<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>

<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>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>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>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>Defining Demographic-Specific Coronary Artery Calcium Percentiles in the Population Aged ≥75: The ARIC Study and MESA.</h4><i>Wang FM, Cainzos-Achirica M, Ballew SH, Coresh J, ... Blaha MJ, Matsushita K</i><br /><b>Background</b><br />Current clinical guidelines recommend a coronary artery calcium (CAC) score of 100 Agatston Units or demographic-specific 75th percentile as high-risk thresholds for guiding atherosclerotic cardiovascular disease preventive therapy. Meanwhile, low CAC can help derisk individuals who may safely defer statin therapy. However, limited data from the early 2000s, including just 208 older Black individuals, inform CAC percentiles for adults aged 75 to 85 years, and none have been established in adults aged ≥85 years. This study aims to characterize the distribution of CAC and establish demographic-specific CAC percentiles in the population aged ≥75 years.<br /><b>Methods</b><br />We assessed 2886 participants aged ≥75 years without clinical coronary heart disease from the ARIC study (Atherosclerosis Risk in Communities) visit 7 (2018-2019; n=2217) and the MESA (Multi-Ethnic Study of Atherosclerosis) visit 5 (2010-2011; n=669). Prevalence of any CAC >0 and sex- and race-specific CAC percentiles across age were estimated nonparametrically with locally weighted regression models and pooled residual ranking.<br /><b>Results</b><br />The median age was 80 (interquartile interval, 77-83) years, and 60% were female. The prevalence of zero CAC was lowest in White males (4%), followed by Black males (13%), White females (14%), and highest in Black females (18%). Regardless of sex and race, most participants had CAC>100 (62.5%). CAC scores increased with age, with CAC identified in ≈95% of participants aged ≥90 years across sex-race subgroups. The 75th percentile corresponded to higher CAC scores for Black older adults (n=741), especially females, than currently used thresholds.<br /><b>Conclusions</b><br />In community-dwelling adults aged ≥75 years free of clinical coronary heart disease, the prevalence of zero CAC was 11%, and CAC >100 as a threshold for high ASCVD risk would categorize most of this older population as high risk. Demographic-specific CAC percentiles from this study are a valuable tool for interpreting CAC in the population aged ≥75 years.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Sep 2023:e015145; epub ahead of print</small></div>

<div><h4>Feasibility of Simultaneous Quantification of Myocardial and Renal Perfusion With Cardiac Positron Emission Tomography.</h4><i>Brown JM, Park MA, Kijewski MF, Weber BN, ... Blankstein R, Di Carli MF</i><br /><b>Background</b><br />Given the central importance of cardiorenal interactions, mechanistic tools for evaluating cardiorenal physiology are needed. In the heart and kidneys, shared pathways of neurohormonal activation, hypertension, and vascular and interstitial fibrosis implicate the relevance of systemic vascular health. The availability of a long axial field of view positron emission tomography (PET)/computed tomography (CT) system enables simultaneous evaluation of cardiac and renal blood flow.<br /><b>Methods</b><br />This study evaluated the feasibility of quantification of renal blood flow using data acquired during routine, clinically indicated <sup>13</sup>N-ammonia myocardial perfusion PET/CT. Dynamic PET image data were used to calculate renal blood flow. Reproducibility was assessed by the intraclass correlation coefficient among 3 independent readers. PET-derived renal blood flow was correlated with imaging and clinical parameters in the overall cohort and with histopathology in a small companion study of patients with a native kidney biopsy.<br /><b>Results</b><br />Among 386 consecutive patients with myocardial perfusion PET/CT, 296 (76.7%) had evaluable images to quantify renal perfusion. PET quantification of renal blood flow was highly reproducible (intraclass correlation coefficient 0.98 [95% CI, 0.93-0.99]) and was correlated with the estimated glomerular filtration rate (<i>r</i>=0.64; <i>P</i><0.001). Compared across vascular beds, resting renal blood flow was correlated with maximal stress myocardial blood flow and myocardial flow reserve (stress/rest myocardial blood flow), an integrated marker of endothelial health. In patients with kidney biopsy (n=12), resting PET renal blood flow was strongly negatively correlated with histological interstitial fibrosis (<i>r</i>=-0.85; <i>P</i><0.001).<br /><b>Conclusions</b><br />Renal blood flow can be reliably measured from cardiac <sup>13</sup>N-ammonia PET/CT and allows for simultaneous assessment of myocardial and renal perfusion, opening a potential novel avenue to interrogate the mechanisms of emerging therapies with overlapping cardiac and renal benefits.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Sep 2023:e015324; epub ahead of print</small></div>

<div><h4>Comparison of CT-derived Plaque Characteristic Index With CMR Perfusion for Ischemia Diagnosis in Stable CAD.</h4><i>Guo WF, Xu HJ, Lu YG, Qiao GY, ... He W, Zeng M</i><br /><b>Background</b><br />Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have been used to diagnose lesion-specific ischemia in patients with coronary artery disease. The aim of this study was to investigate the diagnostic performance of CCTA-derived plaque characteristic index compared with myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) derived from CMR perfusion in the assessment of lesion-specific ischemia.<br /><b>Methods</b><br />Between October 2020 and March 2022, consecutive patients with suspected or known coronary artery disease, who were clinically referred for invasive coronary angiography were prospectively enrolled. All participants sequentially underwent CCTA and CMR and invasive fractional flow reserve within 2 weeks. The diagnostic performance of CCTA-derived plaque characteristics, CMR perfusion-derived stress MBF, and MPR were compared. Lesions with fractional flow reserve ≤0.80 were considered to be hemodynamically significant stenosis.<br /><b>Results</b><br />Nighty-two patients with 141 vessels were included in this study. Plaque length, minimum luminal area, plaque area, percent area stenosis, total atheroma volume, vessel volume, lipid-rich volume, spotty calcium, napkin-ring signs, stress MBF, and MPR in flow-limiting stenosis group were significantly different from nonflow-limiting group. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lesion-specific ischemia diagnosis were 61.0%, 55.3%, 63.1%, 35.6%, and 79.3% for stress MBF, and 89.4%, 89.5%, 89.3%, 75.6%, 95.8% for MPR; meanwhile, 82.3%, 79.0%, 84.5%, 65.2%, and 91.6% for CCTA-derived plaque characteristic index.<br /><b>Conclusions</b><br />In our prospective study, CCTA-derived plaque characteristics and MPR derived from CMR performed well in diagnosing lesion-specific myocardial ischemia and were significantly better than stress MBF in stable coronary artery disease.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Sep 2023; 16:e015773</small></div>

<div><h4>Development and Validation of CCTA-based Radiomics Signature for Predicting Coronary Plaques With Rapid Progression.</h4><i>Chen Q, Xie G, Tang CX, Yang L, ... Yin X, Zhang LJ</i><br /><b>Background</b><br />Rapid plaque progression (RPP) is associated with a higher risk of acute coronary syndromes compared with gradual plaque progression. We aimed to develop and validate a coronary computed tomography angiography (CCTA)-based radiomics signature (RS) of plaques for predicting RPP.<br /><b>Methods</b><br />A total of 214 patients who underwent serial CCTA examinations from 2 tertiary hospitals (development group, 137 patients with 164 lesions; validation group, 77 patients with 101 lesions) were retrospectively enrolled. Conventional CCTA-defined morphological parameters (eg, high-risk plaque characteristics and plaque burden) and radiomics features of plaques were analyzed. RPP was defined as an annual progression of plaque burden ≥1.0% on lesion-level at follow-up CCTA. RS was built to predict RPP using XGBoost method.<br /><b>Results</b><br />RS significantly outperformed morphological parameters for predicting RPP in both the development group (area under the receiver operating characteristic curve, 0.82 versus 0.74; <i>P</i>=0.04) and validation group (area under the receiver operating characteristic curve, 0.81 versus 0.69; <i>P</i>=0.04). Multivariable analysis identified RS (odds ratio, 2.35 [95% CI, 1.32-4.46]; <i>P</i>=0.005) as an independent predictor of subsequent RPP in the validation group after adjustment of morphological confounders. Unlike unchanged RS in the non-RPP group, RS increased significantly in the RPP group at follow-up in the whole dataset (<i>P</i><0.001).<br /><b>Conclusions</b><br />The proposed CCTA-based RS had a better discriminative value to identify plaques at risk of rapid progression compared with conventional morphological plaque parameters. These data suggest the promising utility of radiomics for predicting RPP in a low-risk group on CCTA.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Sep 2023; 16:e015340</small></div>

<div><h4>Prognostic Value of Modified Coronary Flow Capacity Derived From [O]HO Positron Emission Tomography Perfusion Imaging.</h4><i>de Winter RW, Jukema RA, van Diemen PA, Schumacher SP, ... Danad I, Knaapen P</i><br /><b>Background</b><br />Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and coronary flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. This study explores the prognostic value of modified CFC derived from [<sup>15</sup>O]H<sub>2</sub>O positron emission tomography perfusion imaging.<br /><b>Methods</b><br />Quantitative rest/stress perfusion measurements were obtained from 1300 patients with known or suspected coronary artery disease. Patients were classified as having myocardial steal (n=38), severely reduced CFC (n=141), moderately reduced CFC (n=394), minimally reduced CFC (n=245), or normal flow (n=482) using previously defined thresholds. The end point was a composite of death and nonfatal myocardial infarction.<br /><b>Results</b><br />During a median follow-up of 5.5 (interquartile range, 3.7-7.8) years, the end point occurred in 153 (12%) patients. Myocardial steal (hazard ratio [HR], 6.70 [95% CI, 3.21-13.99]; <i>P</i><0.001), severely reduced CFC (HR, 2.35 [95% CI, 1.16-4.78]; <i>P</i>=0.018), and moderately reduced CFC (HR, 1.95 [95% CI, 1.11-3.41]; <i>P</i>=0.020) were associated with worse prognosis compared with normal flow, after adjusting for clinical characteristics. Similarly, in the overall population, increased resting myocardial blood flow (HR, 3.05 [95% CI, 1.68-5.54]; <i>P</i><0.001), decreased hyperemic myocardial blood flow (HR, 0.68 [95% CI, 0.52-0.90]; <i>P</i>=0.007) and decreased coronary flow reserve (HR, 0.55 [95% CI, 0.42-0.71]; <i>P</i><0.001) were independently associated with adverse outcome. In a model adjusted for the combined use of perfusion metrics, modified CFC demonstrated independent prognostic value (overall <i>P</i>=0.017).<br /><b>Conclusions</b><br />[<sup>15</sup>O]H<sub>2</sub>O positron emission tomography-derived resting myocardial blood flow, hyperemic myocardial blood flow, coronary flow reserve, and CFC are prognostic factors for death and nonfatal myocardial infarction in patients with known or suspected coronary artery disease. Importantly, after adjustment for clinical characteristics and the combined use of [<sup>15</sup>O]H<sub>2</sub>O positron emission tomography perfusion metrics, modified CFC remained independently associated with adverse outcome.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Sep 2023; 16:e014845</small></div>

<div><h4>Cardiovascular Molecular Imaging With Fluorine-19 MRI: The Road to the Clinic.</h4><i>van Heeswijk RB, Bauer WR, Bönner F, Janjic JM, ... Schwitter J, Flögel U</i><br /><AbstractText>Fluorine-19 (<sup>19</sup>F) magnetic resonance imaging is a unique quantitative molecular imaging modality that makes use of an injectable fluorine-containing tracer that generates the only visible <sup>19</sup>F signal in the body. This hot spot imaging technique has recently been used to characterize a wide array of cardiovascular diseases and seen a broad range of technical improvements. Concurrently, its potential to be translated to the clinical setting is being explored. This review provides an overview of this emerging field and demonstrates its diagnostic potential, which shows promise for clinical translation. We will describe <sup>19</sup>F magnetic resonance imaging hardware, pulse sequences, and tracers, followed by an overview of cardiovascular applications. Finally, the challenges on the road to clinical translation are discussed.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Sep 2023; 16:e014742</small></div>

<div><h4>Myocardial Flow Reserve, an Independent Prognostic Marker of All-Cause Mortality Assessed by Rb PET Myocardial Perfusion Imaging: A Danish Multicenter Study.</h4><i>Højstrup S, Hansen KW, Talleruphuus U, Marner L, ... Galatius S, Prescott E</i><br /><b>Background</b><br />Rubidium-82 positron emission tomography (<sup>82</sup>Rb PET) myocardial perfusion imaging is used in clinical practice to quantify regional perfusion defects. Additionally, <sup>82</sup>Rb PET provides a measure of absolute myocardial flow reserve (MFR), describing the vasculature state of health. We assessed whether <sup>82</sup>Rb PET-derived MFR is associated with all-cause mortality independently of the extent of perfusion defects.<br /><b>Methods</b><br />We conducted a multicenter clinical registry-based study of patients undergoing <sup>82</sup>Rb PET myocardial perfusion imaging on suspicion of chronic coronary syndromes. Patients were followed up in national registries for the primary outcome of all-cause mortality. Global MFR ≤2 was considered reduced.<br /><b>Results</b><br />Among 7169 patients studied, 38.1% were women, the median age was 69 (IQR, 61-76) years, and 39.0% had MFR ≤2. A total of 667 (9.3%) patients died during a median follow-up of 3.1 (IQR, 2.6-4.0) years, more in patients with MFR ≤2 versus MFR >2 (15.7% versus 5.2%; <i>P</i><0.001). MFR ≤2 was associated with all-cause mortality across subgroups defined by the extent of perfusion defects (all <i>P</i><0.05). In a Cox survival regression model adjusting for sex, age, comorbidities, kidney function, left ventricular ejection fraction, and perfusion defects, MFR ≤2 was a robust predictor of mortality with a hazard ratio of 1.62 (95% CI, 1.31-2.02; <i>P</i><0.001). Among patients with no reversible perfusion defects (n=3101), MFR ≤2 remained strongly associated with mortality (hazard ratio, 1.86 [95% CI, 1.26-2.73]; <i>P</i><0.01). The prognostic value of impaired MFR was similar for cardiac and noncardiac death.<br /><b>Conclusions</b><br />MFR ≤2 predicts all-cause mortality independently of the extent of perfusion defects. Our results support the inclusion of MFR when assessing the prognosis of patients suspected of chronic coronary syndromes.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 02 Aug 2023:e015184; epub ahead of print</small></div>

