A 46 years old male, heavy smoker and mild alcohol consumer without personal of familial history of cardiovascular disease, presented to the emergency department complaining for worsening shortness of breath in the last week with an episode of paroxysmal nocturnal dispnoea during the last night. He denied chest pain, palpitations or syncope; an episode of gastroenteritis was reported 4 months earlier.On physical examination the patient appeared tachypnoic for minimal efforts (respiratory rate 25/min – Sat02 90% in room air); heart rate was 110 bpm and brachial artery pressure 120/90 mmHg. Jugular vein distension, rales over the lower third of both lung fields, a third heart sound (S3 gallop) and an olosystolic apical murmur of grade III were present; no peripheral oedema was appreciable.Chest X-ray showed cardiomegaly and mild pulmonary congestion.Blood cells count, renal and liver function tests, C reactive protein, erythrocyte sedimentation rate and Troponin I were normal; brain natriuretic peptide (BNP) was 1700 pg/ml.ECG showed sinus tachycardia, left atrium enlargement, left ventricular hypertrophy with concordant repolarization anomalies and relative low voltage in the limb leads, if compared with precordial ones.
Once admitted to the Cardiology Ward, echocardiography revealed a dilated left ventricle (EDD 70 mm, EDVi 104 ml/m2) with severe systolic dysfunction (LVEF 25%) and diffuse wall motion asynergy, a restrictive filling pattern and severe functional mitral regurgitation; moreover, right ventricle dilation with severe systolic dysfunction (FAC 23%) and moderate pulmonary hypertension were found.
Coronary angiography ruled out significant coronary artery disease (stenosis>50%).Pulmonary artery catheterization revealed a reduced cardiac index (1,8 l/min/m2) with elevate filling pressures (PCWP 23 mmHg, RAP 12 mmHg) with moderate pulmonary hypertension (MPP 30 mmHg).Symptoms, signs of congestion, hemodynamic parameters (normalization of cardiac index and pulmonary hypertension) and mitral regurgitation (reduction to moderate) improved with intravenous diuretics, vasodilators and dobutamine. Oral therapy with angiotensin converting enzyme inhibitors, beta blockers and aldosterone antagonists was gradually titrated and well tolerated despite the persistence of severe left ventricular dysfunction a week after admission.No major ventricular arrhythmias were found at prolonged monitoring.Cardiac magnetic resonance (CMR) substantially confirmed the morpho-functional findings of echocardiography, whereas did not find any sign suggestive of acute myocarditis (oedema) or of inflammatory cardiomyopathy (LGE with a myocarditic pattern) 1.
SSFP - 4 chambers / diastole SSFP - 4 chambers / systole
T2 weighted - absence of IR-TFE T1 - absence of Latemyocardial edema Gadolinium Enhancement
In consideration of- the absence of history of cardiovascular pathology in a previously healthy subject,- the well-defined and recent onset of symptoms,- the severity of clinical presentation (heart failure requiring medical hemodynamic support)- the discrepancy between the severity of the left ventricular dysfunction and the absence of marked electrocardiographic anomalies (q waves, left bundle branch block),- the absence of severe replacement fibrosis at CMR,- the refractoriness of severe ventricular dysfunction to a short period of maximal medical therapy for heart failure,- the fulfilment of the new ESC Working Group criteria for “clinically suspected myocarditis” the patient underwent endomyocardial biopsy (EMB), in order to exhaustively investigate the myocardial substrate and guide the following clinical management by identifying and characterizing a potentially reversible and treatable pathology (i.e. lymphocytic, granulomatous, or giant cell myocarditis)2-4.Four samples of myocardium were collected from the right ventricular septum via femoral approach and analyzed with traditional histopathological, immunohistochemical and molecular techniques3-4.Traditional histopathology revealed multiple clusters of lymphocytes with evident signs of cardiomyocyte necrosis, in a scenario of active myocarditis according to Dallas Criteria5; moreover mild diffuse interstitial fibrosis was found.Immunohistochemical analysis demonstrated clear myocardial immune cell activation with a marked positivity for HLA-DR staining in cardiomyocytes and endothelial cell layers6.Polymerase chain reaction (PCR) testing for common cardiotropic viruses (CMV, enteroviruses, adenoviruses, PVB19, HHV6) was negative7.
