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Aims: To characterise the prevalence, in-hospital complications, management, and long-term outcome of patients with congestive heart failure but preserved left ventricular systolic function after acute myocardial infarction.Methods: 3166 consecutive patients screened for entry in the Bucindolol Evaluation in Acute Myocardial Infarction Trial with definite acute myocardial infarction and echocardiographic assessment of left ventricular systolic function were included between 1998 and 1999 in this prospective observational study. Main outcome measures were occurrences of in-hospital complications and all cause mortality.Results: Congestive heart failure was seen during hospitalisation in 1464 patients (46%), 717 patients had preserved left ventricular systolic function (wall motion index > or =1.3 corresponding to ejection fraction > or =0.40), and 732 patients had systolic dysfunction (wall motion index <1.3). One year mortality in patients with no heart failure, heart failure with preserved systolic function, and heart failure with systolic dysfunction were 6, 22 and 35%, P<0.0001. Unadjusted risk of death from all causes associated with heart failure and preserved systolic function was 3.3 (95% CI 2.8-4.0), and after adjustment for baseline characteristics and left ventricular systolic function in multivariate Cox proportional hazards analysis the risk was 2.1 (95% CI 1.7-2.6), P<0.0001.Conclusions: Congestive heart failure is frequently present in patients with preserved left ventricular systolic function, and is associated with increased risk of in-hospital complications and death following acute myocardial infarction. [ABSTRACT FROM AUTHOR]

The article discusses an observational study which analyzes the prevalence of left ventricular (LV) systolic and diastolic dysfunction among patients with type 2 diabetes mellitus (T2DM) in relation to the myocardial and vascular disease. It states that 305 patients with T2DM were examined, taking the single day program which includes a Doppler echocardiogram. Results reveal that patients with T2DM have a high prevalence of LV diastolic dysfunction but is not related with vascular function.

Angiogenesis is crucial in tissue repair and prevents scar tissue formation following an ischemic event such as myocardial infarction. The ischemia induces formation of new capillaries, which have high expression of integrin αvβ3. [68Ga]Ga-NODAGA-E[(cRGDyK)]2 ([68Ga]Ga-RGD) is a promising PET-radiotracer reflecting angiogenesis by binding to integrin αvβ3. A Göttingen mini-pig underwent transient catheter-induced left anterior descending artery (LAD) occlusion for 120 min, and after 8 weeks was imaged on a Siemens mMR 3T PET/MR system. A large antero-septal infarction was evident by late gadolinium enhancement (LGE) on the short axis and 2–4 chamber views. The infarcted area corresponded to the area with high [68Ga]Ga-RGD uptake on the fused PET/MR images, with no uptake in the healthy myocardium. To support the hypothesis that [68Ga]Ga-RGD uptake reflects angiogenesis, biopsies were sampled from the infarct border and healthy myocardium. Expression of αvβ3 was evaluated using immunohistochemistry. The staining showed higher αvβ3 expression in the capillaries of the infarct border compared to those in the healthy myocardium. These initial data confirm in vivo detection of angiogenesis using [68Ga]Ga-RGD PET in a translational model, which overall support the method applicability when evaluating novel cardio-protective therapies. [ABSTRACT FROM AUTHOR]

Purpose: Out-of-hospital cardiac arrest (OHCA) survivors face significant risks of complications and death from hypoxic–ischemic brain injury leading to withdrawal of life-sustaining treatment (WLST). Accurate multimodal neuroprognostication, including automated pupillometry, is essential to avoid inappropriate WLST. However, inconsistent study results hinder standardized threshold recommendations. We aimed to validate proposed pupillometry thresholds with no false predictions of unfavorable outcomes in comatose OHCA survivors. Methods: In the multi-center BOX-trial, quantitative measurements of automated pupillometry (quantitatively assessed pupillary light reflex [qPLR] and Neurological Pupil index [NPi]) were obtained at admission (0 h) and after 24, 48, and 72 h in comatose patients resuscitated from OHCA. We aimed to validate qPLR < 4% and NPi ≤ 2, predicting unfavorable neurological conditions defined as Cerebral Performance Category 3–5 at follow-up. Combined with 48-h neuron-specific enolase (NSE) > 60 μg/L, pupillometry was evaluated for multimodal neuroprognostication in comatose patients with Glasgow Motor Score (M) ≤ 3 at ≥ 72 h. Results: From March 2017 to December 2021, we consecutively enrolled 710 OHCA survivors (mean age: 63 ± 14 years; 82% males), and 266 (37%) patients had unfavorable neurological outcomes. An NPi ≤ 2 predicted outcome with 0% false-positive rate (FPR) at all time points (0–72 h), and qPLR < 4% at 24–72 h. In patients with M ≤ 3 at ≥ 72 h, pupillometry thresholds significantly increased the sensitivity of NSE, from 42% (35–51%) to 55% (47–63%) for qPLR and 50% (42–58%) for NPi, maintaining 0% (0–0%) FPR. Conclusion: Quantitative pupillometry thresholds predict unfavorable neurological outcomes in comatose OHCA survivors and increase the sensitivity of NSE in a multimodal approach at ≥ 72 h. [ABSTRACT FROM AUTHOR]

Out-of-hospital cardiac arrest (OHCA) survivors remaining comatose are often circulatory unstable with high mortality in the first days following resuscitation. Elevated lactate will reflect the severity and duration of hypoperfusion in cardiac arrest. Further, the severity of hypoperfusion could modify the effect on survival of different mean arterial blood pressure (MAP) targets. In this sub-study of the BOX trial, adult successfully resuscitated comatose OHCA patients (n = 789) with a presumed cardiac cause were randomized to a MAP target of 63 mmHg vs. 77 mmHg. Patients were arbitrarily grouped in low-lactate: <25% of sample, medium-lactate: 25%–75%, and high >75 percentile according to blood lactate levels at hospital arrival as a surrogate of the severity of hypoperfusion. Invasive hemodynamic evaluations were performed using an arterial catheter and pulmonary artery catheter (PAC), and data from admission to 48 hours (h) were recorded. Logistic regression analysis evaluated whether lactate levels (as continuous and categorical) modify the effect of MAP targets on mortality at 365 days. The three lactate groups had initial lactate levels of low-lactate: <2.9 mmol/L, medium-lactate: 2.9–7.9 mmol/L, and high-lactate > 7.9 mmol/L. All patients were randomized to a 63 mmHg or 77 mmHg MAP target. The proportion of patients in the high-MAP target group was 100/201 (50%), 178/388 (46%), and 114/197 (58%) for low, medium, and high-lactate groups respectively. At admission, the high-lactate groups had a lower MAP compared to the medium-lactate (2.6 mmHg (95% CI: 0.1–5.0 mmHg, p = 0.02), and the low-lactate group, (3.6 mmHg (95% CI: 0.8–6.5 mmHg, p < 0.01). Accordingly, the vasoactive inotropic score was 79% (95%CI: 42%–124%%) higher with increasing initial lactate level (High-lactate vs. low-lactate) with the largest difference at 6 hours (110.6% (95%CI: 54.4%–187.2%) higher in high-lactate patients). No difference in the cardiac index or systemic vascular resistance was observed between lactate groups. The initial lactate level (continuous) modified the effect of the two MAP targets (p = 0.04). In the highest lactate group, the mortality was 100/197 (51%), and with an odds ratio (OR): 1.7 (95%CI: 0.9–3.0) if randomized to MAP 77 mmHg compared to MAP 63 mmHg. In the lowest lactate group, the mortality was 35/201(17%) and similar if randomized to a MAP target of 77 mmHg (OR: 1.1 (95% CI: 0.5–2.3)). Comatose OHCA patients with high initial lactate levels required more vasoactive drugs on the first two days of ICU admission to meet the blood pressure target and had a poorer prognosis. No indication that aiming for a higher MAP target is beneficial in patients with an initial high lactate level was found, however, given the post-hoc nature of this study, these results should be considered hypothesis-generating [ABSTRACT FROM AUTHOR]

