Myocarditis and Chronic Inflammatory Cardiomyopathy, from Acute Inflammation to Chronic Inflammatory Damage: An Update on Pathophysiology and Diagnosis

Abstract

Acute myocarditis covers a wide spectrum of clinical presentations, from uncomplicated myocarditis to severe forms complicated by hemodynamic instability and ventricular arrhythmias; however, all these forms are characterized by acute myocardial inflammation. The term "chronic inflammatory cardiomyopathy" describes a persistent/chronic inflammatory condition with a clinical phenotype of dilated and/or hypokinetic cardiomyopathy associated with symptoms of heart failure and increased risk for arrhythmias. A continuum can be identified between these two conditions. The importance of early diagnosis has grown markedly in the contemporary era with various diagnostic tools available. While cardiac magnetic resonance (CMR) is valid for diagnosis and follow-up, endomyocardial biopsy (EMB) should be considered as a first-line diagnostic modality in all unexplained acute cardiomyopathies complicated by hemodynamic instability and ventricular arrhythmias, considering the local expertise. Genetic counseling should be recommended in those cases where a genotype-phenotype association is suspected, as this has significant implications for patients' and their family members' prognoses. Recognition of the pathophysiological pathway and clinical "red flags" and an early diagnosis may help us understand mechanisms of progression, tailor long-term preventive and therapeutic strategies for this complex disease, and ultimately improve clinical outcomes.

Keywords: endomyocardial biopsy; eosinophilic granulomatosis with polyangiitis; inflammatory cardiomyopathy; myocarditis; sarcoidosis; systemic lupus erythematosus; systemic sclerosis.

Figure 1

Physiopathological processes leading to the persistence of inflammation and the progression from acute myocarditis to chronic inflammatory cardiomyopathy: TLR-3 variants cause reduction in efficacy of innate immune system response against viruses; Bacteroides species triggered autoimmune reaction against cardiac epitopes; antibodies against alpha- and beta-myosin heavy chain constitute a component of the autoimmune response against the heart. MHC, myosin heavy chain; TLR-3, Toll-like receptor-3.

Figure 2

(a) ECG during a hot-phase of arrhythmogenic right ventricular cardiomyopathy, showing low-voltages, QRS fractionation as well as ST-elevation in the inferior leads and T waves inversion with borderline ST-segment depression in leads I-aVL. (b) Cardiac magnetic resonance (CMR) scan is performed during the acute/hot-phase. She was later found to be heterozygous for a pathogenic nonsense variant in Desmoplakin (DSP) gene: c.478C > T p.(Arg160Ter). Cine steady-state free-precession images showing a non-dilated left ventricle (LV) with increased wall thickness in the lateral wall, in keeping with myocardial edema. Intrinsic contrast on cine-imaging in the areas of edema and scar. There is a small patch of fat infiltration in the mid-septum (blue arrow). (c) Irregular LV lateral wall in the lateral segment, which likely represents epicardial fat, infiltrating the LV wall (white arrow). (d) T1 mapping is significantly elevated in the inferolateral wall (1790 ms to 1565 ms; normal range 970–1050 ms). (e) Extracellular volume is elevated in a patchy pattern (79% in basal anterolateral wall).

Figure 3

(a) T2 mappings are massively elevated in the lateral wall (white arrows) (max 119 ms in basal inferolateral, 85 ms in basal anterolateral, normal range 40–54 ms) and within normal range elsewhere. (b) Increased myocardial signal at mid anterolateral and mid inferolateral wall on T2 STIR sequences. (c) ”Ring-like” subepicardial late gadolinium enhancement (LGE), becoming almost transmural towards the anterolateral LV wall.

Figure 4

CMR scan for the same patient performed 3 months after resolution of the “hot phase.” The initially edematous and thicker lateral wall has evolved towards thinning and hypokinesia. Compared to the previous CMR scan, the lateral segments appear less edematous (although T2 values remain mildly elevated in some regions) and have also thinned. The extent of scar has not significantly changed. (a) Extensive ‘ring-like’/circumferential basal to apical mid-wall LGE, becoming epicardial at the basal to mid anterior, anterolateral, inferolateral, and inferior wall segments. (b) Three chamber long axis view of LGE sequences—the amount of scar has not changed, but a thinning of the LV walls can be appreciated. (c) Elevated native myocardial T1 value in patches, with an improvement compared to 3 months before, but representing persistent edema (1240–1359 ms). (d) Mildly elevated native myocardial T2 values (47–59 ms) in patches improved compared to the previous scan.

Figure 5

A proposed practical approach algorithm to facilitate early diagnosis of Infl-CMP, with a close collaboration between general practitioners, cardiologists, and other specialties.