BACKGROUND:Heart transplantation using standard static cold storage is associated with an increased risk of organ injury if the cold ischemic time exceeds 4 to 5 hours. The present study investigated an innovative approach using hypothermic oxygenated perfusion (HOPE) to extend preservation time to 24 hours and assessed its impact on posttransplant graft function. METHODS:This study assessed graft efficacy based on a single preservation strategy across 2 donor types as follows: (1) donation after circulatory death (DCD) (n = 8) and (2) donation after brain death (DBD) (n = 8), both followed by direct procurement and 24 hours of HOPE before transplantation. After weaning from cardiopulmonary bypass (CPB), biventricular function was assessed using biventricular pressure-volume loops and pulmonary artery catheters during a 2-hour observation period. RESULTS:All included transplantations were successfully weaned from CPB and achieved comparable and adequate cardiac outputs (DCD: 5.0 ± 0.56L/min, DBD 4.5 ± 0.21L/min, p = 0.14). Both left (LV) and right ventricular (RV) myocardial contractility were preserved; LV end-systole elastance (Ees) was significantly higher after transplantation compared to baseline (p<0.001), whereas RV Ees showed no significant change over time (p = 0.08). No primary graft dysfunction occurred during the observation period. CONCLUSION:Twenty-four hours of HOPE preservation ensured preserved graft viability after both DCD and DBD heart transplantation in a porcine model. Our results suggest a potential to significantly extend preservation time in clinical heart transplantation.

Aims The DanGer Shock trial demonstrated a mortality benefit with routine use of a microaxial flow pump (mAFP) in ST-elevation acute myocardial infarction complicated by cardiogenic shock (STEMI-CS), but at a cost of more complications. Routine use of a mAFP may, however, expose some patients to unnecessary risk, underscoring the need to identify those who stabilize rapidly and are less likely to derive benefit from device therapy. Methods and results This post hoc exploratory analysis of the DanGer Shock trial, which randomized STEMI-CS patients to mAFP plus standard care (SoC) or SoC alone, defined 'Fast Recovery' as cardiac intensive care unit (CICU) discharge alive within 3 days of randomization. Baseline variables available at catheterization lab admission associated with 'Fast Recovery' in the SoC arm were identified. Among 355 patients (SoC 176; mAFP 179), 'Fast Recovery' occurred in 29% of the SoC group vs. 15% of the mAFP group. Early CICU discharge favoured SoC through day 3 (HR 2.27, 95% CI 1.48-3.49), with no difference thereafter. Median CICU stay beyond day 3 was 13 days (SoC) vs. 12 days (mAFP), and 94 deaths occurred by day 3 (29% SoC; 24% mAFP). Compared with patients with longer CICU stays, 'Fast Recovery' patients required less inotropic support (44% vs. 85%) and mechanical ventilation (35% vs. 82%) and had lower 180-day mortality (9% vs. 46%, P < 0.001). In the SoC arm, 'Fast Recovery' was associated with lower age, initial higher LVEF, lower heart rate, and lower lactate. Model discrimination was modest (AUROC optimism-corrected 0.74). Conclusion The DanGer Shock trial showed a survival benefit of mAFP use in STEMI-CS, yet about one-third of SoC patients experienced rapid haemodynamic recovery. These 'Fast Recovery' patients were characterized by higher LVEF, younger age, and lower lactate, however discrimination between patients with and without rapid recovery was modest. Distinguishing patients who will recover rapidly remains challenging and warrants further investigation.

BACKGROUND:The microaxial flow pump (mAFP) has demonstrated improved outcomes in selected patients with ST-segment elevation acute myocardial infarction and cardiogenic shock (STEMI-CS). However, its use has been associated with bleeding events. OBJECTIVES:The authors analyzed bleeding in the international multicenter randomized DanGer Shock (Danish German Shock) trial. METHODS:A total of 355 patients with ST-segment elevation acute myocardial infarction and cardiogenic shock were randomized to either mAFP (n = 179) or standard care alone (n = 176). Bleeding events were classified according to Bleeding Academic Research Consortium (BARC) type 3-5. RESULTS:In the mAFP group, 47 patients (26.3% [95% CI: 20.3%-33.2%]) experienced BARC type 3-5 bleeding, compared with 27 (15.3% [95% CI: 10.7%-21.4%]) in the standard care group; P < 0.001. Median follow-up was 121 days (Q1-Q3: 3-180 days). Among the 210 patients treated with any mechanical circulatory support (MCS), 2 of 74 bleeding events (2.7%) occurred in the cath lab, 35 (47.3%) while on MCS, and 37 (50.0%) after the MCS was removed. Bleeding increased with complexity of MCS: OR for BARC 3-5 bleeding with mAFP was 4.94 (95% CI: 2.30-10.65); P < 0.001, with venoarterial extracorporeal membrane oxygenation (VA-ECMO) 8.06 (95% CI: 2.81-23.09); P < 0.001, and with combined mAFP+VA-ECMO 27.40 (95% CI: 9.82-76.43); P < 0.001, no device as reference. Multivariable logistic regression identified use of mAFP, renal replacement therapy, and escalation to VA-ECMO as predictors of BARC type 3-5 bleeding. CONCLUSIONS:Patients randomized to mAFP experienced more bleeding than the standard care group. Bleeding was associated with the complexity of MCS, with one-half of the bleeding events occurring after device removal. (Danish Cardiogenic Shock Trial [DanShock]; NCT01633502).

