Journal: JACC Cardiovasc Imaging

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Abstract

Reduction of Myocardial Infarction and All-Cause Mortality Associated to Statins in Patients Without Obstructive CAD.

Øvrehus KA, Diederichsen A, Grove EL, Steffensen FH, ... Bøtker HE, Nørgaard BL
Objective
The aim of this work was to evaluate the prognostic impact of statin therapy in symptomatic patients without obstructive CAD.
Background
Information on the prognostic impact of post-coronary computed tomographic angiography (CTA) statin use in patients with no or nonobstructive coronary artery disease (CAD) is sparse.
Methods
Patients undergoing CTA with suspected CAD in western Denmark from 2008 to 2017 with <50% coronary stenoses were identified. Information on post-CTA use of statin therapy and cardiovascular events were obtained from national registries.
Results
The study included 33,552 patients, median aged 56 years, 58% female, with no (n = 19,669) or nonobstructive (n = 13,883) CAD and a median follow-up of 3.5 years. The absolute risk of the combined end point of myocardial infarction (MI) or all-cause mortality was directly associated with the CAD burden with an event rate/1,000 patient-years of 4.13 (95% CI: 3.69-4.61) in no, 7.74 (95% CI: 6.88-8.71) in mild (coronary artery calcium score [CACS] 0-99), 13.72 (95% CI: 11.61-16.23) in moderate (CACS 100-399), and 32.47 (95% CI: 26.25-40.16) in severe (CACS ≥400) nonobstructive CAD. Statin therapy was associated with a multivariable adjusted HR for MI and death of 0.52 (95% CI: 0.36-0.75) in no, 0.44 (95% CI: 0.32-0.62) in mild, 0.51 (95% CI: 0.34-0.75) in moderate, and 0.52 (95% CI: 0.32-0.86) in severe nonobstructive CAD. The estimated numbers needed to treat to prevent the primary end point were 92 (95% CI: 61-182) in no, 36 (95% CI: 26-58) in mild, 24 (95% CI: 15-61) in moderate, and 13 (95% CI: 7-86) in severe nonobstructive CAD. Residual confounding may persist, but not to an extent explaining all of the observed risk reduction associated with statin treatment.
Conclusions
The risk of MI and all-cause mortality in patients without obstructive CAD is directly associated with the CAD burden. Statin therapy is associated with a reduction of MI and all-cause death across the spectrum of CAD, however, the absolute benefit of treatment is directionally proportional with the CAD burden.

Copyright © 2021. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 09 Jul 2021; epub ahead of print
Øvrehus KA, Diederichsen A, Grove EL, Steffensen FH, ... Bøtker HE, Nørgaard BL
JACC Cardiovasc Imaging: 09 Jul 2021; epub ahead of print | PMID: 34274285
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Abstract

Pulmonary Artery F-Fluorodeoxyglucose Uptake by PET/CMR as a Marker of Pulmonary Hypertension in Sarcoidosis.

Maier A, Liao SL, Lescure T, Robson PM, ... Fayad ZA, Trivieri MG
Objectives
This study investigated whether pulmonary artery (PA) 18F-FDG uptake is associated with hypertension, and if it correlates to elevated pulmonary pressures.
Background
18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography or cardiac magnetic resonance (CMR) has been used to assess inflammation mostly in large arteries of the systemic circulation. Much less is known about inflammation of the vasculature of the pulmonary system and its relationship to pulmonary hypertension (PH).
Methods
In a single-center cohort of 175 patients with suspected cardiac sarcoidosis, who underwent hybrid thoracic PET/CMR, 18F-FDG uptake in the PA was quantified according to maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) and compared with available results from right heart catheterization (RHC) or transthoracic echocardiography (TTE).
Results
Thirty-three subjects demonstrated clear 18F-FDG uptake in the PA wall. In the subgroup of patients who underwent RHC (n = 10), the mean PA pressure was significantly higher in the group with PA 18F-FDG uptake compared with the group without uptake (34.4 ± 7.2 mm Hg vs 25.6 ± 9.3 mm Hg; P = 0.003), and 9 (90%) patients with PA 18F-FDG uptake had PH when a mean PA pressure cutoff of 25 mm Hg was used compared with 18 (45%) in the nonuptake group (P < 0.05). In the subgroup that underwent TTE, signs of PH were present in a significantly higher number of patients with PA 18F-FDG uptake (14 [51.9%] vs 37 [29.8%]; P < 0.05). Qualitative assessment of 18F-FDG uptake in the PA wall showed a sensitivity of 33% and specificity of 96% for separating patients with PH based on RHC-derived PA pressures. SUVmax and TBR in the PA wall correlated with PA pressure derived from RHC and/or TTE.
Conclusions
We demonstrate that 18F-FDG uptake by PET/CMR in the PA is associated with PH and that its intensity correlates with PA pressure.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 07 Jul 2021; epub ahead of print
Maier A, Liao SL, Lescure T, Robson PM, ... Fayad ZA, Trivieri MG
JACC Cardiovasc Imaging: 07 Jul 2021; epub ahead of print | PMID: 34274283
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Abstract

The Added Value of Coronary Calcium Score in Predicting Cardiovascular Events in Familial Hypercholesterolemia.

Gallo A, Pérez de Isla L, Charrière S, Vimont A, ... Béliard S, REFERCHOL and SAFEHEART investigators
Objectives
This study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH).
Background
Common cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD).
Methods
REFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death.
Results
We included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%.
Conclusions
CAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 07 Jul 2021; epub ahead of print
Gallo A, Pérez de Isla L, Charrière S, Vimont A, ... Béliard S, REFERCHOL and SAFEHEART investigators
JACC Cardiovasc Imaging: 07 Jul 2021; epub ahead of print | PMID: 34274263
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Abstract

Functional Mitral Regurgitation Outcome and Grading in Heart Failure With Reduced Ejection Fraction.

Benfari G, Antoine C, Essayagh B, Batista R, ... Michelena HI, Enriquez-Sarano M
Objectives
This study aims to define excess-mortality linked to functional mitral regurgitation (FMR) quantified in routine-practice.
Background
Appraisal of FMR in heart failure with reduced ejection fraction (HFrEF) is challenging because risks of excess mortality remain uncertain and guidelines diverge.
Methods
Cases of HFrEF (ejection-fraction <50%) Stage B-C that were diagnosed between 2003 and 2011 and had routine-practice FMR quantitation (FMR cohort, n = 6,381) were analyzed for excess mortality thresholds/rates within the cohort and in comparison to the general population. These were also compared to those of a degenerative mitral regurgitation (DMR) simultaneous cohort (DMR cohort, n = 2,416).
Results
In the FMR cohort (age: 70 ± 11 years, ejection fraction: 36 ± 10%, effective regurgitant orifice area [EROA]: 0.09 ± 0.13 cm2), EROA distribution was skewed towards low-values (≥0.40 cm2 in only 8% vs 38% for the DMR cohort; P < 0.0001). One-year mortality was high (15.6%), increasing steeply from 13.3% without FMR to 28.5% with EROA ≥0.30 cm2 (adjusted odds ratio: 1.57 [95% CI: 1.19-2.97]; P = 0.001). In the long term, 3,538 FMR cohort patients died with excess mortality threshold ∼0.10 cm2 (vs ∼0.20 cm2 in the DMR cohort), with 0.10 cm2 EROA increments independently associated with considerable mortality increment (adjusted HR: 1.11 [95% CI: 1.08-1.15]; P < 0.0001) and with no detectable interaction. Compared to the general population, FMR excess mortality increased exponentially with higher EROA (risk ratio point estimates 2.8, 3.8, and 5.1 at EROA 0.20, 0.30, and 0.40 cm2, respectively), and was much steeper than that of the DMR cohort (P < 0.0001). In nested models, individualized EROA was the strongest FMR survival marker, and a new expanded FMR grading scale based on 0.10 cm2 EROA increments provided incremental power over current American Heart Association-American College of Cardiology/European Society of Cardiology guidelines (all P < 0.03).
Conclusions
In HFrEF, FMR is skewed towards smaller EROA. Nevertheless, when measured in routine practice, EROA is the strongest independent FMR determinant of survival after diagnosis. Excess mortality increases exponentially above the threshold of 0.10 cm2, with a much steeper slope than in DMR, for any EROA increment. An expanded EROA-based stratification, superior to existing grading schemes in determining survival, should allow guideline harmonization.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print
Benfari G, Antoine C, Essayagh B, Batista R, ... Michelena HI, Enriquez-Sarano M
JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print | PMID: 34274275
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Abstract

Mitral Annular Dynamics in AF Versus Sinus Rhythm: Novel Insights Into the Mechanism of AFMR.

Deferm S, Bertrand PB, Verhaert D, Verbrugge FH, ... Levine RA, Vandervoort PM
Objectives
This study aimed to investigate mitral annular dynamics in atrial fibrillation (AF) and after sinus rhythm restoration, and to assess the relationship between annular dynamics and mitral regurgitation (MR).
Background
AF can be associated with MR that improves after sinus rhythm restoration. Mechanisms underlying this atrial functional MR (AFMR) are ill-understood and generally attributed to left atrial remodeling.
Methods
Fifty-three patients with persistent AF and normal left ventricular ejection fraction were prospectively examined by means of 3-dimensional transesophageal echocardiography before, immediately after, and 6 weeks after electric cardioversion to sinus rhythm. Annular motion was assessed during AF and in sinus rhythm with the use of 3-dimensional analysis software, and the relationship with MR severity was explored.
Results
During AF and immediately after sinus rhythm restoration, the mitral annulus behaved relatively adynamically, with an overall change in annular area of 10.3% (95% CI: 8.7%-11.8%) and 12.2% (95% CI: 10.6%-13.8%), respectively. At follow-up, a significant increase in annular dynamics (19.0%; 95% CI: 17.4%-20.6%; P < 0.001) was observed, owing predominantly to an increase in presystolic contraction (P < 0.001). The effective regurgitant orifice area decreased from 0.15 cm2 (0.10 cm2-0.23 cm2) during AF to 0.09 cm2 (0.05 cm2-0.12 cm2) at follow-up (P < 0.001) in the total cohort, and from 0.27 (0.23-0.33) to 0.16 (0.12-0.29) in the subgroup with effective regurgitant orifice area (EROA) ≥0.20 cm2. The change in presystolic annular motion was the only independent determinant of the decrease in MR severity (P = 0.027), by optimizing annular-leaflet imbalance. Patients with more pronounced blunting of presystolic dynamics had a higher EROA (P < 0.001), because of a lower total-to-closed leaflet area ratio (P < 0.001) at each point in time. This ratio was the strongest independent determinant of AFMR severity (adjusted P = 0.003).
Conclusions
Mitral annular dynamics are impaired in AF, with blunted presystolic narrowing that contributes to AFMR. Sinus rhythm restoration allows gradual recovery of presystolic annular dynamics. Improved annular dynamics decrease AFMR severity by optimizing annular-leaflet imbalance, regardless of LA remodeling.

Copyright © 2021. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print
Deferm S, Bertrand PB, Verhaert D, Verbrugge FH, ... Levine RA, Vandervoort PM
JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print | PMID: 34274270
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Abstract

Diagnostic Accuracy of Cardiovascular Magnetic Resonance for Cardiac Transplant Rejection: A Meta-analysis.

Han D, Miller RJH, Otaki Y, Gransar H, ... Berman D, Tamarappoo B
Objectives
The aim of this meta-analysis was to assess the diagnostic performance of various CMR imaging parameters for evaluating acute cardiac transplant rejection.
Background
Endomyocardial biopsy is the current gold standard for detection of acute cardiac transplant rejection. Cardiac magnetic resonance (CMR) is uniquely capable of myocardial tissue characterization and may be useful as a noninvasive alternative for the diagnosis of graft rejection.
Methods
PubMed and Web of Science were searched for relevant publications reporting on the use of CMR myocardial tissue characterization for detection of acute cardiac transplant rejection with endomyocardial biopsy as the reference standard. Pooled sensitivity, specificity, and hierarchical modeling-based summary receiver-operating characteristic curves were calculated.
Results
Of 478 papers, 10 studies comprising 564 patients were included. The sensitivity and specificity for the detection of acute cardiac transplant rejection were 84.6 (95% CI: 65.6-94.0) and 70.1 (95% CI: 54.2-82.2) for T1, 86.5 (95% CI: 72.1-94.1) and 85.9 (95% CI: 65.2-94.6) for T2, 91.3 (95% CI: 63.9-98.4) and 67.6 (95% CI: 56.1-77.4) for extracellular volume fraction (ECV), and 50.1 (95% CI: 31.2-68.9) and 60.2 (95% CI: 36.7-79.7) for late gadolinium enhancement (LGE). The areas under the hierarchical modeling-based summary receiver-operating characteristic curve were 0.84 (95% CI: 0.81-0.87) for T1, 0.92 (95% CI: 0.89-94) for T2, 0.78 (95% CI: 0.74-0.81) for ECV, and 0.56 (95% CI: 0.51-0.60) for LGE. T2 values demonstrated the highest diagnostic accuracy, followed by native T1, ECV, and LGE (all P values < 0.001 for T1, ECV, and LGE vs T2).
Conclusions
T2 mapping demonstrated higher diagnostic accuracy than other CMR techniques. Native T1 and ECV provide high diagnostic use but lower diagnostic accuracy compared with T2, which was related primarily to lower specificity. LGE showed poor diagnostic performance for detection of rejection.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print
Han D, Miller RJH, Otaki Y, Gransar H, ... Berman D, Tamarappoo B
JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print | PMID: 34274269
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Abstract

Prognostic Significance of Nonischaemic Myocardial Fibrosis in Patients With Normal Left Ventricular Volumes and Ejection-Fraction.

Lota AS, Tsao A, Owen R, Halliday BP, ... Pennell DJ, Prasad SK
Objectives
This study aims to investigate the prognostic significance of late gadolinium enhancement (LGE) in patients without coronary artery disease and with normal range left ventricular (LV) volumes and ejection fraction.
Background
Nonischemic patterns of LGE with normal LV volumes and ejection fraction are increasingly detected on cardiovascular magnetic resonance, but their prognostic significance, and consequently management, is uncertain.
Methods
Patients with midwall/subepicardial LGE and normal LV volumes, wall thickness, and ejection fraction on cardiovascular magnetic resonance were enrolled and compared to a control group without LGE. The primary outcome was actual or aborted sudden cardiac death (SCD).
Results
Of 748 patients enrolled, 401 had LGE and 347 did not. The median age was 50 years (interquartile range: 38 years-61 years), LV ejection fraction 66% (interquartile range: 62%-70%), and 287 (38%) were women. Scan indications included chest pain (40%), palpitation (33%) and breathlessness (13%). No patient experienced SCD and only 1 LGE+ patient (0.13%) had an aborted SCD in the 11th follow-up year. Over a median of 4.3 years, 30 patients (4.0%) died. All-cause mortality was similar for LGE+/- patients (3.7% vs 4.3%; P = 0.71) and was associated with age (hazard ratio: 2.04 per 10 years; 95% confidence interval: 1.46-2.79; P < 0.001). Twenty-one LGE+ and 4 LGE- patients had an unplanned cardiovascular hospital admission (hazard ratio: 7.22; 95% confidence interval: 4.26-21.17; P < 0.0001).
Conclusions
There was a low SCD risk during long-term follow-up in patients with LGE but otherwise normal LV volumes and ejection fraction. Mortality was driven by age and not LGE presence, location, or extent, although the latter was associated with greater cardiovascular hospitalization for suspected myocarditis and symptomatic ventricular tachycardia.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print
Lota AS, Tsao A, Owen R, Halliday BP, ... Pennell DJ, Prasad SK
JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print | PMID: 34274268
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Abstract

Clinical Deployment of Explainable Artificial Intelligence of SPECT for Diagnosis of Coronary Artery Disease.

Otaki Y, Singh A, Kavanagh P, Miller RJH, ... Berman DS, Slomka PJ
Objectives
This study sought to develop and evaluate a novel, general purpose, explainable deep learning model (coronary artery disease-deep learning [CAD-DL]) for the detection of obstructive CAD following single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).
Background
Explainable artificial intelligence (AI) can be integrated within standard clinical software to facilitate the acceptance of the diagnostic findings during clinical interpretation.
Methods
A total of 3,578 patients with suspected CAD undergoing SPECT MPI and invasive coronary angiography within a 6 month interval from 9 centers were studied. CAD-DL computes the probability of obstructive CAD from stress myocardial perfusion, wall motion, and wall thickening maps, as well as left ventricular volumes, age, and sex. Myocardial regions contributing to the CAD-DL prediction are highlighted to explain the findings to the physician. A clinical prototype was integrated using a standard clinical workstation. Diagnostic performance by CAD-DL was compared to automated quantitative total perfusion deficit (TPD) and reader diagnosis.
Results
In total, 2,247 patients (63%) had obstructive CAD. In 10-fold repeated testing, the area under the receiver-operating characteristic curve (AUC) (95% CI) was higher according to CAD-DL (AUC: 0.83; 95% CI: 0.82-0.85]) than stress TPD (AUC: 0.78; 95% CI: 0.77-0.80]) or reader diagnosis (AUC: 0.71; 95% CI: 0.69-0.72]; P < 0.0001 for both). In external testing, the AUC in 555 patients was higher according to CAD-DL (AUC: 0.80; 95% CI: 0.76-0.84]) than stress TPD (AUC: 0.73; 95% CI: 0.69-0.77) or reader diagnosis (AUC: 0.65; 95% CI: 0.61-0.69; P < 0.001). The present model can be integrated within standard clinical software and generates results rapidly (<12 s on a standard clinical workstation) and therefore could readily be incorporated into a typical clinical workflow.
Conclusions
The deep-learning model significantly surpasses the diagnostic accuracy of standard quantitative analysis and clinical visual reading for MPI. Explainable artificial intelligence can be integrated within standard clinical software to facilitate acceptance of artificial intelligence diagnosis of CAD following MPI.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print
Otaki Y, Singh A, Kavanagh P, Miller RJH, ... Berman DS, Slomka PJ
JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print | PMID: 34274267
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Abstract

Regional Replacement and Diffuse Interstitial Fibrosis in Aortic Regurgitation: Prognostic Implications From Cardiac Magnetic Resonance.

