Comparison Between Cardiac Allograft Vasculopathy and Native Coronary Atherosclerosis by Optical Coherence Tomography.

We sought to explore differences in distribution and morphology of coronary lesions comparing cardiac allograft vasculopathy and native coronary atherosclerosis (NCA) using intravascular imaging with optical coherence tomography (OCT). At the time of routine surveillance angiography, 17 heart transplant (HT) recipients with a history of high-grade cellular rejection (HGR) and 43 HT recipients with none/mild (low)-grade rejection underwent OCT imaging of the left anterior descending and were compared to 60 patients with NCA without HT. Compared with patients with NCA, patients with HGR had similar intima areas but smaller external elastic lamina areas (7.9 mm(2) [6.3, 11.2] versus 6.6 mm(2) [4.8, 7.5], p = 0.02) resulting in smaller lumen areas (4.5 mm(2) [3.4, 6.6] versus 3.3 mm(2) [2.8, 4.7], p = 0.04) in distal segments and smaller lumen diameters in side branches (1.28 mm [1.19, 1.37] versus 1.09 mm [0.94, 1.24], p = 0.04). Compared with patients with NCA, lesions in patients with HT were more homogeneous, involving the entire coronary vascular tree. Patients with HGR had a higher prevalence of macrophages involving ≥1 quadrant in all 3 segments compared with patients with NCA. The number of microvessels was greater in patients with both HGR and LGR HT versus NCA. In conclusion, distinct findings in the distribution and morphology of coronary lesions between HT recipients and patients with NCA are evident by OCT imaging, suggesting that OCT might be useful to help differentiate cardiac allograft vasculopathy from NCA in vivo.

Increased coronary lipid accumulation in heart transplant recipients with prior high-grade cellular rejection: novel insights from near-infrared spectroscopy.

Cardiac allograft vasculopathy is a major cause of morbidity and mortality among patients after heart transplantation. We sought to assess the amount of lipid accumulation in the coronary arteries of transplant patients according to rejection grade. Overall, 39 consecutive heart transplant recipients undergoing annual routine surveillance coronary angiography underwent near-infrared spectroscopy and intravascular ultrasound imaging of 1 coronary artery. Rejection history was graded according to the International Society of Heart and Lung Transplantation (ISHLT) classification as none/mild/moderate-grade rejection (ISHLT 0, 1A/1B, or 2) compared to high-grade rejection (≥3A). Patients with prior history of high-grade rejection had larger plaque burden in the distal coronary segments [45.7 % (25.5-63.7) vs 25.1 % (19.9-37.8), p = 0.02] and a higher maximum lipid core burden index in any 4-mm long segment (maxLCBI(4mm)) [243 (91-400) vs 41 (1-170), p = 0.016] as compared with patients with prior history of none/mild/moderate-grade rejection. By multivariable linear regression analysis, prior history of high-grade rejection was an independent predictor for maxLCBI(4mm). A maxLCBI(4mm) >200 distinguished prior history of high-grade from none/mild/moderate rejection with a sensitivity of 61.5 % and specificity of 84.6 %. The current study demonstrates that the coronary arteries of post heart-transplant patients with a prior history of high-grade cellular rejection have increasing amounts of lipid-rich plaque. MaxLCBI(4mm) >200 might differentiate patients with previous high-grade cellular rejection from heart transplant recipients with none/mild/moderate-grade rejection.

In vivo comparison between cardiac allograft vasculopathy and native atherosclerosis using near-infrared spectroscopy and intravascular ultrasound.

AIMS: The aim was to compare cardiac allograft vasculopathy to native atherosclerosis by near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS AND RESULTS: Twenty-seven atherosclerotic (non-transplant) patients and 28 heart transplant recipients undergoing routine surveillance coronary angiography underwent NIRS-IVUS imaging of the left anterior descending coronary artery. In each proximal, middle, and distal coronary artery segment, the maxLCBI4mm [4-mm long segment with maximum lipid core burden index (LCBI)] and corresponding IVUS parameters were compared. MaxLCBI4mm was significantly greater among atherosclerotic patients than the transplant patients in both proximal and middle coronary artery segments, but not in the distal segment. There was a positive linear correlation between maxLCBI4mm and maximum plaque burden in both groups, but atherosclerotic patients demonstrated a smaller maxLCBI4mm than transplant recipients among segments with plaque burden <40%. Among segments with a maximum plaque burden ≥40%, native-atherosclerosis patients had a greater maxLCBI4mm compared with transplant patients (P = 0.015). Calcification was present in 72.9% of native atherosclerosis and 14.7% of transplant segments (P< 0.001). Among the 165 analysed segments, prevalence of lipid-rich plaque (LRP) with superficial attenuation (30.9 vs. 1.2%, P < 0.001) or calcified LRP (13.6 vs. 2.4%, P = 0.03) was significantly greater in native atherosclerosis compared with transplant patients. Conversely, the proportion of segments with non-LRP (46.4 vs. 11.1%, P < 0.001) was higher in transplant patients. CONCLUSION: NIRS-IVUS imaging demonstrated early and accelerated lipid accumulation with smaller plaque burden and less calcium in patients after heart transplant when compared with patients with native atherosclerosis.

