Cavalcante, João L.

Abstract Aims Heart failure (HF) with preserved (HFpEF) and mildly reduced (HFmrEF) ejection fraction are prevalent, yet frequently underdiagnosed syndromes associated with high morbidity and mortality, impaired quality of life, and escalating healthcare expenditures. Although guideline-directed medications like SGLT2 inhibitors have been shown to reduce the risk of hospitalization and cardiovascular death, their use remains limited and substantial residual risk persists. This trial aims to evaluate the safety and performance of a novel left-atrium-to-coronary-sinus shunt (Edwards APTURE transcatheter shunt system) in HFpEF and HFmrEF patients. Methods ALT-FLOW II is a prospective multi-centre, randomized, sham-controlled, double-blinded (patient and assessor) trial. Approximately 100 symptomatic HF patients aged ≥18 years with left ventricular ejection fraction >40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mm Hg with a PCWP to right atrial pressure gradient ≥8 mm Hg will be randomized 1:1 to the APTURE shunt vs sham control. Key exclusion criteria include severe HF, significant valvular disease, and more than mild right ventricular dysfunction. The primary endpoints are the safety of the APTURE device at 30 days and change in workload-corrected PCWP normalized to bodyweight at 6 months. Secondary endpoints include changes in patient-reported outcomes, and hemodynamic and echocardiographic parameters through 5 years. The trial will also explore the impact of the device on short-term cardiac remodelling and intra-cardiac flow patterns using multi-modality imaging. Conclusions The ALT-FLOW II trial will evaluate the safety and performance of the APTURE system in symptomatic HFpEF and HFmrEF patients with elevated left atrial pressure.

Importance Primary mitral regurgitation (MR) is a prevalent valvular lesion. Current American College of Cardiology/American Heart Association guidelines include class I recommendations for intervention for severe primary MR at the onset of symptoms, significant left ventricular (LV) enlargement (end-systolic dimension ≥40 mm), or dysfunction (ejection fraction ≤60%), with a class IIA recommendation for mitral valve repair when performed at an experienced surgical center. Recent data suggest a survival penalty when waiting for class I surgical guideline indications, and novel markers of decompensation are under investigation. Observations Comprehensive assessment of MR severity using echocardiography is critical, and when warranted, cardiac magnetic resonance (CMR) is complementary. Assessment of LV size and function, as well as serial changes in both, is crucial for determining timing of surgery. New-onset atrial fibrillation, left atrial enlargement, pulmonary hypertension, and exercise-induced changes in LV function should also be considered in borderline scenarios. The roles of LV volumes, global longitudinal strain, CMR-derived measures of myocardial dysfunction, and cardiac biomarkers are worthy of further investigation regarding consideration for early surgical intervention. Conclusions and Relevance A more refined approach incorporating assessment of extravalvular cardiac injury, novel imaging markers, and biomarkers is needed to optimize surgical timing in primary MR. Further research is warranted to validate these emerging parameters and refine guidelines to improve patient outcomes.

Background The natural history of asymptomatic moderate or severe aortic regurgitation (AR) remains uncertain, with conflicting reports about its progression and surgical timing. We aimed to quantify adverse outcomes under conservative management and evaluate the association of aortic valve replacement/repair (AVR) with mortality. Methods Systematic searches (inception–July 2025) identified cohort studies of asymptomatic moderate/severe AR. Random-effects models estimated pooled incidence rates of adverse events; fixed-effects models were used for hazard ratios (HRs) of AVR vs conservative management. Results Twenty-seven studies (4720 patients; mean age 49 years; mean follow-up 3.9 years) were included. Pooled incidence rates per 100 person-years were 1.75 (95% CI 1.27 to 2.41) for all-cause mortality, 1.29 for cardiac death, 0.29 for sudden death, 4.30 for new symptoms and 7.01 for AVR. Asymptomatic low left ventricular ejection fraction occurred in only 0.9 per 100 person-years. Mortality rates were more than double those of the general population across age groups—2.45 (1.90 to 3.18) per 100 person-years for cohorts with mean age ≥50 years versus 0.59 (0.29 to 1.21) for younger cohorts. Early AVR was associated with lower mortality (pooled HR 0.33; 95% CI 0.30 to 0.37). Conclusion Asymptomatic moderate/severe AR carries significant excess mortality irrespective of age, contradicting its historically benign reputation. Given the rarity of asymptomatic LV dysfunction, earlier intervention guided by more sensitive markers of LV damage may improve outcomes, although heterogeneity and study quality warrant cautious interpretation. PROSPERO registration number CRD42024522683.

Abstract Growing evidence has demonstrated the clinical benefit of percutaneous left atrial appendage closure (LAAC) in patients with atrial fibrillation. Although procedural complication rates have declined with increasing experience, post-procedural device-related complications persist, impacting prognosis and reducing the long-term benefits of the procedure. Given the potential impact of these complications, surveillance imaging after LAAC is mandatory. Currently, different imaging modalities offer unique advantages to manage these complications which warrant a combined approach to optimize both short- and long-term follow-up. The aims of this review are to explore the distinct characteristics of each imaging modality, highlighting the primary findings to be assessed during follow-up imaging. Additionally, we propose an optimized clinical imaging surveillance roadmap from discharge to long-term follow-up.

