<div><h4>Prognostic Value of Preprocedural LV Global Longitudinal Strain for Post-TAVR-Related Morbidity and Mortality: A Meta-Analysis.</h4><i>Stens NA, van Iersel O, Rooijakkers MJP, van Wely MH, ... van Royen N, Thijssen DHJ</i><br /><b>Background</b><br />Left ventricular ejection fraction (LVEF) demonstrates limited prognostic value for post-transcatheter aortic valve replacement (TAVR) outcomes. Evidence regarding the potential role of left ventricular global longitudinal strain (LV-GLS) in this setting is inconsistent.<br /><b>Objectives</b><br />The aim of this systematic review and meta-analysis of aggregated data was to evaluate the prognostic value of preprocedural LV-GLS for post-TAVR-related morbidity and mortality.<br /><b>Methods</b><br />The authors searched PubMed, Embase, and Web of Science for studies investigating the association between preprocedural 2-dimensional speckle-tracking-derived LV-GLS and post-TAVR clinical outcomes. An inversely weighted random effects meta-analysis was adopted to investigate the association between LV-GLS vs primary (ie, all-cause mortality) and secondary (ie, major cardiovascular events [MACE]) post-TAVR outcomes.<br /><b>Results</b><br />Of the 1,130 identified records, 12 were eligible, all of which had a low-to-moderate risk of bias (Newcastle-Ottawa scale). On average, 2,049 patients demonstrated preserved LVEF (52.6% ± 1.7%), but impaired LV-GLS (-13.6% ± 0.6%). Patients with a lower LV-GLS had a higher all-cause mortality (pooled HR: 2.01; 95% CI: 1.59-2.55) and MACE (pooled odds ratio [OR]: 1.26; 95% CI: 1.08-1.47) risk compared with patients with higher LV-GLS. In addition, each percentage point decrease of LV-GLS (ie, toward 0%) was associated with an increased mortality (HR: 1.06; 95% CI: 1.04-1.08) and MACE risk (OR: 1.08; 95% CI: 1.01-1.15).<br /><b>Conclusions</b><br />Preprocedural LV-GLS was significantly associated with post-TAVR morbidity and mortality. This suggests a potential clinically important role of pre-TAVR evaluation of LV-GLS for risk stratification of patients with severe aortic stenosis. (Prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis undergoing Transcatheter Aortic Valve Implantation: a meta-analysis; CRD42021289626).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Mar 2023; 16:332-341</small></div>

<div><h4>Diagnostic and Prognostic Role of Cardiac Magnetic Resonance in MINOCA: Systematic Review and Meta-Analysis.</h4><i>Mileva N, Paolisso P, Gallinoro E, Fabbricatore D, ... Andreini D, Vassilev D</i><br /><b>Background</b><br />Myocardial infarction with nonobstructive coronary arteries (MINOCA) is common in current clinical practice. Cardiac magnetic resonance (CMR) plays an important role in its management and is increasingly recommended by all the current guidelines. However, the prognostic value of CMR in patients with MINOCA is still undetermined.<br /><b>Objectives</b><br />The purpose of this study was to determine the diagnostic and prognostic value of CMR in the management of patients with MINOCA.<br /><b>Methods</b><br />A systematic review was performed to identify studies reporting the results of CMR findings in patients with MINOCA. Random effects models were used to determine the prevalence of different disease entities: myocarditis, myocardial infarction (MI), or takotsubo syndrome. Pooled odds ratios (ORs) and 95% CIs were calculated to evaluate the prognostic value of CMR diagnosis in the subgroup of studies that reported clinical outcomes.<br /><b>Results</b><br />A total of 26 studies comprising 3,624 patients were included. The mean age was 54.2 ± 5.3 years, and 56% were men. MINOCA was confirmed in only 22% (95% CI: 0.17-0.26) of the cases and 68% of patients with initial MINOCA were reclassified after the CMR assessment. The pooled prevalence of myocarditis was 31% (95% CI: 0.25-0.39), and takotsubo syndrome 10% (95% CI: 0.06-0.12). In a subgroup analysis of 5 studies (770 patients) that reported clinical outcomes, CMR diagnosis of confirmed MI was associated with an increased risk of major adverse cardiovascular events (pooled OR: 2.40; 95% CI: 1.60-3.59).<br /><b>Conclusions</b><br />In patients with MINOCA, CMR has been demonstrated to add an important diagnostic and prognostic value, proving to be crucial for the diagnosis of this condition. Sixty-eight percent of patients with initial MINOCA were reclassified after the CMR evaluation. CMR-confirmed diagnosis of MINOCA was associated with an increased risk of major adverse cardiovascular events at follow-up.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Mar 2023; 16:376-389</small></div>

<div><h4>Excessive Trabeculation of the Left Ventricle: JACC: Cardiovascular Imaging Expert Panel Paper.</h4><i>Petersen SE, Jensen B, Aung N, Friedrich MG, ... Anderson RH, Bluemke DA</i><br /><AbstractText>Excessive trabeculation, often referred to as \"noncompacted\" myocardium, has been described at all ages, from the fetus to the adult. Current evidence for myocardial development, however, does not support the formation of compact myocardium from noncompacted myocardium, nor the arrest of this process to result in so-called noncompaction. Excessive trabeculation is frequently observed by imaging studies in healthy individuals, as well as in association with pregnancy, athletic activity, and with cardiac diseases of inherited, acquired, developmental, or congenital origins. Adults with incidentally noted excessive trabeculation frequently require no further follow-up based on trabecular pattern alone. Patients with cardiomyopathy and excessive trabeculation are managed by cardiovascular symptoms rather than the trabecular pattern. To date, the prognostic role of excessive trabeculation in adults has not been shown to be independent of other myocardial disease. In neonates and children with excessive trabeculation and normal or abnormal function, clinical caution seems warranted because of the reported association with genetic and neuromuscular disorders. This report summarizes the evidence concerning the etiology, pathophysiology, and clinical relevance of excessive trabeculation. Gaps in current knowledge of the clinical relevance of excessive trabeculation are indicated, with priorities suggested for future research and improved diagnosis in adults and children.</AbstractText><br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 06 Feb 2023; epub ahead of print</small></div>

<div><h4>Sex-Specific Stress Perfusion Cardiac Magnetic Resonance Imaging in Suspected Ischemic Heart Disease: Insights From SPINS Retrospective Registry.</h4><i>Heydari B, Ge Y, Antiochos P, Islam S, ... Simonetti OP, Kwong RY</i><br /><b>Background</b><br />Cardiovascular disease (CVD) remains the leading cause of mortality in women, but current noninvasive cardiac imaging techniques have sex-specific limitations.<br /><b>Objectives</b><br />In this study, the authors sought to investigate the effect of sex on the prognostic utility and downstream invasive revascularization and costs of stress perfusion cardiac magnetic resonance (CMR) for suspected CVD.<br /><b>Methods</b><br />Sex-specific prognostic performance was evaluated in a 2,349-patient multicenter SPINS (Stress CMR Perfusion Imaging in the United States [SPINS] Study) registry. The primary outcome measure was a composite of cardiovascular death and nonfatal myocardial infarction; secondary outcomes were hospitalization for unstable angina or heart failure, and late unplanned coronary artery bypass grafting.<br /><b>Results</b><br />SPINS included 1,104 women (47% of cohort); women had higher prevalence of chest pain (62% vs 50%; P < 0.0001) but lower use of medical therapies. At the 5.4-year median follow-up, women with normal stress CMR had a low annualized rate of primary composite outcome similar to men (0.54%/y vs 0.75%/y, respectively; P = NS). In contrast, women with abnormal CMR were at higher risk for both primary (3.74%/y vs 0.54%/y; P < 0.0001) and secondary (9.8%/y vs 1.6%/y; P < 0.0001) outcomes compared with women with normal CMR. Abnormal stress CMR was an independent predictor for the primary (HR: 2.64 [95% CI: 1.20-5.90]; P = 0.02) and secondary (HR: 2.09 [95% CI: 1.43-3.08]; P < 0.0001) outcome measures. There was no effect modification for sex. Women had lower rates of invasive coronary angiography (ICA; 3.6% vs 7.3%; P = 0.0001) and downstream costs ($114 vs $171; P = 0.001) at 90 days following CMR. There was no effect of sex on diagnostic image quality.<br /><b>Conclusions</b><br />Stress CMR demonstrated excellent prognostic performance with lower rates of ICA referral in women. Stress CMR should be considered as a first-line noninvasive imaging tool for the evaluation of women. (Stress CMR Perfusion Imaging in the United States [SPINS] Study [SPINS]; NCT03192891).<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>JACC Cardiovasc Imaging: 27 Jan 2023; epub ahead of print</small></div>

<div><h4>Normalized Echocardiographic Values From Guideline-Directed Dedicated Views for Cardiac Dimensions and Left Ventricular Function.</h4><i>Eriksen-Volnes T, Grue JF, Hellum Olaisen S, Letnes JM, ... Wisløff U, Dalen H</i><br /><b>Background</b><br />Continuous technologic development and updated recommendations for image acquisitions creates a need to update the current normal reference ranges for echocardiography. The best method of indexing cardiac volumes is unknown.<br /><b>Objectives</b><br />The authors used 2- and 3-dimensional echocardiographic data from a large cohort of healthy individuals to provide updated normal reference data for dimensions and volumes of the cardiac chambers as well as central Doppler measurements.<br /><b>Methods</b><br />In the fourth wave of the HUNT (Trøndelag Health) study in Norway 2,462 individuals underwent comprehensive echocardiography. Of these, 1,412 (55.8% women) were classified as normal and formed the basis for updated normal reference ranges. Volumetric measures were indexed to body surface area and height in powers of 1 to 3.<br /><b>Results</b><br />Normal reference data for echocardiographic dimensions, volumes, and Doppler measurements were presented according to sex and age. Left ventricular ejection fraction had lower normal limits of 50.8% for women and 49.6% for men. According to sex-specific age groups, the upper normal limits for left atrial end-systolic volume indexed to body surface area ranged from 44 mL/m<sup>2</sup> to 53 mL/m<sup>2</sup>, and the corresponding upper normal limit for right ventricular basal dimension ranged from 43 mm to 53 mm. Indexing to height raised to the power of 3 accounted for more of the variation between sexes than indexing to body surface area.<br /><b>Conclusions</b><br />The authors present updated normal reference values for a wide range of echocardiographic measures of both left- and right-side ventricular and atrial size and function from a large healthy population with a wide age-span. The higher upper normal limits for left atrial volume and right ventricular dimension highlight the importance of updating reference ranges accordingly following refinement of echocardiographic methods.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 14 Jan 2023; epub ahead of print</small></div>

<div><h4>Managing Patients With Moderate Aortic Stenosis.</h4><i>Stassen J, Ewe SH, Pio SM, Pibarot P, ... Leon MB, Bax JJ</i><br /><AbstractText>Current guidelines recommend that clinical surveillance for patients with moderate aortic stenosis (AS) and aortic valve replacement (AVR) may be considered if there is an indication for coronary revascularization. Recent observational studies, however, have shown that moderate AS is associated with an increased risk of cardiovascular events and mortality. Whether the increased risk of adverse events is caused by associated comorbidities, or to the underlying moderate AS itself, is incompletely understood. Similarly, which patients with moderate AS need close follow-up or could potentially benefit from early AVR is also unknown. In this review, the authors provide a comprehensive overview of the current literature on moderate AS. They first provide an algorithm that helps to diagnose moderate AS correctly, especially when discordant grading is observed. Although the traditional focus of AS assessment has been on the valve, it is increasingly acknowledged that AS is not only a disease of the aortic valve but also of the ventricle. The authors therefore discuss how multimodality imaging can help to evaluate the left ventricular remodeling response and improve risk stratification in patients with moderate AS. Finally, they summarize current evidence on the management of moderate AS and highlight ongoing trials on AVR in moderate AS.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 14 Jan 2023; epub ahead of print</small></div>

<div><h4>PET for Detection and Reporting Coronary Microvascular Dysfunction: A JACC: Cardiovascular Imaging Expert Panel Statement.</h4><i>Schindler TH, Fearon WF, Pelletier-Galarneau M, Ambrosio G, ... Schelbert HR, Dilsizian V</i><br /><AbstractText>Angina pectoris and dyspnea in patients with normal or nonobstructive coronary vessels remains a diagnostic challenge. Invasive coronary angiography may identify up to 60% of patients with nonobstructive coronary artery disease (CAD), of whom nearly two-thirds may, in fact, have coronary microvascular dysfunction (CMD) that may account for their symptoms. Positron emission tomography (PET) determined absolute quantitative myocardial blood flow (MBF) at rest and during hyperemic vasodilation with subsequent derivation of myocardial flow reserve (MFR) affords the noninvasive detection and delineation of CMD. Individualized or intensified medical therapies with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1-receptor blockers, beta-blockers, ivabradine, or ranolazine may improve symptoms, quality of life, and outcome in these patients. Standardized diagnosis and reporting criteria for ischemic symptoms caused by CMD are critical for optimized and individualized treatment decisions in such patients. In this respect, it was proposed by the cardiovascular council leadership of the Society of Nuclear Medicine and Molecular Imaging to convene thoughtful leaders from around the world to serve as an independent expert panel to develop standardized diagnosis, nomenclature and nosology, and cardiac PET reporting criteria for CMD. This consensus document aims to provide an overview of the pathophysiology and clinical evidence of CMD, its invasive and noninvasive assessment, standardization of PET-determined MBFs and MFR into \"classical\" (predominantly related to hyperemic MBFs) and \"endogen\" (predominantly related to resting MBF) normal coronary microvascular function or CMD that may be critical for diagnosis of microvascular angina, subsequent patient care, and outcome of clinical CMD trials.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 11 Jan 2023; epub ahead of print</small></div>

<div><h4>Apical Aneurysms and Mid-Left Ventricular Obstruction in Hypertrophic Cardiomyopathy.</h4><i>Sherrid MV, Bernard S, Tripathi N, Patel Y, ... Fifer MA, Kim B</i><br /><b>Background</b><br />Apical left ventricular (LV) aneurysms in hypertrophic cardiomyopathy (HCM) are associated with adverse outcomes. The reported frequency of mid-LV obstruction has varied from 36% to 90%.<br /><b>Objectives</b><br />The authors sought to ascertain the frequency of mid-LV obstruction in HCM apical aneurysms.<br /><b>Methods</b><br />The authors analyzed echocardiographic and cardiac magnetic resonance examinations of patients with aneurysms from 3 dedicated programs and compared them with 63 normal controls and 47 controls with apical-mid HCM who did not have aneurysms (22 with increased LV systolic velocities).<br /><b>Results</b><br />There were 108 patients with a mean age of 57.4 ± 13.5 years; 40 (37%) were women. One hundred three aneurysm patients (95%) had mid-LV obstruction with mid-LV complete systolic emptying. Of the patients with obstruction, 84% had a midsystolic Doppler signal void, a marker of complete flow cessation, but only 19% had Doppler systolic gradients ≥30 mm Hg. Five patients (5%) had relative hypokinesia in mid-LV without obstruction. Aneurysm size is not bimodal but appears distributed by power law, with large aneurysms decidedly less common. Comparing mid-LV obstruction aneurysm patients with all control groups, the short-axis (SAX) systolic areas were smaller (P < 0.007), the percent SAX area change was greater (P < 0.005), the papillary muscle (PM) areas were larger (P < 0.003), and the diastolic PM areas/SAX diastolic areas were greater (P < 0.005). Patients with aneurysms had 22% greater SAX PM areas compared with those with elevated LV velocities but no aneurysms (median: 3.00 cm<sup>2</sup> [IQR: 2.38-3.70 cm<sup>2</sup>] vs 2.45 [IQR: 1.81-2.95 cm<sup>2</sup>]; P = 0.004). Complete emptying occurs circumferentially around central PMs that contribute to obstruction. Late gadolinium enhancement was always brightest and the most transmural apical of, or at the level of, complete emptying.<br /><b>Conclusions</b><br />The great majority (95%) of patients in the continuum of apical aneurysms have associated mid-LV obstruction. Further research to investigate obstruction as a contributing cause to apical aneurysms is warranted.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 11 Jan 2023; epub ahead of print</small></div>

<div><h4>Atrial Functional Tricuspid Regurgitation: Importance of Atrial Fibrillation and Right Atrial Remodeling and Prognostic Significance.</h4><i>Kwak S, Lim J, Yang S, Rhee TM, ... Cho GY, Park JB</i><br /><b>Background</b><br />Little is known about the determinants and outcomes of significant atrial functional tricuspid regurgitation (AFTR).<br /><b>Objectives</b><br />The authors aimed to identify risk factors for significant TR in relation to atrial fibrillation-flutter (AF-AFL) and assess its prognostic implications.<br /><b>Methods</b><br />The authors retrospectively studied patients with mild TR with follow-up echocardiography examinations. Significant TR was defined as greater than or equal to moderate TR. AFTR was defined as TR, attributed to right atrial (RA) remodeling or isolated tricuspid annular dilatation, without other primary or secondary etiology, except for AF-AFL. The Mantel-Byar test was used to compare clinical outcomes by progression of AFTR.<br /><b>Results</b><br />Of 833 patients with mild TR, 291 (34.9%) had AF-AFL. During the median 4.6 years, significant TR developed in 35 patients, including 33 AFTRs. Significant AFTR occurred in patients with AF-AFL more predominantly than in those patients without AF-AFL (10.3% vs 0.6%; P < 0.001). In Cox analysis, AF-AFL was a strong risk factor for AFTR (adjusted HR: 8.33 [95% CI: 2.34-29.69]; P = 0.001). Among patients with AF-AFL, those who developed significant AFTR had larger baseline RA areas (23.8 vs 19.4 cm<sup>2</sup>; P < 0.001) and RA area-to-right ventricle end-systolic area ratio (3.0 vs 2.3; P < 0.001) than those who did not. These parameters were independent predictors of AFTR progression. The 10-year major adverse cardiovascular event was significantly higher after progression of AFTR than before or without progression (79.8% vs 8.6%; Mantel-Byar P < 0.001).<br /><b>Conclusions</b><br />In patients with mild TR, significant AFTR developed predominantly in patients with AF-AFL, conferring poor prognosis. RA enlargement, especially with increased RA area-to-right ventricle end-systolic area ratio, was a strong risk factor for progression of AFTR.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 11 Jan 2023; epub ahead of print</small></div>

<div><h4>Machine Learning to Optimize the Echocardiographic Follow-Up of Aortic Stenosis.</h4><i>Sánchez-Puente A, Dorado-Díaz PI, Sampedro-Gómez J, Bermejo J, ... Vicente-Palacios V, Sanchez PL</i><br /><b>Background</b><br />Disease progression in patients with mild-to-moderate aortic stenosis is heterogenous and requires periodic echocardiographic examinations to evaluate severity.<br /><b>Objectives</b><br />This study sought to explore the use of machine learning to optimize aortic stenosis echocardiographic surveillance automatically.<br /><b>Methods</b><br />The study investigators trained, validated, and externally applied a machine learning model to predict whether a patient with mild-to-moderate aortic stenosis will develop severe valvular disease at 1, 2, or 3 years. Demographic and echocardiographic patient data to develop the model were obtained from a tertiary hospital consisting of 4,633 echocardiograms from 1,638 consecutive patients. The external cohort was obtained from an independent tertiary hospital, consisting of 4,531 echocardiograms from 1,533 patients. Echocardiographic surveillance timing results were compared with the European and American guidelines echocardiographic follow-up recommendations.<br /><b>Results</b><br />In internal validation, the model discriminated severe from nonsevere aortic stenosis development with an area under the receiver-operating characteristic curve (AUC-ROC) of 0.90, 0.92, and 0.92 for the 1-, 2-, or 3-year interval, respectively. In external application, the model showed an AUC-ROC of 0.85, 0.85, and 0.85, for the 1-, 2-, or 3-year interval. A simulated application of the model in the external validation cohort resulted in savings of 49% and 13% of unnecessary echocardiographic examinations per year compared with European and American guideline recommendations, respectively.<br /><b>Conclusions</b><br />Machine learning provides real-time, automated, personalized timing of next echocardiographic follow-up examination for patients with mild-to-moderate aortic stenosis. Compared with European and American guidelines, the model reduces the number of patient examinations.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 10 Jan 2023; epub ahead of print</small></div>

<div><h4>Deep-Learning for Epicardial Adipose Tissue Assessment With Computed Tomography: Implications for Cardiovascular Risk Prediction.</h4><i>West HW, Siddique M, Williams MC, Volpe L, ... Antoniades C, ORFAN Investigators</i><br /><b>Background</b><br />Epicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented.<br /><b>Objectives</b><br />This study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care.<br /><b>Methods</b><br />The deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value.<br /><b>Results</b><br />External validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio [OR] per SD increase in EAT volume: 1.13 [95% CI: 1.04-1.30]; P = 0.01), and atrial fibrillation (OR: 1.25 [95% CI:1.08-1.40]; P = 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD: 1.28 [95% CI: 1.10-1.37]; P = 0.02), myocardial infarction (HR: 1.26 [95% CI:1.09-1.38]; P = 0.001), and stroke (HR: 1.20 [95% CI: 1.09-1.38]; P = 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR: 2.67 [95% CI: 1.26-3.73]; P ≤ 0.01) and long-term post-cardiac surgery atrial fibrillation (7-year follow-up; HR: 2.14 [95% CI: 1.19-2.97]; P ≤ 0.01).<br /><b>Conclusions</b><br />Automated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 10 Jan 2023; epub ahead of print</small></div>

<div><h4>Too Little of a Good Thing: Strong Associations Between Cardiac Size and Fitness Among Women.</h4><i>Foulkes SJ, Howden EJ, Dillon HT, Janssens K, ... Haykowsky MJ, La Gerche A</i><br /><b>Background</b><br />Cardiorespiratory fitness (CRF) is associated with functional impairment and cardiac events, particularly heart failure (HF). However, the factors predisposing women to low CRF and HF remain unclear.<br /><b>Objectives</b><br />This study sought to evaluate the association between CRF and measures of ventricular size and function and to examine the potential mechanism linking these factors.<br /><b>Methods</b><br />A total of 185 healthy women aged >30 years (51 ± 9 years) underwent assessment of CRF (peak volume of oxygen uptake [Vo<sub>2</sub>peak]) and biventricular volumes at rest and during exercise by using cardiac magnetic resonance (CMR). The relationships among Vo<sub>2</sub>peak, cardiac volumes, and echocardiographic measures of systolic and diastolic function were assessed using linear regression. The effect of cardiac size on cardiac reserve (change in cardiac function during exercise) was assessed by comparing quartiles of resting left ventricular end-diastolic volume (LVEDV).<br /><b>Results</b><br />Vo<sub>2</sub>peak was strongly associated with resting measures of LVEDV and right ventricular end-diastolic volume (R<sup>2</sup> = 0.58-0.63; P < 0.0001), but weakly associated with measures of resting left ventricular (LV) systolic and diastolic function (R<sup>2</sup> = 0.01-0.06; P < 0.05). Increasing LVEDV quartiles were positively associated with cardiac reserve, with the smallest quartile showing the smallest reduction in LV end-systolic volume (quartile [Q]1: -4 mL vs Q4: -12 mL), smallest augmentation in LV stroke volume (Q1: +11 mL vs Q4: +20 mL) and cardiac output (Q1: +6.6 L/min vs Q4: +10.3 L/min) during exercise (interaction P < 0.001 for all).<br /><b>Conclusions</b><br />A small ventricle is strongly associated with low CRF because of the combined effect of a smaller resting stroke volume and an attenuated capacity to increase with exercise. The prognostic implications of low CRF in midlife highlight the need for further longitudinal studies to determine whether women with small ventricles are predisposed to functional impairment, exertional intolerance, and HF later in life.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 05 Jan 2023; epub ahead of print</small></div>

