Abstract Introduction Desmoplakin (DSP) cardiomyopathy is a rare disease, a particular form of arrhythmogenic cardiomyopathy, with a high risk of life-threatening arrhythmia and heart failure. Case presentation A 53-year-old man presented to the emergency department with palpitations. He had no significant medical history, and his family history was unremarkable. The electrocardiogram revealed ventricular tachycardia with left bundle branch block morphology and inferior axis. Following cardioversion, sinus rhythm revealed first-degree AV block and T wave inversion in precordial leads. Echocardiography revealed biventricular dysfunction and right ventricular (RV) dilation, with impaired RV strain and regional kinesis abnormalities. Coronary angiography was normal. Cardiac magnetic resonance (CMR) showed late-gadolinium enhancement in a ring-like pattern, with septal sparring. Genetic testing was positive for the DSP variant, and the diagnosis of DSP cardiomyopathy was established. An implantable cardioverter-defibrillator was placed in secondary prevention, and subsequently, ventricular tachycardia ablation was performed due to repeated arrhythmia. Three years later, the patient presented with a myocardial infarction without ST elevation. Coronary angiography revealed critical stenosis of the circumflex artery, which was treated by implantation of a drug-eluting stent. Family screening revealed DSP cardiomyopathy in his daughter, who had subclinical findings on CMR. Conclusion While DSP cardiomyopathy is a complex disease and patients can sometimes present with myocarditis-like episodes, coronary angiography should always be performed in a patient presenting with acute coronary syndrome.

AIMS:Research has shown that the corrected proximal isovelocity surface area (PISA) method yields larger values for regurgitant volume (RegVol) and effective regurgitant orifice area (EROA) than conventional PISA method. However, it remains unclear whether new threshold values are needed for the corrected PISA method to effectively categorize the severity of secondary tricuspid regurgitation (STR). This study sought to identify threshold values for EROA and RegVol measured by the corrected PISA method for a three-grade classification of STR severity. METHODS AND RESULTS:We used three-dimensional echocardiography to determine the volumetric regurgitant fraction (RegFr), calculated as the difference between the right (RV) and left ventricular (LV) stroke volumes (SV) divided by the RVSV. A total of 213 patients (78 ± 10 years; 64% women) with isolated STR were enrolled. Based on RegFr, we classified STR severity into mild (RegFr < 16%), moderate (RegFr 16-49%), and severe (RegFr > 49%) grades. EROA and RegVol were measured using conventional (EROACONV, RegVolCONV) and corrected (EROACORR, RegVolCORR) PISA methods. The threshold values for identifying patients with mild, moderate, and severe STR were <0.22, 0.22-0.46, and >0.46 cm² for EROACORR, respectively; and <18, 18-42, and >42 mL for RegVolCORR, respectively. The accuracy of these new threshold values in predicting STR severity based on RegFr was 99% for EROACORR and 94% for RegVolCORR. These accuracies were significantly higher than those of EROACONV (90%, P < 0.001) and RegVolCONV (41%, P < 0.001). CONCLUSION:New threshold values for the corrected PISA method must be considered to improve the classification of STR severity.

AIMS:Current guidelines lack sex-specific thresholds for assessing secondary tricuspid regurgitation (STR) severity and right ventricular (RV) and tricuspid annulus (TA) remodelling. We aimed to determine whether risk-based cut-offs for these parameters differ between men and women with STR. METHODS AND RESULTS:We included 554 patients (74 ± 13 years, 51% women) with moderate or severe STR. The primary endpoint was all-cause mortality or heart failure hospitalization. Women were older (P < 0.001) and had a higher prevalence of atrial fibrillation (P = 0.008) and atrial STR (P < 0.001), whereas men more frequently had coronary artery disease (P < 0.001), chronic kidney disease (P = 0.005), and mitral regurgitation (P < 0.001). Women exhibited smaller RV and TA dimensions and higher RV ejection fraction (RVEF) (P < 0.001). Over a median follow-up of 19 (8-27) months, 230 patients reached the composite endpoint. Event-free survival at 2 years was comparable between sexes (P = 0.183), even after inverse propensity weighting (P = 0.342). Sex-specific thresholds for STR severity were lower in women for effective regurgitant orifice area (EROA) (0.36 cm² vs. 0.43 cm²) and regurgitant volume (RegVol) (31 mL vs. 35 mL) but higher for regurgitant fraction (46% vs. 39%). Women also exhibited comparable risk at lower RV end-diastolic (81 mL/m² vs. 96 mL/m²) and end-systolic volumes (37 mL/m² vs. 49 mL/m²), higher RVEF (49% vs. 41%), and smaller TA diameter (19 mm/m² vs. 22 mm/m²). CONCLUSION:In STR, women face a similar risk at lower EROAs and RegVols, along with smaller RV volumes, higher RVEF, and reduced TA dimensions. These findings highlight the importance of incorporating sex-specific thresholds into clinical decision-making when assessing STR severity and right heart remodelling.

