Journal: JACC Cardiovasc Imaging

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Abstract

Insufficient Mitral Leaflet Remodeling in Relation to Annular Dilation and Risk of Residual Mitral Regurgitation After MitraClip Implantation.

Hirasawa K, Namazi F, Milhorini Pio S, Vo NM, ... Bax JJ, Delgado V
Objectives
The purpose of this study was to determine whether the mitral valve (MV) total leaflet area (TLA)-to-mitral annular area (MAA) (TLA/MAA) ratio measured using 3-dimensional (3D) transesophageal echocardiography (TEE) was associated with residual mitral regurgitation (MR) after MitraClip implantation in patients with secondary MR.
Background
The factors influencing the results of MitraClip implantation for secondary MR are controversial. This study hypothesized that insufficient remodeling of the mitral leaflets relative to the annular dilation may be associated with significant MR after MitraClip implantation.
Methods
This study included patients with secondary MR treated with MitraClips. Using 3D TEE dataset, the TLA in diastole and MAA in systole were measured with dedicated software.
Results
In a total cohort of 119 patients (mean age 74 ± 9 years; 61% male), significant residual MR (≥2+) was present in 43 patients (36%). In patients with significant residual MR, MAA was greater than in patients without residual MR (10.7 ± 2.4 cm vs. 9.0 ± 2.1 cm; p < 0.001) whereas no significant difference was observed in TLA (12.2 ± 2.6 cm vs. 12.0 ± 2.9 cm; p = 0.836). TLA/MAA ratio was lower in patients with significant residual MR as compared to their counterparts (1.14 ± 0.15 vs. 1.34 ± 0.16; p < 0.001), suggesting insufficient leaflet remodeling relative to annular dilation. On receiver-operating characteristic curve analysis, the TLA/MAA ratio had better discriminative power to identify patients who will have significant residual MR compared to MAA alone (area under the curve [AUC]: 0.830 vs. 0.723; p = 0.049).
Conclusions
In patients with secondary MR, insufficient mitral leaflet remodeling relative to the annulus dilation, as reflected by a lower TLA/MAA ratio, is associated with significant residual MR after MitraClip implantation.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print
Hirasawa K, Namazi F, Milhorini Pio S, Vo NM, ... Bax JJ, Delgado V
JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print | PMID: 33129743
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Abstract

Association of Asymptomatic Diastolic Dysfunction Assessed by Left Atrial Strain With Incident Heart Failure.

Potter EL, Ramkumar S, Kawakami H, Yang H, ... Negishi T, Marwick TH
Objectives
This study is to establish the association of left atrial reservoir strain (LARS) with incident heart failure (HF), and the impact of substituting LARS for left atrial (LA) volume index (LAVI) in diastolic assessment.
Background
LARS measures passive LA stretch and is a sensitive marker of left ventricular diastolic dysfunction (DD). The potential contribution of LARS to diastolic assessment is unclear.
Methods
Baseline clinical and echocardiographic assessments were obtained in 758 asymptomatic, community-dwelling elderly subjects (age 70 [interquartile range: 67 to 74] years, 53% women) with nonischemic HF risk factors. LARS-defined DD (LARS-DD) was assessed by speckle-tracking echocardiography, and grades were assigned as normal (>35%), grade 1 (25% to 35%) and grade 2 (≤24%). DD grade using current recommendations was compared with grading using LARS <24% in place of LAVI >34 ml/m. Patients were followed for up to 2 years for incident HF.
Results
LA strain analysis was feasible in 738 (97%) patients; average LARS was 39% (range 34% to 43%). Incident HF was associated with LARS-DD grade; 8 (36%) of those had grade 2+, 14 (10%) had grade 1, and 39 (9%) had normal function (p < 0.001). LARS-DD grade 2+ predicted incident HF after adjustment for clinical and echocardiographic markers (adjusted hazard ratio: 2.5; 95% confidence interval: 1.02 to 6.3; p = 0.049); there was no significant HF risk associated with LARS-DD grade 1. Dichotomized abnormal LARS <24% had an adjusted hazard ratio of 2.9 (95% confidence interval: 1.25 to 6.79; p = 0.013). Substituting LARS for LAVI provided a 75% reduction in indeterminate diastolic function; all were recategorized as normal. There was no increased risk associated normal diastolic function by this grading compared to conventional grading (C-statistic = 0.76 for both models).
Conclusions
LARS-DD grade 2+ is associated with incident HF in the elderly, independent of LAVI. The substitution of LARS for LAVI reduces the number of indeterminate cases without impacting prognosis in normal diastolic function and grade 1 DD.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Oct 2020; 13:2316-2326
Potter EL, Ramkumar S, Kawakami H, Yang H, ... Negishi T, Marwick TH
JACC Cardiovasc Imaging: 30 Oct 2020; 13:2316-2326 | PMID: 32771583
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Abstract

Prognostic Value of Computed Tomography-Derived Extracellular Volume in TAVR Patients With Low-Flow Low-Gradient Aortic Stenosis.

Tamarappoo B, Han D, Tyler J, Chakravarty T, ... Friedman J, Makkar R
Objectives
The association between extracellular volume (ECV) measured by computed tomography angiography (CTA) and clinical outcomes was evaluated in low-flow low-gradient (LFLG) aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR).
Background
Patients with LFLG AS comprise a high-risk group with respect to clinical outcomes. Although ECV, a marker of myocardial fibrosis, is traditionally measured with cardiac magnetic resonance, it can also be measured using cardiac CTA. The authors hypothesized that in LFLG AS, increased ECV may be associated with adverse clinical outcomes.
Methods
In 150 LFLG patients with AS who underwent TAVR, ECV was quantified using pre-TAVR CTA. Echocardiographic and clinical information including all-cause death and heart failure rehospitalization (HFH) was obtained from electronic medical records. A Cox proportional hazards model was used to evaluate the association between ECV and death+HFH.
Results
During a median follow-up of 13.9 months (range 0.07 to 28.9 months), there were 31 death+HFH events (21%). Patients who experienced death+HFH had a greater median Society of Thoracic Surgery score (9.9 vs. 4.7; p < 0.01), lower left ventricular ejection fraction (42.3 ± 20.2% vs. 52.7 ± 17.2%; p < 0.01), lower mean transvalvular gradient (24.9 ± 8.9 mm Hg vs. 28.1 ± 7.3 mm Hg; p = 0.04) and increased mean ECV (35.5 ± 9.6% vs. 29.9 ± 8.2%; p < 0.01) compared with patients who did not experience death+HFH. In a multivariable Cox proportional hazards model, increase in ECV was associated with increase in death+HFH, (hazard ratio per 1% increase: 1.04, 95% confidence interval: 1.01 to 1.09; p < 0.01).
Conclusions
In patients with LFLG AS, CTA measured increase in ECV is associated with increased risk of adverse clinical outcomes post-TAVR and may thus serve as a useful noninvasive marker for prognostication.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print
Tamarappoo B, Han D, Tyler J, Chakravarty T, ... Friedman J, Makkar R
JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print | PMID: 33129731
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Abstract

Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging.

Huang L, Zhao P, Tang D, Zhu T, ... Tao Q, Xia L
Objectives
This study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR).
Background
Myocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients\' recovery from COVID-19.
Methods
Twenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Edema ratio and LGE were assessed in post-COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls.
Results
Fifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs. 38.1 ms ± 2.4 vs. 39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs. 24.8% [23.1% to 25.4%] vs. 23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively).
Conclusions
Cardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.

© 2020 by the American College of Cardiology Foundation. Published by Elsevier.

JACC Cardiovasc Imaging: 30 Oct 2020; 13:2330-2339
Huang L, Zhao P, Tang D, Zhu T, ... Tao Q, Xia L
JACC Cardiovasc Imaging: 30 Oct 2020; 13:2330-2339 | PMID: 32763118
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Abstract

Machine Learning Adds to Clinical and CAC Assessments in Predicting 10-Year CHD and CVD Deaths.

Nakanishi R, Slomka PJ, Rios R, Betancur J, ... Budoff MJ, Berman DS
Objectives
The aim of this study was to evaluate whether machine learning (ML) of noncontrast computed tomographic (CT) and clinical variables improves the prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) deaths compared with coronary artery calcium (CAC) Agatston scoring and clinical data.
Background
The CAC score provides a measure of the global burden of coronary atherosclerosis, and its long-term prognostic utility has been consistently shown to have incremental value over clinical risk assessment. However, current approaches fail to integrate all available CT and clinical variables for comprehensive risk assessment.
Methods
The study included data from 66,636 asymptomatic subjects (mean age 54 ± 11 years, 67% men) without established ASCVD undergoing CAC scanning and followed for cardiovascular disease (CVD) and CHD deaths at 10 years. Clinical risk assessment incorporated the ASCVD risk score. For ML, an ensemble boosting approach was used to fit a predictive classifier for outcomes, followed by automated feature selection using information gain ratio. The model-building process incorporated all available clinical and CT data, including the CAC score; the number, volume, and density of CAC plaques; and extracoronary scores; comprising a total of 77 variables. The overall proposed model (ML all) was evaluated using a 10-fold cross-validation framework on the population data and area under the curve (AUC) as metrics. The prediction performance was also compared with 2 traditional scores (ASCVD risk and CAC score) and 2 additional models that were trained using all the clinical data (ML clinical) and CT variables (ML CT).
Results
The AUC by ML all (0.845) for predicting CVD death was superior compared with those obtained by ASCVD risk alone (0.821), CAC score alone (0.781), and ML CT alone (0.804) (p < 0.001 for all). Similarly, for predicting CHD death, AUC by ML all (0.860) was superior to the other analyses (0.835 for ASCVD risk, 0.816 for CAC, and 0.827 for ML CT; p < 0.001).
Conclusions
The comprehensive ML model was superior to ASCVD risk, CAC score, and an ML model fitted using CT variables alone in the prediction of both CVD and CHD death.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print
Nakanishi R, Slomka PJ, Rios R, Betancur J, ... Budoff MJ, Berman DS
JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print | PMID: 33129741
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Abstract

Diagnostic Accuracy of Cardiac Computed Tomography and 18-F Fluorodeoxyglucose Positron Emission Tomography in Cardiac Masses.

D\'Angelo EC, Paolisso P, Vitale G, Foà A, ... Pizzi C, Galiè N
Objectives
This study sought to assess the diagnostic accuracy of cardiac computed tomography (CT) and F-fluorodeoxyglucose (F-FDG) with positron emission tomography/computed tomography (PET/CT) in defining the nature of cardiac masses.
Background
The diagnostic accuracy of cardiac CT and F-FDG PET/CT in identifying the nature of cardiac masses has been analyzed to date only in small samples.
Methods
Of 223 patients with echocardiographically diagnosed cardiac masses, a cohort of 60 cases who underwent cardiac CT and F-FDG PET/CT was selected. All masses had histological confirmation, except for a minority of thrombotic formations. For each mass, 8 morphological CT signs, standardized uptake value (SUV, SUV), metabolic tumor volume, and total lesion glycolysis in F-FDG PET were used as diagnostic markers.
Results
Irregular tumor margins, pericardial effusion, invasion, solid nature, mass diameter, CT contrast uptake, and pre-contrast characteristics were strongly associated with the malignant nature of masses. The coexistence of at least 5 CT signs perfectly identified malignant masses, whereas the detection of 3 or 4 CT signs did not accurately discriminate the masses\' nature. The mean SUV, SUV, metabolic tumor volume, and total lesion glycolysis values were significantly higher in malignant than in benign masses. The diagnostic accuracy of SUV, metabolic tumor volume, and total lesion glycolysis F-FDG PET/CT parameters was excellent in detecting malignant masses. Among patients with 3 or 4 pathological CT signs, the presence of at least 1 abnormal F-FDG PET/CT parameter significantly increased the identification of malignancies.
Conclusions
Cardiac CT is a powerful tool to diagnose cardiac masses as the number of abnormal signs was found to correlate with the lesions\' nature. Similarly, F-FDG PET/CT accurately identified malignant masses and contributed with additional valuable information in diagnostic uncertainties after cardiac CT. These imaging tools should be performed in specific clinical settings such as involvement of great vessels or for disease-staging purposes.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Oct 2020; 13:2400-2411
D'Angelo EC, Paolisso P, Vitale G, Foà A, ... Pizzi C, Galiè N
JACC Cardiovasc Imaging: 30 Oct 2020; 13:2400-2411 | PMID: 32563654
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Abstract

Defining Myocardial Abnormalities Across the Stages of Chronic Kidney Disease: A Cardiac Magnetic Resonance Imaging Study.

Hayer MK, Radhakrishnan A, Price AM, Liu B, ... Edwards NC,
Objectives
A proof of concept cross-sectional study investigating changes in myocardial abnormalities across stages of chronic kidney disease (CKD). Characterizing noninvasive markers of myocardial fibrosis on cardiac magnetic resonance, echocardiography, and correlating with biomarkers of fibrosis, myocardial injury, and functional correlates including exercise tolerance.
Background
CKD is associated with an increased risk of cardiovascular death. Much of the excess mortality is attributed to uremic cardiomyopathy, defined by increased left ventricular hypertrophy, myocardial dysfunction, and fibrosis. The prevalence of these abnormalities across stages of CKD and their impact on cardiovascular performance is unknown.
Methods
A total of 134 nondiabetic, pre-dialysis subjects with CKD stages 2 to 5 without myocardial ischemia underwent cardiac magnetic resonance (1.5-T) including; T mapping (biomarker of diffuse fibrosis), T mapping (edema), late gadolinium enhancement, and assessment of aortic distensibility. Serum biomarkers including collagen turnover (P1NP, P3NP), troponin T, and N-terminal pro-B-type natriuretic peptide were measured. Cardiovascular performance was quantified by bicycle cardiopulmonary exercise testing and echocardiography.
Results
Native myocardial T times increased incrementally from stage 2 to 5 (966 ± 21 ms vs. 994 ± 33 ms; p < 0.001), independent of hypertension and aortic distensibility. Left atrial volume, E/e\', N-terminal pro-B-type natriuretic peptide, P1NP, and P3NP increased with CKD stage (p < 0.05), while effort tolerance (% predicted VOPeak, %VOVT) decreased (p < 0.001). In multivariable linear regression models, estimated glomerular filtration rate was the strongest predictor of native myocardial T time (p < 0.001). Native myocardial T time, left atrial dilatation, and high-sensitivity troponin T were independent predictors of % predicted VOPeak (p < 0.001).
Conclusions
Imaging and serum biomarkers of myocardial fibrosis increase with advancing CKD independent of effects of left ventricular afterload and might be a key intermediary in the development of uremic cardiomyopathy. Further studies are needed to determine whether these changes lead to the increased rates of heart failure and death in CKD. (Left Ventricular Fibrosis in Chronic Kidney Disease [FibroCKD]; NCT03176862).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Oct 2020; 13:2357-2367
Hayer MK, Radhakrishnan A, Price AM, Liu B, ... Edwards NC,
JACC Cardiovasc Imaging: 30 Oct 2020; 13:2357-2367 | PMID: 32682713
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Abstract

Prognostic Value of Right Ventricular Longitudinal Strain in Patients With COVID-19.

