Myocardial Energetics in AL and ATTR Cardiac Amyloidosis: A C-11 Acetate PET/CT Study

Background: Myocardial energy consumption and efficiency are reduced in patients with heart failure and reduced ejection fraction. Preclinical work suggests that AL-cardiomyopathy (AL-CMP) is characterized by increased oxidative stress from mitochondrial dysfunction and impaired mitophagy. Our goal was to determine whether myocardial energy efficiency is lower in patients with AL-cardiomyopathy (AL-CMP) compared to those with ATTR cardiomyopathy.

Methods: We prospectively studied 23 subjects with cardiac amyloidosis diagnosed by systemic or endomyocardial biopsy and elevated cardiac biomarkers (troponin T or age-adjusted NT pro BNP). All subjects underwent echocardiography and rest PET/CT imaging using 3D list mode acquisition after intravenous injection of ~740 MBq of C-11 acetate. Global left ventricular (LV) myocardial blood flow and k₂ values were obtained using PMOD and k_mono values were obtained by fitting the time-activity curves between 5 and 32 minutes post-injection to an exponential function. Myocardial k₂ was obtained using PMOD. Myocardial wall thickness and LV mass were measured by echocardiography. Myocardial stroke volume was measured by C-11 acetate PET/CT and indexed to body surface area. Myocardial work was defined as the product of stroke volume index, heart rate, and systolic blood pressure (x10⁵). Myocardial energy efficiency (x10⁶) was calculated as the ratio of myocardial work to MVO₂ (k_mono). Results: The study cohort included 20 AL-CMP and 3 ATTR-CMP subjects. Mean left ventricular ejection fraction did not differ between subjects with AL-CMP (46±12%) and ATTR-CMP (38±8%, P=0.19). Compared to patients with ATTR-CMP, those with AL-CMP differed in several demographic, cardiac structure, and myocardial metabolic features (Table). Patients with AL-CMP were younger, with smaller body surface area, higher LVEF, smaller LV mass, and lower stroke volume index. Rest myocardial blood flow, k_mono, k₂, and myocardial work were lower in ATTR compared to AL subjects. Myocardial energy efficiency was higher in patients with ATTR-CMP compared to AL-CMP. Conclusions: These results suggest that myocardial structure and energy utilization patterns differ between patients with AL-CMP and ATTR-CMP. Patients with AL-CMP have much lower myocardial mass and lower energy efficiency compared to patients with ATTR-CMP, suggesting better myocardial metabolic adaptation in ATTR-CMP. These findings if confirmed in a larger cohort suggest a role for novel therapeutics to manipulate substrate utilization in AL-CMP.