Fulminant myocarditis spreading from the right ventricle treated with extracorporeal membrane oxygenation and impella

Abstract

Although the pathogenesis of fulminant myocarditis varies, it is usually recognised by symptoms such as chest pain or syncope, echographic findings such as abnormal left ventricular (LV) wall motion, elevated cardiac enzymes and arrhythmias. We encountered a case of acute myocarditis with syncope, electrocardiographic changes suggestive of coronary artery disease in the inferior wall with abnormal wall motion in the right ventricle, which eventually developed into fulminant disease. Multidetector CT showed a contrast effect localised to the right ventricle in the late-contrast phase, suggesting a right ventricular myocardial injury. Thereafter, the LV function rapidly decreased. Finally, mechanical circulatory support with extracorporeal membrane oxygenation and an intra-aortic balloon pump was needed. A myocardial biopsy of the right ventricular septum showed severe degenerative findings such as myocyte tearing and segmentation with infiltration of inflammatory cells including lymphocytes. After insertion of an Impella pump, the right ventricular function gradually improved.

Background

Myocarditis occurs due to infection, exposure to toxic substances or activation of the immune system and is classified as secondary cardiomyopathy.^1–3 It has various degrees of severity or pathology, ranging from mild acute to fulminant and chronic myocarditis.^4–7 Generally, inflammation of the left ventricle or both chambers is shown by endocardial biopsy data,^{8 9} and reports of myocarditis in which only the right ventricle is affected are atypical.

Recently, it was reported that the localisation of pathological findings in the myocardium coincides with delayed-contrast areas in cardiac MRI (CMR) in the acute phase of acute myocarditis, and its usefulness has been recognised. Moreover, some reports correlate delayed-contrast findings on CMR with contrast effects on cardiac multidetector CT (MDCT).¹⁰ Therefore, the use of various modalities according to the situation may aid in diagnosis.

Furthermore, in the acute management of fulminant myocarditis, there are increasing reports that Impella, in addition to extracorporeal membrane oxygenation (ECMO), suppresses myocardial injury both haemodynamically and histologically. It relieves the left ventricular (LV) load, reduces total mechanical workload and myocardial oxygen demand, and decreases wall stress.¹¹

In this study, we report a case of fulminant myocarditis in which delayed-phase contrast enhancement was observed in the right ventricular myocardium on cardiac MDCT in the acute phase. Subsequently, the patient showed rapid haemodynamic deterioration. She required mechanical-assisted circulation and was finally managed with a combination of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella. We thus report a case of fulminant myocarditis resulting from severe right ventricular dysfunction that was successfully rescued with ECMO and Impella.

Case presentation

The patient is a woman in her 70s with a history of phosphatase and tensin homologue (PTEN) hamartoma tumour syndrome, a spectrum of disorders associated with the formation of hamartomas caused by mutations of the tumour suppressor PTEN. She had postcerebellar partial resection for a dysplastic gangliocytoma of the cerebellum associated with Lhermitte-Duclos disease and postoperative for hysterectomy and bilateral adnexal excision due to left ovarian cancer.

In the morning, she collapsed at home and was taken to a nearby hospital. She had a fever of 38.1°C but was conscious, and her vitals were stable without chest pain (blood pressure 131/67 mm Hg, heart rate 60–70 beats/min, transcutaneous oxygen saturation 96% in room air). A 12-lead ECG showed ST-segment elevation in II, III and aVF and ST-segment depression in v4–6. There was a further increase in cardiac enzymes (creatine kinase (CK) 3125 U/L, CK-MB 54 U/L and serum troponin T level 411 ng/L). She was referred to our hospital for suspected acute myocardial infarction.

Transthoracic echocardiography showed wall motion abnormalities in the right ventricle and part of the inferior wall region. Electrocardiographic findings (figure 1) suggested myocardial infarction in the inferior wall region; therefore, emergency catheterisation was performed. There was no significant stenosis in the coronary angiography (figure 2) and no suspicion of takotsubo cardiomyopathy on transthoracic echocardiography; thus, left ventriculography was not performed.

