Recipient age impact on outcome after cardiac transplantation: should it still be considered in organ allocation?†

ORIGINAL ARTICLE – ADULT CARDIAC Interactive CardioVascular and Thoracic Surgery 23 (2016) 573–579 doi:10.1093/icvts/ivw184 Advance Access publication 16 June 2016 Cite this article as: Sponga S, Deroma L, Sappa R, Piani D, Lechiancole A, Spagna E et al. Recipient age impact on outcome after cardiac transplantation: should it still be considered in organ allocation? Interact CardioVasc Thorac Surg 2016;23:573–9. Sandro Sponga*, Laura Deroma, Roberta Sappa, Daniela Piani, Andrea Lechiancole, Enrico Spagna, Vincenzo Tursi, Chiara Nalli and Ugolino Livi Department of Cardiothoracic, University Hospital of Udine, Udine, Italy * Corresponding author. Department of Cardiothoracic, University Hospital of Udine, P.le S.M. della Misericordia 15, 33100 Udine, Italy. Tel: +39-0432-552430/31; fax: +39-0432-552975; e-mail: (S. Sponga). Received 17 September 2015; received in revised form 11 March 2016; accepted 18 March 2016 Abstract OBJECTIVES: Improvement of clinical results in heart transplantation (HTx) has favoured the expansion of indication criteria towards aged population. The impact of increasing recipient age is controversial and, owing to donor shortage, the debate still remains whether HTx is justified for older patients. We analysed age as a prognostic factor at long-term after HTx and if it should be a determinant in organ allocation. METHODS: Data of 364 consecutive patients who underwent cardiac transplantation between 1999 and 2014 at the University Hospital of Udine were analysed. Patients were divided into three groups according to age (Group 1: 18–40, Group 2: 41–59, Group 3: ≥ 60 years) and survival and major complications were evaluated at long-term (mean follow-up 6.7 ± 4.5 years, range 1–15.7 years). RESULTS: Preoperatively, renal failure (2.9, 16.1, 39.5%, P < 0.01) and cardiovascular factors such as diabetes (1.2, 17.1, 36.4%, P < 0.01), systemic hypertension (5.9, 31.5, 40.8%, P < 0.01) and dyslipidaemia (5.9, 40.3, 42.9%, P < 0.01) were more common in older patients (Group 3), as well as ischaemic cardiopathy (0, 42.6, 49.7%, P < 0.01). Donor age was lower in younger recipients (Group 1) (33 ± 15, 39 ± 14, 45 ± 14 years, P < 0.01). Older patients showed a worse long-term survival (hazard ratio 1.7; 1.1–2.5), also after adjusting for major cardiovascular risk factors, renal failure and donor age. In fact, 15-year survival was 100% in Group 1, while at 1, 5, 10 and 15 years survival was 88, 78, 69 and 56% in Group 2, and 87, 68, 49 and 43% in Group 3, respectively. Even major long-term complications were less frequent in younger patients in terms of neoplasms (P < 0.01), rehospitalizations (P < 0.01) and a tendency to higher freedom from other complications such as cytomegalovirus infections, renal failure and dialysis. CONCLUSIONS: Our results showed a significantly different outcome according to recipient age, even when adjusted for major risk factors. Notably, patients younger than 40 years showed 100% long-term survival, and apparent lower rate of complications due to immunosuppression. Since 15-year survival in patients ≤40 years is twice that of patients ≥60 years, recipient age should be taken into account in organ allocation. Keywords: Recipient age • Heart transplantation • Organ allocation INTRODUCTION Heart failure is a major public health burden, being the patient population of at least 10 millions in Europe and
5 millions in North America, with an estimated growth rate of 25% by 2030 [1]. Owing to the more recent improvement in the heart failure treatment, the proportion of patients reaching an advanced phase of the disease, so-called end-stage heart failure, is steadily growing, this representing one of the leading causes of hospitalization and death (1-year mortality rate of
50%) [1]. † Presented at the 29th Annual Meeting of the European Association for CardioThoracic Surgery, Amsterdam, Netherlands, 3–7 October 2015. Cardiac transplantation has been considered the gold standard of end-stage heart disease and achieves long-term patient survival. At the beginning of heart transplantation (HTx) experience, indications were restricted to recipients aged <60 years. However, the continuous improvement of clinical results has encouraged the expansion of selection criteria, enrolling patients older than 60 and even 70 years of age. To date, solid data of the age impact on long-term HTx outcome are limited and controversial. Moreover, owing to a donor shortage, the debate still remains whether HTx is justified for older recipients [2–12]. We analysed the impact of recipients’ age on long-term outcome in terms of survival and rate of major complications following HTx in our institution. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. ORIGINAL ARTICLE Recipient age impact on outcome after cardiac transplantation: should it still be considered in organ allocation?† 574 S. Sponga et al. / Interactive CardioVascular and Thoracic Surgery PATIENTS AND METHODS Between 1999 and 2014, 364 consecutive HTxs in patients ≥18 years were performed at the University Hospital of Udine, Italy. Patients transplanted before 1999 were not included, due to nonhomogeneous surgical techniques and immunosuppression protocols but, since 1999, the bicaval surgical technique was generally adopted and immunosuppression standardized with steroids, cyclosporine and mycophenolate. The study was approved by the Review Board of the University of Udine. Patients were divided into three groups according to age: Group 1 ( patients ≥18 and <40 years of age), Group 2 ( patients >40 and <60 years), Group 3 (≥60 years), and data were prospectively collected and retrospectively analysed. There was no significant difference concerning age distribution during the considered period of recruitment. The mean follow-up was 6.7 ± 4.5 years (range 1–15.7 years). All HTx recipients met the same eligibility criteria [13]. Recipient’s evaluation included the assessment of clinical conditions commonly related to advanced age, such as malignancies, diabetes mellitus, peripheral vascular disease and end-organ dysfunction. Donor and recipient were matched on ABO blood type compatibility and body weight, considering clinical status and time on waiting list as prioritization criteria. There was a tendency to pair young donors to young recipients, but recipient age was not a prioritization criterion. Donor hearts were harvested from beating-heart, brain-dead patients. Graft procurement and preservation was achieved by the combination of cold cardioplegic arrest with St Thomas cardioplegia and topical hypothermia. Organ Care System Transmedics was used in 11 donors. Postoperative and long-term follow-up protocol in our centre has been previously published [14]. Endomyocardial biopsies were made every week during the first month, every 15 days in Months 2 and 3, and monthly or bimonthly up to 12 mon (...truncated)