Li Y, Li H, Zhu S, Xie Y, ... Zhang L, Xie M
Objectives
The aim of this study was to investigate whether right ventricular longitudinal strain (RVLS) was independently predictive of higher mortality in patients with coronavirus disease-2019 (COVID-19).
Background
RVLS obtained from 2-dimensional speckle-tracking echocardiography has been recently demonstrated to be a more accurate and sensitive tool to estimate right ventricular (RV) function. The prognostic value of RVLS in patients with COVID-19 remains unknown.
Methods
One hundred twenty consecutive patients with COVID-19 who underwent echocardiographic examinations were enrolled in our study. Conventional RV functional parameters, including RV fractional area change, tricuspid annular plane systolic excursion, and tricuspid tissue Doppler annular velocity, were obtained. RVLS was determined using 2-dimensional speckle-tracking echocardiography. RV function was categorized in tertiles of RVLS.
Results
Compared with patients in the highest RVLS tertile, those in the lowest tertile were more likely to have higher heart rate; elevated levels of D-dimer and C-reactive protein; more high-flow oxygen and invasive mechanical ventilation therapy; higher incidence of acute heart injury, acute respiratory distress syndrome, and deep vein thrombosis; and higher mortality. After a median follow-up period of 51 days, 18 patients died. Compared with survivors, nonsurvivors displayed enlarged right heart chambers, diminished RV function, and elevated pulmonary artery systolic pressure. Male sex, acute respiratory distress syndrome, RVLS, RV fractional area change, and tricuspid annular plane systolic excursion were significant univariate predictors of higher risk for mortality (p < 0.05 for all). A Cox model using RVLS (hazard ratio: 1.33; 95% confidence interval [CI]: 1.15 to 1.53; p < 0.001; Akaike information criterion = 129; C-index = 0.89) was found to predict higher mortality more accurately than a model with RV fractional area change (Akaike information criterion = 142, C-index = 0.84) and tricuspid annular plane systolic excursion (Akaike information criterion = 144, C-index = 0.83). The best cutoff value of RVLS for prediction of outcome was -23% (AUC: 0.87; p < 0.001; sensitivity, 94.4%; specificity, 64.7%).
Conclusions
RVLS is a powerful predictor of higher mortality in patients with COVID-19. These results support the application of RVLS to identify higher risk patients with COVID-19.

© 2020 by the American College of Cardiology Foundation. Published by Elsevier.

JACC Cardiovasc Imaging: 30 Oct 2020; 13:2287-2299
Li Y, Li H, Zhu S, Xie Y, ... Zhang L, Xie M
JACC Cardiovasc Imaging: 30 Oct 2020; 13:2287-2299 | PMID: 32654963
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Abstract

Extracellular Volume and Global Longitudinal Strain Both Associate With Outcomes But Correlate Minimally.

Fröjdh F, Fridman Y, Bering P, Sayeed A, ... Ugander M, Schelbert EB
Objectives
This study examined how extracellular volume (ECV) and global longitudinal strain (GLS) relate to each other and to outcomes.
Background
Among myriad changes occurring in diseased myocardium, left ventricular imaging metrics of either the interstitium (e.g., ECV) or contractile function (e.g., GLS) may consistently associate with adverse outcomes yet correlate minimally with each other. This scenario suggests that ECV and GLS potentially represent distinct domains of cardiac vulnerability.
Methods
The study included 1,578 patients referred for cardiovascular magnetic resonance (CMR) without amyloidosis, and it quantified how ECV associated with GLS in linear regression models. ECV and GLS were then compared in their associations with incident outcomes (death and hospitalization for heart failure).
Results
ECV and GLS correlated minimally (R = 0.04). Over a median follow-up of 5.6 years, 339 patients experienced adverse events (149 hospitalizations for heart failure, 253 deaths, and 63 with both). GLS (univariable hazard ratio: 2.07 per 5% increment; 95% CI: 1.86 to 2.29) and ECV (univariable hazard ratio: 1.66 per 4% increment; 95% CI: 1.51 to 1.82) were principal variables associating with outcomes in univariable and multivariable Cox regression models. Similar results were observed in several clinically important subgroups. In the whole cohort, ECV added prognostic value beyond GLS in univariable and multivariable Cox regression models.
Conclusions
GLS and ECV may represent principal but distinct domains of cardiac vulnerability, perhaps reflecting their distinct cellular origins. Whether combining ECV and GLS may advance pathophysiological understanding for a given patient, optimize risk stratification, and foster personalized medicine by targeted therapeutics requires further investigation.

Copyright © 2020 American College of Cardiology Foundation. All rights reserved.

JACC Cardiovasc Imaging: 30 Oct 2020; 13:2343-2354
Fröjdh F, Fridman Y, Bering P, Sayeed A, ... Ugander M, Schelbert EB
JACC Cardiovasc Imaging: 30 Oct 2020; 13:2343-2354 | PMID: 32563637
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Abstract

Reduction in CMR Derived Extracellular Volume with Patisiran Indicates Cardiac Amyloid Regression.

Fontana M, Martinez-Naharro A, Chacko L, Rowczenio D, ... Hawkins PN, Gillmore JD
Objectives
The purpose of this study was to determine the effect of patisiran on the cardiac amyloid load as measured by cardiac magnetic resonance and extracellular volume (ECV) mapping in cases of transthyretin cardiomyopathy (ATTR-CM).
Background
Administration of patisiran, a TTR-specific small interfering RNA (siRNA), has been shown to benefit neuropathy in patients with hereditary ATTR amyloidosis, but its effect on ATTR-CM remains uncertain.
Methods
Patisiran was administered to 16 patients with hereditary ATTR-CM who underwent assessment protocols at the UK National Amyloidosis Centre. Twelve of those patients concomitantly received diflunisal as a \"TTR-stabilizing\" drug. Patients underwent serial monitoring using cardiac magnetic resonance, echocardiography, cardiac biomarkers, bone scintigraphy, and 6-min walk tests (6MWTs). Findings of amyloid types and extracellular volumes were compared with those of 16 patients who were retrospectively matched based on cardiac magnetic resonance results.
Results
Patisiran was well tolerated. Median serum TTR knockdown among treated patients was 86% (interquartile range [IQR]: 82% to 90%). A total of 82% of cases showed >80% knockdown. Patisiran therapy was typically associated with a reduction in ECV (adjusted mean difference between groups: -6.2% [95% confidence interval [CI]: -9.5% to -3.0%]; p = 0.001) accompanied by a fall in N-terminal pro-B-type natriuretic peptide concentrations (adjusted mean difference between groups: -1,342 ng/l [95% CI: -2,364 to -322]; p = 0.012); an increase in 6MWT distances (adjusted mean differences between groups: 169 m [95% CI: 57 to 2,80]; p = 0.004) after 12 months of therapy; and a median reduction in cardiac uptake by bone scintigraphy of 19.6% (IQR: 9.8% to 27.1%).
Conclusions
Reductions in ECV by cardiac magnetic resonance provided evidence for ATTR cardiac amyloid regression in a proportion of patients receiving patisiran.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print
Fontana M, Martinez-Naharro A, Chacko L, Rowczenio D, ... Hawkins PN, Gillmore JD
JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print | PMID: 33129740
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Abstract

Empagliflozin Ameliorates Diastolic Dysfunction and Left Ventricular Fibrosis/Stiffness in Nondiabetic Heart Failure: A Multimodality Study.

Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, Garcia-Ropero A, ... Fuster V, Badimon JJ
Objectives
The purpose of this study was to investigate the effect of empagliflozin on diastolic function in a nondiabetic heart failure with reduced ejection fraction (HFrEF) scenario and on the pathways causing diastolic dysfunction.
Background
This group demonstrated that empagliflozin ameliorates adverse cardiac remodeling, enhances myocardial energetics, and improves left ventricular systolic function in a nondiabetic porcine model of HF. Whether empagliflozin also improves diastolic function remains unknown. Hypothetically, empagliflozin would improve diastolic function in HF mediated both by a reduction in interstitial myocardial fibrosis and an improvement in cardiomyocyte stiffness (titin phosphorylation).
Methods
HF was induced in nondiabetic pigs by 2-h balloon occlusion of proximal left anterior descending artery. Animals were randomized to empagliflozin or placebo for 2 months. Cardiac function was evaluated with cardiac magnetic resonance (CMR), 3-dimensional echocardiography, and invasive hemodynamics. In vitro relaxation of cardiomyocytes was studied in primary culture. Myocardial samples were obtained for histological and molecular evaluation. Myocardial metabolite consumption was analyzed by simultaneous blood sampling from coronary artery and coronary sinus.
Results
Despite similar initial ischemic myocardial injury, the empagliflozin group showed significantly improved diastolic function at 2 months, assessed by conventional echocardiography (higher e\' and color M-mode propagation velocity, lower E/e\' ratio, myocardial performance Tei index, isovolumic relaxation time, and left atrial size), echocardiography-derived strain imaging (strain imaging diastolic index, strain rate at at isovolumic relaxation time and during early diastole, and untwisting), and CMR (higher peak filling rate, larger first filling volume). Invasive hemodynamics confirmed improved diastolic function with empagliflozin (better peak LV pressure rate of decay (-dP/dt), shorter Tau, lower end-diastolic pressure-volume relationship (EDPVR), and reduced filling pressures). Empagliflozin reduced interstitial myocardial fibrosis at the imaging, histological and molecular level. Empagliflozin improved nitric oxide signaling (endothelial nitric oxide synthetase [eNOS] activity, nitric oxide [NO] availability, cyclic guanosine monophosphate (cGMP) content, protein kinase G [PKG] signaling) and enhanced titin phosphorylation (which is responsible for cardiomyocyte stiffness). Indeed, isolated cardiomyocytes exhibited better relaxation in empagliflozin-treated animals. Myocardial consumption of glucose and ketone bodies negatively and positively correlated with diastolic function, respectively.
Conclusions
Empagliflozin ameliorates diastolic function in a nondiabetic HF porcine model, mitigates histological and molecular remodeling, and reduces both left ventricle and cardiomyocyte stiffness.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print
Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, Garcia-Ropero A, ... Fuster V, Badimon JJ
JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print | PMID: 33129742
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Abstract

Sex Differences in Compositional Plaque Volume Progression in Patients With Coronary Artery Disease.

Lee SE, Sung JM, Andreini D, Al-Mallah MH, ... Min JK, Chang HJ
Objectives
This study sought to explore sex-based differences in total and compositional plaque volume (PV) progression.
Background
It is unclear whether sex has an impact on PV progression in patients with coronary artery disease (CAD).
Methods
The study analyzed a prospective multinational registry of consecutive patients with suspected CAD who underwent 2 or more clinically indicated coronary computed tomography angiography (CTA) at ≥2-year intervals. Total and compositional PV at baseline and follow-up were quantitatively analyzed and normalized using the analyzed total vessel length. Multivariate linear regression models were constructed.
Results
Of the 1,255 patients included (median coronary CTA interval 3.8 years), 543 were women and 712 were men. Women were older (62 ± 9 years of age vs. 59 ± 9 years of age; p < 0.001) and had higher total cholesterol levels (195 ± 41 mg/dl vs. 187 ± 39 mg/dl; p = 0.002). Prevalence of hypertension, diabetes, and family history of CAD were not different (all p > 0.05). At baseline, men possessed greater total PV (31.3 mm [interquartile range (IQR): 0 to 121.8 mm] vs. 56.7 mm [IQR: 6.8 to 152.1 mm] p = 0.005), and there was an approximately 9-year delay in women in developing total PV than in men. The prevalence of high-risk plaques was greater in men than women (31% vs. 20%; p < 0.001). In multivariate analysis, after adjusting for age, clinical risk factors, medication use, and total PV at baseline, despite similar total PV progression rates, female sex was associated with greater calcified PV progression (β = 2.83; p = 0.004) but slower noncalcified PV progression (β = -3.39; p = 0.008) and less development of high-risk plaques (β = -0.18; p = 0.049) than in men.
Conclusions
The compositional PV progression differed according to sex, suggesting that comprehensive plaque evaluation may contribute to further refining of risk stratification according to sex. (NCT02803411).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Oct 2020; 13:2386-2396
Lee SE, Sung JM, Andreini D, Al-Mallah MH, ... Min JK, Chang HJ
JACC Cardiovasc Imaging: 30 Oct 2020; 13:2386-2396 | PMID: 32828763
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Abstract

Myocardial Infarction Associates With a Distinct Pericoronary Adipose Tissue Radiomic Phenotype: A Prospective Case-Control Study.

Lin A, Kolossváry M, Yuvaraj J, Cadet S, ... Wong DTL, Dey D
Objectives
This study sought to determine whether coronary computed tomography angiography (CCTA)-based radiomic analysis of pericoronary adipose tissue (PCAT) could distinguish patients with acute myocardial infarction (MI) from patients with stable or no coronary artery disease (CAD).
Background
Imaging of PCAT with CCTA enables detection of coronary inflammation. Radiomics involves extracting quantitative features from medical images to create big data and identify novel imaging biomarkers.
Methods
In a prospective case-control study, 60 patients with acute MI underwent CCTA within 48 h of admission, before invasive angiography. These subjects were matched to patients with stable CAD (n = 60) and controls with no CAD (n = 60) by age, sex, risk factors, medications, and CT tube voltage. PCAT was segmented around the proximal right coronary artery (RCA) in all patients and around culprit and nonculprit lesions in patients with MI. PCAT segmentations were analyzed using Radiomics Image Analysis software.
Results
Of 1,103 calculated radiomic parameters, 20.3% differed significantly between MI patients and controls, and 16.5% differed between patients with MI and stable CAD (critical p < 0.0006); whereas none differed between patients with stable CAD and controls. On cluster analysis, the most significant radiomic parameters were texture or geometry based. At 6 months post-MI, there was no significant change in the PCAT radiomic profile around the proximal RCA or nonculprit lesions. Using machine learning (XGBoost), a model integrating clinical features (risk factors, serum lipids, high-sensitivity C-reactive protein), PCAT attenuation, and radiomic parameters provided superior discrimination of acute MI (area under the receiver operator characteristic curve [AUC]: 0.87) compared with a model with clinical features and PCAT attenuation (AUC: 0.77; p = 0.001) or clinical features alone (AUC: 0.76; p < 0.001).
Conclusions
Patients with acute MI have a distinct PCAT radiomic phenotype compared with patients with stable or no CAD. Using machine learning, a radiomics-based model outperforms a PCAT attenuation-based model in accurately identifying patients with MI.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Oct 2020; 13:2371-2383
Lin A, Kolossváry M, Yuvaraj J, Cadet S, ... Wong DTL, Dey D
JACC Cardiovasc Imaging: 30 Oct 2020; 13:2371-2383 | PMID: 32861654
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Impact:
Abstract

Resolving the Disproportionate Left Ventricular Enlargement in Mitral Valve Prolapse Due to Barlow Disease: Insights From Cardiovascular Magnetic Resonance.

