Contemporary Concepts in Prevention and Treatment of Cardiac Allograft Vasculopathy

Abstract

Cardiac allograft vasculopathy (CAV), is characterized by heterogeneous proliferative thickening of the vascular intima of the cardiac allograft vasculature. Since its presentation is commonly clinically silent, early diagnosis and preventative therapy are critical. Preventative therapy including optimization of immunosuppressive therapy and treatment of comorbidities associated with CAV progression must be initiated early since most of the intimal thickening occurs during the first year posttransplant. Longterm use of calcineurin inhibitors is associated with a high incidence of chronic renal disease and also contributes to hyperlipidemia and hypertension, all of which may exacerbate CAV. In addition, statins, antihypertensive agents and anti-CMV agents all have demonstrated benefits in reducing CAV. Once established, the limited treatment options include nonpharmacologic interventions such as retransplantation, percutaneous coronary interventions, coronary artery bypass grafting, transmyocardial laser revascularization and heparin-induced/mediated extracorporeal LDL plasmapheresis (HELP). As the use of new assessment tools increases our understanding of this disease, better preventative and treatment strategies are evolving.

Outcomes and survival following heart retransplantation for cardiac allograft failure: a systematic review and meta-analysis

“…Several therapeutic interventions including aggressive immunosuppressive therapy, percutaneous transluminal coronary angioplasty, laser myocardial therapy, coronary artery bypass grafting, valvular repair and temporary and long term mechanical circulatory assist devices have been proposed; however, heart retransplantation (RTx) remains the only viable long-term treatment for end-stage cardiac allograft failure (4)(5)(6)(7)(8). Despite annual RTx rates of as high as 6% as reported by the 2017 ISHLT data (9), the literature on RTx is ambiguous with several studies reporting conflicting findings in regards to the survival and viability of this therapy (10,11).…”

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“…13 Mycophenolate mofetil has been shown to modestly reduce the intima thickness measured by intravascular ultrasonography compared with older immunosuppressive combi nations using azathioprine. 13 In a randomized controlled trial of 600 patients that evaluated everolimus versus azathioprine in an immuno suppressive regimen that included cyclosporine and corticosteroids, everolimus significantly reduced intima thickness measured by intravascular ultrasonography, although it did not improve graft survival and was associated with dyslipidemia and decreased renal function. 19 It has been shown that CMV infection is an independent risk factor for CAV after transplant, likely due to alteration of endothelial nitric oxide synthase pathway.…”

“…This process is related to both immunologic and nonimmunologic mechanisms. 13 These mechanisms include a chronic alloimmunemediated damage, as well as nonimmunologic factors such as ischemia-reperfusion damage, donor age, hypertension, hyperlipidemia, and cytomegalovirus (CMV) infection. Cellular rejection early and late after heart transplant is an independent risk factor for the development of CAV.…”

Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

“…An explosive mode of brain death such as gunshot wound to the head or fatal intracranial hemorrhage leads to rapid progression of brain death. This promotes cytokine production, catecholamine surge, and evokes significant inflammatory response and endothelialitis [163][164][165][166]. Increased levels of circulating catecholamines stimulate the production of several proinflammatory cytokines, adhesion molecules, hormones, and inflammatory cells that are known to cause myocardial dysfunction.…”