BACKGROUND: The surrogacy of modern composite endpoints for cardiovascular and all-cause mortality is unknown. METHODS: We reviewed all primary publications of RCTs for non-acute atherosclerotic cardiovascular disease ut...BACKGROUND: The surrogacy of modern composite endpoints for cardiovascular and all-cause mortality is unknown. METHODS: We reviewed all primary publications of RCTs for non-acute atherosclerotic cardiovascular disease utilizing composite endpoints published 2019-2023 in first tier journals, and included all trials utilizing composite outcomes of ≥3 components. Trial-level surrogacy of outcomes was assessed using the R coefficient of determination, with a threshold for validating surrogacy at R = 0.8. RESULTS: Forty-five (n = 45) RCTs met the inclusion criteria, of which 19 (42%) tested secondary prevention strategies. The median sample size was 6033 (Q1-Q3, 3684-11,287), median patient age was 64 (Q1-Q3, 62-67), and most participants were males (69%, Q1-Q3 55%-74%). Half (n = 22, 49%) of the RCTs were funded by industry sponsors and the remainder by government agencies. None of the components of the published composite endpoints reached the pre-specified threshold of 0.8 for surrogacy for all-cause mortality. The correlation coefficient for cardiovascular death was 0.54 (95% CI: 0.36-0.72); other correlation coefficients were notably lower. Similar lack of correlation was observed between cardiovascular death and MI, stroke, unstable angina, revascularization and HF. CONCLUSIONS: Large ASCVD RCTs published in high-impact journals use composite endpoints components that do not correlate with patient prognosis. Journal editors, regulators and healthcare professionals should demand clinical trials provide evidence that is better aligned with patient outcomes to improve informed decision making for cardiovascular patients.
BACKGROUND: Despite major advances in the acute management of ST-segment elevation myocardial infarction (STEMI), long-term outcomes remain suboptimal, largely due to persistent gaps in secondary prevention. The IMPACS s...BACKGROUND: Despite major advances in the acute management of ST-segment elevation myocardial infarction (STEMI), long-term outcomes remain suboptimal, largely due to persistent gaps in secondary prevention. The IMPACS study was designed to evaluate a standardized, intensified outpatient management strategy during the first year following STEMI. METHODS: IMPACS is a national, prospective, multicentre study comparing an intensified outpatient disease-management program with standard care. Consecutive STEMI patients were enrolled at four PCI centres. The intervention includes four structured outpatient visits within one year of discharge, focusing on clinical assessment, pharmacotherapy optimisation, and comprehensive risk-factor management. The primary endpoint is a composite of all-cause mortality and cardiovascular hospitalisations, compared with matched administrative-data controls from the six remaining PCI centres nationwide. RESULTS: A total of 1031 patients were included. The mean age was 62 years, and 75% were male. Primary PCI was performed in 96% of patients. Anterior-wall STEMI occurred in 43%, and 6% presented with advanced Killip class (III or IV). The median left ventricular ejection fraction was 45%. Cardiovascular risk factors were highly prevalent: hypertension in 73%, high LDL-C in 75%, diabetes mellitus in 23%, and current smoking in 49%. Prescription of guideline-directed medical therapy at discharge was high, with dual antiplatelet therapy in 95% and statins in 99% of patients. CONCLUSION: IMPACS represents a novel approach to post-ACS care. Baseline findings indicate a relatively young STEMI population with a high burden of cardiovascular risk factors, supporting the need for intensified secondary prevention strategies. Ongoing follow-up will determine its impact on long-term clinical outcomes.
