Assessment of Cardiac Allograft Vasculopathy Late After Heart Transplantation: When Is Coronary Angiography Necessary?

doi:10.1016/j.healun.2006.05.009

The Journal of Heart and Lung Transplantation

Volume 25, Issue 9, September 2006, Pages 1103-1108

https://doi.org/10.1016/j.healun.2006.05.009 Get rights and content

Background

Cardiac allograft vasculopathy (CAV) represents a major prognostic factor in long-term survivors of heart transplantation (HTx). Reliable diagnosis of CAV late after HTx is important but remains the domain of invasive techniques such as coronary angiography.

Methods

To test alternative approaches, 54 consecutive HTx recipients (mean time since HTx: 52 months) were studied with intravascular ultrasound (IVUS), angiography, dobutamine stress echocardiography and immunofluorescence staining against anti-thrombin III (AT-III) in endomyocardial biopsies. Univariate and multivariate predictors as well as receiver-operating-characteristic (ROC) curves of different sets of predictors were calculated.

Results

Using IVUS as reference standard, CAV was present in 80% of subjects. Coronary angiography identified CAV correctly in only 44% of cases. If AT-III staining alone was used as a diagnostic criterion, CAV was correctly identified in 77% of subjects. In a multivariate analysis, only AT-III, donor age and echocardiography at rest emerged as independent predictors of CAV (p < 0.05 for all), yielding an excellent discriminative power.

Conclusions

With almost equal reliability when compared with IVUS, CAV can be identified using information on donor age, wall motion score at rest and AT-III staining late after HTx. Coronary angiography may be limited to patients with a high probability score and should not be used routinely for surveillance of CAV.

Section snippets

Methods

Fifty-four consecutive heart transplant recipients (22% female; age, 49.2 ± 11.5 years; time since transplantation, 52 ± 37 [median, 36; range, 11 to 75] months) were investigated upon routine post-transplant monitoring. DSE was done on the day of admission, and coronary angiography, IVUS and right ventricular endomyocardial biopsy were performed in one session on the next day. The local university ethics review board reviewed the study and all patients gave informed consent to participate.

Results

Presence of CAV was diagnosed in 43 of 54 (80%) subjects using the IVUS criterion of Grade >3.0 (mean). The study characteristics are given in Table 1 for all patients and for sub-groups with and without CAV. Patient characteristics, including the immunosuppressive regimen and the concomitant medication, were comparable between these sub-groups except for donor age, which was higher in the CAV patients (Table 1). Subsequent steps in the diagnostic work-up for CAV are shown in Table 2. Systolic

Discussion

The main finding of this study is that, after a mean of 4 years post-HTx, CAV is present in 80% of cases according to IVUS criteria, and that CAV as detected by IVUS can be reliably identified using information on donor age, wall motion score at rest and AT-III staining. Compared with wall motion score at stress and qualitative coronary angiography, only AT-III staining significantly increased the diagnostic accuracy. Our data underscore the potential of immunohistochemical AT-III staining as a

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Cited by (46)

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era
2023, Journal of Cardiac Failure
Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre–direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test–positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear.
We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT– donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT– cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT– hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV.
These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.
Non-invasive Imaging in the Evaluation of Cardiac Allograft Vasculopathy in Heart Transplantation: A Systematic Review
2022, Current Problems in Cardiology
Citation Excerpt :
There were 30 studies identified for TTE, 24 studies for CT, 14 for MRI and 13 for PET (Consort Diagram). Among the 30 studies that examined TTE as a non-invasive method to detect CAV, 16 studies were included in this study (Table 1)8-23 and examined 1364 patients from 1996-2020. The remaining studies did not contain accessible data.
Cardiac allograft vasculopathy (CAV) is the leading cause of long-term graft dysfunction in patients with heart transplantation and is linked with significant morbidity and mortality. Currently, the gold standard for diagnosing CAV is coronary imaging with intravascular ultrasound during traditional invasive coronary angiography. Invasive imaging, however, carries increased procedural risk and expense to patients in addition to requiring an experienced interventionalist. With the improvements in non-invasive cardiac imaging modalities such as transthoracic echocardiography, computed tomography, magnetic resonance imaging and positron emission tomography, an alternative non-invasive imaging approach for the early detection of CAV may be feasible. In this systematic review, we explored the literature to investigate the utility of non-invasive imaging in diagnosis of CAV in >3000 patients across 49 studies. We also discuss the strengths and weaknesses for each imaging modality. Overall, all 4 imaging modalities show good to excellent accuracy for identifying CAV with significant variations across studies. Majority of the studies compared non-invasive imaging with invasive coronary angiography without intravascular imaging. In summary, non-invasive imaging modalities offer an alternative approach to invasive coronary imaging for CAV. Future studies should investigate longitudinal non-invasive protocols in low-risk patients after heart transplantation.
Imaging of Cardiac Transplantation: An Overview
2021, Seminars in Nuclear Medicine
Citation Excerpt :
In addition, several studies have shown a poor relation between the invasive LV filling pressure and the echocardiographic LV filling pattern in HTx patients.85-87 Dobutamine stress echocardiography with assessment of wall motion abnormalities is widely used for routine CAV surveillance.88-92 However, the diagnostic performance in these studies is variable (sensitivity 50%-100%, specificity 50%-95%).
Heart transplantation (HTx) remains the optimal treatment for selected patients with end-stage advanced heart failure. However, survival is limited early by acute rejection and long term by cardiac allograft vasculopathy (CAV). Even though the diagnosis of rejection is based on histology, cardiac imaging provides a pivotal role for early detection and severity assessment of these hazards. The present review focuses on the use and reliability of different invasive and non-invasive imaging modalities to detect and monitor CAV and rejection after HTx. Coronary angiography remains the corner stone in routine CAV surveillance. However, angiograms are invasive and underestimates the CAV severity especially in the early phase. Intravascular ultrasound and optical coherence tomography are invasive methods for intracoronary imaging that detects early CAV lesions not evident by angiograms. Non-invasive imaging can be divided into myocardial perfusion imaging, anatomical/structural imaging and myocardial functional imaging. The different non-invasive imaging modalities all provide clinical and prognostic information and may have a gatekeeper role for invasive monitoring. Acute rejection and CAV are still significant clinical problems after HTx. No imaging modality provides complete information on graft function, coronary anatomy and myocardial perfusion. However, a combination of invasive and non-invasive modalities at different stages following HTx should be considered for optimal personalized surveillance and risk stratification.
Changes in Outcomes of Cardiac Allograft Vasculopathy Over 30 Years Following Heart Transplantation
2017, JACC: Heart Failure
This study investigated temporal changes in the demographics and the prognosis of cardiac allograft vasculopathy (CAV) over 30 years following heart transplantation (HTx).
Effects of the changing HTx demographics on CAV outcomes, based on International Society for Heart and Lung Transplantation (ISHLT) classification of CAV, have been incompletely investigated.
Patients who underwent HTx at the Montreal Heart Institute were classified according to the severity of CAV (CAV 0 is no presence of CAV; CAV 1 is mild, CAV 2 to 3 is moderate to severe) and era of HTx (early: 1983 to 1998; recent: 1999 to 2011). We compared the risk of progression, survival, and independent predictors of outcomes among the groups.
A total of 298 patients were followed for 11.6 ± 6.6 years. Patients who received transplants in the early era exhibited a higher risk for progression from CAV 1 to a higher grade (adjusted odds ratio: 8.0; 95% confidence interval [CI]: 1.01 to 62.6). The presence of CAV was associated with a significantly increased risk for all-cause mortality in the early era (hazard ratio [HR]: 1.6; 95% CI: 1.1 to 2.5) but not in the recent era (HR: 1.1; 95% CI: 0.2 to 4.9). Regardless of the era, CAV classes 2 to 3 and CAV 1 were associated with a significantly increased risk for all-cause mortality compared to CAV 0 (HR: 6.5; 95% CI: 2.7 to 15.7; and HR: 1.750; 95% CI: 1.001 to 3.046, respectively).
