Clinical Overlap Between Myopericarditis and Stress Induced Cardiomyopathy: A Diagnostic and Therapeutic Challenge

Abstract

Patient: Female, 47

Final Diagnosis: Stress induced cardiomyopathy

Symptoms: Chest pain

Medication: —

Clinical Procedure: Catch • echo

Specialty: Cardiology

Objective:

Challenging differential diagnosis

Background:

Stress induced cardiomyopathy (SIC) is characterized by non-obstructive coronary arteries and characteristic ventricular apical ballooning. The exact pathogenesis of SIC is not well recognized. We present an unusual case of SIC that mimicked acute myopericarditis and discuss the effect of this masquerading presentation of SIC in recognizing pathophysiological association between myopericarditis and SIC and limitations of current diagnostic criteria.

Case Report:

A 47-year-old female presented with flu-like illness and pleuritic chest pain. An electrocardiogram (ECG) showed diffuse PR depressions and ST elevations, troponin 5 ng/mL, hemoglobin 14.2 mg/dL, leukocytosis (white blood cell count of 15.1×10³/uL) and erythrocyte sedimentation rate (ESR) of 22.4 mm/hour. Echocardiogram showed reduced ejection fraction (EF) with apical ballooning. Catheterization showed non-obstructive coronary disease. The patient was given colchicine and ibuprofen for 1 day with symptom resolution over the next 2 days and repeat echocardiogram with preserved EF. Troponin trended down to 3.24 ng/mL and 0.44 ng/mL, 6 hours apart. ECG showed resolution of PR depressions and subsequent T wave inversions in 1, AVl, V1–V6 by day 3. The diagnosis of myopericarditis was favored by viral prodrome, fever, pleuritic pain, pericardial rub, ECG findings, and elevated ESR. History of emotional stress, characteristic ballooning of left ventricle apex with rapid resolution favored SIC.

Conclusions:

This case showed that SIC and myocarditis need not be mutually exclusive and differentiating clinically between these 2 entities can be difficult. Alternatively, SIC can accompany other cardiac conditions like myocardial infarction, pericarditis, and myocarditis making diagnosis and management challenging. Clinicians need to be cautious while making this differentiation as duration and type of therapy may be significantly different. SIC can be considered a variant of regional inflammatory myocarditis wherein pericarditis may result secondary to extension of myocardial inflammation to overlying pericardium. The current Mayo Clinic criteria for diagnosis of SIC appears to be outdated, not accounting for such atypical presentations, and therefore needs to be revised.

Background

Stress induced cardiomyopathy (SIC) is a syndrome which can be seen in any age group but most commonly is seen in post-menopausal women that mimics the clinical presentation of acute coronary syndrome (ACS), and is classically triggered by emotional or physical stress. It is characterized by the absence of obstructive coronary disease [1–7], transient left ventricular (LV) dysfunction, ST segment elevation, and T-wave inversions, and elevated cardiac biomarkers. The exact pathogenesis of SIC is not well understood. Proposed mechanisms include catecholamine excess, coronary artery spasm, and microvascular dysfunction [8,9]. A variant of SIC with clinical features similar to pericarditis or myopericarditis has been described rarely in the literature and may shed light on the underlying pathology of SIC. We describe a unique case, highlighting an overlap in the presentation of SIC and myopericarditis.