BACKGROUND: Microvascular injury (MVI), commonly assessed on cardiac magnetic resonance (CMR) as microvascular obstruction (MVO), is frequently observed in patients with ST-elevation myocardial infarction (STEMI) despite...BACKGROUND: Microvascular injury (MVI), commonly assessed on cardiac magnetic resonance (CMR) as microvascular obstruction (MVO), is frequently observed in patients with ST-elevation myocardial infarction (STEMI) despite timely primary percutaneous coronary intervention (PPCI), and is key to adverse left ventricular (LV) remodelling and poor outcomes. Established invasive indices, such as the index of microvascular resistance (IMR), are obtained after reperfusion and therefore do not capture microvascular compromise present during coronary occlusion. Coronary wedge pressure (CWP), obtained during balloon occlusion, is a simple invasive marker of microvascular function, but its clinical value remains uncertain. OBJECTIVES: To determine whether pre-reperfusion CWP, coronary flow pressure index (CFPI) and related pressure-derived indices are associated with (i) the presence of CMR-defined MVO and (ii) MVO extent in anterior STEMI patients treated with selective intracoronary hypothermia (SIH). Secondary objectives were associations with intramyocardial haemorrhage (IMH) and myocardial salvage index (MSI). METHODS: In this EUROICE substudy, distal coronary pressure was recorded during culprit LAD occlusion in patients randomised to selective intracoronary hypothermia. Systolic, diastolic and mean CWP, CFPI and outflow time (τ) were derived. CMR at 2-7 days quantified MVO, intramyocardial haemorrhage (IMH) and myocardial salvage index (MSI). Associations were analysed using Spearman correlation, parsimonious multivariable logistic regression, and receiver operating characteristic analysis. RESULTS: Of 94 patients randomised to selective intracoronary hypothermia, 82 had paired pre-reperfusion physiology and CMR data available, of whom 65 had interpretable coronary pressure traces. Mean wedge pressure was 21.4 ± 11.0 mmHg, CFPI 0.24 ± 0.11, and τ 5.2 ± 2.6 s. MVO was present in 64% of patients (mean extent 2.7 ± 4.6% of LV mass). Lower CWP and CFPI were associated with MVO presence and extent (CFPI ρ = -0.33, p = 0.008), whereas τ was not. Lower CWP and CFPI were inversely related to IMH, but not to MSI. In complete-case multivariable models, lower CFPI remained associated with MVO presence (adjusted OR 0.91 per 0.01 increase, 95% CI 0.86-0.97, p = 0.002), as did lower mean CWP (adjusted OR 0.91 per 1 mmHg increase, 95% CI 0.85-0.97, p = 0.003). CFPI showed moderate discrimination for MVO, with an AUC of 0.74 (95% CI 0.61-0.87), while mean CWP showed similar discrimination, with an AUC of 0.74 (95% CI 0.61-0.86). CONCLUSIONS: Lower CWP before reperfusion and CFPI during balloon occlusion were associated with greater MVO and IMH on early CMR in anterior STEMI. These indices support the feasibility of pre-reperfusion physiological phenotyping to aid on-table microvascular risk stratification.
BACKGROUND: Proximal left anterior descending (LAD) artery disease is associated with adverse clinical outcomes. Ostial proximal LAD (O-pLAD) lesions represent a technically challenging subset, yet data comparing outcome...BACKGROUND: Proximal left anterior descending (LAD) artery disease is associated with adverse clinical outcomes. Ostial proximal LAD (O-pLAD) lesions represent a technically challenging subset, yet data comparing outcomes with non-ostial proximal LAD (NO-pLAD) lesions are limited. This study aimed to compare 2-year clinical outcomes following percutaneous coronary intervention (PCI) for O-pLAD versus NO-pLAD lesions. METHODS: We conducted a single-center retrospective cohort study including patients who underwent PCI of a significant proximal LAD lesion between June 2017 and September 2023. O-pLAD stenosis was defined as ≥70% diameter stenosis within 5 mm of the LAD ostium; NO-pLAD lesions were defined as ≥70% stenosis distal to this segment and proximal to the first major septal or diagonal branch. The primary endpoint was target lesion failure (TLF), a composite of target lesion revascularization (TLR), target vessel myocardial infarction, and cardiac death, assessed at a maximum follow-up of 730 days. Multivariable Cox regression was performed to adjust for relevant clinical and procedural confounders. RESULTS: A total of 1229 patients were included (522 O-pLAD, 707 NO-pLAD). Patients with O-pLAD lesions were older and had more multivessel disease and lesion calcification. At median follow-up of 730 days, TLF occurred more frequently in the O-pLAD group than in the NO-pLAD group (14.6% vs. 7.9%). NO-pLAD lesions were associated with significantly lower TLF after IPTW weighted analyis. TLR was significantly lower in the NO-pLAD group and remained so after adjustment. No significant differences were observed in cardiac death, target-vessel myocardial infarction, or major adverse cardiovascular events. CONCLUSIONS: Compared with ostial proximal LAD lesions, non-ostial proximal LAD stenting is associated with lower rates of target lesion failure and target lesion revascularization at 2 years. Ostial involvement may be an important consideration when selecting revascularization strategies for proximal LAD disease.
