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First Reported Case of Giant Cell Myocarditis and Acute Lyme
Disease Infection: A Potential Link or Unfortunate Coincidence?
Dr. Alexander Carpenter*, Dr. Peter Scott and Dr. Sern Lim
*Corresponding author, Severn Deanery
Case
A 40 year old lady presented with a 10 day history of breathlessness, palpitations
and chest tightness. The palpitations were short-lived, regular and rapid, and
associated with pre-syncope. She visited her local general physician who organised
some routine blood tests and a Chest X-ray which revealed cardiomegaly, bilateral
opacification and bilateral pleural effusions consistent with congestive heart failure.
Based on these results, the physician advised hospital admission.
On initial examination, her blood pressure was 100/70 and her Jugular Venous
Pressure (JVP) was elevated to her earlobe. She had reduced air entry and
crepitations auscultated at both lung bases. An electrocardiogram (ECG) revealed
markedly low amplitude QRS complex with an incomplete right bundle branch block
morphology. Serum blood analysis revealed normal routine blood tests including
inflammatory markers. High Sensitivity Troponin T was elevated at 2788mmol/L.
She was transferred to the Coronary Care Unit at our hospital.
She had a significant occupational exposure to wildlife, including recent travel to
Eastern Europe to study bats several months prior to admission. She was a nonsmoker with minimal alcohol intake and no significant past medical history of note.
A Computed Tomography Pulmonary Angiogram (CTPA) was organised which
confirmed cardiomegaly and bilateral large pleural effusions, with a suggestion of
bilateral basal ground-glass changes. Urgent transthoracic echocardiography
revealed a non-dilated left ventricle with severe systolic impairment, mild-moderate
functional mitral regurgitation and a small pericardial effusion. (Fig C)
Interestingly Lyme disease acute serological markers returned as IgG positive,
indicating acute infection. Other autoimmune and serological markers of
cardiomyopathy were negative.
Aggressive intravenous diuresis was commenced with an initial clinical improvement.
Urgent cardiac magnetic resonance imaging (MRI) was requested and the case with
discussed with the local transplant centre who accepted for transfer and
assessment. Despite aggressive diuresis, over the next 3 days she continued to
increase in weight with a persistently low blood pressure. There was worsening
derangement of renal and hepatic function. She was commenced on intravenous
dobutamine and noradrenaline and transferred emergently to the transplant centre.
Shortly after arrival she suffered a ventricular tachycardia (VT) cardiac arrest, though
was successfully resuscitated. Cardiac biopsy and right heart catheter study were
performed, the latter confirming elevated filling pressures and a reduced cardiac
output of 2.2 L/min (Table 1). The biopsy results demonstrated large areas of patchy
but diffuse myocyte loss / necrosis associated with a marked inflammatory infiltrate
including lymphocytes and quite prominent eosinophils. Numerous multinucleate
giant cells were seen, which appeared to be of myogenic origin. There was no iron,
amyloid or established fibrosis. These histological features were felt to be consistent
with a diagnosis of Giant Cell Myocarditis (GCM).
The patient was reviewed by the surgical team with a view to possible mechanical
support as a bridge to transplant. Immunosuppressive therapy was initiated with a
combination of ciclosporin, azathioprine and prednisolone. Unfortunately, she
experienced a further VT arrest later that evening, for which resuscitation was
unsuccessful.
Right atrium
A: 24mmHg, V: 23mmHg
Right ventricle
37/4mmHg, EDP 13mmHg
Pulmonary artery
30/22mmHg, mean 26mmHg
Pulmonary capillary wedge
A: 23mmHg, V: 25mmHg, mean 22mmHg
Cardiac output (thermodilution)
2.2 L/min
Table 1: Right heart catheter study values (EDP; end diastolic pressure)
Discussion
GCM is an uncommon but aggressive inflammatory cardiomyopathy. It is rapidly
progressive and often fatal. Indeed, all cases prior to 1987 were identified only
during post-mortem examination. It has been variously referred to as Idiopathic Giant
Cell Myocarditis, Fiedler’s Myocarditis, Pernicious Myocarditis, Granulomatous
Myocarditis and Acute Idiopathic Interstitial Myocarditis. The incidence is estimated
to be as high as 5% of patients diagnosed with idiopathic, interstitial or viral
myocarditis. The mean age of onset is 42.6 +/- 12 years with no gender
predominance and average chronology approximately one month from onset to
hospital presentation(1).
