Ann Thorac Cardiovasc Surg 2016; 22: 237–245
Original Article
Online March 30, 2016 doi: 10.5761/atcs.oa.15-00239
Efficacy of Carperitide in Hemodialysis Patients Undergoing Cardiac Surgery Akira Sezai, MD, PhD, Shunji Osaka, MD, PhD, Hiroko Yaoita, MD, PhD, Yusuke Ishii, MD, PhD, Munehito Arimoto, MD, Hiroaki Hata, MD, PhD, and Motomi Shiono, MD, PhD
Purpose: Recently, performance of cardiac surgery in hemodialysis patients has increased, but the mortality rate is high. Methods: We retrospectively examined the early and long-term outcomes in 128 dialysis patients who underwent cardiac surgery with or without carperitide infusion and were followed for 2 years. Sixty-three patients received carperitide infusion during surgery and 65 patients did not. Results: The hospital mortality rate was 1.6% in the carperitide group and 12.3% in the non-carperitide group, being significantly lower in the carperitide group. The 2-year actuarial survival rate was 90.5% ± 3.7% in the carperitide group, and 76.9% ± 5.2% in the non-carperitide group, while the major adverse cardiovascular and cerebrovascular events (MACCE)-free rate at 2 years postoperatively was 90.5% ± 3.7% in the carperitide group and 67.7% ± 5.8% in the non-carperitide group. Conclusions: These findings suggest that carperitide improves the early postoperative outcome in dialysis patients undergoing cardiac surgery, as has already been demonstrated in non-dialysis patients. An early postoperative cardioprotective effect of carperitide and improvement of renal function in oliguric patients might have contributed to this outcome. However, this was a retrospective study, so a prospective investigation is required to demonstrate the mechanisms involved. In addition, further evaluation of the long-term results would be desirable. Keywords: dialysis, chronic kidney disease, coronary artery bypass grafting, cardiac surgery
Introduction Recently, performance of cardiac surgery in hemodialysis patients has increased, but the early mortality rate is still high.1–11) In addition, many patients develop major cardiac and cerebrovascular events or infections after discharge and the long-term results are not satisfactory. The Department of Cardiovascular Surgery, Nihon University School of Medicine, Tokyo, Japan Received: July 27, 2015; Accepted: March 15, 2016 Corresponding author: Akira Sezai, MD, PhD. The Department of Cardiovascular Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-Ku, Tokyo 173-8610, Japan Email: [email protected] ©2016 The Editorial Committee of Annals of Thoracic and Cardiovascular Surgery. All rights reserved.
Ann Thorac Cardiovasc Surg Vol. 22, No. 4 (2016)
Yeo et al. reported that the operative mortality of coronary artery bypass grafting (CABG) increased significantly with each stage of chronic kidney disease (CKD), and patients in stage 5 (estimated glomerular filtration rate (eGFR) 75 years Gender (male: female) Body surface area (m2) Diagnosis IHD Valvular disease Aortic disease IHD + valve Valve + aorta Cause of CKD Diabetic nephropathy Chronic glomerulonephritis Nephrosclerosis Others Anuria Oliguria Emergency or urgent Re-operation Risk factors Diabetes mellitus Hypertension Dyslipidemia Obesity Smoking LV dysfunction COPD Cerebrovascular disease PAD Previous PCI Ejection fraction (%) Duration of HD (years)
Carperitide group
Non-carperitide group
63 65.4 ± 9.4 11 (17%) 49:14 1.60 ± 0.16
65 67.2 ± 8.2 14 (22%) 44:21 1.54 ± 0.16
p value
43 4 0 12 1
41 15 3 6 0
47 11 2 3 39 24 12 (19%) 1 (2%)
41 21 2 1 50 15 19 (29%) 2 (3%)
42 (67%) 55 (87%) 21 (33%) 18 (29%) 23 (37%) 20 (32%) 3 (5%) 2 (3%) 19 (30%)
40 (62%) 52 (80%) 17 (26%) 8 (12%) 22 (34%) 19 (29%) 0 (0%) 5 (8%) 16 (25%)
0.545 0.265 0.374 0.022 0.752 0.757 0.075 0.261 0.482
11 (17%) 51.6 ± 14.7 6.23 ± 3.86
13 (20%) 51.5 ±14.3 6.97 ±4.73
0.713 0.891 0.251
0.254 0.561 0.201 0.06 0.671
0.186
0.065 0.179 0.578
IHD: ischemic heart disease; CKD: chronic kidney disease; LV: left ventricular; COPD: chronic obstructive pulmonary disease; PAD: peripheral artery disease; PCI: percutaneous coronary intervention; HD: hemodialysis
previously performed several prospective trials to investigate the effects of carperitide in non-dialysis patients undergoing cardiac surgery, and we have reported that this drug has a cardioprotective effect, a renoprotective effect, counteracts the adverse influence of cardiopulmonary bypass, inhibits the renin-angiotensin-aldosterone system (RAAS), inhibits left ventricular remodeling, and has an antiarrhythmic effect.13–19) With regard to the renoprotective effect of carperitide, we have found both acute and longterm avoidance of dialysis, RAAS inhibition, and a potent natriuretic action in non-dialysis patients with CKD.16,17) Accordingly, we performed the present retrospective investigation to assess the effectiveness of carperitide in dialysis patients undergoing cardiac surgery. 238