BACKGROUND: Acute kidney injury (AKI) represents a common and serious complication to out-of-hospital cardiac arrest. The importance of post-resuscitation care targets for blood pressure and oxygenation for the development of AKI is unknown. METHODS: This is a substudy of a randomized 2-by-2 factorial trial, in which 789 comatose adult patients who had out-of-hospital cardiac arrest with presumed cardiac cause and sustained return of spontaneous circulation were randomly assigned to a target mean arterial blood pressure of either 63 or 77 mm Hg. Patients were simultaneously randomly assigned to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pa o 2) of 9 to 10 kPa or a liberal oxygenation target of a Pa o 2 of 13 to 14 kPa. The primary outcome for this study was AKI according to KDIGO (Kidney Disease: Improving Global Outcomes) classification in patients surviving at least 48 hours (N=759). Adjusted logistic regression was performed for patients allocated to high blood pressure and liberal oxygen target as reference. RESULTS: The main population characteristics at admission were: age, 64 (54–73) years; 80% male; 90% shockable rhythm; and time to return of spontaneous circulation, 18 (12–26) minutes. Patients allocated to a low blood pressure and liberal oxygen target had an increased risk of developing AKI compared with patients with high blood pressure and liberal oxygen target (84/193 [44%] versus 56/187 [30%]; adjusted odds ratio, 1.87 [95% CI, 1.21–2.89]). Multinomial logistic regression revealed that the increased risk of AKI was only related to mild-stage AKI (KDIGO stage 1). There was no difference in risk of AKI in the other groups. Plasma creatinine remained high during hospitalization in the low blood pressure and liberal oxygen target group but did not differ between groups at 6- and 12-month follow-up. CONCLUSIONS: In comatose patients who had been resuscitated after out-of-hospital cardiac arrest, patients allocated to a combination of a low mean arterial blood pressure and a liberal oxygen target had a significantly increased risk of mild-stage AKI. No difference was found in terms of more severe AKI stages or other kidney-related adverse outcomes, and creatinine had normalized at 1 year after discharge. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03141099. [ABSTRACT FROM AUTHOR]

Prognostication after out-of-hospital cardiac arrest (OHCA) remains challenging. The inflammatory response after OHCA has been associated with increased mortality. This study investigates the associations and predictive value between inflammatory markers and outcome in resuscitated OHCA patients. The study is based on post hoc analyses of a double-blind controlled trial, where resuscitated OHCA patients were randomized to receive either exenatide or placebo. Blood was analyzed for levels of inflammatory markers the day following admission. Primary endpoint was time to death for up to 180 days. Secondary endpoints included 180-day mortality and poor neurological outcome after 180 days, defined as a cerebral performance category (CPC) of 3 to 5. Among 110 included patients we found significant associations between higher leucocyte quartile and increasing mortality in univariable analysis (OR 2.6 (95%CI 1.6–4.2), p <.001), as well as in multivariable analysis (OR 2.1 (95%CI 1.1–4.0), p =.02). A significant association was found between higher neutrophil quartile and increasing mortality in univariable analysis (OR 3.0 (95%CI 1.8–5.0), p <.001) as well as multivariable analysis (OR 2.4 (95%CI 1.2–4.6), p =.01). Leucocyte and neutrophil levels were predictive of poor outcome after 180 days with area under the receiver operating characteristics curves of 0.79 and 0.81, respectively. We found no associations between CRP and lymphocyte levels versus outcome. Total leucocyte count and neutrophil levels measured the first day following OHCA were significantly associated with 180-day all-cause mortality and may potentially act as early predictors of outcome. , unique identifier: NCT02442791 [ABSTRACT FROM AUTHOR]

Background: The sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors were developed as glucose‐lowering drugs to treat type 2 diabetes (T2D). However, significant reductions in clinical outcomes have now been demonstrated in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of the presence of T2D. Multiple hypotheses have been proposed for the underlying mechanisms, and the data to support these proposals are emerging. Objectives: To review the clinical outcome data with SGLT2 inhibitors in HFrEF and the data to support the mechanisms for these clinical effects. Methods: Literature review was supported by a PubMed search for relevant articles up to 19 April 2022. Findings: Current data support increased diuresis and reverse cardiac remodelling as important mechanisms for the reductions in heart failure hospitalizations and mortality observed with SGLT2 inhibitors (empagliflozin or dapagliflozin) in patients with HFrEF. Alteration in intrarenal haemodynamic is likely contributing to the observed renoprotective effect of SGLT2 inhibitors. Conclusions: Solid clinical data support the current recommendations to use empagliflozin or dapagliflozin in HFrEF. The underlying mechanisms likely include changes in cardiac and intrarenal haemodynamic. Yet, these mechanisms do not seem to solely explain the observed magnitude of clinical effect with SGLT2 inhibitors in HFrEF, and other mechanisms may contribute. [ABSTRACT FROM AUTHOR]

Invasive mechanical ventilation (IMV) is widely used in patients with cardiogenic shock following acute myocardial infarction (AMICS), but evidence to guide practice remains sparse. We sought to evaluate trends in the rate of IMV utilization, applied settings, and short term-outcome of a contemporary cohort of AMICS patients treated with IMV according to out-of-hospital cardiac arrest (OHCA) at admission. Consecutive AMICS patients receiving IMV in an intensive care unit (ICU) at two tertiary centres between 2010 and 2017. Data were analysed in relation to OHCA. A total of 1274 mechanically ventilated AMICS patients were identified, 682 (54%) with OHCA. Frequency of IMV increased during the study period, primarily due to higher occurrence of OHCA admissions. Among 566 patients with complete ventilator data, positive-end-expiratory pressure, inspired oxygen fraction, and minute ventilation during the initial 24 h in ICU were monitored. No differences were observed between 30-day survivors and non-survivors with OHCA. In non-OHCA, these ventilator requirements were significantly higher among 30-day non-survivors (P for all<0.05), accompanied by a lower PaO2/FiO2 ratio (median 143 vs. 230, P < 0.001) and higher arterial lactate levels (median 3.5 vs. 1.5 mmol/L, P < 0.001) than survivors. Physiologically normal PaO2 and pCO2 levels were achieved in all patients irrespective of 30-day survival and OHCA status. In the present contemporary cohort of AMICS patients, physiologically normal blood gas values were achieved both in OHCA and non-OHCA in the early phase of admission. However, increased demand of ventilatory support was associated with poorer survival only in non-OHCA patients. [Display omitted] • Invasive mechanical ventilation is frequently used in patients with AMICS, but clinical data remain sparse. • The increasing proportion of AMICS patients requiring invasive mechanical ventilation was primarily driven by OHCA admissions. • Only among AMICS patients presenting without OHCA, ventilator settings were significantly increased in 30-day non-survivors. [ABSTRACT FROM AUTHOR]

Background: Plasma growth differentiation factor-15 (GDF-15) biomarker levels increase in response to inflammation and tissue injury, and increased levels of GDF-15 are associated with increased risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve outcome in HFrEF, have been shown to increase plasma GDF-15 in diabetic patients. We aimed to investigate the effect of empagliflozin on GDF-15 in HFrEF patients. Methods: This Empire HF Biomarker substudy was from the multicentre, randomized, double-blind, placebo-controlled Empire HF trial that included 190 patients from June 29, 2017, to September 10, 2019. Stable ambulatory HFrEF patients with ejection fraction of ≤ 40% were randomly assigned (1:1) to empagliflozin 10 mg once daily, or matching placebo for 12 weeks. Changes from baseline to 12 weeks in plasma levels of GDF-15, high-sensitive C-reactive protein (hsCRP), and high-sensitive troponin T (hsTNT) were assessed. Results: A total of 187 patients who were included in this study, mean age was 64 ± 11 years; 85% male, 12% with type 2 diabetes, mean ejection fraction 29 ± 8, with no differences between the groups. Baseline median plasma GDF-15 was 1189 (918–1720) pg/mL with empagliflozin, and 1299 (952–1823) pg/mL for placebo. Empagliflozin increased plasma GDF-15 compared to placebo (adjusted between-groups treatment effect; ratio of change (1·09 [95% confidence interval (CI), 1.03–1.15]: p = 0.0040). The increase in plasma GDF15 was inversely associated with a decrease in left ventricular end-systolic (R = – 0.23, p = 0.031), and end-diastolic volume (R = – 0.29, p = 0.0066). There was no change in plasma hsCRP (1.09 [95%CI, 0.86–1.38]: p = 0.48) or plasma hsTNT (1.07 [95%CI, 0.97–1.19]: p = 0.18) compared to placebo. Patients with diabetes and treated with metformin demonstrated no increase in plasma GDF-15 with empagliflozin, p for interaction = 0·01. Conclusion: Empagliflozin increased plasma levels of GDF-15 in patients with HFrEF, with no concomitant increase in hsTNT nor hsCRP. Trial registration: The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585. [ABSTRACT FROM AUTHOR]

