Therapies that raise levels of HDL, which is thought to exert atheroprotective effects via effects on endothelium, are being examined for the treatment or prevention of coronary artery disease (CAD). However, the endothelial effects of HDL are highly heterogeneous, and the impact of HDL of patients with CAD on the activation of endothelial eNOS and eNOS-dependent pathways is unknown. Here we have demonstrated that, in contrast to HDL from healthy subjects, HDL from patients with stable CAD or an acute coronary syndrome (HDL CAD ) does not have endothelial antiinflammatory effects and does not stimulate endothelial repair because it fails to induce endothelial NO production. Mechanistically, this was because HDL CAD activated endothelial lectin-like oxidized LDL receptor 1 (LOX-1), triggering endothelial PKCβII activation, which in turn inhibited eNOS-activating pathways and eNOS-dependent NO production. We then identified reduced HDL-associated paraoxonase 1 (PON1) activity as one molecular mechanism leading to the generation of HDL with endothelial PKCβII-activating properties, at least in part due to increased formation of malondialdehyde in HDL. Taken together, our data indicate that in patients with CAD, HDL gains endothelial LOX-1-and thereby PKCβII-activating properties due to reduced HDL-associated PON1 activity, and that this leads to inhibition of eNOS-activation and the subsequent loss of the endothelial antiinflammatory and endothelial repair-stimulating effects of HDL.

Perfusion findings in (13)N-ammonia PET and CFR are strong outcome predictors. CFR allows further risk stratification, suggesting a "warranty" period of 3 years if normal CFR is associated with normal perfusion. Conversely, in patients with abnormal perfusion, an impaired CFR has added value for predicting adverse outcomes.

This first experience documents the feasibility of prospective ECG-gating for CTCA with diagnostic image quality at a low radiation dose (1.1-3.0 mSv), favouring HR <63 b.p.m.

In patients with IVNC, a decreased CFR is not confined to noncompacted segments, but extends to most segments with wall motion abnormalities. Thus, coronary microcirculatory dysfunction is associated with IVNC.

Background-Intracoronary administration of autologous bone marrow-derived mononuclear cells (BM-MNC) mayimprove remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. Methods and Results-In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was −0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.

Background: Smartphone manufacturers offer mobile health monitoring technology to their customers, including apps using the built-in camera for heart rate assessment. This study aimed to test the diagnostic accuracy of such heart rate measuring apps in clinical practice. Methods: The feasibility and accuracy of measuring heart rate was tested on four commercially available apps using both iPhone 4 and iPhone 5. 'Instant Heart Rate' (IHR) and 'Heart Fitness' (HF) work with contact photoplethysmography (contact of fingertip to built-in camera), while 'Whats My Heart Rate' (WMH) and 'Cardiio Version' (CAR) work with non-contact photoplethysmography. The measurements were compared to electrocardiogram and pulse oximetryderived heart rate. Results: Heart rate measurement using app-based photoplethysmography was performed on 108 randomly selected patients. The electrocardiogram-derived heart rate correlated well with pulse oximetry (r ¼ 0.92), IHR (r ¼ 0.83) and HF (r ¼ 0.96), but somewhat less with WMH (r ¼ 0.62) and CAR (r ¼ 0.60). The accuracy of app-measured heart rate as compared to electrocardiogram, reported as mean absolute error (in bpm AE standard error) was 2 AE 0.35 (pulse oximetry), 4.5 AE 1.1 (IHR), 2 AE 0.5 (HF), 7.1 AE 1.4 (WMH) and 8.1 AE 1.4 (CAR). Conclusions: We found substantial performance differences between the four studied heart rate measuring apps. The two contact photoplethysmography-based apps had higher feasibility and better accuracy for heart rate measurement than the two non-contact photoplethysmography-based apps.

The novel CZT camera allows a more than fivefold reduction in scan time and provides clinical information equivalent to conventional standard SPECT MPI.

The ability to obtain quantitative values of flow and myocardial flow reserve (MFR) has been perceived as an important advantage of PET over conventional nuclear myocardial perfusion imaging (MPI). We evaluated the added diagnostic value of MFR over MPI alone as assessed with 13 N-ammonia and PET/CT to predict angiographic coronary artery disease (CAD). Methods: Seventy-three patients underwent 1-d adenosine stress-rest 13 N-ammonia PET/CT MPI, and MFR was calculated. The added value of MFR as an adjunct to MPI for predicting CAD (luminal narrowing $ 50%) was evaluated using invasive coronary angiography as a standard of reference. Results: Per patient, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MPI for detecting significant CAD were 79%, 80%, 91%, 59%, and 79%, respectively. Adding a cutoff of less than 2.0 for global MFR to MPI findings improved the values to 96% (P , 0.005), 80%, 93%, 89% (P , 0.005), and 92% (P , 0.005), respectively. Conclusion: The quantification of MFR in 13 N-ammonia PET/CT MPI provides a substantial added diagnostic value for detection of CAD. Particularly in patients with normal MPI results, quantification of MFR helps to unmask clinically significant CAD.Key Words: myocardial flow reserve; 13 N-ammonia; positron emission tomography; diagnostic value; myocardial perfusion imaging Nucl Med 2012; 53:1230 53: -1234 53: DOI: 10.2967 The PET technique confers advantages over SPECT related to improved image resolution and intrinsic attenuation correction (1). In addition, in myocardial perfusion imaging (MPI) PET offers quantitative assessment of myocardial blood flow (MBF) at rest and pharmacologic stress allowing calculation of myocardial flow reserve (MFR) (2). The latter is an index to evaluate blood circulation from the epicardial coronary arteries down to the microcirculation (3), which therefore provides functional information far beyond the epicardial section of the coronary vascular tree. Relative MPI such as SPECT (or PET without quantitative measurement) relies on induction of flow heterogeneities by hyperemic stress, which may sometimes underestimate the extent of coronary artery disease (CAD), as only the most severely underperfused territory may be evidenced (4). By contrast, absolute flow and MFR may reveal the true extent of CAD even at an early stage of subclinical atherosclerotic CAD. This possibility is supported by recent results documenting an added prognostic value for MFR over PET MPI alone with either 13 N-ammonia (5) or 82 Rb (6,7). Interestingly, MFR remained predictive throughout a 10-y follow-up period (5). Although many studies have revealed a reversed correlation of increasing coronary artery lesion narrowing with decreasing hyperemic flow and MFR in the respective myocardial territory (8-10), its diagnostic added value over MPI PET has not been assessed systematically. JWe evaluated the hypothesis that patients with decreased MFR (,2.0) would have a higher probability of CAD and that, thus, MFR would co...