<div><h4>Coronary Atherosclerosis Across the Glycemic Spectrum Among Asymptomatic Adults: The Miami Heart Study at Baptist Health South Florida.</h4><i>Patel KV, Budoff MJ, Valero-Elizondo J, Lahan S, ... Fialkow J, Nasir K</i><br /><b>Background</b><br />The contemporary burden and characteristics of coronary atherosclerosis, assessed using coronary computed tomography angiography (CCTA), is unknown among asymptomatic adults with diabetes and prediabetes in the United States. The pooled cohort equations and coronary artery calcium (CAC) score stratify atherosclerotic cardiovascular disease risk, but their association with CCTA findings across glycemic categories is not well established.<br /><b>Methods</b><br />Asymptomatic adults without atherosclerotic cardiovascular disease enrolled in the Miami Heart Study were included. Participants underwent CAC and CCTA testing and were classified into glycemic categories. Prevalence of coronary atherosclerosis (any plaque, noncalcified plaque, plaque with ≥1 high-risk feature, maximal stenosis ≥50%) assessed by CCTA was described across glycemic categories and further stratified by pooled cohort equations-estimated atherosclerotic cardiovascular disease risk and CAC score. Adjusted logistic regression was used to evaluate the associations between glycemic categories and coronary outcomes.<br /><b>Results</b><br />Among 2352 participants (49.5% women), the prevalence of euglycemia, prediabetes, and diabetes was 63%, 30%, and 7%, respectively. Coronary plaque was more commonly present across worsening glycemic categories (euglycemia, 43%; prediabetes, 58%; diabetes, 69%), and similar pattern was observed for other coronary outcomes. In adjusted analyses, compared with euglycemia, prediabetes and diabetes were each associated with higher odds of any coronary plaque (OR, 1.30 [95% CI, 1.05-1.60] and 1.75 [1.17-2.61], respectively), noncalcified plaque (OR, 1.47 [1.19-1.81] and 1.99 [1.38-2.87], respectively), and plaque with ≥1 high-risk feature (OR, 1.65 [1.14-2.39] and 2.53 [1.48-4.33], respectively). Diabetes was associated with stenosis ≥50% (OR, 3.01 [1.79-5.08]; reference=euglycemia). Among participants with diabetes and estimated atherosclerotic cardiovascular disease risk <5%, 46% had coronary plaque and 10% had stenosis ≥50%. Among participants with diabetes and CAC=0, 30% had coronary plaque and 3% had stenosis ≥50%.<br /><b>Conclusions</b><br />Among asymptomatic adults, worse glycemic status is associated with higher prevalence and extent of coronary atherosclerosis, high-risk plaque, and stenosis. In diabetes, CAC was more closely associated with CCTA findings and informative in a larger population than the pooled cohort equations.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 29 Sep 2023:e015314; epub ahead of print</small></div>

<div><h4>Atrial Myopathy Quantified by Speckle-Tracking Echocardiography in Mice.</h4><i>Zhang MJ, Gyberg DJ, Healy CL, Zhang N, ... Dudley SC, O\'Connell TD</i><br /><b>Background</b><br />Emerging evidence suggests that atrial myopathy may be the underlying pathophysiology that explains adverse cardiovascular outcomes in heart failure (HF) and atrial fibrillation. Lower left atrial (LA) function (strain) is a key biomarker of atrial myopathy, but murine LA strain has not been described, thus limiting translational investigation. Therefore, the objective of this study was to characterize LA function by speckle-tracking echocardiography in mouse models of atrial myopathy.<br /><b>Methods</b><br />We used 3 models of atrial myopathy in wild-type male and female C57Bl6/J mice: (1) aged 16 to 17 months, (2) Ang II (angiotensin II) infusion, and (3) high-fat diet+Nω-nitro-<sub>L</sub>-arginine methyl ester (HF with preserved ejection fraction, HFpEF). LA reservoir, conduit, and contractile strain were measured using speckle-tracking echocardiography from a modified parasternal long-axis window. Left ventricular systolic and diastolic function, and global longitudinal strain were also measured. Transesophageal rapid atrial pacing was used to induce atrial fibrillation.<br /><b>Results</b><br />LA reservoir, conduit, and contractile strain were significantly reduced in aged, Ang II and HFpEF mice compared with young controls. There were no sex-based interactions. Left ventricular diastolic function and global longitudinal strain were lower in aged, Ang II and HFpEF, but left ventricular ejection fraction was unchanged. Atrial fibrillation inducibility was low in young mice (5%), moderately higher in aged mice (20%), and high in Ang II (75%) and HFpEF (83%) mice.<br /><b>Conclusions</b><br />Using speckle-tracking echocardiography, we observed reduced LA function in established mouse models of atrial myopathy with concurrent atrial fibrillation inducibility, thus providing the field with a timely and clinically relevant platform for understanding the pathophysiology and discovery of novel treatment targets for atrial myopathy.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 05 Oct 2023:e015735; epub ahead of print</small></div>

