MEDizzy - A 28-year-old man presents to the emergency department for

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Disorders of the cardiovascular system 2

A 28-year-old man presents to the emergency department for dyspnea on exertion. He had an orthotopic heart transplant for non-ischemic cardiomyopathy 5 years ago and, in general, has done quite well except for one cytomegalovirus reactivation within the first year. He reports that for the past 3 months, he has noticed that with decreasing amounts of exertion, he has been having limiting dyspnea. He is adamant that he is experiencing no chest pain or pressure during these episodes. He has been perfectly compliant with his regimen of tacrolimus, mycophenolate mofetil, and low-dose prednisone. Echocardiography reveals a normal LV function with normal LV wall thickness. His resting ECG shows normal sinus rhythm at a rate of 80 bpm. Which of the following is the most likely cause of his symptoms?

ExplanationDespite usually having young donor hearts, cardiac allograft recipients are prone to develop coronary artery disease (CAD). This CAD is generally a difuse, concentric, and longitudinal process that is quite different from “ordinary” atherosclerotic CAD, which is more focal and often eccentric. The underlying etiology most likely is primarily immunologic injury of the vascular endothelium, but a variety of risk factors influence the existence and progression of CAD, including nonimmunologic factors such as dyslipidemia, diabetes mellitus, and cytomegalovirus (CMV) infection (as in this patient). It is hoped that newer and improved immunosuppressive modalities will reduce the incidence and impact of these devastating complications, which currently account for the majority of late posttransplantation deaths. Thus far, the immunosuppressive agent's mycophenolate mofetil and the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus have been shown to be associated with short-term lower incidence and extent of coronary intimal thickening; in anecdotal reports, the institution of sirolimus was associated with some reversal of CAD. The use of statins also is associated with a reduced incidence of this vasculopathy, and these drugs are now used almost universally in transplant recipients unless contraindicated. Palliation of CAD with percutaneous interventions is probably safe and effective in the short term, although the disease often advances relentlessly. Because of the denervated status of the organ, patients rarely experience angina pectoris, even in the advanced stages of the disease. Antibody (humoral)–mediated rejection is exceedingly rare in a patient this far out from transplant, particularly one who fortunately has had no prior rejection episodes. While cellular rejection is possible, the presence of a normal left ventricle (and no arrhythmias) makes it less likely. Tacrolimus most commonly causes hypertension, neurologic complications, and renal insufficiency. Mycophenolate mofetil most commonly causes bone marrow suppression and diarrhea. Low-dose prednisone is generally well tolerated, although chronic steroids carry the incipient risk of diabetes, obesity, skin changes, iatrogenic adrenal insufficiency, osteoporosis, and cataracts. None of these drugs classically causes dyspnea.