El-Tallawi KC, Kitkungvan D, Xu J, Cristini V, ... Zoghbi WA, Shah DJ
Objectives
This study hypothesized that left ventricular (LV) enlargement in Barlow disease can be explained by accounting for the total volume load that consists of transvalvular mitral regurgitation (MR) and the prolapse volume.
Background
Barlow disease is characterized by long prolapsing mitral leaflets that can harbor a significant amount of blood-the prolapse volume-at end-systole. The LV in Barlow disease can be disproportionately enlarged relative to MR severity, leading to speculation of Barlow cardiomyopathy.
Methods
Cardiac magnetic resonance (CMR) was used to compare MR, prolapse volume, and heart chambers remodeling in patients with Barlow disease (bileaflet prolapse [BLP]) and in single leaflet prolapse (SLP).
Results
A total of 157 patients (81 with BLP, 76 with SLP) were included. Patients with SLP were older and more had hypertension. Patients with BLP had more heart failure. Indexed LV end-diastolic volume was larger in BLP despite similar transvalvular MR. However, the prolapse volume was larger in BLP, which led to larger total volume load compared with SLP. Increasing tertiles of prolapse volume and MR both led to an incremental increase in LV end-diastolic volume in BLP. Using the total volume load improved the correlation with indexed LV end-diastolic volume in the BLP group, which closely matched that of SLP. A multivariable model that incorporated the prolapse volume explained left heart chamber enlargement better than a MR-based model, independent of prolapse category.
Conclusions
The prolapse volume is part of the total volume load exerted on the LV during the cardiac cycle and could help explain the disproportionate LV enlargement relative to MR severity noted in Barlow disease.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print
El-Tallawi KC, Kitkungvan D, Xu J, Cristini V, ... Zoghbi WA, Shah DJ
JACC Cardiovasc Imaging: 27 Oct 2020; epub ahead of print | PMID: 33129724
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Abstract

Shear Wave Elastography Using High-Frame-Rate Imaging in the Follow-Up of Heart Transplantation Recipients.

Petrescu A, Bézy S, Cvijic M, Santos P, ... D\'hooge J, Voigt JU
Objectives
The purpose of this study was to investigate whether propagation velocities of naturally occurring shear waves (SWs) at mitral valve closure (MVC) increase with the degree of diffuse myocardial injury (DMI) and with invasively determined LV filling pressures as a reflection of an increase in myocardial stiffness in heart transplantation (HTx) recipients.
Background
After orthotopic HTx, allografts undergo DMI that contributes to functional impairment, especially to increased passive myocardial stiffness, which is an important pathophysiological determinant of left ventricular (LV) diastolic dysfunction. Echocardiographic SW elastography is an emerging approach for measuring myocardial stiffness in vivo. Natural SWs occur after mechanical excitation of the myocardium, for example, after MVC, and their propagation velocity is directly related to myocardial stiffness, thus providing an opportunity to assess myocardial stiffness at end-diastole.
Methods
A total of 52 HTx recipients who underwent right heart catheterization (all) and cardiac magnetic resonance (CMR) (n = 23) during their annual check-up were prospectively enrolled. Echocardiographic SW elastography was performed in parasternal long axis views of the LV using an experimental scanner at 1,135 ± 270 frames per second. The degree of DMI was quantified with T1 mapping.
Results
SW velocity at MVC correlated best with native myocardial T1 values (r = 0.75; p < 0.0001) and was the best noninvasive parameter that correlated with pulmonary capillary wedge pressures (PCWP) (r = 0.54; p < 0.001). Standard echocardiographic parameters of LV diastolic function correlated poorly with both native T1 and PCWP values.
Conclusions
End-diastolic SW propagation velocities, as measure of myocardial stiffness, showed a good correlation with CMR-defined diffuse myocardial injury and with invasively determined LV filling pressures in patients with HTx. Thus, these findings suggest that SW elastography has the potential to become a valuable noninvasive method for the assessment of diastolic myocardial properties in HTx recipients.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Oct 2020; 13:2304-2313
Petrescu A, Bézy S, Cvijic M, Santos P, ... D'hooge J, Voigt JU
JACC Cardiovasc Imaging: 30 Oct 2020; 13:2304-2313 | PMID: 33004291
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Impact:
Abstract

Pre-Menopausal Breast Fat Density Might Predict MACE During 10 Years of Follow-Up: The BRECARD Study.

Sardu C, Gatta G, Pieretti G, Viola L, ... Paolisso G, Marfella R
Objectives
This study sought to determine whether the breast gland adipose tissue is associated with different rates of major adverse cardiac events (MACEs) in pre-menopausal women.
Background
To our knowledge, no study investigated the impact of breast adipose tissue infiltration on MACEs in pre-menopausal women.
Methods
Prospective multicenter cohort study conducted on pre-menopausal women >40 years of age without cardiovascular disease and breast cancer at enrollment. The study started in January 2000 and ended in January 2009, and the end of the follow-up for the evaluation of MACEs was in January 2019. Participants underwent mammography to evaluate breast density and were divided into 4 groups according to their breast density. The primary endpoint was the probability of a MACE at 10 years of follow-up in patients staged for different breast deposition/adipose tissue deposition.
Results
The propensity score matching divided the baseline population of 16,763 pre-menopausal women, leaving 3,272 women according to the category of breast density from A to D. These women were assigned to 4 groups of the study according to baseline breast density. At 10 years of follow-up, we had 160 MACEs in group 1, 62 MACEs in group 2, 27 MACEs in group 3, and 16 MACEs in group 4. MACEs were predicted by the initial diagnosis of lowest breast density (hazard ratio: 3.483; 95% confidence interval: 1.476-8.257). Further randomized clinical trials are needed to translate the results of the present study into clinical practice. The loss of ex vivo breast density models to study the cellular/molecular pathways implied in MACE is another study limitation.
Conclusions
Among pre-menopausal women, a higher evidence of adipose tissue at the level of breast gland (lowest breast density, category A) versus higher breast density shows higher rates of MACEs. Therefore, the screening mammography could be proposed in overweight women to stage breast density and to predict MACEs. (Breast Density in Pre-menopausal Women Is Predictive of Cardiovascular Outcomes at 10 Years of Follow-Up [BRECARD]; NCT03779217).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print
Sardu C, Gatta G, Pieretti G, Viola L, ... Paolisso G, Marfella R
JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print | PMID: 33129736
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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 study (NCT02883088) defined high-risk plaques with simultaneous presence of 4 optical coherence tomography (OCT) features (minimum lumen area <3.5 mm; 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 to PE to PR. Interestingly, nonculprit rupture was rarely found in patients with culprit PE (1.9%), although it was exhibited with comparable prevalence in patients with culprit PE (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 © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print
Cao M, Zhao L, Ren X, Wu T, ... Mintz GS, Yu B
JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print | PMID: 33129735
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Abstract

Warranty Period of a Calcium Score of Zero: Comprehensive Analysis From the Multiethnic Study of Atherosclerosis.

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 © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print
Dzaye O, Dardari ZA, Cainzos-Achirica M, Blankstein R, ... Nasir K, Blaha MJ
JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print | PMID: 33129734
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Impact:
Abstract

Predicting Long-Term Absence of Coronary Artery Calcium in Metabolic Syndrome and Diabetes: The MESA Study.

Razavi AC, Wong N, Budoff M, Bazzano LA, ... Blaha MJ, Whelton SP
Objectives
The purpose of this study was to identify predictors of healthy arterial aging (long-term coronary artery calcification [CAC] of 0) among individuals with metabolic syndrome (MetS) or type 2 diabetes (T2D), which may improve primary prevention strategies.
Background
Individuals with MetS or T2D have a heterogeneously increased risk of atherosclerotic cardiovascular disease and not all have a high-intermediate risk.
Methods
We included 574 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with MetS or T2D who had CAC=0 at baseline and a repeat CAC scan 10 years later. Multivariable logistic regression assessed the association of traditional and novel atherosclerotic cardiovascular disease risk factors and the MetS severity score (based on the 5 MetS criteria) with healthy arterial aging.
Results
The mean age of participants was 58.9 years, 67% were women, 422 participants had MetS, and 152 had T2D. The proportion with long-term CAC=0 was similar for MetS (42%) and T2D (44%). A younger age was the only individual low/normal traditional risk factor associated with an increased likelihood of long-term CAC=0 (odds ratio [OR]: 1.50; 95% confidence interval [CI]: 1.22 to 1.85 per 10-years younger). The strongest associations of nontraditional risk factors were observed for an absence of thoracic calcification (OR: 2.42; 95% CI: 1.24 to 4.72), absence of carotid plaque (OR: 1.81; 95% CI: 1.25 to 2.61), and among persons with a high sensitivity troponin <3 ng/ml (OR: 1.55; 95% CI: 1.01 to 2.38). In addition, persons with the lowest quartile MetS severity score had a substantially higher odds of healthy long-term CAC=0 (OR: 2.71; 95% CI: 1.27 to 5.76).
Conclusions
More than 40% of adults with MetS or T2D and baseline CAC=0 had long-term absence of CAC, which was most strongly associated with an absence of extracoronary atherosclerosis and a low MetS score. An optimal overall cardiovascular profile appears to be more important than an ideal value of any individual risk factor to maintain healthy arterial aging.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print
Razavi AC, Wong N, Budoff M, Bazzano LA, ... Blaha MJ, Whelton SP
JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print | PMID: 33129732
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Impact:
Abstract

Feasibility and Prognostic Value of Vasodilator Stress Perfusion CMR in Patients With Atrial Fibrillation.

Pezel T, Sanguineti F, Kinnel M, Landon V, ... Garot P, Garot J
Objectives
The aim of this study was to assess the feasibility and prognostic value of vasodilator stress perfusion cardiovascular magnetic resonance (CMR) in patients with atrial fibrillation (AF).
Background
Because most studies have excluded arrhythmic patients, the prognostic value of stress perfusion CMR in patients with AF is unknown.
Methods
Between 2008 and 2018, consecutive patients with suspected or stable chronic coronary artery disease and AF referred for vasodilator stress perfusion CMR were included and followed for the occurrence of major adverse cardiovascular event(s) (MACE), defined as cardiovascular death or nonfatal myocardial infarction. The diagnosis of AF was defined by 12-lead electrocardiography before and after CMR. Univariate and multivariate Cox regressions were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR.
Results
Of 639 patients (mean age 72 ± 9 years, 77% men), 602 (94%) completed the CMR protocol, and 538 (89%) completed follow-up (median 5.1 years); 80 had MACE. Using Kaplan-Meier analysis, the presence of ischemia (hazard ratio [HR]: 7.56; 95% confidence interval [CI]: 4.86 to 11.80) or LGE (HR: 2.41; 95% CI: 1.55 to 3.74) was associated with the occurrence of MACE (p < 0.001 for both). In a multivariate Cox regression including clinical and CMR indexes, the presence of ischemia (HR: 5.98; 95% CI: 3.68 to 9.73) or LGE (HR: 2.61; 95% CI: 1.89 to 3.60) was an independent predictor of MACE (p < 0.001 for both).
Conclusions
In patients with AF, stress perfusion CMR is feasible and has good discriminative prognostic value to predict the occurrence of MACE.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print
Pezel T, Sanguineti F, Kinnel M, Landon V, ... Garot P, Garot J
JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print | PMID: 33129729
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Impact:
Abstract

Right Ventricular Strain Curve Morphology and Outcome in Idiopathic Pulmonary Arterial Hypertension.

Badagliacca R, Pezzuto B, Papa S, Poscia R, ... Naeije R, Vizza CD
Objectives
The purpose of this study was to explore speckle tracking echocardiographic right ventricular (RV) post-systolic strain patterns and their clinical relevance in idiopathic pulmonary arterial hypertension (PAH).
Background
The imaging of RV diastolic function in PAH remains incompletely understood.
Methods
Speckle tracking echocardiography of RV post-systolic strain recordings were examined in 108 consecutive idiopathic patients with PAH. Each of them underwent baseline clinical, hemodynamic, and complete echocardiographic evaluation and follow-up.
Results
In total, 3 post-systolic strain patterns derived from the mid-basal RV free wall segments were identified. Pattern 1 was characterized by prompt return of strain-time curves to baseline after peak systolic negativity, like in normal control subjects. Pattern 2 was characterized by persisting negativity of strain-time curves well into diastole, before an end-diastolic returning to baseline. Pattern 3 was characterized by a slow return of strain-time curves to baseline during diastole. The 3 patterns corresponded respectively to mild PH, more advanced PH but with still preserved RV function, and PH with obvious end-stage right heart failure. Patterns were characterized by optimal reproducibility when complementary to quantitative measurement of right ventricular longitudinal early diastolic strain rate (RVLSR-E), and right ventricular longitudinal late diastolic strain rate (RVLSR-A) (Cohen\'s κ = 0.88; p = 0.0001). Multivariable models for clinical worsening prediction demonstrated that the addition of RV post-systolic patterns to clinical and hemodynamic variables significantly increased their prognostic power (0.78 vs. 0.66; p < 0.001). Freedom from clinical worsening rates at 1 and 2 years from baseline were, respectively, 100% and 93% for Pattern 1; 80% and 55% for Pattern 2; and 60% and 33% for Pattern 3.
Conclusions
Speckle tracking echocardiography allows for the identification of 3 phenotypically distinct, reproducible, and clinically meaningful RV strain-derived post-systolic patterns.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print
Badagliacca R, Pezzuto B, Papa S, Poscia R, ... Naeije R, Vizza CD
JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print | PMID: 33129726
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Impact:
Abstract

Cardiac Phenotypes and Markers of Adverse Outcome in Elite Athletes With Ventricular Arrhythmias.

