Survival Beyond 10 Years Following Heart Transplantation: The Cleveland Clinic Foundation Experience

doi:10.1016/j.transproceed.2005.10.021

Transplantation Proceedings

Volume 37, Issue 10, December 2005, Pages 4509-4512

https://doi.org/10.1016/j.transproceed.2005.10.021 Get rights and content

Abstract

Background

Long-term survival after heart transplantation is a desirable although challenging goal.

Methods

We analyzed clinical outcomes in the cohort of 170 patients who have undergone heart transplantation at The Cleveland Clinic Foundation and survived >10 years.

Results

We found 10-year and 15-year survival rates of 54% and 41%, respectively, in these patients, but there was also a high incidence of complications, such as hypertension, renal dysfunction, transplant vasculopathy, and malignancy.

Conclusions

Long-term survival following cardiac transplantation is possible although complications are frequent. Beyond 10 years, malignancy is a major cause of death.

Section snippets

Patient Population

Between August 1, 1984 and May 31, 2004, a total of 1089 adult patients underwent HTx at the Cleveland Clinic Foundation. To study patients who survived beyond 10 years, we evaluated a consecutive cohort of 325 patients who underwent transplantation between August 1, 1984 and May 31, 1994. A total of 170 patients survived more than 10 years. We excluded 11 patients who underwent retransplantation during the first 10-year period.

Data Collection

Our data was retrieved from the Cleveland Clinic Foundation Heart

Survival Analysis

Kaplan-Meier survival plot of all 325 adult patients who underwent HTx between August 1984 and May 1994 is shown in Fig 1. The 10-year and 15-year Kaplan-Meier survival rates were 54% and 41%, respectively. A total of 170 patients survived beyond 10 years after cardiac transplantation and constitute the cohort of the study. Among the cohort of 170 patients, 3 patients comprise the oldest living transplant recipients at the age of 80 years and 1 patient constitutes the longest living patient who

Discussion

This study shows that the 10-year and 15-year survival rates of all patients who underwent transplantation between August 1984 and May 1994 at our institution were 54% and 41%, respectively. Based on the Organ Procurement and Transplant Network database, the reported 10-year and 15-year nationwide survival rates are 48% and 30%, respectively.

Although long-term survival is associated with high quality of life in the majority of the patients, HTx has a high complication rate in long-term

Conclusion

Long-term survival following HTx is not uncommon, although it is associated with a high incidence of chronic complications, including hypertension, hyperlipidemia, diabetes mellitus, ESRD, GCAD, and malignancy. Beyond 10 years, malignancy is a major cause of death.

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Cited by (25)

