First-in-man trial of ß3-adrenoceptor agonist treatment in chronic heart failure - impact on diastolic function.

Diastolic dysfunction (DD) in heart failure (HF) is associated with increased myocardial cytosolic calcium, and calcium-efflux via the sodium-calcium-exchanger depends on the sodium gradient. Beta-3-adrenoceptor (ß3-AR) agonists lower cytosolic sodium and have reversed organ congestion. Accordingly, ß3-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 (HFrEF), NYHA II-III, and LVEF<40% to receive the ß3-AR agonist mirabegron (300 mg/day) or placebo for six months, in addition to recommended HF therapy. We performed echocardiography and cardiac computed tomography (CCT) and measured N-terminal pro-brain natriuretic peptide (NT-proBNP) 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 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 CCT (left atrial volume index: between group follow-up difference 9 ml/m2 [95% CI -3 to 19], p=0.15). DD gradings did not change within or between groups following two algorithms (p=0.72, p=0.75). NT-proBNP remained unchanged in both groups (p=0.74, p=0.64). In patients with HFrEF, no changes were identified in diastolic measurements, gradings or biomarker after ß3-AR stimulation compared to placebo. The findings add to previous literature questioning the role of impaired Na+-Ca2+ mediated calcium-export as a major culprit in DD. NCT01876433.

Early ICD implantation in cardiac arrest survivors with acute coronary syndrome - predictors of implantation, ICD-therapy and long-term survival.

Objectives. Implantable cardioverter defibrillator (ICD) implantation in patients resuscitated from out-of-hospital cardiac arrest (OHCA) due to acute myocardial infarction (AMI) is controversial. Design. Consecutive OHCA-survivors due to AMI from two Danish tertiary heart centers from 2007 to 2011 were included. Predictors of ICD-implantation, ICD-therapy and long-term survival (5 years) were investigated. Patients with and without ICD-implantation during the index hospital admission were included (later described as early ICD-implantation). Patients with an ICD after hospital discharge were censored from further analyses at time of implantation. Results. We identified 1,457 consecutive OHCA-patients, and 292 (20%) of the cohort met the inclusion criteria. An ICD was implanted during hospital admission in 78 patients (27%). STEMI and successful revascularization were inversely and independently associated with ICD-implantation (ORSTEMI = 0.37, 95% CI: 0.14-0.94, ORrevasc = 0.11, 0.03-0.36) whereas age, sex, LVEF <35%, comorbidity burden or shockable first OHCA-rhythm were not associated with ICD-implantation. Appropriate ICD-shock therapy during the follow-up period was noted in 15% of patients (n = 12). Five-year mortality-rate was significantly lower in ICD-patients (18% vs. 28%, plogrank = 0.02), which was persistent after adjustment for prognostic factors (HR = 0.44 (95% CI: 0.23-0.88)). This association was no longer found when using first event (death or appropriate shock whatever came first) as outcome variable (plogrank = 0.9). Conclusions. Mortality after OHCA due to AMI was significantly lower in patients with early ICD-implantation after adjustment for prognostic factors. When using appropriate shock and death as events, ICD-patients had similar outcome as patients without an ICD, which may suggest a survival benefit due to appropriate device therapy.

Refractory out-of-hospital cardiac arrest with ongoing cardiopulmonary resuscitation at hospital arrival - survival and neurological outcome without extracorporeal cardiopulmonary resuscitation.