<div><h4>Second-Line Myocardial Perfusion Imaging to Detect Obstructive Stenosis: Head-to-Head Comparison of CMR and PET.</h4><i>Rasmussen LD, Winther S, Eftekhari A, Karim SR, ... Petersen SE, Böttcher M</i><br /><b>Background</b><br />Guidelines recommend verification of myocardial ischemia by selective second-line myocardial perfusion imaging (MPI) following a coronary computed tomography angiography (CTA) with suspected obstructive coronary artery disease (CAD). Head-to-head data on the diagnostic performance of different MPI modalities in this setting are sparse.<br /><b>Objectives</b><br />The authors sought to compare, head-to-head, the diagnostic performance of selective MPI by 3.0-T cardiac magnetic resonance (CMR) and <sup>82</sup>rubidium positron emission tomography (RbPET) in patients with suspected obstructive stenosis at coronary CTA using invasive coronary angiography (ICA) with fractional flow reserve (FFR) as reference.<br /><b>Methods</b><br />Consecutive patients (n = 1,732, mean age: 59.1 ± 9.5, 57.2% men) referred for coronary CTA with symptoms suggestive of obstructive CAD were included. Patients with suspected stenosis were referred for both CMR and RbPET and subsequently ICA. Obstructive CAD was defined as FFR ≤0.80 or >90% diameter stenosis by visual assessment.<br /><b>Results</b><br />In total, 445 patients had suspected stenosis on coronary CTA. Of these, 372 patients completed both CMR, RbPET and subsequent ICA with FFR. Hemodynamically obstructive CAD was identified in 164 of 372 (44.1%) patients. Sensitivities for CMR and RbPET were 59% (95% CI: 51%-67%) and 64% (95% CI: 56%-71%); P = 0.21, respectively, and specificities 84% (95% CI: 78%-89%) and 89% (95% CI: 84%-93%]); P = 0.08, respectively. Overall accuracy was higher for RbPET compared with CMR (73% vs 78%; P = 0.03).<br /><b>Conclusions</b><br />In patients with suspected obstructive stenosis at coronary CTA, CMR, and RbPET show similar and moderate sensitivities but high specificities compared with ICA with FFR. This patient group represents a diagnostic challenge with frequent mismatch between advanced MPI tests and invasive measurements. (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 [Dan-NICAD 2]; NCT03481712).<br /><br />Copyright © 2023 American College of Cardiology Foundation. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 04 Jan 2023; epub ahead of print</small></div>

<div><h4>Clinical and Echocardiographic Characteristics of Flow-Based Classification Following Balloon-Expandable Transcatheter Heart Valve in PARTNER Trials.</h4><i>Akinmolayemi O, Ozdemir D, Pibarot P, Zhao Y, ... Blanke P, Hahn RT</i><br /><b>Background</b><br />Current expected normal echocardiographic measures of transcatheter heart valve (THV) function were derived from pooled cohorts of the randomized trials; however, THV function by flow state before or following transcatheter aortic valve replacement (TAVR) has not been previously reported.<br /><b>Objectives</b><br />This study sought to assess the expected normal echocardiographic hemodynamics for the balloon-expandable THV grouped by stroke volume index (SVI).<br /><b>Methods</b><br />Patients with severe aortic stenosis enrolled in PARTNER (Placement of Aortic Transcatheter Valves) 1 (high/extreme surgical risk), PARTNER 2 (intermediate surgical risk), or PARTNER 3 (low surgical risk) trials with complete core laboratory echocardiography were included. Patients were grouped by low-flow (SVI<sub>LOW</sub> <35 mL/m<sup>2</sup>) and normal-flow (SVI<sub>NORMAL</sub> ≥35 mL/m<sup>2</sup>). Mean gradient, effective orifice area (EOA), and Doppler velocity index (DVI) were collected at baseline and at 30 days post-TAVR. Prosthesis-patient mismatch (PPM) was both calculated and predicted from normative data, using defined criteria.<br /><b>Results</b><br />In the entire population (N = 4,991), mean age was 81.8 years, 58% of patients were male, and 42% had low flow. Compared with patients with baseline SVI<sub>NORMAL</sub>, those with SVI<sub>LOW</sub> were more likely to be male; have more comorbidities; and lower left ventricular ejection fraction, mean gradient, and EOA. Post-TAVR, SVI<sub>LOW</sub> increased to SVI<sub>NORMAL</sub> in 17.3% and SVI<sub>NORMAL</sub> decreased to SVI<sub>LOW</sub> in 12.3% of patients. Using baseline SVI, follow-up EOA, mean gradient, and DVI for patients with SVI<sub>LOW</sub> tended to be lower than for patients with SVI<sub>NORMAL</sub>. Using the post-TAVR SVI, follow-up EOA, mean gradient, and DVI were significantly lower for patients with SVI<sub>LOW</sub> than for those with SVI<sub>NORMAL</sub> (P < 0.001 for all). The incidence of calculated, but not predicted, severe PPM was higher in patients with low flow than it was in patients with normal flow, suggesting pseudo-PPM in the presence of low flow.<br /><b>Conclusions</b><br />This study demonstrates that flow affects THV hemodynamics and both baseline and follow-up SVI should be considered when predicting THV hemodynamics prior to TAVR, as well as assessing valve function following valve implantation.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jan 2023; 16:1-9</small></div>

<div><h4>Prognostic Value of Right Ventricular Function in Patients With Suspected Myocarditis Undergoing Cardiac Magnetic Resonance.</h4><i>Bernhard B, Schnyder A, Garachemani D, Fischer K, ... Kwong RY, Gräni C</i><br /><b>Background</b><br />Risk-stratification of myocarditis is based on functional parameters and tissue characterization of the left ventricle (LV), whereas right ventricular (RV) involvement remains mostly unrecognized.<br /><b>Objectives</b><br />In this study, the authors sought to analyze the prognostic value of RV involvement in myocarditis by cardiac magnetic resonance (CMR).<br /><b>Methods</b><br />Patients meeting the recommended clinical criteria for suspected myocarditis were enrolled at 2 centers. Exclusion criteria were the evidence of coronary artery disease, pulmonary artery hypertension or structural cardiomyopathy. Biventricular ejection fraction, edema according to T2-weighted images, and late gadolinium enhancement (LGE) were linked to a composite end point of major adverse cardiovascular events (MACE), including heart failure hospitalization, ventricular arrhythmia, recurrent myocarditis, and death.<br /><b>Results</b><br />Among 1,125 consecutive patients, 736 (mean age: 47.8 ± 16.1 years) met the clinical diagnosis of suspected myocarditis and were followed for 3.7 years. Signs of RV involvement (abnormal right ventricular ejection fraction [RVEF], RV edema, and RV-LGE) were present in 188 (25.6%), 158 (21.5%), and 92 (12.5%) patients, respectively. MACE occurred in 122 patients (16.6%) and was univariably associated with left ventricular ejection fraction (LVEF), LV edema, LV-LGE, RV-LGE, RV edema, and RVEF. In a series of nesting multivariable Cox regression models, the addition of RVEF (HR<sub>adj</sub>: 0.974 [95% CI: 0.956-0.993]; P = 0.006) improved prognostication (chi-square test = 89.5; P = 0.001 vs model 1; P = 0.006 vs model 2) compared with model 1 including only clinical variables (chi-square test = 28.54) and model 2 based on clinical parameters, LVEF, and LV-LGE extent (chi-square test = 78.93).<br /><b>Conclusions</b><br />This study emphasizes the role of RV involvement in myocarditis and demonstrates the independent and incremental prognostic value of RVEF beyond clinical variables, CMR tissue characterization, and LV function. (Inflammatory Cardiomyopathy Bern Registry [FlamBER]; NCT04774549; CMR Features in Patients With Suspected Myocarditis [CMRMyo]; NCT03470571).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jan 2023; 16:28-41</small></div>

<div><h4>Acute Response in the Noninfarcted Myocardium Predicts Long-Term Major Adverse Cardiac Events After STEMI.</h4><i>Shanmuganathan M, Masi A, Burrage MK, Kotronias RA, ... Ferreira VM, OxAMI Study Investigators</i><br /><b>Background</b><br />Acute ST-segment elevation myocardial infarction (STEMI) has effects on the myocardium beyond the immediate infarcted territory. However, pathophysiologic changes in the noninfarcted myocardium and their prognostic implications remain unclear.<br /><b>Objectives</b><br />The purpose of this study was to evaluate the long-term prognostic value of acute changes in both infarcted and noninfarcted myocardium post-STEMI.<br /><b>Methods</b><br />Patients with acute STEMI undergoing primary percutaneous coronary intervention underwent evaluation with blood biomarkers and cardiac magnetic resonance (CMR) at 2 days and 6 months, with long-term follow-up for major adverse cardiac events (MACE). A comprehensive CMR protocol included cine, T2-weighted, T2∗, T1-mapping, and late gadolinium enhancement (LGE) imaging. Areas without LGE were defined as noninfarcted myocardium. MACE was a composite of cardiac death, sustained ventricular arrhythmia, and new-onset heart failure.<br /><b>Results</b><br />Twenty-two of 219 patients (10%) experienced an MACE at a median of 4 years (IQR: 2.5-6.0 years); 152 patients returned for the 6-month visit. High T1 (>1250 ms) in the noninfarcted myocardium was associated with lower left ventricular ejection fraction (LVEF) (51% ± 8% vs 55% ± 9%; P = 0.002) and higher NT-pro-BNP levels (290 pg/L [IQR: 103-523 pg/L] vs 170 pg/L [IQR: 61-312 pg/L]; P = 0.008) at 6 months and a 2.5-fold (IQR: 1.03-6.20) increased risk of MACE (2.53 [IQR: 1.03-6.22]), compared with patients with normal T1 in the noninfarcted myocardium (P = 0.042). A lower T1 (<1,300 ms) in the infarcted myocardium was associated with increased MACE (3.11 [IQR: 1.19-8.13]; P = 0.020). Both noninfarct and infarct T1 were independent predictors of MACE (both P = 0.001) and significantly improved risk prediction beyond LVEF, infarct size, and microvascular obstruction (C-statistic: 0.67 ± 0.07 vs 0.76 ± 0.06, net-reclassification index: 40% [IQR: 12%-64%]; P = 0.007).<br /><b>Conclusions</b><br />The acute responses post-STEMI in both infarcted and noninfarcted myocardium are independent incremental predictors of long-term MACE. These insights may provide new opportunities for treatment and risk stratification in STEMI.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jan 2023; 16:46-59</small></div>

<div><h4>Subendocardial and Transmural Myocardial Ischemia: Clinical Characteristics, Prevalence, and Outcomes With and Without Revascularization.</h4><i>Gould KL, Nguyen T, Kirkeeide R, Roby AE, ... Narula J, Johnson NP</i><br /><b>Background</b><br />Subendocardial ischemia is commonly diagnosed but not quantified by imaging.<br /><b>Objectives</b><br />This study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes.<br /><b>Methods</b><br />Regional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization.<br /><b>Results</b><br />Of 6,331 diagnostic PETs, 1,316 (20.7%) had severely reduced CFC with 41.4% having angina or ST-segment depression (STΔ) >1 mm during hyperemic stress, increasing with size. For 5,015 PETs with no severe CFC abnormality, 402 (8%) had angina or STΔ during stress, and 82% had abnormal subendocardial perfusion with 8.7% having angina or STΔ >1 mm during dipyridamole stress. Of 947 cases with stress-induced angina or STΔ >1 mm, 945 (99.8%) had reduced transmural or subendocardial perfusion reflecting sufficient microvascular function to increase coronary blood flow and reduce intracoronary pressure, causing reduced subendocardial perfusion; only 2 (0.2%) had normal subendocardial perfusion, suggesting microvascular disease as the cause of the angina. Over 10-year follow-up (mean 5 years), severely reduced CFC associated with major adverse cardiac events of 44.4% compared to 8.8% for no severe CFC (unadjusted P < 0.00001) and mortality of 15.2% without and 6.9% with revascularization (P < 0.00002) confirmed by multivariable Cox regression modeling. For no severe CFC, mortality was 3% with and without revascularization (P = 0.90).<br /><b>Conclusions</b><br />Reduced subendocardial perfusion on dipyridamole PET without regional stress perfusion defects is common without angina, has low risk of major adverse cardiac events, reflecting asymptomatic nonobstructive diffuse coronary artery disease, or angina without stenosis. Severely reduced CFC causes angina in fewer than one-half of cases but incurs high mortality risk that is significantly reduced after revascularization.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jan 2023; 16:78-94</small></div>

<div><h4>Major Global Coronary Artery Calcium Guidelines.</h4><i>Golub IS, Termeie OG, Kristo S, Schroeder LP, ... Manubolu VS, Budoff MJ</i><br /><AbstractText>This review summarizes the framework behind global guidelines of coronary artery calcium (CAC) in atherosclerotic cardiovascular disease risk assessment, for applications in both the clinical setting and preventive therapy. By comparing similarities and differences in recommendations, this review identifies most notable common features for the application of CAC presented by different cardiovascular societies across the world. Guidelines included from North America are as follows: 1) the 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease; and 2) the 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for Prevention of Adult Cardiovascular Disease. The authors also included European guidelines: 1) the 2019 European Society for Cardiology/European Atherosclerosis Society Guidelines for the Management of Dyslipidemias; and 2) the 2016 National Institute for Health and Care Excellence Clinical Guidelines. In this comparison, the authors also discuss: 1) the Cardiac Society of Australia and New Zealand Guidelines on CAC; 2) the Chinese Society of Cardiology Guidelines; and 3) the Japanese Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases. Last, they include statements made by specialty societies including the National Lipid Association, Society of Cardiovascular Computed Tomography, and U.S. Preventive Services Task Force. Utilizing an in-depth review of clinical evidence, these guidelines emphasize the importance of CAC in the primary and secondary prevention of atherosclerotic cardiovascular disease. International guidelines all empower a dynamic clinician-patient relationship and advocate for individualized discussions regarding disease management and pharmacotherapy treatment. Some differences in precise coronary artery calcium score intervals, risk cut points, treatment thresholds, and stratifiers of specific patient subgroups do exist. However, international guidelines employ more similarities than differences from both a clinical and functional perspective. Understanding the parallels among international coronary artery calcium guidelines is essential for clinicians to correctly adjudicate personalized statin and aspirin therapy and further medical management.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jan 2023; 16:98-117</small></div>

<div><h4>Prognostic Value of RV Abnormalities on CMR in Patients With Known or Suspected Cardiac Sarcoidosis.</h4><i>Wang J, Zhang J, Hosadurg N, Iwanaga Y, ... Han Y, Chen Y</i><br /><b>Background</b><br />Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.<br /><b>Objectives</b><br />This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.<br /><b>Methods</b><br />This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95% CIs were weighted and summarized.<br /><b>Results</b><br />Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 ± 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95% CI: 1.7-5.5; P < 0.01) for composite events and 3.0 (95% CI: 1.3-7.0; P < 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95% CI: 2.4-9.6]; P < 0.01) and a higher risk for SCD (RR: 9.5 [95% CI: 4.4-20.5]; P < 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95% CI: 0.8-0.9), 69% (95% CI: 50%-84%), and 90% (95% CI: 70%-97%), respectively.<br /><b>Conclusions</b><br />In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RVLGE shows good discrimination in identifying CS patients at high risk of SCD.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 26 Dec 2022; epub ahead of print</small></div>

<div><h4>Prognostic Value of Late Gadolinium Enhancement Detected on Cardiac Magnetic Resonance in Cardiac Sarcoidosis.</h4><i>Stevenson A, Bray JJH, Tregidgo L, Ahmad M, ... Providencia R, Kirresh A</i><br /><b>Background</b><br />Sarcoidosis is a complex multisystem inflammatory disorder, with approximately 5% of patients having overt cardiac involvement. Patients with cardiac sarcoidosis are at an increased risk of both ventricular arrhythmias and sudden cardiac death. Previous studies have shown that the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is associated with an increased risk of mortality and ventricular arrhythmias and may be useful in predicting prognosis.<br /><b>Objectives</b><br />This systematic review and meta-analysis assessed the value of LGE on CMR imaging in predicting prognosis for patients with known or suspected cardiac sarcoidosis.<br /><b>Methods</b><br />The authors searched the Embase and MEDLINE databases from inception to March 2022 for studies reporting individuals with known or suspected cardiac sarcoidosis referred for CMR with LGE. Outcomes were defined as all-cause mortality, ventricular arrhythmia, or a composite outcome of either death or ventricular arrhythmias. The primary analysis evaluated these outcomes according to the presence of LGE. A secondary analysis evaluated outcomes specifically according to the presence of biventricular LGE.<br /><b>Results</b><br />Thirteen studies were included (1,318 participants) in the analysis, with an average participant age of 52.0 years and LGE prevalence of 13% to 70% over a follow-up of 3.1 years. Patients with LGE on CMR vs those without had higher odds of ventricular arrhythmias (OR: 20.3; 95% CI: 8.1-51.0), all-cause mortality (OR: 3.45; 95% CI 1.6-7.3), and the composite of both (OR: 9.2; 95% CI: 5.1-16.7). Right ventricular LGE is invariably accompanied by left ventricular LGE. Biventricular LGE is also associated with markedly increased odds of ventricular arrhythmias (OR: 43.6; 95% CI: 16.2-117.2).<br /><b>Conclusions</b><br />Patients with known or suspected cardiac sarcoidosis with LGE on CMR have significantly increased odds of both ventricular arrhythmias and all-cause mortality. The presence of biventricular LGE may confer additional prognostic information regarding arrhythmogenic risk.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 12 Dec 2022; epub ahead of print</small></div>

<div><h4>National Trends in Coronary Artery Disease Imaging: Associations With Health Care Outcomes and Costs.</h4><i>Weir-McCall JR, Williams MC, Shah ASV, Roditi G, ... Newby DE, Nicol ED</i><br /><b>Background</b><br />In 2016, the National Institute for Health and Care Excellence Clinical Guideline Number 95 (\"Chest pain of recent onset\") (CG95) recommended coronary computed tomography angiography (CCTA) as the first-line test for possible angina.<br /><b>Objectives</b><br />The purpose of this study was to determine the impact of temporal trends in imaging use on outcomes for coronary artery disease (CAD) following the CG95 recommendations.<br /><b>Methods</b><br />Investigations from 2012 to 2018 were extracted from a national database and linked-hospital admission and mortality registries. Growth rates were adjusted for population size, with image modality use, cardiovascular hospital admissions, and mortality compared using Kendall\'s rank correlation. The impact of CG95 was assessed using an interrupted time-series analysis.<br /><b>Results</b><br />A total of 1,909,314 investigations for CAD were performed, with an annualized per capita growth of 4.8%. Costs were £0.35 million/100,000 population/year with an increase of 2.8%/year mirroring inflation (2.5%/year). CG95 was associated with a rise in CCTA (exp[β]: 1.10; 95% CI: 1.03-1.18), no change in myocardial perfusion imaging, and a potential modest fall (exp[β]: 0.997; 95% CI: 0.993-1.00]) in invasive coronary angiography. There was an apparent trend between computed tomography angiography growth and invasive catheter angiography reduction across regions (Kendall Tau: -0.19; P = 0.08). CCTA growth was associated with a reduction in cardiovascular mortality (Kendall Tau: -0.21; P = 0.045), and ischemic heart disease deaths (Kendall Tau: -0.22; P = 0.042), with an apparent trend with reduced all-cause mortality (Kendall Tau: -0.19; P = 0.07).<br /><b>Conclusions</b><br />Imaging investigations for CAD are increasing. Greater regional increases in CCTA were associated with fewer hospitalizations for myocardial infarction and a more rapid decline in CAD mortality.<br /><br />Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 12 Dec 2022; epub ahead of print</small></div>

<div><h4>Left Atrial Strain for Assessment of Left Ventricular Diastolic Function: Focus on Populations with Normal LVEF.</h4><i>Nagueh SF, Khan SU</i><br /><AbstractText>Left atrial (LA) strain has emerged as a useful parameter for the assessment of left ventricular (LV) diastolic function and the estimation of LV filling pressures. Some have advocated using LA strain by itself, mainly reservoir strain, as a single stand-alone measurement for this objective. Recent data indicate several challenges for this application in patients with normal left ventricular ejection fraction (LVEF) because of the wide range for normal values and the load dependency of LA strain. Both findings can result in reduced left atrial reservoir strain (LARS) values in normal subjects that overlap those seen in patients with diastolic dysfunction. LARS for the estimation of LV filling pressures is most accurate in patients with depressed LVEF. It is less accurate in patients with normal ejection fraction. In this group of patients, LARS <18% has high specificity for increased LV filling pressures. There are promising data showing the association of LARS with outcome events in patients with normal ejection fraction, and additional data are needed to confirm that it provides incremental information over clinical and other echocardiographic measurements.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 12 Dec 2022; epub ahead of print</small></div>

<div><h4>Noninvasive In Vivo Coronary Artery Thrombus Imaging.</h4><i>Tzolos E, Bing R, Andrews J, MacAskill MG, ... Dweck MR, Newby DE</i><br /><b>Background</b><br />The diagnosis and management of myocardial infarction are increasingly complex, and establishing the presence of intracoronary thrombosis has major implications for both the classification and treatment of myocardial infarction.<br /><b>Objectives</b><br />The aim of this study was to investigate whether positron emission tomographic (PET) and computed tomographic (CT) imaging could noninvasively detect in vivo thrombus formation in human coronary arteries using a novel glycoprotein IIb/IIIa receptor antagonist-based radiotracer, <sup>18</sup>F-GP1.<br /><b>Methods</b><br />In a single-center observational case-control study, patients with or without acute myocardial infarction underwent coronary <sup>18</sup>F-GP1 PET/CT angiography. Coronary artery <sup>18</sup>F-GP1 uptake was assessed visually and quantified using maximum target-to-background ratios.<br /><b>Results</b><br />18F-GP1 PET/CT angiography was performed in 49 patients with and 50 patients without acute myocardial infarction (mean age: 61 ± 9 years, 75% men). Coronary <sup>18</sup>F-GP1 uptake was apparent in 39 of the 49 culprit lesions (80%) in patients with acute myocardial infarction. False negative results appeared to relate to time delays to scan performance and low thrombus burden in small-caliber distal arteries. On multivariable regression analysis, culprit vessel status was the only independent variable associated with higher <sup>18</sup>F-GP1 uptake. Extracoronary cardiac <sup>18</sup>F-GP1 findings included a high frequency of infarct-related intramyocardial uptake (35%) as well as left ventricular (8%) or left atrial (2%) thrombus.<br /><b>Conclusions</b><br />Coronary <sup>18</sup>F-GP1 PET/CT angiography is the first noninvasive selective technique to identify in vivo coronary thrombosis in patients with acute myocardial infarction. This novel approach can further define the role and location of thrombosis within the heart and has the potential to inform the diagnosis, management, and treatment of patients with acute myocardial infarction. (In-Vivo Thrombus Imaging With <sup>18</sup>F-GP1, a Novel Platelet PET Radiotracer [iThrombus]; NCT03943966).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 09 Dec 2022; epub ahead of print</small></div>

