Comprehensive Cardiovascular Magnetic Resonance‐Derived Myocardial Strain Analysis Provides Independent Prognostic Value in Acute Myocarditis

Background Late gadolinium enhancement and left ventricular (LV) ejection fraction on cardiovascular magnetic resonance (CMR) are prognostic markers, but their predictive value for incident heart failure or life‐threatening arrhythmias in acute myocarditis patients is limited. CMR‐derived feature tracking provides a more sensitive analysis of myocardial function and may improve risk stratification in myocarditis. In this study, the prognostic value of LV, right ventricular, and left atrial strain in acute myocarditis patients is evaluated. Methods and Results In this multicenter retrospective study, patients with CMR‐proven acute myocarditis were included. The primary end point was occurrence of major adverse cardiovascular events: all‐cause mortality, heart transplantation, heart failure hospitalizations, and life threatening arrhythmias. LV global longitudinal strain, global circumferential strain and global radial strain, right ventricular‐global longitudinal strain and left atrial strain were measured. Unadjusted and adjusted cox proportional hazard regression analysis were performed. In total, 162 CMR‐proven myocarditis patients were included (41 ± 17 years, 75% men). Mean LV ejection fraction was 51 ± 12%, and 144 (89%) patients had presence of late gadolinium enhancement. Major adverse cardiovascular events occurred in 29 (18%) patients during a follow‐up of 5.5 (2.2–8.3) years. All LV strain parameters were independent predictors of outcome beyond clinical features, LV ejection fraction and late gadolinium enhancement (LV‐global longitudinal strain: hazard ratio [HR] 1.07, P=0.02; LV‐global circumferential strain: HR 1.15, P=0.02; LV‐global radial strain: HR 0.98, P=0.03), but right ventricular or left atrial strain did not predict outcome. Conclusions CMR‐derived LV strain analysis provides independent prognostic value on top of clinical parameters, LV ejection fraction and late gadolinium enhancement in acute myocarditis patients, while left atrial and right ventricular strain seem to be of less importance

Lymphocytic myocarditis occurs with myocardial infarction and coincides with increased inflammation, hemorrhage and instability in coronary artery atherosclerotic plaques

Objective: Although lymphocytic myocarditis (LM) clinically can mimic myocardial infarction (MI), they are regarded as distinct clinical entities. However, we observed a high prevalence (32%) of recent MI in patients diagnosed post-mortem with LM. To investigate if LM changes coronary atherosclerotic plaque, we analyzed in autopsied hearts the inflammatory infiltrate and stability in coronary atherosclerotic lesions in patients with LM and/or MI.Methods: The three main coronary arteries were isolated at autopsy of patients with LM, with MI of 3-6 h old, with LM and MI of 3-6 h old (LM + MI) and controls. In tissue sections of atherosclerotic plaque-containing coronary segments inflammatory infiltration, plaque stability, intraplaque hemorrhage and thrombi were determined via (immuno) histological criteria.Results: In tissue sections of those coronary segments the inflammatory infiltrate was found to be significantly increased in patients with LM, LM + MI and MI compared with controls. This inflammatory infiltrate consisted predominantly of macrophages and neutrophils in patients with only LM or MI, of lymphocytes in LM + MI and MI patients and of mast cells in LM + MI patients. Moreover, in LM + MI and MI patients this coincided with an increase of unstable plaques and thrombi. Finally, LM and especially MI and LM + MI patients showed significantly increased intraplaque hemorrhage.Conclusions: This study demonstrates prevalent co-occurrence of LM with a very recent MI at autopsy. Moreover, LM was associated with remodeling and inflammation of atherosclerotic plaques indicative of plaque destabilization pointing to coronary spasm, suggesting that preexistent LM, or its causes, may facilitate the development of MI. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.</p

Comprehensive Cardiovascular Magnetic Resonance-Derived Myocardial Strain Analysis Provides Independent Prognostic Value in Acute Myocarditis

