Journal: JACC Cardiovasc Imaging

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Abstract

Entropy as a Measure of Myocardial Tissue Heterogeneity in Patients With Ventricular Arrhythmias.

Antiochos P, Ge Y, van der Geest RJ, Madamanchi C, ... Stevenson WG, Kwong RY
Objectives
The authors investigated the incremental prognostic value of entropy, a novel measure of myocardial tissue heterogeneity by cardiac magnetic resonance (CMR) imaging in patients presenting with ventricular arrhythmias (VAs).
Background
CMR can characterize myocardial areas serving as arrhythmogenic substrate.
Methods
Consecutive patients undergoing CMR imaging for VAs were followed for major adverse cardiac events (MACEs) defined by all-cause death, incident VAs requiring therapy, or heart failure hospitalization. Entropy was derived from the probability distribution of pixel signal intensities of the left ventricular (LV) myocardium.
Results
A total of 583 patients (age 54 ± 15 years, female 39%, left ventricular ejection fraction [LVEF] 54 ± 13%) were followed for a median of 4.4 years and experienced 141 MACEs. Entropy showed strong unadjusted association with MACE (HR: 1.88; 95% CI: 1.63-2.17; P < 0.001). In a multivariable model including LVEF, QRS duration, late gadolinium enhancement, and presenting arrhythmia, entropy maintained independent association with MACE (HR: 1.61; 95% CI: 1.32-1.96; P < 0.001). Entropy was further significantly associated with MACE in patients without myocardial scar (HR: 2.43; 95% CI: 1.55-3.82; P < 0.001) and in those presenting with nonsustained VAs (HR: 2.16; 95% CI: 1.43-3.25; P < 0.001). Addition of LV entropy to the baseline multivariable model significantly improved model performance (C-statistic improvement: 0.725 to 0.754; P = 0.003) and risk reclassification.
Conclusions
In patients with VAs, CMR-assessed LV entropy was independently associated with MACE and provided incremental prognostic value, on top of LVEF and late gadolinium enhancement. LV entropy assessment may help risk stratification in patients with absence of myocardial scar or with nonsustained VAs.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 01 May 2022; 15:783-792
Antiochos P, Ge Y, van der Geest RJ, Madamanchi C, ... Stevenson WG, Kwong RY
JACC Cardiovasc Imaging: 01 May 2022; 15:783-792 | PMID: 35512951
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Abstract

Diabetes and Myocardial Fibrosis: A Systematic Review and Meta-Analysis.

Salvador DB, Gamba MR, Gonzalez-Jaramillo N, Gonzalez-Jaramillo V, ... Muka T, Bano A
Objectives
This systematic review and meta-analysis investigated the association of diabetes and glycemic control with myocardial fibrosis (MF).
Background
MF is associated with an increased risk of heart failure, coronary artery disease, arrhythmias, and death. Diabetes may influence the development of MF, but evidence is inconsistent.
Methods
The authors searched EMBASE, Medline Ovid, Cochrane CENTRAL, Web of Science, and Google Scholar for observational and interventional studies investigating the association of diabetes, glycemic control, and antidiabetic medication with MF assessed by histology and cardiac magnetic resonance (ie, extracellular volume fraction [ECV%] and T1 time).
Results
A total of 32 studies (88% exclusively on type 2 diabetes) involving 5,053 participants were included in the systematic review. Meta-analyses showed that diabetes was associated with a higher degree of MF assessed by histological collagen volume fraction (n = 6 studies; mean difference: 5.80; 95% CI: 2.00-9.59) and ECV% (13 studies; mean difference: 2.09; 95% CI: 0.92-3.27), but not by native or postcontrast T1 time. Higher glycosylated hemoglobin levels were associated with higher degrees of MF.
Conclusions
Diabetes is associated with higher degree of MF assessed by histology and ECV% but not by T1 time. In patients with diabetes, worse glycemic control was associated with higher MF degrees. These findings mostly apply to type 2 diabetes and warrant further investigation into whether these associations are causal and which medications could attenuate MF in patients with diabetes.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 01 May 2022; 15:796-808
Salvador DB, Gamba MR, Gonzalez-Jaramillo N, Gonzalez-Jaramillo V, ... Muka T, Bano A
JACC Cardiovasc Imaging: 01 May 2022; 15:796-808 | PMID: 35512952
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Abstract

Bone Marrow Cells Improve Coronary Flow Reserve in Ischemic Nonrevascularized Myocardium: A MiHeart/IHD Quantitative Perfusion CMR Substudy.