Lie ØH, Klaboe LG, Dejgaard LA, Skjølsvik ET, ... Edvardsen T, Haugaa KH
Objectives
This study describes the cardiac phenotypes and markers of adverse outcome in athletes with ventricular arrhythmias with no other discernable etiology than high exercise doses.
Background
Little is known about phenotypes and risk markers of life-threatening arrhythmic events in athletes with ventricular arrhythmia.
Methods
We compared high-performance athletes who have ventricular arrhythmia with healthy controls using clinical data and cardiac imaging. None of the patients had family history of arrhythmogenic cardiomyopathy or any other discernable etiology of ventricular arrhythmia. Right (RV) and left ventricular (LV) function was assessed by echocardiographic longitudinal strain (right ventricular free wall strain longitudinal [RVFWSL] and left ventricular global longitudinal strain [LVGLS]). Mechanical dispersion was defined as the standard deviation of time to peak strain in 16 LV segments. RV ejection fraction and presence of late gadolinium enhancement was assessed by cardiac magnetic resonance.
Results
We included 43 athletes (45 ± 14 years of age, 16% female) with ventricular arrhythmias and 30 healthy athletes (41 ± 9 years of age, 7% female). Athletes with ventricular arrhythmias had worse RV function than healthy athletes by echocardiography (RVFWSL: -22.9 ± 4.8% vs. -26.6 ± 3.3%; p < 0.001) and by cardiac magnetic resonance (RV ejection fraction 48 ± 7% vs. 52 ± 6%; p = 0.04), and had more late gadolinium enhancement (24% vs. 3%; p = 0.03). Life-threatening arrhythmic events (aborted cardiac arrest, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy) had occurred in 23 (53%) athletes with ventricular arrhythmias. These had impaired LV function compared to those with less severe ventricular arrhythmias (LVGLS: -17.1 ± 3.0% vs. -18.8 ± 2.0%; p = 0.04). LV mechanical dispersion was an independent marker of life-threatening events (adjusted odds ratio: 2.2 [1.1 to 4.8] by 10 ms increments; p = 0.03).
Conclusions
Athletes with ventricular arrhythmias had impaired RV function and more myocardial fibrosis compared to healthy athletes. Athletes with life-threatening arrhythmic events had additional LV contraction abnormalities. These phenotypes mimic arrhythmogenic cardiomyopathy and may potentially be induced by high doses of exercise in susceptible individuals.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print
Lie ØH, Klaboe LG, Dejgaard LA, Skjølsvik ET, ... Edvardsen T, Haugaa KH
JACC Cardiovasc Imaging: 26 Oct 2020; epub ahead of print | PMID: 33129723
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Impact:
Abstract

2020 SCCT Guideline for Training Cardiology and Radiology Trainees as Independent Practitioners (Level II) and Advanced Practitioners (Level III) in Cardiovascular Computed Tomography: A Statement from the Society of Cardiovascular Computed Tomography.

Choi AD, Thomas DM, Lee J, Abbara S, ... Villines TC, Blankstein R

Cardiovascular computed tomography (CCT) is a well-validated non-invasive imaging tool with an ever-expanding array of applications beyond the assessment of coronary artery disease. These include the evaluation of structural heart diseases, congenital heart diseases, peri-procedural electrophysiology applications, and the functional evaluation of ischemia. This breadth requires a robust and diverse training curriculum to ensure graduates of CCT training programs meet minimum competency standards for independent CCT interpretation. This statement from the Society of Cardiovascular Computed Tomography aims to supplement existing societal training guidelines by providing a curriculum and competency framework to inform the development of a comprehensive, integrated training experience for cardiology and radiology trainees in CCT.

Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by American College of Cardiology with permission. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 03 Nov 2020; epub ahead of print
Choi AD, Thomas DM, Lee J, Abbara S, ... Villines TC, Blankstein R
JACC Cardiovasc Imaging: 03 Nov 2020; epub ahead of print | PMID: 33168479
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Impact:
Abstract

Radionuclide Image-Guided Repair of the Heart.

Hess A, Thackeray JT, Wollert KC, Bengel FM

As therapeutic approaches have evolved from exogenous bone marrow cell delivery to pharmacological stimulation of endogenous repair, so too has imaging of cardiac repair made significant strides forward. Evaluation of functional outcome remains a staple of noninvasive clinical imaging, which can robustly quantify contractile function, perfusion, and tissue viability. Direct labeling of cells or other novel therapeutics visualizes the whole-body distribution and pharmacokinetics of the therapeutic agent, providing insights into retention, targeting, and drug-tissue interactions. And finally, targeted molecular imaging agents are emerging that may be specifically coupled to drugs targeting the same pathway. This approach enables interrogation of temporal and spatial changes at the molecular level underlying tissue degeneration and regeneration, which facilitates accurate patient selection and timing for therapeutic intervention, as exemplified by recent efforts focusing on the role of inflammation in cardiac repair. The concept of image-guided repair carves out an important and evolving niche for molecular imaging in cardiovascular medicine, with the potential not only to predict outcomes but also to improve patient stratification and progress toward personalized reparative therapy.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Oct 2020; 13:2415-2429
Hess A, Thackeray JT, Wollert KC, Bengel FM
JACC Cardiovasc Imaging: 30 Oct 2020; 13:2415-2429 | PMID: 31864993
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Impact:
Abstract

Heterogenous Distribution of Risk for Cardiovascular Disease Events in Patients With Stable Ischemic Heart Disease.

Mortensen MB, Steffensen FH, Bøtker HE, Jensen JM, ... Blaha MJ, Nørgaard BL
Objectives
The authors sought to assess the distribution of 5-year risk of cardiovascular disease (CVD) events (myocardial infarction, revascularizations, ischemic stroke) and death among symptomatic patients with varying degrees of coronary artery disease (CAD) ascertained from computed tomography angiography (CTA).
Background
CTA is used increasingly as the first-line test for evaluating patients with symptoms suggestive of CAD. This creates the daily clinical challenge of best using the information available from CTA to guide appropriate downstream allocation of preventive treatments.
Methods
Among 21,275 patients from the Western Denmark Heart Registry, the authors developed a model predicting 5-year risk for CVD and death based on traditional risk factors and CAD severity. Only events occurring >90 days after CTA were included.
Results
During a median follow-up of 4.2 years, 1,295 CVD events and deaths occurred. The median 5-year risk for events was 4% (interquartile range: 3% to 8%), and ranged from <5% to >50% in individual patients. The degree of CAD severity was the strongest risk factor; however, traditional risk factors also contributed significantly to risk. Thus, risk distributions in patients with varying degree of CAD overlapped considerably, and patients with extensive nonobstructive CAD could have higher estimated risk than patients with obstructive CAD (stenosis >50%). Among patients with obstructive CAD, 12% had 5-year risk <10% whereas 24% had risk >20%. A similar large overlap in risk was found when revascularizations were excluded from the endpoint.
Conclusions
The 5-year risk for CVD events and death varies substantially in symptomatic patients undergoing CTA, even in the presence of obstructive CAD. These results provide support for individual risk assessment to improve potential benefit when allocating preventive therapies following CTA.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 15 Nov 2020; epub ahead of print
Mortensen MB, Steffensen FH, Bøtker HE, Jensen JM, ... Blaha MJ, Nørgaard BL
JACC Cardiovasc Imaging: 15 Nov 2020; epub ahead of print | PMID: 33221243
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Impact:
Abstract

Evolution of Myocardial Dysfunction in Asymptomatic Patients at Risk of Heart Failure.

Halabi A, Yang H, Wright L, Potter E, ... Negishi K, Marwick TH
Objectives
The determinants of changes in systolic and diastolic parameters in patients aged >65 years, at risk of heart failure (HF), and with and without asymptomatic type 2 diabetes mellitus (T2DM) was assessed by echocardiography. The association between metformin and myocardial function was also assessed.
Background
The increasing prevalence of T2DM will likely further fuel the epidemic of HF. Understanding the development or progression of left ventricular (LV) dysfunction may inform effective measures for HF prevention.
Methods
A total of 982 patients with at least one HF risk factor (hypertension, obesity, or T2DM) were recruited from 2 community-based populations and divided into 2 groups: T2DM (n = 431, age 71 ± 4 years) and non-T2DM (n = 551, age 71 ± 5 years). Associations of metformin therapy were evaluated in the T2DM group. All underwent a comprehensive echocardiogram, including global longitudinal strain (GLS) and diastolic function (transmitral flow [E], annular velocity [e\']) at baseline and follow-up (median 19 months [interquartile range: 17-26]). Comparisons were facilitated by propensity matching.
Results
A reduction in GLS was observed in the T2DM group (baseline -17.8 ± 2.6% vs. follow-up -17.4 ± 2.8%; p = 0.003), but not in the non-T2DM group (-18.7 ± 2.7% vs. -18.6 ± 3.0%; p = 0.41). Estimated LV filling pressures increased in both the T2DM group (p = 0.001) and the non-T2DM group (p = 0.04). Metformin-treated patients with T2DM did not increase estimated LV filling pressure (E/e\' baseline 8.9 ± 2.7 vs. follow-up 9.1 ± 2.7; p = 0.485) or change e\' (7.6 ± 1.5 cm/s vs. 7.6 ± 1.8 cm/s; p = 0.88). After propensity matching, metformin was associated with a smaller change in e\' (β = 0.58 [95% CI 0.13 to 1.03]; p = 0.013) and E/e\' (β = -0.96 [95% CI -1.66 to -0.26]; p = 0.007) but was not associated with a change in GLS (p = 0.46).
Conclusions
Over 2 years, there is a worsening of GLS and LV filling pressures in asymptomatic diabetic patients with HF risk factors. Metformin use is associated with less deterioration of LV filling pressures and myocardial relaxation but had no association with systolic function.

Copyright © 2020. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print
Halabi A, Yang H, Wright L, Potter E, ... Negishi K, Marwick TH
JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print | PMID: 33221236
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Impact:
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
▪▪▪ Background: The sympathetic nervous system (SNS) is vitally linked to cardiovascular regulation and disease. SNS imaging has shown prognostic value. [C]meta-hydroxyephedrine (HED) is the most commonly used positron emission tomographic (PET) tracer for evaluation of sympathetic function in humans, but widespread clinical use is limited because of the short half-life of C. The aim of this study was to investigate the regional distribution of novel F-labeled PET tracer flubrobenguane (FBBG) (whose longer half-life could enable more widespread use) to assess myocardial pre-synaptic sympathetic nerve function in humans in comparison to HED.
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 (r = 0.72; ICC = 0.79; p < 0.0001), DV (r = 0.62; ICC = 0.78; p < 0.0001), and regional denervation (r = 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. F-labeled PET tracers, such as FBBG, are critical for widespread distribution necessary for multicenter clinical trials and to maximize patient impact.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print
Zelt JGE, Britt D, Mair BA, Rotstein BH, ... deKemp RA, Beanlands RS
JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print | PMID: 33221229
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Impact:
Abstract

Artificial Intelligence Aids Cardiac Image Quality Assessment for Improving Precision in Strain Measurements.

Huang KC, Huang CS, Su MY, Hung CL, ... Lin LC, Hwang JJ
Objectives
The aim of this study was to develop an artificial intelligence tool to assess echocardiographic image quality objectively.
Background
Left ventricular global longitudinal strain (LVGLS) has recently been used to monitor cancer therapeutics-related cardiac dysfunction (CTRCD) but image quality limits its reliability.
Methods
A DenseNet-121 convolutional neural network was developed for view identification from an athlete\'s echocardiographic dataset. To prove the concept that classification confidence (CC) can serve as a quality marker, values of longitudinal strain derived from feature tracking of cardiac magnetic resonance (CMR) imaging and strain analysis of echocardiography were compared. The CC was then applied to patients with breast cancer free from CTRCD to investigate the effects of image quality on the reliability of strain analysis.
Results
CC of the apical 4-chamber view (A4C) was significantly correlated with the endocardial border delineation index. CC of A4C >900 significantly predicted a <15% relative difference in longitudinal strain between CMR feature tracking and automated echocardiographic analysis. Echocardiographic studies (n =752) of 102 patients with breast cancer without CTRCD were investigated. The strain analysis showed higher parallel forms, inter-rater, and test-retest reliabilities in patients with CC of A4C >900. During sequential comparisons of automated LVGLS in individual patients, those with CC of A4C >900 had a lower false positive detection rate of CTRCD.
Conclusions
CC of A4C was associated with the reliability of automated LVGLS and could also potentially be used as a filter to select comparable images from sequential echocardiographic studies in individual patients and reduce the false positive detection rate of CTRCD.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 Nov 2020; epub ahead of print
Huang KC, Huang CS, Su MY, Hung CL, ... Lin LC, Hwang JJ
JACC Cardiovasc Imaging: 11 Nov 2020; epub ahead of print | PMID: 33221213
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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 Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes (CECSID) trial (NCT00692237) 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
Seventy-nine 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/m; p = 0.014) and a borderline increase in end-diastolic volume (ΔEDVi = 5.16 ± 14.71 ml/m; 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; 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 © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print
Pofi R, Giannetta E, Galea N, Francone M, ... Carbone I, Isidori AM
JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print | PMID: 33221242
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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 © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print
Taha K, Te Rijdt WP, Verstraelen TE, Cramer MJ, ... van den Berg MP, Teske AJ
JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print | PMID: 33221241
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Abstract

Structural and Functional Correlates of Gradient-Area Patterns in Severe Aortic Stenosis and Normal Ejection Fraction.