Abstract Mitral valve prolapse (MVP) is the most frequent valve condition but remains a conundrum in many aspects, particularly in regard to the existence and frequency of an arrhythmic form (AMVP) and its link to sudden cardiac death. Furthermore, the presence, frequency, and significance of the anatomic functional feature called mitral annular disjunction (MAD) have remained widely disputed. Recent case series and cohorts have shattered the concept that MVP is most generally benign and have emphasized the various phenotypes associated with clinically significant ventricular arrhythmias, including AMVP. The definition, evaluation, follow-up, and management of AMVP represent the focus of the present review, strengthened by recent coherent studies defining an arrhythmic MVP phenotypic that would affect a small subset of patients with MVP at concentrated high risk. The role of MAD in this context is of particular importance, and this review highlights the characteristics of AMVP phenotypes and MAD, their clinical, multimodality imaging, and rhythmic evaluation. These seminal facts lead to proposing a risk stratification clinical pathway with consideration of medical, rhythmologic, and surgical management and have been objects of recent expert consensus statements and of proposals for new research directions.

Abstract Adverse cardiac remodelling is the main determinant of patient prognosis in degenerative valvular heart disease (VHD). However, to give an indication for valvular intervention, current guidelines include parameters of cardiac chamber dilatation or function which are subject to variability, do not directly reflect myocardial structural changes, and, more importantly, seem to be not sensitive enough in depicting early signs of myocardial dysfunction before irreversible myocardial damage has occurred. To avoid irreversible myocardial dysfunction, novel biomarkers are advocated to help refining indications for intervention and risk stratification. Advanced echocardiographic modalities, including strain analysis, and magnetic resonance imaging have shown to be promising in providing new tools to depict the important switch from adaptive to maladaptive myocardial changes in response to severe VHD. This review, therefore, summarizes the current available evidence on the role of these new imaging biomarkers in degenerative VHD, aiming at shifting the clinical perspective from a valve-centred to a myocardium-focused approach for patient management and therapeutic decision-making.

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 < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .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 < .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.

Background— The CoreValve US High-Risk Clinical Study compared clinical outcomes and serial echocardiographic findings in patients with severe aortic valve stenosis after transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis or surgical aortic valve replacement (SAVR). Methods and Results— Eligible patients were randomly assigned 1:1 to TAVR with a self-expanding bioprosthesis or SAVR (N=747). Echocardiograms were obtained at baseline, discharge, 30 days, 6 months, and 1 year after the procedure and were analyzed at a central core laboratory. Compared with SAVR patients (N=357), TAVR patients (N=390) had a lower mean aortic valve gradient, larger valve area, and less patient–prosthesis mismatch (all P <0.001), but more paravalvular regurgitation at discharge, which decreased at 1 year. SAVR patients experienced significant right ventricular systolic dysfunction at discharge and 1 month with normal right ventricular function at 1 year. One-year all-cause mortality was 14.2% for TAVR and 19.1% for SAVR patients. Preimplantation aortic regurgitation ≥mild was associated with reduced mortality hazard for both the TAVR (hazard ratio 0.48, 95% confidence interval 0.27–0.85; P =0.01) and the SAVR groups (hazard ratio 0.53, 95% confidence interval 0.32–0.87; P =0.01). Aortic regurgitation ≥mild after TAVR was associated with increased risk for all-cause mortality (hazard ratio 1.95, 95% confidence interval 1.08–3.53; P =0.03). Conclusions— In patients with severe aortic stenosis at increased surgical risk, TAVR was associated with better systolic valve performance, similar left ventricular remodeling, more paravalvular regurgitation, and less right ventricular systolic dysfunction compared with SAVR. Despite an overall mortality reduction for the TAVR group, ≥mild aortic valve regurgitation after TAVR was associated with an increased mortality hazard. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01240902.

Background— Approximately one third of patients with symptomatic aortic stenosis have reduced left ventricular ejection fraction (LVEF) before transcatheter aortic valve replacement. The incidence, predictors, and significance of early LVEF recovery after CoreValve transcatheter aortic valve replacement have not been described. Methods and Results— We studied 156 patients from the CoreValve Extreme and High-Risk trials with LVEF ≤40% at baseline who had 30-day LVEF data. All patients underwent core laboratory echocardiographic assessment of LVEF at baseline, post procedure, discharge, 30 days, 6 months, and 1 year. Early LVEF recovery was defined as an absolute increase of ≥10% in EF at 30 days. One-year outcomes were compared between patients with and without early recovery. Multivariable analysis was performed to determine independent predictors of early recovery. Early LVEF recovery occurred in 62% of patients, generally before discharge. By 30 days LVEF increased >17% compared with baseline in the early recovery group with minimal increase in the no–early recovery group (48.9±8.8% versus 31.5±6.9%; P <0.001). One-year all-cause mortality was numerically (but not statistically) higher in the no–early recovery group (24% versus 12%; P =0.07). Absence of previous myocardial infarction (odds ratio, 0.44; 95% confidence interval, 0.19–1.03) and baseline mean gradient ≥40 mm Hg (odds ratio, 4.59; 95% confidence interval, 1.76–11.96) were identified as predictors of early LVEF recovery. Conclusions— Nearly two thirds of patients with reduced LVEF will have a marked early improvement after transcatheter aortic valve replacement. Early LVEF recovery is associated with improved clinical outcomes and is most likely among patients with higher baseline aortic valve gradients and no previous myocardial infarction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01240902.