In cardiovascular medicine, claims of 'mortality reduction' are widely used to summarise the benefits of contemporary therapies. The phrase carries a powerful and intuitive meaning, suggesting that deaths have been prevented and lives have been saved. However, a closer examination of many cardiovascular outcome trials shows that this conclusion often reflects an interpretative shortcut rather than a fundamental difference in outcomes.Most trials rely on time-to-event analyses that demonstrate differences in the timing of death within a limited follow-up period. These findings are frequently translated into statements of reduced mortality, even when the observed effect primarily represents a modest extension of survival rather than the prevention of death. Although statistically correct within the predefined time horizon, this framing may overstate clinical benefit and obscure the time-dependent nature of survival outcomes.This Viewpoint examines the conceptual distinction between delaying death and preventing it, and explores how this distinction is often blurred in trial reporting, abstracts, guideline summaries and clinical communication. By converting time gained into categorical claims of deaths avoided, survival benefits may acquire a clinical and moral weight that exceeds their absolute magnitude, influencing therapeutic expectations, guideline recommendations and patient decision-making.The aim is not to question the validity of survival analysis but to highlight the importance of interpretative precision once statistical results are translated into clinical language. Greater clarity in distinguishing survival extension from mortality reduction would support more transparent communication of benefit, facilitate shared decision-making and better align reported outcomes with what patients ultimately experience and value.In an era of increasingly complex cardiovascular interventions, precision in how benefits are described is a necessary component of high-quality, patient-centred care.

BackgroundTime to reperfusion is a predictor of long-term outcomes in ST-segment elevation myocardial infarction (STEMI). Timely primary percutaneous coronary intervention (PCI) is the preferred strategy recommended by guidelines. Fibrinolysis is recommended in patients in whom timely primary PCI is not feasible, though concerns persist about underutilisation of this approach. We examined long-term survival outcomes in STEMI patients according to treatment strategy received in a national STEMI registry in Ireland.MethodsThis was an observational, nationwide, population-based study. We identified all STEMI cases from January 2013 to March 2018. After exclusion of patients with missing data, we divided patients into three groups as per reperfusion strategy—fibrinolysis, delayed primary PCI (>120 min of diagnosis) and timely primary PCI (<120 min of diagnosis)—and analysed mortality through to 3 years follow-up. A multivariate Cox proportional hazards model was used, with a propensity score matching analysis performed as a sensitivity analysis.ResultsOf the 4156 patients included in this analysis, 202 (4.9%) were treated with fibrinolysis, 1075 (25.8%) were treated with delayed primary PCI and 2879 (69.3%) were treated with timely primary PCI. At follow-up, delayed primary PCI was associated with an increased risk of mortality through to 3 years in comparison to fibrinolysis (HRadjusted, 1.36; 95% CI 1.02 to 1.83, p=0.04). Timely primary PCI was associated with a comparable risk of mortality through to 3 years in comparison to fibrinolysis (HRadjusted, 1.10; 95% CI 0.81 to 1.49, p=0.53).ConclusionsA sizeable proportion of STEMI patients continue to receive treatment with delayed primary PCI. This is associated with an increased risk of mortality through 3 years in comparison to fibrinolysis.

ObjectivesVentricular septal defect (VSD) is the most common congenital heart defect. Much remains unclear about the long-term prognosis for VSD patients. This study aimed to investigate the all-cause and cardiovascular mortality in patients with VSD compared with controls without congenital heart disease in Sweden.MethodsSwedish National Patient Register was used to identify all VSD patients born between 1970 and 2017. Mortality data were collected from the Swedish National Cause of Death register. Patients with associated complex congenital heart disease or non-congenital VSD were excluded. The VSD cases were matched by age and sex with 10 controls without congenital heart disease for each case.ResultsA total of 22 855 VSD patients were included. The hazard of death for the entire VSD cohort, including patients with syndromes and associated non-complex congenital cardiac lesions, was increased compared with matched controls without congenital heart disease, with a HR of 6.8 (95% CI 6.1 to 7.6) for ages 0–17 years and HR of 3.1 (95% CI 2.5 to 4.0) for ages >18 years, during a mean follow-up of 14.3 years (±11.1). In isolated, non-syndromic VSD, the hazard of death was still elevated compared with controls, regardless of whether the VSD had been repaired in childhood or not. The HR for death for unrepaired VSDs was 4.8 (95% CI 4.1 to 5.6) for ages 0–17 years and 2.1 (95% CI 1.5 to 3.0) for ages >18 years and for VSDs repaired before 18 years of age HR for death was 2.9 (95% CI 1.2 to 7.1) for ages 0–17 years and 8.2 (95% CI 2.2 to 30.4) for ages >18 years.ConclusionsMortality rates were three times higher in adult VSD patients compared with matched controls. Mortality risk was highest in VSD cohorts that included patients with syndromes and congenital valvular lesions, highlighting VSD patients at extra risk of adverse outcomes.

