Advanced cardiac amyloidosis associated with normal interventricular septal thickness: An uncommon presentation of infiltrative cardiomyopathy

Background Increased interventricular septal (IVS) thickness on echocardiography is a diagnostic criterion for cardiac amyloidosis and classically precedes decrement in left ventricular ejection fraction (LVEF). The investigators describe patients with histologically confirmed cardiac amyloidosis who had significant myocardial dysfunction (LVEF ≤ 40%) despite having normal IVS thickness. Methods All patients with systemic amyloidosis and LVEFs ≤ 40% were analyzed to identify the prevalence of normal IVS thickness. Patients with known histories of cardiomyopathy or coronary artery disease were excluded. Histologic evaluation of tissue included assessment of amyloid burden and average myocyte diameter. Results There were 255 patients with amyloidosis with LVEFs ≤ 40%, of whom seven (3%) had normal IVS thickness and histologic confirmation of cardiac involvement. Of these, six had immunoglobulin light chain amyloidosis, and one had senile amyloidosis. A majority of patients (86%) presented with new-onset cardiac dysfunction associated with edema and/or dyspnea. Electrocardiographic findings included low voltage (43%) and a pseudoinfarct pattern (29%). The 1-year survival from initial tissue diagnosis in the cohort with normal IVS thickness was similar to matched patients with amyloidosis with increased IVS thickness and LVEF ≤ 40% (21% vs 18%, respectively, P =.32). Myocardial tissue amyloid burden and average myocyte diameter were significantly reduced in cases compared with controls. Conclusions Cardiac amyloidosis can uncommonly present with normal IVS thickness despite significant myocardial dysfunction. The prognosis of these patients is as poor as those with increased IVS thickness. Amyloidosis should be considered in the differential diagnosis of patients with cardiomyopathy and reduced LVEFs despite normal IVS thickness.