Composite Of Death Research Articles

Prognostic evaluation of ST-segment elevation acute myocardial infarction according to lung ultrasound in the acute phase

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): JC-M received an Original Research Projects Grant from the Catalan Society of Cardiology and LR-S received Scholarship for Training and Research from the Association of Ischemic Heart Disease and Cardiological Critical Care of the Spanish Society of Cardiology. Introduction Lung ultrasound (LUS) has emerged as a useful diagnostic and prognostic tool in heart failure (HF) and has shown promise in risk stratification for ST-segment elevation myocardial infarction (STEMI) in the acute phase. These studies consistently indicate that the degree of pulmonary congestion, assessed by the number of B-lines on LUS, is significantly associated with a worse prgnosis during hospitalization and short-term follow-up in STEMI patients. However, this prognostic value has mainly been evaluated during hospital admission or a few days after discharge without a long-term follow-up. Purpose To assess the prognostic value of LUS at one year in patients admitted for STEMI. Methods In a prospective multicenter cohort study involving STEMI patients, an independent operator performed LUS during the first 24 hours after revascularization and offline B-line counting was conducted. LUS results were assessed both as a categorical [wet (at least one site with ³3 B-lines)/dry lung] and continuous variable (total number of B-lines). The primary endpoint was a composite of death or hospitalization for HF, acute coronary syndrome, or stroke within one year. Results A total of 173 patients were included. The composite endpoint occurred in 13.7% of the patients over a median follow-up of 368 days. LUS was able to predict the composite outcome with hazard ratios (HR) of adjusted hazard ratios of 4.85 (95% CI 2.79-8.43) for having a wet lung and 1.13 (95% CI 1.09-1.18) for each B-line. After and adjustment for sex, age, chronic kidney disease, previous atrial fibrillation, Killip class and left ventricular ejection fraction HR was 1.72 (95% CI 0.91-3.28) for having a wet lung and 1.06 (95% CI 1.00-1.11) for each B-line. Conclusion Detecting B-lines on LUS predicts adverse events at one year in STEMI patients.Kaplan-Meier curves

Undernutrition increases the risk of unsuccessful treatment outcomes of patients with tuberculosis in Ethiopia: A multicenter retrospective cohort study

While undernutrition has been identified as a common risk factor for tuberculosis (TB), its impact on treatment outcomes has yet to be investigated in high TB burden and low-income countries such as Ethiopia. Therefore, this study aimed to investigate the effect of undernutrition on treatment outcomes among patients with TB in northwest Ethiopia. A retrospective cohort study was conducted using data from different hospitals in northwest Ethiopia, for the period from July 2017 to August 2023. A Cox proportional hazard model was performed to determine the effect of undernutrition on TB treatment outcomes, which were defined as a composite of death, treatment failure, or loss to follow-up. A total of 602 patients with TB were included in the analysis. Of these, 367 (60.9%) were male, and 344 (57.1%) were undernourished. Upon completion of the follow-up period, 65 (10.8%) adults with TB had unsuccessful treatment outcomes. After adjusting for potential confounders, patients with undernutrition had a two times higher risk of experiencing unsuccessful treatment outcomes compared to well-nourished patients (AHR: 2.0, 95% CI: 1.2, 3.6). In addition, patients residing in rural areas (AHR: 3.1, 95% CI: 1.7, 5.4), having a history of prior TB treatment (AHR: 2.2, 95%CI: 1.1, 4.1), and the presence of diabetes comorbidity (AHR: 2.4, 95% CI: 1.1, 5.2) were at higher risk of unsuccessful treatment outcomes. Undernutrition increases the risk of unsuccessful treatment outcomes in Ethiopia. This finding suggests that nutritional support during TB treatment can improve successful treatment outcomes in high TB burden and low-income countries such as Ethiopia.