Patients and Methods One hundred and twenty-eight hemodialysis patients underwent cardiac surgery at Nihon University Itabashi Hospital between April 2001 and March 2013, including 63 patients who received carperitide infusion during surgery (carperitide group) and 65 patients who did not receive carperitide (non-carperitide group). All of the patients had chronic kidney disease and no patients receiving acute or sub-acute hemodialysis were included in this study. A 2-year retrospective investigation of postoperative outcomes was performed in this cohort with a 100% follow-up rate. The details of the study were explained to each patient and informed consent was obtained. Ann Thorac Cardiovasc Surg Vol. 22, No. 4 (2016)
Efficacy of Carperitide for Hemodialysis Patients
Infusion of carperitide was initiated at 0.05 ag/min/kg at the start of cardiopulmonary bypass. Once postoperative oral medication was commenced, the infusion rate was reduced to 0.02 µg/min/kg. The infusion rate was further reduced to 0.01 µg/min/kg 12 h later, and carperitide was discontinued after another 12 h. As shown in Table 1, there were no significant differences of background factors between the carperitide and non-carperitide groups. In patients having elective surgery, dialysis was performed on the day before the operation. Intraoperative hemofiltration was performed in all patients and hemodialysis was resumed 1 or 2 days after surgery based on factors such as the severity of pulmonary congestion on chest X-ray films and the serum potassium level. The following preoperative factors were examined for an influence on outcomes: age ≥75 years, gender, shock, emergency surgery, preoperative use of an intra-aortic balloon pump (IABP), previous percutaneous coronary intervention, re-operation, hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, peripheral artery disease (PAD), chronic obstructive pulmonary disease (COPD), anuria, ejection fraction (EF)
Original Article
Online March 30, 2016 doi: 10.5761/atcs.oa.15-00239
Efficacy of Carperitide in Hemodialysis Patients Undergoing Cardiac Surgery Akira Sezai, MD, PhD, Shunji Osaka, MD, PhD, Hiroko Yaoita, MD, PhD, Yusuke Ishii, MD, PhD, Munehito Arimoto, MD, Hiroaki Hata, MD, PhD, and Motomi Shiono, MD, PhD
Purpose: Recently, performance of cardiac surgery in hemodialysis patients has increased, but the mortality rate is high. Methods: We retrospectively examined the early and long-term outcomes in 128 dialysis patients who underwent cardiac surgery with or without carperitide infusion and were followed for 2 years. Sixty-three patients received carperitide infusion during surgery and 65 patients did not. Results: The hospital mortality rate was 1.6% in the carperitide group and 12.3% in the non-carperitide group, being significantly lower in the carperitide group. The 2-year actuarial survival rate was 90.5% ± 3.7% in the carperitide group, and 76.9% ± 5.2% in the non-carperitide group, while the major adverse cardiovascular and cerebrovascular events (MACCE)-free rate at 2 years postoperatively was 90.5% ± 3.7% in the carperitide group and 67.7% ± 5.8% in the non-carperitide group. Conclusions: These findings suggest that carperitide improves the early postoperative outcome in dialysis patients undergoing cardiac surgery, as has already been demonstrated in non-dialysis patients. An early postoperative cardioprotective effect of carperitide and improvement of renal function in oliguric patients might have contributed to this outcome. However, this was a retrospective study, so a prospective investigation is required to demonstrate the mechanisms involved. In addition, further evaluation of the long-term results would be desirable. Keywords: dialysis, chronic kidney disease, coronary artery bypass grafting, cardiac surgery
Introduction Recently, performance of cardiac surgery in hemodialysis patients has increased, but the early mortality rate is still high.1–11) In addition, many patients develop major cardiac and cerebrovascular events or infections after discharge and the long-term results are not satisfactory. The Department of Cardiovascular Surgery, Nihon University School of Medicine, Tokyo, Japan Received: July 27, 2015; Accepted: March 15, 2016 Corresponding author: Akira Sezai, MD, PhD. The Department of Cardiovascular Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-Ku, Tokyo 173-8610, Japan Email: [email protected] ©2016 The Editorial Committee of Annals of Thoracic and Cardiovascular Surgery. All rights reserved.
