Journal: JACC Cardiovasc Imaging

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Abstract

Cardiac Magnetic Resonance Imaging-Based Right Ventricular Strain Analysis for Assessment of Coupling and Diastolic Function in Pulmonary Hypertension.

Tello K, Dalmer A, Vanderpool R, Ghofrani HA, ... Gall H, Richter MJ
Objectives
This study sought to compare cardiac magnetic resonance (CMR) imaging-derived right ventricular (RV) strain and invasively measured pressure-volume loop-derived RV contractility, stiffness, and afterload and RV-arterial coupling in pulmonary hypertension (PH).
Background
In chronic RV pressure overload, RV-arterial uncoupling is considered the driving cause of RV maladaptation and eventual RV failure. The pathophysiological and clinical value of CMR-derived RV strain relative to that of invasive pressure-volume loop-derived measurements in PH remains incompletely understood.
Methods
In 38 patients with PH, global RV CMR strain was measured within 24 h of diagnostic right heart catheterization and conductance (pressure-volume) catheterization. Associations were evaluated by correlation, multivariate logistic binary regression, and receiver operating characteristic analyses.
Results
Long-axis RV longitudinal and radial strain and short-axis RV radial and circumferential strain were -18.0 ± 7.0%, 28.9% [interquartile range (IQR): 17.4% to 46.6%]; 15.6 ± 6.2%; and -9.8 ± 3.5%, respectively. RV-arterial coupling (end-systolic [Eds]/arterial elastance [Ea]) was 0.76 (IQR: 0.47 to 1.07). Peak RV strain correlated with Ees/Ea, afterload (Ea), RV diastolic dysfunction (Tau), and stiffness (end-diastolic elastance [Eed]) but not with contractility (Ees). In multivariate analysis, long-axis RV radial strain was associated with RV-arterial uncoupling (Ees/Ea: <0.805; odds ratio [OR]: 5.50; 95% confidence interval [CI]: 1.50 to 20.18), whereas long-axis RV longitudinal strain was associated with increased RV diastolic stiffness (Eed: ≥0.124 mm Hg/ml; OR: 1.23; 95% CI: 1.10 to 1.51). The long-axis RV longitudinal strain-to-RV end-diastolic volume/body surface area ratio strongly predicted RV diastolic stiffness (area under receiver operating characteristic curve: 0.908).
Conclusions
In chronic RV overload, CMR-determined RV strain is associated with RV-arterial uncoupling and RV end-diastolic stiffness and represents a promising noninvasive alternative to current invasive methods for assessment of RV-arterial coupling and end-diastolic stiffness in patients with PH. (Right Ventricular Haemodynamic Evaluation and Response to Treatment [Rightheart I]; NCT03403868).

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

JACC Cardiovasc Imaging: 30 Oct 2019; 12:2155-2164
Tello K, Dalmer A, Vanderpool R, Ghofrani HA, ... Gall H, Richter MJ
JACC Cardiovasc Imaging: 30 Oct 2019; 12:2155-2164 | PMID: 30878422
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Abstract

Diffusion Tensor Cardiovascular Magnetic Resonance Imaging: A Clinical Perspective.

Khalique Z, Ferreira PF, Scott AD, Nielles-Vallespin S, Firmin DN, Pennell DJ

Imaging the heart is central to cardiac phenotyping, but in clinical practice, this has been restricted to macroscopic interrogation. Diffusion tensor cardiovascular magnetic resonance (DT-CMR) is a novel, noninvasive technique that is beginning to unlock details of this microstructure in humans in vivo. DT-CMR demonstrates the helical cardiomyocyte arrangement that drives rotation and torsion. Sheetlets (functional units of cardiomyocytes, separated by shear layers) have been shown to reorientate between diastole and systole, revealing how microstructural function facilitates cardiac thickening. Measures of tissue diffusion can also be made: fractional anisotropy (a measure of myocyte organization) and mean diffusivity (a measure of myocyte packing). Abnormal myocyte orientation and sheetlet function has been demonstrated in congenital heart disease, cardiomyopathy, and after myocardial infarction. It is too early to predict the clinical importance of DT-CMR, but such unique in vivo information will likely prove valuable in early diagnosis and risk prediction of cardiac dysfunction and arrhythmias.

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

JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print
Khalique Z, Ferreira PF, Scott AD, Nielles-Vallespin S, Firmin DN, Pennell DJ
JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print | PMID: 31607663
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Abstract

Relationship Between Focal and Diffuse Fibrosis Assessed by CMR and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction.

Kanagala P, Cheng ASH, Singh A, Khan JN, ... Ng LL, McCann GP
Objectives
This study sought to assess the presence and extent of focal and diffuse fibrosis in heart failure in patients with preserved ejection fraction (HFpEF) compared to asymptomatic control subjects, and the relationship of fibrosis to clinical outcome.
Background
Myocardial fibrosis has been implicated in the pathophysiology of HFpEF.
Methods
In this prospective, observational study, 140 subjects of similar age and sex (HFpEF: n = 96; control subjects: n = 44; 73 ± 8 years of age; 49% males) underwent cardiac magnetic resonance imaging. Late gadolinium-enhanced (LGE) imaging and T1 mapping to calculate myocardial extracellular volume indexed to body surface area (iECV) were used to assess fibrosis.
Results
Patients with HFpEF had more concentric remodeling and worse diastolic function. Focal fibrosis was more frequent in HFpEF subjects (overall: n = 49; infarction: n = 17; nonischemic cases: n = 36; mixed patterns: n = 4) than in control subjects (overall: n = 3). Diffuse fibrosis was also greater in HFpEF subjects than control subjects (iECV: 13.7 ± 4.4 ml/m versus 10.9 ± 2.8 ml/m; p < 0.0001). During median follow-up (1,429 days), there were 42 composite events (14 deaths; 28 heart failure hospitalizations) in cases of HFpEF. Myocardial infarction revealed on LGE imaging was a predictor of outcomes on univariate analysis only. With multivariate analysis, iECV (hazard ratio [HR]: 1.689; 95% confidence interval [CI]: 1.141 to 2.501; p = 0.009) was an independent predictor of outcome along with mitral peak velocity of early filling (E)-to-early diastolic mitral annular velocity (E\') (E/E\') ratio (HR: 1.716; 95% CI: 1.191 to 2.472; p = 0.004) and prior HF hospitalization (HR: 2.537; 95% CI: 1.090 to 5.902; p = 0.031). iECV was also significantly associated with ventricular/left atrial remodeling and renal dysfunction: right ventricular end-diastolic volume indexed (r = 0.456; p < 0.0001), left ventricular mass/volume (r = 0.348; p = 0.001), maximal left atrial volume indexed (r = 0. 269; p = 0.009), and creatinine (r = 0.271; p = 0.009).
Conclusions
Both focal and diffuse myocardial fibrosis are more prevalent in HFpEF subjects than in control subjects of similar age and sex. iECV significantly correlates with indices of ventricular/left atrial remodeling and renal dysfunction and is an independent predictor of adverse outcome in HFpEF. (Developing Imaging And plasMa biOmarkers iN Describing Heart Failure With Preserved Ejection Fraction [DIAMONDHFpEF]; NCT03050593).

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

JACC Cardiovasc Imaging: 30 Oct 2019; 12:2291-2301
Kanagala P, Cheng ASH, Singh A, Khan JN, ... Ng LL, McCann GP
JACC Cardiovasc Imaging: 30 Oct 2019; 12:2291-2301 | PMID: 30772227
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Abstract

Diagnostic Performance of Dobutamine Stress Echocardiography in End-Stage Liver Disease.

Doytchinova AT, Feigenbaum TD, Pondicherry-Harish RC, Sepanski P, ... Feigenbaum H, Sawada SG
Objectives
This study determined the test performance of dobutamine stress echocardiography (DSE) in end-stage liver disease (ESLD).
Background
The reported sensitivity of DSE in ESLD has been variable.
Methods
Data from 633 ESLD patients who had coronary angiography within 6 months after DSE was analyzed.
Results
The prevalence of coronary arterial disease (CAD) (≥70% stenosis by quantitative angiography) was 12% (74 of 633 patients). DSE sensitivity was 24% (17 of 72 patients), and specificity was 90% (503 of 559 patients). The positive and negative predictive values were 23% (17 of 73 patients) and 90% (503 of 558 patients), respectively. Stratifying the cohort into low-, intermediate-, and high-risk CAD groups yielded sensitivities of 0%, 21%, and 32%, respectively. Independent predictors of an accurate ischemic DSE result included left ventricular internal dimension at end-diastole (LVIDd) >4.8 cm and assigning ischemia based on tardokinesis or lack of low-to-peak dose hyperkinesis (p < 0.05 for all). DSE sensitivity was 38% in LVIDd >4.8 cm versus 13% with LVIDd ≤4.8 cm (p = 0.013). The sensitivity was 67% when tardokinesis or lack of hyperkinesis was considered abnormal versus 15% (p < 0.001) for readings that did not consider tardokinesis or lack of hyperkinesis abnormal. There was a higher frequency of cardiac events in patients with significant CAD who had abnormal (45%) versus normal (18%) DSE (p = 0.01).
Conclusions
The sensitivity of DSE in ESLD was low. DSE sensitivity was higher for those with larger cavity dimension and when tardokinesis or lack of hyperkinesis was considered abnormal. An abnormal DSE in those with significant CAD was associated with worse outcome.

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

JACC Cardiovasc Imaging: 30 Oct 2019; 12:2115-2122
Doytchinova AT, Feigenbaum TD, Pondicherry-Harish RC, Sepanski P, ... Feigenbaum H, Sawada SG
JACC Cardiovasc Imaging: 30 Oct 2019; 12:2115-2122 | PMID: 30660519
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Abstract

Meta-Analysis of the Prognostic Role of Late Gadolinium Enhancement and Global Systolic Impairment in Left Ventricular Noncompaction.

Grigoratos C, Barison A, Ivanov A, Andreini D, ... Emdin M, Aquaro GD
Objectives
The objective of this meta-analysis was to assess the predictive value of late gadolinium enhancement (LGE) and global systolic impairment for future major adverse cardiovascular events in left ventricular noncompaction (LVNC).
Background
The prognosis of patients with LVNC, with and without left ventricular dysfunction and LGE, is still unclear.
Methods
A systematic review of published research and a meta-analysis reporting a combined endpoint of hard (cardiac death, sudden cardiac death, appropriate defibrillator firing, resuscitated cardiac arrest, cardiac transplantation, assist device implantation) and minor (heart failure hospitalization and thromboembolic events) events was performed.
Results
Four studies with 574 patients with LVNC and 677 with no LVNC and an average follow-up duration of 5.2 years were analyzed. In patients with LVNC, LGE was associated with the combined endpoint (pooled odds ratio: 4.9; 95% confidence interval: 1.63 to 14.6; p = 0.005) and cardiac death (pooled odds ratio: 9.8; 95% confidence interval: 2.44 to 39.5; p < 0.001). Preserved left ventricular systolic function was found in 183 patients with LVNC: 25 with positive LGE and 158 with negative LGE. In LVNC with preserved ejection fraction, positive LGE was associated with hard cardiac events (odds ratio: 6.1; 95% confidence interval: 2.1 to 17.5; p < 0.001). No hard cardiac events were recorded in patients with LVNC, preserved ejection fraction, and negative LGE.
Conclusions
Patients with LVNC but without LGE have a better prognosis than those with LGE. When LGE is negative and global systolic function is preserved, no hard cardiac events are to be expected. Currently available criteria allow diagnosis of LVNC, but to further define the presence and prognostic significance of the disease, LGE and/or global systolic impairment must be considered for better risk stratification.

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

JACC Cardiovasc Imaging: 30 Oct 2019; 12:2141-2151
Grigoratos C, Barison A, Ivanov A, Andreini D, ... Emdin M, Aquaro GD
JACC Cardiovasc Imaging: 30 Oct 2019; 12:2141-2151 | PMID: 30878415
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Abstract

Do Guideline-Based Indications Result in an Outcome Penalty for Patients With Severe Aortic Regurgitation?

de Meester C, Gerber BL, Vancraeynest D, Pouleur AC, ... El Khoury G, Vanoverschelde JL
Objectives
The present study examines whether improvements have reduced the negative impact of guideline triggers on postoperative outcomes.
Background
European and American guidelines for the management of severe aortic regurgitation (AR) define the triggers for AR surgery. These triggers are based on the results of studies performed in the 1990s analyzing outcomes of patients who underwent AR surgery in the 1980s. Although these triggers are used to indicate surgery, they have all been associated with poorer postoperative outcomes. In the meantime, innovations in operative techniques, including aortic valve repair, have allowed reducing the risk of surgery.
Methods
A total of 356 consecutive patients undergoing surgical correction of severe AR were included in this study. Among them, 204 were operated on for a Class I, 17 for a Class IIa, 49 for a Class IIb, and 86 without any guideline triggers. Cox proportional hazards regression models and Kaplan-Meier survival curves were used to compare postoperative outcomes in the different groups. Inverse probability weighing was used to adjust for mismatched baseline characteristics.
Results
Adjusted 10-year survival was better among patients without operative triggers (89 ± 4%) or with Class II triggers (85 ± 6%) than in patients with Class I triggers (71 ± 4%, p = 0.010). Similar results were obtained for cardiovascular survival and hospitalizations for heart failure. Spline function analyses indicated that mortality started to increase for left ventricular (LV) ejection fraction <55% and LV end-systolic dimensions >20 to 22 mm/m. LV end-diastolic dimensions did not influence outcomes.
Conclusions
Guideline-based Class I triggers for AR surgery carry major risks for long-term outcomes. This suggests that patients with severe AR should be operated on before the onset of these triggers; that is, at an asymptomatic stage, before LV ejection fraction falls below 55% or LV end-systolic dimensions exceeds 20 to 22 mm/m.

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

JACC Cardiovasc Imaging: 30 Oct 2019; 12:2126-2138
de Meester C, Gerber BL, Vancraeynest D, Pouleur AC, ... El Khoury G, Vanoverschelde JL
JACC Cardiovasc Imaging: 30 Oct 2019; 12:2126-2138 | PMID: 30660551
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Abstract

Advanced Echocardiographic Imaging for Prediction of SCD in Moderate and Severe LV Systolic Function.

Perry R, Patil S, Marx C, Horsfall M, ... Nucifora G, Selvanayagam JB
Objectives
This study sought to determine the long-term prognostic value of myocardial deformation imaging by echocardiography in risk stratification of sudden cardiac death (SCD) and malignant ventricular arrhythmias (VAs) in a large consecutive cohort of patients with left ventricular (LV) systolic impairment, irrespective of its etiology.
Background
Left ventricular ejection fraction (LVEF) is limited for prediction of SCD. Echocardiographic strain-derived mechanical dispersion (MD) and global longitudinal strain (GLS) has been linked to VA and SCD. However, due to low event rates, the role of these parameters has not been fully elucidated.
Methods
Consecutive clinically stable patients who underwent echocardiographic study performed in an outpatient setting from 2008 to 2014 with a Simpson left ventricular ejection fraction (LVEF) ≤45% were included in the study. Strain analysis was performed in which the LV was separated into 16 segments for regional analysis. Mechanical dispersion (MD) was calculated as the standard deviation of the time to peak of each of the 16 regions. Outcome data were obtained from medical records.
Results
A total of 939 patients were included in the study, with median LVEF of 37% (interquartile range 30% to 42%). At follow-up (91.4 ± 23.4 months), 96 VA events had occurred. Multivariate analysis demonstrated that only MD ≥75 ms (hazard ratio: 9.45; 95% confidence interval: 4.75 to 18.81; p < 0.0001) was predictive of VA events. Low MD predicted a low event rate, irrespective of LVEF.
Conclusions
Using LVEF alone is inferior for prediction of VA and SCD, particularly in patients with moderately reduced LVEF. MD is easily obtained from standard echocardiographic images and can be used to improve risk prognosis, particularly in patients who are currently excluded from cardiac defibrillator implantation based on LVEF.

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print
Perry R, Patil S, Marx C, Horsfall M, ... Nucifora G, Selvanayagam JB
JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print | PMID: 31607658
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Abstract

Multimodality Imaging for Best Dealing With Patients in Atrial Arrhythmias.

Donal E, Galli E, Lederlin M, Martins R, Schnell F

The management of atrial fibrillation (AF) is not only a clinical challenge but also an imaging challenge. The role of different imaging modalities to estimate the thromboembolic risk in AF is a key clinical question. The present review summarizes the advances of myocardial imaging in the stratification of thromboembolic risk, diagnosis, and management of left atrial thrombosis in patients with AF. These imaging techniques are also important for understanding arrhythmias and their consequences. It is becoming fundamental for guiding therapy. Still, large studies are required, but be sure that left atrial imaging will become more and more clinically fundamental.

Copyright © 2019 American College of Cardiology Foundation. All rights reserved.

