Subclinical edema and systolic dysfunction in MINOCA mimics

Background: Approximately 5-9% of all myocardial infarctions have non obstructive coronary arteries (< 50% stenosis) on coronary angiography and are subsequently classified as Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA). Myocarditis is known as a MINOCA mimic and is characterized by edema, systolic dysfunction and myocyte damage, as presence of non-ischemic late gadolinium enhancement (LGE). However, the relationship between edema and functional recovery in MINOCA remain partially unclear. Therefore, the aim of this study was to evaluate the change in edema and function in MINOCA mimics.

Methods: Patients from the second Stockholm myocardial infarction with normal coronaries (SMINC-2) study (1), with the CMR diagnosis of either myocarditis (n=25, aged 57 [47-61] years at index, n=12 (48%) female), or patients classified as ‘normal’ (n=34, aged 54 [49-61] years, n=21 (62%) female) were included in this study. All patients underwent CMR at 1.5T (MAGNETOM Aera, Siemens Healthineers, Forchheim, Germany) at index and 6 months later. Native T1 maps were acquired using a modified Look-Locker inversion recovery research sequence. Pre- and postcontrast T1 maps were used to generate extracellular volume (ECV) maps on the scanner, which were calibrated to the blood hematocrit. LGE imaging was acquired using a free breathing phase-sensitive inversion recovery sequence and a balanced steady state free precession was used for cine imaging. Global and regional native T1, ECV and global longitudinal strain (GLS) and global circumferential strain (GCS) was acquired by one observer. Values and relationships were evaluated using Wilcoxon signed-rank and Mann-Whitney U as appropriate.

Results: All patients diagnosed with myocarditis had non-ischemic LGE at index (3±0.9 days from admission) and in 10 patients (40%) this resolved at follow-up (200±35 days from first scan). Native T1 in the LGE area was elevated in all patients (n=25, 100%) with myocarditis, which resolved to follow-up (n=25, 100%). At index there was no difference (p >0.05) in volumetric parameters between patients with myocarditis compared to ‘normals’. At index, segments affected by myocarditis had higher native T1 and ECV compared to ‘normals’, Table 1. Patients with myocarditis had lower native T1 in the affected segments at follow-up (p=0.01), however there was no change in ECV nor GLS or GCS (p >0.05 for all), Table 2. In patients classified as normal there was an increase in left ventricular mass (p=0.03), GLS (p=0.02) and GCS (p=0.04), and a decrease in global native T1 (p=0.012), Table 2.

Conclusion: In MINOCA mimics, patients with myocarditis have lower native T1, however no change in ECV nor GLS or GCS at follow up. In patients classified as normal there was a reduction in global native T1 values and increase in GLS and GCS at follow-up, suggestive of subclinical edema and systolic dysfunction in the acute phase.

Table I. CMR findings Index

	Myocarditis	Normal	p value
LVEDV, mL	148 [124-177]	140 [125-173]	0.736
LVEDVi, mL/m2	75 [66-89]	77 [70-91]	0.560
LVESV, mL	67 [49-75]	61 [47-77]	0.416
LVESVi, mL/m2	34 [27-37]	33 [26-38]	0.818
LVSV, mL	85 [70-107]	86 [75-100]	0.830
LVSVi, mL/m2	44 [37-51]	45 [41-52]	0.416
LVM, g	92 [78-117]	94 [81-118]	0.836
LVMi, g/m2	48 [39-60]	52 [45-60]	0.602
LVEF, %	58 [53-63]	59 [55-63]	0.275
GLS, %	17 [16-18]	18 [16-19]	0.198
GCS, %	19 [17-21]	19 [17-22]	0.738
Native T1, ms	1017 [983-1033]	996 [969-1015]	0.069
Affected    segments	1060 [1019-1105]	NA	< 0.001a
Remote	1009 [989-1024]	NA	0.267a
ECV, %	27 [25-29]	25 [24-26]	0.010
Affected segments	29 [26-32]	NA	< 0.001a
Remote	26 [25-28]	NA	1.000 a

