‘Clinically suspected myocarditis with pseudoinfarct presentation’ complicated with left ventricular aneurysm

Abstract

A 51-year-old man presented with chest pain, high troponin level, inflammatory syndrome and ST-segment elevation in the anterior leads. While the transthoracic echocardiogram (TTE) showed anteroseptal hypokinesis and apical akinesis, the coronary angiogram was normal. Cardiac MR demonstrated a typical aspect of myocarditis (multiple areas of mid-myocardial late gadolinium enhancement, sparing the subendocardial layer, along with oedema). The initial diagnosis was clinically suspected myocarditis with pseudoinfarct presentation. However, the short-term evolution was not typical of this syndrome, since an apical transmural scar with aneurysm developed within 2 weeks. Seven years later, the patient remained asymptomatic, while Q waves persisted in anterior leads along with an apical aneurysm on TTE. A transmural myocardial necrosis with aneurysm is an unusual complication of acute myocarditis. The potential mechanisms accounting for the development of these lesions are reviewed, and the clinical implications for the diagnosis and monitoring of acute myocarditis are discussed.

Background

Acute myocarditis can often mimic an acute coronary syndrome.^1–8 In the absence of coronary artery stenosis, cardiac MR (CMR) is helpful for initial assessment and follow-up.^{2 9–14} Since the diagnosis of myocarditis requires an endomyocardial biopsy (EMB) to be confirmed, the term ‘clinically suspected myocarditis with pseudoinfarct’ has been proposed when EMB is not performed.¹⁰

We are presenting an observation where a clinically suspected myocarditis was complicated by the development of an apical left ventricular aneurysm. This complication, although uncommon, may be underestimated while its prognosis remains potentially threatening.

Case presentation

A 51-year-old man with medical history of hypertension presented to the emergency department with a 3-day history of crescendo, mid-sternal, crushing chest pain without radiation, associated with nausea and vomiting. The pain was worsened with deep inspiration. The patient was subfebrile (37.8°C), normotensive (122/78 mm Hg) with tachycardia (100/min) and normoxic (arterial oxygen saturation 94% on room air). Auscultation of the heart and lungs was unremarkable.

Investigations

White cell count was elevated (16.8x10⁹/L with 78% neutrophils) along with C reactive protein (12.0 mg/dL). The ECG showed diffuse ST-segment elevation, more pronounced in the anterior leads, and Q waves in the anterior and inferior leads (figure 1). The troponin-I level was elevated (28 ng/mL). Medical treatment with aspirin, clopidogrel, heparin and intravenous nitroglycerin was initiated.¹⁵ The emergent coronary angiogram revealed strictly normal coronary arteries without any atherosclerotic lesion (figure 2), whereas the left ventriculogram demonstrated anterior wall akinesis and apical dyskinesis. Transthoracic echocardiogram (TTE) showed a mildly dilated left ventricle (LV) with a slightly reduced ejection fraction (EF 45%) due to anteroseptal hypokinesis and apical akinesis along with a small LV apical thrombus. There was no pericardial effusion. Of note, apical LV wall thickness was normal at that time with no evidence of aneurysm.

Figure 1.

ECG on admission. Sinus tachycardia with diffuse ST elevation predominant in anterior leads (+4 mm) with Q waves in anterior and inferior leads, suggesting acute anteroseptal myocardial infarction.

Figure 2.

Coronary angiogram, right anterior oblique view of the left coronary circulation showing no evidence of atherosclerosis or thrombosis.

Outcome and follow-up

The diagnosis of clinically suspected myocarditis with pseudoinfarct was proposed.¹⁰ The CMR study performed 13 days later demonstrated a mildly dilated LV with EF 47%, patchy mid-myocardial areas detected with late gadolinium enhancement (LGE), involving the septum, the distal anteroseptal and the proximal posterior walls, sparing the subendocardial layer in a typical myocarditis pattern (figure 3). T2-weighted high-intensity signal indicated myocardial oedema. The pericardium also exhibited LGE, suggesting associated pericarditis. There was also evidence of a newly developed apical aneurysm, with a thin, scarred myocardium (figure 4). Repeated TTE confirmed the aneurysm (2.2 cm width, 3.7 cm length).

Figure 3.

Three-chamber cardiovascular MRI view shows multiple areas of mid-myocardial late gadolinium enhancement involving the distal anteroseptal, the proximal and the mid-posterior walls of the left ventricle (arrows), sparing the endocardium, typical of myocarditis. There is also diffuse pericardial hyperenhancement suggesting associated pericarditis.

Figure 4.

Left panel shows long-axis cardiovascular MRI view of the LV, 13 days after patient’s presentation. The previously akinetic apex is now aneurysmal (white arrow). Right panel shows three-chamber CMR view of the LV with late gadolinium hyperenhancement. There is evidence of transmural distal septal and apical necrosis (white arrow) with white aspect while normal myocardium is black. CMR, cardiac MR; LV, left ventricle.

Six months later, ECG still exhibited Q waves in anterior and inferior leads, and TTE revealed normal LV size with improvement of contractility, EF 55%, but persistence of an apical aneurysm without thrombus. After 7 years, the patient remained asymptomatic without any sign of heart failure, thromboembolic event or arrhythmia.