<div><h4>Comprehensive Phenotypic Characterization of Late Gadolinium Enhancement Predicts Sudden Cardiac Death in Coronary Artery Disease.</h4><i>Jones RE, Zaidi HA, Hammersley DJ, Hatipoglu S, ... Bishop MJ, Prasad SK</i><br /><b>Background</b><br />Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) offers the potential to noninvasively characterize the phenotypic substrate for sudden cardiac death (SCD).<br /><b>Objectives</b><br />The authors assessed the utility of infarct characterization by CMR, including scar microstructure analysis, to predict SCD in patients with coronary artery disease (CAD).<br /><b>Methods</b><br />Patients with stable CAD were prospectively recruited into a CMR registry. LGE quantification of core infarction and the peri-infarct zone (PIZ) was performed alongside computational image analysis to extract morphologic and texture scar microstructure features. The primary outcome was SCD or aborted SCD.<br /><b>Results</b><br />Of 437 patients (mean age: 64 years; mean left ventricular ejection fraction [LVEF]: 47%) followed for a median of 6.3 years, 49 patients (11.2%) experienced the primary outcome. On multivariable analysis, PIZ mass and core infarct mass were independently associated with the primary outcome (per gram: HR: 1.07 [95% CI: 1.02-1.12]; P = 0.002 and HR: 1.03 [95% CI: 1.01-1.05]; P = 0.01, respectively), and the addition of both parameters improved discrimination of the model (Harrell\'s C-statistic: 0.64-0.79). PIZ mass, however, did not provide incremental prognostic value over core infarct mass based on Harrell\'s C-statistic or risk reclassification analysis. Severely reduced LVEF did not predict the primary endpoint after adjustment for scar mass. On scar microstructure analysis, the number of LGE islands in addition to scar transmurality, radiality, interface area, and entropy were all associated with the primary outcome after adjustment for severely reduced LVEF and New York Heart Association functional class of >1. No scar microstructure feature remained associated with the primary endpoint when PIZ mass and core infarct mass were added to the regression models.<br /><b>Conclusions</b><br />Comprehensive LGE characterization independently predicted SCD risk beyond conventional predictors used in implantable cardioverter-defibrillator (ICD) insertion guidelines. These results signify the potential for a more personalized approach to determining ICD candidacy in CAD.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 08 Dec 2022; epub ahead of print</small></div>

<div><h4>Utility of E/e\' Ratio During Low-Level Exercise to Diagnose Heart Failure With Preserved Ejection Fraction.</h4><i>Harada T, Obokata M, Kagami K, Sorimachi H, ... Wada N, Ishii H</i><br /><b>Background</b><br />E/e\' ratio during exercise is the key parameter in identifying elevated pulmonary capillary wedge pressure (PCWP), and thus heart failure with preserved ejection fraction (HFpEF). However, its diagnostic value is limited when mitral inflow or tissue velocities are fused during elevated heart rate.<br /><b>Objectives</b><br />The authors hypothesized that E/e\' ratio during low-level (20 W) exercise (E/e\'<sub>20W</sub>) can help diagnose HFpEF.<br /><b>Methods</b><br />Ergometric exercise stress echocardiography was performed in 215 dyspneic patients with an EF ≥50%. The authors determined the feasibility of E/e\' ratio at each stage (frequency of patients who had measurable E/e\' without E-A fusion among 215 participants) and examined whether E/e\'<sub>20W</sub> could predict normal E/e\' ratio during peak exercise (E/e\'<sub>peak</sub> ≤15). The authors also evaluated whether E/e\'<sub>20W</sub> could predict normal PCWP during exercise (PCWP <25 mm Hg) in a subset of participants (n = 45) who underwent exercise right heart catheterization.<br /><b>Results</b><br />The feasibility of the E/e\' ratio decreased from 100% at rest to 96.3% during 20-W exercise and 74.9% during peak exercise caused by E-A fusion. In patients with E/e\'<sub>peak</sub> >15, there was an increase in E/e\' ratio from rest to 20-W exercise (11.2 ± 2.1 to 16.3 ± 3.5; P < 0.0001), but it did not change significantly from 20-W exercise to peak exercise (P = 0.12). E/e\'<sub>20W</sub> predicted E/e\'<sub>peak</sub> ≤15 (AUC: 0.91; P < 0.0001) with the cutoff value of ≤12.4 showing high specificity (94%) and positive predictive value (98%). During 20-W exercise, 93% of the HFpEF patients developed PCWP ≥25 mm Hg. E/e\'<sub>20W</sub> predicted normal PCWP during exercise (AUC: 0.77; P = 0.01) with the cutoff value of ≤12.4 showing high specificity (83%).<br /><b>Conclusions</b><br />E/e\' ratio during low-level exercise is highly feasible and predicts normal E/e\' ratio or PCWP during peak exercise with high specificity. These data suggest that E/e\'<sub>20W</sub> could be used as an alternative to the peak exercise value to rule out HFpEF in patients with dyspnea.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 02 Dec 2022; epub ahead of print</small></div>

<div><h4>Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement.</h4><i>Vidula MK, Rajewska-Tabor J, Cao JJ, Kang Y, ... Plein S, Han Y</i><br /><b>Background</b><br />Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood.<br /><b>Objectives</b><br />The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR).<br /><b>Methods</b><br />This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR.<br /><b>Results</b><br />In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003).<br /><b>Conclusions</b><br />In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 02 Dec 2022; epub ahead of print</small></div>

<div><h4>Changes in Right Ventricular-to-Pulmonary Artery Coupling After Transcatheter Edge-to-Edge Repair in Secondary Mitral Regurgitation.</h4><i>Adamo M, Inciardi RM, Tomasoni D, Dallapellegrina L, ... Voors A, Metra M</i><br /><b>Background</b><br />Preprocedural right ventricular-to-pulmonary artery (RV-PA) coupling is a major predictor of outcome in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER). However, clinical significance of changes in RV-PA coupling after M-TEER is unknown.<br /><b>Objectives</b><br />The aim of this study was to evaluate changes in RV-PA coupling after M-TEER, their prognostic value, and predictors of improvement.<br /><b>Methods</b><br />This was a retrospective observational study, including patients undergoing successful M-TEER (residual mitral regurgitation ≤2+ at discharge) for SMR at 13 European centers and with complete echocardiographic data at baseline and short-term follow-up (30-180 days). RV-PA coupling was assessed with the use of echocardiography as the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). All-cause death was assessed at the longest available follow-up starting from the time of the echocardiographic reassessment.<br /><b>Results</b><br />Among 501 patients included, 331 (66%) improved their TAPSE/PASP after M-TEER (responders) at short-term follow-up (median: 89 days; IQR: 43-159 days), whereas 170 (34%) did not (nonresponders). Lack of previous cardiac surgery, low postprocedural mitral mean gradient, low baseline TAPSE, high baseline PASP, and baseline tricuspid regurgitation were independently associated with TAPSE/PASP improvement after M-TEER. Compared with nonresponders, responders had lower New York Heart Association functional class and less heart failure hospitalizations at short-term follow-up. Improvement in TAPSE/PASP was independently associated with reduced risk of mortality at long-term follow-up (584 days; IQR: 191-1,243 days) (HR: 0.65 [95% CI: 0.42-0.92]; P = 0.017).<br /><b>Conclusions</b><br />In patients with SMR, improvement in TAPSE/PASP after successful M-TEER is predicted by baseline clinical and echocardiographic variables and postprocedural mitral gradient, and is associated with a better outcome.<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>JACC Cardiovasc Imaging: 01 Dec 2022; 15:2038-2047</small></div>

<div><h4>Prognostic Implications of Left Atrial Stiffness Index in Heart Failure Patients With Preserved Ejection Fraction.</h4><i>Kim D, Seo JH, Choi KH, Lee SH, ... Jeon ES, Yang JH</i><br /><b>Background</b><br />The left atrium (LA) plays an important role in the pathophysiology and disease progression of heart failure with preserved ejection fraction (HFpEF).<br /><b>Objectives</b><br />This study sought to assess the prognostic potential of LA stiffness index in patients who have HFpEF.<br /><b>Methods</b><br />This study retrospectively screened patients with elevated left ventricular end-diastolic pressure (≥16 mm Hg) and preserved ejection fraction (≥50%) between January 1, 2004, and December 31, 2019. All patients underwent left heart catheterization to measure left ventricular end-diastolic pressure. Among these, 307 patients who had suitable image quality for left peak atrial longitudinal strain (PALS) measurement were analyzed. The study population was classified into low LA stiffness (n = 178, early diastolic transmitral inflow velocity/mitral annulus early diastolic velocity [E/e\']/PALS ≤0.26) and high LA stiffness (n = 129, E/e\'/PALS >0.26) according to the best LA stiffness index (E/e\'/PALS) cutoff value. The primary outcome was a composite of mortality or hospitalization caused by heart failure during follow-up.<br /><b>Results</b><br />LA stiffness index showed good correlations with E/e\' (r = 0.737; P < 0.001), LA volume index (r = 0.529; P < 0.001), right ventricular systolic pressure (r = 0.404; P < 0.001), and log N-terminal pro-B-type natriuretic peptide (r = 0.540; P < 0.001). LA stiffness index demonstrated better predictive performance than echocardiographic diastolic parameters did (P < 0.001). Patients with low LA stiffness had better clinical outcomes than those with high LA stiffness during a median follow-up of 6 years did (P < 0.001). In multivariable analysis, LA stiffness index was independently associated with increased risk of the composite endpoint of death or heart failure hospitalization (HR: 1.59 [95% CI: 1.01-2.51]; P = 0.044).<br /><b>Conclusions</b><br />Increased LA stiffness was associated with increased risk for all-cause mortality and hospitalization caused by heart failure in patients who have HFpEF, and its prognostic role was more pronounced than that of indexes of left ventricular filling pressure.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Dec 2022; epub ahead of print</small></div>

<div><h4>Hyperpolarized Metabolic and Parametric CMR Imaging of Longitudinal Metabolic-Structural Changes in Experimental Chronic Infarction.</h4><i>Fuetterer M, Traechtler J, Busch J, Peereboom SM, ... Stoeck CT, Kozerke S</i><br /><b>Background</b><br />Prolonged ischemia and myocardial infarction are followed by a series of dynamic processes that determine the fate of the affected myocardium toward recovery or necrosis. Metabolic adaptions are considered to play a vital role in the recovery of salvageable myocardium in the context of stunned and hibernating myocardium.<br /><b>Objectives</b><br />The potential of hyperpolarized pyruvate cardiac magnetic resonance (CMR) alongside functional and parametric CMR as a tool to study the complex metabolic-structural interplay in a longitudinal study of chronic myocardial infarction in an experimental pig model is investigated.<br /><b>Methods</b><br />Metabolic imaging using hyperpolarized [1-<sup>13</sup>C] pyruvate and proton-based CMR including cine, T<sub>1</sub>/T<sub>2</sub> relaxometry, dynamic contrast-enhanced, and late gadolinium enhanced imaging were performed on clinical 3.0-T and 1.5-T MR systems before infarction and at 6 days and 5 and 9 weeks postinfarction in a longitudinal study design. Chronic myocardial infarction in pigs was induced using catheter-based occlusion and compared with healthy controls.<br /><b>Results</b><br />Metabolic image data revealed temporarily elevated lactate-to-bicarbonate ratios at day 6 in the infarcted relative to remote myocardium. The temporal changes of lactate-to-bicarbonate ratios were found to correlate with changes in T<sub>2</sub> and impaired local contractility. Assessment of pyruvate dehydrogenase flux via the hyperpolarized [<sup>13</sup>C] bicarbonate signal revealed recovery of aerobic cellular respiration in the hibernating myocardium, which correlated with recovery of local radial strain.<br /><b>Conclusions</b><br />This study demonstrates the potential of hyperpolarized CMR to longitudinally detect metabolic changes after cardiac infarction over days to weeks. Viable myocardium in the area at risk was identified based on restored pyruvate dehydrogenase flux.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Dec 2022; 15:2051-2064</small></div>

<div><h4>Native T1 Mapping for the Diagnosis of Myocardial Fibrosis in Patients With Chronic Myocardial Infarction.</h4><i>Kaolawanich Y, Azevedo CF, Kim HW, Jenista ER, ... Judd RM, Kim RJ</i><br /><b>Background</b><br />Myocardial fibrosis is a fundamental process in cardiac injury. Cardiac magnetic resonance native T1 mapping has been proposed for diagnosing myocardial fibrosis without the need for gadolinium contrast. However, recent studies suggest that T1 measurements can be erroneous in the presence of intramyocardial fat.<br /><b>Objectives</b><br />The purpose of this study was to investigate whether the presence of fatty metaplasia affects the accuracy of native T1 maps for the diagnosis of myocardial replacement fibrosis in patients with chronic myocardial infarction (MI).<br /><b>Methods</b><br />Consecutive patients (n = 312) with documented chronic MI (>6 months old) and controls without MI (n = 50) were prospectively enrolled. Presence and size of regions with elevated native T1 and infarction were quantitatively determined (mean + 5SD) on modified look-locker inversion-recovery and delayed-enhancement images, respectively, at 3.0-T. The presence of fatty metaplasia was determined using an out-of-phase steady-state free-precession cine technique and further verified with standard fat-water Dixon methods.<br /><b>Results</b><br />Native T1 mapping detected chronic MI with markedly higher sensitivity in patients with fatty metaplasia than those without fatty metaplasia (85.6% vs 13.3%) with similar specificity (100% vs 98.9%). In patients with fatty metaplasia, the size of regions with elevated T1 significantly underestimated infarct size and there was a better correlation with fatty metaplasia size than infarct size (r = 0.76 vs r = 0.49). In patients without fatty metaplasia, most of the modest elevation in T1 appeared to be secondary to subchronic infarcts that were 6 to 12 months old; the T1 of infarcts >12 months old was not different from noninfarcted myocardium.<br /><b>Conclusions</b><br />Native T1 mapping is poor at detecting replacement fibrosis but may indirectly detect chronic MI if there is associated fatty metaplasia. Native T1 mapping for the diagnosis and characterization of myocardial fibrosis is unreliable.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Dec 2022; 15:2069-2079</small></div>

<div><h4>Parametric Imaging of Biologic Activity of Atherosclerosis Using Dynamic Whole-Body Positron Emission Tomography.</h4><i>Derlin T, Werner RA, Weiberg D, Derlin K, Bengel FM</i><br /><b>Background</b><br />For molecular imaging of atherosclerotic vessel wall activity, tracer kinetic analysis may yield improved contrast versus blood, more robust quantitative parameters, and more reliable characterization of systems biology.<br /><b>Objectives</b><br />The authors introduce a novel dynamic whole-body positron emission tomography (PET) protocol that is enabled by rapid continuous camera table motion, followed by reconstruction of parametric data sets using voxel-based Patlak graphical analysis.<br /><b>Methods</b><br />Twenty-five subjects were prospectively enrolled and underwent dynamic PET up to 90 minutes after injection of 2-[<sup>18</sup>F]fluoro-2-deoxy-D-glucose (FDG). Two sets of images were generated: 1) the established standard of static standardized uptake value (SUV) images; and 2) parametric images of the metabolic rate of FDG (MR<sub>FDG</sub>) using the Patlak plot-derived influx rate. Arterial wall signal was measured and compared using the volume-of-interest technique, and its association with hematopoietic and lymphoid organ signal and atherosclerotic risk factors was explored.<br /><b>Results</b><br />Parametric MR<sub>FDG</sub> images provided excellent arterial wall visualization, with elimination of blood-pool activity, and enhanced focus detectability and reader confidence. Target-to-background ratio (TBR) from MR<sub>FDG</sub> images was significantly higher compared with SUV images (2.6 ± 0.8 vs 1.4 ± 0.2; P < 0.0001), confirming improved arterial wall contrast. On MR<sub>FDG</sub> images, arterial wall signal showed improved correlation with hematopoietic and lymphoid organ activity (spleen P = 0.0009; lymph nodes P = 0.0055; and bone marrow P = 0.0202) and increased with the number of atherosclerotic risk factors (r = 0.49; P = 0.0138), where signal from SUV images (SUV<sub>max</sub>P = 0.9754; TBR<sub>max</sub>P = 0.8760) did not.<br /><b>Conclusions</b><br />Absolute quantification of MR<sub>FDG</sub> is feasible for arterial wall using dynamic whole-body PET imaging. Parametric images provide superior arterial wall contrast, and they might be better suited to explore the relationship between arterial wall activity, systemic organ networks, and cardiovascular risk. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of arterial wall disease.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Dec 2022; 15:2098-2108</small></div>

<div><h4>Insights Into the Metabolic Aspects of Aortic Stenosis With the Use of Magnetic Resonance Imaging.</h4><i>Monga S, Valkovič L, Tyler D, Lygate CA, ... Neubauer S, Mahmod M</i><br /><AbstractText>Pressure overload in aortic stenosis (AS) encompasses both structural and metabolic remodeling and increases the risk of decompensation into heart failure. A major component of metabolic derangement in AS is abnormal cardiac substrate use, with down-regulation of fatty acid oxidation, increased reliance on glucose metabolism, and subsequent myocardial lipid accumulation. These changes are associated with energetic and functional cardiac impairment in AS and can be assessed with the use of cardiac magnetic resonance spectroscopy (MRS). Proton MRS allows the assessment of myocardial triglyceride content and creatine concentration. Phosphorous MRS allows noninvasive in vivo quantification of the phosphocreatine-to-adenosine triphosphate ratio, a measure of cardiac energy status that is reduced in patients with severe AS. This review summarizes the changes to cardiac substrate and high-energy phosphorous metabolism and how they affect cardiac function in AS. The authors focus on the role of MRS to assess these metabolic changes, and potentially guide future (cellular) metabolic therapy in AS.</AbstractText><br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Dec 2022; 15:2112-2126</small></div>

<div><h4>The Future of Cardiac Magnetic Resonance Clinical Trials.</h4><i>Rabbat MG, Kwong RY, Heitner JF, Young AA, ... Bilchick KC, Society for Cardiovascular Magnetic Resonance</i><br /><AbstractText>Over the past 2 decades, cardiac magnetic resonance (CMR) has become an essential component of cardiovascular clinical care and contributed to imaging-guided diagnosis and management of coronary artery disease, cardiomyopathy, congenital heart disease, cardio-oncology, valvular, and vascular disease, amongst others. The widespread availability, safety, and capability of CMR to provide corresponding anatomical, physiological, and functional data in 1 imaging session can improve the design and conduct of clinical trials through both a reduction of sample size and provision of important mechanistic data that may augment clinical trial findings. Moreover, prospective imaging-guided strategies using CMR can enhance safety, efficacy, and cost-effectiveness of cardiovascular pathways in clinical practice around the world. As the future of large-scale clinical trial design evolves to integrate personalized medicine, cost-effectiveness, and mechanistic insights of novel therapies, the integration of CMR will continue to play a critical role. In this document, the attributes, limitations, and challenges of CMR\'s integration into the future design and conduct of clinical trials will also be covered, and recommendations for trialists will be explored. Several prominent examples of clinical trials that test the efficacy of CMR-imaging guided pathways will also be discussed.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Dec 2022; 15:2127-2138</small></div>

<div><h4>Clinical Characteristics and Prognosis of MINOCA Caused by Atherosclerotic and Nonatherosclerotic Mechanisms Assessed by OCT.</h4><i>Zeng M, Zhao C, Bao X, Liu M, ... Jia H, Yu B</i><br /><b>Background</b><br />Myocardial infarction with nonobstructive coronary artery (MINOCA) is a heterogeneous syndrome caused by different pathophysiologic mechanisms. There is limited evidence regarding prognosis of patients with MINOCA caused by different mechanisms.<br /><b>Objectives</b><br />The present study aimed to assess the underlying mechanisms of MINOCA by optical coherence tomography (OCT) and to correlate with clinical outcomes.<br /><b>Methods</b><br />Patients with MINOCA were divided into 2 groups based on OCT findings: atherosclerotic MINOCA (Ath-MINOCA) and nonatherosclerotic MINOCA (non-Ath-MINOCA). Major adverse cardiac events (MACE) were defined as cardiac death, nonfatal MI, target lesion revascularization, stroke, and rehospitalization for unstable or progressive angina.<br /><b>Results</b><br />Among 7,423 patients with a clinical diagnosis of MI who underwent angiography, 190 of 294 MINOCA were studied using OCT. The causes of Ath-MINOCA (n = 99, 52.1%) were plaque erosion (n = 64, 33.7%), plaque rupture (n = 33, 17.4%), and calcified nodule (n = 2, 1.1%) whereas the causes of non-Ath-MINOCA (n = 91, 47.9%) were spontaneous coronary artery dissection (n = 8, 4.2%), coronary spasm (n = 9, 4.7%), and unclassified cause (n = 74, 38.9%). The 1-year MACE was 15.3% for Ath-MINOCA vs 4.5% for non-Ath-MINOCA (P = 0.015). An atherosclerotic cause was an independent predictor of MACE (HR = 5.36 [95% CI: 1.08-26.55]; P = 0.040), mainly driven by target lesion revascularization and rehospitalization, despite the composite endpoint including cardiac death and MI showing no difference.<br /><b>Conclusions</b><br />OCT identified a cause in 61.1% of MINOCA, in which Ath-MINOCA represents an important and distinct MINOCA subset. Ath-MINOCA were more common and associated with worse outcomes. (Incidence Rate of Heart Failure After Acute Myocardial Infarction With Optimal Treatment; NCT03297164) (Paradigm Shift in the Treatment of Patients With ACS; NCT02041650).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 30 Nov 2022; epub ahead of print</small></div>

<div><h4>Clinical and Coronary Plaque Predictors of Atherosclerotic Nonresponse to Statin Therapy.</h4><i>van Rosendael SE, van den Hoogen IJ, Lin FY, Andreini D, ... van Rosendael AR, Bax JJ</i><br /><b>Background</b><br />Statins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse.<br /><b>Objectives</b><br />This study aimed to investigate factors associated with statin nonresponse-defined atherosclerosis progression in patients treated with statins.<br /><b>Methods</b><br />The multicenter PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) registry included patients who underwent serial coronary computed tomography angiography ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen, and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up coronary computed tomography angiography were included. Atherosclerotic statin nonresponse was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. Furthermore, a secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque.<br /><b>Results</b><br />We included 649 patients (age 62.0 ± 9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin nonresponse. Age, diabetes, hypertension, and all atherosclerotic plaque features measured at baseline scan (high-risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin nonresponse, whereas only diabetes, number of HRP features, and noncalcified and calcified PAV were independently associated with atherosclerotic statin nonresponse (odds ratio [OR]: 1.41 [95% CI: 0.95-2.11], OR: 1.15 [95% CI: 1.09-1.21], OR: 1.06 [95% CI: 1.02-1.10], OR: 1.07 [95% CI: 1.03-1.12], respectively). For the secondary endpoint (N = 125, 19.2%), only noncalcified PAV and number of HRP features were the independent determinants (OR: 1.08 [95% CI: 1.03-1.13] and OR: 1.21 [95% CI: 1.06-1.21], respectively).<br /><b>Conclusions</b><br />In patients treated with statins, baseline plaque characterization by plaque burden and HRP is associated with atherosclerotic statin nonresponse. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction.<br /><br />Copyright © 2022 American College of Cardiology Foundation. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 23 Nov 2022; epub ahead of print</small></div>

