Effect of cardiopulmonary bypass on cytochrome P450 enzyme activity: implications for pharmacotherapy

For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities of cytochrome P450 (CYP) isoenzymes. PK changes during cardiac surgery with CPB have the potential to adversely affect the safety and efficacy of pharmacotherapy and increase the risk of drug–drug interactions. Clinically significant changes in drug PK during CPB are likely to be prominent for drugs where CYP metabolism is a major clearance (CL) mechanism. However, clinical data from patients undergoing CPB surgery in support of this hypothesis are lacking, leaving a significant knowledge gap. In this review, we address the effects of CPB on the release of pro-inflammatory cytokines, in surgeries with and without CPB, both pre and post initiation of surgery. We reviewed literature to explore the relationship between the release of pro-inflammatory cytokines, and the expression and activities of CYP enzymes. Through this approach, we provide new insight on the effects of CPB on the PK of drugs administered to patients in the clinical setting. Future research to address this knowledge gap will have considerable impact to assist clinicians with optimizing pharmacotherapy in this patient population.     

Coronary Arteriovenous Fistulae: A Review

Coronary arteriovenous fistulae are a coronary anomaly, presenting in 0.002% of the general population. Their etiology can be congenital or acquired. We present a review of recent literature related to their epidemiology, etiology, pathophysiology, clinical presentation, diagnostic approach, and therapeutic management.     

Neurogenic Stress Cardiomyopathy in Heart Donors

Cardiac transplantation is severely restricted by donor availability. Left ventricular dysfunction due to neurogenic stress cardiomyopathy is often seen during donor evaluation and often presents a clinical dilemma for procurement. We report a case of a 23-year-old man with severe left ventricular dysfunction whose heart was successfully procured for transplantation. The brief case report is followed by an extensive review of neurogenic stress cardiomyopathy as well as donor evaluation for cardiac transplantation in the setting of such cardiomyopathy.     

Outcome of patients with systemic light chain amyloidosis with concurrent renal and cardiac involvement

Cardiac involvement in systemic light chain amyloidosis (AL) is generally associated with a worse outcome, especially if other organs are also involved. We sought to determine whether concurrent cardiac and renal involvement were associated with a worse outcome than either organ alone. We identified 129 patients with AL, who received high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto‐HCT) at our institution between 1997 and 2014. Ninety‐nine patients had either renal (group 1: n = 62, 62%), cardiac (group 2: n = 20, 20%), or both cardiac and renal (group 3: n = 17, 17%) involvement. The overall hematological response rate (CR+VGPR+PR) post‐auto‐HCT in groups 1, 2, and 3 was 69%, 74% and 82%, respectively (P = 0.62). Overall, organ response in groups 1, 2, and 3 was 39%, 42%, and 70%, respectively. The median PFS from auto‐HCT in groups 1, 2, and 3 was not reached (NR), 13.3 and 21 months, respectively (P = 0.02). The median OS in groups 1, 2, and 3 was 120, 46, and 60 months, respectively (P = 0.1). In conclusion, median PFS and OS in patients with concurrent cardiac and renal AL were comparable to patients with cardiac AL only, but worse than patients with renal AL.