Abnormal regional increase of myocardial angiotensin II type 1 receptors in hypertrophic obstructive cardiomyopathy patients as determined with ¹¹C-KR31173 and PET/CT.

Objectives: Stimulation of the myocardial angiotensin II type 1 receptor (AT1R) by an activated renin-angiotensin system (RAS) may play a central role in the remodeling process of the left ventricle in patients with hypertrophic obstructive cardiomyopathy (HCM). In this regard, we aimed to evaluate the regional distribution of myocardial angiotensin II type 1 receptor (AT1R) with the novel radiotracer ¹¹C-KR31173 and dynamic positron emission tomography/computed tomography (PET/CT) in HCM patients in comparison to healthy volunteers as controls (CON).

Methods: Static images were obtained for KR31173 (30 to 60 min) PET/CT. From the last image, static PET data were volumetrically sampled, and myocardial polar maps were generated. For quantitative analysis, myocardial segments defined from static KR31173 images were applied to dynamic series, and time-activity curves were obtained. Subsequently, the regional or segmental retention index (%/min) of the AT1R ligand [11C]-KR31173 was determined from dynamic images acquired with 27 frames 12 x10, 6 x 60, 4 x 180, 2 x 300, 3 x 600 seconds. Regions were grouped according to left-ventricular wall thickness with >15 mm and remote regions with <15 mm in HCM patients as determined with echocardiography.

Results: Four HCM patients and four age-matched CON with a median age of 31 (IQR: 33, 37) years were investigated and they remained without any symptoms during the PET/CT image acquisition after intravenous ¹¹C-KR31173 application. Mean arterial blood pressures and heart rate (systolic and diastolic blood pressure 127 (129, 136) and 83 (85, 87) mmHg before vs. 128 (1130, 138) and 82 (86, 89) mmHg, respectively; and heart rate 64 (66, 68) beats/min vs. 63 (65, 70) were not significantly altered during PET/CT examination in study participants. No adverse effects were noted. In CON myocardial KR31173 uptake was mildly visually detectable and homogenous in the whole left-ventricular myocardium. In HCM patients, myocardial KR31173 uptake was regionally heterogeneous with the highest uptake in the thickened vs. remote myocardial regions. Quantified KR31173 retention index of the whole left ventricle was higher in HCM patients than in CON [1.91 (1.49, 3.27) vs. 0.43 (0.24, 0.44) %/min; p&#8804;0.05]. In HCM patients, regional evaluation of the KR31173 retention index was significantly higher in the thickened than in the remote regions [(3.97 (3.03, 8.97) vs. 0.78 (0.74, 2.16) %/min; p=0.0001]. When compared to CON, KR31173 retention was significantly higher in the thickened region [0.43 (0.24, 0.44) vs. 3.97 (3.03, 8.97) %/min; p&#8804;0.005] and not significantly in the remote region [0.43 (0.24, 0.44) vs. 0.78 (0.74, 2.16) %/min; p=0.016].

Conclusion: Noninvasive in-vivo imaging of myocardial AT1 receptor with the radiotracer ¹¹C-KR31173 and dynamic PET/CT in signifies an abnormal increase of AT1 receptor expression in hypertrophic regions in HCM patients that may reflect a mechanistic link between an activated RAS and negative left-ventricular remodeling deserving further investigations. Research Support: Departmental Fund from Johns Hopkins University (No. 175470 to T.H. Schindler)