Sanna GD, Milani P, Di Simone VA
… +4 more, Carini V, Nuvolone M, Casu G, Palladini G
Eur Heart J Imaging Methods Pract
· 2026 Jan · PMID 42305910
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Amyloidosis refers to a heterogenous group of systemic diseases characterized by the presence of a misfolded protein that deposits as amyloid fibrils in the interstitium of organs and tissues. The vast majority of cases...Amyloidosis refers to a heterogenous group of systemic diseases characterized by the presence of a misfolded protein that deposits as amyloid fibrils in the interstitium of organs and tissues. The vast majority of cases of cardiac involvement (cardiac amyloidosis-CA) are due to immunoglobulin light chain (AL) amyloidosis, or transthyretin (ATTR) amyloidosis (either in its wild-type form-ATTRwt, or variant-ATTRv). The diagnostic workup of these diseases reflects the differences in terms of aetiology. Although imaging techniques represent fundamental tools in the diagnosis and follow-up of patients CA, they present several limitations. Cardiac biomarkers, particularly natriuretic peptides and troponins, overcome most of these limitations. They can be more sensitive in the detection of early phases of the disease but, overall, they currently represent the most powerful tool to define disease stage, organ response and disease progression. There is mounting evidence regarding the use of specific laboratory biomarkers to monitor treatment response. The information provided by advanced imaging techniques should be regarded as complementary and not as substitute for that provided by laboratory biomarkers, as only these can often be able to unveil the unseen.
Swamy AK, Krishnan D, Umredkar PN
… +5 more, Hn A, Palani SR, Rajagopal V, Narayan P, Padmanabhan D
Eur Heart J Digit Health
· 2026 Jun · PMID 42305247
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AIMS: Echocardiography is a key diagnostic modality for cardiac dysfunction but is often over utilized due to variability in pre-test clinical assessment. There is a need for a scalable, cost-effective screening tool tha...AIMS: Echocardiography is a key diagnostic modality for cardiac dysfunction but is often over utilized due to variability in pre-test clinical assessment. There is a need for a scalable, cost-effective screening tool that can reduce unnecessary referrals without compromising diagnostic accuracy. To develop and validate an AI tool that uses standard 12-lead ECG images to predict the presence of major echocardiographic abnormalities, including reduced ejection fraction (EF ≤35%), valvular heart disease, and elevated pulmonary artery pressure, as a triage tool prior to echocardiography. METHODS AND RESULTS: 51,055 patients aged ≥15 years from a tertiary cardiac care centre, which underwent ECG and echocardiography on the same day between January 2021, and February 2024 were identified. ECGs were stored as images and pre-processed for model input. Echocardiographic findings were extracted using structured reports and regular expression-based keyword searches. The final dataset ( = 52,817) was split into training (40,796), epoch-monitoring (2,148), and testing (9,873) sets. An ensemble of 3 deep learning models was trained. Model performance was assessed using AUROC, PRAUC, sensitivity, specificity, positive predictive value, and negative predictive value. The internal test set demonstrated an AUROC of 0.87 (95% CI: 0.86-0.88) and PRAUC of 0.66 (95% CI: 0.65-0.69). At the Youden threshold (0.27), sensitivity, specificity, PPV, and NPV were 0.80, 0.80, 0.46, and 0.95, respectively. External validation was performed on 20,053 patients. It yielded an AUROC of 0.84 and PRAUC of 0.50. CONCLUSION: The proposed AI model accurately identifies major echocardiographic abnormalities from ECG images, achieving high NPV and demonstrating strong generalizability.