Arai M, Suzuki S, Hirota N
… +16 more, Motogi J, Takayanagi T, Umemoto T, Nakai H, Arita T, Yagi N, Kishi M, Kano H, Matsuno S, Kato Y, Otsuka T, Yajima J, Uejima T, Okumura Y, Oikawa Y, Yamashita T
AIMS: A low estimated glomerular filtration rate (eGFR) is the primary diagnostic criterion for chronic kidney disease (CKD), a known risk factor for cardiovascular disease (CVD). Artificial intelligence-enhanced electro...AIMS: A low estimated glomerular filtration rate (eGFR) is the primary diagnostic criterion for chronic kidney disease (CKD), a known risk factor for cardiovascular disease (CVD). Artificial intelligence-enhanced electrocardiography (AI-ECG) has demonstrated high diagnostic performance for CKD. However, it remains unclear whether the diagnostic probability derived from AI-ECG for CKD (AIECG-CKD-DP) can also predict future cardiovascular events. METHODS AND RESULTS: We analysed data from 16,984 patients in the Shinken Database who underwent AI-ECG and were followed up. Based on their baseline AIECG-CKD-DP, they were divided into two groups, Low-DP (<0.6, n = 10,031) and High-DP (≥0.6, n = 6953) groups, and we compared their clinical characteristics and the incidence of cardiovascular events. Patients in the High-DP group were more likely to be male (65.4% vs. 62.4%), older (69.1 vs. 55.2 years), and had lower eGFR (60.5 vs. 74.5 mL/min/1.73m). AIECG-CKD-DP inversely correlated with eGFR (r = -0.461, P < 0.001). During the follow-up period, 894 cardiovascular events were recorded. The incidences of cardiovascular events were 1.14% and 4.73% per year for the Low-DP and High-DP groups, respectively. Multivariable Cox regression analysis generated hazard ratios (HRs) for the High-DP and Low-DP groups of 1.802 (95% confidence interval (CI), 1.512-2.148) and 1.292 (95% CI, 1.114-1.499) for CKD, respectively. When analysed as continuous variables, the HRs per standard deviation were 1.523 (95% CI, 1.368-1.695) for AIECG-CKD-DP and 0.979 (95% CI, 0.910-1.052) for eGFR. CONCLUSION: AIECG-CKD-DP is independently associated with future cardiovascular events and outperforms eGFR and CKD classification as a predictor in a specialist cardiovascular cohort.
Ski CF, Thompson DR, Jennings CS
… +35 more, Kotseva K, McEvoy JW, De Backer G, Erlund I, Ganly S, Vihervaara T, Lip GYH, Ray KK, Rydén L, Adamska A, Abreu A, Almahmeed W, Ambari AM, Ge J, Hasan-Ali H, Huo Y, Jankowski P, Jimenez RM, Li Y, Zuhdi ASM, Makubi A, Mbakwem AC, Mbau L, Estrada JLN, Ogah OS, Ogola EN, Quintero-Baiz A, Sani MU, Liprandi MIS, Tan JWC, Triana MAU, Yeo TJ, Wood DA, De Bacquer D, INTERASPIRE Investigators
Int J Cardiol
· 2026 Oct · PMID 42167412
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BACKGROUND: Optimizing health-related quality of life (HRQoL) is a goal of preventive and therapeutic cardiovascular care worldwide, yet sex disparities in HRQoL remain insufficiently explored at a population level. The...BACKGROUND: Optimizing health-related quality of life (HRQoL) is a goal of preventive and therapeutic cardiovascular care worldwide, yet sex disparities in HRQoL remain insufficiently explored at a population level. The objective of this study was to examine sex differences in HRQoL in relation to secondary prevention in patients with CHD across all six World Health Organization regions. METHODS: Cross-sectional analysis of the INTERASPIRE study of adults hospitalized in the preceding six to 24 months with CHD who underwent standardized interview and examination across 14 countries. Endpoints were HRQoL (EQ-5D-5L; HeartQoL), and an INTERASPIRE-Guideline Target Score (GTS); a 10-point assessment of achieving secondary prevention lifestyle, risk factor, and therapeutic targets. Analyses were adjusted for age and country-level clustering. RESULTS: A total of 4546 patients (21.1% women) were interviewed. Compared to men, women had lower HRQoL across all assessments (p < 0.001) e.g., mean HeartQoL global score 2.1 vs 2.6; EQ-5D-5L self-care 17.8% vs 9.2%, and usual activities 39.1% vs 22.4%. Positive correlations (p < 0.001) were identified between HRQoL and INTERASPIRE-GTS. Female sex was independently associated with poor HRQoL (p < 0.001), either expressed by EQ-5D-5L index score or the HeartQoL overall and subscale scores. CONCLUSIONS: Female sex was independently associated with poorer HRQoL in patients with CHD. Higher HRQoL was associated with ability to achieve secondary prevention guideline targets. Routine integration of HRQoL assessment into secondary prevention programs can inform individualized clinical care and assist in reducing sex-based disparities in cardiovascular outcomes.
