid annular plane systolic excursion (11 studies enrolling 3,551 subjects, -6.3% [95% CI: -11.1% to -1.4%]; P = 0.011), RV fractional area change (9 studies, 2,975 subjects, -4.4% [95% CI: -5.9% to -2.9%]; P < 0.001), tricuspid annular dimension (7 studies, 2,986 subjects, -4.1% [95% CI: -7.6% to -0.5%]; P = 0.026), right atrial area (6 studies, 1,920 subjects, -1.9% [95% CI: -2.5% to -1.3%]; P < 0.001) and mortality. CONCLUSIONS: RV dysfunction parameters are associated to worse clinical outcomes in patients with TR, whereas right atrial dilatation is linked to a better prognostic outcome. Further studies are needed to unravel the pathophysiological differences within the functional TR spectrum. (Right heart remodeling and outcomes in patients with tricuspid regurgitation; CRD42023418667).

Comparison of Transcatheter Edge-to-Edge Mitral Valve Repair for Primary Mitral Regurgitation Outcomes to Hospital Volumes of Surgical Mitral Valve Repair.

BACKGROUND: Transcatheter edge-to-edge mitral valve (MV) repair (TEER) is an effective treatment for patients with primary mitral regurgitation at prohibitive risk for surgical MV repair (MVr). High-volume MVr centers and high-volume TEER centers have better outcomes than low-volume centers, respectively. However, whether MVr volume predicts TEER outcomes remains unknown. We hypothesized that high-volume MV surgical centers would have superior risk-adjusted outcomes for TEER than low-volume centers. METHODS: We combined data from the American College of Cardiology/Society of Thoracic Surgeons Transcatheter Valve Therapy registry and the Society of Thoracic Surgeons adult cardiac surgery database. MVr was defined as leaflet resection or artificial chords with or without annuloplasty and was evaluated as a continuous variable and as predefined categories (<25, 25-49, and ≥50 MV repairs/year). A generalized linear mixed model was used to evaluate risk-adjusted in-hospital/30-day mortality, 30-day heart failure readmission, and TEER success (mitral regurgitation ≤2+ and gradient <5 mm Hg). RESULTS: The study comprised 41 834 patients from 500 sites of which 332 (66.4%) were low, 102 (20.4%) intermediate, and 66 (13.2%) high-volume surgical centers (P<0.001). TEER success was 54.6% and was not statistically significantly different across MV surgical site volumes (P=0.4271). TEER mortality at 30 days was 3.5% with no significant difference across MVr volume on unadjusted (P=0.141) or adjusted (P=0.071) analysis of volume as a continuous variable. One-year mortality was 15.0% and was lower for higher MVr volume centers when adjusted for clinical and demographic variables (P=0.027). Heart failure readmission at 1 year was 9.4% and was statistically significantly lower in high-volume centers on both unadjusted (P=0.017) or adjusted (P=0.015) analysis. CONCLUSIONS: TEER can be safely performed in centers with low volumes of MV repair. However, 1-year mortality and heart failure readmission are superior at centers with higher MVr volume.

The Evolving Concept of Secondary Mitral Regurgitation Phenotypes: Lessons From the M-TEER Trials.

Conflicting results from 2 randomized clinical trials of transcatheter mitral valve edge-to-edge repair in secondary mitral regurgitation (SMR) have led to the recognition that SMR is a heterogeneous disease entity presenting with different functional and morphological phenotypes. This review summarizes the current knowledge on SMR caused primarily by atrial secondary mitral regurgitation (aSMR) and ventricular SMR pathology. Although aSMR is generally characterized by severe left atrial enlargement in the setting of preserved left ventricular anatomy and function, different patterns of mitral annular distortion cause different phenotypes of aSMR. In ventricular SMR, the relation of SMR severity to left ventricular dilation as well as the degree of pulmonary hypertension and right ventricular dysfunction are important phenotypic characteristics, which are key for a better understanding of prognosis and treatment response.

Tricuspid regurgitation burden following transcatheter aortic valve replacement requiring early pacemaker implantation.

