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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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