Magnetic Resonance Characterization of Cardiac Adaptation and Myocardial Fibrosis in Pulmonary Hypertension Secondary to Systemic-To-Pulmonary Shunt

Abstract

Background-Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are strong predictors of morbidity and mortality among patients with congenital heart disease. Early detection of RV involvement may be useful in the management of these patients. We aimed to assess progressive cardiac adaptation and quantify myocardial extracellular volume in an experimental porcine model of PH because of aorto-pulmonary shunt using cardiac magnetic resonance (CMR). Methods and Results-To characterize serial cardiac adaptation, 12 pigs (aorto-pulmonary shunt [n=6] or sham operation[n=6]) were evaluated monthly with right heart catheterization, CMR, and computed tomography during 4 months, followed by pathology analysis. Extracellular volume by CMR in different myocardial regions was studied in 20 animals (aorto-pulmonary shunt [n=10] or sham operation [n=10]) 3 months after the intervention. All shunted animals developed PH. CMR evidenced progressive RV hypertrophy and dysfunction secondary to increased afterload and left ventricular dilatation secondary to volume overload. Shunt flow by CMR strongly correlated with PH severity, left ventricular enddiastolic pressure, and left ventricular dilatation. T1-mapping sequences demonstrated increased extracellular volume at the RV insertion points, the interventricular septum, and the left ventricular lateral wall, reproducing the pattern of fibrosis found on pathology. Extracellular volume at the RV insertion points strongly correlated with pulmonary hemodynamics and RV dysfunction. Conclusions-Prolonged systemic-to-pulmonary shunting in growing piglets induces PH with biventricular remodeling and myocardial fibrosis that can be detected and monitored using CMR. These results may be useful for the diagnosis and management of congenital heart disease patients with pulmonary overcirculation. Cardiac magnetic resonance (CMR) is the gold standard technique for the assessment of ventricular structure, function, and myocardial scarring. Additionally, it allows for accurate measurement of pulmonary-to-systemic flow ratio (Q p /Q s ) and may be helpful for quantifying and monitoring pulmonary vascular resistance (PVR). 6,7 The presence of late gadolinium enhancement (LGE) in children and young adults with CHD is a prognostic marker. [8][9][10] In recent years, T1 mapping has emerged as a noninvasive technique for the quantification of myocardial extracellular volume (ECV), holding the promise of early detection of myocardial involvement not detectable by LGE.11 In contrast to LGE imaging that detects patchy areas of dense scarring, T1 mapping evidences a diffuse fibrotic process. This novel technique has been scarcely used in this scenario. 12 We hypothesized that CMR may be useful to monitor serial changes in cardiac remodeling and pulmonary hemodynamics and may be able to detect early myocardial fibrosis in a translational animal model of aorto-pulmonary shunt.The aorto-pulmonary shunt in growing piglets has become a well-established model of congenital conditions with leftto-ri...

Effects of pulmonary rehabilitation on cardiac magnetic resonance parameters in patients with persistent dyspnea following pulmonary embolism

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Targeted Gene Delivery through the Respiratory System: Rationale for Intratracheal Gene Transfer

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Experimental models of cardiac physiology and pathology

“…However, this approach is associated with high mortality and requires repetitive administration of drugs. In addition to the left heart failure, right heart failure can be induced by pulmonary arterial banding (189), pulmonary vein banding (190,191), pulmonary microbeads injection (192), artery-to-venous shunt (193) and pneumonectomy (194). In contrast to the LV failure models, right ventricular failure models are much less characterized and more research is needed to identify the differences between the right and left heart failures.…”