BACKGROUND:Complete revascularization is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, whether the non-culprit lesions should be evaluated using angiography or fractional flow reserve (FFR) remains uncertain. The aim of this study was to evaluate the long-term outcome of patients with STEMI and multivessel disease who had non-culprit FFR-values >0.80 and thus deferred PCI. METHODS:Of the 627 patients included in the DANAMI-3-PRIMULTI trial, 314 patients were randomized to FFR-guided complete revascularization and 280 were included in this substudy. Patients were divided into a PCI-deferral group who had no PCI of non-culprit lesions (FFR > 0.80) (n = 106) and a PCI group encompassing patients treated with PCI of at least one non-culprit lesion (FFR ≤ 0.80 or an angiographical diameter stenosis of ≥90%) (n = 174). The combined endpoint included all-cause mortality, myocardial infarction, or urgent revascularization. RESULTS:During a median follow-up of 10.5 years (IQR 9.8-11.4), the composite outcome occurred in 62 (36%) patients in the PCI group and in 50 (47%) patients in the PCI-deferral group (adjusted HR 0.64, 95% CI: 0.44-0.95, p = 0.025). PCI-deferral was associated with a significantly higher risk of cardiovascular mortality (adjusted HR 0.48, CI 95% 0.24-0.97, p = 0.040) compared to the PCI group. CONCLUSION:In patients with STEMI and multivessel disease, deferring PCI of non-culprit lesions based on FFR > 0.80 was associated with an increased risk of the combination of all-cause mortality, myocardial infarction, or urgent revascularization as well as cardiovascular mortality compared to patients treated with PCI of FFR-positive non-culprit lesions.

AIMS:The benefit of complete revascularization after primary percutaneous coronary intervention (PCI) is well established in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, but the long-term effect in older patients remains uncertain. We aimed to evaluate the 10-year outcome of complete revascularization in older patients (aged ≥75 years) compared with younger patients. METHODS AND RESULTS:Patients with STEMI and multivessel disease were randomized to either culprit-only or fractional flow reserve-guided complete revascularization in the DANAMI-3-PRIMULTI trial. This long-term sub-study stratified the included 627 patients by <75 years (517) and ≥75 years (110). The primary outcome was a composite of all-cause mortality, recurrent myocardial infarction, or any revascularization occurring during a median follow-up of 10.5 years. Of the older patients, 50 underwent complete and 60 culprit-only revascularization, and of the younger patients, 264 were completely revascularized compared to 253 who had culprit-only PCI performed.In the older group, complete revascularization showed no association with the primary outcome (adjusted hazard ratio [HR] 1.29, 95% confidence interval [CI]: 0.82-2.03, P = 0.27). In contrast, complete revascularization was associated with a lower risk of the primary outcome (adjusted HR 0.68, 95% CI: 0.53-0.88, P = 0.003) in younger patients, primarily driven by a reduction in any revascularization (adjusted HR 0.60, 95% CI: 0.44-0.83, P = 0.002. CONCLUSION:In patients aged ≥75 years, clear evidence of a long-term (10 years) benefit of complete revascularization was not demonstrated. However, the elderly subgroup was small with limited events, and the finding should be interpreted as inconclusive. In contrast, complete revascularization was associated with a 32% lower risk of adverse outcomes among younger patients, primarily driven by a reduction in repeat revascularization, without evidence of reduced all-cause death or recurrent myocardial infarction.

BACKGROUND:In patients presenting with acute coronary syndromes and multivessel coronary artery disease, the question of whether to undertake a strategy of complete revascularisation in cases in which percutaneous coronary intervention (PCI) is performed routinely on non-culprit lesions (in addition to the culprit lesion) or whether to restrict PCI only to the culprit lesion is a common dilemma. The Complete Revascularisation Trialists' Collaboration aimed to determine, based on the totality of data from randomised trials, the effect of a complete revascularisation strategy on major cardiovascular events and whether it reduces cardiovascular death. METHODS:In this individual patient data meta-analysis, trials were included if they enrolled at least 250 patients, compared a complete revascularisation strategy (with PCI) to a culprit lesion-only PCI strategy, and enrolled patients presenting with acute ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction. To ensure that no trials were overlooked, we searched Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomised controlled trials published between 1996 and Sept 15, 2025. The primary outcomes were the composite of cardiovascular death or new myocardial infarction and cardiovascular death alone. Hierarchical testing of cardiovascular death alone was planned contingent on reduction in cardiovascular death or new myocardial infarction based on the prespecified alpha level of 0·04. A one-stage individual patient data meta-analysis was performed using a Cox frailty model. All-cause death was the secondary outcome; non-cardiovascular death and new myocardial infarction were additional outcomes. All analyses included all randomly assigned patients. The meta-analysis was registered in PROSPERO, CRD420251124098. FINDINGS:Six randomised controlled trials involving 8836 individuals were included. The median age was 65·8 years (IQR 57·0-76·0), and 2088 (23·6%) patients were female and 6748 (76·4%) were male. Overall, 7768 (87·9%) patients presented with ST-segment elevation myocardial infarction and 1068 (12·1%) with non-ST-segment elevation myocardial infarction. At a median follow-up of 36·0 months (IQR 30·6-48·0), cardiovascular death or new myocardial infarction occurred in 382 (9·0%) of 4259 patients in the complete revascularisation group compared with 528 (11·5%) of 4577 patients in the culprit lesion-only group (hazard ratio [HR] 0·76 [95% CI 0·67-0·87], p<0·0001). There were 155 (3·6%) cardiovascular deaths in the complete revascularisation group compared with 209 (4·6%) in the culprit lesion-only group (HR 0·76 [95% CI 0·62-0·93], p=0·0091). All-cause death occurred in 308 (7·2%) patients in the complete revascularisation group compared with 370 (8·1%) patients in the culprit lesion-only group (HR 0·85 [95% CI 0·73-0·99], p=0·039). Non-cardiovascular death was similar between the groups (153 [3·6%] in the complete revascularisation group vs 161 [3·5%] in the culprit lesion-only group; HR 0·98 [95% CI 0·78-1·22], p=0·85). Complete revascularisation reduced new myocardial infarctions compared with culprit lesion-only PCI (255 [6·0%] vs 357 [7·8%]; HR 0·76 [95% CI 0·65-0·90], p=0·0011). INTERPRETATION:In patients presenting with acute myocardial infarction and multivessel disease, complete revascularisation reduced the composite of cardiovascular death or new myocardial infarction as well as cardiovascular death alone compared with a culprit lesion-only PCI strategy. In addition, all-cause death was lower with complete revascularisation. These data provide the strongest and most robust evidence to date that complete revascularisation improves important cardiovascular clinical outcomes. FUNDING:None.

