AimsThe aim of this study was to analyse the feasibility, safety, and clinical benefit of the CardioMEMS HF System in different healthcare systems outside the United States of America.Methods and resultsProspective, open-label registry of NYHA class III patients with at least one heart failure hospitalization (HFH) within 12 months before enrolment, regardless of left ventricular ejection fraction. The primary safety endpoints assess the freedom from device/system-related complications (DSRC) and freedom from pressure sensor failure (PSF) at 2 years post-implant. The primary efficacy endpoint was the rate of HFH one year before and one year after implantation.Three hundred and four patients from 37 centres in 6 countries underwent a CardioMEMS implant procedure, which was successful in 98.3% of the cases. At 2 years, there were no DSRCs and only 1 PSF. There were 517 HFH in the year before implant compared with 144 HFH in the year post-implant (risk reduction: 69% (RR: 0.31 95% CI [0.25–0.37]; P < 0.0001). Pulmonary artery (PA) pressures were significantly lowered (mean PA pressure reduction: −3.07 ± 5.91 mmHg, P < 0.0001) with a significant improvement in functional class and quality of life (mean EQ-5D-5L visual analogue score increase 8.1 ± 22.7, P < 0.0001).ConclusionThe results of the COAST study demonstrate that the CardioMEMS HF System is a reliable device, with no device-related complications and very few pressure sensor failures. Its use is associated with a substantial HFH risk reduction, with a significant reduction in PA pressures, an improvement in NYHA classification, and an improvement in quality of life.Clinical registration numberClinicalTrials.gov Identifier: NCT02954341.

Synthetic artificial intelligence (AI) is rapidly redefining biomedical research-yet in cardiovascular medicine, its clinical relevance remains obscure, underexplored, and underestimated. Unlike traditional AI, which interprets data, synthetic AI generates entirely new, patient-like information: from realistic ECG signals to cardiac imaging and virtual cohorts that simulate disease progression. While recent publications have addressed specific synthetic AI tools in cardiology, no prior review has comprehensively synthesized their architectures, clinical applications, and implementation challenges within a single, practice-oriented framework. This State-of-the-Art Review fills that gap. We provide a clear, critical synthesis of core architectures-Generative Adversarial Networks (GANs), Variational Autoencoders (VAEs), Diffusion Models, Transformers, Autoregressive Models, Digital Twins, and Synthetic Cohort Simulators-and map their emerging cardiovascular applications. We examine technical barriers, ethical concerns, regulatory uncertainties, and integration challenges, while anchoring the discussion in real-world clinical priorities. This review is not only a scientific analysis-it is a call to engagement. For academic researchers, it offers conceptual and technical clarity. For clinicians in resource-constrained settings, it presents synthetic AI not as abstract innovation, but as a practical opportunity to enhance diagnostic precision, optimize workflows, and extend clinical insight. Traditional AI supports cardiologists by interpreting data; synthetic AI extends this paradigm by creating new, clinically coherent information that enhances decision-making without replacing physician expertise. As investment grows and methods mature, cardiologists must shape this evolution-not as passive adopters, but as active drivers. This review invites them to take the wheel.

Abstract Background Acute myocardial infarction (AMI) patients face a substantial risk of cardiovascular events and rehospitalization. The impact of the SmartHeart 12-lead ECG telemedicine device on healthcare utilization has not been tested in a US randomized trial. Methods Patients with AMI were randomized at discharge to standard of care without (control group) or with the SmartHeart 12-lead ECG device (intervention group). The primary endpoint was the rate of emergency department (ED) visits, hospital readmissions, and any cardiovascular testing from discharge to 90 days of follow-up. Results The primary endpoint was reached in 57 (59%) patients in the control group and 53 (63%) patients in the intervention group (p = 0.61). However, in the intervention group, only 30% of patients complied with two follow-up training SmartHeart 12-lead ECG transmissions after discharge, and only 24% used the device thereafter. Among device users, ED presentations were lower in the intervention group than in the control group (8.0% vs. 29%, p = 0.04). In all patients advised to present to the ED upon device use (38%) a clinically relevant cardiovascular diagnosis was made. One patient survived a ventricular fibrillation cardiac arrest as advised to present to ED urgently after device use. Conclusion In this U.S.-based RCT, there were no significant differences in the primary outcome in the intention-to-treat analysis. However, according to per-protocol analysis, proper use of the SmartHeart ECG device with 24/7 telemedicine support reduced inappropriate and increased appropriate ED presentations after hospitalization for AMI.