BackgroundTruncating variants in the titin gene (TTNtv) are associated with cardiomyopathy, mainly dilated cardiomyopathy (DCM). The clinical presentation and outcomes of arrhythmogenic phenotypes in these patients are scarcely studied.Methods and resultsThis was a retrospective Swiss national study including 46 cardiomyopathy patients with pathogenic/likely pathogenic (P/LP) TTNtv. 63% were male and median age at diagnosis was 47 years. At baseline, 89% patients formally fulfilled current DCM criteria and 17% the 2024 revised Padua criteria for diagnosis of ACM, of which all were of the left-dominant phenotype (arrhythmogenic left ventricular cardiomyopathy). No patient fulfilled arrhythmogenic right ventricular cardiomyopathy (ARVC) criteria. Most TTNtv were located on the A-band (74%). Median time to last follow-up (FU) was 63 months. Ventricular arrhythmia (VA) events in the primary prevention group significantly increased over time; although, under optimal guideline-directed medical therapy, mean left ventricular ejection fraction and right ventricular function significantly improved during time to last FU. At the time to last FU, 50% fulfilled DCM criteria, whereas 27% fulfilled the criteria for left-dominant ACM. Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) was most commonly in the basal septum, but no patient had higher degree atrioventricular block (AVB). LGE on CMR was not associated with higher rates of VAs.ConclusionsPatients with P/LP TTNtv most frequently present as DCM or left-dominant ACM, whereas TTN is not a classical ARVC-causing gene. The risk of VA remains high despite favourable remodelling. Left ventricular LGE is frequent and often involves the septum. In contrast to sarcoidosis, high degree AVB seems not to be a typical feature of TTN cardiomyopathy.

IntroductionInherited cardiac conditions, including dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), may have a monogenic cause identified through genetic testing (GT). Confirmation of pathogenic gene variants can have important implications for the patient and their relatives. The UK National Genomic Test Directory (NGTD) provides strict criteria on the indications for GT; however, the European Society of Cardiology (ESC) recommends wider GT. We reviewed the prevalence of pathogenic genotypes in patients undergoing GT who did not meet the NGTD criteria.MethodsWe conducted a retrospective analysis of patients who underwent GT with a confirmed diagnosis of HCM or DCM attending the Essex Inherited Cardiac Conditions Clinic between January 2023 and January 2025.Results257 patients were included in the analysis, with 136 patients with DCM (52.9%) and 121 patients with HCM (47.1%). The diagnostic yield of GT was 19.9% in DCM and 17.4% in HCM.14.8% of gene-positive patients with DCM and 14.3% of gene-positive patients with HCM did not meet current UK testing criteria, predominantly due to age of onset. All gene-positive patients in the DCM subgroup not meeting current NGTD criteria for testing had evidence of myocardial fibrosis.ConclusionA significant minority of patients (1 in 7) with cardiomyopathy and a pathogenic genotype did not meet current UK testing criteria; each patient has an average of 4 first-degree relatives at risk who will benefit from predictive GT. We propose the adoption of the wider ESC guidance, removing the strict age-related cut-offs and being guided more by the severity of the phenotype, particularly involving myocardial scarring.

