Use of the thrombolysis in myocardial infarction frame count for the quantitative assessment of transplant-associated arteriosclerosis.

C clinical practice for the assessment of transplant-associated arteriosclerosis (TAA) relies on surveillance coronary angiography.1,2 This approach is limited by an inability to detect microvascular involvement or to provide information regarding the significance of narrowings that are typically diffuse and difficult to quantify. Measurement of coronary blood flow may provide a useful quantitative measurement of TAA because it sums the physiologic consequences of both hemodynamically important epicardial stenoses and diseased microvessels. Resting and hyperemic coronary blood flow can be assessed by more sophisticated techniques, but they require significant expertise and are not widely available outside of the research setting.3–5 The Thrombolysis In Myocardial Infarction trial frame count (TFC) is a reproducible, simple, and therefore widely applicable method of assessing coronary blood flow from routine angiograms based on counting the number of cine frames required to opacify the length of the artery.6 We hypothesized that the TFC may provide a quantitative physiologic assessment of TAA. Specifically, over the first 5 years after cardiac transplantation, we examined the relation between TFC and angiographic evidence of TAA. • • • The study population was derived from the 388 patients who had undergone cardiac transplantation at the Brigham and Women’s Hospital since in 1984. Of this cohort, 42 patients had angiograms performed 1 and 5 years after transplant that were suitable for TFC analysis. Hypertension was defined as use of antihypertensive therapy and diabetes by a medical history of treatment with diet or medications. There were no cigarette smokers. Left ventricular hypertrophy was defined as a left ventricular wall thickness .11 mm at year 5 after transplantation. Blood pressure and heart rate were recorded at the time of cardiac catheterization. Acute rejection was defined by International Society for Heart Lung Transplantation histologic grade $II requiring treatment.7 Angiography was performed using Judkins 6Fr diagnostic catheters, and standard coronary views (right anterior and left anterior oblique with caudal and cranial angulations) using hand injections of contrast medium. All cine angiograms were recorded at 30 frames/s. Nitroglycerin was avoided before angiography because administration of nitrates alters TFC.8 The TFCs were measured by 2 blinded observers (PW and AA) in as many of the 3 major coronary arteries that were suitable for frame count analysis using a previously validated method.6,8–11 Briefly, the number of cine frames required for contrast to first reach standardized distal coronary landmarks was counted to assess an index of coronary blood flow as a continuous variable. The TFC of the left anterior descending and circumflex arteries was assessed primarily in the right anterior oblique view with caudal angulation, and the right coronary artery was assessed in the left anterior oblique view with cranial angulation. The distal landmark for the left anterior descending artery was the apical bifurcation (i.e., “moustache”). The TFC for the circumflex artery was obtained by selecting a suitable distal landmark in an obtuse marginal branch (typically the most distal secondary branching vessel) that could be precisely identified on both the year 1 and 5 angiograms. For the right coronary artery, the standardized landmark was the distal tip of the posterior descending artery.6 For each patient, the same arteries were used for TFC analysis at years 1 and 5 after transplantation. Angiograms were independently reviewed by 4 investigators (JCF, SK, PG, and APS) unfamiliar with the results of the TFC analysis. The presence of coronary arteriosclerosis was qualitatively defined as any focal stenosis, distal tapering, or loss of tertiary branches.12 Because changes in the diameter of an artery between the first and fifth year could affect flow velocity independent of microvascular resistance, the diameter of the arteries at matched proximal and distal segments were measured using digital electronic calipers and scaled against the angiographic catheter (Mitutoyo, Kawasaki-shi, Japan).13 The variables were described using mean (SD) or proportions when appropriate. Student’s t tests were used to assess differences in means between those with and without angiographic disease or progression in angiographic disease. In each patient, a mean TFC at baseline was obtained by averaging the TFCs from suitable arteries. The TFC for each artery measured from the year 1 and 5 angiograms was normalized for heart rate–pressure product at year 1 using the formula: