Surgical revascularization techniques that minimize surgical risk and maximize late survival after coronary artery bypass grafting in patients with diabetes mellitus.

Immunosuppressive therapies after heart transplantation — The balance between under- and over-immunosuppression

Pump thrombosis is a dreaded complication of left ventricular assist devices (LVADs). We completed a systematic review to evaluate the efficacy and complications associated with medical management of LVAD thrombosis. Databases were searched using the terms "vad*" or "ventricular assist device" or "heart assist device" and "thrombus" or "thrombosis" or "thromboembolism." Of 2,383 manuscripts, 49 articles met the inclusion criteria. The risk of partial or no resolution of LVAD thrombosis did not significantly differ between thrombolytic and nonthrombolytic regimens (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.20-1.16). When response to therapy was evaluated based on pump type, there were no significant differences in how patients with a HeartMate II or HeartWare ventricular assist device responded to thrombolytic or nonthrombolytic treatment. Pooled risk of major bleeding in the thrombolytic group was 29% (95% CI, 0.17-0.44) and 12% (95% CI, 0.01-0.57) in the nonthrombolytic group. Odds of death did not differ between thrombolytic and nonthrombolytic regimens (OR, 1.28; 95% CI, 0.42-3.89). Although thrombolytic and nonthrombolytic treatment similarly resolved LVAD thrombosis, major hemorrhage may be increased with the use of thrombolysis. Randomized clinical trials comparing thrombolytic and nonthrombolytic treatment of LVAD thrombosis are needed to establish the most effective and safe option for patients who are not surgical candidates.

Medical Management of Pump-Related Thrombosis in Patients with Continuous-Flow Left Ventricular Assist Devices: A Systematic Review and Meta-Analysis.

Efficacy and effectiveness of on- versus off-pump coronary artery bypass grafting: A meta-analysis of mortality and survival

The primary cause of mortality at 5 years following a cardiac transplantation is the development of atherosclerosis, termed coronary allograft vasculopathy (CAV). This pathology is characterized by diffused intimal hyperplasia and emanates from coronary arterial injuries caused by immune inflammatory cells. Neutrophils play an important role in this inflammatory process; however, their potential participation in the pathogenesis of CAV is poorly understood. Despite their essential contribution to the prevention of graft rejection, immunosuppressive drugs could have detrimental effects owing to their pro-inflammatory activities. Thus, we investigated the impact of different immunosuppressive drugs on the inflammatory response of neutrophils isolated from the blood of healthy volunteers. Under basal conditions, mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) had the most potent anti-inflammatory effect, decreasing both IL-8 release (≈−80%) and vascular endothelial growth factor (VEGF) release (≈−65%) and preserving the release of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA). In TNF-α-treated neutrophils, pre-incubation with everolimus provided the most potent effect, simultaneously reducing the release of both VEGF and IL-8 while doubling the release of IL-1RA. This latter effect of everolimus was maintained even when administered in combination with other immunosuppressive drugs. Sirolimus and everolimus decreased the tumor necrosis factor (TNF)-α-induced adhesion of neutrophils to human endothelial cells and human extracellular matrix. This effect was largely dependent on the ability of these compounds to alter β2-integrin/CD18 activation. Our results suggest a potential mechanism for the beneficial effect of everolimus in the prevention of CAV in heart transplant recipients.

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Effect of everolimus on the immunomodulation of the human neutrophil inflammatory response and activation.