<div><h4>Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial.</h4><i>Negishi T, Thavendiranathan P, Penicka M, Lemieux J, ... Negishi K, Marwick TH</i><br /><b>Background</b><br />Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction and guide initiation of cardioprotection (CPT).<br /><b>Objective</b><br />In this study, the authors sought to determine whether echocardiography GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care at 3 years.<br /><b>Methods</b><br />In this international multicenter prospective randomized controlled trial, patients were enrolled from 28 international sites. All patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or ejection fraction (EF)-guided (>10% absolute reduction of EF to <55%) CPT. The primary end point was the change in 3-dimensional (3D) EF (ΔEF) from baseline to 3 years.<br /><b>Results</b><br />Among 331 patients enrolled, 255 (77%, age 54 ± 12 years, 95% women) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n = 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Although 67 (26%) had hypertension and 32 (13%) had diabetes mellitus, left ventricular function was normal at baseline (EF 59% ± 6%, GLS 20.7% ± 2.3%). CPT was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (P = 0.03). Most patients showed recovery in EF and GLS after chemotherapy; 3-year ΔEF was -0.03% ± 7.9% in the EF-guided group and -0.02% ± 6.5% in the GLS-guided (P = 0.99) group; respective 3-year EFs were 58% ± 6% and 59% ± 5% (P = 0.06). At 3 years, 17 patients (5%) had cancer therapeutics-related cardiac dysfunction (11 in the EF-guided group and 6 in the GLS guided group; P = 0.16); 1 patient in each group was admitted for heart failure.<br /><b>Conclusions</b><br />Among patients taking potentially cardiotoxic chemotherapy for cancer, the 3-year data showed improvement of LV dysfunction compared with 1 year, with no difference in ΔEF between GLS- and EF-guided CPT. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 16 Nov 2022; epub ahead of print</small></div>

<div><h4>3-Dimensional Strain Analysis of Hypertrophic Cardiomyopathy: Insights From the NHLBI International HCM Registry.</h4><i>Heydari B, Satriano A, Jerosch-Herold M, Kolm P, ... Kwong RY, HCMR Investigators</i><br /><b>Background</b><br />Abnormal global longitudinal strain (GLS) has been independently associated with adverse cardiac outcomes in both obstructive and nonobstructive hypertrophic cardiomyopathy.<br /><b>Objectives</b><br />The goal of this study was to understand predictors of abnormal GLS from baseline data from the National Heart, Lung, and Blood Institute (NHLBI) Hypertrophic Cardiomyopathy Registry (HCMR).<br /><b>Methods</b><br />The study evaluated comprehensive three-dimensional left ventricular myocardial strain from cine cardiac magnetic resonance in 2,311 patients from HCMR using in-house validated feature-tracking software. These data were correlated with other imaging markers, serum biomarkers, and demographic variables.<br /><b>Results</b><br />Abnormal median GLS (> -11.0%) was associated with higher left ventricular (LV) mass index (93.8 ± 29.2 g/m<sup>2</sup> vs 75.1 ± 19.7 g/m<sup>2</sup>; P < 0.0001) and maximal wall thickness (21.7 ± 5.2 mm vs 19.3 ± 4.1 mm; P < 0.0001), lower left (62% ± 9% vs 66% ± 7%; P < 0.0001) and right (68% ± 11% vs 69% ± 10%; P < 0.01) ventricular ejection fractions, lower left atrial emptying functions (P < 0.0001 for all), and higher presence and myocardial extent of late gadolinium enhancement (6 SD and visual quantification; P < 0.0001 for both). Elastic net regression showed that adjusted predictors of GLS included female sex, Black race, history of syncope, presence of systolic anterior motion of the mitral valve, reverse curvature and apical morphologies, LV ejection fraction, LV mass index, and both presence/extent of late gadolinium enhancement and baseline N-terminal pro-B-type natriuretic peptide and troponin levels.<br /><b>Conclusions</b><br />Abnormal strain in hypertrophic cardiomyopathy is associated with other imaging and serum biomarkers of increased risk. Further follow-up of the HCMR cohort is needed to understand the independent relationship between LV strain and adverse cardiac outcomes in hypertrophic cardiomyopathy.<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>JACC Cardiovasc Imaging: 15 Nov 2022; epub ahead of print</small></div>

<div><h4>Aortic Stenosis Progression: A Systematic Review and Meta-Analysis.</h4><i>Willner N, Prosperi-Porta G, Lau L, Nam Fu AY, ... Burwash IG, Messika-Zeitoun D</i><br /><b>Background</b><br />Aortic valve stenosis is a progressive disorder with variable progression rates. The factors affecting aortic stenosis (AS) progression remain largely unknown.<br /><b>Objectives</b><br />This systematic review and meta-analysis sought to determine AS progression rates and to assess the impact of baseline AS severity and sex on disease progression.<br /><b>Methods</b><br />The authors searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 1, 2020, for prospective studies evaluating the progression of AS with the use of echocardiography (mean gradient [MG], peak velocity [PV], peak gradient [PG], or aortic valve area [AVA]) or computed tomography (calcium score [AVC]). Random-effects meta-analysis was performed to evaluate the rate of AS progression for each parameter stratified by baseline severity, and meta-regression was performed to determine the impact of baseline severity and of sex on AS progression rate.<br /><b>Results</b><br />A total of 24 studies including 5,450 patients (40% female) met inclusion criteria. The pooled annualized progression of MG was +4.10 mm Hg (95% CI: 2.80-5.41 mm Hg), AVA -0.08 cm<sup>2</sup> (95% CI: 0.06-0.10 cm<sup>2</sup>), PV +0.19 m/s (95% CI: 0.13-0.24 m/s), PG +7.86 mm Hg (95% CI: 4.98-10.75 mm Hg), and AVC +158.5 AU (95% CI: 55.0-261.9 AU). Increasing baseline severity of AS was predictive of higher rates of progression for MG (P < 0.001), PV (P = 0.001), and AVC (P < 0.001), but not AVA (P = 0.34) or PG (P = 0.21). Only 4 studies reported AS progression stratified by sex, with only PV and AVC having 3 studies to perform a meta-analysis. No difference between sex was observed for PV (P = 0.397) or AVC (P = 0.572), but the level of confidence was low.<br /><b>Conclusions</b><br />This study provides progression rates for both hemodynamic and anatomic parameters of AS and shows that increasing hemodynamic and anatomic baseline severity is associated with faster AS progression. More studies are needed to determine if sex differences affect AS progression. (Aortic Valve Stenosis Progression Rate: A Systematic Review and Meta-Analysis [CRD42021207726]).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 10 Nov 2022; epub ahead of print</small></div>

<div><h4>Atrial Functional Mitral Regurgitation: A JACC: Cardiovascular Imaging Expert Panel Viewpoint.</h4><i>Zoghbi WA, Levine RA, Flachskampf F, Grayburn P, ... Vandervoort P, Chandrashekhar Y</i><br /><AbstractText>Functional or secondary mitral regurgitation (MR) is associated with increased cardiovascular morbidity and mortality. Mechanistically, secondary MR is attributable to an imbalance between mitral leaflet tethering and closure forces, leading to poor coaptation. The pathophysiology of functional MR is most often the result of abnormalities in left ventricular function and remodeling, seen in ischemic or nonischemic conditions. Less commonly and more recently recognized is the scenario in which left ventricular geometry and function are preserved, the culprit being mitral annular enlargement associated with left atrial dilatation, termed atrial functional mitral regurgitation (AFMR). This most commonly occurs in the setting of chronic atrial fibrillation or heart failure with preserved ejection fraction. There is variability in the published reports and in current investigations as to the definition of AFMR. This paper reviews the pathophysiology of AFMR and focus on the need for a collective definition of AFMR to facilitate consistency in reported data and enhance much-needed research into outcomes and treatment strategies in AFMR.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Nov 2022; 15:1870-1882</small></div>

<div><h4>Global Circumferential and Radial Strain Among Patients With Immune Checkpoint Inhibitor Myocarditis.</h4><i>Quinaglia T, Gongora C, Awadalla M, Hassan MZO, ... Thavendiranathan P, Neilan TG</i><br /><b>Background</b><br />Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS.<br /><b>Objectives</b><br />This study aimed to detail the role of GCS and GRS in ICI myocarditis.<br /><b>Methods</b><br />In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death.<br /><b>Results</b><br />Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n = 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P < 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002).<br /><b>Conclusions</b><br />GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.<br /><br />Copyright © 2022 American College of Cardiology Foundation. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Nov 2022; 15:1883-1896</small></div>

<div><h4>Plaque Burden and 1-Year Outcomes in Acute Chest Pain: Results From the Multicenter RAPID-CTCA Trial.</h4><i>Meah MN, Tzolos E, Wang KL, Bularga A, ... Williams MC, Roobottom C</i><br /><b>Background</b><br />In patients with stable chest pain, computed tomography (CT) plaque burden is an independent predictor of future coronary events.<br /><b>Objectives</b><br />The purpose of this study was to determine whether plaque burden and characteristics can predict subsequent death or myocardial infarction in patients with acute chest pain.<br /><b>Methods</b><br />In a post hoc analysis of a multicenter trial of early coronary CT angiography, the authors performed quantitative plaque analysis to assess the association between primary endpoint of 1-year all-cause death or nonfatal myocardial infarction and the GRACE (Global Registry of Acute Coronary Events) score, presence of obstructive coronary artery disease, and plaque burden in 404 patients with suspected acute coronary syndrome.<br /><b>Results</b><br />Following the index event, 25 patients had a primary event that was associated with a higher GRACE score (134 ± 44 vs 113 ± 35; P = 0.012), larger burdens of total (46% [IQR: 43%-50%] vs 36% [IQR: 21%-46%]; P < 0.001), noncalcified (41% [IQR: 37%-%47] vs 33% [IQR: 20%-41%]; P < 0.001), and low-attenuation plaque (4.22% [IQR: 3.3%-5.68%] vs 2.14% [IQR: 0.5%-4.88%]; P < 0.001), but not obstructive coronary artery disease (P = 0.065). Total, noncalcified, and low-attenuation plaque burden were the strongest predictors of future events independent of GRACE score and obstructive coronary artery disease (P ≤ 0.002 for all). Patients with a low-attenuation burden above the median had nearly an 8-fold increased risk of the primary endpoint (HR: 7.80 [95% CI: 2.33-26.0]; P < 0.001), outperforming either a GRACE score of >140 (HR: 3.80 [95% CI :1.45-6.98]; P = 0.004) or obstructive coronary artery disease (HR: 2.07 [95% CI: 0.94-4.53]; P = 0.07).<br /><b>Conclusions</b><br />In patients with suspected acute coronary syndrome, low-attenuation plaque burden is a major predictor of 1-year death or recurrent myocardial infarction. (Rapid Assessment of Potential Ischaemic Heart Disease With CTCA [RAPID-CTCA]; NCT02284191).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Nov 2022; 15:1916-1925</small></div>

<div><h4>Effect of Immunosuppressive Therapy and Biopsy Status in Monitoring Therapy Response in Suspected Cardiac Sarcoidosis.</h4><i>Rojulpote C, Bhattaru A, Jean C, Adams SL, ... Goldberg L, Bravo PE</i><br /><b>Background</b><br />Patients with suspected cardiac sarcoidosis frequently undergo fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging to assess disease activity at baseline and after treatment initiation.<br /><b>Objectives</b><br />This study investigated the effect of immunosuppressive therapy and biopsy status to achieve complete treatment response (CTR), partial treatment response (PTR), or no response (NR) on myocardial FDG-PET/CT.<br /><b>Methods</b><br />This study analyzed 83 patients with suspected cardiac sarcoidosis (aged 53 ± 1.8 years, 71% were male, 69% were White, 61% had a history of biopsy-confirmed sarcoidosis) who were treatment naive, had evidence of myocardial FDG at baseline, and underwent repeat PET imaging after treatment initiation. CTR was graded visually, and PTR/NR were measured both visually and quantitatively using the total glycolytic activity. Patients were also evaluated for the occurrence of death, sustained ventricular arrhythmias, and heart failure admissions.<br /><b>Results</b><br />Overall, 59 patients (71%) achieved CTR/PTR (30%/41%) at follow-up scan (P = 0.04). Total glycolytic activity and visual estimate of PTR/NR had excellent agreement (κ = 0.86 [95% CI: 0.72-0.99]; P < 0.0001). In patients receiving prednisone only, the highest rates of CTR/PTR were observed in patients initiated on moderate or high dose (P < 0.01). In a regression model, moderate prednisone start dose (P = 0.03) was more strongly associated with achieving CTR/PTR than was high prednisone start dose. However, the latter patients were tapered faster between start dose and follow-up scan (P < 0.01). After a median follow-up of 4.7 (IQR: 3.1-7.8) years, patients who were biopsy-proven (vs non-biopsy-proven; P = 0.029) and with preserved left ventricular function (P = 002) were less likely to experience major adverse cardiac events. Outcomes based on treatment response status (CTR vs PTR vs NR; P = 0.23) were not significantly different.<br /><b>Conclusions</b><br />Among patients with suspected sarcoidosis and evidence of myocardial inflammation, treatment response by serial FDG-PET was variable, but a favorable response was more common when using moderate-to-high intensity prednisone dose. Biopsy-proven individuals and those with preserved systolic function were less likely to experience adverse outcomes during follow-up.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Nov 2022; 15:1944-1955</small></div>

<div><h4>Feasibility of Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT in Light-Chain Cardiac Amyloidosis.</h4><i>Wang X, Guo Y, Gao Y, Ren C, ... Li X, Huo L</i><br /><b>Background</b><br />Systemic amyloid light chain (AL) amyloidosis is the most common type of amyloidosis, leading to cardiomyocyte necrosis and interstitial fibrosis. Gallium-68-labeled fibroblast activation protein inhibitor 04 (<sup>68</sup>Ga-FAPI-04) has recently been introduced for imaging fibroblast activation in cardiac diseases. To date, cardiac fibroblast and cardiac amyloidosis (CA) phenotype activities have not been mapped.<br /><b>Objectives</b><br />The aim of this study was to evaluate the feasibility of <sup>68</sup>Ga-FAPI-04 positron emission tomography (PET)/computed tomography (CT) in assessing AL CA.<br /><b>Methods</b><br />Thirty consecutive patients (mean age: 59.1 ± 7.7 years; 20 men, 10 women) with biopsy-proven AL amyloidosis were enrolled prospectively (including 27 with AL CA and 3 without AL CA). All patients underwent <sup>68</sup>Ga-FAPI-04 PET/CT (107.4 ± 26.5 MBq). Global standardized uptake values and left ventricular (LV) molecular volume were calculated in correlation to echocardiography (n = 30), cardiac magnetic resonance (n = 18), and clinical biomarkers. Subsequently, the patients were categorized as having patchy (PET-patchy), extensive (PET-extensive), and negative (PET-negative) patterns.<br /><b>Results</b><br />Of all patients, 80% (24 of 30) showed increased LV uptake (PET-patchy [n = 4] vs PET-extensive [n = 20]), whereas 6 patients did not show visible myocardial uptake. Standardized uptake value ratio and LV molecular volume were significantly higher in the PET-extensive than the PET-patchy group (2.79 mL ± 1.22 mL vs 1.53 mL ± 0.66 mL [P = 0.045] and 198.3 mL ± 59.97 mL vs 127.8 mL ± 25.82 [P = 0.005], respectively). Additionally, <sup>68</sup>Ga-FAPI-04 uptake was significantly correlated with clinical biomarkers (Mayo stage and N-terminal pro-brain natriuretic peptide), interventricular septal thickness, left ventricular ejection fraction (LVEF), LV end-systolic volume, extracellular volume, and LV global strain (P < 0.05).<br /><b>Conclusions</b><br /><sup>68</sup>Ga-FAPI-04 PET/CT is feasible in detecting myocardial fibroblast activation in patients with AL CA in correlation with myocardial remodeling. It might provide complementary information on cardiac molecular characterization and staging of disease.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Nov 2022; 15:1960-1970</small></div>

<div><h4>Noninvasive Evaluation of Cardiac Chamber Pressures Using Subharmonic-Aided Pressure Estimation With Definity Microbubbles.</h4><i>Esposito C, Machado P, McDonald ME, Savage MP, ... Forsberg F, Dave JK</i><br /><b>Background</b><br />Noninvasive and accurate assessment of intracardiac pressures has remained an elusive goal of noninvasive cardiac imaging.<br /><b>Objectives</b><br />The purpose of this study was to investigate if errors in intracardiac pressures obtained noninvasively using contrast microbubbles and the subharmonic-aided pressure estimation (SHAPE) technique are <5 mm Hg.<br /><b>Methods</b><br />In a nonrandomized institutional review board-approved clinical trial (NCT03243942, patients scheduled for a left-sided and/or right-sided heart catheterization procedure and providing written informed consent were included. A standard-of-care catheterization procedure was performed advancing clinically used pressure catheters into the left and/or right ventricles and/or the aorta. After pressure catheter placement, patients received an infusion of Definity microbubbles (n = 56; 2 vials diluted in 50 mL of saline; infusion rate: 4-10 mL/min) (Lantheus Medical Imaging). Then SHAPE data was acquired using a validated interface developed on a SonixTablet scanner (BK Medical Systems) synchronously with the pressure catheter data. A conversion factor (mm Hg/dB) was derived from SHAPE data and measurements with a SphygmoCor XCEL PWA device (ATCOR Medical) and was combined with SHAPE data from the left and/or the right ventricles to obtain clinically relevant systolic and diastolic ventricular pressures.<br /><b>Results</b><br />The mean value of absolute errors for left ventricular minimum and end diastolic pressures were 2.9 ± 2.0 and 1.7 ± 1.2 mm Hg (n = 26), respectively, and for right ventricular systolic pressures was 2.2 ± 1.5 mm Hg (n = 11). Two adverse events occurred during Definity infusion; both were resolved.<br /><b>Conclusions</b><br />These results indicate that the SHAPE technique with Definity microbubbles is encouragingly efficacious for obtaining intracardiac pressures noninvasively and accurately. (Noninvasive, Subharmonic Intra-Cardiac Pressure Measurement; NCT03243942).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Nov 2022; epub ahead of print</small></div>

<div><h4>Extracellular Volume Fraction by Computed Tomography Predicts Long-Term Prognosis Among Patients With Cardiac Amyloidosis.</h4><i>Gama F, Rosmini S, Bandula S, Patel KP, ... Hawkins PN, Treibel TA</i><br /><b>Background</b><br />Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis.<br /><b>Objectives</b><br />This study sought to investigate the association of extracellular volume fraction by computed tomography (ECV<sub>CT</sub>), myocardial remodeling, and mortality in patients with systemic amyloidosis.<br /><b>Methods</b><br />Patients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECV<sub>CT</sub> was analyzed. All patients also underwent clinical assessment, electrocardiography, echocardiography, serum amyloid protein component, and/or technetium-99m (<sup>99m</sup>Tc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECV<sub>CT</sub> was compared across different extents of cardiac infiltration (ATTR Perugini grade/AL Mayo stage) and evaluated for its association with myocardial remodeling and all-cause mortality.<br /><b>Results</b><br />A total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age 67 [IQR: 59-76] years, 70.8% male). Mean septal ECV<sub>CT</sub> was 42.7% ± 13.1% and 55.8% ± 10.9% in AL and ATTR amyloidosis, respectively, and correlated with indexed left ventricular mass (r = 0.426; P < 0.001), left ventricular ejection fraction (r = 0.460; P < 0.001), N-terminal pro-B-type natriuretic peptide (r = 0.563; P < 0.001), and high-sensitivity troponin T (r = 0.546; P < 0.001). ECV<sub>CT</sub> increased with cardiac amyloid involvement in both AL and ATTR amyloid. Over a mean follow-up of 5.3 ± 2.4 years, 40 deaths occurred (AL: n = 14 [35.0%]; ATTR: n = 26 [65.0%]). Septal ECV<sub>CT</sub> was independently associated with all-cause mortality in ATTR (not AL) amyloid after adjustment for age and septal wall thickness (HR: 1.046; 95% CI:1.003-1.090; P = 0.037).<br /><b>Conclusions</b><br />Cardiac amyloid burden quantified by ECV<sub>CT</sub> is associated with adverse cardiac remodeling as well as all-cause mortality among ATTR amyloid patients. ECV<sub>CT</sub> may address the need for better identification and risk stratification of amyloid patients, using a widely accessible imaging modality.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 19 Oct 2022; epub ahead of print</small></div>

<div><h4>Direct Risk Assessment From Myocardial Perfusion Imaging Using Explainable Deep Learning.</h4><i>Singh A, Miller RJH, Otaki Y, Kavanagh P, ... Berman DS, Slomka PJ</i><br /><b>Background</b><br />Myocardial perfusion imaging (MPI) is frequently used to provide risk stratification, but methods to improve the accuracy of these predictions are needed.<br /><b>Objectives</b><br />We developed an explainable deep learning (DL) model (HARD MACE [major adverse cardiac events]-DL) for the prediction of death or nonfatal myocardial infarction (MI) and validated its performance in large internal and external testing groups.<br /><b>Methods</b><br />Patients undergoing single-photon emission computed tomography MPI were included, with 20,401 patients in the training and internal testing group (5 sites) and 9,019 in the external testing group (2 different sites). HARD MACE-DL uses myocardial perfusion, motion, thickening, and phase polar maps combined with age, sex, and cardiac volumes. The primary outcome was all-cause mortality or nonfatal MI. Prognostic accuracy was evaluated using area under the receiver-operating characteristic curve (AUC).<br /><b>Results</b><br />During internal testing, patients with normal perfusion and elevated HARD-MACE-DL risk were at higher risk than patients with abnormal perfusion and low HARD-MACE-DL risk (annualized event rate, 2.9% vs 1.2%; P < 0.001). Patients in the highest quartile of HARD MACE-DL score had an annual rate of death or MI (4.8%) 10-fold higher than patients in the lowest quartile (0.48% per year). In external testing, the AUC for HARD MACE-DL (0.73; 95% CI: 0.71-0.75) was higher than a logistic regression model (AUC: 0.70), stress TPD (AUC: 0.65), and ischemic TPD (AUC: 0.63; all P < 0.01). Calibration, a measure of how well predicted risk matches actual risk, was excellent in both groups (Brier score, 0.079 for internal and 0.070 for external).<br /><b>Conclusions</b><br />The DL model predicts death or MI directly from MPI, by estimating patient-level risk with good calibration and improved accuracy compared with traditional quantitative approaches. The model incorporates mechanisms to explain to the physician which image regions contribute to the adverse event prediction.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 19 Oct 2022; epub ahead of print</small></div>

<div><h4>Quantitative Echocardiographic Assessment and Optimal Criteria for Early Intervention in Asymptomatic Tricuspid Regurgitation.</h4><i>Akintoye E, Wang TKM, Nakhla M, Ali AH, ... Griffin BP, Desai MY</i><br /><b>Background</b><br />Significant tricuspid regurgitation (TR) is associated with poor outcome and high operative mortality resulting from late presentation. Yet, the optimal timing for intervention is unknown.<br /><b>Objectives</b><br />The purpose of this study was to evaluate the prognostic value of echocardiographic parameters to inform early intervention in asymptomatic TR.<br /><b>Methods</b><br />Using the Cleveland Clinic echocardiography database 2004 to 2018, the authors identified a consecutive cohort of asymptomatic patients with moderate to severe (3+) or severe (4+) TR. Quantitative TR and right heart parameters were retrospectively determined, and their prognostic utility for all-cause mortality was assessed.<br /><b>Results</b><br />In 325 asymptomatic patients (mean age: 67.9 years; 79.4% female) with at least 3+ TR, there were 132 deaths (40.6%), with a median survival time of 9.9 years (95% CI: 7.9-12.7 years). By contrast, the median survival time in an age- and sex-matched cohort of symptomatic TR patients was 4.4 years (95% CI: 2.8-5.9 years). Among all the echocardiographic parameters evaluated, right ventricle free wall strain (RVFWS) and tricuspid regurgitant volume (RVol) were the strongest predictors of mortality in asymptomatic TR. The optimal discriminatory thresholds for these parameters were RVFWS <-19% and RVol >45 mL. The 5-year survival rates by number of risk factors (RF) were 93% (95% CI: 86%-96%), 65% (95% CI: 55%-74%), and 38% (95% CI: 26%-49%) for no RF, 1 RF, and both RFs, respectively. Compared with symptomatic TR, mortality was lower for asymptomatic TR with no RF (HR: 0.10; 95% CI: 0.04-0.29) or 1 RF (HR: 0.29; 95% CI: 0.14-0.58), but similar for asymptomatic TR with both RFs (HR: 1.11; 95% CI: 0.56-2.19).<br /><b>Conclusions</b><br />RVFWS and RVol are key prognostic markers that can be serially monitored to inform optimal timing of intervention for severe asymptomatic TR.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 19 Oct 2022; epub ahead of print</small></div>

