Main topic Herz 2018 · 43:423–430 B. Maisch1 ·P.Alter2 https://doi.org/10.1007/s00059-018-4719-x 1 Fachbereich Medizin, Philipps-Universität Marburg und Herz- und Gefäßzentrum (HGZ) Marburg, Published online: 15 June 2018 Marburg, Germany © The Author(s) 2018 2 Klinik für Innere Medizin-Pneumologie und Intensivmedizin, UKGM und Philipps-Universität Marburg, Marburg, Germany Treatment options in myocarditis and inflammatory cardiomyopathy Focus on i. v. immunoglobulins In 2012 we reviewed the treatment op- proBNP) and high-sensitivity (hs) tro- curtain of diabetic cardiomyopathy, viral tions in (peri)myocarditis and inflamma- ponin T or I as cardiac biomarkers of heart disease with or without inflamma- tory cardiomyopathy in a special issue of heart failure and necrosis, respectively. tion can be hidden. But which of the this journal devoted to heart failure and Of note, cardiac MRI is an important factors is then the major etiological de- cardiomyopathies [1]. Now, 5 years later, method for clarifying the presence of terminant? itistimelyandappropriatetotakestock inflammation or fibrosis in addition to This issue also holds true for alcoholic of old and new data on this topic. function and pericardial effusion, but it cardiomyopathy [8]. In these patients, al- cannot substitute endomyocardial biopsy cohol consumption of more than 40 g/day Evolution of diagnoses for establishing an etiologically based di- in men and more than 20g/day in women agnosis [1–5]. For the diagnosis of viral formorethan5yearsisthesomewhat In 2013, experts of the European Soci- vs. autoreactive (nonviral) myocarditis arbitrary diagnostic determinant for the ety of Cardiology (ESC) working group and for the diagnosis of eosinophilic or label of alcoholic cardiomyopathy. In en- on myocardial and pericardial diseases giant cell myocarditis, endomyocardial domyocardial biopsy, some infiltrating published a position statement on “The biopsyremainsessential, whilethebiopsy leukocytes may even suggest myocardi- current state of knowledge on aetiol- work-up includes histology, immunohis- tis in immunocompetent alcohol-depen- ogy, diagnosis, management and therapy tology, and polymerase chain reaction dent individuals as a likely differential of myocarditis” [2]. Specifically named (PCR) for RNA or DNA viruses [1–6]. diagnosis. causes of myocarditis were either infec- tive or immune-mediated or toxic [2, 3]. Special considerations for Clinical syndromes associated . Table 1 sums up the long list of pos- complex diagnoses with inflammatory cardio- sible causative pathogens and compares myopathy and myocarditis them with the real-world data of the Mar- Whether diabetic cardiomyopathy is a di- burg Myocarditis Registry (MMR) com- agnosisofitsownisstillunderdiscussion. Depending on the etiology, genetic pre- prising records of 1098 biopsied patients In endomyocardial biopsies of patients disposition, and comorbidities of the in- with suspected inflammatory dilated car- with heart failure and diabetes, histology dividual patient, at least four clinical syn- diomyopathy and/or myocarditis [1, 4]. can show microangiopathy, some infil- dromes can be identified after coronary The comments add important clues on trating macrophages and leukocytes, and artery disease is excluded by angiography how the diagnosis was made in the MMR. also a positive PCR of viral genomes such (. Fig. 1): Not mentioned but self-evident are a full as parvovirus B19. Diabetic cardiomy- 1. Life-threatening heart failure or clinical work-up of the patient includ- opathy can be part of a syndrome com- rhythm disturbance ing a detailed history, electrocardiogram prising hypertrophy and microangiopa- 2. Acute chest wall syndrome with (ECG) at rest and at exercise, imaging thy due to hypertensive heart disease and angina pectoris-like symptoms, often by Doppler echocardiography or cardiac diabetes and viral persistence [7]. For di- after an infection magnetic resonance imaging (MRI), as agnosisoftheunderlyingetiology, acom- 3. Acute onset of heart failure well as a complete laboratory examina- posite view of the clinical evidence and 4. Chronic heart failure tion with C-reactive protein (CRP) as exclusion of other causes of cardiomy- a marker of inflammation and N-termi- opathy by endomyocardial biopsy can be . Table 2 connects these clinical syn- nal pro-B-type natriuretic peptide (NT- an important clue. However, behind the dromes with classic textbook diagnoses Herz 5 · 2018 423 Main topic Life-threatening heart failure or rhythm disturbance • Shock, heart failure NYHA III-IV, elevated Troponin I/T, elevated Nt- proBNP, variable ECG altera ns, CAD ruled out, life-threa ng arrhythmias •Prototype: giantcellmyocardi , eosinophilic myocardi s, toxic myocardi Acute chest wall syndrome Biopsy Posi ve samples