Pseudo-discordance mimicking low-flow low-gradient aortic stenosis in transcatheter aortic valve replacement patients with severe symptomatic aortic stenosis

Background: While the combination of a small aortic valve area (AVA) and low mean gradient is frequently labeled ‘low-flow low-gradient aortic stenosis (AS)’, there are two potential causes for this finding: underestimation of mean gradient and underestimation of AVA. Methods: In order to investigate the prevalence and causes of discordant echocardiographic findings in symptomatic patients with AS and normal left ventricular (LV) function, we evaluated 72 symptomatic patients with AS and normal LV function by comparing Doppler, invasive, computed tomography (CT) LV outflow tract (LVOT) area, and calcium score (CaSc). Results: Thirty-six patients had discordant echocardiographic findings (mean gradient < 40 mmHg, AV area ≤ 1 cm2). Of those, 19 had discordant invasive measurements (true discordant [TD]) and 17 concordant (false discordant [FD]): In 12 of the FD the mean gradient was > 30 mmHg; technical pitfalls were found in 10 patients (no reliable right parasternal Doppler in 6). LVOT area by echocardiography or CT could not differentiate between concordants and discordants nor between TD and FD (p = NS). CaSc was similar in concordants and FD (p = 0.3), and it was higher in true concordants than in TD (p = 0.005). CaSc positive predictive value for the correct diagnosis of severe AS was 95% for concordants and 93% for discordants. Conclusions: Discordant echocardiographic findings are commonly found in patients with symptomatic AS. Underestimation of the true mean gradient due to technical difficulties is an important cause of these discrepant findings. LVOT area by echocardiography or CT cannot differentiate between TD and FD. In the absence of a reliable and compete multi-window Doppler evaluation, patients should undergo CaSc assessment

High-energy Particle Acceleration and Production of Ultra-high-energy Cosmic Rays in the Giant Lobes of Centaurus A

‘The definitive version is available at www3.interscience.wiley.com '. Copyright Royal Astronomical Society. DOI: 10.1111/j.1365-2966.2008.14265.xThe nearby radio galaxy Centaurus A is poorly studied at high frequencies with conventional radio telescopes because of its very large angular size, but is one of a very few extragalactic objects to be detected and resolved by the Wilkinson Microwave Anisotropy Probe (WMAP).We have used the five-year WMAP data for Cen A to constrain the high-frequency radio spectra of the 10-degree giant lobes and to search for spectral changes as a function of position along the lobes. We show that the high-frequency radio spectra of the northern and southern giant lobes are significantly different: the spectrum of the southern lobe steepens monotonically (and is steeper further from the active nucleus) whereas the spectrum of the northern lobe remains consistent with a power law. The inferred differences in the northern and southern giant lobes may be the result of real differences in their high-energy particle acceleration histories, perhaps due to the influence of the northern middle lobe, an intermediate-scale feature which has no detectable southern counterpart. In light of these results, we discuss the prospects for Gamma-ray Large Area Space Telescope (GLAST) detections of inverse-Compton emission from the giant lobes and the lobes’ possible role in the production of the ultra-high energy cosmic rays (UHECR) detected by the Pierre Auger Observatory. We show that the possibility of a GLAST detection depends sensitively on the physical conditions in the giant lobes, with the northern lobe more likely to be detected, and that any emission observed by GLAST is likely to be restricted to the soft end of the GLAST energy band. On the other hand we argue that the estimated conditions in the giant lobes imply that UHECRs can be accelerated there, with a potentially detectable -ray signature at GeV-TeV energies.Peer reviewe

The Impact of Novel Anti-Diabetic Medications on CV Outcomes: A New Therapeutic Horizon for Diabetic and Non-Diabetic Cardiac Patients

It is estimated that in the past two decades the number of patients diagnosed with diabetes mellites (DM) has doubled. Despite significant progress in the treatment of cardiovascular disease (CVD), including novel anti-platelet agents, effective lipid-lowering medications, and advanced revascularization techniques, patients with DM still are least twice as likely to die of cardiovascular causes compared with their non-diabetic counterparts, and current guidelines define patients with DM at the highest risk for atherosclerotic cardiovascular disease and major adverse cardiovascular events (MACE). Over the last few years, there has been a breakthrough in anti-diabetic therapeutics, as two novel anti-diabetic classes have demonstrated cardiovascular benefit with consistently reduced MACE, and for some agents, also improvement in heart failure status as well as reduced cardiovascular and all-cause mortality. These include the sodium-glucose cotransporter-2 inhibitors and the glucagon-like peptide-1 receptor agonists. The benefits of these medications are thought to be derived not only from their anti-diabetic effect but also from additional mechanisms. The purpose of this review is to provide the everyday clinician a detailed review of the various agents within each class with regard to their specific characteristics and the effects on MACE and cardiovascular outcomes

