麻豆传媒

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study.

How to diagnose a 59-year-old man with hypertension who presents to hospital after 2 weeks of continuing fatigue and lightheadedness? That's what Jessica Cao, MD, of Northwestern University Feinberg School of Medicine in Chicago, and colleagues were trying to determine.

As they reported in , an electrocardiogram (ECG) revealed new high-degree atrioventricular block with intermittent complete heart block. Clinicians admitted the patient and ordered lab tests. He tested negative for Lyme disease; other results included a troponin I level of 3.11 ng/mL (reference: 0.00–0.04 ng/mL), and B-type natriuretic peptide of 52 pg/mL.

Transthoracic echocardiography demonstrated an ejection fraction of 62%; results of a coronary angiogram were unremarkable.

Cardiac magnetic resonance imaging revealed irregular thickening of the right ventricle with a "striking pattern of diffuse late gadolinium enhancement, with relative sparing of the left ventricle," the case authors said. Right ventricle ejection fraction was 39%, and high capture thresholds were noted during pacemaker implantation.

The patient's symptoms improved (but didn't disappear), and he was discharged.

On follow-up a week later, the medical team obtained an outpatient fluorodeoxyglucose-positron emission tomography (FDG-PET), which revealed diffuse patchy hypermetabolic activity involving both ventricles; inflammation was more diffuse in the right ventricle, and patchy in the left -- findings suggestive of active myocardial inflammation. Importantly, the scan also showed multiple hypermetabolic, non-enlarged lymph nodes located primarily along the right side of the trachea.

"Our institutional CS [cardiac sarcoidosis] imaging protocol utilizes FDG-PET/computed tomography with a 48-hour low-carbohydrate diet prior. PET imaging assessing perfusion was not performed as our institution does not have current access to PET myocardial radiotracers," the case authors explained.

A biopsy of a lymph node revealed noncaseating granulomas (NCG), which the team noted were consistent with CS. Special stains for microorganisms (Grocott's methenamine silver, acid-fast bacteria) were negative.

The team referred the patient to a sarcoidosis specialist, but 2 days later he returned to the hospital reporting extreme fatigue and shortness of breath.

Another echocardiogram showed an ejection fraction of 20%, with mild dilatation of the left ventricle (left ventricular end-diastolic diameter 5.8 cm). Right heart catheterization identified normal filling pressures and severely depressed cardiac index (1.72 L/minute per m²).

Lab tests showed the following:

• Troponin I: 65.99 ng/mL
• B-type natriuretic peptide: 1746 pg/mL

Lactate was elevated (2.4 mmol/L) and a femoral balloon pump was implanted. Clinicians performed an endomyocardial biopsy (EMBx), which showed extensive giant cell myocarditis (GCM). The team started the patient on cyclosporine and steroids, and listed him for a heart transplant. On hospital day 7, the transplant was performed. The patient received thymoglobulin induction (1 mg/kg), and further doses were discontinued when the patient developed thrombocytopenia.

On post-transplant day 7, the patient reached therapeutic levels of tacrolimus and was maintained on that (goal level 10-15 ng/mL), mycophenolate mofetil (2 g/day), and prednisone taper as per protocol.

On post-transplant day 16, the patient underwent a second routine EMBx. Examination of the specimen revealed "extensive cardiomyocyte damage, early granulation tissue, heavy aggressive inflammatory infiltrate with numerous eosinophils, and multi-nucleate giant cells," the authors noted. There were no granulomas or evidence of fibrosis. Two of five samples indicated a recurrence of GCM; graft function and hemodynamics were normal.

Treatment was initiated with 3 mg/kg of thymoglobulin, and mycophenolate mofetil at an increased dose of 3 g/day with resolution of GCM on EMBx. The patient's tacrolimus level dropped temporarily to 8.6 ng/mL when the prednisone dosage was decreased from 20 to 17.5 mg, but a subsequent biopsy showed another recurrence of GCM.

The patient was treated with a steroid pulse and taper, and his symptoms again resolved, with graft function and hemodynamics remaining normal.

Discussion

These authors reporting diagnosis of a patient with symptoms of subacute heart failure due to GCM said the case "demonstrates an atypical presentation of GCM and highlights the utility of a multimodality diagnostic approach."

Inflammatory cardiomyopathy can be caused by both GCM and CS, and both diseases can present with heart failure and arrhythmias. The authors pointed to a long-standing around whether the two conditions are distinct or if GCM represents a severe phenotype of the CS/granulomatous myocarditis spectrum.

Factors that may help differentiate between the two diseases include that CS is more likely to present with , and typically evolves more gradually, whereas GCM evolves more quickly and often presents with fulminant myocarditis.

Because in CS, biopsy of endomyocardial tissue has shown poor diagnostic performance, with a sensitivity of 20-30%, clinicians tend to extracardiac tissue, the authors explained.

"Our patient's initial presentation of isolated atrioventricular block, extracardiac NCG, and imaging findings initially strongly favored the diagnosis of CS, although magnetic resonance imaging findings of right ventricle fibrosis with relative left ventricle sparing were relatively atypical for CS," Cao and colleagues explained. Their hospital's existing protocol for PET/computed tomography does not assess myocardial perfusion – detection of which could have helped raise suspicion for GCM earlier, the team added.

GCM became the focus of diagnostic efforts when the patient's clinical status rapidly declined. "EMBx, which carries a class I recommendation for suspected GCM, ultimately provided the diagnosis," the authors said.

Noncaseating granulomas compromised of epithelioid cells that can fuse to form occasional Langhans giant cells and well-formed granulomas are characteristic of sarcoidosis, the team continued. Eosinophils are rare and there is generally no necrosis, despite potentially extensive fibrosis.

This is also in contrast to GCM, which rarely presents well-formed granulomas: "The sine qua non is the presence of giant cells and prominent eosinophils with extensive necrosis disproportionate to degree of inflammation. In our patient, lymph node histology was consistent with sarcoidosis," the authors wrote.

They cautioned, though, that extracardiac granulomatous inflammation still occurs in 5-10% of GCM cases, and so the presence of these granulomas outside the heart should not rule out a GCM diagnosis.

"Interestingly, the patient's GCM recurrence at 16 days is the earliest published report," Cao and co-authors said. Recurrence of GCM can be differentiated from allograft rejection by histological evidence of giant cells, necrosis, and prominent eosinophils, along with the absence of aggressive lymphocytic infiltrates which generally characterize allograft rejection.

This patient initially presented with clinical atrioventricular block with extracardiac noncaseating granulomas suggestive of cardiac sarcoidosis, the authors concluded: "Thus, in patients with atypical clinical or imaging findings of CS, regardless of extracardiac presence of NCG, EMBx should be considered for timely diagnosis to hopefully prevent decompensation."

Read previous installments in this series:

Part 1: Heart Failure: A Look at Low Ejection Fraction

Part 2: Exploring Heart Failure With Preserved Ejection Fraction

Part 3: Heart Failure With Reduced Ejection Fraction: Diagnosis and Evaluation