A pooled-analysis of age and sex based coronary artery calcium scores percentiles

Funding The authors of this publication did not receive any grant from funding agencies in the public, commercial, or not-for-profit sector to support this research effort. Dr. Paolo Raggi was supported by a grant (RES0016825) from the Faculty of Medicine and Dentistry at the University of Alberta, Edmonton, AB, Canada. Dr. Matthew J. Budoff has Grant support from general electric and NIH. None of the other authors declares a conflict of interest. Publisher Copyright: © 2020 [The Author/The Authors]Background: Age and sex based coronary artery calcium score (CAC) percentiles have been used to improve coronary artery disease (CAD) risk prediction. However, the main limitation of the CACs percentiles currently in use is that they are often based on single studies. We performed a pooled analysis of all available studies that reported on CAC percentiles, in order to develop more generalizable age and sex nomograms. Methods: PubMed/Medline and Embase were searched for studies that reported nomograms of age and sex-based CACs percentiles. Studies were included if they reported data collected among asymptomatic individuals without a history of cardiovascular disease. Absolute CACs for each specific percentile stratum were pooled and new percentiles were generated taking into account the sample size of the study. Results: We found 831 studies, of which 12 met the inclusion criteria. Data on CACs percentiles of 134,336 Western and 33,488 Asians were pooled separately, rendering a weighted CACs percentile nomogram available at https://www.calciumscorecalculator.com. Our weighted percentiles differed by up to 24% from the nomograms in use today. Conclusions: Our pooled age and sex based CACs percentiles based on over 155,000 individuals should provide a measure of risk that is more applicable to a wider population than the ones currently in use and hopefully will lead to better risk assessment and treatment decisions.Peer reviewe

Comparison of axial and coronal acquisitions by non-contrast-enhanced renal 3D MR angiography using flow-in time-spatial labeling inversion pulse

ObjectiveWe evaluated image quality differences between axial and coronal non-contrast-enhanced renal three-dimensional (3D) magnetic resonance angiography (MRA) acquisitions, using time-spatial labeling inversion pulse (Time-SLIP) with flow-in balanced steady-state free precession (bSSFP).Materials and methodsAxial and coronal images were acquired in 128 subjects using non-contrast-enhanced 3D-MRA with Time-SLIP flow-in bSSFP on a clinical 1.5-T MRI system. Visualization of source and maximum intensity projection (MIP) images of renal arteries were compared between the axial and coronal acquisitions using a four-point scale. For quantitative analysis, vessel-to-background contrast ratios of aorta and renal arteries were calculated.ResultsBoth acquisitions yielded similarly excellent quality. In source image evaluation, coronal acquisitions showed significantly more motion degradation (p < 0.01) than did axial acquisitions. In MIP image evaluation, coronal acquisitions yielded superior image quality, less motion degradation, and better visualization of the number of renal branches than did axial acquisition. The renal artery to background signal contrast was greater in coronal than in axial acquisitions (p < 0.01).ConclusionCoronal acquisition provides superior contrast between the renal arteries and background and allows more persistent visualization than axial acquisitions in non-contrast-enhanced MRA using flow-in bSSFP with Time-SLIP. First-line screening of renal non-contrast-enhanced MRA should involve coronal acquisition

Role of sarcolemmal K(ATP) channels in cardioprotection against ischemia/reperfusion injury in mice

Recently it has been postulated that mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels rather than sarcolemmal K(ATP) (sarcK(ATP)) channels are important as end effectors and/or triggers of ischemic preconditioning (IPC). To define the pathophysiological significance of sarcK(ATP) channels, we conducted functional experiments using Kir6.2-deficient (KO) mice. Metabolic inhibition with glucose-free, dinitrophenol-containing solution activated sarcK(ATP) current and shortened the action potential duration in ventricular cells isolated from wild-type (WT) but not KO mice. MitoK(ATP) channel function was preserved in KO ventricular cells. In anesthetized mice, IPC reduced the infarct size in WT but not KO mice. Following global ischemia/reperfusion, the increase of left ventricular end-diastolic pressure during ischemia was more marked, and the recovery of contractile function was worse, in KO hearts than in WT hearts. Treatment with HMR1098, a sarcK(ATP) channel blocker, but not 5-hydroxydecanoate, a mitoK(ATP) channel blocker, produced a deterioration of contractile function in WT hearts comparable to that of KO hearts. These findings suggest that sarcKATP channels figures prominently in modulating ischemia/reperfusion injury in the mouse. The rapid heart rate of the mouse (>600 beats per minute) may magnify the relative importance of sarcK(ATP) channels during ischemia, prompting caution in the extrapolation of the conclusions to larger mammals

Inhibitory effects of aprindine on the delayed rectifier K(+) current and the muscarinic acetylcholine receptor-operated K(+) current in guinea-pig atrial cells

1. In order to clarify the mechanisms by which the class Ib antiarrhythmic drug aprindine shows efficacy against atrial fibrillation (AF), we examined the effects of the drug on the repolarizing K(+) currents in guinea-pig atrial cells by use of patch-clamp techniques. We also evaluated the effects of aprindine on experimental AF in isolated guinea-pig hearts. 2. Aprindine (3 μM) inhibited the delayed rectifier K(+) current (I(K)) with little influence on the inward rectifier K(+) current (I(K1)) or the Ca(2+) current. Electrophysiological analyses including the envelope of tails test revealed that aprindine preferentially inhibits I(Kr) (rapidly activating component) but not I(Ks) (slowly activating component). 3. The muscarinic acetylcholine receptor-operated K(+) current (I(K.ACh)) was activated by the extracellular application of carbachol (1 μM) or by the intracellular loading of GTPγS. Aprindine inhibited the carbachol- and GTPγS-induced I(K.ACh) with the IC(50) values of 0.4 and 2.5 μM, respectively. 4. In atrial cells stimulated at 0.2 Hz, aprindine (3 μM) per se prolonged the action potential duration (APD) by 50±4%. The drug also reversed the carbachol-induced action potential shortening in a concentration-dependent manner. 5. In isolated hearts, perfusion of carbachol (1 μM) shortened monophasic action potential (MAP) and effective refractory period (ERP), and lowered atrial fibrillation threshold. Addition of aprindine (3 μM) inhibited the induction of AF by prolonging MAP and ERP. 6. We conclude the efficacy of aprindine against AF may be at least in part explained by its inhibitory effects on I(Kr) and I(K.ACh)