BackgroundThe epidemiology of native valve infective endocarditis (IE) has shifted toward older adults with substantial comorbidity burdens, yet contemporary nationwide data on outcomes and surgical impact remain limited.MethodsWe conducted an 18-year nationwide cohort study of adults hospitalised with native valve IE in Korea (2006–2023). Outcomes included in-hospital and 5-year all-cause mortality, IE relapse and a composite of death or relapse. Temporal trends, mortality predictors and surgical associations across age strata were evaluated using multivariable Cox models and stratified survival analyses.ResultsAmong 18 402 patients (mean age 63.7 years), incidence declined in individuals <45 years but increased in those ≥65 years. In-hospital mortality was 25.5%, and 5-year mortality exceeded 50% overall. Advanced age, dialysis dependence, cancer and major complications predicted mortality. Valve surgery, performed in 29.1% of patients, was consistently associated with lower short- and long-term mortality across age groups, with no evidence of age-by-treatment interaction. Both early (≤7 days) and late (>7 days) surgery showed reduced mortality versus medical therapy. IE relapse was more frequent in older adults, and surgery was associated with a lower relapse risk. In the composite outcome of death or relapse, older adults had a higher event burden, whereas surgery remained associated with fewer composite events.ConclusionsNative valve IE in Korea has shifted toward an elderly, multimorbid population with persistently high mortality. Despite declining utilisation, the survival benefit of surgery was preserved across the age spectrum, supporting operative consideration in appropriately selected older adults.

BackgroundDifferentiating type 1 myocardial infarctions (T1MI) from type 2 myocardial infarctions (T2MI) can be challenging based on clinical variables alone. This review aimed to explore the utility of novel and traditional biomarkers to discriminate between these entities and potentially provide additional prognostic information.MethodsA systematic review of observational studies and randomised controlled trials that examined the discriminatory or prognostic roles of either traditional cardiac biomarkers (troponin, creatine kinase or b-type natriuretic peptide) or non-traditional biomarkers. Data sources included PubMed, SCOPUS, Web of Science, EMBASE and clinicaltrials.gov and were last searched on 15 November 2024. The diagnostic accuracy of biomarkers and prognostic utility of identified biomarkers are narratively reported.Results31 studies with 16 111 individuals with a T2MI were included. Most studies (97%) demonstrated moderate or severe risk of bias. Of studies that examined traditional cardiac biomarkers (n=13), the ability to discriminate between T2MI and T1MI ranged from an area under the curve (AUC) of 0.61–0.71. Studies that added traditional cardiac biomarkers to clinical variables (n=4) demonstrated a diagnostic accuracy AUC 0.71–0.82. Studies exploring non-traditional biomarkers, metabolic and proteomic profiles (n=14) demonstrated a wide range of diagnostic accuracy (AUC 0.50–0.77). Traditional cardiac biomarkers inconsistently demonstrated a correlation with subsequent cardiovascular events. The prognostic utility of non-traditional biomarkers was infrequently assessed.ConclusionThe role of biomarkers, metabolic and proteomic profiles in the diagnosis and prognostication of T2MI remains unclear. Higher quality studies and refining the classification of T2MI may improve this further.PROSPERO registration numberCRD42023418095.

BackgroundEbstein’s anomaly (EA) exhibits significant anatomical and clinical heterogeneity, warranting a systematic approach to risk stratification. While the Carpentier classification (CC) is commonly employed for qualitative disease assessment, there is increasing interest in quantitative imaging parameters to personalise monitoring strategies and therapeutic interventions. We sought to evaluate the association between cardiovascular magnetic resonance (CMR) parameters, CC and symptoms of heart failure (HF). Also, we investigated whether CMR-derived markers may predict the need for bidirectional cavopulmonary anastomosis (BCPA) and the occurrence of haemodynamic complications or significant right ventricular (RV) dysfunction in the postoperative stay.MethodsThis retrospective study evaluated consecutive patients diagnosed with EA undergoing 1.5T CMR acquisition at a tertiary care centre. CC and quantitative indices were extracted from steady-state free precession sequences.ResultsIn a total population of 60 patients (53% male, median age 22 years), CMR parameters most strongly associated (p<0.001) with CC included indexed displacement of the septal (SLDi) and inferior (ILDi) leaflets, Ebstein valve rotation angle, functional RV ejection fraction, indexed atrialised RV end-diastolic volume and the ratio of either atrialised or functional RV to anatomical RV. Decreasing left ventricular ejection fraction (OR 0.85, 95% CI 0.75 to 0.97, p=0.01) and increasing ILDi (OR 1.05, 95% CI 1.00 to 1.10, p=0.04) emerged as the most prominent variables associated with HF symptoms. Additionally, ILDi was significantly linked to the need for BCPA (OR 1.15, 95% CI 1.03 to 1.28), the occurrence of haemodynamic complications (OR 1.09, 95% CI 1.01 to 1.18) and significant RV dysfunction in the postoperative stay (OR 1.08, 95% CI 1.01 to 1.17).ConclusionsQuantitative CMR indices proved to be effective in distinguishing between Carpentier classes and they may be valuable in an integrated CMR-based approach to assess EA severity. Among these, ILDi reflects both the extent of tricuspid valve abnormality and RV atrialisation and may serve as a useful metric in guiding personalised therapeutic strategies.