Cartledge S, Lucas M, Dinh D
… +12 more, Brennan A, Lefkovits J, Gauci S, Thomas EE, Miranda PC, Livori A, Gallagher R, O'Neil A, Redfern J, Reid CM, Driscoll A, Stub D
BACKGROUND: Cardiac rehabilitation is a key component of secondary prevention following percutaneous coronary intervention (PCI), yet participation remains suboptimal. Linked health datasets offer an opportunity to bette...BACKGROUND: Cardiac rehabilitation is a key component of secondary prevention following percutaneous coronary intervention (PCI), yet participation remains suboptimal. Linked health datasets offer an opportunity to better understand attendance patterns and associated outcomes across the care continuum. METHODS: A retrospective, observational cohort study was conducted using linked health data from 13 public hospitals between 2019 and 2021. Cardiac rehabilitation attendance was defined as participation in ≥1 session. Predictors of cardiac rehabilitation attendance and 12-month outcomes were assessed. A dose-response analysis was also performed, categorizing participants by cardiac rehabilitation session frequency as non-attenders, low attendance (1-5 sessions) and high attendance (≥6 sessions). RESULTS: Adults undergoing PCI (n = 37,191) were identified, of whom 7126 were successfully linked to the Victorian Integrated Non-Admitted Health (VINAH) dataset. Cardiac rehabilitation attendance was observed in 19.3% of the cohort. Key predictors of attendance were STEMI (OR 1.59, 95% CI 1.32-1.93), NSTEMI (OR 1.24, 95% CI 1.05-1.46), rural/regional program location (OR 1.48, 95% CI 1.25-1.75), and length of stay >3 days (OR 1.04, 95% CI 1.02-1.07). At 12 months, cardiac rehabilitation attendees had lower mortality (1.0% vs 4.9%, p < 0.001) and fewer unplanned readmissions (p = 0.038). A dose-response relationship was found for 12-month mortality. A dose-response relationship was evident for mortality, with lowest rates among high-attendance participants (0.6%), compared with low-attendance (1.5%) and non-attenders (2.9%) (p < 0.001). CONCLUSIONS: Linking Victorian datasets is feasible and provides valuable insights. Cardiac rehabilitation attendance is low, yet participation, particularly at higher doses, is associated with significantly improved outcomes.
BACKGROUND AND AIMS: The timing of aortic valve replacement (AVR) in severe asymptomatic aortic stenosis (AS) remains debated. Preserved ejection fraction (EF) may mask subclinical dysfunction, while global longitudinal...BACKGROUND AND AIMS: The timing of aortic valve replacement (AVR) in severe asymptomatic aortic stenosis (AS) remains debated. Preserved ejection fraction (EF) may mask subclinical dysfunction, while global longitudinal strain (GLS), brain natriuretic peptide (BNP), and diastolic indices (E/E') provide complementary prognostic information. A predictive model for adverse outcomes after AVR integrating GLS, BNP, and E/E' has not been previously investigated. METHODS: Ninety-six patients with severe asymptomatic AS and preserved EF (>50%) undergoing AVR were assessed at baseline and 1, 3, and 6 months. Echocardiography (GLS, EF, LVMI, IVSd, LVIDd, E/E'), BNP, and clinical outcomes were analyzed. Primary endpoint was LV remodeling; secondary endpoint was major adverse cardiovascular events (MACE). RESULTS: Despite preserved EF, 76% had impaired GLS (<15%), and 64% remained in negative remodeling at 6 months. Baseline GLS ≤15% was the only independent predictor of adverse remodeling in multivariable logistic regression (OR 4.7 at 3 months; OR 3.5 at 6 months). For MACE, baseline E/E' >13 was the strongest independent predictor (OR 3.15, 95% CI 1.58-7.57, p = 0.004). The integrated GLS-BNP-E/E' model demonstrated superior predictive strength compared with individual parameters, with Nagelkerke R values of 0.41 for remodeling and 0.31 for MACE. CONCLUSION: A multimodal risk model integrating GLS, BNP, and E/E' predicts adverse remodeling and MACE in severe asymptomatic AS. These findings highlight the complementary role of imaging and biomarkers in risk stratification before AVR-a concept that warrants confirmation in future multicenter studies.
