Update on acute myocarditis

Abstract

Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.

Keywords: Cardiac magnetic resonance imaging; Endomyocardial biopsy; Fulminant myocarditis; Immune checkpoint inhibitors; Mechanical circulatory support.

Fig. 1

Incidence of cardiac death and heart transplantation among patients with fulminant myocarditis affected by 3 specific histologic subtypes. Data derived from the largest available dataset collecting 220 cases of histologically proven acute myocarditis from 16 centers, as highlighted in the map on the top of the image. Fulminant myocarditis was defined as requiring circulatory support with inotropes or mechanical devices. The reported analysis excluded patients with acute nonfulminant myocarditis (n, 55) and 2 patients with fulminant presentation due to a sarcoid myocarditis. Log-rank (Mantel-Cox) test confirmed a significantly (p after Bonferroni test) worse prognosis for patients with giant-cell myocarditis (GCM) versus lymphocytic myocarditis (LM) at 60 days (p < 0.001) and a worse prognosis for patients with GCM versus eosinophilic myocarditis (EM) (p 1⁄4 0.02) and versus LM (p < 0.001) at long-term follow-up. Patients with FM due to EM or LM did not differ in terms of outcome. On the bottom of the image, representative hematoxylin and eosin sections of GCM, EM, and LM. Reprinted with permission of the Journal of the American College of Cardiology .

Fig. 2

Representative case of acute myocarditis based on 2018 cardiac magnetic resonance imaging Lake Louise criteria. At least one T2 marker of myocardial edema and one T1 marker of myocardial injury are required. On the left: main criteria are fulfilled, as there are both (1) signs of myocardial edema (regional increase of SI on T2w images and regional increase of native T2 at T2 mapping, underpinned by head arrows in the anterolateral wall) and of (2) non-ischemic myocardial injury (regional LGE, increase native T1 at T1 mapping and ECV expansion in the anterolateral wall, underpinned by head arrows, with non-ischemic pattern). On the right: one supportive criterion is present, in fact a small pericardial effusion is evident at cine images, whereas there are neither global hypokinesis nor regional wall motion abnormalities in this case. Abbreviations: T2w, T2 weighted; SI, signal intensity; LGE, late gadolinium enhancement; ECV, extra-cellular Volume; LVEF, left ventricular ejection fraction.

Fig. 3

Acute myocarditis scenarios. The figure stratifies acute myocarditis according to the clinical presentation at admission and its corresponding outcome. Uncomplicated acute myocarditis is characterized by a benign course, with a low 1-year mortality or heart transplant rate. Therefore, a CMRI-based diagnosis is recommended in the absence of complicated features. CMRI images within the box of uncomplicated myocarditis are representative, with short tau inversion recovery (STIR) sequences revealing increased signal intensity suggestive of edema and transmural late gadolinium enhancement (LGE) involving LV basal-lateral and -inferior walls. Complicated acute myocarditis, defined by the presence of either impaired left ventricular function or arrhythmias or hemodynamic instability requiring circulatory support (i.e. fulminant myocarditis), is associated with an increased risk of death and heart transplant at 1 year, which is highest in case of fulminant giant cell myocarditis. Complicated acute myocarditis requires active treatment, including an EMB-based diagnosis for optimal management, aggressive circulatory support when deemed necessary and, eventually, immunosuppression. The EKG shows the presence of a high grade atrioventricular block; on the upper right of the image, representative histological specimens show the subtypes of inflammatory cells that can be found in acute myocarditis: (LM) lymphocytic inflammatory infiltrates, (EO) eosinophilic infiltrates, and (GCM) lymphocytic infiltrates with giant cells. Abbreviations: HTx, heart transplant; LM, lymphocytic myocarditis; EO, eosinophilic myocarditis; GCM, giant cell myocarditis; LV, left ventricular; HF, heart failure; LVEF, left ventricular ejection fraction; AV, atrio ventricular; CAD, coronary artery disease; CMRI, cardiac magnetic resonance imaging; EMB, endomyocardial biopsy; MCS, mechanical circulatory support.

Fig. 4

A risk-based approach for clinically suspected acute myocarditis currently in use in our institution. As explained in the text, several clues may lead clinicians to suspect a diagnosis of acute myocarditis. Once clinicians have ruled out differentials, a risk-based approach must be followed to properly manage acute myocarditis. Low risk uncomplicated acute myocarditis deserves admission to ward, CMRI-based diagnosis and symptomatic treatment. Complicated acute myocarditis with features of high risk (e.g. impaired left ventricular function, wide QRS, arrhythmias, hemodynamic instability) requires admission to CCU/ICU and bundles of care, including an EMB-based diagnosis, aggressive circulatory support and immunosuppression in selected cases. Abbreviations: HF heart failure; LCOS, low output cardiac syndrome; AV, atrioventricular; VT, ventricular tachycardia; VF, ventricular fibrillation; WMA, wall motion abnormalities; ACS, acute coronary syndrome; proBNP, pro b-type natriuretic peptide; WBC, white blood cells; CRP, C-reactive protein; ICI, immune checkpoint inhibitors; LVEF, left ventricular ejection fraction; LT, life threatening; CMRI, cardiac magnetic resonance imaging; EMB, endomyocardial biopsy; CCU, coronary care unit; ICU, intensive care unit.