BACKGROUND:Female patients are at greater risk of adverse events following non-ST-elevation acute coronary syndrome but less frequently receive guideline-recommended coronary angiography and revascularization. Routine invasive management benefits high-risk patients, but evidence informing the optimal timing of angiography specifically in female patients is lacking. METHODS:Medline, Web of Science, and Scopus were searched up to November 2023. Randomized controlled trials investigating early versus delayed timing of coronary angiography in patients with non-ST-elevation acute coronary syndrome were included. Individual patient data from female patients were extracted. The primary end point was a composite of all-cause mortality or myocardial infarction at 6 months. We performed a 1-stage individual patient data meta-analysis using random-effects Cox models. RESULTS:Six trials contributed individual patient data from 2257 female patients. Median time to coronary angiography was 5 hours in the early invasive group (n=1141) and 49 hours in the delayed invasive group (n=1116). Overall, there was no significant reduction in the risk of the primary end point in the early invasive group compared with the delayed group (hazard ratio, 0.79 [95% CI, 0.60-1.06]; P=0.12). Early invasive management was associated with a reduction in recurrent ischemia (hazard ratio, 0.60 [95% CI, 0.39-0.94]; P=0.025). In the prespecified subgroup analysis, high-risk female patients with Global Registry of Acute Coronary Events score >140 receiving early invasive management experienced a significantly reduced hazard for all-cause mortality or myocardial infarction at 6 months (hazard ratio, 0.65 [95% CI, 0.45-0.94]; P=0.021; Pinteraction=0.035). Similar benefits were observed for female patients with elevated cardiac biomarkers. CONCLUSIONS:Early invasive management in female patients with non-ST-elevation acute coronary syndrome, compared with delayed invasive management, was not associated with a significant reduction in the hazard for the primary end point. In prespecified subgroup analysis, high-risk female patients as assessed with Global Registry of Acute Coronary Events score >140 or elevated cardiac biomarkers experienced significant reductions in all-cause mortality or myocardial infarction at 6 months following early invasive management. REGISTRATION:URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42023468604.

BACKGROUND:TAP-IT (Thoracentesis to Alleviate Cardiac Pleural Effusion-Interventional Trial) investigated the effect of therapeutic thoracentesis in addition to standard medical therapy in patients with acute heart failure and sizeable pleural effusion. METHODS:This multicenter, unblinded, randomized controlled trial, conducted between August 31, 2021, and March 22, 2024, included patients with acute heart failure, left ventricular ejection fraction ≤45%, and non-negligible pleural effusion. Patients with very large effusions (more than two-thirds of the hemithorax) were excluded. Participants were randomly assigned 1:1 to upfront ultrasound-guided pleural pigtail catheter thoracentesis in addition to standard medical therapy or standard medical therapy alone. The primary outcome was days alive out of the hospital over the following 90 days; key secondary outcomes included length of admission and 90-day all-cause mortality. All outcomes were analyzed according to the intention-to-treat principle. RESULTS:A total of 135 patients (median age, 81 years [25th; 75th percentile, 75; 83]; 33% female; median left ventricular ejection fraction, 25% [25th; 75th percentile, 20%; 35%]) were randomized to either thoracentesis (n=68) or standard medical therapy (n=67). The thoracentesis group had a median of 84 days (77; 86) alive out of the hospital over the following 90 days compared with 82 days (73; 86) in the control group (P=0.42). The mortality rate was 13% in both groups, with no difference in survival probability (P=0.90). There were no differences in the duration of the index admission (control group median, 5 days [3; 8]; thoracentesis group median, 5 days [3; 7], P=0.69). Major complications occurred in 1% of thoracenteses performed during the study period. CONCLUSIONS:For patients with acute heart failure and pleural effusion, a strategy of upfront routine thoracentesis in addition to standard medical therapy did not increase days alive out of the hospital for 90 days, all-cause mortality, or duration of index admission. The current findings lay the groundwork for future research to confirm the results. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05017753.

