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The Potential Benefit of Cardiac Reinnervation after Heart Transplantation

Comment by Maria Simonenko, Secondary Prevention and Rehabilitation Section member

Risk Factors and Prevention

Heart transplantation (HTx) results in hemodynamic restoration, survival and quality of life improvements, and social reintegration in end-stage heart failure patients [1]. However, HTx results in complete denervation of the donor heart with loss of afferent and efferent nerve connections. The majority of patients remain completely denervated during the first 6-12 months following transplantation, while the myocardial reinnervation process is usually found during the second year post-transplant and involves the myocardial muscle, sinoatrial node and coronary vessels [2]. Cornelissen et al. analyzed patients 10 years after HTx and received the following results: the observed changes in heart rate variability during long-term follow-up after HTx are compatible with partial reinnervation of the cardiac sinus node [3]. In contrast to this study, Ciolac et al. investigated the hemodynamic and cardiorespiratory adaptations to exercise in heart-transplanted individuals after 1 year with evidence of cardiac reinnervation versus those without evidence of cardiac reinnervation [1].

Heart rate variability is a widely used non-invasive measure to investigate cardiac autonomic modulation. It is suggested that the efferent vagal activity is the major contributor to the high-frequency component of heart rate variability whereas the interpretation of the low-frequency component is more controversial and complex and includes most likely both vagal and sympathetic influences [4]. In addition, multivariable linear regression analysis showed that the left ventricular ejection fraction of orthotopic HTx patients correlated negatively with the duration from HTx to the date of the measurement of heart rate variability [5]. At the same time, there is no clear consensus about what the normal range of heart rate should be after HTx [5]. Heart rate response is one of the most important predictors of exercise capacity in HTx recipients with complete chronotropic competence and without relevant transplant vasculopathy or acute allograft rejection [6].

Although Ciolac et al. show interesting results, further analysis of long-term processes is required. In addition, there are limitations, caused by the different graft function at 1 year or later after HTx. The 1-year term is usually considered the beginning of post-transplant reinnervation and more conclusive data could be gained from analysis at 2 years after HTx or later.

Ciolac et al. observed greater improvements in ambulatory blood pressure and maximal oxygen consumption in the cardiac reinnervation than in the non-cardiac reinnervation group. Their results suggest that cardiac reinnervation is associated with hemodynamic and cardiorespiratory adaptations to exercise training in individuals with HTx [1]. Regular physical activity and structured exercise training have been shown to improve blood pressure and heart rate in a broad range of cardiovascular pathologies. However, this study was the first to actually analyse both blood pressure and cardiac reinnervation-caused chronotropic incompetence and their impact on allograft electrophysiology. On the other hand, blood pressure is also associated with the immunosuppressive regiment, renal dysfunction and the history of hypertension prior to transplantation, which needs to be taken into account for interpretation of those findings.


Note: The content of this article reflects the personal opinion of the author and is not necessarily the official position of the European Society of Cardiology. 


1. Emmanuel G. Ciolac, Rafael E. Castro, Isabela R. Marcal, Fernando Bacal, Edimar A. Bocchi, Guilherme V. Guimaraes – Cardiac reinnervation affects cardiorespiratory adaptations to exercise training in individuals with heart transplantation, European Journal of Preventive Cardiology, 2019; 0: 1-11. DOI: 10.1177/2047487319880650

2. Avishay Grupper, Henry Gewirtz, Sudhir Kushwaha – Reinnervation post-heart transplantation, European Heart Journal, 2017; 0: 1-8.

3. Veronique A. Cornelissen, Johan Vanhaecke, Andre E. Aubert, Robert H. Fagard – Heart rate variability after heart transplantation: a 10-year longitudinal follow-up study, Journal of Cardiology, 2012; 59: 220-224. DOI: 10.1016/j.jjcc.2011.12.002

4. Task Force of the European Society of Cardiology and The North American Society of Pacing and Electrophysiology. Heart rate variability. Standards of measurement, physiological interpretation and clinical use. European Heart Journal, 1996;17:354—81.

5. Yi.-Ying Lin, Wan-An Lu, Yuan-Chen Hsieh, Hsiao-Huang Chang, Chun-Che Shih, Mei-Jy Jeng, Cheng-Deng Kuo – Effect of position on the residual heart rate variability in patients after orthotopic heart transplantation, Journal of the Chinese Medical Association, 2017; 80: 63-71. DOI: 10.1016/j.jcma.2016.09.007

6. Ariane Kaser, Michele Martinelli, Martin Feller, Thierry Carrel, Paul Mobacsi, Roger Hullin – Heart rate response determines long-term capacity after heart transplantation, Swiss Med WKLY, 2009; 139(21-22): 308-312