Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level: findings from the MORGAM project.

The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1-10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74-1.02), 11% (HR = 0.89; 0.84-0.95) and 5% (HR = 0.95; 0.89-1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82-1.25), 10% (HR = 1.10; 1.02-1.19) and 17% (HR = 1.17; 1.09-1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.

Intracranial haemorrhage in adult patients on venoarterial extracorporeal membrane oxygenation.

AIMS: Intracranial haemorrhage (ICH) is one of the most serious complications of adult patients treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO) and is associated with increased morbidity and mortality. However, the prevalence and risk factors of ICH in this cohort are still insufficiently understood. We hypothesized that a considerable proportion of patients undergoing VA-ECMO support suffer from ICH and that specific risk factors are associated with the occurrence of ICH. Therefore, the purpose of this study was to further investigate the prevalence and associated mortality as well as to identify risk factors for ICH in VA-ECMO patients. METHODS AND RESULTS: We conducted a retrospective multicentre study including adult patients (≥18 years) treated with VA-ECMO in cardiac intensive care units (ICUs) at five German clinical sites between January 2016 and March 2020, excluding patients with ICH upon admission. Differences in baseline characteristics and clinical outcome between VA-ECMO patients with and without ICH were analysed and risk factors for ICH were identified. Among the 598 patients included, 70/598 (12%) developed ICH during VA-ECMO treatment. In-hospital mortality in patients with ICH was 57/70 (81%) and 1-month mortality 60/70 (86%), compared to 332/528 (63%) (P = 0.002) and 340/528 (64%) (P < 0.001), respectively, in patients without ICH. Intracranial haemorrhage was positively associated with diabetes mellitus [odds ratio (OR) 2, 95% confidence interval (CI) 1.11-3.56; P = 0.020] and lactate (per mmol/L) (OR 1.06, 95% CI 1.01-1.11; P = 0.020), and negatively associated with platelet count (per 100 G/L) (OR 0.32, 95% CI 0.15-0.59; P = 0.001) and fibrinogen (per 100 mg/dL) (OR 0.64, 95% CI 0.49-0.83; P < 0.001). CONCLUSION: Intracranial haemorrhage was associated with a significantly higher mortality rate. Diabetes mellitus and lactate were positively, platelet count, and fibrinogen level negatively associated with the occurrence of ICH. Thus, platelet count and fibrinogen level were revealed as potentially modifiable, independent risk factors for ICH. The findings address an area with limited data, provide information about risk factors and the epidemiology of ICH, and may be a starting point for further investigations to develop effective strategies to prevent and treat ICH.

Early risk stratification in patients with cardiogenic shock irrespective of the underlying cause - the Cardiogenic Shock Score.

AIMS: Early risk stratification is essential to guide treatment in cardiogenic shock (CS). Existing CS risk scores were derived in selected cohorts, without accounting for the heterogeneity of CS. The aim of this study was to develop a universal risk score (the Cardiogenic Shock Score, CSS) for all CS patients, irrespective of the underlying cause. METHODS AND RESULTS: Within a registry of 1308 CS unselected patients admitted to a tertiary care hospital between 2009 and 2019, a Cox regression model was fitted to derive the CSS, with 30-day mortality as main outcome. The CSS's predictive ability was compared to the IABP-SHOCK II score, the CardShock score and SCAI classification by C-indices and validated in an external cohort of 934 CS patients. Based on the Cox regression, nine predictors were included in the CSS: age, sex, acute myocardial infarction (AMI-CS), systolic blood pressure, heart rate, pH, lactate, glucose and cardiac arrest. The CSS had the highest C-index in the overall cohort (0.740 vs. 0.677/0.683 for IABP-SHOCK II score/CardShock score), in patients with AMI-CS (0.738 vs. 0.675/0.689 for IABP-SHOCK II score/CardShock score) and in patients with non-AMI-CS (0.734 vs. 0.677/0.669 for IABP-SHOCK II score/CardShock score). In the external validation cohort, the CSS had a C-index of 0.73, which was higher than all other tested scores. CONCLUSION: The CSS provides improved information on the risk of death in unselected patients with CS compared to existing scores, irrespective of its cause. Because it is based on point-of-care variables which can be obtained even in critical situations, the CSS has the potential to guide treatment decisions in CS.

Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study.

AIM: To test the association of alcohol consumption with total and cause-specific mortality risk. DESIGN: Prospective observational multi-centre population-based study. SETTING: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. PARTICIPANTS: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). MEASUREMENTS: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. FINDINGS: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7-14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7-20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10-35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. CONCLUSIONS: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.

Eligibility for mechanical circulatory support devices based on current and past randomised cardiogenic shock trials.

