Comparison of Heart Transplantation Patients with Ischemic and Idiopathic Dilated Cardiomyopathy

Comparison of Heart Transplantation Patients with Ischemic and Idiopathic Dilated Cardiomyopathy H. Gungor, E. Oguz, M.F. Ayik, S. Ertugay, C. Engin, T. Yagdi, S. Nalbantgil, M. Zoghi, and M. Ozbaran ABSTRACT Objective. We retrospectively analyzed our data to compare preoperative demographic, laboratory, echocardiographic, hemodynamic findings mortality and survival rates of heart transplantation patients with ischemic (ICM) and idiopathic dilated (IDCM) cardiomyopathy. Methods. The data of 144 patients transplanted from February 1998 to January 2011 were analyzed. 38 patients with ischemic ICM and 86 patients with IDCM were compared. Results. Recipient age, preoperative creatinine, recipient body mass index, intraoperative cross-clamp time, donor male sex ratio, recipient male sex ratio, hyperlipidemia ratio, and previous nitrate use were significantly higher and left ventricular end systolic diameter significantly lower in patients with ICM. Major causes of death after heart transplantation were infections (31.9%), right ventricle failure (14.8%), and sudden cardiac death (14.8%). Causes of death were not different between the groups. Overall mortality in the entire population was 37.9% (47/124), and it was not different between the groups (39.5% vs 37.2%; P ⫽ .48). Early mortality (⬍30 days) rate was 11.2% (14/124), late mortality rate was 26.6% (33/124), and no statistically significant difference was observed between the groups. Survival analysis showed that ICM patients were not associated with worse survival compared with IDCM (71.1% vs 81.1% after 1 year, 68.1% vs 73.0% at 2 years, and 54.2% vs 62.3% at 5 years; log rank ⫽ 0.57). Multivariate analysis showed that the only predictor of mortality was preoperative urea level and that heart failure etiology was not a predictor of this end point. Conclusions. Patients with ICM had similar survival and mortality rate compared with IDCM. espite advances in therapeutic modalities in recent years, heart failure (HF) remains a common cause of cardiovascular morbidity and mortality.1,2 Ischemic coronary heart disease is the major cause of HF.3,4 Studies have shown that prognosis, survival, outcome, and response to treatment of HF due to ischemic etiology is worse than HF due to nonischemic etiology.5–9 Heart transplantation is a proven and acceptable treatment modality for end-stage HF in experienced centers with similar clinical outcomes10 –12 for ischemic cardiomyopathy (ICM) and idiopathic dilated cardiomyopathy (IDCM), 2 major indications for heart transplantation. Despite earlier studies showing that prognosis, survival, outcome, and response to treatment of HF due to ischemic etiology is worse than HF due to nonischemic etiology, few data exist regarding HF etiology in heart transplantation patients.

D

The aim of the present study was to investigate the difference in preoperative characteristics, mortality, and survival rate of heart transplantation patients with ICM and IDCM. METHODS One hundred forty-four patients with mean age 40.2 ⫾ 14.3 years of 112 men transplanted from February 1998 to January 2011 were studied and analyzed. Preoperative variables were considered From the Department of Cardiology (H.G.), Mus State Hospital, Mus, Turkey; and the Department of Cardiovascular Surgery (E.O., M.F.A., S.E., C.E., T.Y., M.O.) and Department of Cardiology (S. N., M. Z.), Ege University, Izmir, Turkey. Address reprint requests to Hasan Gungor, MD, Mus State Hospital, Cardiology, Mus, Turkey. E-mail: drgungorhasan@ yahoo.com

© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710

0041-1345/–see front matter doi:10.1016/j.transproceed.2011.09.073

Transplantation Proceedings, 43, 3847–3850 (2011)

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GUNGOR, OGUZ, AYIK ET AL

including patient demographics, previous medications, and laboratory, hemodynamic, and echocardiographic parameters. Patients affected by valvular, restrictive, arrhythmogenic right ventricular dysplasia or hypertrophic cardiomyopathies were excluded. 38 patients with ICM (mean age 49.0 ⫾ 8.5 years, 37 men, 16 prior coronary artery bypass graft) and 86 patients with IDCM idiopathic (mean age 37.8 ⫾ 14.3 years, 63 men) were compared.