Aims:This European Association of Cardiovascular Imaging (EACVI) survey evaluated current practice patterns in the imaging assessment of tricuspid regurgitation (TR), focusing on conventional and advanced modalities, the adoption of recent classifications, and barriers to quantitative right heart assessment. Methods and results:A 25-item online questionnaire was launched during EuroEcho Imaging 2024 and distributed via EACVI channels. From 10 December 2024 to 3 July 2025, 530 respondents from 69 countries participated. Most worked in tertiary/university hospitals (62%) and were imaging specialists (41%) or clinical cardiologists (40%). Transthoracic echocardiography (TTE) was almost universally applied (96%), while use of transoesophageal (TOE) and 3D echocardiography was variable. Tricuspid annular plane systolic excursion (TAPSE) and fractional area change (RVFAC) were frequently used, but RV strain and ejection fraction were underutilized due to time constraints and software unavailability. TR quantification relied mainly on colour Doppler-based parameters, with advanced approaches-3D colour Doppler, cardiac magnetic resonance (CMR)-reserved for selected patients. Half of the respondents routinely applied the 5-grade TR severity scheme, and leaflet-based anatomical classification was inconsistently adopted. Cardiac computed tomography, CMR, and invasive haemodynamics were more often used in patients referred for transcatheter interventions. Conclusion:This EACVI survey highlights considerable heterogeneity in TR imaging practice, with increasing yet slow adoption of robust quantitative and advanced modalities for assessing TR severity and right heart morphology/function. These findings underscore the need for improved access to advanced imaging technologies and broader dissemination of contemporary standards to enhance the quality and consistency of TR imaging in clinical and research settings.

AIMS:While pre-defined reference shapes have been used to assess morphological changes in the left ventricle, standardized methods for evaluating right ventricular (RV) remodelling are lacking. This study aimed to develop and test a new 3D echocardiography (3DE)-based method for quantifying RV shape in a large cohort of healthy individuals and across various disease states. METHODS AND RESULTS:3DE-derived RV mesh models were reconstructed in 1043 healthy subjects from the World Alliance of Societies of Echocardiography (WASE) study and in 581 patients with severe aortic stenosis, heart failure with reduced ejection fraction (HFrEF), post-heart transplantation, severe primary mitral regurgitation (MR), atrial secondary tricuspid regurgitation (A-STR), tetralogy of Fallot (TOF), and pulmonary hypertension (PH). To assess global RV shape, hemi-sphericity volume ratio (HSVR) and hemi-conicity angle (HCA) were calculated, where a higher HSVR and a more acute HCA reflect more spherical and conical shapes, respectively. In the WASE population, females had more spherical RVs, whereas males had more conical RVs (P = 0.028). Considering age, younger females had more conical RVs, while older individuals in both sexes showed spherical remodelling (P < 0.05). Comparing disease groups with WASE controls, MR, HFrEF, and A-STR patients had more spherical RVs compared with controls (both P < 0.001), while PH and TOF patients showed conical remodelling (both P < 0.001). In A-STR, a more conical remodelling was associated with adverse clinical outcomes. CONCLUSION:The proposed 3DE-based method comprehensively characterizes RV geometry, demonstrating demographic variation in healthy individuals and disease-specific alterations in patients, with important prognostic implications.

The first Tricuspid Valve Academic Research Consortium publication standardized definitions of disease etiology and severity, as well as standardized endpoints for trials to address the knowledge gaps related to identification and management of patients with tricuspid regurgitation. Based on randomized trials comparing transcatheter tricuspid valve intervention with optimal medical therapy, transcatheter edge-to-edge repair and tricuspid valve replacement were approved by the U.S. Food and Drug Administration and received CE Mark. These technologies represent a major step forward for patients with severe symptomatic tricuspid regurgitation and transcatheter tricuspid valve intervention. This second chapter of the Tricuspid Valve Academic Research Consortium focuses on defining specific trial design and endpoint options for comparisons of emerging technologies, tricuspid valve surgery, and medical therapy.

