Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage

Rodrigo Fernández-Jiménez; Manuel Barreiro-Pérez; Ana Martin-García; Javier Sánchez-González; Jaume Agüero; Carlos Galán-Arriola; Jaime García-Prieto; Elena Díaz-Pelaez; Pedro Vara; Irene Martinez; Ivan Zamarro; Beatriz Garde; Javier Sanz; Valentin Fuster; Pedro L Sánchez; Borja Ibanez

doi:10.1161/CIRCULATIONAHA.116.025582

Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage

Circulation. 2017 Oct 3;136(14):1288-1300. doi: 10.1161/CIRCULATIONAHA.116.025582. Epub 2017 Jul 7.

Authors

Rodrigo Fernández-Jiménez¹, Manuel Barreiro-Pérez¹, Ana Martin-García¹, Javier Sánchez-González¹, Jaume Agüero¹, Carlos Galán-Arriola¹, Jaime García-Prieto¹, Elena Díaz-Pelaez¹, Pedro Vara¹, Irene Martinez¹, Ivan Zamarro¹, Beatriz Garde¹, Javier Sanz¹, Valentin Fuster¹, Pedro L Sánchez², Borja Ibanez²

Affiliations

¹ From Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.-J., J.A., C.G.-A., J.G.-P., J.S., V.F., B.I.); CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (R.F.-J., M.B.-P., A.M.-G., J.A., C.G.-A., J.G.-P., B.G., P.L.S., B.I.); The Zena and Michael A. Wiener CVI, Icahn School of Medicine at Mount Sinai, New York (R.F.-J., J.S., V.F.); Hospital Universitario de Salamanca, Spain (M.B.-P., A.M.-G., E.D.-P., P.V., I.M., I.Z., B.G., P.L.S.); Philips Healthcare, Madrid, Spain (J.S.-G.); Cardiology Department, Hospital Universtitari i Politecnic La Fe, Valencia, Spain (J.A.); and IIS-Fundación Jiménez Díaz Hospital, Madrid, Spain (B.I.).
² From Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.-J., J.A., C.G.-A., J.G.-P., J.S., V.F., B.I.); CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (R.F.-J., M.B.-P., A.M.-G., J.A., C.G.-A., J.G.-P., B.G., P.L.S., B.I.); The Zena and Michael A. Wiener CVI, Icahn School of Medicine at Mount Sinai, New York (R.F.-J., J.S., V.F.); Hospital Universitario de Salamanca, Spain (M.B.-P., A.M.-G., E.D.-P., P.V., I.M., I.Z., B.G., P.L.S.); Philips Healthcare, Madrid, Spain (J.S.-G.); Cardiology Department, Hospital Universtitari i Politecnic La Fe, Valencia, Spain (J.A.); and IIS-Fundación Jiménez Díaz Hospital, Madrid, Spain (B.I.). bibanez@cnic.es pedrolsanchez@secardiologia.es.

Abstract

Background: Clinical protocols aimed to characterize the post-myocardial infarction (MI) heart by cardiac magnetic resonance (CMR) need to be standardized to take account of dynamic biological phenomena evolving early after the index ischemic event. Here, we evaluated the time course of edema reaction in patients with ST-segment-elevation MI by CMR and assessed its implications for myocardium-at-risk (MaR) quantification both in patients and in a large-animal model.

Methods: A total of 16 patients with anterior ST-segment-elevation MI successfully treated by primary angioplasty and 16 matched controls were prospectively recruited. In total, 94 clinical CMR examinations were performed: patients with ST-segment-elevation MI were serially scanned (within the first 3 hours after reperfusion and at 1, 4, 7, and 40 days), and controls were scanned only once. T2 relaxation time in the myocardium (T2 mapping) and the extent of edema on T2-weighted short-tau triple inversion-recovery (ie, CMR-MaR) were evaluated at all time points. In the experimental study, 20 pigs underwent 40-minute ischemia/reperfusion followed by serial CMR examinations at 120 minutes and 1, 4, and 7 days after reperfusion. Reference MaR was assessed by contrast-multidetector computed tomography during the index coronary occlusion. Generalized linear mixed models were used to take account of repeated measurements.

Results: In humans, T2 relaxation time in the ischemic myocardium declines significantly from early after reperfusion to 24 hours, and then increases up to day 4, reaching a plateau from which it decreases from day 7. Consequently, edema extent measured by T2-weighted short-tau triple inversion-recovery (CMR-MaR) varied with the timing of the CMR examination. These findings were confirmed in the experimental model by showing that only CMR-MaR values for day 4 and day 7 postreperfusion, coinciding with the deferred edema wave, were similar to values measured by reference contrast-multidetector computed tomography.

Conclusions: Post-MI edema in patients follows a bimodal pattern that affects CMR estimates of MaR. Dynamic changes in post-ST-segment-elevation MI edema highlight the need for standardization of CMR timing to retrospectively delineate MaR and quantify myocardial salvage. According to the present clinical and experimental data, a time window between days 4 and 7 post-MI seems a good compromise solution for standardization. Further studies are needed to study the effect of other factors on these variables.

Keywords: edema; magnetic resonance imaging; myocardial infarction; translational medical research.

MeSH terms

Animals
Edema / etiology*
Edema / pathology
Female
Heart / physiopathology*
Humans
Male
Middle Aged
Myocardial Infarction / diagnosis*
Myocardial Infarction / pathology
Risk Factors
Swine