The role of inflammation in recent-onset dilated cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Chaloupka ◽  
J Krejci ◽  
H Poloczkova ◽  
P Hude ◽  
E Ozabalova ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Left Ventricular ◽  
Pcr Analysis ◽  
Myocardial Inflammation ◽  
Gene Variants ◽  
Absolute Increase ◽  
Recent Onset ◽  
Cardiotropic Viruses

Abstract Background The aetiology of recent-onset dilated cardiomyopathy (RODCM) includes inflammatory, genetic, toxic and metabolic causes. Delineating the role of inflammation on the genetic background could improve risk stratification. Purpose We aimed to ascertain the role of inflammation evaluated by serum CRP immunohistochemical and PCR analysis of endomyocardial biopsy (EMB) in conjunction with genetic testing in left ventricular reverse remodelling (LVRR) in 12-month follow-up. Methods 83 RODCM patients enrolled in this prospective observational study underwent 12-month echocardiographic follow up whole-exome sequencing, and EMB. Presence of cardiotropic viruses was determined by PCR analysis of the EMB samples. Inflammation was defined according to TIMIC immunohistochemical criteria as the presence of >7 CD3+ lymphocytes/mm2 and/or >14 infiltrating leukocytes (LCA+ cells/mm2). LVRR was defined as an absolute increase in LV ejection fraction > +10% and a relative decrease of LV end-diastolic diameter >−10% at 12 months. Results LVRR occurred in 28 (34%) of all cases. PCR analysis uncovered cardiotropic viruses in 55 (66%) patients, with highest prevalence of parvovirus B19 (47%). (Figure 1) EMB analysis detected inflammation in 28 (34%) cases and inflammation significantly positively predicted LVRR (P=0.019). Sequencing identified disease-related gene variants (ACMG class 3–5) in 45 (54%) patients. Carriers of non-titin gene variants showed a lowest probability of 12-month LVRR (19%) P=0.041. Combination of genetic findings and inflammation did not improve the prediction of LVRR in 12 months. (Table 1) Conclusion Both myocardial inflammation and disease-causing variants can be identified in a large proportion of RODCM cases. Prognostic value of CRP and virus detection is low. Non-titin disease-related variants carriers of are less likely to reach LVRR. In contrast, myocardial inflammation detected by EMB predicts favourable remodelling in 12 months. Figure 1 Funding Acknowledgement Type of funding source: None

P337Natural history, reversibility and arrhythmias associated with truncating titin variants in dilated cardiomyopathy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C R Vissing ◽  
T B Rasmussen ◽  
M S Olesen ◽  
L N Pedersen ◽  
A Dybro ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Medical Therapy ◽  
Ventricular Arrhythmias ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Reverse Remodeling ◽  
Absolute Increase ◽  
The Mean

Abstract Background Truncating genetic variants in titin (TTNtv) are identified in 15–25% of patients with primary dilated cardiomyopathy (DCM). Previous genotype/phenotype studies have reported conflicting results regarding disease severity and pathologic features associated with TTNtv. Purpose To investigate the natural history, reversibility and burden of arrhythmias associated with TTNtv in a Danish cohort with long-term follow-up. Methods Patients with DCM, recruited from two Danish tertiary centers, were included based on the presence of a TTNtv in a cardiac expressed titin exon. Data on patients' medical history including symptoms, demography, family history, comorbidities, treatment, ECG features, and echocardiograms were registered. Outcome data including all-cause mortality, need of heart transplantation (HTX) or left ventricular assist device (LVAD), and presence of ventricular and supraventricular arrhythmias were registered. Left ventricular reverse remodeling (LVRR) was defined as an absolute increase in left ventricular ejection fraction (LVEF) ≥10% points or normalization. Results A total of 104 patients (71 men, 69%; 72 probands) with definite TTNtv-DCM were included. The mean age at DCM diagnosis was (mean±SD) 45±13 years (43±13 for men; 49±14 for women, p<0.04) and median follow-up was 8.1 years. The mean LVEF was 28±13% at time of diagnosis (26±12% for men; 30±13% for women, p=0.173). During follow-up, 31 patients (30%; 24 men) died or needed HTX/LVAD. Medical therapy was associated with LVRR in 79% of patients 3.6 years after diagnosis. LVRR was maintained long-term in 64% of patients. Women had a better response to medical therapy compared to men (mean LVEF increase 19%; vs 15% in men, p<0.04). Atrial fibrillation/flutter was observed in 40% of patients and ventricular arrhythmias in 23% of patients. Men had an earlier occurrence of both supraventricular and ventricular arrhythmias (p=0.005) with half of the men having experienced an arrhythmia at the age of 54 years. Freedom from arrhythmias with age Conclusion TTNtv leads to a DCM phenotype associated with a marked gender-difference in age at DCM diagnosis and high burden of both supraventricular and ventricular arrhythmias. Importantly, the DCM-TTNtv phenotype was associated with a high degree of reversibility of systolic function following medical therapy.