Senapati A, Malahfji M, Debs D, Yang EY, ... Graviss EA, Shah DJ
Objectives
This study used cardiac magnetic resonance (CMR) to assess left ventricular (LV) remodeling in chronic aortic regurgitation (AR) to identify both forms of myocardial fibrosis and examine its association with clinical outcomes.
Background
Chronic AR leads to LV remodeling, which is associated with 2 forms of myocardial fibrosis: regional replacement fibrosis that is directly imaged by late gadolinium enhancement (LGE) CMR; and diffuse interstitial fibrosis, which can be inferred by T1 mapping techniques.
Methods
Patients with chronic AR who were undergoing contrast CMR with T1 mapping for valve assessment from 2011 to 2018 were enrolled. Patients with a confounding etiology of myocardial fibrosis were excluded. In addition to quantification of AR severity and LV volumetrics, LGE and T1 mapping pre- and post-contrast were performed to measure extracellular volume (ECV) and indexed ECV (iECV). Patients were followed up longitudinally to assess for the composite event of death and the need for aortic valve replacement.
Results
A total of 177 patients with isolated chronic AR were included (66% males, median age 58 years [47.0 years-68.0 years]) with a median follow up of 2.5 years (1.07 years-3.56 years). The iECV significantly increased with AR severity (P < 0.001), whereas ECV and replacement fibrosis did not (P = NS). On multivariate analysis, iECV remained associated with the composite event (P = 0.01). On Kaplan-Meier analysis stratified by AR regurgitant fraction (RF) and iECV, patients with AR RF severity ≥30% and iECV ≥24 mL/m2 demonstrated the highest event rate.
Conclusions
Among CMR biomarkers of fibrosis, iECV was more closely associated than replacement fibrosis or ECV with survival free of aortic valve replacement.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print
Senapati A, Malahfji M, Debs D, Yang EY, ... Graviss EA, Shah DJ
JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print | PMID: 34274265
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Abstract

Principal Morphomic and Functional Components of Secondary Mitral Regurgitation.

Bartko PE, Heitzinger G, Spinka G, Pavo N, ... Hülsmann M, Goliasch G
Objectives
The aim of this work was to identify the key morphological and functional features in secondary mitral regurgitation (sMR) and their prognostic impact on outcome.
Background
Secondary sMR in patients with heart failure and reduced ejection fraction typically results from distortion of the underlying cardiac architecture. The morphological components which may account for the clinical impact of sMR have not been systematically assessed or correlated with clinical outcomes.
Methods
Morphomic and functional network profiling were performed on a cohort of patients with stable heart failure optimized on guideline-based medical therapy. Principal component (PC) analysis and subsequent cluster analysis were used to condense the morphomic and functional data first into PCs with varimax rotation (PCVmax) and second into homogeneous clusters. Clusters and PCs were tested for their correlations with clinical outcomes.
Results
Morphomic and functional data from 383 patients were profiled and subsequently condensed into PCs. PCVmax 1 describes high loadings of left atrial morphological information, and PCVmax 2 describes high loadings of left ventricular (LV) topology. Based on these components, 4 homogeneous clusters were derived. sMR was most prominent in clusters 3 and 4, with the morphological difference being left ventricular size (median end-diastolic volume 188 mL [interquartile range: 160 mL-224 mL] vs 315 mL [264 mL-408 mL]; P < 0.001). Clusters were associated with mortality (P < 0.001), but sMR remained independently associated with mortality after adjusting for the clusters (adjusted HR: 1.42; 95% CI: 1.14-1.77; P < 0.01). The detrimental association of sMR with mortality was mainly driven by cluster 3 (HR: 2.18; 95% CI: 1.32-3.60; P = 0.002), the \"small LV cavity\" phenotype.
Conclusions
These results challenge the current perceptions that sMR in heart failure with reduced ejection fraction results exclusively from global or local LV remodeling and are suggestive of a potential role of the left atrial component. The association of sMR with mortality cannot be purely attributed to cardiac morphology alone, supporting other complementary key aspects of mitral valve closure consistent with the force balance theory. Unsupervised clustering supports the association of sMR with mortality predominantly driven by the small LV cavity phenotype, as previously suggested by a conceptional framework and termed disproportionate sMR.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print
Bartko PE, Heitzinger G, Spinka G, Pavo N, ... Hülsmann M, Goliasch G
JACC Cardiovasc Imaging: 06 Jul 2021; epub ahead of print | PMID: 34274262
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Abstract

Primary Prevention Trial Designs Using Coronary Imaging: A National Heart, Lung, and Blood Institute Workshop.

Greenland P, Michos ED, Redmond N, Fine LJ, ... Sterling MR, Thanassoulis G
Coronary artery calcium (CAC) is considered a useful test for enhancing risk assessment in the primary prevention setting. Clinical trials are under consideration. The National Heart, Lung, and Blood Institute convened a multidisciplinary working group on August 26 to 27, 2019, in Bethesda, Maryland, to review available evidence and consider the appropriateness of conducting further research on coronary artery calcium (CAC) testing, or other coronary imaging studies, as a way of informing decisions for primary preventive treatments for cardiovascular disease. The working group concluded that additional evidence to support current guideline recommendations for use of CAC in middle-age adults is very likely to come from currently ongoing trials in that age group, and a new trial is not likely to be timely or cost effective. The current trials will not, however, address the role of CAC testing in younger adults or older adults, who are also not addressed in existing guidelines, nor will existing trials address the potential benefit of an opportunistic screening strategy made feasible by the application of artificial intelligence. Innovative trial designs for testing the value of CAC across the lifespan were strongly considered and represent important opportunities for additional research, particularly those that leverage existing trials or other real-world data streams including clinical computed tomography scans. Sex and racial/ethnic disparities in cardiovascular disease morbidity and mortality, and inclusion of diverse participants in future CAC trials, particularly those based in the United States, would enhance the potential impact of these studies.

Copyright © 2021 American College of Cardiology Foundation. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1454-1465
Greenland P, Michos ED, Redmond N, Fine LJ, ... Sterling MR, Thanassoulis G
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1454-1465 | PMID: 32950442
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Abstract

Regional Distribution of Fluorine-18-Flubrobenguane and Carbon-11-Hydroxyephedrine for Cardiac PET Imaging of Sympathetic Innervation.

Zelt JGE, Britt D, Mair BA, Rotstein BH, ... deKemp RA, Beanlands RS
Objectives
The aim of this study was to investigate the regional distribution of novel 18F-labeled positron emission tomographic (PET) tracer flubrobenguane (FBBG) (whose longer half-life could enable more widespread use) to assess myocardial presynaptic sympathetic nerve function in humans in comparison to [11C]meta-hydroxyephedrine (HED).
Background
The sympathetic nervous system (SNS) is vitally linked to cardiovascular regulation and disease. SNS imaging has shown prognostic value. HED is the most commonly used PET tracer for evaluation of sympathetic function in humans, but widespread clinical use is limited because of the short half-life of 11C.
Methods
A total of 25 participants (n = 6 healthy; n = 14 ischemic cardiomyopathy, left ventricular [LV] ejection fraction [EF] = 34 ± 5%; and n = 5 nonischemic cardiomyopathy, EF = 33 ± 3%) underwent 2 separate PET imaging visits 8.7 ± 7.6 days apart. On 1 visit, participants underwent dynamic HED PET imaging. On a different visit, participants underwent dynamic FBBG PET imaging. The order of testing was random. HED and FBBG global innervation (retention index [RI] and distribution volume [DV]) and regional denervation (% nonuniformity) were quantified to assess regional presynaptic sympathetic innervations.
Results
FBBG RI (r2 = 0.72; ICC = 0.79; p < 0.0001), DV (r2 = 0.62; ICC = 0.78; p < 0.0001), and regional denervation (r2 = 0.97; ICC = 0.98; p < 0.0001) correlated highly with HED. Average LV RI values were highly similar between HED (7.3 ± 2.4%/min) and FBBG (7.0 ± 1.7%/min; p = 0.33). Post-hoc analysis did not reveal any between-tracer differences on a regional level (17-segment), suggesting equivalent regional distributions in both patients with and without ischemic cardiomyopathy.
Conclusions
FBBG and HED yield equivalent global and regional distributions in both patients with and without ischemic cardiomyopathy. 18F-labeled PET tracers, such as FBBG, are critical for widespread distribution necessary for multicenter clinical trials and to maximize patient impact.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1425-1436
Zelt JGE, Britt D, Mair BA, Rotstein BH, ... deKemp RA, Beanlands RS
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1425-1436 | PMID: 33221229
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Abstract

NIRS-IVUS for Differentiating Coronary Plaque Rupture, Erosion, and Calcified Nodule in Acute Myocardial Infarction.

Terada K, Kubo T, Kameyama T, Matsuo Y, ... Madder RD, Akasaka T
Objectives
This study sought to investigate the ability of combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) to differentiate plaque rupture (PR), plaque erosion (PE), or calcified nodule (CN) in acute myocardial infarction (AMI).
Background
Most acute coronary syndromes occur from coronary thrombosis based on PR, PE, or CN. In vivo differentiation among PR, PE, and CN is a major challenge for intravascular imaging.
Methods
The study enrolled 244 patients with AMI who had a de novo culprit lesion in a native coronary artery. The culprit lesions were assessed by both NIRS-IVUS and optical coherence tomography (OCT). Maximum lipid core burden index in 4 mm (maxLCBI4mm) was measured by NIRS. Plaque cavity and convex calcium was detected by IVUS. The OCT diagnosis of PR (n = 175), PE (n = 44), and CN (n = 25) was used as a reference standard.
Results
In the development cohort, IVUS-detected plaque cavity showed a high specificity (100%) and intermediate sensitivity (62%) for identifying OCT-PR. IVUS-detected convex calcium showed a high sensitivity (93%) and specificity (100%) for identifying OCT-CN. NIRS-measured maxLCBI4mm was largest in OCT-PR (705 [interquartile range (IQR): 545 to 854]), followed by OCT-CN (355 [IQR: 303 to 478]) and OCT-PE (300 [IQR: 126 to 357]) (p < 0.001). The optimal cutoff value of maxLCBI4mm was 426 for differentiating between OCT-PR and -PE; 328 for differentiating between OCT-PE and -CN; and 579 for differentiating between OCT-PR and -CN. In the validation cohort, the NIRS-IVUS classification algorithm using plaque cavity, convex calcium, and maxLCBI4mm showed a sensitivity and specificity of 97% and 96% for identifying OCT-PR, 93% and 99% for OCT-PE, and 100% and 99% for OCT-CN, respectively.
Conclusions
By evaluating plaque cavity, convex calcium, and maxLCBI4mm, NIRS-IVUS can accurately differentiate PR, PE, and CN.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1440-1450
Terada K, Kubo T, Kameyama T, Matsuo Y, ... Madder RD, Akasaka T
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1440-1450 | PMID: 33221211
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Abstract

Targeted Coronary Artery Calcium Screening in High-Risk Younger Individuals Using Consumer Genetic Screening Results.

Severance LM, Carter H, Contijoch FJ, McVeigh ER
Objectives
The goal of this study was to assess the utility of a genetic risk score (GRS) in targeted coronary artery calcium (CAC) screening among young individuals.
Background
Early CAC screening and preventive therapy may reduce long-term risk of a coronary heart disease (CHD) event. However, identifying younger individuals at increased risk remains a challenge. GRS for CHD are age independent and can stratify individuals on various risk trajectories.
Methods
Using 142 variants associated with CHD events, we calculated a GRS in 1,927 individuals in the CARDIA (Coronary Artery Risk Development in Young Adults) cohort (aged 32 to 47 years) and 6,600 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort (aged 44 to 87 years). We assessed GRS utility to predict CAC presence in the CARDIA cohort and stratify individuals of varying risk for CAC presence over the lifetime in both cohorts.
Results
The GRS predicted CAC presence in CARDIA males. It was not predictive in CARDIA females, which had a CAC prevalence of 6.4%. In combined analysis of the CARDIA and MESA cohorts, the GRS was predictive of CAC in both males and females and was used to derive an equation for the age at which CAC probability crossed a predetermined threshold. When assessed in combination with traditional risk factors, the GRS further stratified individuals. For individuals with an equal number of traditional risk factors, probability of CAC reached 25% approximately 10 years earlier for those in the highest GRS quintile compared to the lowest.
Conclusions
The GRS may be used to target high-risk younger individuals for early CAC screening.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1398-1406
Severance LM, Carter H, Contijoch FJ, McVeigh ER
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1398-1406 | PMID: 33454274
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Abstract

Progression of Myocardial Fibrosis in Nonischemic DCM and Association With Mortality and Heart Failure Outcomes.

Mandawat A, Chattranukulchai P, Mandawat A, Blood AJ, ... Shah DJ, Klem I
Objectives
The purpose of this study was to assess whether the presence and extent of fibrosis changes over time in patients with nonischemic, dilated cardiomyopathy (DCM) receiving optimal medical therapy and the implications of any such changes on left ventricular ejection fraction (LVEF) and clinical outcomes.
Background
Myocardial fibrosis on cardiovascular magnetic resonance (CMR) imaging has emerged as important risk marker in patients with DCM.
Methods
In total, 85 patients (age 56 ± 15 years, 45% women) with DCM underwent serial CMR (median interval 1.5 years) for assessment of LVEF and fibrosis. The primary outcome was all-cause mortality; the secondary outcome was a composite of heart failure hospitalization, aborted sudden cardiac death, left ventricular (LV) assist device implantation, or heart transplant.
Results
On CMR-1, fibrosis (median 0.0 [interquartile range: 0% to 2.6%]) of LV mass was noted in 34 (40%) patients. On CMR-2, regression of fibrosis was not seen in any patient. Fibrosis findings were stable in 70 (82%) patients. Fibrosis progression (increase >1.8% of LV mass or new fibrosis) was seen in 15 patients (18%); 46% of these patients had no fibrosis on CMR-1. Although fibrosis progression was on aggregate associated with adverse LV remodeling and decreasing LVEF (40 ± 7% to 34 ± 10%; p < 0.01), in 60% of these cases the change in LVEF was minimal (<5%). Fibrosis progression was associated with increased hazards for all-cause mortality (hazard ratio: 3.4 [95% confidence interval: 1.5 to 7.9]; p < 0.01) and heart failure-related complications (hazard ratio: 3.5 [95% confidence interval: 1.5 to 8.1]; p < 0.01) after adjustment for clinical covariates including LVEF.
Conclusions
Once myocardial replacement fibrosis in DCM is present on CMR, it does not regress in size or resolve over time. Progressive fibrosis is often associated with minimal change in LVEF and identifies a high-risk cohort.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1338-1350
Mandawat A, Chattranukulchai P, Mandawat A, Blood AJ, ... Shah DJ, Klem I
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1338-1350 | PMID: 33454264
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Abstract

Topological Data Analysis of Coronary Plaques Demonstrates the Natural History of Coronary Atherosclerosis.

Hwang D, Kim HJ, Lee SP, Lim S, ... Min JK, Chang HJ
Objectives
This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).
Background
Coronary CTA can noninvasively assess coronary plaques quantitatively.
Methods
Patients who underwent 2 coronary CTAs at a minimum of 24 months\' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.
Results
Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm3 [interquartile range (IQR): 0.0 to 39.6 mm3]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm3 [IQR: 0.0 to 127.4 mm3]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm3 [IQR: 96.7 to 306.4 mm3]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features.
Conclusions
The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1410-1421
Hwang D, Kim HJ, Lee SP, Lim S, ... Min JK, Chang HJ
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1410-1421 | PMID: 33454260
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Abstract

CT Angiography Followed by Invasive Angiography in Patients With Moderate or Severe Ischemia-Insights From the ISCHEMIA Trial.

Mancini GBJ, Leipsic J, Budoff MJ, Hague CJ, ... Hochman JS, Maron DJ
Objectives
This study aimed to examine the concordance of coronary computed tomographic angiography (CCTA) assessment of coronary anatomy and invasive coronary angiography (ICA) as the reference standard in patients enrolled in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches).
Background
Performance of CCTA compared with ICA has not been assessed in patients with very high burdens of stress-induced ischemia and a high likelihood of anatomically significant coronary artery disease (CAD). A blinded CCTA was performed after enrollment to exclude patients with left main (LM) disease or no obstructive CAD before randomization to an initial conservative or invasive strategy, the latter guided by ICA and optimal revascularization.
Methods
Rates of concordance were calculated on a per-patient basis in patients randomized to the invasive strategy. Anatomic significance was defined as ≥50% diameter stenosis (DS) for both modalities. Sensitivity analyses using a threshold of ≥70% DS for CCTA or considering only CCTA images of good-to-excellent quality were performed.
Results
In 1,728 patients identified by CCTA as having no LM disease ≥50% and at least single-vessel CAD, ICA confirmed 97.1% without LM disease ≥50%, 92.2% with at least single-vessel CAD and no LM disease ≥50%, and only 4.9% without anatomically significant CAD. Results using a ≥70% DS threshold or only CCTA of good-to-excellent quality showed similar overall performance.
Conclusions
CCTA before randomization in ISCHEMIA demonstrated high concordance with subsequent ICA for identification of patients with angiographically significant disease without LM disease.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1384-1393
Mancini GBJ, Leipsic J, Budoff MJ, Hague CJ, ... Hochman JS, Maron DJ
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1384-1393 | PMID: 33454249
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Abstract

Multicenter Consistency Assessment of Valvular Flow Quantification With Automated Valve Tracking in 4D Flow CMR.

