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

Usefulness of Left Atrial Emptying Fraction to Predict Ventricular Arrhythmias in Patients With Implantable Cardioverter Defibrillators

Impaired left atrial emptying fraction (LAEF) is an important predictor of mortality in patients with heart failure. As it may reflect increased LV wall stress, it might predict ventricular arrhythmia (VA) specifically. This study evaluated the predictive value of LAEF assessed with cardiovascular magnetic resonance (CMR) imaging with respect to appropriate device therapy (ADT) for VA and compared its role with CMR assessed scar size and other risk factors. In total, 229 patients (68% male, 63 ± 10 years, 61% ischemic cardiomyopathy) with LV ejection fraction ≤35% who underwent CMR and implantable cardioverter defibrillator (ICD) implantation for primary prevention in 2005 to 2012 were included. CMR was used to quantify LV volumes and function. LV scar size was quantified when late gadolinium enhancement was available (n = 166). Maximum and minimum left atrial volumes and LAEF were calculated using the biplane area-length method. The occurrence of ADT and mortality was assessed during a median follow-up of 3.9 years. Sixty-two patients (27%) received ADT. Univariable Cox analysis showed that male gender, creatinine level, minimum left atrial volume, LAEF, and total scar size were significant predictors of ADT. In multivariable Cox analysis, LAEF (hazard ratio 0.75 per 10%, p median and scar size median experienced 40% ADT at 5 years (log-rank p = 0.01). In conclusion, LAEF independently predicts ADT in patients with primary prevention ICDs. Combined assessment of LAEF and scar size identifies a group with low risk of ADT. Therefore, LAEF assessment could assist in risk stratification for VA to select patients with the highest benefit from ICD implantation

Additional diagnostic value of CMR to the European Society of Cardiology (ESC) position statement criteria in a large clinical population of patients with suspected myocarditis

Aims: To determine the diagnostic yield of tissue characterization by cardiovascular magnetic resonance (CMR) in a large clinical population of patients with suspected acute myocarditis (AM) and to establish its diagnostic value within the 2013 European Society of Cardiology position statement criteria (ESC-PSC) for clinically suspected myocarditis. Methods and results: In this retrospective study, CMR examinations of 303 hospitalized patients referred for work-up of suspected AM in two tertiary referral centres were analysed. CMR was performed at median 7 days (interquartile range 4-20 days) after clinical presentation and included cine imaging, T2-weighted imaging, and late gadolinium enhancement. CMR images were evaluated to assign each patient to a diagnosis. By using non-CMR criteria only, the 2013 ESC-PSC were positive for suspected myocarditis in 151 patients and negative in 30. In the remaining 122 patients, there was insufficient information available for ESC-PSC assessment, mostly due to lack of coronary angiography (CAG) before the CMR examination (n = 116, 95%). There were no in-hospital deaths. CMR provided a diagnosis in 158 patients (52%), including myocarditis in 104 (34%), myocardial infarction in 44 (15%), and other pathology in 10 patients (3%). Non-urgent CAG (>24 h after presentation) was performed before the CMR examination in 85 patients, of which 20 (24%) were done in patients with subsequently confirmed AM, which could potentially have been avoided if CMR was performed first. ESC-PSC was correct in diagnosing AM before the CMR in 50 of the 151 patients (33%) and was correct in ruling out AM in all the 30 patients (100%). However, ESC-PSC provided an incorrect diagnosis of AM in 27 of the 151 patients (18%), which was corrected by CMR through the identification of new cardiac disease that could explain the clinical syndrome. Patients with insufficient ESC-PSC information had a relatively low pre-test probability of coronary artery disease. In this group, CMR confirmed the diagnosis of AM in a relatively high percentage (44%) but still revealed myocardial infarction in 8% of them. Conclusion: Tissue characterization by CMR provided a good diagnostic yield in this large clinical population of patients with suspected AM. CMR provided incremental diagnostic value to the ESC-PSC by ruling out the diagnosis of AM on one hand and by potentially sparing AM patients from CAG on the other

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

Segment Length in Cine Strain Analysis Predicts Cardiac Resynchronization Therapy Outcome Beyond Current Guidelines