BACKGROUND: The prognosis in refractory out-of-hospital cardiac arrest (OHCA) with ongoing cardiopulmonary resuscitation (CPR) at hospital arrival is often considered dismal. The use of extracorporeal cardiopulmonary resuscitation (eCPR) for perfusion enhancement during resuscitation has shown variable results. We aimed to investigate outcome in refractory OHCA patients managed conservatively without use of eCPR. METHODS: We included consecutive OHCA patients with refractory arrest or prehospital return of spontaneous circulation (ROSC) in the Copenhagen area in 2002-2011. RESULTS: A total of 3992 OHCA patients with resuscitation attempts were included; in 2599, treatment was terminated prehospital, and 1393 (35%) were brought to the hospital either with ROSC (n = 1285, 92%) or with refractory OHCA (n = 108, 8%). Of patients brought in with refractory OHCA, 56 (52%) achieved ROSC in the emergency department. There were no differences between patients with refractory OHCA or prehospital ROSC with regard to age, sex, comorbidities, or etiology of OHCA. Time to emergency medical services (EMS) arrival was similar, whereas time to ROSC (when ROSC was achieved) was longer in refractory OHCA patients (EMS, 6 (5-9] vs. 7 [5-10] min, p = 0.8; ROSC, 15 [9-22] vs. 27 [20-41] min, p < 0.001). Independent factors associated with transport with refractory OHCA instead of prehospital termination of therapy were OHCA in public (OR, 3.6 [95% CI, 2.2-5.8]; p < 0.001), witnessed OHCA (OR, 3.7 [2.0-7.1]; p < 0.001), shockable rhythm (OR, 3.0 [1.9-4.7]; p < 0.001), younger age (OR, 1.2 [1.1-1.2]; p < 0.001), and later calendar year (OR, 1.4 [1.2-1.6]; p < 0.001). Thirty-day survival was 20% in patients with refractory OHCA compared with 42% in patients with prehospital ROSC (p < 0.001). Four of 28 refractory OHCA patients with duration of resuscitation > 60 min achieved ROSC. No difference in favorable neurological outcome in patients surviving to discharge was found (prehospital ROSC 84% vs. refractory OHCA 86%; p = 0.7). CONCLUSIONS: Survival after refractory OHCA with ongoing CPR at hospital arrival was significantly lower than among patients with prehospital ROSC. Despite a lower survival, the majority of survivors with both refractory OHCA and prehospital ROSC were discharged with a similar degree of favorable neurological outcome, indicating that continued efforts in spite of refractory OHCA are not in vain and may still lead to favorable outcome even without eCPR.

Importance of comorbidities in comatose survivors of shockable and non-shockable out-of-hospital cardiac arrest treated with target temperature management.

OBJECTIVE: Comorbidity prior to out-of-hospital cardiac arrest (OHCA) and primary rhythm in relation to survival is not well established. We aimed to assess the prognostic importance of comorbidity in relation to primary rhythm in OHCA-patients treated with Target Temperature Management (TTM). DESIGN: Consecutive comatose survivors of OHCA treated with TTM in hospitals in the Copenhagen area between 2002-2011 were included. Utstein-based pre- and in-hospital data collection was performed. Data on comorbidity was obtained from The Danish National Patient Register and patient charts, assessed by the Charlson Comorbidity Index (CCI). RESULTS: A total of 666 patients were included. A third (n = 233, 35%) presented with non-shockable rhythm, and they were less often male (64% vs. 82%, p < .001), and OHCA in public, witnessed OHCA, and bystander cardiopulmonary resuscitation (CPR) were less common compared to patients with a shockable primary rhythm (public: 27% vs. 48%, p < .001, witnessed: 79% vs. 90%, p < .001, bystander CPR: 47% vs. 63%, p < .001). 30-day mortality was 62% compared to 28% in patients with non-shockable and shockable rhythm, respectively. By Cox-regression analyses, any comorbidity (CCI ≥1) was the only factor independently associated with 30-day mortality in patients with non-shockable rhythm (HR =1.9 (95% CI: 1.2-2.9), p < .01), whereas in patients with shockable rhythm comorbidity was not associated with outcome after adjustment for prognostic factors (HR = 0.82 (0.55-1.2), p = .34). No significant interaction between primary rhythm and comorbidity in terms of mortality was present. CONCLUSION: A higher comorbidity burden was independently associated with a higher 30-day mortality rate in patients presenting with non-shockable primary rhythm but not in patients with shockable rhythm.