Assuncao-Jr AN, Rochitte CE, Kwong RY, Wolff Gowdak LH, Krieger JE, Jerosch-Herold M
Objectives
This study investigated whether intramyocardial bone marrow-derived hematopoietic progenitor cells (BMCs) increase coronary flow reserve (CFR) in ischemic myocardial regions where direct revascularization was unsuitable.
Background
Patients with diffuse coronary artery disease frequently undergo incomplete myocardial revascularization, which increases their risk for future adverse cardiovascular outcomes. The residual regional ischemia related to both untreated epicardial lesions and small vessel disease usually contributes to the disease burden.
Methods
The MiHeart/IHD study randomized patients with diffuse coronary artery disease undergoing incomplete coronary artery bypass grafting to receive BMCs or placebo in ischemic myocardial regions. After the procedure, 78 patients underwent cardiovascular magnetic resonance (CMR) at 1, 6, and 12 months and were included in this cardiac magnetic resonance substudy with perfusion quantification. Segments were classified as target (injected), adjacent (surrounding the injection site), and remote from injection site.
Results
Of 1,248 segments, 269 were target (22%), 397 (32%) adjacent, and 582 (46%) remote. The target had significantly lower CFR at baseline (1.40 ± 0.79 vs 1.64 ± 0.89 in adjacent and 1.79 ± 0.79 in remote; both P < 0.05). BMCs significantly increased CFR in target and adjacent segments at 6 and 12 months compared with placebo. In target regions, there was a progressive treatment effect (27.1% at 6 months, P = 0.037, 42.2% at 12 months, P = 0.001). In the adjacent segments, CFR increased by 21.8% (P = 0.023) at 6 months, which persisted until 12 months (22.6%; P = 0.022). Remote segments in both the BMC and placebo groups experienced similar improvements in CFR (not significant at 12 months compared with baseline).
Conclusions
BMCs, injected in severely ischemic regions unsuitable for direct revascularization, led to the largest CFR improvements, which progressed up to 12 months, compared with smaller but persistent CFR changes in adjacent and no improvement in remote segments.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 01 May 2022; 15:812-824
Assuncao-Jr AN, Rochitte CE, Kwong RY, Wolff Gowdak LH, Krieger JE, Jerosch-Herold M
JACC Cardiovasc Imaging: 01 May 2022; 15:812-824 | PMID: 35512954
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Abstract

Radiomics-Based Precision Phenotyping Identifies Unstable Coronary Plaques From Computed Tomography Angiography.

Lin A, Kolossváry M, Cadet S, McElhinney P, ... Wong DTL, Dey D
Objectives
The aim of this study was to precisely phenotype culprit and nonculprit lesions in myocardial infarction (MI) and lesions in stable coronary artery disease (CAD) using coronary computed tomography angiography (CTA)-based radiomic analysis.
Background
It remains debated whether any single coronary atherosclerotic plaque within the vulnerable patient exhibits unique morphology conferring an increased risk of clinical events.
Methods
A total of 60 patients with acute MI prospectively underwent coronary CTA before invasive angiography and were matched to 60 patients with stable CAD. For all coronary lesions, high-risk plaque (HRP) characteristics were qualitatively assessed, followed by semiautomated plaque quantification and extraction of 1,103 radiomic features. Machine learning models were built to examine the additive value of radiomic features for discriminating culprit lesions over and above HRP and plaque volumes.
Results
Culprit lesions had higher mean volumes of noncalcified plaque (NCP) and low-density noncalcified plaque (LDNCP) compared with the highest-grade stenosis nonculprits and highest-grade stenosis stable CAD lesions (NCP: 138.1 mm3 vs 110.7 mm3 vs 102.7 mm3; LDNCP: 14.2 mm3 vs 9.8 mm3 vs 8.4 mm3; both Ptrend < 0.01). In multivariable linear regression adjusted for NCP and LDNCP volumes, 14.9% (164 of 1,103) of radiomic features were associated with culprits and 9.7% (107 of 1,103) were associated with the highest-grade stenosis nonculprits (critical P < 0.0007) when compared with highest-grade stenosis stable CAD lesions as reference. Hierarchical clustering of significant radiomic features identified 9 unique data clusters (latent phenotypes): 5 contained radiomic features specific to culprits, 1 contained features specific to highest-grade stenosis nonculprits, and 3 contained features associated with either lesion type. Radiomic features provided incremental value for discriminating culprit lesions when added to a machine learning model containing HRP and plaque volumes (area under the receiver-operating characteristic curve 0.86 vs 0.76; P = 0.004).
Conclusions
Culprit lesions and highest-grade stenosis nonculprit lesions in MI have distinct radiomic signatures compared with lesions in stable CAD. Within the vulnerable patient may exist individual vulnerable plaques identifiable by coronary CTA-based precision phenotyping.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 01 May 2022; 15:859-871
Lin A, Kolossváry M, Cadet S, McElhinney P, ... Wong DTL, Dey D
JACC Cardiovasc Imaging: 01 May 2022; 15:859-871 | PMID: 35512957
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Abstract

Pericoronary Adipose Tissue Attenuation, Low-Attenuation Plaque Burden, and 5-Year Risk of Myocardial Infarction.

Tzolos E, Williams MC, McElhinney P, Lin A, ... Newby DE, Dey D
Objectives
We sought to assess the relative and additive values of pericoronary adipose tissue (PCAT) attenuation and low-attenuation noncalcified plaque (LAP) to predict future risk of myocardial infarction.
Background
PCAT attenuation and LAP burden can both predict outcomes.
Methods
In a post hoc analysis of the multicenter SCOT-HEART (Scottish Computed Tomography of the Heart) trial, we investigated the relationships between the future risk of fatal or nonfatal myocardial infarction and PCAT attenuation measured from computed tomography coronary angiography using multivariable Cox regression models including plaque burden, obstructive coronary disease, and cardiac risk score (incorporating age, sex, diabetes, smoking, hypertension, hyperlipidemia, and family history).
Results
In 1,697 evaluable participants (age: 58 ± 10 years), there were 37 myocardial infarctions after a median follow-up of 4.7 years. Mean PCAT was -76 ± 8 HU and median LAP burden was 4.20% (IQR: 0%-6.86%). PCAT attenuation of the right coronary artery (RCA) was predictive of myocardial infarction (HR: 1.55; P = 0.017, per 1 SD increment) with an optimum threshold of -70.5 HU (HR: 2.45; P = 0.01). In multivariable analysis, adding PCAT-RCA of ≥-70.5 HU to an LAP burden of >4% (the optimum threshold for future myocardial infarction; HR: 4.87; P < 0.0001) led to improved prediction of future myocardial infarction (HR: 11.7; P < 0.0001). LAP burden showed higher area under the curve compared to PCAT attenuation for the prediction of myocardial infarction (AUC = 0.71 [95% CI: 0.62-0.80] vs AUC = 0.64 [95% CI: 0.54-0.74]; P < 0.001), with increased area under the curve when the 2 metrics are combined (AUC = 0.75 [95% CI: 0.65-0.85]; P = 0.037).
Conclusion
Computed tomography coronary angiography-defined LAP burden and PCAT attenuation have marked and complementary predictive value for the risk of fatal or nonfatal myocardial infarction.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 13 Apr 2022; epub ahead of print
Tzolos E, Williams MC, McElhinney P, Lin A, ... Newby DE, Dey D
JACC Cardiovasc Imaging: 13 Apr 2022; epub ahead of print | PMID: 35450813
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Abstract

Efficacy of Diltiazem to Improve Coronary Vasomotor Dysfunction in ANOCA: The EDIT-CMD Randomized Clinical Trial.

Jansen TPJ, Konst RE, de Vos A, Paradies V, ... van Royen N, Elias-Smale SE
Objectives
The randomized, placebo-controlled EDIT-CMD (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial) evaluated the effect of diltiazem on coronary vasomotor dysfunction (CVDys), as assessed by repeated coronary function testing (CFT), angina, and quality of life.
Background
Diltiazem is recommended and frequently prescribed in patients with angina and nonobstructive coronary artery disease (ANOCA), suspected of CVDys. However, studies substantiating its effect is this patient group are lacking.
Methods
A total of 126 patients with ANOCA were included and underwent CFT. CVDys, defined as the presence of vasospasm (after intracoronary acetylcholine provocation) and/or microvascular dysfunction (coronary flow reserve: <2.0, index of microvascular resistance: ≥25), was confirmed in 99 patients, of whom 85 were randomized to receive either oral diltiazem or placebo up to 360 mg/d. After 6 weeks, a second CFT was performed. The primary end point was the proportion of patients having a successful treatment, defined as normalization of 1 abnormal parameter of CVDys and no normal parameter becoming abnormal. Secondary end points were changes from baseline to 6-week follow-up in vasospasm, index of microvascular resistance, coronary flow reserve, symptoms (Seattle Angina Questionnaire), or quality of life (Research and Development Questionnaire 36).
Results
In total, 73 patients (38 diltiazem vs 35 placebo) underwent the second CFT. Improvement of the CFT did not differ between the groups (diltiazem vs placebo: 21% vs 29%; P = 0.46). However, more patients on diltiazem treatment progressed from epicardial spasm to microvascular or no spasm (47% vs 6%; P = 0.006). No significant differences were observed between the diltiazem and placebo group in microvascular dysfunction, Seattle Angina Questionnaire, or Research and Development Questionnaire 36.
Conclusions
This first performed randomized, placebo-controlled trial in patients with ANOCA showed that 6 weeks of therapy with diltiazem, when compared with placebo, did not substantially improve CVDys, symptoms, or quality of life, but diltiazem therapy did reduce prevalence of epicardial spasm. (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial [EDIT-CMD]; NCT04777045).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 02 Apr 2022; epub ahead of print
Jansen TPJ, Konst RE, de Vos A, Paradies V, ... van Royen N, Elias-Smale SE
JACC Cardiovasc Imaging: 02 Apr 2022; epub ahead of print | PMID: 35466050
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Abstract

Coronary Artery Calcium for Risk Stratification of Sudden Cardiac Death: The Coronary Artery Calcium Consortium.

Razavi AC, Uddin SMI, Dardari ZA, Berman DS, ... Blaha MJ, Dzaye O
Objectives
Sudden cardiac death (SCD) is a common initial manifestation of coronary heart disease (CHD); however, SCD risk prediction remains elusive.
Background
Coronary artery calcium (CAC) is a marker of plaque burden. Whether CAC improves risk stratification for incident SCD beyond atherosclerotic cardiovascular disease (ASCVD) risk factors is unknown.
Methods
We studied 66,636 primary prevention patients from the CAC Consortium. Multivariable competing risks regression and C-statistics were used to assess the association between CAC and SCD, adjusting for demographics and traditional risk factors.
Results
The mean age was 54.4 years, 33% were women, 11% were of non-White ethnicity, and 55% had CAC >0. A total of 211 SCD events (0.3%) were observed during a median follow-up of 10.6 years, 91% occurring among those with baseline CAC >0. Compared with CAC = 0, there was a stepwise higher risk (P trend < 0.001) in SCD for CAC 100 to 399 (subdistribution hazard ratio [SHR]: 2.8; 95% CI: 1.6-5.0), CAC 400 to 999 (SHR: 4.0; 95% CI: 2.2-7.3), and CAC >1,000 (SHR: 4.9; 95% CI: 2.6-9.9). CAC provided incremental improvements in the C-statistic for the prediction of SCD among individuals with a 10-year risk <7.5% (ΔC-statistic = +0.046; P = 0.02) and 7.5% to 20% (ΔC-statistic = +0.069; P = 0.003), which were larger when compared with persons with a 10-year risk >20% (ΔC-statistic = +0.01; P = 0.54).
Conclusions
Higher CAC burden strongly associates with incident SCD beyond traditional risk factors, particularly among primary prevention patients with low-intermediate risk. SCD risk stratification can be useful in the early stages of CHD through the measurement of CAC, identifying patients most likely to benefit from further downstream testing.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 21 Mar 2022; epub ahead of print
Razavi AC, Uddin SMI, Dardari ZA, Berman DS, ... Blaha MJ, Dzaye O
JACC Cardiovasc Imaging: 21 Mar 2022; epub ahead of print | PMID: 35370113
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Abstract

Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction.