BACKGROUND:Primary percutaneous coronary intervention (PCI) with stenting is recommended in ST-segment-elevation myocardial infarction. Immediate stenting may cause distal embolization, microvascular damage, and flow disturbances, leading to adverse outcomes. We report the 10-year clinical outcomes of deferred stenting versus conventional PCI in patients with ST-segment-elevation myocardial infarction. METHODS:We conducted a 10-year follow-up study of the open-label, randomized DANAMI-3-DEFER trial (Third Danish Study of Optimal Acute Treatment of Patients With STEMI - Deferred Stent Implantation Versus Conventional Treatment), conducted in 4 PCI centers in Denmark. Patients with ST-segment-elevation myocardial infarction and acute chest pain <12 hours were randomized to deferred stenting >24 hours after the index procedure or conventional PCI with immediate stenting. In the deferred group, immediate stable Thrombolysis in Myocardial Infarction flow II to III was established, and intravenous administration of either a glycoprotein IIb/IIIa antagonist or bivalirudin for >4 hours after the index procedure was recommended. The primary outcome was a composite of hospitalization for heart failure or all-cause mortality. Key secondary outcomes included individual components of the primary outcome and target vessel revascularization. RESULTS:Of 1215 patients, 603 were randomized to deferred stenting and 612 to conventional PCI. After 10 years, deferred stenting did not significantly reduce the primary composite outcome (hazard ratio, 0.82 [95% CI, 0.67-1.02]; P=0.08). In the deferred group, 124 (24%) died versus 150 (25%) in the conventional PCI group (hazard ratio, 0.95 [95% CI, 0.75-1.19]). Hospitalization for heart failure was lower in patients treated with deferred stenting compared with conventional PCI (odds ratio, 0.58 [95% CI, 0.39-0.88]). Target vessel revascularization was similar in both groups (odds ratio, 1.20 [95% CI, 0.81-1.79]). CONCLUSIONS:Deferred stenting did not reduce all-cause mortality or the composite primary outcome after 10 years but reduced hospitalization for heart failure compared with conventional PCI. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01435408.

BACKGROUND:We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS:855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS:Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION:Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

BACKGROUND:Complete revascularization is the standard treatment for patients with ST-segment-elevation myocardial infarction and multivessel disease. The FIRE trial (Functional Assessment in Elderly Myocardial Infarction Patients With Multivessel Disease) confirmed the benefit of complete revascularization in a population of older patients, but the follow-up is limited to 1 year. Therefore, the long-term benefit (>1 year) of this strategy in older patients is debated. To address this, an individual patient data meta-analysis was conducted in patients with ST-segment-elevation myocardial infarction ≥75 years of age enrolled in randomized clinical trials investigating complete versus culprit-only revascularization strategies. METHODS:PubMed, Embase, and the Cochrane database were systematically searched to identify randomized clinical trials comparing complete versus culprit-only revascularization. Individual patient-level data were collected from the relevant trials. The primary end point was death, myocardial infarction, or ischemia-driven revascularization. The secondary end point was cardiovascular death or myocardial infarction. RESULTS:Data from 7 randomized clinical trials encompassing 1733 patients (917 randomized to culprit-only and 816 to complete revascularization) were analyzed. The median age was 79 [interquartile range, 77-83] years. Of the patients, 595 (34%) were female. Follow-up ranged from a minimum of 6 months to a maximum of 6.2 years (median, 2.5 [interquartile range, 1-3.8] years). Complete revascularization reduced the primary end point up to 4 years (hazard ratio, 0.78 [95% CI, 0.63-0.96]) but not at the longest available follow-up (hazard ratio, 0.83 [95% CI, 0.69-1.01]). Complete revascularization significantly reduced the occurrence of cardiovascular death or myocardial infarction at the longest available follow-up (hazard ratio, 0.76 [95% CI, 0.58-0.99]). This was observed even when censoring the follow-up at each year. Long-term rate of death did not differ between complete and culprit-only revascularization arms. CONCLUSIONS:In this individual patient data meta-analysis of older patients with ST-segment-elevation myocardial infarction and multivessel disease, complete revascularization reduced the primary end point of death, myocardial infarction, or ischemia-driven revascularization up to 4 years. At the longest follow-up, complete revascularization reduced the composite of cardiovascular death or myocardial infarction but not the primary end point. REGISTRATION:URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022367898.