Aims: To evaluate 1) the relative use of automated external defibrillators (AEDs) at different types of AED locations 2) the percentage of AEDs crossing location types during OHCA before use 3) the AED coverage distance at different types of AED locations, and 4) the 30-day-survival in different subgroups.Methods: From 2014-2018, AEDs used by bystanders during out-of-hospital cardiac arrest (OHCA) in the Region of Southern Denmark were collected. Data regarding registered AEDs was retrieved from the national AED-network. The OHCA site and AED placement was categorized into; 1) Residential; 2) Public; 3) Nursing home, 4) Company/workplace; 5) Institution; 6) Health clinic and 7) Sports facility/recreational. To evaluate 30-day-survival, groups 4-7 were pooled into one Mixed group.Results: In total 509 OHCAs were included. There was high relative usage of AEDs from public places, nursing homes, health clinics and sports facilities, and low relative usage from companies/workplaces, residential areas and institutions. Of AEDs used during residential OHCAs 39% were collected from public places. AEDs placed in residential areas and public places had a coverage of 575 m (IQR 130-1300) and 270 m (IQR5-550), respectively. Thirty-day- survival in public, residential and mixed groups were 49%, 14% and 67%, respectively.Conclusion: The relative use of AEDs from public places, nursing homes, sports facilities and health clinics was high, and AEDs used during OHCA in residential areas were most frequently collected from public places. AEDs placed in both residential areas and public places may have a wider coverage area than proposed in current literature. [ABSTRACT FROM AUTHOR]

Extracorporeal cardiopulmonary resuscitation (ECPR) for selected refractory out-of-hospital cardiac arrest (OHCA) is increasingly used. Detailed knowledge of health-related quality of life (HRQoL) and long-term cognitive function is limited. HRQoL and cognitive function were assessed in ECPR-survivors and OHCA-survivors with prehospital return of spontaneous circulation after standard advanced cardiac life support (sACLS). Fifteen ECPR-survivors and 22 age-matched sACLS-survivors agreed to participate in this follow-up study. Participants were examined with echocardiography, 6-minute walk test, and neuropsychological testing, and answered HRQoL (EQ-5D-5L and Short Form 36 (SF-36)), and mental health questionnaires. Most patients were male (73 % and 82 %) and median age at follow-up was similar between groups (55 years and 60 years). Low flow time was significantly longer for ECPR-survivors (86 min vs. 15 min) and lactate levels were significantly higher (14.1 mmol/l vs. 3.9 mmol/l). No between-group difference was found in physical function nor in cognitive function with scores corresponding to the 23rd worst percentile of the general population. SACLS-survivors had HRQoL on level with the Danish general population while ECPR-survivors scored lower in both EQ-5D-5L (index score 0.73 vs. 0.86, p = 0.03, visual analog scale: 70 vs. 84, p = 0.04) and in multiple SF-36 health domains (role physical, bodily pain, general health, and mental health). Despite substantially longer low flow times with thrice as high lactate levels, ECPR-survivors were similar in cognitive and physical function compared to sACLS-survivors. Nonetheless, ECPR-survivors reported lower HRQoL overall and related to mental health, pain management, and the perception of limitations in physical role. [ABSTRACT FROM AUTHOR]

Bystander defibrillation is associated with increased survival with good neurological outcome after out-of-hospital cardiac arrest (OHCA). Dispatch of lay responders could increase defibrillation rates, however, survival with good neurological outcome in these remain unknown. The aim was to compare long-term survival with good neurological outcome in bystander versus lay responder defibrillated OHCAs. This is a sub-study of the BOX trial, which included OHCA patients from two Danish tertiary cardiac intensive care units from March 2017 to December 2021. The main outcome was defined as 3-month survival with good neurological performance (Cerebral Performance Category of 1or 2, on a scale from 1 (good cerebral performance) to 5 (death or brain death)). For this study EMS witnessed OHCAs were excluded. Of the 715 patients, a lay responder arrived before EMS in 125 cases (16%). In total, 81 patients were defibrillated by a lay responder (11%), 69 patients by a bystander (10%) and 565 patients by the EMS staff (79%). The 3-month survival with good neurological outcome was 65% and 81% in the lay responder and bystander defibrillated groups, respectively (P = 0.03). In patients with OHCA, 3-month survival with good neurological outcome was higher in bystander defibrillated patients compared with lay responder defibrillated patients. [ABSTRACT FROM AUTHOR]

Background: Inhibition of the sodium-glucose cotransporter-2 (SGLT2i) improves outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF), but the mechanism by which they improve outcomes remains unclear.Objectives: This study aimed to investigate the effects of sodium-glucose cotransporter-2 inhibitor empagliflozin on central hemodynamics in patients with HF and HFrEF.Methods: This investigator-initiated, double-blinded, placebo-controlled, randomized trial enrolled 70 patients with HFrEF from March 6, 2018, to September 10, 2019. Patients were assigned to empagliflozin of 10 mg or matching placebo once daily on guideline-driven HF therapy for 12 weeks. The primary outcome was ratio of pulmonary capillary wedge pressure (PCWP) to cardiac index (CI) at peak exercise after 12 weeks. Patients underwent right-heart catheterization at rest and during exercise at baseline and 12-week follow-up.Results: Patients with HFrEF, mean age of 57 years, mean left-ventricular ejection fraction, 26%, and 12 (17%) with type 2 diabetes mellitus were randomized. There was no significant treatment effect on peak PCWP/CI (-0.13 mm Hg/l/min/m2; 95% confidence interval: -1.60 to 1.34 mm Hg/l/min/m2; p = 0.86). Considering hemodynamics over the full range of exercise loads, PCWP was significantly reduced (-2.40 mm Hg; 95% confidence interval: -3.96 to -0.84 mm Hg; p = 0.003), but not CI (-0.09 l/min/m2; 95% confidence interval: -0.14 to 0.32 l/min/m2; p = 0.448) by empagliflozin. This was consistent among patients with and without type 2 diabetes.Conclusions: Among patients with stable HFrEF, empagliflozin for 12 weeks reduced PCWP compared with placebo. There was no significant improvement in neither CI nor PCWP/CI at rest or exercise. [ABSTRACT FROM AUTHOR]

Aim: Heparin administration affects the concentrations of many plasma proteins through their displacement from the endothelial glycocalyx. A differentiated protein response in diabetes will therefore, at least partly, reflect glycocalyx changes. This study aims at identifying biomarkers of endothelial dysfunction in diabetes by statistical exploration of plasma proteome data for interactions between diabetes status and heparin treatment.Methods: Diabetes-by-heparin interactions in relation to protein levels were inspected by regression modelling in plasma proteome data from 497 patients admitted for acute angiography. Analyses were conducted separately for all 273 proteins and as set-based analyses of 44 heparin-relevant proteins identified by gene ontology analysis and 42 heparin-influenced proteins previously reported.Results: Seventy-five patients had diabetes and 361 received heparin before hospitalization. The proteome-wide analysis displayed no proteins with diabetes-heparin interaction to pass correction for multiple testing. The overall set-based analyses revealed significant association for both protein sets (p-values<2*10-4), while constraining on opposite directions of effect in diabetics and none-diabetics was insignificant (p-values = 0.11 and 0.17).Conclusions: Our plasma proteome-wide interaction approach supports that diabetes influences heparin effects on protein levels, however the direction of effects and individual proteins could not be definitively pinpointed, likely reflecting a complex protein-basis for glycocalyx dysfunction in diabetes. [ABSTRACT FROM AUTHOR]