Bradycardia During Targeted Temperature Management: An Early Marker of Lower Mortality and Favorable Neurologic Outcome in Comatose Out-of-Hospital Cardiac Arrest Patients.

OBJECTIVES: Bradycardia is common during targeted temperature management, likely being a physiologic response to lower body temperature, and has recently been associated with favorable outcome following out-of-hospital cardiac arrest in smaller observational studies. The present study sought to confirm this finding in a large multicenter cohort of patients treated with targeted temperature management at 33°C and explore the response to targeted temperature management targeting 36°C. DESIGN: Post hoc analysis of a prospective randomized study. SETTING: Thirty-six ICUs in 10 countries. PATIENTS: We studied 447 (targeted temperature management = 33°C) and 430 (targeted temperature management = 36°C) comatose out-of-hospital cardiac arrest patients with available heart rate data, randomly assigned in the targeted temperature management trial from 2010 to 2013. INTERVENTIONS: Targeted temperature management at 33°C and 36°C. MEASUREMENTS AND MAIN RESULTS: Endpoints were 180-day mortality and unfavorable neurologic function (cerebral performance category 3-5). Patients were stratified by target temperature and minimum heart rate during targeted temperature management (< 50, 50-59, and ≥ 60 beats/min [reference]) at 12, 20, and 28 hours after randomization. Heart rates less than 50 beats/min and 50-59 beats/min were recorded in 132 (30%) and 131 (29%) of the 33°C group, respectively. Crude 180-day mortality increased with increasing minimum heart rate (< 50 beats/min = 32%, 50-59 beats/min = 43%, and ≥ 60 beats/min = 60%; p(log-rank) < 0.0001). Bradycardia less than 50 beats/min was independently associated with lower 180-day mortality (hazard ratio(adjusted) = 0.50 [0.34-0.74; p < 0.001]) and lower odds of unfavorable neurologic outcome (odds ratio(adjusted) = 0.38 [ 0.21-0.68; p < 0.01]) in models adjusting for potential confounders including age, initial rhythm, time to return of spontaneous circulation, and lactate at admission. Similar, albeit less strong, independent associations of lower heart rates and favorable outcome were found in patients treated with targeted temperature management at 36°C. CONCLUSIONS: This study confirms an independent association of bradycardia and lower mortality and favorable neurologic outcome in a large cohort of comatose out-of-hospital cardiac arrest patients treated by targeted temperature management at 33°C. Bradycardia during targeted temperature management at 33°C may thus be a novel, early marker of favorable outcome.

Association diastolic function by echo and infarct size by magnetic resonance imaging after STEMI.

OBJECTIVES: Left ventricular (LV) diastolic dysfunction is a predictor of increased morbidity and mortality; however, little is known about diastolic function and the degree of myocardial damage after myocardial infarction (MI). The aim was to assess the association between diastolic dysfunction by echocardiography and myocardial salvage assessed with cardiac magnetic resonance (CMR) imaging in patients with ST-segment elevation MI (STEMI). DESIGN: In a prospective study, echocardiography and CMR were performed in STEMI patients in the early post-MI phase assessing diastolic dysfunction according to E/A and E/e'average and area at risk, and after three months with measurement of final infarct size and salvage index. Linear regression analyses were performed testing the association of diastolic dysfunction with area at risk, final infarct size and salvage index. RESULTS: A total of 193 patients (61 ± 11 years) were included. Median system delay (first medical contact to primary PCI) was 185 min, 123 patients (63%) had TIMI 0/1 flow before intervention and 85 (46%) sustained an anterior MI. In 74 patients (38%), diastolic function was normal. The presence of diastolic dysfunction was associated with larger area at risk of median 6.6% (p < 0.001), larger final infarct size of 4.5% (p < 0.001), and lower salvage index of -5.9% (p = 0.02) compared with patients with normal diastolic function. CONCLUSION: Diastolic dysfunction in the early phase after STEMI is associated with more extensive myocardial damage and significantly poorer myocardial salvage after three months, and the presence of diastolic dysfunction acutely after STEMI may therefore be used as a marker of worse myocardial outcome.