AIMS:Although body mass index (BMI) is the most commonly used anthropometric measure to assess adiposity, alternative indices such as the waist-to-height ratio may better reflect the location and amount of ectopic fat as well as the weight of the skeleton. METHODS AND RESULTS:The prognostic value of several alternative anthropometric measures was compared with that of BMI in 1116 patients with non-ischaemic heart failure with reduced ejection fraction (HFrEF) enrolled in DANISH. The association between anthropometric measures and all-cause death was adjusted for prognostic variables, including natriuretic peptides. Median follow-up was 9.5 years (25th-75th percentile, 7.9-10.9). Compared to patients with a BMI 18.5-24.9 kg/m2 (n = 363), those with a BMI ≥25 kg/m2 had a higher risk of all-cause and cardiovascular death, although this association was only statistically significant for a BMI ≥35 kg/m2 (n = 91) (all-cause death: hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.28-2.48; cardiovascular death: HR 2.46, 95% CI 1.69-3.58). Compared to a BMI 18.5-24.9 kg/m2, a BMI <18.5 kg/m2 (n = 24) was associated with a numerically, but not a significantly, higher risk of all-cause and cardiovascular death. Greater waist-to-height ratio (as an exemplar of indices not incorporating weight) was also associated with a higher risk of all-cause and cardiovascular death (HR for the highest vs. the lowest quintile: all-cause death: HR 2.11, 95% CI 1.53-2.92; cardiovascular death: HR 2.17, 95% CI 1.49-3.15). CONCLUSION:In patients with non-ischaemic HFrEF, there was a clear association between greater adiposity and higher long-term mortality. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT00542945.

Abstract Background Intermediate-high risk pulmonary embolism (PE) carries a significant risk of hemodynamic deterioration or death. Treatment should balance efficacy in reducing clot burden with the risk of complications, particularly bleeding. Previous studies on high-dose, short-term thrombolysis with alteplase (rtPA) showed a reduced risk of hemodynamic deterioration but no change in mortality and increased bleeding complications. Catheter-based techniques, including ultrasound-assisted thrombolysis (USAT), and low-dose thrombolysis may offer reasonable efficacy with lower risk. However, studies comparing these methods have been few. This trial aims to address this gap by randomizing patients to three treatment modalities. Methods Multicenter, randomized trial with 1:1:1 allocation of 210 patients with acute intermediate-high risk PE, excluding those with absolute contraindications to thrombolysis. Patients are eligible for inclusion if they are > 18 years of age, have had symptoms < 14 days, and are able to give informed consent. Patients are allocated 1:1:1 into three treatment strategies: (1) unfractionated heparin (UFH)/low molecular weight heparin (LMWH), (2) UFH/LMWH + 20 mg rtPA/6 h intravenously (IV), or (3) UFH + 20 mg rtPA/6 h via USAT. Co-primary outcomes include reduction in clot burden as assessed by refined Miller score from pre-treatment to follow-up (48–96 h) computed tomography pulmonary angiogram (CTPA) comparing low-dose rtPA (± USAT) groups to UFH/LMWH group (p < 0.01, N = 210) and reduction in refined Miller score on follow-up CT angiography comparing low-dose rtPA by USAT to intravenous rtPA, p < 0.04, N = 140). Secondary outcomes comprise bleeding complications, duration of index admission, FiO2, blood pressure, respiratory and heart rate at the time of follow-up CT angiography, mortality in the three groups, incidence of tricuspid regurgitation pressure gradient < 40 mmHg at 3 months follow-up echocardiography, 6-min walk test at 3 months comparing the three groups, and health-related quality of life at 3 months follow-up comparing the three groups. Discussion We hypothesize that in patients with intermediate-high risk PE (1) administration of 20 mg rtPA leads to a greater reduction in clot burden compared to heparins and (2) administration of 20 mg rtPA via USAT results in a greater reduction in clot burden compared to 20 mg rtPA intravenous. Trial registration ClinicalTrials.gov NCT04088292. Registered in September 2019 (retrospectively registered).

Aims: Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure, a left ventricular ejection fraction of <= 35%, and New York Heart Association (NYHA) class II-III. However, the evidence regarding the benefit of primary prevention ICD is less consistent in patients with NYHA class III. We investigated the long-term effects of primary prevention ICD implantation according to NYHA class in an extended follow-up study of the DANISH trial. Methods and results: The DANISH trial randomized 1116 patients with non-ischaemic heart failure with reduced ejection fraction (HFrEF) to ICD implantation or usual care. Outcomes were analysed according to NYHA class at baseline (NYHA class II and III/IV). The primary outcome was all-cause mortality. Of the 1116 patients randomized in the DANISH trial, 597 (53.5%) were in NYHA class II at baseline, 505 (45.3%) in NYHA class III, and 14 (1.3%) in NYHA class IV. During a median follow-up of 9.5 years, NYHA class III/IV, compared with NYHA class II, were associated with a greater long-term rate of all-cause mortality (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.20-1.93) and cardiovascular death (HR 1.95 [1.47-2.60]). ICD implantation, compared with usual care, did not reduce the long-term rate of all-cause mortality (all participants: HR 0.89 [95% CI 0.74-1.08]; NYHA class II: HR 0.85 [0.64-1.13]; NYHA class III/IV: HR 0.89 [0.69-1.14]; p(interaction) = 0.78) or cardiovascular death (all participants: HR 0.87 [95% CI 0.70-1.09]; NYHA class II: HR 0.78 [0.54-1.12]; NYHA class III/IV: HR 0.89 [0.67-1.19]; p(interaction) = 0.58), irrespective of NYHA class. Similarly, NYHA class did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (all participants: HR 0.60 [95% CI 0.40-0.92]; NYHA class II: HR 0.73 [0.40-1.36]; NYHA class III/IV: HR 0.52 [0.29-0.94]; p(interaction) = 0.39). Conclusions: In patients with non-ischaemic HFrEF, ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce sudden cardiovascular death, regardless of baseline NYHA class.

