EXPERIMENTAL AND CLINICAL TRANSPLANTATION

We describe a complex case of liver transplant in a 70-year-old male patient with no known history of coronary artery disease, normal preoperative left ventricular function, and negative preoperative cardiac workup who developed progressive intraoperative left ventricular myocardial dysfunction secondary to class I acute myocardial infarction, ultimately requiring intraoperative intra-aortic balloon pump insertion to optimize myocardial perfusion. Management of myocardial ischemia was complicated by bleeding in the setting of coagulopathy necessitating correction. Once hemostasis was achieved, the patient immediately underwent coronary angiography and bare metal stent placement in the mid-left anterior descending coronary artery for an acute plaque rupture.

Key words : Hypertension, Myocardial infarction, Transesophageal echocardiography

Liver transplant for patients with coronary artery disease (CAD) is high risk, with reported 1-year mortality rate of approximately 40%.¹ Despite best efforts to risk-stratify liver transplant candidates for myocardial ischemia with stress provocation studies, sometimes preexisting CAD will not be apparent until exposure to intraoperative physiologic stress, presenting as acute coronary ischemia. In such cases, managing physicians may encounter multiple clinical dilemmas. The Institutional Review Board has waived the requirement for written consent from the patient, and we have received HIPPA authorization for this case report.

Preoperative evaluation
A 70-year-old man with hypertension, type 2 diabetes, and alcohol-induced end-stage liver disease complicated by hepatic encephalopathy, hepatorenal syndrome, and recurrent ascites with spontaneous bacterial peritonitis presented for deceased donor orthotopic liver transplant (OLT). His Model for End-Stage Liver Disease-Na score was 33.

Pretransplant cardiac work-up included a negative nuclear stress test with coronary calcium score of 145, indicating a high negative predictive value for significant CAD.² The patient’s transthoracic echocardiogram demonstrated low-normal left ventricular (LV) ejection fraction (LVEF) of 55% and no regional wall motion abnormalities. Hence, coronary angiography was not indicated.

Intraoperative course
After induction of general anesthesia, a transesophageal echocardiography (TEE) probe was placed, demonstrating moderately diminished LVEF with greater hypokinesis of the anteroseptal and apical segments. No concomitant electrocardiogram (ECG) changes or major hemodynamic changes were present. The suspicion of myocardial ischemia was low; hence, a decision was made to proceed with OLT. As the case progressed, the patient required incremental doses of vasopressors. His LVEF further declined to 10% to 15% prior to reperfusion with some preservation of function in the myocardial base. At this point, the patient required norepinephrine 2 μg/kg/min, epinephrine 1 μg/kg/min, and vasopressin 0.04 U/min. The suspicion for acute myocardial ischemia increased with time. Continuation of the surgery was necessary, as the hepatic artery and bile duct had been ligated. Furthermore, the cold ischemic time of the graft was approaching 8 hours, increasing the risk of severe myocardial instability during reperfusion.

During graft reperfusion, the portal venous clamp was gradually released, reducing the hemodynamic impact. Despite this, the patient required multiple boluses of epinephrine 1 mg and calcium chloride 1 g to maintain mean arterial pressure above 55 mm Hg. The ECG demonstrated a new intraventricular conduction delay, and amiodarone was initiated. Transesophageal echocardiography demonstrated severe LV hypokinesis. To improve myocardial perfusion, an intra-aortic balloon pump (IABP) was placed by the cardiac surgeons. Subsequently, epinephrine and norepinephrine were rapidly weaned down with LVEF improvement.

Fascial closure was delayed, minimizing time to possible percutaneous coronary intervention. Bleeding secondary to fibrinolysis was evident on thromboelastogram, which was corrected through transfusion of blood products and tranexamic acid. The patient was then transported to the coronary catheterization lab as soon as possible.

Left heart catheterization demonstrated an eccentric ulcerative 90% stenosis in the mid-left anterior descending coronary artery (Figure 1). A bare metal stent was deployed after cangrelor was initiated (Figure 2). He also received loading with clopidogrel 600 mg.

Postoperative course
In the surgical intensive care unit, cangrelor infusion was continued for 6 hours. P2Y12 assays showed persistent elevation (Table 1), suggesting insufficient antiplatelet activity, prompting a transition to ticagrelor. Therapy with IABP allowed stable myocardial perfusion pressures and rapid reduction in cardioactive support within the first day. On postoperative day (POD) 1, his abdomen was closed surgically and he was weaned off IABP. Transthoracic echocardiogram showed anteroseptal wall motional abnormality, near akinesia, consistent with the territory of infarct, with LVEF of 35%. On POD3, he was weaned off vasopressors and extubated. He was transferred to the floor on POD13 and discharged to an inpatient rehabilitation center 4 weeks postoperatively.

