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Background: Complete revascularization is the standard treatment for patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. The Functional Assessment in Elderly MI Patients with Multivessel Disease (FIRE) trial 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 STEMI patients aged 75 years or older enrolled in randomized clinical trials investigating complete vs. culprit-only revascularization strategies. Methods: PubMed, Embase, and the Cochrane database, were systematically searched to identify randomized clinical trials comparing complete vs. culprit-only revascularization. Individual patient-level data were collected from the relevant trials. The primary endpoint was death, myocardial infarction (MI), or ischemia-driven revascularization. The secondary endpoint was cardiovascular death or myocardial infarction. Results: Data from seven RCTs, encompassing 1733 patients (917 randomized to culprit-only and 816 to complete revascularization), were analyzed. The median age was 79 [77-83] years. Females were 595 (34%). Follow-up ranged from a minimum of six months to a maximum of 6.2 years (median 2.5 [1-3.8] years). Complete revascularization reduced the primary endpoint up to four years (HR 0.78, 95%CI 0.63-0.96), but not at the longest available follow-up (HR 0.83, 95%CI 0.69-1.01). Complete revascularization significantly reduced the occurrence of cardiovascular death or MI at the longest available follow-up (HR 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 STEMI patients with multivessel disease, complete revascularization reduced the primary endpoint of death, MI or ischemia-driven revascularization up to 4-year. At the longest follow-up, complete revascularization reduced the composite of cardiovascular death or MI, but not the primary endpoint. Clinical Study Registration: PROSPERO 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/m 2 (n = 363), those with a BMI ≥25 kg/m 2 had a higher risk of all-cause and cardiovascular death, although this association was only statistically significant for a BMI ≥35 kg/m 2 (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/m 2 , a BMI <18.5 kg/m 2 (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., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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., Clinical Trial Registration: ClinicalTrials.gov NCT00542945., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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]; P interaction , 0.65). Similarly, ICD implantation did not reduce cardiovascular death (HR 0.87 [95% CI, 0.70-1.09]), regardless of mHFC score (P interaction , 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 (P interaction , 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., Competing Interests: Disclosures JJT reports speaker's fees from Astra Zeneca and BMS and travel grants from AstraZeneca. JCN reports grants from the Novo Nordisk Foundation and Danish Heart Foundation outside the submitted work. NEB reports grants from the Novo Nordisk Foundation, the Augustinus Foundation, Health Insurance Denmark, and the Kaj Hansen Foundation, not related to this work. FG is an aAdvisor to Abbott, Ionis, Alnylam, AstraZeneca, Bayer, and Pfizer and is a speaker at Novartis. CH reports research grants from the Novo Nordisk Foundation, Lundbeck Foundation, and the Danish Heart Foundation (not related to this work). JHS reports a research grant from Medtronic (outside of this work) and speaker's fee from Medtronic and is a member of the Advisory Board for Medtronic and for Vital Beats. SP reports a travel grant from Abbott. LK reports speaker's honoraria from AstraZeneca, Bayer, Boehringer, Novartis, and Novo Nordisk. JHB reports advisory board honoraria from AstraZeneca and Bayer, consultant honoraria from Novartis and AstraZeneca and travel grants from AstraZeneca. All other authors have no disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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] mm 3 ; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm 3 ; patients with ACS: 370 [332-412] vs. 159 [139-182] mm 3 . 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] mm 3 , p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm 3 , p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm 3 ) compared to both asymptomatic individuals (15 [13-18] mm 3 , p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm 3 , p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm 3 , 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., Competing Interests: Declaration of competing interest All authors report no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous two years; and no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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 m 2 ) 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 m 2 ), 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]; P interaction =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]; P interaction =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]; P interaction =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.

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., Competing Interests: Competing interests: AB has received speaker fees from AstraZeneca, Bayer, Boehringer and Novartis unrelated to this study. CT received speakers and consultancy fees from Boehringer Ingelheim, Beyer A/S and Novartis A/S outside of this study. CAB has been a member of the Bayer and Boehringer Ingelheim advisory boards. LK has received speaker fees from AstraZeneca, Bayer, Boehringer and Novartis unrelated to this project. JJT has received speaker fees from AstraZeneca and Pfizer unrelated to this project., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci., Objectives: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated., Patients and Methods: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination., Results: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively., Conclusions: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Disclosures Dr Butt reports advisory board honoraria from Bayer and AstraZeneca, consultant honoraria from Novartis and AstraZeneca, and travel grants from AstraZeneca outside this work. Dr Nielsen reports grant from the Novo Nordisk Foundation (NNF16OC0018658 and NNF17OC0029148) outside this work. Dr Brandes reports lecture honoraria from Boehringer Ingelheim and Bristol-Myers Squibb, as well as research grants from Theravance, the Zealand Region, Canadian Institutes of Health Research, and the Danish Heart Foundation outside this work. Dr Svendsen reports institutional research grants from Medtronic, speaker fees from Medtronic, and membership in a Medtronic advisory board outside this work. Dr Hassager reports research grants from Novo Nordisk Foundation, Lundbeck Foundation, and The Danish Heart Foundation outside this work. Dr Gustafsson reports advisory roles for Abbott, Alnylam, Ionis, Pfizer, Bayer, FineHeart, and Corwave and speaker fees from Orion pharma, AstraZeneca, and Novartis outside this work. Dr Pehrson reports lecture fees from Bayer, BMS, and Abbott, as well as travel grants from Johnson & Johnson. The other authors report no conflicts.

Competing Interests: Disclosures Dr Butt reports advisory board honoraria from Bayer, consultant honoraria from Novartis and AstraZeneca, and travel grants from AstraZeneca, outside the submitted work. Dr Nielsen reports grants from the Novo Nordisk Foundation (NNF16OC0018658 and NNF17OC0029148), outside the submitted work. Dr Kristensen reports advisory honoraria from Bayer and AstraZeneca, outside the submitted work. Dr Svendsen reports honoraria from Medtronic (speaker fee and membership of advisory committee) and research grant from Medtronic, outside the submitted work. Dr Pehrson reports honoraria (speaker fees) from AstraZeneca, Bristol Myers Squibb, and Abbott, outside the submitted work. Dr Hassager reports grants from the Novo Nordisk Foundation, the Lundbeck Foundation, and the Danish Heart Foundation, outside the submitted work. Dr Bruun reports grants from the Novo Nordisk Foundation, Health Insurance Denmark, the Augustinus Foundation, and the Kaj Hansen Foundation, outside the submitted work. Dr Gustafsson reports research grants from Pfizer and the Novo Nordisk Foundation, advisory board honoraria from Bayer, Pfizer, Abbott, Ionis, and Alnylam, and speakers’ fee from AstraZeneca, Novartis, and Orion Pharma, outside the submitted work. The other authors report no conflicts.

Aims: Describe and compare incidences across age groups of rehospitalization, repeated aortic surgery, and death in patients who survived surgery and hospitalization for type A aortic dissection., Methods and Results: From Danish nationwide registries, we identified patients hospitalized with Stanford type A aortic dissections (2006-2018). Survivors of hospitalization and surgery on the ascending aorta and/or aortic arch comprised the study population (n = 606, 36 (38.9%) <60 years old (group I), 194 (32.0%) 60-69 years old (group II), and 176 (29.1%) >69 years old (group III)). During the first year, 62.5% were re-hospitalized and 1.4% underwent repeated aortic surgery with no significant differences across age groups (P = 0.68 and P = 0.39, respectively). Further, 5.9% died (group I: 3.0%, group II: 8.3%, group III: 7.4%, P = 0.04). After 10 years, 8.0% had undergone repeated aortic surgery (group I: 11.5%, group II: 8.5%, group III: 1.6%, P = 0.04) and 10.2% (group I), 17.0% (group II), and 22.2% (group III) had died (P = 0.01). Using multivariable Cox regression analysis, we described long-term outcomes comparing age groups. No age differences were found in one-year outcomes, while age > 69 years compared with age < 60 years was associated with a lower rate of repeated aortic surgery [hazard ratio 0.17, 95% confidence interval (CI) 0.04-0.78] and a higher rate of all-cause mortality (hazard ratio 2.44, 95% CI 1.37-4.34) in the 10-year analyses., Conclusion: Rehospitalisations in the first year after discharge were common in all age groups, but survival was high. Repeated aortic surgery was significantly more common among younger than older patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.)., (Copyright © 2022 Massachusetts Medical Society.)