Slimani A, Roy C, de Meester C, Bouzin C, ... Gerber BL, Vanoverschelde JL
Objectives
The authors sought to characterize the functional and structural myocardial phenotypes of patients with moderate-to-severe aortic stenosis (AS) and to determine whether severe paradoxical low-gradient AS (LG-AS) is specifically associated with left ventricular (LV) remodeling and fibrosis.
Background
Recently, it was suggested that severe paradoxical LG-AS is a more advanced form of AS, with greater reduction of longitudinal deformation, adverse LV remodeling, and more interstitial fibrosis.
Methods
The study population includes 147 patients with moderate-to-severe AS and a normal LV ejection fraction, and 75 normal control subjects. They prospectively underwent 2-dimensional speckle-tracking echocardiography and cardiac magnetic resonance to evaluate myocardial deformation, LV remodeling, and age- and sex-adjusted extravascular volume fraction (ECV, %). Among AS patients, 18 had moderate AS, 74 had severe high-gradient AS (HG-AS), and 55 had severe paradoxical LG-AS.
Results
Reduced longitudinal and circumferential deformation was observed in 21% and 6% of the AS patients, respectively. Multivariate analyses identified increased ECV (ß = 1.99; p = 0.001) and the absence of normal LV geometry (ß = -1.37; p = 0.007) and as independent predictors of reduced longitudinal deformation. Increased ECV was an independent predictor of reduced circumferential deformation (ß = 2.19; p = 0.001). Over a median follow-up of 29 months, reduced longitudinal deformation (hazard ratio: 0.82; p = 0.023) and higher transvalvular gradients (hazard ratio: 1.05; p < 0.001) increased the risk of death or need for aortic valve replacement. LV hypertrophy was more frequently observed among patients with severe HG-AS (65%) than among the other AS patients (14%; p < 0.001). On average, ECV was within normal limits and did not differ among gradient-area subgroups. When present, increased ECV was associated with reduced longitudinal deformation.
Conclusions
This study\'s data show that patients with severe paradoxical LG-AS less frequently display reduced longitudinal deformation, LV hypertrophy, or myocardial fibrosis than patients with HG-AS. Also, interstitial fibrosis only occurs when reduced longitudinal deformation and severe HG-AS are present together. Finally, this study suggests that reduced longitudinal deformation and higher transvalvular gradients adversely affect patients\' outcomes.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print
Slimani A, Roy C, de Meester C, Bouzin C, ... Gerber BL, Vanoverschelde JL
JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print | PMID: 33221240
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Abstract

Label-Free Visualization and Quantification of Biochemical Markers of Atherosclerotic Plaque Progression Using Intravascular Fluorescence Lifetime.

Bec J, Vela D, Phipps JE, Agung M, ... Buja LM, Marcu L
Objectives
This study aimed to systematically investigate whether plaque autofluorescence properties assessed with intravascular fluorescence lifetime imaging (FLIm) can provide qualitative and quantitative information about intimal composition and improve the characterization of atherosclerosis lesions.
Background
Despite advances in cardiovascular diagnostics, the analytic tools and imaging technologies currently available have limited capabilities for evaluating in situ biochemical changes associated with luminal surface features. Earlier studies of small number of samples have shown differences among the autofluorescence lifetime signature of well-defined lesions, but a systematic pixel-level evaluation of fluorescence signatures associated with various histological features is lacking and needed to better understand the origins of fluorescence contrast.
Methods
Human coronary artery segments (n = 32) were analyzed with a bimodal catheter system combining multispectral FLIm with intravascular ultrasonography compatible with in vivo coronary imaging. Various histological components present along the luminal surface (200-μm depth) were systematically tabulated (12 sectors) from each serial histological section (n = 204). Morphological information provided by ultrasonography allowed for the accurate registration of imaging data with histology data. The relationships between histological findings and FLIm parameters obtained from 3 spectral channels at each measurement location (n = 33,980) were characterized.
Results
Our findings indicate that fluorescence lifetime from different spectral bands can be used to quantitatively predict the superficial presence of macrophage foam cells (mFCs) (area under the receiver-operator characteristic curve: 0.94) and extracellular lipid content in advanced lesions (lifetime increase in 540-nm band), detect superficial calcium (lifetime decrease in 450-nm band area under the receiver-operator characteristic curve: 0.90), and possibly detect lesions consistent with active plaque formation such as pathological intimal thickening and healed thrombus regions (lifetime increase in 390-nm band).
Conclusions
Our findings indicate that autofluorescence lifetime provides valuable information for characterizing atherosclerotic lesions in coronary arteries. Specifically, FLIm can be used to identify key phenomena linked with plaque progression (e.g., peroxidized-lipid-rich mFC accumulation and recent plaque formation).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print
Bec J, Vela D, Phipps JE, Agung M, ... Buja LM, Marcu L
JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print | PMID: 33221238
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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 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 © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print
Cainzos-Achirica M, Bittencourt MS, Osei AD, Haque W, ... Blaha MJ, Nasir K
JACC Cardiovasc Imaging: 12 Nov 2020; epub ahead of print | PMID: 33221237
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Impact:
Abstract

Prognostic Value of Radiotracer-Based Perfusion Imaging in Critical Limb Ischemia Patients Undergoing Lower Extremity Revascularization.

Chou TH, Alvelo JL, Janse S, Papademetris X, ... Sinusas AJ, Stacy MR
Objectives
The purpose of this study was to evaluate the prognostic value of single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of angiosome foot perfusion for predicting amputation outcomes in patients with critical limb ischemia (CLI) and diabetes mellitus (DM).
Background
Radiotracer imaging can assess microvascular foot perfusion and identify regional perfusion abnormalities in patients with critical limb ischemia CLI and DM, but the relationship between perfusion response to revascularization and subsequent clinical outcomes has not been evaluated.
Methods
Patients with CLI, DM, and nonhealing foot ulcers (n = 25) were prospectively enrolled for SPECT/CT perfusion imaging of the feet before and after revascularization. CT images were used to segment angiosomes (i.e., 3-dimensional vascular territories) of the foot. Relative changes in radiotracer uptake after revascularization were evaluated within the ulcerated angiosome. Incidence of amputation was assessed at 3 and 12 months after revascularization.
Results
SPECT/CT detected a significantly lower microvascular perfusion response for patients who underwent amputation compared with those who remained amputation free at 3 (p = 0.01) and 12 (p = 0.01) months after revascularization. The cutoff percent change in perfusion for predicting amputation at 3 months was 7.55%, and 11.56% at 12 months. The area under the curve based on the amputation outcome was 0.799 at 3 months and 0.833 at 12 months. The probability of amputation-free survival was significantly higher at 3 (p = 0.002) and 12 months (p = 0.03) for high-perfusion responders than low-perfusion responders to revascularization.
Conclusions
SPECT/CT imaging detects regional perfusion responses to lower extremity revascularization and provides prognostic value in patients with CLI (Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease; NCT03622359).

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 Nov 2020; epub ahead of print
Chou TH, Alvelo JL, Janse S, Papademetris X, ... Sinusas AJ, Stacy MR
JACC Cardiovasc Imaging: 11 Nov 2020; epub ahead of print | PMID: 33221224
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Impact:
Abstract

The Relationship Between Coronary Calcification and the Natural History of Coronary Artery Disease.

Jin HY, Weir-McCall JR, Leipsic JA, Son JW, ... Lee SE, Chang HJ
Objectives
The aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease.
Background
Coronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy.
Methods
This analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) × 100 at a per-plaque and per-patient level (summation of all individual plaques).
Results
CPV was strongly correlated with plaque volume (r = 0.780; p < 0.001) at baseline and with plaque progression (r = 0.297; p < 0.001); however, this association was reversed after accounting for plaque volume at baseline (r = -0.146; p < 0.001). In contrast, PCPV was an independent predictor of a reduction in plaque volume (r = -0.11; p < 0.001) in univariable and multivariable linear regression analyses. Patient-level analysis showed that high CPV was associated with incident major adverse cardiac events (hazard ratio: 3.01: 95% confidence interval: 1.58 to 5.72), whereas high PCPV was inversely associated with major adverse cardiac events (hazard ratio: 0.529; 95% confidence interval: 0.229 to 0.968) in multivariable analysis.
Conclusions
Calcified plaque is a marker for risk of adverse events and disease progression due to its strong association with the total plaque burden. When considered as a percentage of the total plaque volume, increasing PCPV is a marker of plaque stability and reduced risk at both a lesion and patient level. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 Nov 2020; epub ahead of print
Jin HY, Weir-McCall JR, Leipsic JA, Son JW, ... Lee SE, Chang HJ
JACC Cardiovasc Imaging: 11 Nov 2020; epub ahead of print | PMID: 33221216
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Impact:
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 (maxLCBI) 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 maxLCBI 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 maxLCBI 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 maxLCBI 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 maxLCBI, NIRS-IVUS can accurately differentiate PR, PE, and CN.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 Nov 2020; epub ahead of print
Terada K, Kubo T, Kameyama T, Matsuo Y, ... Madder RD, Akasaka T
JACC Cardiovasc Imaging: 11 Nov 2020; epub ahead of print | PMID: 33221211
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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 © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 15 Nov 2020; epub ahead of print
Gould KL, Kitkungvan D, Johnson NP, Nguyen T, ... Zhu H, Lai D
JACC Cardiovasc Imaging: 15 Nov 2020; epub ahead of print | PMID: 33221205
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Impact:
Abstract

Diagnosing Transthyretin Cardiac Amyloidosis by Technetium 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 (Tc-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
Tc-PYP scintigraphy has been repurposed for noninvasive diagnosis of ATTR-CA. Increasing use of Tc-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 Tc-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 Tc-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 © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 Nov 2020; epub ahead of print
Poterucha TJ, Elias P, Bokhari S, Einstein AJ, ... Perotte A, Maurer MS
JACC Cardiovasc Imaging: 11 Nov 2020; epub ahead of print | PMID: 33221204
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Impact:
Abstract

High Prevalence of Pericardial Involvement in College Student Athletes Recovering From COVID-19.

Brito D, Meester S, Yanamala N, Patel HB, ... Monseau AJ, Sengupta PP
Objectives
This study sought to explore the spectrum of cardiac abnormalities in student athletes who returned to university campus in July 2020 with uncomplicated coronavirus disease 2019 (COVID-19).
Background
There is limited information on cardiovascular involvement in young individuals with mild or asymptomatic COVID-19.
Methods
Screening echocardiograms were performed in 54 consecutive student athletes (mean age 19 years; 85% male) who had positive results of reverse transcription polymerase chain reaction nasal swab testing of the upper respiratory tract or immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus type 2. Sequential cardiac magnetic resonance imaging was performed in 48 (89%) subjects.
Results
A total of 16 (30%) athletes were asymptomatic, whereas 36 (66%) and 2 (4%) athletes reported mild and moderate COVID-19 related symptoms, respectively. For the 48 athletes completing both imaging studies, abnormal findings were identified in 27 (56.3%) individuals. This included 19 (39.5%) athletes with pericardial late enhancements with associated pericardial effusion. Of the individuals with pericardial enhancements, 6 (12.5%) had reduced global longitudinal strain and/or an increased native T. One patient showed myocardial enhancement, and reduced left ventricular ejection fraction or reduced global longitudinal strain with or without increased native T values was also identified in an additional 7 (14.6%) individuals. Native T findings were normal in all subjects, and no specific imaging features of myocardial inflammation were identified. Hierarchical clustering of left ventricular regional strain identified 3 unique myopericardial phenotypes that showed significant association with the cardiac magnetic resonance findings (p = 0.03).
Conclusions
More than 1 in 3 previously healthy college athletes recovering from COVID-19 infection showed imaging features of a resolving pericardial inflammation. Although subtle changes in myocardial structure and function were identified, no athlete showed specific imaging features to suggest an ongoing myocarditis. Further studies are needed to understand the clinical implications and long-term evolution of these abnormalities in uncomplicated COVID-19.

Copyright © 2020. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 03 Nov 2020; epub ahead of print
Brito D, Meester S, Yanamala N, Patel HB, ... Monseau AJ, Sengupta PP
JACC Cardiovasc Imaging: 03 Nov 2020; epub ahead of print | PMID: 33223496
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Abstract

Sudden Cardiac Death in Ischemic Heart Disease: From Imaging Arrhythmogenic Substrate to Guiding Therapies.

Gräni C, Benz DC, Gupta S, Windecker S, Kwong RY

Despite substantial medical advances over the past decades, sudden cardiac death (SCD) remains a leading cause of cardiovascular deaths in patients with ischemic heart disease. The presence of structural heart disease with left ventricular ejection fraction <35% is the current criteria for implantable cardioverter-defibrillator therapy as a primary prevention to SCD. However, more than 80% of patients who suffer SCD have a left ventricular ejection fraction >35%, whereas few patients who received an implantable cardioverter-defibrillator required appropriate defibrillation. Cardiac magnetic resonance enables the visualization of the arrhythmogenic myocardial substrate including the presence and pattern of scar and fibrosis. The most promising of these features, besides left ventricular function, strain analysis, and morphology, include tissue characterization using late-gadolinium enhancement, T1 mapping, and extracellular volume fraction calculation. We review the current evidence of SCD relating to ischemic heart disease, provide insights into imaging of the arrhythmogenic substrate that produces lethal ventricular arrhythmia, and discuss how imaging may guide therapies toward SCD prevention.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2223-2238
Gräni C, Benz DC, Gupta S, Windecker S, Kwong RY
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2223-2238 | PMID: 31864982
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Abstract

Shear Stress Estimated by Quantitative Coronary Angiography Predicts Plaques Prone to Progress and Cause Events.

Bourantas CV, Zanchin T, Torii R, Serruys PW, ... Raber L, Stone GW
Objectives
This study examined the value of endothelial shear stress (ESS) estimated in 3-dimensional quantitative coronary angiography (3D-QCA) models in detecting plaques that are likely to progress and cause events.
Background
Cumulative evidence has shown that plaque characteristics and ESS derived from intravascular ultrasound (IVUS)-based reconstructions enable prediction of lesions that will cause cardiovascular events. However, the prognostic value of ESS estimated by 3D-QCA in nonflow limiting lesions is yet unclear.
Methods
This study analyzed baseline virtual histology (VH)-IVUS and angiographic data from 28 lipid-rich lesions (i.e., fibroatheromas) that caused major adverse cardiovascular events or required revascularization (MACE-R) at 5-year follow-up and 119 lipid-rich plaques from a control group that remained quiescent. The segments studied by VH-IVUS at baseline were reconstructed using 3D-QCA software. In the obtained geometries, blood flow simulation was performed, and the pressure gradient across the lipid-rich plaque and the mean ESS values in 3-mm segments were estimated. The additive value of these hemodynamic indexes in predicting MACE-R beyond plaque characteristics was examined.
Results
MACE-R lesions were longer, had smaller minimum lumen area, increased plaque burden (PB), were exposed to higher ESS, and exhibited a higher pressure gradient. In multivariable analysis, PB (hazard ratio: 1.08; p = 0.004) and the maximum 3-mm ESS value (hazard ratio: 1.11; p = 0.001) were independent predictors of MACE-R. Lesions exposed to high ESS (>4.95 Pa) with a high-risk anatomy (minimal lumen area <4 mm and PB >70%) had a higher MACE-R rate (53.8%) than those with a low-risk anatomy exposed to high ESS (31.6%) or those exposed to low ESS who had high- (20.0%) or low-risk anatomy (7.1%; p < 0.001).
Conclusions
In the present study, 3D-QCA-derived local hemodynamic variables provided useful prognostic information, and, in combination with lesion anatomy, enabled more accurate identification of MACE-R lesions.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2206-2219
Bourantas CV, Zanchin T, Torii R, Serruys PW, ... Raber L, Stone GW
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2206-2219 | PMID: 32417338
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Abstract

A Clinical Tool to Identify Candidates for Stress-First Myocardial Perfusion Imaging.