Cardiomyopathies

2016 ◽  
Author(s):  
Patrizio Lancellotti ◽  
Bernard Cosyns
Keyword(s):  
Mitral Valve ◽  
Dilated Cardiomyopathy ◽  
Coronary Arteries ◽  
Takotsubo Cardiomyopathy ◽  
Fatty Infiltration ◽  
Left Ventricular ◽  
Prognostic Role ◽  
Echocardiographic Findings

This chapter focuses on the role of echocardiography in dilated cardiomyopathy, showing diagnostic and associated findings along with the prognostic role of echocardiography. Primary myocardial disease is inadequate hypertrophy, independent of loading conditions and often other affected structures such as mitral valve apparatus, small coronary arteries, and cardiac interstitium. Arrhythmogenic RV cardiomyopathy is fatty or fibro-fatty infiltration of the RV with apoptosis and hypertrophied trabeculae of the RV. This chapter also details diagnostic findings and progression of this condition alongside relevant echocardiographic findings. Previously known as ‘spongy heart syndrome’, left ventricular non compaction is characterized by the absence of involution of LV trabeculae during the embryogenic process. This chapter demonstrates the diagnostic findings of this condition, and looks at the diagnostic findings and complications of Takotsubo cardiomyopathy, illustrating typical, RV apical and variant views. It also shows diagnostic findings in myocarditis in both the acute phase and follow-up.

P1815The impact of PVB19 presence in myocardium in recent onset dilated cardiomyopathy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Krejci ◽  
P Hude ◽  
H Poloczkova ◽  
E Ozabalova ◽  
D Mlejnek ◽  
...  
Keyword(s):  
Viral Load ◽  
Dilated Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Recent Onset ◽  
Echocardiographic Parameters ◽  
One Year ◽  
Replication Activity

Abstract Introduction The most common virus in myocardium of patients with recent onset dilated cardiomyopathy (RODCM) is PVB19. Opinions on its pathogenicity are different. According to some, viral load has to be evaluated and if it is low, the PVB19 has no potential to induce inflammation. Others recommend assessment of viral replication, while “innocent” are those cases where replication activity is low. Purpose To compare the development of echocardiographic parameters in patients with RODCM with isolated presence of PVB19 in low viral load (below 500 copies per μg nucleic acid) against a group in which no virus was detected in the myocardium. Patient and methods 243 patients with RODCM, in 151 cases (62%), the virus was detected in the myocardium (PCR+ group), in 92 cases the finding was negative (PCR−; ie 38%). In the PCR+ group, PVB19 was captured in 135 cases (89% of all PCR+), in 121 cases of them was PVB19 the only one isolated virus (PCRPVB19+; 80% of all PCR+). The viral presence was assessed by real time PCR. Results In the PCR− group, the left ventricular ejection fraction (LVEF) was 23.5±7.2%, in the PCRPVB19+ group 24.6±7.1% (p=0.26). Left ventricle end-diastolic diameter (LVEDD) in PCR− was 66.4±8.9mm vs 65.5±7.9mm in PCRPVB19+ (p=0.42), right ventricle diameter (RV) 33.1±5.7mm vs. 33.4±5.2mm (p=0.69), TAPSE 19.5±4.1mm vs 18.9±4.0mm (p=0.28) and E/é 14.0±5.7 vs. 14.9±7.0 (p=0.32). In the 12-month control, LVEF in the PCR− was 35.5±12.3% (p<0.001 for comparison with baseline), in PCRPVB19+ 35.3±12.3% (p<0.001 for comparison with baseline; p=0.92 for difference between groups); LVEDD in PCR− was 62.0±9.3mm vs 62.1±9.3mm in PCRPVB19+ (both p<0.001 for comparison with baseline, p=0.91 for difference between groups), RV 31.6±5.5mm vs. 31.6±5.4mm (p=0.033, resp. p=0.003 for comparison with baseline; p=0.98 for difference between groups), TAPSE 20.7±4.3mm vs. 20.7±4.4mm (p=0.026, resp. p<0.001 for comparison with baseline; p=0.98 for difference between groups), and E/e' 10.3±4.1 vs. 10.4±4.1 (both p<0.001 for comparison with baseline; p=0.93 for difference between groups). Conclusion PVB19 presence in myocardium had no effect on the development of echocardiographic parameters in RODCM patients in one-year follow-up. Acknowledgement/Funding Supported by Ministry of Health of Czech Republic AZV Grant 16-30537A