Acute myocardial infarction occurring while on chronic clopidogrel therapy ('clopidogrel failure') is associated with high incidence of clopidogrel poor responsiveness and stent thrombosis.

The clinical significance of the laboratory-based phenomenon of clopidogrel hypo-responsiveness and platelet reactivity associated with acute myocardial infarction, despite chronic clopidogrel therapy, is largely unknown. We aimed to determine platelet reactivity and clinical and angiographic features in 29 consecutive patients sustaining an acute myocardial infarction despite chronic (≥1 month) clopidogrel therapy.Platelet reactivity was determined on admission using conventional aggregometry. All patients underwent coronary angiography within 24 hours of admission. Patients were matched with clopidogrel-naïve acute myocardial infarction patients. Clopidogrel-naïve patients received a 600 mg clopidogrel loading dose and 75 mg/day thereafter.Of the 29 study patients, 19 (66%) presented with ST-elevation myocardial infarction, and in 25% the infarction was related to angiographically-proved definite stent thrombosis. Two-thirds of these patients were poor responders to clopidogrel (adenosine diphosphate-induced platelet aggregation >50%) and dual antiplatelet poor responsiveness was found in 57% in the chronic clopidogrel therapy group. Compared with clopidogrel-naïve patients, chronic clopidogrel therapy patients were more likely to demonstrate clopidogrel poor responsiveness (66% versus 38%, p = 0.02), to be diabetic (52% versus 33%, p = 0.1) and to have multi-vessel coronary disease (79% versus 55%, p = 0.03).Patients sustaining acute coronary syndrome despite chronic clopidogrel therapy are more likely to exhibit inadequate platelet inhibition with clopidogrel

Baseline characteristics of clopidogrel-failure and clopidogrel-naïve patients.

<p>Baseline characteristics of clopidogrel-failure and clopidogrel-naïve patients.</p

Incidence and Clinical Features of Early Stent Thrombosis in the Era of New P2y12 Inhibitors (PLATIS-2).

Early stent thrombosis (EST) (≤ 30 days after stent implantation) is a relatively rare but deleterious complication of percutaneous coronary intervention (PCI). Administration of newer P2Y12 inhibitors (prasugrel and ticagrelor) combined with aspirin has been shown to reduce the incidence of sub-acute and late stent thrombosis, compared with clopidogrel. We investigated the "real life" incidence of EST in patients from a large acute coronary syndrome (ACS) national registry, where newer P2Y12 inhibitors are widely used. Patients were derived from the ACS Israeli Survey (ACSIS), conducted during 2006, 2008, 2010 and 2013. Major adverse cardiac events (MACE) at 30days were defined as all-cause death, recurrent ACS, EST and stroke.Of the 4717 ACS patients who underwent PCI and stenting, 83% received clopidogrel and 17% newer P2Y12 inhibitors. The rate of EST was similar in both groups (1.7% in the newer P2Y12 inhibitor group vs. 1.4% in the clopidogrel-treated patients, p = 0.42). Results were consistent after multivariate analysis (adjusted HR = 1.06 [p = 0.89]). MACE occurred in 6.4% in the newer P2Y12 inhibitor group compared with 9.2% in the clopidogrel group (P<0.01). However, multivariate logistic regression modeling showed that treatment with newer P2Y12 inhibitors was not significantly associated with the secondary endpoint of MACE when compared with clopidogrel therapy [OR = 1.26 95%CI (0.93-1.73), P = 0.136]. The incidence of "real life" EST at 1month is relatively low, and appears to be similar in patients who receive newer P2Y12 inhibitors as well as in those who receive clopidogrel

MOESM1 of Clinical impact of diabetes mellitus in patients undergoing transcatheter aortic valve replacement

Additional file 1: Table S1. Complication rates based on HbA1c levels

Secondary end points at 30 days.

<p>Secondary end points at 30 days.</p