Rouhani S, Al Shahrani A, Hossain A, Yam Y, ... Dorbala S, Chow BJW
Objectives
This study sought to develop a clinical model that identifies a lower-risk population for coronary artery disease that could benefit from stress-first myocardial perfusion imaging (MPI) protocols and that can be used at point of care to risk stratify patients.
Background
There is an increasing interest in stress-first and stress-only imaging to reduce patient radiation exposure and improve patient workflow and experience.
Methods
A secondary analysis was conducted on a single-center cohort of patients undergoing single-photon emission computed tomography (SPECT) and positron emission tomography (PET) studies. Normal MPI was defined by the absence of perfusion abnormalities and other ischemic markers and the presence of normal left ventricular wall motion and left ventricular ejection fraction. A model was derived using a cohort of 18,389 consecutive patients who underwent SPECT and was validated in a separate cohort of patients who underwent SPECT (n = 5,819), 1 internal cohort of patients who underwent PET (n=4,631), and 1 external PET cohort (n = 7,028).
Results
Final models were made for men and women and consisted of 9 variables including age, smoking, hypertension, diabetes, dyslipidemia, typical angina, prior percutaneous coronary intervention, prior coronary artery bypass graft, and prior myocardial infarction. Patients with a score ≤1 were stratified as low risk. The model was robust with areas under the curve of 0.684 (95% confidence interval [CI]: 0.674 to 0.694) and 0.681 (95% CI: 0.666 to 0.696) in the derivation cohort, 0.745 (95% CI: 0.728 to 0.762) and 0.701 (95% CI: 0.673 to 0.728) in the SPECT validation cohort, 0.672 (95% CI: 0.649 to 0.696) and 0.686 (95% CI: 0.663 to 0.710) in the internal PET validation cohort, and 0.756 (95% CI: 0.740 to 0.772) and 0.737 (95% CI: 0.716 to 0.757) in the external PET validation cohort in men and women, respectively. Men and women who scored ≤1 had negative likelihood ratios of 0.48 and 0.52, respectively.
Conclusions
A novel model, based on easily obtained clinical variables, is proposed to identify patients with low probability of having abnormal MPI results. This point-of-care tool may be used to identify a population that might qualify for stress-first MPI protocols.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2193-2202
Rouhani S, Al Shahrani A, Hossain A, Yam Y, ... Dorbala S, Chow BJW
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2193-2202 | PMID: 32563652
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Abstract

A Boosted Ensemble Algorithm for Determination of Plaque Stability in High-Risk Patients on Coronary CTA.

Al\'Aref SJ, Singh G, Choi JW, Xu Z, ... Shaw LJ, Min JK
Objectives
This study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque characteristics.
Background
Coronary computed tomography angiography (CTA) has been validated for patient-level prediction of ACS. However, the applicability of coronary CTA to CL assessment is not known.
Methods
Utilizing the ICONIC (Incident COroNary Syndromes Identified by Computed Tomography) study, a nested case-control study of 468 patients with baseline coronary CTA, the study included ACS patients with invasive coronary angiography-adjudicated CLs that could be aligned to CL precursors on baseline coronary CTA. Separate blinded core laboratories adjudicated CLs and performed atherosclerotic plaque evaluation. Thereafter, the study used a boosted ensemble algorithm (XGBoost) to develop a predictive model of CLs. Data were randomly split into a training set (80%) and a test set (20%). The area under the receiver-operating characteristic curve of this model was compared with that of diameter stenosis (model 1), high-risk plaque features (model 2), and lesion-level features of CL precursors from the ICONIC study (model 3). Thereafter, the machine learning (ML) model was applied to 234 non-ACS patients with 864 lesions to determine model performance for CL exclusion.
Results
CL precursors were identified by both coronary angiography and baseline coronary CTA in 124 of 234 (53.0%) patients, with a total of 582 lesions (containing 124 CLs) included in the analysis. The ML model demonstrated significantly higher area under the receiver-operating characteristic curve for discriminating CL precursors (0.774; 95% confidence interval [CI]: 0.758 to 0.790) compared with model 1 (0.599; 95% CI: 0.599 to 0.599; p < 0.01), model 2 (0.532; 95% CI: 0.501 to 0.563; p < 0.01), and model 3 (0.672; 95% CI: 0.662 to 0.682; p < 0.01). When applied to the non-ACS cohort, the ML model had a specificity of 89.3% for excluding CLs.
Conclusions
In a high-risk cohort, a boosted ensemble algorithm can be used to predict CL from non-CL precursors on coronary CTA.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2162-2173
Al'Aref SJ, Singh G, Choi JW, Xu Z, ... Shaw LJ, Min JK
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2162-2173 | PMID: 32682719
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Abstract

Left Atrial Strain as a Predictor of New-Onset Atrial Fibrillation in Patients With Heart Failure.

Park JJ, Park JH, Hwang IC, Park JB, Cho GY, Marwick TH
Objectives
This study sought to identify whether left atrial strain can predict new-onset atrial fibrillation (NOAF) in patients with heart failure (HF) and sinus rhythm.
Background
Both HF and atrial fibrillation have common risk factors, and HF is a risk factor for the development of atrial fibrillation and vice versa.
Methods
Among 4,312 consecutive patients with acute HF from 3 tertiary hospitals, 2,461 patients with sinus rhythm and peak atrial longitudinal strain (PALS) were included in the study. Reduced PALS was defined as PALS ≤18%, and the primary endpoint was 5-year NOAF.
Results
During a 5-year follow-up, 397 (16.1%) patients developed NOAF. Patients with reduced PALS had higher NOAF than their counterparts (18.2% vs. 12.7%; p < 0.001). After adjustment for significant covariates, we identified 6 independent predictors of NOAF, including age >70 years (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.12 to 2.00), hypertension (HR: 1.45; 95% CI: 1.10 to 1.91), left atrial volume index ≥40 ml/m (HR: 2.03; 95% CI: 1.48 to 2.77), PALS <18% (HR: 1.60; 95% CI: 1.18 to 2.17), HF with preserved ejection fraction (HR: 1.47; 95% CI: 1.11 to 1.95), and no beta-blocker prescription at discharge (HR: 1.48; 95% CI: 1.14 to 1.92). A weighted score based on these variables was used to create a composite score, HAS-BAP (H = hypertension; A = age; S = PALS; B = no beta-blocker prescription at discharge; A = atrial volume index; P = HF with preserved ejection fraction [range 0 to 6] with a median of 3 [interquartile range: 2 to 4]). The probability of NOAF increased with HAS-BAP score.
Conclusions
In patients with HF and sinus rhythm, 16.1% developed NOAF, and PALS could be used to predict the risk for NOAF. The HAS-BAP score allows determination of the risk of NOAF. (Strain for Risk Assessment and Therapeutic Strategies in Patients With Acute Heart Failure [STRATS-AHF] Registry; NCT03513653).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2071-2081
Park JJ, Park JH, Hwang IC, Park JB, Cho GY, Marwick TH
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2071-2081 | PMID: 32682715
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Abstract

Lung Ultrasound and Pulmonary Congestion During Stress Echocardiography.

Scali MC, Zagatina A, Ciampi Q, Cortigiani L, ... Picano E,
Objectives
The purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE).
Background
B-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE.
Methods
The authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up.
Results
According to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction.
Conclusions
Severe stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020-The International Stress Echo Study [SE2020]; NCT03049995).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2085-2095
Scali MC, Zagatina A, Ciampi Q, Cortigiani L, ... Picano E,
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2085-2095 | PMID: 32682714
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Abstract

Prognostic Value of Stress CMR Perfusion Imaging in Patients With Reduced Left Ventricular Function.

Ge Y, Antiochos P, Steel K, Bingham S, ... Simonetti OP, Kwong RY
Objectives
The aim of this study was to investigate the prognostic value of stress cardiac magnetic resonance imaging (CMR) in patients with reduced left ventricular (LV) systolic function.
Background
Patients with ischemic cardiomyopathy are at risk from both myocardial ischemia and heart failure. Invasive testing is often used as the first-line investigation, and there is limited evidence as to whether stress testing can effectively provide risk stratification.
Methods
In this substudy of a multicenter registry from 13 U.S. centers, patients with reduced LV ejection fraction (<50%), referred for stress CMR for suspected myocardial ischemia, were included. The primary outcome was cardiovascular death or nonfatal myocardial infarction. The secondary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, hospitalization for unstable angina or congestive heart failure, and unplanned late coronary artery bypass graft surgery.
Results
Among 582 patients (mean age 62 ± 12 years, 34% women), 40% had a history of congestive heart failure, and the median LV ejection fraction was 39% (interquartile range: 28% to 45%). At median follow-up of 5.0 years, 97 patients had experienced the primary outcome, and 182 patients had experienced the secondary outcome. Patients with no CMR evidence of ischemia or late gadolinium enhancement (LGE) experienced an annual primary outcome event rate of 1.1%. The presence of ischemia, LGE, or both was associated with higher event rates. In a multivariate model adjusted for clinical covariates, ischemia and LGE were independent predictors of the primary (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.68 to 4.14; p < 0.001; and HR: 1.86; 95% CI: 1.05 to 3.29; p = 0.03) and secondary (HR: 2.14; 95% CI: 1.55 to 2.95; p < 0.001; and HR 1.70; 95% CI: 1.16 to 2.49; p = 0.007) outcomes. The addition of ischemia and LGE led to improved model discrimination for the primary outcome (change in C statistic from 0.715 to 0.765; p = 0.02). The presence and extent of ischemia were associated with higher rates of use of downstream coronary angiography, revascularization, and cost of care spent on ischemia testing.
Conclusions
Stress CMR was effective in risk-stratifying patients with reduced LV ejection fractions. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2132-2145
Ge Y, Antiochos P, Steel K, Bingham S, ... Simonetti OP, Kwong RY
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2132-2145 | PMID: 32771575
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Abstract

Identifying Cardiac Amyloid in Aortic Stenosis: ECV Quantification by CT in TAVR Patients.

Scully PR, Patel KP, Saberwal B, Klotz E, ... Moon JC, Pugliese F
Objectives
The purpose of this study was to validate computed tomography measured ECV (ECV) as part of routine evaluation for the detection of cardiac amyloid in patients with aortic stenosis (AS)-amyloid.
Background
AS-amyloid affects 1 in 7 elderly patients referred for transcatheter aortic valve replacement (TAVR). Bone scintigraphy with exclusion of a plasma cell dyscrasia can diagnose transthyretin-related cardiac amyloid noninvasively, for which novel treatments are emerging. Amyloid interstitial expansion increases the myocardial extracellular volume (ECV).
Methods
Patients with severe AS underwent bone scintigraphy (Perugini grade 0, negative; Perugini grades 1 to 3, increasingly positive) and routine TAVR evaluation CT imaging with ECV using 3- and 5-min post-contrast acquisitions. Twenty non-AS control patients also had ECV performed using the 5-min post-contrast acquisition.
Results
A total of 109 patients (43% male; mean age 86 ± 5 years) with severe AS and 20 control subjects were recruited. Sixteen (15%) had AS-amyloid on bone scintigraphy (grade 1, n = 5; grade 2, n = 11). ECV was 32 ± 3%, 34 ± 4%, and 43 ± 6% in Perugini grades 0, 1, and 2, respectively (p < 0.001 for trend) with control subjects lower than lone AS (28 ± 2%; p < 0.001). ECV accuracy for AS-amyloid detection versus lone AS was 0.87 (0.95 for Tc-3,3-diphosphono-1,2-propanodicarboxylic acid Perugini grade 2 only), outperforming conventional electrocardiogram and echocardiography parameters. One composite parameter, the voltage/mass ratio, had utility (similar AUC of 0.87 for any cardiac amyloid detection), although in one-third of patients, this could not be calculated due to bundle branch block or ventricular paced rhythm.
Conclusions
ECV during routine CT TAVR evaluation can reliably detect AS-amyloid, and the measured ECV tracks the degree of infiltration. Another measure of interstitial expansion, the voltage/mass ratio, also performed well.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2177-2189
Scully PR, Patel KP, Saberwal B, Klotz E, ... Moon JC, Pugliese F
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2177-2189 | PMID: 32771574
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Abstract

Myocardial Native T Predicts Load-Independent Left Ventricular Chamber Stiffness In Patients With HFpEF.

Omori T, Nakamori S, Fujimoto N, Ishida M, ... Ito M, Dohi K
Objectives
This study sought to evaluate the potential of cardiac magnetic resonance T mapping to detect load-independent left ventricular (LV) chamber stiffness by histological confirmation.
Background
Accurate noninvasive diagnosis of LV diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) remains challenging.
Methods
Nineteen HFpEF patients (14 female, 65 ± 16 years of age) without primary cardiomyopathy were prospectively enrolled. Cine, late gadolinium enhancement cardiac magnetic resonance, and triple-slice T mapping using a modified Look-Locker inversion recovery sequence were performed at 3-T. Extracellular volume (ECV) was quantified from pre- and post-contrast T values of the blood and myocardium with hematocrit correction. LV stiffness constant (beta) was assessed by calculating the slope of the end-diastolic pressure-volume relationship curve during vena cava occlusion. Biopsy samples were used for quantification of collagen volume fraction (CVF) and myocardial cell size.
Results
Six patients showed focal scar on late gadolinium enhancement. There was no significant difference in histological CVF between patients with and without focal myocardial scarring (p = 0.2). Septal ECV rather than native T was a better surrogate marker for detecting histological CVF (r = 0.54; p = 0.02, and r = 0.44; p = 0.06, respectively). Global native T and ECV, but not native T and ECV in the septal myocardium, correlated well with the beta of passive LV stiffness, and had similar ability for predicting LV stiffness to histological CVF (r = 0.54, 0.50, 0.53, all p < 0.05, respectively). When the beta ≥0.054 was considered as moderately increased LV stiffness, global native T ≥1,362 ms provided 88% sensitivity and 64% specificity with the C-statistic of 0.81 (95% confidence interval: 0.56 to 0.95).
Conclusions
Myocardial native T provides comparable ability in predicting LV stiffness to ECV and histological CVF and may be useful for monitoring patients with HFpEF who have renal dysfunction, allergy to gadolinium, or wheezing that can simulate asthma. Our feasibility study shows the potential of native T to allow for insight of heterogeneous pathophysiology and better risk stratification of HFpEF.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2117-2128
Omori T, Nakamori S, Fujimoto N, Ishida M, ... Ito M, Dohi K
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2117-2128 | PMID: 32771571
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Abstract

Left Atrial Strain Impairment Precedes Geometric Remodeling as a Marker of Post-Myocardial Infarction Diastolic Dysfunction.