Optical coherence tomographic evaluation of transplant coronary artery vasculopathy with correlation to cellular rejection.

BACKGROUND: Cardiac allograft vasculopathy is an accelerated fibroproliferative process that affects the coronary arteries of transplanted hearts. Intracoronary imaging with optical coherence tomography enables detection of subangiographic cardiac allograft vasculopathy. METHODS AND RESULTS: At the time of routine surveillance coronary angiography, 48 consecutive heart transplant recipients underwent optical coherence tomographic imaging of 1 coronary artery. Imaging findings were compared per rejection history that was graded according to the International Society of Heart and Lung Transplantation classification as none/mild (International Society of Heart and Lung Transplantation 0, 1A/1B, or 2) or high-grade rejection (≥3A). Compared with the none/mild rejection group (37 patients) using Mann-Whitney U test, patients in the high-grade rejection group (11 patients) had a thicker intima in all coronary segments (distal: 0.22 mm [0.09-0.41] versus 0.09 mm [0.06-0.17], P=0.02; middle: 0.35 mm [0.00-0.45] versus 0.14 mm [0.08-0.24], P=0.002; and proximal: 0.34 mm [0.21-0.44] versus 0.15 mm [0.11-0.21], P=0.005) and a higher prevalence of foamy macrophages (distal: 55% versus 9%, P=0.003; middle: 55% versus 22%, P=0.004; and proximal: 44% versus 13%, P=0.05) using χ(2) statistics. Side branches in the high-grade rejection group had smaller lumen diameters and a higher prevalence of intimal thickening (54% versus 36%; P=0.01). Intimal microvessels were also more prevalent in the high-grade rejection group versus the none/mild rejection group (46% versus 11%; P=0.02). CONCLUSIONS: Coronary optical coherence tomographic evaluation revealed that patients with a history of high-grade cellular rejection, compared with those with none/mild rejection, had more coronary artery intimal thickening with macrophage infiltration, involving all coronary segments and side branches. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01403142.

Volumetric intravascular ultrasound assessment of mechanisms and results of stent expansion in heart transplant patients.

BACKGROUND: Percutaneous coronary intervention with stent placement for the treatment of patients with cardiac allograft vasculopathy is common, but data regarding stent behavior in this setting is lacking. OBJECTIVES: We investigated mechanisms and potential differences in stent expansion among transplant patients vs. patients with native coronary artery atherosclerotic disease ("controls"). METHODS: We compared pre- and poststent intravascular ultrasound in 12 transplant patients (17 lesions) and 33 control patients (34 lesions) matched according to age (60.1 ± 9.2 years), diabetes mellitus, and lesion location. Planar and volumetric analysis was conducted for every 1 mm at the lesion site as well as the first 5 mm proximal and distal to the stent edge. Focal stent expansion was defined as minimum stent area (MSA) divided by mean reference lumen area. Diffuse stent expansion was defined as mean stent area divided by mean reference lumen area. RESULTS: Transplant patients had more plaque than "controls" prestenting, but similar MSA and focal and diffuse stent expansion afterwards. The increase in mean lumen area correlated with the increase in mean vessel area in both groups, transplant (R = 0.64, P = 0.008) and controls (R = 0.70, P < 0.0001), but correlated inversely with changes in mean plaque area only in the transplant group (R = 0.55, P = 0.027). There were no differences in calcification between the two groups and no axial plaque distribution from the lesion into the reference segments in either group. CONCLUSIONS: The mechanism of stent expansion in transplant vasculopathy appears to be similar to de novo atherosclerosis-i.e., mainly vessel expansion to achieve similar acute results.

Value of drug-eluting stents in cardiac transplant recipients.

Transplant allograft vasculopathy (TAV) was a leading cause of death in cardiac transplant recipients after the first year of transplantation. Whether drug-eluting stents (DESs) performed better than bare-metal stents (BMSs) for the treatment of patients with discrete epicardial stenosis was unknown. The aim was to determine the safety and efficacy of DESs compared with BMSs in the treatment of patients with TAV. Outcomes of 32 patients sequentially treated using DESs for TAV were retrospectively reviewed and compared with a historic cohort of 35 patients treated sequentially with BMSs for TAV. Patients treated with DESs were also compared with age- and gender-matched cardiac transplant controls to determine differences in survival. After adjustment for baseline risk factors, there was no difference in 1-year survival between patients treated with DESs or BMSs for TAV. Restenosis rates at 1 year were 49% in lesions treated using BMSs and 19% in those treated using DESs. Compared with an age- and gender-matched control group of cardiac transplant patients who did not have discrete obstructive epicardial TAV, patients who required treatment with DESs for epicardial obstructive disease had significantly worse survival. In conclusion, treatment of patients with TAV with DESs did not seem to alter the natural deleterious history of this disease process.

Determinants of left ventricular thrombus formation after primary percutaneous coronary intervention for anterior wall myocardial infarction.

