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Introduction: Data on the characteristics and outcomes of pregnancy and among patients with Fontan physiology are limited. We aimed to evaluate the immediate and long-term outcomes among these patients who were followed at our centre.

Methods: We included adult patients who had undergone Fontan surgery for congenital heart disease and were pregnant between 1994 and 2021. We examined maternal and obstetric outcomes.

Results: In a cohort of 109 patients following Fontan procedure, 51 patients were women, and 19 patients (37%) had a pregnancy during the follow-up period, accounting for a total of 46 pregnancies. Intrauterine growth retardation of the fetus was common, observed in 23% of all pregnancies and 50% of live births. The main fetal complication was prematurity, observed in 43% of all pregnancies and 90% of live birth. The maternal complications included pre-eclampsia (one patient), placental detachment (one patient), acute heart failure exacerbation (one patient), arrhythmia (three atrial arrhythmias) and major peripartum haemorrhage (two patients), with no peripartum death.

Conclusions: Over one-third of women with Fontan physiology in our cohort had a documented pregnancy. Maternal and obstetric complications were common among these patients, and expanded long-term data is needed. Limitations, including small sample size and survival bias, may have underestimated the risk of adverse outcomes in this cohort.

Background: Growth differentiation factor 15 (GDF15) is a cytokine responding to oxidative stress and inflammation, and it regulates appetite and energy balance. The association between GDF15 and clinical factors and its prognostic value in elderly multimorbid patients with heart failure with preserved ejection fraction (HFpEF) have not been well unknown.

Methods: This exploratory analysis is part of the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF (UMIN000021831). A predefined subcohort of 212 patients underwent multi-biomarker testing. Of these, we analysed 181 patients with available GDF15 data. The primary endpoint was a composite of all-cause death and hospitalisation for HF.

Results: In this analysis population, the median age was 81 (75-85) years, with 48% male patients. GDF15 significantly correlated with cardiac burden, anaemia, renal dysfunction and inflammation. Notably, poor nutritional status was significantly associated with GDF15. GDF15 was linked to poor prognosis in this elderly multimorbid cohort with HFpEF (adjusted HR for log-transformed GDF15: 13.67, 95% CI: 2.78 to 67.22, p=0.001). Furthermore, GDF15 added significant incremental value to the MAGGIC risk score (net reclassification improvement=0.4955 (95% CI: 0.1367 to 0.8543), p=0.007; integrated discrimination improvement=0.0278 (95% CI: 0.0013 to 0.0543), p=0.040).

Conclusions: GDF15 was associated with anaemia, inflammation, renal dysfunction, cardiac burden and malnutrition. It demonstrated prognostic value in elderly multimorbid HFpEF patients, suggesting its potential role as a complementary marker for the prognostic risk assessment of HFpEF patients.

Trial registration number: UMIN-CTR ID: UMIN000021831.

Aims: This study aimed to determine the robustness, reproducibility and representativeness of the landmark Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF) (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF (ROCKET AF) randomised trials through replication in an observational AF patient registry.

Methods and results: Patients from the Global Anticoagulant Registry in the FIELD (GARFIELD)-AF registry treated with apixaban, rivaroxaban or vitamin K antagonist (VKA) were assessed for eligibility for the ARISTOTLE and ROCKET AF trials. HRs of apixaban and rivaroxaban versus comparator for stroke/systemic embolism, major bleeding and all-cause mortality within 2 years follow-up were calculated using propensity score overlap-weighted Cox models. Among GARFIELD-AF patients on apixaban, 2570/3615 (71%) would have been eligible for ARISTOTLE. Among patients using rivaroxaban, 2005/4914 (41%) would have been eligible for ROCKET AF. Eligibility rates were steady over time, with minor differences across medical specialties. Real-world AF patients selected according to trial criteria had lower cardiovascular burden than the original trial participants, especially compared with ROCKET AF. HRs (95% CI) for apixaban versus VKA among ARISTOTLE-eligible users were 0.57 (0.34 to 0.94) for stroke/systemic embolism, 0.76 (0.48 to 1.20) for major bleeding and 0.89 (0.70 to 1.12) for all-cause mortality. Among ROCKET AF-eligible rivaroxaban users, HRs for rivaroxaban versus VKA were 0.90 (0.57 to 1.43), 0.92 (0.59 to 1.43) and 0.86 (0.69 to 1.08), respectively. All safety and efficacy estimates were similar to those in the original trials.