Background Late gadolinium enhancement and left ventricular (LV) ejection fraction on cardiovascular magnetic resonance (CMR) are prognostic markers, but their predictive value for incident heart failure or life-threatening arrhythmias in acute myocarditis patients is limited. CMR-derived feature tracking provides a more sensitive analysis of myocardial function and may improve risk stratification in myocarditis. In this study, the prognostic value of LV, right ventricular, and left atrial strain in acute myocarditis patients is evaluated. Methods and Results In this multicenter retrospective study, patients with CMR-proven acute myocarditis were included. The primary end point was occurrence of major adverse cardiovascular events: all-cause mortality, heart transplantation, heart failure hospitalizations, and life threatening arrhythmias. LV global longitudinal strain, global circumferential strain and global radial strain, right ventricular-global longitudinal strain and left atrial strain were measured. Unadjusted and adjusted cox proportional hazard regression analysis were performed. In total, 162 CMR-proven myocarditis patients were included (41 ± 17 years, 75% men). Mean LV ejection fraction was 51 ± 12%, and 144 (89%) patients had presence of late gadolinium enhancement. Major adverse cardiovascular events occurred in 29 (18%) patients during a follow-up of 5.5 (2.2-8.3) years. All LV strain parameters were independent predictors of outcome beyond clinical features, LV ejection fraction and late gadolinium enhancement (LV-global longitudinal strain: hazard ratio [HR] 1.07, P=0.02; LV-global circumferential strain: HR 1.15, P=0.02; LV-global radial strain: HR 0.98, P=0.03), but right ventricular or left atrial strain did not predict outcome. Conclusions CMR-derived LV strain analysis provides independent prognostic value on top of clinical parameters, LV ejection fraction and late gadolinium enhancement in acute myocarditis patients, while left atrial and right ventricular strain seem to be of less importance

CD45 is a more sensitive marker than CD3 to diagnose lymphocytic myocarditis in the endomyocardiurn

To diagnose lymphocytic myocarditis (LM), immunohistopathological examination of endomyocardial biopsies (EMBs) is used with a cutoff value of at least 14 leukocytes per mm(2), composed of CD3- and CD68-positive cells. We hypothesized that a more common leukocyte marker, CD45, instead of CD3 could increase the diagnostic sensitivity. Hearts of mice with acute viral myocarditis (n = 9) and of controls (n = 7) and the EMB sampling area of the left ventricular posterior wall (LVPW) obtained from autopsied hearts of patients diagnosed with LM (n = 18) and controls (n = 6) were stained with anti-CD68, anti-CD3, and anti-CD45. When applying the threshold of at least 14 leukocytes per mm(2), 33% of the mice would be diagnosed with LM with the use of CD3(+)CD68 and 89% with the use of CD45(+)CD68. In the EMB sampling area of autopsied hearts, using the cutoff value of at least 14 leukocytes per mm(2), CD3(+)CD68 could only confirm 17% of the diagnosis of LM, whereas CD45(+)CD68 could confirm 50% of the LM cases. Moreover, we compared inflammation in the EMB sampling area of the LVPW to the remaining myocardium of the LVPW and observed a significant increase of CD45(+)CD68 cells per mm(2) in patients with LM. In conclusion, the use of the common leukocyte marker CD45 increases the sensitivity of the diagnosis of LM. Furthermore, the inflammatory infiltrate in the EMB sampling area is significantly increased compared with the remaining LVPW, indicating that the sampling area constitutes the highest chance for histological diagnosis of LM. (C) 2017 Elsevier Inc. All rights reserve

The influence of microvascular injury on native T1 and T2* relaxation values after acute myocardial infarction: implications for non-contrast-enhanced infarct assessment

Objectives: Native T1 mapping and late gadolinium enhancement (LGE) imaging offer detailed characterisation of the myocardium after acute myocardial infarction (AMI). We evaluated the effects of microvascular injury (MVI) and intramyocardial haemorrhage on local T1 and T2* values in patients with a reperfused AMI. Methods: Forty-three patients after reperfused AMI underwent cardiovascular magnetic resonance imaging (CMR) at 4 [3-5] days, including native MOLLI T1 and T2* mapping, STIR, cine imaging and LGE. T1 and T2* values were determined in LGE-defined regions of interest: the MI core incorporating MVI when present, the core-adjacent MI border zone (without any areas of MVI), and remote myocardium. Results: Average T1 in the MI core was higher than in the MI border zone and remote myocardium. However, in the 20 (47%) patients with MVI, MI core T1 was lower than in patients without MVI (MVI 1048±78ms, no MVI 1111±89ms, p=0.02). MI core T2* was significantly lower in patients with MVI than in those without (MVI 20 [18-23]ms, no MVI 31 [26-39]ms, p<0.001). Conclusion: The presence of MVI profoundly affects MOLLI-measured native T1 values. T2* mapping suggested that this may be the result of intramyocardial haemorrhage. These findings have important implications for the interpretation of native T1 values shortly after AMI. Key points: • Microvascular injury after acute myocardial infarction affects local T1 and T2* values. • Infarct zone T1 values are lower if microvascular injury is present. • T2* mapping suggests that low infarct T1 values are likely haemorrhage. • T1 and T2* values are complimentary for correctly assessing post-infarct myocardium