Left Atrial Improvement in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial

BackgroundFunctional mitral regurgitation induces adverse effects on the left ventricle and the left atrium. Left atrial (LA) dilatation and reduced LA strain are associated with poor outcomes in heart failure (HF). Transcatheter edge-to-edge repair (TEER) of the mitral valve reduces heart failure hospitalization (HFH) and all-cause death in selected HF patients. ObjectivesThe aim of this study was to evaluate the impact of LA strain improvement 6 months after TEER on the outcomes of patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. MethodsThe difference in LA strain between baseline and the 6-month follow-up was calculated. Patients with at least a 15% improvement in LA strain were labeled as “LA strain improvers.” All-cause death and HFH were assessed between the 6- and 24-month follow-up. ResultsAmong 347 patients (mean age 71 ± 12 years, 63% male), 106 (30.5%) showed improvement of LA strain at the 6-month follow-up (64 [60.4%] from the TEER + guideline-directed medical therapy [GDMT] group and 42 [39.6%] from the GDMT alone group). An improvement in LA strain was significantly associated with a reduction in the composite of death or HFH between the 6-month and 24-month follow-up, with a similar risk reduction in both treatment arms (Pinteraction = 0.27). In multivariable analyses, LA strain improvement remained independently associated with a lower risk of the primary composite endpoint both as a continuous variable (adjusted HR: 0.94 [95% CI: 0.89-1.00]; P = 0.03) and as a dichotomous variable (adjusted HR: 0.49 [95% CI: 0.27-0.89]; P = 0.02). The best outcomes were observed in patients treated with TEER in whom LA strain improved. ConclusionsIn symptomatic HF patients with severe mitral regurgitation, improved LA strain at the 6-month follow-up is associated with subsequently lower rates of the composite endpoint of all-cause mortality or HFH, both after TEER and GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079)

Physiological Assessment with iFR prior to FFR Measurement in Left Main Disease

Despite guideline-based recommendation of the interchangeable use of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) to guide revascularization decision-making, iFR/FFR could demonstrate different physiological or clinical outcomes in some specific patient or lesion subsets. Therefore, we sought to investigate the impact of difference between iFR and FFR-guided revascularization decision-making on clinical outcomes in patients with left main disease (LMD). In this international multicenter registry of LMD with physiological interrogation, we identified 275 patients in whom physiological assessment was performed with both iFR/FFR. Major adverse cardiovascular event (MACE) was defined as a composite of death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The receiver-operating characteristic analysis was performed for both iFR/FFR to predict MACE in respective patients in whom revascularization was deferred and performed. In 153 patients of revascularization deferral, MACE occurred in 17.0% patients. The optimal cut-off values of iFR and FFR to predict MACE were 0.88 (specificity:0.74; sensitivity:0.65) and 0.76 (specificity:0.81; sensitivity:0.46), respectively. The area under the curve (AUC) was significantly higher for iFR than FFR (0.74; 95%CI 0.62–0.85 vs. 0.62; 95%CI 0.48–0.75; p = 0.012). In 122 patients of coronary revascularization, MACE occurred in 13.1% patients. The optimal cut-off values of iFR and FFR were 0.92 (specificity:0.93; sensitivity:0.25) and 0.81 (specificity:0.047; sensitivity:1.00), respectively. The AUCs were not significantly different between iFR and FFR (0.57; 95%CI 0.40–0.73 vs. 0.46; 95%CI 0.31–0.61; p = 0.43). While neither baseline iFR nor FFR was predictive of MACE in patients in whom revascularization was performed, iFR-guided deferral seemed to be safer than FFR-guided deferral.Graphical abstractImpact of Physiological Assessment with iFR and FFR on Clinical Outcomes of Patients with LMD. In the present study, physiological assessment, both with iFR and FFR, provided a high predictability of adverse cardiovascular event in LMD patients with revascularization deferral. Furthermore, the iFR-guided deferral strategy was safer as compared to FFR. Conversely, in patients in whom revascularization was performed for LMD, neither iFR nor FFR was predictive of cardiovascular event. AUC: area under the curve; FFR: fractional flow reserve; iFR: instantaneous wave-free ratio; LMD: left main coronary artery disease.