Juffermans JF, Minderhoud SCS, Wittgren J, Kilburg A, ... Töger J, Westenberg JJM
Objectives
This study determined: 1) the interobserver agreement; 2) valvular flow variation; and 3) which variables independently predicted the variation of valvular flow quantification from 4-dimensional (4D) flow cardiac magnetic resonance (CMR) with automated retrospective valve tracking at multiple sites.
Background
Automated retrospective valve tracking in 4D flow CMR allows consistent assessment of valvular flow through all intracardiac valves. However, due to the variance of CMR scanners and protocols, it remains uncertain if the published consistency holds for other clinical centers.
Methods
Seven sites each retrospectively or prospectively selected 20 subjects who underwent whole heart 4D flow CMR (64 patients and 76 healthy volunteers; aged 32 years [range 24 to 48 years], 47% men, from 2014 to 2020), which was acquired with locally used CMR scanners (scanners from 3 vendors; 2 1.5-T and 5 3-T scanners) and protocols. Automated retrospective valve tracking was locally performed at each site to quantify the valvular flow and repeated by 1 central site. Interobserver agreement was evaluated with intraclass correlation coefficients (ICCs). Net forward volume (NFV) consistency among the valves was evaluated by calculating the intervalvular variation. Multiple regression analysis was performed to assess the predicting effect of local CMR scanners and protocols on the intervalvular inconsistency.
Results
The interobserver analysis demonstrated strong-to-excellent agreement for NFV (ICC: 0.85 to 0.96) and moderate-to-excellent agreement for regurgitation fraction (ICC: 0.53 to 0.97) for all sites and valves. In addition, all observers established a low intervalvular variation (≤10.5%) in their analysis. The availability of 2 cine images per valve for valve tracking compared with 1 cine image predicted a decreasing variation in NFV among the 4 valves (beta = -1.3; p = 0.01).
Conclusions
Independently of locally used CMR scanners and protocols, valvular flow quantification can be performed consistently with automated retrospective valve tracking in 4D flow CMR.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1354-1366
Juffermans JF, Minderhoud SCS, Wittgren J, Kilburg A, ... Töger J, Westenberg JJM
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1354-1366 | PMID: 33582060
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Abstract

3-Dimensional Versus 2-Dimensional STE for Right Ventricular Myocardial Fibrosis in Patients With End-Stage Heart Failure.

Tian F, Zhang L, Xie Y, Zhang Y, ... Li Y, Xie M
Background
Longitudinal strain of the right ventricular (RV) free wall (RVFWLS) assessed by 2-dimensional (2D) speckle-tracking echocardiography (STE) has been recently demonstrated to correlate with the extent of RV myocardial fibrosis (MF). However, the value of 3-dimensional (3D) STE-derived strain parameters in predicting RV MF has not been investigated in patients with end-stage heart failure (HF).
Objectives
This study aimed to determine which RV strain parameter assessed by 2D-STE and 3D-STE was the most reliable parameter for predicting RV MF in patients with end-stage HF against histological confirmation of MF.
Methods
A total of 105 consecutive patients with end-stage HF undergoing heart transplantation were enrolled in our study. The conventional RV function parameters, 2D-RVFWLS, and 3D-RVFWLS were obtained in these patients. The degree of MF was quantified by Masson trichrome staining in RV myocardial samples. The study population was divided into 3 groups according to the degree of MF on histology.
Results
Patients with severe MF had lower 3D-RVFWLS, 2D-RVFWLS, and conventional parameters of RV function compared with those with mild and moderate MF. RV MF strongly correlated with 3D-RVFWLS (r = -0.72; p < 0.001), modestly with 2D-RVFWLS (r = -0.53; p < 0.001), and weakly with conventional RV function parameters (r = -0.21 to -0.49; p < 0.01). 3D-RVFWLS correlated best with the degree of MF (r = -0.72 vs. -0.21 to -0.53; p < 0.05) compared with 2D-RVFWLS and conventional RV function parameters. 3D-RVFWLS had the highest accuracy for detecting severe MF (area under the receiver-operating characteristic curve: 0.90 vs. 0.24-0.80; p < 0.05) compared with 2D-RVFWLS and conventional RV parameters. The model with 3D-RVFWLS (R2 = 0.63; p < 0.001) was better in predicting the degree of RV MF than that with 2D-RVFWLS (R2 = 0.54; p < 0.001).
Conclusions
3D-RVFWLS may be the most robust echocardiographic measure for predicting the extent of RV MF in patients with end-stage HF.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1309-1320
Tian F, Zhang L, Xie Y, Zhang Y, ... Li Y, Xie M
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1309-1320 | PMID: 33744147
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Abstract

Left Ventricular Longitudinal Strain in Characterization and Outcome Assessment of Mixed Aortic Valve Disease Phenotypes.

Saijo Y, Isaza N, Conic JZ, Desai MY, ... Griffin BP, Popović ZB
Objectives
The aims of this study were to characterize the interplay between mixed aortic valve disease (MAVD) phenotypes (defined by concomitant severities of aortic stenosis and aortic regurgitation) and left ventricular global longitudinal strain (LV-GLS), and to assess the prognostic utility of LV-GLS in MAVD.
Background
Little is known about the way LV-GLS separates MAVD phenotypes and if it is associated with their outcomes.
Methods
This observational cohort study evaluated 783 consecutive adult patients with left ventricular ejection fraction ≥50% and MAVD, which was defined as coexisting with at least moderate aortic stenosis and at least moderate aortic regurgitation. We measured the conventional echocardiographic variables and average LV-GLS from apical long, 2- and 4-chamber views. The primary endpoint was all-cause mortality.
Results
Mean age of patients was 69 ± 15 years, and 58% were male. Mean LV-GLS was -14.7 ± 2.9%. In total, 458 patients (59%) underwent aortic valve replacement at a median period of 50 days (25th to 75th percentile range: 6 to 560 days). During a median follow-up period of 5.6 years (25th to 75th percentile range: 1.8 to 9.4 years), 391 patients (50%) died. When stratified patients into tertiles according to LV-GLS values, patients with worse LV-GLS had worse outcomes (p < 0.001). LV-GLS was independently associated with mortality (hazard ratio: 1.09; 95% confidential intervals: 1.04 to 1.14; p < 0.001), with the relationship between LV-GLS and mortality being linear.
Conclusions
LV-GLS is associated with all-cause mortality. LV-GLS may be useful for risk stratification in patients with MAVD.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1324-1334
Saijo Y, Isaza N, Conic JZ, Desai MY, ... Griffin BP, Popović ZB
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1324-1334 | PMID: 33744141
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Abstract

Proposal for a Standard Echocardiographic Tricuspid Valve Nomenclature.

Hahn RT, Weckbach LT, Noack T, Hamid N, ... Hausleiter J, Nabauer M
Objectives
The purpose of this study was to introduce a novel clinically relevant nomenclature system for the TV and determine the relative incidence of each morphological type.
Background
With the rapid development of transcatheter tricuspid valve (TV) repair techniques, there is a growing recognition of the variability in leaflet morphology and a need for a unified nomenclature, which could aid in procedural planning and execution.
Methods
Patients from 4 medical centers (2 in Europe, 2 in the United States) referred for transesophageal echocardiography (TEE) to assess native TV function, were retrospectively analyzed for leaflet morphology with the use of a novel classification scheme. Four morphological types were identified: type I, 3 leaflets; type II, 2 leaflets; type IIIA, 4 leaflets with 2 anterior; type IIIB, 4 leaflets with 2 posterior; type IIIC, 4 leaflets with 2 septal; and type IV, >4 leaflets.
Results
A total of 579 patients were analyzed: mean age 78.1 ± 8.0 years, 50.4% female, 70.9% in atrial fibrillation, and 32.2% with previous left heart surgery or transcatheter intervention. Tricuspid regurgitation was moderate or less in 9.4%, severe in 40.5%, massive in 32.3%, and torrential in 17.7%. The etiology of tricuspid regurgitation was primary in 9.4%, mixed in 10.8%, and secondary in all of the other patients (18.6% atriogenic/isolated). The incidence of type I morphology was 312 of 579 (53.9%), type II was 26 of 579 (4.5%), type IIIA was 15 of 579 (2.6%), type IIIB was 186 of 579 (32.1%), type IIIC was 22 of 579 (3.8%), and type IV was 14 of 579 (2.4%).
Conclusions
A novel TV leaflet nomenclature classification scheme can be used to identify 4 types of TV morphologies with the use of TEE imaging. From this multinational retrospective study, the TV has 3 well defined leaflets in only ∼54% of patients and 4 functional leaflets in ∼39% of patients, with type IIIB (2 posterior leaflets) being the most common of the latter. The utility of this classification scheme deserves further study.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1299-1305
Hahn RT, Weckbach LT, Noack T, Hamid N, ... Hausleiter J, Nabauer M
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1299-1305 | PMID: 33744134
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Abstract

Functional and Economic Impact of INOCA and Influence of Coronary Microvascular Dysfunction.

Schumann CL, Mathew RC, Dean JL, Yang Y, ... Kramer CM, Bourque JM
Objectives
This study sought to better characterize the quality of life and economic impact in patients with symptoms of ischemia and no obstructive coronary disease (INOCA) and to identify the influence of coronary microvascular dysfunction (CMD).
Background
Patients with INOCA have a high symptom burden and an increased incidence of major adverse cardiac events. CMD is a frequent cause of INOCA. The morbidity associated with INOCA and CMD has not been well-characterized.
Methods
Sixty-six patients with INOCA underwent stress cardiac magnetic resonance with calculation of myocardial perfusion reserve (MPR); MPR 2.0 to 2.4 was considered borderline-reduced (possible CMD) and MPR <2.0 was defined as reduced (definite CMD). Subjects completed quality of life questionnaires to assess the morbidity and economic impact of INOCA. Questionnaire results were compared between INOCA patients with and without CMD. In addition, logistic regression was used to determine the predictors of CMD within the INOCA population.
Results
The prevalence of definite CMD was 24%. Definite or borderline CMD was present in 59% (MPR ≤2.4). Patients with INOCA reported greater physical limitation, angina frequency, and reduced quality of life compared to referent stable coronary artery disease and acute myocardial infarction populations. In addition, Patients with INOCA reported frequent time missed from work and work limitations, suggesting a substantial economic impact. No difference was observed in reported symptoms between INOCA patients with and without CMD. Glomerular filtration rate and body-mass index were significant predictors of CMD in multivariable regression analysis.
Conclusions
INOCA is associated with high morbidity similar to other high-risk cardiac populations, and work limitations reported by Patients with INOCA suggest a substantial economic impact. CMD is a common cause of INOCA but is not associated with increased morbidity. These results suggest that there is significant symptom burden in the INOCA population regardless of etiology.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2021; 14:1369-1379
Schumann CL, Mathew RC, Dean JL, Yang Y, ... Kramer CM, Bourque JM
JACC Cardiovasc Imaging: 29 Jun 2021; 14:1369-1379 | PMID: 33865784
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Impact:
Abstract

Maximal Wall Thickness Measurement in Hypertrophic Cardiomyopathy: Biomarker Variability and its Impact on Clinical Care.

Captur G, Manisty CH, Raman B, Marchi A, ... Nihoyannopoulos P, Moon JC
Objectives
The aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM).
Background
Left ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD).
Methods
A 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death.
Results
MWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years\' experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range -59% to 117% [SD ±20%] and -61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk).
Conclusions
Using the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 15 Jun 2021; epub ahead of print
Captur G, Manisty CH, Raman B, Marchi A, ... Nihoyannopoulos P, Moon JC
JACC Cardiovasc Imaging: 15 Jun 2021; epub ahead of print | PMID: 34147459
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Abstract

Interplay of Risk Factors and Coronary Artery Calcium for CHD Risk in Young Patients.

Mortensen MB, Dzaye O, Bødtker H, Steffensen FH, ... Blaha MJ, Nørgaard BL
Objectives
The aim of this study was to examine prevalence, predictors, and impact of coronary artery calcium (CAC) across different risk factor burdens on the prevalence of obstructive coronary artery disease (CAD) and future coronary heart disease (CHD) risk in young patients.
Background
The interplay of risk factors and CAC for predicting CHD in young patients aged ≤45 years is not clear.
Methods
The study included 3,691 symptomatic patients (18-45 years of age) from the WDHR (Western Denmark Heart Registry) undergoing coronary computed tomographic angiography. CHD events were myocardial infarction and late revascularization.
Results
During a median of 4.1 years of follow-up, 57 first-time CHD events occurred. In total, 3,180 patients (86.1%) had CAC = 0 and 511 patients (13.9%) had CAC > 0. Presence of CAC increased with number of risk factors (odds ratio: 4.5 [95% CI: 2.7-7.3] in patients with >3 vs 0 risk factors). The prevalence of obstructive CAD at baseline and the rate of future CHD events increased in a stepwise manner with both higher CAC and number of risk factors. The CHD event rate was lowest at 0.5 (95% CI: 0.1-3.6) per 1,000 person-years in patients with 0 risk factors and CAC = 0. Among patients with >3 risk factors, the event rate was 3.1 (95% CI: 1.0-9.7) in patients with CAC = 0 compared with 36.3 (95% CI: 17.3-76.1) in patients with CAC >10.
Conclusions
In young patients, there is a strong interplay between CAC and risk factors for predicting the presence of obstructive CAD and for future CHD risk. In the presence of risk factors, even a low CAC score is a high-risk marker. These results demonstrate the importance of assessing risk factors and CAC simultaneously when assessing risk in young patients.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 15 Jun 2021; epub ahead of print
Mortensen MB, Dzaye O, Bødtker H, Steffensen FH, ... Blaha MJ, Nørgaard BL
JACC Cardiovasc Imaging: 15 Jun 2021; epub ahead of print | PMID: 34147446
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Impact:
Abstract

Prognostic Value of Vasodilator Stress Perfusion Cardiovascular Magnetic Resonance in Patients With Prior Myocardial Infarction.

Pezel T, Garot P, Kinnel M, Unterseeh T, ... Sanguineti F, Garot J
Objectives
This study sought to assess the incremental prognostic value of vasodilator stress cardiovascular magnetic resonance (CMR) in patients with prior myocardial infarction (MI).
Background
Recurrent MI is a major cause of mortality and morbidity among MI survivors.
Methods
Between 2008 and 2019, consecutive patients with prior MI referred for stress CMR were followed up for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular mortality or recurrent nonfatal MI. Uni- and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia and the extent of myocardial scar.
Results
Among 1,594 patients with prior MI and myocardial scar on CMR, 1,401 (92%) (68.2 ± 11.0 years; 61.4% men) completed the follow-up (median: 6.2 years), and 205 had MACE (14.6%). Patients without inducible ischemia experienced a lower annual rate of MACE (3.1%) than those with 1-2 (4.9%), 3-5 (21.5%), or ≥6 segments of ischemia (45.7%) (all p < 0.01). Using Kaplan-Meier analysis, the presence of inducible ischemia and the extent of scar were associated with MACE (hazard ratio [HR]:3.52; 95% confidence interval [CI]: 2.67 to 4.65 and HR: 1.66; 95% CI: 1.53 to 2.18, respectively; both p < 0.001). In multivariable stepwise Cox regression, the presence of ischemia and the extent of scar were independent predictors of MACE (HR: 2.84; 95% CI: 2.14 to 3.78 and HR: 1.57; 95% CI: 1.44 to 1.72, respectively; both p < 0.001). These findings were significant in both symptomatic and asymptomatic patients. The addition of CMR parameters to the model including traditional risk factors resulted in a better discrimination for MACE (C-statistic: 0.76 vs. 0.62).
Conclusions
In patients with prior MI, vasodilator stress CMR has independent and incremental prognostic value over traditional risk factors.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print
Pezel T, Garot P, Kinnel M, Unterseeh T, ... Sanguineti F, Garot J
JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print | PMID: 34147458
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Abstract

The Mitral Annular Disjunction of Mitral Valve Prolapse: Presentation and Outcome.

Essayagh B, Sabbag A, Antoine C, Benfari G, ... Michelena HI, Enriquez-Sarano M
Objectives
The aim of this study was to assess in patients with mitral valve prolapse (MVP) mitral annular disjunction (MAD) prevalence, phenotypic characteristics, and long-term outcomes (clinical arrhythmic events and excess mortality).
Background
Clinical knowledge regarding MAD of MVP remains limited and controversial, and its potential link with untoward outcomes is unsubstantiated.
Methods
A cohort of 595 (278 women, mean age 61 ± 16 years) consecutive patients with isolated MVP, with comprehensive clinical, rhythmic, Doppler echocardiographic, and consistent MAD assessment, were examined. MAD prevalence, associated MVP phenotypes, and outcomes (survival, clinical arrhythmic events) starting at diagnostic echocardiography were analyzed. To balance important baseline differences, propensity scoring matching was conducted among patients with and those without MAD.
Results
The presence of MAD was common (n = 186 [31%]) in patients with MVP, generally in younger patients, and was not random but was independently associated with severe myxomatous disease involving bileaflet MVP and marked leaflet redundancy (both P ≤ 0.0002). The presence of MAD was also independently associated with a larger left ventricle (P = 0.005). Age-matched cohort survival after MVP diagnosis was not worse with MAD (10-year survival 93% ± 2% for patients without MAD and 97% ± 1% for those with MAD; P = 0.40), even adjusted comprehensively for MVP characteristics (P = 0.80) and accounting for time-dependent mitral surgery (P = 0.60). During follow-up, 170 patients had clinical arrhythmic events (ventricular tachycardia, n = 159; arrhythmia ablation, n = 14; cardioverter-defibrillator implantation, n = 14; sudden cardiac death, n = 3). MAD was independently associated with higher risk for arrhythmic events (adjusted HR: 2.60; 95% CI: 1.87-3.62; P < 0.0001). The link between MAD and arrhythmic events persisted with time-dependent mitral surgery (adjusted HR: 2.54; 95% CI: 1.84-3.50; P < 0.0001), was strong under medical management (adjusted HR: 3.21; 95% CI: 2.03-5.06; P < 0.0001) but was weaker after mitral surgery (adjusted HR: 2.07; 95% CI: 1.24-3.43; P = 0.005).
Conclusions
This large cohort with MVP comprehensively characterized shows that MAD is frequent at MVP diagnosis and is strongly linked to advanced myxomatous degeneration. The presence of MAD was independently associated with long-term excess incidence of clinical arrhythmic events. However, within the first 10 years post-diagnosis, MAD was not linked to excess mortality, and although reassurance should be provided from the survival point of view, careful monitoring for arrhythmias is in order for MAD.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print
Essayagh B, Sabbag A, Antoine C, Benfari G, ... Michelena HI, Enriquez-Sarano M
JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print | PMID: 34147457
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Impact:
Abstract

AI-Assisted Echocardiographic Prescreening of Heart Failure With Preserved Ejection Fraction on the Basis of Intrabeat Dynamics.