<div><h4>Multicenter Evaluation of the Feasibility of Clinical Implementation of SPECT Myocardial Blood Flow Measurement: Intersite Variability and Imaging Time.</h4><i>Wells RG, Bengel FM, Camoni L, Cerudelli E, ... Teng XF, Ruddy TD</i><br /><b>Background</b><br />Single-center studies have shown that single photon emission computed tomography myocardial blood flow (MBF) measurement is accurate compared with MBF measured with microspheres in a porcine model, positron emission tomography, and angiography. Clinical implementation requires consistency across multiple sites. The study goal is to determine the intersite processing repeatability of single photon emission computed tomography MBF and the additional camera time required.<br /><b>Methods</b><br />Five sites (Canada, Italy, Japan, Germany, and Singapore) each acquired 25 to 35 MBF studies at rest and with pharmacological stress using technetium-99m-tetrofosmin on a pinhole-collimated cadmium-zinc-telluride-based cardiac single photon emission computed tomography camera with standardized list-mode imaging and processing protocols. Patients had intermediate to high pretest probability of coronary artery disease. MBF was measured locally and at a core laboratory using commercially available software. The time a room was occupied for an MBF study was compared with that for a standard rest/stress myocardial perfusion study.<br /><b>Results</b><br />With motion correction, the overall correlation in MBF between core laboratory and local site was 0.93 (range, 0.87-0.97) at rest, 0.90 (range, 0.84-0.96) at stress, and 0.84 (range, 0.70-0.92) for myocardial flow reserve. The local-to-core difference in global MBF (bias<sub>-MBF</sub>) was 5.4% (-3.8% to 14.8%; median [interquartile range]) at rest and 5.4% (-6.2% to 19.4%) at stress. Between the 5 sites, bias<sub>-MBF</sub> ranged from -1.6% to 11.0% at rest and from -1.9% to 16.3% at stress; the interquartile range in bias<sub>-MBF</sub> was between 9.3% (4.8%-14.0%) and 22.3% (-10.3% to 12.0%) at rest and between 17.0% (-11.3% to 5.6%) and 33.3% (-10.4% to 22.9%) at stress and was not significantly different between most sites. Both bias and interquartile range were like previously reported interobserver variability and less than the SD of the test-retest difference of 30%. The overall difference in myocardial flow reserve was 1.52% (-10.6% to 11.3%). There were no significant differences between with and without motion correction. The average additional acquisition time varied between sites from 44 to 79 minutes.<br /><b>Conclusions</b><br />The average bias<sub>-MBF</sub> and bias<sub>-MFR</sub> values were small with standard deviations substantially less than the test-retest variability. This demonstrates that MBF can be measured consistently across multiple sites and further supports that this technique can be reliably implemented.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT03427749.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 06 Oct 2023:e015009; epub ahead of print</small></div>

<div><h4>Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer.</h4><i>Gamble DT, Ross J, Khan H, Unger A, ... Sharma R, Dawson D</i><br /><b>Background</b><br />Anthracycline-related cardiac toxicity is a recognized consequence of cancer therapies. We assess resting cardiac and skeletal muscle energetics and myocyte, sarcomere, and mitochondrial integrity in patients with breast cancer receiving epirubicin.<br /><b>Methods</b><br />In a prospective, mechanistic, observational, longitudinal study, we investigated chemotherapy-naive patients with breast cancer receiving epirubicin versus sex- and age-matched healthy controls. Resting energetic status of cardiac and skeletal muscle (phosphocreatine/gamma ATP and inorganic phosphate [Pi]/phosphocreatine, respectively) was assessed with <sup>31</sup>P-magnetic resonance spectroscopy. Cardiac function and tissue characterization (magnetic resonance imaging and 2D-echocardiography), cardiac biomarkers (serum NT-pro-BNP and high-sensitivity troponin I), and structural assessments of skeletal muscle biopsies were obtained. All study assessments were performed before and after chemotherapy.<br /><b>Results</b><br />Twenty-five female patients with breast cancer (median age, 53 years) received a mean epirubicin dose of 304 mg/m<sup>2</sup>, and 25 age/sex-matched controls were recruited. Despite comparable baseline cardiac and skeletal muscle energetics with the healthy controls, after chemotherapy, patients with breast cancer showed a reduction in cardiac phosphocreatine/gamma ATP ratio (2.0±0.7 versus 1.1±0.5; <i>P</i>=0.001) and an increase in skeletal muscle Pi/phosphocreatine ratio (0.1±0.1 versus 0.2±0.1; <i>P</i>=0.022). This occurred in the context of increases in left ventricular end-systolic and end-diastolic volumes (<i>P</i>=0.009 and <i>P</i>=0.008, respectively), T1 and T2 mapping (<i>P</i>=0.001 and <i>P</i>=0.028, respectively) but with preserved left ventricular ejection fraction, mass and global longitudinal strain, and no change in cardiac biomarkers. There was preservation of the mitochondrial copy number in skeletal muscle biopsies but a significant increase in areas of skeletal muscle degradation (<i>P</i>=0.001) in patients with breast cancer following chemotherapy. Patients with breast cancer demonstrated a reduction in skeletal muscle sarcomere number from the prechemotherapy stage compared with healthy controls (<i>P</i>=0.013).<br /><b>Conclusions</b><br />Contemporary doses of epirubicin for breast cancer treatment result in a significant reduction of cardiac and skeletal muscle high-energy <sup>31</sup>P-metabolism alongside structural skeletal muscle changes.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT04467411.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Oct 2023; 16:e015782</small></div>