<div><h4>Noninvasive Assessment of Lipomatous Metaplasia as a Substrate for Ventricular Tachycardia in Chronic Infarct.</h4><i>Xu L, Desjardins B, Witschey WR, Nazarian S</i><br /><AbstractText>Myocardial lipomatous metaplasia (LM) has been increasingly reported in patients with prior myocardial infarction. Cardiac magnetic resonance and cardiac contrast-enhanced computed tomography have been used to noninvasively detect and quantify myocardial LM in postinfarct patients, and may provide useful information for understanding cardiac mechanics, arrhythmia susceptibility, and prognosis. This review aims to summarize the advantages and disadvantages, clinical applications, and imaging features of different cardiac magnetic resonance sequences and cardiac contrast-enhanced computed tomography for LM detection and quantification. We also briefly summarize LM prevalence in different cohorts of postinfarct patients and review the clinical utility of cardiac imaging in exploring myocardial LM as an arrhythmogenic substrate in patients with prior myocardial infarction.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Aug 2023:e014399; epub ahead of print</small></div>

<div><h4>Interplay Between Zero CAC, Quantitative Plaque Analysis, and Adverse Events in a Diverse Patient Cohort.</h4><i>Fattouh M, Kuno T, Pina P, Skendelas JP, ... Garcia MJ, Slipczuk L</i><br /><b>Background</b><br />Coronary artery calcium scoring (CAC) has garnered attention in the diagnostic approach to chest pain patients. However, little is known about the interplay between zero CAC, sex, race, ethnicity, and quantitative coronary plaque analysis.<br /><b>Methods</b><br />We conducted a retrospective analysis from our computed tomography registry of patients with stable angina without prior myocardial infarction or revascularization undergoing coronary computed tomography angiography at Montefiore Healthcare System. Follow-up end points collected included invasive angiography, type-1 myocardial infarction, coronary revascularization, cardiovascular and all-cause death.<br /><b>Results</b><br />A total of 2249 patients were included (66% female). The median follow-up was 5.5 years. The median age of those without CAC was 52 years (interquartile range, 44-59) and 60 years (interquartile range, 53-68) in those with CAC. Most patients were Hispanic (58%), and the rest were non-Hispanic Black (28%), non-Hispanic White (10%), and non-Hispanic Asian (5%). The majority had CAC=0 (55%). The negative predictive value of CAC=0 was 92.8%, 99.9%, and 99.9% for any plaque, obstructive coronary artery stenosis, and the composite outcome of all-cause death, myocardial infarction, or coronary revascularization, respectively. Among patients without CAC (n=1237), 89 patients (7%) had evidence of plaque on their coronary computed tomography angiography with a median low-attenuation noncalcified plaque burden of 4% (2-7). There were no significant differences in the negative predictive value for CAC=0 by sex, race, or ethnicity. Patients with ≥2 risk factors had higher odds of having plaque with zero CAC.<br /><b>Conclusions</b><br />In summary, no sex, race, or ethnicity differences were demonstrated in the negative predictive value of a zero CAC; however, patients with ≥2 risk factors had a higher prevalence of plaque. A small percentage (7%) of symptomatic patients undergoing coronary computed tomography angiography with zero CAC had noncalcified coronary plaque, with the implication that caution is needed for downscaling of preventive treatment in patients with zero CAC, chest pain, and multiple risk factors.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Aug 2023; 16:e015236</small></div>

<div><h4>Prognostic Value of Cardiac Magnetic Resonance Imaging in Patients With a Working Diagnosis of MINOCA-An Outcome Study With up to 10 Years of Follow-Up.</h4><i>Konst RE, Parker M, Bhatti L, Kaolawanich Y, ... Nijveldt R, Kim RJ</i><br /><b>Background</b><br />Patients with a working diagnosis of myocardial infarction with unobstructed coronary arteries (MINOCA) represent a heterogeneous cohort. The prognosis could vary substantially depending on the underlying cause. Although cardiac magnetic resonance (CMR) is considered a key diagnostic tool in these patients, there are limited data linking the CMR diagnosis with the outcome.<br /><b>Methods</b><br />This study is a prospective outcomes registry of consecutive patients presenting with a working diagnosis of MINOCA who were clinically referred for CMR at an academic hospital from October 2003 to February 2020. We assessed the relationships between the prespecified CMR diagnoses of acute myocardial infarction (AMI), myocarditis, nonischemic cardiomyopathy (NICM), normal CMR study, and major adverse cardiac events (MACEs).<br /><b>Results</b><br />Of 252 patients, the CMR diagnosis was AMI in 63 (25%), myocarditis in 33 (13%), NICM in 111 (44%), normal CMR in 37 (15%), and other diagnoses in 8 (3%). A specific nonischemic cause was diagnosed allowing true MINOCA to be ruled-out in 57% of the cohort. During up to 10 years of follow-up (1595 patient-years), MACE occurred in 84 patients (33%), which included 64 deaths (25%). The unadjusted cumulative 10-year rate of MACE was 47% in AMI, 24% in myocarditis, 50% in NICM, and 3.5% in patients with a normal CMR (Log-rank <i>P</i><0.001). The CMR diagnosis provided incremental prognostic value over clinical factors including age, gender, coronary artery disease risk factors, presentation with ST-elevation, and peak troponin (incremental χ² 17.9, <i>P</i><0.001); and patients with diagnoses of AMI, myocarditis, and NICM had worse MACE-free survival than patients with a normal CMR.<br /><b>Conclusions</b><br />In patients with a working diagnosis of MINOCA, CMR allows ruling-out true MINOCA in over half of the patients. CMR diagnoses of AMI, myocarditis, and NICM are associated with worse MACE-free survival, whereas a normal CMR study portends a benign prognosis.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Aug 2023; 16:e014454</small></div>

<div><h4>Sex Differences in Coronary Atherosclerotic Phenotype and Healing Pattern on Optical Coherence Tomography Imaging.</h4><i>Seegers LM, DeFaria Yeh D, Yonetsu T, Sugiyama T, ... Fuster V, Jang IK</i><br /><b>Background</b><br />Layered plaque, a signature of previous plaque disruption, is a known predictor of rapid plaque progression. Layered plaque can be identified in vivo by optical coherence tomography. Studies have reported differences in plaque burden between women and men, but sex differences in the pattern of layered plaque are unknown.<br /><b>Methods</b><br />Preintervention optical coherence tomography images of 533 patients with chronic coronary syndromes were analyzed. Detailed plaque characteristics of layered and nonlayered plaques of the target lesion were compared between men and women.<br /><b>Results</b><br />The prevalence of layered plaque was similar between men (N=418) and women (N=115; 55% versus 54%; <i>P</i>=0.832). In men, more features of plaque vulnerability were identified in layered plaque than in nonlayered plaque: lipid plaque (87% versus 69%; <i>P</i><0.001), macrophages (69% versus 56%; <i>P</i>=0.007), microvessels (72% versus 39%; <i>P</i><0.001), and cholesterol crystals (49% versus 30%; <i>P</i><0.001). No difference in plaque vulnerability between layered and nonlayered plaques was observed in women. Layered plaque in men had more features consistent with previous plaque rupture than in women: interrupted pattern (74% versus 52%; <i>P</i><0.001) and a greater layer index (1198 [781-1835] versus 943 [624-1477]; <i>P</i><0.001).<br /><b>Conclusions</b><br />In men, layered plaques exhibit more features of vascular inflammation and vulnerability as well as evidence of previous plaque rupture, compared with nonlayered plaques, whereas in women, no difference was observed between layered and nonlayered plaques. Vascular inflammation (plaque rupture) may be the predominant mechanism of layered plaque in men, whereas a less inflammatory mechanism may play a key role in women.<br /><b>Registration</b><br />URL: http://www.<br /><b>Clinicaltrials</b><br />gov; Unique Identifier: NCT01110538, NCT04523194.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 28 Jul 2023:e015227; epub ahead of print</small></div>

<div><h4>Prognostic Power of Quantitative Assessment of Functional Mitral Regurgitation and Myocardial Scar Quantification by Cardiac Magnetic Resonance.</h4><i>Wang TKM, Kocyigit D, Choi H, Anthony CM, ... Tang WHW, Kwon DH</i><br /><b>Background</b><br />The severity classification of functional mitral regurgitation (FMR) remains controversial despite adverse prognosis and rapidly evolving interventions. Furthermore, it is unclear if quantitative assessment with cardiac magnetic resonance can provide incremental risk stratification for patients with ischemic cardiomyopathy (ICM) or non-ICM (NICM) in terms of FMR and late gadolinium enhancement (LGE). We evaluated the impact of quantitative cardiac magnetic resonance parameters on event-free survival separately for ICM and NICM, to assess prognostic FMR thresholds and interactions with LGE quantification.<br /><b>Methods</b><br />Patients (n=1414) undergoing cardiac magnetic resonance for cardiomyopathy (ejection fraction<50%) assessment from April 1, 2001 to December 31, 2017 were evaluated. The primary end point was all-cause death, heart transplant, or left ventricular assist device implantation during follow-up. Multivariable Cox analyses were conducted to determine the impact of FMR, LGE, and their interactions with event-free survival.<br /><b>Results</b><br />There were 510 primary end points, 395/782 (50.5%) in ICM and 114/632 (18.0%) in NICM. Mitral regurgitation-fraction per 5% increase was independently associated with the primary end point, hazards ratios (95% CIs) of 1.04 (1.01-1.07; <i>P</i>=0.034) in ICM and 1.09 (1.02-1.16; <i>P</i>=0.011) in NICM. Optimal mitral regurgitation-fraction threshold for moderate and severe FMR were ≥20% and ≥35%, respectively, in both ICM and NICM, based on the prediction of the primary outcome. Similarly, optimal LGE thresholds were ≥5% in ICM and ≥2% in NICM. Mitral regurgitation-fraction×LGE emerged as a significant interaction for the primary end point in ICM (<i>P</i>=0.006), but not in NICM (<i>P</i>=0.971).<br /><b>Conclusions</b><br />Mitral regurgitation-fraction and LGE are key quantitative cardiac magnetic resonance biomarkers with differential associations with adverse outcomes in ICM and NICM. Optimal prognostic thresholds may provide important clinical risk prognostication and may further facilitate the ability to derive selection criteria to guide therapeutic decision-making.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 28 Jul 2023:e015134; epub ahead of print</small></div>

<div><h4>Impact of Diabetes on Myocardial Fibrosis in Patients With Hypertension: The REMODEL Study.</h4><i>Pua CJ, Loo G, Kui M, Moy WL, ... Le TT, Chin CWL</i><br /><b>Background</b><br />Compared with patients with hypertension only, those with hypertension and diabetes (HTN/DM) have worse prognosis. We aimed to characterize morphological differences between hypertension and HTN/DM using cardiovascular magnetic resonance; and compare differentially expressed proteins associated with myocardial fibrosis using high throughput multiplex assays.<br /><b>Methods</b><br />Asymptomatic patients underwent cardiovascular magnetic resonance: 438 patients with hypertension (60±8 years; 59% males) and 167 age- and sex-matched patients with HTN/DM (60±10 years; 64% males). Replacement myocardial fibrosis was defined as nonischemic late gadolinium enhancement on cardiovascular magnetic resonance. Extracellular volume fraction was used as a marker of diffuse myocardial fibrosis. A total of 184 serum proteins (Olink Target Cardiovascular Disease II and III panels) were measured to identify unique signatures associated with myocardial fibrosis in all patients.<br /><b>Results</b><br />Despite similar left ventricular mass (<i>P</i>=0.344) and systolic blood pressure (<i>P</i>=0.086), patients with HTN/DM had increased concentricity and worse multidirectional strain (<i>P</i><0.001 for comparison of all strain measures) compared to hypertension only. Replacement myocardial fibrosis was present in 28% of patients with HTN/DM compared to 16% of those with hypertension (<i>P</i><0.001). NT-proBNP (N-terminal pro-B-type natriuretic peptide) was the only protein differentially upregulated in hypertension patients with replacement myocardial fibrosis and independently associated with extracellular volume. In patients with HTN/DM, GDF-15 (growth differentiation factor 15) was independently associated with replacement myocardial fibrosis and extracellular volume. Ingenuity Pathway Analysis demonstrated a strong association between increased inflammatory response/immune cell trafficking and myocardial fibrosis in patients with HTN/DM.<br /><b>Conclusions</b><br />Adverse cardiac remodeling was observed in patients with HTN/DM. The novel proteomic signatures and associated biological activities of increased immune and inflammatory response may partly explain these observations.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 11 Jul 2023:e015051; epub ahead of print</small></div>

