Serologic work-up revealed polycythemia (Hb 167 g·L−1, PCV 0.51) with normal inflammatory markers (WCC 3.7 × 109·L−1, CRP 3 mg·L−1), mild renal impairment (urea 10.2 mmol·L−1, creatinine 113 μmol·L−1), and elevated bilirubin (56 μmol·L−1). Liver transaminases, corrected calcium, and thyroid function tests were normal. High-sensitivity troponin-I (40 ng·L−1, < 19.8), brain natriuretic peptide (5655 ng·L−1, 0-20), and serum angiotensin converting enzyme (104 U·L−1, 13-64) were elevated. Tuberculosis Elispot test was negative. Despite the polycythemia, molecular diagnostics detected no mutations in JAK2, CALR, and MPL genes.

Computed tomography of the thorax excluded a pulmonary embolus but demonstrated peribronchovascular lung nodules with an upper lobe predominance and multiple enlarged hilar lymph nodes, typical of sarcoidosis (Figure 1).

Computed tomography of the thorax. Lung parenchymal nodules and nodal enlargement in keeping with sarcoidosis. Cardiomegaly and right-sided pleural effusion secondary to decompensated cardiac failure

Echocardiography revealed a markedly dilated left ventricle (LV) with severely reduced ejection fraction (EF) of 14% and multiple regional wall motion abnormalities, not compatible with a coronary distribution. Moderate functional mitral regurgitation (MR) was noted. The myocardium had a speckled appearance especially of the right side of the interventricular septum. The right ventricle (RV) was dilated with severely reduced systolic function (fractional area change [FAC] 6%, 3D RVEF 20%). There was non-coaptation of the tricuspid valve (TV) leaflets due to tricuspid annular dilatation causing torrential tricuspid regurgitation (TR) and a dilated inferior vena cava. Because of the severe RV dysfunction and torrential TR, the RV systolic pressure could not be estimated.

Cardiac magnetic resonance (CMR) imaging confirmed severe biventricular dysfunction with no regions of T2 signal-hyperintensity. Delayed gadolinium imaging revealed near circumferential subendocardial and subepicardial enhancement in the septum, anterior, and inferior walls which became transmural in the basal-mid lateral wall (Figure 2). This appearance on CMR accompanied by the speckled myocardial echotexture on echocardiography raised the possibility of cardiac amyloidosis (CA). The RV free wall and proximal inter-atrial septum displayed diffuse enhancement. The mid-lateral wall and apical septum showed increased native myocardial T1 values (~ 1100 ms at 1.5 T).

Cardiac magnetic resonance imaging. (A) Extensive biventricular delayed enhancement involving the right ventricle trabeculae. “Zebra-like” enhancement of the interventricular septum is often seen in cardiac amyloidosis. (B) Increased native myocardial T1 values in the mid-lateral wall

Subsequent 18F-fludeoxyglucose (FDG) positron emission tomography (PET) revealed intense thoracic and abdominal lymphadenitis with a maximal standardized uptake value (SUVmax) of 14. Patchy intense FDG activity was seen throughout the myocardium (SUVmax 11.9) involving the septum, anterior, inferior, and RV free walls, both atria and the inter-atrial septum (Figure 3A). Multi-territory perfusion-metabolism mismatch was noted in a pattern typical of active CS (Figure 4). Advanced inflammatory and perfusion quantification was undertaken on co-localized Rubidium-82 and FDG-PET/CT images. This revealed significant inflammatory extent comprising 88% of the LV myocardium and a perfusion defect extent of 47%. Mean SUV of the whole myocardium was 6.7. Rare possibility for CA to produce a myocardial inflammatory signal was considered but the high intensity was not in favor of CA. In addition, a normal Tc-99m-DPD and SPECT/CT scan excluded transthyretin amyloidosis (Figure 5) while a normal serum amyloid P component (SAP) scan showed no amyloid deposits. Serum analysis showed no detectable M protein or free light chains, rendering AL amyloidosis highly unlikely. After multidisciplinary discussion endomyocardial biopsy and histological examination of the RV septum was performed revealing extensive fibrosis containing scattered multinucleated giant cells and non-necrotizing granulomas, confirming the diagnosis of CS. Congo red staining was negative for amyloidosis.

Response to immunosuppressive therapy. FDG-PET at baseline (A) with intense myocardial inflammation sparing only parts of the lateral wall and apex and 6 months after treatment (B). FDG-PET = 18F-fludeoxyglucose positron emission tomography

Perfusion and metabolism. Mismatch pattern typical of intensively active sarcoidosis

Technetium 99m (Tc-99m)-DPD and Single-photon emission computed tomography (SPECT). Absence of the bone tracer uptake within the myocardium hence exclusion of transthyretin (ATTR type) amyloidosis. Note Negative Tc-99m DPD imaging does not exclude AL amyloidosis