<div><h4>Mitral Annular Disjunction Assessed Using CMR Imaging: Insights From the UK Biobank Population Study.</h4><i>Zugwitz D, Fung K, Aung N, Rauseo E, ... Petersen SE, Nijveldt R</i><br /><b>Background</b><br />Mitral annular disjunction is the atrial displacement of the mural mitral valve leaflet hinge point within the atrioventricular junction. Said to be associated with malignant ventricular arrhythmias and sudden death, its prevalence in the general population is not known.<br /><b>Objectives</b><br />The purpose of this study was to assess the frequency of occurrence and extent of mitral annular disjunction in a large population cohort.<br /><b>Methods</b><br />The authors assessed the cardiac magnetic resonance (CMR) images in 2,646 Caucasian subjects enrolled in the UK Biobank imaging study, measuring the length of disjunction at 4 points around the mitral annulus, assessing for presence of prolapse or billowing of the leaflets, and for curling motion of the inferolateral left ventricular wall.<br /><b>Results</b><br />From 2,607 included participants, the authors found disjunction in 1,990 (76%) cases, most commonly at the anterior and inferior ventricular wall. The authors found inferolateral disjunction, reported as clinically important, in 134 (5%) cases. Prolapse was more frequent in subjects with disjunction (odds ratio [OR]: 2.5; P = 0.02), with positive associations found between systolic curling and disjunction at any site (OR: 3.6; P < 0.01), and systolic curling and prolapse (OR: 71.9; P < 0.01).<br /><b>Conclusions</b><br />This large-scale study shows that disjunction is a common finding when using CMR. Disjunction at the inferolateral ventricular wall, however, was rare. The authors found associations between disjunction and both prolapse and billowing of the mural mitral valve leaflet. These findings support the notion that only extensive inferolateral disjunction, when found, warrants consideration of further investigation, but disjunction elsewhere in the annulus should be considered a normal finding.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 19 Oct 2022; epub ahead of print</small></div>

<div><h4>Comprehensive Evaluation of Left Ventricle Dysfunction by a New Computed Tomography Scanner: The E-PLURIBUS Study.</h4><i>Andreini D, Conte E, Mushtaq S, Melotti E, ... Onuma Y, Serruys PW</i><br /><b>Background</b><br />Although cardiac magnetic resonance (CMR) is considered the gold standard for myocardial fibrosis detection, cardiac computed tomography (CCT) is emerging as a promising alternative.<br /><b>Objectives</b><br />The purpose of this study was to assess feasibility and diagnostic accuracy of a comprehensive functional and anatomical evaluation with CCT as compared with CMR in patients with newly diagnosed left ventricular dysfunction (LVD).<br /><b>Methods</b><br />A total of 128 consecutive patients with newly diagnosed LVD were screened. Based on the exclusion criteria, 28 cases were excluded. CCT was performed within 10 days from CMR. Biventricular volumes and ejection fraction, and presence and pattern of delayed enhancement (DE), were determined, along with evaluation of coronary arteries among patients undergoing invasive angiography in the 6 months after CCT.<br /><b>Results</b><br />Six cases were excluded because of claustrophobia at CMR. Among the 94 patients who formed the study population, the concordance between CCT and CMR in suggesting the cause of the LVD was high (94.7%, 89/94 patients) in the overall population and was 100% for identifying ischemic cardiomyopathy. The CCT diagnostic rate for DE assessment was also high (96.7%, 1,544/1,598 territories) and similar to that of CMR (97.4%; P = 0.345, CCT vs CMR). Moreover, CCT showed high diagnostic accuracy in the detection of DE (94.8%, 95% CI: 93.6%-95.8%) in a territory-based analysis. Biventricular volumes and function parameters as measured by CCT and CMR were similar, without significant differences with the exception of a modest difference in RV volume. CCT was confirmed to be accurate for assessing arterial coronary circulation. The mean radiation exposure of the whole CCT was 7.78 ± 2.53 mSv (0.84 ± 0.24 mSv for DE).<br /><b>Conclusions</b><br />CCT performed with low-dose whole-heart coverage scanner and high-concentration contrast agent appears an effective noninvasive tool for a comprehensive assessment of patients with newly diagnosed LVD.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 07 Oct 2022; epub ahead of print</small></div>

<div><h4>Diagnostic Accuracy of the 2016 Guideline-Based Echocardiographic Algorithm to Estimate Invasively-Measured Left Atrial Pressure by Direct Atrial Cannulation.</h4><i>Pak M, Kitai T, Kobori A, Sasaki Y, ... Kinoshita M, Furukawa Y</i><br /><b>Background</b><br />Although estimation of left ventricular filling pressure (LVFP) using an integrated echocardiographic algorithm is recommended, the usefulness of this algorithm has not been fully validated.<br /><b>Objectives</b><br />The purpose of this study was to investigate the reliability of an algorithmic classification system using invasively measured left atrial pressure (LAP) in a large-scale cohort.<br /><b>Methods</b><br />The authors enrolled 1,967 patients (age 68 ± 10 years) whose LAP was directly measured within the left atrium during catheter ablation for atrial fibrillation. Patients were classified into 3 groups based on the echocardiographic algorithm: normal (group N, n = 1,282), undetermined (group U, n = 160), and elevated (group E, n = 346) LAP groups. Invasively measured LAP and echocardiographic parameters estimating LVFP were compared among the groups.<br /><b>Results</b><br />The median LAP was 12.6 ± 5.7 mm Hg in the entire cohort. LAP was significantly higher in group E than that in the other groups (groups E vs U vs N, 14.2 ± 6.3 mm Hg vs 13.5 ± 5.9 mm Hg vs 12.0 ± 5.5 mm Hg; P < 0.001). Among group E patients, 43.1% had elevated LAP (≥15 mm Hg), whereas 56.9% had normal LAP (<15 mm Hg). Of the patients in group N, 69.0% had normal LAP, whereas 31% had elevated LAP. Although the correlation between invasively measured LAP and E/e\', peak tricuspid regurgitant velocity, and left atrial volume index was modest, the number of abnormal values correlated significantly with elevated LAP (P < 0.001).<br /><b>Conclusions</b><br />The classification using combined echocardiographic parameters in the recommendations may be useful for detecting patients with normal LVFP but may be limited for detecting elevated LVFP.<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>JACC Cardiovasc Imaging: 01 Oct 2022; 15:1683-1691</small></div>

<div><h4>Clinical Characteristics and Prognostic Importance of Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy.</h4><i>Lee DZJ, Montazeri M, Bataiosu R, Hoss S, ... Rakowski H, Chan RH</i><br /><b>Background</b><br />Left ventricular (LV) apical aneurysms in hypertrophic cardiomyopathy (HCM) are a recognized risk marker for adverse cardiovascular events. There is variable practice among clinicians and discordance between international guidelines regarding treatment recommendations and prognostication for this important phenotype.<br /><b>Objectives</b><br />The authors sought to describe the morphology, clinical course, and risk of adverse events in a large single-center cohort of HCM patients with LV apical aneurysms.<br /><b>Methods</b><br />This study analyzed 160 HCM patients with an LV apical aneurysm who were evaluated in our dedicated HCM clinic between January 1997 and April 2021.<br /><b>Results</b><br />Mean age was 59.1 ± 13.6 years, and 71% of these patients were male. Mean aneurysm size was 1.77 ± 1.04 cm. Over 6.2 ± 4.8 years, 14 (9%) patients had a sudden cardiac death (SCD) event, including appropriate therapy from an implantable cardioverter-defibrillator (ICD) or resuscitation from cardiac arrest (annualized event rate 1.77%/y), 39 (24%) had either a thromboembolic stroke or apical thrombus formation (2.9%/y), and 14 (9%) developed LV systolic dysfunction with an ejection fraction (EF) <50% (1.28%/y). HRs for SCD, stroke or thrombus, and EF <50% per 1-cm increase in aneurysm size were 1.69 (P = 0.007), 1.60 (P = 0.0002), and 1.63 (P = 0.01), respectively. Aneurysm size ≥2 cm was associated with a 5-year SCD rate of 9.7%, compared with 2.9% for aneurysm size <2 cm (log-rank P = 0.037). This subgroup also had higher risk of stroke/thrombus formation (HR: 2.20; P = 0.002), with an annualized event rate of 2.7%/year. A total of 39 (24%) patients reached the combined end point of SCD, stroke, or LV dysfunction (2.12%/y) with an HR of 1.47/cm increase in aneurysm size (P = 0.003) and an HR of 2.22 for patients with aneurysm size ≥2 cm (P = 0.02).<br /><b>Conclusions</b><br />Increasing aneurysm size confers poorer prognosis. Aneurysm size ≥2 cm should alert potential consideration for prophylactic anticoagulation and primary prevention ICDs.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Oct 2022; 15:1696-1711</small></div>

<div><h4>Carotid Plaque Characteristics Predict Recurrent Ischemic Stroke and TIA: The PARISK (Plaque At RISK) Study.</h4><i>van Dam-Nolen DHK, Truijman MTB, van der Kolk AG, Liem MI, ... Kooi ME, PARISK Study Group</i><br /><b>Background</b><br />Patients with symptomatic carotid stenosis are at high risk for recurrent stroke. The decision for carotid endarterectomy currently mainly relies on degree of stenosis (cutoff value >50% or 70%). Nevertheless, also, patients with mild-to-moderate stenosis still have a considerable recurrent stroke risk. Increasing evidence suggests that carotid plaque composition rather than degree of stenosis determines plaque vulnerability; however, it remains unclear whether this also provides additional information to improve clinical decision making.<br /><b>Objectives</b><br />The PARISK (Plaque At RISK) study aimed to improve the identification of patients at increased risk of recurrent ischemic stroke using multimodality carotid imaging.<br /><b>Methods</b><br />The authors included 244 patients (71% men; mean age, 68 years) with a recent symptomatic mild-to-moderate carotid stenosis in a prospective multicenter cohort study. Magnetic resonance imaging (carotid and brain) and computed tomography angiography (carotid) were performed at baseline and after 2 years. The clinical endpoint was a recurrent ipsilateral ischemic stroke or transient ischemic attack (TIA). Cox proportional hazards models were used to assess whether intraplaque hemorrhage (IPH), ulceration, proportion of calcifications, and total plaque volume in ipsilateral carotid plaques were associated with the endpoint. Next, the authors investigated the predictive performance of these imaging biomarkers by adding these markers (separately and simultaneously) to the ECST (European Carotid Surgery Trial) risk score.<br /><b>Results</b><br />During 5.1 years follow-up, 37 patients reached the clinical endpoint. IPH presence and total plaque volume were associated with recurrent ipsilateral ischemic stroke or TIA (HR: 2.12 [95% CI: 1.02-4.44] for IPH; HR: 1.07 [95% CI: 1.00-1.15] for total plaque volume per 100 µL increase). Ulcerations and proportion of calcifications were not statistically significant determinants. Addition of IPH and total plaque volume to the ECST risk score improved the model performance (C-statistics increased from 0.67 to 0.75-0.78).<br /><b>Conclusions</b><br />IPH and total plaque volume are independent risk factors for recurrent ipsilateral ischemic stroke or TIA in patients with mild-to-moderate carotid stenosis. These plaque characteristics improve current decision making. Validation studies to implement plaque characteristics in clinical scoring tools are needed. (PARISK: Validation of Imaging Techniques [PARISK]; NCT01208025).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Oct 2022; 15:1715-1726</small></div>

<div><h4>The Prognostic Value of CAC Zero Among Individuals Presenting With Chest Pain: A Meta-Analysis.</h4><i>Agha AM, Pacor J, Grandhi GR, Mszar R, ... Miller EJ, Nasir K</i><br /><b>Background</b><br />There is little consensus on whether absence of coronary artery calcium (CAC) can identify patients with chest pain (CP) who can safely avoid additional downstream testing.<br /><b>Objectives</b><br />The purpose of this study was to conduct a systematic review and meta-analysis investigating the utility of CAC assessment for ruling out obstructive coronary artery disease (CAD) among patients with stable and acute CP, at low-to-intermediate risk of obstructive CAD undergoing coronary computed tomography angiography (CTA).<br /><b>Methods</b><br />The authors searched online databases for studies published between 2005 and 2021 examining the relationship between CAC and obstructive CAD (≥50% coronary luminal narrowing) on coronary CTA among patients with stable and acute CP.<br /><b>Results</b><br />In this review, the authors included 19 papers comprising 79,903 patients with stable CP and 13 papers including 12,376 patients with acute CP undergoing simultaneous CAC and coronary CTA assessment. Overall, 45% (95% CI: 40%-50%) of patients with stable CP and 58% (95% CI: 50%-66%) of patients with acute CP had CAC = 0. The negative predictive values for CAC = 0 ruling out obstructive CAD were 97% (95% CI: 96%-98%) and 98% (95% CI: 96%-99%) among patients with stable and acute CP, respectively. Additionally, the prevalence of nonobstructive CAD among those with CAC = 0 was 13% (95% CI: 10%-16%) among those with stable CP and 9% (95% CI: 5%-13%) among those with acute CP. A CAC score of zero predicted a low incidence of major adverse cardiac events among patients with stable CP (0.5% annual event rate) and acute CP (0.8% overall event rate).<br /><b>Conclusions</b><br />Among over 92,000 patients with stable or acute CP, the absence of CAC was associated with a very low prevalence of obstructive CAD, a low prevalence of nonobstructive CAD, and a low annualized risk of major adverse cardiac events. These findings support the role of CAC = 0 in a value-based health care delivery model as a \"gatekeeper\" for more advanced imaging among patients presenting with CP.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Oct 2022; 15:1745-1757</small></div>

<div><h4>Association Between Changes in Perivascular Adipose Tissue Density and Plaque Progression.</h4><i>Lee SE, Sung JM, Andreini D, Al-Mallah MH, ... Min JK, Chang HJ</i><br /><b>Background</b><br />The association between the change in vessel inflammation, as quantified by perivascular adipose tissue (PVAT) density, and the progression of coronary atherosclerosis remains to be determined.<br /><b>Objectives</b><br />The purpose of this study was to explore the association between the change in PVAT density and the progression of total and compositional plaque volume (PV).<br /><b>Methods</b><br />Patients were selected from a prospective multinational registry. Patients who underwent serial coronary computed tomography angiography studies with ≥2-year intervals and were scanned with the same tube voltage at baseline and follow-up were included. Total and compositional PV and PVAT density at baseline and follow-up were quantitatively analyzed for every lesion. Multivariate linear regression models using cluster analyses were constructed.<br /><b>Results</b><br />A total of 1,476 lesions were identified from 474 enrolled patients (mean age 61.2 ± 9.3 years; 65.0% men). The mean PVAT density was -74.1 ± 11.5 HU, and total PV was 48.1 ± 83.5 mm<sup>3</sup> (19.2 ± 44.8 mm<sup>3</sup> of calcified PV and 28.9 ± 51.0 mm<sup>3</sup> of noncalcified PV). On multivariate analysis (adjusted for clinical risk factors, medication use, change in lipid levels, total PV at baseline, luminal HU attenuation, location of lesions, and tube voltage), the increase in PVAT density was positively associated with the progression of total PV (estimate = 0.275 [95% CI: 0.004-0.545]; P = 0.047), driven by the association with fibrous PV (estimate = 0.245 [95% CI: 0.070-0.420]; P = 0.006). Calcified PV progression was not associated with the increase in PVAT density (P > 0.050).<br /><b>Conclusions</b><br />Increase in vessel inflammation represented by PVAT density is independently associated with the progression of the lipid component of coronary atherosclerotic plaques. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Oct 2022; 15:1760-1767</small></div>

<div><h4>Clinical Applications of FDG-PET Scan in Arrhythmic Myocarditis.</h4><i>Peretto G, Busnardo E, Ferro P, Palmisano A, ... Della Bella P, Sala S</i><br /><b>Background</b><br /><sup>18</sup>F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan has no recognized role in diagnosis, prognosis, and disease monitoring in patients with arrhythmic myocarditis.<br /><b>Objectives</b><br />The purpose of this study was to investigate the value of FDG-PET scan in arrhythmic myocarditis.<br /><b>Methods</b><br />The authors enrolled 75 consecutive patients (age 47 ± 14 years, 65% men) undergoing FDG-PET scan for arrhythmic myocarditis. Myocarditis was diagnosed by endomyocardial biopsy (EMB) and, whenever applicable, cardiac magnetic resonance (CMR).<br /><b>Results</b><br />Indications for FDG-PET scan included either contraindication to CMR (n = 50) or mismatch between CMR and EMB (n = 25). Overall, 50 patients (67%) had positive FDG-PET. Sensitivity was 75% referring to EMB, and 73% to CMR. Specificity was 67% referring to EMB, and 59% to CMR. FDG-PET accuracy was lower in the presence of borderline myocarditis, and either late (>30 days) or on-immunosuppression FDG-PET scanning. Anteroseptal distribution pattern, found in 12 of 50 (24%) patients including 7 of 7 cardiac sarcoidosis cases, was associated with greater occurrence of ventricular arrhythmias and atrioventricular blocks in 4.2 ± 1.7 years of follow-up (10 of 12 vs 7 of 38, and 7 of 12 vs 0 of 38, respectively; both P < 0.001). In 39 patients (52%), FDG-PET was repeated by 13 ± 2 months, allowing immunosuppression withdrawal after FDG uptake normalization either by first (76%) or second reassessment (24%).<br /><b>Conclusions</b><br />FDG-PET scan may be a clinically useful diagnostic technique in arrhythmic myocarditis, in particular when CMR is unsuitable because of irregular heartbeat or implantable cardioverter-defibrillator-related artifacts. Anteroseptal FDG distribution is associated with a worse arrhythmic outcome and should raise the suspicion of cardiac sarcoidosis. During follow-up, repeated FDG-PET allows myocarditis monitoring to guide immunosuppression withdrawal.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Oct 2022; 15:1771-1780</small></div>

<div><h4>Clinical Utility of Intravascular Imaging: Past, Present, and Future.</h4><i>Mintz GS, Matsumura M, Ali Z, Maehara A</i><br /><AbstractText>Although it is the tool used by most interventional cardiologists to assess the severity of coronary artery disease and guide treatment, coronary angiography has many limitations because it is a shadowgraph, depicting planar projections of the contrast-filled lumen that are often foreshortened rather than imaging the diseased vessel itself. Currently available intravascular imaging technologies include grayscale intravascular ultrasound (IVUS), optical coherence tomography (OCT) (the light analogue of IVUS), and near-infrared spectroscopy that detects lipid within the vessel wall and that has been combined with grayscale IVUS in a single catheter as the first combined imaging device. They provide tomographic or cross-sectional images of the coronary arteries that include the lumen, vessel wall, plaque burden, plaque composition and distribution, and even peri-vascular structures-information promised, but rarely provided angiographically. Extensive literature shows that these tools can be used to answer questions that occur during daily practice as well as improving patient outcomes. Is this stenosis significant? Where is the culprit lesion? What is the anatomy of an unusual or ambiguous angiographic lesion? What is the right stent size and length? What is the likelihood of distal embolization or periprocedural myocardial infarction during stent implantation? Has the intervention been optimized? Why did this stent thrombose or restenose? This review summarizes these uses of intravascular imaging as well as the outcomes data supporting their incorporation into routine clinical practice.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Oct 2022; 15:1799-1820</small></div>

<div><h4>Current Applications of Robot-Assisted Ultrasound Examination.</h4><i>Hidalgo EM, Wright L, Isaksson M, Lambert G, Marwick TH</i><br /><AbstractText>Despite advances in miniaturization and automation, the need for expert acquisition of a full echocardiogram, including Doppler, has restricted access in remote areas. Recent developments in robotics, teleoperation, and upgraded telecommunications infrastructure may provide a solution to this deficiency. Robot-assisted teleoperated ultrasound examination can aid medical diagnosis in remote locations and may improve health inequalities between rural and urban settings. This review aimed to analyze the status of teleoperated robotic systems for ultrasound examinations, evaluate clinical and preclinical applications, identify limitations, and outline future directions for clinical use. Overall, robot-assisted teleoperated ultrasound is feasible and safe in the reported clinical and preclinical studies, with the robots able to follow the hand movements performed by sonographers and researchers from a distance or in local networks. Moreover, multiple types of ultrasound examinations have been performed in remote areas, with a high success rate nearly comparable to that of conventional sonography. The studies showed that although a low-bandwidth link can be used to control a robot, the bandwidth requirements for real-time transmission of video and ultrasound images are significantly higher. Furthermore, if haptic feedback is implemented, the bandwidth requirements are increased. Haptically enabled systems that improve robotic control are necessary for accelerating the introduction to clinical use. Haptic feedback and enhanced front-end interface control for remote users are vital aspects required for clinical application. The incorporation of artificial intelligence through either aiding in window acquisition (knowledge of anatomical landmarks to adjust scanning planes) or through measurement and disease identification is yet to be researched. However, it has the potential to lead to dramatic advances. A new generation of robots is in development, and several projects in the preclinical stage reveal a promising future to overcome the shortage of health professionals in remote areas.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 20 Sep 2022; epub ahead of print</small></div>

<div><h4>Impact of Loading and Myocardial Mechanical Properties on Natural Shear Waves: Comparison to Pressure-Volume Loops.</h4><i>Bézy S, Duchenne J, Orlowska M, Caenen A, ... D\'hooge J, Voigt JU</i><br /><b>Background</b><br />Shear wave elastography (SWE) has been proposed as a novel noninvasive method for the assessment of myocardial stiffness, a relevant determinant of diastolic function. It is based on tracking the propagation of shear waves, induced, for instance, by mitral valve closure (MVC), in the myocardium. The speed of propagation is directly related to myocardial stiffness, which is defined by the local slope of the nonlinear stress-strain relation. Therefore, the operating myocardial stiffness can be altered by both changes in loading and myocardial mechanical properties.<br /><b>Objectives</b><br />This study sought to evaluate the capability of SWE to quantify myocardial stiffness changes in vivo by varying loading and myocardial tissue properties and to compare SWE against pressure-volume loop analysis, a gold standard reference method.<br /><b>Methods</b><br />In 15 pigs, conventional and high-frame rate echocardiographic data sets were acquired simultaneously with pressure-volume loop data after acutely changing preload and afterload and after inducting an ischemia/reperfusion (I/R) injury.<br /><b>Results</b><br />Shear wave speed after MVC significantly increased by augmenting preload and afterload (3.2 ± 0.8 m/s vs 4.6 ± 1.2 m/s and 4.6 ± 1.0 m/s, respectively; P = 0.001). Preload reduction had no significant effect on shear wave speed compared to baseline (P = 0.118). I/R injury resulted in significantly higher shear wave speed after MVC (6.1 ± 1.2 m/s; P < 0.001). Shear wave speed after MVC had a strong correlation with the chamber stiffness constant β (r = 0.63; P < 0.001) and operating chamber stiffness dP/dV before induction of an I/R injury (r = 0.78; P < 0.001) and after (r = 0.83; P < 0.001).<br /><b>Conclusions</b><br />Shear wave speed after MVC was influenced by both acute changes in loading and myocardial mechanical properties, reflecting changes in operating myocardial stiffness, and was strongly related to chamber stiffness, invasively derived by pressure-volume loop analysis. SWE provides a novel noninvasive method for the assessment of left ventricular myocardial properties.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 14 Sep 2022; epub ahead of print</small></div>