Kim J, Yum B, Palumbo MC, Sultana R, ... Devereux RB, Weinsaft JW
Objectives
The aims of this study were to test the magnitude of agreement between echocardiography (echo)- and cardiac magnetic resonance (CMR)-derived left atrial (LA) strain and to study their relative diagnostic performance in discriminating diastolic dysfunction (DD) and predicting atrial fibrillation (AF).
Backgrounds
Peak atrial longitudinal strain (PALS) is a novel performance index. Utility of echo-quantified LA strain has yet to be prospectively tested in relation to current DD guidelines or compared to CMR.
Methods
The study population comprised 257 post-myocardial infarction (MI) patients undergoing echo and CMR, including prospective derivation (n = 157) and clinical validation (n = 100) cohorts. DD was graded on echo using established consensus guidelines blinded to strain results.
Results
PALS on both echo and CMR was nearly 2-fold lower among patients with versus no DD (p < 0.001) and was significantly different in those with mild versus no DD (p < 0.01). In contrast, LA geometric parameters including echo- and CMR-derived volumes were significantly different between advanced versus no DD groups (p < 0.001) but not between groups with mild versus no DD (all p > 0.05). Echo and CMR PALS yielded small differences irrespective of orientation and similar diagnostic performance for DD in the derivation (area under the curve [AUC]: 0.70 to 0.78) and validation (AUC: 0.75 to 0.78) cohorts. Impaired PALS on both modalities was independently associated with MI size (p < 0.001). During 4.4 ± 3.8 years of follow-up in the derivation cohort, 8% developed AF. Both 2-chamber echo- and CMR-derived PALS stratified arrhythmic risk (p = 0.004 and p = 0.02, respectively), including a 4-fold difference among patients in the lowest versus remainder of quartiles of echo-derived PALS (24% vs. 6%). Similarly, echo and CMR PALS were lower (both p < 0.05) among patients with subsequent heart failure hospitalizations.
Conclusions
Echo-derived PALS parallels results of CMR, yields incremental diagnostic utility versus LA geometry for stratifying presence and severity of DD, and improves prediction of AF and congestive heart failure after MI.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2099-2113
Kim J, Yum B, Palumbo MC, Sultana R, ... Devereux RB, Weinsaft JW
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2099-2113 | PMID: 32828776
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Impact:
Abstract

Left Ventricular Structural and Functional Alterations in Patients With Pheochromocytoma/Paraganglioma Before and After Surgery.

Dobrowolski P, Januszewicz A, Klisiewicz A, Gosk-Przybyłek M, ... Eisenhofer G, Prejbisz A
Objectives
This study sought to evaluate left ventricular (LV) structure and function in pheochromocytoma and paraganglioma (PPGL) patients before and after curative surgery.
Background
Data on catecholamine-induced effects on LV structure and function in patients with PPGL are limited and conflicting.
Methods
The study evaluated 81 consecutive patients with a PPGL, among whom 66 were evaluated 12 months after tumor removal. Fifty patients matched for age, sex, hypertension presence, and blood pressure (BP) levels served as a control group (non-PPGL group). Echocardiography was employed to assess the LV mass index (LVMI), systolic function including speckle tracking echocardiography, and diastolic function.
Results
Patients with PPGL were characterized by higher LVMI (median 103 [interquartile range (IQR): 88 to 132] g/m vs. median 94 [IQR: 74 to 106] g/m; p = 0.006) and frequency of LV hypertrophy (44.4% vs. 24.0%; p = 0.018) compared with the non-PPGL group. Patients with PPGLs were characterized by lower global longitudinal strain (GLS) and early diastolic mitral annular velocity compared with patients in the non-PPGL group (median -17.2% [IQR: 15.6% to 18.9%] vs. median -19.3% [IQR: 17.7% to 20.6%]; p < 0.001; and median 11.1 [IQR: 8.3 to 13.0] cm/s vs. median 12.3 [IQR: 10.6 to 14.6] cm/s; p = 0.018, respectively). Presence of LV hypertrophy and GLS were independently associated with plasma free metanephrine concentrations. In operated patients, there were lower frequencies of LV hypertrophy (39.4% vs. 22.7%; p = 0.003), LVMI (median 98 [IQR: 85 to 115] g/m vs. median 90 [IQR: 76 to 109] g/m; p < 0.001), and the ratio of transmitral early diastolic velocity to early diastolic mitral annular velocity (median 6.8 [IQR: 5.5 to 8.6] vs. median 6.0 [IQR: 5.0 to 7.6]; p = 0.005) but higher values for GLS (median -17.4 [IQR: -15.8 to 19.1] vs. median -18.5 [IQR: -17.1 to 20.1] p < 0.001) after compared with before surgery.
Conclusions
Catecholamine excess in patients with PPGLs can lead not only to LV hypertrophy, but also to impairment of systolic LV function and subclinical alterations of diastolic LV function, independently of BP levels. These structural and functional changes are reversible after surgical intervention.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 Sep 2020; epub ahead of print
Dobrowolski P, Januszewicz A, Klisiewicz A, Gosk-Przybyłek M, ... Eisenhofer G, Prejbisz A
JACC Cardiovasc Imaging: 10 Sep 2020; epub ahead of print | PMID: 32950457
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Abstract

Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance.

Redheuil A, Blanchard A, Pereira H, Raissouni Z, ... Kachenoura N, Mousseaux E
Objectives
This study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans.
Background
Experimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake.
Methods
The study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo.
Results
Median plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m vs. 82 ± 15 ml/m; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP.
Conclusions
Only primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2149-2159
Redheuil A, Blanchard A, Pereira H, Raissouni Z, ... Kachenoura N, Mousseaux E
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2149-2159 | PMID: 32950448
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Abstract

Mitral Regurgitation After Percutaneous Mitral Valvuloplasty: Insights Into Mechanisms and Impact on Clinical Outcomes.

Nunes MCP, Levine RA, Braulio R, Pascoal-Xavier MA, ... Aikawa E, Hung J
Objectives
The aim of this study was to assess the incidence, mechanisms, and outcomes of mitral regurgitation (MR) after percutaneous mitral valvuloplasty (PMV).
Background
Significant MR continues to be a major complication of PMV, with a wide range in clinical presentation and prognosis.
Methods
Consecutive patients with mitral stenosis undergoing PMV were prospectively enrolled. MR severity was evaluated by using quantitative echocardiographic criteria, and its mechanism was characterized by 3-dimensional transesophageal echocardiography, divided broadly into 4 categories based on the features contributing to the valve damage. B-type natriuretic peptide levels were obtained before and 24 h after the procedure. Endpoints estimated cardiovascular death or mitral valve (MV) replacement due to predominant MR.
Results
A total of 344 patients, ages 45.1 ± 12.1 years, of whom 293 (85%) were women, were enrolled. Significant MR after PMV was found in 64 patients (18.6%). The most frequent mechanism of MR was commissural, which occurred in 22 (34.4%) patients, followed by commissural with posterior leaflet in 16 (25.0%), leaflets at central scallop or subvalvular damage in 15 (23.4%), and central MR in 11 (17.2%). During the mean follow-up period of 3 years (range 1 day to 10.6 years), 60 patients reached the endpoint. The event-free survival rates were similar among patients with mild or commissural MR, whereas patients with damaged central leaflet scallop or subvalvular apparatus had the worst outcome, with an event-free survival rate at 1 year of only 7%. Long-term outcome was predicted by net atrioventricular compliance (C) at baseline and post-procedural variables, including valve area, mean gradient, and magnitude of decrease in B-type natriuretic peptide levels, adjusted for the mechanism of MR.
Conclusions
Significant MR following PMV is a frequent event, mainly related to commissural splitting, with favorable clinical outcome. Parameters that express the relief of valve obstruction and the mechanism by which MR develops were predictors of long-term outcomes.

Copyright © 2020 American College of Cardiology Foundation. All rights reserved.

JACC Cardiovasc Imaging: 10 Sep 2020; epub ahead of print
Nunes MCP, Levine RA, Braulio R, Pascoal-Xavier MA, ... Aikawa E, Hung J
JACC Cardiovasc Imaging: 10 Sep 2020; epub ahead of print | PMID: 32950446
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Abstract

Body Composition, Natriuretic Peptides, and Adverse Outcomes in Heart Failure With Preserved and Reduced Ejection Fraction.

Selvaraj S, Kim J, Ansari BA, Zhao L, ... Gordon DA, Chirinos JA
Objectives
The purpose of this study was to determine the relationship between body composition, N-terminal B-type natriuretic peptide (NT-proBNP) levels, and heart failure (HF) phenotypes and outcomes.
Background
Abnormalities in body composition can influence metabolic dysfunction and HF severity; however, data assessing fat distribution and skeletal muscle (SM) size in HF with reduced (HFrEF) and preserved EF (HFpEF) are limited. Further, whether NPs relate more closely to axial muscle mass than measures of adiposity is not well studied.
Methods
We studied 572 adults without HF (n = 367), with HFrEF (n = 113), or with HFpEF (n = 92). Cardiac magnetic resonance was used to assess subcutaneous and visceral abdominal fat, paracardial fat, and axial SM size. We measured NT-proBNP in 334 participants. We used Cox regression to analyze the relationship between body composition and mortality.
Results
Compared with controls, pericardial and subcutaneous fat thickness were significantly increased in HFpEF, whereas patients with HFrEF had reduced axial SM size after adjusting for age, sex, race, and body height (p < 0.05 for comparisons). Lower axial SM size, but not fat, was significantly predictive of death in unadjusted (standardized hazard ratio: 0.63; p < 0.0001) and multivariable-adjusted analyses (standardized hazard ratio = 0.72; p = 0.0007). NT-proBNP levels more closely related to lower axial SM rather than fat distribution or body mass index (BMI) in network analysis, and when simultaneously assessed, only SM (p = 0.0002) but not BMI (p = 0.18) was associated with NT-proBNP. However, both NT-proBNP and axial SM mass were independently predictive of death (p < 0.05).
Conclusions
HFpEF and HFrEF have distinct abnormalities in body composition. Reduced axial SM, but not fat, independently predicts mortality. Greater axial SM more closely associates with lower NT-proBNP rather than adiposity. Lower NT-proBNP levels in HFpEF compared with HFrEF relate more closely to muscle mass rather than obesity.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 Sep 2020; epub ahead of print
Selvaraj S, Kim J, Ansari BA, Zhao L, ... Gordon DA, Chirinos JA
JACC Cardiovasc Imaging: 10 Sep 2020; epub ahead of print | PMID: 32950445
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Abstract

Impact of Mitral Regurgitation Severity and Left Ventricular Remodeling on Outcome After Mitraclip Implantation: Results From the Mitra-FR Trial.

Messika-Zeitoun D, Iung B, Armoiry X, Trochu JN, ... Boutitie F, Obadia JF
Objectives
This study aimed to identify a subset of patients based on echocardiographic parameters who might have benefited from transcatheter correction using the Mitraclip system in the MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial.
Background
It has been suggested that differences in the degree of mitral regurgitation (MR) and left ventricular (LV) remodeling may explain the conflicting results between the MITRA-FR and the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trials.
Methods
In a post hoc analysis, we evaluated the interaction between the intervention and subsets of patients defined based on MR severity (effective regurgitant orifice [ERO], regurgitant volume [RVOL] and regurgitant fraction [RF]), LV remodeling (end-diastolic and end-systolic diameters and volumes) and combination of these parameters with respect to the composite of death from any cause or unplanned hospitalization for heart failure at 24 months.
Results
We observed a neutral impact of the intervention in subsets with the highest MR degree (ERO ≥30 mm, RVOL ≥45 ml or RF ≥50%) as in patients with milder MR degree. The same was seen in subsets with the milder LV remodeling using either diastolic or systolic diameters or volumes. When parameters of MR severity and LV remodeling were combined, there was still no benefit of the intervention including in the subset of patients with an ERO/end-diastolic volume ratio ≥ 0.15 despite similar ERO and LV end-diastolic volume compared with COAPT patients.
Conclusions
In the MITRA-FR trial, we could not identify a subset of patients defined based on the degree of the regurgitation, LV remodeling or on their combination, including those deemed as having disproportionate MR, that might have benefited from transcatheter correction using the Mitraclip system. (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation [MITRA-FR]; NCT01920698).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 15 Sep 2020; epub ahead of print
Messika-Zeitoun D, Iung B, Armoiry X, Trochu JN, ... Boutitie F, Obadia JF
JACC Cardiovasc Imaging: 15 Sep 2020; epub ahead of print | PMID: 32950444
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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 © 2020 American College of Cardiology Foundation. All rights reserved.

JACC Cardiovasc Imaging: 10 Sep 2020; epub ahead of print
Greenland P, Michos ED, Redmond N, Fine LJ, ... Sterling MR, Thanassoulis G
JACC Cardiovasc Imaging: 10 Sep 2020; epub ahead of print | PMID: 32950442
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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 2.2% increase in the risk of death over 54 months. For every 1 ml/m increase in RV end-systolic volume index or RV end-diastolic volume index, the risk of clinical worsening increases by 1.3% and 0.7%, respectively, and the risk of mortality increases by 0.9% and 1%. Every 1 ml/m decrease in left ventricular end-systolic volume index or left ventricular end-diastolic volume index increased the risk of death by 2.1% and 2.3%. 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 © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 28 Sep 2020; epub ahead of print
Alabed S, Shahin Y, Garg P, Alandejani F, ... Kiely DG, Swift AJ
JACC Cardiovasc Imaging: 28 Sep 2020; epub ahead of print | 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,

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 © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 25 Sep 2020; epub ahead of print
van den Hoogen IJ, Gianni U, Wood MJ, Taqueti VR, ... Shaw LJ,
JACC Cardiovasc Imaging: 25 Sep 2020; epub ahead of print | PMID: 33011128
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Abstract

Hypertensive Exposure Markers by MRI in Relation to Cerebral Small Vessel Disease and Cognitive Impairment.