Ann Thorac Cardiovasc Surg Vol. 22, No. 4 (2016)
Yeo et al. reported that the operative mortality of coronary artery bypass grafting (CABG) increased significantly with each stage of chronic kidney disease (CKD), and patients in stage 5 (estimated glomerular filtration rate (eGFR) 75 years Gender (male: female) Body surface area (m2) Diagnosis IHD Valvular disease Aortic disease IHD + valve Valve + aorta Cause of CKD Diabetic nephropathy Chronic glomerulonephritis Nephrosclerosis Others Anuria Oliguria Emergency or urgent Re-operation Risk factors Diabetes mellitus Hypertension Dyslipidemia Obesity Smoking LV dysfunction COPD Cerebrovascular disease PAD Previous PCI Ejection fraction (%) Duration of HD (years)
Carperitide group
Non-carperitide group
63 65.4 ± 9.4 11 (17%) 49:14 1.60 ± 0.16
65 67.2 ± 8.2 14 (22%) 44:21 1.54 ± 0.16
p value
43 4 0 12 1
41 15 3 6 0
47 11 2 3 39 24 12 (19%) 1 (2%)
41 21 2 1 50 15 19 (29%) 2 (3%)
42 (67%) 55 (87%) 21 (33%) 18 (29%) 23 (37%) 20 (32%) 3 (5%) 2 (3%) 19 (30%)
40 (62%) 52 (80%) 17 (26%) 8 (12%) 22 (34%) 19 (29%) 0 (0%) 5 (8%) 16 (25%)
0.545 0.265 0.374 0.022 0.752 0.757 0.075 0.261 0.482
11 (17%) 51.6 ± 14.7 6.23 ± 3.86
13 (20%) 51.5 ±14.3 6.97 ±4.73
0.713 0.891 0.251
0.254 0.561 0.201 0.06 0.671
0.186
0.065 0.179 0.578
IHD: ischemic heart disease; CKD: chronic kidney disease; LV: left ventricular; COPD: chronic obstructive pulmonary disease; PAD: peripheral artery disease; PCI: percutaneous coronary intervention; HD: hemodialysis
previously performed several prospective trials to investigate the effects of carperitide in non-dialysis patients undergoing cardiac surgery, and we have reported that this drug has a cardioprotective effect, a renoprotective effect, counteracts the adverse influence of cardiopulmonary bypass, inhibits the renin-angiotensin-aldosterone system (RAAS), inhibits left ventricular remodeling, and has an antiarrhythmic effect.13–19) With regard to the renoprotective effect of carperitide, we have found both acute and longterm avoidance of dialysis, RAAS inhibition, and a potent natriuretic action in non-dialysis patients with CKD.16,17) Accordingly, we performed the present retrospective investigation to assess the effectiveness of carperitide in dialysis patients undergoing cardiac surgery. 238
Patients and Methods One hundred and twenty-eight hemodialysis patients underwent cardiac surgery at Nihon University Itabashi Hospital between April 2001 and March 2013, including 63 patients who received carperitide infusion during surgery (carperitide group) and 65 patients who did not receive carperitide (non-carperitide group). All of the patients had chronic kidney disease and no patients receiving acute or sub-acute hemodialysis were included in this study. A 2-year retrospective investigation of postoperative outcomes was performed in this cohort with a 100% follow-up rate. The details of the study were explained to each patient and informed consent was obtained. Ann Thorac Cardiovasc Surg Vol. 22, No. 4 (2016)
Efficacy of Carperitide for Hemodialysis Patients
Infusion of carperitide was initiated at 0.05 ag/min/kg at the start of cardiopulmonary bypass. Once postoperative oral medication was commenced, the infusion rate was reduced to 0.02 µg/min/kg. The infusion rate was further reduced to 0.01 µg/min/kg 12 h later, and carperitide was discontinued after another 12 h. As shown in Table 1, there were no significant differences of background factors between the carperitide and non-carperitide groups. In patients having elective surgery, dialysis was performed on the day before the operation. Intraoperative hemofiltration was performed in all patients and hemodialysis was resumed 1 or 2 days after surgery based on factors such as the severity of pulmonary congestion on chest X-ray films and the serum potassium level. The following preoperative factors were examined for an influence on outcomes: age ≥75 years, gender, shock, emergency surgery, preoperative use of an intra-aortic balloon pump (IABP), previous percutaneous coronary intervention, re-operation, hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, peripheral artery disease (PAD), chronic obstructive pulmonary disease (COPD), anuria, ejection fraction (EF)