Abstract Background In patients with severe aortic stenosis (AS), the transvalvular flow rate (FR) is a key determinant of the prognostic value of the aortic valve area (AVA). However, the prognostic significance of FR in patients with moderate AS remains unclear. Purpose To assess the association with outcomes of FR in patients with moderate AS. Methods 292 outpatients (mean age 80 ± 9 years, 45% female) with moderate degenerative AS (defined as AVA between 1 cm² and 1.5 cm²) underwent transthoracic echocardiography between January 2019 and July 2022 and were retrospectively included in this study. The FR was calculated using the derivation method [FRder= mean jet velocity (cm/s) x AVA(cm²)], and was validated in a random sample of 90 patients. In these patients, FR was also calculated using the direct method [FRdir = stroke volume (mL)/ejection time (s)]. The primary study endpoint was a composite of all-cause mortality and hospitalization for heart failure (HHF). Results After median follow-up of 19.3 (Interquartile-Range 12.3–26.0) months, 73 patients reached the primary endpoint, with 22 experiencing HHF and 51 deaths. Patients who met the combined endpoint had lower values of FRder compared to those who didn’t experience these outcomes (201±47 mL/s vs 225±48 mL/s). The FRder showed excellent correlation with FRdir (R²=0.93, p<0.0001) (Figure 1). The best threshold value for identifying patients at higher risk of experiencing adverse outcomes of FRder was determined to be 210 mL/s through spline curve analysis. Female sex [Odds Ratio (OR) 5.3 (C.I.95% 2.8-10.3), p<0.0001], chronic kidney disease (eGFR<60 ml/min) [OR 3.2 (C.I.95% 1.5-7.0), p=0.003], previous myocardial infarction (OR 3.9 [C.I. 95%1.7-8.6], p=0.001), stroke volume indexed (SVi) [OR 0.8 (C.I.95% 0.8-0.9), p<0.0001] and at least moderate tricuspid regurgitation (OR 2.9 [C.I. 95% 1.2-6.8], p=0.017) resulted independent predictors of FRder less than 210 mL/s. At Cox multivariable regression analysis, FRder less than 210 mL/s resulted associated with events (adjusted Hazard Ratio 2.17 [C.I. 95% 1.14 – 4.12], p=0.018), after adjustment for age, coronary artery disease, left-ventricular ejection fraction, right-ventricular dysfunction and low flow state-defined as SVi <35 mL/m². Conclusion In patients with moderate degenerative AS under medical management, FRder less than 210 mL/s is independently associated with increased mortality and HHF at medium term follow-up. Further research is needed to determine whether patients with moderate AS and impaired flow rates might benefit from more intensive monitoring or earlier aortic valve replacement. Figure 1

Abstract Background Predicting outcomes in patients with significant secondary tricuspid regurgitation (STR) is extremely challenging. Purpose This study sought to develop and validate the TRIVO-SCORE, utilizing advanced echocardiographic parameters, for predicting hospitalization for heart failure (HF) and mortality in moderate and severe STR patients. Methods We retrospectively studied 504 consecutive STR outpatients (mean age 74 ± 13 years, 44% men), randomly divided into derivation (49%) and validation (51%) cohorts. The primary endpoint included all-cause death and/or heart failure HF hospitalization, whereas the secondary endpoint focused on HF hospitalization or all-cause death. Score discrimination was assessed using time-dependent area under the receiver operating characteristic curve (AUROC), and calibration was evaluated via the Hosmer-Lemeshow goodness-of-fit test. In a subset of patients (162/504, 29%) with severe STR and comprehensive clinical, laboratory, and echocardiographic data, we compared TRIVO-SCORE with TRI-SCORE and TRIO-SCORE. Results After Multivariable Cox Regression Analysis, four variables were incorporated into the final model: moderate to severe chronic kidney disease (CKD, GFR <30 mL/min), effective Right Ventricular Ejection Fraction (eRVEF <20%), right Ventricular free wall longitudinal strain/pulmonary artery systolic pressure (RVFWLS/PASP) <0.48, and effective regurgitant orifice area (EROA) >0.41cm². The final score ranged from 0 to a maximum of 5 points. The TRIVO-SCORE demonstrated satisfactory performance in both the derivation cohort (AUROC 0.78, 95% CI 0.73-0.84) and the validation cohort (AUROC 0.71, 95% CI: 0.65-0.77) at 2-year. TRIVO-SCORE accurately predicted separate endpoints for HF hospitalization or mortality. Per each point of TRIVO-SCORE, the risk of experiencing the composite endpoint increased by 1.5 times (HR 1.55 [95% CI 1.35–1.80], p<0.001, for each stage increase). This progressive increase in risk persisted when stratifying the population into atrial and ventricular STR. The discrimination and calibration for mortality prediction were superior to those of TRI-SCORE (1) (AUROC 0.61) and TRIO-SCORE (2) (AUROC 0.57). Conclusions The TRIVO-SCORE, integrating both clinical and advanced echocardiographic variables, proved to be a robust tool for enhancing risk stratification in patients with moderate to severe STR, providing a stronger association with outcomes than previously validated risk scores.