Obesity, Inflammation, and Clinical Outcomes in COVID-19: A Multicenter Prospective Cohort Study.

Obesity is a risk factor for coronavirus disease 2019 (COVID-19)-related outcomes; however, the mechanism remains unclear. The objective of this analysis was to determine whether inflammation mediates the association between obesity and COVID-19 outcomes. The International Study of Inflammation in Covid-19 (ISIC): A Prospective Multi-Center Observational Study Examining the Role of Biomarkers of Inflammation in Predicting Covid-19 Related Outcomes in Hospitalized Patients. Ten hospitals in the United States and Europe. Adults hospitalized specifically for COVID-19 between February 1, 2020, through October 19, 2022. Inflammatory biomarkers, including soluble urokinase plasminogen activator receptor (suPAR), were measured at admission. Associations were examined between body-mass index (BMI, kg/m2) and a composite of death, need for mechanical ventilation, and renal replacement therapy, stratified by pre- and post-Omicron variants. The contribution of inflammation to the relationship between obesity and outcomes was assessed. Among 4644 participants (mean age 59.3, 45.6% male, 21.8% BMI≥35), those with BMI>40 (n=485) had 55% higher odds of the composite outcome (95% CI[1.21 to 1.98]) compared to non-obese individuals (BMI<30, n=2358) in multivariable analysis. In multiple mediation analysis, only suPAR remained a significant mediator between BMI and composite outcome. Associations were amplified for participants younger than 65 years and with pre-Omicron variants. Obesity is associated with worse outcomes in COVID-19, notably in younger participants and in the pre-Omicron era. Inflammation, as measured by suPAR, is a significant mediator of the association between obesity and COVID-19 outcomes.

Protocol for a Randomized Controlled Trial to Evaluate a Permissive Blood Pressure Target Versus Usual Care in Critically Ill Children with Hypotension (PRESSURE).

Management of hypotension is a fundamental part of pediatric critical care, with cardiovascular support in the form of fluids or vasoactive drugs offered to every hypotensive child. However, optimal blood pressure (BP) targets are unknown. The PRotocolised Evaluation of PermiSSive BP Targets Versus Usual CaRE (PRESSURE) trial aims to evaluate the clinical and cost-effectiveness of a permissive mean arterial pressure (MAP) target of greater than a fifth centile for age compared with usual care. Pragmatic, open, multicenter, parallel-group randomized control trial (RCT) with integrated economic evaluation. Eighteen PICUs across the United Kingdom. Infants and children older than 37 weeks corrected gestational age to 16 years accepted to a participating PICU, on mechanical ventilation and receiving vasoactive drugs for hypotension. Adjustment of hemodynamic support to achieve a permissive MAP target greater than fifth centile for age during invasive mechanical ventilation. Randomization is 1:1 to a permissive MAP target or usual care, stratified by site and age group. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred until after randomization. The primary clinical outcome is a composite of death and days of ventilatory support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of BP and organ support, and discharge outcomes. This RCT received Health Research Authority approval (reference 289545), and a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee on May 10, 2021 (reference number 21/EE/0084). The trial is registered and has an International Standard RCT Number (reference 20609635). Trial findings will be disseminated in U.K. national and international conferences and in peer-reviewed journals.

Long-term efficacy and safety of tailored immunosuppressive therapy in immune-mediated biopsy-proven myocarditis: A propensity-weighted study.