Statistical Analysis All data were analyzed with the use of SPSS for Windows version 17.0 software (SPSS, Chicago, IL, USA). Qualitative data are presented as mean ⫾ SD, and quantitative data are presented as percentage (%). Categoric data between groups were compared with the chi-square test, and continuous data were analyzed with Mann-Whitney U and independent Student t tests. A multiple logistic regression model was constructed to determine independent predictors of mortality. Survival analysis was accomplished using Kaplan-Meier analysis and compared with log-rank test. A P value of ⬍.05 was considered to be statistically significant.

RESULTS

ICM patients were significantly older than IDCM patients (49.0 ⫾ 8.5 vs 37.8 ⫾ 14.3 years; P ⬍ .001). Preoperative creatinine (1.20 ⫾ 0.35 vs 0.99 ⫾ 0.27 mg/dL; P ⫽ .001), recipient body mass index (24.5 ⫾ 3.3 vs 22.7 ⫾ 4.3 kg/m2; P ⫽ .02) and intraoperative cross-clamp time (89.9 ⫾ 31.3 vs 81.5 ⫾ 13.4 minutes; P ⫽ .04) were significantly higher in patients with ICM. Preoperative left ventricular end-systolic diameter (LVESD) was significantly lower (5.6 ⫾ 0.7 vs 6.1 ⫾ 1.1 cm; P ⫽ .02) in ICM group. Donor male sex, recipient male sex, hyperlipidemia ratio, and previous nitrate use were significantly higher in the ICM group. No statistically significant differences were observed in other demographics, laboratory, echocardiography, and catheteterization findings, and previous medications (Tables 1–3). Major causes of death after heart transplantation were infections (31.9%), right ventricle failure (14.8%), and sudden cardiac death (14.8%). Causes of death were not different between the groups. Overall mortality in the entire population was 37.9% (47/124), and it was not different between the groups (39.5% vs 37.2%; P ⫽ .48). Early Table 1. Comparison of Baseline Characteristics

Variables

Ischemic Group (n ⫽ 38)

Nonischemic Group (n ⫽ 86)

Recipient age (y) Recipient sex (% male) Recipient BMI (kg/m2) Donor age (y) Donor gender (% male) Donor weight (kg) Donor height (cm) Recipient DM (%) Recipient HT (%) Recipient HLP (%)

49.0 ⫾ 8.5 97.0 24.5 ⫾ 3.3 28.8 ⫾ 10.9 94.7 73.5 ⫾ 6.5 174.7 ⫾ 4.5 7.9 5.3 18.4

37.8 ⫾ 14.3 73.3 22.7 ⫾ 4.3 28.2 ⫾ 13.1 76.7 69.7 ⫾ 14.4 171.2 ⫾ 8.3 5.8 2.3 2.3

P Values

⬍.001 .001 .02 .82 .011 .16 .02 .46 .35 .004

Abbreviations: BMI, body mass index; DM, diabetes mellitus; HT, hypertension; HLP, hyperlipidemia.