Abstract Background In hypertrophic cardiomyopathy (HCM) patients, quantification of left ventricular (LV) mass carries important prognostic implications. Two-dimensional echocardiography (2DE) has limited accuracy for LV mass calculation, due to plane position errors, geometric assumptions and asymmetric distribution of LV hypertrophy in HCM. Purpose We aimed to explore: (1) the accuracy of three-dimensional echocardiography (3DE) vs 2DE to quantify LV mass in HCM compared to cardiac magnetic resonance (CMR); (2) the relationship of 3DE LV mass with non-sustained ventricular tachycardia (NSVT) and late gadolinium enhancement (LGE)≥15% by CMR. Methods In consecutive HCM patients referred to our Cardiomyopathy Clinic between 2020 and 2023, 2DE and 3DE were used to assess LV mass. LV systolic function was assessed by 3DE ejection fraction (LVEF) and peak global 2D longitudinal strain (2DGLS). Clinical, 24h ECG Holter and CMR data were collected. Results A total of 180 HCM patients (pts, age 58±18 years, 55% men) were enrolled. Apical HCM was present in 56 pts (31%) and obstructive HCM in 69 pts (38%). Maximal LV wall thickness (MWT) by 2DE was 19.5±4.6 mm. LV mass was 150±51 g/m2 by 2DE, 80±25 g/m2 by 3DE, and 79±26 g/m2 by CMR. Fifty-seven pts (32%) had evidence of NSVT at ECG Holter monitoring. LGE≥15% was present in 32% pts. Aim #1: In a subset of 63 pts who underwent CMR, 3DE LV mass was strongly correlated with CMR LV mass (r=0.85, p<0.001), while 2DE LV mass was not (p=0.38). LV mass by 3DE showed a better agreement with LV mass (bias 3.8 g/m2, LOA -25 to 32 g/m2) by CMR than 2DE (bias 68 g/m2, LOA -35 to 172 g/m2). Aim #2: In the entire cohort, 3DE LV mass had a stronger association compared to 2DE LV mass with the presence of LGE≥15% (AUC 0.68 for 3DE versus 0.56 for 2DE, p=0.08) and NSVT (AUC 0.65 for 3DE versus 0.54 for 2DE, p=0.06). By multivariable analysis, LV mass by 3DE was an independent predictor of LGE≥15% (HR 1.03) and of NSVT (HR 1.03), outperforming 2DGLS and MWT in the latter regression. Using the Youden Index from ROC curve, the optimal cutoff for predicting LGE≥15% using 3DE mass was 87 g/m² (sensitivity 47%, specificity 91%). The addition of 3DE LV mass to a model including 2DE MWT, 2DE LV mass and 2DGLS had a significant incremental value for the prediction of LGE≥15% (Figure 1). Conclusions In HCM patients, LV mass by 3DE was strongly correlated to LV mass by CMR and was an independent predictor of significant LV myocardial fibrosis and ventricular arrhythmias. In centers with low access to CMR, implementation of 3DE to measure LV mass in HCM patients may improve arrhythmic risk stratification compared to 2DE.

In hypertrophic cardiomyopathy (HCM), the presence of pathogenic/likely pathogenic (P/LP) disease-causing genetic variants may indicate a worse prognosis. Few data exist on the effects of these genetic variants on cardiopulmonary exercise test (CPET) performance in HCM patients. We analysed asymptomatic and slightly symptomatic HCM patients (NYHA I-II) whose genetic analysis and CPET were available; at baseline, left ventricular function was normal and severe left ventricular outflow trait obstruction was excluded. Out of 120 HCM patients, we excluded 13 carrying variants of uncertain significance; of the remaining 107 patients, 54 were genotype negative [gene (−)], and 53 had a P/LP variant in sarcomeric genes [gene (+)]. Patients in the two groups had similar NYHA class, cardiovascular risk factors and echocardiographic characteristics. Gene (+) patients showed a lower peak VO2% and O2 pulse % (p < 0.05). Moreover, among gene (+), patients with P/LP variants in the so called “thin-filament” genes (TNNT2, TPM1 and MYL3) had the poorest CPET results. In asymptomatic or slightly symptomatic HCM patients with similar echocardiographic characteristics, exercise tolerance is affected by the genetic background. Indeed, exercise capacity is poorer in gene (+) compared to gene (−) patients and those carrying P/LP variants in “thin-filament” genes show the worst performance.

Abstract Background In hypertrophic cardiomyopathy (HCM), atrial fibrillation (AF) is a marker of disease progression and worse outcome, increasing the risk of thromboembolic events. Identification of HCM patients (pts) at risk of AF is pivotal for their clinical management and follow-up. Purpose We aimed to explore whether a detailed echocardiographic evaluation of the left atrium (LA) remodeling and function in HCM pts might improve the predictive value for new AF compared to standard parameters. Methods In consecutive HCM pts referred to our Cardiomyopathy Clinic between 2020 and 2023, we assess left ventricular (LV) and LA volumes and strain by two-dimensional echocardiography (2DE), and LV and LA volumes and total LA emptying fraction (EF) by three-dimensional (3DE) echocardiography. 3DE left atrioventricular coupling index (LACI) was calculated as the ratio of respective LA to LV end-diastolic volumes and expressed as percentage %. Clinical, ECG, and 48h ECG Holter data were also collected. Results A total of 180 HCM pts (58±18 years, 55% men) were followed for 23±13 months. Twenty-seven patients experienced at least one episode of AF during follow-up. They were older and had more impaired LV global longitudinal strain (GLS) (-13±4% vs -15±4%, p=0.004), total LA EF (31±12 vs 42±11%, p=0.001) and LA reservoir strain (LASr, 10±6 vs 16 ±8%, p=0.001) compared to pts without AF. In addition, larger values of 3DE LACI (75±51% vs 43±25%p=0.009) were found in the HCM pts with new AF episode during follow-up. At Cox univariable analysis, 3DE LACI, LA EF and LASr were associated with AF (AUC 0.68, 0.69 and 0.72, respectively, p<0.001 for all). The optimal cutoffs for predicting AF were > 59% for 3DE LACI and < 26% for LA EF with significant discriminative value in Kaplan-Meier analysis. The addition of 3DE LACI and LA EF to a model including LV GLS and 2DE LA volume had a significant incremental value for predicting the occurrence of AF (Figure 1). Conclusions In HCM patients, the advanced evaluation of LA function and left atrio-ventricular coupling by 3DE may improve the identification of patients at risk for subsequent AF episodes within 1 year follow-up. Predictive Model

