antisynthetase syndrome ( ass ) belongs to the category of autoimmune inflammatory myopathies and is characterized by the presence of various but mutually exclusive anti - trna - synthetase autoantibodies . its spectrum often includes myositis with interstitial pneumonia , raynaud 's phenomenon , inflammatory polyarthralgia / polyarthritis , and mechanic 's hands . cardiac involvement in inflammatory myopathies is polymorphic and includes subclinical ( electromyographic ) changes or different features like congestive heart failure , pulmonary hypertension , pericarditis , and myocarditis . this latter manifestation seems to be particularly rare in ass , with only a few case reports published to date . myocarditis can occur in contexts other than myopathies , including infectious or inflammatory diseases or hypereosinophilia . diagnosing myocarditis remains difficult and the clinical classification criteria are still a matter of debate . based on the who classification , myocarditis is an inflammatory myocardial injury and is defined based on an endomyocardial biopsy ( eb ) with specific histological and immunological features . however , performing an eb is risky and is now only rarely performed , especially when cardiac - magnetic resonance imaging ( mri ) is suggestive . diagnosing myocarditis remains a challenge in patients with an autoimmune disease , particularly with inflammatory myopathies . this is because the clinical manifestations can be subclinical , nonspecific , or concealed by other clinical features , including pericarditis or lung involvement . it is however crucial to diagnose myocarditis , due to the need for specific treatments , and to avoid a potentially fatal early evolution or the development of chronic heart failure at a later stage . we have conducted the largest retrospective series to date , with the objective of describing myocarditis in the context of ass , specifying its prevalence and outcomes . the myocarditis cases occurring during ass ( n  =  12 ) were retrospectively selected from the french national registry ( n  =  352 , 10 university centers , 20002014 ) . myocarditis was defined by the occurrence of acute ( < 24  hours ) or subacute ( 2472  hours ) cardiac symptoms associated with either increased troponin i or t ( which are highly specific for cardiomyocyte necrosis ) and suggestive cardiac - mri or eb ( patient # 10 ) and in the absence of any other significant cause ( including viral infection , coronaropathy , or valvulopathy ) . it should be noted that 2 eligible patients who died before specific morphological examination were not included , despite a compatible myocarditis diagnosis . demographic data , clinical , biological and morphological findings , treatments , and outcomes were retrospectively reviewed by cd , cd , and bh , using the same form . the study was approved by local ethical committees , and patients were reported anonymously , in accordance with french law . of the entire cohort , 12 patients ( 3.4% , woman / man ratio  =  3 , median age 54 , range 1767 ) were identified as meeting the classification criteria . cardiovascular risk factors were found in half of the cases ( n  =  6 ) but rarely significant . their distribution was smoking habit ( n  =  2 ) , systemic hypertension ( n  =  2 ) , dyslipidemia ( n  =  2 ) , obesity ( n  =  2 ) , and mild diabetes mellitus ( n  =  3 ) , see table 1  . patient characteristics patient characteristics among the clinical features of ass , myocarditis was one of the first ass manifestations in 42% ( n  =  5 ) of the cases . in the other cases , myocarditis occurred during the follow - up period ( median 36 months , range 8156 ) . in only 3 ( 43% ) of these cases were the patients treated with immunosuppressive drugs at the time of the myocarditis diagnosis . myocarditis manifestations included left and/or right ventricular dysfunction ( n  =  10 ) , which was often severe ( leading to congestive heart failure with new york heart association stage iii : n  =  9 ) . these clinical features were acute ( n  =  4 ) or subacute ( n  =  6 ) . electrocardiography showed sinusal tachycardia ( n  =  6 ) , heart branch block ( n  =  5 ) , and/or atrial arrhythmias ( n  =  2 ) . repolarization defects were also observed ( n  =  4 , see table 1  ) . troponin i or t levels were significantly elevated in all of the tested cases ( 19 times the normal range , 1.5160 ) , as was creatine kinase ( 38 times the normal range , 2190 ) . transthoracic echocardiography revealed pericarditis in 6 cases ( 50% ) , with compression in 1 case . left - ventricular ejection fraction was decreased in 7 cases ( median of 46% , 2755 ) and normal in the remaining 5 cases . cardiac - mri ( n  =  11 ) revealed a spontaneous t2 hypersignal in 3 cases ( 27% ) and/or a t1-gadolinium late signal suggestive of myocarditis in 7 cases ( 73% , see figure 1 ) and no t1-gadolinium early