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Combined heart and liver transplantation in an adult with familial heterozygous hypercholesterolemia and severe ischemic cardiomyopathy
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COMMENT AND OPINION Combined heart and liver transplantation in an adult with familial heterozygous hypercholesterolemia and severe ischemic cardiomyopathy Snehal R. Patel, MD, David D’alessandro, MD, and Jooyoung J. Shin, MD From the Center for Advanced Cardiac Therapy, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
Familial hypercholesterolemia (FH) is an autosomal-dominant disorder caused by mutations in the low-density lipoprotein (LDL) receptor.1 The clinical manifestations of FH include severe atherosclerosis and premature heart disease.1 Liver transplantation restores defective LDL receptors and has been used for long-term treatment in homozygous FH.2 We report a 34-year-old man who underwent combined heart-liver transplantation (CHLT) for end-stage ischemic heart failure and heterozygous FH. The patient presented with heart failure and was found to have severe left ventricular dysfunction. Cardiac catheterization demonstrated multivessel coronary disease not amenable to revascularization, and he was initiated on heart failure and anti-lipid therapy. Further cardiac evaluation revealed a peak oxygen consumption of 15.7 ml/ kg/min (36% predicted) and a depressed cardiac index with moderate pulmonary hypertension. Despite multidrug antilipid therapy, his values remained at 491 mg/dl for total cholesterol and 415 mg/dl for LDL cholesterol. LDL apheresis was initiated. The following options were considered: (1) medical management of heart failure with apheresis, (2) heart transplant with apheresis, or (3) CHLT. The patient ultimately underwent simultaneous CHLT from a single donor. Heart transplantation was performed using the bicaval technique. After separation from cardiopulmonary bypass, the aortic and inferior vena cava cannulae were removed. Liver transplantation was performed using a right femoral vein inflow catheter with return to the superior vena cava cannula. The sternum was closed after the liver was implanted. The heart allograft tolerated the anhepatic phase and reperfusion of the liver graft without difficulty. His postoperative course was unremarkable. The patient was managed with a standard cardiac immunosuppression regimen consisting of tacrolimus, mycophenolate, and prednisone. At 16 months after transplant, he has experienced no complications. There has been no evidence of cardiac graft rejection. Coronary angiography at 1 year demonstrated normal coronary arteries. Results of liver tests have remained within
normal reference ranges. Total and LDL cholesterol levels were 136 mg/dl and 70 mg/dl, respectively, at 1-year on pravastatin at 20 mg daily. In FH, defective LDL receptors result in decreased LDL clearance and, consequently, high levels of total and LDL cholesterol and unfavorable changes in vascular endothelial function.1 Homozygous FH is relatively rare; however, the lipid abnormalities are severe, leading to heart disease in the first 2 decades.1 Heterozygous FH is much more common, affecting 1/500 individuals, and manifests with heart disease in the third through fifth decades.1 Unfortunately, the diagnosis of heterozygous FH is often made at the time of the clinical presentation of heart disease. Patients with FH resulting in end-stage ischemic heart failure present a difficult clinical dilemma. The best long-term heart failure treatment in these patients is heart transplantation; however, persistently elevated cholesterol levels place the transplanted heart at risk of accelerated atherosclerosis and early transplant vasculopathy.3 Medical therapy, in this situation, is insufficient to provide adequate lipid control. In published reports, patients with homozygous FH and severe ischemic cardiomyopathy have experienced excellent long-term outcomes with CHLT.2 Our patient, an adult with heterozygous FH underwent dual-organ heart-liver transplantation and had an excellent outcome. In conclusion, CHLT is a viable option for the management of this challenging group of patients.
Disclosure statement The authors thank Paul Gaglio, MD, and Milan Kinkhabwala, MD, for their careful review of this manuscript. None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.
References 1. Goldstein JL, Hobbs HH, Brown MS. Familial Hypercholesterolemia. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill Companies Inc; 2001:2863–914. 2. Revell SP, Noble-Jamieson G, Johnston P, Rasmussen A, Jamieson N, Barnes ND. Liver transplantation for homozygous familial hypercholesterolaemia. Arch Dis Child 1995;73:456-8. 3. Kapadia SR, Nissen SE, Ziada KM, et al. Impact of lipid abnormalities in development and progression of transplant coronary disease: a serial intravascular ultrasound study. J Am Coll Cardiol 2001;38:206-13.