Wearable wireless electrocardiographic (ECG) monitoring is well-proven for arrythmia detection, but ischemia detection accuracy is not well-described. We aimed to assess the agreement of ST-segment deviation from single- versus 12-lead ECG and their accuracy for the detection of reversible ischemia. Bias and limits of agreement (LoA) were calculated between maximum deviations in ST segments from single- and 12-lead ECG during 82 Rb PET-myocardial cardiac stress scintigraphy. Sensitivity and specificity for reversible anterior-lateral myocardial ischemia detection were assessed for both ECG methods, using perfusion imaging results as a reference. Out of 110 patients included, 93 were analyzed. The maximum difference between single- and 12-lead ECG was seen in II (-0.019 mV). The widest LoA was seen in V5, with an upper LoA of 0.145 mV (0.118 to 0.172) and a lower LoA of -0.155 mV (-0.182 to -0.128). Ischemia was seen in 24 patients. Single-lead and 12-lead ECG both had poor accuracy for the detection of reversible anterolateral ischemia during the test: single-lead ECG had a sensitivity of 8.3% (1.0-27.0%) and specificity of 89.9% (80.2-95.8%), and 12-lead ECG a sensitivity of 12.5% (3.0-34.4%) and a specificity of 91.3% (82.0-96.7%). In conclusion, agreement was within predefined acceptable criteria for ST deviations, and both methods had high specificity but poor sensitivity for the detection of anterolateral reversible ischemia. Additional studies must confirm these results and their clinical relevance, especially in the light of the poor sensitivity for detecting reversible anterolateral cardiac ischemia.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Stent implantation during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) occasionally results in flow disturbances and distal embolization, which may cause adverse clinical outcomes. Deferred stent implantation seems to reduce the impairment on myocardial function, although the mechanisms have not been clarified. We sought to evaluate whether deferred stenting could reduce flow disturbance in patients treated with primary PCI., Methods and Results: Patients with STEMI included in the DANAMI-3-DEFER trial were randomized to deferred versus immediate stent implantation. The primary and secondary outcomes of this substudy were the incidences of slow/no reflow and distal embolization. A total of 1205 patients were included. Deferred stenting (n = 594) resulted in lower incidences of distal embolization [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.46-0.98, P = 0.040] and slow/no reflow (OR 0.60, 95%CI 0.37-0.97, P = 0.039). In high-risk subgroups, the protective effect was greatest in patients >65 years of age (slow/no reflow: OR 0.36, 95% CI 0.17-0.72, P = 0.004 and distal embolization: OR 0.34, 95% CI 0.18-0.63, P = 0.001), in patients presenting with occluded culprit artery at admission (slow/no reflow: OR 0.33, 95% CI 0.16-0.65, P = 0.001 and distal embolization: OR 0.54, 95% CI 0.31-0.96, P = 0.036) and in patients with thrombus grade >3 (slow/no reflow: OR 0.37, 95% CI 0.20-0.67, P = 0.001 and distal embolization: OR 0.39, 95% CI 0.24-0.64, P < 0.001) with a significant P for interaction for all., Conclusion: Deferred stent implantation reduces the incidences of slow/no reflow and distal embolization, especially in older patients and in those with total coronary occlusion or high level of thrombus burden., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown., Methods: In this randomized trial with a 2-by-2 factorial design, we randomly assigned comatose adults with out-of-hospital cardiac arrest in a 1:1 ratio to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao 2 ) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao 2 of 13 to 14 kPa (98 to 105 mm Hg); patients were also assigned to one of two blood-pressure targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4; categories range from 1 to 5, with higher values indicating more severe disability), whichever occurred first within 90 days after randomization. Secondary outcomes were neuron-specific enolase levels at 48 hours, death from any cause, the score on the Montreal Cognitive Assessment (ranging from 0 to 30, with higher scores indicating better cognitive ability), the score on the modified Rankin scale (ranging from 0 to 6, with higher scores indicating greater disability), and the CPC at 90 days., Results: A total of 789 patients underwent randomization. A primary-outcome event occurred in 126 of 394 patients (32.0%) in the restrictive-target group and in 134 of 395 patients (33.9%) in the liberal-target group (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P = 0.69). At 90 days, death had occurred in 113 patients (28.7%) in the restrictive-target group and in 123 (31.1%) in the liberal-target group. On the CPC, the median category was 1 in the two groups; on the modified Rankin scale, the median score was 2 in the restrictive-target group and 1 in the liberal-target group; and on the Montreal Cognitive Assessment, the median score was 27 in the two groups. At 48 hours, the median neuron-specific enolase level was 17 μg per liter in the restrictive-target group and 18 μg per liter in the liberal-target group. The incidence of adverse events was similar in the two groups., Conclusions: Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.)., (Copyright © 2022 Massachusetts Medical Society.)

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.)., (Copyright © 2022 Massachusetts Medical Society.)

Purpose: Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis., Methods: This is a re-specified substudy of the randomized POET endocarditis trial, which included 400 patients. Patients completed the single-question self-assessed health status from the Short-Form 36 questionnaire at time of randomization and were categorized as having poor or non-poor (excellent/very good, good, or fair) health status. Self-assessed health status and all-cause mortality were examined by a Cox regression model., Results: Self-assessed health status was completed by 266 (67%) patients with a mean age of 68.0 years (± 11.8), 54 (20%) were females, and 86 (32%) had one or more major concurrent medical conditions besides endocarditis. The self-assessed health status distribution was poor (n = 21, 8%) and non-poor (n = 245, 92%). The median follow-up was 3.3 years and death occurred in 9 (43%) and 48 (20%) patients reporting poor and non-poor health status, respectively, and mortality rates [mortality/100 person-years, 95% confidence interval (CI)] were 18.1 (95% CI 9.4-34.8) and 5.4 (95% CI 4.1-7.2), i.e., the crude hazard ratio for death was 3.4 (95% CI: 1.7-7.0, p < 0.01)., Conclusion: Self-assessed poor health status compared with non-poor health status as assessed by a single question was associated with a threefold increased long-term mortality in patients with endocarditis. POET ClinicalTrials.gov number, NCT01375257., Trial Registry: POET ClinicalTrials.gov number, NCT01375257., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Coronary angiography (CAG) and percutaneous coronary intervention (PCI) are performed via the femoral or radial arteries. In patients examined via transfemoral access, closure devices facilitate hemostasis, but it is unknown whether it is safe to mobilize these patients immediately and how acceptable this may be in terms of patient comfort., Objective: The aims of this study were to investigate bleeding complications in patients mobilized immediately after transfemoral CAG or PCI compared with patients on bed rest (BR) for 2 hours after the procedure and, furthermore, to investigate patient comfort in relation to mobilization and BR., Methods: SAMOVAR was a noninferiority trial with patients randomized to immediate mobilization (IM) or 2 hours of BR after transfemoral CAG or PCI and use of the AngioSeal as a closure device and reversal of heparin effect. The primary end point was development of hematoma greater than 5 cm, pseudoaneurysm, or bleeding requiring blood transfusion. Secondary end points were oozing from the puncture site, small hematoma, and patient comfort., Results: Of 2027 patients (IM, 1010; BR, 1017), 40% underwent PCI. The primary outcome was recorded in 0.7% patients randomized to IM versus 0.5% in BR ( P = .58). There was no difference in the incidence of small hematoma, whereas persistent oozing was seen slightly more often after IM compared with BR (12% vs 9%, P = .04). Patients mobilized immediately reported less back pain and micturition problems ( P < .001)., Conclusions: In patients who had CAG and PCI performed through transfemoral access, reversal of anticoagulation and use of closure devices allowed IM with low rates of complications and improved patient comfort., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Men and women may respond differently to certain therapies for heart failure with reduced ejection fraction, including implantable cardioverter defibrillators (ICD). In an extended follow-up study of the DANISH trial (Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heart Failure on Mortality), adding 4 years of additional follow-up, we examined the effect of ICD implantation according to sex., Methods: In the DANISH trial, 1116 patients with nonischemic systolic heart failure were randomized to receive an ICD (N=556) or usual clinical care (N=550). The primary outcome was all-cause mortality., Results: Of the 1116 patients randomized in the DANISH trial, 307 (27.5%) were women. During a median follow-up of 9.5 years, women had a lower associated rate of all-cause mortality (hazard ratio [HR], 0.60 [95% CI, 0.47-0.78]) cardiovascular death (HR, 0.62 [95% CI, 0.46-0.84]), nonsudden cardiovascular death (HR, 0.59 [95% CI, 0.42-0.85]), and a numerically lower rate of sudden cardiovascular death (HR, 0.70 [95% CI, 0.40-1.25]), compared with men. Compared with usual clinical care, ICD implantation did not reduce the rate of all-cause mortality, irrespective of sex (men, HR, 0.85 [95% CI, 0.69-1.06]; women, HR, 0.98 [95% CI, 0.64-1.50]; P interaction=0.51). In addition, sex did not modify the effect of ICD implantation on sudden cardiovascular death (men, HR, 0.57 [95% CI, 0.36-0.92]; women, HR, 0.68 [95% CI, 0.26-1.77]; P interaction=0.76)., Conclusions: In patients with nonischemic systolic heart failure, ICD implantation did not provide an overall survival benefit, but reduced sudden cardiovascular death, irrespective of sex., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT00542945.