AIMS: Mechanical circulatory support devices (MCS) are potentially effective treatments for cardiogenic shock (CS) and are thus evaluated in several randomised controlled trials (RCTs). However, it is not clear how enrolment criteria of these RCTs apply to a real-world CS population. This study aimed to shed light on eligibility to these trials. METHODS AND RESULTS: Pragmatic enrolment criteria for the IABP-SHOCK II, the DanGer-SHOCK, the ECLS-SHOCK and the EURO-SHOCK trials were retrospectively applied to 1305 CS patients admitted to a tertiary care hospital between 2009 and 2019. Based on this, major enrolment criteria were identified and outcome between eligible and ineligible patients was assessed. In this study, 415 (31.8%) patients were eligible for any study. Lowest eligibility was observed for DanGer-SHOCK (11.9%) and the highest for IABP-SHOCK II (26.9%). Over all trials, inclusion criteria were more restrictive than exclusion criteria and absence of CS caused by acute myocardial infarction (AMI) was the primary reason for non-eligibility. However, even in CS caused by AMI, enrolment criteria were only met in 65.4% of patients. Importantly, 30-day mortality was high across all patients/trials, irrespective of eligibility or non-eligibility. CONCLUSION: The present study highlights that current and past RCTs only reflect about a third of the overall CS population. While enrolment criteria are a necessary aspect of RCTs, their application limits generalisability of the trials' findings. More trials on CS sub-populations not represented by current or past trials, e.g. CS not caused by AMI, are needed, especially as mortality is high irrespective of eligibility status.

Sex differences in patients with cardiogenic shock.

AIMS: Differences between female and male patients in clinical presentation, causes and treatment of cardiogenic shock (CS) are poorly understood. We aimed to investigate sex differences in presentation with and treatment of CS. METHODS AND RESULTS: We analysed data of 978 patients presenting with CS to a tertiary care hospital between October 2009 and October 2017. Multivariable adjusted logistic/Cox regression models were fitted to investigate the association between sex and clinical presentation, use of treatments and 30 day mortality. Median age was 70 years (interquartile range 58-79 years), and 295 (30.2%) patients were female. After adjustment for multiple relevant confounders, female patients were more likely to be older [odds ratio (OR) 1.21, 95% confidence interval (CI) 1.02-1.42, P = 0.027], but other relevant presentation characteristics did not differ between both sexes. Despite the similar presentation, female patients were less likely to be treated with percutaneous left ventricular assist devices (OR 0.78, 95% CI 0.64-0.94, P = 0.010), but more likely to be treated with catecholamines (OR 1.21, 95% CI 1.02-1.44, P = 0.033) or vasopressors (OR 1.26, 95% CI 1.05-1.50, P = 0.012). A 30 day mortality risk in female patients was as high as in male patients (hazard ratio 1.08, 95% CI 1.00-1.18, P = 0.091). CONCLUSIONS: In this large, contemporary cohort, clinical presentation was comparable in female and male patients, and both sexes were associated with a comparably high mortality risk. Nevertheless, female patients received different treatment for CS and were most importantly less likely to be treated with percutaneous left ventricular assist devices.

Temporal trends in incidence, causes, use of mechanical circulatory support and mortality in cardiogenic shock.

AIM: The management of cardiogenic shock remains a clinical challenge even in well-developed healthcare systems, best illustrated by its high mortality despite numerous innovative proposals for management. The aim of this study was to describe temporal trends in incidence, causes, use of mechanical circulatory support, and mortality in cardiogenic shock in Germany. METHODS AND RESULTS: Data on all cardiogenic shock patients treated in German hospitals between 2005 and 2017 were obtained from the Federal Bureau of Statistics. The data set comprised 441 696 patients with cardiogenic shock, mean age 71 (±13.8) years, 171 383 (39%) female patients. Incidence rates increased from 33.1/100 000 population in 2005 (27 246 cases) to 51.7/100 000 population in 2017 (42 779 cases). Acute myocardial infarction was the most common cause of cardiogenic shock in 2005-07 (43 422 of 82 037 cases, 52.9%), but the proportion of cases caused by it decreased until 2014-17 (73 274 of 165 873 cases, 44.2%). Over time, intra-aortic balloon pump (2005: 5104; 2017: 973 cases) was used less frequently, whereas use of extracorporeal-membrane-oxygenation (2007: 35; 2017: 2414 cases) and percutaneous left ventricular assist devices (2005: 27; 2017: 1323 cases) increased. Mortality remained high at around 60% without relevant temporal trends in patients without acute myocardial infarction and slightly decreased in patients with acute myocardial infarction. CONCLUSIONS: In this large, nation-wide study, annual incidence of cardiogenic shock was growing, its causes were changing, and mortality was high despite a shift towards use of novel mechanical circulatory support devices. This highlights the need to address the evidence gap in this field, in particular for cardiogenic shock caused by diseases other than acute myocardial infarction.

Influence of age and shock severity on short-term survival in patients with cardiogenic shock.

