Noninvasive diagnosis of cardiac allograft rejection. Another of many searches for the grail.

Survival after cardiac transplantation has improved steadily over the past decade, with mortality at 1 year falling to as low as 10% in many centers. This improvement in survival is owed in part to better, more specific immunosuppressive agents such as cyclosporine and antilymphocyte an-tibodies.'-3 Also, to a large extent survival has improved because of the early diagnosis of rejection by surveillance endomyocardial biopsy, in most instances made before the development of allograft dysfunction.4,5 This early diagnosis is exceedingly important, as most clinicians experienced in trans-plantation are aware of the very high mortality in patients with acute rejection associated with consequent allograft dysfunction. Unfortunately, this early rejection diagnosis is purchased with up to 20 biopsy procedures for each patient within the first year after cardiac transplantation. Aside from the obvious costs associated with endomyocardial biopsy (approximately $1,300 at Oregon Health Sciences University, including hospital and professional charges), there is patient discomfort and potential risks from the multiple invasive procedures. Accordingly, the search for a noninvasive technique for the diagnosis of cardiac allograft rejection has continued to receive much interest in the field. See p 61 What is required for a perfect screening test for cardiac allograft rejection is not dissimilar to any ideal screening test. It should be easy to administer repetitively and should be noninvasive, low cost, and most importantly, it should have a high sensitivity. The need for specificity varies, depending on implications for further diagnosis. In the diagnosis of cardiac allograft rejection, the screening test must be nearly 100% sensitive, given the potentially fatal implications of missing acute rejection. Even if spec-The opinions expressed in this editorial comment are not necessarily those of the editors or of the American Heart Association. ificity is only 50%, this would result in a decrement of one half of the biopsies performed on a routine basis. Three general classes of studies have been investigated as possible screening tests for cardiac rejection: cardiac functional assessment, biochemical/im-munologic assays, and myocardial imaging. It has been long appreciated that systolic function as assessed by ejection phase indexes is neither sensitive nor specific for allograft rejection.67 This has led to several studies investigating the use of diastolic indexes of left ventricular function as potentially more sensitive in this diagnosis. Paulsen and colleagues7 first demonstrated that echocardiographic-derived indexes of diastolic function were abnormal in patients with acute allograft rejection. Subsequently, Valantine et al,8,9 Haverich et al,10 and …