signal was observed . in the remaining case , eb showed focal active and chronic inflammatory lesions with both lymphocytes and neutrophils invading the myocardium , consistent with the diagnosis of myocarditis . coronarography ( n  =  7 ) and coro - ct - scan ( n  =  2 ) were normal or did not show significant atheroma explaining the ventricular lesions . viral screening was negative ( n  =  11 ) , with the exception of patient 7 , who presented with a slightly positive cytomegalovirus blood replication ( blood copy number by polymerase chain reaction  =  3.2 log ) . ( a ) white arrow : myocardium spontaneous t2-hypersignal of the left ventricle consistent an inflammatory process ( edema , patient 11 ) . ( b ) white arrow : myocardium late - t1-post - gadolinium enhancement of the left ventricle consistent an inflammatory process . ( a ) white arrow : myocardium spontaneous t2-hypersignal of the left ventricle consistent an inflammatory process ( edema , patient 11 ) . ( b ) white arrow : myocardium late - t1-post - gadolinium enhancement of the left ventricle consistent an inflammatory process . no pericardial effusion ( patient 7 ) . according to these findings , and based on sagar et al , myocarditis was ruled a definite myocarditis in 1 case with eb ( 8% ) , a probable acute myocarditis in 6 cases ( 50% ) , and only a possible subclinical acute myocarditis in the 5 remaining cases ( 42% ) . aside from heart involvement , other clinical ass features observed at the time of ass initial diagnosis or during the follow - up period were similar to those commonly described in larger ass cohorts . these manifestations however included active myositis in all cases , interstitial pneumonia in 83% of the cases , and less commonly dermatologic and rheumatic manifestations ( see table 1  ) . of note , various anti - trna - synthetase autoantibody specificities were found anti - jo1 ( n  =  8) , anti - pl7 ( n  =  3 ) , and anti - pl12 ( n  =  1 ) . the prevalence of other associated autoantibodies , including anti - ro / ssa and anti - la / ssb , was similar to what has been reported previously . all patients were anticitrullinated peptide / protein antibody negative . the treatments targeted both the heart and the immune system . cardiac treatment consisted of diuretic ( n  =  9 ) , beta - blockers ( n  =  6 ) , angiotensin inhibitors ( n  =  4 ) , antiarrhythmic drugs ( n  =  2 ) , and inotropic drugs ( n  =  2 ) . immunosuppressive drugs initially included steroids in all of the cases associated with intravenous immunoglobulins ( n  =  4 ) , intravenous cyclophosphamide ( n  =  4 ) , and anti - cd20 monoclonal antibodies ( n  =  3 ) . oral immunosuppressive drugs were also administered , among which mycophenolate mophetil or azathioprine were the most common ( n  =  4 cases each , see table 1  ) . of note , a second therapeutic line was necessary in 3 cases ( 30% ) . with a median follow - up of 11 months ( 084 ) , 2 different outcomes were observed . eight patients ( 75% ) presented with normal heart examinations , despite a relapse of pericarditis in 1 case . however , 3 patients developed chronic heart failure , with several relapsing episodes ( n  =  3 ) . in these 3 cases , transthoracic echocardiography showed altered left ventricular function , with significant left ventricle dilation in 2 cases . taken as a whole and consistent with cooper et al , these results suggest the following myocarditis distribution : an acute myocardial infarction - like syndrome with normal coronary arteries ( n  =  6 , 50% ) , heart failure with normal - sized or dilated left ventricle and hemodynamic compromise ( n  =  3 , 25% ) , and heart failure with dilated left ventricle , new ventricular arrhythmia , and 3rd degree heart block ( n  =  3 , 25% ) , respectively . however , the limitation of this study is inherent to its retrospective design , and these data could have been either underestimated due to severe undiagnosed cases or overestimated due to recruitment bias ( all centers being tertiary care centers ) . there have been no reports to date in the literature providing this specific figure for ass , but it is comparable to what has been reported for other inflammatory myopathies . myocarditis was associated to pericarditis in half of the cases , which is more than expected , since the frequency of isolated pericarditis is roughly 10% in inflammatory myopathies . however , as confirmed by this study , pericarditis may be more frequent in the context of ass . myocarditis inaugurated ass in 42% of the cases and was always associated with extra - cardiac symptoms in accordance with ass activity , including active myositis in all cases . these data outline the importance of seeking extra - cardiac symptoms in cases of myocarditis to make the ass diagnosis , which could be confirmed by the seropositivity of anti - trna - synthetase autoantibodies . the extra - cardiac features were typical of ass and did not predict the occurrence of myocarditis in this context . clinical examination as well as first line biological and morphological exams is not very helpful in guiding the myocarditis diagnosis . in fact , dyspnea is common in ass because of interstitial lung disease or respiratory muscle involvement . creatine kinase levels are difficult to interpret , particularly in the context of myositis , and troponin t and i are not a sensitive enough indicator for diagnosing myocarditis . early echocardiography is absolutely necessary when diagnosing alternative diseases , as well as when evaluating the severity of myocarditis . eb should therefore be the cornerstone of a positive diagnosis , but the patient 's condition rarely allows for such an invasive procedure . this leaves us with cardiac - mri as the main noninvasive tool for the diagnosis of myocarditis . when performed early , t2-weighted images are suggestive of myocardic edema as a spontaneous hyperintensity . early t1-contrast after the gadolinium injection reveals hypoperfusion zones , whereas late t1-post - gadolinium contrasts are consistent with inflammatory process and fibrosis . however , these delayed t1-post - gadolinium enhancements might not distinguish myocarditis from chronic scarring . it is generally accepted that the combination of these mri features provides the highest sensitivity and specificity . however , all mri features are not always concomitantly found and the mere presence of just one of these indicators is associated with a good positive predictive value ( above 2/3 ) . in this case series , this is likely due to the fact that the cardiac mris were performed rather late ( up to 3 months after first cardiac symptoms , patient 3 ) and/or after the patients had begun a steroids treatment . since myocarditis implies severe organ involvement , it is an important condition to diagnose in ass . myocarditis can indeed lead to the development of dilated cardiomyopathy in 30% of cases . moreover , in inflammatory myopathies , heart involvement seems to be a major cause of death ( about 20% of the cases ) . in this series , though intensive care was required for half of the patients , no deaths occurred . moreover and though 2 severe patients could have been missed , the patients survival does not differ from that of other ass patients . three patients ( 30% ) developed chronic left ventricle dysfunction , among which 2 presented with dilated cardiomyopathy despite appropriate treatments . thus , early and aggressive therapy , including immunosuppressive drugs , seems recommended . in summary , although rare and difficult to diagnose , myocarditis must be carefully sought out in ass patients , especially those with pericarditis . starting specific treatments early on could be important to preventing the development of chronic dilated cardiomyopathy . prevalence of ass - related myocarditis is 3.4% , similar to that of other inflammatory myopathies . although difficult in the context of ass , the myocarditis diagnosis is important to make : the outcome can be severe and require specific medications .
abstractantisynthetase syndrome ( ass ) corresponds to an overlapping inflammatory myopathy identified by various myositis - specific autoantibodies ( directed against trna - synthetases ) . 
 myocardial involvement in this condition is poorly described.from a registry of 352 ass patients , 12 cases of myocarditis were retrospectively identified on the basis of an unexplained increase in troponin t / i levels associated with either suggestive cardiac magnetic resonance imaging ( mri ) findings , nonsignificant coronary artery abnormalities or positive endomyocardial biopsy.the prevalence of myocarditis in ass is 3.4% and was not linked to any autoantibody specificity : anti - jo1 ( n  =  8) , anti - pl7 ( n  =  3 ) , and anti - pl12 ( n  =  1 ) . 
 myocarditis was a part of the first ass manifestations in 42% of the cases and was asymptomatic ( n  =  2 ) or revealed by an acute ( n  =  4 ) or a subacute ( n  =  6 ) cardiac failure . 
 it should be noted that myocarditis was always associated with an active myositis . when performed ( n  =  11 ) 
 , cardiac mri revealed a late hypersignal in the t1-images in 73% of the cases ( n  =  8) . 
 half of the patients required intensive care . 
 ten patients ( 83% ) received dedicated cardiotropic drugs . 
 steroids and at least 1 immunosuppressive drug were given in all cases . 
 after a median follow - up of 11 months ( range 084 ) 9 ( 75% ) patients recovered whereas 3 ( 25% ) developed a chronic cardiac insufficiency . 
 no patient died.the prevalence of myocarditis in ass is similar to that of other inflammatory myopathies . 
 although the prognosis is relatively good , myocarditis is a severe condition and should be carefully considered as a possible manifestation in active ass patients .