Discussion

Myocarditis remains defined histologically as an inflammatory disease of the myocardium according to 1996 WHO,¹⁶ 2007 European Society of Cardiology (ESC)¹⁷ and 2013 ESC working group on myocardial and pericardial diseases.¹⁰

The clinical diagnosis of acute myocarditis remains challenging due to the large spectrum of clinical presentations, ranging from asymptomatic non-specific ECG changes to heart failure, arrhythmias, cardiogenic shock or sudden death.^{2 13 18} Myocarditis mimicking acute myocardial infarct1 3–5 8 19–23 is a frequent mode of presentation.1 3 5 7 24 In a patient with sudden onset of chest pain, ECG changes and elevated cardiac enzymes, but with normal coronary angiogram, the diagnosis of myocarditis is suspected based on history of viral illness, fever, presence of inflammatory markers, global or regional ventricular wall motion abnormalities on the angiogram and/or TTE.⁹ CMR has become a major tool for non-invasive diagnosis of myocarditis, according to the ‘Lake Louise criteria’.¹¹ However, EMB remains the gold standard to establish the diagnosis of acute myocarditis and its aetiology, an approach that has been greatly enhanced by the addition of immunohistochemical analysis and viral genome search.¹⁰

The clinical course of an acute myocarditis is often benign with spontaneous resolution within 2–4 weeks in 50%–57% of cases, whereas 12% to 25% progress to severe dilated cardiomyopathy and heart failure.^{10 25 26} Indeed, acute myocarditis may sometimes evolve towards ongoing inflammation (autoreactive myocarditis), causing further myocardial injury and eventually leading to dilated cardiomyopathy and heart failure.^{10 18} A similar evolution has also been reported in myocarditis with pseudoinfarct, which despite a usual good prognosis has been found to develop a persistent reduced pump function in several retrospective studies.^{1 3 5}

The mechanism leading to the development of myocardial necrosis during myocarditis has been primarily accounted for by direct viral infection and microvascular ischaemic injury. The latter results from endothelial dysfunction produced by intense focal inflammation.^27–29 It has also been proposed that viral myocarditis could be associated with an exaggerated coronary vasoconstrictive response to acetylcholine, suggesting that coronary vasospasm may occur in these patients.³⁰ In addition, coronary thrombosis has been reported in fulminant,¹⁹ giant cell²⁰ or hypereosinophilic myocarditis.²² Regardless of the mechanisms, local myocardial necrosis can result in wall thinning and aneurysmal remodelling as demonstrated in animal models.^{31 32}

Ventricular aneurysms have been described in a variety of inflammatory myocardial diseases, but remain a relatively rare complication. Most cases are related to immune-mediated diseases such as sarcoidosis (10% of the patients with sarcoidosis have a ventricular aneurysm),³³ giant cell myocarditis,^34–37 Behcet’s disease^34–37 or Takayasu’s arteritis.^34–37 The remaining observations are associated with bacterial (listeriosis, syphilis),^{38 39} fungal (aspergillosis),⁴⁰ parasitic (Chagas disease)^{41 42} or viral (particularly Coxsackievirus B)31 32 43–45 myocarditis. Frustaci et al⁴⁶ have found the presence of microaneurysms, sometimes multiple, located in the right or left ventricles, in about 3% of patients with EMB-proven myocarditis from viral or immunological origin. The prevalence of macroaneurysms remains unknown. While large aneurysms associated with myocarditis can lead to life-threatening LV free wall rupture,^{47 48} microaneurysms can be complicated by ventricular arrhythmias or Brugada syndrome.^{46 49} Nevertheless, microaneurysms with preserved pump function seem to have a favourable outcome, without any fatal arrhythmia in the study by Frustaci et al,⁴⁶ and may even sometimes get spontaneously occluded.

Data are not available to know if a specific antiviral, anti-inflammatory or immunomodulatory treatment would prevent the formation of aneurysms or more generally prevent myocardial necrosis and scar. Yet, there is evidence that the course of the disease may be stalled by these treatments. A study of 102 patients with idiopathic cardiomyopathy showed an improvement in systolic function with immunosuppressive therapy only in the subgroup with evidence of inflammatory disease.⁵⁰ Recent clinical trials have since confirmed that the course of such ‘reactive’ myocarditis, that is, with active ongoing inflammation, could be improved with immunomodulation or antiviral therapy.^51–54 The recent ESC recommendations support immunosuppressive therapy, including steroids, in selected cases with EMB-proven virus-negative myocarditis, but not in the presence of virus to avoid exacerbation in patients with ongoing infection. Identifying patients who could benefit from such aetiology-directed treatment justifies the current recommendations for EMB.^{7 10 18} Furthermore, since many of the myocarditis causes leading to aneurysm formation are immune-mediated and treatable (ie, sarcoidosis or giant cell myocarditis), EMB is also recommended in those patients.^{9 10 15}

In conclusion, clinically suspected myocarditis with pseudoinfarct presentation may be complicated by myocardial necrosis and development of an aneurysm. The prevalence of such aneurysms and their prognosis remain unknown. Since many aneurysms could be related to a treatable form of myocarditis, EMB should be proposed to establish the diagnosis, the aetiology and guide therapy. It would also provide a rational framework to understand better the natural history and time course of this heterogeneous disease.

Learning points.

• Myocarditis with pseudoinfarct presentation may be complicated with ventricular aneurysm.

• Myocardial necrosis with left ventricular aneurysm can develop in myocarditis in the absence of coronary lesions.

• Since some aneurysms could be related to a treatable form of myocarditis, endomyocardial biopsy should be proposed to establish the diagnosis, the aetiology and guide therapy.