Abstract Background Differently from the effective regurgitant orifice area (EROA) and regurgitant volume (RegVol), RegFr directly accounts for the size and the function of the right ventricle (RV). Objectives To assess the relationship between regurgitant fraction (RegFr) evaluated using three-dimensional echocardiography (3DE) and the outcome in patients with secondary tricuspid regurgitation (STR). Methods 331 patients with at least mild STR were enrolled. RegFr was computed as ratio between the RegVol, calculated using the proximal isovolumic surface area (PISA) method by Doppler and the total stroke volume (SV) of the RV computed as difference between 3DE RV end-diastolic (RVEDV) and end-systolic (RVESV) volumes. To compare the association of EROA, RegFr and RegVol with outcome, we used a composite endpoint of heart failure hospitalization (HFH) and death for any cause. Results After a median follow-up of 20 months, 133 patients (40%) reached the combined endpoint. Among the quantitative parameters of STR severity, RegFr had the highest area under the curve at ROC analysis (AUC= 0.65, 95%CI: 0.59-0.71). At Cox regression, RegFr was associated with outcome both in the univariate analysis (HR 1.012, CI 1.003-1.020, p=0.006) and in multivariate, adjusted for several clinical and echocardiography correlates. By testing each single quantitative parameter of STR severity, only RegFr significantly increased the prediction of the basal model (p=0.007) and improved the risk-stratification of the patients on top of EROA (Net Reclassification Index: 0.2833, p=0.011). In the subgroup of patients with non-severe STR (i.e., EROA<0.4 cm²), the RegFr identified the patients with significantly higher risk of events (cumulative incidence of the combined endpoint of 73% in patients with EROA<0.4 cm2 but RegFr≥50% vs 51 % in patients with RegFr<50%, p= 0.02). Conclusions Compared to EROA and RegVol obtained by PISA method, RegFr obtained by 3DE was more strongly associated with the outcome of patients with STR.

Abstract Background 2D echocardiography requires multiple views for the assessment of left ventricular (LV) systolic function and does not enable the calculation of right ventricular (RV) ejection fraction (EF). 3D echocardiography (3DE) has clear incremental value over 2D echocardiography; nevertheless, its availability and feasibility is limited. Purpose We aimed to develop a dual-task deep learning model – EF2Net – for predicting 3DE-derived LVEF and RVEF from 2D apical 4-chamber (A4C) view echocardiographic videos. Methods The EF2Net model comprises two video transformers, which were first pre-trained on 29,424 unlabeled A4C videos from 15,533 echocardiographic studies in a self-supervised fashion. In the subsequent supervised training phase, one of the transformers was trained for predicting LVEF on the publicly available EchoNet-Dynamic dataset and a dual-center international 3DE dataset comprising 5,341 labeled A4C videos from 1,408 echocardiographic studies, whereas the other transformer was trained for predicting RVEF only on the latter. Beyond testing the model internally on 20% of the dual-center dataset (i.e., internal test set), it was also validated in a labeled external validation set comprising (1) 244 A4C videos of 244 patients with different cardiac diseases and available outcome data and (2) 4,421 A4C videos of 853 healthy adults from the World Alliance of Societies of Echocardiography (WASE) study. Last, we evaluated the model on a low-risk, community-based cohort (1,166 unlabeled A4C videos of 1,166 individuals) with a 10-year follow-up to investigate the associations between the predictions and all-cause mortality. Results In the internal test set and the labeled external validation set, EF2Net predicted 3DE-derived LVEF with a mean absolute error (MAE) of 4.58 and 4.67 percentage points, respectively, whereas it achieved an MAE of 4.82 and 5.43 percentage points in predicting 3DE-derived RVEF. In the labeled external validation set, the model identified an LVEF <50% and an RVEF <45% with an area under the receiver operating characteristic curve of 0.95 and 0.86, respectively. In patients with cardiac diseases, the EF2Net-predicted LVEF and RVEF values were associated with the composite of all-cause death and heart failure hospitalization (LVEF – HR: 0.94 [0.91-0.98], p=0.001; RVEF – HR: 0.92 [0.88-0.98], p=0.004) independent of age and sex. Moreover, in the community-based cohort, the EF2Net-predicted EF values were also associated with 10-year all-cause mortality (LVEF – HR: 0.97 [0.95-0.99], p=0.026; RVEF – HR: 0.91 [0.88-0.95], p<0.001) independent of age, sex, and LV diastolic function. Conclusions EF2Net enabled the automated and accurate assessment of biventricular systolic function based on a single 2D echocardiographic view. It also exhibited robust performance when validated in a multi-ethnic dataset, and the prognostic value of its predictions was confirmed in patients with cardiac diseases and in the community.