<div><h4>Role of Cardiac Energetics in Aortic Stenosis Disease Progression: Identifying the High-risk Metabolic Phenotype.</h4><i>Monga S, Valkovič L, Myerson SG, Neubauer S, Mahmod M, Rider OJ</i><br /><b>Background</b><br />Severe aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and cardiac metabolic alterations with evidence of steatosis and impaired myocardial energetics. Despite this common phenotype, there is an unexplained and wide individual heterogeneity in the degree of hypertrophy and progression to myocardial fibrosis and heart failure. We sought to determine whether the cardiac metabolic state may underpin this variability.<br /><b>Methods</b><br />We recruited 74 asymptomatic participants with AS and 13 healthy volunteers. Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to adenosine triphosphate ratio. Myocardial lipid content was determined using proton spectroscopy. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging.<br /><b>Results</b><br />Phosphocreatine/adenosine triphosphate was reduced early and significantly across the LV wall thickness quartiles (Q2, 1.50 [1.21-1.71] versus Q1, 1.64 [1.53-1.94]) with a progressive decline with increasing disease severity (Q4, 1.48 [1.18-1.70]; <i>P</i>=0.02). Myocardial triglyceride content levels were overall higher in all the quartiles with a significant increase seen across the AV pressure gradient quartiles (Q2, 1.36 [0.86-1.98] versus Q1, 1.03 [0.81-1.56]; <i>P</i>=0.034). While all AS groups had evidence of subclinical LV dysfunction with impaired strain parameters, impaired systolic longitudinal strain was related to the degree of energetic impairment (<i>r</i>=0.219; <i>P=</i>0.03). Phosphocreatine/adenosine triphosphate was not only an independent predictor of LV wall thickness (<i>r</i>=-0.20; <i>P</i>=0.04) but also strongly associated with myocardial fibrosis (<i>r</i>=-0.24; <i>P</i>=0.03), suggesting that metabolic changes play a role in disease progression. The metabolic and functional parameters showed comparable results when graded by clinical severity of AS.<br /><b>Conclusions</b><br />A gradient of myocardial energetic deficit and steatosis exists across the spectrum of hypertrophied AS hearts, and these metabolic changes precede irreversible LV remodeling and subclinical dysfunction. As such, cardiac metabolism may play an important and potentially causal role in disease progression.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Oct 2023; 16:e014863</small></div>

<div><h4>State-of-the-Art Imaging of Infiltrative Cardiomyopathies: A Scientific Statement From the American Heart Association.</h4><i>Kottam A, Hanneman K, Schenone A, Daubert MA, ... Garcia MJ, American Heart Association Council on Cardiovascular Radiology and Intervention</i><br /><AbstractText>Infiltrative cardiomyopathies comprise a broad spectrum of inherited or acquired conditions caused by deposition of abnormal substances within the myocardium. Increased wall thickness, inflammation, microvascular dysfunction, and fibrosis are the common pathological processes that lead to abnormal myocardial filling, chamber dilation, and disruption of conduction system. Advanced disease presents as heart failure and cardiac arrhythmias conferring poor prognosis. Infiltrative cardiomyopathies are often diagnosed late or misclassified as other more common conditions, such as hypertrophic cardiomyopathy, hypertensive heart disease, ischemic or other forms of nonischemic cardiomyopathies. Accurate diagnosis is also critical because clinical features, testing methodologies, and approach to treatment vary significantly even within the different types of infiltrative cardiomyopathies on the basis of the type of substance deposited. Substantial advances in noninvasive cardiac imaging have enabled accurate and early diagnosis. thereby eliminating the need for endomyocardial biopsy in most cases. This scientific statement discusses the role of contemporary multimodality imaging of infiltrative cardiomyopathies, including echocardiography, nuclear and cardiac magnetic resonance imaging in the diagnosis, prognostication, and assessment of response to treatment.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 02 Nov 2023:e000081; epub ahead of print</small></div>