Nicholls SJ, Kataoka Y, Nissen SE, Prati F, ... Pompili G, Psaltis PJ
Objectives
The purpose of this study was to determine the effect of evolocumab on optical coherence tomography (OCT) measures of plaque composition.
Background
The proprotein convertase subtilisin kexin type-9 inhibitor evolocumab produced coronary atheroma regression in statin-treated patients.
Methods
Patients with a non-ST-segment elevation myocardial infarction were treated with monthly evolocumab 420 mg (n = 80) or placebo (n = 81) for 52 weeks. Patients underwent serial OCT and intravascular ultrasound imaging within a matched arterial segment of a nonculprit vessel. The primary analysis determined the change in the minimum fibrous cap thickness and maximum lipid arc throughout the imaged arterial segment. Additional analyses determined changes in OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were evaluated.
Results
Among treated patients, (age 60.5 ± 9.6 years; 28.6% women; low-density lipoprotein cholesterol [LDL-C], 141.3 ± 33.1 mg/dL), 135 had evaluable imaging at follow-up. The evolocumab group achieved lower LDL-C levels (28.1 vs 87.2 mg/dL; P < 0.001). The evolocumab group demonstrated a greater increase in minimum fibrous cap thickness (+42.7 vs +21.5 μm; P = 0.015) and decrease in maximum lipid arc (-57.5o vs. -31.4o; P = 0.04) and macrophage index (-3.17 vs -1.45 mm; P = 0.04) throughout the arterial segment. Similar benefits of evolocumab were observed in lipid-rich plaque regions. Greater regression of percent atheroma volume was observed with evolocumab compared with placebo (-2.29% ± 0.47% vs -0.61% ± 0.46%; P = 0.009). The groups did not differ regarding changes in microchannels or calcium.
Conclusions
The combination of statin and evolocumab after a non-ST-segment elevation myocardial infarction produces favorable changes in coronary atherosclerosis consistent with stabilization and regression. This demonstrates a potential mechanism for the improved clinical outcomes observed achieving very low LDL-C levels following an acute coronary syndrome. (Imaging of Coronary Plaques in Participants Treated With Evolocumab; NCT03570697).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 16 Mar 2022; epub ahead of print
Nicholls SJ, Kataoka Y, Nissen SE, Prati F, ... Pompili G, Psaltis PJ
JACC Cardiovasc Imaging: 16 Mar 2022; epub ahead of print | PMID: 35431172
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Abstract

Cardiovascular Imaging for Ischemic Heart Disease in Women: Time for a Paradigm Shift.

Rodriguez Lozano PF, Rrapo Kaso E, Bourque JM, Morsy M, ... Kramer CM, Salerno M
Heart disease is the leading cause of death among men and women. Women have a unique phenotype of ischemic heart disease with less calcified lesions, more nonobstructive plaques, and a higher prevalence of microvascular disease compared with men, which may explain in part why current risk models to detect obstructive coronary artery disease (CAD) may not work as well in women. This paper summarizes the sex differences in the functional and anatomical assessment of CAD in women presenting with stable chest pain and provides an approach for using multimodality imaging for the evaluation of suspected ischemic heart disease in women in accordance to the recently published American Heart Association/American College of Cardiology guidelines for the evaluation and diagnosis of chest pain. A paradigm shift in the approach to imaging ischemic heart disease women is needed including updated risk models, a more profound understanding of CAD in women where nonobstructive disease is more prevalent, and algorithms focused on the evaluation of ischemia with nonobstructive CAD and myocardial infarction with nonobstructive CAD.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 16 Mar 2022; epub ahead of print
Rodriguez Lozano PF, Rrapo Kaso E, Bourque JM, Morsy M, ... Kramer CM, Salerno M
JACC Cardiovasc Imaging: 16 Mar 2022; epub ahead of print | PMID: 35331658
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Abstract

Biomarkers of Vascular Inflammation for Cardiovascular Risk Prognostication: A Meta-Analysis.

Antonopoulos AS, Angelopoulos A, Papanikolaou P, Simantiris S, ... Antoniades C, Tousoulis D
Objectives
The purpose of this study was to systematically explore the added value of biomarkers of vascular inflammation for cardiovascular prognostication on top of clinical risk factors.
Background
Measurement of biomarkers of vascular inflammation is advocated for the risk stratification for coronary heart disease (CHD).
Methods
We systematically explored published reports in MEDLINE for cohort studies on the prognostic value of common biomarkers of vascular inflammation in stable patients without known CHD. These included common circulating inflammatory biomarkers (ie, C-reactive protein, interleukin-6 and tumor necrosis factor-a, arterial positron emission tomography/computed tomography and coronary computed tomography angiography-derived biomarkers of vascular inflammation, including anatomical high-risk plaque features and perivascular fat imaging. The main endpoint was the difference in c-index (Δ[c-index]) with the use of inflammatory biomarkers for major adverse cardiovascular events (MACEs) and mortality. We calculated I2 to test heterogeneity. This study is registered with PROSPERO (CRD42020181158).
Results
A total of 104,826 relevant studies were screened and a final of 39 independent studies (175,778 individuals) were included in the quantitative synthesis. Biomarkers of vascular inflammation provided added prognostic value for the composite endpoint and for MACEs only (pooled estimate for Δ[c-index]% 2.9, 95% CI: 1.7-4.1 and 3.1, 95% CI: 1.8-4.5, respectively). Coronary computed tomography angiography-related biomarkers were associated with the highest added prognostic value for MACEs: high-risk plaques 5.8%, 95% CI: 0.6 to 11.0, and perivascular adipose tissue (on top of coronary atherosclerosis extent and high-risk plaques): 8.2%, 95% CI: 4.0 to 12.5). In meta-regression analysis, the prognostic value of inflammatory biomarkers was independent of other confounders including study size, length of follow-up, population event incidence, the performance of the baseline model, and the level of statistical adjustment. Limitations in the published literature include the lack of reporting of other metrics of improvement of risk stratification, the net clinical benefit, or the cost-effectiveness of such biomarkers in clinical practice.
Conclusions
The use of biomarkers of vascular inflammation enhances risk discrimination for cardiovascular events.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Feb 2022; 15:460-471
Antonopoulos AS, Angelopoulos A, Papanikolaou P, Simantiris S, ... Antoniades C, Tousoulis D
JACC Cardiovasc Imaging: 27 Feb 2022; 15:460-471 | PMID: 34801448
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Abstract