Comorbidity burden is not associated with higher mortality after out-of-hospital cardiac arrest.

OBJECTIVES: We investigated whether comorbidity burden of comatose survivors of out-of-hospital cardiac arrest (OHCA) affects outcome and if comorbidity modifies the effect of target temperature management (TTM) on final outcome. DESIGN: The TTM trial randomized 939 patients to 24 h of TTM at either 33 or 36 °C with no difference regarding mortality and neurological outcome. This post-hoc study of the TTM-trial formed a modified comorbidity index (mCI), based on available comorbidities from the Charlson comorbidity index (CCI). RESULTS: Bystander cardiopulmonary resuscitation (CPR) decreased with higher comorbidity group, p = 0.01. Comorbidity groups were univariately associated with higher mortality compared to mCI0 (HRmCI1: 1.55, CI: 1.25-1.93, p < 0.001, HRmCI2: 2.01, CI: 1.55-2.62, p < 0.001, HRmCI ≥ 3: 2.16, CI: 1.57-2.97, p < 0.001). When adjusting for confounders there was a consistent, nonsignificant association between level of comorbidity and mortality (HRmC11: 1.17, CI: 0.92-1.48, p = 0.21, HRmCI2: 1.28, CI: 0.96-1.71, p = 0.10, HRmCI ≥ 3: 1.37, CI: 0.97-1.95, p = 0.08). There was no interaction between comorbidity burden and level of TTM on outcome, p = 0.61. CONCLUSION: Comorbidity burden was associated with higher mortality following OHCA, but when adjusting for confounders, the influence was no longer significant. The association between mCI and mortality was not modified by TTM. Comorbidity burden is associated with lower rates of bystander cardiopulmonary resuscitation after OHCA.

Factors Associated With Successful Resuscitation After Out-of-Hospital Cardiac Arrest and Temporal Trends in Survival and Comorbidity.

STUDY OBJECTIVE: Out-of-hospital cardiac arrest has an overall poor prognosis. We sought to identify what temporal trends and influencing factors existed for this condition in one region. METHODS: We studied consecutive out-of-hospital cardiac arrest patients from 2007 to 2011 with attempted resuscitation in Copenhagen. From an Utstein database, we assessed survival to admission and comorbidity with the Charlson comorbidity index from the National Patient Registry and employment status from the Danish Rational Economic Agents Model database. We used logistic regression analyses to identify factors associated with outcome. RESULTS: Of a total of 2,527 attempted resuscitations in out-of-hospital cardiac arrest patients, 40% (n=1,015) were successfully resuscitated and admitted to the hospital. The strongest independent factors associated with successful resuscitation were shockable primary rhythm (multivariate odds ratio [OR]=3.9; 95% confidence interval [CI] 3.1 to 5.0), witnessed arrest (multivariate OR=3.5; 95% CI 2.7 to 4.6), and out-of-hospital cardiac arrest in a public area (multivariate OR=2.1; 95% CI 1.6 to 2.8), whereas no comorbidity (multivariate OR=1.1; 95% CI 0.8 to 1.45), sex (multivariate OR=1.14; 95% CI 0.91 to 1.44), and employment status (multivariate OR=1.17; 95% CI 0.89 to 1.56) were not independently associated with outcome. The number of patients with a high comorbidity burden (Charlson comorbidity index ≥3) increased during the study period (P trend <.001), from 18% to 31% (P trend <.001), whereas the percentage of out-of-hospital cardiac arrest patients with successful resuscitation to hospital admission increased by 3% per year during the study period, from 37% in 2007 to 43% in 2011 (P trend <.001). CONCLUSION: Our observations confirm the importance of key features that influence out-of-hospital cardiac arrest survival to hospital admission but are not highly influenced by public health actions. Despite increased illness burden, this short term outcome from cardiac arrest improved as care system efforts matured.

