Abstract
Pregnancy-associated myocarditis is uncommon and remains poorly described. The spectrum of the disorder is wide, with the severe cases culminating in heart failure, cardiogenic shock and even maternal death. Diagnosis is typically made on imaging, serology and endocardiac biopsy findings with treatment being directed towards the underlying cause. We describe a case of likely peripartum myocarditis associated with severe early-onset pre-eclampsia.
Introduction
Acute heart failure in pregnancy is relatively uncommon, but rates are increasing particularly in the postpartum period. 1 Women with established chronic medical disorders such as diabetes and hypertension as well as women with heart disease (both congenital and acquired) appear to be at greater risk of heart failure. 2 We describe a case of a young woman with early-onset pre-eclampsia who developed acute heart failure following delivery where an absolute definitive cause could not be identified.
Case report
A 21-year-old black afro-Caribbean nulliparous woman was transferred to our centre at 24 weeks of gestation with early-onset pre-eclampsia. She had presented a few days prior with abdominal pain and headache. Blood tests showed a thrombocytopenia, platelets were 72 × 109/L (no fragments on film), with a prolonged activated partial thromboplastin time (APTT) and elevated alanine transaminase (ALT) of 257 IU/L. Blood pressure was normal. Urine:protein creatinine ratio was 240 mg/mmol. Fetal ultrasound demonstrated significant intrauterine growth restriction; estimated fetal weight was 400 g. Repeat blood tests revealed a worsening thrombocytopenia with a platelet level of 53 × 109/L.
The woman was counselled regarding the diagnosis and termination of pregnancy was offered, but declined. Immediate induction of labour in view of worsening maternal health was commenced. A live female infant weighing 370 g was delivered the subsequent day (corrected birthweight less than the 1st centile). Soon after delivery, the woman complained of severe persistent headaches and abdominal pain. Neurological examination was unremarkable. Magnetic resonance cranial venogram was performed to exclude a possible venous sinus thrombosis. This was normal. On day 6 post-delivery, the woman developed fevers, shortness of breath and pleuritic chest discomfort. A septic screen was sent, and intravenous antibiotics were commenced. Bloods revealed an elevated C-reactive protein (CRP) of 200 mg/L, and a raised troponin T of 1780 ng/L and NT-pro-BNP level was 4,998 ng/L. Chest radiograph was normal. An ECG demonstrated sinus tachycardia with 1 mm ST depression infero-laterally, and T-wave inversion in leads III and avF. CT pulmonary angiogram revealed multiple pulmonary emboli in both lungs; accordingly, treatment dose dalteparin was commenced. An echocardiogram demonstrated basal septal, inferior and lateral hypokinesia with an estimated left ventricular ejection fraction of 25% (Figure 1). Coronary angiography demonstrated normal unobstructed coronary arteries. On further review, there was no family history of cardiomyopathy and the woman had not smoked or taken illicit drugs during the pregnancy.
Four chamber view echocardiogram showing dilated left ventricle.
The woman was transferred to the heart failure unit with a working diagnosis of myocarditis. There was a continued rise in serum troponin T level, peaking at 8091 ng. An endomyocardial right ventricular biopsy was performed and showed mild patchy acute and chronic inflammation. No viral inclusions, granulomata or giant cells were witnessed. Nevertheless, confluent myocyte necrosis was seen. Viral polymerase chain reaction (PCR) testing was performed and was negative. Cardiac magnetic resonance imaging was performed and showed a severely dilated left ventricle with akinesis. End-diastolic left ventricular volume index was 146 mL/mm (normal range 65–99). T2 images showed oedema of the mid to apical inferoseptal and lateral walls, felt to be in keeping with myocarditis. There was also evidence of subendocardial infarction which correlated with the very elevated troponin levels.
Immunological testing demonstrated a weakly positive perinuclear antineutrophil cytoplasmic antibody (pANCA), dsDNA negative, negative anticardiolipin antibody, positive anti-nuclear antibody and positive lupus anticoagulant. Following discussion with the Rheumatology and Haematology teams, intravenous methylprednisolone was given. There was felt to be little clinical response and so on further multidisciplinary discussion (including clinicians from another teaching hospital) the decision was made to give intravenous immunoglobulin (IVIG). There was only a modest fall in inflammatory markers and troponin following this and a decision was made that longer term immunosuppression was of uncertain clinical benefit.
Over the next four weeks, there was a gradual clinical improvement with medical management including oral diuretics, beta blocker and angiotensin receptor inhibitor (ACE) inhibitor. During this time, her troponin levels gradually declined. Repeated echocardiography remained largely unchanged. The woman was converted from low molecular weight heparin to warfarin and was discharged 38 days after delivery. During this period, breast feeding was not established, but the woman did intermittently express breast milk. Prior to discharge, the woman was counselled to avoid further pregnancy and to consider long-acting reversible contraception. She declined fitting of any contraceptives whilst in hospital. She was also informed there was a degree of uncertainty regarding myocardial recovery and the need for long-term follow-up, but has not as yet attended the local follow-up that was arranged.