Chiou YA, Hung CL, Lin SF
Objectives
The aim of this study was to establish a rapid prescreening tool for heart failure with preserved ejection fraction (HFpEF) by using artificial intelligence (AI) techniques to detect abnormal echocardiographic patterns in structure and function on the basis of intrabeat dynamic changes in the left ventricle and the left atrium.
Background
Although diagnostic criteria for HFpEF have been established, rapid and accurate assessment of HFpEF using echocardiography remains challenging and highly desirable.
Methods
In total, 1,041 patients with HFpEF and 1,263 asymptomatic individuals were included in the study. The participants\' 4-chamber view images were extracted from the echocardiographic files and randomly separated into training, validation, and internal testing data sets. An external testing data set comprising 150 patients with symptomatic chronic obstructive pulmonary disease and 315 patients with HFpEF from another hospital was used for further model validation. The intrabeat dynamics of the geometric measures were extracted frame by frame from the image sequence to train the AI models.
Results
The accuracy, sensitivity, and specificity of the best AI model for detecting HFpEF were 0.91, 0.96, and 0.85, respectively. The model was further validated using an external testing data set, and the accuracy, sensitivity, and specificity became 0.85, 0.79, and 0.89, respectively. The area under the receiver-operating characteristic curve was used to evaluate model classification ability. The highest area under the curve in the internal testing data set and external testing data set was 0.95.
Conclusions
The AI system developed in this study, incorporating the novel concept of intrabeat dynamics, is a rapid, time-saving, and accurate prescreening method to facilitate HFpEF diagnosis. In addition to the classification of diagnostic outcomes, such an approach can automatically generate valuable quantitative metrics to assist clinicians in the diagnosis of HFpEF.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print
Chiou YA, Hung CL, Lin SF
JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print | PMID: 34147456
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Abstract

Lateral Wall Dysfunction Signals Onset of Progressive Heart Failure in Left Bundle Branch Block.

Sletten OJ, Aalen JM, Izci H, Duchenne J, ... Smiseth OA, Skulstad H
Objectives
This study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT).
Background
LBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT.
Methods
In 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EFpreserved), 36% to 49% (EFmid), and ≤35% (EFlow). Sixty-four patients underwent CRT and were re-examined after 6 months.
Results
Septal work was successively reduced from controls, through EFpreserved, EFmid, and EFlow (all p < 0.005), and showed a strong correlation to left ventricular ejection fraction (LVEF; r = 0.84; p < 0.005). In contrast, LV lateral wall work was numerically increased in EFpreserved and EFmid versus controls, and did not significantly correlate with LVEF in these groups. In EFlow, however, LV lateral wall work was substantially reduced (p < 0.005). There was a moderate overall correlation between LV lateral wall work and LVEF (r = 0.58; p < 0.005). In CRT recipients, LVEF was normalized (≥50%) in 54% of patients with preserved LV lateral wall work, but only in 13% of patients with reduced LV lateral wall work (p < 0.005).
Conclusions
In early stages, LBBB-induced heart failure is associated with impaired septal function but preserved lateral wall function. The advent of LV lateral wall dysfunction may be an optimal time-point for CRT.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print
Sletten OJ, Aalen JM, Izci H, Duchenne J, ... Smiseth OA, Skulstad H
JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print | PMID: 34147454
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Abstract

Structural Cardiac Remodeling in Atrial Fibrillation.

Beyer C, Tokarska L, Stühlinger M, Feuchtner G, ... Schönbauer R, Plank F
Objectives
This study sought to evaluate preablation computed tomography angiography (CTA) for atrial and epicardial features to predict atrial fibrillation (AF) recurrence after ablation.
Background
Structural atrial remodeling is a process associated with occurrence or persistence of AF. Different anatomical imaging features have been proposed to influence atrial remodeling both negatively and positively as substrate for AF.
Methods
Patients with nonvalvular AF underwent cardiac CTA before pulmonary vein isolation at 2 high-volume centers. Left atrial (LA) and right atrial volumes, LA wall thickness (LAWT), and epicardial adipose tissue volume and attenuation were evaluated. Additional subanalyses of electroanatomical maps were made. Follow-up was performed for at least 12 months, including subanalysis of repeated cardiac CTA studies. Interrater variability was assessed.
Results
Of 732 patients, 270 (36.9%) had AF recurrence after a mean of 7 months. CT analysis revealed larger indexed LA volume (47.3 mL/m2 vs 43.6 mL/m2; P = 0.0001) and higher mean anterior (1.91 mm vs 1.65 mm; P < 0.0001) and posterior (1.61 mm vs 1.39 mm; P = 0.001) LAWT in patients with AF recurrence. Epicardial adipose tissue volume in patients with AF recurrence was higher (144.5 mm³ vs 128.5 mm³; P < 0.0001) and further progressed significantly in a subset of 85 patients after 2 years (+11.8 mm2 vs -3.5 mm2; P = 0.041). Attenuation levels were lower, indicating a higher lipid component associated with AF recurrence (-69.1 HU vs -67.5 HU; P = 0.001). A total of 103 atrial voltage maps were highly predictive of AF recurrence and showed good discriminatory power for patients with low voltage >50% and LAWT (1.55 ± 0.5 mm vs 1.81 ± 0.6 mm; P = 0.032). Net reclassification improvement (NRI) showed a significant incremental benefit (NRI = 0.279; P < 0.0001) when adding LAWT to established risk models.
Conclusions
Atrial wall thickness, epicardial fat volume, and attenuation are associated with AF recurrence in patients undergoing ablation therapy.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print
Beyer C, Tokarska L, Stühlinger M, Feuchtner G, ... Schönbauer R, Plank F
JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print | PMID: 34147453
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Impact:
Abstract

Impact of COVID-19 on Cardiovascular Testing in the United States Versus the Rest of the World: The INCAPS-COVID Study.

Hirschfeld CB, Shaw LJ, Williams MC, Lahey R, ... Einstein AJ, INCAPS-COVID Investigators Group
Objectives
This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.
Background
The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.
Methods
Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.
Results
Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis.
Conclusions
We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print
Hirschfeld CB, Shaw LJ, Williams MC, Lahey R, ... Einstein AJ, INCAPS-COVID Investigators Group
JACC Cardiovasc Imaging: 09 Jun 2021; epub ahead of print | PMID: 34147434
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Impact:
Abstract

Machine Learning of ECG Waveforms to Improve Selection for Testing for Asymptomatic Left Ventricular Dysfunction Prompt.

Potter EL, Rodrigues CHM, Ascher DB, Abhayaratna WP, Sengupta PP, Marwick TH
Objectives
To identify whether machine learning from processing of continuous wave transforms (CWTs) to provide an \"energy waveform\" electrocardiogram (ewECG) could be integrated with echocardiographic assessment of subclinical systolic and diastolic left ventricular dysfunction (LVD).
Background
Asymptomatic LVD has management implications, but routine echocardiography is not undertaken in subjects at risk of heart failure. Signal processing of the surface ECG with the use of CWT can identify abnormal myocardial relaxation.
Methods
EwECG and echocardiography were undertaken in 398 participants at risk of heart failure (HF). Reduced global longitudinal strain (GLS ≤16%)), diastolic abnormalities (E/e\' >15, left atrial enlargement with E/e\' >10 or impaired relaxation) or LV hypertrophy defined LVD. EwECG feature selection and supervised machine-learning by random forest (RF) classifier was undertaken with 643 CWT-derived features and the Atherosclerosis Risk in Communities (ARIC) heart failure risk score.
Results
The ARIC score and 18 CWT features were selected to build a RF predictive model for LVD in a training dataset (n = 287; 60% female, median age 71 [interquartile range: 68 to 74] years). Model performance was tested in an independent group (n = 111; 49% female, median age 61 years [59 to 66 years]), demonstrating 85% sensitivity and 72% specificity (area under the receiver-operating characteristic curve [AUC]: 0.83; 95% confidence interval [CI]: 0.74 to 0.92). With ARIC score removed, sensitivity was 88% and specificity, 70% (AUC: 0.78; 95% CI: 0.70 to 0.86). RF models for reduced GLS and diastolic abnormalities including similar features had sensitivities that were unsuitable for screening. Conventional candidates for LVD screening (ARIC score, N-terminal pro-B-type natriuretic peptide, and standard automated ECG analysis) had inferior discriminative ability. Integration of ewECG in screening of people at risk of HF would reduce need for echocardiography by 45% while missing 12% of LVD cases.
Conclusions
Machine learning applied to ewECG is a sensitive screening test for LVD, and its integration into screening of patients at risk for HF would reduce the number of echocardiograms by almost one-half.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 08 Jun 2021; epub ahead of print
Potter EL, Rodrigues CHM, Ascher DB, Abhayaratna WP, Sengupta PP, Marwick TH
JACC Cardiovasc Imaging: 08 Jun 2021; epub ahead of print | PMID: 34147443
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Impact:
Abstract

Artificial Intelligence for Automatic Measurement of Left Ventricular Strain in Echocardiography.

Salte IM, Østvik A, Smistad E, Melichova D, ... Lovstakken L, Grenne B
Objectives
This study sought to examine if fully automated measurements of global longitudinal strain (GLS) using a novel motion estimation technology based on deep learning and artificial intelligence (AI) are feasible and comparable with a conventional speckle-tracking application.
Background
GLS is an important parameter when evaluating left ventricular function. However, analyses of GLS are time consuming and demand expertise, and thus are underused in clinical practice.
Methods
In this study, 200 patients with a wide range of left ventricle (LV) function were included. Three standard apical cine-loops were analyzed using the AI pipeline. The AI method measured GLS and was compared with a commercially available semiautomatic speckle-tracking software (EchoPAC v202, GE Healthcare, Chicago, Illinois).
Results
The AI method succeeded to both correctly classify all 3 standard apical views and perform timing of cardiac events in 89% of patients. Furthermore, the method successfully performed automatic segmentation, motion estimates, and measurements of GLS in all examinations, across different cardiac pathologies and throughout the spectrum of LV function. GLS was -12.0 ± 4.1% for the AI method and -13.5 ± 5.3% for the reference method. Bias was -1.4 ± 0.3% (95% limits of agreement: 2.3 to -5.1), which is comparable with intervendor studies. The AI method eliminated measurement variability and a complete GLS analysis was processed within 15 s.
Conclusions
Through the range of LV function this novel AI method succeeds, without any operator input, to automatically identify the 3 standard apical views, perform timing of cardiac events, trace the myocardium, perform motion estimation, and measure GLS. Fully automated measurements based on AI could facilitate the clinical implementation of GLS.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 08 Jun 2021; epub ahead of print
Salte IM, Østvik A, Smistad E, Melichova D, ... Lovstakken L, Grenne B
JACC Cardiovasc Imaging: 08 Jun 2021; epub ahead of print | PMID: 34147442
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Abstract

Effect of Coronary CTA on Chronic Total Occlusion Percutaneous Coronary Intervention: A Randomized Trial.

Hong SJ, Kim BK, Cho I, Kim HY, ... Jang Y, CT-CTO Investigators
Objectives
The purpose of this study was to test whether the success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) increased with pre-procedural coronary computed tomography angiography (CTA).
Background
Coronary CTA provides valuable information before and during CTO-PCI. However, there are no randomized data that explore whether coronary CTA increases its success rate.
Methods
In this multicenter, randomized trial, a total of 400 patients with CTO were randomized to receive PCI with pre-procedural coronary CTA (coronary CTA-guided group; n = 200) or without coronary CTA (angiography-guided group; n = 200) between January 2014 and September 2019. The primary endpoint was the successful recanalization rate, a final TIMI (Thrombolysis In Myocardial Infarction) grade ≥2, and ≤30% residual stenosis on the final angiogram.
Results
A total of 10 operators performed PCI. Successful recanalization was achieved in 187 patients (93.5%) in the coronary CTA-guided group and in 168 patients (84.0%) in the angiography-guided group (absolute difference, 9.5% [95% confidence interval: 3.4% to 15.6%]; p = 0.003). When comparing the success rates according to the Multicenter CTO Registry of Japan score (J-CTO), the coronary CTA guidance was favored over the angiography-guidance in the subset of J-CTO ≥2 versus in the subset of J-CTO <2 (p interaction = 0.035). Coronary perforations occurred in 2 (1%) and 8 patients (4%) in the coronary CTA- and angiography-guided groups, respectively (p = 0.055). Periprocedural myocardial infarction was not observed in the coronary CTA-guided group, whereas it occurred in 4 patients (2%) in the angiography-guided group (p = 0.123). Total procedure and fluoroscopic times were not different. There were no differences between the groups in the occurrences of cardiac death, target vessel-related myocardial infarction, or target-vessel revascularization at 1 year.
Conclusions
Pre-procedural coronary CTA-guidance for CTO resulted in higher success rates with numerically fewer immediate periprocedural complications such as coronary perforations or periprocedural myocardial infarction than angiography guidance. Higher success rates were more prominently observed in patients with CTO who had a high J-CTO score than those who did not. (Role of CT Scan for the Successful Recanalization of Chronic Total Occlusion; a Randomized Comparison Between 3D CT-guided PCI vs. Conventional Treatment [CT-CTO Trial]; NCT02037698).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 08 Jun 2021; epub ahead of print
Hong SJ, Kim BK, Cho I, Kim HY, ... Jang Y, CT-CTO Investigators
JACC Cardiovasc Imaging: 08 Jun 2021; epub ahead of print | PMID: 34147439
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Impact:
Abstract

Diagnostic Applications of Ultrasmall Superparamagnetic Particles of Iron Oxide for Imaging Myocardial and Vascular Inflammation.

Merinopoulos I, Gunawardena T, Stirrat C, Cameron D, ... Newby DE, Vassiliou VS
Cardiac magnetic resonance (CMR) is at the forefront of noninvasive methods for the assessment of myocardial anatomy, function, and most importantly tissue characterization. The role of CMR is becoming even more significant with an increasing recognition that inflammation plays a major role for various myocardial diseases such as myocardial infarction, myocarditis, and takotsubo cardiomyopathy. Ultrasmall superparamagnetic particles of iron oxide (USPIO) are nanoparticles that are taken up by monocytes and macrophages accumulating at sites of inflammation. In this context, USPIO-enhanced CMR can provide valuable additional information regarding the cellular inflammatory component of myocardial and vascular diseases. Here, we will review the recent diagnostic applications of USPIO in terms of imaging myocardial and vascular inflammation, and highlight some of their future potential.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1249-1264
Merinopoulos I, Gunawardena T, Stirrat C, Cameron D, ... Newby DE, Vassiliou VS
JACC Cardiovasc Imaging: 30 May 2021; 14:1249-1264 | PMID: 32861658
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Impact:
Abstract

Pancoronary Plaque Characteristics in STEMI Caused by Culprit Plaque Erosion Versus Rupture: 3-Vessel OCT Study.

Cao M, Zhao L, Ren X, Wu T, ... Mintz GS, Yu B
Objectives
This study sought to investigate nonculprit plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI) presenting with plaque erosion (PE) and plaque rupture (PR). Pancoronary vulnerability was considered at nonculprit sites: 1) the CLIMA (Relationship Between OCT Coronary Plaque Morphology and Clinical Outcome) study (NCT02883088) defined high-risk plaques with simultaneous presence of 4 optical coherence tomography (OCT) features (minimum lumen area <3.5 mm2; fibrous cap thickness [FCT] <75 μm; maximum lipid arc >180º; and macrophage accumulation); and 2) the presence of plaque ruptures or thin-cap fibroatheromas (TCFA).
Background
PE is a unique clinical entity associated with better outcomes than PR. There is limited evidence regarding pancoronary plaque characteristics of patients with culprit PE versus culprit PR.
Methods
Between October 2016 and September 2018, 523 patients treated by 3-vessel OCT at the time of primary percutaneous intervention were included with 152 patients excluded from final analysis.
Results
Overall, 458 nonculprit plaques were identified in 202 STEMI patients with culprit PE; and 1,027 nonculprit plaques were identified in 321 STEMI patients with culprit PR. At least 1 CLIMA-defined OCT nonculprit high-risk plaque was seen in 11.4% of patients with culprit PE, but twice as many patients were seen with culprit PR (25.2%; p < 0.001). This proportion was also seen when individual high-risk features were analyzed separately. When patients with PE were divided by a heterogeneous substrate (fibrous or lipid-rich plaque) underlying the culprit site, the prevalence of nonculprits with FCT <75 μm, macrophages, and TCFA showed a significant gradient from PE(Fibrous) to PElipid-rich plaque (LRP) to PR. Interestingly, nonculprit rupture was rarely found in patients with culprit PE(Fibrous) (1.9%), although it was exhibited with comparable prevalence in patients with culprit PE(LRP) (16.3%) versus PR (17.8%). Culprit PE predicted decreased pancoronary vulnerability independent of conventional risk factors.
Conclusions
STEMI patients with culprit PE have a limited pancoronary vulnerability that may explain better outcomes in these patients than in STEMI patients with culprit PR.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1235-1245
Cao M, Zhao L, Ren X, Wu T, ... Mintz GS, Yu B
JACC Cardiovasc Imaging: 30 May 2021; 14:1235-1245 | PMID: 33129735
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Impact:
Abstract

Diabetic Cardiomiopathy Progression is Triggered by miR122-5p and Involves Extracellular Matrix: A 5-Year Prospective Study.

Pofi R, Giannetta E, Galea N, Francone M, ... Carbone I, Isidori AM
Objectives
The purpose of this study was to follow the long-term progression of diabetic cardiomyopathy by combining cardiac magnetic resonance (CMR) and molecular analysis.
Background
The evolution of diabetic cardiomyopathy to heart failure affects patients\'morbidity and mortality. CMR is the gold standard to assess cardiac remodeling, but there is a lack of markers linked to the mechanism of diabetic cardiomyopathy progression.
Methods
Five-year longitudinal study on patients with type 2 diabetes mellitus (T2DM) enrolled in the CECSID (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes) trial compared with nondiabetic age-matched controls. CMR with tagging together with metabolic and molecular assessments were performed at baseline and 5-year follow-up.
Results
A total of 79 men (age 64 ± 8 years) enrolled, comprising 59 men with T2DM compared with 20 nondiabetic age-matched controls. Longitudinal CMR with tagging showed an increase in ventricular mass (ΔLVMi = 13.47 ± 29.66 g/m2; p = 0.014) and a borderline increase in end-diastolic volume (ΔEDVi = 5.16 ± 14.71 ml/m2; p = 0.056) in men with T2DM. Cardiac strain worsened (Δσ = 1.52 ± 3.85%; p = 0.033) whereas torsion was unchanged (Δθ = 0.24 ± 4.04°; p = 0.737), revealing a loss of the adaptive equilibrium between strain and torsion. Contraction dynamics showed a decrease in the systolic time-to-peak (ΔTtP = -35.18 ± 28.81 ms; p < 0.001) and diastolic early recoil-rate (ΔRR = -20.01 ± 19.07 s-1; p < 0.001). The ejection fraction and metabolic parameters were unchanged. Circulating miR microarray revealed an up-regulation of miR122-5p. Network analysis predicted the matrix metalloproteinases (MMPs) MMP-16 and MMP-2 and their regulator (tissue inhibitors of metalloproteinases) as targets. In db/db mice we demonstrated that miR122-5p expression is associated with diabetic cardiomyopathy, that in the diabetic heart is overexpressed, and that, in vitro, it regulates MMP-2. Finally, we demonstrated that miR122-5p overexpression affects the extracellular matrix through MMP-2 modulation.
Conclusions
Within 5 years of diabetic cardiomyopathy onset, increasing cardiac hypertrophy is associated with progressive impairment in strain, depletion of the compensatory role of torsion, and changes in viscoelastic contraction dynamics. These changes are independent of glycemic control and paralleled by the up-regulation of specific microRNAs targeting the extracellular matrix. (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes [CECSID]; NCT00692237).

