AIMS:Among statin-treated participants with elevated triglycerides and known cardiovascular disease or with diabetes and other risk factors, icosapent ethyl reduced the risk of cardiovascular events in the REDUCE-IT study. In this post hoc analysis of REDUCE-IT, we quantified the effects of icosapent ethyl on total hospitalizations and days lost to hospitalization and death. METHODS:Randomization to treatment with 2 g twice daily of icosapent ethyl or matching placebo was performed among 8179 participants receiving statin therapy with established cardiovascular disease or age ≥50 years with diabetes and ≥1 additional risk factor, fasting triglyceride 1.69-5.63 mmol/L, and low-density lipoprotein cholesterol 1.06-2.59 mmol/L. Total hospitalizations were analyzed with a competing risks marginal model for total events. The likelihood of no days lost to hospitalization and death and the rate of days lost among those who were hospitalized or died during the study were analyzed with a zero-inflated Poisson regression model. RESULTS:During a median 5.0 years of follow-up, icosapent ethyl treatment was associated with fewer total hospitalizations (HR (95% CI) = 0.91 (0.84, 0.98), P=0.017). Participants randomized to icosapent ethyl were more likely to survive until the end of the study without hospitalization (OR (95% CI) = 1.12 (1.02, 1.22), p=0.016) and had fewer days lost among those who were hospitalized or died (RR (95% CI) = 0.93 (0.93, 0.94), p<0.001). CONCLUSION:Icosapent ethyl was associated with fewer total hospitalizations and fewer days lost due to hospitalization and death, providing additional insights on the effects of icosapent ethyl on patient-centered measures of total disease burden.

BACKGROUND:Clinical trials are an important part of evidence generation in medicine but remain burdened by escalating costs, inefficiencies and manual processes. Artificial intelligence (AI) has emerged as a promising approach to address these limitations by improving efficiency across the trial lifecycle. METHODS:In this review, we examine emerging applications of AI across the clinical trial lifecycle. We highlight key examples demonstrating feasibility and potential impact. RESULTS:AI-based approaches show promise in optimizing trial design, improving recruitment, streamlining conduct and enhancing data interpretation. Despite the potential of AI in trials, challenges persist, including data quality, regulatory and privacy concerns, as well as infrastructure issues. Ethical use will require strong governance frameworks emphasizing transparency and human oversight. The success of these technologies will depend on their continuous validation and monitoring of these technologies. CONCLUSIONS:With appropriate validation, monitoring and governance, AI could enable a more efficient, cost-saving and effective clinical trial landscape that accelerates discovery.

Background Hypertension is a leading modifiable risk factor for cardiovascular disease and premature death among adults. Up to 18% of individuals with hypertension have resistant hypertension (rHTN), which substantially increases the risk of adverse clinical outcomes. Endogenous hypercortisolism can result in rHTN through multiple mechanisms. Objectives MOMENTUM (NCT06829537) is the first large, observational, multicenter study examining the prevalence of endogenous hypercortisolism among adults with rHTN in the United States. Methods Target enrollment is approximately 1,000 participants. To be eligible, adults aged ≥18 years must have rHTN, defined using the American Heart Association criteria (systolic blood pressure ≥130 mm Hg despite ≥3 antihypertensive medications of different classes at maximally tolerated doses, including a diuretic, or ≥4 medications from different classes regardless of systolic blood pressure). Endogenous hypercortisolism is defined as cortisol level >1.8 μg/dL on the 1-mg overnight dexamethasone suppression test with adequate dexamethasone (≥140 ng/dL). The primary endpoint is endogenous hypercortisolism prevalence. Conclusions MOMENTUM will provide new insight into endogenous hypercortisolism in patients with resistant hypertension.