controls • Angina- like symptoms, CAD ruled out, variable ST/T altera in ECG, variable arrhythmias, intermi ent Troponin I/T- and NT- proBNP eleva ns •Prototype: Parvovirus B19 or other cardiotropic virus infec +/- pericardi Acute heart failure(AHF) • Dyspnea, edema, reduced EF, but also diastolic AHF, variable ECG, non ischemic cardiomyopathy, intermi ent Troponin I/T- and NT- proBNP eleva ns •Prototype: viral ornon-viral myocardi s or inflammatory cardiomyopathy (DCMi) Fig. 1 9 Clinical and his- tological phenotypes of myocarditis and in- Chronic heart failure(CHF) flammatory cardiomy- opathy. CAD coronary • All CHF symptoms for longer span, CAD ruled out, ECG with artery disease, ECG elec- LBBB, RBBB, AV-Block variable ST-/T-alteraons, intermient Troponin I/T-and NT-proBNP elevaons trocardiogram, EF ejection • Prototype: every viral or non-viral(autoreac ve) focal myocardi s fraction, LBBB left bundle or DCMi branch block, NYHA New York Heart Association, RBBB right bundle branch block such as fulminant, acute, chronic, or as the CONSENSUS trial with enalapril, glycosides were tested in the DIG trial, persistent chronic myocarditis. the SOLVD trial with captopril, the AT- which demonstrated a reduction of all- LAS trial with lisinopril, or the HOPE cause and heart failure-related hospital- Treatment trial with ramipril. In the CHARM and ization with no change in mortality rate. ELITE II trials, angiotensin receptor Their use in patients with tachyarrhyth- Restriction of physical activity blockers demonstrated a similar ben- mia reduces heart rate and improves the efit. Today, beta-blockade is part of quality of life. In suspected or histologically validated the therapeutic armamentarium in the Antiphlogistic treatment with non- myocarditis, restriction of physical activ- treatment of any form of heart failure steroidal anti-inflammatory drugs ity for at least 6 months is part of the inter- as demonstrated in the MERIT-HF trial (NSAIDs) such as ibuprofen or in- national guidelines. This is highly rec- for metoprolol, the CIBIS trial for biso- domethacin should be reserved for pa- ommended until the inflammation has prolol, and the COPERNICUS trial for tients with pericardial involvement, since disappeared—evidenced by cardiac MRI carvedilol. In acute cardiac decompen- in murine coxsackie B3 myocarditis this or endomyocardial biopsy—and cardiac sation, loop diuretics are effective and treatment was shown to be detrimental function has normalized. aldosterone receptor blockers should be [12]. For treatment of peri(myo)carditis, givenontopoftheotherheartfailure we prefer colchicine instead, not only Heart failure therapy for drugs as demonstrated by the RALES inrecurrentformsbutalsoforthefirst inflammatory cardiomyopathy trials for spironolactone in heart failure attack [13]. and by the EPHESUS trial for eplerenone Heart failure therapy is part of the treat- in heart failure patients after myocardial Antiarrhythmic treatment ment of inflammatory cardiomyopathy. infarction. According to the findings of It was successfully demonstrated in many the SHIFT trial, ivabradine can be given Apart from beta-blockers, antiarrhyth- heart failure trials on angiotensin-con- to treat sinus tachycardia and to reduce mic treatments for heart failure and for verting enzyme (ACE) inhibition such heart rate to below 70 bpm. Cardiac cardiomyopathy patients have been dis- 424 Herz 5 · 2018 Abstract · Zusammenfassung appointing. A meta-analysis of all trials Herz 2018 · 43:423–430 https://doi.org/10.1007/s00059-018-4719-x with amiodarone demonstrated a reduc- © The Author(s) 2018 tion in total mortality of 13% [14], but the SCD-HeFT trial, in which patients B.Maisch·P.Alter with a single-chamber implantable car- Treatment options in myocarditis and inflammatory dioverter-defibrillator (ICD) were ran- cardiomyopathy. Focus on i.v. immunoglobulins domized to amiodarone or to placebo, showed a decrease in mortality for the Abstract treatment group only [15]. The discus- For myocarditis and inflammatory cardiomy- disease can resolve spontaneously, often opathy, an etiologically driven treatment is specific treatment directed against the sion of whether rate or rhythm control today the best option beyond heart failure causative agent is required. For fulminant, is more beneficial in the treatment of therapy. Prerequisites for this are nonin- acute, and chronic autoreactive myocarditis, atrial fibrillation is still ongoing. Suffi- vasive and invasive biomarkers including immunosuppressive treatment has proven to cient anticoagulation is important under endomyocardial biopsy and polymerase be beneficial in the TIMIC and ESETCID trials; all circumstances. chainreactiononcardiotropicagents. for viral cardiomyopathy and myocarditis, Imaging by Doppler echocardiography