Incidence of temporary mechanical circulatory support before heart transplantation and impact on post-transplant outcomes
2018, Journal of Heart and Lung Transplantation
Proposed changes to the United Network for Organ Sharing heart transplant allocation protocol will prioritize patients receiving temporary mechanical circulatory support (tMCS), including extracorporeal membrane oxygenation (ECMO), percutaneous ventricular assist devices (PVADs), and intra-aortic balloon pumps (IABPs). We sought to evaluate contemporary trends in the incidence and outcomes of patients who required tMCS during the hospitalization before heart transplantation.
Using the National Inpatient Sample from 1998 to 2014, we identified 6,892 patients who received an orthotopic heart transplant and classified them by pre-transplant ECMO, PVAD, or IABP placement or no pre-transplant tMCS. We compared baseline characteristics and in-hospital outcomes between patients who underwent pre-transplant ECMO, PVAD, or IABP and patients who did not receive tMCS before heart transplantation.
Of patients who underwent heart transplantation, 456 (6.6%) received tMCS before transplant. During the study period, the use of tMCS more than doubled, from 17 cases per year from 1998 to 2002 to 40 cases per year from 2012 to 2014 (p < 0.001 for trend). Of patients with tMCS, 341 (74.8%) were supported by IABP, 130 (28.5%) were supported by ECMO, and 21 (4.6%) were supported by PVAD. Before 2007, patients who required tMCS had higher in-hospital mortality than patients who did not require tMCS before transplant (14.3% vs 7.5%, p = 0.05). In the subsequent era (2007 to 2014), mortality was not significantly different (4.7% vs 5.1%, p = 0.9). Hospital mortality improved over time for all patients but most significantly in patients who required tMCS (9.6% absolute risk reduction). However, patients who received tMCS had increased lengths of stays and rates of acute renal, hepatic, and respiratory failure, sepsis, bleeding complications, and surgical reoperations.
The use of tMCS before cardiac transplantation is increasing, with no difference in in-patient post-transplant mortality in the recent era between patients who did and did not receive tMCS but with increased complication rates among those who received tMCS. These data support the use of tMCS before cardiac transplantation in appropriately selected patients. Clinicians should balance the above outcomes when making decisions to implant tMCS, given the impending changes to the United Network for Organ Sharing heart allocation protocol.
Continuous improvement in outcome after heart transplantation — Long-term follow-up after three decades of experience
2017, International Journal of Cardiology
Citation Excerpt :
The survival after HTx in our institution is well in line with the best results published, with very similar survival to those reported from Nantes in France (75%, 58% and 42% survival after 5, 10 and 15 years, respectively) [6] and also well in line with results previously reported from Scandinavia [2]. Moreover, our survival is in concordance with what has been reported from Cleveland Clinic, USA (54% and 42% survival at 10 and 15 years, respectively) [7]. Our results compare favourable to the ISHLT registry, reporting 10-year survival of 40–50% and a median survival below 11 years for the last cohort [8].
Heart transplantation (HTx) has become the standard treatment for patients with end-stage heart disease. We report on the long-term outcome after HTx at our centre and investigate trends in outcome over time.
During the period, between 1984 and 2014, a total of 610 HTx procedures were performed in 595 patients (median 48 years; IQR 31–57 years; range 24 days-71 years; mean 43 years; 75% male) in our institution. Long-term outcome was investigated in the whole cohort, among children (n = 76), bridged with mechanical circulatory support (MCS, n = 131), re-transplanted (n = 17), and concomitant kidney transplantation (n = 12).
Long-term survival was at 1, 5, 10, 15 and 20 years: 86% (95CI 0.83–0.89); 77% (95CI 0.73–0.80); 63% (95CI 0.59–0.68); 48% (95CI 0.43–0.54) and 30% (95CI 0.25–0.36), respectively. The median survival for the whole cohort was 14.1 years. Patients transplanted during the most recent time period (2010–2014) had a better survival compared to previous eras, with a 1- and 3-year survival of 94% (95CI 0.89–0.97) and 93% (95CI 0.88–0.96), respectively (p < 0.001). However, when survival was analysed for long-term MCS (n = 80) versus short term MCS (n = 35), there was a significantly poorer survival for the short-term MCS group (p = 0.001). Independent predictors of long-term mortality included recipient age (p = 0.041); previous smoking (p = 0.034); ischemic heart disease (p = 0.002); and preoperative ventilator therapy (p = 0.004).