Background and Aims Low-density lipoprotein cholesterol (LDL-C)-lowering therapies are proven effective in atherosclerotic cardiovascular disease (ASCVD), but real-world evidence for proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) monoclonal antibodies (mAb) remains limited. This study evaluated their impact in patients with ASCVD without prior ischaemic events. Methods Patients initiating PCSK9i mAb from January 2016 to December 2022 were identified in the Optum Research Database. A 1:2 propensity score-matched comparator cohort of PCSK9i non-initiators was developed. The primary endpoint was a composite of non-fatal myocardial infarction, non-fatal ischaemic stroke, or all-cause mortality. Key outcomes from the parametric G-formula were 5-year event rates, relative risk reduction (RRR) and absolute risk reduction (ARR), with intention-to-treat (ITT) analysis. Additional outcomes for PCSK9i mAb initiators included absolute and percent LDL-C reduction from baseline. Results Overall, 19 670 patients met selection criteria (6545 PCSK9i mAb initiators; 13 125 non-initiators). Baseline characteristics were well-balanced. Under ITT, estimated 5-year event rates were 17.5% [95% confidence interval (CI) 15.5%, 19.5%] with PCSK9i mAb vs 25.4% (95% CI 23.6%, 27.1%) without PCSK9i, yielding a RRR of 30.9% and ARR of 7.8%. Individual endpoints showed RRRs of 28.3% for myocardial infarction (P < .0001), 26.4% for ischaemic stroke (P = .02), and 28.5% for all-cause mortality (P < .0001). Among initiators, mean baseline and follow-up LDL-C were 117.8 and 54.7 mg/dL (on-treatment analysis), respectively, representing an absolute reduction of 63.1 mg/dL and percent reduction of 53.6%. Conclusions In ASCVD patients without prior events in clinical practice, PCSK9i mAb treatment was associated with lower ischaemic event and mortality rates.

Over the past two decades, approaches to managing patients with coronary artery disease have improved substantially with advances in percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) surgery, pharmacological secondary prevention, anti-anginal agents and lifestyle interventions. Accordingly, clinical management choices in non-acute myocardial ischaemic syndromes (NAMIS) remain a timely and important topic. The risks and benefits of an invasive strategy combined with optimal medical therapy (OMT) versus a conservative strategy of OMT alone should be discussed with patients to facilitate shared clinical decision making. The findings from high-quality, randomized, controlled trials in the era of modern OMT form an essential platform for these informed conversations. In totality, the evidence from randomized, controlled trials supports OMT as the first-line therapeutic approach in patients with NAMIS, whereas selected patients at high anatomical risk or those with persistent anginal symptoms despite initial OMT often derive further symptom relief from invasive therapy with PCI. In patients with high-risk NAMIS, including those with multivessel disease and diabetes mellitus, CABG surgery improves survival, whereas the benefit is less clear for PCI. In this Review, we discuss the findings from contemporary trials evaluating outcomes in patients with NAMIS treated invasively or conservatively with OMT alone, and we conclude with proposed management pathways.

BACKGROUND:Second-generation aldosterone-synthase inhibitors (ASIs) may offer a novel treatment for hypertension. OBJECTIVES:The objective of the study was to assess the efficacy and safety of ASIs in this clinical setting. METHODS:We searched major databases for randomized controlled trials (RCTs) assessing ASIs (baxdrostat, lorundrostat, and vicadrostat) in patients with hypertension. For efficacy outcomes, mean differences (MD) with 95% credible intervals (CrIs) were estimated using a Bayesian random-effects model. For adverse events, OR with 95% CrI were estimated using a Bayesian binomial-normal hierarchical model. The protocol was registered in Prospective Register of Systematic Reviews (CRD420251132306). RESULTS:Eight RCTs were included (n = 3,369; 2,430 [72%] randomized to ASI). ASI reduced systolic blood pressure (SBP) (MD: -6.7 mm Hg; CrI: -8.78, -4.59; τ2 3.24), diastolic blood pressure (MD: -2.09 mm Hg; CrI: -3.68, -0.44; τ2 1.44), and hypertensive urgency (OR: 0.36; CrI: 0.13, 0.90; τ2 0.07) compared with placebo. There was no difference in all-cause mortality (OR: 0.45; CrI: 0.06, 3.20; τ2 0.10) or adrenal insufficiency (OR: 0.5; CrI: 0.1, 3.1; τ2 0.3) between groups. However, ASIs increased the odds of hyperkalemia (OR: 7.1; CrI: 3.56, 15.2; τ2 0.23), hyponatremia (OR: 2.6; CrI: 1.25, 5.98; τ2 0.1), and hypotension (OR: 3.28; CrI: 1.43, 8.16; τ2 0.1). In subgroup analysis, the probability of achieving a clinically meaningful reduction in SBP (MD < -5 mm Hg) was 87.5% with baxdrostat and 94.3% with lorundrostat. CONCLUSIONS:Second-generation ASIs had a high likelihood of a clinically significant reduction in SBP compared with placebo. However, hyperkalemia, hyponatremia, and hypotension were more frequent with ASIs.