<div><h4>Rare Forms of Cardiac Amyloidosis: Diagnostic Clues and Phenotype in Apo AI and AIV Amyloidosis.</h4><i>Ioannou A, Porcari A, Patel RK, Razvi Y, ... Gillmore JD, Fontana M</i><br /><b>Background</b><br />Apo AI amyloidosis (AApoAI) and Apo AIV amyloidosis (AApoAIV) are rare but increasingly recognized causes of cardiac amyloidosis (CA). We sought to define the cardiac phenotype in AApoAI and AApoAIV using multimodality imaging.<br /><b>Methods</b><br />We identified all patients with AApoAI and AApoAIV assessed at our center between 2000 and 2021, and 2 cohorts of patients with immunoglobulin light-chain amyloidosis (AL) and transthyretin amyloidosis matched for age, sex, and cardiac involvement.<br /><b>Results</b><br />Forty-five patients had AApoAI, 13 (29%) of whom had cardiac involvement, 32 (71%) renal involvement, 28 (62%) splenic involvement, 27 (60%) hepatic involvement, and 7 (16%) laryngeal involvement. AApoAI-CA commonly presented with heart failure (n=8, 62%) or dysphonia (n=7, 54%). The Arg173Pro variant universally caused cardiac and laryngeal involvement (n=7, 100%). AApoAI-CA was associated with right-sided involvement, with a thicker right ventricular free wall (8.6±1.9 versus 6.3±1.3 mm versus 7.7±1.2 mm, <i>P</i>=0.004), greater incidence of tricuspid stenosis (4 [31%] versus 0 [0%] versus 0 [0%], <i>P</i>=0.012) and tricuspid regurgitation (6 [46%] versus 1 [8%] versus 2 [15%], <i>P</i>=0.048) than AL-CA and transthyretin CA. Twenty-one patients had AApoAIV, and cardiac involvement was more common than in AApoAI (15 [71%] versus 13 [29%], <i>P</i>=0.001). AApoAIV-CA most commonly presented with heart failure (n=12, 80%), and a lower median estimated glomerular filtration rate than AL-CA and transthyretin CA (36 mL/[min·1.73 m²] versus 65 mL/[min·1.73 m²] versus 63 mL/[min·1.73 m²], <i>P</i><0.001). All AApoAIV-CA patients had classical CA features on echocardiography/ cardiac magnetic resonance, including an apical-sparing strain pattern, which was less common in AApoAI-CA (15 [100%] versus 7 [54%], <i>P</i>=0.003), whereas cardiac uptake on bone scintigraphy was less common in AApoAIV-CA than AApoAI-CA (all grade 1) (14% versus 82%, <i>P</i><0.001). Patients with AApoAI and AApoAIV had a good prognosis (median survival >172 and >30 months, respectively), and a lower risk of mortality than matched patients with AL-amyloidosis (AL versus AApoAI: hazard ratio, 4.54 [95% CI, 2.02-10.14]; <i>P</i><0.001; AL versus AApoAIV: hazard ratio, 3.07 [95% CI, 1.27-7.44]; <i>P</i>=0.013).<br /><b>Conclusions</b><br />Dysphonia, multisystem involvement, or right-sided cardiac disease should raise suspicion of AApoAI-CA. AApoAIV-CA presents most commonly with heart failure and always displays classical CA imaging features, mimicking common forms of CA. Both AApoAI and AApoAIV are associated with a good prognosis and a lower risk of mortality than matched patients with AL-amyloidosis.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 11 Jul 2023:e015259; epub ahead of print</small></div>

<div><h4>Diagnostic Performance and Safety of a Novel Ferumoxytol-Enhanced Coronary Magnetic Resonance Angiography.</h4><i>Dong Z, Si G, Zhu X, Li C, ... Gu N, Li C</i><br /><b>Background</b><br />Currently, noninvasive arteriography for the diagnosis of coronary artery disease is clinically limited to the computed tomography scanning, where patients have to be exposed to the radiation and risks associated with iodinated contrast. We aimed to investigate the diagnostic performance and safety of a novel ferumoxytol-enhanced coronary magnetic resonance angiography (CMRA) in patients with suspected coronary artery disease.<br /><b>Methods</b><br />Thirty patients, 19 males, with a median age of 63 years old, and 17 with renal insufficiency, who were scheduled for invasive coronary angiography, were enrolled. Ferumoxytol was administered intravenously with a dose of 3 mg/kg during CMRA. Images were acquired with an ECG-triggered, navigator-gated, inversion recovery-prepared 3D fast low-angle shot sequence, and the image quality was assessed by a 4-point scale. Eighteen-segment coronary artery model was adopted to evaluate the visibility of the coronary arteries, and the image quality and stenosis were evaluated in nine segments. The diagnostic performance of CMRA is described as sensitivity, specificity, positive and negative predictive values, and accuracy with the invasive coronary angiography results as reference. The patients\' vital signs were monitored during CMRA, and their hepatic and renal functions were followed up for 3 months to evaluate the safety of ferumoxytol.<br /><b>Results</b><br />Two hundred fifty-two of the 270 study segments were identified by CMRA, and their quality score reached 3.6±0.7. Referring to the invasive coronary angiography results, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ferumoxytol-enhanced CMRA reached 100.0%, 66.7%, 92.3%, 100.0%, and 93.3% respectively in patient-based analysis; 91.4%, 90.9%, 86.5%, 94.3%, and 91.1%, respectively in vessel-based analysis; and 92.3%, 96.7%, 83.7%, 98.6%, and 96.0%, respectively in segment-based analysis. No ferumoxytol-related adverse event was observed during the 3-month follow-up.<br /><b>Conclusions</b><br />Ferumoxytol-enhanced CMRA demonstrated good diagnostic performance and excellent safety in the diagnosis of significant coronary stenosis, providing an alternative to coronary computed tomography angiography for the diagnosis of coronary artery disease.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT05032937.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Jul 2023; 16:580-590</small></div>

<div><h4>Association of Tricuspid Regurgitation With Outcome in Acute Heart Failure.</h4><i>Cocianni D, Stolfo D, Perotto M, Contessi S, ... Altinier A, Sinagra G</i><br /><b>Background</b><br />Tricuspid regurgitation (TR) is common in chronic heart failure (HF) and is associated with negative prognosis. However, evidence on prognostic implications of TR in acute HF is lacking. We sought to investigate the association between TR and mortality and the interaction with pulmonary hypertension (PH) in patients admitted for acute HF.<br /><b>Methods</b><br />We enrolled 1176 consecutive patients with a primary diagnosis of acute HF and with available noninvasive estimation of TR and pulmonary arterial systolic pressure.<br /><b>Results</b><br />Moderate-severe TR was present in 352 patients (29.9%) and was associated with older age and more comorbidities. The prevalence of PH (ie, pulmonary arterial systolic pressure >40 mm Hg), right ventricular dysfunction, and mitral regurgitation was higher in moderate-severe TR. At 1 year, 184 (15.6%) patients died. Moderate-severe TR was associated with higher 1-year mortality risk after adjustment for other echocardiographic parameters (pulmonary arterial systolic pressure, left ventricle ejection fraction, right ventricular dysfunction, mitral regurgitation, left and right atrial indexed volumes; hazard ratio, 1.718; <i>P</i>=0.009), and the association with outcome was maintained when clinical variables (eg, natriuretic peptides, serum creatinine and urea, systolic blood pressure, atrial fibrillation) were added to the multivariable model (hazard ratio, 1.761; <i>P</i>=0.024). The association between moderate-severe TR and outcome was consistent in patients with versus without PH, with versus without right ventricular dysfunction, and with versus without left ventricle ejection fraction <50%. Patients with coexistent moderate-severe TR and PH had 3-fold higher 1-year mortality risk compared with patients with no TR or PH (hazard ratio, 3.024; <i>P</i><0.001).<br /><b>Conclusions</b><br />In patients hospitalized for acute HF, the severity of TR is associated with 1-year survival, regardless of the presence of PH. The coexistence of moderate-severe TR and estimated PH was associated with a further increase in mortality risk. Our data must be interpreted in the context of potential underestimation of pulmonary arterial systolic pressure in patients with severe TR.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 29 Jun 2023:e014988; epub ahead of print</small></div>

<div><h4>Lack of Incremental Prognostic Value of Pericoronary Adipose Tissue Computed Tomography Attenuation Beyond Coronary Artery Disease Reporting and Data System for Major Adverse Cardiovascular Events in Patients With Acute Chest Pain.</h4><i>Wen D, Ren Z, Xue R, An R, ... Li J, Zheng M</i><br /><b>Background</b><br />Pericoronary adipose tissue (PCAT) and Coronary Artery Disease Reporting and Data System (CAD-RADS) category had prognostic values for major adverse cardiovascular events (MACEs). However, little is known about the difference between CAD-RADS and PCAT computed tomography (CT) attenuation for predicting MACEs. This study was to compare the prognostic value of PCAT and CAD-RADS for MACEs in patients with acute chest pain.<br /><b>Methods</b><br />Between January 2010 and December 2021, all consecutive emergency patients with acute chest pain referred for coronary computed tomography angiography were enrolled in this retrospective study. MACEs included unstable angina requiring hospitalization, coronary revascularization, nonfatal myocardial infarction, and all-cause death. Patients\' clinical characteristics, CAD-RADS, and PCAT CT attenuation were used to evaluate risk factors of MACEs using multivariable Cox regression analysis.<br /><b>Results</b><br />A total of 1313 patients were evaluated (mean age, 57.13±12.57 years; 782 men). During a median follow-up of 38 months, 142 of the 1313 patients (10.81%) experienced MACEs. Multivariable Cox regression analysis showed that CAD-RADS categories 2, 3, 4, 5 (hazard ratio range, 2.286-8.325; all <i>P</i><0.005) and right coronary artery PCAT CT attenuation (hazard ratio, 1.033; <i>P</i>=0.006) were independent predictors of MACEs after adjusting for clinical risk factors. The C statistics revealed that CAD-RADS improved risk stratification compared with PCAT CT alone (C-index, 0.760 versus 0.712; <i>P</i>=0.036). However, the benefit of right coronary artery PCAT CT attenuation combined with CAD-RADS was not significant compared with CAD-RADS alone (0.777 versus 0.760; <i>P</i>=0.129).<br /><b>Conclusions</b><br />Right coronary artery PCAT CT attenuation and CAD-RADS were independent predictors of MACEs. However, no incremental prognostic value of right coronary artery PCAT CT attenuation beyond CAD-RADS was detected for MACEs in patients with acute chest pain.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 29 Jun 2023:e015120; epub ahead of print</small></div>

<div><h4>Predictors of Major Adverse Cardiovascular Events in Patients With Moderate Aortic Stenosis: Implications for Aortic Valve Replacement.</h4><i>Howard T, Majmundar M, Sarin S, Kumar A, ... Kalra A, Puri R</i><br /><b>Background</b><br />Although the prognosis and management of severe aortic stenosis has been extensively studied, the risk stratification and outcomes of patients with moderate aortic stenosis remain elusive.<br /><b>Methods</b><br />This study included 674 patients from the Cleveland Clinic Health System with moderate aortic stenosis (aortic valve area, 1-1.5 cm<sup>2</sup>; mean gradient, 20-40 mm Hg; and peak velocity <4 m/s) and an NT-proBNP (N-terminal pro-B-type natriuretic peptide) level within 3 months of index diagnosis. The primary outcome of major adverse cardiovascular events (defined as the composite outcome of progression to severe aortic stenosis requiring aortic valve replacement, heart failure hospitalization, or death) was extracted from the electronic medical record.<br /><b>Results</b><br />The mean age was 75.3±12 years, and 57% were men. During a median follow-up of 316 days, the composite end point occurred in 305 patients. There were 132 (19.6%) deaths, 144 (21.4%) heart failure hospitalizations, and 114 (16.9%) patients underwent aortic valve replacement. Elevated NT-proBNP (1.41 [95% CI, 1.01-1.95]; <i>P</i>=0.048), diabetes (1.46 [95% CI, 1.08-1.96]; <i>P</i>=0.01), elevated averaged mitral valve E/e\' ratio (hazard ratio, 1.57 [95% CI, 1.18-2.10]; <i>P</i><0.01), and presence atrial fibrillation at the time of index echocardiogram (hazard ratio, 1.83 [95% CI, 1.15-2.91]; <i>P</i>=0.01) were each independently associated with an increased hazard for the composite outcome and when taken collectively, each of these factors incrementally increased risk.<br /><b>Conclusions</b><br />These results further elucidate the relatively poor short-medium term outcomes and risk stratification of patients with moderate aortic stenosis, supporting randomized trials assessing the efficacy of transcatheter aortic valve replacement in this population.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 29 Jun 2023:e015475; epub ahead of print</small></div>

