Reduced 30-day mortality in men after elective coronary artery bypass surgery with minimized extracorporeal circulation-a propensity score analysis

Background Impact of minimized extracorporeal circulation (MECC) for coronary surgery on mortality remains controversial and gender significantly influence outcome. Methods We analyzed 3,139 male patients undergoing elective coronary surgery between 01/2004 and 05/2009. Using propensity score matching after binary logistic regression, 1,005 patients (from 1,119 patients) undergoing surgery with MECC could be matched with 1,005 patients (from 2,020 patients) undergoing surgery with conventional extracorporeal circulation (CECC). Primary outcome was 30-day mortality. Results Unadjusted 30-day mortality was 2.7% in patients with CECC and 0.8% in those with MECC (mean difference -1.9%; p < 0.001). The adjusted mean difference (average treatment effect of the treated) after matching was -1.5% (95% confidence interval (CI) -2.6 to -0.4; p = 0.006). Postoperative hospital stay was shorter in patients operated with minimized systems (adjusted mean difference -0.8 days; 95% CI -1.46 to -0.09; p = 0.03) and incidence of postoperative neurocognitive dysfunction was also lower (adjusted mean difference -1.3%; 95% CI -2.2 to -0.4; p = 0.001). Chest tube drainage (adjusted mean difference +22 mL; 95% CI -47 to 91; p = 0.5) and risk for acute kidney injury, kidney injury and failure according to RIFLE criteria (adjusted mean difference -1.0%; 95% CI -2.5 to 0.6; p = 0.24) proved to be insignificant between both groups. Apart from reduced 30-day mortality, however, average treatment effects for intensive care unit stay, postoperative hospital stay, chest tube drainage and kidney injury did not significantly differ. Conclusion Using propensity score analysis, we observed an association between MECC and reduced 30-day mortality in men, but our results call for further analysis

Veno-arterial extracorporeal membrane oxygenation support for severe cardiac failure in a pediatric patient with intracranial hemorrhage after spontaneous aneurysmatic rupture

Introduction: Extracorporeal life support in adult patients with extended intracranial hemorrhage is controversial. In pediatric patients, it has traditionally been considered a contraindication as systemic anticoagulation may worsen the hemorrhage and neurological outcome. Case history: We present a nine-year-old female patient who was admitted with extended intracranial hemorrhage after spontaneous rupture of an aneurysm. On day four after the emergency craniotomy, she required veno-arterial extracorporeal membrane oxygenation for septic shock. Using an adapted anticoagulation protocol aimed at lower activated partial thromboplastin time target values, we did not observe any new bleeding or clotting complications during systemic anticoagulation and the patient had good neurological recovery. Conclusion: Extracorporeal life support with low dose systemic anticoagulation can be considered as a treatment option in pediatric patients after craniotomy for intracranial aneurysmatic hemorrhage

Female Patients With Sleep-Disordered Breathing Display More Frequently Heart Failure With Preserved Ejection Fraction

Objective: Sleep-disordered breathing (SDB) is a widespread disease that is often associated with heart failure (HF) with preserved ejection fraction (HFpEF). HFpEF is more frequent in women than in men, but detailed pathomechanisms remain unclear. We investigated HFpEF in women and men in a high-risk cohort with SDB monitoring. Methods and Results: Three hundred twenty-seven patients (84.4% men) undergoing elective coronary artery bypass grafting were prospectively subjected to SDB monitoring, and an apnea–hypopnea index (AHI) ≥15/h defined SDB. HF was classified according to current guidelines. HFpEF was significantly more frequent in SDB patients compared to those without SDB (28 vs. 17%, P = 0.016). This distribution was driven by an increased frequency of HFpEF in female SDB patients (48% vs. only 25% in male, P = 0.022). In accordance, female patients with SDB exhibited significantly more impaired diastolic left ventricular filling compared to men (echocardiographic E/e′). In contrast to men, in women, minimum oxygen saturation (O2min, measured by polygraphy, R2 = 0.470, P < 0.001) and time of oxygen saturation <90% (R2 = 0.165, P = 0.044) were significantly correlated with E/e′. Moreover, the correlation between O2min and E/e′ was significantly different in women compared to men (P < 0.001). Intriguingly, this association remained independent of clinical covariates in women [age, body mass index, systolic contractile dysfunction, diabetes mellitus, and glomerular filtration rate (GFR), R2 = 0.534, P = 0.042, multivariate regression analysis]. Since angiotensin II signaling has been mechanistically linked to HF, we measured protein expression of its cleavage enzyme ACE2 in human right atrial appendage biopsies (Western blot). Intriguingly, we found a significantly decreased ACE2 expression preferentially in women with SDB (2.66 ± 0.42 vs. 4.01 ± 2.47 in men with SDB, P = 0.005). In accordance, left ventricular mass index was significantly increased in women with SDB compared to women without SDB. Conclusion: In patients with SDB, HFpEF and diastolic dysfunction were more frequent in women compared to men. In contrast to men, the severity of SDB was associated with the degree of diastolic dysfunction in women. These insights might help to find sex-specific therapies for patients with sleep-disordered breathing and heart failure. Clinical Trial Registration: Unique identifier: NCT02877745, URL: http://www.clinicaltrials.gov

Multi‐organ dysfunction syndrome in patients undergoing extracorporeal life support