We have shown that continuous improvement in outcome after HTx still occurs. In the last time era, direct transplantation from short-term MCS was abandoned, which may have inflicted outcome during the last time era.
Surviving 20 years after heart transplantation: A success story
2014, Annals of Thoracic Surgery
We report the long-term outcomes of patients who survived 20 years or greater after heart transplantation.
From 1985 to 2012, 386 patients underwent heart transplantation at our institution. Patient data were analyzed retrospectively for transplants performed from 1985 to 1991. The Kaplan-Meier method was used for survival analyses.
In total, 133 patients were included. The mean age of the 20-year survivors at transplant was 43.6 ± 11.4 years. The mean ischemic time was 71.2 ± 34.0 minutes. The overall actuarial survival rates at 1, 10, and 20 years were 82.7%, 63.9%, and 55.6%, respectively. The most common causes of death were graft rejection (21%), malignancy (21%), infection (15%), and cardiac allograft vasculopathy (CAV, 14%). After 1, 10, and 20 years, the rejection-free survival rates were 19%, 13%, and 13%, respectively, and the malignancy-free survival rates were 99%, 67%, and 61%. The CAV-free survival rates were 97%, 48%, and 42%, respectively, and the infection-free survival rates were, respectively, 70%, 15%, and 14%. The actuarial diabetes-free survival rates at 1, 10, and 20 years were 85%, 80%, and 79%, respectively. Actuarial hypertension-free survival was 56% after 1 year and 26% after 10 and 20 years. Two patients received a second heart transplant.
A remarkable number of patients survived 20 years or greater after heart transplantation, confirming the procedure as the gold standard for end-stage heart failure. Complications resulting from immunologic events and immunosuppressive therapy determine post-transplant mortality and morbidity. Due to improvements in immunosuppressive management in recent years, long-term survival is likely to increase.
Malignancies after heart transplantation: Incidence, risk factors, and effects of calcineurin inhibitor withdrawal
2010, Transplantation Proceedings
Citation Excerpt :
In fact, these practices explain the higher prevalence of PTLDs in cardiac transplant recipients compared with renal transplant recipients (6.5% vs 0.7%).19 In this study, overall incidence of lymphomas was low (3.3% of all transplant recipients), which might be attributed to the generally low level of immunosuppression and T-cell monitoring during administration of RATG as induction therapy in order to minimize drug exposure.2 Earlier reports have linked the use of a CNI to the development of PTLD.15
The objectives of the present study were to evaluate the incidence of malignancies and to describe the effects of immunosuppression on survival and recurrence of malignancies after heart transplantation (HTX). Data were analyzed in 211 cardiac allograft recipients, in whom HTX was performed between 1989 and 2005. All of these patients survived for more than 2 years after HTX and received induction therapy with antithymocyte globulin (RATG) guided by T-cell monitoring since 1994. An immunosuppressive regimen consisting of cyclosporine A (CsA) combined with azathioprine was followed by CsA and mycophenolate mofetil (MMF) in 2001; mammalian target of rapamycin (mTOR) inhibitors (everolimus/sirolimus) were used since 2003. Mean patient age at HTX was 51.4 ± 10.5 years; mean follow-up time after HTX 9.2 ± 4.7 years. Overall incidence of neoplasias was 30.8%. Individual risk factors associated with a higher risk of malignancy after HTX were higher age at transplantation (P = .003), male gender (P = .005) and ischemic cardiomyopathy before HTX (P = .04). Administration of azathioprine (P < .0001) or a calcineurin inhibitor (CNI) (P = .02) for more than 1 year was associated with development of malignancy, whereas significantly fewer malignancies were noticed in patients receiving an mTOR-inhibitor (P < .0001). Kaplan-Meier analysis demonstrated a strong statistical trend toward an improved survival in patients with a noncutaneous neoplasia switched to a CNI-free protocol (P = .05). This study demonstrated the impact of a variety of individual risk factors and immunosuppressive drugs on development of malignancy after HTX. Markedly fewer patients with noncutaneous malignancies died after switch to a CNI-free regimen, not quite reaching statistical significance by Kaplan-Meier analysis, however.
Natural course and risk factors for impaired renal function during the first year after heart transplantation
2010, Journal of Heart and Lung Transplantation