Combined cCTA and TAVR Planning for Ruling Out Significant CAD: Added Value of ML-Based CT-FFR.

Gohmann RF, Pawelka K, Seitz P, Majunke N, ... Abdel-Wahab M, Gutberlet M
Objectives
The purpose of this study was to analyze the ability of machine-learning (ML)-based computed tomography (CT)-derived fractional flow reserve (CT-FFR) to further improve the diagnostic performance of coronary CT angiography (cCTA) for ruling out significant coronary artery disease (CAD) during pre-transcatheter aortic valve replacement (TAVR) evaluation in patients with a high pre-test probability for CAD.
Background
CAD is a frequent comorbidity in patients undergoing TAVR. Current guidelines recommend its assessment before TAVR. If significant CAD can be excluded on cCTA, invasive coronary angiography (ICA) may be avoided. Although cCTA is a very sensitive test, it is limited by relatively low specificity and positive predictive value, particularly in high-risk patients.
Methods
Overall, 460 patients (age 79.6 ± 7.4 years) undergoing pre-TAVR CT were included and examined with an electrocardiogram-gated CT scan of the heart and high-pitch scan of the vascular access route. Images were evaluated for significant CAD. Patients routinely underwent ICA (388/460), which was omitted at the discretion of the local Heart Team if CAD could be effectively ruled out on cCTA (72/460). CT examinations in which CAD could not be ruled out (CAD+) (n = 272) underwent additional ML-based CT-FFR.
Results
ML-based CT-FFR was successfully performed in 79.4% (216/272) of all CAD+ patients and correctly reclassified 17 patients as CAD negative. CT-FFR was not feasible in 20.6% because of reduced image quality (37/56) or anatomic variants (19/56). Sensitivity, specificity, positive predictive value, and negative predictive value were 94.9%, 52.0%, 52.2%, and 94.9%, respectively. The additional evaluation with ML-based CT-FFR increased accuracy by Δ+3.4% (CAD+: Δ+6.0%) and raised the total number of examinations negative for CAD to 43.9% (202/460).
Conclusions
ML-based CT-FFR may further improve the diagnostic performance of cCTA by correctly reclassifying a considerable proportion of patients with morphological signs of obstructive CAD on cCTA during pre-TAVR evaluation. Thereby, CT-FFR has the potential to further reduce the need for ICA in this challenging elderly group of patients before TAVR.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Feb 2022; 15:476-486
Gohmann RF, Pawelka K, Seitz P, Majunke N, ... Abdel-Wahab M, Gutberlet M
JACC Cardiovasc Imaging: 27 Feb 2022; 15:476-486 | PMID: 34801449
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Abstract

Mean Versus Peak Coronary Calcium Density on Non-Contrast CT: Calcium Scoring and ASCVD Risk Prediction.

Dzaye O, Razavi AC, Dardari ZA, Berman DS, ... Whelton SP, Blaha MJ
Objectives
This study sought to assess the relationship between mean vs peak calcified plaque density and their impact on calculating coronary artery calcium (CAC) scores and to compare the corresponding differential prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) mortality.
Background
The Agatston CAC score is quantified per lesion as the product of plaque area and a 4-level categorical peak calcium density factor. However, mean calcium density may more accurately measure the heterogenous mixture of lipid-rich, fibrous, and calcified plaque reflective of ASCVD risk.
Methods
We included 10,373 individuals from the CAC Consortium who had CAC >0 and per-vessel measurements of peak calcium density factor and mean calcium density. Area under the curve and continuous net reclassification improvement analyses were performed for CHD and ASCVD mortality to compare the predictive abilities of mean calcium density vs peak calcium density factor when calculating the Agatston CAC score.
Results
Participants were on average 53.4 years of age, 24.4% were women, and the median CAC score was 68 Agatston units. The average values for mean calcium density and peak calcium density factor were 210 ± 50 HU and 3.1 ± 0.5, respectively. Individuals younger than 50 years of age and/or those with a total plaque area <100 mm2 had the largest differences between the peak and mean density measures. Among persons with CAC 1-99, the use of mean calcium density resulted in a larger improvement in ASCVD mortality net reclassification improvement (NRI) (NRI = 0.49; P < 0.001 vs. NRI = 0.18; P = 0.08) and CHD mortality discrimination (Δ area under the curve (AUC) = +0.169 vs +0.036; P < 0.001) compared with peak calcium density factor. Neither peak nor mean calcium density improved mortality prediction at CAC scores >100.
Conclusion
Mean and peak calcium density may differentially describe plaque composition early in the atherosclerotic process. Mean calcium density performs better than peak calcium density factor when combined with plaque area for ASCVD mortality prediction among persons with Agatston CAC 1-99.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Feb 2022; 15:489-500
Dzaye O, Razavi AC, Dardari ZA, Berman DS, ... Whelton SP, Blaha MJ
JACC Cardiovasc Imaging: 27 Feb 2022; 15:489-500 | PMID: 34801452
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Abstract

A Noncontrast CMR Risk Score for Long-Term Risk Stratification in Reperfused ST-Segment Elevation Myocardial Infarction.

