Recent Developments on Coronary Microvasculopathy after Heart Transplantation:A New Target in the Therapy of Cardiac Allograft Vasculopathy

Francesco      Tona; Martina      Perazzolo Marra; Marny      Fedrigo; Giulia      Famoso; Roberto      Bellu; Gaetano      Thiene; Gino      Gerosa; Annalisa      Angelini; Sabino      Iliceto

doi:10.2174/157016112799304987

Abstract

Heart transplantation (HTx) is the treatment of choice for patients with refractory end-stage heart diseases. Although the procedure is considered effective in extending and improving quality of life, the onset of cardiac allograft vasculopathy (CAV) continues to limit the long-term success of HTx. Emerging data indicate that the endothelium plays a significant role in the onset, progression and complication of this multifactorial disease, with both immunologic and nonimmunologic risk factors contributing to its development. Improving our understanding of the integral role of the coronary microcirculation in CAV is of crucial clinical interest since it could provide further insights into the related pathophysiological mechanisms and possible new strategies for CAV prevention and therapy. Assessment of coronary microvasculopathy has been shown to be of predictive value after HTx. Predominant allograft microvascular dysfunction is detectable in 15-20% of patients after HTx. Very recently, stenotic microvasculopathy (detected in biopsy samples) has been characterized as a prognostic factor for long-term survival after HTx. The ability to detect and distinguish changes in epicardial and microvascular function may aid in identifying modifiable factors that lead to CAV. Improved immunosuppressive drugs, including mycophenolate mofetil and proliferation signal inhibitors, as well as statins (in part via immunomodulation), may have a beneficial effect on coronary microcirculation after HTx, although there is still a need to confirm the impact of vasodilators in improving the prognosis of HTx patients. We review the role of coronary microvasculopathy in HTx, its prevention and new potential pharmacological interventions.

Keywords: Heart transplantation, microcirculation, cardiac allograft vasculopathy, immunosuppression, rejection, diagnosis, statins, vasodilators, CMV infection, nitric oxide