BACKGROUND:Microaxial flow pump (mAFP) use in selected patients with ST-segment-elevation myocardial infarction complicated by cardiogenic shock improves survival. The present study aimed to assess the influence of delay from first symptoms to randomization on the benefit of an mAFP in patients with ST-segment-elevation myocardial infarction complicated by cardiogenic shock. METHODS:This was a secondary analysis of the international, multicenter, randomized, open-labeled DanGer Shock trial (Danish-German Cardiogenic Shock). A total of 345 of 355 patients with ST-segment-elevation myocardial infarction and cardiogenic shock were enrolled in this substudy. Patients were stratified into quartiles according to delay from first symptoms to randomization to either an mAFP or standard care alone. The end point was death from any cause at 180 days for treatment with an mAFP versus standard of care, according to time from onset of symptoms to randomization obtained by logistic regression analysis. RESULTS:Mortality at 180 days increased across quartiles of time from onset of symptoms to randomization: Q1 (0-140 minutes), 36%; Q2 (141-248 minutes), 53%; Q3 (249-650 minutes), 59%; and Q4 (> 651 minutes), 62%, respectively (log-rank P=0.002). However, those with longer delays were also older and more often women. Median age rose from 66 years (interquartile range, 57-73) in the earliest quartile to 71 years (interquartile range, 62-79) in the latest quartile (P=0.005), and the proportion of women increased from 15% to 34%, respectively. Combining the 3 lowest quartiles for the time from onset of symptoms to randomization, the mAFP treatment was associated with an odds ratio of 0.51 (95% CI, 0.31-0.84), whereas the odds ratio for the highest quartile was 0.92 (95% CI, 0.38-2.22; P for interaction = 0.26). CONCLUSIONS:In patients with ST-segment-elevation myocardial infarction complicated with cardiogenic shock, treatment with an mAFP was associated with reduced all-cause mortality, but the treatment benefit appeared to weaken with prolonged time from the onset of symptoms to randomization. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01633502.

BACKGROUND:Left ventricular lead position is a key determinant of optimal biventricular pacing for heart failure. Observational data indicate better outcomes in patients with late myocardial activation at the left ventricular lead site. We aimed to test whether targeting the left ventricular lead at site of latest electrical activation improves outcomes. METHODS:In this national, randomised, controlled, double-blinded, superiority trial we included patients from all five Danish university centres performing device implantation who had heart failure and wide QRS on guideline-directed medication, eligible for biventricular pacing. We randomly assigned (1:1) patients to either the intervention group, with left ventricular lead placement at the latest electrically activated site within the coronary sinus branches, or to control group, with left ventricular lead placement in a posterolateral non-apical branch. Primary outcome was a composite of time to death or first unplanned heart failure hospitalisation. We used block randomisation and masked patients and all study personnel (except operating room personnel) to treatment allocation. The primary outcome was a composite of time to death or first unplanned hospitalisation for heart failure. Analysis followed a modified intention-to-treat approach. Safety was assessed in all correctly assigned patients. The trial is registered at ClinicalTrials.gov (NCT03280862) and is complete. FINDINGS:From March 20, 2018, to June 3, 2024, we included 1001 patients (255 females and 746 males); 499 were randomly assigned to the intervention group and 502 to the control group. One incorrectly enrolled patient was excluded, leaving 1000 patients for the modified intention-to-treat analysis. Electrical activation at left ventricular lead was a mean of 9 milliseconds (95% CI 5-13) later in the intervention group. Follow-up was completed on Feb 27, 2026, after a median 45·8 months (IQR 28·5-65·7). The primary endpoint occurred in 139 (28%) of 499 patients in the intervention group and 128 (26%) of 501 in control group (hazard ratio 1·10 [95% CI 0·86-1·39]; p=0·45). Overall complication risk was similar between groups (71 [14%] patients in the intervention group vs 64 [13%] in the control group), but lead-related complications were more frequent in the intervention group. One procedure-related death occurred in the intervention group. INTERPRETATION:In patients with heart failure and prolonged QRS, targeted left ventricular lead placement at the site of latest electrical activation did not reduce the composite endpoint of death or unplanned hospitalisation for heart failure compared with conventional lead placement in a posterolateral, non-apical position. FUNDING:Novo Nordisk Foundation, Danish Heart Foundation, Danish Pacemaker and ICD Registry, and Independent Research Fund Denmark.

