Interplay of CT Coronary Plaque Characteristics and Ischemia to Predict Adverse Outcomes.

In 134 patients with stable coronary artery disease, high-risk plaque features at CT and physiologic stenosis were found to act in a synergistic fashion to predict adverse outcomes.

Impact of 2016 SCCT/STR guidelines for coronary artery calcium scoring of noncardiac chest CT scans on lung cancer screening CT reporting.

The 2016 SCCT/STR guideline for coronary artery calcification (CAC) scoring on non-cardiac chest CT (NCCT) scans explicitly calls for the reporting of CAC. Whether the publication of the 2016 SCCT/STR guideline has had any impact on CAC reporting in lung cancer screening (LCS) scans has not been investigated. Consecutive patients with a LCS scan were identified from the University of Minnesota LCS registry and evaluated for CAC reporting in 3 separate cohorts: 6 months before, 6 months after, and 1 year after the publication of the 2016 SCCT/STR guideline. Scans were evaluated for CAC and quantified using the Agatston method. CAC reporting, downstream testing and initiation of preventive therapy were assessed. Among 614 patients (50% male, mean age 64.1 ± 6.0 years), CAC was present in 460 (74.9%) with a median Agatston score of 62 (IQR 0, 230). Of these, 196 (31.9%) had a CAC score of 1-100, 125 (20.4%) had 101-300, and 118 (19.2%) had > 300. Overall, CAC was reported in 325 (70.7%) patients with CAC present. CAC reporting relative to publication of the 2016 SCCT/STR guideline was as follows: 6 months prior-74.1%, 6 months after-64.6%, and 1 year after-77.5%. In the 308 patients with a new diagnosis of sub-clinical CAD based on CAC presence, 6 (1.9%) patients were referred to cardiology, and 15 (4.9%) patients underwent testing for obstructive CAD. Only 6 (1.9%) and 9 (2.9%) patients were newly started on aspirin and statin respectively. CAC detected incidentally on lung cancer screening CT scans is prevalent, and rarely acted upon clinically. CAC reporting is fairly high, and publication of the 2016 SCCT/STR guideline for CAC scoring on NCCT scans did not have any significant impact on CAC reporting.

Transgenic overexpression of the SUR2A-55 splice variant in mouse heart reduces infract size and promotes protective mitochondrial function.

ATP-sensitive potassium channels found in both the sarcolemma (sarcKATP) and mitochondria (mitoKATP) of cardiomyocytes are important mediators of cardioprotection during ischemic heart disease. Sulfonylurea receptor isoforms (SUR2), encoded by Abcc9, an ATP-binding cassette family member, form regulatory subunits of the sarcKATP channel and are also thought to regulate mitoKATP channel activity. A short-form splice variant of SUR2 (SUR2A-55) was previously shown to target mitochondria and display diaxoxide and ATP insensitive KATP activity when co-expressed with the inward rectifier channels Kir6.2 and Kir6.1. We hypothesized that mice with cardiac specific overexpression of SUR2A-55 would mediate cardioprotection from ischemia by altering mitoKATP properties. Mice overexpressing SUR2A-55 (TGSUR2A-55) in cardiomyocytes were generated and showed no significant difference in echocardiographic measured chamber dimension, percent fractional shortening, heart to body weight ratio, or gross histologic features compared to normal mice at 11-14 weeks of age. TGSUR2A-55 had improved hemodynamic functional recovery and smaller infarct size after ischemia reperfusion injury compared to WT mice in an isolated hanging heart model. The mitochondrial membrane potential of TGSUR2A-55 mice was less sensitive to ATP, diazoxide, and Ca2+ loading. These data suggest that the SUR2A-55 splice variant favorably affects mitochondrial function leading to cardioprotection. These data support a role for the regulation of mitoKATP activity by SUR2A-55.

Transient complex I inhibition at the onset of reperfusion by extracellular acidification decreases cardiac injury.

A reversible inhibition of mitochondrial respiration by complex I inhibition at the onset of reperfusion decreases injury in buffer-perfused hearts. Administration of acidic reperfusate for a brief period at reperfusion decreases cardiac injury. We asked if acidification treatment decreased cardiac injury during reperfusion by inhibiting complex I. Exposure of isolated mouse heart mitochondria to acidic buffer decreased the complex I substrate-stimulated respiration, whereas respiration with complex II substrates was unaltered. Evidence of the rapid and reversible inhibition of complex I by an acidic environment was obtained at the level of isolated complex, intact mitochondria and in situ mitochondria in digitonin-permeabilized cardiac myocytes. Moreover, ischemia-damaged complex I was also reversibly inhibited by an acidic environment. In the buffer-perfused mouse heart, reperfusion with pH 6.6 buffer for the initial 5 min decreased infarction. Compared with untreated hearts, acidification treatment markedly decreased the mitochondrial generation of reactive oxygen species and improved mitochondrial calcium retention capacity and inner mitochondrial membrane integrity. The decrease in infarct size achieved by acidic reperfusion approximates the reduction obtained by a reversible, partial blockade of complex I at reperfusion. Extracellular acidification decreases cardiac injury during reperfusion in part via the transient and reversible inhibition of complex I, leading to a reduction of oxyradical generation accompanied by a decreased susceptibility to mitochondrial permeability transition during early reperfusion.