Leon, Martin B.

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.

Importance Although the results of A Study to Evaluate the Corvia Medical Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF II) trial were neutral overall, atrial shunt therapy demonstrated potential efficacy in responders (no latent pulmonary vascular disease and no cardiac rhythm management device). Post hoc analyses were conducted to evaluate the effect of shunt vs sham stratified by responder status. Objective To evaluate the effect of atrial shunt vs sham control on cardiac structure/function in the overall study and stratified by responder status. Design, Setting, and Participants This was a sham-controlled randomized clinical trial of an atrial shunt device in heart failure with preserved ejection fraction (HFpEF)/HF with mildly reduced EF (HFmrEF). Trial participants with evaluable echocardiography scans were recruited from 89 international medical centers. Data were analyzed from April 2023 to January 2024. Interventions Atrial shunt device or sham control. Main Outcome Measures Changes in echocardiographic measures from baseline to 1, 6, 12, and 24 months after index procedure. Results The modified intention-to-treat analysis of the REDUCE LAP-HF II trial included 621 randomized patients (median [IQR] age, 72.0 [66.0-77.0] years; 382 female [61.5%]; shunt arm, 309 [49.8%]; sham control arm, 312 [50.2%]). Through 24 months, 212 of 217 patients (98%) in the shunt arm with evaluable echocardiograms had patent shunts. In the overall trial population, the shunt reduced left ventricular (LV) end-diastolic volume (mean difference, −5.65 mL; P &amp;lt;.001), left atrial (LA) minimal volume (mean difference, −2.8 mL; P =.01), and improved LV systolic tissue Doppler velocity (mean difference, 0.69 cm/s; P &amp;lt;.001) and LA emptying fraction (mean difference, 1.88 percentage units; P =.02) compared with sham. Shunt treatment also increased right ventricular (RV; mean difference, 9.58 mL; P &amp;lt;.001) and right atrial (RA; mean difference, 9.71 mL; P &amp;lt;.001) volumes but had no effect on RV systolic function, pulmonary artery pressure, or RA pressure compared with sham. In the shunt arm, responders had smaller increases in RV end-diastolic volume (mean difference, 5.71 mL vs 15.18 mL; interaction P =.01), RV end-systolic volume (mean difference, 1.58 mL vs 7.89 mL; interaction P =.002), and RV/LV ratio (mean difference, 0.07 vs 0.20; interaction P &amp;lt;.001) and larger increases in transmitral A wave velocity (mean difference, 5.08 cm/s vs −1.97 cm/s; interaction P =.02) compared with nonresponders randomized to the shunt, suggesting greater ability to accommodate shunted blood through the pulmonary circulation enabling LA unloading. Conclusions and Relevance In this post hoc analysis of the REDUCE LAP-HF II trial, over 2 years of follow-up, atrial shunting led to reverse remodeling of left-sided chambers and increases in volume of right-sided chambers consistent with the shunt flow but no change in RV systolic function compared with sham. Changes in cardiac structure/function were more favorable in responders compared with nonresponders treated with the shunt, supporting the previously identified responder group hypothesis and mechanism, although further evaluation with longer follow-up is needed. Trial Registration ClinicalTrials.gov Identifier: NCT03088033

Abstract Aims Obesity is causally related to the development of heart failure with preserved ejection fraction (HFpEF) but complicates the diagnosis and treatment of this disorder. We aimed to determine the relationship between severity of obesity and clinical, echocardiographic and haemodynamic parameters in a large cohort of patients with documented HFpEF. Methods and results The REDUCE LAP-HF II trial randomized 626 patients with ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg to atrial shunt or sham procedure. We tested for associations between body mass index (BMI), clinical characteristics, cardiac structural and functional abnormalities, physical limitations, quality of life and outcomes with atrial shunt therapy. Overall, 60.9% of patients had BMI ≥30 kg/m2. As the severity of obesity increased, symptoms (Kansas City Cardiomyopathy Questionnaire score) and 6-min walk distance worsened. More severe obesity was associated with lower natriuretic peptide levels despite more cardiac remodelling, higher cardiac filling pressures, and higher cardiac output. Lower cut points for E/e′ were needed to identify elevated PCWP in more obese patients. Strain measurements in all four chambers were maintained as BMI increased. Pulmonary vascular resistance at rest and exercise decreased with higher BMI. Obesity was associated with more first and recurrent heart failure events. However, there was no significant interaction between obesity and treatment effects of the atrial shunt. Conclusions Increasing severity of obesity was associated with greater cardiac remodelling, higher right and left ventricular filling pressures, higher cardiac output and increased subsequent heart failure events. Despite significant obesity, many HFpEF patients have preserved right heart and pulmonary vascular function and thus, may be appropriate candidates for atrial shunt therapy.