BACKGROUND:The Heart Failure Collaboratory (HFC) score integrates types and dosages of guideline-directed pharmacotherapies for heart failure (HF) with reduced ejection fraction (HFrEF). We examined the effects of cardioverter-defibrillator (ICD) implantation according to the modified HFC (mHFC) score in 1116 patients with nonischemic HFrEF from the Danish Study to Assess the Efficacy of ICDs in Patients with Nonischemic Systolic HF on Mortality (DANISH). METHODS AND RESULTS:Patients were assigned scores for renin-angiotensin-system inhibitors, beta-blockers and mineralocorticoid receptor antagonists (0, no use; 1, < 50% of maximum dosage; 2, ≥ 50% of maximum dosage). The maximum score was 6, corresponding to ≥ 50% of maximum dosage for all therapies. The median baseline mHFC score was 4, and the median follow-up was 9.5 years. Compared with an mHFC score of 3-4, an mHFC score of 1-2 was associated with a higher rate of all-cause death (mHFC = 1-2: adjusted HR 1.67 [95% CI, 1.23-2.28]; mHFC = 3-4, reference; mHFC = 5-6: adjusted HR 1.07 [95% CI, 0.87-1.31]). ICD implantation did not reduce all-cause death compared with control (reference) (HR 0.89 [95% CI, 0.74-1.08]), regardless of mHFC score (mHFC = 1-2: HR 0.98 [95% CI, 0.56-1.71]; mHFC = 3-4: HR 0.89 [95% CI,0.66-1.20]; mHFC = 5-6: HR 0.85 [95% CI, 0.64-1.12]; Pinteraction, 0.65). Similarly, ICD implantation did not reduce cardiovascular death (HR 0.87 [95% CI, 0.70-1.09]), regardless of mHFC score (Pinteraction, 0.59). The ICD group had a lower rate of sudden cardiovascular death (HR, 0.60 [95% CI,0.40-0.92]); this association was not modified by mHFC score (Pinteraction, 0.35). CONCLUSIONS:Lower mHFC scores were associated with higher rates of all-cause death. ICD implantation did not result in an overall survival benefit in patients with nonischemic HFrEF, regardless of mHFC score.

Introduction Pleural effusion is present in half of the patients hospitalised with acute heart failure. The condition is treated with diuretics and/or therapeutic thoracentesis for larger effusions. No evidence from randomised trials or guidelines supports thoracentesis to alleviate pleural effusion due to acute heart failure. The Thoracentesis to Alleviate cardiac Pleural effusion Interventional Trial (TAP-IT) will investigate if a strategy of referring patients with acute heart failure and pleural effusion to up-front thoracentesis by pleural pigtail catheter insertion in addition to pharmacological therapy compared with pharmacological therapy alone can increase the number of days the participants are alive and not hospitalised during the 90 days following randomisation.Methods and analysis TAP-IT is a pragmatic, multicentre, open-label, randomised controlled trial aiming to include 126 adult patients with left ventricular ejection fraction ≤45% and a non-negligible pleural effusion due to heart failure. Participants will be randomised 1:1, stratified according to site and anticoagulant treatment, and assigned to referral to up-front ultrasound-guided pleural pigtail catheter thoracentesis in addition to standard pharmacological therapy or to standard pharmacological therapy only. Thoracentesis is performed according to local guidelines and can be performed in participants in the pharmacological treatment arm if their condition deteriorates or if no significant improvement is observed within 5 days. The primary endpoint is how many days participants are alive and not hospitalised within 90 days from randomisation and will be analysed in the intention-to-treat population. Key secondary outcomes include 90-day mortality, complications, readmissions, and quality of life.Ethics and dissemination The study has been approved by the Capital Region of Denmark Scientific Ethical Committee (H-20060817) and Knowledge Center for Data Reviews (P-2021–149). All participants will sign an informed consent form. Enrolment began in August 2021. Regardless of the nature, results will be published in a peer-reviewed medical journal.Trial registration number NCT05017753.