Table 2. Medications Before Heart Transplantation Variables (%)

Ischemic Group (n ⫽ 38)

Nonischemic Group (n ⫽ 86)

P Values

Nitrate Beta-blocker ACE inhibitor Furosemide ASA Digital Amiodarone Varfarin Inotropic agent IABP LVAD ICD

34.2 10.5 65.8 92.1 68.4 55.3 23.3 39.5 52.6 2.6 9.3 10.5

4.7 4.7 55.8 95.3 60.5 57.0 21.1 40.7 36.5 3.5 13.2 8.1

⬍.001 .20 .20 0.37 0.26 0.51 0.49 0.53 0.07 0.64 0.36 0.45

Abbreviations: ACE, angiotensin-converting enzyme; ASA, acetylsalicylic acid; IABP, intra-aortic balloon pump; LVAD, left ventricular asist device; ICD, implantable cardioverter defibrillator.

mortality (⬍30 days) rate was 11.2% (14/124) and late mortality rate was 26.6% (33/124), and there was no statistically significant difference between the groups. Survival analysis showed that ICM patients were not associated with worse survival compared with IDCM patients (71.1% vs 81.1% after 1 year, 68.1% vs 73.0% at 2 years, and 54.2% vs 62.3% at 5 years; log rank ⫽ 0.57; Fig 1). Multivariate analysis showed that the only predictor of mortality was preoperative urea level (Odds ratio 0.005, 95% confidence interval 0.001– 0.010; P ⫽ .015) and that heart failure etiology was not a predictor of this end point. DISCUSSION

In this study we found that heart transplantation patients with ICM had higher creatinine level, body mass index, Table 3. Laboratory, Echocardiographic, and Hemodynamic Parameters Variables

Urea (mg/dL) Creatinine (mg/dL) Creatinine clearance (mL/min) TC (mg/dL) HDL (mg/dL) LDL (mg/dL) TG (mg/dL) LVEF (%) RVEF (%) SPAP (mm Hg) PCWP (mm Hg) MPAP (mm Hg) CPB (min) X-Clamp (min) Ischemia time (min)

Ischemic Group (n ⫽ 38)

Nonischemic Group (n ⫽ 86)

P Values

48.9 ⫾ 31.9 1.2 ⫾ 0.3 62.2 ⫾ 34.6

48.0 ⫾ 22.9 1.0 ⫾ 0.3 73.3 ⫾ 29.7

.86 ⬍.001 .13

176.7 ⫾ 75.9 40.0 ⫾ 21.4 99.5 ⫾ 36.7 141.5 ⫾ 101.9 22.1 ⫾ 4.1 36.9 ⫾ 14.9 45.3 ⫾ 15.6 23.9 ⫾ 9.4 33.1 ⫾ 11.8 124.8 ⫾ 27.3 89.9 ⫾ 31.3 188.2 ⫾ 67.2

159.8 ⫾ 51.1 35.2 ⫾ 13.0 99.8 ⫾ 39.0 116.8 ⫾ 63.8 21.9 ⫾ 7.3 34.8 ⫾ 12.5 42.2 ⫾ 15.0 23.6 ⫾ 7.7 32.2 ⫾ 10.0 119.2 ⫾ 44.3 81.5 ⫾ 13.4 170.6 ⫾ 59.3

.19 .17 .97 .14 .91 .43 .30 .87 .69 .48 .04 .15

Abbreviations: CPB, cardiopulmonary bypass; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LVEF, left ventricular ejection fraction; MPAP, mean pulmonary arterial pressure; PCWP, pulmonary capillary wedge pressure; RVEF, right ventricular ejection fraction; SPAP, systolic pulmonary arterial pressure; TC, total cholesterol; TG, triglyceride.

HEART TRANSPLANTATION ETIOLOGY

Fig 1. Cumulative survival between the groups.