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common cardiac disease clinically-recognized worldwide; however, limited information is available concerning the demographic profile and significance of its evolving pee...BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common cardiac disease clinically-recognized worldwide; however, limited information is available concerning the demographic profile and significance of its evolving peer-reviewed literature. OBJECTIVES: Assess the global distribution and characteristics of the HCM-related literature from 1960 to 2024 . METHODS: Publications describing HCM were retrieved from the National Library of Medicine via PubMed from 1960 to 2025. Changes in publication counts across the 66 years were quantified. Additionally, trends were stratified by country of origin and geographic region. RESULTS: The number of HCM publications increased significantly over time (P < 0.001), from 59 in 1960-1965 to 6454 in 2020-2025, a 109-fold increase that notably exceeded the increase in overall cardiovascular publications during the same time-period. The number of countries from which papers originated also increased significantly (P < 0.001), from 11 in 1960-1965 to 78 in 2020-2025, a 7-fold increase. Overall, the largest contributor was the U.S. (n = 5513 publications comprising 30% of the literature), followed by China (n = 1819, 10%), Japan (n = 1729, 9%), Italy (n = 1302, 7%), and United Kingdom (n = 1194, 7%). Notably, publications from China increased by 203-fold from 1960 to 2000 to 2020-2025, with Asia becoming the predominant continent in 2025. Fifty-percent of publications from countries contributing only >2010 were not original investigations, and none appeared in high-impact journals. CONCLUSIONS: While the US has remained the largest contributor of HCM-related publications >65 years, the peer-reviewed literature has become increasingly diverse, now including almost 100 countries globally and an increasingly substantial proportion from China and the Asian continent. This evolving profile has allowed for enhanced understanding of HCM and its particularly broad clinical spectrum, likely improving care for patients with this disease worldwide. However, sparse data from several populous regions constitute an unmet need in HCM.
BACKGROUND: Heart failure with preserved ejection fraction is common, obesity-related, and associated with high symptom burden and healthcare use. Tirzepatide, a dual GIP/GLP-1 receptor agonist, improved symptoms and out...BACKGROUND: Heart failure with preserved ejection fraction is common, obesity-related, and associated with high symptom burden and healthcare use. Tirzepatide, a dual GIP/GLP-1 receptor agonist, improved symptoms and outcomes in SUMMIT, but its acquisition cost raises concerns about value and affordability. METHODS: We developed a Markov model comparing tirzepatide versus placebo, both added to standard care, in the SUMMIT population from the German statutory health insurance perspective. The model used monthly cycles over 5 years with four Kansas City Cardiomyopathy Questionnaire clinical summary score-defined health states (Q1-Q4) plus death. Arm-specific transitions and rates of all-cause death and worsening heart failure were derived from SUMMIT. Deterministic and probabilistic sensitivity analyses, including tirzepatide price-reduction scenarios, were conducted to explore parameter uncertainty and price thresholds simultaneously. A prevalence-based budget impact analysis extrapolated results to the German HFpEF-obesity population under alternative eligibility (SUMMIT-like vs broad) and uptake (30%, 50%, 100%) scenarios. RESULTS: Discounted per-patient costs were €5827 (placebo) and €31,052 (tirzepatide), with quality-adjusted life years of 3.539 and 3.638. Tirzepatide generated 0.100 additional quality-adjusted life years at an incremental cost of €25,225, yielding an incremental cost-effectiveness ratio of 252,611€/quality-adjusted life year, with low probability of cost-effectiveness at €100,000/QALY. Five-year incremental spending was ∼€1.9-6.2 billion with SUMMIT-like and ∼ €3.8-12.6 billion with broad eligibility, depending on uptake. CONCLUSIONS: Tirzepatide provides modest quality-adjusted life year gains at substantially higher costs and, at current price, appears neither cost-effective nor affordable at scale in German care. Substantial price reductions would be required to improve economic attractiveness and budgetary impact.
