Michelena, Héctor I.

Background Bicuspid aortic valve (BAV) is the most common congenital heart defect, associated with a lifetime morbidity burden exceeding 80% and an estimated 7% probability of transmission to first-degree relatives. Hence, echocardiographic screening of relatives is recommended. The aim of our study is to develop an artificial intelligence-enabled electrocardiogram (AI-ECG) model for the detection of BAV. Methods Between January 1, 1990, and June 30, 2023, the Mayo Clinic healthcare system database was searched for patients aged ≥18 years with echocardiograms performed for family history of BAV, abnormal auscultation, a BAV-related diagnosis, or to rule out the condition, and with an electrocardiogram (ECG) obtained within 6 months. Cases were patients with a confirmed BAV diagnosis, and controls were those with normal aortic valves. ECGs were randomly assigned into training (80%), internal validation (10%), and test (10%) groups. The AI-ECG model was built using Keras under TensorFlow. Results A total of 13,065 valid ECG–echocardiogram pairs were included (mean [SD] age, 58 [17] years; 44% women), with a median time of 1 day (interquartile range, 0–3 days) between studies. With a 45% BAV prevalence in the test group ( n = 1301), the area under the curve was 0.704, positive predictive value (PPV) 60.1%, and negative predictive value (NPV) 69.4%. At a prevalence of 7%, the NPV increased to 96.1%, but the PPV decreased to 12.2%. Conclusions In this retrospective cohort and using the current AI-ECG model, BAV detection showed modest diagnostic performance and limited standalone clinical utility, suggesting that ECG-only screening for BAV may require additional modalities or more refined phenotyping.

Abstract Aims Significant secondary tricuspid regurgitation (STR) is associated with worse morbidity and mortality. To-date, evidence on isolated tricuspid valve surgery in STR remains controversial with uncertainty regarding management strategies. We aimed to investigate sex differences in the association of isolated tricuspid valve surgical repair/replacement (TVR) with outcomes of mortality and heart failure (HF) hospitalizations in STR. Methods and results Patients with severe STR without significant aortic valve or organic mitral valve disease, congenital heart disease, pacemakers, previous valve intervention, malignancy, or end-stage kidney/liver disease were identified. Isolated TVR was studied as a time-dependent covariate in association with mortality and HF hospitalizations. Among 2,857 patients (median age 76 years; 62% women), 143 underwent isolated TVR (58% repair; 42% replacement; 64% with low TRI-SCORE risk category) at median 56 days. Over median 1.6 (IQR 0.2-5.2) years, 1,771 patients died and 1,259 had HF hospitalization. When adjusting to age, comorbidities, left/right ventricular function, pulmonary hypertension, hemoglobin level, and dyspnea, isolated TVR was associated with lower mortality in females (HR 0.54 95% CI 0.35-0.83) but not males (HR 1.29 95% CI 0.90-1.83), p-interaction<0.01; this remained the case when restricting to groups with normal left/right ventricular function. Isolated TVR was associated with HF hospitalization without interaction with sex (HR 0.68 95% CI 0.46-0.998), p-interaction=0.51. Conclusion Isolated TVR for STR was associated with decreased HF hospitalizations in both females and males but improved survival only in females. Future studies are needed to understand differences in the natural history of TR between sexes and stratify outcomes after TR intervention by sex.

Abstract Aims Prognosis in tricuspid regurgitation (TR) is shaped by complex clinical and haemodynamic interactions, complicating risk stratification. We aimed to use explainable artificial intelligence (EAI) to model these relationships and identify key predictors of outcomes. Methods and results We analysed long-term all-cause mortality in a large prospective registry of patients with native TR across the full severity spectrum. Patients underwent detailed clinical evaluation and quantitative Doppler-echocardiography. Supervised EAI models were applied to identify and rank predictors of mortality under medical therapy, capturing non-linear associations and interactions among baseline characteristics. Among 9761 patients [mean age 73 ± 15 years; 56.9% women; effective regurgitant orifice area (EROA) 40 (30–56) mm2; regurgitant volume 39 (29–53) mL/beat; 42% severe TR], 2676 deaths occurred during 3.8 ± 4.6 years of follow-up. EAI identified and ranked 20 prognostic determinants of survival. Haemodynamic measures, led by elevated pulmonary-artery systolic and right-atrial pressures, were strongest, followed by age and comorbidity. TR-related variables ranked next, led by right ventricular dysfunction and EROA, which outperformed integrative TR grade and TRIScore. Left-ventricular parameters were less influential. Non-linear effects, including those involving ejection fraction, and interactions such as higher EROA-related risk with elevated pulmonary pressures or lower TRIScore (both P < 0.03) were observed. Proportional hazards models confirmed EROA as the strongest TR severity marker (P < 0.0001), with excess mortality beginning at 40 mm2 and increasing further at 60 mm2. Conclusion EAI ranked mortality predictors in TR, highlighting patient factors, haemodynamics, TR-specific measures, and left-ventricular function. Among TR-specific measures, EROA and TRIScore were most prognostic. Recognizing their impact can refine risk stratification, guide intervention timing, and inform long-term management.

Abstract Objectives The progression of extra-mitral valve (MV) cardiac damage in patients with primary mitral regurgitation (MR) following surgical repair has not been described. We aimed to investigate the evolution of extra-MV cardiac damage after MV repair and to assess its prognostic significance. Methods Patients with severe primary MR undergoing surgical repair at 5 referral centres were included when echocardiographic follow-up assessment was available. Based on echocardiographic parameters at baseline and at a median follow-up of 7 (interquartile range [IQR] 4-11) months after MV repair, patients were hierarchically classified as follows: stage 0: no cardiac damage; stage 1: left ventricular dilatation and/or dysfunction; stage 2: left atrial dilatation and/or atrial fibrillation; stage 3: pulmonary hypertension and/or significant tricuspid regurgitation. The primary outcome was all-cause mortality. Results A total of 764 patients (mean age 62 ± 13 years, 70% men) were included. Compared to baseline, 43% improved at least 1 stage, 49% remained unchanged, and 8% worsened at least 1 stage during follow-up after MV repair. At a median follow-up of 91 months after MV repair, 94 patients (12%) died. By multivariate Cox regression analysis, after adjusting for potential confounders, extra-MV cardiac damage staging at follow-up (HR per-1-stage-increase = 1.571; P = .009) and cardiac damage evolution (improved group, HR = 0.467; P = .034; worsened group, HR = 2.481, P = .037) were independently associated with all-cause mortality and had incremental prognostic value over preprocedural assessment. Conclusions Extra-MV cardiac damage improves significantly after MV repair, and its evolution is independently associated with all-cause mortality, suggesting the importance of comparative echocardiographic assessment following MV repair to improve risk stratification.

Abstract Background The tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (SPAP) ratio (TAPSE/SPAP) is touted as a measure of right ventricular (RV) to pulmonary artery (PA) coupling, but its intrinsic, independent and incremental impact on outcome remains uncertain, particularly across the quantified severity spectrum of tricuspid regurgitation (TR). Methods We enrolled a prospective repository of patients with native TR, in whom TR quantitation using proximal-isovelocity-surface-area (PISA), SPAP and TAPSE, were all prospectively measured between 09/2003 and 04/2023. We included only patients with functional TR, without congenital or organic heart disease and without indwelling catheter/lead. The primary outcome was mortality under medical management. Results A total of 3,436 patients (median age 77 years, 57.6% female, median effective-regurgitant-orifice-area 39 mm2) were included. The median TAPSE/SPAP ratio was 0.36 (interquartile-range 0.26-0.51). Over a mean follow-up period of 2.4±2.8 years, 854 (24.9%) patients died. Spline regression, adjusted for age, sex, left ventricular ejection fraction, EROA, comorbidity index, and heart failure severity (TriScore), demonstrated that a TAPSE/SPAP remain linked to mortality, with ratio below 0.4 significantly associated with excess mortality risk (Figure). Multivariable models confirmed that higher TAPSE/SPAP ratio remained independently inversely associated with mortality (adjusted-hazard-ratio 0.76 [0.72-0.80] per 0.1 increment, p<0.001). Furthermore TAPSE/SPAP ratio provided incremental and independent prognostic value above and beyond the individual values of TAPSE or SPAP (p<0.001) and threshold for excess mortality remained consistently at 0.4, irrespective of quantified TR severity. Conclusion The TAPSE/SPAP ratio measured prospectively in routine clinical practice, is a strong and independent prognostic indicator in patients with functional TR, that adds to the prognostic value of its components. A TAPSE/SPAP ratio below 0.4 consistently identifies a subgroup at high-risk of mortality under medical management. These data suggest that therapeutic interventions that may impact positively the TAPSE/SPAP ratio should be tested in patients with functional TR.Mortality risk across TAPSE/SPAP ratio