AIMS:In STEMI-related cardiogenic shock, left ventricular unloading with a micro-axial flow pump (mAFP) improved survival in the Danish German (DanGer) Shock trial, though some patients in both groups required escalation to higher volume temporary mechanical circulatory support systems (tMCS). This study aims to investigate tMCS escalation strategies and outcome in non-comatose patients with STEMI-related cardiogenic shock. METHODS AND RESULTS:In this post hoc analysis of the DanGer Shock trial, patients in both study groups were stratified as escalated vs. not escalated to treatments other than a percutaneously implanted mAFP (Impella CP®). Logistic regression models were fitted to investigate the differential association of baseline markers with the likelihood of an escalation in patients randomized to mAFP vs. standard of care, adjusted for age and country. The 180-day all-cause mortality risk for the four groups was evaluated using the Kaplan-Meier method. Of the 355 patients included in the DanGer Shock trial, 60 underwent tMCS escalation, 25/179 (14%) allocated to the mAFP group, and 35/176 (20%) allocated to the control group (adjusted odds ratio 0.52, 95% confidence interval 0.30-0.91). Median time from randomization to escalation was 12 h (2.7-66.5) in the mAFP arm vs. 0.7 h (IQR: 0.4-2.7) in the standard of care arm (P < 0.001). A higher baseline lactate predicted an escalation in the standard of care arm (odds ratio 1.80, 95% confidence interval 1.14-3.13), but not in the mAFP arm (odds ratio 0.57, 95% confidence interval 0.29-1.15, interaction-P < 0.01). Mortality was significantly higher in patients who underwent tMCS escalation (71.7% vs. 48.1%, P < 0.01) and highest in escalated patients from the standard of care arm (80.0%). Interestingly, those escalated in the mAFP arm had a comparable mortality risk to the non-escalated patients in the standard of care group (60.0% vs. 53.2%). CONCLUSION:In the DanGer Shock trial of STEMI-related cardiogenic shock, escalation to tMCS occurred in almost 1/5 patients, was more likely in the control group, and was associated with a higher mortality risk. Even with early escalation (<1 h), patients escalated from the control group had the highest mortality, underscoring the need for future trials to define optimal escalation strategies.

Abstract Purpose Standard static cold storage is associated with unacceptable organ injury if the cold ischemic time exceeds 4-5 hours. Our study investigates an innovative approach using hypothermic oxygenated machine perfusion (HOPE) to extend preservation time to 24 hours and assess its impact on post-transplant graft function. Methods This randomized experimental porcine study compared two groups: 1) Donation after circulatory death (DCD) (n=8), and 2) Donation after brain death (DBD) (n=8), both followed by direct procurement and 24 hours of HOPE before transplantation. After weaning from cardiopulmonary bypass (CPB), biventricular function was assessed using admittance and Swan-Ganz catheters. Results All DCD and DBD hearts were explanted and underwent 24-hour HOPE. After weaning, one recipient in each group was excluded due to pulmonary hypertension and pulmonary artery bleeding, respectively. All the included transplantations in both the DCD and the DBD group achieved comparable and adequate cardiac output to ensure sufficient circulation after 24 hours of HOPE. Both left and right ventricular myocardial contractility were preserved after extended machine perfusion and heart transplantation. Conclusion Our findings suggest that 24-hour HOPE preservation can maintain graft viability in both DCD and DBD hearts, indicating a revolutionary potential for future clinical applications. This approach could significantly extend preservation times, thereby improving organ availability and outcomes in heart transplantation.Figure 1