Standardized immunosuppressive therapy (IS) had been previously investigated in biopsy-proven (BP) lymphocytic myocarditis with heart failure (HF). This study evaluated efficacy and safety of tailored IS in BP immune-mediated myocarditis, irrespective of histology and clinical presentation. Consecutive BP myocarditis patients treated with long-term tailored IS on top of optimal medical therapy (OMT), were compared with OMT non-IS controls using propensity-score weighting. The primary outcome was a composite of death or heart transplant, the secondary outcome was a composite of biventricular function, New York Heart Association (NYHA) class variation, and relapse. IS was managed by a multidisciplinary Cardioimmunology Team, involved a safety checklist and active patients' education. Ninety-one IS patients were compared with 267 non-IS patients. IS patients more frequently had systemic immune-mediated diseases (35% vs. 9.7%), lower baseline echocardiographic left ventricular ejection fraction (35% vs. 43%), lower right ventricular fractional area change (34% vs. 41%) and higher frequency of active lymphocytic, eosinophilic and giant cell myocarditis (71% vs. 58%, 12% vs. 1.1%, and 6.6% vs. 1.5%, respectively). At 5-year follow up, no difference was observed in the primary outcome (survival rate 93% in IS vs. 87% in non-IS), but IS patients had a higher relapse rate. Thus, IS patients, with a lower biventricular function and a higher risk profile at baseline, presented similar biventricular function and NYHA class to non-IS patients at follow-up. Minor adverse drug reactions occurred in 13% of patients, all resolved with therapy switch. Prolonged tailored IS is effective and safe in BP immune-mediated myocarditis irrespective of histology and clinical presentation.

Partial versus Complete Sternotomy for Aortic Valve Replacement—Multicenter Study

Abstract Background The benefits of minimally invasive techniques in cardiac surgery remain poorly defined. We evaluated the short- and mid-term outcomes after surgical aortic valve replacement through partial upper versus complete median sternotomy (MS) in a large, German multicenter cohort. Methods A total of 2,929 patients underwent isolated surgical aortic valve replacement via partial upper sternotomy (PUS, n = 1,764) or MS (n = 1,165) at nine participating heart centers between 2016 and 2020. After propensity-score matching, 1,990 patients were eligible for analysis. The primary end point was major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke at 30 days and in follow-up, up to 5 years. Secondary end points were acute kidney injury, length of hospital stay, transfusions, deep sternal wound infection, Dressler's syndrome, rehospitalization, and conversion to sternotomy. Results Unadjusted MACCE rates were significantly lower in the PUS group both at 30 days (p = 0.02) and in 5-year follow-up (p = 0.01). However, after propensity-score matching, differences between the groups were no more statistically significant: MACCE rates were 3.9% (PUS) versus 5.4% (MS, p = 0.14) at 30 days, and 9.9 versus 11.3% in 5-year follow-up (p = 0.36). In the minimally invasive group, length of intensive care unit (ICU) stay was shorter (p = 0.03), Dressler's syndrome occurred less frequently (p = 0.006), and the rate of rehospitalization was reduced significantly (p &lt; 0.001). There were 3.8% conversions to full sternotomy. Conclusion In a large, German multicenter cohort, MACCE rates were comparable in surgical aortic valve replacement through partial upper and complete sternotomies. Shorter ICU stay and lower rates of Dressler's syndrome and rehospitalization were in favor of the partial sternotomy group.

Long-term outcomes after catheter ablation for idiopathic atypical atrial flutter