JACC Cardiovasc Imaging: 30 Oct 2019; 12:2245-2261
Donal E, Galli E, Lederlin M, Martins R, Schnell F
JACC Cardiovasc Imaging: 30 Oct 2019; 12:2245-2261 | PMID: 30878420
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Abstract

Cardiovascular Imaging Techniques to Assess Microvascular Dysfunction.

Mathew RC, Bourque JM, Salerno M, Kramer CM

The understanding of microvascular dysfunction without evidence of epicardial coronary artery disease pales in comparison with that of obstructive epicardial coronary artery disease. A primary limitation in the past had been the lack of development of noninvasive methods of detecting and quantifying microvascular dysfunction. This limitation has particularly affected the ability to study the pathophysiology, morbidity, and treatment of this disease. More recently, almost all of the noninvasive cardiac imaging modalities have been used to quantify blood flow and advance understanding of microvascular dysfunction.

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

JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print
Mathew RC, Bourque JM, Salerno M, Kramer CM
JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print | PMID: 31607665
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Abstract

How to Image Cardiac Amyloidosis: A Practical Approach.

Dorbala S, Cuddy S, Falk RH

Cardiac amyloidosis (CA) is one of the most rapidly progressive forms of heart disease, with a median survival from diagnosis, if untreated, ranging from <6 months for light chain amyloidosis to 3 to 5 years for transthyretin amyloidosis. Early diagnosis and accurate typing of CA are necessary for optimal management of these patients. Emerging novel disease modifying therapies increase the urgency to diagnose CA at an early stage and identify patients who may benefit from these life-saving therapies. The goal of this review is to provide a practical approach to echocardiography, cardiac magnetic resonance, and radionuclide imaging in patients with known or suspected CA.

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

JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print
Dorbala S, Cuddy S, Falk RH
JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print | PMID: 31607664
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Abstract

Impact of Multiple Myocardial Scars Detected by CMR in Patients Following STEMI.

Ekström K, Nepper-Christensen L, Ahtarovski KA, Kyhl K, ... Lønborg J, Engstrøm T
Objectives
This study investigated the incidence and long-term prognostic importance of multiple myocardial scars in cardiac magnetic resonance (CMR) in a large contemporary cohort of patients with ST-segment elevation myocardial infarction (STEMI).
Background
Patients presenting with STEMI may have multiple infarctions/scars caused by multiple culprit lesions, previous myocardial infarction (MI) or procedure-related MI due to nonculprit interventions. However, the incidence, long-term prognosis, and distribution of causes of multiple myocardial scars remain unknown.
Methods
CMR was performed in 704 patients with STEMI 1 day after primary percutaneous coronary intervention (PCI) and again 3 months later. Myocardial scars were assessed by late gadolinium enhancement (LGE). T2-weighted technique was used to differentiate acute from chronic infarctions. The presence of multiple scars was defined as scars located in different coronary territories. The combined endpoints of all-cause mortality and hospitalization for heart failure were assessed at 39 months (interquartile range [IQR]: 31 to 48 months).
Results
At 3 months, 59 patients (8.4%) had multiple scars. Of these, multiple culprits in STEMI were detected in 7 patients (1%), and development of a second nonculprit scar at follow-up occurred in 10 patients (1.4%). The most frequent cause of multiple scars was a chronic scar in the nonculprit myocardium. The presence of multiple scars was independently associated with an increased risk of all-cause mortality and hospitalization for heart failure (hazard ratio: 2.7; 95% confidence interval: 1.1 to 6.8; p = 0.037).
Conclusions
Multiple scars were present in 8.4% of patients with STEMI and were independently associated with an increased risk of long-term morbidity and mortality. The presence of multiple myocardial scars on CMR may serve as a useful tool in risk stratification of patients following STEMI. (DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction [DANAMI-3]; NCT01435408) (Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization [PRIMULTI]; NCT01960933).

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

JACC Cardiovasc Imaging: 30 Oct 2019; 12:2168-2178
Ekström K, Nepper-Christensen L, Ahtarovski KA, Kyhl K, ... Lønborg J, Engstrøm T
JACC Cardiovasc Imaging: 30 Oct 2019; 12:2168-2178 | PMID: 31005537
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Abstract

Why Clinicians Should Care About the Cardiac Interstitium.

Schelbert EB, Butler J, Diez J

Interstitial heart disease, whether primarily from myocardial fibrosis or cardiac amyloidosis, indicates excess protein accumulation in the interstitium and constitutes a major source of heart failure with excess cardiac morbidity and mortality. Myocardial fibrosis (defined as excess myocardial collagen concentration that distorts myocardial architecture) is prevalent and causes cardiac symptoms and ultimately adverse cardiac events, such as heart failure, arrhythmia, and death. Conversely, cardiac amyloidosis is far less prevalent than myocardial fibrosis but represents a more extreme form of interstitial heart disease with marked interstitial expansion, profound architectural distortion, and then rapid clinical decline. Myocardial extracellular volume measures fundamentally advance the understanding of myocardium and specifically highlights the role of the interstitium. Rather than conceptualizing myocardium as a homogenous tissue, dichotomizing the myocardium into its interstitial (including the microvasculature) and cardiomyocyte phenotypes promotes additional understanding of heart failure pathophysiology that may spur the development of more effective therapies.

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

JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print
Schelbert EB, Butler J, Diez J
JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print | PMID: 31422140
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Abstract

Clinical and Computed Tomography Angiographic Predictors of Coronary Lesions That Later Progressed to Chronic Total Occlusion.

Kang J, Chun EJ, Park HJ, Cho YS, ... Chae IH, Choi DJ
Objectives
This study aimed to investigate clinical and coronary computed tomographic angiography (CTA) characteristics of lesions that progressed to chronic total occlusion (CTO).
Background
CTO is one of the most common reasons for referral to coronary artery bypass surgery. Prediction and adequate early management for future CTO lesions may be beneficial.
Methods
The study evaluated patients with at least 1 vessel with a diameter stenosis of ≥70% on invasive coronary angiography (ICA) who underwent previous coronary CTA >12 months before ICA, from 2006 to 2015. The study compared the baseline clinical and coronary CTA characteristics of the patients with future CTO lesions with those of the patients with future non-CTO lesions (patient-level analysis) and compared coronary CTA findings between the future CTO lesion with the most stenotic non-CTO lesion in each CTO patient (lesion-level analysis).
Results
Among the 216 patients, 32 (14.8%) had a CTO lesion on ICA. In patient-level analysis, no significant differences in clinical characteristics were found, whereas the coronary CTA culprit lesions of the CTO group had a smaller minimal lumen diameter (MLD) with more adverse plaque characteristics. In lesion-level analysis, future CTO lesions had a smaller MLD, a smaller reference segment diameter (RD), and longer lesion length. These lesions were more likely to be noncalcified plaques with a noneccentric cross-sectional distribution, and had a higher remodeling index, lower mean plaque attenuation (MPA), and more napkin-ring signs. In multivariate analysis and receiver-operating characteristic curve analysis, MLD of <2.0 mm, RD of <3.2 mm, and MPA of <50 Hounsfield units were independent predictors of future CTO lesions. The risk of CTO development in lesions with triple risk factors was 14-fold higher than that of the lesions with no risk factors.
Conclusions
Lesions that progressed to CTO had more severe baseline coronary CTA features than non-CTO lesions. A small MLD, small RD, and low MPA were independent predictors of progression to CTO.

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

JACC Cardiovasc Imaging: 30 Oct 2019; 12:2196-2206
Kang J, Chun EJ, Park HJ, Cho YS, ... Chae IH, Choi DJ
JACC Cardiovasc Imaging: 30 Oct 2019; 12:2196-2206 | PMID: 30772219
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Abstract

Improvement in the Assessment of Aortic Valve and Aortic Aneurysm Repair by 3-Dimensional Echocardiography.

Hagendorff A, Evangelista A, Fehske W, Schäfers HJ

Reconstructive surgery of the aortic valve is being increasingly used in patients with aortic regurgitation and/or aortic aneurysm. Its success depends on restoring normal aortic valve and root form. Echocardiography is the most reliable and precise imaging technique because it defines abnormal morphology and function, essential for selecting appropriate substrates and guiding the surgical strategy. Despite technical advances in echocardiography, aortic valve and aortic root morphology and function are still assessed mainly using 2-dimensional echocardiography in clinical practice. This review focuses on the need to use 3-dimensional echocardiography to characterize different forms of aortic valve and root abnormalities and attempts to define echocardiographic predictors of successful valve-root complex repair.

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

JACC Cardiovasc Imaging: 30 Oct 2019; 12:2225-2244
Hagendorff A, Evangelista A, Fehske W, Schäfers HJ
JACC Cardiovasc Imaging: 30 Oct 2019; 12:2225-2244 | PMID: 30878428
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Abstract

Diagnostic Value of Advanced Imaging Modalities for the Detection and Differentiation of Prosthetic Valve Obstruction: A Systematic Review and Meta-Analysis.

Kim JY, Suh YJ, Han K, Kim YJ, Choi BW
Objectives
This meta-analysis investigated the diagnostic values of transthoracic echocardiography (TTE), 2-dimensional (2D) and 3-dimensional (3D) transesophageal echocardiography (TEE), and multidetector-row computed tomography (MDCT) in patients with suspected mechanical prosthetic valve obstruction (PVO) for detecting subprosthetic mass and differentiating its causes.
Background
Diagnostic values of advanced imaging modalities, such as MDCT and TEE, for the detection and differentiation of PVO have not been investigated.
Methods
PubMed and EMBASE were systematically searched for studies that evaluated PVO using imaging modalities. The modified Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to evaluate study quality. Pooled sensitivity of each modality for PVO detection and pooled diagnostic accuracy of TEE and MDCT for differentiating the causes of PVO were analyzed. Study heterogeneity was also assessed.
Results
Seventeen studies (229 patients) that used at least 1 index tool among TTE, TEE, or MDCT were included. For detecting a subprosthetic mass that caused PVO, 3D TEE and MDCT showed a higher sensitivity of 81% (95% confidence interval [CI]: 40% to 95%) and 88% (95% CI: 81% to 93%), respectively, compared with TTE (20%; 95% CI: 7% to 47%) and 2D TEE (68%; 95% CI: 46% to 84%). Pooled sensitivity and specificity for diagnosing thrombus as a cause of PVO was 75% (95% CI: 54% to 88%) and 75% (95% CI: 40% to 93%), respectively, for TEE and 45% (95% CI: 16% to 77%) and 90% (95% CI: 77% to 96%), respectively, for MDCT. Pooled sensitivity for diagnosing pannus as a cause of PVO was 62% (95% CI: 46% to 76%) for TEE and 85% (95% CI: 70% to 93%) for MDCT.
Conclusions
This meta-analysis suggested that MDCT and 3D TEE have higher sensitivity than do TTE and 2D TEE, and can be reliable imaging modalities for detecting a subprosthetic mass that causes PVO. Moreover, MDCT can more accurately differentiate the cause of PVO than does TEE.

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

JACC Cardiovasc Imaging: 30 Oct 2019; 12:2182-2192
Kim JY, Suh YJ, Han K, Kim YJ, Choi BW
JACC Cardiovasc Imaging: 30 Oct 2019; 12:2182-2192 | PMID: 30772236
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Abstract

Structural and Physiological Imaging to Predict the Risk of Lethal Ventricular Arrhythmias and Sudden Death.

Malhotra S, Canty JM

Identifying patients at risk of sudden cardiac death remains a major challenge in cardiovascular medicine. Advances in cardiovascular imaging have identified several anatomic and functional variables that can be quantified as continuous variables to predict the risk of developing lethal ventricular tachyarrhythmias in patients with depressed left ventricular (LV) systolic function. Some, such as LV mass, volume, and the dyssynchrony of contraction, can be derived from currently available echocardiographic and nuclear imaging modalities. Others require advanced cardiac imaging modalities with quantification of myocardial scar with gadolinium-enhanced cardiac magnetic resonance and myocardial sympathetic denervation using norepinephrine analogs and positron emission tomography or single-photon emission computed tomography offering the most promise. There is an immediate need to develop a sequential cost-effective approach that capitalizes on readily available clinical information complemented with advanced imaging modalities in selected patients to improve risk stratification for arrhythmic death beyond LV ejection fraction.

Published by Elsevier Inc.

JACC Cardiovasc Imaging: 29 Sep 2019; 12:2049-2064
Malhotra S, Canty JM
JACC Cardiovasc Imaging: 29 Sep 2019; 12:2049-2064 | PMID: 31601379
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Abstract

Expanding the Scope of Multimodality Imaging in Durable Mechanical Circulatory Support.

Almarzooq ZI, Varshney AS, Vaduganathan M, Pareek M, ... Estep JD, Mehra MR

An increasing number of patients transition to advanced-stage heart failure refractory to medical therapy. Left ventricular assist systems (LVAS) provide a bridge to candidates awaiting heart transplantation and extended device durability allows permanent implantation referred to as destination therapy. Noninvasive imaging plays a pivotal role in the optimal management of patients implanted with durable mechanical circulatory support (MCS) devices. Several advances require an updated perspective of multi-modality imaging in contemporary LVAS management. First, there has been substantial evolution of devices such as the introduction of the fully magnetically levitated HeartMate 3 pump (Abbott, Abbott Park, Illinois). Second, imaging beyond the device, of the peripheral system, is increasingly recognized as clinically relevant. Third, U.S. Food and Drug Administration recalls have called attention to LVAS complications beyond pump thrombosis that are amenable to imaging-based diagnosis. Fourth, there is increased availability of multimodality imaging, such as computed tomography and positron emission tomography, at many centers across the world. In this review, the authors provide a practical and contemporary approach to multi-modality imaging of current-generation durable MCS devices. As the use of LVAS and other novel MCS devices increases globally, it is critical for clinicians caring for LVAS patients to understand the roles of various imaging modalities in patient evaluation and management.

Copyright © 2019. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print
Almarzooq ZI, Varshney AS, Vaduganathan M, Pareek M, ... Estep JD, Mehra MR
JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print | PMID: 31542528
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Abstract

CT FFR for Ischemia-Specific CAD With a New Computational Fluid Dynamics Algorithm: A Chinese Multicenter Study.

Tang CX, Liu CY, Lu MJ, Schoepf UJ, ... Xu L, Zhang LJ
Objectives
The aim of this study was to validate the feasibility of a novel structural and computational fluid dynamics-based fractional flow reserve (FFR) algorithm for coronary computed tomography angiography (CTA), using alternative boundary conditions to detect lesion-specific ischemia.
Background
A new model of computed tomographic (CT) FFR relying on boundary conditions derived from structural deformation of the coronary lumen and aorta with transluminal attenuation gradient and assumptions regarding microvascular resistance has been developed, but its accuracy has not yet been validated.
Methods
A total of 338 consecutive patients with 422 vessels from 9 Chinese medical centers undergoing CTA and invasive FFR were retrospectively analyzed. CT FFR values were obtained on a novel on-site computational fluid dynamics-based CT FFR (uCT-FFR [version 1.5, United-Imaging Healthcare, Shanghai, China]). Performance characteristics of uCT-FFR and CTA in detecting lesion-specific ischemia in all lesions, intermediate lesions (luminal stenosis 30% to 70%), and \"gray zone\" lesions (FFR 0.75 to 0.80) were calculated with invasive FFR as the reference standard. The effect of coronary calcification on uCT-FFR measurements was also assessed.
Results
Per vessel sensitivities, specificities, and accuracies of 0.89, 0.91, and 0.91 with uCT-FFR, 0.92, 0.34, and 0.55 with CTA, and 0.94, 0.37, and 0.58 with invasive coronary angiography, respectively, were found. There was higher specificity, accuracy, and AUC for uCT-FFR compared with CTA and qualitative invasive coronary angiography in all lesions, including intermediate lesions (p < 0.001 for all). No significant difference in diagnostic accuracy was observed in the \"gray zone\" range versus the other 2 lesion groups (FFR ≤0.75 and >0.80; p = 0.397) and in patients with \"gray zone\" versus FFR ≤0.75 (p = 0.633) and versus FFR >0.80 (p = 0.364), respectively. No significant difference in the diagnostic performance of uCT-FFR was found between patients with calcium scores ≥400 and <400 (p = 0.393).
Conclusions
This novel computational fluid dynamics-based CT FFR approach demonstrates good performance in detecting lesion-specific ischemia. Additionally, it outperforms CTA and qualitative invasive coronary angiography, most notably in intermediate lesions, and may potentially have diagnostic power in gray zone and highly calcified lesions.

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

JACC Cardiovasc Imaging: 13 Aug 2019; epub ahead of print
Tang CX, Liu CY, Lu MJ, Schoepf UJ, ... Xu L, Zhang LJ
JACC Cardiovasc Imaging: 13 Aug 2019; epub ahead of print | PMID: 31422138
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Abstract

Coronary Plaque Features on CTA Can Identify Patients at Increased Risk of Cardiovascular Events.