Background and Aims The long-term prognostic value of standard C-reactive protein (CRP) in patients with myocardial infarction is unknown. Methods Using Danish nationwide registries, we identified patients with a first diagnosis of myocardial infarction from 2013 through 2020, who had a CRP measurement <=24 hours of index hospitalization. The primary outcome was death from any cause, and the secondary outcome was hospitalization or outpatient contact for new-onset heart failure. Absolute and relative risks for outcomes according to CRP quartiles at days 0-30 and 31-365 were calculated using multivariable Cox regression with average treatment effect modeling, adjusted for demographics and clinical features, including high-sensitivity troponin concentrations. Results A total of 29,035 patients with myocardial infarction were included. Median CRP was 4 mg/l, and quartile intervals were: quartile 1: <2.9 mg/l, quartile 2: 2.9 to <4 mg/l, quartile 3: 4 to <12 mg/l, and quartile 4: >=12 mg/l. At 0-30 days, 1,660 patients had died, and 1,861 died between days 31-365. The standardized absolute risk of death at both 0-30 and 31-365 days was lowest among patients in quartile 1 (0-30 days: 2.8%, 31-365 days: 4.1%) and highest among patients in quartile 4 (0-30 days: 9.7%, 31-365 days: 9.5%). The standardized relative risks of death increased in a stepwise fashion from quartile 2 to quartile 4 when using quartile 1 as the comparator. Similar findings were observed for heart failure. Conclusion Among patients with myocardial infarction, higher CRP concentrations were significantly associated with a higher risk of death and incident heart failure.

Importance:Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce chronic kidney disease (CKD) progression in individuals with type 2 diabetes, CKD, or heart failure. However, their effects in those with stage 4 CKD or little to no albuminuria remain uncertain. Objective:To assess whether estimated glomerular filtration rate (eGFR) or degree of albuminuria, measured by urinary albumin to creatinine ratio (UACR), modifies the effects of SGLT2 inhibitors on kidney outcomes. Data Sources:SGLT2 inhibitor trials participating in the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium (SMART-C). Study Selection:Randomized, double-blind, placebo-controlled trials within SMART-C evaluating an SGLT2 inhibitor with label indications for reducing CKD progression including at least 500 participants in each group with at least 6 months of follow-up. Data Extraction and Synthesis:Treatment effects in individual trials were pooled using inverse variance-weighted meta-analysis. Main Outcomes and Measures:CKD progression, defined as kidney failure, at least 50% reduction in eGFR, or death due to kidney failure. Other outcomes included annual rate of eGFR decline and kidney failure. Results:Among 70 361 participants (mean [SD] age, 64.8 [8.7] years; 24 595 [35.0%] females) in 10 randomized trials, 2314 (3.3%) experienced CKD progression and 988 (1.4%) reached kidney failure. SGLT2 inhibitors reduced the risk of CKD progression (25.4 vs 40.3 events per 1000 patient-years; hazard ratio [HR], 0.62 [95% CI, 0.57-0.68]), irrespective of baseline eGFR (HR of 0.61 [95% CI, 0.52-0.71] for eGFR ≥60 mL/min/1.73 m2; 0.57 [95% CI, 0.47-0.70] for eGFR of 45 to <60 mL/min/1.73 m2; 0.64 [95% CI, 0.54-0.75] for eGFR of 30 to <45 mL/min/1.73 m2; and 0.71 [95% CI, 0.60-0.83] for eGFR <30 mL/min/1.73 m2; P for trend = .16) and baseline albuminuria (HR of 0.58 [95% CI, 0.44-0.76] for albuminuria ≤30 mg/g; 0.74 [95% CI, 0.57-0.96] for >30-300 mg/g; and 0.57 [95% CI, 0.52-0.64] for more than 300 mg/g; P for trend = .49). Although the magnitude of protection varied, SGLT2 inhibitors reduced the annual rate of eGFR decline across all eGFR and UACR subgroups, including when participants with and without diabetes were analyzed separately. SGLT2 inhibitors also reduced the risk of kidney failure alone (HR, 0.66 [95% CI, 0.58-0.75]). Conclusions and Relevance:In this meta-analysis, SGLT2 inhibitors were found to lower the risk of CKD progression regardless of baseline eGFR or albuminuria, including in patients with stage 4 CKD or minimal albuminuria, supporting their routine use to improve kidney outcomes across the full spectrum of kidney function among patients with type 2 diabetes, CKD, or heart failure.