Health-related quality of life and cognitive function after out-of-hospital cardiac arrest; a comparison of prehospital return-of-spontaneous circulation and refractory arrest managed with extracorporeal cardiopulmonary resuscitation.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Return to Work After Refractory Out-of-Hospital Cardiac Arrest in Patients Managed With or Without Extracorporeal Cardiopulmonary Resuscitation: A Nationwide Register-Based Study.

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.

Lactate and lactate clearance as predictors of one-year survival in extracorporeal cardiopulmonary resuscitation - An international, multicentre cohort study.

AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) can be considered in selected patients with refractory cardiac arrest. Given the risk of patient futility and high resource utilisation, identifying ECPR candidates, who would benefit from this therapy, is crucial. Previous ECPR studies investigating lactate as a potential prognostic marker have been small and inconclusive. In this study, it was hypothesised that the lactate level (immediately prior to initiation of ECPR) and lactate clearance (within 24 hours after ECPR initiation) are predictors of one-year survival in a large, multicentre study cohort of ECPR patients. METHODS: Adult patients with refractory cardiac arrest at three German and four Danish tertiary cardiac care centres between 2011 and 2021 were included. Pre-ECPR lactate and 24-hour lactate clearance were divided into three equally sized tertiles. Multivariable logistic regression analyses and Kaplan-Meier analyses were used to analyse survival outcomes. RESULTS: 297 adult patients with refractory cardiac arrest were included in this study, of which 65 (22%) survived within one year. The pre-ECPR lactate level and 24-hour lactate clearance were level-dependently associated with one-year survival: OR 5.40 [95% CI 2.30-13.60] for lowest versus highest pre-ECPR lactate level and OR 0.25 [95% CI 0.09-0.68] for lowest versus highest 24-hour lactate clearance. Results were confirmed in Kaplan-Meier analyses (each p log rank < 0.001) and subgroup analyses. CONCLUSION: Pre-ECPR lactate levels and 24 hour-lactate clearance after ECPR initiation in patients with refractory cardiac arrest were level-dependently associated with one-year survival. Lactate is an easily accessible and quickly available point-of-care measurement which might be considered as an early prognostic marker when considering initiation or continuation of ECPR treatment.

Heart Failure with Preserved vs. Reduced Ejection Fraction: Patient Characteristics, In-hospital Treatment and Mortality-DanAHF, a Nationwide Prospective Study.

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.

Hemodynamic Effects of Cyclic Guanosine Monophosphate-Dependent Signaling Through ß3 Adrenoceptor Stimulation in Patients With Advanced Heart Failure: A Randomized Invasive Clinical Trial.

BACKGROUND: ß3-AR (ß3-adrenergic receptor) stimulation improved systolic function in a sheep model of systolic heart failure (heart failure with reduced ejection fraction [HFrEF]). Exploratory findings in patients with New York Heart Association functional class II HFrEF treated with the ß3-AR-agonist mirabegron supported this observation. Here, we measured the hemodynamic response to mirabegron in patients with severe HFrEF. METHODS: In this randomized, double-blind, placebo-controlled trial we assigned patients with New York Heart Association functional class III-IV HFrEF, left ventricular ejection fraction <35% and increased NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels to receive mirabegron (300 mg daily) or placebo orally for a week, as add on to recommended HF therapy. Invasive hemodynamic measurements during rest and submaximal exercise at baseline, 3 hours after first study dose and repeated after 1 week's treatment were obtained. Predefined parameters for analyses were changes in cardiac- and stroke volume index, pulmonary and systemic vascular resistance, heart rate, and blood pressure. RESULTS: We randomized 22 patients (age 66±11 years, 18 men, 16, New York Heart Association functional class III), left ventricular ejection fraction 20±7%, median NT-proBNP 1953 ng/L. No significant changes were seen after 3 hours, but after 1 week, there was a significantly larger increase in cardiac index in the mirabegron group compared with the placebo group (mean difference, 0.41 [CI, 0.07-0.75] L/min/BSA; P=0.039). Pulmonary vascular resistance decreased significantly more in the mirabegron group compared with the placebo group (-1.6 [CI, -0.4 to -2.8] Wood units; P=0.02). No significant differences were seen during exercise. There were no differences in changes in heart rate, systemic vascular resistance, blood pressure, or renal function between groups. Mirabegron was well-tolerated. CONCLUSIONS: Oral treatment with the ß3-AR-agonist mirabegron for 1 week increased cardiac index and decreased pulmonary vascular resistance in patients with moderate to severe HFrEF. Mirabegron may be useful in patients with worsening or terminal HF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: 2016-002367-34.