Background: ST-segment elevation myocardial infarction (STEMI) is treated with stenting, but the underlying stenosis is often not severe, and stenting may potentially be omitted., Aims: The aim of the study was to investigate outcomes of patients with STEMI treated with percutaneous coronary intervention (PCI) without stenting., Methods: Patients were identified through the DANAMI-3-DEFER study. Stenting was omitted in the patients with stable flow after initial PCI and no significant residual stenosis on the deferral procedure, who were randomised to deferred stenting. These patients were compared to patients randomised to conventional PCI treated with immediate stenting. The primary endpoint was a composite of all-cause mortality, recurrent myocardial infarction (MI), and target vessel revascularisation (TVR)., Results: Of 603 patients randomised to deferred stenting, 84 were treated without stenting, and in patients randomised to conventional PCI (n=612), 590 were treated with immediate stenting. Patients treated with no stenting had a median stenosis of 40%, median vessel diameter of 2.9 mm, and median lesion length of 11.4 mm. During a median follow-up of 3.4 years, the composite endpoint occurred in 14% and 16% in the no and immediate stenting groups, respectively (unadjusted hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.48-1.60; p=0.66). The association remained non-significant after adjusting for confounders (adjusted HR 0.53, 95% CI: 0.22-1.24; p=0.14). The rates of TVR and recurrent MI were 2% vs 4% (p=0.70) and 4% vs 6% (p=0.43), respectively., Conclusions: Patients with STEMI, with no significant residual stenosis and stable flow after initial PCI, treated without stenting, had comparable event rates to patients treated with immediate stenting.

Introduction: A higher 30-day mortality has been observed in patients with first-presentation ST elevation myocardial infarction (STEMI) who have no standard modifiable cardiovascular risk factors (SMuRFs), i. e., diabetes, hypertension, hyperlipidemia, and current smoker. In this study, we evaluate the clinical outcomes and CMR imaging characteristics of patients with and without SMuRFs who presented with first-presentation STEMI., Methods: Patients from the Third DANish Study of Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction (DANAMI-3) with first-presentation STEMI were classified into those with no SMuRFs vs. those with at least one SMuRF., Results: We identified 2,046 patients; 283 (14%) SMuRFless and 1,763 (86%) had >0 SMuRF. SMuRFless patients were older (66 vs. 61 years, p < 0.001) with more males (84 vs. 74%, p < 0.001), more likely to have left anterior descending artery (LAD) as the culprit artery (50 vs. 42%, p = 0.009), and poor pre-PCI (percutaneous coronary intervention) TIMI (thrombolysis in myocardial infarction) flow ≤1 (78 vs. 64%; p < 0.001). There was no difference in all-cause mortality, non-fatal reinfarction, or hospitalization for heart failure at 30 days or at long-term follow-up. CMR imaging was performed on 726 patients. SMuRFless patients had larger acute infarct size (17 vs. 13%, p = 0.04) and a smaller myocardial salvage index (42 vs. 50%, p = 0.02). These differences were attenuated when the higher LAD predominance and/or TIMI 0-1 flow were included in the model., Conclusion: Despite no difference in 30-day mortality, SMuRFless patients had a larger infarct size and a smaller myocardial salvage index following first-presentation STEMI. This association was mediated by a larger proportion of LAD culprits and poor TIMI flow pre-PCI., Clinical Trial Registration: clinicaltrials.gov, unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI)., Competing Interests: Author LK reports Speakers honorarium from Novo, Novartis, AstraZeneca and Bohringer, unrelated to this manuscript. TE reports personal fees from Abbott, Bayer, and AstraZeneca outside the submitted work. GF reports personal consulting fees from CSL and grants from Abbott Diagnostic outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mazhar, Ekström, Kozor, Grieve, Nepper-Christensen, Ahtarovski, Kelbæk, Høfsten, Køber, Vejlstrup, Vernon, Engstrøm, Lønborg and Figtree.)

