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Background Heart failure is associated with impaired myocardial metabolism with a shift from fatty acids to glucose utilization for ATP generation. We hypothesized that cardiac accumulation of toxic lipid intermediates inhibits insulin signaling in advanced heart failure and that mechanical unloading of the failing myocardium corrects impaired cardiac metabolism. Methods and Results We analyzed myocardium and serum of 61 patients with heart failure (BMI 26.5±5.1 kg/m2, age 51±12 years) obtained during left ventricular assist device (LVAD) implantation and at explantation (mean duration 185±156 days) and from 9 controls. Systemic insulin resistance in heart failure was accompanied by decreased myocardial triglyceride and overall fatty acid content but increased toxic lipid intermediates, diacylglycerol and ceramide. Increased membrane localization of protein kinase C isoforms, inhibitors of insulin signaling, and decreased activity of insulin signaling molecules Akt and FOXO, were detectable in heart failure compared to controls. LVAD implantation improved whole body insulin resistance (HOMA-IR: 4.5±0.6 to 3.2±0.5; p<0.05) and decreased myocardial levels of diacylglycerol and ceramide while triglyceride and fatty acid content remained unchanged. Improved activation of the insulin/PI3kinase/Akt signaling cascade after LVAD implantation was confirmed by increased phosphorylation of Akt and FOXO, which was accompanied by decreased membrane localization of protein kinase C isoforms after LVAD implantation. Conclusions Mechanical unloading after LVAD implantation corrects systemic and local metabolic derangements in advanced heart failure leading to reduced myocardial levels of toxic lipid intermediates and improved cardiac insulin signaling.

Objective Develop a novel approach of optimizing continuous flow left ventricular assist device (CF-LVAD) function and diagnosing device malfunctions. Background In CF-LVAD patients, the dynamic interaction of device speed, left and right ventricular decompression, and valve function can be assessed during an echocardiography-monitored speed ramp-test. Methods We devised a unique ramp-test protocol to be routinely done at the time of discharge for speed optimization and/or if device malfunction was suspected. The patient’s left ventricular end diastolic dimension (LVEDD), frequency of aortic valve (AV) opening, valvular insufficiency, blood pressure, and CF-LVAD parameters were recorded at increments of 400 rpm from 8,000 rpm to 12,000 rpm. The results of the speed designations were plotted, and linear function slopes for LVEDD, PI, and power were calculated. Results Fifty-two ramp-tests from 39 patients were prospectively collected and analyzed. Twenty-eight ramp-tests were performed for speed optimization, and speed was changed in 17 (61%) with a mean absolute value adjustment of 424±211 rpm. Seventeen patients had ramp-tests performed for suspected device thrombosis and 10 tests were suspicious for device thrombosis; these patients were then treated with intensified anticoagulation and/or device exchange/emergent transplant. Device thrombosis was confirmed in 8/10 cases at the time of emergent device exchange or transplant. All patients with device thrombosis, but none of the remaining patients, had a LVEDD slope > −0.16. Conclusion Ramp-tests facilitated optimal speed changes and device malfunction detection, and may be used to monitor the effects of therapeutic interventions and need for surgical intervention in CF-LVAD patients.

Extracorporeal membrane oxygenation (ECMO) has been used increasingly for both respiratory and cardiac failure in adult patients. Indications for ECMO use in cardiac failure include severe refractory cardiogenic shock, refractory ventricular arrhythmia, active cardiopulmonary resuscitation for cardiac arrest, and acute or decompensated right heart failure. Evidence is emerging to guide the use of this therapy for some of these indications, but there remains a need for additional evidence to guide best practices. As a result, the use of ECMO may vary widely across centers. The purpose of this document is to highlight key aspects of care delivery, with the goal of codifying the current use of this rapidly growing technology. A major challenge in this field is the need to emergently deploy ECMO for cardiac failure, often with limited time to assess the appropriateness of patients for the intervention. For this reason, we advocate for a multidisciplinary team of experts to guide institutional use of this therapy and the care of patients receiving it. Rigorous patient selection and careful attention to potential complications are key factors in optimizing patient outcomes. Seamless patient transport and clearly defined pathways for transition of care to centers capable of providing heart replacement therapies (e.g., durable ventricular assist device or heart transplantation) are essential to providing the highest level of care for those patients stabilized by ECMO but unable to be weaned from the device. Ultimately, concentration of the most complex care at high-volume centers with advanced cardiac capabilities may be a way to significantly improve the care of this patient population.