The patient was discharged two weeks after admission in stable hemodynamic compensation (NYHA II, BNP 300 pg/ml) and oral therapy with loop diuretics, angiotensin converting enzyme inhibitors, beta blockers and aldosterone antagonists.Immunosuppressive therapy was not started in consideration of the optimal clinical (NYHA IV->II) and laboratoristic (BNP 1770->300 pg/ml) response to medical therapy4.For the same reasons, in consideration of the frequent improvement of ventricular function in the short-term in the context of active myocarditis and in keeping with the recent ESC WG consensus paper on myocarditis4, an implantable Cardioverter Defibrillator (ICD) was not placed.A short-term serial follow-up revaluation was planned to monitor the clinical and instrumental evolution of the patient8. One month after discharge the patients presented for his first follow-up visit in good hemodynamic compensation, symptomatic for shortness of breath only for moderate efforts (NYHA II).Medical therapy was well tolerated and the left ventricular systolic function had moderately improved (LVEF 38%).What is the prognosis of this patient?After six months the patients presented to our clinic asymptomatic and optimal compensation (NYHA I; BNP 12 pg/ml). An impressive positive reverse remodelling of the left ventricle was evident, with a normalization of end diastolic diameters, volumes (EDD 58 mm; VTDi 74 ml/m2) and left ventricular systolic function (LVEF 55%); also mitral regurgitation reduced markedly.
Notably, also the electrocardiographic anomalies found at disease presentation completely resolved at this follow-up.
- EMB represents the gold standard for myocarditis.- EMB is indicated for the diagnostic assessment and clinical management of clinically suspected myocarditis 4;- The indication to perform an EMB is strictly clinical and has not to be discouraged by negative CMR findings4.- Myocarditis may be associated with short-term improvement of ventricular function under optimal medical treatment, which has been shown to represent a predictor of good prognosis in the long term in a recent single center series8. However, confirmatory data on larger multicentre prospective series are needed.- Long-term follow-up in this case is needed, since myocarditis may relapse.
1. Friedrich MG, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009;53:1475–87.2. Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Eur Heart J. 2007;28:3076–93.3. Leone O, Veinot JP, Angelini A, et al. 2011 Consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology. Cardiovasc Pathol. 2012;21:245–74.4. Caforio ALP, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Heliö T, Heymans S, Jahns R, Klingel K, Linhart A, Maisch B, McKenna W J, Mogensen J, Pinto Y, Ristic A, Schultheiss HP, Hubert Seggewiss H, Tavazzi L, Thiene G, Yilmaz A, Charron P, Elliott PM. Current state of knowledge on aetiology, diagnosis, management and therapy of myocarditis. A Position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013: 34:2636-48.5. Aretz HT, Billingham ME, Edwards WD, et al. Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol. 1987;1:3–14.6. Wojnicz R, Nowalany-kozielska E, Wojciechowska C, et al. Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: two-year follow-up results. Circulation. 2001;104:39–45.7. Frustaci A, Russo MA, Chimenti C. Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study. Eur Heart J. 2009;30:1995–2002.8. Anzini M, Merlo M, Sabbadini G, et al. Long-term evolution and prognostic stratification of biopsy-proven active myocarditis. Circulation. 2013;128:2384–94. Abbreviations listBNP: brain natriuretic peptideEDD: end diastolic diameter; EDV: end diastolic volume;EDVi: end diastolic volume indexed for body surface area;LVEF: left ventricular ejection fraction;FAC: fractional area change;PCWP: pulmonary capillary wedge pressure;RAP: right atrium pressure;MPP: mean pulmonary artery pressure;CMR: cardiac magnetic resonance;SSFP: steady-state free precession;IR-TFE: inversion recovery turbo field echo sequence;EMB: endomyocardial biopsy;HLA: human leukocyte antigenPCR: polymerase chain reaction;CMV: citomegalovirus;PVB19: parvovirus B19;HHV6: human herpesvirus 6;NYHA: New York Heart Association;ICD: Implantable Cardioverter Defibrillator.
Marco Anzini, Marco Merlo, Gianfranco Sinagra MD FESCCardiovascular Department, “Ospedali Riuniti di Trieste” and University of Trieste, Trieste, Italy
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