BACKGROUND:Three cardiogenic shock (CS) phenotypes have been proposed and validated in various datasets: noncongested (phenotype I), cardiorenal (phenotype II), and cardiometabolic CS (phenotype III). The DanGer Shock trial demonstrated a mortality benefit of microaxial flow pump (mAFP) use in myocardial infarction-related CS. In this post-hoc analysis, we aimed to assess the trajectories and outcomes of these phenotypes in the DanGer Shock population. METHODS:Patients randomized to the DanGer Shock trial were retrospectively assigned to 1 of 3 CS phenotypes at admission. Missing values for phenotyping were imputed using multiple random forest imputation. Outcomes were 180-day mortality and the trajectories of key clinical, laboratory and hemodynamic parameters first 72 hours within phenotypes, stratified by allocation to mAFP or standard of care. RESULTS:Of 355 adult patients in the trial, 145 (41%), 38 (11%), and 172 (48%) patients were in the noncongested, cardiorenal, and cardiometabolic phenotypes, respectively. The 180-day mortality was greater in cardiometabolic (69%) compared with the noncongested (33%) and cardiorenal CS (47%) groups. Clinical metabolic and hemodynamic trajectories and their treatment response differed between phenotypes. mAFP use was associated with lower mortality in noncongested CS (odds ratio, 0.51 [0.28-0.91], P = .02). The odds of mortality were 0.81 [0.57-1.16] (P = .25) in cardiometabolic and 0.91 [0.35-2.34] (P = .84) in cardiorenal CS (P for interaction: .43). CONCLUSION:In this post-hoc analysis of the DanGer Shock trial, predefined CS phenotypes showed distinct outcomes, with the noncongested phenotype faring best and the cardiometabolic the worst. The greatest apparent benefit of mAFP was observed in noncongested CS. These findings are hypothesis-generating and warrant confirmation in prospective studies. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov unique identifier: NCT01633502. Condensed Abstract In this DanGer Shock post-hoc analysis, study participants were retrospectively assigned to 1 of 3 cardiogenic shock (CS) phenotypes: noncongested, cardiorenal, or cardiometabolic CS. In total, 41%, 11%, and 48% of all 355 patients were in these phenotypes, respectively. The 180-day mortality was greater in the cardiometabolic (69%) compared with the noncongested (33%) and cardiorenal CS (47%) groups. mAFP use was associated with lower mortality in the noncongested and numerically in the cardiometabolic, but not in cardiorenal CS group. In summary, CS phenotypes showed distinct outcomes, with the noncongested phenotype faring best and the cardiometabolic faring the worst. The greatest apparent benefit of mAFP was observed in noncongested CS.

BACKGROUND:Noninvasive assessment of cardiac allograft vasculopathy (CAV) is desirable. This study evaluates cardiac computed tomography angiography (CCTA) for CAV assessment, including agreement with invasive coronary angiography (ICA), and correlation of mild vessel wall changes with optical coherence tomography (OCT). METHODS:In this prospective, observational, single-center study, adult heart transplant (HTx) recipients underwent CCTA 1 wk before protocol ICA, with 3-vessel OCT performed when feasible. CCTA and ICA were graded by the International Society for Heart and Lung Transplantation (ISHLT) criteria by blinded readers. OCT provided quantitative vessel wall metrics. Major adverse cardiac events (heart failure hospitalization, CAV progression/percutaneous coronary intervention/occlusion, or cardiovascular death) were assessed. RESULTS:Fifty patients (median age 51 y; 74% male; median 7.7 y post-HTx) completed imaging. CCTA provided diagnostic quality in 98% of segments and enabled classification in all patients. CCTA identified CAV in 70% of patients versus 42% by ICA. The negative predictive value (95% confidence interval) of CCTA for any ICA-defined CAV was 93% (68%-100%) at the patient level and 89% (81%-95%) at the vessel level. In patients with no CAV on ICA but with minor signs of CAV (ie, ISHLT class 1) on CCTA, OCT revealed lower lumen/intima ratio compared with patients without CCTA-detected CAV. Over a median 2.3-y follow-up, 18% experienced a major adverse cardiac event; risk was higher with moderate-to-severe CAV (ie, ISHLT class 2-3). CONCLUSIONS:CCTA is feasible for CAV surveillance in selected HTx recipients and reliably identifies ICA-defined CAV. CCTA also detects mild vessel wall abnormalities supported by OCT, suggesting potential value for earlier noninvasive CAV detection and risk stratification.