Case Report

A 47-year-old female with a history of hypertension, bipolar disorder, and chronic low back pain status post lumbar fusion, presented with a 1-week history of flu-like illness and pleuritic chest pain. Her only home medications were amlodipine 5 mg daily and she was not currently on treatment for bipolar disorder. Physical examination at presentation revealed a fever 38.5°C (101.3°F) and a pericardial rub. An electrocardiogram (ECG) showed diffuse PR depressions and ST elevations (Figure 1). The patient’s troponin was elevated at 5 ng/mL (<0.05 ng/mL), hemoglobin was 14.2 mg/dL (normal range 12–14 mg/dL), an elevated white blood cell count of 15.1×10³/uL (normal range 4000–11 000/uL) and erythrocyte sedimentation rate (ESR) of 22.4 mm/hour (0–29 mm/hour). Procalcitonin and C-reactive protein were not measured. Echocardiogram revealed LV ejection fraction (EF) 35–40% and hypokinesis of mid, apical, anteroseptal, anterior and lateral, inferior and apical myocardium with apical ballooning. The patient was admitted for further evaluation with a differential diagnosis of ACS versus myopericarditis. She was taken urgently for ventriculography and coronary angiogram, which revealed characteristic apical ballooning (Figure 2) and non-obstructive coronary artery disease (Figures 3, 4). Subsequent troponin downtrended (Table 1) and ECG evolved into T wave inversions with resolution of PR depressions over the next 2 days (Figure 5A, 5B) She was given colchicine and ibuprofen for 1 day. She was unable to undergo cardiac magnetic resonance imaging (cMRI) due to metallic lumbar implant. Her symptoms resolved over the next 2 days and repeat echocardiogram revealed an EF of 50–55% and resolution of apical and anterior wall motion abnormality. On repeat questioning, she reported an acute emotional stress 1 day prior to presentation during an encounter with the police. She was discharged in improved condition on a low dose of beta blocker.

Figure 1.

Electrocardiogram at admission showing diffuse PR depressions suggesting pericarditis.

Figure 2.

Ventriculography showing apical ballooning of heart characteristic of stress induced cardiomyopathy.

Figure 3.

Normal right coronary circulation without evidence of obstructive disease.

Figure 4.

Normal left coronary circulation without obstructive disease.

Table 1.

Cardiac biomarker pattern.

Cardiac marker	Reference value	Day 1	After 6 hours	After 12 hours
Troponin	<0.05 ng/mL	5.02 ng/mL	3.24 ng/mL	0.44 ng/mL
Creatinine kinase-MB	0–8 ng/mL	25 ng/mL	18 ng/mL
Creatinine kinase	22–269 IU/L	1709 IU/L	1591 IU/L

Figure 5.

(A, B) Electrocardiogram taken 6 hours later showing rapid progression to T wave inversion favoring stress induced cardiomyopathy over myocarditis.

Discussion

This case describes a clinical syndrome with overlap of myopericarditis and SIC. The diagnosis of pericarditis was initially favored due to pleuritic chest pain, pericardial rub, diffuse PR depressions on ECG, elevated inflammatory markers, and leukocytosis. Myocardial involvement suggesting myopericarditis was indicated after identification of hypokinesis. Interestingly, the wall motion involved the anterior wall and apex, without a culprit left anterior descending (LAD) lesion, suggesting SIC or myocarditis with a coincidental wall motion abnormality mimicking Takotsubo cardiomyopathy. Furthermore, a history of emotional stress prior to the onset of chest pain, complete resolution of symptoms and LV dysfunction within 3 days of onset favors the diagnosis of SIC. Rare similar cases have been described in the literature of a “myopericarditis variant” of SIC.

Classic SIC has been described in post-menopausal women with a mean age of 66 years [10]. However, since initial description in 1990, there have been multiple case reports recognizing the incidence in other age groups [11–15], as well as atypical clinical presentations [16–18]. There have been 9 reported cases of clinical association between SIC and acute pericarditis. In 3 of these cases, the course of SIC was complicated by pericarditis [19–21] and in the other 6 cases, an acute pericarditis picture preceded the development of SIC [22–26]. To explain the confounding clinical picture, we support the “inflammatory hypothesis”. According to this proposed mechanism, SIC can be considered a variant of regional inflammatory myocarditis with extension of the myocardial inflammation to the overlying pericardium, leading to pericarditis [27–29]. The evidence of inflammation of the myocardium has been previously reported both on endomyocardial biopsy [27,30] and on cMRI [31]. The role of intense catecholamine surge secondary to the chest pain caused by pericardial inflammation has also been proposed and may explain how pericarditis can trigger SIC [27,32]. Given the overlap described, the disease processes may represent a spectrum of inflammation and be viewed as myopericarditis-variant SIC (Table 2).

Table 2.

Comparing characteristics of myocarditis, Takotsubo cardiomyopathy, and their combined variant.