<div><h4>Ischemia With Nonobstructive Coronary Arteries: Insights From the ISCHEMIA Trial.</h4><i>Reynolds HR, Diaz A, Cyr DD, Shaw LJ, ... Maron DJ, ISCHEMIA Research Group</i><br /><b>Background</b><br />Ischemia with nonobstructive coronary arteries (INOCA) is common clinically, particularly among women, but its prevalence among patients with at least moderate ischemia and the relationship between ischemia severity and non-obstructive atherosclerosis severity are unknown.<br /><b>Objectives</b><br />The authors investigated predictors of INOCA in enrolled, nonrandomized participants in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), sex differences, and the relationship between ischemia and atherosclerosis in patients with INOCA.<br /><b>Methods</b><br />Core laboratories independently reviewed screening noninvasive stress test results (nuclear imaging, echocardiography, magnetic resonance imaging or nonimaging exercise tolerance testing), and coronary computed tomography angiography (CCTA), blinded to results of the screening test. INOCA was defined as all stenoses <50% on CCTA in a patient with moderate or severe ischemia on stress testing. INOCA patients, who were excluded from randomization, were compared with randomized participants with ≥50% stenosis in ≥1 vessel and moderate or severe ischemia.<br /><b>Results</b><br />Among 3,612 participants with core laboratory-confirmed moderate or severe ischemia and interpretable CCTA, 476 (13%) had INOCA. Patients with INOCA were younger, were predominantly female, and had fewer atherosclerosis risk factors. For each stress testing modality, the extent of ischemia tended to be less among patients with INOCA, particularly with nuclear imaging. There was no significant relationship between severity of ischemia and extent or severity of nonobstructive atherosclerosis on CCTA. On multivariable analysis, women female sex was independently associated with INOCA (odds ratio: 4.2 [95% CI: 3.4-5.2]).<br /><b>Conclusions</b><br />Among participants enrolled in ISCHEMIA with core laboratory-confirmed moderate or severe ischemia, the prevalence of INOCA was 13%. Severity of ischemia was not associated with severity of nonobstructive atherosclerosis. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 13 Sep 2022; epub ahead of print</small></div>

<div><h4>CAD-RADS™ 2.0 - 2022 Coronary Artery Disease-Reporting and Data System: An Expert Consensus Document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Cardiology (ACC), the American College of Radiology (ACR), and the North America Society of Cardiovascular Imaging (NASCI).</h4><i>Cury RC, Leipsic J, Abbara S, Achenbach S, ... Villines TC, Blankstein R</i><br /><AbstractText>Coronary Artery Disease Reporting and Data System (CAD-RADS) was created to standardize reporting system for patients undergoing coronary CT angiography (CCTA) and to guide possible next steps in patient management. The goal of this updated 2022 CAD-RADS 2.0 is to improve the initial reporting system for CCTA by considering new technical developments in Cardiac CT, including data from recent clinical trials and new clinical guidelines. The updated CAD-RADS classification will follow an established framework of stenosis, plaque burden, and modifiers, which will include assessment of lesion-specific ischemia using CT fractional-flow-reserve (CT-FFR) or myocardial CT perfusion (CTP), when performed. Similar to the method used in the original CAD-RADS version, the determinant for stenosis severity classification will be the most severe coronary artery luminal stenosis on a per-patient basis, ranging from CAD-RADS 0 (zero) for absence of any plaque or stenosis to CAD-RADS 5 indicating the presence of at least one totally occluded coronary artery. Given the increasing data supporting the prognostic relevance of coronary plaque burden, this document will provide various methods to estimate and report total plaque burden. The addition of P1 to P4 descriptors are used to denote increasing categories of plaque burden. The main goal of CAD-RADS, which should always be interpreted together with the impression found in the report, remains to facilitate communication of test results with referring physicians along with suggestions for subsequent patient management. In addition, CAD-RADS will continue to provide a framework of standardization that may benefit education, research, peer-review, artificial intelligence development, clinical trial design, population health and quality assurance with the ultimate goal of improving patient care.</AbstractText><br /><br />Copyright © 2022 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 09 Sep 2022; epub ahead of print</small></div>

<div><h4>Reverse Remodeling Assessed by Left Atrial and Ventricular Strain Reflects Treatment Response to Sacubitril/Valsartan.</h4><i>Moon MG, Hwang IC, Lee HJ, Kim SH, ... Kim YJ, Cho GY</i><br /><b>Background</b><br />The left ventricular global longitudinal strain (LVGLS) and left atrial reservoir strain (LARS) are considered as sensitive and reliable markers of cardiac remodeling and function. However, their temporal changes during optimal management of heart failure with reduced ejection fraction (HFrEF) are unknown.<br /><b>Objectives</b><br />This study investigated the time trajectories of the LARS and LVGLS in patients with HFrEF treated with angiotensin receptor-neprilysin inhibitors, and assessed whether the LARS and LVGLS could define left heart reverse remodeling (LHRR) and reflect the treatment response and prognosis.<br /><b>Methods</b><br />Using a retrospective cohort of patients with HFrEF prescribed sacubitril/valsartan, we assessed the time trajectories of the LVGLS and LARS in 409 patients (1,258 echocardiograms), and investigated their association with the occurrence of cardiovascular death and hospitalization for heart failure (HHF), after the determination of LHRR, during a median follow-up of 27.1 (IQR: 18.3-36.3) months.<br /><b>Results</b><br />Among patients with HFrEF prescribed sacubitril/valsartan, both the LVGLS and LARS improved over time. The improvements in the LVGLS and LARS were prominent within 6 months of sacubitril/valsartan treatment: the LVGLS improved from 10.2% (IQR: 7.9%-12.7%) to 13.9% (IQR: 10.5%-16.3%) (P < 0.001), and the LARS improved from 11.4% (IQR: 8.4%-15.6%) to 15.9% (IQR: 11.5%-21.4%) (P < 0.001). These improvements were larger among patients who did not experience the study outcome than in patients with events. Improvement in the LVGLS to ≥13% and LARS to ≥12.5% (ie, complete LHRR) was significantly associated with a lower risk of cardiovascular death and HHF, and this association was stronger than that of changes in other conventional echocardiographic parameters.<br /><b>Conclusions</b><br />In patients with HFrEF treated with sacubitril/valsartan, the LVGLS and LARS were improved, typically within 6 months of treatment. Complete LHRR, defined by improvement in the LVGLS and LARS, can be an indicator of treatment response and prognosis.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Sep 2022; 15:1525-1541</small></div>

<div><h4>Ventricular-Arterial Coupling Derived From Proximal Aortic Stiffness and Aerobic Capacity Across the Heart Failure Spectrum.</h4><i>Pugliese NR, Balletti A, Armenia S, De Biase N, ... Antonini-Canterin F, Masi S</i><br /><b>Background</b><br />Ventricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulsed wave velocity [PWV]) and myocardial deformation (global longitudinal strain [GLS]).<br /><b>Objectives</b><br />This study aimed to evaluate VAC across the spectrum of heart failure (HF).<br /><b>Methods</b><br />The authors introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). They measured PWVs and GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association stage A-B) and 236 patients in stage C heart failure with preserved ejection fraction (HFpEF) (n = 104) or heart failure with reduced ejection fraction (HFrEF) (n = 132). They evaluated peak oxygen consumption and peripheral extraction using combined cardiopulmonary-echocardiography exercise stress.<br /><b>Results</b><br />aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (P < 0.01). PWVs were directly related and increased with age (all P < 0.0001). cf-PWV/GLS was similarly compromised in HFrEF (1.09 ± 0.35) and HFpEF (1.05 ± 0.21), whereas aa-PWV/GLS was more impaired in HFpEF (0.70 ± 0.10) than HFrEF (0.61 ± 0.14; P < 0.01). Stage A-B had values of cf-PWV/GLS and aa-PWV/GLS (0.67 ± 0.27 and 0.48 ± 0.14, respectively) higher than controls (0.46 ± 0.11 and 0.39 ± 0.10, respectively) but lower than stage C (all P < 0.01). Peak arteriovenous oxygen difference (AVO<sub>2</sub>diff) was inversely related with cf-PWV/GLS and aa-PWV/GLS (all P < 0.01). Although cf-PWV/GLS and aa-PWV/GLS independently predicted peak VO<sub>2</sub> in the overall population (adjusted R<sup>2</sup> = 0.33 and R<sup>2</sup>= 0.36; all P < 0.0001), only aa-PWV/GLS was independently associated with flow reserve during exercise (R<sup>2</sup> = 0.52; P < 0.0001).<br /><b>Conclusions</b><br />Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/GLS.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Sep 2022; 15:1545-1559</small></div>

<div><h4>Peak Troponin and CMR to Guide Management in Suspected ACS and Nonobstructive Coronary Arteries.</h4><i>Williams MGL, Liang K, De Garate E, Spagnoli L, ... Luscher T, Bucciarelli-Ducci C</i><br /><b>Background</b><br />Patients presenting with acute coronary syndrome (ACS) and nonobstructive coronary arteries are a diagnostic dilemma. Cardiac magnetic resonance (CMR) has an overall diagnostic yield of ∼75%; however, in ∼25% of patients, CMR does not identify any myocardial injury. Identifying the underlying diagnosis has important clinical implications for patients\' management and outcome.<br /><b>Objectives</b><br />The authors sought to assess whether the combination of CMR and peak troponin levels in patients with ACS and nonobstructive coronary arteries would lead to increased diagnostic yield.<br /><b>Methods</b><br />Consecutive patients with ACS and nonobstructive coronary arteries without an obvious cause underwent CMR. The primary endpoint of the study was the diagnostic yield of CMR. The Youden index was used to find the optimal diagnostic cut point for peak troponin T to combine with CMR to improve diagnostic yield. Logistic or Cox regression models were used to estimate predictors of a diagnosis by CMR.<br /><b>Results</b><br />A total of 719 patients met the inclusion criteria. The peak troponin T threshold for optimal diagnostic sensitivity and specificity was 211 ng/L. Overall, CMR has a diagnostic yield of 74%. CMR performed <14 days from presentation and with a peak troponin of ≥211 ng/L (n = 198) leads to an improved diagnostic yield (94% vs 72%) compared with CMR performed ≥14 days (n = 245). When CMR was performed <14 days and with a peak troponin of <211 ng/L, the diagnostic yield was 76% (n = 86) compared with 53% (n = 190) when performed ≥14 days. An increase in 1 peak troponin decile increases the odds of the CMR identifying a diagnosis by 20% (OR: 1.20; P = 0.008, 95% CI: 1.05-1.36).<br /><b>Conclusions</b><br />The combination of CMR performed <14 days from presentation and peak troponin T ≥211 ng/L leads to a very high diagnostic yield (94%) on CMR. The diagnostic yield remains high (72%) even when CMR is performed ≥14 days from presentation, but reduces to 53% when peak troponin T was <211 ng/L.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Sep 2022; 15:1578-1587</small></div>

<div><h4>Fractal Analysis of Dynamic Stress CT-Perfusion Imaging for Detection of Hemodynamically Relevant Coronary Artery Disease.</h4><i>Michallek F, Nakamura S, Kurita T, Ota H, ... Dewey M, Kitagawa K</i><br /><b>Background</b><br />Combined computed tomography-derived myocardial blood flow (CTP-MBF) and computed tomography angiography (CTA) has shown good diagnostic performance for detection of coronary artery disease (CAD). However, fractal analysis might provide additional insight into ischemia pathophysiology by characterizing multiscale perfusion patterns and, therefore, may be useful in diagnosing hemodynamically significant CAD.<br /><b>Objectives</b><br />The purpose of this study was to investigate, in a multicenter setting, whether fractal analysis of perfusion improves detection of hemodynamically relevant CAD over myocardial blood flow quantification (CTP-MBF) using dynamic, 4-dimensional, dynamic stress myocardial computed tomography perfusion (CTP) imaging.<br /><b>Methods</b><br />In total, 7 centers participating in the prospective AMPLIFiED (Assessment of Myocardial Perfusion Linked to Infarction and Fibrosis Explored with Dual-source CT) study acquired CTP and CTA data in patients with suspected or known CAD. Hemodynamically relevant CAD was defined as ≥90% stenosis on invasive coronary angiography or fractional flow reserve <0.80. Both fractal analysis and CTP-MBF quantification were performed on CTP images and were combined with CTA results.<br /><b>Results</b><br />This study population included 127 participants, among them 61 patients, or 79 vessels, with CAD as per invasive reference standard. Compared with the combination of CTP-MBF and CTA, combined fractal analysis and CTA improved sensitivity on the per-patient level from 84% (95% CI: 72%-92%) to 95% (95% CI: 86%-99%; P = 0.01) and specificity from 70% (95% CI: 57%-82%) to 89% (95% CI: 78%-96%; P = 0.02). The area under the receiver-operating characteristic curve improved from 0.83 (95% CI: 0.75-0.90) to 0.92 (95% CI: 0.86-0.98; P = 0.01).<br /><b>Conclusions</b><br />Fractal analysis constitutes a quantitative and pathophysiologically meaningful approach to myocardial perfusion analysis using dynamic stress CTP, which improved diagnostic performance over CTP-MBF when combined with anatomical information from CTA.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Sep 2022; 15:1591-1601</small></div>

<div><h4>Coronary Atherosclerosis in an Asymptomatic U.S. Population: Miami Heart Study at Baptist Health South Florida.</h4><i>Nasir K, Cainzos-Achirica M, Valero-Elizondo J, Ali SS, ... Fialkow J, Cury RC</i><br /><b>Background</b><br />The burden of total coronary plaque, plaque subtypes, and high-risk plaque features was unknown in asymptomatic individuals from the general U.S. primary prevention population.<br /><b>Objectives</b><br />In a large, asymptomatic U.S. cohort evaluated using coronary computed tomography angiography (CCTA), we aimed to assess the burden of total coronary plaque, plaque subtypes, and high-risk plaque features; the interplay between CCTA findings and coronary artery calcium (CAC) scores; and identify independent predictors of coronary plaque.<br /><b>Methods</b><br />Cross-sectional analysis in the MiHeart (Miami Heart Study), a cohort of 2,359 asymptomatic individuals from the Greater Miami Area (mean age 53 years, 50% women, 47% Hispanic/Latino, 43% non-Hispanic White). We estimated the burden of CAC (=0, >0 to <100, ≥100), CCTA-based plaque features (any plaque, stenosis ≥50%, ≥70%, high-risk features), and their interplay.<br /><b>Results</b><br />Overall, 58% participants had CAC = 0, 28% CAC >0 to <100, and 13% CAC ≥100. A total of 49% participants had plaque on the CCTA, including 16% among those with CAC = 0. Overall, 6% participants had coronary stenosis ≥50% (12% among those with coronary plaque), 1.8% had stenosis ≥70% (3.7% among those with plaque), and 7% had at least 1 coronary plaque with ≥1 high-risk feature (13.8% among those with plaque). Only 0.8% participants with CAC = 0 had stenosis ≥50%, 0.1% stenosis ≥70%, and 2.3% plaque with high-risk features. In logistic regression models, independent predictors of coronary plaque and high-risk plaque were older age, male sex, tobacco use, diabetes, overweight, and obesity. Male sex, overweight, and obesity were independent predictors of plaque if CAC = 0.<br /><b>Conclusions</b><br />The Miami Heart Study confirms substantial prevalence of coronary plaque in asymptomatic individuals. Overall, 49% of participants had coronary plaque, 6% had stenosis ≥50%, and 7% had plaques with at least 1 high-risk feature. These proportions were 16%, 0.8%, and 2.3%, respectively, among those with CAC = 0. Longitudinal follow-up will shed further light on the prognostic implications of these findings in asymptomatic individuals.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Sep 2022; 15:1604-1618</small></div>

<div><h4>Incidence and Predictors of Atrial Fibrillation in Cardiac Sarcoidosis: A Multimodality Imaging Study.</h4><i>Niemelä M, Uusitalo V, Pöyhönen P, Schildt J, Lehtonen J, Kupari M</i><br /><b>Background</b><br />In cardiac sarcoidosis (CS), the risk and predictors of new-onset atrial fibrillation (AF) are poorly known.<br /><b>Objectives</b><br />The authors evaluated the incidence and characteristics of AF in newly diagnosed CS.<br /><b>Methods</b><br />The authors studied 118 patients (78 women, mean age 50 years) with AF-naive CS having undergone cardiac <sup>18</sup>F-fluorodexoyglucose positron emission tomography (<sup>18</sup>F-FDG PET) at the time of diagnosis. Details of patient characteristics and medical or device therapy were collected from hospital charts. The PET scans were re-analyzed for presence of atrial and ventricular inflammation, and coincident cardiac magnetic resonance (CMR) studies and single-photon emission computed tomography (SPECT) perfusions were analyzed for cardiac structure and function, including the presence and extent of myocardial scarring. Detection of AF was based on interrogation of intracardiac devices and on ambulatory or 12-lead electrocardiograms.<br /><b>Results</b><br />Altogether 34 patients (29%) suffered paroxysms of AF during follow-up (median, 3 years) with persistent AF developing in 7 patients and permanent AF in 4. The estimated 5-year incidence of AF was 55% (95% CI: 34%-72%) in the 39 patients with atrial <sup>18</sup>F-FDG uptake at the time of diagnosis vs 18% (95% CI: 10%-28%) in the 79 patients without atrial uptake (P < 0.001). In cause-specific Cox regression analysis, atrial uptake was an independent predictor of AF (P < 0.001) with HR of 6.01 (95% CI: 2.64-13.66). Other independent predictors were an increased left atrial maximum volume (P < 0.01) and history of sleep apnea (P < 0.01). Ventricular involvement by PET, SPECT, or CMR was nonpredictive. Symptoms of AF prompted electrical cardioversion in 12 patients (35%). Three of the 34 patients (9%) experiencing AF suffered a stroke versus none of those remaining free of AF.<br /><b>Conclusions</b><br />In newly diagnosed CS, future AF is relatively common and associated with atrial inflammation and enlargement on multimodality cardiac imaging.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Sep 2022; 15:1622-1631</small></div>

<div><h4>Association of Sex, Reduced Myocardial Flow Reserve, and Long-Term Mortality Across Spectrum of Atherosclerotic Disease.</h4><i>Patel KK, Shaw L, Spertus JA, Sperry B, ... Chan PS, Bateman TM</i><br /><b>Background</b><br />Coronary vasomotor dysfunction (defined by reduced myocardial blood flow reserve [MBFR]) is associated with high cardiac risk in both men and women in absence of significant coexisting epicardial disease. Whether there is a sex-specific difference in prognostic value of reduced MBFR in patients with a greater burden of coexisting epicardial atherosclerotic disease is not well understood.<br /><b>Objectives</b><br />The purpose of this study was to examine the association of sex, MBFR, and mortality in consecutive patients with suspected or known coronary artery disease undergoing positron emission tomography myocardial perfusion imaging.<br /><b>Methods</b><br />Unique consecutive patients undergoing rubidium (Rb)-82 rest/stress positron emission tomography myocardial perfusion imaging from 2010-2016 were followed for a median of 3.2 years. Multivariable Cox models were built to describe the interaction of sex and MBFR on all-cause and cardiac death for the overall population and stratified by extent of calcified atherosclerosis (none: coronary artery calcium score = 0, subclinical: coronary artery calcium >0, clinical: prior myocardial infarction/percutaneous coronary intervention) and abnormal perfusion (no significant obstructive disease: summed stress score = 0, 1%-9.9%, and ≥10%) at baseline.<br /><b>Results</b><br />Among 12,594 patients, 52.8% were women. Compared with men, women had a lower prevalence of known coronary artery disease (16.5% vs 29.5%; P < 0.001) and were less likely to undergo revascularization after myocardial perfusion imaging (4.9% vs 9.7%; P < 0.001), but were more likely to have a reduced MBFR of <2 (56.2% vs 50.6%; P < 0.001). There were 1,699 (13.5%) all-cause and 490 (3.9%) cardiac deaths. In fully adjusted Cox models, reduced MBFR was independently associated with higher risk of death (HR per 0.1-U decrease: 1.09 [95% CI: 1.08-1.10]; P < 0.001), but female sex was not (HR: 0.95 [95% CI: 0.85-1.05]; P = 0.27). There was no significant interaction between sex and MBFR on death (P = 0.22) and cardiac death (P = 0.35) overall or in subgroups of patients with clinical, subclinical, and no atherosclerosis or across categories of perfusion abnormality at baseline.<br /><b>Conclusions</b><br />The association between reduced MBFR and higher risk of all-cause and cardiac death did not differ by sex, regardless of extent of coexisting atherosclerosis or perfusion abnormality.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Sep 2022; 15:1635-1644</small></div>

<div><h4>Understanding and Improving Risk Assessment After Myocardial Infarction Using Automated Left Ventricular Shape Analysis.</h4><i>Corral Acero J, Schuster A, Zacur E, Lange T, ... Eitel I, Grau V</i><br /><b>Background</b><br />Left ventricular ejection fraction (LVEF) and end-systolic volume (ESV) remain the main imaging biomarkers for post-acute myocardial infarction (AMI) risk stratification. However, they are limited to global systolic function and fail to capture functional and anatomical regional abnormalities, hindering their performance in risk stratification.<br /><b>Objectives</b><br />This study aimed to identify novel 3-dimensional (3D) imaging end-systolic (ES) shape and contraction descriptors toward risk-related features and superior prognosis in AMI.<br /><b>Methods</b><br />A multicenter cohort of AMI survivors (n = 1,021; median age 63 years; 74.5% male) who underwent cardiac magnetic resonance (CMR) at a median of 3 days after infarction were considered for this study. The clinical endpoint was the 12-month rate of major adverse cardiac events (MACE; n = 73), consisting of all-cause death, reinfarction, and new congestive heart failure. A fully automated pipeline was developed to segment CMR images, build 3D statistical models of shape and contraction in AMI, and find the 3D patterns related to MACE occurrence.<br /><b>Results</b><br />The novel ES shape markers proved to be superior to ESV (median cross-validated area under the receiver-operating characteristic curve 0.681 [IQR: 0.679-0.684] vs 0.600 [IQR: 0.598-0.602]; P < 0.001); and 3D contraction to LVEF (0.716 [IQR: 0.714-0.718] vs 0.681 [IQR: 0.679-0.684]; P < 0.001) in MACE occurrence prediction. They also contributed to a significant improvement in a multivariable setting including CMR markers, cardiovascular risk factors, and basic patient characteristics (0.747 [IQR: 0.745-0.749]; P < 0.001). Based on these novel 3D descriptors, 3 impairments caused by AMI were identified: global, anterior, and basal, the latter being the most complementary signature to already known predictors.<br /><b>Conclusions</b><br />The quantification of 3D differences in ES shape and contraction, enabled by a fully automated pipeline, improves post-AMI risk prediction and identifies shape and contraction patterns related to MACE occurrence.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Sep 2022; 15:1563-1574</small></div>