Background Patients with heart failure and chronic kidney disease (CKD) may have an increased risk of death from causes competing with arrhythmic death, which could have implications for the efficacy of implantable cardioverter‐defibrillators (ICDs). We examined the long‐term effects of primary prophylactic ICD implantation, compared with usual care, according to baseline CKD status in an extended follow‐up study of DANISH (Danish Study to Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality). Methods and Results In the DANISH trial, 1116 patients with nonischemic heart failure with reduced ejection fraction were randomized to receive an ICD (N=556) or usual care (N=550). Outcomes were analyzed according to CKD status (estimated glomerular filtration rate ≥/<60 mL/min per 1.73 m2) at baseline. In total, 1113 patients had an available estimated glomerular filtration rate measurement at baseline (median estimated glomerular filtration rate 73 mL/min per 1.73 m2), and 316 (28%) had CKD. During a median follow‐up of 9.5 years, ICD implantation, compared with usual care, did not reduce the rate of all‐cause mortality (no CKD, HR, 0.82 [95% CI, 0.64–1.04]; CKD, HR, 1.02 [95% CI, 0.75–1.38]; Pinteraction=0.31) or cardiovascular death (no CKD, HR, 0.77 [95% CI, 0.58–1.03]; CKD, HR, 1.05 [95% CI, 0.73–1.51]; Pinteraction=0.20), irrespective of baseline CKD status. Similarly, baseline CKD status did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (no CKD, HR, 0.57 [95% CI, 0.32–1.00]; CKD, HR, 0.65 [95% CI, 0.34–1.24]; Pinteraction=0.70). Conclusions ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce the rate of sudden cardiovascular death, regardless of baseline kidney function in patients with nonischemic heart failure with reduced ejection fraction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00542945.