AbstractThe development of new technology to treat unmet clinical needs is an important component of modern cardiovascular disease. The need for this has been emphasized in the past several years beginning with the Food and Drug Administration (FDA) guidance document on Early Feasibility Studies in 2012 and then the 21st Century Cures legislation. A number of steps need to be considered in this process by the stakeholders involved including physician innovators and scientists, professional societies such as Society for Cardiovascular Angiography & Interventions, regulatory agencies, and medical device companies. This article focuses on the early iterative steps required to optimize the process and achieve the goal of timely efficient innovation and device development in cardiovascular disease.

Introduction: Transcatheter mitral valve replacement (TMVR) using aortic transcatheter heart valves (THV) is developing as an alternative to surgery for patients with severely degenerated mitral valve (MV) bioprostheses. Retrospective self-reported registries have collected outcomes on these TMVR procedures in the STS/ACC Transcatheter Valve Therapy Registry and in the Valve-in-Valve International Database. Most reported TMVR procedures for failed surgical bioprostheses have been performed using a transapical access approach. A prospective comprehensive evaluation of mitral Valve-in-Valve (VIV) outcomes, including transseptal access has not previously been conducted. Objectives: To evaluate in-hospital and 30-day clinical outcomes of transseptal mitral VIV with SAPIEN 3 THV in patients with very high surgical risk. Methods: Prospective enrollment of very high surgical risk patients with symptomatic severely degenerated MV surgical bioprostheses in 30 patients at 15 sites in the U.S. Candidates were assessed by a case review committee prior to approval. Baseline qualifying echocardiograms and cardiac CT studies were analyzed by independent core labs. Echocardiograms, cardiac CT studies and neurology evaluations were also performed after mitral VIV procedures. Clinical events were adjudicated by a clinical events committee and safety was monitored by a data safety monitoring board. Results: 26 patients have been enrolled between July 2016 and June 2017. Mean age was 83 years, 62% female, mean STS score was 10% and 62% were in New York Heart Association class III or IV. Transseptal access was used in all procedures. Technical success was achieved in all patients and there was no in-hospital mortality. There was no 30-day cardiovascular mortality and 4% (1 patient) 30-day all-cause mortality (1 patient died of asphyxia on day 29 after choking on pills at home), which was lower than the 30-day mortality in the TVT registry (9%). Detailed procedural, in-hospital and 30-day outcomes will be presented on the complete cohort of 30 patients. Conclusions: In patients without surgical alternatives, transseptal mitral ViV procedures in failed surgical bioprostheses are associated with high technical and procedural success and low 30-day mortality.

Introduction: Transcatheter mitral valve replacement (TMVR) using aortic transcatheter heart valves (THV) is developing as an alternative to surgery for patients with severe mitral valve disease due to degenerated mitral bioprostheses or failed surgical rings who are poor surgical candidates. Outcomes of off-label procedures in the United States are being collected in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) Registry. A comprehensive analysis of mitral Valve-in-Valve (VIV) versus Valve-in-Ring (VIR) outcomes has not previously been performed. Objectives: To evaluate in-hospital and 30-day clinical outcomes of mitral VIV and VIR procedures in the United States. Methods: Retrospective analysis of data from the STS/ACC TVT Registry on patients who underwent mitral VIV or VIR procedures. Results: 587 patients underwent TMVR VIV (n=494) or VIR (n=93) procedures between January 2013 and December 2016 at 144 hospitals. Median age was 76 (VIV) and 73 (VIR) years, (p=0.024), 60.9% (VIV) and 44.1% (VIR) were female (p=0.003), median left ventricular ejection fraction was 55% in VIV and 50% in VIR (p <0.001), and median STS score was 10.5% (VIV) and 9.2% (VIR), p=0.131. Transseptal access was utilized in 35% VIV and 46.2% VIR procedures, p=0.081. Procedural success was achieved in 74.4% of VIV and 57.8%VIR (p=0.239). Left ventricular outflow tract (LVOT) obstruction was more common in VIR (5.4%) vs VIV (0.06%), p=0.003. Post-procedure median mean mitral valve gradient was 4mmHg in both groups. 95.7% of VIV and 86% of VIR patients had post-procedure mitral regurgitation ≤1(+), p<0.001. In-hospital mortality was 6.9% for VIV and 9.7% for VIR (p=0.343). 30-day mortality was 9% for VIV and 12% for VIR (p=0.387). At 30-day follow up, 85.6% of VIV and 77.7% of VIR patients were in New York Heart Association class I or II (p=0.398). Conclusions: TMVR VIV and VIR using aortic transcatheter heart valves in high surgical risk patients are associated with similar in-hospital and 30-day mortality and symptom benefit. LVOT obstruction post-TMVR and residual mitral regurgitation ≥2 (+) were more frequent in VIR procedures. The long-term effect of these procedures is not known and requires further evaluation.

