Lore Schrutka

Impaired antioxidant HDL function is associated with premature myocardial infarction.

There is growing evidence that the predictive value of HDL cholesterol levels for cardiovascular risk stratification is limited in patients with coronary artery disease (CAD). HDL function seems to be a more sensitive surrogate of cardiovascular risk estimation than simple serum levels. Therefore, we aimed to assess whether impaired antioxidant HDL function is involved in the development of premature acute myocardial infarction (AMI).

Urinary Output Predicts Survival in Patients Undergoing Extracorporeal Membrane Oxygenation Following Cardiovascular Surgery.

Objectives:Extracorporeal membrane oxygenation represents a valuable and rapidly evolving therapeutic option in patients with severe heart or lung failure following cardiovascular surgery. However, survival remains poor and accurate risk stratification challenging. Therefore, we evaluated the predictive value of urinary output within 24 hours after extracorporeal membrane oxygenation initiation on mortality in patients undergoing venoarterial extracorporeal membrane oxygenation support following cardiovascular surgery and aimed to improve established risk prediction models. Design:Single-center, observational registry. Setting:University-affiliated tertiary care center. Patients:We included 205 patients undergoing veno-arterial extracorporeal membrane oxygenation therapy following cardiovascular surgery at a university-affiliated tertiary-care center into our single-centre registry. Interventions:None. Measurements and Main Results:During a median follow-up time of 35 months (interquartile range, 19–69), 64% of patients died. Twenty-four–hour urinary output was the strongest predictor of outcome among renal function variables with an adjusted hazard ratio per 1 SD of 0.55 (95% CI, 0.40–0.76; p < 0.001) for 30-day mortality and of 0.65 (95% CI, 0.53–0.86; p = 0.002) for 2-year long-term mortality. Most remarkably, 24-hour urinary output showed additional prognostic value beyond that achievable with the simplified acute physiology score-3 and sequential organ failure assessment score indicated by improvements in the category-free net reclassification index for 30-day mortality (simplified acute physiology score-3: 36%, p = 0.015; sequential organ failure assessment score: 36%, p = 0.02), as well as for 2-year mortality (simplified acute physiology score-3: 33%, p = 0.02; sequential organ failure assessment score: 43%, p = 0.005). Conclusions:We identified 24-hour urinary output as a strong and easily available predictor of mortality in patients undergoing extracorporeal membrane oxygenation therapy following cardiovascular surgery. Implementation of 24-hour urinary output leads to a substantial improvement of established risk prediction models in this vulnerable patient population. These results are particularly compelling because measurement of urinary output is inexpensive and routinely performed in all critical care units.

Pro-oxidant HDL predicts poor outcome in patients with ST-elevation acute coronary syndrome

Oxidative stress affects clinical outcome in patients with ST-elevation acute coronary syndrome (STE-ACS). Although high-density lipoprotein (HDL) particles are generally considered protective, deleterious properties of HDL have been observed in patients with acute myocardial infarction. Here, we analysed the association between pro-oxidant HDL and all-cause mortality in STE-ACS patients. We determined the antioxidant function of HDL in 247 prospectively enrolled patients undergoing primary percutaneous coronary intervention for STE-ACS. Patients were stratified as by a pro-oxidant serum HDL oxidant index (HOI≥ 1) or with an antioxidant serum HOI (HOL< 1) capacity. Multivariate regression analysis was used to relate HOI to survival. The median follow-up time was 23 months (IQR 14.4-40.0 months). Pro-oxidant HDL was observed in 44.1 % of STE-ACS patients and was independently associated with all-cause mortality with a hazard ratio of 3.30(95 %CI 1.50-7.27, p = 0.003). Mortality rates were higher in patients with baseline pro-oxidant HDL compared to patients with preserved HDL function at 30 days (11.9 % vs 2.2 %, p=0.002), and at 4 years (22.9 % vs 8.7 %, p=0.002). Elevated neutrophil counts were a strong and independent predictor for pro-oxidant HDL with an odds ratio per standard deviation of 1.50 (95 %CI 1.11-2.03, p=0.008), as was history of prior acute myocardial infarction, elevated triglycerides levels and reduced glomerular filtration rate. In conclusion, pro-oxidant HDL represents a strong and independent predictor of long-term as well as short-term all-cause mortality in STE-ACS patients. Elevated neutrophil counts predicted the presence of serum pro-oxidant HDL. The maintenance of HDL functions might be a promising therapeutic target in STE-ACS patients.