scholarly journals Myocardial Tissue Reverse Remodeling after Guideline-directed Medical Therapy in Idiopathic Dilated Cardiomyopathy

2020 ◽  
Author(s):  
Yuanwei Xu ◽  
Weihao Li ◽  
Ke Wan ◽  
Yaodan Liang ◽  
Xincheng Jiang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Dilated Cardiomyopathy ◽  
Medical Therapy ◽  
Left Ventricular ◽  
T Test ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Reverse Remodeling ◽  
Absolute Increase ◽  
Significant Difference

Background - The prognosis of idiopathic dilated cardiomyopathy (DCM) patients has improved remarkably in recent decades with guideline-directed medical therapy (GDMT). Left ventricular reverse remodeling (LVRR) is one of the major therapeutic goals. Whether myocardial fibrosis or inflammation would reverse associated with LVRR remains unknown. Methods - A total of 157 prospectively enrolled DCM patients underwent baseline and follow-up CMR examinations with a median interval of 13.7 months (interquartile range: 12.2-18.5 months). LVRR was defined as an absolute increase in LV ejection fraction (LVEF) of >10% to the final value of ≥ 35% and a relative decrease in LV end-diastolic volume (EDV) of >10%. Statistical analyses were performed using paired t-test and student t-test, logistic regression analysis, and linear regression analysis. Results - Forty-eight (31%) patients reached LVRR. At baseline, younger age, worse NYHA class, new-onset heart failure, lower LVEF, absence of late gadolinium enhancement (LGE), lower myocardial T2, and extracellular volume (ECV) were significant predictors of LVRR. During the follow-up, patients with and without LVRR both showed a significant decrease of myocardial native T1 (LVRR: [baseline]1303.0±43.6ms; [follow-up]1244.7±51.8ms; without LVRR: [baseline]1308.5±80.5ms; [follow-up]1287.6±74.9ms, both p < 0.001), matrix and cellular volumes while no significant difference was observed in T2 or ECV values after treatment. Conclusions - In idiopathic DCM patients, the absence of LGE, lower T2, and ECV values at baseline are significant predictors of LVRR. The myocardial T1, matrix, and cell volume decrease significantly in patients with LVRR after GDMT.

Myocardial work analysis in screening of familial dilated cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Triantafyllou ◽  
R Monteiro ◽  
A Protonotarios ◽  
T Gossios ◽  
P Elliott ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dilated Cardiomyopathy ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Systemic Hypertension ◽  
Work Efficiency ◽  
Work Analysis ◽  
Significant Difference ◽  
Global Work

