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



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 end-diastolic 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.



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.
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.).
Daniel
D
Pereda
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.).
Inés
I
García-Lunar
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.).
Federico
F
Sierra
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.).
Damián
D
Sánchez-Quintana
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.).
Evelyn
E
Santiago
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.).
Constanza
C
Ballesteros
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.).
Juan F
JF
Encalada
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.).
Javier
J
Sánchez-González
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.).
Valentín
V
Fuster
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.). ana.garcia@cnic.es anagarci@clinic.ub.es bibanez@cnic.es.
Borja
B
Ibáñez
From the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.P., I.G.-L., F.S., C.B., V.F., B.I., A.G.-Á.); Hospital Clínic, IDIBAPS, Barcelona, Spain (D.P., E.S., J.F.E., A.G.-Á.); Hospital Universitario Quirón Madrid, UEM, Spain (I.G.-L.); Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain (D.S.-Q.); IIS-Fundación Jiménez Díaz, Madrid, Spain (B.I.); Philips Healthcare, Madrid, Spain (J.S.-G.); and Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York (V.F.). ana.garcia@cnic.es anagarci@clinic.ub.es bibanez@cnic.es.
Ana
A
García-Álvarez
D000222:Adaptation, Physiological; D000818:Animals; D001706:Biopsy; D009202:Cardiomyopathies / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009206:Myocardium / Q000473:pathology*; D011237:Predictive Value of Tests; D011652:Pulmonary Circulation; D034421:Sus scrofa; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016277:Ventricular Function, Left; D016278:Ventricular Function, Right; D020257:Ventricular Remodeling
T1 mapping; cardiac magnetic resonance; congenital heart disease; experimental models; pulmonary hypertension