AimsHypoxia-inducible factor (HIF) signalling influences cardiomyocyte differentiation, maturation, and metabolic adaptation under pathological conditions. HIF-Prolyl hydroxylase domain (HIF-PH) inhibitors, which target this pathway, have been introduced for the treatment of renal anaemia. Their precise effect or safety on cardiac function remains unclear because their pharmacokinetics and distribution are not well-understood. This study aimed to examine HIF signalling activation in adult cardiomyocytes (CMs).Methods and resultsWe used tamoxifen (TAM)-inducible, CM-specific von Hippel–Lindau (VHL) knockout (VHL-MCM) mice to activate CM HIF signalling. Then we subjected the mice to normal ageing or high-fat diet (HFD) and L-NAME feeding, a murine model of heart failure with preserved ejection fraction (HFpEF). In normal ageing group, there was no difference in the echocardiographic parameters or tissue fibrosis between VHL-MCM and control mice. VHL-MCM mice exhibited significantly increased capillary density and higher expression levels of HIF-target genes (P = 0.0248, two-way ANOVA). Under HFD + L-NAME treatment, VHL-MCM mice showed transient but significantly preserved global longitudinal strain (GLS) at 12 weeks post-TAM injection compared to controls (P = 0.0284, two-way ANOVA). Sirius red staining indicated a trend towards reduced whole-heart and interstitial fibrosis with significant increase in capillary density in VHL-MCM mice.ConclusionSustained HIF signalling activation in adult CM does not impair the cardiac structure and function in normal ageing process and shows transient yet beneficial effect in murine HFpEF model.

Estriol (E3) is a natural estrogen produced during pregnancy whose physiological role in the adult cardiovascular and pulmonary systems remains poorly understood. Given the established association between estrogens and obesity, our study aims to investigate the interplay between obesity, E3, and their potential cardiopulmonary effects. Effect of E3 on the cardiopulmonary system was evaluated in lean and high-fat diet-induced obese mice using right heart catheterization. Plasma triglyceride and adipokines were quantified using immunological assays, and circulating E3 levels were measured via LC-MS/MS. In vitro experiments were carried out in a human adipocyte cell line and pulmonary artery smooth muscle cells (PASMCs) isolated from rats and patients with pulmonary arterial hypertension. E3 reduces visceral adipose tissue mass in vivo, primarily by attenuating adipocyte inflammation and proliferation. E3 treatment significantly reduced plasma leptin levels, contributing to improved metabolic profiles. In adipocytes, E3 reduced pro-proliferation and inflammatory markers while increasing the expression of antioxidant genes. Additionally, E3 reduced proliferation in isolated PASMCs and E3-induced signalling was observed to be mediated through the ERα receptors. Our findings demonstrate, for the first time, that E3 reduces visceral adipose tissue mass, indicating its role in modulating adipose tissue characteristics while concurrently enhancing metabolic profiles. These results lay the groundwork for future research to investigate the role of E3 in disease prevention and its therapeutic application in cardiopulmonary disorders.

Cardiogenic shock (CS) is the leading cause of in-hospital mortality in patients suffering acute myocardial infarction (AMI). Despite advances in their management, short- and long-term mortality remain unacceptably high. We assessed short and intermediate-term outcomes for a contemporary cohort of patients with AMI-CS managed at a referral centre with a large catchment area, and sought to identify clinical factors portending a favourable prognosis. Of 1162 consecutive, unselected patients with CS we studied 316 with AMI-CS. Our primary endpoint was native heart survival (NHS) defined as survival to discharge without advanced heart failure (HF) therapies. Our secondary endpoints were adverse events, overall survival, and readmissions up to 1 year following discharge. Association of clinical data with NHS was analysed using logistic regression. Of 316 patients, 168 (53.2%) achieved NHS, 140 (44.3%) died, and 8 (2.5%) were discharged after receiving advanced HF therapies. Overall, 181 patients (57.3%) received temporary mechanical circulatory support (MCS), with 78 (24.7%) receiving intra-aortic balloon pump, 107 (33.9%) percutaneous ventricular assist device, and 62 (19.6%) veno-arterial extracorporeal membrane oxygenation. Of 176 discharged patients (55.7%), 170 (53.8%) were alive at 30 days, and 156 (49.4%) at 1-year post-discharge, while 56 (31.8%) had at least one readmission and 30 (17.0%) one HF-related readmission, by 1-year post-discharge. Patients with NHS were younger, had lower CS severity by SCAI stage, less commonly underwent intubation, or received temporary MCS, had a shorter time from CS onset to MCS deployment, and more commonly underwent coronary intervention with fewer stents deployed, compared to patients who died or underwent advanced HF therapies. Bleeding and vascular complications were less common in patients achieving NHS compared to patients who died or received advanced HF therapies. After multivariable adjustments, clinical variables associated with NHS included: younger age, lower vasoactive-inotropic score, lower serum creatinine, and lactate at shock onset, successful coronary intervention with fewer stents deployed, and absence of intubation, or use of veno-arterial extracorporeal membrane oxygenation (all P ≤ 0.05). We studied a contemporary cohort of patients with AMI-CS and high rates of temporary MCS use, and identified clinical factors associated with a higher likelihood for successful outcomes. The need for transfer to an advanced CS centre, the impact and management of adverse events, and the type and timing of temporary MCS as opposed to intensification of pharmacologic therapy, should be studied as clinical practice targets for improving patient outcomes.