<div><h4>Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement: Meta-Analysis of Kaplan-Meier-Derived Individual Patient Data.</h4><i>Sá MP, Jacquemyn X, Van den Eynde J, Tasoudis P, ... Pibarot P, Ramlawi B</i><br /><b>Background</b><br />It remains controversial whether prosthesis-patient mismatch (PPM) (in general considered moderate if indexed effective orifice area is 0.65-0.85 cm<sup>2</sup>/m<sup>2</sup> and severe when <0.65 cm<sup>2</sup>/m<sup>2</sup>) affects the outcomes after transcatheter aortic valve replacement (TAVR).<br /><b>Objectives</b><br />The purpose of this study is to evaluate the time-varying effects and association of PPM with the risk of overall mortality.<br /><b>Methods</b><br />Study-level meta-analysis of reconstructed time-to-event data from Kaplan-Meier curves of studies published by December 30, 2021.<br /><b>Results</b><br />In total, 23 studies met our eligibility criteria and included a total of 81,969 patients included in the Kaplan-Meier curves (19,612 with PPM and 62,357 without PPM). Patients with moderate/severe PPM had a significantly higher risk of mortality compared with those without PPM (HR: 1.09 [95% CI: 1.04-1.14]; P < 0.001). In the first 30 months after the procedure, mortality rates were significantly higher in the moderate/severe PPM group (HR: 1.1 [95% CI: 1.05-1.16]; P < 0.001). In contrast, the landmark analysis beyond 30 months yielded a reversal of the HR (0.83 [95% CI: 0.68-1.01]; P = 0.064), but without statistical significance. In the sensitivity analysis, although we observed that severe PPM showed higher risk of mortality in comparison with no PPM (HR: 1.25 [95% CI: 1.16-1.36]; P < 0.001), we did not observe a statistically significant difference for mortality between moderate PPM and no PPM (HR: 1.03 [95% CI: 0.96-1.10]; P = 0.398).<br /><b>Conclusions</b><br />Severe PPM, but not moderate PPM, was associated with higher risk of mortality following TAVR. These results provide support to implementation of preventive strategies to avoid severe PPM following TAVR.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 30 Aug 2022; epub ahead of print</small></div>

<div><h4>Normal Ranges of Right Atrial Strain: A Systematic Review and Meta-Analysis.</h4><i>Krittanawong C, Maitra NS, Hassan Virk HU, Farrell A, ... Wang Z, Marwick TH</i><br /><b>Background</b><br />Standard measures for the clinical assessment of right atrial (RA) function are lacking.<br /><b>Objectives</b><br />In this systematic review and meta-analysis, we sought to report a reference range for RA deformation parameters in healthy subjects and to identify factors that contribute to reported variations.<br /><b>Methods</b><br />We conducted a comprehensive search of MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; Embase; Scopus; and the Cochrane Central Register of Controlled Trials from database inception through October 2021. Studies were included if they reported RA strain or strain rate (SR) using 2-dimensional speckle-tracking echocardiography in healthy volunteers or apparently healthy control patients. Data were extracted by 1 reviewer and then reviewed by 2 independent reviewers. Conflicts were resolved through consensus. Data were combined using the method developed by Siegel and adjusted using the restricted maximum likelihood random-effects model. The normal range was defined as the 95% CI of the mean. Heterogeneity was assessed by the Cochran Q-statistic and the inconsistency index (I<sup>2</sup>). The quality of the included studies and publication bias were assessed. Effects of clinical variables were sought in a metaregression.<br /><b>Results</b><br />The search identified 4,111 subjects from 21 studies. The average RA reservoir strain was 44% (95% CI: 25%-63%), contractile strain was 17% (95% CI: 2%-32%), and conduit strain was 18% (95% CI: 7%-28%), with significant between-study heterogeneity and inconsistency. The systolic SR was 2.1 s-1 (95% CI: 0.9-3.4 s-1), early-diastolic SR was -2.0 s-1 (95% CI: -3.3 to -0.8 s-1), and late-diastolic SR was -1.9 s-1 (95% CI: -2.4 to -1.3 s-1), with nonsignificant heterogeneity and inconsistency. Ranges remained wide in healthy volunteers. The metaregression identified only age as significantly associated with systolic SR and no other significant determinants of variation among normal ranges of strain.<br /><b>Conclusions</b><br />There are wide reference ranges for RA deformation, and these may limit the utility of this test in clinical practice.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 24 Aug 2022; epub ahead of print</small></div>

<div><h4>Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank.</h4><i>Raisi-Estabragh Z, McCracken C, Hann E, Condurache DG, ... Piechnik SK, Petersen SE</i><br /><b>Background</b><br />Cardiovascular magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.<br /><b>Objectives</b><br />The associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.<br /><b>Methods</b><br />Native T1-mapping was performed in one midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5 Tesla scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, non-ischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.<br /><b>Results</b><br />Higher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10<sup>-9</sup>) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10<sup>-4</sup>). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10<sup>-4</sup>), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10<sup>-11</sup>), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10<sup>-5</sup>), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).<br /><b>Conclusions</b><br />This large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 20 Aug 2022; epub ahead of print</small></div>

<div><h4>Multi-Imaging Characterization of Cardiac Phenotype in Different Types of Amyloidosis.</h4><i>Ioannou A, Patel RK, Razvi Y, Porcari A, ... Gillmore JD, Fontana M</i><br /><b>Background</b><br />Bone scintigraphy is extremely valuable when assessing patients with suspected cardiac amyloidosis (CA), but the clinical significance and associated phenotype of different degrees of cardiac uptake across different types is yet to be defined.<br /><b>Objectives</b><br />This study sought to define the phenotypes of patients with varying degrees of cardiac uptake on bone scintigraphy, across multiple types of systemic amyloidosis, using extensive characterization comprising biomarkers as well as echocardiographic and cardiac magnetic resonance (CMR) imaging.<br /><b>Methods</b><br />A total of 296 patients (117 with immunoglobulin light-chain amyloidosis [AL], 165 with transthyretin (TTR) amyloidosis [ATTR], 7 with apolipoprotein AI amyloidosis [AApoAI], and 7 with apolipoprotein AIV amyloidosis [AApoAIV]) underwent deep characterization of their cardiac phenotype.<br /><b>Results</b><br />AL patients with grade 0 myocardial radiotracer uptake spanned the spectrum of CMR findings from no CA to characteristic CA, whereas AL patients with grades 1 to 3 always produced characteristic CMR features. In ATTR, the CA burden strongly correlated with myocardial tracer uptake, except in Ser77Tyr. AApoAI presented with grade 0 or 1 and disproportionate right-sided involvement. AApoAIV always presented with grade 0 and characteristic CA. AL grade 1 patients (n = 48; 100%) had characteristic CA, whereas only ATTR grade 1 patients with Ser77Tyr had characteristic CA on CMR (n = 5; 11.4%). After exclusion of Ser77Tyr, AApoAI, and AApoAIV, CMR showing characteristic CA or an extracellular volume of >0.40 in patients with grade 0 to 1 cardiac uptake had a sensitivity and specificity of 100% for AL.<br /><b>Conclusions</b><br />There is a wide variation in cardiac phenotype between different amyloidosis types across different degrees of cardiac uptake. The combination of CMR and bone scintigraphy can help to define the diagnostic differentials and the clinical phenotype in each individual patient.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 13 Aug 2022; epub ahead of print</small></div>

<div><h4>Deep Learning of Coronary Calcium Scores From PET/CT Attenuation Maps Accurately Predicts Adverse Cardiovascular Events.</h4><i>Pieszko K, Shanbhag A, Killekar A, Miller RJH, ... Dey D, Slomka PJ</i><br /><b>Background</b><br />Assessment of coronary artery calcium (CAC) by computed tomographic (CT) imaging provides an accurate measure of atherosclerotic burden. CAC is also visible in CT attenuation correction (CTAC) scans, always acquired with cardiac positron emission tomographic (PET) imaging.<br /><b>Objectives</b><br />The aim of this study was to develop a deep-learning (DL) model capable of fully automated CAC definition from PET CTAC scans.<br /><b>Methods</b><br />The novel DL model, originally developed for video applications, was adapted to rapidly quantify CAC. The model was trained using 9,543 expert-annotated CT scans and was tested in 4,331 patients from an external cohort undergoing PET/CT imaging with major adverse cardiac events (MACEs) (follow-up 4.3 years), including same-day paired electrocardiographically gated CAC scans available in 2,737 patients. MACE risk stratification in 4 CAC score categories (0, 1-100, 101-400, and >400) was analyzed and CAC scores derived from electrocardiographically gated CT scans (standard scores) by expert observers were compared with automatic DL scores from CTAC scans.<br /><b>Results</b><br />Automatic DL scoring required <6 seconds per scan. DL CTAC scores provided stepwise increase in the risk for MACE across the CAC score categories (HR up to 3.2; P < 0.001). Net reclassification improvement of standard CAC scores over DL CTAC scores was nonsignificant (-0.02; 95% CI: -0.11 to 0.07). The negative predictive values for MACE of zero CAC with standard (85%) and DL CTAC (83%) CAC scores were similar (P = 0.19).<br /><b>Conclusions</b><br />DL CTAC scores predict cardiovascular risk similarly to standard CAC scores quantified manually by experienced operators from dedicated electrocardiographically gated CAC scans and can be obtained almost instantly, with no changes to PET/CT scanning protocol.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 08 Aug 2022; epub ahead of print</small></div>

<div><h4>Diagnostic and Prognostic Value of Myocardial Work Indices for Identification of Cancer Therapy-Related Cardiotoxicity.</h4><i>Calvillo-Argüelles O, Thampinathan B, Somerset E, Shalmon T, ... Marwick TH, Thavendiranathan P</i><br /><b>Background</b><br />Echocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment-related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation.<br /><b>Objectives</b><br />This work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD.<br /><b>Methods</b><br />In this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3 months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regression tree analysis was used to explore the combined use of GLS and MW for the diagnostic/prognostic assessment of CTRCD.<br /><b>Results</b><br />Baseline left ventricular ejection fraction (LVEF) was 63.2 ± 4.0%. Thirty-seven (27.2%) patients developed CTRCD. An absolute change in GLS (standardized odds ratio [sOR]: 1.97 [95% CI: 1.07-3.66]; P = 0.031) and GWI (sOR: 1.73 [95% CI: 1.04-2.85]; P = 0.033) were associated with concurrent CTRCD. An absolute change in GLS (sOR: 1.79 [95% CI: 1.22-2.62]; P = 0.003), GWI (sOR: 1.67 [95% CI: 1.20-2.32]; P = 0.003), and GCW (sOR: 1.65 [95% CI: 1.17-2.34]; P = 0.005) were associated with subsequent CTRCD. Change in GWI and GCW demonstrated incremental value over GLS and clinical factors for the diagnosis of concurrent CTRCD. In a small group with a GLS change <3.3% (absolute), and a >21 mm Hg reduction in systolic blood pressure, worsening of GWI identified patients with higher probability of concurrent CTRCD (24.0% vs 5.2%). MWIs did not improve identification of subsequent CTRCD beyond knowledge of GLS change.<br /><b>Conclusions</b><br />GLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Aug 2022; 15:1361-1376</small></div>

<div><h4>Improving the Characterization of Stage A and B Heart Failure by Adding Global Longitudinal Strain.</h4><i>Haji K, Huynh Q, Wong C, Stewart S, Carrington M, Marwick TH</i><br /><b>Background</b><br />Current guidelines distinguish stage B heart failure (SBHF) (asymptomatic left ventricular [LV] dysfunction) from stage A heart failure (SAHF) (asymptomatic with heart failure [HF] risk factors) on the basis of myocardial infarction, LV remodeling (hypertrophy or reduced ejection fraction [EF]) or valvular disease. However, subclinical HF with preserved EF may not be identified with these criteria.<br /><b>Objectives</b><br />The purpose of this study was to assess the prediction of incident HF with global longitudinal strain (GLS) in patients with SAHF and SBHF.<br /><b>Methods</b><br />The authors analyzed echocardiograms (including GLS) in 447 patients (age 65 ± 11 years; 77% male) enrolled in a prospective study of HF in individuals at risk of incident HF, with normal or mildly impaired EF (≥40%). Long-term follow-up was obtained via data linkage. Analysis was performed using a competing risks model.<br /><b>Results</b><br />After a median of 9 years of follow-up, 50 (10%) of the 447 patients had new HF admissions, and 87 (18%) died. In multivariable analysis, all imaging variables were independent predictors of HF admissions, including left ventricular ejection fraction (LVEF) (HR: 0.97 [95% CI: 0.94-0.99]), LV mass index (HR: 1.01 [95% CI: 1.00-1.02]), left atrial volume index (HR: 1.02 [95% CI: 1.00-1.05]), and E/e\' (HR: 1.05 [95% CI: 1.01-1.24]), incremental to clinical variables (age and Charlson comorbidity score). However, the addition of GLS provided value incremental to both clinical and other echocardiographic parameters (P = 0.004). Impaired GLS (<18%) (HR: 4.09 [95% CI: 1.87-8.92]) was independent and incremental to all clinical and other echocardiographic variables in predicting HF, and impaired LVEF, left ventricular hypertrophy, left atrial enlargement, high E/e\', or SBHF were not predictive.<br /><b>Conclusions</b><br />The inclusion of GLS as a criterion for SBHF would add independent and incremental information to standard markers of SBHF for the prediction of subsequent HF admissions.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Aug 2022; 15:1380-1387</small></div>

<div><h4>Prognostic Value of Stress CMR in Symptomatic Patients With Coronary Stenosis on CCTA.</h4><i>Pezel T, Hovasse T, Lefèvre T, Sanguineti F, ... Chevalier B, Garot J</i><br /><b>Background</b><br />Noninvasive functional imaging is often performed in patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA). However, the prognostic value of stress cardiac magnetic resonance (CMR) is unknown in patients with coronary stenosis of unknown significance on coronary CTA.<br /><b>Objectives</b><br />This study assessed the prognostic value of stress CMR in symptomatic patients with obstructive CAD of unknown significance on coronary CTA.<br /><b>Methods</b><br />Between 2008 and 2020, consecutive symptomatic patients without known CAD referred for coronary CTA were screened. Patients with obstructive CAD (at least 1 ≥50% stenosis on coronary CTA) were further referred for stress CMR and followed for the occurrence of major adverse cardiovascular events (MACEs), defined as cardiovascular death or nonfatal myocardial infarction.<br /><b>Results</b><br />Of 2,210 patients who completed CMR, 2,038 (46.5% men; mean age 69.8 ± 12.2 years) completed follow-up (median 6.8 years; IQR: 5.9-9.2 years); 281 experienced a MACE (13.8%). Inducible ischemia and late gadolinium enhancement (LGE) were significantly associated with MACEs (HR: 4.51 [95% CI: 3.55-5.74], and HR: 3.32 [95% CI: 2.55-4.32], respectively; P < 0.001). In multivariable Cox regression, the number of segments with >70% stenosis, with noncalcified plaques and the number of vessels with obstructive CAD were prognosticators (P < 0.001). The presence of inducible ischemia and LGE were independent predictors of MACEs (HR: 3.97 [95% CI: 3.43-5.13]; HR: 2.30 [95% CI: 1.52-3.33]; P < 0.001). After adjustment, stress CMR showed the best improvement in model discrimination and reclassification above traditional risk factors and coronary CTA (C-statistic improvement: 0.04; net reclassification improvement = 0.421; integrative discrimination index = 0.047).<br /><b>Conclusions</b><br />In symptomatic patients with obstructive CAD of unknown significance on coronary CTA, stress CMR had incremental prognostic value to predict MACEs.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Aug 2022; 15:1408-1422</small></div>

<div><h4>Coronary Atherosclerosis, Cardiac Troponin, and Interleukin-6 in Patients With Chest Pain: The PROMISE Trial Results.</h4><i>Ferencik M, Mayrhofer T, Lu MT, Bittner DO, ... Douglas PS, Hoffmann U</i><br /><b>Background</b><br />Increased inflammation and myocardial injury can be observed in the absence of myocardial infarction or obstructive coronary artery disease (CAD).<br /><b>Objectives</b><br />The authors determined whether biomarkers of inflammation and myocardial injury-interleukin (IL)-6 and high-sensitivity cardiac troponin (hs-cTn)-were associated with the presence and extent of CAD and were independent predictors of major adverse cardiovascular events (MACEs) in stable chest pain.<br /><b>Methods</b><br />Using participants from the PROMISE trial, the authors measured hs-cTn I and IL-6 concentrations and analyzed computed tomography angiography (CTA) images in the core laboratory for CAD characteristics: significant stenosis (≥70%), high-risk plaque (HRP), Coronary Artery Disease Reporting and Data System (CAD-RADS) categories, segment involvement score (SIS), and coronary artery calcium (CAC) score. The primary endpoint was a composite MACE (death, myocardial infarction, or unstable angina).<br /><b>Results</b><br />The authors included 1,796 participants (age 60.2 ± 8.0 years; 47.5% men, median follow-up 25 months). In multivariable linear regression adjusted for atherosclerotic cardiovascular disease (ASCVD) risk, hs-cTn was associated with HRP, stenosis, CAD-RADS, and SIS. IL-6 was only associated with stenosis and CAD-RADS. hs-cTn above median (1.5 ng/L) was associated with MACEs in univariable analysis (HR: 2.1 [95% CI: 1.3-3.6]; P = 0.006), but not in multivariable analysis adjusted for ASCVD and CAD. IL-6 above median (1.8 ng/L) was associated with MACEs in multivariable analysis adjusted for ASCVD and HRP (HR: 1.9 [95% CI: 1.1-3.3]; P = 0.03), CAC (HR: 1.9 [95% CI: 1.0-3.4]; P = 0.04), and SIS (HR: 1.8 [95% CI: 1.0-3.2]; P = 0.04), but not for stenosis or CAD-RADS. In participants with nonobstructive CAD (stenosis 1%-69%), the presence of both hs-cTn and IL-6 above median was strongly associated with MACEs (HR: 2.5-2.7 after adjustment for CAD characteristics).<br /><b>Conclusions</b><br />Concentrations of hs-cTn and IL-6 were associated with CAD characteristics and MACEs, indicating that myocardial injury and inflammation may each contribute to pathways in CAD pathophysiology. This association was most pronounced among participants with nonobstructive CAD representing an opportunity to tailor treatment in this at-risk group. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Aug 2022; 15:1427-1438</small></div>

<div><h4>The PROMISE Minimal Risk Score Improves Risk Classification of Symptomatic Patients With Suspected CAD.</h4><i>Rasmussen LD, Fordyce CB, Nissen L, Hill CL, ... Douglas PS, Winther S</i><br /><b>Background</b><br />Guidelines for evaluating patients with suspected coronary artery disease (CAD) recommend pretest probability (PTP) estimation but provide no clear recommendations regarding diagnostic testing in patients with >5% to 15% risk of obstructive CAD. The diagnostic and prognostic value of PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk score (PMRS) calculation in this patient group is unknown.<br /><b>Objectives</b><br />This work aims to improve the evaluation of stable patients with suspected CAD by using the PMRS, which identifies patients at minimal risk of CAD and events in patients with >5% to 15% PTP of obstructive CAD.<br /><b>Methods</b><br />Greater than 5% to 15% PTP patients from 2 large clinical trials were used for subcohort derivation: PROMISE (N = 10,003) and Dan-NICAD (Danish study of Non-Invasive Testing in Coronary Artery Disease) (N = 3,252). First, the PMRS cutoff associated with a prevalence of obstructive CAD ≤5% was determined in the >5% to 15% PTP PROMISE core lab computed tomographic angiography patients (discovery cohort: n = 2,191). This cutoff was validated for obstructive CAD in >5% to 15% PTP Dan-NICAD patients (CAD validation cohort: n = 1,386) and for prognostic impact on death and myocardial infarction in >5% to 15% PTP PROMISE non-core lab computed tomographic angiography patients (prognosis validation cohort: n = 2,753).<br /><b>Results</b><br />In the discovery cohort, a CAD prevalence of ≤5% was found at a PMRS of ≥34%. In the CAD validation cohort, this cutoff down-classified 442 (31.9%) of >5% to 15% PTP patients into the low PTP group (CAD ≤5%); the prevalence of obstructive CAD in down-classified patients was 3.2% compared to 7.1% in non-down-classified patients. A PMRS ≥34% was nonsignificantly associated with a lower risk of myocardial infarction and death in the prognosis validation cohort (HR: 0.58 [95% CI: 0.29-1.18]; P = 0.13).<br /><b>Conclusions</b><br />For evaluating patients with suspected CAD, a combined use of traditional PTP and the PMRS correctly down-classified one-third of >5% to 15% PTP patients into a group with very low prevalence of obstructive CAD and adverse events. The proposed strategy may improve risk stratification and help reduce unneeded diagnostic testing.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Aug 2022; 15:1442-1454</small></div>

<div><h4>Monoclonal Autoantibody Against a Cryptic Epitope on Tissue-Adherent Low-Density Lipoprotein for Molecular Imaging in Atherosclerosis.</h4><i>Khamis RY, Hartley A, Caga-Anan M, Pandey SS, ... Nilsson J, Haskard DO</i><br /><b>Background</b><br />Antibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis.<br /><b>Objectives</b><br />The authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants.<br /><b>Methods</b><br />The authors created hybridomas from an unimmunized low-density lipoprotein (LDL) receptor-deficient (Ldlr<sup>-/-</sup>) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization.<br /><b>Results</b><br />LO9 reacted well with native LDL bound to immobilized matrix components and less well to oxidized LDL. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. The authors localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. Furthermore, in vivo near-infrared fluorescence molecular tomographic imaging, and ex vivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr<sup>-/-</sup> mice, in the vicinity of macrophages.<br /><b>Conclusions</b><br />The authors believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Aug 2022; 15:1458-1470</small></div>

<div><h4>Accuracy of Cardiac Magnetic Resonance Imaging in Diagnosing Pediatric Cardiac Masses: A Multicenter Study.</h4><i>Beroukhim RS, Ghelani S, Ashwath R, Balasubramanian S, ... Valsangiacomo E, Geva T</i><br /><b>Background</b><br />After diagnosis of a cardiac mass, clinicians must weigh the benefits and risks of ascertaining a tissue diagnosis. Limited data are available on the accuracy of previously developed noninvasive pediatric cardiac magnetic resonance (CMR)-based diagnostic criteria.<br /><b>Objectives</b><br />The goals of this study were to: 1) evaluate the CMR characteristics of pediatric cardiac masses from a large international cohort; 2) test the accuracy of previously developed CMR-based diagnostic criteria; and 3) expand diagnostic criteria using new information.<br /><b>Methods</b><br />CMR studies (children 0-18 years of age) with confirmatory histological and/or genetic diagnosis were analyzed by 2 reviewers, without knowledge of prior diagnosis. Diagnostic accuracy was graded as: 1) single correct diagnosis; 2) correct diagnosis among a differential; or 3) incorrect diagnosis.<br /><b>Results</b><br />Of 213 cases, 174 (82%) had diagnoses that were represented in the previously published diagnostic criteria. In 70% of 174 cases, both reviewers achieved a single correct diagnosis (94% of fibromas, 71% of rhabdomyomas, and 50% of myxomas). When ≤2 differential diagnoses were included, both reviewers reached a correct diagnosis in 86% of cases. Of 29 malignant tumors, both reviewers indicated malignancy as a single diagnosis in 52% of cases. Including ≤2 differential diagnoses, both reviewers indicated malignancy in 83% of cases. Of 6 CMR sequences examined, acquisition of first-pass perfusion and late gadolinium enhancement were independently associated with a higher likelihood of a single correct diagnosis.<br /><b>Conclusions</b><br />CMR of cardiac masses in children leads to an accurate diagnosis in most cases. A comprehensive imaging protocol is associated with higher diagnostic accuracy.<br /><br />Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Aug 2022; 15:1391-1405</small></div>