Aims Timely, accurate assessment of electrocardiograms (ECGs) is crucial for diagnosing, triaging, and managing patients. However, this often relies on expert interpretation, a major bottleneck in low-resource settings. We developed and validated ECG-GPT, a format-independent vision encoder-decoder model that generates expert-level interpretations from 12-lead ECG images. Methods and results We developed ECG-GPT using 12-lead ECGs and their corresponding diagnosis statements performed at a large US health system between 2000 and 2022. Using structured clinical assessment, semantic similarity, and conventional metrics, we validated ECG-GPT across seven distinct health settings, including three large and diverse US health systems, ECGs from Minas Gerais, Brazil, the UK Biobank, the Germany-based PTB-XL dataset, and a community hospital in Missouri. In total, 2.9 million ECGs were used for model development, and 4.1 million ECGs for validation. The model performed well in clinical assessment across 26 extracted labels, with diagnostic accuracy ranging from 0.93 to 0.99. For rhythm abnormalities, including atrial fibrillation, sinus tachycardia, sinus bradycardia, premature atrial contractions, and premature ventricular contractions, AUROCs ranged from 0.80 to 0.95. For conduction abnormalities, including left bundle branch block, right bundle branch block, first degree atrioventricular block, left anterior fascicular block, and left posterior fascicular block, AUROCs ranged from 0.88 to 0.96. ECG-GPT identified the full context of diagnosis statements with allied conditions with a median pairwise similarity of 0.90, significantly greater than baseline (P < 0.001). Results were comparable across external validation sites. Conclusion We developed and validated a vision encoder-decoder model that generates expert-level interpretations from ECG images, a scalable strategy for accessible automated ECG analysis.

Colchicine has been studied as an anti-inflammatory treatment for cardiovascular prevention, but findings from randomized trials have been inconsistent. This meta-analysis evaluated the efficacy and safety of colchicine in reducing major adverse cardiovascular events (MACE) and its individual components, using ChatGPT as an assistant throughout the process. Randomized trials of colchicine for cardiovascular prevention were systematically identified, and data extraction, risk of bias assessment, and meta-analyses were performed with ChatGPT under human supervision. The primary outcome was MACE, while secondary outcomes included myocardial infarction (MI), stroke, revascularization, cardiovascular mortality, and all-cause mortality. Eleven trials involving 30,888 patients were included. Colchicine significantly reduced MACE (risk ratio 0.75, 95% CI 0.63–0.88), though no significant effects were observed for MI, stroke, cardiovascular mortality, or all-cause mortality. In addition to its clinical findings, this study illustrates the potential of ChatGPT to assist in systematic reviews and meta-analyses by automating screening, data extraction, bias assessment, and statistical code generation. This integration reduced researcher time by over 70% while maintaining accuracy through human validation. Overall, colchicine appears to lower the risk of MACE but the results of the CLEAR trial have lowered certainty, while the findings highlight the feasibility and efficiency gains of using large language models in evidence synthesis workflows.