BACKGROUND:The most common causes of death may change over time in heart failure with reduced ejection fraction (HFrEF). These shifts can influence the risk-benefit balance of interventions such as implantable cardioverter-defibrillators (ICDs), which are designed to prevent sudden cardiac death. Long-term follow-up is therefore essential to determine whether early benefits are sustained, attenuated, or lost over time. OBJECTIVES:This study sought to examine the long-term effect of primary prevention ICD implantation, compared with usual clinical care, in patients with nonischemic HFrEF enrolled in the DANISH (Danish Study To Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality) trial. METHODS:The DANISH trial enrolled 1,116 patients with nonischemic HFrEF, left ventricular ejection fraction ≤35%, NYHA functional class II-III (class IV if cardiac resynchronization therapy was planned), and elevated natriuretic peptide levels. The primary outcome was all-cause death, and secondary outcomes were cardiovascular death and sudden cardiovascular death. In this study with extended follow-up, patients were followed until death or January 31, 2024, whichever came first. RESULTS:During a median follow-up of 13.2 years (Q1-Q3: 11.6-14.6 years), 294 patients (52.9%) in the ICD group and 299 (53.4%) in the control group died. Compared with usual clinical care, ICD implantation did not significantly reduce the long-term rate of all-cause death (HR: 0.96; 95% CI: 0.82-1.13), but it did reduce the long-term rate of sudden cardiovascular death (HR: 0.54; 95% CI: 0.36-0.80). The effect of ICD implantation on all-cause death was consistent regardless of age (Pinteraction = 0.89). However, age significantly modified the effect of ICD implantation on sudden cardiovascular death, such that ICD implantation reduced the rate of this outcome in patients ≤70 years (HR: 0.38; 95% CI: 0.23-0.62), but not in those >70 years (HR: 1.27; 95% CI: 0.56-2.89; Pinteraction = 0.01). Similar trends were observed when age was analyzed as a continuous variable. The effect of ICD implantation was generally consistent across other key subgroups, including cardiac resynchronization therapy use at baseline. CONCLUSIONS:In patients with nonischemic HFrEF, during a median follow-up of 13.2 years, primary prevention ICD implantation did not reduce all-cause death, but it did reduce sudden cardiovascular death, and younger individuals appeared to derive a greater benefit. (Danish ICD Study in Patients With Dilated Cardiomyopathy [DANISH]; NCT00542945).

BACKGROUND:Due to differences in clinical profiles and outcomes among patients with different causes of non-ischemic heart failure (HF), the risk of sudden cardiovascular death and the effect of implantable cardioverter-defibrillators (ICDs) may vary depending on HF etiology. We examined the effects of primary-prevention ICDs according to HF etiology in an extended follow-up study of DANISH (Danish Study to Assess the Efficacy of ICDs in Patients With Non-ischemic Systolic Heart Failure on Mortality). METHODS:DANISH randomized 1116 patients with non-ischemic HF to ICD implantation (N = 556) or usual care (N = 550). In this study, outcomes were analyzed by HF etiology. RESULTS:In total, 849 patients (76 %) had idiopathic HF, and 267 (24 %) had non-idiopathic HF (valvular, n = 41; hypertensive, n = 117; other, n = 109). During a median follow-up of 9.5 years, non-idiopathic HF was not associated with a significantly different rate of death from any cause (HR 1.03 [95 %CI,0.82-1.29]) or sudden cardiovascular death (HR 0.92 [95 %CI,0.55-1.55]) compared with idiopathic HF. Compared with usual care, ICD implantation did not reduce the rate of death from any cause in idiopathic (HR 0.89 [95 %CI,0.72-1.11]) or non-idiopathic HF (HR 0.86 [95 %CI,0.59-1.25]), with no interaction between HF etiology and treatment effect (Pinteraction = 0.84). The beneficial effect of ICD implantation on sudden cardiovascular death was not modified by HF etiology (idiopathic: HR 0.60 [95 %CI,0.37-0.97]; non-idiopathic: HR 0.59 [95 %CI,0.24-1.48]; Pinteraction = 0.99). CONCLUSIONS:Rates of sudden cardiovascular death (or all-cause death) did not differ across different etiologies of non-ischemic HF. HF etiology did not modify the effects of primary-prevention ICD implantation compared with usual care.