BACKGROUND AND AIMS: Low-dose mineralocorticoid receptor antagonists (MRAs) are guideline-recommended heart failure (HF) therapies. However, MRAs increase aldosterone production, and the sub-saturating doses utilized may...BACKGROUND AND AIMS: Low-dose mineralocorticoid receptor antagonists (MRAs) are guideline-recommended heart failure (HF) therapies. However, MRAs increase aldosterone production, and the sub-saturating doses utilized may allow continued mineralocorticoid receptor (MR) stimulation. The aim of the current analysis was to understand how baseline and change in aldosterone concentrations during MRA therapy impacts MR activity and clinical outcomes. METHODS: HF cohorts with MRA exposure and plasma aldosterone concentrations available were included in patient-level, pooled cohort analyses [DOSE, CARRESS-HF, MDR, and TOPCAT (n = 1019)]. In the MDR cohort (n = 136), urine sodium to potassium ratio was utilized to quantitate MR activity. The relationship of pre-MRA aldosterone concentration, MRA use, and clinical outcomes were meta-analysed utilizing the above pooled cohorts in addition to the EARLIER (n = 300) and EPHESUS (n = 453) trials. RESULTS: MRA use was associated with significantly higher median aldosterone concentrations [MRA = 310 (interquartile range, IQR 180, 533) pg/mL vs no MRA = 174 (IQR 106, 299) pg/mL, P < .001] in the pooled cohort. In the MDR cohort, higher aldosterone was correlated with higher MR activity, with a similar relationship on MRA (r = -.52, P < .001) vs off MRA (r = -.44, P < .001, P interaction = .65), differing only in that higher aldosterone concentrations were required on MRA to achieve the same level of MR activity. In patients with high pre-MRA aldosterone, new MRA initiation reduced MR activity, but MRA initiation increased MR activity in patients with low pre-MRA aldosterone [median change in urine Na/K with high aldosterone =1.4 (IQR 1.1, 2.9) vs low aldosterone = -.9 (IQR -2.1, -.1), P < .001]. In the pooled cohort, the association between MRA use and clinical outcomes was dependent on pre-MRA aldosterone concentration (P interaction = .005). In patients with high pre-MRA aldosterone, MRA was associated with substantially improved clinical outcomes [hazard ratio (HR) .63, 95% confidence interval (CI) .42-.92, P = .02]. However, in patients with low pre-MRA aldosterone, MRA use was associated with worse clinical outcomes (HR 1.66, 95% CI 1.12-2.45, P = .01). CONCLUSIONS: Low-dose MRAs significantly increase aldosterone but inadequately block MR activity (measured by urine Na/K) at these new higher aldosterone concentrations. In patients with high pre-MRA aldosterone, MRA use is associated with improved MR activity and clinical outcomes. However, in patients with lower pre-MRA aldosterone concentrations, MRA use is associated with worsened MR activity and clinical outcomes. MRAs remain guideline-directed HF medications with established population level benefit, but these hypothesis-generating findings indicate additional research is warranted to understand if outcomes can be further improved.
BACKGROUND AND AIMS: The role of genetic testing as part of universal screening programmes for familial hypercholesterolaemia (FH) in children is not well defined. Here, a two-step approach to identify children carrying...BACKGROUND AND AIMS: The role of genetic testing as part of universal screening programmes for familial hypercholesterolaemia (FH) in children is not well defined. Here, a two-step approach to identify children carrying FH-causing variants was investigated. METHODS: In this study from Southern Germany, paediatricians were invited to offer FH screening to all children aged 4.8-14.9 years at routine paediatric examinations. The FH screening programme began in September 2020 in Bavaria and has involved up to 480 paediatricians. It included biochemical and genetic testing using 0.2 mL of blood taken from a fingertip. In case of low-density lipoprotein cholesterol (LDL-C) serum concentration ≥3.36 mmol/L (≥130 mg/dL), FH-causing variants were determined in the same sample with a focused panel covering most frequent variants (n = 48) and sequencing of relevant genes. RESULTS: Out of 25 431 children screened so far, 1689 children had an LDL-C ≥ 3.36 mmol/L (>130 mg/dL), which defined this concentration as the 93rd percentile. Pathogenic variants were identified by the focused panel in 157 and by next-generation sequencing in 283 children, respectively. While 17% (283/1670) of all genetically analysed children tested positive, the fraction of individuals with FH-causing variants increased across the spectrum of LDL-C serum concentrations from 4.7% (23/492) at 3.36-3.49 mmol/L (130-135 mg/dL) to 78.6% (81/103) above 5.17 mmol/L (200 mg/dL). Overall, the prevalence of FH-causing variants was high (1:90). One reason was a founder variant (n = 63) within the LDLR gene, found 40 times more frequent than European average. The analysis of recruitment data revealed significant ascertainment bias, with lower recruitment rate practices exhibiting higher prevalence. After adjustment for the bias using a generalized linear mixed model, the predicted prevalence was 1 in 163 (0.61%), which is highly consistent with large-scale genomic benchmarks as gnomAD (1:165, n = 622 057) and the UK Biobank (1:176, n = 48 741). CONCLUSIONS: The prevalence of FH determined in this study is significantly higher than previously published estimates (∼1:250), highlighting the importance of this condition for public health and supporting calls for a national paediatric screening programme, given the availability of effective treatment options. For children between 5 and 15 years, biochemical screening is an effective way to select patients for genetic testing, with sequencing of candidate genes being superior to variant screening. In summary, the VRONI study demonstrates the feasibility and efficacy of a combined biochemical and genetic screening for FH in children.