AbstractObjectivesTo assess the impact of pulmonary hypertension (PH) on outcomes of patients with severe mitral annular calcification (MAC) undergoing transcatheter mitral valve replacement (TMVR).BackgroundPH is associated with poor outcomes after mitral valve surgery. Whether the presence of PH in patients with MAC undergoing (TMVR) is associated with poor outcomes, is unknown.MethodsRetrospective evaluation of 116 patients from 51 centers in 11 countries who underwent TMVR with valve in mitral annular calcification (ViMAC) using balloon‐expandable aortic transcatheter valves (THVs) from September 2012 to March 2017. Pulmonary artery systolic blood pressure (PASP) by echocardiogram was available in 90 patients. The subjects were stratified based on PASP: No PH = PASP ≤35 mmHg (n = 11); mild to moderate PH = PASP 36–49 mmHg (n = 21) and severe PH = PASP ≥50 mmHg (n = 58). Clinical, procedural, and echocardiographic outcomes were assessed.ResultsMean age was 72.7 (±12.8) years, 59 (65.6%) were female, Society of Thoracic Surgeons score was 15.8 + 11.8% and 90.0% where in New York Heart Association (NYHA) class III–IV. There was no significant difference in all‐cause mortality at 30 days (no PH = 27.3%, mild–moderate PH = 19.0%, severe PH = 31.6%; p = 0.55) or at 1 year (no PH = 54.5%, mild–moderate PH = 38.1%, severe PH = 56.1%; p = 0.36). No difference in adverse events, NYHA class or amount of residual mitral regurgitation at 1 year were observed between the groups.ConclusionThis study suggests that the presence of PH in patients with predominantly mitral stenosis with MAC undergoing TMVR does not impact mortality or adverse events. Further studies are needed to fully understand the effect of PH in this group of patients.

Background: Women have a higher rate of adverse events after mitral valve surgery. We sought to evaluate whether outcomes after transcatheter edge-to-edge repair intervention by sex have similar trends to mitral valve surgery. Methods: The primary outcome was 1-year major adverse events defined as a composite of all-cause mortality, stroke, and any bleeding in the overall study cohort. Patients who underwent transcatheter edge-to-edge repair for mitral regurgitation with the MitraClip system in the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy registry were evaluated. Linked administrative claims from the Centers for Medicare and Medicaid Services were used to evaluate 1-year clinical outcomes. Associations between sex and outcomes were evaluated using a multivariable logistic regression model for in-hospital outcomes and Cox model for 1-year outcomes. Results: From November 2013 to March 2017, 5295 patients, 47.6% (n=2523) of whom were female, underwent transcatheter edge-to-edge repair. Females were less likely to have >1 clip implanted ( P <0.001) and had a lower adjusted odds ratio of device success (adjusted odds ratio, 0.78 [95% CI, 0.67–0.90]), driven by lower odds of residual mitral gradient <5 mm Hg (adjusted odds ratio, 0.54 [CI, 0.46–0.63]) when compared with males. At 1-year follow-up, the primary outcome did not differ by sex. Female sex was associated with lower adjusted 1-year risk of all-cause mortality (adjusted hazard ratio, 0.80 [CI, 0.68–0.94]), but the adjusted 1-year risk of stroke and any bleeding did not differ by sex. Conclusions: No difference in composite outcome of all-cause mortality, stroke, and any bleeding was observed between females and males. Adjusted 1-year all-cause mortality was lower in females compared with males.