Andreini D, Magnoni M, Conte E, Masson S, ... Maseri A,
Objectives
This study sought to assess whether coronary atherosclerosis analysis by coronary computed tomography angiography (CTA) may improve prognostic stratification among patients with diffuse coronary artery disease (CAD) Background: Coronary CTA has recently emerged as a promising noninvasive tool for advanced analysis of coronary atherosclerosis.
Methods
The multicenter CAPIRE (Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation) study is part of the GISSI Outlier Project. A prospective cohort of subjects who underwent coronary CTA for suspected CAD was enrolled. Based on risk factor (RF) burden, patients were defined as having a low clinical risk (0 to 1 RF with the exclusion of patients with diabetes mellitus as single RF) or at high clinical risk (3 or more RFs). Patients with 2 RFs were not enrolled in the study. Coronary CTA advanced plaque assessment was performed. Outcome measures were 3 combined endpoints: acute coronary syndrome (ACS), cardiac death + ACS, and cardiac death + ACS + late revascularization.
Results
Among the 544 patients enrolled in the CAPIRE study, in 522 patients, a mean follow-up of 37 ± 10 months was obtained (16 patients were excluded due to 1 < segment involvement score <5 at core lab coronary CTA analysis and 6 patients were lost at follow-up). Higher atherosclerotic burden was found in patients with higher clinical risk, but prevalence of elevated noncalcified plaque volume did not significantly differ between low- versus high-risk patients. Quantitative plaque parameters by coronary CTA were associated with composite endpoints at multivariable analysis when corrected for univariate predictors. Elevated noncalcified plaque volume, expressed as dichotomic variable, was associated with all combined endpoints. Even if the low absolute number of events represents a limitation to the present study, patients with low noncalcified plaque volume had similar risk of cardiac events independently from the presence of multivessel disease, while patients with high noncalcified plaque volume had higher rates of cardiac events.
Conclusions
The CAPIRE study confirmed the prognostic value of atherosclerosis assessment by coronary CTA, demonstrating high noncalcified plaque volume as the most ACS-predictive parameter in patients with extensive CAD. (GISSE Outliers CAPIRE [CAPIRE]; NCT02157662).

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

JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print
Andreini D, Magnoni M, Conte E, Masson S, ... Maseri A,
JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print | PMID: 31422137
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Abstract

Sex-Related Differences in the Extent of Myocardial Fibrosis in Patients With Aortic Valve Stenosis.

Tastet L, Kwiecinski J, Pibarot P, Capoulade R, ... Dweck M, Clavel MA
Objectives
The aim of this study was to assess the effect of sex on myocardial fibrosis as assessed by using cardiac magnetic resonance (CMR) imaging in aortic stenosis (AS).
Background
Previous studies reported sex-related differences in the left ventricular (LV) remodeling response to pressure overload in AS. However, there are very few data regarding the effect of sex on myocardial fibrosis, a key marker of LV decompensation and adverse cardiac events in AS.
Methods
A total of 249 patients (mean age 66 ± 13 years; 30% women) with at least mild AS were recruited from 2 prospective observational cohort studies and underwent comprehensive Doppler echocardiography and CMR examinations. On CMR, T1 mapping was used to quantify extracellular volume (ECV) fraction as a marker of diffuse fibrosis, and late gadolinium enhancement (LGE) was used to assess focal fibrosis.
Results
There was no difference in age between women and men (age 66 ± 15 years vs 66 ± 12 years; p = 0.78). However, women presented with a better cardiovascular risk profile than men with less hypertension, dyslipidemia, diabetes, and coronary artery disease (all, p ≤ 0.10). As expected, LV mass index measured by CMR imaging was smaller in women than in men (p < 0.0001). Despite fewer comorbidities, women presented with larger ECV fraction (median: 29.0% [25th-75th percentiles: 27.4% to 30.6%] vs. 26.8% [25th-75th percentiles: 25.1% to 28.7%]; p < 0.0001) and similar LGE (median: 4.5% [25th-75th percentiles: 2.3% to 7.0%] vs. 2.8% [25th-75th percentiles: 0.6% to 6.8%]; p = 0.20) than men. In multivariable analysis, female sex remained an independent determinant of higher ECV fraction and LGE (all, p ≤ 0.05).
Conclusions
Women have greater diffuse and focal myocardial fibrosis independent of the degree of AS severity. These findings further emphasize the sex-related differences in LV remodeling response to pressure overload.

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

JACC Cardiovasc Imaging: 13 Aug 2019; epub ahead of print
Tastet L, Kwiecinski J, Pibarot P, Capoulade R, ... Dweck M, Clavel MA
JACC Cardiovasc Imaging: 13 Aug 2019; epub ahead of print | PMID: 31422128
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Abstract

CT Perfusion Versus Coronary CT Angiography in Patients With Suspected In-Stent Restenosis or CAD Progression.

Andreini D, Mushtaq S, Pontone G, Conte E, ... Bartorelli AL, Pepi M
Objectives
The goal of this study was to assess the diagnostic performance of coronary computed tomography angiography (CTA) alone, adenosine-stress myocardial perfusion assessed by computed tomography (CTP) alone, and coronary CTA + CTP by using a 16-cm Z-axis coverage scanner versus invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the clinical standard.
Background
Diagnostic performance of coronary CTA for in-stent restenosis detection is still challenging. Recently, CTP showed additional diagnostic power over coronary CTA in patients with suspected coronary artery disease. However, few data are available on CTP performance in patients with previous stent implantation.
Methods
Consecutive stable patients with previous coronary stenting referred for ICA were enrolled. All patients underwent stress myocardial CTP and rest CTP + coronary CTA. Invasive FFR was performed during ICA when clinically indicated. The diagnostic rate and diagnostic accuracy of coronary CTA, CTP, and coronary CTA + CTP were evaluated in stent-, territory-, and patient-based analyses.
Results
In the 150 enrolled patients (132 men; mean age 65.1 ± 9.1 years), the CTP diagnostic rate was significantly higher than that of coronary CTA in all analyses (territory based [96.7% vs. 91.1%; p < 0.0001] and patient based [96% vs. 68%; p < 0.0001]). When ICA was used as gold standard, CTP diagnostic accuracy was significantly higher than that of coronary CTA in all analyses (territory based [92.1% vs. 85.5%, p < 0.03] and patient based [86.7% vs. 76.7%, p < 0.03]). The concordant coronary CTA + CTP assessment exhibited the highest diagnostic accuracy values versus ICA (95.8% in the territory-based analysis). The diagnostic accuracy of CTP was significantly higher than that of coronary CTA (75% vs. 30.5%; p < 0.001). The radiation exposure of coronary CTA + CTP was 4.15 ± 1.5 mSv.
Conclusions
In patients with coronary stents, CTP significantly improved the diagnostic rate and accuracy of coronary CTA alone compared with both ICA and invasive FFR as gold standard.

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

JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print
Andreini D, Mushtaq S, Pontone G, Conte E, ... Bartorelli AL, Pepi M
JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print | PMID: 31422127
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Abstract

Myocardial Amyloidosis: The Exemplar Interstitial Disease.

Fontana M, Ćorović A, Scully P, Moon JC

Cardiac involvement drives prognosis and treatment choices in cardiac amyloidosis. Echocardiography is the first-line examination for patients presenting with heart failure, and it is the imaging modality that most often raises the suspicion of cardiac amyloidosis. Echocardiography can provide an assessment of the likelihood of cardiac amyloid infiltration versus other hypertrophic phenocopies and can assess the severity of cardiac involvement. Visualizing myocardial amyloid infiltration is challenging and, until recently, was restricted to the domain of the pathologist. Two tests are transforming this: cardiac magnetic resonance (CMR) imaging and bone scintigraphy. After the administration of contrast, CMR is highly sensitive and specific for the 2 main types of ventricular myocardial amyloidosis, light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). CMR structural and functional assessment combined with tissue characterization can redefine cardiac involvement by tracking different disease processes, ranging from amyloid infiltration, to the myocardial response associated with amyloid deposition, through the visualization and quantification of myocardial edema and myocyte response. Bone scintigraphy (paired with exclusion of serum free light chains) is emerging as the technique of choice for distinguishing ATTR from light chain cardiac amyloidosis and other cardiomyopathies; it has transformed the diagnostic pathway for ATTR, allowing noninvasive diagnosis of ATTR without the need for a tissue biopsy in the majority of patients. CMR with tissue characterization and bone scintigraphy are rewriting disease understanding, classification, and definition, and leading to a change in patient care.

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

JACC Cardiovasc Imaging: 08 Aug 2019; epub ahead of print
Fontana M, Ćorović A, Scully P, Moon JC
JACC Cardiovasc Imaging: 08 Aug 2019; epub ahead of print | PMID: 31422120
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Abstract

State-of-the-Art Deep Learning in Cardiovascular Image Analysis.

Litjens G, Ciompi F, Wolterink JM, de Vos BD, ... Teuwen J, Išgum I

Cardiovascular imaging is going to change substantially in the next decade, fueled by the deep learning revolution. For medical professionals, it is important to keep track of these developments to ensure that deep learning can have meaningful impact on clinical practice. This review aims to be a stepping stone in this process. The general concepts underlying most successful deep learning algorithms are explained, and an overview of the state-of-the-art deep learning in cardiovascular imaging is provided. This review discusses >80 papers, covering modalities ranging from cardiac magnetic resonance, computed tomography, and single-photon emission computed tomography, to intravascular optical coherence tomography and echocardiography. Many different machines learning algorithms were used throughout these papers, with the most common being convolutional neural networks. Recent algorithms such as generative adversarial models were also used. The potential implications of deep learning algorithms on clinical practice, now and in the near future, are discussed.

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

JACC Cardiovasc Imaging: 30 Jul 2019; 12:1549-1565
Litjens G, Ciompi F, Wolterink JM, de Vos BD, ... Teuwen J, Išgum I
JACC Cardiovasc Imaging: 30 Jul 2019; 12:1549-1565 | PMID: 31395244
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Abstract

Optimizing the Assessment of Patients\' Clinical Risk at the Time of Cardiac Stress Testing.

Rozanski A, Berman D

Due to a marked temporal decline in inducible myocardial ischemia over recent decades, most diagnostic patients now referred for cardiac stress testing have nonischemic studies. Among nonischemic patients, however, long-term risk is heterogeneous and highly influenced by a variety of clinical parameters. Herein, we review 8 factors that can govern long-term clinical risk: coronary risk factor burden; patients\' symptoms; exercise capacity and exercise test responses; the need for pharmacologic stress testing; autonomic function; musculoskeletal status; subclinical atherosclerosis; and psychosocial risk. To capture the clinical benefit provided by both assessing myocardial ischemia and these additional parameters, we propose that a cardiac stress tests report have an additional component beyond statements as to the likelihood of obstructive coronary artery disease and/or magnitude of ischemia. This added component could be a comment section designed to make referring physicians aware of aspects of long-term risk that may influence clinical management and potentially lead to changes in the intensity of risk factor management, frequency of follow-up, need for further testing, or other management decisions. In this manner, the increasingly frequent normal stress test result might more commonly influence treatment recommendations and even patient behavior, thus leading to improvement in patient outcomes even in the setting of normal stress test results.

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

JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print
Rozanski A, Berman D
JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print | PMID: 31326497
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Abstract

The Prognostic Role of Late Gadolinium Enhancement in Aortic Stenosis: A Systematic Review and Meta-Analysis.

Papanastasiou CA, Kokkinidis DG, Kampaktsis PN, Bikakis I, ... Garcia MJ, Karamitsos TD
Objectives
The aim of this systematic review was to explore the prognostic value of late gadolinium enhancement (LGE) in patients with aortic stenosis (AS).
Background
Myocardial fibrosis is a common feature of many cardiac diseases. Cardiac magnetic resonance (CMR) has the ability to noninvasively detect regional fibrosis by using the LGE technique. Several studies have explored whether LGE is associated with adverse outcome in patients with AS.
Methods
Electronic databases were searched to identify studies investigating the ability of LGE to predict all-cause mortality in patients with AS. A random effects model meta-analysis was conducted. Heterogeneity was assessed with the I statistic.
Results
Six studies comprising 1,151 patients met our inclusion criteria. LGE was present in 49.1% of patients with AS. In the pooled analysis, LGE was found to be a strong univariate predictor of all-cause mortality (pooled unadjusted odds ratio: 2.56; 95% confidence interval: 1.83 to 3.57; I = 0%). Four of the included studies reported adjusted hazard ratios for mortality. LGE was independently associated with mortality, even after adjusting for baseline characteristics (pooled adjusted hazard ratio: 2.50; 95% confidence interval: 1.64 to 3.83; I = 0%).
Conclusions
Fibrosis on LGE-CMR is a powerful predictor of all-cause mortality in patients with AS and may serve as a novel marker for risk stratification. Future studies should explore whether LGE-CMR can also be used to optimize timing of AS-related interventions.

Copyright © 2019. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print
Papanastasiou CA, Kokkinidis DG, Kampaktsis PN, Bikakis I, ... Garcia MJ, Karamitsos TD
JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print | PMID: 31326491
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Abstract

Myocardial Mechanics in Patients With Normal LVEF and Diastolic Dysfunction.

Bianco CM, Farjo PD, Ghaffar YA, Sengupta PP

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical entity that is poorly understood yet present in up to 5.5% of the general population. Proven therapies for this disorder are lacking, even though it has a similar prognosis to that of heart failure with reduced ejection fraction (HFrEF). Innovative imaging techniques have provided in-depth understanding of the unique pattern of left ventricular mechanics in patients with HFpEF who progress through preclinical (Stages A to B) and clinical (Stages C to D) American College of Cardiology/American Heart Association heart failure stages. This review highlights the mechanical basis of this disorder from the cellular and myofiber level to chamber dysfunction. As each chamber of the heart is examined, specific biomarkers and echocardiographic parameters with diagnostic and prognostic values are discussed. Finally, novel phenotyping methods including machine learning are reviewed that integrate these mechanics into clinical groups to advise and treat patients.

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

JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print
Bianco CM, Farjo PD, Ghaffar YA, Sengupta PP
JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print | PMID: 31202770
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Abstract

Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: Understanding Mechanisms by Using Noninvasive Methods.

Obokata M, Reddy YNV, Borlaug BA

Research in the last decade has substantially advanced our understanding of the pathophysiology of heart failure with preserved ejection fraction (HFpEF). However, treatment options remain limited as clinical trials have largely failed to identify effective therapies. Part of this failure may be related to mechanistic heterogeneity. It is speculated that categorizing HFpEF patients based upon underlying pathophysiological phenotypes may represent the key next step in delivering the right therapies to the right patients. Echocardiography may provide valuable insight into both the pathophysiology and underlying phenotypes in HFpEF. Echocardiography also plays a key role in the evaluation of patients with unexplained dyspnea, where HFpEF is suspected but the diagnosis remains unknown. The combination of the E/e\' ratio and right ventricular systolic pressure has recently been shown to add independent value to the diagnostic evaluation of patients suspected of having HFpEF. Finally, echocardiography enables identification of the different causes that mimic HFpEF but are treated differently, such as valvular heart disease, pericardial constriction, and high-output heart failure or infiltrative myopathies such as cardiac amyloid. This review summarizes the current understanding of the pathophysiology and phenotyping of HFpEF with particular attention to the role of echocardiography in this context.

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

JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print
Obokata M, Reddy YNV, Borlaug BA
JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print | PMID: 31202759
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Abstract

Determinants of Intima-Media Thickness in the Young: The ALSPAC Study.

Chiesa ST, Charakida M, Georgiopoulos G, Dangardt F, ... Hughes AD, Deanfield JE
Objectives
This study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years.
Background
Greater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood.
Methods
Associations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences.
Results
Fat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: -0.0032; 95% CI: 0.004 to -0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor-associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor.
Conclusions
Subtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures might be more appropriate for the identification of arterial disease before adulthood.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print
Chiesa ST, Charakida M, Georgiopoulos G, Dangardt F, ... Hughes AD, Deanfield JE
JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print | PMID: 31607674
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Impact:
Abstract

Identification and Quantification of Cardiovascular Structures From CCTA: An End-to-End, Rapid, Pixel-Wise, Deep-Learning Method.

