Effectiveness of combined plasma cell therapy and costimulation blockade based desensitization regimen in heart transplant candidates.

BACKGROUND: Desensitization is one of the strategies to reduce antibodies and facilitate heart transplantation in highly sensitized patients. We describe our center's desensitization experience with combination of plasma cell (PC) depletion therapy (with proteasome inhibitor or daratumumab) and costimulation blockade (with belatacept). METHODS: We reviewed five highly sensitized patients who underwent desensitization therapy with plasma cell depletion and costimulation blockade. We evaluated the response to therapy by measuring the changes in cPRA, average MFI, and number of positive beads > 5000MFI. RESULTS: Five patients, mean age of 56 (37-66) years with average cPRA of 98% at 5000 MFI underwent desensitization therapy. After desensitization, mean cPRA decreased from 98% to 70% (p = .09), average number of beads > 5000 MFI decreased from 59 to 37 (p = .15), and average MFI of beads > 5000 MFI decreased from 16713 to 13074 (p = .26). CONCLUSION: Combined PC depletion and CoB could be a reasonable strategy for sustained reduction in antibodies in highly sensitized patients being listed for heart transplantation.

Waitlist and post-transplant outcomes in patients listed with intra-aortic balloon pump for heart transplant: United Network for Organ Sharing registry.

BACKGROUND: Intra-aortic balloon pump as bridge-to-transplant (BTT) has been used successfully in patients with refractory cardiogenic shock. However, the waitlist mortality in this population is high and predictors of waitlist mortality in this population are not known. We sought to identify predictors for waitlist mortality in patients listed with intra-aortic balloon pump and risk factors for 1-year mortality after heart transplant in this population. METHODS: We identified patients listed for heart transplantation with intra-aortic balloon pump in the United Network for Organ Sharing data set from 1994 to 2015. Univariable and multivariable Cox proportional hazards models were used to identify predictors of waitlist mortality and 1-year post-transplant mortality. RESULTS: From 1945 patients listed with intra-aortic balloon pump, 67.5% (N = 1313) were alive at 1 year and waitlist mortality was 32.5% (N = 632). We found that higher pulmonary vascular resistance, need for inotropes, and need for mechanical ventilation were associated with higher waitlist mortality. Mechanical ventilation and dialysis prior to transplantation were important predictors of 1-year post-transplant mortality. CONCLUSION: Predictors of mortality such as high pulmonary vascular resistance, dialysis dependence, inotrope, and ventilator dependence in patients listed with intra-aortic balloon pump can help us identify those patients that are at high risk of dying prior to a heart transplantation.

Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function.

OBJECTIVE: A significant number of patients have coronary artery disease that is not amenable to traditional revascularization. Prospective, randomized clinical trials have demonstrated therapeutic benefits with transmyocardial laser revascularization in this cohort. The molecular mechanisms underlying this therapy, however, are poorly understood. The focus of this study was evaluation of the proposed vasculogenic mechanisms involved in transmyocardial laser revascularization. METHODS: Male Yorkshire pigs (30-35 kg, n = 25) underwent left thoracotomy and placement of ameroid constrictors around the proximal left circumflex coronary artery. During the next 4 weeks, a well-defined region of myocardial ischemia developed, and the animals underwent a redo left thoracotomy. The animals were randomly assigned to sham treatment (thoracotomy only, control, n = 11) or transmyocardial laser revascularization of hibernating myocardium with a holmium:yttrium-aluminum-garnet laser (n = 14). After an additional 4 weeks, the animals underwent median sternotomy, echocardiographic analysis of wall motion, and hemodynamic analysis with an ascending aortic flow probe and pulmonary artery catheter. The hearts were explanted for molecular analysis. RESULTS: Molecular analysis demonstrated statistically significant increases in the proangiogenic proteins nuclear factor kappaB (42 +/- 27 intensity units vs 591 +/- 383 intensity units, P = .03) and angiopoietin 1 (0 +/- 0 intensity units vs 241 +/- 87 intensity units, P = .003) relative to sham control values with transmyocardial laser revascularization within the ischemic myocardium. There were also increases in vasculogenesis (18.8 +/- 8.7 vessels/high-power field vs 31.4 +/- 10.2 vessels/high-power field, P = .02), and perfusion (0.028 +/- 0.009 microm3 blood/microm3 tissue vs 0.044 +/- 0.004 microm3 blood/microm3 tissue, P = .01). Enhanced myocardial viability was demonstrated by increased myofilament density (40.7 +/- 8.5 cardiomyocytes/high-power field vs 50.8 +/- 7.5 cardiomyocytes/high-power field, P = .03). Regional myocardial function within the treated territory demonstrated augmented contractility. Global hemodynamic function was significantly improved relative to the control group with transmyocardial laser revascularization (cardiac output 2.1 +/- 0.2 L/min vs 2.7 +/- 0.2 L/min, P = .007, mixed venous oxygen saturation 64.7% +/- 3.6% vs 76.1% +/- 3.4%, P = .008). CONCLUSION: Transmyocardial laser revascularization with the holmium-YAG laser enhances perfusion, with resultant improvement in myocardial contractility.