Cardiac arrest does not affect survival in post-operative cardiovascular surgery patients undergoing extracorporeal membrane oxygenation

BACKGROUND Veno-arterial extracorporeal membrane oxygenation (ECMO) is rapidly evolving as bailout option in patients with refractory cardiogenic shock after cardiovascular surgery (CV). Cardiac arrest represents a common and severe complication in the immediate post-operative phase. We therefore evaluated the impact of cardiac arrest at time of ECMO implantation on short- and long-term mortality in patients following CV surgery. METHODS AND RESULTS We included 385 patients undergoing veno-arterial extracorporeal membrane oxygenation therapy following CV surgery at a university-affiliated tertiary-care center into our single-center registry. Thirty patients underwent cardiopulmonary resuscitation (CPR) followed by immediate initiation of ECMO support. During a median follow-up time of 44 months (IQR 21-76 months), 68% of patients (n=262) died. We did not detect a significant impact of CPR during ECMO initiation on 30-day mortality (HR 1.04, 95%CI 0.89-1.83, P=0.86) as well as for long-term mortality (HR 1.01, 95%CI 0.63-1.61, P=0.97). Results were virtually unchanged for 30-day (HR 0.88, 95%CI 0.44-1.73, P=0.70) and long-term mortality (HR 0.93, 95%CI 0.54-1.60, P=0.79) after adjustment for age, sex, left ventricular ejection fraction, SAPS2 score, type of CV surgery, and year of study inclusion in order to unveil a potential negative confounding. CONCLUSION Cardiac arrest did not affect short-tem and long-term mortality in a large cohort of patients with therapy refractory cardiogenic shock undergoing ECMO support following CV surgery. Our results suggest that the decision to initiate ECMO support in this specific patient population should not be influenced by the occurrence of cardiac arrest.

Impaired High‐Density Lipoprotein Anti‐Oxidative Function Is Associated With Outcome in Patients With Chronic Heart Failure

Background Oxidative stress is mechanistically linked to the pathogenesis of chronic heart failure (CHF). Antioxidative functions of high‐density lipoprotein (HDL) particles have been found impaired in patients with ischemic cardiomyopathy; however, the impact of antioxidative HDL capacities on clinical outcome in CHF patients is unknown. We therefore investigated the predictive value of antioxidative HDL function on mortality in a representative cohort of patients with CHF. Methods and Results We prospectively enrolled 320 consecutive patients admitted to our outpatient department for heart failure and determined antioxidative HDL function using the HDL oxidative index (HOI). During a median follow‐up time of 2.8 (IQR: 1.8‐4.9) years, 88 (27.5%) patients reached the combined cardiovascular endpoint defined as the combination of death due to cardiovascular events and heart transplantation. An HOI ≥1 was significantly associated with survival free of cardiovascular events in Cox regression analysis with a hazard ratio (HR) of 2.28 (95% CI 1.48‐3.51, P<0.001). This association remained significant after comprehensive multivariable adjustment for potential confounders with an adjusted HR of 1.83 (95% CI 1.1‐2.92, P=0.012). Determination of HOI significantly enhanced risk prediction beyond that achievable with N‐terminal pro‐B‐type natriuretic peptide indicated by improvements in net reclassification index (32.4%, P=0.009) and integrated discrimination improvement (1.4%, P=0.04). Conclusions Impaired antioxidative HDL function represents a strong and independent predictor of mortality in patients with CHF. Implementation of HOI leads to a substantial improvement of risk prediction in patients with CHF.

Impact of Right Ventricular Performance in Patients Undergoing Extracorporeal Membrane Oxygenation Following Cardiac Surgery

Background Extracorporeal membrane oxygenation following cardiac surgery safeguards end‐organ oxygenation but unfavorably alters cardiac hemodynamics. Along with the detrimental effects of cardiac surgery to the right heart, this might impact outcome, particularly in patients with preexisting right ventricular (RV) dysfunction. We sought to determine the prognostic impact of RV function and to improve established risk‐prediction models in this vulnerable patient cohort. Methods and Results Of 240 patients undergoing extracorporeal membrane oxygenation support following cardiac surgery, 111 had echocardiographic examinations at our institution before implantation of extracorporeal membrane oxygenation and were thus included. Median age was 67 years (interquartile range 60‐74), and 74 patients were male. During a median follow‐up of 27 months (interquartile range 16‐63), 75 patients died. Fifty‐one patients died within 30 days, 75 during long‐term follow‐up (median follow‐up 27 months, minimum 5 months, maximum 125 months). Metrics of RV function were the strongest predictors of outcome, even stronger than left ventricular function (P<0.001 for receiver operating characteristics comparisons). Specifically, RV free‐wall strain was a powerful predictor univariately and after adjustment for clinical variables, Simplified Acute Physiology Score‐3, tricuspid regurgitation, surgery type and duration with adjusted hazard ratios of 0.41 (95%CI 0.24‐0.68; P=0.001) for 30‐day mortality and 0.48 (95%CI 0.33‐0.71; P<0.001) for long‐term mortality for a 1‐SD (SD=−6%) change in RV free‐wall strain. Combined assessment of the additive EuroSCORE and RV free‐wall strain improved risk classification by a net reclassification improvement of 57% for 30‐day mortality (P=0.01) and 56% for long‐term mortality (P=0.02) compared with the additive EuroSCORE alone. Conclusions RV function is strongly linked to mortality, even after adjustment for baseline variables and clinical risk scores. RV performance improves established risk prediction models for short‐ and long‐term mortality.