CMR findings divided into myocarditis patients and patients classified as normal by CMR.  The findings are presented as median [interquartile range]. P values were calculated using Mann Whitney U test. Abbreviations: LVEDV=left ventricular end-diastolic volume, LVEDVi=left ventricular end-diastolic volume indexed, LVESV=left ventricular end-systolic volume, LVESVi=left ventricular end-systolic volume indexed, LVM=left ventricular mass, LVMi=left ventricular mass indexed, LVEF=left ventricular ejection fraction, GLS=global longitudinal strain, GCS=global circumferencial strain, ECV=extra cellular volume. The parameters that include “i” in the end, are indexed for body surface area according to the Mosteller formula. ^a compared to global native T1 for patients classified as normal.Table II. CMR findings index vs follow-up

	Myocarditis			Normals
	Index	Follow-up	P	Index	Follow-up	P
HR,	63 [55-75]	63 [56-72]	0.394	62 [55-70]	63 [57-68]	0.856
LVEDV, mL	148 [124-177]	162 [139-186]	0.042	140 [125-173]	143 [124-187]	0.085
LVEDVi, mL/m2	75 [66-89]	81 [71-91]	0.044	77 [70-91]	80 [66-93]	0.073
LVESV, mL	67 [49-75]	65 [58-81]	0.605	61 [47-77]	63 [48-80]	0.761
LVESVi, mL/m2	34 [27-37]	32 [31-40]	0.777	33 [26-38]	34 [26-41]	0.378
LVSV, mL	85 [70-107]	94 [80-110]	0.042	86 [75-100]	83 [73-107]	0.446
LVSVi, mL/m2	44 [37-51]	46 [42-54]	0.053	45 [41-52]	46 [40-53]	0.412
LVM, g	92 [78-117]	100 [81-112]	0.616	94 [81-118]	101 [86-115]	0.018
LVMi, g/m2	48 [39-60]	49 [41-56]	0.744	52 [45-60]	55 [49-59]	0.033
LVEF, %	58 [53-63]	59 [56-61]	0.162	59 [55-63]	57 [54-63]	0.396
GLS, %	17 [16-18]	19 [17-20]	0.136	18 [16-19]	19 [17-21]	0.017
GCS, %	19 [17-21]	19 [17-20]	0.088	19 [17-22]	20 [17-22]	0.037
Native T1, ms	1017 [983-1033]	999 [992-1015]	0.670	996 [969-1015]	984 [969-1005]	0.012
Affected    segments	1060 [1019-1105]	1004 [990-1035]	0.010	NA
Remote	1009 [989-1024]	999 [991-1019]	0.472	NA
ECV, %	27 [25-29]	26 [25-29]	0.952	25 [24-26]	25 [24-26]	0.711
Affected segments	29 [26-32]	27 [25-31]	0.213	NA
Remote	26 [25-28]	25 [25-29]	0.695	NA

CMR findings for patients classified as myocarditis and normal by CMR.  The findings are presented as p values which were calculated using Wilcoxon signed-rank test. P values compare the index vs follow up results in the respective group. Abbreviations: LVEDV=left ventricular end-diastolic volume, LVEDVi=left ventricular end-diastolic volume indexed, LVESV=left ventricular end-systolic volume, LVESVi=left ventricular end-systolic volume indexed, LVM=left ventricular mass, LVMi=left ventricular mass indexed, LVEF=left ventricular ejection fraction, GLS=global longitudinal strain, GCS=global circumferencial strain, ECV=extra cellular volume. The parameters that include “i” in the end, are indexed for body surface area according to the Mosteller formula.AcknowledgementsThe authors wish to acknowledge Kelvin Chow at Siemens Healthcare Ltd, Calgary, AB, Canada, for providing the research sequence for T1 and ECV mapping.