Post-operative renal failure is a common and potentially hazardous complication after heart transplantation (HTx). In this study we characterized pre- and post-operative risk factors for acute renal failure requiring renal replacement therapy (RRT).
Ninety-three patients underwent orthotopic HTx between 2000 and 2007. The risk factors for RRT during the early post-operative period and predictors contributing to impaired renal function within the first post-transplant year were analyzed by regression analysis. The impact of pre-operative renal failure and early post-operative RRT on renal function within 1 year were studied.
Before HTx, 55% of patients (51 of 93) had normal renal function or mild renal failure (glomerular filtration rate [GFR] >60 ml/min/1.73 m²). Before discharge from the hospital, 25% (23 of 93) developed acute renal failure and required RRT. Of these, 16% (8 of 51) had pre-operatively normal renal function or mild renal failure, and 36% (15 of 42) had moderate or severe renal failure (GFR <60 ml/min/1.73 m²; p = 0.02). The prognosticators for early RRT were prolonged graft dysfunction, re-admission to the operating room due to post-operative bleeding, poor diuresis during surgery (<1,000 ml), pre-operative pacemaker implantation, intubation time >24 hours, pre-operative GFR <60 ml/min/1.73 m², post-operative troponin T >6 μg/liter and pre-operative use of angiotensin receptor blocker.
Pre-operative renal failure is a significant risk factor for RRT during the immediate post-operative period and requires aggressive treatment. Patients with pre-operative renal failure secondary to severe heart failure and acute post-operative renal failure requiring RRT tend to recover within the first year post-HTx.
Outcome of Heart Transplants 15 to 20 Years Ago: Graft Survival, Post-transplant Morbidity, and Risk Factors for Mortality
2008, Journal of Heart and Lung Transplantation
Citation Excerpt :
However, HTx remains the therapy of choice for end-stage cardiopathies, as demonstrated by this study with long-term survivals unequalled by other treatments. Indeed, the follow-up reached by several international transplantation centers allows them to publish very satisfactory survival rates at 10 years,5–7 but few teams have assessed their patients' survival for longer than 15 years of follow-up. The ISHLT registry estimates that about 30% of HTx patients are still alive at this stage of transplantation, whereas in our series we report a survival rate of 42% at 15 years.
The study was conducted to determine the long-term outcome of patients who underwent heart transplantation 15 to 20 years ago, in the cyclosporine era, and identify risk factors for death.
A retrospective analysis was done of 148 patients who had undergone heart transplantation between 1985 and 1991 at a single center. Operative technique and immunosuppressive treatment were comparable in all patients.
Actuarial survival rates were 75% (n = 111), 58% (n = 86), and 42% (n = 62) at 5, 10, and 15 years, respectively. The mean follow-up period was 12.1 ± 5.6 years for patients who survived more than 3 months after transplantation (n = 131). The major causes of death were malignancy (35.8%) and cardiac allograft vasculopathy (24.7%). No death related to acute rejection was reported after the first month of transplantation. Graft coronary artery disease was detected on angiography in 66 (50.3%), and 7 (5.3%) had retransplantation. Malignancies developed in 131 patients (48.1%), including skin cancers in 31 (23.6%), solid tumors in 26 (19.8%), and hematologic malignancies in 14 (10.6%). Severe renal function requiring dialysis or renal transplantation developed in 27 patients (20.6%). By multivariable analysis, the only pre-transplant risk factor found to affect long-term survival was a history of cigarette use (p < 0.0004).
Long-term survival at 15 years after cardiac transplantation remains excellent in the cyclosporine era. Controlling acute allograft rejection can be achieved but seems to carry a high rate of cancers and renal dysfunction. History of cigarette use affects significantly long-term survival in our study.

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Thoracic transplantationSurvival Beyond 10 Years Following Heart Transplantation: The Cleveland Clinic Foundation Experience

Abstract

Background

Methods

Results

Conclusions

Section snippets

Patient Population

Data Collection

Survival Analysis

Discussion

Conclusion

J Heart Lung Transplant

Ann Thorac Surg

J Am Coll Cardiol

J Heart Lung Transplant

J Am Coll Cardiol

Am J Kidney Dis

J Heart Lung Transplant

Liver Transpl

J Am Coll Cardiol

J Am Coll Cardiol

J Heart Lung Transplant

Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients

N Engl J Med

Thoracic transplantation
Survival Beyond 10 Years Following Heart Transplantation: The Cleveland Clinic Foundation Experience