Bulluck H, Carberry J, Carrick D, McCartney PJ, ... Oldroyd KG, Berry C
Objectives
This study compared the prognostic value of a noncontrast CMR risk score for the composite of all-cause death, nonfatal myocardial infarction, and new congestive heart failure.
Background
A cardiovascular magnetic resonance (CMR) risk score including left ventricular ejection fraction (LVEF), myocardial infarct (MI) size, and microvascular obstruction (MVO) was recently proposed to risk-stratify patients with ST-segment elevation myocardial infarction (STEMI).
Methods
The Eitel CMR risk score and GRACE (Global Registry of Acute Coronary Events) score were used as a reference (Score 1: acute MI size ≥19% LV, LVEF ≤47%, MVO >1.4% LV and GRACE score). MVO was replaced by intramyocardial hemorrhage (IMH) in Score 2 (acute MI size ≥19% LV, LVEF ≤47%, IMH, and GRACE score). Score 3 included only LVEF ≤45%, IMH, and GRACE score.
Results
There were 370 patients in the derivation cohort and 234 patients in the validation cohort. In the derivation cohort, the 3 scores performed similarly and better than GRACE score to predict the 1-year composite endpoint with C-statistics of 0.83, 0.83, 0.82, and 0.74, respectively. In the validation cohort, there was good discrimination and calibration of score 3, with a C-statistic of 0.87 and P = 0.71 in a Hosmer-Lemeshow test for goodness of fit, on the 1-year composite outcome. Kaplan-Meier curves for 5-year composite outcome showed that those with LVEF ≤45% (high-risk) and LVEF >45% and IMH (intermediate-risk) had significantly higher cumulative events than those with LVEF >45% and no IMH (low-risk), log-rank tests: P = 0.02 and P = 0.03, respectively. The HR for the high-risk group was 2.3 (95% CI: 1.1-4.7) and for the intermediate-risk group was 2.0 (95% CI: 1.0-3.8), and these remained significant after adjusting for the GRACE score.
Conclusions
This noncontrast CMR risk score has performance comparable to an established risk score, and patients with STEMI could be stratified into low risk (LVEF >45% and no IMH), intermediate risk (LVEF >45% and IMH), and high risk (LVEF ≤45%). (A Trial of Low-dose Adjunctive alTeplase During prIMary PCI [T-TIME]; NCT02257294) (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Feb 2022; 15:431-440
Bulluck H, Carberry J, Carrick D, McCartney PJ, ... Oldroyd KG, Berry C
JACC Cardiovasc Imaging: 27 Feb 2022; 15:431-440 | PMID: 35272808
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Abstract

Using Deep-Learning Algorithms to Simultaneously Identify Right and Left Ventricular Dysfunction From the Electrocardiogram.

Vaid A, Johnson KW, Badgeley MA, Somani SS, ... Nadkarni GN, Glicksberg BS
Objectives
This study sought to develop DL models capable of comprehensively quantifying left and right ventricular dysfunction from ECG data in a large, diverse population.
Background
Rapid evaluation of left and right ventricular function using deep learning (DL) on electrocardiograms (ECGs) can assist diagnostic workflow. However, DL tools to estimate right ventricular (RV) function do not exist, whereas those to estimate left ventricular (LV) function are restricted to quantification of very low LV function only.
Methods
A multicenter study was conducted with data from 5 New York City hospitals: 4 for internal testing and 1 serving as external validation. We created novel DL models to classify left ventricular ejection fraction (LVEF) into categories derived from the latest universal definition of heart failure, estimate LVEF through regression, and predict a composite outcome of either RV systolic dysfunction or RV dilation.
Results
We obtained echocardiogram LVEF estimates for 147,636 patients paired to 715,890 ECGs. We used natural language processing (NLP) to extract RV size and systolic function information from 404,502 echocardiogram reports paired to 761,510 ECGs for 148,227 patients. For LVEF classification in internal testing, area under curve (AUC) at detection of LVEF ≤40%, 40% < LVEF ≤50%, and LVEF >50% was 0.94 (95% CI: 0.94-0.94), 0.82 (95% CI: 0.81-0.83), and 0.89 (95% CI: 0.89-0.89), respectively. For external validation, these results were 0.94 (95% CI: 0.94-0.95), 0.73 (95% CI: 0.72-0.74), and 0.87 (95% CI: 0.87-0.88). For regression, the mean absolute error was 5.84% (95% CI: 5.82%-5.85%) for internal testing and 6.14% (95% CI: 6.13%-6.16%) in external validation. For prediction of the composite RV outcome, AUC was 0.84 (95% CI: 0.84-0.84) in both internal testing and external validation.
Conclusions
DL on ECG data can be used to create inexpensive screening, diagnostic, and predictive tools for both LV and RV dysfunction. Such tools may bridge the applicability of ECGs and echocardiography and enable prioritization of patients for further interventions for either sided failure progressing to biventricular disease.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Feb 2022; 15:395-410
Vaid A, Johnson KW, Badgeley MA, Somani SS, ... Nadkarni GN, Glicksberg BS
JACC Cardiovasc Imaging: 27 Feb 2022; 15:395-410 | PMID: 34656465
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Abstract

Detection and Characterization of Thrombosis in Humans Using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance.