Patients with frailty are often perceived to have a less favorable risk/benefit profile for pharmacological and device-based therapies. We examined the long-term effects of a primary prevention implantable cardioverter-defibrillator (ICD), compared with usual care, according to frailty status in an extended follow-up study of the Danish Study to Assess the Efficacy of ICDs in Patients with nonischemic Systolic Heart failure on Mortality (DANISH) trial. The DANISH trial randomized 1,116 patients with nonischemic heart failure with reduced ejection fraction (HFrEF) to ICD implantation or usual care. Frailty was measured using the Rockwood cumulative deficit approach. The primary outcome was all-cause death, and secondary outcomes were cardiovascular death and sudden cardiovascular death. A frailty index (FI) was calculable in 1,109 patients. In total, 618 (55.7%) patients were in frailty class 1 (FI <0.210, i.e., not frail), 361 (32.6%) in frailty class 2 (FI 0.211 to 0.310, i.e., more frail), and 130 (11.7%) in frailty class 3 (FI >0.311, i.e., most frail). Compared with patients in FI class 1, those in FI class 2 and 3 had a higher rate of all outcomes. The effect of ICD implantation on all-cause death did not vary significantly by frailty class (class 1, HR 0.92 [95% CI, 0.68 to 1.24]; class 2 to 3, 0.93 [0.73 to 1.19]; Pinteraction = 0.99). Consistent effects were observed for cardiovascular death (Pinteraction = 0.94), but not for sudden cardiovascular death (Pinteraction = 0.03); the beneficial effect of ICD implantation on this outcome appeared to be greater in patients who were more frail. However, when the FI was analyzed as a continuous variable, frailty no longer significantly modified the effects of ICD implantation on any outcome. In conclusion, in patients with nonischemic HFrEF, frailty did not significantly modify the effects of ICD implantation compared with usual care. However, the need for a primary prevention ICD in frail patients with HFrEF receiving contemporary guideline-directed medical therapy remains uncertain. Clinical Trial Registration Number: NCT00542945.

Background Assessment of activities of daily living (ADL) and cognitive screening are widely used in the care of out-of-hospital cardiac arrest (OHCA) survivors. Evidence linking them to post-discharge outcomes is limited, but could support targeted rehabilitation efforts. Aim To assess whether ADL ability measures and cognitive screening at hospital discharge were associated with post-discharge ADL ability, health-related quality of life (HRQoL) and return to work. Methods This prospective cohort study included 200 OHCA survivors admitted to Aarhus University Hospital. Self-reported ADL ability was measured using the Activities of Daily Living Interview (ADL-I). Observed ADL ability was measured with the Assessment of Motor and Process Skills (AMPS), dichotomised into age-matched or below-ability. Cognitive function was assessed with Montreal Cognitive Assessment (MoCA). Multivariable regressions, with multiple imputation, analysed associations between variables and outcomes, adjusting for age, sex, and comorbidities. Results Adjusted analyses showed significant associations between personal ADL-I (βadjusted = 0.3, 95%CI: 0.2;0.5) and AMPS (βadjusted = -0.6, 95%CI:-1.2;-0.03) at discharge and self-reported ADL ability six months after cardiac arrest. Baseline AMPS was statistically significantly associated with age-matched ADL ability six months after cardiac arrest (ORadjusted 5.5, 95%CI: 1.5;10.0), and personal ADL-I (VAS: βadjusted = 3.00, 95%CI: 1.3;4.6/index score: βadjusted = 0.03, 95%CI 0.01;0.05) and MoCA (index: βadjusted = -0.09, 95%CI: -0.2;-0.02) with HRQoL. The association between MoCA and return to work one-year after cardiac arrest showed an OR of 3.0 (95%CI: 0.5;9.0), although not statistically significant (p = 0.06). Conclusions Decreased ADL ability at hospital discharge was associated with poorer post-discharge outcomes in OHCA survivors, while cognitive screening was also associated with certain aspects of recovery.

Microaxial flow pump treatment improves survival in selected patients with infarct-related cardiogenic shock; however, treatment carries substantial risks, and benefit may vary by patient subgroup. Systolic blood pressure (SBP) has been proposed as a modifier of the survival benefit. To investigate whether SBP at randomization modifies the survival benefit of microaxial flow pump treatment in ST-segment elevation myocardial infarction–related cardiogenic shock. This was a post hoc analysis of the Danish-German (DanGer) Shock open-label randomized clinical trial among adult patients with ST-segment elevation myocardial infarction complicated by cardiogenic shock, conducted between 2013 and 2023 at 14 tertiary invasive cardiac centers in Denmark, Germany, and the United Kingdom. Data analysis was performed from January 7 to April 7, 2024. Microaxial flow pump therapy plus standard care vs standard care alone. All-cause mortality at 180 days according to randomization SBP. Of 355 patients included in the DanGer Shock trial, 351 patients had available SBP at randomization (median [IQR] age, 69 [59-76] years; 277 [79%] male). In a dichotomized regression analysis, microaxial flow pump treatment significantly reduced mortality for SBPs lower than 82 mm Hg compared with standard care alone (odds ratio [OR], 0.34; 95% CI, 0.18-0.63; P < .001). This was not evident for higher pressures (OR, 0.96; 95% CI, 0.53-1.70; P = .90; P for interaction = .02). Kaplan-Meier survival analysis and spline regression analysis supported these findings ( P for interaction = .02; P for nonlinearity = .01). Randomization SBP was associated with the survival benefit of microaxial flow pump treatment, with the most hypotensive patients deriving the largest survival benefit. Early SBP may help identify patients most likely to gain a net benefit from microaxial flow pump treatment. Findings are hypothesis generating. ClinicalTrials.gov Identifier: NCT01633502