BackgroundIdiopathic atypical (non–cavotricuspid isthmus–dependent) atrial flutter (IAAFL) may be seen in patients without structural heart disease and without previous cardiac surgery or ablation. ObjectiveThis study sought to determine the patient characteristics, electrophysiologic and electroanatomic properties, and clinical outcomes after ablation in patients with IAAFL. MethodsWe retrospectively compared IAAFL patients with cavotricuspid isthmus–dependent AFL (C-AFL) patients undergoing catheter ablation. The primary outcome was a composite of death from cardiovascular causes, ischemic stroke, and hospitalization for worsening of heart failure. ResultsOf 180 patients who underwent catheter ablation for AFL, 89 were included in this study (22 IAAFL and 67 C-AFL). Electrophysiologic study showed significantly longer intra-atrial conduction time and lower atrial voltage during sinus rhythm in the IAAFL group compared with the C-AFL group. The atrial scar was observed in all 22 IAAFL patients, with the most common sites being the posterior or lateral wall of the right atrium in 10 (45.5%) and the anterior wall of the left atrium in 8 (36.4%). During 3.5 ± 2.8 years of follow-up, the composite primary end point occurred significantly more frequently in the IAAFL group (hazard ratio [HR], 3.45; 95% confidence interval [CI], 1.20–9.89; P = .015). In multivariable analysis, brain natriuretic peptide levels (HR, 1.01; 95% CI, 1.00–1.01, per 1 pg/mL; P = .01) and IAAFL (HR, 4.14; 95% CI, 1.21–14.07; P = .02) were independently associated with the primary outcome. ConclusionIAAFL in patients had distinct electrophysiologic features suggestive of atrial cardiomyopathy. These patients are at risk for development of cardiovascular adverse events after ablation.

FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction

BackgroundThe benefit of fractional flow reserve (FFR)–guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear.MethodsIn this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization.ResultsA total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P=0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes.ConclusionsAmong patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.)

Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT): a multicentre, open-label, randomised controlled trial

Acute coronary syndrome and sudden cardiac death are often caused by rupture and thrombosis of lipid-rich atherosclerotic coronary plaques (known as vulnerable plaques), many of which are non-flow-limiting. The safety and effectiveness of focal preventive therapy with percutaneous coronary intervention of vulnerable plaques in reducing adverse cardiac events are unknown. We aimed to assess whether preventive percutaneous coronary intervention of non-flow-limiting vulnerable plaques improves clinical outcomes compared with optimal medical therapy alone. PREVENT was a multicentre, open-label, randomised controlled trial done at 15 research hospitals in four countries (South Korea, Japan, Taiwan, and New Zealand). Patients aged 18 years or older with non-flow-limiting (fractional flow reserve >0·80) vulnerable coronary plaques identified by intracoronary imaging were randomly assigned (1:1) to either percutaneous coronary intervention plus optimal medical therapy or optimal medical therapy alone, in block sizes of 4 or 6, stratified by diabetes status and the performance of percutaneous coronary intervention in a non-study target vessel. Follow-up continued annually in all enrolled patients until the last enrolled patient reached 2 years after randomisation. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischaemia-driven target-vessel revascularisation, or hospitalisation for unstable or progressive angina, assessed in the intention-to-treat population at 2 years. Time-to-first-event estimates were calculated with the Kaplan-Meier method and were compared with the log-rank test. This report is the principal analysis from the trial and includes all long-term analysed data. The trial is registered at ClinicalTrials.gov, NCT02316886, and is complete. Between Sept 23, 2015, and Sept 29, 2021, 5627 patients were screened for eligibility, 1606 of whom were enrolled and randomly assigned to percutaneous coronary intervention (n=803) or optimal medical therapy alone (n=803). 1177 (73%) patients were men and 429 (27%) were women. 2-year follow-up for the primary outcome assessment was completed in 1556 (97%) patients (percutaneous coronary intervention group n=780; optimal medical therapy group n=776). At 2 years, the primary outcome occurred in three (0·4%) patients in the percutaneous coronary intervention group and in 27 (3·4%) patients in the medical therapy group (absolute difference -3·0 percentage points [95% CI -4·4 to -1·8]; p=0·0003). The effect of preventive percutaneous coronary intervention was directionally consistent for each component of the primary composite outcome. Serious clinical or adverse events did not differ between the percutaneous coronary intervention group and the medical therapy group: at 2 years, four (0·5%) versus ten (1·3%) patients died (absolute difference -0·8 percentage points [95% CI -1·7 to 0·2]) and nine (1·1%) versus 13 (1·7%) patients had myocardial infarction (absolute difference -0·5 percentage points [-1·7 to 0·6]). In patients with non-flow-limiting vulnerable coronary plaques, preventive percutaneous coronary intervention reduced major adverse cardiac events arising from high-risk vulnerable plaques, compared with optimal medical therapy alone. Given that PREVENT is the first large trial to show the potential effect of the focal treatment for vulnerable plaques, these findings support consideration to expand indications for percutaneous coronary intervention to include non-flow-limiting, high-risk vulnerable plaques. The CardioVascular Research Foundation, Abbott, Yuhan Corp, CAH-Cordis, Philips, and Infraredx, a Nipro company.

