Patrick Sulzgruber

C‐reactive protein predicts mortality in patients referred for coronary angiography and symptoms of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) has a different pathophysiological background compared to heart failure with reduced ejection fraction (HFrEF). Tailored risk prediction in this separate heart failure group with a high mortality rate is of major importance. Inflammation may play an important role in the pathogenesis of HFpEF because of its significant contribution to myocardial fibrosis. We therefore aimed to assess the predictive value of C‐reactive protein (CRP) in patients with HFpEF.

Age-specific prognostication after out-of-hospital cardiac arrest – The ethical dilemma between ‘life-sustaining treatment’ and ‘the right to die’ in the elderly:

Background: While prognostic values on survival after out-of-hospital cardiac arrest have been well investigated, less attention has been paid to their age-specific relevance. Therefore, we aimed to identify suitable age-specific early prognostication in elderly patients suffering out-of-hospital cardiac arrest in order to reduce the burden of unnecessary treatment and harm. Methods: In a prospective population-based observational trial on individuals suffering out-of-hospital cardiac arrest, a total of 2223 patients receiving resuscitation attempts by the local emergency medical service in Vienna, Austria, were enrolled. Patients were stratified according to age as follows: young and middle-aged individuals (<65 years), young old individuals (65–74 years), old individuals (75–84 years) and very old individuals (>85 years). Results: There was an increasing rate of 30-day mortality (+21.8%, p < 0.001) and unfavourable neurological outcome (+18.8%, p < 0.001) with increasing age among age groups. Established predictive variables lost their prognostic potential with increasing age, even after adjusting for potential confounders. Independently, an initially shockable electrocardiogram proved to be directly associated with survival, with an adjusted hazard ratio (HR) of 2.04 (95% confidence interval (CI) 1.89–2.38, p = 0.003) for >85-year-olds. Frailty was directly associated with mortality (HR 1.22, 95% CI 1.01–1.51, p = 0.049), showing a 30-day survival of 5.6% and a favourable neurological outcome of 1.1% among elderly individuals. Conclusion: An initially shockable electrocardiogram proved to be a suitable tool for risk assessment and decision making in order to predict a successful outcome in elderly victims of out-of-hospital cardiac arrest. However, the outcomes of elderly patients seemed to be exceptionally poor in frail individuals and need to be considered in order to reduce unnecessary treatment decisions.

Fibroblast Growth Factor 23 Is an Independent and Specific Predictor of Mortality in Patients With Heart Failure and Reduced Ejection Fraction

Background—Strategies to improve risk prediction are of major importance in patients with heart failure (HF). Fibroblast growth factor 23 (FGF-23) is an endocrine regulator of phosphate and vitamin D homeostasis associated with an increased cardiovascular risk. We aimed to assess the prognostic effect of FGF-23 on mortality in HF patients with a particular focus on differences between patients with HF with preserved ejection fraction and patients with HF with reduced ejection fraction (HFrEF). Methods and Results—FGF-23 levels were measured in 980 patients with HF enrolled in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study including 511 patients with HFrEF and 469 patients with HF with preserved ejection fraction and a median follow-up time of 8.6 years. FGF-23 was additionally measured in a second cohort comprising 320 patients with advanced HFrEF. FGF-23 was independently associated with mortality with an adjusted hazard ratio per 1-SD increase of 1.30 (95% confidence interval, 1.14–1.48; P<0.001) in patients with HFrEF, whereas no such association was found in patients with HF with preserved ejection fraction (for interaction, P=0.043). External validation confirmed the significant association with mortality with an adjusted hazard ratio per 1 SD of 1.23 (95% confidence interval, 1.02–1.60; P=0.027). FGF-23 demonstrated an increased discriminatory power for mortality in addition to N-terminal pro–B-type natriuretic peptide (C-statistic: 0.59 versus 0.63) and an improvement in net reclassification index (39.6%; P<0.001). Conclusions—FGF-23 is independently associated with an increased risk of mortality in patients with HFrEF but not in those with HF with preserved ejection fraction, suggesting a different pathophysiologic role for both entities.

Admission of out-of-hospital cardiac arrest victims to a high volume cardiac arrest center is linked to improved outcome ☆