Extracorporeal cardiopulmonary resuscitation: a national study on the association between favourable neurological status and biomarkers of hypoperfusion, inflammation, and organ injury.

AIMS: In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischaemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. METHODS AND RESULTS: This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011-2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favourable neurological status (Cerebral Performance Category 1-2) at hospital discharge was estimated by logistic regression analyses. Cut-off values were calculated using the Youden's index. Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favourable neurological status. Factors independently associated with favourable neurological status were low flow time <81 min, admission leukocytes ≥12.8 × 109/L, admission lactate <13.2 mmol/L, alkaline phosphatase (ALP) < 56 (day1) or <55 U/L (day2), and day 1 creatine kinase MB (CK-MB) < 500 ng/mL. Selected biomarkers (leukocytes, C-reactive protein, and lactate) were significantly better predictors of favourable neurological status than classic OHCA-variables (sex, age, low-flow time, witnessed arrest, shockable rhythm) alone (P = 0.001) after hospital admission. CONCLUSION: Biomarkers of hypoperfusion (lactate), inflammation (leucocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

Case report: spontaneous coronary artery dissection and suspicion of takotsubo cardiomyopathy in a patient presenting with T-wave inversions, severe QTc prolongation, elevated cardiac biomarkers, and apical akinesia.

BACKGROUND: In patients suspected of acute coronary syndrome, but where the coronary angiography (CAG) has shown unobstructed coronary arteries differential diagnoses include spontaneous coronary artery dissection and takotsubo cardiomyopathy. This case report presents a patient with spontaneous coronary artery dissection but diagnostic signs suspicious of takotsubo cardiomyopathy. Which leads to a consideration of the co-existence of the diseases. CASE SUMMARY: A 57-year-old woman was acutely admitted to the emergency ward with sudden development of chest discomfort, palpitations, and dyspnoea. At hospitalization, the electrocardiography showed T-wave inversions in I, aVL, and V2, and Troponin I was elevated. Initial echocardiography revealed apical akinesia consistent with takotsubo cardiomyopathy. Initially, a diagnosis of acute coronary syndrome or takotsubo cardiomyopathy was suspected. The patient was further diagnostically assessed with CAG including optical coherence tomography which showed spontaneous coronary artery dissection in the left anterior descending artery. At follow-up 3 months later, CAG showed a fully healed coronary artery, and repeated echocardiography showed normalization of the left ventricular function. DISCUSSION: In this case report, initially, acute coronary syndrome was suspected due to electrocardiography with T-wave inversions and elevated cardiac biomarkers. Takotsubo cardiomyopathy was suspected when echocardiography showed apical ballooning, but CAG with optical coherence tomography revealed a spontaneous coronary artery dissection. Interestingly no severe obstructions of coronary arteries were seen, and follow-up echocardiography showed fully regained myocardial function. This leads to the debate as to whether this might be a case of co-existing spontaneous coronary artery dissection and takotsubo cardiomyopathy.

Cancer is not associated with higher short or long-term mortality after successful resuscitation from out-of-hospital cardiac arrest when adjusting for prognostic factors.