<div><h4>Myocardial Flow Assessment After Heart Transplantation Using Dynamic Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography With Tl and Tc Tracers and Validated by N-NH Positron Emission Tomography.</h4><i>Ko KY, Ko CL, Lee CM, Cheng JS, ... Yen RF, Cheng MF</i><br /><b>Background</b><br />Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy and is the most common cause of long-term cardiovascular mortality in heart transplant patients. This study aimed to investigate the diagnostic performance of <sup>99m</sup>Tc and <sup>201</sup>Tl tracers in the assessment of CAV using cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) for myocardial blood flow (MBF) and myocardial flow reserve (MFR) quantification, which was further validated using <sup>13</sup> N-NH<sub>3</sub> positron emission tomography (PET).<br /><b>Methods</b><br />Thirty-eight patients with prior heart transplantation who underwent CZT SPECT and <sup>13</sup> N-NH<sub>3</sub> PET dynamic scans were included in this study. CZT SPECT with <sup>99m</sup>Tc-sestamibi was used in the first 19 patients and <sup>201</sup>Tl-chloride for the remaining patients. To determine the diagnostic accuracy of angiographically defined moderate-to-severe CAV, the analysis included patients who underwent angiographic examinations within 1 year of their second scan.<br /><b>Results</b><br />There were no significant differences in the patient characteristics between the <sup>201</sup>Tl and <sup>99m</sup>Tc tracer groups. Both <sup>201</sup>Tl and <sup>99m</sup>Tc CZT SPECT-derived stress MBF and MFR values globally and in 3 coronary territories showed good correlations with <sup>13</sup> N-NH<sub>3</sub> PET. The <sup>201</sup>Tl and <sup>99m</sup>Tc cohorts did not differ significantly in the correlation coefficients of CZT SPECT versus PET for MBF and MFR, except for stress MBF (<sup>201</sup>Tl:0.95 versus <sup>99m</sup>Tc:0.80, <i>P</i>=0.03). <sup>201</sup>Tl and <sup>99m</sup>Tc CZT SPECT were satisfactory for detecting PET MFR <2.0 (<sup>201</sup>Tl area under the curve, 0.92 [0.71-0.99], <sup>99m</sup>Tc area under the curve, 0.87 [0.64-0.97]) and angiographically defined moderate-to-severe CAV, and CZT SPECT results were comparable to that of <sup>13</sup> N-NH<sub>3</sub> PET (CZT area under the curve, 0.90 [0.70-0.99], PET area under the curve, 0.86 [0.64-0.97]).<br /><b>Conclusions</b><br />This small study suggests that CZT SPECT using <sup>201</sup>Tl and <sup>99m</sup>Tc tracers showed comparable MBF and MFR, and the results correlated well with those of <sup>13</sup> N-NH<sub>3</sub> PET. Hence, CZT SPECT with <sup>201</sup>Tl or <sup>99m</sup>Tc tracers can be used to detect moderate-to-severe CAV in patients with prior heart transplantation. However, validation using larger studies is warranted.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 14 Jun 2023:e015034; epub ahead of print</small></div>

<div><h4>Left Atrial Function Predicts Atrial Arrhythmia Recurrence Following Ablation of Long-Standing Persistent Atrial Fibrillation.</h4><i>Khan HR, Yakupoglu HY, Kralj-Hans I, Haldar S, ... Wong T, CASA AF Investigators</i><br /><b>Background</b><br />Left atrial (LA) function following catheter or surgical ablation of de-novo long-standing persistent atrial fibrillation (AF) and its impact on AF recurrence was studied in patients participating in the CASA-AF trial (Catheter Ablation vs. Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation).<br /><b>Methods</b><br />All patients underwent echocardiography preablation, 3 and 12 months post-ablation. LA structure and function were assessed by 2-dimensional volume and speckle tracking strain measurements of LA reservoir, conduit, and contractile strain. Left ventricular diastolic function was measured using transmitral Doppler filling velocities and myocardial tissue Doppler velocities to derive the e\', E/e\', and E/A ratios. Continuous rhythm monitoring was achieved using an implantable loop recorder.<br /><b>Results</b><br />Eighty-three patients had echocardiographic data suitable for analysis. Their mean age was 63.6±9.7 years, 73.5% were male, had AF for 22.8±11.6 months, and had a mean LA maximum volume of 48.8±13.8 mL/m<sup>2</sup>. Thirty patients maintained sinus rhythm, and 53 developed AF recurrence. Ablation led to similar reductions in LA volumes at follow-up in both rhythm groups. However, higher LA emptying fraction (36.3±10.6% versus 27.9±9.9%; <i>P</i><0.001), reservoir strain (22.6±8.5% versus 16.7±5.7%; <i>P</i>=0.001), and contractile strain (9.2±3.4% versus 5.6±2.5%; <i>P</i><0.001) were noted in the sinus rhythm compared with AF recurrence group following ablation at 3 months. Diastolic function was better in the sinus rhythm compared with the AF recurrence group with an E/A ratio of 1.5±0.5 versus 2.2±1.2 (<i>P</i><0.001) and left ventricular E/e\' ratio of 8.0±2.1 versus 10.3±4.1 (<i>P</i><0.001), respectively. LA contractile strain at 3 months was the only independent predictor of AF recurrence.<br /><b>Conclusions</b><br />Following ablation for long-standing persistent AF, improvement in LA function was greater in those who maintained sinus rhythm. LA contractile strain at 3 months was the most important determinant of AF recurrence following ablation.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT02755688.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 08 Jun 2023:e015352; epub ahead of print</small></div>

<div><h4>Cardiac Magnetic Resonance Imaging Versus Invasive-Based Strategies in Patients With Chest Pain and Detectable to Mildly Elevated Serum Troponin: A Randomized Clinical Trial.</h4><i>Miller CD, Mahler SA, Snavely AC, Raman SV, ... Kutcher MA, Hundley WG</i><br /><b>Background</b><br />The optimal diagnostic strategy for patients with chest pain and detectable to mildly elevated serum troponin is not known. The objective was to compare clinical outcomes among an early decision for a noninvasive versus an invasive-based care pathway.<br /><b>Methods</b><br />The CMR-IMPACT trial (Cardiac Magnetic Resonance Imaging Strategy for the Management of Patients with Acute Chest Pain and Detectable to Elevated Troponin) was conducted at 4 United States tertiary care hospitals from September 2013 to July 2018. A convenience sample of 312 participants with acute chest pain symptoms and a contemporary troponin between detectable and 1.0 ng/mL were randomized early in their care to 1 of 2 care pathways: invasive-based (n=156) or cardiac magnetic resonance (CMR)-based (n=156) with modification allowed as the patient condition evolved. The primary outcome was a composite including death, myocardial infarction, and cardiac-related hospital readmission or emergency visits.<br /><b>Results</b><br />Participants (N=312, mean age, 60.6 years, SD 11.3; 125 women [59.9%]), were followed over a median of 2.6 years (95% CI, 2.4-2.9). Early assigned testing was initiated in 102 out of 156 (65.3%) CMR-based and 110 out of 156 (70.5%) invasive-based participants. The primary outcome (CMR-based versus invasive-based) occurred in 59% versus 52% (hazard ratio, 1.17 [95% CI, 0.86-1.57]), acute coronary syndrome after discharge 23% versus 22% (hazard ratio, 1.07 [95% CI, 0.67-1.71]), and invasive angiography at any time 52% versus 74% (hazard ratio, 0.66 [95% CI, 0.49-0.87]). Among patients completing CMR imaging, 55 out of 95 (58%) were safely identified for discharge based on a negative CMR and did not have angiography or revascularization within 90 days. Therapeutic yield of angiography was higher in the CMR-based arm (52 interventions in 81 angiographies [64.2%] versus 46 interventions in 115 angiographies [40.0%] in the invasive-based arm [<i>P</i>=0.001]).<br /><b>Conclusions</b><br />Initial management with CMR or invasive-based care pathways resulted in no detectable difference in clinical and safety event rates. The CMR-based pathway facilitated safe discharge, enriched the therapeutic yield of angiography, and reduced invasive angiography utilization over long-term follow-up.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT01931852.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Jun 2023; 16:e015063</small></div>

<div><h4>Machine Learning for Prediction of Adverse Cardiovascular Events in Adults With Repaired Tetralogy of Fallot Using Clinical and Cardiovascular Magnetic Resonance Imaging Variables.</h4><i>Ishikita A, McIntosh C, Hanneman K, Lee MM, ... Barron DJ, Wald RM</i><br /><b>Background</b><br />Existing models for prediction of major adverse cardiovascular events (MACE) after repair of tetralogy of Fallot have been limited by modest predictive capacity and limited applicability to routine clinical practice. We hypothesized that an artificial intelligence model using an array of parameters would enhance 5-year MACE prediction in adults with repaired tetralogy of Fallot.<br /><b>Methods</b><br />A machine learning algorithm was applied to 2 nonoverlapping, institutional databases of adults with repaired tetralogy of Fallot: (1) for model development, a prospectively constructed clinical and cardiovascular magnetic resonance registry; (2) for model validation, a retrospective database comprised of variables extracted from the electronic health record. The MACE composite outcome included mortality, resuscitated sudden death, sustained ventricular tachycardia and heart failure. Analysis was restricted to individuals with MACE or followed ≥5 years. A random forest model was trained using machine learning (n=57 variables). Repeated random sub-sampling validation was sequentially applied to the development dataset followed by application to the validation dataset.<br /><b>Results</b><br />We identified 804 individuals (n=312 for development and n=492 for validation). Model prediction (area under the curve [95% CI]) for MACE in the validation dataset was strong (0.82 [0.74-0.89]) with superior performance to a conventional Cox multivariable model (0.63 [0.51-0.75]; <i>P</i>=0.003). Model performance did not change significantly with input restricted to the 10 strongest features (decreasing order of strength: right ventricular end-systolic volume indexed, right ventricular ejection fraction, age at cardiovascular magnetic resonance imaging, age at repair, absolute ventilatory anaerobic threshold, right ventricular end-diastolic volume indexed, ventilatory anaerobic threshold % predicted, peak aerobic capacity, left ventricular ejection fraction, and pulmonary regurgitation fraction; 0.81 [0.72-0.89]; <i>P</i>=0.232). Removing exercise parameters resulted in inferior model performance (0.75 [0.65-0.84]; <i>P</i>=0.002).<br /><b>Conclusions</b><br />In this single-center study, a machine learning-based prediction model comprised of readily available clinical and cardiovascular magnetic resonance imaging variables performed well in an independent validation cohort. Further study will determine the value of this model for risk stratification in adults with repared tetralogy of Fallot.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Jun 2023; 16:e015205</small></div>

<div><h4>Sex Differences in the Density of Lipidic Plaque Materials: Insights From the REASSURE-NIRS MultiCenter Registry.</h4><i>Kataoka Y, Nicholls SJ, Puri R, Kitahara S, ... Asaumi Y, Noguchi T</i><br /><b>Background</b><br />Intravascular imaging has shown better response of coronary atheroma to statin-mediated lowering of low-density lipoprotein cholesterol in women. However, its detailed mechanism remains to be determined yet. Modifiability of coronary atheroma under lipid-lowering therapies is partly driven by lipidic plaque component. Given a smaller plaque volume in women, lipidic plaque features including their density may differ between sex. Therefore, the current study sought to characterize sex-related differences in the density of lipidic plaque.<br /><b>Methods</b><br />We analyzed 1429 coronary lesions (culprit/nonculprit lesions=825/604) in 758 coronary artery disease patients (men/women=608/150) from the REASSURE-NIRS multicenter registry (Revelation of Pathophysiological Phenotypes of Vulnerable Lipid-Rich Plaque on Near-Infrared Spectroscopy). Total atheroma volume at 4-mm segment, maximum 4-mm-lipid-core burden index, and lipid plaque density index (=maximum 4-mm-lipid-core burden index/total atheroma volume at 4-mm segment) on near-infrared spectroscopy/intravascular ultrasound imaging at culprit and nonculprit lesions were compared in men and women.<br /><b>Results</b><br />Statin and high-intensity statin were used in 72.4 (<i>P</i>=0.81) and 22.9% (<i>P</i>=0.32) of study subjects, respectively. Women exhibited a smaller adjusted total atheroma volume at 4-mm segment (culprit lesions: 50.3±0.4 versus 54.2±0.3mm<sup>3</sup>, <i>P</i><0.001, nonculprit lesions: 31.5±3.0 versus 44.4±2.1mm<sup>3</sup>, <i>P</i><0.001), whereas their adjusted maximum 4-mm-lipid-core burden index did not differ between sex (culprit lesions: 544.7±29.9 versus 501.7±19.1, <i>P</i>=0.11, nonculprit lesions: 288.8±26.7 versus 272.7±18.9, <i>P</i>=0.51). Furthermore, a greater adjusted lipid plaque density index was observed in women (culprit lesions: 18.2±0.9 versus 9.8±0.6, <i>P</i><0.001, nonculprit lesions: 23.0±2.0 versus 7.8±1.4, <i>P</i><0.001). These adjustments of total atheroma volume at 4-mm segment, maximum 4-mm-lipid-core burden index, and lipid plaque density index included age, body mass index, hypertension, dyslipidemia, diabetes, smoking, a history of myocardial infarction and chronic kidney disease, low-density lipoprotein cholesterol level, statin and ezetimibe use, vessel volume, and hospital unit. The aforementioned plaque features consistently existed in both acute coronary syndrome and stable coronary artery disease subjects.<br /><b>Conclusions</b><br />Women harbored greater condensed lipidic plaque features, accompanied by smaller atheroma volume. These observations indicate potentially better modifiable disease in women, which underscores the need to intensify their lipid-lowering therapies for further improving their outcomes.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov/; Unique identifier: NCT04864171.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 10 May 2023:e015107; epub ahead of print</small></div>