Bleeding is known to influence the prognosis in patients with acute coronary syndromes. In this predefined secondary outcome analysis of the Very EaRly vs Deferred Invasive evaluation using Computerized Tomography (VERDICT) trial, we investigated whether a very early invasive coronary angiography (ICA), compared with one performed within 48 to 72 hours (standard care), was associated with fewer serious bleedings. Furthermore, we tested the association between demographic data including GRACE score and serious bleedings as well as bleedings and mortality. In the 2,147 patients included in the main study, bleedings within 30 days of admission were assessed based on Thrombolysis In Myocardial Infarction and Bleeding Academic Research Consortium criteria. Differences were calculated by cumulative incidence methods and Grays test. Variables associated with bleeding and mortality were estimated by Cox proportional hazard models. Serious (Bleeding Academic Research Consortium 3abc) bleeding rates were low (15 [1.4%, standard] vs 12 [1.2%, early], p = 0.56). There were no fatal bleedings or serious bleedings before ICA in either group. By multivariate analysis, there was no difference in bleedings between the 2 groups. Female gender (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.2 to 6.4; p = 0.02), anemia (HR 7.0, 95% CI 2.8 to 17.0; p <0.001), and increasing blood pressure (HR 1.3, 95% CI 1.1 to 1.5; p = 0.01) were individually associated with serious bleeding, whereas GRACE score >140 was not (HR 1.03, 95% CI 0.4 to 2.9; p = 0.96). In conclusion, serious bleedings were few, and there were none before ICA in either group. A very early invasive strategy did not reduce serious bleedings within 30 days, which was associated with female gender, increasing blood pressure, and anemia., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (iPOST) have shown ambiguous results in minimizing reperfusion injury. Previous findings show beneficial effects of iPOST in patients with STEMI treated without thrombectomy. However, it remains unknown whether the cardioprotective effect of iPOST in these patients persist on long term. In the current study, all patients were identified through the DANAMI-3-iPOST database. Patients were randomized to conventional primary percutaneous coronary intervention (PCI) or iPOST in addition to PCI. Cumulative incidence rates were calculated, and multivariable analyses stratified according to thrombectomy use were performed. The primary end point was a combination of cardiovascular mortality and hospitalization for heart failure. From 2011 to 2014, 1,234 patients with STEMI were included with a median follow-up of 4.8 years. In patients treated without thrombectomy (n = 520), the primary end point occurred in 15% (48/326) in the iPOST group and in 22% (42/194) in the conventional group (unadjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41 to 0.94, p = 0.023). In adjusted Cox analysis, iPOST remained associated with reduced long-term risk of cardiovascular mortality (HR 0.53, 95% CI 0.29 to 0.97, p = 0.039). In patients treated with thrombectomy (n = 714), there was no significant difference between iPOST (17%, 49/291) and conventional treatment (17%, 72/423) on the primary end point (unadjusted HR 1.01, 95% CI 0.70 to 1.45, p = 0.95). During a follow-up of nearly 5 years, iPOST reduced long-term occurrence of cardiovascular mortality and hospitalization for heart failure in patients with STEMI treated with PCI but without thrombectomy., Competing Interests: Disclosures Dr. Mæng has received lecture fees and advisory board fees from Novo Nordisk and a research grant from Bayer. Dr. Torp-Pedersen has received grants for studies from Bayer and Novo Nordisk. Dr. Køber has received speaker's honorarium from Novo Nordisk, AstraZeneca, Boehringer, and Novartis, unrelated to this topic. Dr. Engstrøm has received speakers/advisory board fee from Abbot Vascular, Boston Scientific, Bayer, and Novo Nordisk., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: In this extended follow-up study of the DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality) trial, adding 4 years of additional follow-up, we examined the effect of implantable cardioverter-defibrillator (ICD) implantation according to baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) level., Background: In the DANISH trial, NT-proBNP level at baseline appeared to modify the response to ICD implantation., Methods: In the DANISH trial, 1,116 patients with nonischemic systolic HF were randomized to receive an ICD (N = 556) or usual clinical care (N = 550). Outcomes were analyzed according to NT-proBNP levels (below/above median) at baseline. The primary outcome was death from any cause., Results: All 1,116 patients in the DANISH trial had an available NT-proBNP measurement at baseline (median: 1,177 pg/mL; range: 200-22,918 pg/mL). There was a trend toward a reduction in all-cause death with ICD implantation, compared with usual clinical care, in patients with NT-proBNP levels lower than the median (HR: 0.75 [95% CI: 0.55-1.03]), but not in those with higher NT-proBNP levels (HR: 0.95 [95% CI: 0.74-1.21]) (P interaction  = 0.28). Similarly, ICD implantation significantly reduced the rate of cardiovascular (CV) and sudden cardiovascular death (SCD) in patients with NT-proBNP levels lower than the median (CV death, HR: 0.69 [95% CI: 0.47-1.00]; SCD, HR: 0.37 [95% CI: 0.19-0.75]), but not in those with higher levels (CV death, HR: 0.94 [95% CI: 0.70-1.25]; SCD, HR: 0.86 [95% CI: 0.49-1.51]) (P interaction  = 0.20 and 0.08 for CV death and SCD, respectively)., Conclusions: Lower baseline NT-proBNP levels could identify patients with nonischemic systolic HF who may derive benefit from ICD implantation. (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality [DANISH]; NCT00542945)., Competing Interests: Funding Support and Author Disclosures Dr Butt has received advisory board honoraria from Bayer, outside the submitted work. Dr Nielsen is supported by a grant from the Novo Nordisk Foundation (NNF16OC0018658) outside this work. Dr Bruun has received funding from the Novo Nordisk Foundation, the Augustinus Foundation, the Kaj Hansen Foundation, and from Health Insurance Denmark outside this work. Dr Brandes has received a research grant from Theravance and the Regions of Southern Denmark and Zealand; has received speaker honoraria from Bayer, Boehringer Ingelheim, and Bristol-Myers Squibb; and has received a travel grant from Biotronik outside this work. Dr Gustafsson has received speaker honorarium from Orion, Novartis, and Vifor Pharma; and has received advisory board honorarium from Abott, Bayer, Alnylam, Ionis, Pfizer, Corvia, and Pharmacosmos. Dr Hassager has received speaker honorarium from Abiomed. Dr Svendsen has received speaker honorarium from Medtronic. Dr Pehrson has received lecture fees from Abbott, Bristol Myers Squibb, and AstraZeneca. Dr Køber has received speaker honorarium from Novartis, AstraZeneca, Boehringer, and Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Partial-Oral versus Intravenous Antibiotic Treatment of Endocarditis Trial (POET) found that partial-oral outpatient treatment was non-inferior to conventional in-hospital intravenous treatment in patients with left-sided infective endocarditis. We examined the impact of treatment strategy on levels of anxiety and depression., Methods: Patients completed the Hospital Anxiety and Depression Scale (HADS) at randomization, at antibiotic completion, and after month 3 and month 6. Changes in anxiety and depression (each subdimension 0-21, high scores indicating worse) were calculated using a repeated measure analysis of covariance model with primary assessment after 6 months. Change in score of 1.7 represented a minimal clinical important difference (MCID)., Results: Among the 400 patients enrolled in the POET trial, 263 (66%) completed HADS at randomization with reassessment rates of 86-87% at the three subsequent timepoints. Patients in the partial-oral group and the intravenous group had similar improvements after 6 months in levels of anxiety (-1.8 versus -1.6, P = 0.62) and depression (-2.1 versus -1.9, P = 0.63), although patients in the partial-oral group had numerically lower levels of anxiety and depression throughout. An improvement in MCID scores after 6 months was reported by 47% versus 45% (p = 0.80) patients for anxiety and by 51% versus 54% (p = 0.70) for depression., Conclusion: Patients with endocarditis receiving partial-oral outpatient treatment reported similar significant improvements in anxiety and depression at 6 months, as compared to conventionally treated, but numerically lower levels throughout. These findings support the usefulness of partial-oral treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: DANISH (The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators [ICDs] in Patients With Nonischemic Systolic Heart Failure on Mortality) found that primary-prevention ICD implantation was not associated with an overall survival benefit in patients with nonischemic systolic heart failure during a median follow-up of 5.6 years, although there was a beneficial effect on all-cause mortality in patients ≤70 years. This study presents an additional 4 years of follow-up data from DANISH., Methods: In DANISH, 556 patients with nonischemic systolic heart failure were randomized to receive an ICD and 560 to receive usual clinical care and followed until June 30, 2016. In this long-term follow-up study, patients were followed until May 18, 2020. Analyses were conducted for the overall population and according to age (≤70 and >70 years)., Results: During a median follow-up of 9.5 years (25th-75th percentile, 7.9-10.9 years), 208/556 patients (37%) in the ICD group and 226/560 patients (40%) in the control group died. Compared with the control group, the ICD group did not have significantly lower all-cause mortality (hazard ratio [HR] 0.89, [95% CI, 0.74-1.08]; P = 0.24). In patients ≤70 years (n = 829), all-cause mortality was lower in the ICD group than the control group (117/389 [30%] versus 158/440 [36%]; HR, 0.78 [95% CI, 0.61-0.99]; P = 0.04), whereas in patients >70 years (n = 287), all-cause mortality was not significantly different between the ICD and control group (91/167 [54%] versus 68/120 [57%]; HR, 0.92 [95% CI, 0.67-1.28]; P = 0.75). Cardiovascular death showed similar trends (overall, 147/556 [26%] versus 164/560 [29%]; HR, 0.87 [95% CI, 0.70-1.09]; P = 0.20; ≤70 years, 87/389 [22%] versus 122/440 [28%]; HR, 0.75 [95% CI, 0.57-0.98]; P = 0.04; >70 years, 60/167 [36%] versus 42/120 [35%]; HR, 0.97 [95% CI, 0.65-1.45]; P = 0.91). The ICD group had a significantly lower incidence of sudden cardiovascular death in the overall population (35/556 [6%] versus 57/560 [10%]; HR, 0.60 [95% CI, 0.40-0.92]; P = 0.02) and in patients ≤70 years (19/389 [5%] versus 49/440 [11%]; HR, 0.42 [95% CI, 0.24-0.71]; P = 0.0008), but not in patients >70 years (16/167 [10%] versus 8/120 [7%]; HR, 1.34 [95% CI, 0.56-3.19]; P = 0.39)., Conclusions: During a median follow-up of 9.5 years, ICD implantation did not provide an overall survival benefit in patients with nonischemic systolic heart failure. In patients ≤70 years, ICD implantation was associated with a lower incidence of all-cause mortality, cardiovascular death, and sudden cardiovascular death. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00542945.