Management of non-ST elevation acute myocardial infarction presents particular challenges during OLT involving a multidisciplinary approach with tight coordination of all activities, hemodynamic support with considerations for mechanical support, and management of the hemostatic system.

Role of perioperative transesophageal echocardiography
When ECG changes are not present, intraoperative TEE becomes a key diagnostic tool to evaluate for myocardial ischemia.³ A TEE can elucidate new-onset regional and global LV systolic dysfunction, as well as diastolic dysfunction, as markers of ischemia. Furthermore, TEE is indicated in management of hemodynamic instability to guide selection of interventions.

Intraoperative management of myocardial ischemia
Maintenance of the optimal myocardial supply-to-demand ratio is the cornerstone of intraoperative management. This involves use of vasoactive, inotropic, and antiarrhythmic agents and cardioversion or defibrillation as necessary. On occasion, use of mechanical hemodynamic support is necessary. In cardiogenic shock, IABP is the first line of treatment for hemodynamic support4 and, on rare occasions, has been used in noncardiac surgical procedures.⁵ This procedure improves myocardial perfusion through augmentation of the systemic diastolic pressure, thus optimizing myocardial supply-to-demand ratio until coronary revascularization becomes possible. In our patient, the use of IABP reduced requirements of vasopressor and inotropic medications, improved LV systolic function, and provided sufficient time to achieve surgical hemostasis until definitive intervention could be performed in the cardiac catheterization lab. However, it is prudent to be aware of the possible complications of IABP, which are mainly related to malposition and mechanical destruction of platelets and red blood cells. Of note, there have been case reports of liver injury secondary to malposition of IABP.⁶

Role of imaging in diagnosis of myocardial ischemia and coronary intervention
Although preoperative testing for myocardial ischemia is widely implemented in evaluations of liver transplant candidates, perioperative myocardial ischemia still occurs.⁷ Current preoperative work up, such as nuclear stress testing, has been shown to lack sensitivity and has not been shown to predict outcomes after OLT.8 Coronary angiography is the gold standard for diagnosis of CAD and acute coronary syndrome, with subsequent interventions including angioplasty and stenting dependent on the coronary anatomy.⁹ However, because of its invasive nature, risk of complications, and cost, it is restricted to high-risk patients. Per our institutional guidelines, coronary angiography is recommended for patients who have a positive provoked ischemia on noninvasive ischemic testing or nondiagnostic stress testing if clinically indicated and those without stress testing and with a calcium score of more than 400.

Management of coagulopathy
Management of coagulopathy during OLT is complex in the setting of ongoing myocardial ischemia due to opposing concerns: correction of coagulopathy may cause plaque-associated thrombus propagation, but not correcting coagulopathy leads to the cascade of bleeding, hypotension, reduced preload, and myocardial perfusion pressure, as well as exacerbation of ischemia. Under circumstances of reduced LV systolic function, massive transfusion creates an additional risk of pulmonary edema and poor gas exchange. The use of antifibrinolytics in an attempt to achieve hemostasis had to be made cautiously in the setting of myocardial ischemia, with the understanding that it could potentially worsen myocardial blood supply via thrombosis propagation. Platelet transfusions in the setting of antiplatelet medications also appear counterintuitive but necessary to correct coagulopathy, A modest goal of platelet count above 50 × 10³/mL was chosen to balance the benefit of hemostasis with the risk of in-stent thrombosis. The decision to correct coagulopathy lies on balancing these opposing priorities and should be goal-directed using clinical findings and point-of-care laboratory tests, particularly viscoelastic tests such as the use of thromboelastogram.

Antiplatelet therapy during the perioperative period of orthotopic liver transplant
Care of the liver transplant recipient after percutaneous coronary intervention is challenging, as the prodrug clopidogrel requires hepatic activation and the pharmacokinetics are thus unpredictable in patients with cirhossis¹⁰ and likely in newly transplanted patients. In this setting, point-of-care P2Y12 assays are useful in monitoring the adequacy of antiplatelet therapies. Ticagrelor may be preferred as it does not require metabolic activation by the liver. In our posttransplant patient with expected thrombocytopenia, the risk of bleeding from thrombocytopenia and antiplatelet therapy required balance against the risk of in-stent thrombosis from fresh stent placement, with consideration of judicious transfusion if needed.

Importance of a coordinated team effort
The successful outcome of this medically challenging patient was largely dependent on the coordinated effort of a multidisciplinary team, which included the transplant surgeons, anesthesiologists, cardiac surgeons, interventional cardiologists, critical care physicians, and transplant hepatologists. Timely management was crucial to patient stabilization, prompt diagnosis, and targeted intervention necessary to treat the unexpected and severe intraoperative myocardial dysfunction. Shared decision-making among the different disciplines was of utmost importance to ensure the smooth and successful delivery of care for this patient.

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