Transcatheter or Surgical Treatment of Aortic-Valve Stenosis

BackgroundAmong low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice.MethodsIn this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year.ResultsA total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan–Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively.ConclusionsAmong patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.)

Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus

BackgroundPatients with severe aortic stenosis and a small aortic annulus are at risk for impaired valvular hemodynamic performance and associated adverse cardiovascular clinical outcomes after transcatheter aortic-valve replacement (TAVR).MethodsWe randomly assigned patients with symptomatic severe aortic stenosis and an aortic-valve annulus area of 430 mm2 or less in a 1:1 ratio to undergo TAVR with either a self-expanding supraannular valve or a balloon-expandable valve. The coprimary end points, each assessed through 12 months, were a composite of death, disabling stroke, or rehospitalization for heart failure (tested for noninferiority) and a composite end point measuring bioprosthetic-valve dysfunction (tested for superiority).ResultsA total of 716 patients were treated at 83 sites in 13 countries (mean age, 80 years; 87% women; mean Society of Thoracic Surgeons Predicted Risk of Mortality, 3.3%). The Kaplan–Meier estimate of the percentage of patients who died, had a disabling stroke, or were rehospitalized for heart failure through 12 months was 9.4% with the self-expanding valve and 10.6% with the balloon-expandable valve (difference, −1.2 percentage points; 90% confidence interval [CI], −4.9 to 2.5; P<0.001 for noninferiority). The Kaplan–Meier estimate of the percentage of patients with bioprosthetic-valve dysfunction through 12 months was 9.4% with the self-expanding valve and 41.6% with the balloon-expandable valve (difference, −32.2 percentage points; 95% CI, −38.7 to −25.6; P<0.001 for superiority). The aortic-valve mean gradient at 12 months was 7.7 mm Hg with the self-expanding valve and 15.7 mm Hg with the balloon-expandable valve, and the corresponding values for additional secondary end points through 12 months were as follows: mean effective orifice area, 1.99 cm2 and 1.50 cm2; percentage of patients with hemodynamic structural valve dysfunction, 3.5% and 32.8%; and percentage of women with bioprosthetic-valve dysfunction, 10.2% and 43.3% (all P<0.001). Moderate or severe prosthesis–patient mismatch at 30 days was found in 11.2% of the patients in the self-expanding valve group and 35.3% of those in the balloon-expandable valve group (P<0.001). Major safety end points appeared to be similar in the two groups.ConclusionsAmong patients with severe aortic stenosis and a small aortic annulus who underwent TAVR, a self-expanding supraannular valve was noninferior to a balloon-expandable valve with respect to clinical outcomes and was superior with respect to bioprosthetic-valve dysfunction through 12 months. (Funded by Medtronic; SMART ClinicalTrials.gov number, NCT04722250.)

Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction

BackgroundMost trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin–angiotensin–aldosterone system antagonists.MethodsIn a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction.ResultsFrom September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no–beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P=0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no–beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no–beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%.ConclusionsAmong patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.)

Use of the Win Ratio Analysis in Critical Care Trials.