Background: In the management of patients resuscitated from out-of-hospital cardiac arrest, a primary goal is to restore sufficient oxygen delivery (DO 2 ) to meet demands in oxygen consumption (VO 2 )., Methods and Results: This post hoc analysis of the BOX (Blood Pressure and Oxygen Targets) study included adult patients who were comatose and experienced out-of-hospital cardiac arrest from a presumed cardiac cause, who were randomized to a mean arterial blood pressure (MAP) target of 63 mm Hg (MAP63) or 77 mm Hg (MAP77) and a Restrictive PaO 2 target of 9 to 10 kPa versus a Liberal target of 13 to 14 kPa in a 2×2 factorial design. A pulmonary artery catheter was inserted following randomization. DO 2 and VO 2 were calculated as: DO 2 =cardiac output × arterial oxygen content, and VO 2 = cardiac output × arteriovenous oxygen difference. Of 789 patients, 730 (92.5%) were included in this substudy. A total of 362 patients were randomized to MAP77, and 368 to MAP63, 368 to a liberal Pao 2 target, and 362 to a restrictive target. At all prespecified time points, DO 2 in MAP77 was higher compared with MAP63, with a cumulative treatment effect of 203 L (95% CI, 132-274) O 2 after 36 hours. VO 2 was higher in MAP77 after 36 hours, with a cumulative treatment effect of 21.9 L (95% CI, 5.8-38) O 2 , compared with the MAP63 group., Conclusions: Targeting a MAP of 77 mm Hg resulted in an overall increase in DO 2 and a smaller increase in VO 2 compared with a MAP target of 63 mm Hg. A higher Pao 2 target did not result in any difference in DO 2 or VO 2 .

Background: Accelerometer-measured physical activity is an increasingly used endpoint in heart failure (HF) trials. We investigated the determinants of accelerometer-measured physical activity and the relationship with patient-reported health status., Methods: Post-hoc analysis of the Empire HF trial, including outpatients with HF with reduced ejection fraction (HFrEF). Physical activity was quantified as average accelerometer counts per minute (CPM) with higher values representing higher activity. We investigated associations between activity level and clinical variables, including age, sex, and body mass index, as well as patient-reported health status assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)., Results: Complete data were available in 180 (95%) patients (86% male, mean age 65 year). Baseline median physical activity level was 1,318 CPM (Q1-Q3 1,111-1,585). Age and anemia were independently associated with activity level (β-coefficients: -10 CPM per year age increase [95% CI -16 to -5.1], P = .00015, and -126 CPM for anemia [95% CI -9.1 to -244], P = .035). Significant independent associations were observed between activity level and all KCCQ summary scores (β-coefficient point estimates of 3.7, 4.6, and 4.9 CPM, all P < .02). For 12-week changes in KCCQ-summary scores, only the KCCQ-CSS was associated with activity level; mean increase of 17.5 CPM [95% CI 1.5 to 34.0], P = 0.032, per 5-point increase in KCCQ-CSS. Associations were not modified by treatment allocation (interaction P-values > .05)., Conclusions: In patients with HFrEF, older age and anemia were independently associated with lower activity. Moreover, physical activity only weakly increased with better health status, suggesting that changes in physical activity reflect improvements in patients' health status to a limited degree. This highlights the need to better understand the endpoint with regards to all other health parameters to ease interpretation in future HF trials., Competing Interests: Conflict of Interest C.F.A. reports grant from the Danish Heart Foundation, Toyota-Fonden Denmark, Arvid Nilsson's Foundation, Aase & Ejnar Danielsen's Foundation, Fru Asta Florida Bolding's Memorial Grant, KV Foundation and The Research and Innovation Foundation of the Department of Cardiology (FUHAS, formerly FUKAP), Herlev and Gentofte University Hospital, Herlev, Denmark; personal fees from AstraZeneca, all outside the submitted work. J.J. reports grants from The Danish Heart Foundation, Denmark, and The CARDIOHGH at the Department of Cardiology, Herlev and Gentofte University Hospital, Denmark, during the conduct of the submitted work; personal fees from scientific advisory board from AstraZeneca and Boehringer Ingelheim, outside the submitted work; grants from The Research Council at Herlev and Gentofte University Hospital, Denmark, grants from The CARDIOHGH (formerly FUHAS), Herlev and Gentofte University Hospital, Denmark, and grants from The A.P. Møller Foundation for the Advancement of Medical Science, Denmark [as sub-investigator of the Empire HF trial]. M.A.O reports grants from the Danish Heart Foundation, grants from The Steno Diabetes Center Odense, Denmark and grants from A.P. Møller Foundation during the conduct of the study. C.T. reports speaker fees from Orion Pharma, personal fees for advisory board participation from Boehringer Ingelheim and Bayer A/S, all outside the submitted work. F.G. reports speaker fees from Orion Pharma, Vifor Pharma and Novartis, and personal fees for advisory board participation from Abbott, Pfizer, Astra-Zeneca, Ionis, Alnylam and Bayer, all outside the submitted work. J.E.M. reports speaker fees from Novartis, Boehringer Ingelheim, Abiomed, Orion and Abbott, advisory board from Orion and Boehringer Ingelheim, and research grant Abiomed and Roche, all outside submitted work. M.S. reports grants from The Capital Region of Denmark, grants from The Danish Heart Foundation, during the conduct of the study; personal fees and nonfinancial support from AstraZeneca, personal fees from Novo Nordisk and Boehringer Ingelheim, outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To discuss future research themes and study design in cardiogenic shock., Recent Findings: Cardiogenic shock research faces multiple challenges, hindering progress in understanding and treating this life-threatening condition. Cardiogenic shock's heterogeneous nature poses challenges in patient selection for clinical trials, potentially leading to variability in treatment responses and outcomes. Ethical considerations arise due to the acuity and severity of the condition, posing challenges in obtaining informed consent and conducting randomized controlled trials where time to treatment is pivotal., Summary: This review discusses research in this area focusing on the importance of phenotyping patients with cardiogenic shock, based on artificial intelligence, machine learning, and unravel new molecular mechanisms using proteomics and metabolomics. Further, the future research focus in mechanical circulatory support and targeting inflammation is reviewed. Finally, newer trial designs including adaptive platform trials are discussed., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Acute kidney injury (AKI) is a significant risk factor associated with reduced survival following out-of-hospital cardiac arrest (OHCA). Whether the severity of AKI simply serves as a surrogate measure of worse peri-arrest conditions, or represents an additional risk to long-term survival remains unclear., Methods: This is a sub-study derived from a randomized trial in which 789 comatose adult OHCA patients with presumed cardiac cause and sustained return of spontaneous circulation (ROSC) were enrolled. Patients without prior dialysis dependent kidney disease and surviving at least 48 h were included (N = 759). AKI was defined by the kidney disease: improving global outcome (KDIGO) classification, and patients were divided into groups based on the development of AKI and the need for continuous kidney replacement therapy (CKRT), thus establishing three groups of patients-No AKI, AKI no CKRT, and AKI CKRT. Primary outcome was overall survival within 365 days after OHCA according to AKI group. Adjusted Cox proportional hazard models were used to assess overall survival within 365 days according to the three groups., Results: In the whole population, median age was 64 (54-73) years, 80% male, 90% of patients presented with shockable rhythm, and time to ROSC was median 18 (12-26) min. A total of 254 (33.5%) patients developed AKI according to the KDIGO definition, with 77 requiring CKRT and 177 without need for CKRT. AKI CKRT patients had longer time-to-ROSC and worse metabolic derangement at hospital admission. Overall survival within 365 days from OHCA decreased with the severity of kidney injury. Adjusted Cox regression analysis found that AKI, both with and without CKRT, was significantly associated with reduced overall survival up until 365 days, with comparable hazard ratios relative to no AKI (HR 1.75, 95% CI 1.13-2.70 vs. HR 1.76, 95% CI 1.30-2.39)., Conclusions: In comatose patients who had been resuscitated after OHCA, patients developing AKI, with or without initiation of CKRT, had a worse 1-year overall survival compared to non-AKI patients. This association remains statistically significant after adjusting for other peri-arrest risk factors., Trial Registration: The BOX trial is registered at ClinicalTrials.gov: NCT03141099., (© 2024. The Author(s).)

Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have previously demonstrated cardioprotective properties in patients with type 2 diabetes, suggesting a preventive effect on heart failure (HF). The Empire Prevent trial program investigates the therapeutic potential for HF prevention by evaluating the cardiac, metabolic, and renal effects of the SGLT2 inhibitor empagliflozin in patients with increased risk of developing HF, but without diabetes or established HF., Methods: The Empire Prevent trial program is an investigator-initiated, double-blind, randomized clinical trial program including elderly and obese patients (60-84 years, body mass index >28 kg/m 2 ) with at least one manifestation of hypertension, cardiovascular or chronic kidney disease, but no history of diabetes or HF. The aims are to investigate the effects of empagliflozin on 1) physical capacity and left ventricular and atrial structural changes with peak oxygen consumption and left ventricular mass as primary endpoints (Empire Prevent Cardiac), and 2) cardiac-adipose tissue interaction and volume homeostasis with primary endpoints of changes in epicardial adipose tissue and estimated extracellular volume (Empire Prevent Metabolic). At present, 138 of 204 patients have been randomized in the Empire Prevent trial program. Patients are randomized 1:1 to 180 days treatment with empagliflozin 10 mg daily or placebo, while undergoing a comprehensive examination program at baseline and follow-up., Discussion: The Empire Prevent trial program will mark the first step towards elucidating the potential of SGLT2 inhibition for HF prevention in an outpatient setting in elderly and obese patients with increased risk of developing HF, but with no history of diabetes or established HF. Furthermore, the Empire Prevent trial program will supplement the larger event-driven trials by providing mechanistic insights to the beneficial effects of SGLT2 inhibition., Trial Registration: Both parts of the trial program have been registered on September 13th 2021 (Clinical Trial Registration numbers: NCT05084235 and NCT05042973) before enrollment of the first patient. All patients will provide oral and written informed consent. The trial is approved by The Regional Committee on Health Research Ethics and the Danish Medicines Agency. Data will be disseminated through scientific meetings and peer-reviewed journals irrespective of outcome., Competing Interests: Conflict of interest C.F.A. reports grants from the Danish Heart Foundation, Toyota-Fonden, Arvid Nilsson's Foundation, Aase & Ejnar Danielsen's Foundation, Fru Asta Florida Bolding's Memorial Grant, KV Foundation and The Research and Innovation Foundation of the Department of Cardiology (FUHAS, formerly FUKAP), Herlev and Gentofte University Hospital, Herlev, Denmark, during the conduct of the submitted work; personal fees from AstraZeneca and has acted as an unpaid sub-investigator in two trials from Novo Nordisk, outside the submitted work. J.H.L. reports grants from Danish Heart Foundation, Odense University Hospital Ph.D. Foundation, Steno Diabetes Center Odense Ph.D. Foundation, Eva and Henry Frænkel's Memorial Grant, Kurt and Grethe Bønnelykke's Foundation, Guldsmed A.L. Rasmussen's Memorial Grant. Funding organizations had no role in the trial program design, data collection, writing of the article or decision to submit the paper. J.J. reports grants from the Danish Heart Foundation, The CARDIOHGH at the Department of Cardiology, Herlev and Gentofte University Hospital, and The Capital Region of Denmark; personal fees from AstraZeneca (advisory board) and Boehringer Ingelheim (advisory board and contribution to the KARDINAL study), all outside the submitted work. M.A.O reports grants from the Danish Heart Foundation; Steno Diabetes Center Odense, Denmark; and the A.P. Møller Foundation, outside the submitted work. N.N. reports speaker fees from AstraZeneca and Bayer, all outside the submitted work. C.K. has received speaker fees or served on advisory boards for AstraZeneca, Boehringer Ingelheim, Novartis Genzyme, Amicus and Chiesi. C.T. reports speaker fees from Orion Pharma, personal fees for advisory board participation from Boehringer Ingelheim and Bayer A/S, all outside the submitted work. F.G. reports speaker fees from Orion Pharma, Vifor Pharma and Novartis, and personal fees for advisory board participation from Abbott, Pfizer, AstraZeneca, Ionis, Alnylam and Bayer, all outside the submitted work. F.K.K. has served on scientific advisory panels and/or been part of speaker's bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, Lupin, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Pharmacosmos, Sanofi, ShouTi, Zealand Pharma and Zucara; and is a minority shareholder in Antag Therapeutics and co-owner of the weight loss clinic Medicinsk Vægttabsbehandling ApS. F.S.D. reports grants from The CARDIOHGH at the Department of Cardiology, Herlev and Gentofte University Hospital, the Novo Nordisk Foundation and speaker fees from Bayer, all outside the submitted work. K.H. reports grants from the Novo Nordisk Foundation, the Independent Research Fund Denmark, the Region of Southern Denmark, Odense University Hospital, Lilly and Herbert Hansen's Foundation, Jascha Fonden, the Ministry of Higher Education and Science, and the Danish Diabetes Academy all outside submitted work. L.K. reports speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis and Bayer. L.A. reports speaker fees from Novartis. M.S. reports grants from the Danish Heart Foundation, during the conduct of the study; personal fees and non-financial support from AstraZeneca, personal fees from Novo Nordisk and Boehringer Ingelheim, outside the submitted work. J.E.M. reports speaker fees from Novartis, Boehringer Ingelheim, Abiomed, Orion and Abbott, advisory board from Orion and Boehringer Ingelheim, and research grant Abiomed and Roche, all outside submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Abstract: Diastolic dysfunction (DD) in heart failure is associated with increased myocardial cytosolic calcium and calcium-efflux through the sodium-calcium exchanger depends on the sodium gradient. Beta-3-adrenoceptor (β3-AR) agonists lower cytosolic sodium and have reversed organ congestion. Accordingly, β3-AR agonists might improve diastolic function, which we aimed to assess. In a first-in-man, randomized, double-blinded trial, we assigned 70 patients with HF with reduced ejection fraction, New York Heart Association II-III, and left ventricular ejection fraction <40% to receive the β3-AR agonist mirabegron (300 mg/day) or placebo for 6 months, in addition to recommended heart failure therapy. We performed echocardiography and cardiac computed tomography and measured N-terminal probrain natriuretic peptide at baseline and follow-up. DD was graded per multiple renowned algorithms. Baseline and follow-up data were available in 57 patients (59 ± 11 years, 88% male, 49% ischemic heart disease). No clinically significant changes in diastolic measurements were found within or between the groups by echocardiography (E/e' placebo: 13 ± 7 to 13 ± 5, P = 0.21 vs. mirabegron: 12 ± 6 to 13 ± 8, P = 0.74, between-group follow-up difference 0.2 [95% CI, -3 to 4], P = 0.89) or cardiac computed tomography (left atrial volume index: between-group follow-up difference 9 mL/m 2 [95% CI, -3 to 19], P = 0.15). DD gradings did not change within or between the groups following 2 algorithms ( P = 0.72, P = 0.75). N-terminal probrain natriuretic peptide remained unchanged in both the groups ( P = 0.74, P = 0.64). In patients with HF with reduced ejection fraction, no changes were identified in diastolic measurements, gradings or biomarker after β3-AR stimulation compared with placebo. The findings add to the previous literature questioning the role of impaired Na + -Ca 2+ -mediated calcium export as a major culprit in DD. NCT01876433., Competing Interests: H. Bundgaard and H. Rasmussen are named inventors on a patent owned by Royal North Shore Hospital and the University of Sydney for the use of 𝛽3-AR agonists to treat heart failure. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used for refractory out-of-hospital cardiac arrest (OHCA). However, survivors managed with ECPR are at risk of poor functional status. The purpose of this study was to investigate return to work (RTW) after refractory OHCA., Methods and Results: Of 44 360 patients with OHCA in the period of 2011 to 2020, this nationwide registry-based study included 805 patients with refractory OHCA in the working age (18-65 years) who were employed before OHCA (2% of the total OHCA cohort). Demographics, prehospital characteristics, status at hospital arrival, employment status, and survival were retrieved through the Danish national registries. Sustainable RTW was defined as RTW for ≥6 months without any long sick leave relapses. Median follow-up time was 4.1 years. ECPR and standard advanced cardiovascular life support were applied in 136 and 669 patients, respectively. RTW 1 year after OHCA was similar (39% versus 54%; P =0.2) and sustainable RTW was high in both survivors managed with ECPR and survivors managed with standard advanced cardiovascular life support (83% versus 85%; P >0.9). Younger age and shorter length of hospitalization were associated with RTW in multivariable Cox analysis, whereas ECPR was not., Conclusions: In refractory OHCA-patients employed prior to OHCA, approximately 1 out of 2 patients were employed after 1 year with no difference between patients treated with ECPR or standard advanced cardiovascular life support. Younger age and shorter length of hospitalization were associated with RTW while ECPR was not.