AimsLittle is known about how patient frailty affects mortality and hospitalization following mitral valve intervention for mitral regurgitation (MR).Methods and resultsUsing Danish nationwide registries, we identified patients undergoing first-time mitral valve intervention for MR during the period 1996–2022. Patients were categorized as frail or non-frail based on the Hospital Frailty Risk Score. We assessed 1 year mortality with the reverse Kaplan–Meier estimator, and adjusted comparisons were computed using multivariable-adjusted Cox regression analysis. A composite outcome of death or time in hospital >14 days within 1 year was examined using multivariable-adjusted logistic regression analysis. A total of 7000 patients (90.0%) were considered non-frail (median age 67.0 years, 66.3% male) and 782 (10.0%) were considered frail (median age 71.0 years, 56.3% male). One year mortality was 8.2% among non-frail patients and 13.4% among frail patients (P-value <0.0001), but no statistically significant difference was observed [hazard ratio = 1.16, 95% confidence interval (CI): 0.88–1.54, reference: non-frail patients] in the adjusted analysis. Within the first year after mitral valve intervention, 42.8% of non-frail patients were never admitted, 42.1% were admitted for 1–14 days, 6.2% for 14–28 days, and 5.1% for >28 days. Among frail patients, the corresponding proportions were 26.6%, 46.3%, 9.1%, and 9.8%. In the adjusted analysis, frail patients were associated with higher odds of the composite outcome [odds ratio = 1.65 (95% CI: 1.37–2.00)].ConclusionFrail patients were associated with more time spent in hospital within the first year following surgery compared with non-frail patients, but no statistically significant difference was found in the 1 year mortality according to frailty status in adjusted analysis.

AimsTo assess for the first time the impact of socio-demographic variables on prescription of guideline-directed medical therapy (GDMT) after an episode of heart failure (HF) decompensation in the Italian healthcare system.Methods and resultsUtilizing ‘GENERATOR-HF DataMart’, a cross-sectional analysis was performed. We included patients with HF and reduced ejection fraction discharged between January 2019 and July 2024. The degree of GDMT implementation across the different socio-demographic variables (i.e. patient's age, sex, marital status, nationality, place of residence, and educational level) was evaluated through the modified optimal medical therapy (mOMT) score (i.e. a ratio between the number of pillars actually prescribed and the number of pillars that could be prescribed on the basis of each specific contraindication). A multivariable logistic regression model was also fitted to assess the association between the socio-demographic variables and the prescription of each pillar and loop diuretics. 1730 patients (median age: 72 years; 24% females) were included. The mOMT score was significantly lower in elderly patients, but comparable across other pre-specified socio-demographic categories. In multivariable regression analysis, older age was the only independent socio-demographic predictor of under-prescription both overall and for ACEi/ARB/ARNI (OR0.70; 95% CI 0.55–0.89), beta-blockers (OR0.59; 95% CI 0.41–0.84) and SGLT2i (OR0.66, 95% CI 0.47–0.93), while also associated with a loop diuretics use (OR1.56; 95% CI 1.13–2.17). A higher mOMT score was significantly associated with a reduced incidence of early adverse events (i.e. 30-day all-cause death and urgent re-admissions) (4.1% vs. 8.5%; P = 0.001).ConclusionOlder age was the only independent predictor of under-prescription of GDMT and enhanced use of loop diuretics, whereas no discrepancies were found across the other socio-demographic subgroups.

AimsThe prevalence of adults with congenital heart disease (ACHD) is rising due to improved paediatric care. In parallel, updated data on prognosis in adult life are needed.ObjectivesThe aim was to calculate the standardized mortality ratio (SMR) and death rates in ACHD compared to the general population.Methods and resultsData were obtained from the national register of congenital heart disease. The general Swedish population served as a reference. SMR was calculated as the ratio between observed and expected deaths. 9089 patients (median age 28 years, interquartile range [IQR] 20–45, 47% females) were followed for a median of 8 years (IQR 4–14). 525 deaths occurred during observation. The SMR increased by lesion complexity: atrial septal defect [1.3 (95% CI: 1.1–1.5)]; ventricular septal defect [2.0 (1.4–2.7)]; congenital aortic valve disease [2.2 (1.6–2,9)]; Ebstein’s anomaly [3.2 (1.8–5.2)]; tetralogy of Fallot [3.8 (2.6–5.2)]; congenitally corrected transposition of the great arteries [5.6 (2.9–9.6)]; Eisenmenger syndrome [8.7 (5.5–13.1)]; transposition of the great arteries with a previous atrial redirection operation [12.3 (6.8–20.1)]; and Fontan physiology [22.5 (12.5–37.0)]. Calculations were also performed by severity (mild, moderate, and severe) and age by six age groups. SMR was generally higher in younger age, and the difference in mortality from the general population was estimated to be lower for older age groups. The mortality distribution and death rate per 1000 person-years have also been calculated for each lesion.ConclusionThe mortality in ACHD remains increased compared to the general population and reflects the severity of the lesion. In higher ages, the observed mortality is more in line with the general population, probably because of survival of the least affected patients, and that few persons with severe lesions have reached advanced age.