Abstract Background The threshold value of the effective regurgitant orifice area (EROA) that identifies patients with secondary tricuspid regurgitation (STR) at high risk of events during follow-up remains unclear. Purpose Our study aimed to identify the threshold value of the EROA defining patients with STR at high-risk of events during follow-up and to evaluate the impact of right ventricular (RV) remodeling in modulating the outcome of low-risk STR patients according to EROA. Methods 513 consecutive outpatients with STR were included. Using the threshold value derived by spline curves, we divided our cohort into two groups: low- (EROA≤ 0.47cm2) and high- (EROA> 0.47cm2) risk STR patients. The endpoint was a composite of heart failure hospitalization and death. Results At 18±15 months from enrolment, 195 patients (38%) reached the endpoint. The Kaplan-Meier curves demonstrated a higher rate of events for high-risk patients (54±6% vs 30±7%, p <0.0001). EROA> 0.47 cm2 was associated with a 2-fold increased risk of experiencing the outcome (Hazard Ratio [HR]: 2.08, 95% Confidence Interval [CI] 1.56-2.77, p<0.0001). Patients with atrial STR had a significantly lower threshold value (0.44 cm²) than patients with ventricular STR (0.49 cm²). In multivariate Cox regression analysis, EROA remained independently associated with the composite endpoint (adjusted HR: 1.01, 95% CI 1.00-1.02, p<0.0001) both in the entire cohort and in high-risk patients. Patients with low-risk STR were associated with a dismal prognosis only if they had dilated or dysfunctioning RV. In patients with EROA≤ 0.47cm2, the event rate at two years for RV end-diastolic volume >90 mL/m2, RV end-systolic volume (RV ESV) >46 mL/m2, RV ejection fraction <45% and RV forward stroke volume/RV ESV< 0.40 were respectively: 42±4%, 51±4%, 44±4%, and 47±4%). Conclusions Our results refine the independent association between STR severity assessed by EROA and outcomes. In patients with low-risk STR, the assessment of RV function and RV-PA coupling may improve the patient’s risk prediction, demonstrating a clinically relevant link between STR severity and RV geometry and function.

INTRODUCTION AND OBJECTIVES:Significant secondary tricuspid regurgitation (STR) is associated with poor prognosis, but its heterogeneity makes predicting patient outcomes challenging. Our objective was to identify STR prognostic phenogroups. METHODS:We analyzed 758 patients with moderate-to-severe STR: 558 (74±14 years, 55% women) in the derivation cohort and 200 (73±12 years, 60% women) in the external validation cohort. The primary endpoint was a composite of heart failure hospitalization and all-cause mortality. RESULTS:We identified 3 phenogroups. The low-risk phenogroup (2-year event-free survival 80%, 95%CI, 74%-87%) had moderate STR, preserved right ventricular (RV) size and function, and a moderately dilated but normally functioning right atrium. The intermediate-risk phenogroup (HR, 2.20; 95%CI, 1.44-3.37; P<.001) included older patients with severe STR, and a mildly dilated but uncoupled RV. The high-risk phenogroup (HR, 4.67; 95%CI, 3.20-6.82; P<.001) included younger patients with massive-to-torrential tricuspid regurgitation, as well as severely dilated and dysfunctional RV and right atrium. Multivariable analysis confirmed the clustering as independently associated with the composite endpoint (HR, 1.40; 95%CI, 1.13-1.70; P=.002). A supervised machine learning model, developed to assist clinicians in assigning patients to the 3 phenogroups, demonstrated excellent performance both in the derivation cohort (accuracy=0.91, precision=0.91, recall=0.91, and F1 score=0.91) and in the validation cohort (accuracy=0.80, precision=0.78, recall=0.78, and F1 score=0.77). CONCLUSIONS:The unsupervised cluster analysis identified 3 risk phenogroups, which could assist clinicians in developing more personalized treatment and follow-up strategies for STR patients.

