Comparison of the Peripheral Reactive Hyperemia Index with Myocardial Perfusion Reserve by ⁸²Rb PET/CT in HIV-Infected Patients

After the introduction of antiretroviral therapy (ART) the life expectancy of patients infected with human immunodeficiency virus (HIV) is now approaching that of the general population and the importance of non-AIDS co-morbidities is increasing. Specifically, the risk of coronary artery disease (CAD) seems to be higher in HIV-infected patients and an accurate risk prediction of CAD is of high importance for optimal long term treatment. In this study, we assessed the correlation of the endoPAT, which is an office-based CVD screening tool with the myocardial perfusion reserve by 82-rubidium PET/CT. We measured the reactive hyperemia index, which is a measure of the endothelial responsiveness, by the use of an endoPAT device (Itamar Medical, Caesarea, Israel) in 48 ART treated HIV-infected patients with high CD 4 cell counts and viral suppression (HIV-RNA < 20 copies/mL), who had previously undergone measurement of the myocardial perfusion reserve by 82-rubidium PET/CT for study purposes. We found an inverse correlation between the reactive hyperemia index and the myocardial perfusion reserve which most likely indicates different vascular physiology. This study did not find evidence to suggest the immediate implementation of the reactive hyperemia index as a screening tool for early coronary artery disease in well-treated HIV-infected patients pending further validation in larger prospective studies

Angiogenesis PET Tracer Uptake (⁶⁸Ga-NODAGA-E[(cRGDyK)]₂) in Induced Myocardial Infarction and Stromal Cell Treatment in Minipigs

Angiogenesis is considered integral to the reparative process after ischemic injury. The αvβ3 integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68Ga-NODAGA-E[(cRGDyK)]2 (RGD) is a positron-emission-tomography (PET) ligand targeted towards αvβ3 integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82Rubidium (82Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUVmean) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUVmean: 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUVmean: 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated

Retention and Functional Effect of Adipose-Derived Stromal Cells Administered in Alginate Hydrogel in a Rat Model of Acute Myocardial Infarction

Background. Cell therapy for heart disease has been proven safe and efficacious, despite poor cell retention in the injected area. Improving cell retention is hypothesized to increase the treatment effect. In the present study, human adipose-derived stromal cells (ASCs) were delivered in an in situ forming alginate hydrogel following acute myocardial infarction (AMI) in rats. Methods. ASCs were transduced with luciferase and tested for ASC phenotype. AMI was inducted in nude rats, with subsequent injection of saline (controls), 1 × 106 ASCs in saline or 1 × 106 ASCs in 1% (w/v) alginate hydrogel. ASCs were tracked by bioluminescence and functional measurements were assessed by magnetic resonance imaging (MRI) and 82rubidium positron emission tomography (PET). Results. ASCs in both saline and alginate hydrogel significantly increased the ejection fraction (7.2% and 7.8% at 14 days and 7.2% and 8.0% at 28 days, resp.). After 28 days, there was a tendency for decreased infarct area and increased perfusion, compared to controls. No significant differences were observed between ASCs in saline or alginate hydrogel, in terms of retention and functional salvage. Conclusion. ASCs improved the myocardial function after AMI, but administration in the alginate hydrogel did not further improve retention of the cells or myocardial function

Area of ischemia assessed by physicians and software packages from myocardial perfusion scintigrams.

The European Society of Cardiology recommends that patients with >10% area of ischemia should receive revascularization. We investigated inter-observer variability for the extent of ischemic defects reported by different physicians and by different software tools, and if inter-observer variability was reduced when the physicians were provided with a computerized suggestion of the defects