Baskaran L, Maliakal G, Al\'Aref SJ, Singh G, ... Shaw LJ, Min JK
Objectives
This study designed and evaluated an end-to-end deep learning solution for cardiac segmentation and quantification.
Background
Segmentation of cardiac structures from coronary computed tomography angiography (CCTA) images is laborious. We designed an end-to-end deep-learning solution.
Methods
Scans were obtained from multicenter registries of 166 patients who underwent clinically indicated CCTA. Left ventricular volume (LVV) and right ventricular volume (RVV), left atrial volume (LAV) and right atrial volume (RAV), and left ventricular myocardial mass (LVM) were manually annotated as ground truth. A U-Net-inspired, deep-learning model was trained, validated, and tested in a 70:20:10 split.
Results
Mean age was 61.1 ± 8.4 years, and 49% were women. A combined overall median Dice score of 0.9246 (interquartile range: 0.8870 to 0.9475) was achieved. The median Dice scores for LVV, RVV, LAV, RAV, and LVM were 0.938 (interquartile range: 0.887 to 0.958), 0.927 (interquartile range: 0.916 to 0.946), 0.934 (interquartile range: 0.899 to 0.950), 0.915 (interquartile range: 0.890 to 0.920), and 0.920 (interquartile range: 0.811 to 0.944), respectively. Model prediction correlated and agreed well with manual annotation for LVV (r = 0.98), RVV (r = 0.97), LAV (r = 0.78), RAV (r = 0.97), and LVM (r = 0.94) (p < 0.05 for all). Mean difference and limits of agreement for LVV, RVV, LAV, RAV, and LVM were 1.20 ml (95% CI: -7.12 to 9.51), -0.78 ml (95% CI: -10.08 to 8.52), -3.75 ml (95% CI: -21.53 to 14.03), 0.97 ml (95% CI: -6.14 to 8.09), and 6.41 g (95% CI: -8.71 to 21.52), respectively.
Conclusions
A deep-learning model rapidly segmented and quantified cardiac structures. This was done with high accuracy on a pixel level, with good agreement with manual annotation, facilitating its expansion into areas of research and clinical import.

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

JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print
Baskaran L, Maliakal G, Al'Aref SJ, Singh G, ... Shaw LJ, Min JK
JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print | PMID: 31607673
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Impact:
Abstract

Plasma ACE2 Activity Predicts Mortality in Aortic Stenosis and Is Associated With Severe Myocardial Fibrosis.

Ramchand J, Patel SK, Kearney LG, Matalanis G, ... Srivastava PM, Burrell LM
Objectives
This study investigated the relationship between plasma angiotensin-converting enzyme 2 (ACE2) activity levels and the severity of stenosis and myocardial remodeling in patients with aortic stenosis (AS) and determined if plasma ACE2 levels offered incremental prognostic usefulness to predict all-cause mortality.
Background
ACE2 is an integral membrane protein that degrades angiotensin II and has an emerging role as a circulating biomarker of cardiovascular disease.
Methods
Plasma ACE2 activity was measured in 127 patients with AS; a subgroup had myocardial tissue collected at the time of aortic valve replacement.
Results
The median plasma ACE2 activity was 34.0 pmol/ml/min, and levels correlated with increased valvular calcification (p = 0.023) and the left ventricular (LV) mass index (r = 0.34; p < 0.001). Patients with above-median plasma ACE2 had higher LV end-diastolic volume (57 ml/m vs. 48 ml/m; p = 0.021). Over a median follow-up of 5 years, elevated plasma ACE2 activity was an independent predictor of all-cause mortality after adjustment for relevant clinical, imaging, and biochemical parameters (HR: 2.28; 95% CI: 1.03 to 5.06; p = 0.042), including brain natriuretic peptide activation (integrated discrimination improvement: 0.08; p < 0.001). In 22 patients with plasma and tissue, increased circulating ACE2 was associated with reduced myocardial ACE2 gene expression (0.7-fold; p = 0.033) and severe myocardial fibrosis (p = 0.027).
Conclusions
In patients with AS, elevated plasma ACE2 was a marker of myocardial structural abnormalities and an independent predictor of mortality with incremental value over traditional prognostic markers. Loss of ACE2 from the myocardium was associated with increased fibrosis and higher circulating ACE2 levels.

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print
Ramchand J, Patel SK, Kearney LG, Matalanis G, ... Srivastava PM, Burrell LM
JACC Cardiovasc Imaging: 10 Oct 2019; epub ahead of print | PMID: 31607667
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Impact:
Abstract

Transcatheter Interventions for Mitral Regurgitation: Multimodality Imaging for Patient Selection and Procedural Guidance.

Bax JJ, Debonnaire P, Lancellotti P, Ajmone Marsan N, ... Hahn RT, Delgado V

Transcatheter therapies to treat mitral regurgitation are rapidly developing. Currently, there are several devices commercially available to treat mitral regurgitation. The underlying cause of mitral regurgitation and specific anatomical aspects of the mitral valve and surrounding structures are considered when patients with symptomatic severe mitral regurgitation for transcatheter mitral valve therapies are selected. Multimodality imaging plays an important central role in the selection of patients, providing information about the mechanism of mitral regurgitation, the anatomy of the mitral valve and spatial relationships with the coronary sinus, the circumflex coronary artery and left ventricular outflow tract and to predict the procedural outcomes. During the transcatheter procedure, transesophageal echocardiography and fluoroscopy are key for monitoring the procedural steps to maximize the outcomes and minimize the complications. This paper provides a comprehensive review of the most important aspects to visualize in order to appropriately select patients for transcatheter mitral valve repair and replacement and to guide the procedure for the different transcatheter devices.

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

JACC Cardiovasc Imaging: 29 Sep 2019; 12:2029-2048
Bax JJ, Debonnaire P, Lancellotti P, Ajmone Marsan N, ... Hahn RT, Delgado V
JACC Cardiovasc Imaging: 29 Sep 2019; 12:2029-2048 | PMID: 31601378
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Impact:
Abstract

Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction: Validation Against Invasive Coronary Physiology.

Kotecha T, Martinez-Naharro A, Boldrini M, Knight D, ... Kellman P, Fontana M
Objectives
This study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two.
Background
Differentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow.
Methods
Fifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography.
Results
Twenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p < 0.001). In patients without regional perfusion defects, global stress MBF <1.82 ml/g/min accurately discriminated between obstructive 3-vessel disease and MVD (area under the curve: 0.94; p < 0.001).
Conclusions
This novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation.

Copyright © 2019. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 29 Sep 2019; 12:1958-1969
Kotecha T, Martinez-Naharro A, Boldrini M, Knight D, ... Kellman P, Fontana M
JACC Cardiovasc Imaging: 29 Sep 2019; 12:1958-1969 | PMID: 30772231
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Impact:
Abstract

Peri-Coronary Adipose Tissue Density Is Associated With F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques.

Kwiecinski J, Dey D, Cadet S, Lee SE, ... Slomka PJ, Berman DS
Objectives
This study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary F-sodium fluoride (F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA).
Background
Coronary F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized.
Methods
Patients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm). Patients with HRPs were recruited to undergo F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion-corrected F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured.
Results
Forty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary F-NaF activity. Lesions with F-NaF uptake had higher surrounding PCAT density than those without F-NaF uptake (-73 HU; interquartile range -79 to -68 HU vs. -86 HU; interquartile range -94 to -80 HU; p < 0.001). F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP).
Conclusions
In patients with HRP features on coronary CTA, increased density of PCAT was associated with focal F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features.

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

JACC Cardiovasc Imaging: 29 Sep 2019; 12:2000-2010
Kwiecinski J, Dey D, Cadet S, Lee SE, ... Slomka PJ, Berman DS
JACC Cardiovasc Imaging: 29 Sep 2019; 12:2000-2010 | PMID: 30772226
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Abstract

Prognostic Role of CMR and Conventional Risk Factors in Myocardial Infarction With Nonobstructed Coronary Arteries.

Dastidar AG, Baritussio A, De Garate E, Drobni Z, ... Johnson T, Bucciarelli-Ducci C
Objectives
This study sought to assess the prognostic impact of cardiac magnetic resonance (CMR) and conventional risk factors in patients with myocardial infarction with nonobstructed coronaries (MINOCA).
Background
Myocardial infarction with nonobstructed coronary arteries (MINOCA) represents a diagnostic dilemma, and the prognostic markers have not been clarified.
Methods
A total of 388 consecutive patients with MINOCA undergoing CMR assessment were identified retrospectively from a registry database and prospectively followed for a primary clinical endpoint of all-cause mortality. A 1.5-T CMR was performed using a comprehensive protocol (cines, T2-weighted, and late gadolinium enhancement sequences). Patients were grouped into 4 categories based on their CMR findings: myocardial infarction (MI) (embolic/spontaneous recanalization), myocarditis, cardiomyopathy, and normal CMR.
Results
CMR (performed at a median of 37 days from presentation) was able to identify the cause for the troponin rise in 74% of the patients (25% myocarditis, 25% MI, and 25% cardiomyopathy), whereas a normal CMR was identified in 26%. Over a median follow-up of 1,262 days (3.5 years), 5.7% patients died. The cardiomyopathy group had the worst prognosis (mortality 15%; log-rank test: 19.9; p < 0.001), MI had 4% mortality, and 2% in both myocarditis and normal CMR. In a multivariable Cox regression model (including clinical and CMR parameters), CMR diagnosis of cardiomyopathy and ST-segment elevation on presentation electrocardiogram (ECG) remained the only 2 significant predictors of mortality. Using presentation with ECG ST-segment elevation and CMR diagnosis of cardiomyopathy as risk markers, the mortality risk rates were 2%, 11%, and 21% for presence of 0, 1, and 2 factors, respectively (p < 0.0001).
Conclusions
In a large cohort of patients with MINOCA, CMR (median 37 days from presentation) identified a final diagnosis in 74% of patients. Cardiomyopathy had the highest mortality, followed by MI. The strongest predictors of mortality were a CMR diagnosis of cardiomyopathy and ST-segment elevation on presentation ECG.

Copyright © 2019. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 29 Sep 2019; 12:1973-1982
Dastidar AG, Baritussio A, De Garate E, Drobni Z, ... Johnson T, Bucciarelli-Ducci C
JACC Cardiovasc Imaging: 29 Sep 2019; 12:1973-1982 | PMID: 30772224
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Abstract

Radiomic Analysis of Myocardial Native T Imaging Discriminates Between Hypertensive Heart Disease and Hypertrophic Cardiomyopathy.

Neisius U, El-Rewaidy H, Nakamori S, Rodriguez J, Manning WJ, Nezafat R
Objectives
This study sought to examine the diagnostic ability of radiomic texture analysis (TA) on quantitative cardiovascular magnetic resonance images to differentiate between hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM).
Background
HHD and HCM are associated with increased left ventricular wall thickness (LVWT). Contemporary guidelines define HCM as LVWT ≥15 mm that is unexplained by other disease, which complicates diagnosis in cases of co-occurrences. Conventional global native T mapping involves calculation of mean T values as a surrogate for fibrosis. However, there may be differences in its spatial localization, such as diffuse and more focal fibrosis in HHD and HCM, respectively.
Methods
This study identified 232 subjects (53 with HHD, 108 with HCM, and 71 control subjects) for TA who consecutively underwent free-breathing multislice native T mapping. Four sets of texture descriptors were applied to capture spatially dependent and independent pixel statistics. Six texture features were sequentially selected with the best discriminatory capacity between HHD and HCM and were tested using a support vector machine (SVM) classifier. Each disease group was randomly split 4:1 (feature selection/test validation), in which the reproducibility of the pattern was analyzed in the test validation dataset.
Results
The selected texture features provided the maximum diagnostic accuracy of 86.2% (c-statistic: 0.820; 95% confidence interval [CI]: 0.769 to 0.903) using the SVM. For the test validation dataset, the accuracy of the pattern remained high at 80.0% (c-statistic: 0.89; 95% CI: 0.77 to 1.00). Global native T, with an accuracy of 64%, separated HHD and HCM patients modestly (c-statistic: 0.549; 95% CI: 0.452 to 0.640).
Conclusions
Radiomics analysis of native T images discriminates between HHD and HCM patients and provides incremental value over global native T mapping.

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

JACC Cardiovasc Imaging: 29 Sep 2019; 12:1946-1954
Neisius U, El-Rewaidy H, Nakamori S, Rodriguez J, Manning WJ, Nezafat R
JACC Cardiovasc Imaging: 29 Sep 2019; 12:1946-1954 | PMID: 30660549
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Abstract

Superior Risk Stratification With Coronary Computed Tomography Angiography Using a Comprehensive Atherosclerotic Risk Score.

van Rosendael AR, Shaw LJ, Xie JX, Dimitriu-Leen AC, ... Min JK, Bax JJ
Objectives
This study was designed to assess the prognostic value of a new comprehensive coronary computed tomography angiography (CTA) score compared with the stenosis severity component of the Coronary Artery Disease-Reporting and Data System (CAD-RADS).
Background
Current risk assessment with coronary CTA is mainly focused on maximal stenosis severity. Integration of plaque extent, location, and composition in a comprehensive model may improve risk stratification.
Methods
A total of 2,134 patients with suspected but without known CAD were included. The predictive value of the comprehensive CTA score (ranging from 0 to 42 and divided into 3 groups: 0 to 5, 6 to 20, and >20) was compared with the CAD-RADS combined into 3 groups (0% to 30%, 30% to 70% and ≥70% stenosis). Its predictive performance was internally and externally validated (using the 5-year follow-up dataset of the CONFIRM [Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry], n = 1,971).
Results
The mean age of patients was 55 ± 13 years, mean follow-up 3.6 ± 2.8 years, and 130 events (myocardial infarction or death) occurred. The new, comprehensive CTA score showed strong and independent predictive value using the Cox proportional hazard analysis. A model including clinical variables plus comprehensive CTA score showed better discrimination of events compared with a model consisting of clinical variables plus CAD-RADS (0.768 vs. 0.742, p = 0.001). Also, the comprehensive CTA score correctly reclassified a significant proportion of patients compared with the CAD-RADS (net reclassification improvement 12.4%, p < 0.001). Good predictive accuracy was reproduced in the external validation cohort.
Conclusions
The new comprehensive CTA score provides better discrimination and reclassification of events compared with the CAD-RADS score based on stenosis severity only. The score retained similar prognostic accuracy when externally validated. Anatomic risk scores can be improved with the addition of extent, location, and compositional measures of atherosclerotic plaque. (Comprehensive CTA risk score calculator is available at: http://18.224.14.19/calcApp/).

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

JACC Cardiovasc Imaging: 29 Sep 2019; 12:1987-1997
van Rosendael AR, Shaw LJ, Xie JX, Dimitriu-Leen AC, ... Min JK, Bax JJ
JACC Cardiovasc Imaging: 29 Sep 2019; 12:1987-1997 | PMID: 30660516
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Abstract

Myocardial Tissue Characterization and Fibrosis by Imaging.

Karamitsos TD, Arvanitaki A, Karvounis H, Neubauer S, Ferreira VM

Myocardial fibrosis, either focal or diffuse, is a common feature of many cardiac diseases and is associated with a poor prognosis for major adverse cardiovascular events. Although histological analysis remains the gold standard for confirming the presence of myocardial fibrosis, endomyocardial biopsy is invasive, has sampling errors, and is not practical in the routine clinical setting. Cardiac imaging modalities offer noninvasive surrogate biomarkers not only for fibrosis but also for myocardial edema and infiltration to varying degrees, and have important roles in the diagnosis and management of cardiac diseases. This review summarizes important pathophysiological features in the development of commonly encountered cardiac diseases, and the principles, advantages, and disadvantages of various cardiac imaging modalities (echocardiography, single-photon emission computer tomography, positron emission tomography, multidetector computer tomography, and cardiac magnetic resonance) for myocardial tissue characterization, with an emphasis on imaging focal and diffuse myocardial fibrosis.

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

JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print
Karamitsos TD, Arvanitaki A, Karvounis H, Neubauer S, Ferreira VM
JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print | PMID: 31542534
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Abstract

Myocardial T1 and ECV Measurement: Underlying Concepts and Technical Considerations.

Robinson AA, Chow K, Salerno M

Myocardial native T1 and extracellular volume fraction (ECV) mapping have emerged as cardiac cardiac magnetic resonance biomarkers providing unique insight into cardiac pathophysiology. Single breath-hold acquisition techniques, available on clinical scanners across multiple vendor platforms, have made clinical T1 and ECV mapping a reality. Although the relationship between changes in native T1 and alterations in cardiac microstructure is complex, an understanding of how edema, blood volume, myocyte and interstitial expansion, lipids, and paramagnetic substances affect T1 and ECV can provide insight into how and why these parameters change in various cardiac pathologies. The goals of this state-of-the-art review will be to review factors influencing native T1 and ECV, to describe how native T1 and ECV are measured, to discuss potential challenges and pitfalls in clinical practice, and to describe new T1 mapping techniques on the horizon.

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

JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print
Robinson AA, Chow K, Salerno M
JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print | PMID: 31542529
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Abstract

The Interstitium in the Hypertrophied Heart.

Halliday BP, Prasad SK

Pathological left ventricular hypertrophy is a common feature of many cardiac diseases. It results from both myocyte hypertrophy and interstitial expansion. Interstitial expansion is most commonly secondary to the accumulation of mature cross-linked collagen fibers due to dysregulated metabolism, known as interstitial fibrosis. This occurs secondary to a variety of stimuli including ischemic, toxic, metabolic, infective, genetic, and hemodynamic factors. Less commonly, interstitial expansion may occur because of the accumulation of misfolded amyloid protein or interstitial edema. It is now well recognized that the presence and extent of interstitial disease are associated with adverse outcomes. There is therefore interest in the development of novel therapies that target the pathways that drive these disease processes. With the emergence of such therapies, it is becoming increasingly important to be able to characterize the type and extent of interstitial disease to enable the use of such targeted therapies in a personalized manner.

