Analysis of risk factors for prognostically unfavorable MI features as determined by cardiac MRI with contrast enhancement

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): A.L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research and Production Complex, Ministry of Health of Russia, Moscow, Russia Background A growing number of publications describe the role of cardiac MRI in STEMI prognostic assessment. Infarct size, microvascular obstruction (MVO) and myocardial heterogeneity are among the most prognostically significant MRI parameters in MI. Primary PCI (pPCI) is the current standard of STEMI treatment. The impact of clinical factors on the development of MVO, myocardial heterogeneity and infarct size remains insufficiently investigated. Purpose To investigate the impact of certain medical history aspects, clinical and laboratory parameters on the most prognostically significant MRI measures of acute MI (MVO, infarct size, myocardial heterogeneity). Methods The study included 52 patients with first STEMI within <48 hours of onset. All patients urgently underwent coronary angiography with pPCI of infarct-related arteries (IRA). On Days 3-7 contrast-enhanced cardiac MRI was done. Tissue analysis of scans was performed using CVI 42 software evaluating infarct size, MVO, myocardial heterogeneity, and left ventricle (LV) ejection fraction (EF). Results 85% patients were men, with mean age of 59.09 ± 7.7 years. All patients underwent pPCI for reperfusion. The median time from symptom onset to pPCI was 3 hours. We analyzed the influence clinical and laboratory factors impacting cardiovascular prognosis on the development of MVO, infarct size, and myocardial heterogeneity. Odds ratios demonstrated no significant relationship between arterial hypertension (OR 2.10, CI 0.57-7.79 р=0,2), smoking (OR 1.01 CI 0.32-3.20, р=0.9), obesity defined as BMI >30 kg/m2) (OR 0.83 CI 0,50-1.39, р=0.16) and MVO development. However, diabetes mellitus had significant effect on MVO development (OR 4.34 CI 1.34-14.03, р=0.01). With regards to laboratory parameters, relationship between hs-Troponin elevation > >8400 pg/mL and MVO occurrence (OR 7.00, CI 0.79 – 61.74, р=0.04). Correlation analysis demonstrated association between myocardial heterogeneity and BNP (r 0.612, р<0.0001), as well as advanced age (r 0,544, р<0,0001). Inverse correlation was found between myocardial heterogeneity and LV EF (r -0.461, р=0.0006). We also analyzed the factors associated with infarct size and found correlation between this parameter and BNP levels (r 0,553, p = 0,0003), as well as MVO magnitude (r 0,383, p = 0,005). Inverse correlation was found between infarct size and history of hypertension (r -0.380, p = 0.0054) Conclusions Type 2 diabetes mellitus, was found to be an independent predictor of microvascular obstruction on MRI. Elevation of hs-Troponin >8400 pg/mL was found to be associated with MVO development. Correlation data analysis demonstrated that high BNP may indicate higher infarct size and myocardial heterogeneity values (r 0.612, р<0.0001).

Transmural Cellular Heterogeneity in Myocardial Electromechanics

Myocardial heterogeneity is an attribute of the normal heart. We have developed integrative models of cardiomyocytes from the subendocardial (ENDO) and subepicardial (EPI) ventricular regions that take into account experimental data on specific features of intracellular electromechanical coupling in the guinea pig heart. The models adequately simulate experimental data on the action potential and contraction of the ENDO and EPI cells. The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes via cooperative mechanisms of mechano-calcium-electric feedback are essential to produce the differences in Ca2+ transients and contraction profiles and may further enhance transmural differences in the electrical properties between the cells. Simulation results predict that ENDO cells have greater sensitivity to changes in afterload than EPI cells. These data are important for understanding the behavior of cardiomyocytes in the intact heart.

Abstract 18663: Myocardial Heterogeneity in Heart With Postinfarction LV Remodeling and its Response to Cell Therapy

Rationale and Objective: Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury. Here, we investigated the functional impact and myocardial heterogeneity of bioenergetics using a porcine model of post infarction LV remodeling, and 2 dimensional chemical shift imaging (2D CSI) P-31 MR spectroscopy. Methods and Results: Ischemia-reperfusion (I/R) injury was surgically induced by occlusion distal LAD (OCCL) for 60 minutes in female Yorkshire farm swine (≈15kg), then randomly assigned to experimental groups: 1) 16 million human induced pluripotent stem cells (hiPSC) derived cardio myocytes (CMs), smooth muscle cells (SMC) and Endothelia cells (ECs) were directly myocardial injected through an epicardial fibrin patch (P+Cell, n= 4), 2) open patch (fibrin patch with no cell) were placed over the injury site (P w/o Cell, n=4). Size matched normal (n=9) and OCCL only (n=5) pigs were also studied. Four weeks after I/R, 2D CSI MRS studies were performed in a 9.4T/ 65 cm bore magnet. In vivo myocardial energetic mapping was achieved using 31 P 2D CSI. To measure the forward flux rate PCr to ATP, 2D CSI data were acquired with or without saturation on ATPγ resonance. I/R injury has a heterogeneous effect on LV myocardial bioenergetics. Myocardial creatine phosphate (PCr)/ATP ratio is significantly decreased in border zone (BZ) of the infarction than the myocardial areas remote from the scar (RZ) in cell treated and patch only groups (1.54+/- 0.05 vs 2.25 +/- 0.10, 1.49+/-0.07 vs 2.34 +/- 0.07, BZ vs RZ, p<0.05). The BZ PCr/ATP ratio is improved in the cell treated group compared with open patch group (1.71 +/- 0.05 vs. 1.54 +/- 0.05, p<0.05). The forward flux rate constant of PCr/ATP (k pcr→ATP ) in the border zone is slightly increased in cell treated group compared with patch only group (0.29 +/- 0.02 vs 0.22 +/- 0.04 , p<0.05) Conclusion: The approach of 2D CSI 31 P MRS can effectively map the heterogeneity of myocardial ATP flux rate via CK In Vivo porcine hearts. Postinfarction LV remodeling heart manifests pronounced heterogeneity in myocardial bioenergetics with most severe alterations in BZ. Cell therapy may effectively improve BZ myocardial bioenergetics.