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1130-1142
Pofi R, Giannetta E, Galea N, Francone M, ... Carbone I, Isidori AM
JACC Cardiovasc Imaging: 30 May 2021; 14:1130-1142 | PMID: 33221242
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Impact:
Abstract

Diagnosing Transthyretin Cardiac Amyloidosis by Technetium Tc 99m Pyrophosphate: A Test in Evolution.

Poterucha TJ, Elias P, Bokhari S, Einstein AJ, ... Perotte A, Maurer MS
Objectives
This study aimed to characterize trends in technetium Tc 99m pyrophosphate (99mTc-PYP) scanning for amyloid transthyretin cardiac amyloidosis (ATTR-CA) diagnosis, to determine whether patients underwent appropriate assessment with monoclonal protein and genetic testing, to evaluate use of single-photon emission computed tomography (SPECT) in addition to planar imaging, and to identify predictive factors for ATTR-CA.
Background
99mTc-PYP scintigraphy has been repurposed for noninvasive diagnosis of ATTR-CA. Increasing use of 99mTc-PYP can facilitate identification of ATTR-CA, but appropriate use is critical for accurate diagnosis in an era of high-cost targeted therapeutics.
Methods
Patients undergoing 99mTc-PYP scanning 1 h after injection at a quaternary care center from 2010 to 2019 were analyzed; clinical information was abstracted; and SPECT results were analyzed.
Results
Over the decade, endomyocardial biopsy rates remained stable with scanning rates peaking at 132 in 2019 (p < 0.001). Among 753 patients (516 men, mean age 77 years), 307 (41%) had a visual score of 0, 177 (23%) of 1, and 269 (36%) of 2 or 3. Of 751 patients with analyzable heart to contralateral chest ratios, 249 (33%) had a ratio ≥1.5. Monoclonal protein testing status was assessed in 550 patients, of these, 174 (32%) did not undergo both serum immunofixation and serum free light chain analysis tests, and 331 (60%) did not undergo all 3 tests-serum immunofixation, serum free light chain analysis, and urine protein electrophoresis. Of 196 patients with confirmed ATTR-CA, 143 (73%) had genetic testing for transthyretin mutations. In 103 patients undergoing cardiac biopsy, grades 2 and 3 99mTc-PYP had sensitivity of 94% and specificity of 89% for ATTR-CA with 100% specificity for grade 3 scans. With respect to SPECT as a reference standard, planar imaging had false positive results in 16 of 25 (64%) grade 2 scans.
Conclusions
Use of noninvasive testing with 99mTc-PYP scanning for evaluation of ATTR-CA is increasing, and the inclusion of monoclonal protein testing and SPECT imaging is crucial to rule out amyloid light chain amyloidosis and distinguish myocardial retention from blood pooling.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1221-1231
Poterucha TJ, Elias P, Bokhari S, Einstein AJ, ... Perotte A, Maurer MS
JACC Cardiovasc Imaging: 30 May 2021; 14:1221-1231 | PMID: 33221204
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Impact:
Abstract

High-Risk Coronary Plaque Regression After Intensive Lifestyle Intervention in Nonobstructive Coronary Disease: A Randomized Study.

Henzel J, Kępka C, Kruk M, Makarewicz-Wujec M, ... Dzielińska Z, Demkow M
Objectives
The authors sought to study the impact of diet and lifestyle intervention on changes in atherosclerotic plaque volume and composition.
Background
Lifestyle and diet modification are the leading strategies to manage coronary artery disease; however, their direct impact on atherosclerosis remains unknown. Coronary plaque composition is related to the risk of future cardiovascular events independent of stenosis severity and can be conveniently evaluated with computed tomography angiography (CTA).
Methods
We enrolled 92 patients (41% women; mean age 60 ± 7.7 years) with nonobstructive (<70% stenosis) coronary atherosclerosis identified by CTA. Participants were randomized (1:1) to either the DISCO (Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography) intervention group (systematic follow-up by a dietitian to adhere to the Dietary Approaches to Stop Hypertension nutrition model together with optimal medical therapy [OMT]) or the control group (OMT alone). In all patients, CTA was repeated after 66.9 ± 13.7 weeks. The outcome was change (Δ) in atheroma volume and plaque composition. Based on atherosclerotic tissue attenuation ranges in Hounsfield units (HU), the following components of coronary plaque were distinguished: dense calcium (>351 HU), fibrous plaque (151 to 350 HU), and fibrofatty plaque combined with necrotic core (-30 to 150 HU), referred to as noncalcified plaque.
Results
Percent atheroma volume increased in the control arm (Δ = +1.1 ± 3.4%; p = 0.033) versus no significant change in the experimental arm (Δ = +1.0% ± 4.2%; p = 0.127; intergroup p = 0.851). There was a reduction in noncalcified plaque in both the experimental arm (Δ = -51.3 ± 79.5 mm3 [-1.7 ± 2.7%]; p < 0.001) and the control arm (Δ = -21.3 ± 57.7 [-0.7 ± 1.9%]; p = 0.018), which was greater in the DISCO intervention group (intergroup p = 0.045). No differences in fibrous component or dense calcium changes were observed between the groups.
Conclusions
Controlled diet and lifestyle intervention together with OMT may slow the progression of atherosclerosis and reduce noncalcified plaque volume compared to OMT alone. (Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography [DISCO-CT]; NCT02571803).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1192-1202
Henzel J, Kępka C, Kruk M, Makarewicz-Wujec M, ... Dzielińska Z, Demkow M
JACC Cardiovasc Imaging: 30 May 2021; 14:1192-1202 | PMID: 33341413
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Impact:
Abstract

Extracellular Volume in Primary Mitral Regurgitation.

Kitkungvan D, Yang EY, El Tallawi KC, Nagueh SF, ... Quinones MA, Shah DJ
Objectives
This study used cardiovascular magnetic resonance (CMR) to evaluate whether elevated extracellular volume (ECV) was associated with mitral valve prolapse (MVP) or if elevated ECV was a consequence of remodeling independent of primary mitral regurgitation (MR) etiology.
Background
Replacement fibrosis in primary MR is more prevalent in MVP; however, data on ECV as a surrogate for diffuse interstitial fibrosis in primary MR are limited.
Methods
Patients with chronic primary MR underwent comprehensive CMR phenotyping and were stratified into an MVP cohort (>2 mm leaflet displacement on a 3-chamber cine CMR) and a non-MVP cohort. Factors associated with ECV and replacement fibrosis were assessed. The association of ECV and symptoms related to MR and clinical events (mitral surgery and cardiovascular death) was ascertained.
Results
A total of 424 patients with primary MR (229 with MVP and 195 non-MVP) were enrolled. Replacement fibrosis was more prevalent in the MVP cohort (34.1% vs. 6.7%; p < 0.001), with bi-leaflet MVP having the strongest association with replacement fibrosis (odds ratio: 10.5; p < 0.001). ECV increased with MR severity in a similar fashion for both MVP and non-MVP cohorts and was associated with MR severity but not MVP on multivariable analysis. Elevated ECV was independently associated with symptoms related to MR and clinical events.
Conclusions
Although replacement fibrosis was more prevalent in MVP, diffuse interstitial fibrosis as inferred by ECV was associated with MR severity, regardless of primary MR etiology. ECV was independently associated with symptoms related to MR and clinical events. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1146-1160
Kitkungvan D, Yang EY, El Tallawi KC, Nagueh SF, ... Quinones MA, Shah DJ
JACC Cardiovasc Imaging: 30 May 2021; 14:1146-1160 | PMID: 33341409
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Impact:
Abstract

Empagliflozin Reduces Myocardial Extracellular Volume in Patients With Type 2 Diabetes and Coronary Artery Disease.

Mason T, Coelho-Filho OR, Verma S, Chowdhury B, ... Yan AT, Connelly KA
Objectives
This study sought to evaluate the effects of empagliflozin on extracellular volume (ECV) in individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).
Background
Empagliflozin has been shown to reduce left ventricular mass index (LVMi) in patients with T2DM and CAD. The effects on myocardial ECV are unknown.
Methods
This was a prespecified substudy of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes) CardioLink-6 trial in which 97 participants were randomized to receive empagliflozin 10 mg daily or placebo for 6 months. Data from 74 participants were included: 39 from the empagliflozin group and 35 from the placebo group. The main outcome was change in left ventricular ECV from baseline to 6 months determined by cardiac magnetic resonance (CMR). Other outcomes included change in LVMi, indexed intracellular compartment volume (iICV) and indexed extracellular compartment volume (iECV), and the fibrosis biomarkers soluble suppressor of tumorgenicity (sST2) and matrix metalloproteinase (MMP)-2.
Results
Baseline ECV was elevated in the empagliflozin group (29.6 ± 4.6%) and placebo group (30.6 ± 4.8%). Six months of empagliflozin therapy reduced ECV compared with placebo (adjusted difference: -1.40%; 95% confidence interval [CI]: -2.60 to -0.14%; p = 0.03). Empagliflozin therapy reduced iECV (adjusted difference: -1.5 ml/m2; 95% CI: -2.6 to -0.5 ml/m2; p = 0.006), with a trend toward reduction in iICV (adjusted difference: -1.7 ml/m2; 95% CI: -3.8 to 0.3 ml/m2; p = 0.09). Empagliflozin had no impact on MMP-2 or sST2.
Conclusions
In individuals with T2DM and CAD, 6 months of empagliflozin reduced ECV, iECV, and LVMi. No changes in MMP-2 and sST2 were seen. Further investigation into the mechanisms by which empagliflozin causes reverse remodeling is required. (Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes [EMPA-HEART]; NCT02998970).

Copyright © 2021. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 30 May 2021; 14:1164-1173
Mason T, Coelho-Filho OR, Verma S, Chowdhury B, ... Yan AT, Connelly KA
JACC Cardiovasc Imaging: 30 May 2021; 14:1164-1173 | PMID: 33454272
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Impact:
Abstract

Fast Strain-Encoded Cardiac Magnetic Resonance for Diagnostic Classification and Risk Stratification of Heart Failure Patients.

Korosoglou G, Giusca S, Montenbruck M, Patel AR, ... Kelle S, Steen H
Objectives
The purpose of this study was to compare the ability of fast-strain encoded magnetic resonance (fast-SENC) cardiac magnetic resonance (CMR) to classify and risk stratify all-comer patients with different stages of chronic heart failure (Stages of heart failure A to D) based on American College of Cardiology/American Heart Association guidelines with standard clinical and CMR imaging data.
Background
Heart failure is a major cause of morbidity and mortality, resulting in millions of deaths and hospitalizations annually.
Methods
The study population consisted of 1,169 consecutive patients between September 2017 and February 2019 who underwent CMR for clinical reasons, and 61 healthy volunteers. In addition, clinical follow-up was performed in Stages A and B patients after 1.9 ± 0.4 years. Wall motion score and late gadolinium enhancement score indexes, left ventricular (LV) ejection fraction, and global circumferential and longitudinal strain based on fast-SENC acquisitions, were calculated in all subjects. The percentage of myocardial segments with strain ≤-17% (% normal myocardium) was determined in all subjects.
Results
LV ejection fraction, global circumferential and longitudinal strain, and % normal myocardium significantly decreased with increasing heart failure stages (p < 0.001 for all by analysis of variance). By multivariable analysis, % normal myocardium remained an independent predictor of heart failure stages, exhibiting closer association than LV ejection fraction (rpartial = 0.76 vs. rpartial = 0.30; p < 0.001). Importantly, 149 of 399 (37%) with Stage A were reclassified to Stage B, that is, as having subclinical LV dysfunction based on % normal myocardium <80%. Such patients exhibited significantly higher rates of all-cause mortality and hospital stay due to heart failure during follow-up, compared with patients with % normal myocardium ≥80% (chi-square = 6.9; p = 0.03).
Conclusions
The % normal myocardium, determined by fast-SENC, enables improved identification of asymptomatic patients with subclinical LV dysfunction compared with LV ejection fraction and risk stratification of patients with so far asymptomatic heart failure. The identification of such presumably healthy patients at high risk for heart failure-related outcomes may bear important medical implications.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1177-1188
Korosoglou G, Giusca S, Montenbruck M, Patel AR, ... Kelle S, Steen H
JACC Cardiovasc Imaging: 30 May 2021; 14:1177-1188 | PMID: 33454266
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Impact:
Abstract

Cost-Effectiveness of Coronary Artery Calcium Scoring in People With a Family History of Coronary Disease.

Venkataraman P, Kawakami H, Huynh Q, Mitchell G, ... Marwick TH, CAUGHT-CAD investigators
Objectives
To assess the cost effectiveness of coronary artery calcium (CAC) compared with traditional risk factor-based prediction alone in those with an family history of premature coronary artery disease (FHCAD).
Background
The use of CAC scoring to guide primary prevention statin therapy in those with a FHCAD is inconsistently recommended in guidelines, and usually not reimbursed by insurance.
Methods
A microsimulation model was constructed in TreeAge Healthcare Pro using data from 1,083 participants in the CAUGHT-CAD (Coronary Artery Calcium Score: Use to Guide Management of HerediTary Coronary Artery Disease) trial. Outcomes assessed were quality-adjusted life years (QALYs): cost-effectiveness was assessed over a 15-year time horizon from the perspective of the US health care sector using real-world statin prescribing, accounting for the effect of knowledge of subclinical disease on adherence to guideline-directed therapies. Costs were assessed in 2020 USD, with discounting undertaken at 3%.
Results
Statins were indicated in 45% of the cohort using the CAC strategy and 27% using American College of Cardiology/American Heart Association (2019) treatment strategies. Compared with applying a statin treatment threshold of 7.5%, the CAC strategy was more costly ($145) and more effective (0.0097 QALY) with an incremental cost-effective ratio (ICER) of $15,014/QALY. CAC ICER was driven by CAC acquisition and statin prescription cost and improved with certain patient subgroups: male, age >60 years, and 10-year risk pooled cohort equation risk ≥7.5%. CAC scanning of low-risk patients (10-year risk <5%) or those 40 to 50 years of age was not cost-effective.
Conclusions
Systematic CAC screening and treatment of those with FHCAD and subclinical disease was more cost-effective than management using statin treatment thresholds, in the US health care system.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1206-1217
Venkataraman P, Kawakami H, Huynh Q, Mitchell G, ... Marwick TH, CAUGHT-CAD investigators
JACC Cardiovasc Imaging: 30 May 2021; 14:1206-1217 | PMID: 33454262
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Impact:
Abstract

Prognostic Implications of a Novel Algorithm to Grade Secondary Tricuspid Regurgitation.

Fortuni F, Dietz MF, Prihadi EA, van der Bijl P, ... Delgado V, Marsan NA
Objectives
A novel tricuspid regurgitation (TR) grading system, using vena contracta (VC) width and effective regurgitant orifice area (EROA), was proposed and validated based on its prognostic usefulness.
Background
The clinical need of a new grading system for TR has recently been emphasized to depict the whole spectrum of TR severity, particularly beyond severe TR (massive or torrential).
Methods
TR severity was characterized in 1,129 patients with moderate or severe secondary TR (STR). Recently proposed cutoff values of VC width were more effective in differentiating the prognosis of patients with moderate STR, whereas EROA cutoff values performed better in characterizing the risk of patients with more severe STR. Therefore, these 2 parameters were combined into a novel grading system to define moderate (VC <7 mm), severe (VC ≥7 mm and EROA <80 mm2), and torrential (VC ≥7 mm and EROA ≥80 mm2) STR.
Results
A total of 143 patients (13%) showed moderate STR, whereas 536 patients (47%) had severe STR, and 450 (40%) had torrential STR. Patients with torrential STR had larger right ventricular (RV) dimensions, lower RV systolic function, and were more likely to receive diuretics. The cumulative 10-year survival rate was 53% for moderate, 45% for severe, and 35% for torrential STR (p = 0.007). After adjusting for potential confounders, torrential STR retained an association with worse prognosis compared with other STR grades (hazard ratio: 1.245; 95% confidence interval: 1.023 to 1.516; p = 0.029).
Conclusions
A novel STR grading system was able to capture the whole range of STR severity and identified patients with torrential STR who were characterized by a worse prognosis.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1085-1095
Fortuni F, Dietz MF, Prihadi EA, van der Bijl P, ... Delgado V, Marsan NA
JACC Cardiovasc Imaging: 30 May 2021; 14:1085-1095 | PMID: 33582056
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Impact:
Abstract

Aortic Stenosis Progression, Cardiac Damage, and Survival: Comparison Between Bicuspid and Tricuspid Aortic Valves.