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

JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print
Halliday BP, Prasad SK
JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print | PMID: 31542527
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Abstract

Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy.

Upshaw JN, Finkelman B, Hubbard RA, Smith AM, ... Carver JR, Ky B
Objectives
This study determined the effects of doxorubicin and/or trastuzumab on diastolic function and the relationship between diastolic function and systolic dysfunction.
Background
Doxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on diastolic function remain incompletely defined.
Methods
In a rigorously phenotyped, longitudinal cohort study of 362 breast cancer participants treated with doxorubicin, doxorubicin followed by trastuzumab, or trastuzumb alone, changes in diastolic function were evaluated using linear models estimated via generalized estimating equations. Associations between baseline and changes in diastolic function with LVEF and longitudinal strain were also determined using generalized estimating equations. The Kaplan-Meier estimator derived the proportion of participants who experienced incident diastolic dysfunction. Cox proportional hazards models estimated the associations between participant characteristics and diastolic dysfunction risk, and between diastolic function and cancer therapy-related cardiac dysfunction risk, defined by an LVEF decline of ≥10% to <50%.
Results
Over a median of 2.1 years (interquartile range [IQR]: 1.3 to 4.2 years), participants treated with doxorubicin or doxorubicin followed by trastuzumab demonstrated a persistent worsening in diastolic function, with reductions in the E/A ratio, lateral and septal e\' velocities, and increases in E/e\' (p < 0.01). These changes were not observed with trastuzumab alone. Incident abnormal diastolic function grade occurred in 60% at 1 year, 70% by 2 years, and 80% by 3 years. Abnormal diastolic function grade was associated with a subsequent decrease in LVEF (-2.1%; 95% confidence intervals [CI]: -3.1 to -1.2; p < 0.001) and worsening in longitudinal strain (0.6%; 95% CI: 0.1 to 1.1; p = 0.013) over time. Changes in E/e\' ratio were modestly associated with worsening longitudinal strain (0.1%; 95% CI: 0.0 to 0.2; p = 0.022).
Conclusions
A modest, persistent worsening of diastolic function is observed with contemporary breast cancer therapy. Abnormal and worsening diastolic dysfunction is associated with a small risk of subsequent systolic dysfunction. (Cardiotoxicity of Cancer Therapy [CCT]; NCT01173341).

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

JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print
Upshaw JN, Finkelman B, Hubbard RA, Smith AM, ... Carver JR, Ky B
JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print | PMID: 31542526
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Impact:
Abstract

Cardiac Magnetic Resonance for Evaluating Nonculprit Lesions After Myocardial Infarction: Comparison With Fractional Flow Reserve.

Everaars H, van der Hoeven NW, Janssens GN, van Leeuwen MA, ... van Royen N, Nijveldt R
Objectives
This study sought to determine the agreement between cardiac magnetic resonance (CMR) imaging and invasive measurements of fractional flow reserve (FFR) in the evaluation of nonculprit lesions after ST-segment elevation myocardial infarction (STEMI). In addition, we investigated whether fully quantitative analysis of myocardial perfusion is superior to semiquantitative and visual analysis.
Background
The agreement between CMR and FFR in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease is unknown.
Methods
Seventy-seven patients with STEMI with at least 1 intermediate (diameter stenosis 50% to 90%) nonculprit lesion underwent CMR and invasive coronary angiography in conjunction with FFR measurements at 1 month after primary intervention. The imaging protocol included stress and rest perfusion, cine imaging, and late gadolinium enhancement. Fully quantitative, semiquantitative, and visual analysis of myocardial perfusion were compared against a reference of FFR. Hemodynamically obstructive was defined as FFR ≤0.80.
Results
Hemodynamically obstructive nonculprit lesions were present in 31 (40%) patients. Visual analysis displayed an area under the curve (AUC) of 0.74 (95% confidence interval [CI]: 0.62 to 0.83), with a sensitivity of 73% and a specificity of 70%. For semiquantitative analysis, the relative upslope of the stress signal intensity time curve and the relative upslope derived myocardial flow reserve had respective AUCs of 0.66 (95% CI: 0.54 to 0.77) and 0.71 (95% CI: 0.59 to 0.81). Fully quantitative analysis did not augment diagnostic performance (all p > 0.05). Stress myocardial blood flow displayed an AUC of 0.76 (95% CI: 0.64 to 0.85), with a sensitivity of 69% and a specificity of 77%. Similarly, MFR displayed an AUC of 0.82 (95% CI: 0.71 to 0.90), with a sensitivity of 82% and a specificity of 71%.
Conclusions
CMR and FFR have moderate-good agreement in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease. Fully quantitative, semiquantitative, and visual analysis yield similar diagnostic performance.

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

JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print
Everaars H, van der Hoeven NW, Janssens GN, van Leeuwen MA, ... van Royen N, Nijveldt R
JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print | PMID: 31542525
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Impact:
Abstract

Stress Myocardial Blood Flow Ratio by Dynamic CT Perfusion Identifies Hemodynamically Significant CAD.

Yang J, Dou G, He B, Jin Q, ... Chen Y, Blankstein R
Objectives
The aim of this study was to evaluate the diagnostic accuracy of stress myocardial blood flow ratio (SFR), a novel parameter derived from stress dynamic computed tomographic perfusion (CTP), for the detection of hemodynamically significant coronary stenosis.
Background
A comprehensive cardiac computed tomographic protocol combining coronary computed tomographic angiography (CTA) and CTP can provide a simultaneous assessment of both coronary artery anatomy and ischemia.
Methods
Patients with chest pain scheduled for invasive angiography were prospectively enrolled in this study. Stress dynamic CTP was performed followed by coronary CTA using a second-generation dual-source computed tomographic system. At subsequent invasive angiography, fractional flow reserve was performed to identify hemodynamically significant stenosis. For each coronary territory, SFR was defined as the ratio of hyperemic myocardial blood flow (MBF) in an artery with stenosis to hyperemic MBF in a nondiseased artery. The diagnostic accuracy of SFR to identify hemodynamically significant stenosis was determined against the reference standard of invasive fractional flow reserve ≤0.80.
Results
A total of 82 patients (mean age 58.5 ± 10 years) with 101 vessels with either 1- or 2-vessel disease were included. By FFR, 48 (47.5%) vessels were deemed hemodynamically significant. Hyperemic MBF and SFR were lower for vessels with hemodynamically significant lesions (95.1 ± 32.4 min/100 ml/min vs. 142.5 ± 31.2 min/100 ml/min and 0.66 ± 0.14 vs. 0.90 ± 0.07, respectively; p < 0.01 for both). When compared with ≥50% stenosis by CTA, the specificity for detecting ischemia by SFR increased from 43% to 91%, while the sensitivity decreased from 95% to 62%. Accordingly, the positive and negative predictive values were 85% and 73%, respectively. The combination of stenosis ≥50% by CTA and SFR resulted in an area under the curve of 0.91, which was significantly higher compared with hyperemic MBF (area under the curve = 0.79; p = 0.013).
Conclusions
Calculation of SFR by dynamic CTP provides a novel and accurate method to identify flow-limiting coronary stenosis.

Copyright © 2019. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print
Yang J, Dou G, He B, Jin Q, ... Chen Y, Blankstein R
JACC Cardiovasc Imaging: 11 Sep 2019; epub ahead of print | PMID: 31542524
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Impact:
Abstract

2- and 3-Dimensional Myocardial Strain in Cardiac Health and Disease.

Voigt JU, Cvijic M

Advances in speckle-tracking echocardiography allowed the rise of deformation imaging as a feasible, robust, and valuable tool for clinical routine. The global or segmental measurement of strain can objectively quantify myocardial deformation and can characterize myocardial function in a novel way. However, the proper interpretation of deformation measurements requires understanding of cardiac mechanics and the influence of loading conditions, ventricular geometry, conduction delays, and myocardial tissue characteristics on the measured values. The purpose of this manuscript is to review the basic concepts of deformation imaging, briefly describe imaging modalities for strain assessment, and discuss in depth the underlying physical and pathophysiological mechanisms which lead to the respective findings in a specific disease.

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

JACC Cardiovasc Imaging: 30 Aug 2019; 12:1849-1863
Voigt JU, Cvijic M
JACC Cardiovasc Imaging: 30 Aug 2019; 12:1849-1863 | PMID: 31488253
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Impact:
Abstract

Why and How to Measure Aortic Valve Calcification in Patients With Aortic Stenosis.

Pawade T, Sheth T, Guzzetti E, Dweck MR, Clavel MA

The first-line evaluation of aortic stenosis severity is Doppler echocardiography. However, in up to 40% of patients, resting echocardiographic assessment of aortic stenosis severity is discordant, leading to clinical uncertainty. Interest has therefore grown in aortic valve calcium scoring by multidetector computed tomography (CT-AVC) as an alternative load independent assessment of aortic stenosis severity. This paper will briefly review the pathophysiology of aortic stenosis and the crucial role that calcification plays in driving progressive obstruction of the valve. Subsequently, it will describe published reports that have investigated CT-AVC, validating this parameter against histology, and establishing its diagnostic accuracy versus echocardiography as well as its powerful independent prognostic capability. Finally, this review seeks to provide a practical guide about how best to acquire and interpret CT-AVC with a close focus on potential pitfalls and how these might be best avoided as this technique becomes more widely adopted in to clinical practice.

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

JACC Cardiovasc Imaging: 30 Aug 2019; 12:1835-1848
Pawade T, Sheth T, Guzzetti E, Dweck MR, Clavel MA
JACC Cardiovasc Imaging: 30 Aug 2019; 12:1835-1848 | PMID: 31488252
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Impact:
Abstract

Randomized Comparison of Clinical Effectiveness of Pharmacologic SPECT and PET MPI in Symptomatic CAD Patients.

Patel KK, Al Badarin F, Chan PS, Spertus JA, ... Heller GV, Bateman TM
Objectives
This study compared the clinical effectiveness of pharmacologic stress myocardial perfusion imaging (MPI) plus positron emission tomography (PET) with single-photon emission computed tomography (SPECT) in patients with known coronary artery disease (CAD) presenting with symptoms suggestive of ischemia.
Background
Although PET MPI has been shown to have higher diagnostic accuracy in detecting hemodynamically significant CAD than SPECT MPI, whether this impacts downstream management has not been formally evaluated in randomized trials.
Methods
This study consisted of a single-center trial in which patients with known CAD and suspected ischemia were randomized to undergo PET or attenuation-corrected SPECT MPI between June 2009 and September 2013. Post-test management was at the discretion of the referring physician, and patients were followed for 12 months. The primary endpoint was diagnostic failure, defined as unnecessary angiography (absence of ≥50% stenosis in ≥1 vessel) or additional noninvasive testing within 60 days of the MPI. Secondary endpoints were post-test escalation of antianginal therapy, referral for angiography, coronary revascularization, and health status at 3, 6, and 12 months.
Results
A total of 322 patients with an evaluable MPI were randomized (n = 161 in each group). At baseline, 88.8% of patients were receiving aspirin therapy, 76.7% were taking beta-blockers, and 77.3% were taking statin therapy. Diagnostic failure within 60 days occurred in only 7 patients (2.2%) (3 [1.9%] in the PET group and 4 [2.5%] in the SPECT group; p = 0.70). There were no significant differences between the 2 groups in subsequent rates of coronary angiography, coronary revascularization, or health status at 3, 6, and 12 months of follow-up (all p values ≥0.20); however, when subjects were stratified by findings on MPI in a post hoc analysis, those with high-risk MPI on PET testing had higher rates of angiography and revascularization on follow-up than those who had SPECT MPI, whereas those undergoing low-risk PET studies had lower rates of both procedures than those undergoing SPECT (interaction between randomized modality ∗high-risk MPI for 12-month catheterization [p = 0.001] and 12-month revascularization [p = 0.09]).
Conclusions
In this contemporary cohort of symptomatic CAD patients who were optimally medically managed, there were no discernible differences in rates of diagnostic failure at 60 days, subsequent coronary angiography, revascularization, or patient health status at 1 year between patients evaluated by pharmacologic PET compared with those evaluated by SPECT MPI. Downstream invasive testing rates with PET MPI were more consistent with high-risk features than those with SPECT MPI. (Effectiveness Study of Single Photon Emission Computed Tomography [SPECT] Versus Positron Emission Tomography [PET] Myocardial Perfusion Imaging; NCT00976053).

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

JACC Cardiovasc Imaging: 30 Aug 2019; 12:1821-1831
Patel KK, Al Badarin F, Chan PS, Spertus JA, ... Heller GV, Bateman TM
JACC Cardiovasc Imaging: 30 Aug 2019; 12:1821-1831 | PMID: 31326480
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Impact:
Abstract

Acute Microvascular Impairment Post-Reperfused STEMI Is Reversible and Has Additional Clinical Predictive Value: A CMR OxAMI Study.

Borlotti A, Jerosch-Herold M, Liu D, Viliani D, ... Kharbanda RK, Dall\'Armellina E
Objectives
This study sought to investigate the clinical utility and the predictive relevance of absolute rest myocardial blood flow (MBF) by cardiac magnetic resonance (CMR) in acute myocardial infarction.
Background
Microvascular obstruction (MVO) remains one of the worst prognostic factors in patients with reperfused ST-segment elevation myocardial infarction (STEMI). Clinical trials have focused on cardioprotective strategies to maintain microvascular functionality, but there is a need for a noninvasive test to determine their efficacy.
Methods
A total of 64 STEMI patients post-primary percutaneous coronary intervention underwent 3-T CMR scans acutely and at 6 months (6M). The protocol included cine function, T-weighted edema imaging, pre-contrast T1 mapping, rest first-pass perfusion, and late gadolinium enhancement imaging. Segmental MBF, corrected for rate pressure product (MBF), was quantified in remote, edematous, and infarcted myocardium.
Results
Acute MBF was significantly reduced in infarcted myocardium compared with remote MBF (MBF 0.76 ± 0.20 ml/min/g vs. MBF 1.02 ± 0.21 ml/min/g, p < 0.001), but it significantly increased at 6M (MBF 0.76 ± 0.20 ml/min/g acute vs. 0.85 ± 0.22 ml/min/g at 6M, p < 0.001). On a segmental basis, acute MBF had incremental prognostic value for infarct size at 6M (odds of no LGE at 6M increased by 1.4:1 [p < 0.001] for each 0.1 ml/min/g increase of acute MBF) and functional recovery (odds of wall thickening >45% at 6M increased by 1.38:1 [p < 0.001] for each 0.1 ml/min/g increase of acute MBF). In subjects with coronary flow reserve >2 or index of myocardial resistance <40, acute MBF was associated with long-term functional recovery and was an independent predictor of infarct size reduction.
Conclusions
Acute MBF by CMR could represent a novel quantitative imaging biomarker of microvascular reversibility, and it could be used to identify patients who may benefit from more intensive or novel therapies.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Aug 2019; 12:1783-1793
Borlotti A, Jerosch-Herold M, Liu D, Viliani D, ... Kharbanda RK, Dall'Armellina E
JACC Cardiovasc Imaging: 30 Aug 2019; 12:1783-1793 | PMID: 30660541
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Impact:
Abstract

Sex Differences in Coronary Artery and Thoracic Aorta Calcification and Their Association With Cardiovascular Mortality in Heavy Smokers.

Lessmann N, de Jong PA, Celeng C, Takx RAP, ... van Ginneken B, Išgum I
Objectives
The aim of this study was to investigate sex differences in the prevalence, extent, and association of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) scores with cardiovascular mortality in a population eligible for lung screening.
Background
CAC and TAC scores derived from chest computed tomography (CT) might be useful biomarkers for individualized cardiovascular disease prevention and could be especially relevant in high-risk populations such as heavy smokers. Therefore, it is important to know the prevalence of arterial calcifications in male and female heavy smokers, and if there are differences in the predictive value calcifications carry.
Methods
We performed a nested case-control study with 5,718 participants of the CT arm of the NLST (National Lung Screening Trial). Prevalence and extent of CAC and TAC were resampled to the full cohort to provide unbiased estimates of the typical calcium burden of male and female heavy smokers. Weighted Cox proportional hazards regression was used to assess differences in the association of CAC and TAC scores with all-cause and cardiovascular mortality.
Results
CAC was substantially more common and more severe in men (prevalence: 81% vs. 60%; median volume: 104 mm³ vs. 12 mm³). Women had CAC comparable to that of men who were 10 years younger. TAC was equally common in men and women, with a tendency to be more pronounced in women (prevalence: 92% vs. 93%; median volume: 388 mm³ vs. 404 mm³). Both types of calcification were associated with increased cardiovascular and all-cause mortality. TAC scores improved the prediction of coronary heart disease mortality over CAC in men, but not in women. In both sexes, TAC, but not CAC, was associated with cardiovascular mortality other than coronary heart disease.
Conclusions
CAC develops later in women, whereas TAC develops equally in both sexes. CAC is strongly associated with coronary heart disease, whereas TAC is especially associated with extracardiac vascular mortality in either sex.