Conclusion: Real-world representativeness of the selection criteria was greater for ARISTOTLE than ROCKET AF. The pivotal randomised trials of apixaban and rivaroxaban versus warfarin can be successfully emulated in real-world AF patients by applying trial-specific selection criteria and appropriate methodology for non-randomised treatment allocation.

Trial registration number: NCT01090362.

Background: Cardiogenic shock (CS) induced by severe aortic stenosis (AS) is a life-threatening condition with high mortality. Despite advancements in emergency interventions, the optimal treatment approach remains uncertain.

Aim: This study aimed to systematically review and analyse the existing evidence on outcomes of emergency transcatheter aortic valve implantation (eTAVI) and emergency balloon aortic valvuloplasty (eBAV) in CS patients.

Methods: A systematic literature review and meta-analysis was performed. The primary endpoint was mortality at 30 days. Secondary endpoints were in-hospital mortality, 1-year mortality, bleeding, major vascular complications, myocardial infarction, stroke, incidence of pacemaker implantation, acute kidney injury and aortic regurgitation.

Results: Seventeen studies were included, totalling 2811 patients. The analysis revealed a 30-day mortality pooled estimated rate for eTAVI of 19% (CI 0.17 - 0.20) and for eBAV 39% (CI 0.32 - 0.46). In-hospital mortality pooled estimated rates were 11% for eTAVI (CI 0.06 - 0.18) and for eBAV 40% (CI 0.28 - 0.54). One-year mortality pooled estimated rates for eTAVI were 29% (CI 0.20 - 0.40) and for eBAV 67% (CI 0.58 - 0.74). Pooled estimated rates of any bleeding were 12% for eTAVI (CI 0.06 - 0.20) and 15% for eBAV (CI 0.10 - 0.21). The rate of major vascular complications for eTAVI was 8% (CI 0.07 - 0.10) and 3% for eBAV (CI 0.0 - 0.23).

Conclusions: This meta-analysis indicates that mortality in CS due to AS remains high despite emergency interventional treatment. These findings offer critical insights for clinical decision-making optimising patient care in this critically ill population.

Background: The role of cyclic guanosine 3',5'-monophosphate (cGMP) after acute myocardial infarction (AMI) is not well understood despite its significance as a second messenger of natriuretic peptides (NPs) in cardiovascular disease. We investigated the association between the NP-cGMP cascade and left ventricular reverse remodelling (LVRR) in anterior AMI.

Methods: 67 patients with their first anterior AMI (median age, 64 years; male, 76%) underwent prospective evaluation of plasma concentrations of the molecular forms of A-type and B-type natriuretic peptide (BNP) and cGMP from immediately after primary percutaneous coronary intervention (PPCI) to 10 months post-AMI. The estimated mature BNP (emBNP) concentration was calculated as the difference between total BNP and prohormone of BNP (proBNP) concentrations. Patients were divided into LVRR and non-LVRR groups on the basis of residuals between observed change in left ventricular end-systolic volume index on MR during the first 11 months after AMI and change adjusted for proBNP concentration immediately post-PPCI, which was calculated with regression. The LVRR group (n=33) had residuals below the median; the non-LVRR group (n=34) had residuals at or above the median.

Results: The LVRR group had higher freedom from major adverse cardiac and cerebrovascular events (MACCEs) than the non-LVRR group during a median follow-up of 9.9 years (p=0.008). The presence of LVRR (HR 0.256; 95% CI 0.081 to 0.809; p=0.028) and peak creatine phosphokinase-myocardial band level (per 100 IU/L) (HR 1.22; 95% CI 1.02 to 1.46; p=0.027) were independent predictors of MACCE after adjusting for age, male sex, infarct size and hypertension. Multivariable analyses identified logarithmic proBNP and emBNP concentrations from 12 hours to 5 days post-AMI and logarithmic cGMP concentration from immediately post-PPCI to 3 days post-AMI as independent predictors of LVRR (p<0.05).

Conclusions: Early-phase BNP-cGMP cascade activation might play a crucial role in LVRR in anterior AMI.

Background: Visual assessment of coronary CT angiography (CCTA) is time-consuming, influenced by reader experience and prone to interobserver variability. This study evaluated a novel algorithm for coronary stenosis quantification (atherosclerosis imaging quantitative CT, AI-QCT).