Figure 1.

Twelve-lead ECG on admission showed ST-T elevation in inferior leads and reciprocal change in aVF leads (A, B). Right bundle brunch block pattern was seen in ECG on the third day (C). ECG on the fifth day demonstrated a wide QRS complex and 1° atrial ventricular block (D).

Figure 2.

Normal coronary angiography on admission: left coronary artery (A) and right coronary artery (B).

The patient remained symptom-free. Although her blood pressure and heart rate were stable, she maintained a fever in the 38°C range after the second day. Furthermore, her blood pressure gradually dropped. Thus, it was necessary to use a low dose of norepinephrine (0.01–0.02 µg/kg/min) to maintain the patient’s mean blood pressure. The PCR test for SARS-CoV-2 was negative at the time of admission.

The blood test data showed that the C reactive protein (CRP) fluctuated between 2 mg/dL and 4 mg/dL, but her white blood cell count and its fractions were almost normal. Her procalcitonin level did not suggest bacterial infection.

On transthoracic echocardiography, wall motion was reduced in the inferior wall and right ventricle, but there was no change from the initial examination. The left ventricular outflow tract time velocity integral (LVOT VTI) was maintained at approximately 13 cm with no signs of left heart failure. On the other hand, the ST-segment elevation in the inferior wall region of the ECG was unchanged, the QRS width was wide (figure 1), and the elevation of cardiac enzymes was prolonged (table 1).

Table 1.

Laboratory data

	Day 1 (admission)	Day 2	Day 3	Day 4	Day 5
CK (U/L)	3125	2919	1980	1610	1292
CK-MB (U/L)	54	69	63	76	91
C reactive protein (mg/dL)	4.65	6.46	7.27	7.88	4.7

There are cardiac and inflammatory markers of persistent elevation.

On the third day, the patient still did not report any symptoms. Meanwhile, hypotension neither worsened nor improved, and the fever persisted in the 38°C range. ECG changed in the right bundle branch block (figure 1). Cardiac MDCT was performed instead of MRI as we used metal-containing medical devices such as syringe pumps, and delayed contrast of the right ventricular myocardium was observed (figure 3).

Figure 3.

Delayed enhancement cardiac CT in the right ventricle (white arrows, vertical long axis (A) and apical short axis (B)).

On the fourth day, the patient’s condition remained the same, and cardiac enzymes tended to increase. On the fifth day, ECG showed that ST-segment elevation spread to all inductions (figure 1).

Additionally, transthoracic echocardiography showed that wall motion decreased, and there was myocardial oedema in the left ventricle. LVOT VTI decreased to approximately 7 cm. The patient’s blood pressure further decreased, suggesting progression of circulatory disturbance. Based on this rapid course of events, we assumed fulminant myocarditis. Therefore, we performed an urgent right ventricular myocardial biopsy and right heart catheterisation.

In right heart catheterisation, the mean pulmonary artery wedge pressure was 17 mm Hg, and the mean pulmonary artery pressure was 23 mm Hg in systole, 20 mm Hg in diastole and 21 mm Hg on average.

Furthermore, the mean right atrial pressure was elevated to 17 mm Hg, suggesting severe right heart failure.

The cardiac output was 0.22 watts, and the pulmonary artery pulsatility index was significantly decreased to 0.176. Three biopsies were performed on the right ventricular septum. As the patient’s blood pressure dropped further and her cardiac output was low, an intra-aortic balloon pump (IABP) was implanted through the left femoral artery. Maintaining haemodynamic status was difficult; thus, VA-ECMO was established, and the patient was returned to the intensive care unit.

