Assessment Of Cardiac Allograft Vasculopathy Research Articles

Recent trends in coronary intravascular ultrasound: Tracking atherosclerosis, pursuit of vulnerable plaques, and beyond

Within the past decade, intravascular ultrasound (IVUS) has proved to be a useful modality for guiding coronary interventions and assessment of cardiac allograft vasculopathy. During the last few years, IVUS has been used increasingly for the evaluation of the efficacy of various possible antiatherosclerotic therapies including high-dose statins, antihypertensives, and recombinant apolipoprotein A-I Milano. The recently introduced radiofrequency signal analysis is an advanced method for evaluation of IVUS signals to determine various histologic components of atherosclerotic plaques. Elastography is an allied technology for measuring the tissue strain that occurs in response to changes in intraluminal pressure. Whether radiofrequency signal analysis or elastography will become clinically useful tools for detecting vulnerable plaques remains an unanswered, burning question.

Neointimal Inflammation and Adventitial Angiogenesis Correlate With Severity of Cardiac Allograft Vasculopathy in Pediatric Recipients

Chronic inflammation and angiogenesis have been implicated in the pathogenesis of both cardiac allograft vasculopathy (CAV) and age-related vasculopathy. Because concurrent atherosclerosis does not complicate assessment of CAV in children, we sought to characterize the spectrum of coronary lesions in this population and determine whether inflammatory infiltrates and angiogenesis correlate with severity of CAV. In 18 pediatric heart specimens CAV was graded 1 to 4 (none to severe). Each case was assigned to either: Group I, no inflammation; Group II, perivascular inflammation; or Group III, perivascular and neointimal inflammation. Inflammatory infiltrates were immunophenotyped using anti-CD3, anti-CD20 and HAM 56. Angiogenesis was assessed by determining microvascular density (MVD) in 5 high-power fields (HPFs) per section. CAV was evident in 94% of cases, and inflammation in 61%. Cases with neointimal inflammation had significantly more severe CAV compared with cases without inflammation (2.7 +/- 0.16 vs 1.9 +/- 0.2, p = 0.002). MVD was significantly higher in both inflammation groups (Groups II and III) compared with Group I (4.1 +/- 0.5 per HPF and 5.9 +/- 0.5 vs 3.1 +/- 0.7, p = 0.018 and p = 0.002) and correlated with the degree of CAV (p = 0.007). The perivascular infiltrates (Group II, n = 5) contained lymphocytes, macrophages and plasma cells, and 67% of neointimal infiltrates (Group III, n = 6) also contained eosinophils. CAV in children is more common than previously reported. Our data indicate that CAV is often associated with inflammation and that adventitial angiogenesis correlated with the severity of CAV.

Quantitative assessment of cardiac allograft vasculopathy by real-time myocardial contrast echocardiography

Cardiac allograft vasculopathy (CAV) remains a major long-term complication after heart transplantation (HTx). We recently demonstrated semi-quantitatively that myocardial contrast echocardiography (MCE) is a promising noninvasive technique to evaluate microvascular perfusion and to identify significant coronary stenosis caused by CAV. The aim of this study was to evaluate the prognostic value of a quantitative assessment of stress MCE to detect CAV.

Coronary Doppler measurements do not predict progression of cardiac allograft vasculopathy: analysis by serial intracoronary Doppler, dobutamine stress echocardiography, and intracoronary ultrasound

Coronary flow velocity reserve (CFVR) (maximum/baseline flow velocity, 16 μg adenosine) was compared with dobutamine stress echocardiography (DSE) (5 to 40 μg/kg/min) to assess the progression of angiographically silent cardiac allograft vasculopathy (CAV). As a reference for the morphologic assessment of CAV, serial intracoronary ultrasound (ICUS) measurements were performed. An increase in CFVR could be observed in all transplant patients despite morphologic or functional progression of CAV or non-progressive CAV as assessed by ICUS or DSE. Thus, serial intracoronary Doppler flow analysis is not useful to predict morphologic or functional progression of CAV.

Impact of chronic infection with chlamydia pneumoniae on incidence of cardiac allograft vasculopathy.