Background: Many patients with coronary artery disease (CAD) and valvular heart disease (VHD) suffer from psychological distress. Such stress is associated with increased morbidity, reduced quality of life and delayed return to work. European guidelines emphasize recognition and intervention, but evidence-based treatment options are limited and perceived as costly. The present study will test the effect of brief, group-based cognitive therapy as an adjunct to usual cardiac rehabilitation in a randomized design., Methods: A total of 148 patients with CAD and/or VHD after surgical intervention and concomitant psychological distress (defined as HADS anxiety (A) or depression (D) score ≥8) will be randomized to either usual out-patient cardiac rehabilitation (CR) comprising an 8-week multidisciplinary programme or usual care supplemented by five group-based cognitive therapy sessions performed by trained CR nurses. A structured, standardized treatment manual will be used. Patients will be randomized 1:1 at three different sites. Additionally, a non-randomized sub-group of 40 matched patients without signs of psychological distress will be followed to investigate spontaneous variation in HADS. The primary outcome is Hospital Anxiety and Depression Score (HADS). Secondary outcomes are adherence to cardiac rehabilitation (CR), health-related quality of life measured by HeartQoL, time to return to work, adherence to lifestyle interventions and cardiovascular readmissions. Patients are followed up for 12 months., Discussion: To our knowledge, this is the first randomized controlled trial (RCT) on patients with cardiac disease with an intensive group-based programme of cognitive therapy performed by CR nurses, which makes it affordable and widely implementable. The outcome will elucidate the feasibility and effect of cognitive therapy as an adjunct to CR in patients with post-surgery CAD and/or VHD and psychological distress and could possibly benefit patients with other heart conditions as well. The clinical trial complies with the Declaration of Helsinki. The trial has been approved by The Regional Research Ethics Committee (file number H-16042832) and The Danish Data Protection Agency. The results will be disseminated as original research in peer-reviewed manuscripts., Trial Registration: www.clinicaltrials.gov NCT04254315 . Retrospectively registered on 30 January 2020., (© 2021. The Author(s).)

Background: Up to 40% of patients with ST-segment elevation myocardial infarction (STEMI) present later than 12 hours after symptom onset. However, data on clinical outcomes in STEMI patients treated with primary percutaneous coronary intervention 12 or more hours after symptom onset are non-existent. We evaluated the association between primary percutaneous coronary intervention performed later than 12 hours after symptom onset and clinical outcomes in a large all-comer contemporary STEMI cohort., Methods: All STEMI patients treated with primary percutaneous coronary intervention in eastern Denmark from November 2009 to November 2016 were included and stratified by timing of the percutaneous coronary intervention. The combined clinical endpoint of all-cause mortality and hospitalisation for heart failure was identified from nationwide Danish registries., Results: We included 6674 patients: 6108 (92%) were treated less than 12 hours and 566 (8%) were treated 12 or more hours after symptom onset. During a median follow-up period of 3.8 (interquartile range 2.3-5.6) years, 30-day, one-year and long-term cumulative rates of the combined endpoint were 11%, 17% and 25% in patients treated 12 or fewer hours and 21%, 29% and 37% in patients treated more than 12 hours ( P <0.001 for all) after symptom onset. Late presentation was independently associated with an increased risk of an adverse clinical outcome (hazard ratio 1.42, 95% confidence interval 1.22-1.66; P <0.001)., Conclusions: Increasing duration from symptom onset to primary percutaneous coronary intervention was associated with an increased risk of an adverse clinical outcome in patients with STEMI, especially when the delay exceeded 12 hours.

Background: In patients with ST-segment-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention, reperfusion injury accounts for a significant fraction of the final infarct size, which is directly related to patient prognosis. In animal studies, brief periods of ischemia in noninfarct-related (nonculprit) coronary arteries protect the culprit myocardium via remote ischemic preconditioning. Positive fractional flow reserve (FFR) documents functional significant coronary nonculprit stenosis, which may offer remote ischemic preconditioning of the culprit myocardium. The aim of the study was to investigate the association between functional significant, multivessel disease (MVD) and reduced culprit final infarct size or increased myocardial salvage (myocardial salvage index [MSI]) in a large contemporary cohort of STEMI patients., Methods: Cardiac magnetic resonance was performed in 610 patients with STEMI at day 1 and 3 months after primary percutaneous coronary intervention. Patients were stratified into 3 groups according to FFR measurements in nonculprit stenosis (if any): angiographic single vessel disease (SVD), FFR nonsignificant MVD (functional SVD), or FFR-significant, functional MVD., Results: A total of 431 (71%) patients had SVD, 35 (6%) had functional SVD, and 144 (23%) had functional MVD. There was no difference in final infarct size (mean infarct size [%left ventricular mass] SVD, 9±3%; functional SVD, 9±3%; and functional MVD, 9±3% [ P =0.82]) or in MSI between groups (mean MSI [%left] SVD, 66±23%; functional SVD, 68±19%; and functional MVD, 69±19% [ P =0.62]). In multivariable analyses, functional MVD was not associated with larger MSI ( P =0.56) or smaller infarct size ( P =0.55)., Conclusions: Functional MVD in nonculprit myocardium was not associated with reduced culprit final infarct size or increased MSI following STEMI. This is important knowledge for future studies examining a cardioprotective treatment in patients with STEMI, as a possible confounding effect of FFR-significant, functional MVD can be discarded. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI).

Objectives: The DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 × 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT)., Methods: Symptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4 years., Results: As of May 2020, 296 patients have been randomized at 20 centers in Denmark., Conclusion: The H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of 2 commonly prescribed drugs with limited randomized data in patients with HFrEF., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Guidelines recommend the use of transthoracic echocardiography (TTE) and clinical scores to risk stratify patients after ST-elevation myocardial infarction (STEMI). High sensitivity troponin T (hs-cTnT) is predictive of outcome after STEMI but the predictive value of hs-cTnT relative to other risk assessment tools has not been established. We aimed to compare the predictive value of hs-cTnT to other risk assessment tools in patients with STEMI. A subset of 578 patients with STEMI were included in this post-hoc study from the Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction trial. Patients underwent cardiac magnetic resonance imaging (CMR) during index hospitalization as well as TTE at 1 year after their STEMI. The predictive value of hs-cTnT was compared with CKMB, infarct size (IS)/left ventricular ejection fraction (LVEF) assessed with CMR, LVEF assessed at discharge with TTE and the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI) risk-scores. The primary outcome was LV systolic dysfunction defined as LVEF ≤40% after 1 year on TTE. The area under the receiver operating characteristic curve analyses showed no significant difference between hs-cTnT and early CMR-assessed IS or LVEF in predicting subsequent LVEF ≤40%. Area under the curve for hs-cTnT was 0.82, 0.85 for IS (p = 0.22), and 0.87 for LVEF (p = 0.23). For predischarge TTE-assessed LVEF, the value was 0.85 (p = 0.45), 0.63 for creatine kinase-MB (p <0.001), 0.61 for the GRACE score (p <0.001), and 0.70 for the TIMI score (p = 0.02). A peak hs-cTnT value <3,500 ng/L ruled out LVEF ≤40% with probability of 98%. In conclusion, in patients presenting with STEMI undergoing PCI, hs-cTnT level strongly predicted long-term LV dysfunction and could be used as a clinical risk stratification tool to identify patients at high risk of progressing to LV dysfunction due to its general availability and high-predictive accuracy., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Primary percutaneous coronary intervention is used to restore blood flow in the infarct-related coronary artery, followed by immediate stenting to prevent reocclusion. Stents implanted in thrombus-laden arteries cause distal embolization, which paradoxically impairs myocardial reperfusion and ventricular function. Whether a strategy of delayed stenting improves outcomes in patients with acute ST-elevation myocardial infarction (STEMI) is uncertain., Methods: The Primary Reperfusion Secondary Stenting (PRIMACY) is a Bayesian prospective, randomized, open-label, blinded end point trial in which delayed vs immediate stenting in patients with STEMI were compared for prevention of cardiovascular death, nonfatal myocardial infarction, heart failure, or unplanned target vessel revascularization at 9 months. All participants were immediately reperfused, but those assigned to the delayed arm underwent stenting after an interval of 24 to 48 hours. This interval was bridged with antithrombin therapy to reduce thrombus burden. In the principal Bayesian hierarchical random effects analysis, data from exchangeable trials will be combined into a study prior and updated with PRIMACY into a posterior probability of efficacy., Results: A total of 305 participants were randomized across 15 centres in France and Canada between April 2014 and September 2017. At baseline, the median age of participants was 59 years, 81% were male, and 3% had a history of percutaneous coronary intervention. Results from PRIMACY will be updated from the patient-level data of 1568 participants enrolled in the Deferred Stent Trial in STEMI (DEFER; United Kingdom), Minimalist Immediate Mechanical Intervention (MIMI; France), Danish Trial in Acute Myocardial Infarction-3 (DANAMI-3; Denmark), and Impact of Immediate Stent Implantation Versus Deferred Stent Implantation on Infarct Size and Microvascular Perfusion in Patients With ST Segment-Elevation Myocardial Infarction (INNOVATION, South Korea) trials., Conclusions: We expect to clarify whether delayed stenting can safely reduce the occurrence of adverse cardiovascular end points compared with immediate stenting in patients with STEMI., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this substudy was to investigate the correlation between fractional flow reserve (FFR) and diameter stenosis in patients with STEMI with and without left ventricular hypertrophy (LVH), and the influence of LVH on complete FFR-guided revascularisation versus culprit only, in terms of risk of clinical outcome., Methods and Results: In this DANAMI-3-PRIMULTI substudy, 279 patients with STEMI had cardiac magnetic resonance (CMR) imaging for assessment of left ventricular mass index. Ninety-six patients had FFR evaluation of a non-culprit lesion. Diameter stenosis of the non-culprit lesion was determined with two-dimensional quantitative coronary analysis. The diameter stenosis (56.9% vs 54.3%, p=0.38) and FFR value (0.83 vs 0.85, p=0.34) were significantly correlated in both groups (Spearman's ρ=-0.40 and -0.41 without LVH and with LVH, respectively; p<0.001) but were not different between patients without and with LVH (p for interaction=0.87). FFR-guided complete revascularisation was associated with reduced risk of death, myocardial infarction or ischaemia-driven revascularisation both for patients without LVH (HR 0.42, 95% CI: 0.20-0.85) and for patients with LVH (HR 0.50, 95% CI: 0.17-1.47), with no interaction between the FFR-guided complete revascularisation and LVH (p for interaction=0.82)., Conclusions: LVH did not interact with the correlation between diameter stenosis and FFR and did not modify the impact of complete revascularisation on the occurrence of subsequent clinical events.

