Surgical and percutaneous coronary artery intervention revascularization are traditionally considered isolated options. A simultaneous hybrid approach may allow an opportunity to match the best strategy for a particular anatomic lesion. Concerns regarding safety and feasibility of such an approach exist. We examined the safety, feasibility, and early outcomes of a simultaneous hybrid revascularization strategy (minimally invasive direct coronary bypass grafting of the left anterior descending [LAD] artery and drug-eluting stent [DES] to non-LAD lesions) in 13 patients with multivessel coronary artery disease that underwent left internal mammary artery to LAD minimally invasive direct coronary bypass performed through a lateral thoracotomy, followed by stenting of non-LAD lesions, in a fluoroscopy-equipped operating room. Assessment of coagulation parameters was also undertaken. Inhospital and postdischarge outcomes of these patients were compared to a group of 26 propensity score matched parallel controls that underwent standard off-pump coronary artery bypass. Baseline characteristics were similar in both groups. All hybrid patients were successfully treated with DES and no inhospital mortality occurred in either group. Hybrid patients had a shorter length of stay (3.6 +/- 1.5 vs 6.3 +/- 2.3 days, P < .0001) and intubation times (0.5 +/- 1.3 vs 11.7 +/- 9.6 hours, P < .02). Despite aggressive anticoagulation and confirmed platelet inhibition, hybrid patients had less blood loss (581 +/- 402 vs 1242 +/- 941 mL, P < .05) and decreased transfusions (0.33 +/- 0.49 vs 1.47 +/- 1.53 U, P < .01). Six-month angiographic vessel patency and major adverse cardiac events were similar in the hybrid and off-pump coronary artery bypass groups. A simultaneous hybrid approach consisting of minimally invasive coronary artery bypass grafting with left internal mammary artery to LAD combined with revascularization of the remaining coronary targets using percutaneous coronary artery intervention with DES is a feasible option accomplished with acceptable clinical outcomes without increased bleeding risk.
We report orthotopic (life‐supporting) survival of genetically engineered porcine cardiac xenografts (with six gene modifications) for almost 9 months in baboon recipients. This work builds on our previously reported heterotopic cardiac xenograft (three gene modifications) survival up to 945 days with an anti‐CD40 monoclonal antibody‐based immunosuppression. In this current study, life‐supporting xenografts containing multiple human complement regulatory, thromboregulatory, and anti‐inflammatory proteins, in addition to growth hormone receptor knockout (KO) and carbohydrate antigen KOs, were transplanted in the baboons. Selective “multi‐gene” xenografts demonstrate survival greater than 8 months without the requirement of adjunctive medications and without evidence of abnormal xenograft thickness or rejection. These data demonstrate that selective “multi‐gene” modifications improve cardiac xenograft survival significantly and may be foundational for paving the way to bridge transplantation in humans.
Perioperative management of cardiovascular surgical procedures requiring cardiopulmonary bypass (CPB) in patients with hemophilia A poses a clinical challenge in coagulation management. Use of CPB requires the administration of an anticoagulant, usually unfractionated heparin, and also causes dilutional coagulopathy, platelet dysfunction or platelet consumption coagulopathy. Hypothermia and activation of the inflammatory cascade also affect coagulation. The effects of CPB on circulating levels of factor VIII have not been clearly defined. In this review, the effects of CPB and hemodilution on FVIII are shown in a case presentation, and perioperative laboratory testing in patients with hemophilia A having cardiac surgery is discussed along with perioperative and postoperative coagulation management.
Background.-Peri-operative cardiac xenograft dysfunction (PCXD) was described by McGregor et al. to be a major barrier to the translation of heterotopic cardiac xenotransplantaton into the orthotopic position. It is characterized by graft dysfunction in the absence of rejection within 24-48 hours of transplantation. We describe our experience with PCXD at a single program.Methods.-Orthotopic transplantation of genetically engineered pig hearts was performed in 6 healthy baboons. The immunosuppression regimen included induction by anti-CD20 mAb, Thymoglobulin, cobra venom factor and anti-CD40 mAb and maintenance with anti-CD40 mAb, MMF and tapering doses of steroids. Telemetry was used to asses graft function. Extracorporeal membrane oxygenation was used to support one recipient. A full human clinical transplant team was involved in these experiments and the procedure was performed by skilled transplant surgeons.Results.-A maximal survival of 40 hours was achieved in these experiments. The surgical procedures were uneventful and all hearts were weaned from cardiopulmonary bypass (CPB) without issue. Support with inotropes and vasopressors was generally required after separation from CPB. The cardiac xenografts performed well immediately, but within the first several hours required increasing support and ultimately suffered arrest despite maximal interventions. All hearts were explanted immediately; histology showed no signs of rejection.
Intracardiac thrombosis (ICT) and pulmonary thromboembolism (PE) after cardiopulmonary bypass (CPB) are life-threatening events, but pathological mechanisms are not yet well defined. The aim of this review is to provide an update of case literature of a postbypass hypercoagulable state. Case commonalities among 48 ICT/PE events included congestive heart failure (50%), platelet transfusion (37.5%), CPB duration greater than 3 hours (37.5%), and aortic injury (27.1%). Preexisting thrombophilia was rarely reported, and 16.7% had low activated clotting time, ≤400 seconds during CPB. Mortality rate was very high (85.4%), despite attempted thrombectomy and supportive therapy. Thrombolytic therapy was infrequently used (5 of 48 times), but its efficacy is questionable due to common use of antifibrinolytic therapy (77.1% of cases). Acute ICT/PE events appear to rarely occur, but common features include prolonged CPB, depressed myocardial function, major vascular injury, and hemostatic interventions. Further efforts to elucidate pathomechanisms and optimize anticoagulation during CPB and hemostatic interventions after CPB are warranted.
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