Comparison between cardiac magnetic resonance stress T1 mapping and [15O]H2O positron emission tomography in patients with suspected obstructive coronary artery disease

Aims To compare cardiac magnetic resonance (CMR) measurement of T1 reactivity (DT1) with [ 15O]H 2O positron emission tomography (PET) measurements of quantitative myocardial perfusion. ................................................................................................................................................................................................... Methods Forty-three patients with suspected obstructed coronary artery disease underwent [ 15O]H 2O PET and CMR at and results 1.5-T, including rest and adenosine stress T1 mapping (ShMOLLI) and late gadolinium enhancement to rule out presence of scar tissue. DT1 was determined for the three main vascular territories and compared with [ 15O]H 2O PET-derived regional stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). DT1 showed a significant but poor correlation with stress MBF (R 2 = 0.04, P = 0.03) and MFR (R 2 = 0.07, P = 0.004). Vascular territories with impaired stress MBF (i.e. <_2.30 mL/min/g) demonstrated attenuated DT1 compared with vascular territories with preserved stress MBF (2.9 ± 2.2% vs. 4.1 ± 2.2%, P = 0.008). In contrast, DT1 did not differ between vascular territories with impaired (i.e. <2.50) and preserved MFR (3.2 ± 2.6% vs. 4.0 ± 2.1%, P = 0.25). Receiver operating curve analysis of DT1 resulted in an area under the curve of 0.66 [95% confidence interval (CI): 0.57–0.75, P = 0.009] for diagnosing impaired stress MBF and 0.62 (95% CI: 0.53–0.71, P = 0.07) for diagnosing impaired MFR. ................................................................................................................................................................................................... Conclusions CMR stress T1 mapping has poor agreement with [ 15O]H 2O PET measurements of absolute myocardial perfusion. Stress T1 and DT1 are lower in vascular territories with reduced stress MBF but have poor accuracy for detecting impaired myocardial perfusion

Ventricular myocarditis coincides with atrial myocarditis in patients

Atrial fibrillation (AF) is a common complication in myocarditis. Atrial inflammation has been suggested to play an important role in the pathophysiology of AF. However, little is known about the occurrence of atrial inflammation in myocarditis patients. Here, we analyzed inflammatory cell numbers in the atria of myocarditis patients without symptomatic AF. Cardiac tissue was obtained postmortem from lymphocytic myocarditis patients (n=6), catecholamine-induced myocarditis patients (n=5), and control patients without pathological evidence of heart disease (n=5). Tissue sections of left and right ventricle and left and right atrium were stained for myeloperoxidase (neutrophilic granulocytes), CD45 (lymphocytes), and CD68 (macrophages). These cells were subsequently quantified in atrial and ventricular myocardium and atrial adipose tissue. In lymphocytic myocarditis patients, a significant increase was observed for lymphocytes in the left atrial adipose tissue. In catecholamine-induced myocarditis patients, significant increases were found in the atria for all three inflammatory cell types. Infiltrating inflammatory cell numbers in the atrial myocardium correlated positively with those in the ventricles, especially in catecholamine-induced myocarditis patients. To a varying extent, atrial myocarditis occurs concurrently with ventricular myocarditis in patients diagnosed with myocarditis of different etiology. This provides a substrate that potentially predisposes myocarditis patients to the development of AF and subsequent complications such as sudden cardiac death and heart failur

Association between remote zone native T1 and patient characteristics.

<p>Association between remote zone native T1 and patient characteristics.</p