The increasing complexity of cardiovascular procedures, regulatory constraints, and heightened patient safety requirements have necessitated a fundamental transformation in medical education of interventional cardiology...The increasing complexity of cardiovascular procedures, regulatory constraints, and heightened patient safety requirements have necessitated a fundamental transformation in medical education of interventional cardiology and cardiac surgery beyond traditional apprenticeship models. A comprehensive review of simulation-based training (SBT) in cardiovascular medicine and surgery was conducted, analysing evidence from 2020 to 2025 across multiple databases and incorporating data from systematic reviews, randomized controlled trials, and international surveys. SBT demonstrates significant educational benefits with moderate to large effect sizes across all training domains. Meta-analyses of over 6000 participants show technical skill improvements of 20%-40%, medical error reduction of 51%, and large effect sizes for skill acquisition (Cohen's d = 0.85-2.2). Contemporary platforms, including virtual reality, haptic feedback systems, and artificial intelligence-powered adaptive, learning achieve high simulation accuracy for complex procedures. Despite proven efficacy, implementation of SBT faces barriers including cost ($50 000-$200 000 per high-fidelity system) and limited access, with 71% of practitioners reporting insufficient simulation exposure. SBT represents a paradigm shift in cardiovascular education, offering standardized, patient risk-free environments for technical skill development. While evidence demonstrates improved procedural competency and knowledge acquisition with SBT, the critical gap remains in demonstrating direct patient outcome improvements. Future integration of artificial intelligence, digital twins, and personalized learning platforms promises to further transform training in interventional cardiology and cardiothoracic surgery.
AIMS: Current guidelines recommend considering long-term oral anticoagulation in patients with new-onset postoperative atrial fibrillation (POAF) after cardiac surgery, balancing stroke and bleeding risk. However, no spe...AIMS: Current guidelines recommend considering long-term oral anticoagulation in patients with new-onset postoperative atrial fibrillation (POAF) after cardiac surgery, balancing stroke and bleeding risk. However, no specific approach to bleeding risk assessment is provided. We explored in a proof-of-concept study whether a bleeding risk score can identify patients with POAF after coronary artery bypass grafting (CABG) with increased risk of post-discharge major bleeding. METHODS AND RESULTS: This observational cohort study included 4436 patients with POAF after CABG in 2009-2020 without oral anticoagulation. The four-item PRECISE-DAPT score (based on age, creatinine clearance, preoperative hemoglobin concentration, and previous bleeding) was calculated for all patients. Bleeding risk was defined as high (≥25 points), medium (16-24 points), or low (≤15 points). Associations between bleeding risk and major bleeding events during the first postoperative year were assessed by Cox regression. Discrimination was evaluated with C-statistics, and calibration by comparing expected and observed bleeding rates. Major bleeding occurred in 2.1% of patients during the first year. The score classified 36.0% of patients as high bleeding risk. The hazard ratio for high versus low bleeding risk was 4.81 (95% CI 2.59-8.96). The area under the receiver operating characteristic curve was 0.68 (95% CI 0.63-0.73). Calibration showed good agreement between expected and observed bleeding events in patients with an annual bleeding risk up to 7%. CONCLUSIONS: A bleeding risk score can be used to stratify patients with POAF after CABG into groups with different post-discharge bleeding risk. Further studies are necessary to identify the optimal risk score and its role in OAC decision pathway to improve clinical outcomes.
