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Risk Factors Affecting Survival in Heart Transplant Patients
Risk Factors Affecting Survival in Heart Transplant Patients L. Almenar, M.L. Cardo, L. Martı´nez-Dolz, C. Garcı´a-Palomar, J. Rueda, E. Zorio, M.Á. Arnau, A. Osa, and M. Palencia ABSTRACT Background. Certain cardiovascular risk factors have been linked to morbidity and mortality in heart transplant (HT) patients. The sum of various risk factors may have a large cumulative negative effect, leading to a substantially worse prognosis and the need to consider whether HT is contraindicated. The objective of this study was to determine whether the risk factors usually available prior to HT result in an excess mortality in our setting that contraindicates transplantation. Materials and methods. Consecutive patients who underwent heart transplantation from November 1987 to January 2004 were included. Heart–lung transplants, retransplants, and pediatric transplants were excluded. Of the 384 patients, 89% were men. Mean age was 52 years (range, 12 to 67). Underlying disease included ischemic heart disease (52%), idiopathic dilated cardiomyopathy (36%), valvular disease (8%), and other (4%). Variables considered risk factors were obesity (BMI ⬎25), dyslipidemia, hypertension, prior thoracic surgery, diabetes, and history of ischemic heart disease. Survival curves by number of risk factors using Kaplan-Meier and log-rank for comparison of curves. Results. Overall patient survival at 1, 5, 10, and 13 years was 76%, 68%, 54%, and 47%, respectively. Survival at 10 years, if fewer than two risk factors were present, was 69%; 59% if two or three factors were present; and 37% if more than three associated risk factors were present (P ⫽ .04). Conclusions. The presence of certain risk factors in patients undergoing HT resulted in lower survival rates. The combination of various risk factors clearly worsened outcomes. However, we do not believe this should be an absolute contraindication for transplantation.
H
EART TRANSPLANTATION (HT) has emerged as the therapy of choice for patients with severe irreversible heart disease refractory to medical therapy.1 Improvements in immunosuppressive therapy and management of infectious complications have increased short- and long-term survival rates of HT patients and reduced contraindications such as age to include patients on the waiting list for HT. This has led to an increase in the number of patients who are candidates for HT without a corresponding increase in the number of donors. Therefore it is important to study the factors affecting survival to select the most suitable candidates for transplantation. The objective of our study was to assess whether the most important classic cardiovascular risk factors (diabetes mellitus, [DM], hypertension, obesity) and others such as a history of ischemic heart disease or prior thoracic surgery resulted in an excess mortality in our setting that contraindicated heart transplantation.
MATERIALS AND METHODS We studied 384 consecutive patients who underwent heart transplantation from November 1987 to January 2004. Heart–lung transplants, retransplants, and pediatric transplants were excluded. Eighty-nine percent of patients were men and 11% were women. Mean age was 52 years (range, 12 to 77 years). The underlying heart disease in over half of patients was ischemic heart disease (52%), followed by idiopathic dilated cardiomyopathy (36%), valvular heart disease (8%), and other causes (4%). The variables considered as risk factors were obesity (body mass index [BMI] ⬎25); dyslipidemia; DM; arterial hypertension; prior thoracic surgery; and a history of ischemic heart disease.
From the Department of Cardiology, La Fe University Hospital, Valencia, Spain. Address reprint requests to Luis Almenar Bonet, Avd. Primado Reig 189-37, 46020 Valencia, Spain. E-mail: lu.almenarb5@ comv.es
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.09.160
Transplantation Proceedings, 37, 4011– 4013 (2005)
4011
4012
ALMENAR, CARDO, MARTÍNEZ-DOLZ ET AL
Fig 1. Overall patient survival curve. The Kaplan-Meier method was used to calculate survival curves and the log-rank test for comparison of the curves. A P-value ⬍ .05 was considered statistically significant in all cases.
than two risk factors (69%), two risk factors (59%), and more than two risk factors (39%; P ⫽ .004). DISCUSSION
RESULTS
As can be seen in Figure 1, the probabilities of survival at 1, 5, and 10 years were 85%, 77% and 60% respectively. Figure 2 shows the survival curves (eight curves for zero to seven risk factors) according to the number of risk factors. There were differences between the curves (P ⫽ .04). Figure 2 show the survival curves for the presence of fewer
Fig 2. Survival curves by number of risk factors.
Overall survival in our series was 85% at 1 year and 77% and 60% at 5 and 10 years, respectively. In Spain, the expected survival for a heart transplant patient is 75% at 1 year and 60% at 5 years. Mean survival time (Time until survival is 50%) was 8 years 6 months. Actuarial survival in national and international HT registries is similar in the medium and long term, with an annual decrease of approximately 4%.2
RISK FACTORS AFFECTING SURVIVAL
4013
Fig 3. Survival curve by presence of fewer than two, two, or more than two risk factors.