Abstract Introduction Early detection of affected family relatives of patients with dilated cardiomyopathy (DCM) is essential in order to guide follow up, outcomes and initiate early treatment. Myocardial work analysis is a novel method which integrated strain imaging and blood pressure and has the potential to identify patients with subclinical disease. Purpose We analysed myocardial work in family relatives of DCM patients with positive genotype but negative phenotype in order to identify whether myocardial work can identify early changes. Methods Seventy-four family relatives of DCM patients attending for screening were examined. All individuals were asymptomatic with either positive (45/74, G+) or negative (29/74, G-) genotype and no echocardiographic evidence of left ventricular dilatation or systolic impairment. Non-invasive myocardial work analysis using two-dimensional (2D) speckle tracking echocardiography was analysed. Global longitudinal strain (GLS) was measured by the same vendor specific software used for myocardial work analysis. Left ventricular (LV) ejection fraction (EF) was measured with the Simpson's biplane method. The peak systolic arm cuff blood pressure (BP) measurement at the time of echocardiography was used for the myocardial work study. Results In total we included 74 individuals (37±15 years old, 50.7% women) with mean systolic and diastolic BP of 121.3±14 and 73.2±10 mmHg respectively, mean EF was 58±5% and mean GLS at 18.4±2.5%. G+ individuals had pathogenic and very likely pathogenic mutations in 8 different genes (TTN, BAG3, DSP, FLNC, LMNA, DMD, RBM20, TPM1). There was no difference in age, systemic hypertension, diabetes or medical treatment between the 2 groups. No significant difference was found among G+ and G- individuals in mean systolic and diastolic BP (121.2±14.7 vs 121.2±15.2 mmHg), mean EF (57.3±5 vs 59.1±4%), GLS (−18.2±1.5 vs −18.6±2.9%), mean global work index (1818±403 vs 1928±295 mmHg%) and global constructive work (2192±464 vs 2260±318 mmHg%). However, we found significant reduction of the global work efficiency (GWE) with a GWE of 94.4±2.7% in the G+ versus 95.9±1.6% in the G- individuals (p 0.02). Moreover, the global wasted work (GWW) was increased in the G+ with a GWW of 111±58 mmHg% versus 82±41 mmHg% in the G- individuals (p 0.03). Conclusion DCM gene carriers show, early on, decreased myocardial work efficiency and increased wasted work compared to unaffected family members, which appears to be earlier than other parameters such as EF and GLS. Myocardial work analysis could potentially recognize individuals showing early cardiac involvement and guide closer follow up and early initiation of treatment. Funding Acknowledgement Type of funding source: None

scholarly journals Strain parameters for predicting the prognosis of non‐ischemic dilated cardiomyopathy using cardiovascular magnetic resonance tissue feature tracking

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Chengjie Gao ◽  
Yajie Gao ◽  
Jingyu Hang ◽  
Meng Wei ◽  
Jingbo Li ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Dilated Cardiomyopathy ◽  
Feature Tracking ◽  
Systolic Function ◽  
Radial Strain ◽  
Left Ventricular ◽  
Multivariate Logistic Regression Model ◽  
Non Ischemic Dilated Cardiomyopathy

Abstract Background A considerable number of non-ischemic dilated cardiomyopathy (NDCM) patients had been found to have normalized left ventricular (LV) size and systolic function with tailored medical treatments. Accordingly, we aimed to evaluate if strain parameters assessed by cardiovascular magnetic resonance (CMR) feature tracking (FT) analysis could predict the NDCM recovery. Methods 79 newly diagnosed NDCM patients who underwent baseline and follow-up CMR scans were enrolled. Recovery was defined as a current normalized LV size and systolic function evaluated by CMR. Results Among 79 patients, 21 (27%) were confirmed recovered at a median follow-up of 36 months. Recovered patients presented with faster heart rates (HR) and larger body surface area (BSA) at baseline (P < 0.05). Compared to unrecovered patients, recovered pateints had a higher LV apical radial strain divided by basal radial strain (RSapi/bas) and a lower standard deviation of time to peak radial strain in 16 segments of the LV (SD16-TTPRS). According to a multivariate logistic regression model, RSapi/bas (P = 0.035) and SD16-TTPRS (P = 0.012) resulted as significant predictors for differentiation of recovered from unrecovered patients. The sensitivity and specificity of RSapi/bas and SD16-TTPRS for predicting recovered conditions were 76%, 67%, and 91%, 59%, with the area under the curve of 0.75 and 0.76, respectively. Further, Kaplan Meier survival analysis showed that patients with RSapi/bas ≥ 0.95% and SD16-FTPRS ≤ 111 ms had the highest recovery rate (65%, P = 0.027). Conclusions RSapi/bas and CMR SD16-TTPRS may be used as non-invasive parameters for predicting LV recovery in NDCM. This finding may be beneficial for subsequent treatments and prognosis of NDCM patients. Registration number: ChiCTR-POC-17012586.