Impaired High-Density Lipoprotein Anti-Oxidant Function Predicts Poor Outcome in Critically Ill Patients

Introduction Oxidative stress affects clinical outcome in critically ill patients. Although high-density lipoprotein (HDL) particles generally possess anti-oxidant capacities, deleterious properties of HDL have been described in acutely ill patients. The impact of anti-oxidant HDL capacities on clinical outcome in critically ill patients is unknown. We therefore analyzed the predictive value of anti-oxidant HDL function on mortality in an unselected cohort of critically ill patients. Method We prospectively enrolled 270 consecutive patients admitted to a university-affiliated intensive care unit (ICU) and determined anti-oxidant HDL function using the HDL oxidant index (HOI). Based on their HOI, the study population was stratified into patients with impaired anti-oxidant HDL function and the residual study population. Results During a median follow-up time of 9.8 years (IQR: 9.2 to 10.0), 69% of patients died. Cox regression analysis revealed a significant and independent association between impaired anti-oxidant HDL function and short-term mortality with an adjusted HR of 1.65 (95% CI 1.22–2.24; p = 0.001) as well as 10-year mortality with an adj. HR of 1.19 (95% CI 1.02–1.40; p = 0.032) when compared to the residual study population. Anti-oxidant HDL function correlated with the amount of oxidative stress as determined by Cu/Zn superoxide dismutase (r = 0.38; p<0.001). Conclusion Impaired anti-oxidant HDL function represents a strong and independent predictor of 30-day mortality as well as long-term mortality in critically ill patients.

Beneficial effects of levosimendan on survival in patients undergoing extracorporeal membrane oxygenation after cardiovascular surgery

BACKGROUND The impact of levosimendan treatment on clinical outcome in patients undergoing extracorporeal membrane oxygenation (ECMO) support after cardiovascular surgery is unknown. We hypothesized that the beneficial effects of levosimendan might improve survival when adequate end-organ perfusion is ensured by concomitant ECMO therapy. We therefore studied the impact of levosimendan treatment on survival and failure of ECMO weaning in patients after cardiovascular surgery. METHODS We enrolled a total of 240 patients undergoing veno-arterial ECMO therapy after cardiovascular surgery at a university-affiliated tertiary care centre into our observational single-centre registry. RESULTS During a median follow-up period of 37 months (interquartile range 19-67 months), 65% of patients died. Seventy-five per cent of patients received levosimendan treatment within the first 24 h after initiation of ECMO therapy. Cox regression analysis showed an association between levosimendan treatment and successful ECMO weaning [adjusted hazard ratio (HR) 0.41; 95% confience interval (CI) 0.22-0.80; P=0.008], 30 day mortality (adjusted HR 0.52; 95% CI 0.30-0.89; P=0.016), and long-term mortality (adjusted HR 0.64; 95% CI 0.42-0.98; P=0.04). CONCLUSIONS These data suggest an association between levosimendan treatment and improved short- and long-term survival in patients undergoing ECMO support after cardiovascular surgery.

Polyunsaturated fatty acids supplementation impairs anti-oxidant high-density lipoprotein function in heart failure

The underlying reasons for the highly inconsistent clinical outcome data for omega‐3‐polyunsaturated fatty acids (n3‐PUFAs) supplementation in patients with cardiac disease have not been understood yet. The aim of this prospective, randomized, double‐blind, placebo controlled study was to determine the effects of oral treatment with n3‐PUFAs on the anti‐oxidant capacity of HDL in heart failure (HF) patients.

ASSOCIATION OF VENOARTERIAL EXTRA-CORPOREAL MEMBRANE OXYGENATION CANNULATION SITE WITH WEANING TIME AND SURVIVAL

Venoarterial extracorporeal membrane oxygenation (ECMO) is a life-saving measure in patients with refractory heart failure after cardiac surgery. However, femoral-femoral cannulation is associated with distal limb ischemia, poor upper body oxygenation and may lead to a rise of left ventricular