This study aims to describe baseline characteristics and in-hospital management of a patient cohort hospitalized with acute heart failure (AHF). Adult patients in Denmark admitted with a medical diagnosis during a 7-day period were reviewed for symptoms and clinical findings suggestive of AHF. HFpEF was defined as LVEF ≥ 45%. Of 5194 patients, 290 (6%) had AHF. Sixty-two percent (n = 179) was diagnosed with HFpEF. Compared to HFrEF patients, HFpEF patients were more often women (48% vs. 31%, p = 0.004), less likely to have ischemic heart disease (31% vs. 53%, p = 0.002) and a pacemaker/ICD (7% vs. 21%, p < 0.001/1% vs. 8%, p < 0.001). Fewer HFpEF patients received intravenous diuretics (43% vs. 73%, p < 0.001) and inotropes (2% vs. 7%, p = 0.02), while more HFpEF patients received nitro-glycerine (59% vs. 44%, p = 0.02). Intubation/NIV, ICU admission, and revascularization were used similarly. Hospitalization was shorter for HFpEF patients (4 vs. 6 days, p < 0.001), with no significant difference in survival to discharge (96% vs. 91%, p = 0.07). Of AHF admissions, nearly two-thirds was due to HFpEF. Compared to HFrEF, HFpEF patients had a lower cardiac comorbidity and a 2-day shorter hospitalization., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: The NatIonal Danish endocarditis stUdieS (NIDUS) registry aims to investigate the mechanisms contributing to the increasing incidence of infective endocarditis (IE) and to discover risk factors associated to the course, treatment and clinical outcomes of the disease., Methods: The NIDUS registry was created to investigate a nationwide unselected group of patients hospitalized for IE. The National Danish healthcare registries have been queried for validated IE diagnosis codes (International Classification of Disease, 10 th edition [ICD-10]: DI33, DI38, and DI398). Subsequently, a team of 28 healthcare professionals, including experts in endocarditis, will systematically review and evaluate all identified patient records using the modified Duke Criteria and the 2015 European Society of Cardiology modified diagnostic criteria. The registry will contain all cases with definite or possible IE found in primary data sources in Denmark between January 1, 2016, and December 31, 2021. We will gather individual patient data, such as clinical, microbiological, and echocardiographic characteristics, treatment regimens, and clinical outcomes. A digital data collection form will be used to the gathering of data. A sample of approximately 4,300 individual patients will be evaluated using primary data sources., Conclusions and Perspectives: The NIDUS registry will be the first comprehensive nationwide IE registry, contributing critical knowledge about the course, treatment, and clinical outcomes of the disease. Additionally, it will significantly aid in identifying areas in which future research is needed., Competing Interests: Disclosures Peter L. Graversen: None Katra Hadji-Turdeghal: None Jacob Eifer Møller: Institutional research grant from Novo Nordic Foundation, Danish Hear Foundation and Abiomed outside submitted work. Unrelated to this study. Niels Eske Bruun: has received investigator initiated grants from: The Novo Nordisk Foundation, The Augustinus Foundation, The Kaj Hansen Foundation, and Health Insurance Denmark, unrelated to this study. Hicham Laghmoch: None Andreas Dalsgaard Jensen: None Jeppe K. Petersen: None Henning Bundgaard: has received lecture fees from Amgen, BMS, MSD and Sanofi, unrelated to this study. Kasper Iversen: None Jonas A Povlsen: None Claus Moser: has received an independent research grant from the Novo Nordisk Foundation in translational research grant number (NNF17OC0025074). Unrelated to this study. Morten Smerup: None Hanne Sortsøe Jensen: None Peter Søgaard: None Jannik Helweg-Larsen: None Daniel Faurholt-Jepsen: None Lauge Østergaard: has received an independent research grant from the Novo Nordisk Foundation (NNF23OC0081668) related to mitral valve regurgitation. Unrelated to this study. Lars Køber speakers fee from AstraZeneca, Baer, Boehringer, Novartis and Novo, unrelated to this study Emil L. Fosbøl: has received independent research grants related to valvular heart disease and endocarditis from the Novo Nordisk Foundation and the Danish Heart Association., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Background: The clinical spectrum of acute myocardial infarction complicated by cardiogenic shock (AMICS) varies. Out-of-hospital cardiac arrest (OHCA) can be the first sign of cardiac failure, whereas others present with various degrees of hemodynamic instability (non-OHCA). The aim of the present study was to explore differences in prehospital management and characteristics of survivors and nonsurvivors in AMICS patients with OHCA or non-OHCA. Methods: Data analysis was based on patient data from the RETROSHOCK cohort comprising consecutive AMICS patients admitted to two tertiary cardiac centers between 2010 and 2017. Results: 1,716 AMICS patients were included and 42% presented with OHCA. Mortality in OHCA patients was 47% versus 57% in the non-OHCA group. Almost all OHCA patients were intubated before admission (96%). In the non-OHCA group, prehospital intubation (25%) was associated with a better survival ( P < 0.001). Lactate level on admission demonstrated a linear relationship with mortality in OHCA patients. In non-OHCA, probability of death was higher for any given lactate level <12 mmol/L compared with OHCA. However, a lactate level >7 mmol/L in non-OHCA did not increase mortality odds any further. Conclusion: Mortality was almost doubled for any admission lactate level up to 7 mmol/L in non-OHCA patients. Above this level, mortality remained unchanged in non-OHCA patients but continued to increase in OHCA patients. Prehospital intubation was performed in almost all OHCA patients but only in one of four patients without OHCA. Early intubation in non-OHCA patients was associated with a better outcome., Competing Interests: Dr Christian Hassager has received research grants from Lundbeck Foundation (R186-2015-2132), Novo Nordisk Foundation (NNF20OC0064043), and the Danish Heart Foundation (21-R151-A10091-22200). Dr Jacob Eifer Møller has received an institutional research grant from Abiomed and Novo Nordic Foundation. Speakers' fees were received from Abbott, Abiomed, and Boehringer Ingelheim. The remaining authors have no disclosures and report no conflicts of interest., (Copyright © 2023 by the Shock Society.)

Cardiogenic shock due to ST-elevation myocardial infarction remains a critical condition with a high mortality rate, even with current revascularization techniques. The use of mechanical circulatory support, such as the microaxial flow pump device (Impella CP®), presents a promising approach to enhance cardiac output and systemic perfusion. The DanGer Shock trial explored the efficacy of Impella CP® in addition to standard care compared to standard care alone in improving survival outcomes for these patients. Despite the potential for increased adverse events, the Impella CP® device significantly reduces mortality in patients with ST-elevation myocardial infarction complicated by cardiogenic shock. Future research should focus on refining patient selection criteria and minimizing device-related complications to maximize the therapeutic benefits of mechanical circulatory support in this critical population.