Abstract Background Left ventricular (LV) remodeling in patients with valvular heart disease may vary according to the type of overload (pressure vs volume) as well as patients’ characteristics and comorbidities. Different LV remodeling patterns can be defined based on either an increase in LV mass index (LVMI), relative wall thickness (RWT), or both, and have been largely studied in patients with aortic valve disease but not in patients with primary mitral regurgitation (PMR). Purpose To describe the prevalence and baseline characteristics of the different LV remodeling patterns in PMR patients undergoing mitral valve (MV) surgery, and their association with outcome. Methods Four LV remodeling patterns were identified before MV surgery according to LVMI and RWT (Fig1-a). A cutoff of >115 g/m2 in males or >95 g/m2 in females was used to define high LVMI, and >0.42 was used to define high RWT. Patients with more than mild concomitant aortic stenosis were excluded. The study outcome was all-cause mortality. Results A total of 1538 patients were included, of which 362 (23.5%) had normal LV geometry (NG), 774 (50.3%) had eccentric hypertrophy (EH), 286 (18.6%) had concentric hypertrophy (CH), and 116 (7.5%) had concentric remodeling (Fig 1-a). Compared to the NG group (Fig 2), the EH group had more females, with larger LV size and left atrial volume index (LAVI). Compared to the NG group, patients in the CH group were significantly older and had more proportion of females. Moreover, they were more symptomatic, had higher prevalence of arterial hypertension, atrial fibrillation, and worse renal function, with smaller LV end-diastolic diameters and thicker LV walls.. Compared to the NG group, the CR group included patients with significantly smaller LV cavities and thicker LV walls, but interestingly similar LAVI and systolic pulmonary pressure, suggesting that this group might represent patients with a rather acute onset MR. Of note, there was no difference among the groups as regards LV systolic dysfunction (ejection fraction ≤ 60%, P=0.314). However, patients with CH and CR had significantly worse e’ and E/e’ ratio. After a median follow-up of 6.2 years, 211 (13.7%) patients died. Kaplan-Meier analysis showed similar survival between the NG and EH groups (91.4 vs 91.6%, P = 0.964), with significantly lower survival in the CH (76.6%, P<0.001) and CR (81.9%, P=0.028) groups, compared to NG (Fig 1-b). On multivariable analysis, after correcting for all the significant variables (Fig 1-c), CH and CR patterns carried higher risk of mortality (HR 1.7, P=0.024 and 2.0, P=0.017) compared to NG, while EH carried no additional risk (P=0.768). Conclusion LV remodeling patterns help in phenotyping patients with PMR undergoing MV surgery, and are independently associated with different risks of post-operative mortality.Figure 1:Prevalence and outcome Figure 2:Baseline characteristics

Abstract Background Aortic valve calcification (AVC), as measured by gold-standard computed tomography (CT) Agatston score, provides an anatomic assessment of aortic stenosis (AS) severity and is a key predictor of AS progression and need for valve replacement. AVC detection and quantification from transthoracic echocardiography (TTE) could expand AS early diagnosis and risk stratification, currently limited by CT availability and radiation exposure. Methods A multi-view video-based deep learning framework was developed using 1166 TTE aortic valve videos from 187 TTE studies acquired in 110 patients with available AVC score by CT. EchoAVC architecture includes a feature extraction model followed by a quality-aware model that aggregates video-level information to obtain patient-level predictions for AVC detection and quantification (score). The framework was validated internally with 173 TTE studies from 86 patients across seven centres, and externally using 430 TTE studies from 280 patients across four different centres. The associations between EchoAVC estimations and AS severity, progression, and need for aortic valve replacement were examined. Results EchoAVC demonstrated excellent performance in AVC detection (AUROC 0.98, accuracy 94.4%), and quantification (R = 0.64) in the external multi-centre testing set. EchoAVC score was correlated with echocardiographic AS severity descriptors, including aortic valve mean pressure gradient (ρ = 0.749) and peak velocity (ρ = 0.757), and predicted future increase in mean pressure gradient (ρ = 0.382), peak velocity (ρ = 0.433) and calcium score by CT (ρ = 0.650). In 361 patients followed for a median of 3.8 years, 139 underwent aortic valve replacement. Baseline presence and extent of AVC as predicted by EchoAVC showed strong risk-stratification power for aortic valve replacement, remarkably in line with those obtained by CT, and incremental over TTE AS descriptors. EchoAVC was further tested in routine clinical practice images, confirming strong associations with AS severity and progression, including stratification for incident AS in previously unaffected individuals (p<0.001). Conclusions EchoAVC enables accurate and non-invasive detection and quantification of AVC, offering substantial diagnostic and prognostic value for aortic stenosis progression and need for valve replacement. This technique holds promise as a scalable tool for early detection and clinical management of aortic valve stenosis. Clinical Perspective What Is New? * Aortic valve calcification can be detected and quantified on standard, two-dimensional transthoracic echocardiography * EchoAVC score is associated with echocardiographic metrics of aortic stenosis severity * EchoAVC predicts progressive increase in aortic stenosis severity and need for aortic valve replacement What Are the Clinical Implications? * This openly available deep learning framework can be used to estimate aortic valve calcium in patients at risk of or presenting aortic stenosis to predict aortic stenosis progression * EchoAVC may help identify patients likely to have high aortic valve calcium and prioritize them for confirmatory CT assessment, thereby supporting earlier identification of calcific aortic valve disease in clinical pathways.

BACKGROUND: Chronic aortic regurgitation (AR) is associated with significant cardiac remodeling, but the prevalence and prognostic impact of extravalvular cardiac damage remain unexplored. METHODS: Adults with moderate or greater chronic AR identified on echocardiogram between January 2008 and July 2024 were included. Exclusion criteria were acute AR, hypertrophic and infiltrative cardiomyopathies, prior cardiac surgery, and valve stenosis. Cardiac damage was classified into hierarchical stages: no cardiac damage (stage 0), left ventricular damage (stage 1), moderate or greater mitral regurgitation or left atrial enlargement or atrial fibrillation (stage 2), pulmonary hypertension or moderate or greater tricuspid regurgitation (stage 3), and significant right ventricular dysfunction (stage 4). The primary outcome was the association between cardiac damage stages and all-cause mortality under medical surveillance. RESULTS: Of 4026 patients (median age, 72 [61–80] years), 78% had moderate AR, 11% had moderate-severe, and 11% had severe AR. Cardiac damage was present in 87% of patients: 14% in stage 1, 53% in stage 2, 18% in stage 3, and 2% in stage 4. In a multivariable model, including age, sex, AR severity, and Charlson Comorbidity Index, cardiac damage stages were associated with mortality. Adjusted hazard ratios were 1.42 (95% CI, 1.04–1.96) for stage 1, 1.58 (95% CI, 1.21–2.06) for stage 2, 2.78 (95% CI, 2.10–3.67) for stage 3, and 5.34 (95% CI, 3.67–7.76) for stage 4. Adding cardiac damage staging to multivariable models improved predictive accuracy for mortality, increasing the concordance statistics from 0.73 (95% CI, 0.71–0.75) to 0.76 (95% CI, 0.74–0.77). CONCLUSIONS: Cardiac damage is present in nearly 90% of patients with moderate or greater AR and is associated with increased mortality, highlighting the need for a more comprehensive evaluation of cardiac structure and function beyond the aortic valve and left ventricle.

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.