Background: Treatment with newer direct-acting anti-platelet drugs (Ticagrelor and Prasugrel) prior to primary percutaneous coronary intervention (PCI) is associated with improved outcome in patients with ST-segment elevation myocardial infarction (STEMI) when compared with Clopidogrel. We compared infarct size following treatment with Ticagrelor/Prasugrel versus Clopidogrel in the DANish trial in Acute Myocardial Infarction (DANAMI-3) population of STEMI patients treated with primary PCI., Methods and Results: Patients were loaded with Clopidogrel, Ticagrelor or Prasugrel in the ambulance before primary PCI. Infarct size and myocardial salvage index were calculated using cardiac magnetic resonance (CMR) during index admission and at three-month follow-up. Six-hundred-and-ninety-three patients were included in this analysis. Clopidogrel was given to 351 patients and Ticagrelor/Prasugrel to 342 patients. The groups were generally comparable in terms of baseline and procedural characteristics. Median infarct size at three-month follow-up was 12.9% vs 10.0%, in patients treated with Clopidogrel and Ticagrelor/ Prasugrel respectively (p < 0.001), and myocardial salvage index was 66% vs 71% (p < 0.001). Results remained significant in a multiple regression model (p < 0.001)., Conclusions: Pre-hospital loading with Ticagrelor or Prasugrel compared to Clopidogrel, was associated with smaller infarct size and larger myocardial salvage index at three-month follow-up in patients with STEMI treated with primary PCI., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Eustachian tube dysfunction (ETD) may result in hearing loss, chronic otitis and cholesteatoma. With advances in treatment options, the identification of patients with obstructive ETD is becoming increasingly important. The objective of this study was to validate a Danish translation of the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7)., Methods: All participants underwent tympanometry, otomicroscopy and completed the ETDQ-7. We included 34 ears from patients with obstructive ETD who had abnormal tympanometry curves but no history of cholesteatoma or adhesive otitis. As a control group, 48 otherwise healthy ears with a normal tympanometry curve were included from patients with known sensorineural hearing loss or normal hearing., Results: A Cronbach's alpha of 0.77 indicated a good internal consistency reliability of the questionnaire. The mean ETDQ-7 score in the obstructive ETD group was 31 versus 13.5 in the control group (p = 0.00). A receiver operating characteristics analysis produced an area under the curve of 94%, showing excellent discriminatory abilities between the groups., Conclusions: The ETDQ-7 has previously been validated in English, German, Dutch and Portuguese, demonstrating good clinical relevance. The Danish translation of the ETDQ-7 has produced similar results and may be valuable in diagnosing obstructive ETD and in monitoring the effect of balloon dilation of the Eustachian tube., Funding: none. The study was approved by the Danish Data Protection Agency (VD-2018-33, I-Suite 6229)., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Objective: The Third Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction - Ischaemic Postconditioning (DANAMI-3-iPOST) did not show improved clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with ischaemic postconditioning. However, the use of thrombectomy was frequent and thrombectomy may in itself diminish the effect of ischaemic postconditioning. We evaluated the effect of ischaemic postconditioning in patients included in DANAMI-3-iPOST stratified by the use of thrombectomy., Methods: Patients with STEMI were randomised to conventional primary percutaneous coronary intervention (PCI) or ischaemic postconditioning plus primary PCI. The primary endpoint was a combination of all-cause mortality and hospitalisation for heart failure., Results: From March 2011 until February 2014, 1234 patients were included with a median follow-up period of 35 (interquartile range 28 to 42) months. There was a significant interaction between ischaemic postconditioning and thrombectomy on the primary endpoint (p=0.004). In patients not treated with thrombectomy (n=520), the primary endpoint occurred in 33 patients (10%) who underwent ischaemic postconditioning (n=326) and in 35 patients (18%) who underwent conventional treatment (n=194) (adjusted hazard ratio (HR) 0.55 (95%confidence interval (CI) 0.34 to 0.89), p=0.016). In patients treated with thrombectomy (n=714), there was no significant difference between patients treated with ischaemic postconditioning (n=291) and conventional PCI (n=423) on the primary endpoint (adjusted HR 1.18 (95% CI 0.62 to 2.28), p=0.62)., Conclusions: In this post-hoc study of DANAMI-3-iPOST, ischaemic postconditioning, in addition to primary PCI, was associated with reduced risk of all-cause mortality and hospitalisation for heart failure in patients with STEMI not treated with thrombectomy., Trial Registration Number: NCT01435408., Competing Interests: Competing interests: LK reports grants from Danish Research Foundation during the conduct of the study. TE reports personal fees from Boston Scitienfic, Abbott, Bayer, Novo Nordisk and Astra Zeneca outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study investigated the incidence and long-term prognostic importance of multiple myocardial scars in cardiac magnetic resonance (CMR) in a large contemporary cohort of patients with ST-segment elevation myocardial infarction (STEMI)., Background: Patients presenting with STEMI may have multiple infarctions/scars caused by multiple culprit lesions, previous myocardial infarction (MI) or procedure-related MI due to nonculprit interventions. However, the incidence, long-term prognosis, and distribution of causes of multiple myocardial scars remain unknown., Methods: CMR was performed in 704 patients with STEMI 1 day after primary percutaneous coronary intervention (PCI) and again 3 months later. Myocardial scars were assessed by late gadolinium enhancement (LGE). T2-weighted technique was used to differentiate acute from chronic infarctions. The presence of multiple scars was defined as scars located in different coronary territories. The combined endpoints of all-cause mortality and hospitalization for heart failure were assessed at 39 months (interquartile range [IQR]: 31 to 48 months)., Results: At 3 months, 59 patients (8.4%) had multiple scars. Of these, multiple culprits in STEMI were detected in 7 patients (1%), and development of a second nonculprit scar at follow-up occurred in 10 patients (1.4%). The most frequent cause of multiple scars was a chronic scar in the nonculprit myocardium. The presence of multiple scars was independently associated with an increased risk of all-cause mortality and hospitalization for heart failure (hazard ratio: 2.7; 95% confidence interval: 1.1 to 6.8; p = 0.037)., Conclusions: Multiple scars were present in 8.4% of patients with STEMI and were independently associated with an increased risk of long-term morbidity and mortality. The presence of multiple myocardial scars on CMR may serve as a useful tool in risk stratification of patients following STEMI. (DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction [DANAMI-3]; NCT01435408) (Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization [PRIMULTI]; NCT01960933)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with nonischemic systolic heart failure (HF) have increased risk of sudden cardiac death (SCD) and death from progressive pump failure. Whether the risk of SCD changes over time is unknown. We seek here to investigate the relation between duration of HF, mode of death, and effect of implantable cardioverter-defibrillator implantation., Methods and Results: We examined the risk of all-cause death and SCD according to the duration of HF among patients with nonischemic systolic HF enrolled in the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality). In all, 1116 patients were included. Patients were divided according to quartiles of HF duration (≤8, 9≤18, 19≤65, and ≥66 months). Patients with the longest duration of HF were older, more often men, had more comorbidity, and more often received a cardiac resynchronization therapy device. Doubling of HF duration was an independent predictor of both all-cause mortality (hazard ratio [HR], 1.27; 95% CI, 1.17-1.38; P<0.0001), and SCD (HR, 1.29; 95% CI, 1.11-1.50; P=0.0007). The proportion of deaths caused by SCD was not different between HF quartiles (P=0.91), and the effect of implantable cardioverter-defibrillator implantation on all-cause mortality was not modified by the duration of HF (P=0.59)., Conclusions: Duration of HF predicted both all-cause mortality and risk of SCD independently of other risk indicators. However, the proportion of death caused by SCD did not change with longer duration of HF, and the effect of implantable cardioverter-defibrillator was not modified by the duration of HF., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945.