<div><h4>Discordance Between Coronary Artery Calcium Area and Density Predicts Long-Term Atherosclerotic Cardiovascular Disease Risk.</h4><i>Razavi AC, van Assen M, De Cecco CN, Dardari ZA, ... Blaha MJ, Dzaye O</i><br /><b>Background</b><br />Coronary artery calcium (CAC) is commonly quantified as the product of two generally correlated measures: plaque area and calcium density.<br /><b>Objective</b><br />We sought to determine whether discordance between calcium area and density has long-term prognostic importance in atherosclerotic cardiovascular disease (ASCVD) risk.<br /><b>Methods</b><br />We studied 10,373 primary prevention participants from the CAC Consortium with CAC>0. Based on their median values, calcium area and mean calcium density were divided into four mutually exclusive concordant/discordant groups. Cox proportional hazards regression assessed the association of calcium area/density groups with ASCVD mortality over a median of 11.7 years, adjusting for traditional risk factors and the Agatston CAC score.<br /><b>Results</b><br />The mean age was 56.7 years old and 24% were female. The prevalence of plaque discordance was 19% (9% low calcium area-high calcium density, 10% high calcium area-low calcium density). Female sex (OR=1.48, 95% CI: 1.27-1.74) and body mass index (OR=0.81, 0.76-0.87, per 5 kg/m<sup>2</sup> higher) significantly associated with high calcium density discordance, whereas diabetes (OR=2.23, 95% CI: 1.85-3.19) was most strongly associated with discordantly low calcium density. Compared to those with low calcium area-low calcium density, individuals with low calcium area-high calcium density had a 71% lower risk of ASCVD death (HR=0.29, 95% CI: 0.09-0.95).<br /><b>Conclusions</b><br />For a given CAC score, high calcium density relative to plaque area confers lower long-term ASCVD risk, likely serving as an imaging marker of biological resilience for lesion vulnerability. Additional research is needed to define a robust definition of calcium area-density discordance for routine clinical risk prediction.<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>JACC Cardiovasc Imaging: 11 Jul 2022; epub ahead of print</small></div>

<div><h4>Transcatheter Mitral Valve Repair in Patients With Atrial Functional Mitral Regurgitation.</h4><i>Doldi P, Stolz L, Orban M, Karam N, ... Metra M, Hausleiter J</i><br /><b>Background</b><br />Among patients with severe functional mitral regurgitation (FMR), atrial functional MR (aFMR) represents an underrecognized entity. Data regarding outcomes after mitral valve transcatheter edge-to-edge repair (M-TEER) in aFMR remain scarce.<br /><b>Objectives</b><br />The objective was to analyze the outcome of aFMR patients undergoing M-TEER.<br /><b>Methods</b><br />Using patients from the international EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry undergoing M-TEER for FMR, we analyzed baseline characteristics and 2-year outcomes in aFMR in comparison to non-aFMR and ventricular FMR. Additionally, the impact of right ventricular dysfunction (RVD, defined as right ventricular to pulmonary artery uncoupling) on outcome after M-TEER was assessed.<br /><b>Results</b><br />Among 1,608 FMR patients treated by M-TEER, 126 (7.8%) were categorized as aFMR. All 126 aFMR patients had preserved left ventricular function without regional wall motion abnormalities, left arterial dilatation and Carpentier leaflet motion type I. Procedural success (defined as mitral regurgitation ≤2+ at discharge) was 87.2% (P < 0.001) and New York Heart Association (NYHA) functional class significantly improved during follow-up (NYHA class III/IV: 86.5% at baseline to 36.6% at follow-up; P < 0.001). The estimated 2-year survival rate in aFMR patients was 70.4%. Two-year survival did not differ significantly between aFMR, non-aFMR and ventricular FMR. Besides NYHA class IV, RVD was identified as strong independent predictor for 2-year survival (HR: 2.82 [95% CI: 1.24-6.45]; P = 0.014).<br /><b>Conclusions</b><br />aFMR is a frequent cause of FMR and can be effectively treated with M-TEER to improve symptoms at follow-up. Advanced heart failure symptoms and RVD were identified as important risk factors for survival in aFMR patients.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 08 Jul 2022; epub ahead of print</small></div>

<div><h4>Differences in Cardiac Remodeling in Left-Sided Valvular Regurgitation: Implications for Optimal Definition of Significant Aortic Regurgitation.</h4><i>Vejpongsa P, Xu J, Quinones MA, Shah DJ, Zoghbi WA</i><br /><b>Background</b><br />Grading of aortic regurgitation (AR) and mitral regurgitation (MR) is similar in the cardiology guidelines despite distinct differences in left ventricular (LV) adaptive pathophysiology.<br /><b>Objectives</b><br />This study compared differences in LV remodeling in patients with similar degrees of AR and MR severity and evaluated optimal cutoffs for significant AR in relation to the outcome of aortic valve replacement or repair (AVR) during follow-up.<br /><b>Methods</b><br />From 2008 to 2018, consecutive patients with isolated AR or MR who had cardiovascular magnetic resonance (CMR) were identified and CMR parameters were compared. Patients with left ventricular ejection fraction (LVEF) <50%, ischemic scar >5%, valve stenosis, or concomitant regurgitation were excluded. Patients were followed longitudinally for AVR.<br /><b>Results</b><br />Baseline characteristics of isolated AR (n = 418) and isolated MR (n = 1,073) were comparable except for higher male proportion and hypertension in AR, while heart failure was more prevalent in MR. Indexed LV end-diastolic and end-systolic volumes and mass were higher in AR compared with MR at the same level of regurgitant fraction. During follow-up (mean 2.1 years), 18.7% of AR patients underwent AVR based on symptoms or LV remodeling. Interestingly, 38.0% of patients that underwent AVR within 3 months after CMR did not meet severe AVR by current guidelines of AR severity. AR regurgitant fraction>35% had high sensitivity (86%) and specificity (88%) for identifying patients who underwent AVR.<br /><b>Conclusions</b><br />For similar regurgitation severity, LV remodeling is different in AR compared with MR. Cardiac symptoms and significant LV remodeling in AR requiring AVR occur frequently in patients with less severity than currently proposed. The study findings suggest that the optimal threshold for severe AR with CMR is different than MR and is lower than currently stated in the guidelines.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 07 Jul 2022; epub ahead of print</small></div>

<div><h4>Thoracic Aortic F-Sodium Fluoride Activity and Ischemic Stroke in Patients With Established Cardiovascular Disease.</h4><i>Fletcher AJ, Tew YY, Tzolos E, Joshi SS, ... Newby DE, Dweck MR</i><br /><b>Background</b><br />Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke.<br /><b>Objectives</b><br />The purpose of this study was to investigate whether thoracic <sup>18</sup>F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke.<br /><b>Methods</b><br />In a post hoc observational cohort study, we quantified thoracic aortic and coronary <sup>18</sup>F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of <sup>18</sup>F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable Cox regression.<br /><b>Results</b><br />After 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic <sup>18</sup>F-sodium fluoride activity (n = 140; r = 0.31; P = 0.00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6.1 ± 2.3 years of follow-up. High thoracic aortic <sup>18</sup>F-sodium fluoride activity was strongly associated with ischemic stroke (HR: 10.3 [95% CI: 3.1-34.8]; P = 0.00017), but not myocardial infarction (P = 0.40). Conversely, high coronary <sup>18</sup>F-sodium fluoride activity was associated with myocardial infarction (HR: 4.8 [95% CI: 1.9-12.2]; P = 0.00095) but not ischemic stroke (P = 0.39). In a multivariable Cox regression model including imaging and clinical risk factors, thoracic aortic <sup>18</sup>F-sodium fluoride activity was the only variable associated with ischemic stroke (HR: 8.19 [95% CI: 2.33-28.7], P = 0.0010).<br /><b>Conclusions</b><br />In patients with established cardiovascular disease, thoracic aortic <sup>18</sup>F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial <sup>18</sup>F-sodium fluoride activity identifies localized areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events. (DIAMOND-Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND], NCT02110303; Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis [SALTIRE II], NCT02132026; Novel Imaging Approaches To Identify Unstable Coronary Plaques, NCT01749254; and Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis, NCT01358513).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jul 2022; 15:1274-1288</small></div>

<div><h4>Sex Differences in LV Remodeling and Hemodynamics in Aortic Stenosis: Sex-Specific Criteria for Severe Stenosis?</h4><i>Ito S, Miranda WR, Nkomo VT, Lewis BR, Oh JK</i><br /><b>Background</b><br />The current criteria for aortic stenosis (AS) severity have not incorporated sex-related differences.<br /><b>Objectives</b><br />The authors investigated sex-related serial changes in left ventricular (LV) structure/function and hemodynamics in AS.<br /><b>Methods</b><br />Serial echocardiograms of patients with severe AS (time 0; aortic valve area [AVA] ≤1 cm<sup>2</sup>) and ≥1 previous echocardiogram were compared between sexes.<br /><b>Results</b><br />Of 927 patients (time 0: AVA 0.87 ± 0.11 cm<sup>2</sup>, peak velocity 4.03 ± 0.65 m/s, mean Doppler systolic pressure gradient [MG] 40.6 ± 13.1 mm Hg), 393 (42%) were women. Women had smaller body surface area (BSA) (1.77 ± 0.22 m<sup>2</sup> vs 2.03 ± 0.20 m<sup>2</sup>; P < 0.001), lower stroke volume (SV) (81.1 ± 17.2 mL vs 88.3 ± 18.6 mL; P < 0.001), and more frequent low-gradient severe AS (n = 196 [50%] vs n = 181 [34%]; P < 0.001). Women consistently had smaller AVA, indexed AVA (AVAi), peak velocity, and MG than men. The difference in aortic valve gradient lessened when AVAi ≤0.6 cm<sup>2</sup>/m<sup>2</sup> was applied as severe AS (n = 694, women 43%, AVA 0.95 ± 0.17 cm<sup>2</sup>, AVAi 0.50 ± 0.07 cm<sup>2</sup>/m<sup>2</sup>). Peak velocity (3.83 ± 0.66 m/s) and MG (36.5 ± 13.2 mm Hg) were lower based on AVAi severity criteria compared to those based on AVA. Men had a lower left ventricular ejection fraction (LVEF) (55.8% ± 14.8% vs 61.1% ± 11.7%; P < 0.001) and greater reduction in SV (-13.3 ± 19.6 mL vs -7.4 ± 16.4 mL; P < 0.001) as AS progressed from moderate to severe. Concentric LV hypertrophy was more common and E/e\' higher in women (21.2 ± 10.9 vs 18.8 ± 9.1; P < 0.001). SV, LVEF, AVA, peak velocity, and MG became precipitously worse when AVA reached 1.2 cm<sup>2</sup> in both sexes.<br /><b>Conclusions</b><br />Smaller BSA in women yields lower SV, resulting in lower aortic valve gradient than men. Indexed parameters by BSA are thus important in sex-related differences of aortic valve hemodynamics, but AVAi ≤0.6 cm<sup>2</sup>/m<sup>2</sup> includes individuals with moderate AS. Elevated filling pressure is more common in women. Men experience a larger reduction in SV and LVEF as AS progresses. The definition of AS severity may require different criteria between sexes.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jul 2022; 15:1175-1189</small></div>

<div><h4>Coronary Flow Assessment Using 3-Dimensional Ultrafast Ultrasound Localization Microscopy.</h4><i>Demeulenaere O, Sandoval Z, Mateo P, Dizeux A, ... Papadacci C, Pernot M</i><br /><b>Background</b><br />Direct assessment of the coronary microcirculation has long been hampered by the limited spatial and temporal resolutions of cardiac imaging modalities.<br /><b>Objectives</b><br />The purpose of this study was to demonstrate 3-dimensional (3D) coronary ultrasound localization microscopy (CorULM) of the whole heart beyond the acoustic diffraction limit (<20 μm resolution) at ultrafast frame rate (>1000 images/s).<br /><b>Methods</b><br />CorULM was performed in isolated beating rat hearts (N = 6) with ultrasound contrast agents (Sonovue, Bracco), using an ultrasonic matrix transducer connected to a high channel-count ultrafast electronics. We assessed the 3D coronary microvascular anatomy, flow velocity, and flow rate of beating hearts under normal conditions, during vasodilator adenosine infusion, and during coronary occlusion. The coronary vasculature was compared with micro-computed tomography performed on the fixed heart. In vivo transthoracic CorULM was eventually assessed on anaesthetized rats (N = 3).<br /><b>Results</b><br />CorULM enables the 3D visualization of the coronary vasculature in beating hearts at a scale down to microvascular structures (<20 μm resolution). Absolute flow velocity estimates range from 10 mm/s in tiny arterioles up to more than 300 mm/s in large arteries. Fitting to a power law, the flow rate-radius relationship provides an exponent of 2.61 (r<sup>2</sup> = 0.96; P < 0.001), which is consistent with theoretical predictions and experimental validations of scaling laws in vascular trees. A 2-fold increase of the microvascular coronary flow rate is found in response to adenosine, which is in good agreement with the overall perfusion flow rate measured in the aorta (control measurement) that increased from 8.80 ± 1.03 mL/min to 16.54 ± 2.35 mL/min (P < 0.001). The feasibility of CorULM was demonstrated in vivo for N = 3 rats.<br /><b>Conclusions</b><br />CorULM provides unprecedented insights into the anatomy and function of coronary arteries at the microvasculature level in beating hearts. This new technology is highly translational and has the potential to become a major tool for the clinical investigation of the coronary microcirculation.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jul 2022; 15:1193-1208</small></div>

<div><h4>Myocardial Contractile Mechanics in Ischemic Mitral Regurgitation: Multicenter Data Using Stress Perfusion Cardiovascular Magnetic Resonance.</h4><i>Kochav JD, Kim J, Judd R, Tak KA, ... Kim RJ, Weinsaft JW</i><br /><b>Background</b><br />Left ventricular (LV) ischemia has been variably associated with functional mitral regurgitation (FMR). Determinants of FMR in patients with ischemia are poorly understood.<br /><b>Objectives</b><br />This study sought to test whether contractile mechanics in ischemic myocardium underlying the mitral valve have an impact on likelihood of FMR.<br /><b>Methods</b><br />Vasodilator stress perfusion cardiac magnetic resonance was performed in patients with coronary artery disease (CAD) at multiple centers. FMR severity was confirmed quantitatively via core lab analysis. To test relationship of contractile mechanics with ischemic FMR, regional wall motion and strain were assessed in patients with inducible ischemia and minimal (≤5% LV myocardium, nontransmural) infarction.<br /><b>Results</b><br />A total of 2,647 patients with CAD were studied; 34% had FMR (7% moderate or greater). FMR severity increased with presence (P < 0.001) and extent (P = 0.01) of subpapillary ischemia: patients with moderate or greater FMR had more subpapillary ischemia (odds ratio [OR]: 1.13 per 10% LV; 95% CI: 1.05-1.21; P = 0.001) independent of ischemia in remote regions (P = NS); moderate or greater FMR prevalence increased stepwise with extent of ischemia and infarction in subpapillary myocardium (P < 0.001); stronger associations between FMR and infarction paralleled greater wall motion scores in infarct-affected territories. Among patients with inducible ischemia and minimal infarction (n = 532), wall motion and radial strain analysis showed impaired subpapillary contractile mechanics to associate with moderate or greater FMR (P < 0.05) independent of remote regions (P = NS). Conversely, subpapillary ischemia without contractile dysfunction did not augment FMR likelihood. Mitral and interpapillary dimensions increased with subpapillary radial strain impairment; each remodeling parameter associated with impaired subpapillary strain (P < 0.05) independent of remote strain (P = NS). Subpapillary radial strain (OR: 1.13 per 5% [95% CI: 1.02-1.25]; P = 0.02) and mitral tenting area (OR: 1.05 per 10 mm<sup>2</sup> [95% CI: 1.00-1.10]; P = 0.04) were associated with moderate or greater FMR controlling for global remodeling represented by LV end-systolic volume (P = NS): when substituting sphericity for LV volume, moderate or greater FMR remained independently associated with subpapillary radial strain impairment (OR: 1.22 per 5% [95% CI: 1.02-1.47]; P = 0.03).<br /><b>Conclusions</b><br />Among patients with CAD and ischemia, FMR severity and adverse mitral apparatus remodeling increase in proportion to contractile dysfunction underlying the mitral valve.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jul 2022; 15:1212-1226</small></div>

<div><h4>Magnetic Resonance Imaging in Pediatric Myocarditis: Trends and Associations With Cost and Outcome.</h4><i>O\'Halloran CP, Robinson JD, Watanabe K, Zumpf KB, ... Marino BS, Johnson JT</i><br /><b>Background</b><br />Cardiac magnetic resonance (CMR) provides tissue characterization and structural and functional data. CMR has high sensitivity and specificity for myocarditis in adults and children. The relationship between pediatric CMR use, cost, and clinical outcome has not been studied.<br /><b>Objectives</b><br />This work aims to describe temporal trends in CMR imaging for pediatric myocarditis and examine associations between CMR use, hospital cost, and outcomes.<br /><b>Methods</b><br />A retrospective cohort study of all inpatients <21 years of age with a diagnosis of myocarditis reported to the Pediatric Health Information System (2004-2019) was performed. Trends in CMR use were examined. A propensity-matched subcohort using center and patient level variables was used to assess whether outcomes differed by CMR use.<br /><b>Results</b><br />A total of 4,195 children with myocarditis from 47 hospitals were identified. The median age was 11.5 years (IQR: 1.5-16.0 years) and 2,617 (62%) were male. CMR was used in 23% and mortality occurred in 6%. CMR use during hospitalization increased from 2% in 2004 to 37% in 2019 (odds ratio [OR]: 1.19 [95% CI: 1.17-1.21]). After propensity score matching, CMR use was associated with higher median cost (+$5,340 [95% CI: +$1,739 to +$9,936]) and similar median length of stay (0 days [95% CI: -1 to +1 days]). Using quantile regression, CMR was associated with lower 90th percentile cost (-$77,200 [95% CI: -$127,373 to -$31,339]). More children receiving CMR were discharged alive in the first 30 days after admission (OR: 1.89 days [95% CI: 1.28-2.29]). Within the propensity matched cohort, <10 of 790 CMR recipients died compared to 42 of 790 in the non-CMR group.<br /><b>Conclusions</b><br />CMR use in children with myocarditis has increased over the past 15 years. CMR use is associated with higher cost of hospitalization and similar length of stay for most children but lower cost among the sickest children. CMR use in specific patients may improve clinical outcomes at a lower cost.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jul 2022; 15:1230-1238</small></div>

<div><h4>Clinical Validation of a Virtual Planner for Coronary Interventions Based on Coronary CT Angiography.</h4><i>Sonck J, Nagumo S, Norgaard BL, Otake H, ... De Bruyne B, Collet C</i><br /><b>Background</b><br />Low fractional flow reserve (FFR) values after percutaneous coronary intervention (PCI) carry a worse prognosis than high post-PCI FFR values. Therefore, the ability to predict post-PCI FFR might play an important role in procedural planning. Post-PCI FFR values can now be computed from pre-PCI coronary computed tomography angiography (CTA) using the fractional flow reserve derived from coronary computed tomography angiography revascularization planner (FFR<sub>CT</sub> Planner).<br /><b>Objectives</b><br />The aim of this study was to validate the accuracy of the FFR<sub>CT</sub> Planner.<br /><b>Methods</b><br />In this multicenter, investigator-initiated, prospective study, patients with chronic coronary syndromes and significant lesions based on invasive FFR ≤0.80 were recruited. The FFR<sub>CT</sub> Planner was applied to the fractional flow reserve derived from coronary computed tomography angiography (FFR<sub>CT</sub>) model, simulating PCI. The primary objective was the agreement between the predicted post-PCI FFR by the FFR<sub>CT</sub> Planner and measured post-PCI FFR. Accuracy of the FFR<sub>CT</sub> Planner\'s luminal dimensions was assessed by using post-PCI optical coherence tomography as the reference.<br /><b>Results</b><br />Overall, 259 patients were screened, with 120 patients (123 vessels) included in the final analysis. The mean patient age was 64 ± 9 years, and 24% had diabetes. Measured FFR post-PCI was 0.88 ± 0.06, and the FFR<sub>CT</sub> Planner FFR was 0.86 ± 0.06 (mean difference: 0.02 ± 0.07 FFR unit; limits of agreement: -0.12 to 0.15). Optical coherence tomography minimal stent area was 5.60 ± 2.01 mm<sup>2</sup>, and FFR<sub>CT</sub> Planner minimal stent area was 5.0 ± 2.2 mm<sup>2</sup> (mean difference: 0.66 ± 1.21 mm<sup>2</sup>; limits of agreement: -1.7 to 3.0). The accuracy and precision of the FFR<sub>CT</sub> Planner remained high in cases with focal and diffuse disease and with low and high calcium burden.<br /><b>Conclusions</b><br />The FFR<sub>CT</sub>-based technology was accurate and precise for predicting FFR after PCI. (Precise Percutaneous Coronary Intervention Plan Study [P3]; NCT03782688).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jul 2022; 15:1242-1255</small></div>

<div><h4>F-Sodium Fluoride Positron Emission Tomography and Computed Tomography in Acute Aortic Syndrome.</h4><i>Syed MBJ, Fletcher AJ, Debono S, Forsythe RO, ... van Beek EJR, Newby DE</i><br /><b>Background</b><br />Acute aortic syndrome is associated with aortic medial degeneration. <sup>18</sup>F-sodium fluoride (<sup>18</sup>F-NaF) positron emission tomography (PET) detects microscopic tissue calcification as a marker of disease activity.<br /><b>Objectives</b><br />In a proof-of-concept study, this investigation aimed to establish whether <sup>18</sup>F-NaF PET combined with computed tomography (CT) angiography could identify aortic medial disease activity in patients with acute aortic syndrome.<br /><b>Methods</b><br />Patients with aortic dissection or intramural hematomas and control subjects underwent <sup>18</sup>F-NaF PET/CT angiography of the aorta. Aortic <sup>18</sup>F-NaF uptake was measured at the most diseased segment, and the maximum value was corrected for background blood pool activity (maximum tissue-to-background ratio [TBR<sub>max</sub>]). Radiotracer uptake was compared with change in aortic size and major adverse aortic events (aortic rupture, aorta-related death, or aortic repair) over 45 ± 13 months.<br /><b>Results</b><br />Aortic <sup>18</sup>F-NaF uptake co-localized with histologically defined regions of microcalcification and elastin disruption. Compared with control subjects, patients with acute aortic syndrome had increased <sup>18</sup>F-NaF uptake (TBR<sub>max</sub>: 1.36 ± 0.39 [n = 20] vs 2.02 ± 0.42 [n = 47] respectively; P < 0.001) with enhanced uptake at the site of intimal disruption (+27.5%; P < 0.001). <sup>18</sup>F-NaF uptake in the false lumen was associated with aortic growth (+7.1 mm/year; P = 0.011), and uptake in the outer aortic wall was associated with major adverse aortic events (HR: 8.5 [95% CI: 1.4-50.4]; P = 0.019).<br /><b>Conclusions</b><br />In patients with acute aortic syndrome, <sup>18</sup>F-NaF uptake was enhanced at sites of disease activity and was associated with aortic growth and clinical events. <sup>18</sup>F-NaF PET/CT holds promise as a noninvasive marker of disease severity and future risk in patients with acute aortic syndrome. (<sup>18</sup>F Sodium Fluoride PET/CT in Acute Aortic Syndrome [FAASt]; NCT03647566).<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>JACC Cardiovasc Imaging: 01 Jul 2022; 15:1291-1304</small></div>