Izquierdo-Garcia D, Désogère P, Philip AL, Mekkaoui C, ... Caravan P, Sosnovik DE
Objectives
The authors present a novel technique to detect and characterize LAA thrombus in humans using combined positron emission tomography (PET)/cardiac magnetic resonance (CMR) of a fibrin-binding radiotracer, [64Cu]FBP8.
Background
The detection of thrombus in the left atrial appendage (LAA) is vital in the prevention of stroke and is currently performed using transesophageal echocardiography (TEE).
Methods
The metabolism and pharmacokinetics of [64Cu]FBP8 were studied in 8 healthy volunteers. Patients with atrial fibrillation and recent TEEs of the LAA (positive n = 12, negative n = 12) were injected with [64Cu]FBP8 and imaged with PET/CMR, including mapping the longitudinal magnetic relaxation time (T1) in the LAA.
Results
[64Cu]FBP8 was stable to metabolism and was rapidly eliminated. The maximum standardized uptake value (SUVMax) in the LAA was significantly higher in the TEE-positive than TEE-negative subjects (median of 4.0 [interquartile range (IQR): 3.0-6.0] vs 2.3 [IQR: 2.1-2.5]; P < 0.001), with an area under the receiver-operating characteristic curve of 0.97. An SUVMax threshold of 2.6 provided a sensitivity of 100% and specificity of 84%. The minimum T1 (T1Min) in the LAA was 970 ms (IQR: 780-1,080 ms) vs 1,380 ms (IQR: 1,120-1,620 ms) (TEE positive vs TEE negative; P < 0.05), with some overlap between the groups. Logistic regression using SUVMax and T1Min allowed all TEE-positive and TEE-negative subjects to be classified with 100% accuracy.
Conclusions
PET/CMR of [64Cu]FBP8 is able to detect acute as well as older platelet-poor thrombi with excellent accuracy. Furthermore, the integrated PET/CMR approach provides useful information on the biological properties of thrombus such as fibrin and methemoglobin content. (Imaging of LAA Thrombosis; NCT03830320).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Feb 2022; 15:504-515
Izquierdo-Garcia D, Désogère P, Philip AL, Mekkaoui C, ... Caravan P, Sosnovik DE
JACC Cardiovasc Imaging: 27 Feb 2022; 15:504-515 | PMID: 34656469
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Abstract

AI Based CMR Assessment of Biventricular Function: Clinical Significance of Intervendor Variability and Measurement Errors.

Wang S, Patel H, Miller T, Ameyaw K, ... Mor-Avi V, Patel AR
Objectives
The aim of this study was to determine whether left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) and left ventricular mass (LVM) measurements made using 3 fully automated deep learning (DL) algorithms are accurate and interchangeable and can be used to classify ventricular function and risk-stratify patients as accurately as an expert.
Background
Artificial intelligence is increasingly used to assess cardiac function and LVM from cardiac magnetic resonance images.
Methods
Two hundred patients were identified from a registry of individuals who underwent vasodilator stress cardiac magnetic resonance. LVEF, LVM, and RVEF were determined using 3 fully automated commercial DL algorithms and by a clinical expert (CLIN) using conventional methodology. Additionally, LVEF values were classified according to clinically important ranges: <35%, 35% to 50%, and ≥50%. Both ejection fraction values and classifications made by the DL ejection fraction approaches were compared against CLIN ejection fraction reference. Receiver-operating characteristic curve analysis was performed to evaluate the ability of CLIN and each of the DL classifications to predict major adverse cardiovascular events.
Results
Excellent correlations were seen for each DL-LVEF compared with CLIN-LVEF (r = 0.83-0.93). Good correlations were present between DL-LVM and CLIN-LVM (r = 0.75-0.85). Modest correlations were observed between DL-RVEF and CLIN-RVEF (r = 0.59-0.68). A >10% error between CLIN and DL ejection fraction was present in 5% to 18% of cases for the left ventricle and 23% to 43% for the right ventricle. LVEF classification agreed with CLIN-LVEF classification in 86%, 80%, and 85% cases for the 3 DL-LVEF approaches. There were no differences among the 4 approaches in associations with major adverse cardiovascular events for LVEF, LVM, and RVEF.
Conclusions
This study revealed good agreement between automated and expert-derived LVEF and similarly strong associations with outcomes, compared with an expert. However, the ability of these automated measurements to accurately classify left ventricular function for treatment decision remains limited. DL-LVM showed good agreement with CLIN-LVM. DL-RVEF approaches need further refinements.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Feb 2022; 15:413-427
Wang S, Patel H, Miller T, Ameyaw K, ... Mor-Avi V, Patel AR
JACC Cardiovasc Imaging: 27 Feb 2022; 15:413-427 | PMID: 34656471
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Abstract

Virtual and Augmented Reality in Cardiovascular Care: State-of-the-Art and Future Perspectives.