BACKGROUND AND AIMS:Patients with established atherosclerotic cardiovascular disease (ASCVD) are at high risk of developing heart failure (HF). However, incident HF is not part of the risk assessment of current guideline-recommended models. The aim of this study was to develop and externally validate the SMART2-HF model for prediction of incident HF in patients with ASCVD. METHODS:SMART2-HF was developed in 7698 individuals with established ASCVD (coronary, cerebrovascular, or peripheral artery disease, or abdominal aortic aneurysm) but without prior HF from the UCC-SMART cohort. Cox proportional hazards models including sex-predictor interactions and with age as the time scale were derived to estimate the 10-year and lifetime risk of incident HF (hospitalization for HF or HF-related death), accounting for competing non-HF mortality. Predictors, limited to routinely available clinical characteristics, were aligned with the SMART2 risk model for recurrent cardiovascular risk in the same population. External validation was performed in 240 741 patients with ASCVD from six data sources: the Clinical Practice Research Datalink, the HUNT3 study, the SWEDEHEART Registry, the ASCVD-Particles cohort, the Estonian Biobank and the international REACH Registry. RESULTS:During a median follow-up of 11.2 years (interquartile range 6.1-16.4 years), 1031 incident HF events (13%) occurred in the UCC-SMART cohort. In the external validation data sources, a total of 24 885 incident HF events (10%) occurred. The pooled C-statistic was 0.696 (95% confidence interval 0.674-0.717), with consistent performance in subgroups by sex and type of ASCVD. Predicted risks matched observed incidence in external validation. CONCLUSIONS:The SMART2-HF model enables the prediction of incident HF in patients with ASCVD. Aligned with the guideline-recommended SMART2 model for recurrent cardiovascular risk, SMART2-HF can be used as a complementary tool in this population.

Background Cognitive decline has been reported after coronary artery revascularization, but whether it reflects procedure-specific effects or the burden of underlying vascular disease remains uncertain. Objectives To determine whether incident dementia risk differs according to coronary revascularization strategy among older adults with acute coronary syndrome (ACS). Methods We conducted a longitudinal cohort study among adults aged ≥65 years hospitalized for ACS between 2010 and 2020 (n = 25,176). Patients underwent percutaneous coronary intervention (n = 8,043), coronary artery bypass grafting (n = 797), or received no revascularization (n = 16,336). A second comparator cohort included patients with stable coronary artery disease (CAD) without revascularization (n = 154,299). The primary outcome was incident dementia identified using validated International Classification of Diseases codes after a 1-year washout. Propensity-matched analyses used Cox models accounting for the competing risk of death. Results Revascularized patients were younger (74.8 ± 6.9 vs 77.1 ± 8.2 years), more often male (66.2% vs 54.0%), and had lower Elixhauser multimorbidity scores (4.6 ± 2.8 vs 5.4 ± 3.0, all P < 0.001). Over a median 4.8 years of follow-up, 9.0% of ACS patients developed dementia. Revascularization was not associated with increased dementia risk compared with ACS without revascularization (sub-hazard ratio: 1.05; 95% CI: 0.95-1.17) or stable CAD. Dementia risk was also similar between percutaneous coronary intervention and coronary artery bypass grafting. Conclusions We found that among older adults with ACS, coronary revascularization was not statistically significantly associated with increased dementia risk compared with no revascularization or stable CAD. These findings reflect the hypothesis that the majority of dementia risk is potentially driven more by cumulative vascular and systemic factors than by procedure-specific neurotoxicity.