AIM Cardiac arrest centers have been associated with improved outcome for patients after cardiac arrest. Aim of this study was to investigate the effect on outcome depending on admission to high-, medium- or low volume centers. METHODS Analysis from a prospective, multicenter registry for out of hospital cardiac arrest patients treated by the emergency medical service of Vienna, Austria. The frequency of cardiac arrest patients admitted per center/year (low <50; medium 50-100; high >100) was correlated to favorable outcome (30-day survival with cerebral performance category of 1 or 2). RESULTS Out of 2238 patients (years 2013-2015) with emergency medical service resuscitation, 861 (32% female, age 64 (51;73) years) were admitted to 7 different centers. Favorable outcome was achieved in 267 patients (31%). Survivors were younger (58 vs. 66 years; p<0.001), showed shockable initial heart rhythm more frequently (72 vs. 35%; p<0.001), had shorter CPR durations (22 vs. 29min; p<0.001) and were more likely to be treated in a high frequency center (OR 1.6; CI: 1.2-2.1; p=0.001). In multivariate analysis, age below 65 years (OR 15; CI: 3.3-271.4; p=0.001), shockable initial heart rhythm (OR 10.1; CI: 2.4-42.6; p=0.002), immediate bystander or emergency medical service CPR (OR 11.2; CI: 1.4-93.3; p=0.025) and admission to a center with a frequency of >100 OHCA patients/year (OR 5.2; CI: 1.2-21.7; p=0.025) was associated with favorable outcome. CONCLUSIONS High frequency of post-cardiac arrest treatment in a specialized center seems to be an independent predictor for favorable outcome in an unselected population of patients after out of hospital cardiac arrest.

Von Willebrand Factor Improves Risk Prediction in Addition to N-Terminal Pro–B-type Natriuretic Peptide in Patients Referred to Coronary Angiography and Signs and Symptoms of Heart Failure and Preserved Ejection Fraction

Background—Heart failure with preserved ejection fraction (HFpEF) represents a growing health burden associated with substantial mortality and morbidity. Consequently, risk prediction is of highest importance. Endothelial dysfunction has been recently shown to play an important role in the complex pathophysiology of HFpEF. We therefore aimed to assess von Willebrand factor (vWF), a marker of endothelial damage, as potential biomarker for risk assessment in patients with HFpEF. Methods and Results—Concentrations of vWF were assessed in 457 patients with HFpEF enrolled as part of the LUdwigshafen Risk and Cardiovascular Health (LURIC) study. All-cause mortality was observed in 40% of patients during a median follow-up time of 9.7 years. vWF significantly predicted mortality with a hazard ratio (HR) per increase of 1 SD of 1.45 (95% confidence interval, 1.26–1.68; P<0.001) and remained a significant predictor after adjustment for age, sex, body mass index, N-terminal pro–B-type natriuretic peptide (NT-proBNP), renal function, and frequent HFpEF-related comorbidities (adjusted HR per 1 SD, 1.22; 95% confidence interval, 1.05–1.42; P=0.001). Most notably, vWF showed additional prognostic value beyond that achievable with NT-proBNP indicated by improvements in C-Statistic (vWF×NT-proBNP: 0.65 versus NT-proBNP: 0.63; P for comparison, 0.004) and category-free net reclassification index (37.6%; P<0.001). Conclusions—vWF is an independent predictor of long-term outcome in patients with HFpEF, which is in line with endothelial dysfunction as potential mediator in the pathophysiology of HFpEF. In particular, combined assessment of vWF and NT-proBNP improved risk prediction in this vulnerable group of patients.

Prognostic relevance of circulating endothelial progenitor cells in patients with chronic heart failure

Novel strategies for a tailored risk prediction in chronic heart failure (CHF) are crucial to identify patients at very high risk for an improved patient management and to specify treatment regimens. Endothelial progenitor cells (EPCs) are an important endogenous repair mechanism with the ability to counteract endothelial injury and the possibility of new vessel formation. We hypothesised that exhaustion of circulating EPCs may be a suitable prognostic biomarker in patients with CHF. EPCs, defined as CD34+CD45dimKDR+ cells, were analysed using fluorescence-activated cell sorting. EPCs were measured in 185 patients with CHF including 87 (47 %) patients with ischaemic aetiology and 98 (53 %) patients with non-ischaemic CHF and followed for a median time of 2.7 years. During this period, 34.7 % of patients experienced the primary study endpoint all-cause mortality. EPC count was a significant and independent inverse predictor of mortality with an hazard ratio hazard ratio (HR) per increase of one standard deviation (1-SD) of 0.47 (95 % confidence interval [CI]: 0.35-0.61; p<0.001) and remained significant after multivariable adjustment for a comprehensive set of cardiovascular risk factors and potential confounders with a HR per 1-SD of 0.54 (95 % CI: 0.4-0.73; p<0.001). EPCs further demonstrated additional prognostic information indicated by improvements in C-statistic, net reclassification index and integrated discrimination increment. In conclusion, in our study circulating EPCs turned out as strong and independent inverse predictors of mortality underlining the importance of an impaired endothelial repair mechanism in the pathophysiology and progression of CHF.

Editor’s Choice-Progress in the chain of survival and its impact on outcomes of patients admitted to a specialized high-volume cardiac arrest center during the past two decades

Aim: Cardiac arrest (CA) is still associated with high mortality and morbidity. Data on the changes in management and outcomes over a long period of time are limited. Using data from a single emergency department (ED), we assessed changes over two decades. Methods: In this single-center observational study, we prospectively included 4133 patients receiving cardiopulmonary resuscitation and being admitted to the ED of a tertiary care hospital between January 1992 and December 2012. Results: There was a significant improvement in both 6-month survival rates (+10.8%; p < 0.001) and favorable neurological outcome (+4.7%; p < 0.001). While the number of witnessed CA cases decreased (-4.7%; p < 0.001) the proportion of patients receiving bystander basic life support increased (+8.3%; p < 0.001). The proportion of patients with initially shockable ECG rhythms remained unchanged, but cardiovascular causes of CA decreased (-9.6%; p < 0.001). Interestingly, the time from CA until ED admission increased (+0.1 hours; p = 0.024). The use of percutaneous coronary intervention and therapeutic hypothermia were significantly associated with survival. Conclusions: Outcomes of patients with CA treated at a specialized ED have improved significantly within the last 20 years. Improvements in every link in the chain of survival were noted.

Platelet count predicts cardiovascular mortality in very elderly patients with myocardial infarction

The prognosis of elderly patients with acute myocardial infarction (AMI) is poor, and information on specific risk factors remains scarce. The aim of our study was to assess the influence of platelet count on cardiovascular mortality in very elderly patients with acute myocardial infarction (≥ 85 years of age).

The impact of airway strategy on the patient outcome after out-of-hospital cardiac arrest: A propensity score matched analysis:

Background: While guidelines mentioned supraglottic airway management in the case of out-of- hospital cardiac arrest, robust data of their impact on the patient outcome remain scare and results are inconclusive. Methods: To assess the impact of the airway strategy on the patient outcome we prospectively enrolled 2224 individuals suffering cardiac arrest who were treated by the Viennese municipal emergency medical service. To control for potential confounders, propensity score matching was performed. Patients were matched in four groups with a 1:1:1:1 ratio (n=210/group) according to bag-mask-valve, laryngeal tube, endotracheal intubation and secondary endotracheal intubation after primary laryngeal tube ventilation. Results: The laryngeal tube subgroup showed the lowest 30-day survival rate among all tested devices (p<0.001). However, in the case of endotracheal intubation after primary laryngeal tube ventilation, survival rates were comparable to the primary endotracheal tube subgroup. The use of a laryngeal tube was independently and directly associated with mortality with an adjusted odds ratio of 1.97 (confidence interval: 1.14–3.39; p=0.015). Additionally, patients receiving laryngeal tube ventilation showed the lowest rate of good neurological performance (6.7%; p<0.001) among subgroups. However, if patients received endotracheal intubation after initial laryngeal tube ventilation, the outcome proved to be significantly better (9.5%; p<0.001). Conclusion: We found that the use of a laryngeal tube for airway management in cardiac arrest was significantly associated with poor 30-day survival rates and unfavourable neurological outcome. A primary endotracheal airway management needs to be considered at the scene, or an earliest possible secondary endotracheal intubation during both pre-hospital and in-hospital post-return of spontaneous circulation critical care seems crucial and most beneficial for the patient outcome.

History of previous bleeding and C-reactive protein improve assessment of bleeding risk in elderly patients (≥ 80 years) with myocardial infarction

We aimed to assess whether the CRUSADE risk score represents a robust instrument for stratification of bleeding risk in elderly myocardial infarction (MI) patients (≥ 80 years) and further aimed to identify age-specific predictors of major bleeding events. Binary logistic regression models were applied to assess the effect of variables on the occurrence of bleeding events during hospital stay. Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory power. Out of 387 patients in the final study cohort, 74 patients (19.1 %) experienced a major bleeding event according to the definition of the International Society on Thrombosis and Haemostasis. The CRUSADE risk score demonstrated only a weak discriminatory power to predict bleeding in this group of patients (area under the ROC curve: 0.57 [0.51-0.65]; p=0.05). In the multivariate regression analysis, history of bleeding with an adjusted hazard ratio (HR) of 3.21 (95 % confidence interval: 1.29-8.03, p=0.01) and C-reactive protein with an adjusted HR per increase of 10 mg/l of 1.05 (1.01-1.10) were independent predictors of major bleeding. Integration of both variables into the CRUSADE score demonstrated a significantly improved performance for bleeding as indicated by a significant increase in the ROC analysis (area under the curve: 0.64 vs 0.57; for comparison p< 0.045), net reclassification index (35.6 %; p=0.006) and integrated discrimination increment (0.0242; p=0.02). In conclusion, bleeding history and C-reactive protein significantly improve the modest predictive power of the CRUSADE risk score in elderly patients with MI. These results point towards a specific risk profile for bleeding events in this high-risk group of patients.