Invasive coronary function testing (CFT) is indicated in patients with refractory angina with non-obstructed coronary arteries (ANOCA). Despite this, questions remain regarding patient selection for testing, safety and integration of CFT within clinical pathways and the impact that endotyping has on long term management of these patients. This study aims to investigate the safety of CFT in patients presenting with anginal chest pain, the prevalence of ANOCA endotypes in the tested population, and the impact of CFT on prescribed medical therapy and secondary care resource utilisation. A retrospective analysis of electronic case records of 159 consecutive patients who underwent complete invasive CFT at two UK centres between June 2022 and December 2024 was performed. All patients were tested for endothelium-independent coronary microvascular dysfunction (CMD) and coronary vasospasm (vasospastic angina (VSA)). 44 patients (27.6%) also underwent endothelial function assessment. The median length of follow-up was 9 months (IQR 4-16). An ANOCA endotype was identified in 101 patients (63.5%) (CFT+ve). Of those, 24 (23.8%) were diagnosed with isolated CMD, 53 (52.4%) with isolated VSA and 24 (23.8%) with a mixed endotype. Five (3.1%) experienced intraprocedural adverse events. In 123 patients (77.3%), CFT led to a change in medical therapy. Re-hospitalisation for recurrent chest pain occurred in 21.7% of CFT+ve and 13.7% of CFT-ve patients, with the majority re-presenting within 6 months of CFT. VSA was linked to higher re-hospitalisation odds (OR 2.64 (1.10-6.33), p=0.03), and patients with VSA tended to re-present earlier than others (p=0.017). Higher antianginal therapy prescription and prior emergency presentations were also predictive of risk of re-presentation (OR 1.61, p=0.02 and OR 4.18, p=0.001, respectively). CFT testing had low intraprocedural risk and influenced onward management. Hospitalisation for chest pain post CFT testing was common. Further refinement of clinical pathways, including early follow-up for medical optimisation, is suggested.

The obesity paradox has been described in different cardiovascular conditions. Data on the association between obesity and outcomes in patients with Takotsubo syndrome (TTS) are lacking. The aim of this study was to determine the relationship between body weight and mortality in TTS patients. Patients enrolled in the International Takotsubo Registry from January 2011 to July 2021 and with available data on body mass index (BMI) were included in the analysis. Patients were stratified according to BMI (underweight, <18.5 kg/m2; normal weight, 18.5-24.9 kg/m2; overweight, 25.0-29.9 kg/m2; obese, 30.0-34.9 kg/m2; and very obese, ≥35.0 kg/m2). The primary endpoint was mortality at 1 year. Of the 2707 patients, 222 (8.2%) were underweight, 1340 (49.5%) of normal weight, 759 (28.0%) overweight, 268 (9.9%) obese and 118 (4.4%) very obese (p=0.02). Rates of mortality at 1 year were 11.3%, 6.9%, 5.5%, 4.9% and 9.3% in underweight, normal weight, overweight, obese and very obese patients (p=0.02). Being overweight or obese was significantly associated with a lower mortality rate at 1 year (HR 0.70, 95% CI 0.51 to 0.96, p=0.03), and this association remained significant after multivariable adjustments (adjusted HR 0.67, 95% CI 0.46 to 0.97, p=0.03). A U-shaped mortality curve across BMI categories was observed in TTS patients, with the highest mortality rates observed in underweight and the lowest rates observed in obese patients. These observations provide the first evidence for the existence of the obesity paradox in TTS. NCT01947621.