BACKGROUND Whether age impacts the recently demonstrated survival benefit of microaxial flow pump (mAFP) treatment in patients with ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock (CS) is unknown. OBJECTIVES The purpose of this study was to assess the impact of age on mortality and complication rates in patients with STEMI-related CS randomized to standard care or mAFP on top of standard care. METHODS This is a secondary analysis of the Danish-German Cardiogenic Shock (DanGer Shock) trial, an international, multicenter, open-label trial, in which 355 adult patients with STEMI-related CS were randomized to receive an mAFP (Impella CP) plus standard care or standard care alone. The primary outcome of 180-day all-cause mortality is analyzed according to age and intervention. RESULTS From lowest to highest age quartile, the median ages (range) were 54 years (Q1-Q3: 31-59 years), 65 years (Q1-Q3: 60-69 years), 73 years (Q1-Q3: 70-76 years), and 81 years (Q1-Q3: 77-92 years). There were no differences in blood pressure, lactate level, left ventricular ejection fraction, or shock severity at randomization across age groups. Mortality increased from lowest to highest quartile (31%, 47%, 61%, and 73%, respectively; log-rank P < 0.001), with an adjusted OR for death at 180 days of 7.85 (95% CI: 3.37-19.2; P < 0.001) in the highest quartile compared to the lowest. The predicted risk of mortality was higher in the standard-care group until approximately 77 years, after which the predicted risk became higher in the mAFP group (P = 0.20). In patients <77 years, a reduced 180-day mortality was observed in patients randomized to the mAFP (OR: 0.45; 95% CI: 0.28-0.73; P = 0.001), opposed to patients aged >= 77 years (OR: 1.52; 95% CI: 0.57-4.08; P = 0.40), P for interaction = 0.028. Complications were more frequent in the mAFP group, but there were no apparent differences in incidence of complications across all ages. CONCLUSIONS This exploratory secondary analysis of the DanGer Shock trial demonstrates that older patients with STEMI-related CS experience high mortality and may not attain the same benefit from routine treatment with an mAFP as younger patients. Incorporating age as a factor in patient selection may enhance the overall benefit of this therapy.

BACKGROUND:The microaxial flow pump (mAFP) has been shown to improve outcomes in selected patients with ST-elevation myocardial infarction (STEMI) and cardiogenic shock (STEMI-CS), but this effect appears to be less evident in women compared with men. OBJECTIVES:The objective of this secondary analysis of the Danish-German Cardiogenic Shock Trial (DanGer Shock) was to determine sex differences in baseline characteristics, in-hospital course, and the effectiveness of mAFP in STEMI-CS. METHODS:This was a prespecified sex-specific secondary analysis of the international, multicenter, open-label, randomized DanGer Shock Trial. The primary outcome was 180-day all-cause mortality, analyzed by sex and randomized treatment assignment. RESULTS:From 2013 to 2023, 355 patients (74 [20.8%] women, 281 [79.2%] men) with STEMI-CS excluding comatose cardiac arrest were enrolled; 179 were randomized to mAFP (37 women) and 176 to standard care (37 women). In an accompanying registry of excluded patients (n = 495), women represented 25.7% (P = 0.10). At baseline, women were significantly older, and time from symptom onset to randomization was 2.2-fold longer in women than in men. Compared with men, women had significantly higher 180-day all-cause mortality (64.9% vs 48.8%; P = 0.015). There was no significant interaction for sex and treatment assignment with respect to 180-day all-cause mortality (P value for interaction = 0.18), yet women (HR: 1.01 [95% CI: 0.58-1.79]) appeared to derive less benefit from mAFP treatment than male patients (HR: 0.66 [95% CI: 0.47-0.93]). This difference was attenuated in patients aged ≤76 years: women (n = 41) HR: 0.66 (95% CI: 0.25-1.76) and men (n = 233) HR: 0.61 (95% CI: 0.40-0.92) (P value for interaction = 0.92). Data from up to 10 years of follow-up support the treatment effect in younger patients, regardless of sex: women HR: 0.45 (95% CI: 0.19-1.09); men HR: 0.57 (95% CI: 0.40-0.82). CONCLUSIONS:In DanGer Shock, women with STEMI-CS were older and presented later after onset of symptoms, resulting in higher mortality rates. This may have led to the apparent reduced treatment effect in women, but interaction between treatment allocation and sex was not significant, and data showing a benefit of mAFP appeared particularly in younger patients, regardless of sex. As this is a secondary, nonpowered analysis that includes few women, its results must be considered hypothesis generating. (Danish Cardiogenic Shock Trial [DanShock]; NCT01633502).