Chronic infection with Chlamydia pneumoniae (CP) is associated with development of coronary disease. However, little information exists concerning CP infection and impact on posttransplant cardiac allograft vasculopathy (CAV). A total of 202 patients were investigated 5.5+/-3.1 years after cardiac transplantation (46.5+/-11.0 years; 169 male, 33 female). Assessment of CAV was performed by annual coronary angiograms. Chlamydia serology (IgG/IgA) was performed using micro-immunofluorescence. Statistics comprised analysis of variance and Kaplan-Meier analysis. A total of 152 patients were CAV positive. Elevated titers were present in 45% (IgG) and 72.8% (IgA) of patients. Generally, serostatus was not associated with development of CAV when evaluated over the total postoperative interval. However, after month 14 there was a significant trend toward lower actuarial freedom from CAV in patients with elevated IgA titers. CP seems not to play a significant role in the development of CAV early after heart transplantation but might be a predicting risk factor after the first postoperative year.

Role of Dobutamine Stress Echocardiography for Diagnosis of Cardiac Allograft Vasculopathy

CARDIAC allograft vasculopathy (CAV) remains a main factor limiting long-term survival after heart transplantation (HTX). Manifestations of CAV include focal stenoses as well as diffuse longitudinal involvement of vessels and small vessel disease. The clinical diagnosis is difficult, as the heart is denervated and usually remains without functionally relevant reinnervation. Routine coronary angiography is therefore the mainstay of diagnosis of CAV; this technique, however, shows a pure luminogram and is not able to detect early changes of CAV, ie, changes in the thickness of the vessel wall. Intravascular ultrasound (IVUS) has emerged as most sensitive invasive method for diagnosis of CAV. IVUS, however, can only be used to analyze the major epicardial vessels and is not able to investigate the entire coronary artery tree. In addition, both angiography and IVUS are invasive, costly and not free of risk. Several tests employed for noninvasive detection of CAV have proven unsatisfactory. In some studies, this may be related to the mode of provocation of ischemia: physical exercise may be not adequate after HTX, as the chronotropic response to exercise is blunted due to denervation. Stress tests using vasodilators as dipyridamole, which induces relative differences of perfusion, may be less reliable in diffuse CAV, but appear to be superior to exercise tests. Pharmacologic stress testing using dobutamine can overcome the problems associated with other stress modalities. Indeed, dobutamine stress echocardiography (DSE) has emerged as the most promising noninvasive method for diagnosis of CAV. This article reviews our experience and published data on assessment of CAV by DSE.

Predictive model to assess risk for cardiac allograft vasculopathy: An intravascular ultrasound study

This study was performed to assess the influence and interdependence of immunologic and nonimmunologic risk factors in the development of cardiac allograft vasculopathy. Another primary objective was to establish a clinically useful model for risk assessment of cardiac allograft vasculopathy that would facilitate identifying those heart transplant recipients likely to have severe intimal proliferation and thereby at greater risk for adverse clinical events. To our knowledge, no comprehensive intravascular ultrasound study has assessed the relative influences of both nonimmunologic and immunologic factors in the development of cardiac allograft vasculopathy, currently the major limitation to long-term cardiac allograft survival. Using a computer-assisted model of stepwise logistic regression, immunologic and nonimmunologic risk factors were evaluated to help identify the development of severe intimal thickening in 101 subjects who underwent intravascular ultrasound. Prospective validation of the findings was performed in a separate consecutive cohort of 37 heart transplant recipients, and the accuracy of this model to predict a relative risk > 1 for the development of severe intimal hyperplasia was assessed. Significant independent predictors of severe intimal hyperplasia in this model included a donor age > 35 years, a first-year mean biopsy score > 1 (a measure not only of severity of rejection, but also of frequency of insidious rejection) and hypertriglyceridemia at two incremental levels of risk (150 to 250 mg/dl [1.70 to 2.83 mmol/liter] and > 250 mg/dl [2.83 mmol/liter]). Based on the absence (0) or presence (1) of these factors, 12 individual categories of risk were ascertained with increasing relative risks and predicted probabilities for severe intimal hyperplasia. Prospective validation of this model revealed a sensitivity and specificity of 70% and 90%, respectively, and the positive and negative predictive values were 85% and 80%, respectively. Additionally, subjects with severe intimal thickening had a four-fold higher cardiac event rate than those without severe intimal proliferation on intravascular ultrasound. This study establishes a clinically useful predictive model that can be applied to individual heart transplant recipients to assess their risk for developing significant cardiac allograft vasculopathy and, thus, aids in the identification of patients at risk for cardiac events in whom closer surveillance and risk factor modification may be warranted.