Abstract Background In patients hospitalized for heart failure with reduced ejection fraction (HFrEF), the occurrence of right ventricular (RV) dysfunction emerged as a prognostic factor for morbidity and mortality. Standard two-dimensional echocardiographic (2DE) parameters have been utilized to assess risk of cardiac death in these patients, but their predictive accuracy varies across different cardiac conditions. This underscores the necessity for more reliable novel parameters, to improve prognosis and to guide therapeutical and interventional management. Purpose To assess independent and comparative prognostic utility of three-dimensional (3D) against standard 2D parameters of RV function in predicting mortality and HF hospitalization (HFH). Methods We prospectively enrolled 366 patients hospitalized for HFrEF (60±13 years, 81% men), of ischemic and non-ischemic etiology (51% vs. 49%). Patients underwent comprehensive 2D and 3D echocardiography, including full volume acquisition of the right (RV) and left ventricles (LV). By 2DE, we measured TAPSE, RV fractional area change (FAC), S’ systolic velocity, and RV global (GLS) and free wall longitudinal strain (FWLS). By 3DE, we measured RV volumes and RVEF, and derived RVFAC and TAPSE. Primary outcome was cardiac death (CD). Secondary outcome was heart failure hospitalization (HFH). Follow up was 24±8 months. Results Mean 3D LVEF was 31±10%, while mean 3D RVEF was 39±10%. Binary logistic regression identified 3D RVEF as an independent significant predictor of CD (β=-0.16, OR 0.84, 95%CI 0.81-0.89, p<0.001) and HFH (β=-0.09, OR 0.92, 95%CI 0.88-0.95, p<0.001), better than standard 2DE parameters, such as 2D RVFAC (β=-0.04, OR 0.96, 95%CI 0.93-0.98 for CD and β=-0.02, OR 0.97, 95%CI 0.96-0.99 for HFH, both p<0.05) and 2D TAPSE (β=-0.13, OR 0.88, 95%CI 0.82-0.95 for CD and β=-0.08, OR 0.92, 95%CI 0.86-0.99 for HFH, both p<0.05). Comparative ROC analysis showed that 3D RVEF was superior for predicting CD (Fig. A) and HFH (AUCs of 0.82 and 0.71, respectively) to 2D TAPSE (AUCs of 0.63 and 0.60, respectively), 2D RVFAC (AUCs of 0.62 and 0.60, respectively), and S’ (AUC 0.56 and 0.50, respectively), all p<0.05. Kaplan-Meier survival analysis (Fig. B) showed that a 3D RVEF of 35% (χ²=25.1, p<0.001) differentiates the best between survivors and non-survivors. Conclusion 3D RVEF provides superior prognostic information for mortality and heart failure hospitalization in patients with HFrEF, better than 2D echo parameters. Inclusion of 3D RVEF in routine clinical assessment of patients with HFrEF might improve risk stratification and targeted interventions in this population.

Cardiac amyloidosis (CA) is a progressive infiltrative cardiomyopathy commonly linked to heart failure (HF) symptoms. Ventricular arrhythmias (VA) may occur in a small subset of patients, typically in advanced stages when amyloid deposits compromise myocardial and conduction system integrity. Managing VA in asymptomatic patients with CA remains complex and debated, particularly regarding beta–blockers due to potential adverse effects. A 65–year–old male, an experienced runner (10 km/day), presented for a primary prevention cardiological assessment. His history included dyslipidemia and smoking. He denied symptoms such as dyspnea, angina, syncope or palpitations. An electrocardiogram (ECG) showed sinus bradycardia, first–degree AV block, inferoseptal QS waves and altered lateral leads repolarization. Recent transthoracic echocardiography (TTE) suggested hypertrophic cardiomyopathy. 24–hour ECG Holter monitoring identified frequent asymptomatic non–sustained ventricular tachycardia (NSVT), prompting Emergency Department evaluation. Blood tests showed normal complete blood count, electrolytes, and thyroid function, with Troponin T at 55 ng/L, CK–MB 7.5 ng/mL, BNP 219 pg/mL, and NT–proBNP 3776 pg/mL. During hospitalization in our Cardiology department, the patient remained asymptomatic. Complete TTE showed severe biventricular wall thickening with a granular sparkling appearance, severe impairment of global left ventricular (LV) longitudinal myocardial deformation (GLS = –7.8%) with “apical sparing” pattern, a mildly impaired LV ejection fraction (EF), LV diastolic dysfunction, and thickening of interatrial septum, raising suspicion for cardiac amyloidosis (Figure 1-2). Tests for AL amyloidosis were negative, including serum/urine immunofixation and free light chain assay (kappa/lambda). Bone scintigraphy (99mTc–HMDP) revealed a Perugini score of 3. Cardiac magnetic resonance imaging confirmed severe increase in LV wall thickness with global hypokinesia (LVEF of 41%) and extensive biventricular late gadolinium enhancement, sparing the apical segments (Figure 3). Coronary angiography found no significant lesions. Telemetry documented recurrent asymptomatic NSVT episodes, leading to initiation of bisoprolol, titrated to 2.5 mg twice daily. The patient was discharged on this well–tolerated regimen, which reduced the arrhythmic burden. HF therapy was initiated. Genetic testing for transthyretin CA and extended genetic analysis for cardiomyopathies are ongoing.Figure 1 Figure 2 Figure 3

