A Rare Case of Infiltrative Cardiomyopathy: Diagnostic Dilemma

Abstract

Presentation A 73-year-old white female with history of bilateral carpal tunnel syndrome, lumbar spinal stenosis, and family history of cardiomyopathy presented with worsening dyspnea on exertion. Exam showed right-sided crackles. There was no jugular venous distention, edema, macroglossia, or peri-orbital ecchymosis. Evaluation ECG demonstrated low voltage in all leads and no significant ST segment changes (Figure 1A). Labs showed undetectable troponin-I and normal NT-proBNP (119pg/mL). TTE revealed LVEF 55-65%, grade II diastolic dysfunction, thick and bright ventricular walls and global longitudinal strain of -17.9% with relative apical sparing (Figure 1B, Figure 1C). TTE findings raised concern for an infiltrative cardiomyopathy, specifically amyloidosis. Additional labs found polyclonal gammopathy on serum immunofixation with increased IgA (590mg/dL), kappa (20.4mg/L) and lambda (14.0mg/L). However, free kappa-to-lambda ratio (1.46) was normal. There was no monoclonal spike on urine immunofixation. Anti-neutrophil antibody screen was negative, and cobalt was undetectable. Ferritin (17ng/mL), C-reactive protein (0.8mg/L), and erythrocyte sedimentation rate (27mm/hr) were normal. Cardiac MRI found mild concentric left ventricular wall thickening up to 11 mm and late gadolinium enhancement throughout the myocardium (Figure 1D). Endomyocardial biopsy showed patchy fibrosis but no evidence of amyloidosis on Congo red staining. No granulomatous disease or inflammatory infiltrate was seen. Cutaneous nerve biopsy was also negative for amyloidosis. Technetium-99m pyrophosphate scan was negative for transthyretin amyloidosis with normal heart-to-lung ratio (1.3). Genetic testing for infiltrative cardiomyopathy genotypes revealed phenotypically silent heterozygosity for HFE hereditary hemochromatosis. Hereditary amyloidosis testing was negative. Follow-up Twelve-day ambulatory cardiac monitoring showed 11% PVC burden with multiple morphologies and three episodes of non-sustained VT. Amiodarone 200mg daily was initiated as opposed to therapeutic ablation due to multifocal nature of PVCs. The patient continued to have dyspnea on exertion but remained functionally independent. PET imaging was attempted, however the patient did not tolerate the dietary preparation. Conclusions A total evaluation is essential for infiltrative cardiomyopathy. History, exam, and preliminary testing in this case suggested cardiac amyloidosis; however, comprehensive evaluation could not support this diagnosis or an alternate mechanism. Despite diagnostic innovations including advanced cardiac imaging and genetic testing, the cause of infiltrative cardiomyopathy can remain obscure.