OBJECTIVE: As the prevalence of malignancies in the general population increases, the odds of an out-of-hospital cardiac arrest (OHCA) patient having a history of cancer likewise increases, and the impact on post-cardiac arrest care and mortality is not well known. We aimed to investigate 30-day and 1-year mortality after successful resuscitation in patients with cancer prior to OHCA compared with OHCA patients without a previous cancer diagnosis. METHODS: A cohort of 993 consecutive OHCA patients with successful resuscitation during 2007-2011 was included. Vital status was obtained from the Danish Civil Register, and cancer diagnoses from the Danish National Patient Register dating back to 1994. Primary endpoints were 30-day, 1-year and long-term mortality (no cancer: mean 811 days; cancer: mean 406 days), analysed by Cox regression. Functional status assessed by cerebral performance category at discharge and use of post-resuscitation care were secondary endpoints. RESULTS: A total of 119 patients (12%) were diagnosed with cancer prior to OHCA. Mortality was higher in patients with cancer (30-day 69% vs. 58%, P=0.01); however, after adjustment for prognostic factors cancer was no longer associated with higher mortality (hazard ratio (HR)30 days 0.98, 95% confidence interval (CI) 0.76-1.27, P=0.88; HR1 year 0.99, 95% CI 0.78-1.27, P=0.96 HRend of follow-up 0.95, 95% CI 0.75-1.20, P=0.67). Favourable cerebral performance category scores in patients alive at discharge did not differ (cerebral performance category 1 or 2 n=310 (84%) vs. n=31 (84%), P=1). CONCLUSION: Cancer prior to OHCA was not associated with higher mortality in patients successfully resuscitated from OHCA when adjusting for confounders. Cancer prior to OHCA should be used with caution when performing prognostication after OHCA.

Silent atrial fibrillation detected by home-monitoring: Cardiovascular disease and stroke prevention in patients with diabetes.

OBJECTIVE: Patients with silent and undiagnosed paroxysmal atrial fibrillation and flutter (AF) have increased risk of ischemic stroke. Patients with diabetes have a higher risk of both AF and ischemic stroke compared to patients without diabetes. Our aim was to investigate the prevalence of silent AF in patients with diabetes in an outpatient cohort and to identify the possible risk factors associated with AF. RESEARCH DESIGN AND METHODS: This prospective observational study was performed in the outpatient diabetes clinic at a single University Hospital. We included 217 patients with type 1 or type 2 diabetes with at least one additional risk factor from the CHA2DS2VASc Score for Stroke Risk Assessment in Atrial Fibrillation. The primary outcome was prevalence of AF, with a duration of at least 30 s, recorded by a seven-day home-monitor, external loop recorder (ELR) in comparison to a standard resting ECG. Seventeen patients were excluded due to premature removal of the device. RESULTS: In the final cohort of 200 patients the majority were male (58.5%) with a mean age of 66 ±â€¯0.7 years. The mean BMI was 29 ±â€¯6 and patients had a mean diabetes history of 23 ±â€¯14 years with the majority diagnosed with type 2 diabetes (59%). Comorbidity was common with hypertension in 86%, and dyslipidemia in 80%. The total prevalence of silent AF [n = 20 (10%)] or flutter [n = 1 (0.5%)] was 10.5% using the ELR compared to a 0.0% detection-rate in the standard ECG method (p < 0.001). Higher age, male gender, albuminuria, and elevated systolic blood pressure were associated with AF in univariate analyses, but only age [OR 1.14 (95% CI = 1.00-2.04) (p = 0.048)], male gender [OR 4.9 (95% CI = 1.30-18.65) (p = 0.019)] and albuminuria [OR 2.7 (95% CI =1.08-6.98) (p = 0.034) were independently associated with AF. Mean CHA2DS2VASc Score was ≥2 (4.1, SD ±â€¯1.6), and patients with AF were referred to further cardiac evaluation. CONCLUSION: Undiagnosed, silent AF is common in high-risk cohort with a long history of diabetes followed in a University Hospital outpatient clinic. Non-invasive monitoring with ELR enhances detection of AF and identifies candidates for early anticoagulation treatment with the possible effect of stroke prevention.