Clinical features	Myopericarditis	Takotsubo cardiomyopathy (TCM)	Combined variant
Viral prodrome, fever, pleuritic chest pain	Present	Absent	Present
History of emotional stressor	Absent	Present	May be present
Cardiac enzymes	Elevated	Elevated	Elevated
Typical ECG findings	Diffuse PR depressions	Non-specific: Most common ST elevations in anterior leads	Diffuse PR depressions
Most common echocardiographic findings	Left ventricular dilation, development of a more spheroid shape	Characteristic ballooning of apex	Apical ballooning similar to TCM
Cardiac MRI	Patchy LGE1	LGE usually absent, may be present in some cases2	Suggested when the amount of LGE cannot reliably explain the WMA
Coronary angiogram	No obstructive coronary disease	No obstructive coronary disease	No obstructive coronary disease
Duration of illness/time to recovery	3–6 months	Days to weeks	Days to weeks
Duration of therapy	3–6 months of GDMT for HFrEF, avoidance of strenuous physical activity	Days to weeks until resolution; no proven role of therapy to prevent recurrence	Days to weeks: similar to TCM

ECG – electrocardiogram; MRI – magnetic resonance imaging; LGE – late gadolinium enhancement; GDMT – guideline-directed medical therapy.

Differentiating clinically between the 2 entities can be difficult [27–36]. Sequential ECG may be helpful in differentiating myopericarditis-variant SIC from classic myopericarditis. The general evolution of T wave changes is similar between the 2 entities, though it tends to occur at different rates. Rapid development of T wave inversions following ST elevation, as in our case, favors SIC [27,32]. Whereas classic pericarditis tends to have a slower progression to T wave inversion. Late gadolinium enhancement (LGE) on cMRI may also be useful. Myocarditis is characterized by patchy LGE on cMRI. However, when a low threshold for LGE is used (e.g., 3 standard deviations above the mean signal intensity of remote myocardium), LGE can occasionally be detected in stress cardiomyopathy, leading to erroneous diagnosis of myocarditis [37]. Despite this potential confusion, one can consider if the degree of wall motion abnormality is not explained by the amount of LGE present, this would support myopericarditis-variant SIC [26]. While a widely established non-invasive tool allowing a rapid and reliable diagnosis of Takotsubo syndrome is currently lacking, according to the International Expert Consensus Document on Takotsubo Syndrome [33,34], coronary angiography with left ventriculography is considered the gold standard diagnostic tool to exclude or confirm TTS. However, cMRI is essential to exclude infectious myocarditis. In addition to the aforementioned discussed limitations of MRI in diagnosing myocarditis, MRI is not always feasible in these cases, due to lack of availability, patient factors (presence of a permanent pacemaker, or metallic implant as in our patient), or prohibitive cost.

Clarification of diagnosis has important treatment implications. Non-steroidal anti-inflammatory agents are the treatment of choice in acute pericarditis, but can be harmful in myocarditis and SIC [47–40]. In either case, if reduced EF is present, guideline-directed medical therapy (GDMT) is indicated. However, the recommended duration of therapy differs greatly. In myopericarditis, 3–6 months of GDMT is usually recommended after resolution of symptoms. However, for cases of SIC, GDMT is generally discontinued following normalization of EF, which occurs rapidly over days to weeks. Although routine use of beta blocker therapy to prevent recurrence of SIC has been proposed, literature has not supported decreased recurrence [10,40]. Patients with myopericarditis-variant SIC tend to have a better overall prognosis and need to avoid strenuous activity for 3–6 months as in cases of pure myocarditis. In certain patient populations, the 3–6 months of GDMT can have a significant impact, including for women of child-bearing age, young men known to be particularly sensitive to beta blocker side effects, or cases where antihypertensives or those without blood pressure indications for antihypertensives.

Finally, although we support a shared myocardial inflammatory process for both entities, the question of why inflammation in myopericarditis-variant SIC resolves rapidly compared to inflammation associated with pure myocarditis remains unanswered. Additionally, since SIC has been shown to accompany other cardiac conditions like myocardial infarction, it is possible that this entity is capable of accompanying pericarditis and myocarditis as well.

Conclusions

Takotsubo cardiomyopathy and myopericarditis may comprise a clinical spectrum of myocardial inflammation (Table 1). This case describes a case of “myopericarditis–variant TC”, the underlying pathophysiologic mechanism of which needs to be further elucidated. Current diagnostic criteria need to be updated to account for atypical presentations of Takotsubo cardiomyopathy which may have therapeutic implications [26,28,29].