Amier RP, Marcks N, Hooghiemstra AM, Nijveldt R, ... van Rossum AC,
Objectives
This study sought to investigate the extent of hypertensive exposure as assessed by cardiovascular magnetic resonance imaging (MRI) in relation to cerebral small vessel disease (CSVD) and cognitive impairment, with the aim of understanding the role of hypertension in the early stages of deteriorating brain health.
Background
Preserving brain health into advanced age is one of the great challenges of modern medicine. Hypertension is thought to induce vascular brain injury through exposure of the cerebral microcirculation to increased pressure/pulsatility. Cardiovascular MRI provides markers of (subclinical) hypertensive exposure, such as aortic stiffness by pulse wave velocity (PWV), left ventricular (LV) mass index (LVMi), and concentricity by mass-to-volume ratio.
Methods
A total of 559 participants from the Heart-Brain Connection Study (431 patients with manifest cardiovascular disease and 128 control participants), age 67.8 ± 8.8 years, underwent 3.0-T heart-brain MRI and extensive neuropsychological testing. Aortic PWV, LVMi, and LV mass-to-volume ratio were evaluated in relation to presence of CSVD and cognitive impairment. Effect modification by patient group was investigated by interaction terms; results are reported pooled or stratified accordingly.
Results
Aortic PWV (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 1.05 to 1.30 in patient groups only), LVMi (in carotid occlusive disease, OR: 5.69; 95% CI: 1.63 to 19.87; in other groups, OR: 1.30; 95% CI: 1.05 to 1.62]) and LV mass-to-volume ratio (OR: 1.81; 95% CI: 1.46 to 2.24) were associated with CSVD. Aortic PWV (OR: 1.07; 95% CI: 1.02 to 1.13) and LV mass-to-volume ratio (OR: 1.27; 95% CI: 1.07 to 1.51) were also associated with cognitive impairment. Relations were independent of sociodemographic and cardiac index and mostly persisted after correction for systolic blood pressure or medical history of hypertension. Causal mediation analysis showed significant mediation by presence of CSVD in the relation between hypertensive exposure markers and cognitive impairment.
Conclusions
The extent of hypertensive exposure is associated with CSVD and cognitive impairment beyond clinical blood pressure or medical history. The mediating role of CSVD suggests that hypertension may lead to cognitive impairment through the occurrence of CSVD.

Copyright © 2020. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 27 Sep 2020; epub ahead of print
Amier RP, Marcks N, Hooghiemstra AM, Nijveldt R, ... van Rossum AC,
JACC Cardiovasc Imaging: 27 Sep 2020; epub ahead of print | PMID: 33011127
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Abstract

Predictors of Rapid Plaque Progression: An Optical Coherence Tomography Study.

Araki M, Yonetsu T, Kurihara O, Nakajima A, ... Kakuta T, Jang IK
Objectives
This study sought to identify morphological predictors of rapid plaque progression.
Background
Two patterns of plaque progression have been described: slow linear progression and rapid step-wise progression. The former pattern will cause stable angina when the narrowing reaches a critical threshold, whereas the latter pattern may lead to acute coronary syndromes or sudden cardiac death.
Methods
Patients who underwent optical coherence tomography (OCT) imaging during the index procedure and follow-up angiography with a minimum interval of 6 months were selected. Nonculprit lesions with a diameter stenosis of ≥30% on index angiography were assessed. Lesion progression was defined as a decrease of angiographic minimum lumen diameter ≥0.4 mm at follow-up (mean, 7.1 months). Baseline morphological characteristics of plaques with rapid progression were evaluated by OCT. In a subgroup with follow-up OCT imaging for plaques with rapid progression, morphological changes from baseline to follow-up were assessed.
Results
Among 517 lesions in 248 patients, 50 lesions showed rapid progression. These lesions had a significantly higher prevalence of lipid-rich plaque (76.0% vs. 50.5%, respectively), thin-cap fibroatheroma (TCFA) (20.0% vs. 5.8%, respectively), layered plaque (60.0% vs. 34.0%, respectively), macrophage accumulation (62.0% vs. 42.4%, respectively), microvessel (46.0% vs. 29.1%, respectively), plaque rupture (12.0% vs. 4.7%, respectively), and thrombus (6.0% vs. 1.1%, respectively) at baseline compared with those without rapid progression. Multivariate analysis identified lipid-rich plaque (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.02 to 4.62; p = 0.045]), TCFA (OR: 5.85; 95% CI: 2.01 to 17.03; p = 0.001), and layered plaque (OR: 2.19; 95% CI: 1.03 to 4.17; p = 0.040) as predictors of subsequent rapid lesion progression. In a subgroup analysis for plaques with rapid progression, a new layer was detected in 25 of 41 plaques (61.0%) at follow-up.
Conclusions
Lipid-rich plaques, TCFA, and layered plaques were predictors of subsequent rapid plaque progression. A new layer, a signature of previous plaque disruption and healing, was detected in more than half of the lesions with rapid progression at follow-up. (Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 28 Sep 2020; epub ahead of print
Araki M, Yonetsu T, Kurihara O, Nakajima A, ... Kakuta T, Jang IK
JACC Cardiovasc Imaging: 28 Sep 2020; epub ahead of print | PMID: 33011121
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Abstract

Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping.

Kotecha T, Chacko L, Chehab O, O\'Reilly N, ... Patel N, Fontana M
Objectives
The authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD).
Background
VA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD.
Methods
One hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps.
Results
In patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%).
Conclusions
VA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making.

Copyright © 2020 American College of Cardiology Foundation. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; epub ahead of print
Kotecha T, Chacko L, Chehab O, O'Reilly N, ... Patel N, Fontana M
JACC Cardiovasc Imaging: 29 Sep 2020; epub ahead of print | PMID: 33011115
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Impact:
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 ± 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 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/m, 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 © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print
Habib M, Adler A, Fardfini K, Hoss S, ... Rakowski H, Chan RH
JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print | PMID: 33248971
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Abstract

Magnetic Resonance Mapping of Catheter Ablation Lesions After Post-Infarction Ventricular Tachycardia Ablation.

Dabbagh GS, Ghannam M, Siontis KC, Attili A, ... Morady F, Bogun F
Objectives
This study sought to describe cardiac magnetic resonance (CMR) characteristics of ablation lesions within post-infarction scar.
Background
Chronic ablation lesions created during radiofrequency ablation of ventricular tachycardia (VT) in the setting of prior myocardial infarction have not been described in humans.
Methods
Seventeen patients (15 men, ejection fraction 25 ± 8%, 66 ± 6 years of age) with CMR imaging prior to repeat ablation procedures for VT were studied. Electroanatomic maps from first-time procedures and subsequent CMR images were merged and retrospectively compared with electroanatomic maps from repeat procedures.
Results
The delay between the index ablation procedure and the CMR study was 30 ± 29 months. Late gadolinium-enhanced CMR revealed a confluent nonenhancing subendocardial dark core within the infarct-related scar tissue in all patients. Intracardiac thrombi were ruled out by transthoracic and intracardiac echocardiography. These core lesions matched the distribution of prior ablation lesions, and corresponded to unexcitable areas at repeat procedures.
Conclusions
Ablation lesions can be detected by CMR after VT ablation in post-infarction patients and have a different appearance than scar tissue. These lesions can be observed many months after an initial ablation.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print
Dabbagh GS, Ghannam M, Siontis KC, Attili A, ... Morady F, Bogun F
JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print | PMID: 33248970
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Impact:
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: MBF / MBF), and subendocardial MPR (MPR). 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, MPR 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 © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print
Rahman H, Scannell CM, Demir OM, Ryan M, ... Perera D, Chiribiri A
JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print | PMID: 33248969
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Abstract

Implementing Coronary Computed Tomography Angiography in the Catheterization Laboratory.

Collet C, Sonck J, Leipsic J, Monizzi G, ... Andreini D, De Bruyne B

Coronary computed tomography angiography (CCTA) is now an established tool in the diagnostic work-up of patients suspected to have coronary artery disease. Yet, its usefulness beyond this phase has not been fully explored. The current review focuses on the implementation of CCTA as a tool to plan and guide coronary interventions in the catheterization laboratory. Specifically, we explore the potential of CCTA to improve patient selection for percutaneous revascularization, provide the rationale for better resource use, and present a novel approach to incorporate 3-dimensional CT guidance for percutaneous coronary interventions.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print
Collet C, Sonck J, Leipsic J, Monizzi G, ... Andreini D, De Bruyne B
JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print | PMID: 33248968
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Abstract

CMR in Evaluating Valvular Heart Disease: Diagnosis, Severity, and Outcomes.

Myerson SG

Cardiac magnetic resonance (CMR) is a versatile imaging tool that brings much to the assessment of valvular heart disease. Although it is best known for myocardial imaging (even in valve disease), it provides excellent assessment of all 4 heart valves, with some distinct advantages, including a free choice of image planes and accurate flow and volumetric quantification. These allow the severity of each valve lesion to be characterized, in addition to optimal visualization of the surrounding outflow tracts and vessels, to deliver a comprehensive package. It can assess each valve lesion separately (in multiple valve disease) and is not affected by hemodynamic status. The accurate quantitation of regurgitant lesions and the ability to characterize myocardial changes also provides an ability to predict future clinical outcomes in asymptomatic patients. This review outlines how CMR can be used in cardiac valve disease to compliment echocardiography and enhance the patient assessment. It covers the main CMR methods used, their strengths and limitations, and the optimal way to apply them to evaluate valve disease.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print
Myerson SG
JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print | PMID: 33248967
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Abstract

Long-Term Prognosis of Patients With Coronary Microvascular Disease Using Stress Perfusion Cardiac Magnetic Resonance.

Zhou W, Lee JCY, Leung ST, Lai A, ... Pennell DJ, Ng MY
Objectives
This study investigated the prognosis of coronary microvascular disease (CMD) as determined by stress perfusion cardiac magnetic resonance (CMR) in patients with ischemic symptoms but without significant coronary artery disease (CAD).
Background
Patients with CMD have poorer prognosis with various cardiac diseases. The myocardial perfusion reserve index (MPRI) derived from noninvasive stress perfusion CMR has been established to diagnose microvascular angina with a threshold MPRI <1.4. The prognosis of CMD as determined by MPRI is unknown.
Methods
Chest pain patients without epicardial CAD or myocardial disease from January 2009 to December 2017 were retrospectively included from 3 imaging centers in Hong Kong (HK). Stress perfusion CMR examinations were performed using either adenosine or adenosine triphosphate. Adequate stress was assessed by achieving splenic switch-off sign. Measurement of MPRI was performed in all stress perfusion CMR scans. Patients were followed for major adverse cardiovascular events defined as all-cause death, acute coronary syndrome (ACS), epicardial CAD development, heart failure hospitalization and non-fatal stroke.
Results
A total of 218 patients were studied (mean age 59 ± 12 years; 49.5% male) and the average MPRI of that cohort was 1.56 ± 0.33. Females and a history of hyperlipidemia were predictors of lower MPRI. Major adverse cardiovascular events (MACE) occurred in 15.6% of patients during a median follow-up of 5.5 years (interquartile range: 4.6 to 6.8 years). The optimal cutoff value of MPRI in predicting MACE was found with a threshold MPRI ≤1.47. Patients with MPRI ≤1.47 had three-fold increased risk of MACE compared with those with MPRI >1.47 (hazard ratio [HR]: 3.14; 95% confidence interval [CI]: 1.58 to 6.25; p = 0.001). Multivariate Cox regression after adjusting for age and hypertension demonstrated that MPRI was an independent predictor of MACE (HR: 0.10; 95% CI: 0.03 to 0.34; p < 0.001).
Conclusion
Stress perfusion CMR-derived MPRI is an independent imaging marker that predicts MACE in patients with ischemic symptom and no overt CAD over the medium term.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print
Zhou W, Lee JCY, Leung ST, Lai A, ... Pennell DJ, Ng MY
JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print | PMID: 33248966
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Abstract

CT Angiographic and Plaque Predictors of Functionally Significant Coronary Disease and Outcome Using Machine Learning.

Yang S, Koo BK, Hoshino M, Lee JM, ... Kakuta T, Narula J
Objectives
The goal of this study was to investigate the association of stenosis and plaque features with myocardial ischemia and their prognostic implications.
Background
Various anatomic, functional, and morphological attributes of coronary artery disease (CAD) have been independently explored to define ischemia and prognosis.
Methods
A total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography were analyzed. Stenosis and plaque features of the target lesion and vessel were evaluated by an independent core laboratory. Relevant features associated with low FFR (≤0.80) were identified by using machine learning, and their predictability of 5-year risk of vessel-oriented composite outcome, including cardiac death, target vessel myocardial infarction, or target vessel revascularization, were evaluated.
Results
The mean percent diameter stenosis and invasive FFR were 48.5 ± 17.4% and 0.81 ± 0.14, respectively. Machine learning interrogation identified 6 clusters for low FFR, and the most relevant feature from each cluster was minimum lumen area, percent atheroma volume, fibrofatty and necrotic core volume, plaque volume, proximal left anterior descending coronary artery lesion, and remodeling index (in order of importance). These 6 features showed predictability for low FFR (area under the receiver-operating characteristic curve: 0.797). The risk of 5-year vessel-oriented composite outcome increased with every increment of the number of 6 relevant features, and it had incremental prognostic value over percent diameter stenosis and FFR (area under the receiver-operating characteristic curve: 0.706 vs. 0.611; p = 0.031).
Conclusions
Six functionally relevant features, including minimum lumen area, percent atheroma volume, fibrofatty and necrotic core volume, plaque volume, proximal left anterior descending coronary artery lesion, and remodeling index, help define the presence of myocardial ischemia and provide better prognostication in patients with CAD. (CCTA-FFR Registry for Risk Prediction; NCT04037163).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print
Yang S, Koo BK, Hoshino M, Lee JM, ... Kakuta T, Narula J
JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print | PMID: 33248965
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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 © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 24 Nov 2020; epub ahead of print
Houbois CP, Nolan M, Somerset E, Shalmon T, ... Wintersperger BJ, Thavendiranathan P
JACC Cardiovasc Imaging: 24 Nov 2020; epub ahead of print | PMID: 33248962
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Abstract

Neo-LVOT and Transcatheter Mitral Valve Replacement: Expert Recommendations.

Reid A, Ben Zekry S, Turaga M, Tarazi S, ... Blanke P, Leipsic J

With the advent of transcatheter mitral valve replacement (TMVR), the concept of the neo-left ventricular outflow tract (LVOT) was introduced and remains an essential component of treatment planning. This paper describes the LVOT anatomy and provides a step-by-step computed tomography methodology to segment and measure the neo-LVOT while discussing the current evidence and outstanding challenges. It also discusses the technical and hemodynamic factors that play a major role in assessing the neo-LVOT. A summary of expert-based recommendations about the overall risk of LVOT obstruction in different scenarios is presented along with the currently available methods to reduce the risk of LVOT obstruction and other post-procedural complications.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print
Reid A, Ben Zekry S, Turaga M, Tarazi S, ... Blanke P, Leipsic J
JACC Cardiovasc Imaging: 18 Nov 2020; epub ahead of print | PMID: 33248959
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This program is still in alpha version.