Yang LT, Boler A, Medina-Inojosa JR, Scott CG, ... Tribouilloy C, Michelena HI
Objectives
This study sought to compare aortic stenosis (AS) progression rates, AS-related cardiac damage (AS-CD) indicator incidence and determinants, and survival between patients with tricuspid aortic valve (TAV)-AS and those with bicuspid aortic valve (BAV)-AS.
Background
Differences in AS progression and AS-CD between patients with BAV and patients with TAV are unknown.
Methods
We retrospectively studied consecutive patients with baseline peak aortic valve velocity (peakV) ≥2.5 m/s and left ventricular ejection fraction ≥50%. Follow-up echocardiograms (n = 4,818) provided multiparametric AS progression rates and AS-CD.
Results
The study included 330 BAV (age 54 ± 14 years) and 581 patients with TAV (age 72 ± 11 years). At last echocardiogram (median: 5.9 years; interquartile range: 3.9 to 8.5 years), BAV-AS exhibited similar peakV and mean pressure gradient (MPG) as TAV-AS, but larger calculated aortic valve area due to larger aortic annulus (p < 0.0001). Multiparametric progression rates were similar between BAV-AS and TAV-AS (all p ≥ 0.08) and did not predict age-/sex-adjusted survival (p ≥ 0.45). Independent determinants of rapid progression were male sex and baseline AS severity for TAV (all p ≤ 0.024), and age, baseline AS severity, and cardiac risk factors (age interaction: p = 0.02) for BAV (all p ≤ 0.005). At 12 years, patients with TAV-AS had a higher incidence of AS-CD than BAV-AS patients (p < 0.0001), resulting in significantly worse survival compared to BAV-AS (p < 0.0001). AS-CD were independently determined by multiple factors (MPG, age, sex, comorbidities, cardiac function; all p ≤ 0.039), and BAV was independently protective of most AS-CD (all p ≤ 0.05).
Conclusions
In this cohort, TAV-AS and BAV-AS progression rates were similar. Rapid progression did not affect survival and was determined by cardiac risk factors for BAV-AS (particularly in patients with BAV <60 years of age) and unmodifiable factors for TAV-AS. AS-CD and mortality were significantly higher in TAV-AS. Independent determinants of AS-CD were multifactorial, and BAV morphology was AS-CD protective. Therefore, the totality of AS burden (cardiac damage) is clinically crucial for TAV-AS, whereas attention to modifiable risk factors may be preventive for BAV-AS.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1113-1126
Yang LT, Boler A, Medina-Inojosa JR, Scott CG, ... Tribouilloy C, Michelena HI
JACC Cardiovasc Imaging: 30 May 2021; 14:1113-1126 | PMID: 33744153
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Impact:
Abstract

Valve Strain Quantitation in Normal Mitral Valves and Mitral Prolapse With Variable Degrees of Regurgitation.

El-Tallawi KC, Zhang P, Azencott R, He J, ... Lawrie GM, Zoghbi WA
Objectives
The aim of this study was to quantitate patient-specific mitral valve (MV) strain in normal valves and in patients with mitral valve prolapse with and without significant mitral regurgitation (MR) and assess the determinants of MV strain.
Background
Few data exist on MV deformation during systole in humans. Three-dimensional echocardiography allows for dynamic MV imaging, enabling digital modeling of MV function in health and disease.
Methods
Three-dimensional transesophageal echocardiography was performed in 82 patients, 32 with normal MV and 50 with mitral valve prolapse (MVP): 12 with mild mitral regurgitation or less (MVP - MR) and 38 with moderate MR or greater (MVP + MR). Three-dimensional MV models were generated, and the peak systolic strain of MV leaflets was computed on proprietary software.
Results
Left ventricular ejection fraction was normal in all groups. MV annular dimensions were largest in MVP + MR (annular area: 13.8 ± 0.7 cm2) and comparable in MVP - MR (10.6 ± 1 cm2) and normal valves (10.5 ± 0.3 cm2; analysis of variance: p < 0.001). Similarly, MV leaflet areas were largest in MVP + MR, particularly the posterior leaflet (8.7 ± 0.5 cm2); intermediate in MVP - MR (6.5 ± 0.7 cm2); and smallest in normal valves (5.5 ± 0.2 cm2; p < 0.0001). Strain was overall highest in MVP + MR and lowest in normal valves. Patients with MVP - MR had intermediate strain values that were higher than normal valves in the posterior leaflet (p = 0.001). On multivariable analysis, after adjustment for clinical and MV geometric parameters, leaflet thickness was the only parameter that was retained as being significantly correlated with mean MV strain (r = 0.34; p = 0.008).
Conclusions
MVs that exhibit prolapse have higher strain compared to normal valves, particularly in the posterior leaflet. Although higher strain is observed with worsening MR and larger valves and annuli, mitral valve leaflet thickness-and, thus, underlying MV pathology-is the most significant independent determinant of valve deformation. Future studies are needed to assess the impact of MV strain determination on clinical outcome.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 May 2021; 14:1099-1109
El-Tallawi KC, Zhang P, Azencott R, He J, ... Lawrie GM, Zoghbi WA
JACC Cardiovasc Imaging: 30 May 2021; 14:1099-1109 | PMID: 33744129
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Impact:
Abstract

Mechanisms Underlying the Association of Chronic Obstructive Pulmonary Disease With Heart Failure.

Lagan J, Schelbert EB, Naish JH, Vestbo J, ... Schmitt M, Miller CA
Objectives
The purposes of this study were to determine why chronic obstructive pulmonary disease (COPD) is associated with heart failure (HF). Specific objectives included whether COPD is associated with myocardial fibrosis, whether myocardial fibrosis is associated with hospitalization for HF and death in COPD, and whether COPD and smoking are associated with myocardial inflammation.
Background
COPD is associated with HF independent of shared risk factors. The underlying pathophysiological mechanism is unknown.
Methods
A prospective, multicenter, longitudinal cohort study of 572 patients undergoing cardiac magnetic resonance (CMR), including 450 patients with COPD and 122 age- and sex-matched patients with a median: 726 days (interquartile range: 492 to 1,160 days) follow-up. Multivariate analysis was used to examine the relationship between COPD and myocardial fibrosis, measured using cardiac magnetic resonance (CMR). Cox regression analysis was used to examine the relationship between myocardial fibrosis and outcomes; the primary endpoint was composite of hospitalizations for HF or all-cause mortality; secondary endpoints included hospitalizations for HF and all-cause mortality. Fifteen patients with COPD, 15 current smokers, and 15 healthy volunteers underwent evaluation for myocardial inflammation, including ultrasmall superparamagnetic particles of iron oxide CMR.
Results
COPD was independently associated with myocardial fibrosis (p < 0.001). Myocardial fibrosis was independently associated with the primary outcome (hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.08 to 1.20; p < 0.001), hospitalization for HF (HR: 1.25 [95% CI: 1.14 to 1.36]); p < 0.001), and all-cause mortality. Myocardial fibrosis was associated with outcome measurements more strongly than any other variable. Acute and stable COPD were associated with myocardial inflammation.
Conclusions
The associations between COPD, myocardial inflammation and myocardial fibrosis, and the independent prognostic value of myocardial fibrosis elucidate a potential pathophysiological link between COPD and HF.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print
Lagan J, Schelbert EB, Naish JH, Vestbo J, ... Schmitt M, Miller CA
JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print | PMID: 34023272
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Impact:
Abstract

High-Risk Morphological and Physiological Coronary Disease Attributes as Outcome Markers After Medical Treatment and Revascularization.

Yang S, Koo BK, Hwang D, Zhang J, ... Kakuta T, Narula J
Objectives
This study sought to evaluate the prognostic impact of plaque morphology and coronary physiology on outcomes after medical treatment or percutaneous coronary intervention (PCI).
Background
Although fractional flow reserve (FFR) is currently best practice, morphological characteristics of coronary artery disease also contribute to outcomes.
Methods
A total of 872 vessels in 538 patients were evaluated by invasive FFR and coronary computed tomography angiography. High-risk attributes (HRA) were defined as high-risk physiological attribute (invasive FFR ≤0.8) and high-risk morphological attributes including: 1) local plaque burden (minimum lumen area <4 mm2 and plaque burden ≥70%); 2) adverse plaque characteristics ≥2; and 3) global plaque burden (total plaque volume ≥306.5 mm3 and percent atheroma volume ≥32.2%). The primary outcome was the composite of revascularization, myocardial infarction, or cardiac death at 5 years.
Results
The mean FFR was 0.88 ± 0.08, and PCI was performed in 239 vessels. The primary outcome occurred in 54 vessels (6.2%). All high-risk morphological attributes were associated with the increased risk of adverse outcomes after adjustment for FFR ≤0.8 and demonstrated direct prognostic effect not mediated by FFR ≤0.8. The 5-year event risk proportionally increased as the number of HRA increased (p for trend <0.001) with lower risk in the PCI group than the medical treatment group in vessels with 1 or 2 HRA (9.7% vs. 14.7%), but not in vessels with either 0 or ≥3 HRA. Of the vessels with pre-procedural FFR ≤0.8, ischemia relief by PCI (pre-PCI FFR ≤0.8 and post-PCI FFR >0.8) significantly reduced vessel-oriented composite outcome risk compared with medical treatment alone in vessels with 0 or 1 high-risk morphological attributes (hazard ratio: 0.33; 95% confidence interval: 0.12 to 0.93; p = 0.035), but the risk reduction was attenuated in vessels with ≥2 high-risk morphological attributes.
Conclusions
High-risk morphological attributes offered additive prognostic value to coronary physiology and may optimize selection of treatment strategies by adding to FFR-based risk predictions (CCTA-FFR Registry for Development of Comprehensive Risk Prediction Model; NCT04037163).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print
Yang S, Koo BK, Hwang D, Zhang J, ... Kakuta T, Narula J
JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print | PMID: 34023270
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Impact:
Abstract

Prognostic Value of Pulmonary Transit Time and Pulmonary Blood Volume Estimation Using Myocardial Perfusion CMR.

Seraphim A, Knott KD, Menacho K, Augusto JB, ... Manisty C, Kellman P
Objectives
The purpose of this study was to explore the prognostic significance of PTT and PBVi using an automated, inline method of estimation using CMR.
Background
Pulmonary transit time (PTT) and pulmonary blood volume index (PBVi) (the product of PTT and cardiac index), are quantitative biomarkers of cardiopulmonary status. The development of cardiovascular magnetic resonance (CMR) quantitative perfusion mapping permits their automated derivation, facilitating clinical adoption.
Methods
In this retrospective 2-center study of patients referred for clinical myocardial perfusion assessment using CMR, analysis of right and left ventricular cavity arterial input function curves from first pass perfusion was performed automatically (incorporating artificial intelligence techniques), allowing estimation of PTT and subsequent derivation of PBVi. Association with major adverse cardiovascular events (MACE) and all-cause mortality were evaluated using Cox proportional hazard models, after adjusting for comorbidities and CMR parameters.
Results
A total of 985 patients (67% men, median age 62 years [interquartile range (IQR): 52 to 71 years]) were included, with median left ventricular ejection fraction (LVEF) of 62% (IQR: 54% to 69%). PTT increased with age, male sex, atrial fibrillation, and left atrial area, and reduced with LVEF, heart rate, diabetes, and hypertension (model r2 = 0.57). Over a median follow-up period of 28.6 months (IQR: 22.6 to 35.7 months), MACE occurred in 61 (6.2%) patients. After adjusting for prognostic factors, both PTT and PBVi independently predicted MACE, but not all-cause mortality. There was no association between cardiac index and MACE. For every 1 × SD (2.39-s) increase in PTT, the adjusted hazard ratio for MACE was 1.43 (95% confidence interval [CI]: 1.10 to 1.85; p = 0.007). The adjusted hazard ratio for 1 × SD (118 ml/m2) increase in PBVi was 1.42 (95% CI: 1.13 to 1.78; p = 0.002).
Conclusions
Pulmonary transit time (and its derived parameter pulmonary blood volume index), measured automatically without user interaction as part of CMR perfusion mapping, independently predicted adverse cardiovascular outcomes. These biomarkers may offer additional insights into cardiopulmonary function beyond conventional predictors including ejection fraction.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print
Seraphim A, Knott KD, Menacho K, Augusto JB, ... Manisty C, Kellman P
JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print | PMID: 34023269
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Impact:
Abstract

Prognostic Implications of Associated Cardiac Abnormalities Detected on Echocardiography in Patients With Moderate Aortic Stenosis.

Amanullah MR, Pio SM, Ng ACT, Sin KYK, ... Ewe SH, Bax JJ
Objectives
This study aimed to evaluate the prevalence and prognostic value of the extent of extra-aortic valvular cardiac abnormalities in a large multicenter registry of patients with moderate AS.
Background
The prognostic significance of a new classification system that incorporates the extent of cardiac injury (beyond the aortic valve) has been proposed in patients with severe aortic stenosis (AS). Whether this can be applied to patients with moderate AS is unclear.
Methods
Based on the echocardiographic findings at the time of diagnosis of moderate AS (aortic valve area between 1.0 and 1.5 cm2 and dimensionless velocity index ratio of ≥0.25), a total of 1,245 patients were included and analyzed retrospectively. They were recategorized into 5 groups according to the extent of extra-aortic valvular cardiac abnormalities: none (Group 0), involving the left ventricle (Group 1), the left atrial or mitral valve (Group 2), the pulmonary artery vasculature or tricuspid valve (Group 3), or the right ventricle (Group 4). Patients were followed for all-cause mortality and combined endpoint (all-cause mortality, stroke, heart failure, or myocardial infarction).
Results
The distribution of patients according to the proposed classification was 13.1%, 26.8%, 42.6%, 10.6%, and 6.9% in Groups 0, 1, 2, 3, and 4, respectively. During a median follow-up of 4.3 (2.4 to 6.9) years, 564 (45.3%) patients died. There was a significant higher mortality rates with increasing extent of extra-aortic valvular cardiac abnormalities (log-rank p < 0.001). On multivariate analysis, the presence of extra-aortic valvular cardiac abnormalities remained independently associated with all-cause mortality and combined outcome, adjusted for aortic valve replacement as a time-dependent covariable. In particular, Group 2 and above were independently associated with all-cause mortality.
Conclusions
In patients with moderate AS, the presence of extra-aortic valvular cardiac abnormalities is associated with poor outcome.

Copyright © 2021. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print
Amanullah MR, Pio SM, Ng ACT, Sin KYK, ... Ewe SH, Bax JJ
JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print | PMID: 34023268
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Abstract

Multimodality Intravascular Imaging of High-Risk Coronary Plaque.

Li J, Montarello NJ, Hoogendoorn A, Verjans JW, ... McLaughlin RA, Psaltis PJ
The majority of coronary atherothrombotic events presenting as myocardial infarction (MI) occur as a result of plaque rupture or erosion. Understanding the evolution from a stable plaque into a life-threatening, high-risk plaque is required for advancing clinical approaches to predict atherothrombotic events, and better treat coronary atherosclerosis. Unfortunately, none of the coronary imaging approaches used in clinical practice can reliably predict which plaques will cause an MI. Currently used imaging techniques mostly identify morphological features of plaques, but are not capable of detecting essential molecular characteristics known to be important drivers of future risk. To address this challenge, engineers, scientists, and clinicians have been working hand-in-hand to advance a variety of multimodality intravascular imaging techniques, whereby 2 or more complementary modalities are integrated into the same imaging catheter. Some of these have already been tested in early clinical studies, with other next-generation techniques also in development. This review examines these emerging hybrid intracoronary imaging techniques and discusses their strengths, limitations, and potential for clinical translation from both an engineering and clinical perspective.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print
Li J, Montarello NJ, Hoogendoorn A, Verjans JW, ... McLaughlin RA, Psaltis PJ
JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print | PMID: 34023267
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Impact:
Abstract

Deep-Learning Models for the Echocardiographic Assessment of Diastolic Dysfunction.

Pandey A, Kagiyama N, Yanamala N, Segar MW, ... Tokodi M, Sengupta PP
Objectives
The authors explored a deep neural network (DeepNN) model that integrates multidimensional echocardiographic data to identify distinct patient subgroups with heart failure with preserved ejection fraction (HFpEF).
Background
The clinical algorithms for phenotyping the severity of diastolic dysfunction in HFpEF remain imprecise.
Methods
The authors developed a DeepNN model to predict high- and low-risk phenogroups in a derivation cohort (n = 1,242). Model performance was first validated in 2 external cohorts to identify elevated left ventricular filling pressure (n = 84) and assess its prognostic value (n = 219) in patients with varying degrees of systolic and diastolic dysfunction. In 3 National Heart, Lung, and Blood Institute-funded HFpEF trials, the clinical significance of the model was further validated by assessing the relationships of the phenogroups with adverse clinical outcomes (TOPCAT [Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function] trial, n = 518), cardiac biomarkers, and exercise parameters (NEAT-HFpEF [Nitrate\'s Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction] and RELAX-HF [Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure] pooled cohort, n = 346).
Results
The DeepNN model showed higher area under the receiver-operating characteristic curve than 2016 American Society of Echocardiography guideline grades for predicting elevated left ventricular filling pressure (0.88 vs. 0.67; p = 0.01). The high-risk (vs. low-risk) phenogroup showed higher rates of heart failure hospitalization and/or death, even after adjusting for global left ventricular and atrial longitudinal strain (hazard ratio [HR]: 3.96; 95% confidence interval [CI]: 1.24 to 12.67; p = 0.021). Similarly, in the TOPCAT cohort, the high-risk (vs. low-risk) phenogroup showed higher rates of heart failure hospitalization or cardiac death (HR: 1.92; 95% CI: 1.16 to 3.22; p = 0.01) and higher event-free survival with spironolactone therapy (HR: 0.65; 95% CI: 0.46 to 0.90; p = 0.01). In the pooled RELAX-HF/NEAT-HFpEF cohort, the high-risk (vs. low-risk) phenogroup had a higher burden of chronic myocardial injury (p < 0.001), neurohormonal activation (p < 0.001), and lower exercise capacity (p = 0.001).
Conclusions
This publicly available DeepNN classifier can characterize the severity of diastolic dysfunction and identify a specific subgroup of patients with HFpEF who have elevated left ventricular filling pressures, biomarkers of myocardial injury and stress, and adverse events and those who are more likely to respond to spironolactone.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print
Pandey A, Kagiyama N, Yanamala N, Segar MW, ... Tokodi M, Sengupta PP
JACC Cardiovasc Imaging: 11 May 2021; epub ahead of print | PMID: 34023263
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Impact:
Abstract

A Machine-Learning Framework to Identify Distinct Phenotypes of Aortic Stenosis Severity.