<div><h4>Atrial Dysfunction in Significant Atrial Functional Mitral Regurgitation: Phenotypes and Prognostic Implications.</h4><i>Cramariuc D, Alfraidi H, Nagata Y, Levine RA, ... Andrews C, Hung J</i><br /><b>Background</b><br />Atrial functional mitral regurgitation (AFMR) is associated with increased morbidity and mortality. Left atrial (LA) size and function in AFMR are poorly characterized. We aimed to assess LA function by reservoir strain (LASr) and estimated reservoir work (LAWr) and their impact on outcome in AFMR.<br /><b>Methods</b><br />Consecutive patients at our institution between 2001 and 2019 and with significant (moderate or greater) AFMR were examined. LAWr was estimated as LASr×LA reservoir volume, and patients were grouped by median LASr and LAWr. Outcomes were all-cause death or heart failure hospitalizations.<br /><b>Results</b><br />Five hundred fifteen AFMR patients were followed up for 5 (1-17) years. Patients had previously documented atrial fibrillation (AF; 37%), heart failure with preserved ejection fraction (HFpEF) without AF (24%), or both (HFpEF+AF, 39%). LA volume was largest in AF, while LA function parameters were most impaired in the combined HFpEF+AF group. During follow-up, patients with low LASr or LAWr had higher risk of death (<i>P</i><0.001) and heart failure hospitalization (<i>P</i><0.05). In Cox regression analyses, low LASr and LAWr, but not LA volume or left ventricular function, were associated with a higher risk of death (LASr: hazard ratio, 2.3 [95% CI, 1.6-3.5]; LAWr: hazard ratio, 3.4 [95% CI, 2.4-4.9]; both <i>P</i><0.001) after adjustment for clinical and echocardiographic confounders. Low LASr and LAWr were strongest associated with death in HFpEF and HFpEF+AF.<br /><b>Conclusions</b><br />LA reservoir function but not LA size is a robust predictor of outcome in significant AFMR. This provides mechanistic insights into the interplay of functional versus geometric LA changes in AFMR.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 09 May 2023:e015089; epub ahead of print</small></div>

<div><h4>Assessment of Left Ventricular Myocardial Fibrosis in Adult Patients With Ebstein Anomaly: A Retrospective Cohort Study Based on Cardiac Magnetic Resonance and Histopathological Samples.</h4><i>Fernandez-Badillo V, Serrano-Roman J, Antonio-Villa NE, Cabello-Ganem A, ... Alexanderson-Rosas E, Espinola-Zavaleta N</i><br /><b>Background</b><br />The association between Ebstein anomaly and myocardial fibrosis, particularly in the left ventricle, has been controversial. We aimed to assess the prevalence of replacement fibrosis with a focus on the left ventricle (LV) using cardiac magnetic resonance (CMR), make a histopathological association between LV fibrosis and CMR findings, and explore whether LV fibrosis is an independent risk factor for cardiovascular disease mortality using a derived risk score.<br /><b>Methods</b><br />We performed a 12-year (2009-2021) retrospective cohort of adult patients with Ebstein anomaly who underwent CMR. The CMR evaluation included a comprehensive assessment of myocardial fibrosis by late gadolinium enhancement (LGE). Four postmortem samples were obtained from our cohort and stained using Masson trichrome to characterize LV fibrosis. We used Cox-regression analysis to identify and derive a prediction score that associated LV fibrosis with cardiovascular disease mortality.<br /><b>Results</b><br />We included 57 adults with Ebstein anomaly (52% men; median age, 29.52 [interquartile range, 21.24-39.17] years), of whom 12 died during follow-up. LGE prevalence by CMR was observed in 52.6% in any chamber; LV-LGE in 29.8%. Histopathological findings revealed a mid-wall pattern with predominantly interstitial fibrosis and minimal replacement fibrosis. LV-LGE was associated with increased risk of cardiovascular disease mortality (hazard ratio, 6.02 [95% CI, 1.22-19.91]) attributable to lateral and mid-wall LV segment involvement. Our mortality score achieved an overall good prediction capacity (R<sup>2</sup>, 0.435; C statistic, 0.93; D<sub>xy</sub>, 0.86).<br /><b>Conclusions</b><br />There is a high prevalence of LV fibrosis replacement in adults with Ebstein anomaly, characterized by specific CMR and histological patterns. Furthermore, LV-LGE fibrosis is an independent predictor of cardiovascular disease mortality, which could be integrated into risk assessment in clinical management.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 08 May 2023:e015011; epub ahead of print</small></div>

<div><h4>Influence of Obesity on Coronary Artery Disease and Clinical Outcomes in the ADVANCE Registry.</h4><i>Lowenstern A, Ng N, Takagi H, Rymer JA, ... Leipsic J, Daubert MA</i><br /><b>Background</b><br />The relationship between body size and cardiovascular events is complex. This study utilized the ADVANCE (Assessing Diagnostic Value of Noninvasive FFR<sub>CT</sub> in Coronary Care) Registry to investigate the association between body mass index (BMI), coronary artery disease (CAD), and clinical outcomes.<br /><b>Methods</b><br />The ADVANCE registry enrolled patients undergoing evaluation for clinically suspected CAD who had >30% stenosis on cardiac computed tomography angiography. Patients were stratified by BMI: normal <25 kg/m<sup>2</sup>, overweight 25-29.9 kg/m<sup>2</sup>, and obese ≥30 kg/m<sup>2</sup>. Baseline characteristics, cardiac computed tomography angiography and computed tomography fractional flow reserve (FFR<sub>CT</sub>), were compared across BMI groups. Adjusted Cox proportional hazards models assessed the association between BMI and outcomes.<br /><b>Results</b><br />Among 5014 patients, 2166 (43.2%) had a normal BMI, 1883 (37.6%) were overweight, and 965 (19.2%) were obese. Patients with obesity were younger and more likely to have comorbidities, including diabetes and hypertension (all <i>P</i><0.001), but were less likely to have obstructive coronary stenosis (65.2% obese, 72.2% overweight, and 73.2% normal BMI; <i>P</i><0.001). However, the rate of hemodynamic significance, as indicated by a positive FFR<sub>CT</sub>, was similar across BMI categories (63.4% obese, 66.1% overweight, and 67.8% normal BMI; <i>P</i>=0.07). Additionally, patients with obesity had a lower coronary volume-to-myocardial mass ratio compared with patients who were overweight or had normal BMI (obese BMI, 23.7; overweight BMI, 24.8; and normal BMI, 26.3; <i>P</i><0.001). After adjustment, the risk of major adverse cardiovascular events was similar regardless of BMI (all <i>P</i>>0.05).<br /><b>Conclusions</b><br />Patients with obesity in the ADVANCE registry were less likely to have anatomically obstructive CAD by cardiac computed tomography angiography but had a similar degree of physiologically significant CAD by FFR<sub>CT</sub> and similar rates of adverse events. An exclusively anatomic assessment of CAD in patients with obesity may underestimate the burden of physiologically significant disease that is potentially due to a significantly lower volume-to-myocardial mass ratio.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 May 2023; 16:e014850</small></div>

<div><h4>Epicardial Adipose Tissue Assessed by Computed Tomography and Echocardiography Are Associated With Adverse Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.</h4><i>Chong B, Jayabaskaran J, Ruban J, Goh R, ... Dimitriadis GK, Chew NWS</i><br /><b>Background</b><br />Epicardial adipose tissue (EAT) has garnered attention as a prognostic and risk stratification factor for cardiovascular disease. This study, via meta-analyses, evaluates the associations between EAT and cardiovascular outcomes stratified across imaging modalities, ethnic groups, and study protocols.<br /><b>Methods</b><br />Medline and Embase databases were searched without date restriction on May 2022 for articles that examined EAT and cardiovascular outcomes. The inclusion criteria were (1) studies measuring EAT of adult patients at baseline and (2) reporting follow-up data on study outcomes of interest. The primary study outcome was major adverse cardiovascular events. Secondary study outcomes included cardiac death, myocardial infarction, coronary revascularization, and atrial fibrillation.<br /><b>Results</b><br />Twenty-nine articles published between 2012 and 2022, comprising 19 709 patients, were included in our analysis. Increased EAT thickness and volume were associated with higher risks of cardiac death (odds ratio, 2.53 [95% CI, 1.17-5.44]; <i>P</i>=0.020; n=4), myocardial infarction (odds ratio, 2.63 [95% CI, 1.39-4.96]; <i>P</i>=0.003; n=5), coronary revascularization (odds ratio, 2.99 [95% CI, 1.64-5.44]; <i>P</i><0.001; n=5), and atrial fibrillation (adjusted odds ratio, 4.04 [95% CI, 3.06-5.32]; <i>P</i><0.001; n=3). For 1 unit increment in the continuous measure of EAT, computed tomography volumetric quantification (adjusted hazard ratio, 1.74 [95% CI, 1.42-2.13]; <i>P</i><0.001) and echocardiographic thickness quantification (adjusted hazard ratio, 1.20 [95% CI, 1.09-1.32]; <i>P</i><0.001) conferred an increased risk of major adverse cardiovascular events.<br /><b>Conclusions</b><br />The utility of EAT as an imaging biomarker for predicting and prognosticating cardiovascular disease is promising, with increased EAT thickness and volume being identified as independent predictors of major adverse cardiovascular events.<br /><b>Registration</b><br />URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42022338075.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 May 2023; 16:e015159</small></div>

<div><h4>Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.</h4><i>Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, ... Raisi-Estabragh Z, Petersen SE</i><br /><AbstractText>Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 12 Apr 2023:e014519; epub ahead of print</small></div>

<div><h4>Cardioprotective Effect of Empagliflozin and Circulating Ketone Bodies During Acute Myocardial Infarction.</h4><i>Santos-Gallego CG, Requena-Ibáñez JA, Picatoste B, Fardman B, ... Fuster V, Badimon JJ</i><br /><b>Background</b><br />SGLT2i (sodium-glucose cotransporter-2 inhibitors) improve clinical outcomes in patients with heart failure, but the mechanisms of action are not completely understood. SGLT2i increases circulating levels of ketone bodies, which has been demonstrated to enhance myocardial energetics and induce reverse ventricular remodeling. However, the role of SGLT2i or ketone bodies on myocardial ischemia reperfusion injury remains in the dark. The objective of this study is to investigate the cardioprotective potential of empagliflozin and ketone bodies during acute myocardial infarction (MI).<br /><b>Methods</b><br />We used a nondiabetic porcine model of ischemia reperfusion using a percutaneous occlusion of proximal left anterior descending artery for 45 minutes. Animals received 1-week pretreatment with either empagliflozin or placebo prior to MI induction. Additionally, a third group received intravenous infusion of the ketone body beta-hydroxybutyrate BOHB (beta-hydroxybutyrate) during the MI induction. Acute effects of the treatments were assessed 4-hour post-MI by cardiac magnetic resonance and histology (thioflavin for area at risk, triphenyltetrazolium chloride staining for MI size). All animals were euthanized immediately postcardiac magnetic resonance, and heart samples were collected.<br /><b>Results</b><br />The area at risk was similar in all groups. Empagliflozin treatment increased BOHB levels. Empagliflozin-treated animals showed significantly higher myocardial salvage, smaller MI size (both by cardiac magnetic resonance and histology), less microvascular obstruction, and improved cardiac function (left ventricle ejection fraction and strain). Furthermore, empagliflozin-treated animals demonstrated reduced biomarkers of cardiomyocyte apoptosis and oxidative stress compared with placebo. The BOHB group showed similar results to the empagliflozin group.<br /><b>Conclusions</b><br />One-week pretreatment with empagliflozin ameliorates ischemia reperfusion injury, reduces MI size and microvascular obstruction, increases myocardial salvage, preserves left ventricle systolic function, and lowers apoptosis and oxidative stress. Periprocedural intravenous infusion of BOHB during myocardial ischemia also induces cardioprotection, suggesting a role for BOHB availability as an additional mechanism within the wide spectrum of actions of SGLT2i.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 12 Apr 2023:e015298; epub ahead of print</small></div>

<div><h4>Prognostic Value of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging for Predicting Venous Thromboembolism in Children With Lymphoma.</h4><i>Beall M, Deep K, Tram NK, Nabavinia M, ... Audino AN, Stacy MR</i><br /><b>Background</b><br />Positron emission tomography (PET)/computed tomography (CT) imaging can detect changes in arterial inflammation, but has not been used to evaluate chemotherapy-induced venous inflammation or assess risk for venous thromboembolism (VTE) in pediatric oncology. Therefore, the purpose of this study was to evaluate the prognostic value of fluorine-18-fluorodeoxyglucose PET/CT imaging of venous inflammation for predicting VTE occurrence in the 12 months after lymphoma diagnosis in pediatric, adolescent, and young adult patients.<br /><b>Methods</b><br />Pediatric, adolescent, and young adult patients with lymphoma diagnoses (n=71) who underwent whole-body PET/CT imaging at initial staging of disease and first therapeutic follow-up were retrospectively evaluated for serial changes in lower extremity venous uptake of fluorine-18-fluorodeoxyglucose. PET/CT images were used to segment and quantify serial changes in fluorine-18-fluorodeoxyglucose uptake for veins of interest (ie, popliteal and femoral). Incidence of VTE was assessed for 12 months after lymphoma diagnosis.<br /><b>Results</b><br />PET/CT detected a significantly higher inflammatory response in the femoral (<i>P</i>=0.012) and popliteal (<i>P</i>=0.013) veins of patients who experienced a VTE event compared with those who remained VTE free in the 12 months after diagnosis. The area under the curve values for receiver operator characteristics analyses were 0.76 (femoral vein) and 0.77 (popliteal vein) based on incidence of VTE occurrence. Univariate analyses demonstrated that PET/CT-derived changes in femoral (<i>P</i>=0.008) and popliteal (<i>P</i>=0.002) vein inflammation were significantly associated with VTE-free survival at 12 months after diagnosis.<br /><b>Conclusions</b><br />Fluorine-18-fluorodeoxyglucose PET/CT imaging detects treatment-induced venous toxicity that may provide insight into risk of VTE events in pediatric and adolescent and young adult patients with lymphoma.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 04 Apr 2023:e014992; epub ahead of print</small></div>