BACKGROUND AND AIMS:Standard modifiable risk factors (SMuRFs), including hypertension, diabetes, hyperlipidaemia, and smoking, are prevalent among patients undergoing percutaneous coronary intervention (PCI). This study aimed to assess the prevalence and impact of controlled SMuRFs in patients undergoing PCI. METHODS:Data of patients who underwent PCI at a single tertiary-care centre between 2012 and 2023 were analysed. SMuRF control was assessed using pre-procedural measurements: systolic blood pressure <140 mmHg, fasting glucose <126 mg/dL or a haemoglobin A1c < 7%, low-density lipoprotein <100 mg/dL, and smoking status (non-smoker). Patients were stratified by the number of controlled risk factors (CRF): 4, 3, 2, and ≤1. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause mortality, myocardial infarction, and stroke, at one-year post-PCI. RESULTS:Among 19 651 patients, 5876 (29.9%) had 4-CRF, 8199 (41.7%) had 3-CRF, 4415 (22.5%) had 2-CRF, and 1161 (5.9%) had ≤1-CRF. Compared with 4-CRF, the risk for MACE increased progressively with fewer controlled risk factors (3-CRF: adjHR 1.17, 95% CI 0.98-1.40; 2-CRF: adjHR 1.39, 95% CI 1.14-1.69; ≤1-CRF: adjHR 1.48, 95% CI 1.10-2.00). Glycaemic control had the most significant association with lower MACE (adjHR 0.56, 95% CI 0.49-0.65). CONCLUSIONS:Comprehensive SMuRF control before PCI remains infrequent, though it is associated with lower MACE rates. Prioritizing glycaemic control may yield the greatest benefit in improving post-PCI prognosis.

BACKGROUND:Rural residents have been experiencing higher stroke mortality than urban residents, and the gap has widened. Disparity in postacute care after stroke may increase the rural-urban gaps of mortality and disability. We aimed to examine whether rural patients with stroke receive the same postacute care and achieve comparable outcomes to urban patients. METHODS:We conducted a cohort study of Medicare beneficiaries aged ≥65 years treated in the Get With The Guidelines-Stroke participating hospitals for acute ischemic stroke during 2017 to 2022. We used restricted mean home-time to compare 1-year home-time among patients discharged from rural versus urban hospitals and the Cox proportional hazards model for all-cause mortality and readmission, adjusting for patient and hospital characteristics. RESULTS:The analysis included 29 734 patients treated in rural hospitals and 478 122 in urban hospitals, with a mean age of 79 years, and 55.5% were women. Compared with patients in urban hospitals, patients in rural hospitals were less commonly discharged to inpatient rehabilitation facilities (20.1% versus 25.1%; adjusted odds ratio, 0.76 [95% CI, 0.69-0.84]) and more frequently to skilled nursing facilities (24.5% versus 20.9%; adjusted odds ratio, 1.21 [95% CI, 1.11-1.32]). Compared with urban patients, rural patients had 1.8 fewer days of home-time (95% CI, -3.2 to -0.3) overall; rural patients discharged to skilled nursing facilities had 5.7 fewer days of home-time (95% CI, -9.0 to -2.3), and those discharged home had 2.2 fewer days of home-time (95% CI, -3.7 to -0.7). Rural patients overall had comparable all-cause mortality with urban patients (adjusted hazard ratio, 1.01 [95% CI, 0.98-1.05]) and lower all-cause readmission (adjusted hazard ratio, 0.92 [95% CI, 0.90-0.95]). However, rural patients who were discharged home had higher all-cause mortality than urban patients (adjusted hazard ratio, 1.11 [95% CI, 1.05-1.17]). CONCLUSIONS:Compared with urban patients, rural patients with stroke had less inpatient rehabilitation facility and more skilled nursing facility utilization, less home-time, but similar mortality. Further efforts are needed to ensure equitable postacute care in rural areas.