Abstract Introduction Secondary tricuspid regurgitation (STR) is currently classified into atrial (A-STR) and ventricular (V-STR) phenotypes. In the multiparametric definition framework of A-STR, an end-systolic (ES) right atrial (RA) to right ventricular (RV) volume ratio ≥1.5 has been proposed among the criteria that favor the diagnosis of A-STR over V-STR. However, no previous study has tested or validated this specific cut-off value. Purpose We aimed to determine the threshold value of the ES RA:RV volume ratio for distinguishing A-STR and V-STR in a large cohort of STR patients evaluated with three-dimensional echocardiography (3DE). Methods Consecutive patients with a first diagnosis of STR (ranging from mild to severe) who underwent complete 3DE evaluation were included in the study. Results 350 patients (75±13 years, 65% women, 59% with severe STR) were included in the final cohort. Even though patients with A-STR and V-STR displayed similar STR severity and comparable RA size, the ES RA:RV volume ratio was significantly higher in A-STR than in V-STR (1.75 [interquartile range (IQR) 1.35-2.45] vs. 1.18 [IQR 0.81-1.66], respectively; p<0.001). On receiver operating characteristic (ROC) analysis, the ES RA:RV volume ratio exhibited a significantly higher predictive power for the A-STR diagnosis [Area under the curve (AUC) 0.73, 95% CI 0.68-0.78] compared to RA maximum volume (AUC 0.6, 95% CI 0.54–0.66, p=0.01), RA minimum volume (AUC 0.59, 95%CI 0.53–0.65, p=0.007), and RA minimum volume: RV end-diastolic volume ratio (AUC 0.57, 95%CI 0.51-0.63, p<0.001) (Figure 1). Additionally, in ROC analysis, the cut-off value of ES RA:RV volume ratio that most effectively differentiated between A-STR and V-STR, yielding the highest AUC (0.68, 95% CI 0.63–0.73) was 1.40. In single-variable logistic regression analyses, the ES RA:RV volume showed a significant association with the A-STR phenotype [Odds ratio (OR) 2.96, 95% CI 2.14 – 4.23, p<0.001]. However, a multivariable model which included ES RA:RV volume ratio, left ventricular (LV) ejection fraction, RV ejection fraction, RA maximum volume, and pulmonary artery systolic pressure (PASP) resulted in an AUC= 0.97 to differentiate between the A-STR and the V-STR phenotypes. Ultimately, the additive diagnostic utility of the ES RA:RV volume ratio was assessed in a hierarchical model χ² analysis, wherein the addition of the ES RA:RV volume ratio to a model including LV ejection fraction, RV ejection fraction, RA maximum volume, and PASP improved the model, strengthening the prediction for the A-STR phenotype (Figure 2). Conclusions ES RA:RV volume ratio ≥1.4 favors A-STR over V-STR. This echocardiographic parameter should be consistently evaluated and reported in STR patients due to its increased diagnostic power. Figure 1. Figure 2.

Abstract Background In patients with heart failure with reduced ejection fraction (HFrEF), a left ventricular ejection fraction (LVEF) less than 35% has been identified as a significant risk factor for increased mortality. As a result, all studies assessing the indications and outcomes of implantable cardioverter-defibrillators and cardiac resynchronization therapy in HFrEF used this cut-off, measured by 2-dimensional echocardiography (2DE). However, many patients with HFrEF and a LVEF >35% by 2DE, who do not qualify for device therapy, still experience significant mortality. Purpose To investigate whether, in patients hospitalized with both ischemic and non-ischemic HFrEF, the LVEF measured by 3-dimensional echocardiography (3DE) could identify better patients at high risk of death, thereby indicating the need for device therapy. Methods 322 consecutive patients (60±11 years, 72% men), hospitalized for HFrEF or HFmrEF, were assessed using both 2DE and 3DE, including full-volume acquisitions of the LV. From 2D datasets, LV end-systolic (LVESV) and LV end-diastolic (LVEDV) volumes, and LVEF were estimated. From the 3D volumes, the same parameters were measured. Patients were discharged on optimal HF treatment, according to current ESC guidelines, and were followed for 24±8 months after the initial event. The primary outcome was cardiovascular death (CD). Results At admission, 43% patients were in NYHA class II, 25% in NYHA class III, and 33% in NYHA class IV. There was a similar burden of ischemic and non-ischemic etiology (52% vs 48%). Mean 2D LVEF was 31±11%, while mean 3D LVEF was 30±10% (p=NS). There were 62 CD (19%) during follow-up. Binary logistic regression for the 2D and 3DE parameters showed that only 3D LVEF was a significant predictor of death (β=-0.04, OR 0.96, 95%CI 0.93-0.98, p=0.003). By 2DE, 206 patients (64%) had LVEF <35%, of whom 47 patients died (23%) and 159 patients survived (77%), whereas by 3DE, 215 patients (67%) had LVEF <35%, of whom 60 patients died (28%) and 155 patients survived (72%). Consequently, 2D LVEF <35% identified 47 out of 62 deaths (76%), whereas 3D LVEF <35% identified 60 out of 62 deaths (97%). By ROC Analysis, 3DE was superior to 2DE for prediction of survival: AUC 0.62, p=0.03 for 3D LVEF vs. AUC 0.56, p=0.09 for 2D LVEF. Kaplan-Meier analysis (Figure) showed that 2D LVEF <35% discriminated between survivors and non-survivors with a Chi-square of 6.8, p=0.01, whereas 3D LVEF <35% discriminated between survivors and non-survivors with a Chi-square of 30.3, p<0.001. Conclusion 3DE assessment of LVEF and its cut-off of 35% enhances the identification of patients with HFrEF at high risk of death. This suggests that 3DE should be utilized for risk stratification in HFrEF, potentially leading to more accurate indications for device therapy. Survival according to 2D vs 3D LVEF