AIMS:Atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death. Therefore, the effect of an implantable cardioverter-defibrillator (ICD) may be greater in patients with AF. We examined the long-term effects of primary prevention ICD implantation vs. usual clinical care according to AF status in DANISH. METHODS AND RESULTS:Outcomes were analysed according to AF status at baseline (history and/or on enrollment ECG). The primary outcome was all-cause death, and secondary outcomes were cardiovascular and sudden cardiovascular death. Of the 1116 patients with non-ischaemic heart failure with reduced ejection fraction randomized in DANISH, 418 (37.5%) had AF at baseline, of whom 24.2% had paroxysmal AF, 17.0% persistent AF, and 58.9% permanent AF. AF status did not significantly modify the effect of ICD implantation on all-cause death, although there was a suggestion of a greater effect in patients with [hazard ratio (HR) 0.78 (95% CI, 0.59-1.03)] vs. without AF [HR 0.98 (0.75-1.27)] (Pinteraction = 0.15). AF status significantly modified the effect of ICD implantation on cardiovascular death, such that ICD implantation was associated with a lower rate of this outcome in patients with AF [HR 0.67 (0.48-0.94)], but not in those without AF [HR 1.04 (0.76-1.41)] (Pinteraction = 0.04). Although AF status did not significantly modify the effect of ICD implantation on sudden cardiovascular death, there was a suggestion of a greater effect in patients with [HR 0.45 (0.24-0.82)] vs. without AF [HR 0.76 (0.41-1.38)] (Pinteraction = 0.20). CONCLUSION:In the DANISH trial, the presence of AF was associated with a greater effect of ICD implantation on cardiovascular death, and although similar trends were observed for all-cause and sudden cardiovascular death, the treatment-by-subgroup interaction was not statistically significant for these outcomes. REGISTRATION:URL: https://www.clinicaltrials.gov; unique identifier: NCT00542945.

Importance:Microaxial flow pump treatment improves survival in selected patients with infarct-related cardiogenic shock; however, treatment carries substantial risks, and benefit may vary by patient subgroup. Systolic blood pressure (SBP) has been proposed as a modifier of the survival benefit. Objective:To investigate whether SBP at randomization modifies the survival benefit of microaxial flow pump treatment in ST-segment elevation myocardial infarction-related cardiogenic shock. Design, Setting, and Participants:This was a post hoc analysis of the Danish-German (DanGer) Shock open-label randomized clinical trial among adult patients with ST-segment elevation myocardial infarction complicated by cardiogenic shock, conducted between 2013 and 2023 at 14 tertiary invasive cardiac centers in Denmark, Germany, and the United Kingdom. Data analysis was performed from January 7 to April 7, 2024. Intervention:Microaxial flow pump therapy plus standard care vs standard care alone. Main Outcomes and Measures:All-cause mortality at 180 days according to randomization SBP. Results:Of 355 patients included in the DanGer Shock trial, 351 patients had available SBP at randomization (median [IQR] age, 69 [59-76] years; 277 [79%] male). In a dichotomized regression analysis, microaxial flow pump treatment significantly reduced mortality for SBPs lower than 82 mm Hg compared with standard care alone (odds ratio [OR], 0.34; 95% CI, 0.18-0.63; P < .001). This was not evident for higher pressures (OR, 0.96; 95% CI, 0.53-1.70; P = .90; P for interaction = .02). Kaplan-Meier survival analysis and spline regression analysis supported these findings (P for interaction = .02; P for nonlinearity = .01). Conclusions and Relevance:Randomization SBP was associated with the survival benefit of microaxial flow pump treatment, with the most hypotensive patients deriving the largest survival benefit. Early SBP may help identify patients most likely to gain a net benefit from microaxial flow pump treatment. Findings are hypothesis generating. Trial Registration:ClinicalTrials.gov Identifier: NCT01633502.