Aims: To assess the impact of sampling bias due to reported as well as unreported exclusion of the target population in a multi-center randomized controlled trial (RCT) of ST-elevation myocardial infarction (STEMI)., Methods and Results: We compared clinical characteristics and mortality between participants in the DANAMI-3 trial to contemporary non-participants with STEMI using unselected registries. A total of 179 DANAMI-3 participants (8%) and 617 contemporary non-participants (22%) had died (Log-Rank: P < 0.001) after a median follow-up of 1333 days (range: 1-2021 days). In an unadjusted Cox regression model all groups of non-participants had a higher hazard ratio to predict mortality compared to participants: eligible excluded (n = 144) (hazard ratio: 3.41 (95% CI: (2.69-4.32)), ineligible excluded (n = 472) (hazard ratio: 3.42 (95% CI: (2.44-4.80), eligible non-screened (n = 154) (hazard ratio: 3.37 (95% CI: (2.36-4.82)), ineligible non-screened (n = 154) (hazard ratio: 6.48 (95% CI: (4.77-8.80)., Conclusion: Sampling bias had occurred due to both reported and unreported exclusion of eligible patients and the difference in mortality between participants and non-participants could not be explained only by the trial exclusion criteria. Thus, screening logs may not be suited to address the risks of sampling bias., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: This study aims to identify patients with nonischemic heart failure who are more likely to benefit from implantable cardioverter-defibrillator (ICD) implantation by use of established risk prediction models., Background: It has been debated whether an ICD for primary prevention reduces mortality in patients with nonischemic heart failure., Methods: The Seattle Heart Failure Model (SHFM) predicts all-cause mortality whereas the Seattle Proportional Risk Model (SPRM) predicts the proportion of sudden cardiac death (SCD) versus nonsudden death, with a higher score indicating a greater proportion of SCD. We report the effect of ICD implantation on all-cause mortality and SCD, according to median SPRM and SHFM scores in all 1,116 patients enrolled in the DANISH (Danish study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on mortality) trial., Results: Among patients with an SPRM score above the median (n = 558), ICD implantation reduced all-cause mortality (hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.43 to 0.94), whereas patients with lower SPRM scores (n = 558) had no effect (HR: 1.08; 95% CI: 0.78 to 1.49, p for interaction = 0.04). The corresponding numbers for SHFM score above and below the median were HR: 0.84; 95% CI: 0.62 to 1.13 and HR: 0.82; 95% CI: 0.53 to 1.28, respectively (p for interaction = 0.980). In 177 patients with upper SPRM/upper SHFM, ICD implantation reduced all-cause mortality (HR: 0.45; 95% CI: 0.25 to 0.80) when compared to 381 patients with lower SPRM/upper SHFM (HR: 1.09; 95% CI: 0.76 to 1.55) (p for interaction <0.001)., Conclusions: Nonischemic heart failure patients with high predicted relative likelihood of SCD, as estimated by higher SPRM score, seemed to benefit from ICD implantation. (DANISH [Danish ICD Study in Patients With Ditaled Cardiomyopathy]; NCT00542945)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Implantable cardioverter-defibrillator (ICD) implantation reduce the risk of sudden cardiac death, but not all-cause death in patients with non-ischaemic systolic heart failure (HF). Whether co-existence of diabetes affects ICD treatment effects is unclear., Methods and Results: We examined the effect of ICD implantation on risk of all-cause death, cardiovascular death, and sudden cardiac death (SCD) according to diabetes status at baseline in the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial. Outcomes were analysed by use of cumulative incidence curves and Cox regressions models. Of the 1116 patients enrolled, 211 (19%) had diabetes at baseline. Patients with diabetes were more obese, had worse kidney function and more were in New York Heart Association Class III/IV. The risk of device infections and other complications in the ICD group was similar among patients with and without diabetes (6.1% vs. 4.6% P = 0.54). Irrespective of treatment group, diabetes was associated with higher risk of all-cause death, cardiovascular death, and SCD. The treatment effect of ICD in patients with diabetes vs. patients without diabetes was hazard ratio (HR) = 0.92 (0.57-1.50) vs. HR = 0.85 (0.63-1.13); Pinteraction = 0.60 for all-cause mortality, HR = 0.99 (0.58-1.70) vs. HR = 0.70 (0.48-1.01); Pinteraction = 0.25 for cardiovascular death, and HR = 0.81 (0.35-1.88) vs. HR = 0.40 (0.22-0.76); Pinteraction = 0.16 for sudden cardiac death., Conclusion: Among patients with non-ischaemic systolic HF, diabetes was associated with higher incidence of all-cause mortality, primarily driven by cardiovascular mortality including SCD. Treatment effect of ICD therapy was not significantly modified by diabetes which might be due to lack of power., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Treatment of the infarct-related artery only (IRA only) in ST-segment elevation myocardial infarction (STEMI) is associated with a significantly higher rate of ischaemia-driven revascularisation (ID-RV) during follow-up than fractional flow reserve-guided complete revascularisation (FFR-CRV). This study aimed to characterise all lesions which underwent ID-RV in the DANAMI-3-PRIMULTI trial with respect to location, stenosis grade and functional significance., Methods and Results: The study included 627 patients with STEMI and multivessel disease; 313 patients were randomised to treatment of the IRA only versus 314 undergoing staged FFR-CRV during the index admission. Rates of admission for suspected cardiac ischaemia (17%) were similar in both groups; however, ID-RV was significantly less frequent in the FFR-CRV group than in the IRA-only group (5% vs. 17%; p<0.001). In both groups, the primary reason for ID-RV was related to non-culprit, non-treated lesions (N=71/82 lesions in IRA-only; N=13/26 in FFR-CRV). De novo lesions or revascularisation of previously treated lesions were rarely causes of ID-RV. In the IRA-only group, there was a trend towards a higher ID-RV rate for lesions with a higher stenosis grade and located in more proximal segments - in particular, ≥80% stenosis of the left anterior descending and right coronary artery also led to angina class IV/unstable angina. In the FFR-CRV group, an FFR value ≤0.80 was shown to be an appropriate threshold for revascularisation., Conclusions: FFR-CRV in STEMI is associated with a significantly lower rate of ID-RV at follow-up than treatment of the IRA only. This is due to a difference in non-culprit, non-treated lesions between both groups and not in de novo lesions or repeat revascularisation of previously treated lesions. Further considerations are warranted in case of high-grade non-culprit stenosis at proximal coronary segments, borderline FFR values and/or anticipated complex PCI.