HomeCirculationVol. 148, No. 15Implantable Cardioverter Defibrillator in Patients With Nonischemic Systolic Heart Failure With and Without Cardiac Resynchronization Therapy: Extended Follow-Up Study of the DANISH Trial No AccessResearch ArticleRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessResearch ArticleRequest AccessFull TextImplantable Cardioverter Defibrillator in Patients With Nonischemic Systolic Heart Failure With and Without Cardiac Resynchronization Therapy: Extended Follow-Up Study of the DANISH Trial Jawad H. Butt, Adelina Yafasova, Seiko N. Doi, Jens C. Nielsen, Jens Haarbo, Hans Eiskjær, Axel Brandes, Anna M. Thøgersen, Finn Gustafsson, Christian Hassager, Jesper H. Svendsen, Dan E. Høfsten, Lars Videbæk, Christian Torp-Pedersen, Steen Pehrson, Jens Jakob Thune and Lars Køber Jawad H. ButtJawad H. Butt Correspondence to: Jawad H. Butt, MD, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark. Email E-mail Address: [email protected] https://orcid.org/0000-0002-7380-4144 Department of Cardiology, Copenhagen University Hospital–Rigshospitalet, Denmark (J.W.B., A.Y., S.N.D., F.G., C.H., J.H.S., D.E.H., S.P., L.K.). Search for more papers by this author , Adelina YafasovaAdelina Yafasova https://orcid.org/0000-0003-3889-0080 Department of Cardiology, Copenhagen University Hospital–Rigshospitalet, Denmark (J.W.B., A.Y., S.N.D., F.G., C.H., J.H.S., D.E.H., S.P., L.K.). Search for more papers by this author , Seiko N. DoiSeiko N. Doi Department of Cardiology, Copenhagen University Hospital–Rigshospitalet, Denmark (J.W.B., A.Y., S.N.D., F.G., C.H., J.H.S., D.E.H., S.P., L.K.). Search for more papers by this author , Jens C. NielsenJens C. Nielsen https://orcid.org/0000-0001-9414-1653 Department of Cardiology, Aarhus University Hospital, Denmark (J.C.N., H.E.). Department of Clinical Medicine, Aarhus University, Denmark (J.C.N.). Search for more papers by this author , Jens HaarboJens Haarbo Department of Cardiology, Copenhagen University Hospital–Herlev and Gentofte, Hellerup, Denmark (J.H., L.K.). Search for more papers by this author , Hans EiskjærHans Eiskjær https://orcid.org/0000-0003-1520-1924 Department of Cardiology, Aarhus University Hospital, Denmark (J.C.N., H.E.). Search for more papers by this author , Axel BrandesAxel Brandes https://orcid.org/0000-0001-9145-6887 Department of Cardiology, Odense University Hospital, Denmark (A.B.). Department of Clinical Research, University of Southern Denmark, Odense (A.B.). Department of Cardiology, University Hospital of Southern Denmark, Esbjerg (A.B.). Search for more papers by this author , Anna M. ThøgersenAnna M. Thøgersen Department of Cardiology, Aalborg University Hospital, Denmark (A.M.T.). Search for more papers by this author , Finn GustafssonFinn Gustafsson https://orcid.org/0000-0003-2144-341X Department of Cardiology, Copenhagen University Hospital–Rigshospitalet, Denmark (J.W.B., A.Y., S.N.D., F.G., C.H., J.H.S., D.E.H., S.P., L.K.). Department of Clinical Medicine, University of Copenhagen, Denmark (F.G., C.H., J.H.S., D.E.H., J.J.T.). Search for more papers by this author , Christian HassagerChristian Hassager https://orcid.org/0000-0002-1199-0981 Department of Cardiology, Copenhagen University Hospital–Rigshospitalet, Denmark (J.W.B., A.Y., S.N.D., F.G., C.H., J.H.S., D.E.H., S.P., L.K.). Department of Clinical Medicine, University of Copenhagen, Denmark (F.G., C.H., J.H.S., D.E.H., J.J.T.). Search for more papers by this author , Jesper H. SvendsenJesper H. Svendsen https://orcid.org/0000-0001-8466-8515 Department of Cardiology, Copenhagen University Hospital–Rigshospitalet, Denmark (J.W.B., A.Y., S.N.D., F.G., C.H., J.H.S., D.E.H., S.P., L.K.). Department of Clinical Medicine, University of Copenhagen, Denmark (F.G., C.H., J.H.S., D.E.H., J.J.T.). Search for more papers by this author , Dan E. HøfstenDan E. Høfsten https://orcid.org/0000-0002-7609-4141 Department of Cardiology, Copenhagen University Hospital–Rigshospitalet, Denmark (J.W.B., A.Y., S.N.D., F.G., C.H., J.H.S., D.E.H., S.P., L.K.). Department of Clinical Medicine, University of Copenhagen, Denmark (F.G., C.H., J.H.S., D.E.H., J.J.T.). Search for more papers by this author , Lars VidebækLars Videbæk https://orcid.org/0000-0001-7740-1564 Department of Cardiology, Odense University Hospital, Svendborg, Denmark (L.V.). Search for more papers by this author , Christian Torp-PedersenChristian Torp-Pedersen https://orcid.org/0000-0003-2892-6131 Department of Cardiology, Nordsjællands Hospital, Hillerød, Denmark (C.T.-P.). Department of Public Health, University of Copenhagen, Denmark (C.T.-P.). Search for more papers by this author , Steen PehrsonSteen Pehrson https://orcid.org/0000-0002-7149-4613 Department of Cardiology, Copenhagen University Hospital–Rigshospitalet, Denmark (J.W.B., A.Y., S.N.D., F.G., C.H., J.H.S., D.E.H., S.P., L.K.). Search for more papers by this author , Jens Jakob ThuneJens Jakob Thune https://orcid.org/0000-0002-3621-3775 Department of Clinical Medicine, University of Copenhagen, Denmark (F.G., C.H., J.H.S., D.E.H., J.J.T.). Department of Cardiology, Copenhagen University Hospital–Bispebjerg and Frederiksberg, Copenhagen, Denmark (J.J.T.). Search for more papers by this author and Lars KøberLars Køber https://orcid.org/0000-0002-6635-1466 Department of Cardiology, Copenhagen University Hospital–Rigshospitalet, Denmark (J.W.B., A.Y., S.N.D., F.G., C.H., J.H.S., D.E.H., S.P., L.K.). Department of Cardiology, Copenhagen University Hospital–Herlev and Gentofte, Hellerup, Denmark (J.H., L.K.). Search for more papers by this author Originally published9 Oct 2023https://doi.org/10.1161/CIRCULATIONAHA.123.065560Circulation. 2023;148:1179–1181FootnotesRegistration: URL, https://www.clinicaltrials.gov; Unique identifier: NCT00542945.Circulation is available at www.ahajournals.org/journal/circFor Sources of Funding and Disclosures, see page 1181.Correspondence to: Jawad H. Butt, MD, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark. Email jawad_butt91@hotmail.comREFERENCES1. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Circulation. 2022; 145:e895–e1032. doi: 10.1161/CIR.0000000000001063LinkGoogle Scholar2. Shen L, Jhund PS, Petrie MC, Claggett BL, Barlera S, Cleland JGF, Dargie HJ, Granger CB, Kjekshus J, Køber L, et al. Declining risk of sudden death in heart failure.N Engl J Med. 2017; 377:41–51. doi: 10.1056/NEJMoa1609758CrossrefMedlineGoogle Scholar3. Køber L, Thune JJ, Nielsen JC, Haarbo J, Videbæk L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, et al; DANISH Investigators. Defibrillator implantation in patients with nonischemic systolic heart failure.N Engl J Med. 2016; 375:1221–1230. doi: 10.1056/NEJMoa1608029CrossrefMedlineGoogle Scholar4. Doran B, Mei C, Varosy PD, Kao DP, Saxon LA, Feldman AM, DeMets D, Bristow MR. The addition of a defibrillator to resynchronization therapy decreases mortality in patients with nonischemic cardiomyopathy.JACC Heart Fail. 2021; 9:439–449. doi: 10.1016/j.jchf.2021.02.013CrossrefMedlineGoogle Scholar5. ClinicalTrials.gov. Re-evaluation of Optimal Re-synchronisation Therapy in Patients With Chronic Heart Failure.Accessed August 1, 2023. https://clinicaltrials.gov/ct2/show/NCT03494933Google Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails October 10, 2023Vol 148, Issue 15 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.123.065560PMID: 37812653 Originally publishedOctober 9, 2023 Keywordscardiac resynchronization therapyclinical trialdeath, sudden, cardiacheart failureimplantable cardioverter defibrillatormortalityPDF download Advertisement SubjectsHeart Failure

BACKGROUND:Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking. METHODS:We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months. RESULTS:A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events. CONCLUSIONS:Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