AIMS: Cardiogenic shock (CS) is associated with poor outcomes in older patients, but it remains unclear if this is due to higher shock severity. We sought to determine the associations between age and shock severity on mortality among patients with CS. METHODS AND RESULTS: Patients with a diagnosis of CS from Mayo Clinic (2007-15) and University Clinic Hamburg (2009-17) were subdivided by age. Shock severity was graded using the Society for Cardiovascular Angiography and Intervention (SCAI) shock stages. Predictors of 30-day survival were determined using Cox proportional-hazards analysis. We included 1749 patients (934 from Mayo Clinic and 815 from University Clinic Hamburg), with a mean age of 67.6 ± 14.6 years, including 33.6% females. Acute coronary syndrome was the cause of CS in 54.0%. The distribution of SCAI shock stages was 24.1%; C, 28.0%; D, 33.2%; and E, 14.8%. Older patients had similar overall shock severity, more co-morbidities, worse kidney function, and decreased use of mechanical circulatory support compared to younger patients. Overall 30-day survival was 53.3% and progressively decreased as age or SCAI shock stage increased, with a clear gradient towards lower 30-day survival as a function of increasing age and SCAI shock stage. Progressively older age groups had incrementally lower adjusted 30-day survival than patients aged <50 years. CONCLUSION: Older patients with CS have lower short-term survival, despite similar shock severity, with a high risk of death in older patients with more severe shock. Further research is needed to determine the optimal treatment strategies for older CS patients.

Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: Results From an International, Multicenter Cohort Study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. METHODS: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score-matched cohort. RESULTS: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63-0.98]; P=0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site-related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). CONCLUSIONS: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

Patient Characteristics, Treatment and Outcome in Non-Ischemic vs. Ischemic Cardiogenic Shock.

: Aim: Evidence on non-ischemic cardiogenic shock (CS) is scarce. The aim of this study was to investigate differences in patient characteristics, use of treatments and outcomes in patients with non-ischemic vs. ischemic CS. METHODS: Patients with CS admitted between October 2009 and October 2017 were identified and stratified as non-ischemic/ischemic CS based on the absence/presence of acute myocardial infarction. Logistic/Cox regression models were fitted to investigate the association between non-ischemic CS and patient characteristics, use of treatments and 30-day in-hospital mortality. RESULTS: A total of 978 patients were enrolled in this study; median age was 70 (interquartile range 58, 79) years and 70% were male. Of these, 505 patients (52%) had non-ischemic CS. Patients with non-ischemic CS were more likely to be younger and female; were less likely to be active smokers, to have diabetes or decreased renal function, but more likely to have a history of myocardial infarction; and they were more likely to present with unfavorable hemodynamics and with mechanical ventilation. Regarding treatments, patients with non-ischemic CS were more likely to be treated with catecholamines, but less likely to be treated with extracorporeal membrane oxygenation or percutaneous left-ventricular assist devices. After adjustment for multiple relevant confounders, non-ischemic CS was associated with a significant increase in the risk of 30-day in-hospital mortality (hazard ratio 1.14, 95% confidence interval 1.04-1.24, p < 0.01). CONCLUSION: In this large study, non-ischemic CS accounted for more than 50% of all CS cases. Non-ischemic CS was not only associated with relevant differences in patient characteristics and use of treatments, but also with a worse prognosis. These findings highlight the need for effective treatment strategies for patients with non-ischemic CS.

Application of the SCAI classification in a cohort of patients with cardiogenic shock.

BACKGROUND: The Society of Cardiovascular Angiography and Interventions (SCAI) have recently proposed a new classification of cardiogenic shock (CS) dividing patients into five subgroups. OBJECTIVE: Aim of this study was to apply the SCAI classification to a cohort of patients presenting with CS and to evaluate its ability to predict 30-day survival. METHODS: SCAI CS subgroups were interpreted based on the recent consensus statement and then applied to N = 1,007 consecutive patients presenting with CS or large myocardial infarction (MI) between October 2009 and October 2017. The association between SCAI classification and 30-day all-cause mortality was assessed by logistic regression analysis. RESULTS: Mean age in the study cohort was 67 (±15) years, 72% were male. Mean lactate at baseline was 6.05 (±5.13) mmol/l and 51% of the patients had prior cardiac arrest. Overall survival probability was 50.6% (95% confidence interval [CI] 47.5-54.0%). In view of the SCAI classification, the survival probability was 96.4% (95% CI 93.7-99.0%) in class A, 66.1% (95% CI 50.2-87.1%) in class B, 46.1% (95% CI 40.6-52.4%) in class C, 33.1% (95% CI 26.6-41.1%) in class D, and 22.6% (95% CI 17.1-30.0%) in class E. Higher SCAI classification was significantly associated with lower 30-day survival (p < .01). CONCLUSION: In this large clinical cohort, the SCAI classification was significantly associated with 30-day survival. This finding supports the rationale of the SCAI CS classification and calls for a validation in a prospective trial.