Discussion
The causes for acute heart failure presenting peripartum are wide, with management strategies that differ depending on the underlying cause. A list of possible causes and reasons justifying each cause is outlined in Table 1. Importantly our woman had no history or family history of cardiac disease that might suggest a chronic dilated cardiomyopathy exacerbated by pre-eclampsia and her troponin levels were out of keeping with that presentation. Whilst a peripartum cardiomyopathy (PPCM) was considered in this case as a possible cause we felt the rapid presentation so soon after delivery, with very raised and rising troponins made this diagnosis more unlikely. Nevertheless, PPCM is common in the context of pre-eclampsia and our woman was nulliparous and of African descent. We recognise that inflammation is seen in a significant proportion of cardiac biopsies in women with PPCM. 3 However, myocarditis was felt more likely in this case because of the combination of a significant troponin rise with normal coronary arteries, MRI images suggestive of oedema and the endomyocardial biopsy suggesting a myocardial inflammatory state; however, we note the absence of lymphocytic infiltration. PPCM could present in a similar fashion but in this case the MRI findings and the very raised troponin level were felt to be more supportive of an alternative diagnosis.
Differential diagnoses for heart failure.
The Lake Louise criteria that was updated in 2018 sets out a consensus of expert recommendations with regards to myocarditis. 4 The hallmark features include cardiac oedema, hyperaemia and subsequent necrosis and fibrosis. Both the European Society of Cardiology and American Heart Association have set out recommendations to establish a diagnosis of myocarditis, which includes use of endomyocardial biopsy alongside MRI imaging. Hyperaemia occurs as there is regional vasodilatation due to inflammation. Fibrosis is witnessed with late gadolinium enhancement and indicates irreversible myocardial injury. 5 Cardiac mapping is used on both T1 and T2 images.6,7 One of the hallmark requirements for myocarditis is subepicardial distribution with late gadolinium enhancement on T1-weighted imaging. 4 This was reported in our case, but we recognise these findings are not exclusive to myocarditis and may be seen in other cardiomyopathies. 8 Cardiac magentic resonance imaging (CMR) is helpful in identifying non-ischaemic inflammation, although its utility alone as a diagnostic tool is less clear especially in those presenting with acute heart failure. 4
The underlying aetiology of myocarditis is complex, but is thought to be due to an interplay between environmental and genetic factors to cause myocardial injury. There are three broad categories of underlying causes which are infectious, drugs and toxins and immune-mediated. In North American and Western Europe, viruses such as adenovirus and enterovirus appear to be the most commonly identified aetiology. 9 Systemic disorders like systemic lupus erythematosus may also be implicated. 10 Our woman developed thrombotic emboli, multi-organ involvement and had positive antiphospholipid antibodies. Whilst a diagnosis of catastrophic antiphospholipid syndrome (CAPS) could be considered, the woman does not fulfil the true immunological criteria for CAPS. Certainly, she did not meet the American College of Rheumatology or the European League Against Rheumatism criteria for systemic lupus erythematosus. 11 However, follow-up is important as these features many manifest at a later date which unfortunately has not happened as yet. Nevertheless, it was felt a trial of IVIG may help given the severe cardiac impairment. Treatment of myocarditis is directed to treat not only cardiac impairment (i.e. standard heart failure therapy) but also to identify and treat possible underlying causes.12,13 Evidence for use of antivirals to treat viral causes is limited. 1 Steroid treatment can be considered in non-infective myocarditis.1,5 Antibiotics should be used where bacterial cause is suspected1,5 and immunoglobulin therapy may be of use if a systemic autoimmune cause is suspected. 1
The first published report of myocarditis in pregnancy was by Melvin in 1982. 14 Subsequent cases demonstrate variable maternal outcomes even in severe cases.15,16 Nevertheless, myocarditis is seen in up to 12% of young adults who present with sudden death 17 so it is likely to be underdiagnosed in the obstetric population. Whether pregnancy made this woman more susceptible to myocarditis is unclear. In a mouse model it has been shown that the myocardium of pregnant mice is more susceptible to infection compared to non-pregnant mice. 18 It is also possible that severe pre-eclampsia contributed to acute heart failure in this case as it has been shown in other studies to be risk factor that is significantly associated with heart failure, 1 but the mechanism in which it interacts with myocarditis remains ill-defined.
Conclusion
The underlying aetiology of acute severe heart failure is complex and wide and may require extensive investigation to identify the underlying aetiology, which can take time. It is rare for myocarditis to cause such overt cardiac dysfunction in pregnancy. Long-term follow-up is crucial to assess for recovery and assist with making a formal diagnosis when there is some clinical uncertainty at initial presentation. Counselling with regard to future pregnancies needs to take into account the degree of myocardial recovery and aetiology of heart failure.
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethical approval
NA
Informed consent
Written consent was obtained from the patient(s) for their anonymised information to be published in this article.
Guarantor
MC acts as a guarantor for the manuscript.
Contributorship
LE, AS and CC wrote the first draft. MC edited this. All authors approved the final draft.