In our study, we found that the sum of various risk factors had a negative impact on survival. We did not find any study in the literature jointly analyzing all the factors in our study, although they were considered separately (Fig 3).3 Diabetes Mellitus
One of the studies analyzing the impact of DM on survival of HT patients4 analyzed 773 consecutive HT patients, 140 with DM and 663 without. Patients with DM were older and had a higher incidence of ischemic cardiomyopathy compared to those without DM. Ten-year survival in patients with DM was 40% and 58% in patients without DM, log-rank ⬍0.025. Ischemic Heart Disease
There are few articles5,6 in the literature analyzing the impact of a history of ischemic heart disease on survival of HT patients. In this study,5 a multivariate analysis was used to compare factors predicting 10-year survival. For this, a comparison was done between two groups of HT patients: one group consisted of patients who survived ⬎6 months and ⬍10 years and the other of patients who survived ⬎10 years. One of the factors that had a negative impact on survival was a history of ischemic heart disease. Graft vascular disease is the third leading cause of death after infections and rejection in the first year after HT and the first leading cause in the following years. BMI7 and dyslipidemia8 act as predictors for the development of graft vascular disease and therefore as risk factors for survival. Prior Cardiac Surgery
In this study,9 702 consecutive patients who underwent HT between 1984 and 1997 were analyzed retrospectively for
the causes of death at 30 days and at 5 years, and the only factor that coincided with the increased mortality found in our study was prior cardiac surgery. In summary, we concluded that the risk factors analyzed in our study have a significant influence on long-term survival. However, they should not be considered an absolute contraindication for transplantation but should be assessed individually in each case. REFERENCES 1. Castro PF, Bourge RC, Jalil JE, et al: Selección y evolución de pacientes candidatos a trasplante cardiaco. Rev Esp Cardiol 52: 604, 1999 2. Almenar L, Vicente JL, Torregrosa S, et al: Variables predictoras de mortalidad precoz tras el trasplante cardiaco ortotópico en adultos. Rev Esp Cardiol 50:628, 1997 3. Pulpón L, Almenar L, Crespo MG, et al: Guı´as de actuación clinica de la Sociedad Española de Cardiologia. Trasplante cardiaco y de corazón-pulmones. Rev Esp Cardiol 52:821– 839, 1999 4. Czerny M, Sahin V, Fasching P, et al: The impact of diabetes mellitus at time of heart transplantation on long-term survival. Diabetologia 45:1498, 2002 5. Shiba N, Chan MC, Valantine HA, et al: Longer-term risks associated with 10-year survival after heart transplantation in the cyclosporine era. Heart Lung Transplant 22:1098, 2003 6. Ranjit J, Hiranya A, Rajasinghe, et al: Factors affecting long-term survival (⬎10 years) after cardiac transplantation in the cyclosporine era. J Am Coll Cardiol 37:189, 2001 7. Vasslli G, Gallino A, Weis M, et al: Alloinmunity and nonimmunologic risk factors in cardiac allograft vasculopathy. Eur Heart J 24:1180, 2003 8. Kapadia SR, Nissen SE, Ziada KM, et al: Impact of lipid abnormalities in development and progression transplant coronary disease: a serial intravascular ultrasound. J Am Coll Cardiol 38:206, 2001 9. Zuckermann AO, Ofner P, Holzinger C, et al: Pre-and early postoperative risk factors for death after cardiac transplantation: a single center analysis. Transpl Int 13:28, 2000
H
EART TRANSPLANTATION (HT) has emerged as the therapy of choice for patients with severe irreversible heart disease refractory to medical therapy.1 Improvements in immunosuppressive therapy and management of infectious complications have increased short- and long-term survival rates of HT patients and reduced contraindications such as age to include patients on the waiting list for HT. This has led to an increase in the number of patients who are candidates for HT without a corresponding increase in the number of donors. Therefore it is important to study the factors affecting survival to select the most suitable candidates for transplantation. The objective of our study was to assess whether the most important classic cardiovascular risk factors (diabetes mellitus, [DM], hypertension, obesity) and others such as a history of ischemic heart disease or prior thoracic surgery resulted in an excess mortality in our setting that contraindicated heart transplantation.
MATERIALS AND METHODS We studied 384 consecutive patients who underwent heart transplantation from November 1987 to January 2004. Heart–lung transplants, retransplants, and pediatric transplants were excluded. Eighty-nine percent of patients were men and 11% were women. Mean age was 52 years (range, 12 to 77 years). The underlying heart disease in over half of patients was ischemic heart disease (52%), followed by idiopathic dilated cardiomyopathy (36%), valvular heart disease (8%), and other causes (4%). The variables considered as risk factors were obesity (body mass index [BMI] ⬎25); dyslipidemia; DM; arterial hypertension; prior thoracic surgery; and a history of ischemic heart disease.
