Very low-dose (VLD) factor Xa (FXa) inhibition, in combination with acetylsalicylic acid (ASA) and clopidogrel, is associated with improved outcomes in patients with acute coronary syndrome (ACS) with a tolerable bleeding risk profile. To date, there are no data documenting platelet inhibition and the anticoagulatory effects of VLD FXa inhibition on top of guideline-adherent dual-antiplatelet therapy (DAPT) in patients with ACS. Patients with non-ST-elevation myocardial infarction (NSTEMI) receiving oral DAPT (ASA + clopidogrel, n = 20; or ASA + ticagrelor, n = 20) were prospectively enrolled in a nonrandomized study. Coagulation- and platelet-dependent thrombin generation (TG), measured by means of the calibrated automated thrombogram, were significantly decreased after in vitro and in vivo addition of rivaroxaban. As shown by a total thrombus-formation analysis approach, rivaroxaban treatment led to a significantly decreased coagulation-dependent (AR-chip) thrombus formation in patients treated with ASA plus P2Y inhibitor (clopidogrel/ticagrelor), whereas the pure platelet-dependent (PL-chip) thrombus formation was not affected at all. Adjunctive rivaroxaban therapy was not associated with significant differences in platelet aggregation assessed by light-transmission aggregometry (LTA). Nevertheless, according to fluorescence-activated cell sorter analysis, VLD rivaroxaban treatment resulted in a significantly reduced expression of platelet HMGB-1, whereas P-selectin exposure was not affected. Furthermore, an enhanced effect of rivaroxaban on total thrombus formation and TG was observed in particular in clopidogrel nonresponder patients defined as adenosine 5'-diphosphate-induced LTA ≥40%. VLD rivaroxaban reduces thrombus formation and platelet-dependent TG in patients with ACS receiving DAPT, which can be of potential ischemic benefit. This trial was registered at www.clinicaltrials.gov as #NCT01417884.

There has been a lack of standardized workup guidelines for patients with congenital abnormal origin of a coronary artery from the opposite sinus (ACAOS). We aimed to evaluate the use of cardiac hybrid imaging using multi-detector row CT (MDCT) for coronary CT angiography (Coronary CTA) and stress-rest myocardial perfusion SPECT (MPS) for comprehensive diagnosis of symptomatic adult patients with ACAOS. Seventeen symptomatic patients (12 men; 54 ± 13 years) presenting with ACAOS underwent coronary CTA and MPS. Imaging data were analyzed by conventional means, and with additional use of 3D image fusion to allocate stress induced perfusion defects (PD) to their supplying coronary arteries. An anomalous RCA arose from the left anterior sinus in eight patients, an abnormal origin from the right sinus was detected in nine patients (5 left coronary arteries, LCA and 4 LCx). Five of the 17 patients (29%) demonstrated a reversible PD in MPS. There was no correlation between the anatomical variants of ACAOS and the presence of myocardial ischemia. Image fusion enabled the allocation of reversible PD to the anomalous vessel in three patients (two cases in the RCA and the other in the LCA territory); PD in two patients were allocated to the territory of artery giving rise to the anomalies, rather than the anomalies themselves. In a small cohort of adult symptomatic patients with ACAOS anomaly there was no relation found between the specific anatomical variant and the appearance of stress induced myocardial ischemia using cardiac hybrid imaging.

The present study aimed to distinguish responders to cardiac resynchronization therapy (CRT ) from nonresponders, using electrocardiogram-gated 18 F-FDG PET/CT. Methods: Seven consecutive CRT nonresponders were included in the study, along with 7 age-and sex-matched CRT responders, serving as reference material. Therapy response was defined as clinical improvement ($1 New York Heart Association class) and evidence of reverse remodeling. Besides PET/CT, we measured brain natriuretic peptide levels and assessed dyssynchrony using transthoracic echocardiography. Results: Compared with nonresponders, CRT responders showed significant differences in the declines of left-ventricular end-systolic volume and brain natriuretic peptide and in left-ventricular dyssynchrony (global left-ventricular entropy), extent of the myocardial scar burden, and biventricular pacemaker leads positioned within viable myocardial regions. Among the nonresponders, further therapy management was guided by the PET/CT results in 4 of 7 patients. Conclusion: Cardiac hybrid imaging using gated 18 F-FDG PET/CT enabled the identification of potential reasons for nonresponse to CRT therapy, which can guide subsequent therapy.

Endomyocardial expression of SDF-1 is enhanced in inflammatory cardiomyopathy, positively correlates with myocardial fibrosis and identifies high-risk patients with suspected myocarditis.

Platelet adhesion, activation, and aggregation are essential for primary hemostasis, but are also critically involved in the development of acute arterial thrombotic occlusion. Stimulation of the collagen receptor glycoprotein VI (GPVI) leads to phospholipase Cγ2-dependent inositol triphosphate (IP) production with subsequent platelet activation, due to increased intracellular Ca concentration ([Ca]). Although tricyclic antidepressants have been shown to potentially impair platelet activation, nothing is hitherto known about potential effects of the tricyclic antidepressant doxepin on platelet Ca signaling and thrombus formation. As shown in the present study, doxepin significantly diminished the stimulatory effect of GPVI agonist collagen-related peptide (CRP) on intracellular Ca release as well as subsequent extracellular Ca influx. Doxepin was partially effective by impairment of CRP-dependent IP production. Moreover, doxepin abrogated CRP-induced platelet degranulation and integrin αβ activation and aggregation. Finally, doxepin markedly blunted in vitro platelet adhesion to collagen and thrombus formation under high arterial shear rates (1,700). In conclusion, doxepin is a powerful inhibitor of GPVI-dependent platelet Ca signaling, platelet activation, and thrombus formation.