Composite outcomes are commonly used in critical care trials to estimate the treatment effect of an intervention. A significant limitation of classical analytic approaches is that they assign equal statistical importance to each component in a composite, even if these do not have the same clinical importance (i.e., in a composite of death and organ failure, death is clearly more important). The win ratio (WR) method has been proposed as an alternative for trial outcomes evaluation, as it effectively assesses events based on their clinical relevance (i.e., hierarchical order) by comparing each patient in the intervention group with their counterparts in the control group. This statistical approach is increasingly used in cardiovascular outcome trials. However, WR may be useful to unveil treatment effects also in the critical care setting, because these trials are typically moderately sized, thus limiting the statistical power to detect small differences between groups, and often rely on composite outcomes that include several components of different clinical importance. Notably, the advantages of this approach may be offset by several drawbacks (such as ignoring ties and difficulties in selecting and ranking endpoints) and challenges in appropriate clinical interpretation (i.e., establishing clinical meaningfulness of the observed effect size). In this perspective article, we present some key elements to implementing WR statistics in critical care trials, providing an overview of strengths, drawbacks, and potential applications of this method. To illustrate, we conduct a reevaluation of the HYPO-ECMO (Hypothermia during Venoarterial Extracorporeal Membrane Oxygenation) trial using the WR framework as a case example.

Utilidad de los biomarcadores en el trasplante cardiaco para predecir el pronóstico

Introduction and objectivesHeart transplant (HT) represents a major physiological stress, resulting in elevated levels of analytical biomarkers. This study aimed to determine whether changes in biomarker levels after HT can identify patients with a poor prognosis. MethodsA prospective longitudinal noninterventional study was conducted in 149 consecutive patients undergoing HT from July 2017 to July 2023. Biomarkers were assessed before HT and at 6, 24, 48, 72, and 96hours after HT. The biomarkers analyzed were high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatinine, and lactic acid. The primary outcome was a composite of death and severe primary graft failure (PGF). ResultsNT-proBNP and troponin levels remained highly elevated throughout the period and stabilized from the first 24hours post-HT. Lactate levels stabilized after the first 24hours, and creatinine from the second day onward. Exitus occurred in 23 (15%) of the patients, and severe PGF in 26 (17%). All biomarkers were significantly associated with the incidence of the combined event (P <.0001). Receiver operating characteristic curve analysis at 24hours showed significant areas under the curve (P=.0001). The greatest discriminatory power was observed for the NT-proBNP curve. A value of 10 000 pg/mL had a sensitivity of 90% and specificity of 80%. ConclusionsA significant elevation of post-HT analytical biomarkers was associated with mortality and/or severe PGF. Among the biomarkers analyzed, NT-proBNP was the most accurate in classifying patients.

Regional Differences in Outcomes with Ablation Versus Drug Therapy for Atrial Fibrillation: Results from the CABANA Trial

The finding of unexpected variations in treatment benefits by geographic region in international clinical trials raises complex questions about the interpretation and generalizability of trial findings. We observed such geographical variations in outcome and in the effectiveness of atrial fibrillation (AF) ablation versus drug therapy in the Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial. This paper describes these differences and investigates potential causes. The examination of treatment effects by geographic region was a prespecified analysis. CABANA enrolled patients from 10 countries, with 1,285 patients at 85 North American (NA) sites and 919 at 41 non-NA sites. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Death and first atrial fibrillation recurrence were secondary endpoints. At least 1 primary endpoint event occurred in 157 patients (12.2%) from NA and 33 (3.6%) from non-NA sites over a median 54.9 and 40.5 months of follow-up, respectively (NA/non-NA adjusted hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.48-3.21, P < .001). In NA patients, 78 events occurred in the ablation and 79 in the drug arm, (HR 0.91, 95% CI 0.66, 1.24) while 11 and 22 events occurred in non-NA patients (HR 0.51, 95% CI 0.25,1.05, interaction P = .154). Death occurred in 53 ablation and 51 drug therapy patients in the NA group (HR 0.96, 95% CI 0.65,1.42) and in 5 ablation and 16 drug therapy patients in the non-NA group (HR 0.32, 95% CI 0.12,0.86, interaction P = .044). Adjusting for baseline regional differences or prognostic risk variables did not account for the regional differences in treatment effects. Atrial fibrillation recurrence was reduced by ablation in both regions (NA: HR 0.54, 95% CI 0.46, 0.63; non-NA: HR 0.44, 95% CI 0.30, 0.64, interaction P = .322). In CABANA, primary outcome events occurred significantly more often in the NA group but assignment to ablation significantly reduced all-cause mortality in the non-NA group only. These differences were not explained by regional variations in procedure effectiveness, safety, or patient characteristics. ClinicalTrials.gov Identifier: NCT0091150; https://clinicaltrials.gov/study/NCT00911508.