Methods: The study included 208 patients with suspected coronary artery disease (CAD) undergoing CCTA in Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography-1. AI-QCT and blinded readers assessed coronary artery stenosis following the Coronary Artery Disease Reporting and Data System consensus. Accuracy of AI-QCT was compared with a level 3 and two level 2 clinical readers against an invasive quantitative coronary angiography (QCA) reference standard (≥50% stenosis) in an area under the curve (AUC) analysis, evaluated per-patient and per-vessel and stratified by plaque volume.

Results: Among 208 patients with a mean age of 58±9 years and 37% women, AI-QCT demonstrated superior concordance with QCA compared with clinical CCTA assessments. For the detection of obstructive stenosis (≥50%), AI-QCT achieved an AUC of 0.91 on a per-patient level, outperforming level 3 (AUC 0.77; p<0.002) and level 2 readers (AUC 0.79; p<0.001 and AUC 0.76; p<0.001). The advantage of AI-QCT was most prominent in those with above median plaque volume. At the per-vessel level, AI-QCT achieved an AUC of 0.86, similar to level 3 (AUC 0.82; p=0.098) stenosis, but superior to level 2 readers (both AUC 0.69; p<0.001).

Conclusions: AI-QCT demonstrated superior agreement with invasive QCA compared to clinical CCTA assessments, particularly compared to level 2 readers in those with extensive CAD. Integrating AI-QCT into routine clinical practice holds promise for improving the accuracy of stenosis quantification through CCTA.

Introduction: Conductive disturbances requiring permanent pacemaker (PPM) implantation remain a major concern after transcatheter aortic valve implantation (TAVI).

Aims: To assess the impact of aortic valve calcium score (AVCS) on conductive disturbances requiring PPM after TAVI.

Methods: All patients who underwent TAVI with accessible AVCS from the preprocedural CT scan report were included in this retrospective single-centre study. The primary endpoint was the occurrence of a conductive disturbance requiring PPM at 30 days. The association between PPM and AVCS, with its incremental prognostic value, was analysed using multivariable logistic regression, receiver operating characteristic curve analysis and likelihood ratio (LR) test.

Results: We included 761 patients of which 125 (16%) required PPM at 30 days. AVCS score was significantly higher in patients requiring PPM (3788 (2487-5218) vs 3050 (2043-4367) AU, p<0.001). Using multivariable analysis, preprocedural right bundle branch block (RBBB) (OR 6.61, 95% CI 3.82 to 11.5, p<0.001), first atrioventricular block (OR 1.71, 95% CI 1.03 to 2.83, p=0.037), self-expanding valve (OR 3.25, 95% CI 1.17 to 9.09, p=0.025) and AVCS>4510 AU (OR 1.83, 95% CI 1.04 to 3.20, p=0.035) were independently associated with PPM. AVCS had an incremental discriminative value (C-index 0.79 vs 0.77, LR test p=0.036) over and above traditional PPM risk factors. An algorithm was proposed based on the initial presence of RBBB, AVCS and the type of implanted valve.

Conclusion: Even if RBBB remained the strongest predictor of PPM post-TAVI, this study suggests that a high AVCS may help identifying patients at increased risk of PPM after TAVI, especially among those without pre-existing RBBB.

Purpose: We examined whether end-to-end deep-learning models could detect moderate (≥50%) or severe (≥70%) stenosis in the left anterior descending artery (LAD), right coronary artery (RCA) or left circumflex artery (LCX) in iodine contrast-enhanced ECG-gated coronary CT angiography (CCTA) scans.

Methods: From a database of 6293 CCTA scans, we used pre-existing curved multiplanar reformations (CMR) images of the LAD, RCA and LCX arteries to create end-to-end deep-learning models for the detection of moderate or severe stenoses. We preprocessed the images by exploiting domain knowledge and employed a transfer learning approach using EfficientNet, ResNet, DenseNet and Inception-ResNet, with a class-weighted strategy optimised through cross-validation. Heatmaps were generated to indicate critical areas identified by the models, aiding clinicians in understanding the model's decision-making process.

