A 56-year-old woman is eight years post-heart transplant for familial dilated cardiomyopathy. She has not had any episodes of rejection since the first year post-transplant, and has enjoyed an excellent level of function. Immunosuppression includes tacrolimus and mycophenolate mofetil. She now describes some mild shortness of breath on exertion, and her echocardiogram demonstrates abnormal left ventricular filling indicating moderate diastolic dysfunction. Coronary angiography reveals no flow limiting stenoses. Her right heart catheterization reveals a right atrial pressure of 10 mmHg that increases to 16mmHg with inspiration (Kussmaul’s sign).
What do you expect to see on biopsy?
Chronic allograft dysfunction in heart transplants is often associated with histologic findings of myocyte hypertrophy and interstitial fibrosis. There may also be evidence of small vessel vasculopathy. While any change in allograft function may be related to acute cellular rejection or acute antibody mediated rejection (AMR), chronic allograft dysfunction usually results from a combination of coronary allograft vasculopathy (leading to ischemia) and interstitial fibrosis. Donor age is a powerful predictor of cardiac allograft dysfunction.
Across all organs, vascular changes and fibrosis are common biopsy findings in chronic allograft dysfunction. Often, there is no evidence of acute cellular or antibody-mediated rejection, although previous rejection episodes may contribute to the chronic changes. These changes are likely multifactorial, and may develop secondary to immune injury/rejection, endothelial dysfunction, metabolic factors (dyslipidemia, diabetes), toxins such as alcohol (in liver) or cigarette smoking (in lung transplants), viruses (such as hepatitis B or C in a liver transplant) and chronic CNI toxicity.