longer intraoperative cross-clamp time, previous nitrate treatment, male sex, and hyperlipidemia. Patients with ICM had similar survival and mortality rate compared with IDCM patients. ICM and IDCM, constitute ⬃90% of indications for heart transplantation. Patients with ICM are older and have longer history of illness with multiple ischemic attacks and recurrent revascularization procedures. The atherosclerotic process affects cerebral, renal, splanchnic and lower-extremity vessels as a systemic disease. It is known that patients with ICM diagnosis have worse prognosis and long-term outcomes than those with IDCM.13–15 IDCM patients are usually younger, with a shorter history of disease than ICM group. Transplantation can be performed with a more dramatic hemodynamic picture with rapidly developing cardiac failure in this patients. However, there are few publications comparing ICM and IDCM group. Apart from the annual report of International Society of Heart and Lung Transplantation (ISHLT), there are limited data comparing ICM and IDCM patients. According to ISHLT registries of 2010, the average life expectancy in the IDCM group is higher than the ICM group (11.0 vs 9.3 years; P ⬍ .001) with higher survival rate.16 Martinelli et al13 evaluated 128 heart transplanted patients with ICM and 147 with IDCM. They showed that ICM patients, before the transplantation procedure, presented with less compromised hemodynamics requiring less inotropic support and less frequent mechanical assistance. This group, after the procedure, needed more mechanical assistance, inotropic support, and prolonged mechanical ventilation with a longer stay in the intensive care unit and hospital. Also, in-hospital mortality rate was 2-fold higher in the ICM group. Five-year actuarial survival rate was higher in the IDCM group. In conclusion, they reported that patients with ICM have a more critical stay in hospital and long-term postoperative course and a worse survival rate.13

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Lanza et al17 divided 54 heart transplantation patients into 4 groups: 29 patients with ICM, 17 patients with IDCM, 4 patients with rheumatic heart disease (RHD), and 4 patients with mixed or other pathology. The RHD group had a survival rate for a mean period ⬎3 times as long as those with either IDCM or ICM. Although IDCM patients were on average more than a decade younger than those in other groups, they had a lower survival rate. There was a higher incidence of death from chronic rejection in patients with ICM; there was also a higher incidence of thromboembolic episodes in these patients. In addition, major infections were more than twice as frequent in ICM patients as in IDCM patients. RHD is considered to be a favorable survival factor compared with ICM, with IDCM being particularly unfavorable (17). In an other study,18 133 patients with ICM and 87 patients with IDCM were analyzed and compared. The operative mortality was similar in patients with ICM compared with IDCM patients. No differences were observed in intracardiac pressures or incidence of renal dysfunction, infection, or malignancy between the 2 groups. The incidence of peripheral vascular events was significantly higher in ICM recipients. The survival at 1, 5, and 10 years, respectively, was 77%, 62%, and 39% for ICM recipients compared with 85%, 82%, and 80% for IDCM recipients (P ⫽ .7; P ⬍ .0001; and P ⬍ .0001). According to these findings after heart transplantation, midterm and long-term outcomes are significantly better for IDCM than ICM patients.18 In contrast, our data showed that patients with ICM had similar survival and mortality rate compared with IDCM patients. Further research is required to obtain a clear idea about survival and mortality rate of ICM and IDCM groups.

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GUNGOR, OGUZ, AYIK ET AL 13. Martinelli L, Rinaldi M, Pederzolli C et al: Different results of cardiac transplantation in patients with ischemic and dilated cardiomyopathy. Eur J Cardiothorac Surg 9:644, 1995 14. Jamleson SW, Oyer PE, Baldwin J, et al: Heart transplantation for end-stage ischemic heart disease: the Stanford experience. J Heart Transplant 3:224, 1984 15. Kaye MP. The Registry of the International Society of Heart and Lung Transplantation: 9th official report—1992. J Heart Lung Transplant 11:599, 1992 16. Stehlik J, Edwards LB, Kucheryavaya AY, et al: The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult heart transplant report—2010. J Heart Lung Transplant 29:1089, 2010 17. Lanza RP, Cooper DK, Boyd ST, et al: Comparison of patients with ischemic, myopathic, and rheumatic heart diseases as cardiac transplant recipients. Am Heart J 107:8, 1984 18. Aziz T, Burgess M, Rahman AN, et al: Cardiac transplantation for cardiomyopathy and ischemic heart disease: differences in outcome up to 10 years. J Heart Lung Transplant 20:525, 2001