BACKGROUND: Implantable cardioverter-defibrillators (ICDs) reduce sudden cardiac death in selected populations. However, their long-term prognosis may differ according to the underlying cardiomyopathy. We aimed to evalua...BACKGROUND: Implantable cardioverter-defibrillators (ICDs) reduce sudden cardiac death in selected populations. However, their long-term prognosis may differ according to the underlying cardiomyopathy. We aimed to evaluate long-term survival after ICD implantation according to cardiomyopathy etiology and to contextualize outcomes relative to the expected survival of the general population. METHODS: This retrospective cohort included 1091 consecutive adults who underwent ICD implantation at the regional referral center in Asturias, Spain, between 2015 and 2024. Patients were classified as ischemic cardiomyopathy (ICM, n = 588), non-ischemic dilated cardiomyopathy (NI-DCM, n = 332), or other arrhythmogenic cardiac conditions (ACC, n = 171), including hypertrophic cardiomyopathy (HCM). Observed survival was estimated using Kaplan-Meier methods. Expected survival was derived from national life tables matched by age, sex, calendar year, and region. Relative survival and excess mortality were calculated using the Ederer II method at 4, 8, and 12 years. Multivariable Cox regression analysis was performed to adjust for major clinical confounders. RESULTS: The cohort was predominantly male (82.1%), with a mean age of 63.1 ± 13.1 years and mean LVEF of 37.9 ± 19.3%. ICD implantation was performed for primary prevention in 75.6% of patients. ICM was the most frequent substrate (53.9%), followed by NI-DCM (30.4%) and ACC (15.7%). ICM patients showed the poorest prognosis, with excess mortality compared with the general population. NI-DCM demonstrated intermediate outcomes, whereas ACC showed survival trajectories closely approximating expected population survival. CONCLUSIONS: Long-term survival after ICD implantation differed according to cardiomyopathy etiology. These findings support an etiology-informed approach to risk stratification, patient selection, and long-term management beyond a purely LVEF-based strategy.
BACKGROUND: Red blood cell distribution width (RDW), a routine and inexpensive blood parameter, is widely available and may serve as a useful screening marker for heart failure (HF). This study aims to evaluate RDW's pre...BACKGROUND: Red blood cell distribution width (RDW), a routine and inexpensive blood parameter, is widely available and may serve as a useful screening marker for heart failure (HF). This study aims to evaluate RDW's predictive value for new-onset HF in the general population and examine its incremental predictive performance alongside NT-proBNP. METHODS: From a prospective population-based cohort, RDW and NT-proBNP were available for 5814 and 3393 individuals without prior HF, respectively. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Fully adjusted model included variables from the Pooled Cohort Equations (PCE): age, sex, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking, and antihypertensive medication use. Predictive improvement was assessed using the Δc-statistic. RESULTS: Over a median follow-up of 7 years, 433 individuals developed HF (incidence rate: 10.4 per 1000 person-years). Each 1% increase in RDW was associated with a 22% higher HF risk (HR 1.22, 95%CI, 1.12-1.32), and those in the highest RDW quartile had a 71% higher risk (HR 1.71, 95%CI, 1.29-2.25). NT-proBNP showed similar associations (HR 1.68, 95%CI, 1.40-2.01 per 1-unit increase). Adding RDW to the PCE model significantly improved predictive performance (Δc-statistic = 0.008), comparable to NT-proBNP (Δc-statistic = 0.014). CONCLUSIONS: RDW is a robust and accessible predictor of incident HF. Its predictive value, low costs, and routine availability highlight its potential as a useful biomarker for HF risk stratification in the general population. The design and findings are summarized in the graphical abstract.