BACKGROUND:Changes in QRS duration (∆QRS) are often used in the clinical setting to evaluate the effect of cardiac resynchronization therapy (CRT), although an association between ∆QRS and outcomes is not firmly established. We aimed to assess the association between mortality and ∆QRS after CRT in patients from the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-Ischemic Systolic Heart Failure on Mortality) study. METHODS:We included all patients from DANISH who received a CRT device and had available QRS duration data before and after implantation. Cox proportional hazards models were used to assess associations between ∆QRS (post-CRT QRS minus pre-CRT QRS) and mortality. RESULTS:Complete data were available in 572 patients. Median baseline QRS duration was 160 ms (IQR [146;180]). Post-CRT QRS was recorded a median of 48 days (IQR [33;86]) after implantation, and the median ∆QRS was -14 ms (IQR [-38;-3]). During a median follow-up of 4.1 years (IQR [2.5;5.8]), 106 patients died. In crude Cox regression, all-cause mortality was reduced by 6% per 10 ms shortening of QRS (HR 0.94; CI: 0.88-1.00, p = 0.04). The effect did not remain significant after multivariable adjustment (HR 1.01, CI: 0.93-1.10, p = 0.77). Further, no association was found between ∆QRS and improvement of New York Heart Association functional class at 6 months (OR 1.03, CI: 0.96-1.10, p = 0.42). CONCLUSION:In a large cohort of patients with non-ischemic cardiomyopathy, reduction of QRS duration after CRT was not associated with changes in mortality during long-term follow-up.

Background The ability of coronary CT angiography (cCTA) to rule out significant coronary artery disease (CAD) in older patients with non-ST segment elevation acute coronary syndromes (NSTEACS) is unclear since valid cCTA analysis may be limited by extensive coronary artery calcification. In addition, the effect of very early invasive coronary angiography (ICA) with possible revascularisation is debated. Methods This is a posthoc analysis of patients ≥75 years included in the Very Early vs Standard Care Invasive Examination and Treatment of Patients with Non-ST-Segment Elevation Acute Coronary Syndrome Trial. cCTA was performed prior to the ICA. The diagnostic accuracy of cCTA was investigated. Presence of a coronary artery stenosis ≥50% by subsequent ICA was used as reference. Patients were randomised to a very early (within 12 hours of diagnosis) or a standard ICA (within 48–72 hours of diagnosis). The primary composite endpoint was 5-year all-cause mortality, non-fatal recurrent myocardial infarction or hospital admission for refractory myocardial ischaemia or heart failure. Results Of 452 (21%) patients ≥75 years, 161 (35.6%) underwent cCTA. 19% of cCTAs excluded significant CAD. The negative predictive value (NPV) of cCTA was 94% (95% CI 79 to 99) and the sensitivity 98% (95% CI 94 to 100). No significant differences in the frequency of primary endpoints were seen in patients randomised to very early ICA (at 5-year follow-up, n=100 (46.9%) vs 122 (51.0%), log-rank p=0.357). Conclusion In patients ≥75 years with NSTEACS, cCTA before ICA showed a high NPV. A very early ICA <12 hours of diagnosis did not significantly improve long-term clinical outcomes.

BACKGROUND Evidence to support the choice of blood-pressure targets for the treatment of comatose survivors of out-of-hospital cardiac arrest who are receiving intensive care is limited. METHODS In a double-blind, randomized trial with a 2-by-2 factorial design, we evaluated a mean arterial blood-pressure target of 63 mm Hg as compared with 77 mm Hg in comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause; patients were also assigned to one of two oxygen targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category (CPC) of 3 or 4 within 90 days (range, 0 to 5, with higher categories indicating more severe disability; a category of 3 or 4 indicates severe disability or coma). Secondary outcomes included neuron-specific enolase levels at 48 hours, death from any cause, scores on the Montreal Cognitive Assessment (range, 0 to 30, with higher scores indicating better cognitive ability) and the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 3 months, and the CPC at 3 months. RESULTS A total of 789 patients were included in the analysis (393 in the high-target group and 396 in the low-target group). A primary-outcome event occurred in 133 patients (34%) in the high-target group and in 127 patients (32%) in the low-target group (hazard ratio, 1.08; 95% confidence interval [CI], 0.84 to 1.37; P = 0.56). At 90 days, 122 patients (31%) in the high-target group and 114 patients (29%) in the low-target group had died (hazard ratio, 1.13; 95% CI, 0.88 to 1.46). The median CPC was 1 (interquartile range, 1 to 5) in both the high-target group and the low-target group; the corresponding median modified Rankin scale scores were 1 (interquartile range, 0 to 6) and 1 (interquartile range, 0 to 6), and the corresponding median Montreal Cognitive Assessment scores were 27 (interquartile range, 24 to 29) and 26 (interquartile range, 24 to 29). The median neuron-specific enolase level at 48 hours was also similar in the two groups. The percentages of patients with adverse events did not differ significantly between the groups. CONCLUSIONS Targeting a mean arterial blood pressure of 77 mm Hg or 63 mm Hg in patients who had been resuscitated from cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).