scholarly journals Cardiologic evaluation of patients undergoing chemoterapy

2015 ◽  
Vol 82 (2) ◽  
Author(s):  
Barbara Bordoni ◽  
Stefano Urbinati ◽  
Alicia Tosoni ◽  
Graziana Labanti ◽  
Alba Brandes
Keyword(s):  
Ventricular Dysfunction ◽  
Troponin I ◽  
Coronary Spasm ◽  
Left Ventricular ◽  
Cardiac Damage ◽  
Common Risk Factors ◽  
Selection For ◽  
Chemotherapy Cardiotoxicity

Life expectancy in patients affected by cancer has recently increased because of early diagnosis and actual therapies. In recent years, Oncology and Cardiology developed a tight relationship because of common risk factors (i.e. obesity, smoking, alcool intake, etc…), and for preventing the prothrombotic status due to cancer and the potential cardiotoxicity of chemotherapy. Cardiotoxicity incidence is reported from 1% up to 70% in retrospective analyses of drug protocols, mainly representing by left ventricular dysfunction (both reversible or irreversible), but also by arrhythmias, hypertension, atrioventricular block, coronary spasm, and arterial or venous thromboembolism. The early detection of the chemoterapy induced cardiotoxicity is now mandatory and can be obtained through a proper patients selection for different treatments and a strict monitoring during the follow-up period. The role of biomarkers of early cardiac damage, mainly, troponin I and brain natriuretic peptide-BNP, has been recently challenged, and algorithms are currently available. In the present paper, we propose how to perform a cardiological evaluation of patients undergoing chemoterapy tailored by the known adverse effects of the drugs.

scholarly journals Serum autotaxin level predicts future cardiac events in patients with dilated cardiomyopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T Araki ◽  
T Okumura ◽  
T Mizutani ◽  
Y Kimura ◽  
S Kazama ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Dilated Cardiomyopathy ◽  
Volume Fraction ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Left Ventricular Ejection ◽  
Myocardial Inflammation ◽  
Prognostic Impact ◽  
Cardiac Events ◽  
Ventricular Ejection Fraction

Abstract Background Autotaxin (ATX) has been reported to promote myocardial inflammation and subsequent cardiac remodeling through lysophosphatidic acid (LPA) production. However, the prognostic impact of ATX has not been clarified in dilated cardiomyopathy (DCM). Purpose We aimed to investigate the prognostic impact of ATX in patients with DCM. Methods We enrolled 104 DCM patients (49.8 years, 76 males). The subjects underwent blood sampling, echocardiography, cardiac catheterization, and endomyocardial biopsy. Gender differences in serum ATX levels have been reported, thus we divided the subjects into two groups using median serum ATX levels for men and women: High-ATX group and Low-ATX group. All patients were followed up by expert cardiologists. The cardiac event was defined as a composite of cardiac death and hospitalization for worsening heart failure. Results Eighty-nine percent of the subjects were classified as New York Heart Association functional class I or II. Female patients had higher serum ATX levels than male patients, with median values of 257.0 ng/mL and 203.5 ng/mL, respectively (Figure A). The average left ventricular ejection fraction and brain natriuretic peptide levels were 30.6% and 122.5 pg/mL. In survival analysis, cumulative event-free probability was significantly lower in High ATX group (p=0.007, Figure B). In Cox proportional hazards analysis, High-ATX was one of the independent predictors of composite cardiac events (Hazards Ratio, 2.575; p=0.043). On the other hand, high sensitive C-reactive protein and collagen volume fraction in myocardial samples were not significant predictors. Conclusion High serum ATX level was associated with poor prognosis in patients with DCM. FUNDunding Acknowledgement Type of funding sources: None. Gender difference in autotaxin levels Survival analysis of cardiac events

scholarly journals Inter- Not Intraindividual Differences in sTWEAK Levels Predict Functional Deterioration and Mortality in Patients with Dilated Cardiomyopathy