Despite controlling fluid management and increasing the blood flow with a rotation of 2600–3000 rpm to prevent multiple organ failure, the total flow rate of ECMO was approximately 2.5–3.0 L/min. Transthoracic echocardiogram revealed continuous closure of the aortic valve with a further decrease in LV contractility to approximately ejection fraction (EF) 5% and a giant thrombus at the tricuspid valve level (figure 4). The patient was treated with increasing vasodilators and positive inotropic agents such as low doses of dobutamine and milrinone to control LV afterload, but she showed no improvement, and achieving aortic valve release was difficult (figure 5). Therefore, additional unloading of the left ventricle by Impella and right ventricular assistance were immediately deemed necessary.

Figure 4.

Large mass on the right atrium suggesting thrombus (white arrow).

Figure 5.

M mode echocardiography showing the absence of aortic valve opening (white arrow) and slight opening (yellow arrow).

The patient was rushed to a nearby university hospital. During this time, as she developed complete atrioventricular block and went into cardiac arrest, she was transferred under percutaneous pacing. On the same day, the IABP was removed, and Impella CP was added. Complete atrioventricular block did not improve, so a ventricular temporary pacing lead was jugulary inserted after confirming that the thrombus had disappeared. The pacing threshold at the right ventricular apex was high, probably due to myocardial oedema associated with inflammation. The left ventricle seemed to collapse due to decreased right ventricular function, and Impella was managed at a low flow rate (P2) of about 1.6 L/min due to repeated sacking.

On the day after the patient was transferred to the hospital, her cardiac function gradually recovered. The LV flow increased largely due to improved right ventricular flow; thus, the Impella flow was increased, and the patient was weaned off ECMO. Self-pulsation began, but rapid pacing continued because of ventricular tachycardia. The patient was weaned from VA-ECMO on the seventh day of transfer, and the Impella was removed on the ninth day. The pathological findings of the right ventricular myocardium showed a variety of inflammatory cell infiltrates, including mainly lymphocytes, neutrophils, eosinophils and plasma cells. There was a high degree of degeneration, such as eosinophilia and tearing of cardiomyocytes. There were no findings to indicate such things as giant cell myocarditis, necrotising eosinophilic myocarditis and cardiac sarcoidosis (figure 6). Based on the rapid improvement in cardiac function and the findings of the biopsy, it was decided that standard treatment without steroids would be effective.

Figure 6.

Histopathology inflammatory cell infiltration, mainly of lymphocytes and plasma cells, fragmentation of the muscle bundles, myocytolytic changes, swelling and scarcity of the cytoplasm and swelling of nuclei, variation in size of the myocytes, disarrangement of the muscle bundles and interstitial oedema were observed.

Outcome and follow-up

When the patient was weaned from the ventilator, her consciousness level did not improve even after sedation was gradually decreased; however, blinking was observed. A CT scan showed that the cortical border of the entire cerebrum had disappeared, and there was oedema, indicating hypoxic encephalopathy. This finding was not observed on the first day of transfer.

Echocardiography showed diffuse wall motion abnormalities in the left ventricle, but the right ventricular function improved, and the catecholamines were terminated. However, the patient’s consciousness level remained unchanged, and she was transferred to a convalescent hospital 2 months after the tracheostomy.

Discussion

When acute ST-segment changes are consistent with vascular territory in ECG leads or when regional wall motion abnormalities or elevation of cardiac enzymes are observed, cardiovascular disease in the same region is often suspected. In the case of normal coronary arteries, acute myocarditis, takotsubo cardiomyopathy, coronary artery vasospasm and pulmonary embolism should be considered.¹²

In this case, right ventricular predominant disease without coronary artery disease can be differentiated from acute pulmonary embolism or arrhythmogenic right ventricular cardiomyopathy, but the former was not strongly suspected because the D-dimer was low on admission when taking oral anticoagulation, and cardiac CT showed no pulmonary artery embolism. As for arrhythmogenic right ventricular cardiomyopathy, although the ECG showed ST changes, the patient was in sinus rhythm, and no other findings met the diagnostic criteria. Stress cardiomyopathy, such as takotsubo cardiomyopathy, was not typical because the wall motion abnormalities on echocardiography in the acute phase were limited to the lower wall region.