Background: Conduction abnormality requiring the implantation of a permanent pacemaker (PPM) is a well-known and clinically important complication of transcatheter aortic valve replacement (TAVR). However, PPM implantation may result in lead-associated tricuspid valve regurgitation (TR). This study sought to determine the incidence and progression of TR following PPM implantation after TAVR. Methods: This was a retrospective review of all echocardiograms of patients who underwent PPM following TAVR at the Baylor Scott & White hospitals from 2012 to 2021. The primary endpoint was TR progression at 30 days and 1 year. A subanalysis comparing the change in TR progression between small and large TAVR devices was also conducted. Secondary outcomes included all-cause death at 30 days and 1 year. Results: Out of the 2744 patients who underwent TAVR between April 2012 and August 2021, 177 patients (6.5%) subsequently received a new PPM. There was a statistically significant progression of TR at 1-year follow-up (McNemar's P value = 0.02). TR progression rates were comparable between the small and large valve groups at 1-year follow-up (4% vs 11%, P = 0.09, respectively). Conclusion: In this single healthcare system study, we demonstrated a significant progression of TR in patients with PPM post TAVR at 1 year.

Guidelines for the Evaluation of Prosthetic Valve Function With Cardiovascular Imaging: A Report From the American Society of Echocardiography Developed in Collaboration With the Society for Cardiovascular Magnetic Resonance and the Society of Cardiovascular Computed Tomography.

In patients with significant cardiac valvular disease, intervention with either valve repair or valve replacement may be inevitable. Although valve repair is frequently performed, especially for mitral and tricuspid regurgitation, valve replacement remains common, particularly in adults. Diagnostic methods are often needed to assess the function of the prosthesis. Echocardiography is the first-line method for noninvasive evaluation of prosthetic valve function. The transthoracic approach is complemented with two-dimensional and three-dimensional transesophageal echocardiography for further refinement of valve morphology and function when needed. More recently, advances in computed tomography and cardiac magnetic resonance have enhanced their roles in evaluating valvular heart disease. This document offers a review of the echocardiographic techniques used and provides recommendations and general guidelines for evaluation of prosthetic valve function on the basis of the scientific literature and consensus of a panel of experts. This guideline discusses the role of advanced imaging with transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance in evaluating prosthetic valve structure, function, and regurgitation. It replaces the 2009 American Society of Echocardiography guideline on prosthetic valves and complements the 2019 guideline on the evaluation of valvular regurgitation after percutaneous valve repair or replacement.

Echocardiographic Outcomes With Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients.

BACKGROUND: The CLASP IID randomized trial (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial) demonstrated the safety and effectiveness of the PASCAL system for mitral transcatheter edge-to-edge repair (M-TEER) in patients at prohibitive surgical risk with significant symptomatic degenerative mitral regurgitation (DMR). OBJECTIVES: This study describes the echocardiographic methods and outcomes from the CLASP IID trial and analyzes baseline variables associated with residual mitral regurgitation (MR) ≤1+. METHODS: An independent echocardiographic core laboratory assessed echocardiographic parameters based on American Society of Echocardiography guidelines focusing on MR mechanism, severity, and feasibility of M-TEER. Factors associated with residual MR ≤1+ were identified using logistic regression. RESULTS: In 180 randomized patients, baseline echocardiographic parameters were well matched between the PASCAL (n = 117) and MitraClip (n = 63) groups, with flail leaflets present in 79.2% of patients. Baseline MR was 4+ in 76.4% and 3+ in 23.6% of patients. All patients achieved MR ≤2+ at discharge. The proportion of patients with MR ≤1+ was similar in both groups at discharge but diverged at 6 months, favoring PASCAL (83.7% vs 71.2%). Overall, patients with a smaller flail gap were significantly more likely to achieve MR ≤1+ at discharge (adjusted OR: 0.70; 95% CI: 0.50-0.99). Patients treated with PASCAL and those with a smaller flail gap were significantly more likely to sustain MR ≤1+ to 6 months (adjusted OR: 2.72 and 0.76; 95% CI: 1.08-6.89 and 0.60-0.98, respectively). CONCLUSIONS: The study used DMR-specific echocardiographic methodology for M-TEER reflecting current guidelines and advances in 3-dimensional echocardiography. Treatment with PASCAL and a smaller flail gap were significant factors in sustaining MR ≤1+ to 6 months. Results demonstrate that MR ≤1+ is an achievable benchmark for successful M-TEER. (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID]; NCT03706833).