Features typically include rapidly progressive left-sided or biventricular heart failure –
which is the presenting feature in ~75%(2) – and often complicated by conduction
abnormalities and ventricular tachycardia, seen in approximately 15% and 29% of
cases respectively(1), often with limited response to conventional heart failure
medical therapy. Some modern case series report atrioventricular block as the
presenting feature as commonly as heart failure(3). Definitive diagnosis requires left
or right ventricular Endo-Myocardial Biopsy (EMB) which has a class 1 indication in
fulminant myocarditis(4) and a reported sensitivity of 80-85% in the diagnosis of
GCM(5). This increases significantly with repeat biopsies, particularly if guided by
evidence of areas of active inflammation or infiltration on imaging such as MRI or
Positron Emission Tomography (PET)(3). This typically shows multinucleated giant
cells, lymphocytes, diffuse or multifocal inflammatory infiltrate and eosinophilia, with
a variable degree of fibrosis(2,6).
Historically there has been debate as to whether GCM and Cardiac Sarcoidosis (CS)
represented a single disease entity, owing to high levels of giant cells present in
both. However there have subsequently been distinctions observed both
pathologically and clinically, with GCM demonstrating increased myocyte necrosis
and carrying a substantially worse prognosis(1). The prognosis of GCM is poor, with
rates of death or cardiac transplantation reaching 70% within 1 year and almost 90%
overall(2), with little evidence of recovery of left ventricular function(7).
Cardiac Magnetic Resonance (CMR) imaging provides robust differentiation of CS
(8,9) but so far there are only sporadic case reports describing CMR investigation of
GCM (10–12), showing heterogeneous areas of sub-endocardial and mid-wall
fibrosis demonstrated on late gadolinium enhancement imaging, all eventually
diagnosed via EMB. At present, however, there are no established reliable markers
for the diagnosis of GCM by CMR, and EMB remains the gold standard. CMR is
helpful, however, in excluding other causes for fulminant heart failure.
EMB can be continued as a surveillance measure. Treatment has traditionally
revolved around the use of immunosuppressive therapy including
cyclosporine(23,24), pulsed and long-term steroids with transplant-free survival
reported as low as 10% at five years(1). There are reports of successful outcomes
following use of contemporary immunosuppressive agents including azathioprine(3),
mycophenalate mofetil , Rabbit Anti-Thymocyte Globulin (ATG) and tacrolimus as
well as biological agents such as muromonab(23). With these novel
immunosuppressive combination therapies, transplant-free survival has been
reported at approximately 75% at one year(3,23). Due to the sudden-onset, rapidly
progressive nature of the disease with an often fatal outcome, aggressive
immunosuppression and early transplantation is advocated.
There is an established link with systemic autoimmune disease and in particular
myasthenia gravis(13) and inflammatory bowel disease(14,15). Furthermore, there
are suggestions of associations with thymoma(16), drug hypersensitivity(17),
measles myocarditis(18) and even syphilis(19). The exact aetiological mechanism,
however, remains unknown.
Although no previous link with Lyme Disease and GCM has been documented to
date, Lyme Disease has been linked with Giant Cell Arteritis (GCA) in case
reports(20) and indeed a ‘Lyme carditis’ with features mimicking those of GCM(21).
Lyme carditis has long been described as a cardiac manifestation of systemic Lyme
disease, with prominence of conduction defects and more rarely, heart failure.
Diagnosis is made by serological testing, but myocardial biopsy shows extensive
lymphocytic infiltration and necrosis with variable fibrosis. Occasionally, spirochetes
can be directly visualised or Borrelia Burgdorferi detected by Polymerase Chain
Reaction (PCR) of affected tissues(22). Although there is currently no established
link between GCM and Lyme Disease, the similarity in clinical presentation and
pathological findings begs the question as to whether they could represent states on
a spectrum of disease, with GCM as manifestation of those most severe forms and
Lyme disease as one possible cause.
Conclusion
Giant Cell Myocarditis is an aggressive and rapidly progressive cardiomyopathy
which often presents with early heart failure and/or conduction deficits. In the
absence of rapid and aggressive management including immunosuppression and
transplant, the prognosis is poor. Endomyocardial biopsy should not be delayed as it
may provide a definite diagnosis. Though known to be associated with several
systemic illnesses, similar histological appearance and the association in this case
raises the possibility of a link between giant cell myocarditis and Lyme disease,
which warrants further investigation.
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