Although fever and elevated CRP levels persisted from the time of admission, generally, myocardial inflammation in acute myocarditis occurs in the free wall of the left ventricle or both ventricles and rarely in the right ventricle alone.¹³ In some reports, subendocardial biopsies of both ventricles in 481 patients with clinically suspected myocarditis depressed LV function showed that both ventricles were involved in approximately 70% of patients, and only 8% reported right ventricular involvement alone.⁸ These results on the localisation of inflammation are similar to those in other studies.¹⁴

At the time of coronary angiography on the day of admission, we hesitated to perform a myocardial biopsy. As the patient was haemodynamically stable, we did not suspect myocarditis strongly. Moreover, the frequency of sampling errors was high,¹⁵ and evaluation with other diagnostic imaging was considered. Generally, CMR with gadolinium contrast shows late gadolinium enhancement on early T1 and delayed-contrast images in addition to cine mode, and T2-weighted images show oedema consistent with inflammation. Additionally, T2-weighted images show oedema to be consistent with inflammatory areas, which helps in diagnosing myocarditis and the localisation of the lesion.^{16 17}

Furthermore, the myocardial contrast effect of cardiac CT helps in diagnosing acute myocarditis and correlates well with the delayed-contrast image of CMR; it can differentiate between myocardial infarction and myocarditis with accuracy in the acute phase compared with MR. It assists in diagnosis, including the fact that coronary artery evaluation can be performed simultaneously.^18–20

In this case, the patient presented with delayed contrast in the right ventricular myocardium only, suggesting the localisation of myocardial inflammation to the right ventricle. Although acute myocarditis originating in the right ventricle was considered atypical based on the reported frequency,^21–24 right ventricular involvement is a poor prognostic factor.²⁵ Low cardiac output syndrome alone delayed us in getting a definitive diagnosis because there were no typical signs of heart failure in the early stage. Multiple imaging modality was helpful for the diagnosis.

In cases of fulminant myocarditis, adequate stabilisation, including immediate mechanical circulatory support (MCS), is often required to maintain haemodynamics and longitudinal evaluation. Determining the timing of their introduction is essential to ensure time to initiate anti-inflammatory strategies.²⁶ In this case, when the retrograde flow from ECMO was increased to improve organ dysfunction, the aortic valve became continuously closed, though we treated this with ECMO combined with IABP to reduce LV afterload.²⁷ Therefore, we tried to use vasodilators and positive inotropic agents to decrease LV afterload and to ensure the aortic valve was continuously open. However, there was no improvement, and we immediately considered adding other MCS. The continuous monitoring by echocardiography helped us in making a decision.

The LV afterload increases when ECMO is used, which may lead to increased LV pressure and worsen pulmonary oedema. This increased load can also lead to an increase in systolic myocardial wall stress, further causing an inflammatory response.²⁸ In inflammatory diseases such as myocarditis, a therapeutic strategy for appropriate circulatory support, reduction of LV load, decrease in wall stress and subsequent mitigation of the inflammatory response are necessary. It has been reported that the use of the Impella system, which is a transvalvular microaxial flow pump capable of ejecting oxygenated blood from the LV to the ascending aorta in such conditions, directly unloads the left ventricle throughout the cardiac cycle and reduces total mechanical workload and myocardial oxygen demand. Moreover, it decreases wall stress, cardiac innate immunity, adhesion molecule expression and immune cell infiltration.^{11 29 30} In this case with right ventricular failure, Impella may have reduced the load on the right ventricle and led to improvement.^{31 32}

Learning points.

• Acute myocarditis should be considered a cause of acute right ventricle heart failure in patients without coronary artery disease.

• When cardiac MRI is not available, cardiac CT is useful to indicate inflammation localisation and cardiac fibrosis.

• In case of fulminant myocarditis with haemodynamic compromise, Impella may be a useful alternative to the conventional management of extracorporeal membrane oxygenation plus intra-aortic balloon pump to reduce the myocardial load associated with left and right ventricular unloading.

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