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Kai-Uwe Jarr ◽  
Manfred Nelles ◽  
Hugo A. Katus ◽  
Emmanuel Chorianopoulos
Keyword(s):  
Risk Factor ◽  
Dilated Cardiomyopathy ◽  
Disease Progression ◽  
Scavenger Receptor ◽  
Disease Monitoring ◽  
Exact Role ◽  
Additional Information ◽  
Functional Deterioration

Background. TNF-like weak inducer of apoptosis (TWEAK) has been reported to predict mortality in patients with dilated cardiomyopathy. However, whether it can be used as a biomarker for disease monitoring or rather represents a risk factor for disease progression remains unclear.Aim of the Study. To evaluate the potential of sTWEAK as a biomarker in patients with dilated cardiomyopathy.Results. We conducted a serial study of sTWEAK levels in 78 patients with dilated cardiomyopathy. Soluble TWEAK levels predicted not only a combined mortality/heart transplantation endpoint after 4 years (P=0.0001), but also the risk for clinical deterioration (P=0.0001). Compared to NT-proBNP, sTWEAK remained relatively stable in individual patients on follow-up indicating that inter- rather than intraindividual differences in sTWEAK levels predicted outcome. Finally, neither did the scavenger receptor sCD163 correlate with sTWEAK levels nor did its determination add additional information on outcome in patients with dilated cardiomyopathy.Conclusion. Soluble TWEAK levels in patients with dilated cardiomyopathy may not be of value for disease monitoring but may represent a risk factor for disease progression and death. Further research will be necessary to elucidate the exact role of sTWEAK as a potential modulator of immune response in the setting of dilated cardiomyopathy.

Abstract 17607: MicroRNA Expression Profiles in Endomyocardial Biopsies From Patients With Myocarditis - Association With Left Ventricular Function and Clinical Events

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Christian Besler ◽  
Daniel Urban ◽  
Stefan Watzka ◽  
Karin Klingel ◽  
Reinhard Kandolf ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Expression Profiles ◽  
Left Ventricular ◽  
Lv Function ◽  
Rt Pcr ◽  
Skeletal Muscle Function ◽  
Cardiovascular Pathology ◽  
Clinical Events ◽  
Kaplan Meier

Background: Myocarditis represents an important cause of chronic dilated cardiomyopathy. Predicting the clinical course of patients with myocarditis is difficult and the prognostic value of current histological markers remains controversial. We tested whether expression of selected microRNAs (miRNAs) in endomyocardial biopsies is related to left ventricular (LV) function and clinical events in patients with myocarditis. Methods: Endomyocardial biopsies were obtained from patients with non-inflammatory dilated cardiomyopathy (n=22) and histologically proven myocarditis (n=81). Based on literature search, we predefined a set of 6 miRNAs implicated in inflammation (miR-155, miR-146b), heart failure (miR-21, miR-133a), endothelial cell (miR-126) and skeletal muscle function (miR-206). Expression of these miRNAs in endomyocardial biopsies was quantified by RT-PCR. Results: Expression of miR-133a, miR-206 and miR-155 was markedly upregulated in endomyocardial biopsies from patients with myocarditis as compared to patients with dilated cardiomyopathy, irrespective of viral or non-viral etiology. Levels of miR-133a (R=0,68, P<0,01) and miR-155 (R=0,65, P<0,01) significantly correlated with CD68 cell count in endomyocardial biopsies from patients with myocarditis. Patients with myocarditis and preserved LV function at study entry displayed higher endomyocardial expression of miR-133a than patients with reduced LV function. Higher expression levels of miR-133a were associated with improved LV function during a mean follow-up of 3,1 years. Importantly, in a Kaplan-Meier estimate, patients with myocarditis and miR-133a levels above median showed longer survival free of death and malignant arrhythmias. Conclusion: The present study demonstrates that in a predefined set of miRNAs, relevant to cardiovascular pathology, endomyocardial miR-133a levels correlate with macrophage infiltration, improved LV function and clinical outcome in a comparatively large cohort of patients with histologically proven myocarditis. miR-133a may serve as a potential novel biomarker and therapeutic target in human myocarditis.

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