<div><h4>Abnormal Mechanics Relate to Myocardial Fibrosis and Ventricular Arrhythmias in Patients With Mitral Valve Prolapse.</h4><i>Nagata Y, Bertrand PB, Baliyan V, Kochav J, ... Weinsaft JW, Levine RA</i><br /><b>Background</b><br />The relation between ventricular arrhythmia and fibrosis in mitral valve prolapse (MVP) is reported, but underlying valve-induced mechanisms remain unknown. We evaluated the association between abnormal MVP-related mechanics and myocardial fibrosis, and their association with arrhythmia.<br /><b>Methods</b><br />We studied 113 patients with MVP with both echocardiogram and gadolinium cardiac magnetic resonance imaging for myocardial fibrosis. Two-dimensional and speckle-tracking echocardiography evaluated mitral regurgitation, superior leaflet and papillary muscle displacement with associated exaggerated basal myocardial systolic curling, and myocardial longitudinal strain. Follow-up assessed arrhythmic events (nonsustained or sustained ventricular tachycardia or ventricular fibrillation).<br /><b>Results</b><br />Myocardial fibrosis was observed in 43 patients with MVP, predominantly in the basal-midventricular inferior-lateral wall and papillary muscles. Patients with MVP with fibrosis had greater mitral regurgitation, prolapse, and superior papillary muscle displacement with basal curling and more impaired inferior-posterior basal strain than those without fibrosis (<i>P</i><0.001). An abnormal strain pattern with distinct peaks pre-end-systole and post-end-systole in inferior-lateral wall was frequent in patients with fibrosis (81 versus 26%, <i>P</i><0.001) but absent in patients without MVP with basal inferior-lateral wall fibrosis (n=20). During median follow-up of 1008 days, 36 of 87 patients with MVP with >6-month follow-up developed ventricular arrhythmias associated (univariable) with fibrosis, greater prolapse, mitral annular disjunction, and double-peak strain. In multivariable analysis, double-peak strain showed incremental risk of arrhythmia over fibrosis.<br /><b>Conclusions</b><br />Basal inferior-posterior myocardial fibrosis in MVP is associated with abnormal MVP-related myocardial mechanics, which are potentially associated with ventricular arrhythmia. These associations suggest pathophysiological links between MVP-related mechanical abnormalities and myocardial fibrosis, which also may relate to ventricular arrhythmia and offer potential imaging markers of increased arrhythmic risk.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Apr 2023; 16:e014963</small></div>

<div><h4>Aortic Valve Calcium in Relation to Subclinical Cardiac Dysfunction and Risk of Heart Failure.</h4><i>Zhu F, Kaiser Y, Boersma E, Bos D, Kavousi M</i><br /><b>Background</b><br />The link between (mild) aortic valve calcium (AVC) with subclinical cardiac dysfunction and with risk of heart failure (HF) remains unclear. This research aims to determine the association of computed tomography-assessed AVC with echocardiographic measurements of cardiac dysfunction, and with HF in the general population.<br /><b>Methods</b><br />We included 2348 participants of the Rotterdam Study cohort (mean age 68.5 years, 52% women), who had AVC measurement between 2003 and 2006, and without history of HF at baseline. Linear regression models were used to explore relationship between AVC and echocardiographic measures at baseline. Participants were followed until December 2016. Fine and Gray subdistribution hazard models were used to assess the association of AVC with incident HF, accounting for death as a competing risk.<br /><b>Results</b><br />The presence of AVC or greater AVC were associated with larger mean left ventricular mass and larger mean left atrial size. In particular, AVC ≥800 showed a strong association (body surface area indexed left ventricular mass, β coefficient: 22.01; left atrium diameter, β coefficient: 0.17). During a median of 9.8 years follow-up, 182 incident HF cases were identified. After accounting for death events and adjusting for cardiovascular risk factors, one-unit larger log (AVC+1) was associated with a 10% increase in the subdistribution hazard of HF (subdistribution hazard ratio, 1.10 [95% CI, 1.03-1.18]), but the presence of AVC was not significantly associated with HF risk in fully adjusted models. Compared with the AVC=0, AVC between 300 and 799 (subdistribution hazard ratio, 2.36 [95% CI, 1.32-4.19]) and AVC ≥800 (subdistribution hazard ratio, 2.54 [95% CI, 1.31-4.90]) were associated with a high risk of HF.<br /><b>Conclusions</b><br />Presence and high levels of AVC were associated with markers of left ventricular structure, independent of traditional cardiovascular risk factors. Larger computed tomography-assessed AVC is an indicative of increased risk for the development of HF.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 07 Mar 2023:e014323; epub ahead of print</small></div>

<div><h4>Differences in Myocardial Remodeling and Tissue Characteristics in Chronic Isolated Aortic and Mitral Regurgitation.</h4><i>Malahfji M, Kitkungvan D, Senapati A, Nguyen DT, ... Zoghbi WA, Shah DJ</i><br /><b>Background</b><br />The left ventricular hemodynamic load differs between aortic regurgitation (AR) and primary mitral regurgitation (MR). We used cardiac magnetic resonance to compare left ventricular remodeling patterns, systemic forward stroke volume, and tissue characteristics between patients with isolated AR and isolated MR.<br /><b>Methods</b><br />We assessed remodeling parameters across the spectrum of regurgitant volume. Left ventricular volumes and mass were compared against normal values for age and sex. We calculated forward stroke volume (planimetered left ventricular stroke volume-regurgitant volume) and derived a cardiac magnetic resonance-based systemic cardiac index. We assessed symptom status according to remodeling patterns. We also evaluated the prevalence of myocardial scarring using late gadolinium enhancement imaging, and the extent of interstitial expansion via extracellular volume fraction.<br /><b>Results</b><br />We studied 664 patients (240 AR, 424 primary MR), median age of 60.7 (49.5-69.9) years. AR led to more pronounced increases in ventricular volume and mass compared with MR across the spectrum of regurgitant volume (<i>P</i><0.001). In ≥moderate regurgitation, AR patients had a higher prevalence of eccentric hypertrophy (58.3% versus 17.5% in MR; <i>P</i><0.001), whereas MR patients had normal geometry (56.7%) followed by myocardial thinning with low mass/volume ratio (18.4%). The patterns of eccentric hypertrophy and myocardial thinning were more common in symptomatic AR and MR patients (<i>P</i><0.001). Systemic cardiac index remained unchanged across the spectrum of AR, whereas it progressively declined with increasing MR volume. Patients with MR had a higher prevalence of myocardial scarring and higher extracellular volume with increasing regurgitant volume (<i>P</i> value for trend <0.001), whereas they were unchanged across the spectrum of AR (<i>P</i>=0.24 and 0.42, respectively).<br /><b>Conclusions</b><br />Cardiac magnetic resonance identified significant heterogeneity in remodeling patterns and tissue characteristics at matched degrees of AR and MR. Further research is needed to examine if these differences impact reverse remodeling and clinical outcomes after intervention.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 07 Mar 2023:e014684; epub ahead of print</small></div>

<div><h4>Coronary Inflammation and Plaque Vulnerability: A Coronary Computed Tomography and Optical Coherence Tomography Study.</h4><i>Yuki H, Sugiyama T, Suzuki K, Kinoshita D, ... Kakuta T, Jang IK</i><br /><b>Background</b><br />Vascular inflammation plays a key role in atherogenesis and in the development of acute coronary syndromes. Coronary inflammation can be measured by peri-coronary adipose tissue (PCAT) attenuation on computed tomography angiography. We examined the relationships between the level of coronary artery inflammation assessed by PCAT attenuation and coronary plaque characteristics by optical coherence tomography.<br /><b>Methods</b><br />A total of 474 patients (198 acute coronary syndromes and 276 stable angina pectoris) who underwent preintervention coronary computed tomography angiography and optical coherence tomography were included. To compare the relationships between the level of coronary artery inflammation and detailed plaque characteristics, we divided the subjects into high (n=244) and low (n=230) PCAT attenuation groups using a threshold value of -70.1 Hounsfield units.<br /><b>Results</b><br />The high PCAT attenuation group, compared with the low PCAT attenuation group, had more males (90.6% versus 69.6%; <i>P</i><0.001), more non-ST-segment elevation myocardial infarction (38.5% versus 25.7%; <i>P</i>=0.003), and less stable angina pectoris (51.6% versus 65.2%; <i>P</i>=0.003). Aspirin, dual antiplatelet, and statins were less frequently used in the high PCAT attenuation group compared to the low PCAT attenuation group. Patients with high PCAT attenuation, compared with those with low PCAT attenuation, had lower ejection fraction (median 64% versus 65%; <i>P</i>=0.014) and lower levels of high-density lipoprotein cholesterol (median 45 versus 48 mg/dL; <i>P</i>=0.027). Optical coherence tomography features of plaque vulnerability were significantly more common in patients with high PCAT attenuation, compared to those with low PCAT attenuation, including lipid-rich plaque (87.3% versus 77.8%; <i>P</i>=0.006), macrophage (76.2% versus 67.8%; <i>P</i>=0.041), microchannels (61.9% versus 48.3%; <i>P</i>=0.003), plaque rupture (38.1% versus 23.9%; <i>P</i><0.001), and layered plaque (60.2% versus 50.0%; <i>P</i>=0.025).<br /><b>Conclusions</b><br />Optical coherence tomography features of plaque vulnerability were significantly more common in patients with high PCAT attenuation, compared with those with low PCAT attenuation. Vascular inflammation and plaque vulnerability are intimately related in patients with coronary artery disease.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT04523194.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 03 Mar 2023:e014959; epub ahead of print</small></div>

<div><h4>Modeling of the Tricuspid Valve and Right Ventricle in Hypoplastic Left Heart Syndrome With a Fontan Circulation.</h4><i>Nam HH, Flynn M, Lasso A, Herz C, ... Fichtinger G, Jolley MA</i><br /><b>Background</b><br />In hypoplastic left heart syndrome, tricuspid regurgitation (TR) is associated with circulatory failure and death. We hypothesized that the tricuspid valve (TV) structure of patients with hypoplastic left heart syndrome with a Fontan circulation and moderate or greater TR differs from those with mild or less TR, and that right ventricle volume is associated with TV structure and dysfunction.<br /><b>Methods</b><br />TV of 100 patients with hypoplastic left heart syndrome and a Fontan circulation were modeled using transthoracic 3-dimensional echocardiograms and custom software in SlicerHeart. Associations of TV structure to TR grade and right ventricle function and volume were investigated. Shape parameterization and analysis was used to calculate the mean shape of the TV leaflets, their principal modes of variation, and to characterize associations of TV leaflet shape to TR.<br /><b>Results</b><br />In univariate modeling, patients with moderate or greater TR had larger TV annular diameters and area, greater annular distance between the anteroseptal commissure and anteroposterior commissure, greater leaflet billow volume, and more laterally directed anterior papillary muscle angles compared to valves with mild or less TR (all <i>P</i><0.001). In multivariate modeling greater total billow volume, lower anterior papillary muscle angle, and greater distance between the anteroposterior commissure and anteroseptal commissure were associated with moderate or greater TR (<i>P</i><0.001, C statistic=0.85). Larger right ventricle volumes were associated with moderate or greater TR (<i>P</i><0.001). TV shape analysis revealed structural features associated with TR, but also highly heterogeneous TV leaflet structure.<br /><b>Conclusions</b><br />Moderate or greater TR in patients with hypoplastic left heart syndrome with a Fontan circulation is associated with greater leaflet billow volume, a more laterally directed anterior papillary muscle angle, and greater annular distance between the anteroseptal commissure and anteroposterior commissure. However, there is significant heterogeneity of structure in the TV leaflets in regurgitant valves. Given this variability, an image-informed patient-specific approach to surgical planning may be needed to achieve optimal outcomes in this vulnerable and challenging population.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 03 Mar 2023:e014671; epub ahead of print</small></div>

<div><h4>Apical Ischemia Is a Universal Feature of Apical Hypertrophic Cardiomyopathy.</h4><i>Hughes RK, Augusto JB, Knott K, Davies R, ... Captur G, Moon JC</i><br /><b>Background</b><br />Apical hypertrophic cardiomyopathy (ApHCM) accounts for ≈10% of hypertrophic cardiomyopathy cases and is characterized by apical hypertrophy, apical cavity obliteration, and tall ECG R waves with ischemic-looking deep T-wave inversion. These may be present even with <15 mm apical hypertrophy (relative ApHCM). Microvascular dysfunction is well described in hypertrophic cardiomyopathy. We hypothesized that apical perfusion defects would be common in ApHCM.<br /><b>Methods</b><br />A 2-center study using cardiovascular magnetic resonance short- and long-axis quantitative adenosine vasodilator stress perfusion mapping. One hundred patients with ApHCM (68 overt hypertrophy [≥15 mm] and 32 relative ApHCM) were compared with 50 patients with asymmetrical septal hypertrophy hypertrophic cardiomyopathy and 40 healthy volunteer controls. Perfusion was assessed visually and quantitatively as myocardial blood flow and myocardial perfusion reserve.<br /><b>Results</b><br />Apical perfusion defects were present in all overt ApHCM patients (100%), all relative ApHCM patients (100%), 36% of asymmetrical septal hypertrophy hypertrophic cardiomyopathy, and 0% of healthy volunteers (<i>P</i><0.001). In 10% of patients with ApHCM, perfusion defects were sufficiently apical that conventional short-axis views missed them. In 29%, stress myocardial blood flow fell below rest values. Stress myocardial blood flow was most impaired subendocardially, with greater hypertrophy or scar, and with apical aneurysms. Impaired apical myocardial blood flow was most strongly predicted by thicker apical segments (β-coefficient, -0.031 mL/g per min [CI, -0.06 to -0.01]; <i>P</i>=0.013), higher ejection fraction (-0.025 mL/g per min [CI, -0.04 to -0.01]; <i>P</i><0.005), and ECG maximum R-wave height (-0.023 mL/g per min [CI, -0.04 to -0.01]; <i>P</i><0.005).<br /><b>Conclusions</b><br />Apical perfusion defects are universally present in ApHCM at all stages. Its ubiquitous presence along with characteristic ECG suggests ischemia may play a disease-defining role in ApHCM.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Mar 2023; 16:e014907</small></div>

