Journal of Nuclear Cardiology

Little is known about the sequelae of chronic sympathetic nervous system (SNS) activation in patients with pulmonary arterial hypertension (PAH) and right heart failure (RHF). We aimed to, (1) validate the use of [11C]-meta-hydroxyephedrine (HED) for assessing right ventricular (RV) SNS integrity, and (2) determine the effects of β-receptor blockade on ventricular function and myocardial SNS activity in a PAH rat model. PAH was induced in male Sprague-Dawley rats (N = 36) using the Sugen+chronic hypoxia model. At week 5 post-injection, PAH rats were randomized to carvedilol (15 mg·kg−1·day−1 oral; N = 16) or vehicle (N = 16) for 4 weeks. Myocardial SNS function was assessed with HED positron emission tomography(PET). With increasing PAH disease severity, immunohistochemistry confirmed selective sympathetic denervation within the RV and sparing of parasympathetic nerves. These findings were confirmed on PET with a significant negative relationship between HED volume of distribution(DV) and right ventricular systolic pressure (RVSP) in the RV (r = −0.90, p = 0.0003). Carvedilol did not reduce hemodynamic severity compared to vehicle. RV ejection fraction (EF) was lower in both PAH groups compared to control (p < 0.05), and was not further reduced by carvedilol. Carvedilol improved SNS function in the LV with significant increases in the HED DV, and decreased tracer washout in the LV (p < 0.05) but not RV. PAH disease severity correlated with a reduction in HED DV in the RV. This was associated with selective sympathetic denervation. Late carvedilol treatment did not lead to recovery of RV function. These results support the role of HED imaging in assessing SNS innervation in a failing right ventricle.

Stress electrocardiogram(ECG)-gated single photon emission computed tomography (SPECT) imaging is highly effective in risk stratification of diabetic patients for adverse cardiac events. While patients with diabetes are predisposed to a more aggressive progression of vascular disease, the impact of its duration and type of therapy on risk stratification are unknown. From the Hartford Hospital Nuclear Cardiology clinical database, 886 diabetic patients who underwent exercise or pharmacologic stress ECG-gated SPECT were identified, with complete follow-up regarding the occurrence of adverse cardiac events and information regarding the duration of diabetes and the type of therapy (insulin vs oral medication only) at the time of testing. Images were interpreted using the American College of Cardiology/ASNC standard 17-segment scoring model. Of the 886 diabetic patients, 98 (11%) suffered cardiac death or non-fatal myocardial infarction during follow-up (2.5 ± 1.6 years). A receiver operator characteristics curve demonstrated that diabetes ≥10 years in duration provided the maximal sum of sensitivity and specificity for the prediction of adverse cardiac outcomes. Multivariate analysis identified the following as independent predictors of adverse outcome: Post-stress ejection fraction (EF) <40% (P = .001), age (P = .004), insulin therapy (P = .031), diabetes duration >10 years (P = .038), summed stress score (SSS) >8 (P = .046). For patients with an SSS >8, diabetes duration and type of therapy significantly enhanced risk stratification. Similar findings emerged for patients with a post-stress EF <40%. For diabetic patients undergoing stress ECG-gated SPECT myocardial perfusion imaging, disease duration and type of therapy provide independent and incremental prognostic information. Integration of these variables with this cardiovascular imaging technology significantly enhances cardiac risk stratification.

We report on a patient with a previous CABG and symptoms similar to syndrome X who had normal angiography and significant abnormal 201Tl perfusion. The discrepancy of the two imaging modalities could have occurred because, fundamentally, SPECT is a physiologic measurement that reflects perfusion of the myocardium, while coronary angiography reflects only anatomy, and it is known that anatomy may not predict perfusion well. Coronary angiography may underestimate the severity of coronary disease, atheromatosis involving coronary vascular wall, and its related perfusion. Another possibility is that coronary blood supply was diverted/stolen by 1 proximal branch of the left internal mammary artery during the exercise. Lastly, during stress there was an inability to increase flow reserve, resulting in decreased perfusion pressure to the collateral supply of the septal perforators from the saphenous venous graft to the distal right coronary artery. Stress and delayed 201Tl SPECT imaging provide insight into regional flow, cellular integrity, and viability, providing a valuable technique of assessing the presence of resting and provokable ischemia.