Diagnosis Of Cardiac Allograft Vasculopathy Research Articles

Non-invasive myocardial tissue deformation and discoordination indices predict cardiac allograft vasculopathy in pediatric heart transplantation patients.

There is an urgent need for non-invasive imaging-based biomarkers suitable for diagnostic surveillance of cardiac allograft vasculopathy (CAV) in pediatric heart transplant (PHT) patients. The purpose of this study was to comprehensively investigate left ventricular (LV) myocardial deformation in conjunction with electromechanical discoordination in PHT. PHT patients with and without CAV were evaluated for echocardiography derived global longitudinal strain (GLS) and electromechanical discoordination indices including systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF). SSF was increased in CAV(+) patients at the time of CAV diagnosis (median CAV(+) 5.0 vs. median CAV(-) 0.0, P = 0.008) and in the echocardiogram preceding the CAV diagnosis (median CAV(+) 29.0 vs. median CAV(-) 0.0, P < 0.001). DRF was also increased in the echocardiogram that preceded CAV diagnosis in CAV(+) patients (0.31 ± 0.08 vs. 0.25 ± 0.05, P = 0.008). The final model using indices 6-12 months prior to CAV diagnosis included GLS, SSF, and DRF providing AUC of 0.94 with sensitivity 98.5%, specificity 80.0%, positive predictive value 85.0%, and negative predictive value 94.1%. Systolic and diastolic electro-mechanical discoordination indices are significantly worse in PHT patients experiencing CAV. Non-invasive imaging guided surveillance using echocardiographic myocardial deformation indices can be improved by adding SSF and DRF to standard GLS measurements.

Cardiac Allograft Vasculopathy: Challenges and Advances in Invasive and Non-Invasive Diagnostic Modalities.

Cardiac allograft vasculopathy (CAV) is a distinct form of coronary artery disease that represents a major cause of death beyond the first year after heart transplantation. The pathophysiology of CAV is still not completely elucidated; it involves progressive circumferential wall thickening of both the epicardial and intramyocardial coronary arteries. Coronary angiography is still considered the gold-standard test for the diagnosis of CAV, and intravascular ultrasound (IVUS) can detect early intimal thickening with improved sensitivity. However, these tests are invasive and are unable to visualize and evaluate coronary microcirculation. Increasing evidence for non-invasive surveillance techniques assessing both epicardial and microvascular components of CAV may help improve early detection. These include computed tomography coronary angiography (CTCA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and vasodilator stress myocardial contrast echocardiography perfusion imaging. This review summarizes the current state of diagnostic modalities and their utility and prognostic value for CAV and also evaluates emerging tools that may improve the early detection of this complex disease.

Capabilities of intravascular imaging techniques in the diagnosis of cardiac allograft vasculopathy: Literature review

Cardiac allograft vasculopathy (CAV) is a coronary heart disease (CHD), arising after an orthotopic heart transplant (OHT), and it is one of the leading causes of death in heart recipients. The probability of death is 10%. CAV can manifest as early as 1 year after OHT. Patients do not have pain syndrome that is typical for CHD due to cardiac denervation. The first clinical manifestations may be congestive heart failure, ventricular arrhythmias or even sudden cardiac death. Coronary angiography is the routine technique for CAV detection. However, it is not sensitive enough (about 44%) for CAV detection at an early stage of the disease. Today, intravascular imaging methods (intravascular ultrasound, optical coherence tomography), which allow the evaluation of the morphology of coronary artery lesions, including CAV, have become widespread. This article is devoted to the modern capabilities of intravascular imaging methods in the diagnosis of CAV. CAV is the main cause of myocardial infarction and chronic heart failure in patients after OHT. Intravascular imaging techniques allow early detection of this condition and prevention of unfavorable outcomes in a complex category of heart recipients. Given the advantages of optical coherence tomography (OCT) and disadvantages of intravascular ultrasound (IVUS), OCT appears to be a more informative method of CAV detection.

Reduction of cardiac allograft vasculopathy by PCI: Quantification and correlation with outcome after heart transplantation

Abstract Background Percutaneous coronary intervention (PCI) might improve outcome of heart transplanted (HTx) patients at severe stages of cardiac allograft vasculopathy (CAV). Yet, risk stratification of HTx patients after PCI remains challenging. The International Society for Heart and Lung Transplantation (ISHLT) provides a nomenclature for CAV classification that does not include patients after PCI (1). It is unclear how to define an individual optimal CAV reduction and how to stratify patients with CAV after PCI. Besides, whether risk-stratification tools of non-transplanted patients apply to HTx patients with CAV is uncertain. Purpose To assess whether the ISHLT CAV classification remains prognostic after PCI, and whether risk stratification models of non-transplanted patients can be applied to HTx patients with CAV. Methods At two European academic centers, 203 patients were stratified according to CAV severity and PCI history, and patients were assigned to only one cohort: cohort 1 (ISHLT CAV grade 1, without PCI, n=126) or cohort 2 (ISHLT CAV grades 2&amp;3, with PCI). At first diagnosis of CAV or first PCI, respectively, ISHLT CAV grades, SYNTAX scores I and II (SXS-I and SXS-II) were used to quantify baseline and residual CAV (rISHLT, rSXS-I, rSXS-II). A rSXS-I&amp;gt;0 defined incomplete revascularization (IR). Five-year mortality was assessed. For cohort 2, first reintervention was a secondary outcome. Baseline parameters were also included into analysis. Results SXS-II predicted mortality in cohort 1 (Hazard ratio [HR] 2.5 [1.4–4.8], p=0.004), whereas SXS-I (HR 4.2 [1.4–12.2], p=0.009) and SXS-II (HR 7.1 [2.0–24.5], p=0.002) predicted mortality in cohort 2. Post-PCI, IR (HR 5.4 [1.7–17.0], p=0.004), high rISHLT (HR 3.6 [1.3–10.2], p=0.02) and highest tertile of rSXS-II (HR 5.1 [1.6–15.9], p=0.006) were associated with higher mortality. In cohort 2, post-transplant interval and KDIGO category of renal function at timepoint 0 were also predictors of 5-year mortality after first PCI (HR 1.1 [1.0 – 1.2], p=0.004 and HR 4.5 [1.8–11.3], p=0.01, respectively). In bivariable Cox analysis, baseline SXS-II, IR, rSXS-II, post-transplant interval and KDIGO category of renal function remained predictors of 5-year mortality. The interval to first reintervention was inversely related to baseline SXS-I (r=-0.55, p&amp;lt;0.001) and rSXS-I (r=-0.50, p=0.003). Conclusion A higher reduction of stenotic CAV was associated with improved 5-year survival rate after first PCI. ISHLT CAV classification could apply for risk stratification after PCI and SYNTAX-scores could be complemental for risk stratification and individualization of invasive follow-up of HTx patients with CAV.Figure 1.Study flow chart.Figure 2.Kaplan-Meier curves (cohort 2)

Transplant Vasculopathy Versus Native Atherosclerosis: Similarities and Differences.

Cardiac allograft vasculopathy (CAV) is one of the leading causes of graft failure and death after heart transplantation. Alloimmune-dependent and -independent factors trigger the pathogenesis of CAV through activation of the recipients' (and to a lesser extent donor-derived) immune system. Early diagnosis of CAV is complicated by the lack of clinical symptoms for ischemia in the denervated heart, by the impact of early functional coronary alterations, by the insensitivity of coronary angiography, and by the involvement of small intramyocardial vessels. CAV in general is a panarterial disease confined to the allograft and characterized by diffuse concentric longitudinal intimal hyperplasia in the epicardial coronary arteries and concentric medial disease in the microvasculature. Plaque composition in CAV may include early fibrous and fibrofatty tissue and late atheromatous calcification. In contrast, native coronary atherosclerosis usually develops over decades, is focal, noncircumferential, and typically diminishes proximal parts of the epicardial vessels. The rapid and early development of CAV has an adverse prognostic impact, and current prevention and treatment strategies are of limited efficacy compared with established strategies in native atherosclerosis. Following acute coronary syndromes, patients after heart transplantation were more likely to have accompanying cardiogenic shock and higher mortality compared with acute coronary syndromes patients with native hearts.

Recurrent Mild Acute Rejections and Donor-specific Antibodies as Risk Factors for Cardiac Allograft Vasculopathy in a National Pediatric Heart Transplant Cohort.

Immune-mediated factors such as acute cellular rejections and donor-specific antibodies (DSAs) are risk factors for cardiac allograft vasculopathy (CAV). We studied a national cohort with a unified setting and thorough protocol endomyocardial biopsy (EMB) data for an association between cellular rejections, especially when mild and recurrent, and DSAs with CAV in pediatric heart transplant (HTx) patients. This is a retrospective, national cohort study of 94 pediatric HTxs performed between 1991 and 2019 and followed until December 31, 2020. Diagnosis of CAV was based on reevaluation of angiographies. Protocol and indication EMB findings with other patient data were collected from medical records. Associations between nonimmune and immune-mediated factors and CAV were analyzed with univariable and multivariable Cox regression analyses. Angiographies performed on 76 patients revealed CAV in 23 patients (30%). Altogether 1138 EMBs (92% protocol biopsies) were performed on 78 patients (83%). During the first posttransplant year, grade 1 rejection (G1R) appeared in 45 patients (58%), and recurrent (≥2) G1R findings in 14 patients (18%). Pretransplant DSAs occurred in 13 patients (17%) and posttransplant DSAs in 37 patients (39%). In univariable analysis, pretransplant DSAs, appearance and recurrence of G1R findings, and total rejection score during the first posttransplant year, as well as recurrent G1R during follow-up, were all associated with CAV. In multivariable analysis, pretransplant DSAs and recurrent G1R during the first posttransplant year were found to be associated with CAV. Our results indicate that pretransplant DSA and recurrent G1R findings, especially during the first posttransplant year, are associated with CAV after pediatric HTx.

Coronary allograft vasculopathy in post-heart transplant patients: pathogenesis and role of cardiac computed tomography in diagnosis-a comprehensive review.

Coronary allograft vasculopathy, often known as cardiac allograft vasculopathy (CAV), is a substantial source of morbidity and mortality in people who have had heart transplants. Early detection and monitoring of CAV are crucial for improving outcomes in this population. Although cardiac computed tomography (CT) has emerged as a possible method for finding and evaluating CAV, invasive coronary angiography has long been thought of as the gold standard for recognizing CAV. This study focuses on the utility of cardiac CT for CAV diagnosis and treatment in the post-heart transplant population. It provides an overview of recent studies on the application of cardiac CT in CAV and highlights the advantages and disadvantages of this imaging modality. The potential application of cardiac CT for CAV risk assessment and care is also examined in the study. Overall, the data point to a potential role for cardiac CT in the detection and treatment of CAV in post-heart transplant patients. It enables evaluation of the whole coronary tree and low-radiation, high-resolution imaging of the coronary arteries. Hence, further study is required to determine how best to employ cardiac CT in treating CAV in this group.

Increased fibrosis and microvessel disease in allograft endomyocardial biopsies of children with chronic graft failure due to cardiac allograft vasculopathy

IntroductionChronic graft failure (CGF) is the leading cause of mortality in pediatric heart transplant (PHT) patients and has multifactorial pathogenesis including cardiac allograft vasculopathy (CAV). CGF can present with microvessel disease (MVD) and myocardial fibrosis on endomyocardial biopsies (EMB). We investigated if CGF due to moderate- severe (M-S) CAV has histopathologic MVD and fibrosis prior to or at the time of CAV diagnosis. MethodThis retrospective case-control study included PHT with CGF secondary to M-S CAV. Control patients had no CAV or CGF. EMBs from CAV (3 sets: at 1-year post-transplant 1yrCAV, pre-CAV, and at the time of CAV diagnosis) and non-CAV cohorts were reviewed to grade the fibrosis and quantify MVD. Histopathologic changes were correlated and compared between CAV/non-CAV groups. ResultsEach group had 8 patients. The median age at transplantation and time since transplant were similar between the two groups (P=.71 and P=.91, respectively). Fibrosis grade was 3.0 for CAV cohort compared to 1.0 for control (P= .003) and MVD score was 2.1 in CAV and 0.5 in non-CAV patients (P=.003). Similar degrees of fibrosis and MVD were present even before any evidence of CAV (1yrCAV fibrosis grade 2.5, pre-CAV fibrosis grade 2; 1yrCAV vs CAV P=.75, pre-CAV vs CAV P=.63; 1yrCAV MVD score 2, pre-CAV MVD score 2; 1yrCAV vs CAV P=1, pre-CAV vs CAV P=.91). The degree of MVD correlated with fibrosis (r=0.63, P<.0001) for all EMBs. ConclusionSimultaneous myocardial fibrosis and MVD are noted in CGF secondary to M-S CAV, changes that occur before angiographic CAV. EMBs can reveal significant changes in patients with subsequent development of CAV and may be used to modify the follow-up and treatment for these high-risk patients.

PET Myocardial Blood Flow for Post-transplant Surveillance and Cardiac Allograft Vasculopathy in Heart Transplant Recipients.

Cardiac allograft vasculopathy (CAV) is a late-occurring complication of heart transplantation significantly limiting overall graft survival. In the last few years, evidence has been growing about the use of positron emission tomography (PET) myocardial perfusion imaging with integrated myocardial blood flow (MBF) quantification in heart transplant recipients. Multiple studies have demonstrated that PET MBF assessment can be utilized to establish the diagnosis of CAV noninvasively and can be employed for prognostication. PET MBF quantification has also helped to define the link between transplant rejection and CAV. In addition, limited data suggests that PET MBF quantification can be used in heart transplant patients for serial monitoring of CAV. PET myocardial perfusion imaging integrating MBF quantification shows great promise for the evaluation of CAV with good diagnostic and prognostic performance.

Non-invasive Imaging in the Evaluation of Cardiac Allograft Vasculopathy in Heart Transplantation: A Systematic Review.

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.

Finding the Road to Rome in Cardiac Allograft Vasculopathy Imaging Surveillance.

Finding the Road to Rome in Cardiac Allograft Vasculopathy Imaging Surveillance.

Cardiac allograft vasculopathy in pediatric heart transplant recipients does early-onset portend a worse prognosis?

We sought to evaluate the association between timing of cardiac allograft vasculopathy (CAV) occurrence post-heart transplant (HT) with graft survival and progression of CAV severity in pediatric HT recipients. Data from the Pediatric Heart Transplant Society for pediatric (<18 years old) HT recipients between 1993-2019 with available angiographic data were obtained (N=5,075). The timing of CAV diagnosis (<3; 3-<5; 5-<10; and ≥10 years post-HT) and severity of disease at each assessment (CAV 1-3) was determined. Associations between CAV timing, graft survival, and CAV progression were evaluated using Kaplan-Meier survival curves, multivariable COX proportional hazard regression analyses, and competing risk analyses. Over a median follow-up period of 4.1 (IQR 1.3-8.3) years, CAV was identified in 17% (885/5,075), 28% (252/885) of which were early-onset CAV. Compared with late onset CAV ≥10 years post-HT, patients with early CAV were older at the time of transplant (8.3 ± 6.2 vs. 3.8 ± 4.8 years, p < .0001). While the five-year graft-survival in the ≥10-year group (79.2%, p=0.03) was significantly higher than the <3, 3-<5, and 5-<10 years post-HT groups (65.0%-67%) (p=0.03), overall post-CAV graft survival was not significantly different across the CAV time-points. CAV disease progression did not vary with CAV timing post-HT, with an overall five-year freedom from CAV ≥2 of 75.4% (73.1%-77.6%). Later onset CAV (≥10-years post-HT) was associated with improved five-year graft survival compared with CAV onset at earlier time-points, but similar and poor long-term outcomes. CAV timing post-HT was not associated with progression of CAV disease severity.

Abstract 14045: Increased Fibrosis and Microvessel Disease in Allograft Endomyocardial Biopsies of Children With Chronic Graft Failure Due to Cardiac Allograft Vasculopathy

Introduction: The pathogenesis of chronic graft failure (CGF) in pediatric heart transplant recipients (PHT) is multifactorial and includes cardiac allograft vasculopathy (CAV). Prior research has shown that CGF can present as microvessel disease (MVD) and fibrosis on endomyocardial biopsies (EMB), however, optimal routine surveillance is not established. We analyzed EMB specimens to establish histopathologic findings of CGF represented by PHT with CAV. Hypothesis: PHT recipients with CGF secondary to CAV have increased fibrosis and MVD on EMB. Method: We performed a retrospective case-control study. PHT with moderate to severe (M-S) CAV diagnosed on cardiac catheterization between 2017-2020 were identified. EMB from time of M-S CAV diagnosis (CAV-EMB) was reviewed (excluding those with significant intercurrent rejection) and compared to their EMB prior to any CAV diagnosis (pre-CAV-EMB) and controls that were matched for age at and time since transplant (Tx) . Fibrosis was qualitatively graded on a scale of 0-5 and MVD was scored as number of capillaries with stenotic wall thickening (due to either endothelial cell swelling or medial hypertrophy) per fields of view. Results: Eight PHT with CAV-EMB and pre-CAV-EMB and 8 controls were identified. CAV-EMB group was 2.5 years (IQR: 0.9,8.0) old at time of Tx and 10.6 years post-Tx (8.3,15.5) at EMB. Pre-CAV-EMB was 1.8 years (1.1,2.8) prior to CAV-EMB. In the CAV, pre-CAV, and control groups median fibrosis score was 3.0 (2.0, 3.0) vs 2.0 (2.0, 3.0) vs 1.0 (0, 1.0) (p= 0.001) and MVD score was 2.1 (1.3, 2.9) vs 2.0 (1.6, 2.8) vs 0.5 (0.2, 0.7), respectively (p= 0.007). These were significantly different between pre-CAV-EMB vs controls (fibrosis p=0.003, MVD p=0.007) and CAV-EMB vs controls (fibrosis p=0.001, MVD p=0.005), but not between pre-CAV-EMB vs CAV-EMB. Furthermore, fibrosis and MVD scores were strongly correlated (r=0.78, p&lt;0.001). Conclusion: Histopathological evidence of increased fibrosis and MVD is noted in EMB with CGF secondary to CAV and these findings pre-date angiographic CAV diagnosis. Further studies in larger PHT cohorts are needed to assess time course of fibrosis and MVD to improve surveillance of CAV and CGF.

Early diagnosis and management of cardiac allograft vasculopathy: is it time for a standardized approach?

Cardiac allograft vasculopathy (CAV) still represents the main cause of long-term graft loss after heart transplantation. Its silent clinical presentation makes an early identification difficult, with relevant implications for a standardized follow-up. Although technological advances have provided sophisticated non-invasive techniques for CAV assessment, intravascular ultrasound in conjunction with coronary angiography is still the gold standard to detect rapidly progressive CAV and to provide prognostic information during follow-up. Current guidelines recommend annual coronary angiography during the first 5 years and every 2 years thereafter. Although commonly performed, coronary angiography has multiple limitations, especially in young patients and in case of chronic kidney disease. This article aims to review the literature about the monitoring of CAV and to propose an ideal and individualized pathway for early diagnosis of CAV in transplanted patients, based on their cardiovascular risk.

Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Recipients: Does Early Onset Portend a Worse Prognosis?

<h3>Purpose</h3> We sought to evaluate the association between early-onset cardiac allograft vasculopathy (CAV) [<3 years post heart transplant (HT)] & graft survival (freedom from death & re-transplantation), compared with CAV development at later time-points in pediatric HT recipients. <h3>Methods</h3> Data from the Pediatric Heart Transplant Society (PHTS) for pediatric (<18 years old) HT recipients between 1993-2019 with available angiographic data were obtained (N = 5,075). Patients with a diagnosis of CAV were categorized according to the timing of disease post-HT; <3 years; 3-<5 years; 5-<10 years; & ≥10 years. CAV severity was graded at each assessment (CAV 1-3). Kaplan-Meier survival curves were generated to evaluate the association between CAV timing & graft survival (primary outcome). A competing risk analysis was used to evaluate the association between CAV timing & the progression of CAV severity (secondary outcome). <h3>Results</h3> Over a median follow-up period of 4.1 (IQR 1.3 - 8.3) years, angiographic evidence of CAV was identified in 17% (885/5,075) of patients, 28% (252/885) of which were early-onset CAV. Compared to those who developed CAV >10 years post HT, patients with early-onset CAV were older at transplant (8.3 +/- 6.2 vs. 3.8 +/- 4.8 years, p < .0001). Five-year graft survival following CAV diagnosis at any time point was 68.7% (66.8% - 70.4%). Graft survival post-CAV diagnosis was not significantly different for early-onset CAV compared with CAV at later time points (Figure). For patients with CAV-1, freedom from progression to CAV-2 did not vary according to the timing of CAV onset, with an overall five-year freedom from CAV-2 of 75.4% (73.1%-77.6%). <h3>Conclusion</h3> Following diagnosis, the progression of CAV & graft survival was similar for patients with early-onset CAV compared with CAV at other time points. These findings suggest that early-onset CAV does not necessarily represent a more aggressive phenotype of disease.

Moderate Association of Coronary Artery Calcium and Cardiac Allograft Vasculopathy in Heart Transplant Recipients on Non-Gated CT

<h3>Purpose</h3> Cardiac allograft vasculopathy (CAV) is common in patients who have undergone orthotopic heart transplant (OHT) and is associated with significant morbidity and mortality. Non-invasive methods for identifying CAV are an appealing alternative to standard clinical practice of routine invasive angiography. We explored the association of CAV with incidental coronary artery calcium (CAC) from non-ECG gated, clinically indicated chest CT scans. <h3>Methods</h3> This is a single-center, retrospective, observational study of OHT patients >1 year from transplant who underwent left heart catheterization between 2015 and 2019 and had a clinically indicated, non-ECG gated chest CT obtained for a variety of indications within 6 months of the catheterization. CAC was graded by a blinded reviewer in a semi-quantitative manner based on extent and distribution across the coronary tree. Angiographically significant CAV was obtained from left heart catheterizations results obtained per standard institutional protocol. <h3>Results</h3> 73 patients were included, 56 (77%) were male, mean age was 60±12 years and median time from heart transplant was 4 years [IQR 2, 8]. 34 patients (47%) were found to have CAC, of which 7 (21%) were found to have moderate or severe CAC. 38 patients (52%) were found to have CAV on angiography. In the CAC group, 25 were found to have CAV (74%). Of those with moderate to severe CAC, 7 (100%) were found to have CAV. In the no CAC group, 13 (33%) were found to have CAV. The presence of CAC had a sensitivity, specificity, positive predictive value and negative predictive value of 66%, 74%, 73%, and 67% respectively for the diagnosis of CAV. <h3>Conclusion</h3> The absence of CAC on non-ECG gated CT demonstrated a moderate ability to rule out CAV, while moderate to severe CAC was strongly associated with CAV. As chest CT scans are common in this population, informing clinical decision making with this "free" information is potentially beneficial.

Detection of cardiac allograft vasculopathy by multi-layer left ventricular longitudinal strain in heart transplant recipients.

Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse type of coronaropathy that develops in the transplanted human heart, representing a major cause of graft failure and mortality. Nowadays the gold standard for the diagnosis of CAV is coronary angiography (CA). Non-invasive CAV detection, especially in the early stages of the disease, is still challenging. Our study aimed to investigate the role of speckle tracking echocardiography (STE), in particular three-layer STE, in predicting CAV at early stages, and if other traditional echocardiographic, clinical or biochemical parameters could relate to CAV. The study population was composed of a total of 33 heart transplanted patients, divided accordingly to the presence or absence of CAV (12 CAV+ , 22 CAV-). All subjects underwent a complete transthoracic echocardiographic examination on the same day of the CA, and all conventional parameters of myocardial function were obtained, including strain values assessed by STE. Strain values were significantly reduced in presence of CAV, at each myocardial layer but in particular the endocardial-epicardial gradient (-4.15 ± 1.6 vs -1.7 ± 0.4% < .0001) that was also highly predictive of CAV (AUC at ROC curve 0.97). Among diastolic parameters, the E wave deceleration time (DT) and the mean E/e' ratio were strongly positively associated with CAV. In our population, left ventricular global longitudinal strain (GLS), layer-specific GLS and the endocardial-epicardial LS gradient, E wave DT and E/e' ratio were the best independent non-invasive predictors of CAV.

Mid-term survival after heart retransplantation in late cardiac allograft failure

Introduction Among patients who survive heart transplant, recurrent end-stage heart failure is a major cause of morbidity and mortality secondary to acute rejection, primary graft failure or coronary artery vasculopathy, and heart retransplantation (HRT) offers the potential for long-term survival. However, there is controversy about the appropriateness of retransplantation because of limited organ availability and outcomes that tend to be worse than in primary transplantation. Internationally, between 2 and 4% of the available donor hearts are distributed to retransplant patients.1 The aim of this study was to determine the mid-term survival after heart retransplantation. Methods After obtaining Institutional Review Board approval, the authors retrospectively studied all consecutive adult patients who underwent orthotopic heart transplantation between January 2009 and December 2018 at a tertiary care university hospital and followed them up until December 2019. Patients included in the analysis had undergone HRT and were 18 years or older. Recipient demographic data, hemodynamic profile and postoperative outcomes were analyzed. Results During the study period, 250 patients underwent orthotopic heart transplantation. Among these patients, 2% (n=5) underwent HRT. The end-stage heart failure diagnoses leading to first heart transplant in our study were hypertrophic cardiomyopathy (40%), idiopathic cardiomyopathy (40%) and myocarditis (20%); and the major indications for HRT were chronic rejection (60%) and cardiac allograft vasculopathy (40%). Grafts failed at a median follow-up of 9 (5) years after first heart transplantation. The majority of patients (80%) required combined simultaneous second cardiac and first renal transplantation. Heart-kidney combined transplantation were performed with organs coming from the same donor and with no-staged modality. Actuarial survival rate was 60%, after a median follow-up of 17.8 (39.6) months. Discussion Although HRT survival is still inferior to primary transplantation, it has improved over the decades and is a viable treatment option for patients with late failing allografts. Outcome after HRT strongly depends on the indication for retransplantation and the interval between first and second transplantation. Different studies suggest that a diagnosis of cardiac allograft vasculopathy or chronic rejection and an interval between first and second transplantation greater than 1 year have a significantly favorable impact on mortality.2 3 Judicious patient selection and careful perioperative care are of utmost importance considering limited allograft availability.

Coronary Artery Vasospasm: A Under-recognized Phenomenon in Orthotopic Heart Transplant

Introduction Cardiac allograft vasculopathy (CAV) is known as the primary cause of death in the first year after orthotopic heart transplant (OHT). Coronary artery spasm (CAS) in OHT is a rare and under-recognized phenomenon in patients undergoing surveillance. The mechanism of coronary vasospasm in OHT remain largely unknown. The presentation can vary from an incidental finding to severe episodes of symptomatic ventricular arrhythmias, high-degree atrioventricular block, syncope, cardiac arrest, or even myocardial infarction in cases of prolonged ischemia. Case Presentation 65 yo female with history of chronic kidney disease, diabetes mellitus type 2, hypertension, hyperlipidemia, and orthotopic heart transplantation with CMV mismatch in 2016 secondary to apical hypertrophic cardiomyopathy. Prior coronary angiography (CA) done at our institution had shown no evidence of vasculopathy. During one of her follow-up visits in the Clinic, she complained of increasing dyspnea on exertion, prompting urgent referral for CA, as per our surveillance protocols. Prior to the procedure, echocardiography was performed which revealed normal graft function and no valvular abnormalities. She underwent CA which showed a proximal significant diffuse luminal narrowing of the right coronary artery (RCA) (Image 1) and normal left coronary artery anatomy (Image 2). We proceed to repeat CA with intracoronary administration of nitroglycerin (ICN) and measurement of fractional flow reserve (FFR) of RCA (Image 3, 4). Angiography revealed near resolution of the RCA lesion, ultimately suggesting that transient vasospasm had been responsible for the previous angiographic appearance (Image 1). Summary CAS can present in patients with or without vasculopathy. It can produce luminal narrowing and can be difficult to distinguish angiographically from CAV. Misdiagnosis of this entity has led to the incorrect diagnosis of CAV and subsequent unnecessary stenting. ICN use can improve angiographic visualization, and prevent the adverse effects of coronary spasm. In conclusion, CAS is a rare and potential complication post OHT. It is a difficult entity to prognosticate due to scarcity of clinical evidence, as prevalence ranges from 4.9% to 12.1%. Some authors hypothesize that CAS in OHT carries a poor prognosis as it is often an early manifestation of CAV. However, this remains largely hypothetical and further studies are needed to better understand this disease.

Cost-Effectiveness of Cardiac Magnetic Resonance Imaging in the Diagnosis of Cardiac Allograft Vasculopathy as Well as the Detection of Myocardial Inflammation Associated with Treatment-Requiring Cellular Rejection

The purpose of this study is to assess the cost-impact of cardiac magnetic resonance imaging (CMR) and its advantages over conventional cardiac catheterization to detect cardiac allograft vasculopathy (CAV) and myocardial inflammation derived from possible rejection in heart transplant (HTx) recipients. A sizable institutions still perform an endomyocardial biopsy (EMB) and coronary artery angiogram (CAG) in routine practice. Non-invasive diagnostic tools such as echocardiography and gene expression profiling have been reported as a possible alternative to EMBs, but its application is limited. Stress echo is a powerful tool for sorting those who require invasive assessment, but it cannot detect ongoing CAV. CMR is free from radiation exposure and allows the visualization of coronary artery narrowing without using contrast agents. We estimated medical care expense needed for rejection and CAV surveillance for HTx recipients at 3 years to 15 year-posttransplant in Japan (n=320), consisting of those with 10 % rejection rate up to 5 years and 20% CAV occurrence thereafter, as a hypothetical cohort. Three models were created. Model-1: Annual investigation using CMR-angiography to assess CAV, and T2W imaging to detect myocardial inflammation. For patients with a suspicion of the development of rejection or CAV, EMBs and CAG are performed. Model-2: Annual evaluation using CAG and EMBs up to 10 years posttransplant. After 10 year-posttransplant, the invasive procedure is done as needed. Model-3: Using echocardiography as a primary modality to detect rejection. CAG biennial and EMBs if any change in echo. If patients never developed rejection or CAV, Model-1 is the least costly with ¥228,800 to 324,860 per patient, whereas Model-2 costs ¥1,064,000 to 2,190,000 and Model-3, ¥445,200 to 689,000, respectively. When we include patients with rejection or CAV according to a hypothetical cohort, Model-1 and Model-3 were equally cost-effective. When we set sensitivity and specificity of CMR and echo as 70%, 80% and 70%, 90%, respectively, Model-1 is most cost-effective with sufficient diagnostic accuracy. Utilization of CMR as an annual follow-up tool in HTx recipients would be beneficial from a viewpoint of medical economics.