Although repeated testing of lipoprotein(a) (Lp(a)) is generally not recommended due to the genetically determined nature of concentrations, reports of significant intra-individual variability in serial assessments have challenged the single lifetime measurement framework. Using Lp(a) assessments at baseline, month 12, and month 24 from participants in the REDUCE-IT trial, we identified characteristics that could support repeated testing. Among 386 participants (36.3%) with baseline Lp(a) 50 to <70 mg/dL, 140 (36.3%) had at least one subsequent assessment ≥70mg/dL, whereas among 630 participants with baseline Lp(a) ≥70mg/dL, 133 (21.1%) had at least one subsequent assessment <70 mg/dL. Baseline Lp(a), sex, race, and several other characteristics were related to variability. Consequently, among individuals at high cardiovascular risk with hypertriglyceridemia and controlled LDL-C on statin therapy, considerable variability was observed over 24 months. These findings suggest multiple assessments may be warranted for Lp(a)-related risk stratification and, potentially, eligibility for Lp(a)-targeted treatments, particularly among individuals with relatively high concentrations or certain demographic and clinical characteristics.

AIMS:To investigate the association between serial high-sensitivity cardiac troponin-T (hs-TnT) concentrations and subsequent heart failure in individuals presenting with suspected acute coronary syndrome (ACS). METHODS AND RESULTS:Utilizing Danish nationwide registries, we identified individuals without known heart failure who underwent serial hs-TnT assessment for suspected ACS between 2012 and 2019. Individuals were categorized based on the hs-TnT concentration patterns from the first to the second measurement (normal, rising, persistently elevated, or falling), the extent of hs-TnT concentration change (≤20%, >20 to 50%, or > 50%), and quartiles of peak hs-TnT levels (≤9 ng/l, 10-19 ng/l, 20-263 ng/l, and ≥ 264 ng/l). Standardized absolute and relative risks of incident hospitalization or outpatient contact for heart failure were computed using cause-specific multivariable Cox regression with average treatment effect modeling. Of 26,835 individuals, 38.8% received a discharge diagnosis of myocardial infarction, 5.1% of unstable angina, and 56.1% of suspected myocardial infarction or chest pain. Within the initial 30 days, 1122/26,835 (4.2%) persons received a heart failure diagnosis, with an additional 707/25,085 (2.8%) diagnosed between days 31-365. Subjects with two normal hs-TnT values exhibited the lowest standardized absolute risk (0-30 days: 0.3%; 31-365 days: 0.4%), while those with persistently elevated concentrations demonstrated the highest risk (0-30 days: 6.6%; 31-365 days: 4.3%). Heart failure risk also exhibited a significant, positive association with peak hs-TnT concentration. CONCLUSIONS:In individuals presenting with suspected ACS, persistent hs-TnT elevation was associated with the highest risk of subsequent heart failure. A dose-response association was observed between peak hs-TnT concentrations and incident heart failure.

Preeclampsia is a hypertensive disorder of pregnancy associated with substantial maternal morbidity and long-term cardiovascular risk, but the consistency of echocardiographic remodeling remains unclear. We conducted a mega-meta-analysis of left ventricular function and geometry, enabled by a large language model based suite of tools. A PROSPERO-registered review (CRD420251109103) searched PubMed, Scopus, and Embase without date limits. Synthesa AI screened more than 138,000 abstracts, extracted data, assessed risk of bias, and generated Bayesian analytic code, with all outputs validated by human reviewers. Seventy-five studies including met eligibility criteria. Preeclampsia was associated with a small but statistically significant reduction in ejection fraction (mean difference –0.87%, 95% CrI –1.58 to –0.16) and a clinically meaningful impairment in global longitudinal strain (–3.08%, 95% CrI –4.13 to –2.06). Left ventricular mass index was substantially higher in the preeclampsia group (+13.10 g/m 2 , 95% CrI 10.06 to 16.21), as was relative wall thickness (+0.062, 95% CrI 0.042 to 0.081), whereas fractional shortening showed no significant difference (–0.60%, 95% CrI –2.15 to +0.86). Moderator analyses revealed that BMI and parity significantly influenced strain, while gestational age at diagnosis accounted for nearly all variance in ventricular mass. This mega-meta-analysis defines a remodeling phenotype of preserved ejection fraction, impaired strain, and hypertrophic adaptation consistent with subclinical systolic dysfunction. Equally, it demonstrates the transformative role of LLM-based tools, showing that evidence syntheses of this magnitude can be automated, scaled, and standardized in ways previously unattainable.