Aim: The Danish Study to Assess the Efficacy of Implantable Cardioverter-Defibrillators (ICD) in Patients with Non-ischaemic Systolic Heart Failure (HF) on Mortality (DANISH) found no overall effect on all-cause mortality. The effect of ICD implantation on health-related quality of life (HRQoL) remains to be established as previous trials have demonstrated conflicting results. We investigated the impact of ICD implantation on HRQoL in patients with non-ischaemic systolic HF, a prespecified secondary endpoint in DANISH., Methods and Results: In DANISH, a total of 1116 patients with non-ischaemic systolic HF were randomly assigned (1:1) to ICD implantation or usual clinical care (control). Patients completed disease-specific HRQoL as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ; 0-105, high indicating worse). Changes in HRQoL 8 months after randomization were assessed with a mixed-effects model. At randomization, MLHFQ was completed by 935 (84%) patients (n = 472 in the ICD group and n = 463 in the control group) and was reassessed in 274 (58%) and 292 (63%) patients, respectively after 8 months for the primary analysis. Patients in the ICD group vs. the control group had similar improvements in MLHFQ after 8 months [least square mean -7.0 vs. -4.2 (P = 0.13)]. A clinically relevant improvement (decrease ≥5) in the MLHFQ overall score at 8 months was observed in 151 patients in the ICD group and 148 patients in the control group [55% vs. 51%, respectively (P = 0.25)]., Conclusion: Implantable cardioverter-defibrillator implantation in patients with non-ischaemic systolic HF did not significantly alter HRQoL compared with patients randomized to usual clinical care., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Elevated heart rate is associated with poor clinical outcome in patients with acute myocardial infarction. However, in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention the importance of elevated heart rate in the very early phase remains unknown. We evaluated the impact of elevated heart rate in the very early pre-hospital phase of ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention on cardiovascular magnetic resonance markers of reperfusion success and clinical outcome., Methods: In this DANAMI-3 substudy, 1560 ST-segment elevation myocardial infarction patients in sinus rhythm without cardiogenic shock were included in the analyses of clinical outcome and 796 patients underwent cardiovascular magnetic resonance to evaluate area at risk, infarct size and left ventricular ejection fraction. Heart rate was assessed on the first electrocardiogram with ST-elevation (time of diagnosis)., Results: Despite equal area at risk (33%±11 versus 36%±16, p =0.174) patients with a pre-hospital heart rate ⩾100 beats per minute developed larger infarcts (19% (interquartile range, 9-17) versus 11% (interquartile range, 10-28), p =0.001) and a lower left ventricular ejection fraction (54%±12 versus 58%±9, p =0.047). Pre-hospital heart rate ⩾100 beats per minute was independently associated with an increased risk of all-cause mortality and heart failure (hazard ratio 2.39 (95% confidence interval 1.58-3.62), p <0.001)., Conclusions: Very early heart rate ⩾100 beats per minute in ST-segment elevation myocardial infarction was independently associated with larger infarct size, reduced left ventricular ejection fraction and an increased risk of all-cause mortality and heart failure, and thus serves as an easily obtainable and powerful tool to identify ST-segment elevation myocardial infarction patients at high risk.

Background: Left ventricle mass (LVM) can be influenced by various conditions including hypertension and/or inherent cardiomyopathies. Dysglycemia is also thought to exert an anabolic effect on heart tissue by hyperinsulinemia and thereby promoting increased LVM. The primary aim of this study was to assess the influence of dysglycemia on LVM evaluated by an oral glucose tolerance test (OGTT) in patients admitted with a first myocardial infarction (MI) without hypertension. The secondary aim was to assess the impact of dysglycemia on major adverse cardiovascular events (MACE) and all-cause mortality during long-term follow-up., Methods: Patients admitted with a first MI without known history of hypertension were included. All patients without previously known type 2 diabetes mellitus (T2DM) had a standardized 2-hour OGTT performed and were categorized as: normal glucose tolerance (NGT), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) and newly detected T2DM (new T2DM). LVM was measured by echocardiography using Devereaux formula and indexed by body surface area. Multivariate linear regression analysis was used to assess the impact of confounders (dysglycemia by OGTT, known T2DM, age, sex and type of MI) on LVM. Cox proportional hazard model was used to assess the impact of dysglycemia on all-cause mortality and a composite endpoint of MACE (all-cause mortality, MI, revascularisation due to stable angina, coronary artery bypass graft, ischemic stroke or hemorrhagic stroke)., Results: Two-hundred-and-five patients were included and followed up to 14 years. In multivariate regression analysis, LVM was only significantly increased in patients categorized as new T2DM (β = 25.3; 95% CI [7.5-43.0]) and known T2DM (β = 37.3; 95% CI [10.0-64.5]) compared to patients with NGT. Patients with new T2DM showed higher rates of MACE and all-cause mortality compared to patients with IFG/IGT and NGT; however no significantly increased hazard ratio was detected., Conclusions: Dysglycemia is associated with increasing LVM in normotensive patients with a first acute myocardial infarction and the strongest association was observed in patients with new T2DM and patients with known T2DM. Dysglycemia in normotensive patients with a first MI is not an independent predictor of neither MACE nor all-cause mortality during long-term follow-up compared to normotensive patients without dysglycemia.

Objectives: The aim of this study was to evaluate the effect of fractional flow reserve (FFR)-guided revascularization compared with culprit-only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) on infarct size, left ventricular (LV), function, LV remodeling, and the presence of nonculprit infarctions., Background: Patients with STEMI with multivessel disease might have improved clinical outcomes after complete revascularization compared with PCI of the infarct-related artery only, but the impact on infarct size, LV function, and remodeling as well as the risk for periprocedural infarction are unknown., Methods: In this substudy of the DANAMI-3 (Third Danish Trial in Acute Myocardial Infarction)-PRIMULTI (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization) randomized trial, patients with STEMI with multivessel disease were randomized to receive either complete FFR-guided revascularization or PCI of the culprit vessel only. The patients underwent cardiac magnetic resonance imaging during index admission and at 3-month follow-up., Results: A total of 280 patients (136 patients with infarct-related and 144 with complete FFR-guided revascularization) were included. There were no differences in final infarct size (median 12% [interquartile range: 5% to 19%] vs. 11% [interquartile range: 4% to 18%]; p = 0.62), myocardial salvage index (median 0.71 [interquartile range: 0.54 to 0.89] vs. 0.66 [interquartile range: 0.55 to 0.87]; p = 0.49), LV ejection fraction (mean 58 ± 9% vs. 59 ± 9%; p = 0.39), and LV end-systolic volume remodeling (mean 7 ± 22 ml vs. 7 ± 19 ml; p = 0.63). New nonculprit infarction occurring after the nonculprit intervention was numerically more frequent among patients treated with complete revascularization (6 [4.5%] vs. 1 [0.8%]; p = 0.12)., Conclusions: Complete FFR-guided revascularization in patients with STEMI and multivessel disease did not affect final infarct size, LV function, or remodeling compared with culprit-only PCI., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Given the novelty of proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i), little is known regarding overall implementation or clinical characteristics among patients who initiate treatment. We aimed to assess the total number of patients initiated on PCSK9i along with a description of the clinical characteristics and lipid lowering treatment (LLT) of such patients., Setting: A register-based descriptive cohort study of patients receiving a PCSK9i in the time period from 01 January 2016 to 31 March 2017 using a cross linkage between three nationwide Danish registers. Information regarding PCSK9i prescriptions, patient demographics, concurrent pharmacotherapy, comorbidities and previous coronary procedures was identified., Results: Overall, 137 patients initiated treatment with PCSK9i in the study period from 11 in the first quarter of 2016 to 40 in the first quarter of 2017. The majority had a history of ischaemic heart disease (IHD) (67.9%) with ischaemic stroke and diabetes mellitus being present in 7.3% and 16.8% of patients, respectively. All patients initiated on PCSK9i had been previously prescribed statin treatment with atorvastatin and simvastatin being most frequently prescribed in 53% and 36% of patients, respectively. The majority of patients had received both statins and ezetimibe (94.9%) and approximately half of these patients had also received bile acid sequestrant (45.3%). Clinical characteristics mainly differed in patients receiving triple LLT compared with patients not receiving triple LLT in the regards of heart failure., Conclusion: Patients treated with PCSK9i were rare, characterised by having IHD and had received various and intensive conventional LLT prior to PCSK9i initiation in agreement with current international guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)