<div><h4>Left Atrial Strain in the Assessment of Diastolic Function in Heart Failure: A Machine Learning Approach.</h4><i>Carluccio E, Cameli M, Rossi A, Dini FL, ... Maffeis C, Ambrosio G</i><br /><b>Background</b><br />Diastolic dysfunction (DD) assessment in heart failure is still challenging. Peak atrial longitudinal strain (PALS) is strongly related to end-diastolic pressure and prognosis, but it is still not part of standard DD assessment. We tested the hypothesis that a machine learning approach would be useful to include PALS in DD classification and refine prognostic stratification.<br /><b>Methods</b><br />In a derivation cohort of 864 heart failure patients in sinus rhythm (age, 66.6±12 years; heart failure with reduced ejection fraction, n=541; heart failure with mildly reduced ejection fraction, n=129; heart failure with preserved ejection fraction, n=194), machine learning techniques were retrospectively applied to PALS and guideline-recommended diastolic variables. Outcome (death/heart failure rehospitalization) of the identified DD-clusters was compared with that by guidelines-based classification. To identify the best combination of variables able to classify patients in one of the identified DD-clusters, classification and regression tree analysis was applied (with DD-clusters as dependent variable and PALS plus guidelines-recommended diastolic variables as explanatory variables). The algorithm was subsequently validated in a prospective cohort of 189 heart failure outpatients (age, 65±13 years).<br /><b>Results</b><br />Three distinct echocardiographic DD-clusters were identified (cluster-1, n=212; cluster-2, n=376; cluster-3 DD, n=276), with modest agreement with guidelines-recommended classification (kappa=0.40; <i>P</i><0.001). DD-clusters were predicted by a simple algorithm including E/A ratio, left atrial volume index, E/e\' ratio, and PALS. After 36.5±29.4 months follow-up, 318 events occurred. Compared to guideline-based classification, DD-clusters showed a better association with events in multivariable models (C-index 0.720 versus 0.733, <i>P</i>=0.033; net reclassification improvement 0.166 [95% CI, 0.035-0.276], <i>P</i>=0.013), without interaction with ejection fraction category. In the validation cohort (median follow-up: 18.5 months), cluster-based classification better predicted outcome than guideline-based classification (C-index 0.80 versus 0.78, <i>P</i>=0.093).<br /><b>Conclusions</b><br />Integrating PALS by machine learning algorithm in DD classification improves risk stratification over recommended current criteria, regardless of ejection fraction status. This proof of concept study needs further validation of the proposed algorithm to assess generalizability to other populations.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 08 Feb 2023:e014605; epub ahead of print</small></div>

<div><h4>Cardiovascular Risk Stratification by Automatic Coronary Artery Calcium Scoring on Pretreatment Chest Computed Tomography in Diffuse Large B-Cell Lymphoma Receiving Anthracycline-Based Chemotherapy: A Multicenter Study.</h4><i>Shen H, Lian Y, Yin J, Zhu M, ... Li X, Zhang J</i><br /><b>Background</b><br />Balancing the cardiovascular risk and benefit of anthracycline-based chemotherapy in patients with diffuse large B-cell lymphoma is an important clinical issue. We aimed to evaluate whether the pretreatment coronary artery calcium score (CACS) can stratify the risk of cancer therapy-related cardiac dysfunction (CTRCD) and major adverse cardiovascular events (MACEs) in patients with diffuse large B-cell lymphoma receiving anthracycline-based chemotherapy.<br /><b>Methods</b><br />The patients with diffuse large B-cell lymphoma from 4 hospitals were retrospectively enrolled. The CACS was automatically calculated on nongated chest computed tomography before treatment using artificial intelligence-CACS software and divided into 3 categories (0, 1-100, and >100). The associations between the CACS and CTRCD and between the CACS and MACEs were assessed by logistic regression and Fine-Gray competing-risk regression model. Nelson-Aalen cumulative risk curve was performed to assess the cumulative incidence of MACEs.<br /><b>Results</b><br />A total of 1468 patients (785 men and 683 women; 100% Asian) were enrolled, and 362 and 185 patients developed CTRCD and MACEs, respectively. Compared with a CACS of 0 (n=826), there was stepwise higher odds of CTRCD with a CACS between 1 and 100 (n=356; odds ratio, 2.587) and a CACS >100 (n=286; odds ratio, 5.239). The CACS was associated with MACEs (1-100 versus 0: subdistribution hazard ratio 3.726; >100 versus 0: subdistribution hazard ratio 7.858; all <i>P</i><0.001). Competing risk-adjusted MACEs rates for patients with a CACS of 0, 1 to 100, and >100 were 1.21%, 8.43%, and 11.19%, respectively, at 3 years, and 3.27%, 16.01%, 31.12%, respectively, at 5 years.<br /><b>Conclusions</b><br />The automatic CACS derived from chest computed tomography before treatment was helpful to identify high-risk patients of CTRCD and MACE and guide clinicians to implement cardiovascular protection strategies in patients with diffuse large B-cell lymphoma who received anthracycline-based chemotherapy.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 07 Feb 2023:e014829; epub ahead of print</small></div>

<div><h4>Myocardial Work in Echocardiography.</h4><i>Marzlin N, Hays AG, Peters M, Kaminski A, ... Tajik AJ, Jain R</i><br /><AbstractText>Myocardial work is an emerging tool in echocardiography that incorporates left ventricular afterload into global longitudinal strain analysis. Myocardial work correlates with myocardial oxygen consumption, and work efficiency can also be assessed. Myocardial work has been evaluated in a variety of clinical conditions to assess the added value of myocardial work compared to left ventricular ejection fraction and global longitudinal strain. This review showcases the current use of myocardial work in adult echocardiography and its possible role in cardiac pathologies.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 03 Feb 2023:e014419; epub ahead of print</small></div>

<div><h4>Pericoronary Adipose Tissue Attenuation in Patients With Acute Coronary Syndrome Versus Stable Coronary Artery Disease.</h4><i>Kuneman JH, van Rosendael SE, van der Bijl P, van Rosendael AR, ... Knuuti J, Bax JJ</i><br /><b>Background</b><br />Pericoronary adipose tissue (PCAT) attenuation has been associated with coronary inflammation and can be evaluated with coronary computed tomography angiography. The aims of this study were to compare the PCAT attenuation across precursors of culprit and nonculprit lesions of patients with acute coronary syndrome versus stable coronary artery disease (CAD).<br /><b>Methods</b><br />In this case-control study, patients with suspected CAD who underwent coronary computed tomography angiography were included. Patients who developed an acute coronary syndrome within 2 years after the coronary computed tomography angiography scan were identified, and patients with stable CAD (defined as any coronary plaque ≥30% luminal diameter stenosis) were 1:2 propensity score matched for age, sex, and cardiac risk factors. The mean PCAT attenuation was analyzed at lesion level and compared between precursors of culprit lesions, nonculprit lesions, and stable coronary plaques.<br /><b>Results</b><br />In total, 198 patients (age 62±10 years, 65% male) were selected, including 66 patients who developed an acute coronary syndrome and 132 propensity matched patients with stable CAD. Overall, 765 coronary lesions were analyzed (culprit lesion precursors: n=66; nonculprit lesion precursors: n=207; and stable lesions: n=492). Culprit lesion precursors had larger total plaque volume, fibro-fatty plaque volume, and low-attenuation plaque volume compared to nonculprit and stable lesions. The mean PCAT attenuation was significantly higher across culprit lesion precursors compared to nonculprit and stable lesions (-63.8±9.7 Hounsfield units versus -68.8±10.6 Hounsfield units versus -69.6±10.6 Hounsfield units, respectively; <i>P</i><0.001), whereas the mean PCAT attenuation around nonculprit and stable lesions was not significantly different (<i>P</i>=0.99).<br /><b>Conclusions</b><br />The mean PCAT attenuation is significantly increased across culprit lesion precursors in patients with acute coronary syndrome, compared to nonculprit lesions of these patients and to lesions of patients with stable CAD, which may suggest a higher intensity of inflammation. PCAT attenuation on coronary computed tomography angiography may be a novel marker to identify high-risk plaques.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Feb 2023; 16:e014672</small></div>

<div><h4>Computed Tomography Radiomics Model Predicts Procedure Success of Coronary Chronic Total Occlusions.</h4><i>Ling R, Chen X, Yu Y, Yu L, ... Li Y, Zhang J</i><br /><b>Background</b><br />Coronary computed tomography (CT) angiography imaging is useful for the preprocedural evaluation of chronic total occlusion (CTO). However, the predictive value of CT radiomics model for successful percutaneous coronary intervention (PCI) has not been studied. We aimed to develop and validate a CT radiomics model for predicting PCI success of CTOs.<br /><b>Methods</b><br />In this retrospective study, a radiomics-based model for predicting PCI success was developed on the training and internal validation sets of 202 and 98 patients with CTO, collected from 1 tertiary hospital. The proposed model was validated on an external test set of 75 CTO patients enrolled from another tertiary hospital. CT radiomics features of each CTO lesion were manually labeled and extracted. Other anatomical parameters, including occlusion length, entry morphology, tortuosity, and calcification burden, were also measured. Fifteen radiomics features, 2 quantitative plaque features, and CT-derived Multicenter CTO Registry of Japan score were used to train different models. The predictive values of each model were evaluated for predicting revascularization success.<br /><b>Results</b><br />In the external test set, 75 patients (60 men; 65 years [58.5, 71.5]) with 83 CTO lesions were assessed. Occlusion length was shorter (13.00 mm versus 29.30 mm, <i>P</i>=0.007) in PCI success group whereas the presence of tortuous course was more commonly presented in PCI failure group (1.49% versus 25.00%, <i>P</i>=0.004). The radiomics score was significantly smaller in PCI success group (0.10 versus 0.55, <i>P</i><0.001). The area under the curve of CT radiomics-based model was significantly higher than that of CT-derived Multicenter CTO Registry of Japan score for predicting PCI success (area under the curve=0.920 versus 0.752, <i>P</i>=0.008). The proposed radiomics model accurately identified 89.16% (74/83) CTO lesions with procedure success.<br /><b>Conclusions</b><br />CT radiomics-based model outperformed CT-derived Multicenter CTO Registry of Japan score for predicting PCI success. The proposed model is more accurate than the conventional anatomical parameters to identify CTO lesions with PCI success.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Feb 2023; 16:e014826</small></div>

<div><h4>Coronary Artery Calcium Density and Cardiovascular Events by Volume Level: The MESA.</h4><i>Bhatia HS, McClelland RL, Denenberg J, Budoff MJ, Allison MA, Criqui MH</i><br /><b>Background</b><br />The Agatston coronary artery calcium (CAC) score provides robust cardiovascular disease risk prediction but upweights plaque area by a density factor. Density, however, has been shown to be inversely associated with events. Using CAC volume and density separately improves risk prediction, but it is unclear how to apply this method clinically. We aimed to evaluate the association between CAC density and cardiovascular disease across the spectrum of CAC volume to better understand how to incorporate these metrics into a single score.<br /><b>Methods</b><br />We performed an analysis of MESA (Multi-Ethnic Study of Atherosclerosis) participants with detectable CAC to evaluate the association between CAC density and events by level of CAC volume using multivariable Cox regression models.<br /><b>Results</b><br />In a cohort of 3316 participants, there was a significant interaction (<i>P</i><0.001) between CAC volume and density for coronary heart disease (CHD) risk (myocardial infarction, CHD death, resuscitated cardiac arrest). Models using CAC volume and density resulted in improvement in the <i>C</i>-index (0.703, SE 0.012 versus 0.687, SE 0.013) and a significant net reclassification improvement (0.208 [95% CI, 0.102-0.306]) compared with the Agatston score for CHD risk prediction. Density was significantly associated with lower CHD risk at volumes ≤130 mm<sup>3</sup> (hazard ratio, 0.57 per unit of density [95% CI, 0.43-0.75]), but the inverse association at volumes >130 mm<sup>3</sup> was not significant (hazard ratio, 0.82 per unit of density [95% CI, 0.55-1.22]).<br /><b>Conclusions</b><br />The lower risk for CHD associated with higher CAC density varied by level of volume, and volume ≤130 mm<sup>3</sup> is a potentially clinically useful cut point. Further study is needed to integrate these findings into a unified CAC scoring method.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Feb 2023; 16:e014788</small></div>

<div><h4>Nuclear Methods for Immune Cell Imaging: Bridging Molecular Imaging and Individualized Medicine.</h4><i>Heo GS, Diekmann J, Thackeray JT, Liu Y</i><br /><AbstractText>Inflammation is a key mechanistic contributor to the progression of cardiovascular disease, from atherosclerosis through ischemic injury and overt heart failure. Recent evidence has identified specific roles of immune cell subpopulations in cardiac pathogenesis that diverges between individual patients. Nuclear imaging approaches facilitate noninvasive and serial quantification of inflammation severity, offering the opportunity to predict eventual outcome, stratify patient risk, and guide novel targeted molecular therapies against specific leukocyte subpopulations. Here, we will discuss the established and emerging nuclear imaging methods to label and track exogenous and endogenous immune cells, with a particular focus on clinical situations in which targeted molecular inflammation imaging would be advantageous. The expanding options for imaging inflammation provide the foundation to bridge between molecular imaging and individual therapy.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Jan 2023; 16:e014067</small></div>

