Predisposing factors for late mortality in heart transplant patients
Abstract
Background: Because of the growing prevalence of terminal heart failure on the one hand and organ shortage on the other hand, an optimal care of heart transplant recipients based on the knowledge of potential risk factors not only early, but also in a long-term course after heart transplantation is of great importance. Therefore, the aim of the present study was to identify predisposing factors for late mortality in this patient collective.
Methods: Data from long-term heart transplant patients collected during follow-up visits in the current center were retrospectively analyzed. Clinical, laboratory, including immune monitoring and apparative examination results were studied with regard to all-cause mortality.
Results: One hundred and seventy-two patients after heart transplantation (mean: 13.2 ± 6.4 years) were divided into two groups: survivors (n = 133) and non-survivors (n = 39). In comparison with survivors, non-survivors were characterized by significantly more pronounced renal insufficiency with more frequent dialysis, anemia and worse functional status. Additionally, non-survivors obtained hearts from relevantly more obese donors. In a multivariate Cox regression analysis the following parameters were shown to be independent risk factors for increased mortality: CD4 percentage < 42%, C-reactive protein ≥ 0.5 mg/dL, presence of rejections requiring therapies in the past, onset of cardiac allograft vasculopathy < 5 years following heart transplantation and no use of beta-blockers.
Conclusions: Low CD4+ cell percentages, sustained inflammation, relevant organ rejections, early onset of transplant vasculopathy and no use of beta-blockers are risk factors for higher mortality in a long-term follow-up after heart transplantation.
Keywords: heart transplantationimmune monitoringinflammationorgan rejectiontransplant vasculopathybeta-blocker therapy
References
- Ponikowski P, Voors A, Anker S, et al. ESC Scientific Document Group 2016. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; 37(27): 2129–2200.
- Mehra MR, Canter CE, Hannan MM, et al. International Society for Heart Lung Transplantation (ISHLT) Infectious Diseases, Pediatric and Heart Failure and Transplantation Councils. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update. J Heart Lung Transplant. 2016; 35(1): 1–23.
- Zamperetti N, Bellomo R, Piccinni P, et al. Reflections on transplantation waiting lists. Lancet. 2011; 378(9791): 632–635.
- Luckraz H, Goddard M, Charman SC, et al. Early mortality after cardiac transplantation: should we do better? J Heart Lung Transplant. 2005; 24(4): 401–405.
- Foroutan F, Alba AC, Guyatt G, et al. Predictors of 1-year mortality in heart transplant recipients: a systematic review and meta-analysis. Heart. 2018; 104(2): 151–160.
- Tjang YS, van der Heijden GJ, Tenderich G, et al. Survival analysis in heart transplantation: results from an analysis of 1290 cases in a single center. Eur J Cardiothorac Surg. 2008; 33(5): 856–861.
- Jung SH, Kim JJ, Choo SJ, et al. Long-term mortality in adult orthotopic heart transplant recipients. J Korean Med Sci. 2011; 26(5): 599–603.
- Jaramillo N, Segovia J, Gómez-Bueno M, et al. Characteristics of patients with survival longer than 20 years following heart transplantation. Rev Esp Cardiol (Engl Ed). 2013; 66(10): 797–802.
- DeCampli WM, Luikart H, Hunt S, et al. Characteristics of patients surviving more than ten years after cardiac transplantation. J Thorac Cardiovasc Surg. 1995; 109(6): 1103–1114.
- Bergenfeldt H, Lund LH, Stehlik J, et al. Time-dependent prognostic effects of recipient and donor age in adult heart transplantation. J Heart Lung Transplant. 2019; 38(2): 174–183.
- Chaudhri B. Heart transplantation: new realities, challenges and developments - surgical perspectives. J Cardiol Curr Res. 2014; 1(3): 58–63.
- Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. 2005; 24(11): 1710–1720.
- Blanc B, Finch CA, Hallberg L, et al. Nutritional anaemias. Report of a WHO Scientific Group. WHO Tech Rep Ser. 1968; 405: 1–40.
- Pietra BA, Wiseman A, Bolwerk A, et al. CD4 T cell-mediated cardiac allograft rejection requires donor but not host MHC class II. J Clin Invest. 2000; 106(8): 1003–1010.
- Ducloux D, Carron PL, Rebibou JM, et al. CD4 lymphocytopenia as a risk factor for skin cancers in renal transplant recipients. Transplantation. 1998; 65(9): 1270–1272.
- Kahan BD. Cyclosporine. N Engl J Med. 1989; 321: 1725–1738.
- Sato Y, Yanagita M. Immunology of the ageing kidney. Nat Rev Nephrol. 2019; 15(10): 625–640.
- Yoon JW, Gollapudi S, Pahl MV, et al. Naïve and central memory T-cell lymphopenia in end-stage renal disease. Kidney Int. 2006; 70(2): 371–376.
- Wallin EF, Hill DL, Linterman MA, et al. The Calcineurin Inhibitor Tacrolimus Specifically Suppresses Human T Follicular Helper Cells. Front Immunol. 2018; 9: 1184.
- Li Y, Zhong X, Cheng G, et al. Hs-CRP and all-cause, cardiovascular, and cancer mortality risk: A meta-analysis. Atherosclerosis. 2017; 259: 75–82.
- Chapman JR, Webster AC, Wong G. Cancer in the transplant recipient. Cold Spring Harb Perspect Med. 2013; 3(7): a015677.
- Ducloux D, Challier B, Saas P, et al. CD4 cell lymphopenia and atherosclerosis in renal transplant recipients. J Am Soc Nephrol. 2003; 14(3): 767–772.
- Gupta S. Drugs for the prevention and treatment of cardiac allograft vasculopathy. Cardiol Pharmacol. 2014; 3: 2.
- Ibanez B, James S, Agewall S, et al. ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018; 39(2): 119–177.
- Rehsia NS, Dhalla NS. Mechanisms of the beneficial effects of beta-adrenoceptor antagonists in congestive heart failure. Exp Clin Cardiol. 2010; 15(4): e86–e95.
- Ciarka A, Lund LH, Van Cleemput J, et al. Effect of Heart Rate and Use of Beta Blockers on Mortality After Heart Transplantation. Am J Cardiol. 2016; 118(12): 1916–1921.
- Page RL, Miller GG, Lindenfeld J. Drug therapy in the heart transplant recipient: part IV: drug-drug interactions. Circulation. 2005; 111(2): 230–239.
- Varnado S, Peled-Potashnik Y, Huntsberry A, et al. Effect of diltiazem on exercise capacity after heart transplantation. Clin Transplant. 2017; 31(8).
- Hoerning A, Köhler S, Jun C, et al. Cyclosporin but not everolimus inhibits chemokine receptor expression on CD4+ T cell subsets circulating in the peripheral blood of renal transplant recipients. Clin Exp Immunol. 2012; 168(2): 251–259.