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

JACC Cardiovasc Imaging: 30 Aug 2019; 12:1808-1817
Lessmann N, de Jong PA, Celeng C, Takx RAP, ... van Ginneken B, Išgum I
JACC Cardiovasc Imaging: 30 Aug 2019; 12:1808-1817 | PMID: 30660540
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Impact:
Abstract

Noninvasive Imaging to Assess Atherosclerotic Plaque Composition and Disease Activity: Coronary and Carotid Applications.

Daghem M, Bing R, Fayad ZA, Dweck MR

Cardiovascular disease is one of the leading causes of mortality and morbidity worldwide. Atherosclerosis imaging has traditionally focused on detection of obstructive luminal stenoses or measurements of plaque burden. However, with advances in imaging technology it has now become possible to noninvasively interrogate plaque composition and disease activity, thereby differentiating stable from unstable patterns of disease and potentially improving risk stratification. This manuscript reviews multimodality imaging in this field, focusing on carotid and coronary atherosclerosis and how these novel techniques have the potential to complement current imaging assessments and improve clinical decision making.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 08 Aug 2019; epub ahead of print
Daghem M, Bing R, Fayad ZA, Dweck MR
JACC Cardiovasc Imaging: 08 Aug 2019; epub ahead of print | PMID: 31422147
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Impact:
Abstract

Prediction of Coronary Revascularization in Stable Angina: Comparison of FFR With CMR Stress Perfusion Imaging.

Rønnow Sand NP, Nissen L, Winther S, Petersen SE, ... Bøtker HE, Bøttcher M
Objectives
This study was designed to compare head-to-head fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFR) and cardiac magnetic resonance (CMR) stress perfusion imaging for prediction of standard-of-care-guided coronary revascularization in patients with stable chest pain and obstructive coronary artery disease by coronary CTA.
Background
FFR is a novel modality for noninvasive functional testing. The clinical utility of FFR compared to CMR stress perfusion imaging in symptomatic patients with coronary artery disease is unknown.
Methods
Prospective study of patients (n=110) with stable angina pectoris and 1 or more coronary stenosis ≥50% by coronary CTA. All patients underwent invasive coronary angiography. Revascularization was FFR-guided in stenoses ranging from 30% to 90%. FFR ≤0.80 in 1 or more coronary artery or a reversible perfusion defect (≥2 segments) by CMR categorized patients with ischemia. FFR and CMR were analyzed by core laboratories blinded for patient management.
Results
A total of 38 patients (35%) underwent revascularization. Per-patient diagnostic performance for identifying standard-of-care-guided revascularization, (95% confidence interval) yielded a sensitivity of 97% (86 to 100) for FFR versus 47% (31 to 64) for CMR, p < 0.001; corresponding specificity was 42% (30 to 54) versus 88% (78 to 94), p < 0.001; negative predictive value of 97% (91 to 100) versus 76% (67 to 85), p < 0.05; positive predictive value of 47% (36 to 58) versus 67% (49 to 84), p < 0.05; and accuracy of 61% (51 to 70) versus 74% (64 to 82), p > 0.05, respectively.
Conclusions
In patients with stable chest pain referred to invasive coronary angiography based on coronary CTA, FFR and CMR yielded similar overall diagnostic accuracy. Sensitivity for prediction of revascularization was highest for FFR whereas specificity was highest for CMR.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 13 Aug 2019; epub ahead of print
Rønnow Sand NP, Nissen L, Winther S, Petersen SE, ... Bøtker HE, Bøttcher M
JACC Cardiovasc Imaging: 13 Aug 2019; epub ahead of print | PMID: 31422146
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Impact:
Abstract

Considerations for Clinical Trials Targeting the Myocardial Interstitium.

Lewis GA, Dodd S, Naish JH, Selvanayagam JB, Dweck MR, Miller CA

The myocardial interstitium has emerged as a potential therapeutic target and as a biological entity to improve risk stratification and better guide existing interventions. Clinical trials focusing on the myocardial interstitium are required to establish causality and improve patient outcomes. This review will discuss issues around clinical trials targeting the myocardial interstitium, including antifibrotic therapies, efficacy outcome measurements, mechanistic outcome measurements and mediation analysis, sample size, trial duration, considerations for multicenter trials, stratifying trial recruitment according to the interstitium, and approaches to enrich recruitment, using examples of ongoing clinical trials.

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

JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print
Lewis GA, Dodd S, Naish JH, Selvanayagam JB, Dweck MR, Miller CA
JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print | PMID: 31422145
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Impact:
Abstract

Influence of Coronary Calcium on Diagnostic Performance of Machine Learning CT-FFR: Results From MACHINE Registry.

Tesche C, Otani K, De Cecco CN, Coenen A, ... Nieman K, Schoepf UJ
Objectives
This study was conducted to investigate the influence of coronary artery calcium (CAC) score on the diagnostic performance of machine-learning-based coronary computed tomography (CT) angiography (cCTA)-derived fractional flow reserve (CT-FFR).
Background
CT-FFR is used reliably to detect lesion-specific ischemia. Novel CT-FFR algorithms using machine-learning artificial intelligence techniques perform fast and require less complex computational fluid dynamics. Yet, influence of CAC score on diagnostic performance of the machine-learning approach has not been investigated.
Methods
Four hundred eighty-two vessels from 314 patients (62.3 ± 9.3 years, 77% male) who underwent cCTA followed by invasive FFR were investigated from the MACHINE (Machine Learning based CT Angiography derived FFR: a Multi-center Registry) registry data. CAC scores were quantified using the Agatston convention. The diagnostic performance of CT-FFR to detect lesion-specific ischemia was assessed across all Agatston score categories (CAC 0, >0 to <100, 100 to <400, and ≥400) on a per-vessel level with invasive FFR as the reference standard.
Results
The diagnostic accuracy of CT-FFR versus invasive FFR was superior to cCTA alone on a per-vessel level (78% vs. 60%) and per patient level (83% vs. 73%) across all Agatston score categories. No statistically significant differences in the diagnostic accuracy, sensitivity, or specificity of CT-FFR were observed across the categories. CT-FFR showed good discriminatory power in vessels with high Agatston scores (CAC ≥ 400) and high performance in low-to-intermediate Agatston scores (CAC >0 to <400) with a statistically significant difference in the area under the receiver-operating characteristic curve (AUC) (AUC: 0.71 [95% confidence interval (CI): 0.57-0.85] vs. 0.85 [95% CI: 0.82-0.89], p = 0.04). CT-FFR showed superior diagnostic value over cCTA in vessels with high Agatston scores (CAC ≥ 400: AUC 0.71 vs. 0.55, p = 0.04) and low-to-intermediate Agatston scores (CAC >0 to <400: AUC 0.86 vs. 0.63, p < 0.001).
Conclusions
Machine-learning-based CT-FFR showed superior diagnostic performance over cCTA alone in CAC with a significant difference in the performance of CT-FFR as calcium burden/Agatston calcium score increased. (Machine Learning Based CT Angiography Derived FFR: a Multicenter, Registry [MACHINE] NCT02805621).

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

JACC Cardiovasc Imaging: 13 Aug 2019; epub ahead of print
Tesche C, Otani K, De Cecco CN, Coenen A, ... Nieman K, Schoepf UJ
JACC Cardiovasc Imaging: 13 Aug 2019; epub ahead of print | PMID: 31422141
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Impact:
Abstract

Optimizing Cardiac CT Protocols for Comprehensive Acquisition Prior to Percutaneous MV and TV Repair/Replacement.

Pulerwitz TC, Khalique OK, Leb J, Hahn RT, ... Kodali SK, Einstein AJ

Clinical trials of transcatheter mitral valve and tricuspid valve repair and replacement devices have begun in earnest, with the ultimate goal of providing definitive, nonsurgical treatment for the millions of patients with severe, symptomatic regurgitation, many of whom are too high risk or inoperable for a surgical approach. Computed tomography (CT) angiography offers the potential for detailed anatomic assessment in this patient population, but its optimal implementation for patients with mitral and tricuspid disease requires patient-centered protocol specification reflecting the goal of the scan, an understanding of complex anatomy and pathophysiology, and particulars of CT scanner capabilities. In this paper, the need for new interventional approaches to mitral and tricuspid valve disease is discussed, followed by a detailed review of how to perform a high-quality CT angiography examination, taking into consideration scanner- and patient-specific variables when preparing a pre-mitral or tricuspid protocol. The many possible clinical challenges affecting the performance of cardiac and vascular CT angiography for pre-procedure mitral and tricuspid repair/replacement are reviewed and specific tips, trouble-shooting approaches, and recommendations are provided for how to conduct the best-quality study, be it at an experienced imaging center with the most advanced scanner or at a novice center using an earlier generation CT platform.

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

JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print
Pulerwitz TC, Khalique OK, Leb J, Hahn RT, ... Kodali SK, Einstein AJ
JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print | PMID: 31422136
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Impact:
Abstract

Intravascular Polarimetry in Patients With Coronary Artery Disease.

Otsuka K, Villiger M, Karanasos A, van Zandvoort LJC, ... Regar E, Bouma BE
Objectives
The aims of this first-in-human pilot study of intravascular polarimetry were to investigate polarization properties of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional optical frequency domain imaging (OFDI) and with clinical presentation.
Background
Polarization-sensitive OFDI measures birefringence and depolarization of tissue together with conventional cross-sectional optical frequency domain images of subsurface microstructure.
Methods
Thirty patients undergoing polarization-sensitive OFDI (acute coronary syndrome, n = 12; stable angina pectoris, n = 18) participated in this study. Three hundred forty-two cross-sectional images evenly distributed along all imaged coronary arteries were classified into 1 of 7 plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross section were compared among plaque types and with structural parameters. Furthermore, the polarization properties in cross sections (n = 244) of the fibrous caps of acute coronary syndrome and stable angina pectoris culprit lesions were assessed and compared with structural features using a generalized linear model.
Results
The median birefringence and depolarization showed statistically significant differences among plaque types (p < 0.001 for both, 1-way analysis of variance). Depolarization differed significantly among individual plaque types (p < 0.05), except between normal arteries and fibrous plaques and between fibrofatty and fibrocalcified plaques. Caps of acute coronary syndrome lesions and ruptured caps exhibited lower birefringence than caps of stable angina pectoris lesions (p < 0.01). In addition to clinical presentation, cap birefringence was also associated with macrophage accumulation as assessed using normalized standard deviation.
Conclusions
Intravascular polarimetry provides quantitative metrics that help characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print
Otsuka K, Villiger M, Karanasos A, van Zandvoort LJC, ... Regar E, Bouma BE
JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print | PMID: 31422135
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Abstract

Ticagrelor to Reduce Myocardial Injury in Patients With High-Risk Coronary Artery Plaque.

Moss AJ, Dweck MR, Doris MK, Andrews JPM, ... Newby DE, Adamson PD
Objectives
The goal of this study was to determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque.
Background
High-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy.
Methods
In a randomized, double-blind, placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary F-fluoride positron emission tomography/coronary computed tomography scanning and measurement of high-sensitivity cardiac troponin I. Patients were randomized (1:1) to receive ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary F-fluoride uptake.
Results
In total, 202 patients were randomized to treatment, and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary F-fluoride uptake (120 of 191), there was no evidence that ticagrelor had an effect on plasma troponin concentrations at 30 days (ratio of geometric means for ticagrelor vs. placebo: 1.11; 95% confidence interval: 0.90 to 1.36; p = 0.32). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary F-fluoride uptake (ratio of geometric means: 0.86; 95% confidence interval: 0.63 to 1.17; p = 0.33).
Conclusions
Dual antiplatelet therapy with ticagrelor did not reduce plasma troponin concentrations in patients with high-risk coronary plaque, suggesting that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting. (Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND]; NCT02110303).

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print
Moss AJ, Dweck MR, Doris MK, Andrews JPM, ... Newby DE, Adamson PD
JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print | PMID: 31422134
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Impact:
Abstract

Adverse Plaque Characteristics Relate More Strongly With Hyperemic Fractional Flow Reserve and Instantaneous Wave-Free Ratio Than With Resting Instantaneous Wave-Free Ratio.

Driessen RS, de Waard GA, Stuijfzand WJ, Raijmakers PG, ... Narula J, Knaapen P
Objectives
The current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)-derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices.
Background
Next to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR.
Methods
Of 120 patients (62% men, age 58.3 ± 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements.
Results
Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to ≥70% stenosis (-0.10, p < 0.001 and -0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (-0.10, p < 0.001 and -0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR.
Conclusions
CT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.

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

JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print
Driessen RS, de Waard GA, Stuijfzand WJ, Raijmakers PG, ... Narula J, Knaapen P
JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print | PMID: 31422133
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Impact:
Abstract

Augmentation of Tissue Perfusion in Patients With Peripheral Artery Disease Using Microbubble Cavitation.

Mason OR, Davidson BP, Sheeran P, Muller M, ... Powers J, Lindner JR
Objectives
The authors investigated ideal acoustic conditions on a clinical scanner custom-programmed for ultrasound (US) cavitation-mediated flow augmentation in preclinical models. We then applied these conditions in a first-in-human study to test the hypothesis that contrast US can increase limb perfusion in normal subjects and patients with peripheral artery disease (PAD).
Background
US-induced cavitation of microbubble contrast agents augments tissue perfusion by convective shear and secondary purinergic signalling that mediates release of endogenous vasodilators.
Methods
In mice, unilateral exposure of the proximal hindlimb to therapeutic US (1.3 MHz, mechanical index 1.3) was performed for 10 min after intravenous injection of lipid microbubbles. US varied according to line density (17, 37, 65 lines) and pulse duration. Microvascular perfusion was evaluated by US perfusion imaging, and in vivo adenosine triphosphate (ATP) release was assessed using in vivo optical imaging. Optimal parameters were then used in healthy volunteers and patients with PAD where calf US alone or in combination with intravenous microbubble contrast infusion was performed for 10 min.
Results
In mice, flow was augmented in the US-exposed limb for all acoustic conditions. Only at the lowest line density was there a stepwise increase in perfusion for longer (40-cycle) versus shorter (5-cycle) pulse duration. For higher line densities, blood flow consistently increased by 3-fold to 4-fold in the US-exposed limb irrespective of pulse duration. High line density and long pulse duration resulted in the greatest release of ATP in the cavitation zone. Application of these optimized conditions in humans together with intravenous contrast increased calf muscle blood flow by >2-fold in both healthy subjects and patients with PAD, whereas US alone had no effect.
Conclusions
US of microbubbles when using optimized acoustic environments can increase perfusion in limb skeletal muscle, raising the possibility of a therapy for patients with PAD. (Augmentation of Limb Perfusion With Contrast Ultrasound; NCT03195556).

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

JACC Cardiovasc Imaging: 13 Aug 2019; epub ahead of print
Mason OR, Davidson BP, Sheeran P, Muller M, ... Powers J, Lindner JR
JACC Cardiovasc Imaging: 13 Aug 2019; epub ahead of print | PMID: 31422129
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Impact:
Abstract

Subtypes of Atrial Functional Mitral Regurgitation: Imaging Insights Into Their Mechanisms and Therapeutic Implications.

Kagiyama N, Mondillo S, Yoshida K, Mandoli GE, Cameli M

Functional mitral regurgitation (MR) in patients with atrial fibrillation (AF) without left ventricular dysfunction, namely, atrial functional MR, has been increasingly recognized. Whether mitral annular dilatation causes MR in patients without left ventricular dysfunction has remained controversial; however, recent studies using novel imaging technologies, including 3-dimensional echocardiography, have shown that significant functional MR can sometimes occur in AF patients with significant dilatation of mitral annulus and left atrium. Additional contributors such as atriogenic leaflet tethering, annulus area to leaflet area imbalance resulting from insufficient leaflet remodeling and reduced annular contractility, increased valve stress by flattened saddle shape of the annulus, and left atrial dysfunction may be important triggers of atrial functional MR in the presence of dilated mitral annulus and left atrium. The prevalence of atrial functional MR is reported to be between 3% and 15% in AF patients and those with atrial functional MR are associated with worse clinical outcomes. Because there are few published data regarding therapeutic strategies of atrial functional MR, understanding the principles of therapeutic options and their target mechanisms is important with regards to clinical practice until sufficient evidence is established. In this review, the known mechanisms, clinical implications and, when possible, potential therapeutic options of atrial functional MR are discussed.

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

JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print
Kagiyama N, Mondillo S, Yoshida K, Mandoli GE, Cameli M
JACC Cardiovasc Imaging: 07 Aug 2019; epub ahead of print | PMID: 31422123
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Impact:
Abstract

Multimodality Imaging Markers of Adverse Myocardial Remodeling in Aortic Stenosis.