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor. To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

The Value of a Coronary Computed Tomography Angiography plus Stress Cardiac Magnetic Resonance Imaging Strategy for the Evaluation of Patients with Chronic Coronary Syndrome.

Background: Noninvasive imaging methods, either anatomical or functional tests, serve as essential instruments for the appropriate management of patients with established or suspected coronary artery disease (CAD). We sought to evaluate the safety and efficacy of a coronary computed tomography angiography (CCTA) plus stress cardiac magnetic resonance imaging (S-CMR) strategy in patients with chronic coronary syndrome (CCS). Methods: Patients with suspected CCS showing intermediate coronary plaques (stenosis 30-70%) at CCTA underwent S-CMR. Patients with a positive S-CMR were referred to invasive coronary angiography (ICA) plus instantaneous wave-free ratio (iFR), and myocardial revascularization if recommended. All patients received guideline-directed medical therapy (GDMT), including high-dose statins, regardless of myocardial revascularization. The primary endpoint was a composite of death from cardiovascular causes, non-fatal myocardial infarction, and unplanned revascularization. Results: According to the results of CCTA, 62 patients showing intermediate coronary plaques underwent S-CMR, which was positive for a myocardial perfusion deficit in n = 17 (27%) and negative in n = 45 (73%) patients. According to the results of ICA plus iFR, revascularization was performed in 13 patients. No differences in the primary endpoint between the positive and negative S-CMR groups were observed at 1 year (1 [5.9%] vs. 1 [2.2%], p = 0.485) and after a median of 33.4 months (2 [11.8%] vs. 3 [6.7%]; p = 0.605). Conclusions: Our study suggests that a CCTA plus S-CMR strategy is effective for the evaluation of patients with suspicion of CCS at low-intermediate risk, and it may help to refine the selection of patients with intermediate coronary plaques at CCTA needing coronary revascularization.

Impact of pre-admission physical activity on benefits of physiology-guided complete revascularization in older patients with myocardial infarction: insights from the FIRE trial.

The present analysis from the Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial aims to explore the significance of pre-admission physical activity and assess whether the benefits of physiology-guided complete revascularization apply consistently to sedentary and active older patients. Patients aged 75 years or more with myocardial infarction (MI) and multivessel disease were randomized to receive physiology-guided complete revascularization or culprit-only strategy. The primary outcome was a composite of death, MI, stroke, or any revascularization within a year. Secondary endpoints included the composite of cardiovascular death or MI, as well as single components of the primary endpoint. Pre-admission physical activity was categorized into three groups: (i) absent (sedentary), (ii) light, and (iii) vigorous. Among 1445 patients, 692 (48%) were sedentary, whereas 560 (39%) and 193 (13%) performed light and vigorous physical activity, respectively. Patients engaging in light or vigorous pre-admission physical activity exhibited a reduced risk of the primary outcome compared with sedentary individuals [light hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.55-0.91 and vigorous HR 0.14, 95% CI 0.07-0.91, respectively]. These trends were also observed for death, cardiovascular death, or MI. When comparing physiology-guided complete revascularization vs. culprit-only strategy, no significant interaction was observed for primary and secondary endpoints when stratified by sedentary or active status. In older patients with MI, pre-admission physical activity emerges as a robust and independent prognostic determinant. Physiology-guided complete revascularization stands out an effective strategy in reducing ischaemic adverse events, irrespective of pre-admission physical activity status. ClinicalTrials.gov NCT03772743.