Background Multiple organ failure is a common complication in patients undergoing ECLS significantly affecting patient outcomes. Gaining knowledge about the mechanisms of onset, clinical course, risk factors, and potential therapeutic targets is highly desirable. Methods Data of 354 patients undergoing ECLS with one-, two, three-, and four organ failures were retrospectively analyzed. Incidence of multiple organ dysfunction (MODS), its impact on survival, risk factors for its occurrence, and the impact of proinflammatory mediators on the occurrence of MODS in patients undergoing ECLS were investigated. Results The median follow-up was 66 (IQR 6; 820) days. 245 (69.2%) patients could be weaned from ECLS, 30-day survival and 1-year survival were 194 (54.1%) and 157 (44.4%), respectively. The duration of mechanical support was 4 (IQR 2; 7) days in the median. Increasing severity of MODS resulted in significant prolongation of mechanical circulatory support and worsening of the outcome. Liver dysfunction had the strongest impact on patient mortality (OR = 2.5) and survival time (19 vs 367 days). The serum concentration of analyzed interleukins rose significantly with each, additional organ affected by dysfunction (p < 0.001). All analyzed proinflammatory cytokines showed significant predictivity relative to the occurrence of MODS with interleukin 8 serum level prior to ECLS showing the strongest predictive potential for the occurrence of MODS (AUC 0.78). Conclusion MODS represents a frequent complication in patients undergoing ECLS with a significant impact on survival. Proinflammatory cytokines show prognostic capacity regarding the occurrence and severity of multi-organ dysfunction

Left ventricular support adjustment to aortic valve opening with analysis of exercise capacity

Background LVAD speed adjustment according to a functioning aortic valve has hypothetic advantages but could lead to submaximal support. The consequences of an open aortic valve policy on exercise capacity and hemodynamics have not yet been investigated systematically. Methods Ambulatory patients under LVAD support (INCOR®, Berlin Heart, mean support time 465 ± 257 days, average flow 4.0 ± 0.3 L/min) adjusted to maintain a near normal aortic valve function underwent maximal cardiopulmonary exercise testing (CPET) and right heart catheterization (RHC) at rest and during constant work rate exercise (20 Watt). Results Although patients (n = 8, mean age 45 ± 13 years) were in NYHA class 2, maximum work-load and peak oxygen uptake on CPET were markedly reduced with 69 ± 13 Watts (35% predicted) and 12 ± 2 mL/min/kg (38% predicted), respectively. All patients showed a typical cardiac limitation pattern and severe ventilatory inefficiency with a slope of ventilation to carbon dioxide output of 42 ± 12. On RHC, patients showed an exercise-induced increase of mean pulmonary artery pressure (from 16 ± 2.4 to 27 ± 2.8 mmHg, p < 0.001), pulmonary artery wedge pressure (from 9 ± 3.3 to 17 ± 5.3 mmHg, p = 0.01), and cardiac output (from 4.7 ± 0.5 to 6.2 ± 1.0 L/min, p = 0.008) with a corresponding slight increase of pulmonary vascular resistance (from 117 ± 35.4 to 125 ± 35.1 dyn*sec*cm−5, p = 0.58) and a decrease of mixed venous oxygen saturation (from 58 ± 6 to 32 ± 9%, p < 0.001). Conclusion An open aortic valve strategy leads to impaired exercise capacity and hemodynamics, which is not reflected by NYHA-class. Unknown compensatory mechanisms can be suspected. Further studies comparing higher vs. lower support are needed for optimization of LVAD adjustment strategies

Ablation of atrial fibrillation with the Epicor system: a prospective observational trial to evaluate safety and efficacy and predictors of success

<p>Abstract</p> <p>Background</p> <p>High intensity focused ultrasound (HIFU) energy has evolved as a new surgical tool to treat atrial fibrillation (AF). We evaluated safety and efficacy of AF ablation with HIFU and analyzed predictors of success in a prospective clinical study.</p> <p>Methods</p> <p>From January 2007 to June 2008, 110 patients with AF and concomitant open heart surgery were enrolled into the study. Main underlying heart diseases were aortic valve disease (50%), ischemic heart disease (48%), and mitral valve disease (18%). AF was paroxysmal in 29%, persistent in 31%, and long standing persistent in 40% of patients, lasting for 1 to 240 months (mean 24 months). Mean left atrial diameter was 50 ± 7 mm. Each patient underwent left atrial ablation with the Epicor system prior to open heart surgery. After surgery, the patients were treated with amiodarone and coumadin for 6 months. Follow-up studies including resting ECG, 24 h Holter ECG, and echocardiography were obtained at 6 and 12 months.</p> <p>Results</p> <p>All patients had successful application of the system on the beating heart prior to initiation of extracorporeal circulation. On average, 11 ± 1 ultrasound transducer elements were used to create the box lesion. The hand-held probe for additional linear lesions was employed in 83 cases. No device-related deaths occurred. Postoperative pacemaker insertion was necessary in 4 patients. At 6 months, 62% of patients presented with sinus rhythm. No significant changes were noted at 12 months. Type of AF and a left atrial diameter > 50 mm were predictors for failure of AF ablation.</p> <p>Conclusion</p> <p>AF ablation with the Epicor system as a concomitant procedure during open heart surgery is safe and acceptably effective. Our overall conversion rate was lower than in previously published reports, which may be related to the lower proportion of isolated mitral valve disease in our study population. Left atrial size may be useful to determine patients who are most likely to benefit from the procedure.</p

Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance

The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging