Diffuse myocardial fibrosis among healthy pediatric heart transplant recipients: Correlation of histology, cardiovascular magnetic resonance, and clinical phenotype

Feingold, Brian; Salgado, Cláudia; Reyes‐Múgica, Miguel; Drant, Stacey; Miller, Susan A.; Kennedy, Mark; Kellman, Peter; Schelbert, Erik B.; Wong, Timothy C.

doi:10.1111/petr.12986

Cited by 19 publications

(10 citation statements)

References 63 publications

(140 reference statements)

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“…In a prior study of obese diabetic and nondiabetic adolescents, BMI was also associated with ECV, even after adjusting for HTN (33). These subtle alterations to the myocardial interstitium preceded LV dysfunction, as has been shown in the pediatric heart transplant population (34). Our findings are consistent with prior studies in other populations, demonstrating changes to the extracellular matrix with obesity.…”

Section: Discussionsupporting

confidence: 90%

Donor and Recipient Characteristics in Heart Transplantation Are Associated with Altered Myocardial Tissue Structure and Cardiac Function

Dolan

Rahsepar²,

Blaisdell

et al. 2019

Radiology: Cardiothoracic Imaging

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H eart transplantation (HTx) is performed in nearly 5000 patients with advanced heart failure annually (1). HTx candidates and donor hearts are carefully evaluated to determine which donor-recipient matches have the highest chances of survival. Considerations include the assessment of the donor heart (eg, age and comorbidities) and matching to the characteristics of the recipient (eg, sex and size matching) (2,3). Previous studies have shown that mismatched donor-recipient characteristics (eg, sex and weight) are associated with increased mortality (4-6) and increased risk of acute cardiac allograft rejection (ACAR) and cardiac allograft vasculopathy (CAV) (7,8). Other individual demographic factors, such as donor age, sex, and body size (7,8), or comorbidities, such as donor hypertension (HTN), diabetes mellitus (DM), and smoking, are associated with increased post-HTx mortality (9,10).Nonetheless, little is understood regarding the impact of donor and recipient factors on global and regional changes in cardiac tissue structure and function. Cardiac MRI is a useful tool for cardiac allograft surveillance due to its ability to quantify changes in global and regional myocardial tissue structure and function. Cardiac MRI techniques include left ventricular (LV) two-dimensional cine steady-state free precession (SSFP) imaging to assess global cardiac function (11,12), T2 mapping to evaluate the composition of the myocardium related to water or fat content such as edematous and inflammatory myocardial change (13,14), precontrast and postcontrast T1 mapping to calculate extracellular volume fraction (ECV) for the assessment of interstitial changes such as myocardial fibrosis (15-17), and tissue phase mapping (TPM) (18,19) for the quantification of regional myocardial velocities and twist. Although some studies have examined associations between demographic factors and cardiac MRI measures of structure and function in the general population, no dedicated studies have investigated the influence of donor and recipient characteristics on cardiac MRI structural and functional measures of cardiac health. Subtle alterations

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Section: Discussionsupporting

confidence: 90%

Donor and Recipient Characteristics in Heart Transplantation Are Associated with Altered Myocardial Tissue Structure and Cardiac Function

Dolan

Rahsepar²,

Blaisdell

et al. 2019

Radiology: Cardiothoracic Imaging

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“…In recent years, CMR has shown substantial promise for detection of graft dysfunction in adult heart transplant recipients [ 21 , 23 , 24 , 28 , 37 , 49 – 53 ], however, data are quite limited in PHT [ 37 , 38 , 40 , 43 , 54 , 55 ]. Our study demonstrates the safety and feasibility of comprehensive CMR with regadenoson stress perfusion for graft surveillance in PHT.…”

Section: Discussionmentioning

confidence: 99%

Multi-parametric cardiovascular magnetic resonance with regadenoson stress perfusion is safe following pediatric heart transplantation and identifies history of rejection and cardiac allograft vasculopathy

Husain

Watanabe

Berhane

et al. 2021

Journal of Cardiovascular Magnetic Resonance

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Background The progressive risk of graft failure in pediatric heart transplantation (PHT) necessitates close surveillance for rejection and coronary allograft vasculopathy (CAV). The current gold standard of surveillance via invasive coronary angiography is costly, imperfect and associated with complications. Our goal was to assess the safety and feasibility of a comprehensive multi-parametric CMR protocol with regadenoson stress perfusion in PHT and evaluate for associations with clinical history of rejection and CAV. Methods We performed a retrospective review of 26 PHT recipients who underwent stress CMR with tissue characterization and compared with 18 age-matched healthy controls. CMR protocol included myocardial T2, T1 and extracellular volume (ECV) mapping, late gadolinium enhancement (LGE), qualitative and semi-quantitative stress perfusion (myocardial perfusion reserve index; MPRI) and strain imaging. Clinical, demographics, rejection score and CAV history were recorded and correlated with CMR parameters. Results Mean age at transplant was 9.3 ± 5.5 years and median duration since transplant was 5.1 years (IQR 7.5 years). One patient had active rejection at the time of CMR, 11/26 (42%) had CAV 1 and 1/26 (4%) had CAV 2. Biventricular volumes were smaller and cardiac output higher in PHT vs. healthy controls. Global T1 (1053 ± 42 ms vs 986 ± 42 ms; p < 0.001) and ECV (26.5 ± 4.0% vs 24.0 ± 2.7%; p = 0.017) were higher in PHT compared to helathy controls. Significant relationships between changes in myocardial tissue structure and function were noted in PHT: increased T2 correlated with reduced LVEF (r = − 0.57, p = 0.005), reduced global circumferential strain (r = − 0.73, p < 0.001) and reduced global longitudinal strain (r = − 0.49, p = 0.03). In addition, significant relationships were noted between higher rejection score and global T1 (r = 0.38, p = 0.05), T2 (r = 0.39, p = 0.058) and ECV (r = 0.68, p < 0.001). The presence of even low-grade CAV was associated with higher global T1, global ECV and maximum segmental T2. No major side effects were noted with stress testing. MPRI was analyzed with good interobserver reliability and was lower in PHT compared to healthy controls (0.69 ± − 0.21 vs 0.94 ± 0.22; p < 0.001). Conclusion In a PHT population with low incidence of rejection or high-grade CAV, CMR demonstrates important differences in myocardial structure, function and perfusion compared to age-matched healthy controls. Regadenoson stress perfusion CMR could be safely and reliably performed. Increasing T2 values were associated with worsening left ventricular function and increasing T1/ECV values were associated with rejection history and low-grade CAV. These findings warrant larger prospective studies to further define the role of CMR in PHT graft surveillance.

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“…The authors concluded that, BNP may have utility in monitoring of cardiac performance with the caveat that a low hematocrit can also affect its levels. A correlation between diffuse myocardial fibrosis which is considered secondary to microvascular coronary disease after HT and BNP level has been reported [18]. Linear correlations between worsening of global longitudinal strain with high BNP levels, end-diastolic left ventricular volume, and pulmonary capillary wedge pressure have also been reported [19].…”

Section: Bnp Level and Cardiac Allograft Vasculopathymentioning

confidence: 96%

Is B-type natriuretic peptide clinically useful after pediatric heart transplantation?

Das¹

2019

Trends in Transplant

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The evidence for BNP-guided management of pediatric heart transplant recipients is scarce. A search in PubMed with no date or language restriction resulted in 8 studies reporting relation between BNP and rejection, 2 studies on the time course of BNP levels after heart transplantation, one study each reporting relationship of BNP with cardiac allograft vasculopathy and post-transplant mortality. So far, the data available can only support BNP as an adjunctive marker, not a stand-alone test, in the screening of hemodynamically significant cardiac pathology in pediatric heart transplant recipients. A serial intraindividual measurements of BNP level rather than an absolute cut-off value, can be useful in combination with the patient's clinical condition to facilitate management of post-heart transplant care in children.

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Diffuse myocardial fibrosis among healthy pediatric heart transplant recipients: Correlation of histology, cardiovascular magnetic resonance, and clinical phenotype

Cited by 19 publications

References 63 publications

Donor and Recipient Characteristics in Heart Transplantation Are Associated with Altered Myocardial Tissue Structure and Cardiac Function

Donor and Recipient Characteristics in Heart Transplantation Are Associated with Altered Myocardial Tissue Structure and Cardiac Function

Multi-parametric cardiovascular magnetic resonance with regadenoson stress perfusion is safe following pediatric heart transplantation and identifies history of rejection and cardiac allograft vasculopathy

Is B-type natriuretic peptide clinically useful after pediatric heart transplantation?

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