The 12-item version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) was originally developed for patients with heart failure but has been used and tested among patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation. Whether the instrument is suitable for patients with AS who underwent surgical aortic valve replacement (SAVR) is currently unknown. Thus, we aimed to investigate the psychometric properties of the KCCQ-12 before and after SAVR among patients with severe AS. We conducted a prospective cohort of 184 patients with AS who completed the KCCQ-12 and the EuroQol 5 Dimension 5 Levels before and 4 weeks after surgery. Construct validity was investigated with hypothesis testing and an analysis of Spearman's correlation between the two instruments. Structural validity was investigated with explorative and confirmatory factor analyses and reliability with Cronbach's α. All analyses were conducted on data from the two time points (preoperatively and four weeks after surgery). The hypothesis testing revealed how the New York Heart Association class was significantly correlated with the preoperative KCCQ-12 total score (higher New York Heart Association class, worse score). A longer length of hospital stay and living alone were significantly associated with poorer postoperative KCCQ-12 total score. KCCQ-12 and EuroQol 5 Dimension 5 Levels were moderately correlated in most domains/the total score/Visual Analogue Scale score. Principal component analyses revealed two 3-factor structures. The confirmatory factor analyses did not support the original model at any time point. Cronbach's α ranged from 0.22 to 0.84 in three preoperative factors and from 0.39 to 0.76 in the postoperative factors. The total Cronbach's α was 0.83 for the suggested preoperative 3-factor model and 0.83 for the postoperative model. In conclusion, the Danish version of the KCCQ-12 tested in a population of patients with AS who underwent SAVR appears to have acceptable construct validity, whereas structural validity cannot be confirmed for the original four-factor model. Overall reliability is good., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

In patients with cardiogenic shock (CS), particularly those with acute myocardial infarction (AMI), evidence suggests that timely diagnosis and treatment interventions are critical in the prevention of haemo-metabolic compromise. Temporary mechanical circulatory support (tMCS) has shown potential in facilitating revascularization and recovery of patients with acute myocardial infarction cardiogenic shock (AMI-CS). Timing of treatment strategies for CS patients needs to be optimized for use of tMCS devices that are applicable to this heterogeneous patient population. Here, the latest evidence as well as the gaps in knowledge surrounding the role of time in the management of patients with CS is summarized., Competing Interests: Conflict of interest Giuseppe Tarantini has received lecture fees from Edwards Lifesciences, Medtronic, Abbott, Boston Scientifics, Abiomed. Giulia Masiero has nothing to disclose. Alaide Chieffo has received lecture/consultant fees from Abbott, Abiomed, Biosensor, Boston Scientifics, Medtronic, Menarini, Shockwave Medical. Jacob Eifer Møller has received an institutional research grant from Abiomed and Novo Nordic Foundation and lecture honorary from Abbott, Abiomed, Boehringer Ingelheim, and Orion. Christian Hassager has received lecture honorarium from Abiomed and research grants from Novo Nordisk Foundation, Lundbeck Foundation, and the Danish Heart Foundation. Benedikt Schrage has received lecture honorarium from Abbott, Abiomed, and AstraZeneca as well as research grants from Abiomed, the German Research Foundation, the Else Kröner-Fresenius-Stiftung and the University of Hamburg., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Monitoring of the patient supported with a temporary mechanical circulatory support (tMCS) is crucial in achieving the best possible outcome. Monitoring is a continuous and labour-intensive process, as cardiogenic shock (CS) patients can rapidly deteriorate and may require new interventions within a short time period. Echocardiography and invasive haemodynamic monitoring form the cornerstone of successful tMCS support. During monitoring, it is particularly important to ensure that adequate end-organ perfusion is achieved and maintained. Here, we provide a comprehensive overview of best practices for monitoring the CS patient supported by a micro-axial flow pump, veno-arterial extracorporeal membrane oxygenation, and both devices simultaneously (ECMELLA approach). It is a complex process that encompasses device control, haemodynamic control and stabilization, monitoring of interventions, and assessment of end-organ function. The combined, continuous, and preferably protocol-based approach of echocardiography, evaluation of biomarkers, end-organ assessment, and haemodynamic parameters is crucial in assessing this critically ill CS patient population., Competing Interests: Conflict of interest: C.V. received manuscript support from Abiomed, honoraria from Abiomed, and travel support from Abiomed. C.V. is supported by a research grant of the FWO-flanders (FKM 1803923N). J.B. is on a board for AstraZeneca and BoehringerIngelheim and received consulting fees from Abiomed, Getinge, Resuscitec, and Xenios. C.H. has received research grants from Novo Nordisk Foundation, Lundbeck Foundation, and Danish Heart Foundation and honoraria from Abiomed and is in an unpaid leadership role as Chair of the Danish Heart Foundation and board member of ESC. M.P. has received manuscript preparation support, consulting fees, and honoraria from Abiomed. A.P. has received manuscript preparation support from Abiomed, a research grant from the German Research Council, and honoraria from Abbott, Bayer, Bristol-Myers Squibb, Pfizer, Daiichi, and Medtronic. M.S. reports no disclosures or conflicts of interest. J.E.M. has received grants from Abiomed and Novo Nordic, honoraria from Abiomed, Boehringer Ingelheim, Abbott, and Orion, and travel support from Abiomed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Anxiety, depression, and post-traumatic stress disorder (PTSD) among out-of-hospital cardiac arrest (OHCA) survivors may impact long-term recovery. Coping and perception of symptoms may vary between sexes. The aim was to explore sex differences in psychological consequences following OHCA., Methods and Results: This was a prospective observational study of OHCA survivors who attended a structured 3-month follow-up. Symptoms of anxiety/depression were measured using the Hospital Anxiety and Depression Scale, range 0-21, with a cut-off score of ≥8 for significant symptoms; PTSD was measured with the PTSD Checklist for DSM-5 (PCL-5), range 0-80. A score of ≥33 indicated PTSD symptoms. Cognitive function was assessed by the Montreal Cognitive Assessment. From 2016 to 2021, 381 consecutive comatose OHCA survivors were invited. Of these, 288 patients (76%) participated in the follow-up visit [53 (18%) females out of 80 survivors and 235 (82%) males out of 300 alive at follow-up (78%)]. Significant symptoms of anxiety were present in 47 (20%) males and 19 (36%) females (P = 0.01). Significant symptoms of PTSD were present in 30% of males and 55% of females (P = 0.01). Adjusting for pre-specified covariates using multivariable logistic regression, female sex was significantly associated with anxiety [odds ratio (OR): 2.18, confidence interval (CI): 1.09-4.38, P = 0.03]. This difference was especially pronounced among young females (below median age, ORadjusted: 3.31, CI: 1.32-8.29, P = 0.01) compared with young males. No significant sex difference was observed for depression or cognitive function., Conclusion: Symptoms of anxiety and PTSD are frequent in OHCA survivors, and female survivors report significantly more symptoms of anxiety and PTSD compared with males. In particular, young females were significantly more symptomatic than young males., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Anthracycline-based chemotherapy has improved the prognosis of various malignancies, but increases the long-term risk of heart failure (HF). Identification of patients at risk prior to treatment initiation is warranted. Therefore, the aim of this study was to evaluate if a familial predisposition to HF increases the risk of anthracycline related HF., Methods: Using nationwide Danish registries, all patients treated with anthracycline from 2004 to 16 were identified. The primary outcome was long-term HF risk. First-degree relatives were identified in the Danish Family Registry and exposure was defined as a first-degree biological relative with prior HF. Risk of HF was evaluated in a cumulative incidence function and the association in a multivariable Cox regression model., Results: A total of 11,651 patients (median age 49.1 years (IQR: 43.6-53.7), 12.2% male) were included after exclusion of 46 with preanthracycline HF. Median follow-up was 3.8 years (IQR 1.9-6.4). In the group with a first-degree relative with HF (n = 1,608) 35 patients (2.2%) were diagnosed with HF vs 133 (1.3%) in the group without a first-degree relative with HF (n = 10,043), corresponding to incidence rates per 1,000 patient-years of 5.2 (CI:3.8-7.3) vs 3.0 (CI:2.5-3.5). The cumulative incidence of HF after 10 years was higher in the first-degree relative group (3.2% vs 2.0%, P = .004); adjusted hazard ratio 1.53 (CI:1.05-2.23, P = .03)., Conclusion: In this nationwide register-based study having a first-degree relative with HF was associated with increased risk of anthracycline related HF, suggesting that attention towards family predisposition may be warranted when estimating the risk of anthracycline related cardiotoxicity., Competing Interests: Disclosures None declared., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Resuscitation guidelines propose a multimodal prognostication strategy algorithm at ≥72 hours after the return of spontaneous circulation to evaluate neurological outcome for unconscious cardiac arrest survivors. Even though guidelines suggest quantitative pupillometry for assessing pupillary light reflex, threshold values are not yet validated.This study aims to validate pre-specified thresholds of quantitative pupillometry by quantitatively assessing the percentage reduction of pupillary size (qPLR) <4% and Neurological Pupil index (NPi) ≤2 and in predicting unfavorable neurological outcome. Both as an isolated predictor and combined with guideline-suggested neuron-specific enolase (NSE) threshold >60 μg L -1 in the current prognostication strategy algorithm., Methods: We conduct this pre-planned diagnostic sub-study in the randomized, controlled, multicenter clinical trial "Blood Pressure and Oxygenation Targets after Out-of-Hospital Cardiac Arrest-trial". Blinded to treating physicians and outcome assessors, measurements of qPLR and NPi are obtained from cardiac arrest survivors at time points (±6 hours) of admission, after 24, 48, and 72 hours, or until the time of awakening or death., Discussion: This study will be the largest prospective study investigating the predictive performance of automated quantitative pupillometry in unconscious patients resuscitated from cardiac arrest. We will test specific threshold values of NPi ≤2 and qPLR <4% to predict unfavorable outcome following cardiac arrest. The validation of pupillometry alone and combined with NSE with the criteria of the current prognostication strategy algorithm will hopefully increase the level of evidence and support clinical neuroprognostication with automated quantitative pupillometry in unconscious post-cardiac arrest patients., Trial Registration: Registered March 30, 2017, at ClinicalTrials.gov (Identifier: NCT03141099)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All co-authors were supported outside the submitted work. JEM’s salary is supported by the University of Southern Denmark through an institutional research grant from Abiomed, and CH received grants from Lundbeck Foundation (R186-2015-2132), Novo Nordisk Foundation (NNF20OC0064043), and The Danish Heart Foundation (21-R151-A10091-22200). JG’s salary is supported by a research grant from the Danish Cardiovascular Academy, which is funded by the Novo Nordisk Foundation (NNF20SA0067242) and The Danish Heart Foundation., (© 2023 The Author(s).)