Results: Among the 900 CMR cases, 279 involved the LAD artery, 259 the RCA artery and 253 the LCX artery. EfficientNet models outperformed others, with EfficientNetB3 and EfficientNetB0 demonstrating the highest accuracy for LAD, EfficientNetB2 for RCA and EfficientNetB0 for LCX. The area under the curve for receiver operating characteristic (AUROC) reached 0.95 for moderate and 0.94 for severe stenosis in the LAD. For the RCA, the AUROC was 0.92 for both moderate and severe stenosis detection. The LCX achieved an AUROC of 0.88 for the detection of moderate stenoses, though the calibration curve exhibited significant overestimation. Calibration curves matched probabilities for the LAD but showed discrepancies for the RCA. Heatmap visualisations confirmed the models' precision in delineating stenotic lesions. Decision curve analysis and net reclassification index assessments reinforced the efficacy of EfficientNet models, confirming their superior diagnostic capabilities.

Conclusion: Our end-to-end deep-learning model demonstrates, for the LAD artery, excellent discriminatory ability and calibration during internal validation, despite a small dataset used to train the network. The model reliably produces precise, highly interpretable images.

Background and aims: Hypertrophic cardiomyopathy (HCM) has various aetiologies, including genetic conditions like Fabry disease (FD), a lysosomal storage disorder. FD prevalence in high-risk HCM populations ranges from 0.3% to 11.8%. Early diagnosis of FD is crucial due to available treatments, but its rarity and diverse symptoms complicate identification. Heart-specific FD variants often lead to late diagnoses due to the absence of typical FD symptoms. This prospective study (NCT04943991) was conducted to identify patients with undiagnosed FD using electronic health records (EHR) at a German tertiary-care hospital.

Methods: Over 20 years (2000-2020), 2824 patients with 'left ventricular hypertrophy (LVH)' or 'hypertrophic cardiomyopathy (HCM)' were identified by full-text search. Exclusion criteria were age over 85, other diagnosed cardiomyopathies, significant valvular heart disease, death, active malignancy and prior FD testing. The remaining patients received an invitation for FD genetic testing.

Results: Of the 2824 identified patients, 2626 (93%) fulfilled the exclusion criteria. Among the 198 included patients, 96 responded, and 55 underwent genetic testing, yielding a response rate of 48% and a testing rate of 28%. In one patient (1.8% of tested), FD was diagnosed with the p.N215S variant. Subsequent family screening revealed six additional FD cases, with four initiating FD-specific therapies. Comprehensive clinical evaluations were conducted in five of the seven identified patients.

Conclusions: Genetic testing of patients with unexplained LVH/HCM using EHR is effective for identifying FD. Subsequent family screening further identified at-risk individuals, promoting regular follow-ups and if needed FD-specific therapies. This approach highlights the potential for broader application in high-risk populations to uncover treatable genetic conditions. The next phase should focus on automating the executed search process.

Trial registration number: NCT04943991.

Background: The majority of functional ischemia tests in patients with suspected chronic coronary syndromes (CCS) yield normal results. Implementing gatekeepers for patient preselection, such as pretest probability (PTP) and/or coronary artery calcium score (CACS), could reduce the number of normal scan results, radiation exposure and costs. However, the efficacy and safety of these approaches remain unclear.

Methods: Three diagnostic algorithms based on PTP, as summarised in the 2019 European Society of Cardiology (ESC) CCS guidelines, were retrospectively applied to 1792 patients with suspected CCS referred for 82Rb-Positron Emission Tomography (⁸²Rb-PET): (1) defer testing if PTP ≤5%; (2) defer if PTP <15%; and (3) defer if PTP ≤5% or PTP 5-15% and CACS 0. The proportion of missed ischemia, number of scans and reduction of normal scan results, radiation exposure and costs were compared with the current gold standard (CACS+PET in every patient). Endpoints were defined as small ischemia (SDS ≥2) and relevant ischemia (≥10% of myocardium).

Results: The mean age of the patients was 65±11 years, and 43% were female. PTP ≤5% and <15% were present in 7.5% and 41.0%, respectively. Algorithm 1 reduced scans, radiation and costs by 7.5% without significantly missing ischemia (sensitivity/negative predictive value (NPV) 98.6%/99.7%). Algorithm 2 showed the largest reduction (41.0%), but sensitivity was significantly reduced (80.2%). Algorithm 3 demonstrated optimal performance, reducing radiation by 17.0% and costs by 17.3% without significantly missing ischemia suggesting excellent safety (sensitivity/NPV 98.0%/99.5%).

Conclusion: Using a diagnostic algorithm combining PTP and CACS (algorithm 3), the number of normal scan results, radiation exposure and costs could be significantly reduced without a significant increase in missed diagnoses suggesting similar outcome and excellent patients safety. Consequently, this approach could help to optimally allocate limited healthcare resources while maintaining patient's safety.