INTRODUCTION: Cascade testing in gene-positive cardiomyopathy families facilitates the identification of relatives at risk of cardiomyopathy. Conventional clinical screening is often unremarkable, particularly in younger...INTRODUCTION: Cascade testing in gene-positive cardiomyopathy families facilitates the identification of relatives at risk of cardiomyopathy. Conventional clinical screening is often unremarkable, particularly in younger individuals. This study evaluated the potential role of cardiopulmonary exercise testing (CPET) in detecting subclinical disease among gene-positive phenotype-negative (G + P-) relatives. METHODS: In this single-centre case series, relatives of probands with likely/definite pathogenic cardiomyopathy variants underwent cascade testing. Gene-positive relatives underwent extensive phenotyping (ECG, echocardiography, holter monitor, cardiac MRI). Individuals with morpho-functional abnormalities suggestive of early cardiomyopathy and those fulfilling diagnostic criteria were excluded. Consecutively recruited (March 2017-December 2024) G + P- relatives underwent CPET ergometry. Those who completed a maximal test were included. A cardiac limitation was defined as VO2MAX <80% and/or ≥ 2 abnormal CPET variables. RESULTS: Twenty-two subjects were included (59.1% female, mean age of 32.1 ± 16.0 years). Most had a TTN (27.3%), ACTC1 (22.7%) and DSG2 (22.7%) variant. All subjects are under follow-up (42.4 ± 24.0 months). Nearly ¾ (72.7%) had evidence of cardiac limitation during CPET, irrespective of haemoglobin, creatinine and body mass index. More than a third (40.9%) had a reduced VO2MAX. Two thirds (59.1%) had abnormal stroke volume kinetics (O2/pulse). Nearly half (45.5%) had reduced ventilatory efficiency (VE/VCO2) and two thirds (63.6%) had reduced aerobic efficiency (VO2/WR). A fifth (22.7%) had ventricular arrhythmias at peak exercise. CONCLUSION: This is the first proof-of-concept study to demonstrate that CPET in cardiomyopathy families can identify a considerable proportion of G + P- relatives with early cardiac functional limitations. Long-term surveillance, and larger prospective studies are warranted to validate these findings.
Sakamoto D, Matsuoka Y, Nakatani D
… +18 more, Okada K, Sunaga A, Mas HK, Sato T, Kitamura T, Tamaki S, Seo M, Yano M, Hayashi T, Nakagawa A, Nakagawa Y, Yasumura Y, Yamada T, Ohtani T, Hikoso S, Sotomi Y, Sakata Y, OCVC-Heart Failure Investigators
BACKGROUND: In heart failure with preserved ejection fraction (HFpEF), the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and echocardiographic parameters and the influence of atrial fib...BACKGROUND: In heart failure with preserved ejection fraction (HFpEF), the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and echocardiographic parameters and the influence of atrial fibrillation (AF) on the relationship remain poorly understood. METHODS: This study analyzed data from the Prospective mUlticenteR obServational stUdy of patIenTs with HFpEF (PURSUIT HFpEF). Patients hospitalized for acute decompensated HF with a left ventricular ejection fraction (LVEF) ≥ 50% were included. The association between longitudinal NT-proBNP levels and echocardiographic parameters was assessed using linear mixed-effects models, with further stratification by AF status. RESULTS: Of 1238 enrolled patients (median age 83[77, 87] years; 551[45%] male), 617 patients with longitudinal NT-proBNP data available (407 without AF, 210 with AF) were analyzed. In patients without AF, even after covariates adjusted, NT-proBNP levels were positively associated with left ventricular diastolic diameter (β-coefficient: 1.878 ± 0.736, P < 0.001), left ventricular mass index (β-coefficient: 1.467 ± 0.280, P < 0.001), left atrial volume index (β-coefficient: 0.795 ± 0.232, P < 0.001), E/e' (β-coefficient: 1.041 ± 0.214, P < 0.001), and tricuspid regurgitation pressure gradient (TRPG) (β-coefficient: 0.849 ± 0.261, P < 0.001). Conversely, left ventricular ejection fraction was negatively associated (β-coefficient: -1.632 ± 0.607, P < 0.001). However, in patients with AF, most of these parameters except for E/e', TRPG, and interventricular septal thickness at end-diastole had no correlation with NT-proBNP levels. CONCLUSIONS: In HFpEF patients without AF, longitudinal NT-proBNP levels were broadly associated with both structural and functional echocardiographic parameters. Whereas, patients with AF showed limited associations. Notably, E/e' and TRPG remained associated with NT-proBNP irrespective of AF status. TRIAL REGISTRATION: UMIN-CTR ID: UMIN000021831.