Treibel TA, Badiani S, Lloyd G, Moon JC

Aortic stenosis (AS) causes left ventricular remodeling (hypertrophy, remodeling, fibrosis) and other cardiac changes (left atrial dilatation, pulmonary artery and right ventricular changes). These changes, and whether they are reversible (reverse remodeling), are major determinants of timing and outcome from transcatheter or surgical aortic valve replacement. Cardiac changes in response to AS afterload can either be adaptive and reversible, or maladaptive and irreversible, when they may convey residual risk after intervention. Structural and hemodynamic assessment of AS therefore needs to evaluate more than the valve, and, in particular, the myocardial remodeling response. Imaging plays a key role in this. This review assesses how multimodality imaging evaluates AS myocardial hypertrophy and its components (cellular hypertrophy, fibrosis, microvascular changes, and additional features such as cardiac amyloid) both before and after intervention, and seeks to highlight how care and outcomes in AS could be improved.

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

JACC Cardiovasc Imaging: 30 Jul 2019; 12:1532-1548
Treibel TA, Badiani S, Lloyd G, Moon JC
JACC Cardiovasc Imaging: 30 Jul 2019; 12:1532-1548 | PMID: 31395243
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Impact:
Abstract

Use of Contemporary Imaging Techniques for Electrophysiological and Device Implantation Procedures.

Auricchio A, Faletra FF

Recent technological advances in cardiac imaging allow the visualization of anatomic details up to millimeter size in 3-dimensional format. Thus, it is not surprising that electrophysiologists increasingly rely upon cardiac imaging for the diagnosis, treatment, and subsequent management of patients affected by various arrhythmic disorders. Cardiac imaging methods reviewed in the present work involve: 1) the prediction of arrhythmic risk for sudden cardiac death in patients with heart disease; 2) catheter ablation of atrial fibrillation or ventricular tachycardia; and 3) cardiac resynchronization therapy. Future integration of diagnostic and interventional cardiac imaging will further increase the effectiveness of cardiac electrophysiological procedures and will help in delivering patient-specific therapies with ablation and cardiac implantable electronic devices.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print
Auricchio A, Faletra FF
JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print | PMID: 31326496
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Impact:
Abstract

CMR for Identifying the Substrate of Ventricular Arrhythmia in Patients With Normal Echocardiography.

Andreini D, Dello Russo A, Pontone G, Mushtaq S, ... Tondo C, Pepi M
Objectives
This study sought to determine whether cardiac magnetic resonance (CMR) may identify structural heart disease (SHD) in patients with ventricular arrhythmia who had echocardiography ruled out pathological findings.
Background
Approximately one-half of sudden cardiac deaths are attributable to malignant VA. Echocardiography is commonly used to identify SHD that is the most frequent substrate of VA.
Methods
A single-center prospective study was conducted in consecutive patients with significant VA, categorized as >1,000 but <10,000 ventricular ectopic beats [VEBs]/24 h; ≥10,000 VEBs/24 h; nonsustained ventricular tachycardia, sustained ventricular tachycardia (SVT), or a history of resuscitated cardiac arrest, and no pathological findings at echocardiography, requiring a clinically indicated CMR. Primary endpoint was CMR detection of SHD. Secondary endpoints were a composite of CMR detection of SHD and abnormal findings not specific for a definite SHD diagnosis.
Results
A total of 946 patients were enrolled (mean 41 ± 16 years of age; 64% men). CMR studies were used to diagnose SHD in 241 patients (25.5%) and abnormal findings not specific for a definite SHD diagnosis in 187 patients (19.7%). Myocarditis (n = 91) was the more frequent disease, followed by arrhythmogenic cardiomyopathy (n = 55), dilated cardiomyopathy (n = 39), ischemic heart disease (n = 22), hypertrophic cardiomyopathy (n = 13), congenital cardiac disease (n = 10), left ventricle noncompaction (n = 5), and pericarditis (n = 5). The strongest univariate and multivariate predictors of SHD on CMR images were chest pain (odds ratios [OR]: 2.52 and 2.38, respectively) and SVT (ORs: 2.67 and 2.23, respectively).
Conclusions
SHD was able to be identified on CMR imaging in a sizable number of patients with significant VA and completely normal echocardiography. Chest pain and SVT were the strongest predictors of positive CMR imaging results.

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

JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print
Andreini D, Dello Russo A, Pontone G, Mushtaq S, ... Tondo C, Pepi M
JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print | PMID: 31326488
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Impact:
Abstract

Clinical Use of CT-Derived Fractional Flow Reserve in the Emergency Department.

Chinnaiyan KM, Safian RD, Gallagher ML, George J, ... Crile J, Raff GL
Objectives
The study sought to examine the feasibility, safety, clinical outcomes, and costs associated with computed tomography-derived fractional flow reserve (FFR) in acute chest pain (ACP) patients in a coronary computed tomography angiography (CTA)-based triage program.
Background
FFR is useful in determining lesion-specific ischemia in patients with stable ischemic heart disease, but its utility in ACP has not been studied.
Methods
ACP patients with no known coronary artery disease undergoing coronary CTA and coronary CTA with FFR were studied. FFR ≤0.80 was considered positive for hemodynamically significant stenosis.
Results
Among 555 patients, 297 underwent coronary CTA and FFR (196 negative, 101 positive), whereas 258 had coronary CTA only. The rejection rate for FFR was 1.6%. At 90 days, there was no difference in major adverse cardiac events (including death, nonfatal myocardial infarction, and unexpected revascularization after the index visit) between the coronary CTA and FFR groups (4.3% vs. 2.7%; p = 0.310). Diagnostic failure, defined as discordance between the coronary CTA or FFR results with invasive findings, did not differ between the groups (1.9% vs. 1.68%; p = NS). No deaths or myocardial infarction occurred with negative FFR when revascularization was deferred. Negative FFR was associated with higher nonobstructive disease on invasive coronary angiography (56.5%) than positive FFR (8.0%) and coronary CTA (22.9%) (p < 0.001). There was no difference in overall costs between the coronary CTA and FFR groups ($8,582 vs. $8,048; p = 0.550).
Conclusions
In ACP, FFR is feasible, with no difference in major adverse cardiac events and costs compared with coronary CTA alone. Deferral of revascularization is safe with negative FFR, which is associated with higher nonobstructive disease on invasive angiography.

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

JACC Cardiovasc Imaging: 16 Jul 2019; epub ahead of print
Chinnaiyan KM, Safian RD, Gallagher ML, George J, ... Crile J, Raff GL
JACC Cardiovasc Imaging: 16 Jul 2019; epub ahead of print | PMID: 31326487
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Abstract

Changes in Myocardial Native T and T After Exercise Stress: A Noncontrast CMR Pilot Study.

Nakamori S, Fahmy A, Jang J, El-Rewaidy H, ... Manning WJ, Nezafat R
Objectives
This study assessed changes in myocardial native T and T values after supine exercise stress in healthy subjects and in patients with suspected ischemia as potential imaging markers of ischemia.
Background
With emerging data on the long-term retention of gadolinium in the body and brain, there is a need for an alternative noncontrast cardiovascular magnetic resonance (CMR)-based myocardial ischemia assessment.
Methods
Twenty-eight healthy adult subjects and 14 patients with coronary artery disease (CAD) referred for exercise stress and/or rest single-photon emission computed tomography/myocardial perfusion imaging (SPECT/MPI) for evaluation of chest pain were prospectively enrolled. Free-breathing myocardial native T and T mapping were performed before and after supine bicycle exercise stress using a CMR-compatible supine ergometer positioned on the MR table. Differences in T, T and T, T values were calculated as T and T reactivity, respectively.
Results
The mean exercise intensity was 104 W, with exercise duration of 6 to 12 min. After exercise, native T was increased in healthy subjects (p < 0.001). T reactivity, but not T reactivity, correlated with the rate-pressure product as the index of myocardial blood flow during exercise (r = 0.62; p < 0.001). In patients with CAD, T reactivity was associated with the severity of myocardial perfusion abnormality on SPECT/MPI (normal: 4.9%; quartiles: 3.7% to 6.3%, mild defect: 1.2%, quartiles: 0.08% to 2.5%; moderate defect: 0.45%, quartiles: -0.35% to 1.4%; severe defect: 0.35%, quartiles: -0.44% to 0.8%) and had similar potential as SPECT/MPI to detect significant CAD (>50% diameter stenosis on coronary angiography). The area under the receiver-operating characteristic curve was 0.80 versus 0.72 (p = 0.40). The optimum cutoff value of T reactivity for predicting flow-limiting stenosis was 2.5%, with a sensitivity of 83% and a specificity of 92%, a negative predictive value of 96%, a positive predictive value of 71%, and an area under the curve of 0.86.
Conclusions
Free-breathing stress/rest native T mapping, but not T mapping, can detect physiological changes in the myocardium during exercise. Our feasibility study in patients shows the potential of this technique as a method for detecting myocardial ischemia in patients with CAD without using a pharmacological stress agent.

Copyright © 2019. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 16 Jul 2019; epub ahead of print
Nakamori S, Fahmy A, Jang J, El-Rewaidy H, ... Manning WJ, Nezafat R
JACC Cardiovasc Imaging: 16 Jul 2019; epub ahead of print | PMID: 31326484
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Impact:
Abstract

Diagnostic Accuracy of FDG PET/CT in Suspected LVAD Infections: A Case Series, Systematic Review, and Meta-Analysis.

Tam MC, Patel VN, Weinberg RL, Hulten EA, ... Corbett JR, Murthy VL
Objectives
The purpose of this study was to describe our experience with fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET/CT) in diagnosing left ventricular assist device (LVAD) infections and perform a meta-analysis of published studies to determine overall diagnostic accuracy.
Background
Device-related infections are a common complication of LVADs and are linked to worse outcomes. Diagnosis of LVAD infections remains challenging. FDG PET/CT has demonstrated good diagnostic accuracy in several other infectious conditions.
Methods
This was a single-center, retrospective case series of FDG PET/CT scans in suspected LVAD infection between September 2015 and February 2018. A systematic review of PubMed from database inception through March 2018 was also conducted to identify additional studies.
Results
Nineteen FDG PET/CT scans were identified for the retrospective case series. The systematic review identified an additional 3 publications, for a total of 4 studies involving 119 scans assessing diagnostic performance. Axial (n = 36) and centrifugal (n = 83) flow LVADs were represented. Pooled sensitivity was 92% (95% confidence interval [CI]: 82% to 97%) and specificity was 83% (95% CI: 24% to 99%) for FDG PET/CT in diagnosing LVAD infections. Summary receiver-operating characteristic curve analysis demonstrated an AUC of 0.94 (95% CI: 0.91 to 0.95).
Conclusions
FDG PET/CT for suspected LVAD infections demonstrates good diagnostic accuracy, with overall high sensitivity but variable specificity.

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

JACC Cardiovasc Imaging: 16 Jul 2019; epub ahead of print
Tam MC, Patel VN, Weinberg RL, Hulten EA, ... Corbett JR, Murthy VL
JACC Cardiovasc Imaging: 16 Jul 2019; epub ahead of print | PMID: 31326483
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Abstract

Preventive Management of Nonobstructive CAD After Coronary CT Angiography in the Emergency Department.

Honigberg MC, Lander BS, Baliyan V, Jones-O\'Connor M, ... Ghoshhajra BB, Natarajan P
Objectives
This study sought to assess medical management of patients found to have nonobstructive coronary artery disease (CAD) on coronary computed tomography angiography (CCTA) performed in the emergency department (ED).
Background
Contemporary recognition and management of nonobstructive CAD discovered on CCTA performed in the ED is unknown.
Methods
Patients undergoing CCTA in the authors\' hospital\'s ED between November 2013 and March 2018 who also received primary care within the authors\' health system were studied. All patients with nonobstructive CAD, defined as 1% to 49% maximum luminal stenosis on CCTA, were included, along with a control group without CAD in a 1 case:1 control fashion. Ten-year atherosclerotic cardiovascular disease (ASCVD) risk prior to CCTA was estimated using the Pooled Cohort Equations. Management changes were recorded until 6 months after CCTA. Multivariate logistic regression tested the association between CCTA result and follow-up statin prescription, adjusting for cardiovascular risk factors and baseline statin use.
Results
The cohort included 510 patients with nonobstructive CAD and 510 controls. Prevalence of statin prescription increased from 38.8% to 56.1% among patients with nonobstructive CAD (p < 0.001) and 18.0% to 20.4% among controls (p = 0.01), representing a 7.1-fold relative difference (95% confidence interval [CI]: 4.4 to 23.0; p < 0.001) in multivariate analysis. However, 30.0% of patients with nonobstructive CAD and ≥20% 10-year ASCVD risk were not prescribed a statin at the end of follow-up. Cardiologist evaluation was independently associated with statin prescription after adjustment for ASCVD risk factors (odds ratio [OR] 4.4; 95% CI: 2.4 to 8.5; p < 0.001). A Coronary Artery Disease Reporting and Data System class 1 to 2 result was associated with lower low-density lipoprotein cholesterol by 12.1 mg/dl at mean 1.9-year follow-up (p < 0.001).
Conclusions
Incidental subclinical atherosclerosis on CCTA performed in the ED increases the likelihood of statin prescription, but opportunities to improve allocation of indicated preventive therapies remain.

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

JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print
Honigberg MC, Lander BS, Baliyan V, Jones-O'Connor M, ... Ghoshhajra BB, Natarajan P
JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print | PMID: 31326481
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Abstract

Nuclear Imaging of the Cardiac Sympathetic Nervous System: A Disease-Specific Interpretation in Heart Failure.

Zelt JGE, deKemp RA, Rotstein BH, Nair GM, ... Beanlands RS, Mielniczuk LM

Abnormalities in the cardiac sympathetic nervous system have been documented in various heart diseases and have been directly implicated in their pathogenesis and disease progression. Noninvasive techniques using single-photon-emitting radiotracers for planar scintigraphy and single-photon emission computed tomography, and positron-emitting tracers for positron emissions tomography, have been used to characterize the cardiac sympathetic nervous system with norepinephrine analogs [I]meta-iodobenzylguanidine for planar and single-photon emission computed tomography imaging and [C]meta-hydroxyephedrine for positron emissions tomography. Their usefulness in prognostication and risk stratification for cardiac events has been demonstrated. This review bridges basic and clinical research and focuses on applying an understanding of tracer kinetics and neuronal biology, to aid in the interpretation of nuclear imaging of cardiac sympathetic innervation.

Copyright © 2019. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print
Zelt JGE, deKemp RA, Rotstein BH, Nair GM, ... Beanlands RS, Mielniczuk LM
JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print | PMID: 31326479
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Abstract

The Detrimental Effect of RA Pacing on LA Function and Clinical Outcome in Cardiac Resynchronization Therapy.

Martens P, Deferm S, Bertrand PB, Verbrugge FH, ... Vandervoort PM, Mullens W
Objectives
This study assessed the impact of right-atrial (RA) pacing on left-atrial (LA) physiology and clinical outcome.
Background
Data for the effects of RA pacing on LA synchronicity, function, and structure after cardiac resynchronization therapy (CRT) are scarce.
Methods
The effect of RA pacing on LA function, morphology, and synchronicity was assessed in a prospective imaging cohort of heart failure (HF) patients in sinus rhythm with a guideline-based indication for CRT. Additionally, in a retrospective outcome cohort of consecutive HF patients undergoing CRT implantation, the relationship to RA pacing was assessed using various outcome endpoints. High versus low atrial pacing burden was defined as atrial pacing above or below 50% in both cohorts.
Results
A total of 36 patients were included in the imaging cohort (68 ± 11 years of age). Six months after CRT, patients with high RA pacing burden showed less improvement in LA maximum and minimum volumes and total emptying fraction (p < 0.05). Peak atrial longitudinal strain and reservoir and booster strain rates but not conduit strain rate improved after CRT in patients with low RA pacing burden but worsened in patients with high RA pacing burden (p < 0.05 for all). A high RA pacing burden induced significant intra-atrial dyssynchrony (maximum opposing wall delay: 44 ± 13 ms vs. 97 ± 17 ms, respectively; p = 0.022). A total of 569 patients were included in the outcome cohort. After covariate adjustments were made, a high RA pacing burden was associated with reduced LV reverse remodeling (β = 8.738; 95% confidence interval [CI]: 3.101 to 14.374; p = 0.002) and new-onset or recurrent atrial fibrillation (41% vs. 22%, respectively, at a median of 31 months [range 22 to 44 months follow-up]; p < 0.001). There were no differences in time to first HF hospitalization or all-cause mortality (p = 0.185) after covariate adjustment. However, in a recurrent event analysis, HF readmissions were more common in patients exposed to a high RA pacing burden (p = 0.003).
Conclusions
RA pacing in CRT patients negatively influences LA morphology, function, and synchronicity, which is associated with worse clinical outcome, including diminished LV reverse remodeling, increased risk for new-onset or recurrent AF and heart failure readmission. Strategies reducing RA pacing burden may be warranted.