The progression and prognosis of CAV have improved over 30 years. The ISHLT CAV classification accurately and independently predicts long-term outcome following HTx.
Post-transplant surveillance for acute rejection and allograft vasculopathy by echocardiography: Usefulness of myocardial velocity and deformation imaging
2017, Journal of Heart and Lung Transplantation
Citation Excerpt :
Another advantage of DSE when compared with exercise-stress echocardiography is related to the better inotropic response (with higher myocardial oxygen demand) to dobutamine than to exercise. Nevertheless, clinical studies have revealed no definite advantages of DSE in comparison to exercise-stress echocardiography for diagnosis of significant CAV (Table 1).30–39 Also, for DSE, there is a wide range of sensitivity and specificity reported (0% to 100% and 55% to 99%, respectively) for detection of CAV, which appears mainly related to differences in prevalence of resting WMA in the groups studied, differences in defining the presence and severity of CAV, and whether the gold standard being used is CA or CA plus intravascular ultrasound (IVUS).24,29–35
Diagnosing and monitoring acute rejection (AR) and cardiac allograft vasculopathy (CAV) is essential for graft and transplant patient survival and, consequently, a major objective for heart transplant patient surveillance. Because functionally relevant CAV can arise and progress without clinical symptoms and sub-clinical ARs can facilitate the development of CAV, standard surveillance of AR and CAV includes routine endomyocardial biopsy (EMB) and coronary angiography (CA) screenings at pre-defined time intervals. However, these invasive screenings (distressing and risky for the patients) cannot solely diagnose all sub-clinical AR episodes and also not always detect coronary stenoses before a clinical event. Additional close-meshed, non-invasive AR and CAV surveillance strategies are therefore mandatory. After the introduction of tissue Doppler imaging (TDI) and strain imaging for myocardial wall motion and deformation analysis, echocardiography became particularly promising for that purpose. Allowing quantification of minor myocardial dysfunction not detectable by standard echocardiography, TDI and strain imaging can reveal sub-clinical AR. Thus, these approaches can be a valuable supplement to EMB, enabling more efficient AR monitoring with fewer EMBs (only diagnostic EMBs) instead of unnecessary and distressing routine EMB screenings. Their use can also improve therapeutic decisions and monitoring of myocardial function during anti-rejection therapy. Myocardial velocity and deformation imaging is also suited to early detection of myocardial dysfunction induced by CAV and may be useful for prognostic evaluation and timing of CAs, with an aim of reducing the number of routine CA screenings. However, further studies are necessary before specific recommendations for the use of TDI and strain imaging for CAV surveillance become possible.
Allograft Vasculopathy the Achilles' Heel of Heart Transplantation
2016, Journal of the American College of Cardiology
Cardiac allograft vasculopathy (CAV) remains the Achilles’ heel of long-term survival after heart transplantation. Almost one-third of patients develop CAV by 5 years post-transplant and 1 in 8 deaths beyond a year are due to CAV. Abnormal vascular fibroproliferation in CAV occurs as a result of coronary endothelial inflammation, injury, and dysfunction triggered by immune and nonimmune insults. Surveillance methods for CAV have significant limitations, particularly for detecting early disease. Areas of investigation include myocardial and coronary blood flow quantification, and intracoronary imaging to detect early changes in the vessel wall and high-risk plaques. Treatment approaches continue to evolve, but prevention remains the focus. Newer mammalian target of rapamycin inhibitors can significantly delay the progression of CAV; however, their optimal use remains to be established. Further investigation is needed to understand the complex pathophysiology of CAV, improve surveillance techniques, and develop therapies to prevent and slow disease progression.

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: Supported by a grant from the Ernst & Berta Grimmke Stiftung, Düsseldorf, Germany (to S.S. and T.M.B.).

¹: The first two authors (S.S. and T.M.B.) contributed equally to this study.

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Allograft vasculopathyAssessment of Cardiac Allograft Vasculopathy Late After Heart Transplantation: When Is Coronary Angiography Necessary?

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

J Heart Lung Transplant

J Heart Lung Transplant

J Heart Lung Transplant

J Heart Lung Transplant

JAMA

J Heart Lung Transplant

J Heart Lung Transplant

Am J Cardiol

Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factorsCardiac Transplant Research Database

J Heart Lung Transplant

Cardiac allograft vasculopathy: a review

Circulation

Pathologic markers of allograft arteriopathy: insight into the pathophysiology of cardiac allograft chronic rejection

Curr Opin Cardiol

Diagnostic accuracy of coronary angiography and risk factors for post-heart-transplant cardiac allograft vasculopathy

Transplantation

Allograft vasculopathy
Assessment of Cardiac Allograft Vasculopathy Late After Heart Transplantation: When Is Coronary Angiography Necessary?