Women have a worse prognosis and undergo fewer coronary angiographies after out-of-hospital cardiac arrest than men.

BACKGROUND: Out-of-hospital cardiac arrest is more often reported in men than in women. OBJECTIVES: We aimed to assess sex-related differences in post-resuscitation care; especially with regards to coronary angiography, percutaneous coronary intervention, mortality and functional status after out-of-hospital cardiac arrest. METHODS: We included 704 consecutive adult out-of-hospital cardiac arrest-patients with cardiac aetiology in the Copenhagen area from 2007-2011. Utstein guidelines were used for the pre-hospital data. Vital status and pre-arrest comorbidities were acquired from Danish registries and review of patient charts. Logistic regression was used to assess differences in functional status and use of post-resuscitation care. Cox regression was used to assess differences in 30-day mortality. We used 'smcfcs' and 'mice' imputation to handle missing data. RESULTS: Female sex was associated with higher 30-day mortality after adjusting for age and comorbidity (hazard ratio (HR): 1.42, confidence interval (CI): 1.13-1.79, p<0.01), this was not significant when adjusting for primary rhythm (HR: 1.12, CI: 0.88-1.42, p=0.37). Women less frequently received coronary angiography <24 h in multiple regression after out-of-hospital cardiac arrest (odds ratio (OR)CAG=0.55, CI: 0.31-0.97, p=0.041), however no difference in percutaneous coronary intervention was found (ORPCI=0.55, CI: 0.23-1.36, p=0.19). Coronary artery bypass grafting was less often performed in women (ORCABG: 0.10, CI: 0.01-0.78, p=0.03). There was no difference in functional status at discharge between men and women ( p=1). CONCLUSION: Female sex was not significantly associated with higher mortality when adjusting for confounders. Women less often underwent coronary angiography and coronary artery bypass grafting, but it is not clear whether this difference can be explained by other factors, or an actual under-treatment in women.

Survival after out-of-hospital cardiac arrest in nursing homes - A nationwide study.

BACKGROUND: Survival among nursing home residents who suffers out-of-hospital cardiac arrest (OHCA) is sparsely studied. Deployment of automated external defibrillators (AEDs) in nursing home facilities in Denmark is unknown. We examined 30-day survival following OHCA in nursing and private home residents. METHODS: This register-based, nationwide, follow-up study identified OHCA-patients ≥18 years of age with a resuscitation attempt in nursing homes and private homes using Danish Cardiac Arrest Register data from June 1, 2001 to December 31, 2014. The primary outcome measure was 30-day survival. Multiple logistic regression analyses were used to assess factors potentially associated with survival among nursing and private home residents separately. RESULTS: Of 26,999 OCHAs, 2516 (9.3%) occurred in nursing homes, and 24,483 (90.7%) in private homes. Nursing home residents were older (median 83 (Q1-Q3: 75-89) vs. 71 (Q1-Q3: 61-80) years), had more witnessed arrest (55.4% vs. 43.4%), received more bystander cardiopulmonary resuscitation (CPR) (49.7% vs. 35.3%), but less pre-hospital defibrillation (15.1% vs. 29.8%). Registered AEDs increased in the period 2007-2014 from 1 to 211 in nursing homes vs. 1 to 488 in private homes. Average 30-day survival in nursing homes was 1.7% [95%CI: 1.2-2.2%] vs. 4.9% [95%CI: 4.6-5.2%] in private homes (P < 0.001). If bystanders witnessed the arrest, performed CPR, and pre-hospital defibrillation was performed, 30-day survival was 7.7% [95%CI: 3.5-11.9%] vs. 24.2% [95%CI: 22.5-25.9%] in nursing vs. private home residents. CONCLUSIONS: Average 30-day survival after OHCA was very low in nursing home residents, but those who received early resuscitative efforts had higher chance of survival.