<div><h4>Molecular Imaging of Valvular Diseases and Cardiac Device Infection.</h4><i>Tarkin JM, Chen W, Dweck MR, Dilsizian V</i><br /><AbstractText>The use of positron emission tomography imaging with <sup>18</sup>F-fluorodeoxyglucose in the diagnostic workup of patients with suspected prosthetic valve endocarditis and cardiac device infection (implantable electronic device and left ventricular assist device) is gaining momentum in clinical practice. However, in the absence of prospective randomized trials, guideline recommendations about <sup>18</sup>F-fluorodeoxyglucose positron emission tomography in this setting are currently largely based on expert opinion. Measurement of aortic valve microcalcification occurring as a healing response to valvular inflammation using <sup>18</sup>F-sodium fluoride positron emission tomography represents another promising clinical approach, which is associated with both the risk of native valve stenosis progression and bioprosthetic valve degeneration in research trials. In this review, we consider the role of molecular imaging in cardiac valvular diseases, including aortic stenosis and valvular endocarditis, as well as cardiac device infections.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Jan 2023; 16:e014652</small></div>

<div><h4>Imaging Methods: Magnetic Resonance Imaging.</h4><i>Thomas KE, Fotaki A, Botnar RM, Ferreira VM</i><br /><AbstractText>Myocardial inflammation occurs following activation of the cardiac immune system, producing characteristic changes in the myocardial tissue. Cardiovascular magnetic resonance is the non-invasive imaging gold standard for myocardial tissue characterization, and is able to detect image signal changes that may occur resulting from inflammation, including edema, hyperemia, capillary leak, necrosis, and fibrosis. Conventional cardiovascular magnetic resonance for the detection of myocardial inflammation and its sequela include T2-weighted imaging, parametric T1- and T2-mapping, and gadolinium-based contrast-enhanced imaging. Emerging techniques seek to image several parameters simultaneously for myocardial tissue characterization, and to depict subtle immune-mediated changes, such as immune cell activity in the myocardium and cardiac cell metabolism. This review article outlines the underlying principles of current and emerging cardiovascular magnetic resonance methods for imaging myocardial inflammation.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Jan 2023; 16:e014068</small></div>

<div><h4>Clinical Utilization of Multimodality Imaging for Myocarditis and Cardiac Sarcoidosis.</h4><i>Chareonthaitawee P, Gutberlet M</i><br /><AbstractText>Myocarditis is defined as inflammation of the myocardium according to clinical, histological, biochemical, immunohistochemical, or imaging findings. Inflammation can be categorized histologically by cell type or pattern, and many causes have been implicated, including infectious, most commonly viral, systemic autoimmune diseases, vaccine-associated processes, environmental factors, toxins, and hypersensitivity to drugs. Sarcoid myocarditis is increasingly recognized as an important cause of cardiomyopathy and has important diagnostic, prognostic, and therapeutic implications in patients with systemic sarcoidosis. The clinical presentation of myocarditis may include an asymptomatic, subacute, acute, fulminant, or chronic course and may have focal or diffuse involvement of the myocardium depending on the cause and time point of the disease. For most causes of myocarditis except sarcoidosis, myocardial biopsy is the gold standard but is limited due to risk, cost, availability, and variable sensitivity. Diagnostic criteria have been established for both myocarditis and cardiac sarcoidosis and include clinical and imaging findings particularly the use of cardiac magnetic resonance and positron emission tomography. Beyond diagnosis, imaging findings may also provide prognostic value. This case-based review focuses on the current state of multimodality imaging for the diagnosis and management of myocarditis and cardiac sarcoidosis, highlighting multimodality imaging approaches with practical clinical vignettes, with a discussion of knowledge gaps and future directions.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Jan 2023; 16:e014091</small></div>

<div><h4>Imaging Targets to Visualize the Cardiac Immune Landscape in Heart Failure.</h4><i>Wienecke LM, Leid JM, Leuschner F, Lavine KJ</i><br /><AbstractText>Heart failure involves a complex interplay between diverse populations of immune cells that dynamically shift across the natural history of disease. Within this context, the character of the immune response is a key determinant of clinical outcomes. Recent technological advances in single-cell transcriptomic, spatial, and proteomic technologies have fueled an explosion of new and clinically relevant insights into distinct immune cell populations that reside within the diseased heart including potential targets for molecular imaging and therapy. In this review, we will discuss the immune cell types and their respective functions with respect to myocardial infarction remodeling, dilated cardiomyopathy, and heart failure with preserved ejection fraction. In addition, we give a brief overview regarding myocarditis and cardiac sarcoidosis as inflammatory heart failure etiologies. We will highlight markers and cell populations as targets for molecular imaging to visualize inflammation and tissue healing and discuss clinical implications including the development and implementation of precision medicine approaches.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Jan 2023; 16:e014071</small></div>

<div><h4>Positron Emission Tomography Imaging of Vessel Wall Matrix Metalloproteinase Activity in Abdominal Aortic Aneurysm.</h4><i>Toczek J, Gona K, Liu Y, Ahmad A, ... Gropler RJ, Sadeghi MM</i><br /><b>Background</b><br />Matrix metalloproteinases (MMPs) play a key role in the pathogenesis of abdominal aortic aneurysm (AAA). Imaging aortic MMP activity, especially using positron emission tomography to access high sensitivity, quantitative data, could potentially improve AAA risk stratification. Here, we describe the design, synthesis, characterization, and evaluation in murine AAA and human aortic tissue of a first-in-class MMP-targeted positron emission tomography radioligand, <sup>64</sup>Cu-RYM2.<br /><b>Methods</b><br />The broad spectrum MMP inhibitor, RYM2 was synthetized, and its potency as an MMP inhibitor was evaluated by a competitive inhibition assay. Toxicology studies were performed. Tracer biodistribution was evaluated in a murine model of AAA induced by angiotensin II infusion in Apolipoprotein E-deficient mice. <sup>64</sup>Cu-RYM2 binding to normal and aneurysmal human aortic tissues was assessed by autoradiography.<br /><b>Results</b><br />RYM2 functioned as an MMP inhibitor with nanomolar affinities. Toxicology studies showed no adverse reaction in mice. Upon radiolabeling with Cu-64, the resulting tracer was stable in murine and human blood in vitro. Biodistribution and metabolite analysis in mice showed rapid renal clearance and acceptable in vivo stability. In vivo positron emission tomography/computed tomography in a murine model of AAA showed a specific aortic signal, which correlated with ex vivo measured MMP activity and <i>Cd68</i> gene expression. <sup>64</sup>Cu-RYM2 specifically bound to normal and aneurysmal human aortic tissues in correlation with MMP activity.<br /><b>Conclusions</b><br /><sup>64</sup>Cu-RYM2 is a first-in-class MMP-targeted positron emission tomography tracer with favorable stability, biodistribution, performance in preclinical AAA, and importantly, specific binding to human tissues. These data set the stage for <sup>64</sup>Cu-RYM2-based translational imaging studies of vessel wall MMP activity, and indirectly, inflammation, in AAA.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Jan 2023; 16:e014615</small></div>

<div><h4>Impact of Metabolic Activity of Vertebra and Amygdala on Stroke Recurrence: A Prospective Cohort Study.</h4><i>Kim JM, Lee R, Kim Y, Jeong HB, ... Park KY, Won Seok J</i><br /><b>Background</b><br />Elevated metabolic activity of amygdala is known to be related to atherosclerotic cardiovascular event by increasing inflammatory cell production from bone marrow. We tried to identify the factors of metabolic activity in the amygdala, vertebrae, liver, spleen, and internal carotid artery related to the future vascular events after stroke.<br /><b>Methods</b><br />A total of 110 patients with acute stroke were included (72±10 years of age, 39% women) and underwent whole-body <sup>18</sup>F-fluorodeoxyglucose (FDG) positron emission tomography between August 1, 2015 and February 28, 2020. We compared the FDG uptake in the amygdala, vertebrae, liver, spleen, and internal carotid artery between patients with and without recurrent vascular event. Cox proportional hazards model was used to identify factors related to recurrent stroke and vascular event.<br /><b>Results</b><br />During the median follow-up period of 18 months, 22 patients experienced vascular events, including 15 stroke recurrence. Patients with recurred vascular event had a significantly higher FDG uptake in the amygdala and vertebrae than those without. The Cox proportional hazard model including diabetes, renal function, and carotid stenosis showed that a higher FDG uptake in the amygdala was independently associated with total vascular events (hazard ratio, 3.11 [95% CI, 1.11-8.70]) and higher FDG uptake in the vertebrae with stroke recurrence (hazard ratio, 4.94 [95% CI, 1.29-18.9]).<br /><b>Conclusions</b><br />The increased metabolic activities of the vertebrae and amygdala are related to future vascular event among stroke survivors.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 01 Jan 2023; 16:e014544</small></div>

<div><h4>Utilization of Cardiovascular Magnetic Resonance Imaging for Resumption of Athletic Activities Following COVID-19 Infection: An Expert Consensus Document on Behalf of the American Heart Association Council on Cardiovascular Radiology and Intervention Leadership and Endorsed by the Society for Cardiovascular Magnetic Resonance.</h4><i>Ruberg FL, Baggish AL, Hays AG, Jerosch-Herold M, ... Weinsaft JW, Woodard PK</i><br /><AbstractText>The global pandemic of COVID-19 caused by infection with SARS-CoV-2 is now entering its fourth year with little evidence of abatement. As of December 2022, the World Health Organization Coronavirus (COVID-19) Dashboard reported 643 million cumulative confirmed cases of COVID-19 worldwide and 98 million in the United States alone as the country with the highest number of cases. Although pneumonia with lung injury has been the manifestation of COVID-19 principally responsible for morbidity and mortality, myocardial inflammation and systolic dysfunction though uncommon are well-recognized features that also associate with adverse prognosis. Given the broad swath of the population infected with COVID-19, the large number of affected professional, collegiate, and amateur athletes raises concern regarding the safe resumption of athletic activity (return to play) following resolution of infection. A variety of different testing combinations that leverage ECG, echocardiography, circulating cardiac biomarkers, and cardiovascular magnetic resonance imaging have been proposed and implemented to mitigate risk. Cardiovascular magnetic resonance in particular affords high sensitivity for myocarditis but has been employed and interpreted nonuniformly in the context of COVID-19 thereby raising uncertainty as to the generalizability and clinical relevance of findings with respect to return to play. This consensus document synthesizes available evidence to contextualize the appropriate utilization of cardiovascular magnetic resonance in the return to play assessment of athletes with prior COVID-19 infection to facilitate informed, evidence-based decisions, while identifying knowledge gaps that merit further investigation.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 21 Dec 2022:e014106; epub ahead of print</small></div>

<div><h4>Association of Lipoprotein (a) With Coronary-Computed Tomography Angiography-Assessed High-Risk Coronary Disease Attributes and Cardiovascular Outcomes.</h4><i>Dai N, Chen Z, Zhou F, Zhou Y, ... Qian J, Ge J</i><br /><b>Background</b><br />Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular events. This study evaluated the relationship between Lp(a) and high-risk attributes by coronary computed tomography angiography as well as their prognostic value.<br /><b>Methods</b><br />Lp(a) and coronary computed tomography angiography from 377 consecutive patients at Zhongshan Hospital (Shanghai, China) were evaluated. High-risk attributes were defined as high-risk morphological attributes (low attenuation plaque, positive remodeling, napkin-ring sign, spotty calcification, minimum lumen area <4 mm<sup>2</sup>, or plaque burden [ratio between cross-sectional plaque area at the site of maximum stenosis and cross-sectional vessel area] ≥70%); inflammatory attribute represented by fat attenuation index; high-risk physiological attributes [lesion-specific ischemia defined by fractional flow reserve by coronary computed tomography angiography ≤0.8, physiologic diffuseness defined by fractional flow reserve by coronary computed tomography angiography pullback pressure gradient]. Total plaque volume in mm<sup>3</sup> was also quantified. Quintiles or binary classification of Lp(a) levels were used to evaluate its relationships with plaque features and clinical outcomes with ANOVA, Cox models, and log-rank tests, as appropriate. The major adverse cardiovascular event included cardiovascular death, nonfatal myocardial infarction, and target vessel revascularization.<br /><b>Results</b><br />Lp(a) was significantly associated with total plaque volume (<i>P</i>=0.004), fat attenuation index (<i>P</i>=0.031), and fractional flow reserve by coronary computed tomography angiography pullback pressure gradient (<i>P</i>=0.038). Patients with a high Lp(a) level had a higher total plaque volume (393.3 mm<sup>3</sup> versus 293.9 mm<sup>3</sup>, <i>P</i><0.001), lower pullback pressure gradient (0.62 versus 0.69, <i>P</i>=0.023), higher fat attenuation index (-70.5HU versus -73.9HU, <i>P</i>=0.004), and higher incidence of major adverse cardiovascular event (14.5% versus 6.3%, adjusted hazard ratio: 2.52, 95% CI: 1.12-5.63, <i>P</i>=0.025). In a 4-group classification according to Lp(a) and high-risk attributes, patients with high Lp(a) and ≥3 high-risk attributes had the highest risk of major adverse cardiovascular event (25.9%; overall <i>P</i><0.001). Causal mediation analysis revealed that around 40% of the prognostic effect of Lp(a) was mediated by high-risk attributes.<br /><b>Conclusions</b><br />Lp(a) level is associated with coronary computed tomography angiography high-risk characteristics, including morphologic, physiologic, and inflammatory attributes as well as major adverse cardiovascular event. This effect is partly mediated by inflammation and vulnerable plaque.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT05323227.<br /><br /><br /><br /><small>Circ Cardiovasc Imaging: 12 Dec 2022:e014611; epub ahead of print</small></div>