Aims Centrifugal continuous flow pumps are currently the state of the art in left ventricular assist device therapy. This study was conducted to compare the results after implantation of the HVAD® and the HeartMate 3®. Methods and results We retrospectively analysed preoperative and post-operative patient data of all 106 patients, who received a HeartMate 3 (HM3) at our centre between 2014 and 2018. A total of 392 patients receiving a sintered HVAD® served as controls. Patient matching was performed for age, sex, Interagency Registry for Mechanically Assisted Circulatory Support level at the time of implant, perioperative right heart failure, and implantation strategy, that is, bridge to transplant or destination therapy, as well as preoperative renal function, that is, as indicated by serum creatinine levels. A total of 79 matched pairs could be identified. During a median follow-up of 15.3 months (range: 0-30 months), 23 (29.1%) and 19 (24.1%) patients died in the HVAD and HM3 groups, respectively, with a hazard ratio for mortality of 0.84 [95% confidence interval (CI): 0.46-1.54; P = 0.568]. Freedom from cerebrovascular events did not differ significantly between study groups, with a hazard ratio of 0.57 (95% CI: 0.23-1.45; P = 0.241). The risk of driveline infection was significantly lower in the HM3 (n = 33) than in the HVAD (n = 55) group (hazard ratio = 0.54; 95% CI: 0.35-0.84; P = 0.006). Eight HVAD, but no HM3, patients developed a pump thrombosis during follow-up (P = 0.148). Conclusions Performance of both currently used centrifugal left ventricular assist device systems is comparable in terms of short-term patient survival and freedom from cerebrovascular events. In our single-centre experience, HM3 patients less frequently develop driveline infections and no pump thrombosis, which requires further evaluation.

Comparing short-term outcome after implantation of the HeartWare® HVAD® and the Abbott® HeartMate 3®.

https://www.annalsthoracicsurgery.org/article/S0003-4975(13)00883-7/pdf

Coronary Revascularization in Diabetic Patients: Off-Pump Versus On-Pump Surgery

The calcineurin inhibitor cyclosporine (CSA) displays nephrotoxic side effects. We switched 95 maintenance heart transplant recipients with chronic kidney disease (CKD) stages 3–4 from CSA to everolimus (EVL). The CSA dosage was reduced by 50%. Kidney function, lipid metabolism, and cardiac function investigated during a 2-year follow-up were compared with heart transplant recipients with CKD stages 2–3 who continued to receive CSA (CSA group; n = 84). Whereas 64/95 patients received reduced CSA plus EVL during the entire follow-up period (EVL continued subgroup, ECN), 31 discontinued EVL (EVL discontinued subgroup, EDS) after 4.3 months (median) because of various clinically relevant adverse events. Glomerular filtration rates (estimated using the modification of diet in renal disease formula) increased by 4.0 mL/min/1.73 m2 in the ECN subgroup but decreased by 2.4 mL/min/1.73 m2 and 9.0 mL/min/1.73 m2 in the EDS subgroup and the CSA group, respectively (P < .001). Triglyceride and total cholesterol concentrations increased significantly among the ECN group, but remained constant in the EDS subgroup and the CSA group. Statin use was increased by 15% in the ECN group (P < .01). Mortality and cardiac rejection rates did not differ significantly among the 3 groups. In summary, EVL combined with low-dose CSA had modest beneficial effects on kidney function in heart transplant recipients with CKD stages 3–4. A significant percentage of patients had to stop EVL because of various adverse events.

Everolimus Plus Dosage Reduction of Cyclosporine in Cardiac Transplant Recipients with Chronic Kidney Disease: A Two-Year Follow-up Study

Coronary Revascularization in diabetic patients: Off-pump versus on-pump surgery

Here we present a patient after implantation of a left ventricular assist device (HeartWare) for destination therapy complicated by recurrent thrombosis of the device. At 14 months after implantation, the patient presented with a pump thrombosis after an INR incompliance period. A surgical pump exchange was performed and the patient recovered uneventfully. Five months later a pump thrombosis occurred again, and the patient refused surgery. Systemic thrombolysis was carried out this time. Three and 6 months later the same clinical picture was presented again, and repeat thrombolysis was performed successfully. The patient was discharged and has remained stable since, without any symptoms of thrombosis of the device.

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K Hakim-Meibodi

Papers

Comparing short-term outcome after implantation of the HeartWare® HVAD® and the Abbott® HeartMate 3®.

Coronary Revascularization in Diabetic Patients: Off-Pump Versus On-Pump Surgery

Everolimus Plus Dosage Reduction of Cyclosporine in Cardiac Transplant Recipients with Chronic Kidney Disease: A Two-Year Follow-up Study

Coronary Revascularization in diabetic patients: Off-pump versus on-pump surgery

Successful repeated thrombolysis in a patient with HeartWare thrombosis - the importance of Doppler flow pattern.