Sengupta PP, Shrestha S, Kagiyama N, Hamirani Y, ... Dweck MR, Artificial Intelligence for Aortic Stenosis at Risk International Consortium
Objectives
The authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity.
Background
In AS, symptoms and adverse events develop secondarily to valvular obstruction and left ventricular decompensation. The current echocardiographic grading of AS severity focuses on the valve and is limited by diagnostic uncertainty.
Methods
Using echocardiography (ECHO) measurements (ECHO cohort, n = 1,052), we performed patient similarity analysis to derive high-severity and low-severity phenogroups of AS. We subsequently developed a supervised machine-learning classifier and validated its performance with independent markers of disease severity obtained using computed tomography (CT) (CT cohort, n = 752) and cardiovascular magnetic resonance (CMR) imaging (CMR cohort, n = 160). The classifier\'s prognostic value was further validated using clinical outcomes (aortic valve replacement [AVR] and death) observed in the ECHO and CMR cohorts.
Results
In 1,964 patients from the 3 multi-institutional cohorts, 1,346 (68%) subjects had either nonsevere or discordant AS severity. Machine learning identified 1,117 (57%) patients as having high-severity and 847 (43%) as having low-severity AS. High-severity patients in CT and CMR cohorts had higher valve calcium scores and left ventricular mass and fibrosis, respectively than the low-severity group. In the ECHO cohort, progression to AVR and progression to death in patients who did not receive AVR was faster in the high-severity group. Compared with the conventional classification of disease severity, machine-learning-based severity classification improved discrimination (integrated discrimination improvement: 0.07; 95% confidence interval: 0.02 to 0.12) and reclassification (net reclassification improvement: 0.17; 95% confidence interval: 0.11 to 0.23) for the outcome of AVR at 5 years. For both ECHO and CMR cohorts, we observed prognostic value of the machine-learning classifications for subgroups with asymptomatic, nonsevere or discordant AS.
Conclusions
Machine learning can integrate ECHO measurements to augment the classification of disease severity in most patients with AS, with major potential to optimize the timing of AVR.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 May 2021; epub ahead of print
Sengupta PP, Shrestha S, Kagiyama N, Hamirani Y, ... Dweck MR, Artificial Intelligence for Aortic Stenosis at Risk International Consortium
JACC Cardiovasc Imaging: 10 May 2021; epub ahead of print | PMID: 34023273
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Abstract

Clinical Implications of Post-Stent Optical Coherence Tomographic Findings: Severe Malapposition and Cardiac Events.

Kim BG, Kachel M, Kim JS, Guagliumi G, ... Choi D, Jang Y
Objectives
This study sought to evaluate the impact of post-stent optical coherence tomography (OCT) findings, including severe malapposition, on long-term clinical outcomes.
Background
Suboptimal OCT findings following percutaneous coronary intervention (PCI) are highly prevalent; however, their clinical implications remain controversial.
Methods
Of the patients registered in the Yonsei OCT registry, a total of 1,290 patients with 1,348 lesions, who underwent OCT immediately post-stenting, were consecutively enrolled for this study. All patients underwent implantation of drug-eluting stents. Post-stent OCT findings were assessed to identify predictors of device-oriented clinical endpoints (DoCE), including cardiac death, target vessel-related myocardial infarction (MI) or stent thrombosis, and target lesion revascularization (TLR). Significant malapposition criteria associated with major safety events (MSE) were also investigated, such as cardiac death, target vessel-related MI, or stent thrombosis.
Results
The median follow-up period was 43.0 months (interquartile range [IQR] 21.4 to 56.0 months). The incidence rates of stent edge dissection, tissue prolapse, thrombus, and malapposition after intervention were not associated with occurrence of DoCE. However, patients with significant malapposition (total malapposition volume [TMV] ≥7.0 mm3] exhibited more frequent MSE. A smaller minimal stent area (MSA) was identified as an independent predictor for DoCE (hazard ratio [HR]: 1.20 [95% confidence interval [CI]: 1.00 to 1.43]; p = 0.045). Malapposition with TMV ≥7.0 mm3 was found to be an independent predictor of MSE (HR: 6.12 [95% CI: 1.88 to 19.95]; p = 0.003). Follow-up OCT at 3, 6, or 9 months after PCI showed that post-stent TMV ≥7.0 mm3 was related to a greater occurrence of late malapposition and uncovered struts.
Conclusions
Although most suboptimal OCT findings were not associated with clinical outcomes, a smaller MSA was associated with DoCE, driven mainly by TLR, and significant malapposition with TMV ≥7.0 mm3 was associated with more MSE after PCI. (Yonsei OCT [Optical Coherence Tomography] Registry for Evaluation of Efficacy and Safety of Coronary Stenting; Yonsei OCT registry; NCT02099162).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 May 2021; epub ahead of print
Kim BG, Kachel M, Kim JS, Guagliumi G, ... Choi D, Jang Y
JACC Cardiovasc Imaging: 10 May 2021; epub ahead of print | PMID: 34023255
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Abstract

Multimodality Imaging Assessment of Myocardial Fibrosis.

Gupta S, Ge Y, Singh A, Gräni C, Kwong RY
Myocardial fibrosis, seen in ischemic and nonischemic cardiomyopathies, is associated with adverse cardiac outcomes. Noninvasive imaging plays a key role in early identification and quantification of myocardial fibrosis with the use of an expanding array of techniques including cardiac magnetic resonance, computed tomography, and nuclear imaging. This review discusses currently available noninvasive imaging techniques, provides insights into their strengths and limitations, and examines novel developments that will affect the future of noninvasive imaging of myocardial fibrosis.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 May 2021; epub ahead of print
Gupta S, Ge Y, Singh A, Gräni C, Kwong RY
JACC Cardiovasc Imaging: 10 May 2021; epub ahead of print | PMID: 34023250
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Abstract

Prospective Case-Control Study of Cardiovascular Abnormalities 6 Months Following Mild COVID-19 in Healthcare Workers.

Joy G, Artico J, Kurdi H, Seraphim A, ... Moon JC, COVIDsortium Investigators
Objectives
The purpose of this study was to detect cardiovascular changes after mild severe acute respiratory syndrome coronavirus 2 infection.
Background
Concern exists that mild coronavirus disease 2019 may cause myocardial and vascular disease.
Methods
Participants were recruited from COVIDsortium, a 3-hospital prospective study of 731 health care workers who underwent first-wave weekly symptom, polymerase chain reaction, and serology assessment over 4 months, with seroconversion in 21.5% (n = 157). At 6 months post-infection, 74 seropositive and 75 age-, sex-, and ethnicity-matched seronegative control subjects were recruited for cardiovascular phenotyping (comprehensive phantom-calibrated cardiovascular magnetic resonance and blood biomarkers). Analysis was blinded, using objective artificial intelligence analytics where available.
Results
A total of 149 subjects (mean age 37 years, range 18 to 63 years, 58% women) were recruited. Seropositive infections had been mild with case definition, noncase definition, and asymptomatic disease in 45 (61%), 18 (24%), and 11 (15%), respectively, with 1 person hospitalized (for 2 days). Between seropositive and seronegative groups, there were no differences in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T1, T2, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro-B-type natriuretic peptide). With abnormal defined by the 75 seronegatives (2 SDs from mean, e.g., ejection fraction <54%, septal T1 >1,072 ms, septal T2 >52.4 ms), individuals had abnormalities including reduced ejection fraction (n = 2, minimum 50%), T1 elevation (n = 6), T2 elevation (n = 9), late gadolinium enhancement (n = 13, median 1%, max 5% of myocardium), biomarker elevation (borderline troponin elevation in 4; all N-terminal pro-B-type natriuretic peptide normal). These were distributed equally between seropositive and seronegative individuals.
Conclusions
Cardiovascular abnormalities are no more common in seropositive versus seronegative otherwise healthy, workforce representative individuals 6 months post-mild severe acute respiratory syndrome coronavirus 2 infection.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 04 May 2021; epub ahead of print
Joy G, Artico J, Kurdi H, Seraphim A, ... Moon JC, COVIDsortium Investigators
JACC Cardiovasc Imaging: 04 May 2021; epub ahead of print | PMID: 33975819
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Abstract

Imaging Interstitial Fibrosis, Left Ventricular Remodeling, and Function in Stage A and B Heart Failure.

Pezel T, Viallon M, Croisille P, Sebbag L, ... Lima JAC, Mewton N
Myocardial interstitial fibrosis is part of the advanced disease stage of most cardiovascular pathologies. It has been characterized histologically in various disease settings from hypertensive heart disease and diabetic cardiomyopathy to severe aortic stenosis. It is also involved in the process of aging. In cardiovascular medicine, myocardial interstitial fibrosis is associated with several adverse outcomes, especially heart failure (HF) and sudden cardiac death. Until recently, clinical measures of interstitial fibrosis could only be made by invasive myocardial biopsy. The availability of cardiac magnetic resonance (CMR) T1 mapping techniques allows for the indirect measurement of interstitial space characteristics and extracellular volume size, which is closely correlated with collagen content and interstitial infiltration by amyloid and other molecules. There has been significant improvement in the accuracy and reproducibility of T1 acquisition sequences in the last decade; however, the correct use of this technique requires a solid CMR expertise in daily imaging practice. CMR has become the gold standard to assess left ventricular (LV) remodeling and functional features associated with interstitial fibrosis. These features can be detected in the early stages of HF. The main objective of this paper is to review the relevant results of preclinical and clinical observational studies that demonstrate the prognostic impact of interstitial fibrosis assessed by T1 mapping, as well as adverse left ventricular remodeling, as determinants of HF. Therefore, this review focuses on the pathological mechanisms underlying LV remodeling and interstitial fibrosis, in addition to the technical considerations involved in the assessment of interstitial LV fibrosis by CMR. It provides a thorough review of clinical evidence that demonstrates the association of interstitial fibrosis and other-CMR derived LV phenotypes with Stages A and B HF.

Copyright © 2021. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:1038-1052
Pezel T, Viallon M, Croisille P, Sebbag L, ... Lima JAC, Mewton N
JACC Cardiovasc Imaging: 29 Apr 2021; 14:1038-1052 | PMID: 32828781
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Abstract

Cardiac-MRI Predicts Clinical Worsening and Mortality in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

Alabed S, Shahin Y, Garg P, Alandejani F, ... Kiely DG, Swift AJ
Objectives
This meta-analysis evaluates assessment of pulmonary arterial hypertension (PAH), with a focus on clinical worsening and mortality.
Background
Cardiac magnetic resonance (CMR) has prognostic value in the assessment of patients with PAH. However, there are limited data on the prediction of clinical worsening, an important composite endpoint used in PAH therapy trials.
Methods
The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Science databases were searched in May 2020. All CMR studies assessing clinical worsening and the prognosis of patients with PAH were included. Pooled hazard ratios of univariate regression analyses for CMR measurements, for prediction of clinical worsening and mortality, were calculated.
Results
Twenty-two studies with 1,938 participants were included in the meta-analysis. There were 18 clinical worsening events and 8 deaths per 100 patient-years. The pooled hazard ratios show that every 1% decrease in right ventricular (RV) ejection fraction is associated with a 4.9% increase in the risk of clinical worsening over 22 months of follow-up and a 2.1% increase in the risk of death over 54 months. For every 1 ml/m2 increase in RV end-systolic volume index or RV end-diastolic volume index, the risk of clinical worsening increases by 1.3% and 1%, respectively, and the risk of mortality increases by 0.9% and 0.6%. Every 1 ml/m2 decrease in left ventricular stroke volume index or left ventricular end-diastolic volume index increased the risk of death by 2.5% and 1.8%. Left ventricular parameters were not associated with clinical worsening.
Conclusions
This review confirms CMR as a powerful prognostic marker in PAH in a large cohort of patients. In addition to confirming previous observations that RV function and RV and left ventricular volumes predict mortality, RV function and volumes also predict clinical worsening. This study provides a strong rationale for considering CMR as a clinically relevant endpoint for trials of PAH therapies.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:931-942
Alabed S, Shahin Y, Garg P, Alandejani F, ... Kiely DG, Swift AJ
JACC Cardiovasc Imaging: 29 Apr 2021; 14:931-942 | PMID: 33008758
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Abstract

The Clinical Spectrum of Myocardial Infarction and Ischemia With Nonobstructive Coronary Arteries in Women.

van den Hoogen IJ, Gianni U, Wood MJ, Taqueti VR, ... Shaw LJ, American College of Cardiology’s Cardiovascular Disease in Women Committee
Women exhibit less burden of anatomic obstructive coronary atherosclerotic disease as compared with men of the same age, but contradictorily show similar or higher cardiovascular mortality rates. The higher prevalence of nonexertional cardiac symptoms and nonobstructive coronary atherosclerotic disease in women may lead to lack of recognition and appropriate management, resulting in undertesting and undertreatment. Leaders in women\'s health from the American College of Cardiology\'s Cardiovascular Disease in Women Committee present novel imaging cases that may provoke thought regarding the broad clinical spectrum of myocardial infarction and ischemia with nonobstructive coronary arteries in women. These unique imaging approaches are based on the concept of targeting sex-specific differences in acute and stable ischemic heart disease.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:1053-1062
van den Hoogen IJ, Gianni U, Wood MJ, Taqueti VR, ... Shaw LJ, American College of Cardiology’s Cardiovascular Disease in Women Committee
JACC Cardiovasc Imaging: 29 Apr 2021; 14:1053-1062 | PMID: 33011128
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Impact:
Abstract

Warranty Period of a Calcium Score of Zero: Comprehensive Analysis From MESA.

Dzaye O, Dardari ZA, Cainzos-Achirica M, Blankstein R, ... Nasir K, Blaha MJ
Objectives
This study sought to quantify and model conversion of a normal coronary artery calcium (CAC) scan to an abnormal CAC scan.
Background
Although the absence of CAC is associated with excellent prognosis, progression to CAC >0 confers increased risk. The time interval for repeated scanning remains poorly defined.
Methods
This study included 3,116 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with baseline CAC = 0 and follow-up scans over 10 years after baseline. Prevalence of incident CAC, defined by thresholds of CAC >0, CAC >10, or CAC >100, was calculated and time to progression was derived from a Weibull parametric survival model. Warranty periods were modeled as a function of sex, race/ethnicity, cardiovascular risk, and desired yield of repeated CAC testing. Further analysis was performed of the proportion of coronary events occurring in participants with baseline CAC = 0 that preceded and followed repeated CAC testing at different time intervals.
Results
Mean participants\' age was 58 ± 9 years, with 63% women, and mean 10-year cardiovascular risk of 14%. Prevalence of CAC >0, CAC >10, and CAC >100 was 53%, 36%, and 8%, respectively, at 10 years. Using a 25% testing yield (number needed to scan [NNS] = 4), the estimated warranty period of CAC >0 varied from 3 to 7 years depending on sex and race/ethnicity. Approximately 15% of participants progressed to CAC >10 in 5 to 8 years, whereas 10-year progression to CAC >100 was rare. Presence of diabetes was associated with significantly shorter warranty period, whereas family history and smoking had small effects. A total of 19% of all 10-year coronary events occurred in CAC = 0 prior to performance of a subsequent scan at 3 to 5 years, whereas detection of new CAC >0 preceded 55% of future events and identified individuals at 3-fold higher risk of coronary events.
Conclusions
In a large population of individuals with baseline CAC = 0, study data provide a robust estimation of the CAC = 0 warranty period, considering progression to CAC >0, CAC >10, and CAC >100 and its impact on missed versus detectable 10-year coronary heart disease events. Beyond age, sex, race/ethnicity, diabetes also has a significant impact on the warranty period. The study suggests that evidence-based guidance would be to consider rescanning in 3 to 7 years depending on individual demographics and risk profile.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:990-1002
Dzaye O, Dardari ZA, Cainzos-Achirica M, Blankstein R, ... Nasir K, Blaha MJ
JACC Cardiovasc Imaging: 29 Apr 2021; 14:990-1002 | PMID: 33129734
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Abstract

Early Mechanical Alterations in Phospholamban Mutation Carriers: Identifying Subclinical Disease Before Onset of Symptoms.

Taha K, Te Rijdt WP, Verstraelen TE, Cramer MJ, ... van den Berg MP, Teske AJ
Objectives
This study aimed to explore echocardiographic characteristics of phospholamban (PLN) p.Arg14del mutation carriers to investigate whether structural and/or functional abnormalities could be identified before onset of symptoms.
Background
Carriers of the genetic PLN p.Arg14del mutation may develop arrhythmogenic and/or dilated cardiomyopathy. Overt disease is preceded by a pre-symptomatic phase of variable length in which disease expression seems to be absent.
Methods
PLN p.Arg14del mutation carriers with an available echocardiogram were included. Mutation carriers were classified as pre-symptomatic if they had no history of ventricular arrhythmias (VAs), a premature ventricular complex count of <500/24 h, and a left ventricular (LV) ejection fraction of ≥45%. In addition, we included 70 control subjects with similar age and sex distribution as the pre-symptomatic mutation carriers. Comprehensive echocardiographic analysis (including deformation imaging) was performed.
Results
The final study population consisted of 281 PLN p.Arg14del mutation carriers, 139 of whom were classified as pre-symptomatic. In comparison to control subjects, pre-symptomatic mutation carriers had lower global longitudinal strain and higher LV mechanical dispersion (both p < 0.001). In addition, post-systolic shortening (PSS) in the LV apex was observed in 43 pre-symptomatic mutation carriers (31%) and in none of the control subjects. During a median follow-up of 3.2 years (interquartile range: 2.1 to 5.6 years) in 104 pre-symptomatic mutation carriers, nonsustained VA occurred in 13 (13%). Presence of apical PSS was the strongest echocardiographic predictor of VA (multivariable hazards ratio: 5.11; 95% confidence interval [CI]: 1.37 to 19.08; p = 0.015), which resulted in a negative predictive value of 96% (95% CI: 89% to 98%) and a positive predictive value of 29% (95% CI: 21% to 40%).
Conclusions
Global and regional LV mechanical alterations in PLN p.Arg14del mutation carriers precede arrhythmic symptoms and overt structural disease. Pre-symptomatic mutation carriers with normal deformation patterns in the apex are at low risk of developing VA within 3 years, whereas mutation carriers with apical PSS appear to be at higher risk.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:885-896
Taha K, Te Rijdt WP, Verstraelen TE, Cramer MJ, ... van den Berg MP, Teske AJ
JACC Cardiovasc Imaging: 29 Apr 2021; 14:885-896 | PMID: 33221241
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Impact:
Abstract

Coronary Artery Calcium to Improve the Efficiency of Randomized Controlled Trials in Primary Cardiovascular Prevention.