Jung C, Wolff G, Wernly B, Bruno RR, ... Bhatt DL, Kelm M
Applications of virtual reality (VR) and augmented reality (AR) assist both health care providers and patients in cardiovascular education, complementing traditional learning methods. Interventionalists have successfully used VR to plan difficult procedures and AR to facilitate complex interventions. VR/AR has already been used to treat patients, during interventions in rehabilitation programs and in immobilized intensive care patients. There are numerous additional potential applications in the catheterization laboratory. By using AR, interventionalists could combine visual fluoroscopy information projected and registered on the patient body with data derived from preprocedural imaging and live fusion of different imaging modalities such as fluoroscopy with echocardiography. Persistent technical challenges to overcome include the integration of different imaging modalities into VR/AR and the harmonization of data flow and interfaces. Cybersickness might exclude some patients and users from the potential benefits of VR/AR. Critical ethical considerations arise in the application of VR/AR in vulnerable patients. In addition, digital applications must not distract physicians from the patient. It is our duty as physicians to participate in the development of these innovations to ensure a virtual health reality benefit for our patients in a real-world setting. The purpose of this review is to summarize the current and future role of VR and AR in different fields within cardiology, its challenges, and perspectives.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Feb 2022; 15:519-532
Jung C, Wolff G, Wernly B, Bruno RR, ... Bhatt DL, Kelm M
JACC Cardiovasc Imaging: 27 Feb 2022; 15:519-532 | PMID: 34656478
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Abstract

Hybrid Cardiac Magnetic Resonance/Fluorodeoxyglucose Positron Emission Tomography to Differentiate Active From Chronic Cardiac Sarcoidosis.

Greulich S, Gatidis S, Gräni C, Blankstein R, ... la Fougère C, Krumm P
Objectives
The purpose of this study was to investigate the diagnostic value of simultaneous hybrid cardiac magnetic resonance (CMR) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for detection and differentiation of active (aCS) from chronic (cCS) cardiac sarcoidosis.
Background
Late gadolinium enhancement (LGE) CMR and FDG-PET are both established imaging techniques for the detection of CS. However, there are limited data regarding the value of a comprehensive simultaneous hybrid CMR/FDG-PET imaging approach that includes CMR mapping techniques.
Methods
Forty-three patients with biopsy-proven extracardiac sarcoidosis (median age: 48 years, interquartile range: 37-57 years, 65% male) were prospectively enrolled for evaluation of suspected CS. After dietary preparation for suppression of myocardial glucose metabolism, patients were evaluated on a 3-T hybrid PET/MR scanner. The CMR protocol included T1 and T2 mapping, myocardial function, and LGE imaging. We assumed aCS if PET and CMR (ie, LGE or T1/T2 mapping) were both positive (PET+/CMR+), cCS if PET was negative but CMR was positive (PET-/CMR+), and no CS if patients were CMR negative regardless of PET findings.
Results
Among the 43 patients, myocardial glucose uptake was suppressed successfully in 36 (84%). Hybrid CMR/FDG-PET revealed aCS in 13 patients (36%), cCS in 5 (14%), and no CS in 18 (50%). LGE was present in 14 patients (39%); T1 mapping was abnormal in 10 (27%) and T2 mapping abnormal in 2 (6%). CS was diagnosed based on abnormal T1 mapping in 4 out of 18 CS patients (22%) who were LGE negative. PET FDG uptake was present in 17 (47%) patients.
Conclusions
Comprehensive simultaneous hybrid CMR/FDG-PET imaging is useful for the detection of CS and provides additional value for identifying active disease. Our results may have implications for enhanced diagnosis as well as improved identification of patients with aCS in whom anti-inflammatory therapy may be most beneficial.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Feb 2022; 15:445-456
Greulich S, Gatidis S, Gräni C, Blankstein R, ... la Fougère C, Krumm P
JACC Cardiovasc Imaging: 27 Feb 2022; 15:445-456 | PMID: 34656480
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Abstract

Left Atrial Strain Determinants During the Cardiac Phases.

Mălăescu GG, Mirea O, Capotă R, Petrescu AM, Duchenne J, Voigt JU
Objectives
The present study investigated the determinants of left atrial (LA) strain in all phases of the cardiac cycle.
Background
LA strain by speckle-tracking echocardiography allows the assessment of LA function in each phase of the cardiac cycle. However, its determinants and its relation with left ventricular (LV) function have not yet been fully described.
Methods
The authors performed a retrospective analysis in 127 patients with different cardiovascular pathologies. Using 2-dimensional speckle tracking in 4- and 2-chamber apical views we derived both LA and LV strain curves. Strain-strain loops were reconstructed using LV strain and the corresponding, synchronized LA strain data. Linear regressions were calculated for the entire strain-strain loop as well as for the 3 phases of the cardiac cycle (systole, and early and late diastole). The association between LA strain parameters and LV systolic and diastolic parameters was studied. The prediction of cardiovascular events was evaluated for both measured and predicted LA strain and other parameters.
Results
LA and LV strain curves presented excellent correlations with an R2 > 0.90 for the cardiac cycle, and R2 > 0.97 for its phases. Moreover, the ratios of LV/LA maximal volumes and the slopes of the LA-LV strain-strain loops of the individual patients correlated well (R2 = 0.75). In each phase of the cardiac cycle, LA strain parameters correlated well with the corresponding LV strain and the LV-LA volume ratio (R2 > 0.78). No significant difference in predictive ability of cardiovascular events or atrial fibrillation between the measured and predicted LA strain was observed (P > 0.05 for both).
Conclusions
In the absence of abnormal LA/LV volume exchange, LA strain is, to a large extent, determined by LV strain and further modulated by the ratio of LV and LA volumes. Nonetheless, measuring LA strain is of high clinical interest because it integrates several parameters into a single, robust, and reproducible measurement.

Copyright © 2022. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 27 Feb 2022; 15:381-391
Mălăescu GG, Mirea O, Capotă R, Petrescu AM, Duchenne J, Voigt JU
JACC Cardiovasc Imaging: 27 Feb 2022; 15:381-391 | PMID: 34656486
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This program is still in alpha version.