Christina Binder

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.

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.

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.

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.

Impact of HIV infection and antiretroviral treatment on N-terminal prohormone of brain natriuretic peptide as surrogate of myocardial function.

Objective: Vasoactive cardiovascular hormones such as the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are produced upon ventricular stretch and play a central role in neurohumoral pathways of the heart regulating cardiovascular remodeling and volume homeostasis. The impact of HIV infection on these neurohumoral pathways of the heart and its potential reversibility by combinations of antiretroviral therapies remain unclear. Methods: We assessed serum levels of NT-proBNP in 219 antiretroviral therapy–naïve HIV-infected patients with a normal cardiac and renal status at treatment initiation and after attainment of viremic control. Results: Before antiretroviral therapy, NT-proBNP as a surrogate of myocardial function displayed a significant correlation with absolute CD4+ cell count (r = −0.31; P < 0.001) as well as with HIV viral load (r = 0.26; P < 0.001). The median levels of NT-proBNP were 80 pg/ml (36–205) in patients with a CD4+ cell count less than 200 cells/&mgr;l and 42 pg/ml (20–80; P < 0.001) with a CD4+ cell count more than 500 cells/&mgr;l. After viremic control, no statistical correlation was present. Conclusion: Higher NT-proBNP levels were observed in treatment-naïve patients with low CD4+ cell count and high HIV viral load, indicating a subclinical impact of HIV infection on myocardial function. This association is reversible by the initiation of antiretroviral therapy and subsequent viral suppression.

Gender-related differences in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) affects more women than men, suggesting gender to play a major role in disease evolution. However, studies investigating gender differences in HFpEF are limited. In the present study we aimed to describe gender differences in a well-characterized HFpEF cohort. Consecutive HFpEF patients underwent invasive hemodynamic assessment, cardiac magnetic resonance imaging and exercise testing. Study endpoints were: cardiac death, a combined endpoint of HF hospitalization or cardiac death and all-cause death. 260 HFpEF patients were prospectively enrolled. Men were more compromised with regard to exercise capacity and had significantly more co-morbidities. Men had more pronounced pulmonary vascular disease with higher diastolic pressure gradients and a lower right ventricular EF. During follow-up, 9.2% experienced cardiac death, 33.5% the combined endpoint and 17.3% all-cause death. Male gender was independently associated with cardiac death, but neither with the combined endpoint nor with all-cause mortality. We detected clear gender differences in HFpEF patients. Cardiac death was more common among men, but not all-cause death. While men are more prone to develop a right heart phenotype and die from HFpEF, women are more likely to die with HFpEF.

Cardiac Magnetic Resonance T1 Mapping in Cardiac Amyloidosis

In cardiac amyloidosis (CA), extracellular deposition of amyloid fibrils within the myocardium significantly expands the extracellular volume (ECV). Affected patients develop severe heart failure and face a dismal prognosis. Cardiac magnetic resonance (CMR) T1 mapping allows ECV measurement [(1)][1

Duration of extracorporeal membrane oxygenation support and survival in cardiovascular surgery patients

Objective: The overall therapeutic goal of venoarterial extracorporeal membrane oxygenation (ECMO) in patients with postcardiotomy shock is bridging to myocardial recovery. However, in patients with irreversible myocardial damage prolonged ECMO treatment would cause a delay or even withholding of further permanent potentially life‐saving therapeutic options. We therefore assessed the prognostic effect of duration of ECMO support on survival in adult patients after cardiovascular surgery. Methods: We enrolled into our single‐center registry a total of 354 patients who underwent venoarterial ECMO support after cardiovascular surgery at a university‐affiliated tertiary care center. Results: Through a median follow‐up period of 45 months (interquartile range, 20–81 months), 245 patients (69%) died. We observed an increase in mortality with increasing duration of ECMO support. The association between increased duration of ECMO support and mortality persisted in patients who survived ECMO support with a crude hazard ratio of 1.96 (95% confidence interval, 1.40–2.74; P < .001) for 2‐year mortality compared with the third tertile and the second tertile of ECMO duration. This effect was even more pronounced after multivariate adjustment using a bootstrap‐selected confounder model with an adjusted hazard ratio of 2.30 (95% confidence interval, 1.52–3.48; P < .001) for 2‐year long‐term mortality. Conclusions: Prolonged venoarterial ECMO support is associated with poor outcome in adult patients after cardiovascular surgery. Our data suggest reevaluation of therapeutic strategies after 7 days of ECMO support because mortality disproportionally increases afterward.

Riociguat for the treatment of pulmonary hypertension: a safety evaluation

ABSTRACT Introduction: The development of pulmonary hypertension (PH) has multifactorial underlying pathophysiological causes and can be classified into five groups. While three different classes of therapeutic drugs are licensed for the treatment of pulmonary arterial hypertension (PAH, WHO group 1), specific medical therapies are lacking for other forms of PH, such as PH due to left heart disease. In 2013 riociguat, a first-in class soluble guanylate cyclase stimulator, has also become available for the treatment of PAH. Riociguat was further introduced as the first approved pharmacotherapy for the treatment of patients with chronic thromboembolic PH (WHO group 4, CTEPH). Despite these advances in therapeutic options for patients with PH, none of these agents have been approved for the treatment of PH due to left heart disease. Areas covered: We aim to give an overview of the pathophysiology of PH, pharmacodynamics and pharmacokinetic properties, safety and efficacy of riociguat, including adverse events, contraindications and drug interactions. Expert opinion: Considering the increasingly broad indications for riociguat in patients with PH, substantial knowledge of data and properties on safety and efficacy of riociguat are becoming more and more important for physicians prescribing riociguat to PH patients.