From the Department of Cardiology, La Fe University Hospital, Valencia, Spain. Address reprint requests to Luis Almenar Bonet, Avd. Primado Reig 189-37, 46020 Valencia, Spain. E-mail: lu.almenarb5@ comv.es
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.09.160
Transplantation Proceedings, 37, 4011– 4013 (2005)
4011
4012
ALMENAR, CARDO, MARTÍNEZ-DOLZ ET AL
Fig 1. Overall patient survival curve. The Kaplan-Meier method was used to calculate survival curves and the log-rank test for comparison of the curves. A P-value ⬍ .05 was considered statistically significant in all cases.
than two risk factors (69%), two risk factors (59%), and more than two risk factors (39%; P ⫽ .004). DISCUSSION
RESULTS
As can be seen in Figure 1, the probabilities of survival at 1, 5, and 10 years were 85%, 77% and 60% respectively. Figure 2 shows the survival curves (eight curves for zero to seven risk factors) according to the number of risk factors. There were differences between the curves (P ⫽ .04). Figure 2 show the survival curves for the presence of fewer
Fig 2. Survival curves by number of risk factors.
Overall survival in our series was 85% at 1 year and 77% and 60% at 5 and 10 years, respectively. In Spain, the expected survival for a heart transplant patient is 75% at 1 year and 60% at 5 years. Mean survival time (Time until survival is 50%) was 8 years 6 months. Actuarial survival in national and international HT registries is similar in the medium and long term, with an annual decrease of approximately 4%.2
RISK FACTORS AFFECTING SURVIVAL
4013
Fig 3. Survival curve by presence of fewer than two, two, or more than two risk factors.
In our study, we found that the sum of various risk factors had a negative impact on survival. We did not find any study in the literature jointly analyzing all the factors in our study, although they were considered separately (Fig 3).3 Diabetes Mellitus
One of the studies analyzing the impact of DM on survival of HT patients4 analyzed 773 consecutive HT patients, 140 with DM and 663 without. Patients with DM were older and had a higher incidence of ischemic cardiomyopathy compared to those without DM. Ten-year survival in patients with DM was 40% and 58% in patients without DM, log-rank ⬍0.025. Ischemic Heart Disease
There are few articles5,6 in the literature analyzing the impact of a history of ischemic heart disease on survival of HT patients. In this study,5 a multivariate analysis was used to compare factors predicting 10-year survival. For this, a comparison was done between two groups of HT patients: one group consisted of patients who survived ⬎6 months and ⬍10 years and the other of patients who survived ⬎10 years. One of the factors that had a negative impact on survival was a history of ischemic heart disease. Graft vascular disease is the third leading cause of death after infections and rejection in the first year after HT and the first leading cause in the following years. BMI7 and dyslipidemia8 act as predictors for the development of graft vascular disease and therefore as risk factors for survival. Prior Cardiac Surgery
In this study,9 702 consecutive patients who underwent HT between 1984 and 1997 were analyzed retrospectively for
the causes of death at 30 days and at 5 years, and the only factor that coincided with the increased mortality found in our study was prior cardiac surgery. In summary, we concluded that the risk factors analyzed in our study have a significant influence on long-term survival. However, they should not be considered an absolute contraindication for transplantation but should be assessed individually in each case. REFERENCES 1. Castro PF, Bourge RC, Jalil JE, et al: Selección y evolución de pacientes candidatos a trasplante cardiaco. Rev Esp Cardiol 52: 604, 1999 2. Almenar L, Vicente JL, Torregrosa S, et al: Variables predictoras de mortalidad precoz tras el trasplante cardiaco ortotópico en adultos. Rev Esp Cardiol 50:628, 1997 3. Pulpón L, Almenar L, Crespo MG, et al: Guı´as de actuación clinica de la Sociedad Española de Cardiologia. Trasplante cardiaco y de corazón-pulmones. Rev Esp Cardiol 52:821– 839, 1999 4. Czerny M, Sahin V, Fasching P, et al: The impact of diabetes mellitus at time of heart transplantation on long-term survival. Diabetologia 45:1498, 2002 5. Shiba N, Chan MC, Valantine HA, et al: Longer-term risks associated with 10-year survival after heart transplantation in the cyclosporine era. Heart Lung Transplant 22:1098, 2003 6. Ranjit J, Hiranya A, Rajasinghe, et al: Factors affecting long-term survival (⬎10 years) after cardiac transplantation in the cyclosporine era. J Am Coll Cardiol 37:189, 2001 7. Vasslli G, Gallino A, Weis M, et al: Alloinmunity and nonimmunologic risk factors in cardiac allograft vasculopathy. Eur Heart J 24:1180, 2003 8. Kapadia SR, Nissen SE, Ziada KM, et al: Impact of lipid abnormalities in development and progression transplant coronary disease: a serial intravascular ultrasound. J Am Coll Cardiol 38:206, 2001 9. Zuckermann AO, Ofner P, Holzinger C, et al: Pre-and early postoperative risk factors for death after cardiac transplantation: a single center analysis. Transpl Int 13:28, 2000