AIMS: End-stage hypertrophic cardiomyopathy (HCM), defined as a left ventricular (LV) ejection fraction (LVEF) < 50%, is associated with poor prognosis; however, predictors of progression remain unclear. We aimed to iden...AIMS: End-stage hypertrophic cardiomyopathy (HCM), defined as a left ventricular (LV) ejection fraction (LVEF) < 50%, is associated with poor prognosis; however, predictors of progression remain unclear. We aimed to identify prognostic factors for progression to end-stage HCM. METHODS AND RESULTS: We analyzed 925 patients with HCM between 2007 and 2023 who underwent ≥1 year of follow-up echocardiography. The primary outcome was progression to end-stage HCM, defined as an LVEF <50% without reversible causes. A CMR subcohort included 491 patients with baseline CMR. During a median follow-up of 6.5 years (IQR: 3.3-10.7), 35 patients (3.8%) progressed to end-stage HCM (10-year cumulative incidence: 4.4%, 95% CI: 2.5-6.2%). LVEF, LV apical aneurysm, and LARS were independent predictors of progression to end-stage HCM (per 1% decrease in LARS: adjusted HR 1.10, 95% CI 1.04-1.17, p < 0.001), and impaired LARS (<16.9%) was associated with a higher risk. In the CMR subcohort, LARS remained an independent predictor after adjusting for late gadolinium enhancement (LGE%) (adjusted HR 1.11, 95% CI 1.02-1.20, p = 0.011). Adding LARS to a model including LVEF, LV apical aneurysm, and LA size yielded significant incremental prognostic value (global χ2 27.1 to 40.1; p < 0.001). Similar incremental value was observed in models including LGE% in the CMR subcohort. After progression to end-stage HCM, prognosis was poor, with 2-year cardiovascular event-free survival rate of 71.0%. CONCLUSIONS: Progression to end-stage HCM is infrequent but associated with poor prognosis. Impaired LARS independently predicts disease progression beyond conventional markers, supporting its role in risk stratification.
Transcatheter aortic valve implantation (TAVI) is increasingly used for the treatment of aortic stenosis. Recently published guidelines favour now TAVI in all patients 70 years or older who have tricuspid valves and suit...Transcatheter aortic valve implantation (TAVI) is increasingly used for the treatment of aortic stenosis. Recently published guidelines favour now TAVI in all patients 70 years or older who have tricuspid valves and suitable anatomy. However, while a number of randomized controlled trials confirm that TAVI and surgical aortic valve replacement (SAVR) provide equivalent outcomes up to 5 years, data beyond 5 years are still scarce and real-world registry data report indeed conflicting results. Higher rates of complications after TAVI such as pacemaker requirement and paravalvular regurgitation, which have been shown to be associated with worse outcome may become more relevant after 5 years and still favour surgery on long-term. In addition, long-term durability data for TAVI are still insufficient. Thus, the question whether SAVR should still be the first choice for patients with a life expectance beyond 5 years is therefore justified. This debate summarizes the pros and cons for this claim.