BACKGROUND: Patients with a class I recommendation for cardiac resynchronization therapy (CRT) are likely to benefit, but the effect of CRT in class II patients is more heterogeneous and additional selection parameters are needed in this group. The recently validated segment length in cine strain analysis of the septum (SLICE-ESS sep) measurement on cardiac magnetic resonance cine imaging predicts left ventricular functional recovery after CRT but its prognostic value is unknown. This study sought to evaluate the prognostic value of SLICE-ESS sep for clinical outcome after CRT. METHODS: Two hundred eighteen patients with a left bundle branch block or intraventricular conduction delay and a class I or class II indication for CRT who underwent preimplantation cardiovascular magnetic resonance examination were enrolled. SLICE-ESS sep was manually measured on standard cardiovascular magnetic resonance cine imaging. The primary combined end point was all-cause mortality, left ventricular assist device, or heart transplantation. Secondary end points were (1) appropriate implantable cardioverter defibrillator therapy and (2) heart failure hospitalization. RESULTS: Two-thirds (65%) of patients had a positive SLICE-ESS sep ≥0.9% (ie, systolic septal stretching). During a median follow-up of 3.8 years, 66 (30%) patients reached the primary end point. Patients with positive SLICE-ESS sep were at lower risk to reach the primary end point (hazard ratio 0.36; P<0.001) and heart failure hospitalization (hazard ratio 0.41; P=0.019), but not for implantable cardioverter defibrillator therapy (hazard ratio, 0.66; P=0.272). Clinical outcome of class II patients with a positive ESS sep was similar to those of class I patients (hazard ratio, 1.38 [95% CI, 0.66-2.88]; P=0.396). CONCLUSIONS: Strain assessment of the septum (SLICE-ESS sep) provides a prognostic measure for clinical outcome after CRT. Detection of a positive SLICE-ESS sep in patients with a class II indication predicts improved CRT outcome similar to those with a class I indication whereas SLICE-ESS sep negative patients have poor prognosis after CRT implantation

Size Matters: Normalization of QRS Duration to Left Ventricular Dimension Improves Prediction of Long-Term Cardiac Resynchronization Therapy Outcome

BACKGROUND: In patients with left bundle branch block (LBBB), QRS duration (QRSd) depends on left ventricular (LV) dimension. Previously, we demonstrated that normalizing QRSd to LV dimension, to adjust for variations in LV size, improved prediction of hemodynamic response to cardiac resynchronization therapy (CRT). In addition, sex-specific differences in CRT outcome have been attributed to normalized QRSd. The present study evaluates the effect of normalization of QRSd to LV dimension on prediction of survival after CRT implantation. METHODS: In this 2-center study, we studied 250 heart failure patients with LV ejection fraction ≤35% and QRSd ≥120 ms who underwent cardiac magnetic resonance imaging before CRT implantation. LV end-diastolic volumes were used for QRSd normalization (ie, QRSd/LV end-diastolic volumes). The primary end point was a combined end point of death, LV assist device, or heart transplantation. RESULTS: During a median follow-up of 3.9 years, 79 (32%) patients reached the primary end point. Using univariable Cox regression, unadjusted QRSd was unrelated to CRT outcome ( P=0.116). In contrast, normalized QRSd was a strong predictor of survival (hazard ratio, 0.81 per 0.1 ms/mL; P=0.008). Women demonstrated higher normalized QRSd than men (0.62±0.17 versus 0.55±0.17 ms/mL; P=0.003) and showed better survival after CRT (hazard ratio, 0.52; P=0.018). A multivariable prognostic model included normalized QRSd together with age, atrial fibrillation, renal function, and heart failure cause, whereas sex, diabetes mellitus, strict left bundle branch block morphology, and LV end-diastolic volumes were expelled from the model. CONCLUSIONS: Normalization of QRSd to LV dimension improves prediction of survival after CRT implantation. In addition, sex-specific differences in CRT outcome might be attributed to the higher QRSd/LV end-diastolic volumes ratio that was found in selected women, indicating more conduction delay

Myocardial adaptation after surgical therapy differs for aortic valve stenosis and hypertrophic obstructive cardiomyopathy

International audienc

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