1053-2498/$ -see front matter © 2012 International Society for Heart and Lung Transplantation. All rights reserved. doi:10.1016/j.healun.2011.11.022
COMMENT AND OPINION Combined heart and liver transplantation in an adult with familial heterozygous hypercholesterolemia and severe ischemic cardiomyopathy Snehal R. Patel, MD, David D’alessandro, MD, and Jooyoung J. Shin, MD From the Center for Advanced Cardiac Therapy, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
Familial hypercholesterolemia (FH) is an autosomal-dominant disorder caused by mutations in the low-density lipoprotein (LDL) receptor.1 The clinical manifestations of FH include severe atherosclerosis and premature heart disease.1 Liver transplantation restores defective LDL receptors and has been used for long-term treatment in homozygous FH.2 We report a 34-year-old man who underwent combined heart-liver transplantation (CHLT) for end-stage ischemic heart failure and heterozygous FH. The patient presented with heart failure and was found to have severe left ventricular dysfunction. Cardiac catheterization demonstrated multivessel coronary disease not amenable to revascularization, and he was initiated on heart failure and anti-lipid therapy. Further cardiac evaluation revealed a peak oxygen consumption of 15.7 ml/ kg/min (36% predicted) and a depressed cardiac index with moderate pulmonary hypertension. Despite multidrug antilipid therapy, his values remained at 491 mg/dl for total cholesterol and 415 mg/dl for LDL cholesterol. LDL apheresis was initiated. The following options were considered: (1) medical management of heart failure with apheresis, (2) heart transplant with apheresis, or (3) CHLT. The patient ultimately underwent simultaneous CHLT from a single donor. Heart transplantation was performed using the bicaval technique. After separation from cardiopulmonary bypass, the aortic and inferior vena cava cannulae were removed. Liver transplantation was performed using a right femoral vein inflow catheter with return to the superior vena cava cannula. The sternum was closed after the liver was implanted. The heart allograft tolerated the anhepatic phase and reperfusion of the liver graft without difficulty. His postoperative course was unremarkable. The patient was managed with a standard cardiac immunosuppression regimen consisting of tacrolimus, mycophenolate, and prednisone. At 16 months after transplant, he has experienced no complications. There has been no evidence of cardiac graft rejection. Coronary angiography at 1 year demonstrated normal coronary arteries. Results of liver tests have remained within
normal reference ranges. Total and LDL cholesterol levels were 136 mg/dl and 70 mg/dl, respectively, at 1-year on pravastatin at 20 mg daily. In FH, defective LDL receptors result in decreased LDL clearance and, consequently, high levels of total and LDL cholesterol and unfavorable changes in vascular endothelial function.1 Homozygous FH is relatively rare; however, the lipid abnormalities are severe, leading to heart disease in the first 2 decades.1 Heterozygous FH is much more common, affecting 1/500 individuals, and manifests with heart disease in the third through fifth decades.1 Unfortunately, the diagnosis of heterozygous FH is often made at the time of the clinical presentation of heart disease. Patients with FH resulting in end-stage ischemic heart failure present a difficult clinical dilemma. The best long-term heart failure treatment in these patients is heart transplantation; however, persistently elevated cholesterol levels place the transplanted heart at risk of accelerated atherosclerosis and early transplant vasculopathy.3 Medical therapy, in this situation, is insufficient to provide adequate lipid control. In published reports, patients with homozygous FH and severe ischemic cardiomyopathy have experienced excellent long-term outcomes with CHLT.2 Our patient, an adult with heterozygous FH underwent dual-organ heart-liver transplantation and had an excellent outcome. In conclusion, CHLT is a viable option for the management of this challenging group of patients.
Disclosure statement The authors thank Paul Gaglio, MD, and Milan Kinkhabwala, MD, for their careful review of this manuscript. None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.
References 1. Goldstein JL, Hobbs HH, Brown MS. Familial Hypercholesterolemia. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill Companies Inc; 2001:2863–914. 2. Revell SP, Noble-Jamieson G, Johnston P, Rasmussen A, Jamieson N, Barnes ND. Liver transplantation for homozygous familial hypercholesterolaemia. Arch Dis Child 1995;73:456-8. 3. Kapadia SR, Nissen SE, Ziada KM, et al. Impact of lipid abnormalities in development and progression of transplant coronary disease: a serial intravascular ultrasound study. J Am Coll Cardiol 2001;38:206-13.
1053-2498/$ -see front matter © 2012 International Society for Heart and Lung Transplantation. All rights reserved. doi:10.1016/j.healun.2011.11.022