Hsieh PN, Agrawal P, Alok A
… +9 more, Kumar S, Ramanathan C, Murthy VL, Varma N, Nagarajan V, Ambrosy AP, Ramsis M, Armoundas AA, Singh JP
Eur Heart J Digit Health
· 2026 Jun · PMID 42294406
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AIMS: Artificial intelligence (AI)-enabled electrocardiograms (AI-ECG) can detect left ventricular systolic dysfunction (LVSD), but demographic imbalance in training datasets may introduce bias. Foundational models, pret...AIMS: Artificial intelligence (AI)-enabled electrocardiograms (AI-ECG) can detect left ventricular systolic dysfunction (LVSD), but demographic imbalance in training datasets may introduce bias. Foundational models, pretrained on large and diverse datasets, may mitigate such concerns. We aimed to assess the impact of demographic composition in training datasets on the performance of an ECG Foundational Model (ECGFM) for diagnosing LVSD. METHODS AND RESULTS: We developed an ECG foundational model (ECGFM) using transformer architecture and self-supervised pretraining on 983 200 ECGs. Using 44 815 paired ECG-echocardiogram datasets, we trained the model under three biased scenarios: (1) sex-skewed (male-only or female-only), (2) race-skewed (White-only or non-White), and (3) balanced. Models were evaluated on a test cohort consisting of 4663 male patients (52%) and 4300 female patients (48%) for the sex configuration and 4440 (49.5%) White, 558 (6.2%) Black, 925 Asian (10.3%), and 3040 other (33.9%) patients, for the race-based configuration using area under the receiver operating characteristic curve (AUROC). The ECGFM demonstrated consistent performance across all demographic configurations. Training on male-only or female-only cohorts yielded comparable AUROC scores of 0.85-0.90 for both sexes in the test set in predicting LVSD. Similarly, training on White-only or non-White cohorts resulted in robust AUROC scores (≥0.90) across all racial groups, including Asian, Black, Hispanic/Latino, and American Indian/Native Alaskan subgroups. Balanced and imbalanced training produced comparable accuracy, sensitivity, and specificity. The performance of the model was externally tested in EchoNext, revealing AUROC scores 0.823-0.917 for sex and 0.822-0.917 for race. CONCLUSION: Our transformer-based ECG foundational model pretrained using self-supervised learning demonstrated preserved diagnostic accuracy for LVSD across diverse demographic groups, even when trained on demographically imbalanced datasets.
Vecchiato M, Zorzi A, Pilichou K
… +2 more, Pescatore V, Brugin E
Eur Heart J Case Rep
· 2026 Jun · PMID 42292508
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BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by adrenergically mediated ventricular arrhythmias occurring in structurally normal hearts. C...BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by adrenergically mediated ventricular arrhythmias occurring in structurally normal hearts. CASE SUMMARY: A young asymptomatic female competitive football player with a structurally normal heart developed progressively complex exercise-induced ventricular arrhythmias over several years, leading to the diagnosis of CPVT confirmed by identification of a novel pathogenic RYR2 variant through familial cosegregation. DISCUSSION: This case illustrates how CPVT may present with a subtle and fluctuating phenotype, remaining concealed for years despite regular cardiovascular screening in athletes. Serial exercise-based testing was crucial to unmask the arrhythmic substrate when resting investigations and family history were initially unremarkable. Comprehensive family evaluation enabled reclassification of a novel RYR2 variant, emphasizing the importance of integrating clinical and genetic data in inherited arrhythmia syndromes.
Eur Heart J Case Rep
· 2026 Jun · PMID 42292506
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BACKGROUND: Idiopathic pulmonary artery dilatation (IPAD) is a rare condition characterized by isolated dilatation of the pulmonary artery in the absence of congenital heart defects or other secondary causes. Here, we re...BACKGROUND: Idiopathic pulmonary artery dilatation (IPAD) is a rare condition characterized by isolated dilatation of the pulmonary artery in the absence of congenital heart defects or other secondary causes. Here, we report a rare case of IPAD complicated by severe aortic stenosis (AS), managed with simultaneous aortic valve replacement (AVR) and pulmonary artery graft replacement. CASE SUMMARY: A 74-year-old woman with type 1 diabetes was followed for IPAD. Initial evaluations ruled out shunt diseases and secondary causes of pulmonary artery dilatation. Over 5 years of follow-up, mild AS progressed to severe AS, leading to exertional dyspnoea. A heart team decided on simultaneous AVR with Inspiris Resilia 23 mm and pulmonary artery replacement with an expanded polytetrafluoroethylene (ePTFE) graft. Pulmonary regurgitation was also repaired. Postoperative recovery was uneventful, and the patient was discharged on postoperative day 22. This case highlights the importance of multidisciplinary approaches in managing rare vascular pathologies and concurrent cardiac diseases. DISCUSSION: This is the first report of IPAD with severe AS managed via simultaneous AVR and pulmonary artery graft replacement. This report underscores the importance of individualized management strategies in rare cases where standard guidelines are unavailable.