Competing Interests: Conflict of interest: J.K. has received a grant from the NovoNordisk Foundation for the DANOHCA trial NCT05895838. J.E.M. receives institutional grant from Abiomed outside the current work.

The use of mechanical circulatory support using percutaneous ventricular assist devices (pVAD) has increased rapidly during the last decade without substantial new evidence for their effect on outcome. In addition, many gaps in knowledge still exist such as timing and duration of support, haemodynamic monitoring, management of complications, concomitant medical therapy, and weaning protocols. This clinical consensus statement summarizes the consensus of an expert panel of the Association for Acute CardioVascular Care, European Society of Intensive Care Medicine, European Extracorporeal Life Support Organization, and European Association for Cardio-Thoracic Surgery. It provides practical advice regarding the management of patients managed with pVAD in the intensive care unit based on existing evidence and consensus on best current practice., Competing Interests: Conflict of interest: J.E.M.: speaker honorarium from Abbott, Abiomed, Boehringer Ingelheim, and Orion. Institutional research grant: Abiomed, Novo Nordic Foundation, and Danish Heart Foundation; A.S.: no disclosures, N.A.: no disclosures, A.A.: no disclosures, J.B.: consultant for Getinge, Abiomed, and Xenios; D.B.: no disclosures, G.F.: no disclosures, C.G.T.: no disclosures, A.M.: has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; has received honoraria for lectures from Roche Diagnostics, Bayer, and MSD; and is a consultant for Corteria Pharmaceuticals, S-Form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; S.P.: no disclosures, J.S.: no disclosures, H.T.: no disclosures, and C.H.: speaker honorarium from Abiomed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: Quantitative pupillometry is the guideline-recommended method for assessing pupillary light reflex for multimodal prognostication in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). However, threshold values predicting an unfavorable outcome have been inconsistent across studies; therefore, we aimed to identify specific thresholds for all quantitative pupillometry parameters., Methods: Comatose post-OHCA patients were consecutively admitted to the cardiac arrest center at Copenhagen University Hospital Rigshospitalet from April 2015 to June 2017. The parameters of quantitatively assessed pupillary light reflex (qPLR), Neurological Pupil index (NPi), average/max constriction velocity (CV/MCV), dilation velocity (DV), and latency of constriction (Lat) were recorded on the first three days after admission. We evaluated the prognostic performance and identified thresholds achieving zero percent false positive rate (0% PFR) for an unfavorable outcome of 90-day Cerebral Performance Category (CPC) 3-5. Treating physicians were blinded for pupillometry results., Results: Of the 135 post-OHCA patients, the primary outcome occurred for 53 (39%) patients.On any day during hospitalization, a qPLR < 4%, NPi < 2.45, CV < 0.1 mm/s, and an MCV < 0.335 mm/s predicted 90-day unfavorable neurological outcome with 0% FPR (95%CI: 0-0%), with sensitivities of 28% (17-40%), 9% (2-19%), 13% (6-23%), and 17% (8-26%), respectively on day 1., Conclusion: We found that specific thresholds of all quantitative pupillometry parameters, measured at any time following hospital admission until day 3, predicted a 90-day unfavorable outcome with 0% FPR in comatose patients resuscitated from OHCA. However, at 0% FPR, thresholds resulted in low sensitivity. These findings should be further validated in larger multicenter clinical trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Aims: Cardiogenic shock (CS) is known to induce an inflammatory response. The prognostic utility of this remains unclear. To investigate the association between C-reactive protein (CRP) levels and leucocyte count and mortality in patients with acute myocardial infarction complicated by CS (AMICS)., Methods and Results: Consecutive patients (N = 1716) admitted between 2010 and 2017 with an individually validated diagnosis of AMICS were included. The analysis was restricted to patients alive at 48 h after first medical contact and a valid CRP and leucocyte measurement at 48 ± 12 h from the first medical contact. A combined inflammatory score for each patient was computed by summing the CRP and leucocyte count z-scores to normalize the response on a standard deviation scale. Associations with mortality were analysed using a multivariable Cox proportional hazards model stratified by inflammatory response quartiles: Of the 1716 patients in the cohort, 1111 (64.7%) fulfilled inclusion criteria. The median CRP level at 48 h was 145 mg/dL [interquartile range (IQR) 96-211]. The median leucocyte count was 12.6 × 10-9/L (IQR 10.1-16.4). Patients with the highest inflammatory response (Q4) had lower median left ventricular ejection fractions and higher lactate levels at the time of diagnosis. The 30-day all-cause mortality rates were 46% in Q4 and 21% in Q1 (P < 0.001). In multivariable models, the inflammatory response remained associated with mortality [hazard ratio (HR)Q4 2.32, 95% confidence interval (CI) 1.59-3.39, P < 0.001]. The finding was also significant in AMICS patients presenting with out-of-hospital cardiac arrest following multivariable adjustment (HRQ4 3.37, 95% CI 2.02-4.64, P < 0.001)., Conclusion: Cardiogenic shock induces an acute inflammatory response, the severity of which is associated with mortality., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)