Previous studies have reported that left ventricular (LV) thrombus is a complication in 10-56% of ST-segment elevation acute anterior wall myocardial infarctions (AWMI). Data suggest that changes in acute myocardial infarction management such as early anticoagulation, thrombolysis, and most recently, primary percutaneous coronary intervention (PCI), may decrease thrombus occurrence. Early time to reperfusion has been shown to decrease mortality and improve LV function recovery. To determine if door-to-balloon time (DTBT) affects the incidence of LV thrombus, we retrospectively analyzed data on 43 consecutive patients who underwent successful PCI of a primary acute ST-segment elevation AWMI. Transthoracic echocardiography was performed for detecting LV thrombus and measuring LV ejection fraction (EF) within 5 days on all patients (average time: 2.17 days post event). Nineteen patients underwent PCI within 2 h of arrival to the Emergency Department (Group A, average 88 min) and 24 patients underwent PCI with DTBT of more than 2 h (Group B, average 193 min). Clinically significant LV thrombus was detected in 35% of all patients. The incidence of LV thrombus formation in Group A was not significantly different from that in Group B (42.1% vs. 29.0%, respectively; P = 0.52). The risk of LV thrombus was independent of in-hospital anticoagulation and medical management, peak enzyme levels, and LVEF but did relate to age (odds ratio = 1.96, 95% CI 1.03-3.73, P = 0.04 per decade). No embolic events in hospital were observed (average hospital stay 9.2 days). We conclude that the incidence of LV thrombus remains high despite PCI. Also, we find that DTBT in patients presenting with an ST-segment elevation AWMI does not affect the incidence of LV thrombus formation. Increased age, however, does appear to increase the risk of LV thrombus development.

Anti-human leukocyte antigen antibodies are associated with restenosis after percutaneous coronary intervention for cardiac allograft vasculopathy.

BACKGROUND: Percutaneous coronary intervention (PCI) to palliate cardiac allograft vasculopathy (CAV) has been associated with high restenosis rates, possibly related to increased inflammation associated with this disease. Whether markers of immunologic rejection are associated with restenosis in this population is unknown. The goal of the study was to determine the predictors of restenosis after PCI for CAV. METHODS: Records were reviewed retrospectively from a single, high-volume cardiac transplant center. Clinical, angiographic, and immunologic data were collected on all patients postorthotopic heart transplantation (OHT) that had subsequent PCI. Restenosis was defined as greater than 50% stenosis at the previous intervention site. RESULTS: PCI was successfully performed on 62 de novo lesions in 40 patients an average of 6.8+/-3.9 years after OHT. Angiographic follow-up data was available for 79%, with an average follow-up of 1.54+/-1.22 years. The 1-year restenosis rate was 49% (64% for balloon percutaneous transluminal coronary angioplasty and 33% for coronary stenting [P=0.09 for difference]). The frequency of immunoglobulin (Ig)G antibody to major histocompatibility complex (MHC) class I antigen was highly associated with risk of restenosis (hazard ratio [HR] 11.33, P=0.01). Greater stenosis severity and smaller target vessel diameter were also predictors of restenosis as in the nontransplant population. CONCLUSIONS: The findings suggest that in patients postPCI for CAV, humoral allo-immunity may contribute to restenosis and that IgG antibodies to MHC class I antigen may help predict the risk of restenosis after PCI in this population.

A rapid-response alphanumeric paging design decreases door-to-balloon times in patients undergoing primary percutaneous coronary intervention for ST elevation acute myocardial infarction.

INTRODUCTION: In acute ST elevation myocardial infarction (STEMI), rapid reperfusion of the infarcted artery improves cardiovascular outcomes; however, many hospitals have difficulty achieving recommended times. We hypothesized that a Rapid-Response Alphanumeric Paging Design (RAPiD) would reduce door-to-balloon time for primary percutaneous coronary intervention (PCI) in STEMI. METHODS: A chest pain algorithm and interdisciplinary team was established in December 2000. In August 2002, RAPiD was instituted to transmit the diagnosis and location of a STEMI to the chest pain team through a speed-dial button. All patients presenting to our emergency department from February 2002 through July 2003 with STEMI were included. Exclusion criteria included lack of chest pain, cardiopulmonary arrest before PCI, and catheterization or PCI not performed. Outside-referral STEMI, in-patient STEMI, and failed thrombolysis patients were excluded. Data was obtained from medical records. Log transform of door-to-balloon (DTB) times was performed. RESULTS: Forty-seven events satisfied inclusion and exclusion criteria with 32 occurring after RAPiD (post-RAPiD). Fifteen events occurred during on-hours (8 am to 7 pm on weekdays). Mean untransformed DTB times pre- and post-RAPiD were 162 +/- 137 (standard deviation) minutes and 112 +/- 41 minutes. The main effects analysis of variance model showed a significant reduction in post-RAPiD DTB time (P = 0.03) with a mean reduction of 26% during off-hours and 20% during on-hours. The post-RAPiD estimate of mean DTB time, derived from the antilog of the log transform, was 96.7 minutes (95% confidence interval, 83.7-111.7). CONCLUSIONS: The institution of RAPiD in a hospital with a preexisting chest pain algorithm significantly decreases DTB times so as to satisfy current ACC/AHA guidelines.