Launching the New American College of Cardiology Research Network: Advancing High-Value Collaborative Research via “Innovative Networking”

The landscape of research and academic medicine is changing significantly, especially for the early career professional (ECP) cardiologist. The recent viewpoint paper in the Journal detailing the challenges of the early career academic cardiologist crystallizes this complex situation. Although there is a clear desire to conduct research among those surveyed, there are major obstacles to achieving a successful research career. Two of the major challenges identified by ECPs are a lack of collaborators and a lack of research mentors to assist in generating the needed data to produce a competitive grant application. As identified by the survey, a lack of collaborators and mentors negatively affects one’s ability to achieve viable research funding. The most vulnerable are cardiology fellows and junior investigators who are new to research, especially those with nontraditional research interests, who can struggle to find mentorship within their institutions. Those who are new to research must often rely on informal networking with speakers who are invited to give grand rounds within their institution or at national conferences. For a minority, these haphazard meetings may turn into successful long-term research collaborations, but for many, they unfortunately do not. Additionally, for ECPs already involved in research, there is inadequate access to new techniques and innovations as a direct result of the absence of comprehensive and collaborative research-oriented networks. For example, short-term access to expensive equipment or needed reagents may be the limiting factor in one’s research endeavors. Indeed, as highlighted in a recent Leadership Page in the Journal, there is little national investment in research networks, leading to many inefficiencies and unnecessary delays

Effects of deep sedation or general anesthesia on cardiac function in mice undergoing cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Genetically engineered mouse models of human cardiovascular disease provide an opportunity to understand critical pathophysiological mechanisms. Cardiovascular magnetic resonance (CMR) provides precise reproducible assessment of cardiac structure and function, but, in contrast to echocardiography, requires that the animal be immobilized during image acquisition. General anesthetic regimens yield satisfactory images, but have the potential to significantly perturb cardiac function. The purpose of this study was to assess the effects of general anesthesia and a new deep sedation regimen, respectively, on cardiac function in mice as determined by CMR, and to compare them to results obtained in mildly sedated conscious mice by echocardiography.</p> <p>Results</p> <p>In 6 mildly sedated normal conscious mice assessed by echo, heart rate was 615 ± 25 min^-1(mean ± SE) and left ventricular ejection fraction (LVEF) was 0.94 ± 0.01. In the CMR studies of normal mice, heart rate was slightly lower during deep sedation with morphine/midazolam (583 ± 30 min^-1), but the difference was not statistically significant. General anesthesia with 1% inhaled isoflurane significantly depressed heart rate (468 ± 7 min^-1, p < 0.05 vs. conscious sedation). In 6 additional mice with ischemic LV failure, trends in heart rate were similar, but not statistically significant. In normal mice, deep sedation depressed LVEF (0.79 ± 0.04, p < 0.05 compared to light sedation), but to a significantly lesser extent than general anesthesia (0.60 ± 0.04, p < 0.05 vs. deep sedation).</p> <p>In mice with ischemic LV failure, ejection fraction measurements were comparable when performed during light sedation, deep sedation, and general anesthesia, respectively. Contrast-to-noise ratios were similar during deep sedation and during general anesthesia, indicating comparable image quality. Left ventricular mass measurements made by CMR during deep sedation were nearly identical to those made during general anesthesia (r²= 0.99, mean absolute difference < 4%), indicating equivalent quantitative accuracy obtained with the two methods. The imaging procedures were well-tolerated in all mice.</p> <p>Conclusion</p> <p>In mice with normal cardiac function, CMR during deep sedation causes significantly less depression of heart rate and ejection fraction than imaging during general anesthesia with isoflurane. In mice with heart failure, the sedation/anesthesia regimen had no clear impact on cardiac function. Deep sedation and general anesthesia produced CMR with comparable image quality and quantitative accuracy.</p

Biventricular adaptation to volume overload in mice with aortic regurgitation

<p>Abstract</p> <p>Background</p> <p>Aortic valve regurgitation is usually caused by impaired coaptation of the aortic valve cusps during diastole. Hypercholesterolemia produces aortic valve lipid deposition, fibrosis, and calcification in both mice and humans, which could impair coaptation of cusps. However, a link between hypercholesterolemia and aortic regurgitation has not been established in either species. The purpose of this study was to ascertain the prevalence of aortic regurgitation in hypercholesterolemic mice and to determine its impact on the left and right ventricles.</p> <p>Methods and Results</p> <p>Eighty <it>Ldlr</it>^-/-/<it>Apob</it>^100/100/<it>Mttp</it>^fl/fl/Mx1Cre^+/+("Reversa") hypercholesterolemic mice and 40 control mice were screened for aortic regurgitation (AR) with magnetic resonance imaging at age 7.5 months. The prevalence of AR was 40% in Reversa mice, with moderate or severe regurgitation (AR⁺) in 19% of mice. In control mice, AR prevalence was 13% (p = 0.004 <it>vs</it>. Reversa), and was invariably trace or mild in severity. In-depth evaluation of cardiac response to volume overload was performed in 12 AR-positive and 12 AR-negative Reversa mice. Regurgitant fraction was 0.34 ± 0.04 in AR-positive <it>vs</it>. 0.02 ± 0.01 in AR-negative (mean ± SE; p < 0.001). AR-positive mice had significantly increased left ventricular end-diastolic volume and mass and reduced ejection fraction in both ventricles. When left ventricular ejection fraction fell below 0.60 in AR-positive (<it>n </it>= 7) mice, remodeling occurred and right ventricular systolic function progressively worsened.</p> <p>Conclusion</p> <p>Hypercholesterolemia causes aortic valve regurgitation with moderate prevalence in mice. When present, aortic valve regurgitation causes volume overload and pathological remodeling of both ventricles.</p