Cainzos-Achirica M, Bittencourt MS, Osei AD, Haque W, ... Blaha MJ, Nasir K
Objectives
This study sought to assess the value, in terms of sample size and cost, of using the coronary artery calcium (CAC) score to enrich the study population of primary prevention randomized controlled trials (RCTs) with participants at high absolute risk of atherosclerotic cardiovascular disease (ASCVD) events.
Background
The feasibility of RCTs assessing the efficacy of novel add-on therapies for primary prevention among high-risk individuals treated with statins may be limited by sample size and cost.
Methods
We evaluated 3,075 statin-naive participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with estimated 10-year ASCVD risk of ≥7.5%. CAC of >100, CAC of >400, high sensitivity C-reactive protein levels of >2 and >3 mg/l, ankle-brachial index of <0.9, and triglyceride levels of >175 mg/dl were each evaluated as enrichment criteria on top of estimated ASCVD risk of ≥7.5%, ≥10%, ≥15% and ≥20%. For each criterion, using the observed 5-year incidence of CVD, we projected the incidence of CVD assuming a 28% relative risk reduction with high-intensity statin therapy and after addition of novel therapy with additive relative risk reductions of 15% and 25%. Sample size and cost of a hypothetical primary prevention 5-year RCT of a novel therapy on top of statins versus statins alone were then computed by using the projected incidences. Yearly costs per included participant of $6,000 to $9,000 and of $500/$600 per screened nonparticipant were assumed.
Results
CAC of >400, present in 15% to 23% participants, consistently identified the subgroups with highest 5-year incident events and outperformed the other features yielding the smallest projected sample size, ranging 33% to 58% lower than using risk estimations alone for participant selection. CAC of >400 also yielded the lowest projected RCT costs, at least $40 million lower than using risk estimations alone. CAC of >100 showed the second-best performance in most scenarios.
Conclusions
High CAC scores used as study entry criteria can improve the efficiency and feasibility of primary prevention RCTs evaluating the incremental efficacy of novel add-on therapies.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:1005-1016
Cainzos-Achirica M, Bittencourt MS, Osei AD, Haque W, ... Blaha MJ, Nasir K
JACC Cardiovasc Imaging: 29 Apr 2021; 14:1005-1016 | PMID: 33221237
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Impact:
Abstract

Mortality Prediction by Quantitative PET Perfusion Expressed as Coronary Flow Capacity With and Without Revascularization.

Gould KL, Kitkungvan D, Johnson NP, Nguyen T, ... Zhu H, Lai D
Objectives
This study sought to determine the relationship between the severity of reduced quantitative perfusion parameters and mortality with and without revascularization.
Background
The physiological mechanisms for differential mortality risk of coronary flow reserve (CFR) and coronary flow capacity (CFC) before and after revascularization are unknown.
Methods
Global and regional rest-stress (ml/min/g), CFR, their regional per-pixel combination as CFC, and relative stress in ml/min/g were measured as percent of LV in all serial routine 5,274 diagnostic PET scans with systematic follow-up over 10 years (mean 4.2 ± 2.5 years) for all-cause mortality with and without revascularization.
Results
Severely reduced CFR of 1.0 to 1.5 and stress perfusion ≤1.0 cc/min/g incurred increasing size-dependent risks that were additive because regional severely reduced CFC (CFCsevere) was associated with the highest major adverse cardiac event rate of 80% (p < 0.0001 vs. either alone) and a mortality risk of 14% (vs. 2.3% for no CFCsevere; p = 0.001). Small regions of CFCsevere ≤0.5% predicted high risk (p < 0.0001 vs. no CFCsevere) related to a wave front of border zones at risk around the small most severe center. By receiver-operating characteristic analysis, relative stress topogram maps of stress (ml/min/g) as a fraction of LV defined these border zones at risk or for mildly reduced CFC (area under the curve [AUC]: 0.69) with a reduced relative tomographic subendocardial-to-subepicardial ratio. CFCsevere incurred the highest mortality risk that was reduced by revascularization (p = 0.005 vs. no revascularization) for artery-specific stenosis not defined by global CFR or stress perfusion alone.
Conclusions
CFC is associated with the size-dependent highest mortality risk resulting from the additive risk of CFR and stress (ml/min/g) that is significantly reduced after revascularization, a finding not seen for global CFR. Small regions of CFCsevere ≤0.5% of LV also carry a high risk because of the surrounding border zones at risk defined by relative stress perfusion and a reduced relative subendocardial-to-subepicardial ratio.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:1020-1034
Gould KL, Kitkungvan D, Johnson NP, Nguyen T, ... Zhu H, Lai D
JACC Cardiovasc Imaging: 29 Apr 2021; 14:1020-1034 | PMID: 33221205
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Abstract

Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Cardiac Magnetic Resonance Study.

Habib M, Adler A, Fardfini K, Hoss S, ... Rakowski H, Chan RH
Objectives
This study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making.
Background
Myocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM.
Methods
A total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years.
Results
At the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p < 0.0001), with an average LGE progression rate of 0.5 ± 1.0%/year. LGE mass progression was correlated with higher LGE mass and extent on CMR-1 (p = 0.0017 and p = 0.007, respectively), greater indexed left ventricular (LV) mass (p < 0.0001), greater LV maximal wall thickness (p < 0.0001), apical aneurysm at CMR-1 (p < 0.0001), and lower LV ejection fraction (EF) (p = 0.029). Patients who were more likely to have a higher rate of LGE progression presented with more severe disease at baseline, characterized by LGE extent >8% of LV mass, indexed LV mass >100 g/m2, maximal wall thickness ≥20 mm, LVEF ≤60%, and apical aneurysm. There was a significant correlation between the magnitude of LGE progression and future implantation of insertable cardioverter-defibrillators (p = 0.004), EF deterioration to ≤50% (p < 0.0001), and admission for heart failure (p = 0.0006).
Conclusions
Myocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:947-958
Habib M, Adler A, Fardfini K, Hoss S, ... Rakowski H, Chan RH
JACC Cardiovasc Imaging: 29 Apr 2021; 14:947-958 | PMID: 33248971
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Abstract

High-Resolution Cardiac Magnetic Resonance Imaging Techniques for the Identification of Coronary Microvascular Dysfunction.

Rahman H, Scannell CM, Demir OM, Ryan M, ... Perera D, Chiribiri A
Objectives
This study assessed the ability to identify coronary microvascular dysfunction (CMD) in patients with angina and nonobstructive coronary artery disease (NOCAD) using high-resolution cardiac magnetic resonance (CMR) and hypothesized that quantitative perfusion techniques would have greater accuracy than visual analysis.
Background
Half of all patients with angina are found to have NOCAD, while the presence of CMD portends greater morbidity and mortality, it now represents a modifiable therapeutic target. Diagnosis currently requires invasive assessment of coronary blood flow during angiography. With greater reliance on computed tomography coronary angiography as a first-line tool to investigate angina, noninvasive tests for diagnosing CMD warrant validation.
Methods
Consecutive patients with angina and NOCAD were enrolled. Intracoronary pressure and flow measurements were acquired during rest and vasodilator-mediated hyperemia. CMR (3-T) was performed and analyzed by visual and quantitative techniques, including calculation of myocardial blood flow (MBF) during hyperemia (stress MBF), transmural myocardial perfusion reserve (MPR: MBFHYPEREMIA / MBFREST), and subendocardial MPR (MPRENDO). CMD was defined dichotomously as an invasive coronary flow reserve <2.5, with CMR readers blinded to this classification.
Results
A total of 75 patients were enrolled (57 ± 10 years of age, 81% women). Among the quantitative perfusion indices, MPRENDO and MPR had the highest accuracy (area under the curve [AUC]: 0.90 and 0.88) with high sensitivity and specificity, respectively, both superior to visual assessment (both p < 0.001). Visual assessment identified CMD with 58% accuracy (41% sensitivity and 83% specificity). Quantitative stress MBF performed similarly to visual analysis (AUC: 0.64 vs. 0.60; p = 0.69).
Conclusions
High-resolution CMR has good accuracy at detecting CMD but only when analyzed quantitatively. Although omission of rest imaging and stress-only protocols make for quicker scans, this is at the cost of accuracy compared with integrating rest and stress perfusion. Quantitative perfusion CMR has an increasingly important role in the management of patients frequently encountered with angina and NOCAD.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:978-986
Rahman H, Scannell CM, Demir OM, Ryan M, ... Perera D, Chiribiri A
JACC Cardiovasc Imaging: 29 Apr 2021; 14:978-986 | PMID: 33248969
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Abstract

Serial Cardiovascular Magnetic Resonance Strain Measurements to Identify Cardiotoxicity in Breast Cancer: Comparison With Echocardiography.

Houbois CP, Nolan M, Somerset E, Shalmon T, ... Wintersperger BJ, Thavendiranathan P
Objectives
This study sought to compare the prognostic value of cardiovascular magnetic resonance (CMR) and 2-dimensional echocardiography (2DE) derived left ventricular (LV) strain, volumes, and ejection fraction for cancer therapy-related cardiac dysfunction (CTRCD) in women with early stage breast cancer.
Background
There are limited comparative data on the association of CMR and 2DE derived strain, volumes, and LVEF with CTRCD.
Methods
A total of 125 prospectively recruited women with HER2+ early stage breast cancer receiving sequential anthracycline/trastuzumab underwent 5 serial CMR and 6 of 2DE studies before and during treatment. CMR LV volumes, left ventricular ejection fraction tagged-CMR, and feature-tracking (FT) derived global systolic longitudinal (GLS) and global circumferential strain (GCS) and 2DE-based LV volumes, function, GLS, and GCS were measured. CTRCD was defined by the cardiac review and evaluation committee criteria.
Results
Twenty-eight percent of patients developed CTRCD by CMR and 22% by 2DE. A 15% relative reduction in 2DE-GLS increased the CTRCD odds by 133% at subsequent follow-up, compared with 47%/50% by tagged-CMR GLS/GCS and 87% by FT-GCS. CMR and 2DE-LVEF and indexed left ventricular end-systolic volume (LVESVi) were also associated with subsequent CTRCD. The prognostic threshold change in CMR-left ventricular ejection fraction and FT strain for subsequent CTRCD was similar to the known minimum-detectable difference for these measures, whereas for tagged-CMR strain it was lower than the minimum-detectable difference; for 2DE, only the prognostic threshold for GLS was greater than the minimum-detectable difference. Of all strain methods, 2DE-GLS provided the highest increase in discriminatory value over baseline clinical risk factors for subsequent CTRCD. The combination of 2DE-left ventricular ejection fraction or LVESVi and strain provided greater increase in the area under the curve for subsequent CTRCD over clinical risk factors than CMR left ventricular ejection fraction or LVESVi and strain (18% to 22% vs. 9% to 14%).
Conclusions
In women with HER2+ early stage breast cancer, changes in CMR and 2DE strain, left ventricular ejection fraction, and LVESVi were prognostic for subsequent CTRCD. When LVEF can be measured precisely by CMR, FT strain may function as an additional confirmatory prognostic measure, but with 2DE, GLS is the optimal prognostic measure. (Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:962-974
Houbois CP, Nolan M, Somerset E, Shalmon T, ... Wintersperger BJ, Thavendiranathan P
JACC Cardiovasc Imaging: 29 Apr 2021; 14:962-974 | PMID: 33248962
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Abstract

Right Ventricular Functional Abnormalities in Arrhythmogenic Cardiomyopathy: Association With Life-Threatening Ventricular Arrhythmias.

Kirkels FP, Lie ØH, Cramer MJ, Chivulescu M, ... Teske AJ, Haugaa KH
Objectives
This study aimed to perform an external validation of the value of right ventricular (RV) deformation patterns and RV mechanical dispersion in patients with arrhythmogenic cardiomyopathy (AC). Secondly, this study assessed the association of these parameters with life-threatening ventricular arrhythmia (VA).
Background
Subtle RV dysfunction assessed by echocardiographic deformation imaging is valuable in AC diagnosis and risk prediction. Two different methods have emerged, the RV deformation pattern recognition and RV mechanical dispersion, but these have neither been externally validated nor compared.
Methods
We analyzed AC probands and mutation-positive family members, matched from 2 large European referral centers. We performed speckle tracking echocardiography, whereby we classified the subtricuspid deformation patterns from normal to abnormal and assessed RV mechanical dispersion from 6 segments. We defined VA as sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator therapy, or aborted cardiac arrest.
Results
We included 160 subjects, 80 from each center (43% proband, 55% women, age 41 ± 17 years). VA had occurred in 47 (29%) subjects. In both cohorts, patients with a history of VA showed abnormal deformation patterns (96% and 100%) and had greater RV mechanical dispersion (53 ± 30 ms vs. 30 ± 21 ms; p < 0.001 for the total cohort). Both parameters were independently associated to VA (adjusted odds ratio: 2.71 [95% confidence interval: 1.47 to 5.00] per class step-up, and 1.26 [95% confidence interval: 1.07 to 1.49]/10 ms, respectively). The association with VA significantly improved when adding RV mechanical dispersion to pattern recognition (net reclassification improvement 0.42; p = 0.02 and integrated diagnostic improvement 0.06; p = 0.01).
Conclusions
We externally validated 2 RV dysfunction parameters in AC. Adding RV mechanical dispersion to RV deformation patterns significantly improved the association with life-threatening VA, indicating incremental value.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:900-910
Kirkels FP, Lie ØH, Cramer MJ, Chivulescu M, ... Teske AJ, Haugaa KH
JACC Cardiovasc Imaging: 29 Apr 2021; 14:900-910 | PMID: 33582062
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Abstract

Prognosis of Severe Low-Flow, Low-Gradient Aortic Stenosis by Stroke Volume Index and Transvalvular Flow Rate.

Sen J, Huynh Q, Stub D, Neil C, Marwick TH
Objectives
This study determined whether flow state classified by stroke volume index (SVi) or transvalvular flow rate (FR) improved risk stratification of all-cause mortality, hospitalization due to heart failure, and aortic valvular interventions for patients with severe aortic stenosis (AS).
Background
SVi is a widely accepted classification for flow state in severe low-flow, low-gradient (LFLG) AS. Recent studies suggest that FR more closely approximates true AS severity and provides more useful prognostication than SVi.
Methods
Patients with severe AS over a 7-year period were subclassified by echocardiographic parameters. LFLG-AS was defined as severe AS (aortic valve area index [AVAi]: <0.6 cm2/m2), with a mean transvalvular pressure gradient of <40 mm Hg in the setting of low flow state: SVi of <35 ml/m2 and/or FR of <200 ml/s and subclassified into preserved (≥50%; paradoxical) or reduced (<50%; classical) left ventricular ejection fraction (LVEF).
Results
Among 621 consecutive patients with severe AS, the proportions of patients classified as LFLG-AS were different between SVi and FR (p < 0.001). Classification using SVi, FR, and LVEF was a strong predictor of the composite endpoint at the 2-year follow-up. The addition of SVi to the echocardiographic and clinical model provided significant improvement in reclassification (net reclassification improvement: 0.089; 95% confidence interval [CI]: 0.045 to 0.133; p = 0.04), whereas addition of FR did not (net reclassification improvement: 0.061; 95% CI: 0.016 to 0.106; p = 0.17). C-statistics indicated improved risk discrimination when AVAi, LVEF, and SVi or FR were added as predictive variables to the clinical model (p = 0.006).
Conclusions
Low SVi or FR was associated with adverse cardiovascular events and showed improvement in discrimination, but only SVi, not FR, significantly improved risk reclassification compared to other conventional clinical and echocardiographic predictors. This suggests that FR is not superior to SVi in distinguishing true severe from pseudosevere forms of AS and identification of patients with LFLG-AS who have worse outcomes.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Apr 2021; 14:915-927
Sen J, Huynh Q, Stub D, Neil C, Marwick TH
JACC Cardiovasc Imaging: 29 Apr 2021; 14:915-927 | PMID: 33744157
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Abstract

Prognostic Value of RCA Pericoronary Adipose Tissue CT-Attenuation Beyond High-Risk Plaques, Plaque Volume, and Ischemia.

van Diemen PA, Bom MJ, Driessen RS, Schumacher SP, ... Danad I, Knaapen P
Objectives
This study was designed to assess the prognostic value of pericoronary adipose tissue (PCAT) computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)-derived plaque volume and positron emission tomography determined ischemia.
Background
Inflammation plays a crucial role in atherosclerosis. PCATa has been shown to assess coronary-specific inflammation and is of prognostic value in patients with suspected coronary artery disease (CAD).
Methods
A total of 539 patients who underwent CCTA and [15O]H2O PET perfusion imaging because of suspected CAD were included. Imaging assessment included coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRPs), total plaque volume (TPV), calcified/noncalcified plaque volume (CPV/NCPV), PCATa, and myocardial ischemia. The endpoint was a composite of death and nonfatal myocardial infarction. Prognostic thresholds were determined for quantitative CCTA variables.
Results
During a median follow-up of 5.0 (interquartile range: 4.7 to 5.0) years, 33 events occured. CACS >59 Agatston units, obstructive CAD, HRPs, TPV >220 mm3, CPV >110 mm3, NCPV >85 mm3, and myocardial ischemia were associated with shorter time to the endpoint with unadujsted hazard ratios (HRs) of 4.17 (95% confidence interval [CI]: 1.80 to 9.64), 4.88 (95% CI: 1.88 to 12.65), 3.41 (95% CI: 1.72 to 6.75), 7.91 (95% CI: 3.05 to 20.49), 5.82 (95% CI: 2.40 to 14.10), 8.07 (95% CI: 3.33 to 19.55), and 4.25 (95% CI: 1.84 to 9.78), respectively (p < 0.05 for all). Right coronary artery (RCA) PCATa above scanner specific thresholds was associated with worse prognosis (unadjusted HR: 2.84; 95% CI: 1.44 to 5.63; p = 0.003), whereas left anterior descending artery and circumflex artery PCATa were not related to outcome. RCA PCATa above scanner specific thresholds retained is prognostic value adjusted for imaging variables and clincal chacteristics associated with the endpoint (adjusted HR: 2.45; 95% CI: 1.23 to 4.93; p = 0.011).
Conclusions
Parameters associated with atherosclerotic burden and ischemia were more strongly associated with outcome than RCA PCATa. Nonetheless, RCA PCATa was of prognostic value beyond clinical characteristics, CACS, obstructive CAD, HRPs, TPV, CPV, NCPV, and ischemia.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 26 Apr 2021; epub ahead of print
van Diemen PA, Bom MJ, Driessen RS, Schumacher SP, ... Danad I, Knaapen P
JACC Cardiovasc Imaging: 26 Apr 2021; epub ahead of print | PMID: 33958312
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This program is still in alpha version.