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

JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print
Martens P, Deferm S, Bertrand PB, Verbrugge FH, ... Vandervoort PM, Mullens W
JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print | PMID: 31326478
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Impact:
Abstract

Fully Automated, Quality-Controlled Cardiac Analysis From CMR: Validation and Large-Scale Application to Characterize Cardiac Function.

Ruijsink B, Puyol-Antón E, Oksuz I, Sinclair M, ... Razavi R, King AP
Objectives
This study sought to develop a fully automated framework for cardiac function analysis from cardiac magnetic resonance (CMR), including comprehensive quality control (QC) algorithms to detect erroneous output.
Background
Analysis of cine CMR imaging using deep learning (DL) algorithms could automate ventricular function assessment. However, variable image quality, variability in phenotypes of disease, and unavoidable weaknesses in training of DL algorithms currently prevent their use in clinical practice.
Methods
The framework consists of a pre-analysis DL image QC, followed by a DL algorithm for biventricular segmentation in long-axis and short-axis views, myocardial feature-tracking (FT), and a post-analysis QC to detect erroneous results. The study validated the framework in healthy subjects and cardiac patients by comparison against manual analysis (n = 100) and evaluation of the QC steps\' ability to detect erroneous results (n = 700). Next, this method was used to obtain reference values for cardiac function metrics from the UK Biobank.
Results
Automated analysis correlated highly with manual analysis for left and right ventricular volumes (all r > 0.95), strain (circumferential r = 0.89, longitudinal r > 0.89), and filling and ejection rates (all r ≥ 0.93). There was no significant bias for cardiac volumes and filling and ejection rates, except for right ventricular end-systolic volume (bias +1.80 ml; p = 0.01). The bias for FT strain was <1.3%. The sensitivity of detection of erroneous output was 95% for volume-derived parameters and 93% for FT strain. Finally, reference values were automatically derived from 2,029 CMR exams in healthy subjects.
Conclusions
The study demonstrates a DL-based framework for automated, quality-controlled characterization of cardiac function from cine CMR, without the need for direct clinician oversight.

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print
Ruijsink B, Puyol-Antón E, Oksuz I, Sinclair M, ... Razavi R, King AP
JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print | PMID: 31326477
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Impact:
Abstract

Heterogeneity of Plaque Structural Stress Is Increased in Plaques Leading to MACE: Insights From the PROSPECT Study.

Costopoulos C, Maehara A, Huang Y, Brown AJ, ... Stone GW, Bennett MR
Objectives
This study sought to determine if plaque structural stress (PSS) and other plaque stress parameters are increased in plaques that cause future major adverse cardiovascular events (MACE) and if incorporating these parameters improves predictive capability of intravascular ultrasonography (IVUS).
Background
Less than 10% of coronary plaques identified as high-risk by intravascular imaging result in subsequent MACE. Thus, more specific measurements of plaque vulnerability are required for effective risk stratification.
Methods
Propensity score matching in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study plaque cohort resulted in 35 nonculprit lesions (NCL) associated with future MACE and 66 matched NCL that remained clinically silent. PSS was calculated by finite element analysis as the mechanical loading within the plaque structure in the periluminal region.
Results
PSS was increased in the minimal luminal area (MLA) regions of NCL MACE versus no MACE plaques for all plaques (PSS: 112.1 ± 5.5 kPa vs. 90.4 ± 3.3 kPa, respectively; p = 0.001) and virtual histology thin-cap fibroatheromas (VH-TCFAs) (PSS: 119.2 ± 6.6 kPa vs. 95.8 ± 5.0 kPa, respectively; p = 0.005). However, PSS was heterogeneous over short segments, and PSS heterogeneity index (HI) was markedly greater in NCL MACE than in no-MACE VH-TCFAs (HI: 0.43 ± 0.05 vs. 0.29 ± 0.03, respectively; p = 0.01). Inclusion of PSS in plaque assessment improved the identification of NCLs that led to MACE, including in VH-TCFAs (p = 0.03) and plaques with MLA ≤4 mm (p = 0.03). Incorporation of an HI further improved the ability of PSS to identify MACE NCLs in a variety of plaque subtypes including VH-TCFA (p = 0.001) and plaques with MLA ≤4 mm (p = 0.002).
Conclusions
PSS and variations in PSS are increased in the peri-MLA regions of plaques that lead to MACE. Moreover, longitudinal heterogeneity in PSS is markedly increased in MACE plaques, especially VH-TCFAs, potentially predisposing to plaque rupture. Incorporation of PSS and heterogeneity in PSS may improve the ability of IVUS to predict MACE.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print
Costopoulos C, Maehara A, Huang Y, Brown AJ, ... Stone GW, Bennett MR
JACC Cardiovasc Imaging: 10 Jul 2019; epub ahead of print | PMID: 31326476
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Abstract

Relative Contribution of Afterload and Interstitial Fibrosis to Myocardial Function in Severe Aortic Stenosis.

Slimani A, Melchior J, de Meester C, Pierard S, ... El Khoury G, Vanoverschelde JL
Objectives
The present study aimed at investigating the respective contribution of afterload and myocardial fibrosis to pre- and post-operative left ventricular (LV) function by using stress-strain relationships.
Background
Separating the effect of myocardial dysfunction and afterload on pump performance has important implications for the prognosis and management of patients with severe aortic stenosis (AS).
Methods
A total of 101 patients with isolated severe AS (57% men; mean age 71 years) and 75 healthy control subjects underwent resting 2-dimensional and speckle-tracking echocardiography to measure global circumferential strain (GCS) and global longitudinal strain (GLS), as well as end-systolic wall stress (ESWS). Normal stress-strain relationships were constructed using control subjects\' data and fitted to linear regression. End-systolic stress-strain indexes (the number of SDs from the mean regression line) were used as an afterload-independent index of myocardial function and compared with myocardial fibrosis, measured on transmural myocardial biopsies harvested at the time of surgery.
Results
GCS and GLS were afterload-dependent in both control subjects and patients. The GLS-ESWS relationship of patients was shifted downward compared with control subjects. Patients with reduced pre-operative end-systolic stress-strain indexes exhibited larger degrees of interstitial myocardial fibrosis than patients without (3.8 ± 2.9% vs. 8.3 ± 6.3%, p < 0.001; and 4.9 ± 4.4% vs. 9.5 ± 6.4%; p < 0.001, for GLS and GCS, respectively). By multivariate analysis, pre-operative end-systolic stress-strain indexes were the only predictors of post-operative longitudinal and circumferential end-systolic stress-strain indexes (ß = 0.49 and ß = 0.60, respectively; p < 0.001).
Conclusions
Myocardial strains are afterload-dependent. In patients with severe AS, pre-operative stress-strain indexes allow identification of patients with increased myocardial fibrosis and predict the extent of functional recovery after aortic valve replacement.

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

JACC Cardiovasc Imaging: 16 Jul 2019; epub ahead of print
Slimani A, Melchior J, de Meester C, Pierard S, ... El Khoury G, Vanoverschelde JL
JACC Cardiovasc Imaging: 16 Jul 2019; epub ahead of print | PMID: 31326472
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Impact:
Abstract

Controversies in Diagnostic Imaging of Patients With Suspected Stable and Acute Chest Pain Syndromes.

Shaw LJ, Blankstein R, Brown DL, Dhruva SS, ... Williams MC, Chandrasekhar Y

There has been a tremendous growth quantity of high-quality imaging evidence in the area of acute and stable ischemic heart disease (SIHD). A number of recent comparative effectiveness trials have spurned significant controversies in the field of cardiovascular imaging. The result of this evidence is that many health care policies and national guidelines have undergone significant revisions. With all of this evidence, many challenges remain and the optimal evaluation strategy for evaluation of patients presenting with chest pain remains ill-defined. This paper enlisted the guidance of numerous experts in the field of cardiovascular imaging to garner their perspective on available imaging research in chest pain syndromes. Each of these vignettes represent editorial perspectives and diverse opinions as to which, if any, should be the primary test in the evaluation of stable chest pain. These perspectives are not meant to be all inclusive but to highlight many of the commonly discussed controversies in the evaluation of chest pain symptoms. These perspectives are presented as a pre-amble to an upcoming American College of Cardiology/American Heart Association clinical practice guideline that is undergoing revision from the previous report published in 2012. The evidence has changed considerably since the 2012 SIHD guideline, and the current perspectives represent the diversity of available evidence as to the optimal imaging strategy for evaluation of the symptomatic patient.

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

JACC Cardiovasc Imaging: 29 Jun 2019; 12:1254-1278
Shaw LJ, Blankstein R, Brown DL, Dhruva SS, ... Williams MC, Chandrasekhar Y
JACC Cardiovasc Imaging: 29 Jun 2019; 12:1254-1278 | PMID: 31272608
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Impact:
Abstract

Focused Cardiac Ultrasonography.

Spencer KT, Flachskampf FA

Focused cardiac ultrasonography (FCU) is the use of ultrasonography as an adjunct to physical examination at the point of care. There are ample data supporting the fact that noncardiology trained users using small ultrasonography devices can assess left ventricular (LV) enlargement, LV systolic dysfunction, right ventricular (RV) enlargement, left atrial (LA) enlargement, LV hypertrophy, pericardial effusion, and right atrial (RA) pressure elevation more accurately than performing a physical examination. In addition, FCU-trained providers may have skills to perform ultrasonography imaging of body systems outside the heart to supplement their cardiac evaluation. FCU training, including didactic education, proctored imaging, independent imaging, and image interpretation, has been established by several specialties and medical schools. Cardiologists should embrace FCU in their facilities, as the clinical value to patient care is clear. Cardiologists have the responsibility to maintain excellence in the practice of echocardiography while enabling the use of ultrasonography by other medical professionals to augment their clinical assessments conventionally based on physical examination alone.

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

JACC Cardiovasc Imaging: 29 Jun 2019; 12:1243-1253
Spencer KT, Flachskampf FA
JACC Cardiovasc Imaging: 29 Jun 2019; 12:1243-1253 | PMID: 31272607
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Impact:
Abstract

The Role of Cardiac Imaging in the Diagnosis and Management of Anderson-Fabry Disease.

Perry R, Shah R, Saiedi M, Patil S, ... Linhart A, Selvanayagam JB

Anderson-Fabry disease (AFD) is a rare X-linked inherited metabolic disorder which results in a deficiency or absence of the enzyme α-galactosidase A, leading to the accumulation of glycosphingolipids in various cells and organs including the heart. Cardiac involvement is common and results in increased myocardial inflammation, left ventricular hypertrophy (LVH), and myocardial fibrosis. Echocardiography and cardiovascular magnetic resonance (CMR) offer distinctive and often complementary use to assist in the diagnosis and monitoring pharmacologic therapy in AFD, including detection of the AFD cardiac phenotype, differentiation from other forms of LVH, and patient selection for therapeutic intervention. Advanced cardiac imaging holds promise in subclinical detection of AFD-related abnormalities as well as disease staging and prognostication.

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Jun 2019; 12:1230-1242
Perry R, Shah R, Saiedi M, Patil S, ... Linhart A, Selvanayagam JB
JACC Cardiovasc Imaging: 29 Jun 2019; 12:1230-1242 | PMID: 31272606
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Impact:
Abstract

Application of Low Tube Potentials in CCTA: Results From the PROTECTION VI Study.

Stocker TJ, Leipsic J, Hadamitzky M, Chen MY, ... Massberg S, Hausleiter J
Objectives
The aim of this study was to assess the use of low tube potentials for coronary computed tomography angiography (CCTA) in worldwide clinical practice and its influence on radiation exposure, contrast agent volume, and image quality.
Background
CCTA is frequently used in clinical practice. Lowering of tube potential is a potent method to reduce radiation exposure and to economize contrast agent volume.
Methods
CCTAs of 4,006 patients from 61 international study sites were analyzed regarding very-low (≤80 kVp), low (90 to 100 kVp), conventional (110 to 120 kVp), and high (≥130 kVp) tube potentials. The impact on dose-length product (DLP) and contrast agent volume was analyzed. Image quality was determined by evaluation of the diagnostic applicability and assessment of the objective image parameters signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR).
Results
When compared with conventional tube potentials, low tube potentials were used in 56% of CCTAs (≤80 kVp: 9%; 90 to 100 kVp: 47%), which varied among sites from 0% to 100%. Tube potential reduction was associated with low-cardiovascular risk profile, low body mass index (BMI), and new-generation scanners. Median radiation exposure was lowered by 68% or 50% and median contrast agent volume by 25% or 13% for tube potential protocols of ≤80 kVp or 90 to 100 kVp when compared with conventional tube potentials, respectively (all p < 0.001). With the use of lower tube potentials, the frequency of diagnostic scans was maintained (p = 0.41), whereas SNR and CNR significantly improved (both p < 0.001). Considering BMI eligibility criteria, 58% (n = 946) of conventionally scanned patients would have been suitable for low tube potential protocols, and 44% (n = 831) of patients scanned with 90 to 100 kVp would have been eligible for very-low tube potential CCTA imaging of ≤80 kVp.
Conclusions
This large international registry confirms the feasibility of tube potential reduction in clinical practice leading to lower radiation exposure and lower contrast volumes. The current registry also demonstrates that this strategy is still underused in daily practice. PROspective multicenter registry on radiaTion dose Estimates of cardiac CT angIOgraphy iN daily practice in 2017 [PROTECTION-VI]; NCT02996903).

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

JACC Cardiovasc Imaging: 06 Jun 2019; epub ahead of print
Stocker TJ, Leipsic J, Hadamitzky M, Chen MY, ... Massberg S, Hausleiter J
JACC Cardiovasc Imaging: 06 Jun 2019; epub ahead of print | PMID: 31202772
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Impact:
Abstract

Prediction of Ventricular Arrhythmias With Left Ventricular Mechanical Dispersion: A Systematic Review and Meta-Analysis.

Kawakami H, Nerlekar N, Haugaa KH, Edvardsen T, Marwick TH
Objectives
The aim of this study was to assess the association between left ventricular mechanical dispersion (LVMD) and the incidence of ventricular arrhythmias (VAs).
Background
Recent, mainly single-center, studies have demonstrated that LVMD assessed using speckle tracking might be a powerful marker in risk stratification for VA. A systematic review and meta-analysis provides a means of understanding the prognostic value of this parameter, relative to other parameters, the most appropriate cutoff for designating risk.
Methods
A systemic review of studies reporting the predictive value of LVMD for VA was undertaken from a search of MEDLINE and Embase. VA events were defined as sudden cardiac death, cardiac arrest, documented ventricular tachyarrhythmia, and appropriate implantable cardioverter-defibrillator (ICD) therapy. Hazard ratios were extracted from univariate and multivariate models reporting on the association of LVMD and VA and described as pooled estimates with 95% confidence intervals. In a meta-analysis, the predictive value of LVMD was compared with that of left ventricular ejection fraction and global longitudinal strain.
Results
Among 3,198 patients in 12 published studies, 387 (12%) had VA events over follow-up ranging from 17 to 70 months. Patients with VAs had greater LVMD than those without (weighted mean difference -20.3 ms; 95% confidence interval: -27.3 to -13.2; p < 0.01). Each 10 ms increment of LVMD was significantly and independently associated with VA events (hazard ratio: 1.19; 95% confidence interval: 1.09 to 1.29; p < 0.01). The predictive value of LVMD was superior to that of left ventricular ejection fraction or global longitudinal strain.
Conclusions
LVMD assessed using speckle tracking provides important predictive value for VA in patients with a number of cardiac diseases and appears to have superior predictive value over left ventricular ejection fraction and global longitudinal strain for risk stratification.

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

JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print
Kawakami H, Nerlekar N, Haugaa KH, Edvardsen T, Marwick TH
JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print | PMID: 31202762
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Impact:
Abstract

Prognostic Value of Global Longitudinal Strain and Etiology After Surgery for Primary Mitral Regurgitation.

Hiemstra YL, Tomsic A, van Wijngaarden SE, Palmen M, ... Delgado V, Ajmone Marsan N
Objectives
This study sought to investigate whether left ventricular (LV) global longitudinal strain (GLS) is associated with long-term outcome after mitral valve (MV) surgery for primary mitral regurgitation (MR) and assess the differences in outcome according to MR etiology: Barlow\'s disease (BD), fibroelastic deficiency (FED), and forme fruste (FF).
Background
Appropriate timing of MV surgery for primary MR is still challenging and may differ according to the etiology. In these patients, LV-GLS has been proposed as more sensitive measure to detect subtle LV dysfunction as compared with LV ejection fraction.
Methods
Echocardiography was performed in 593 patients (64% men, age 65 ± 12 years) with severe primary MR who underwent MV surgery, including assessment of LV-GLS. The etiology (BD, FED, or FF) was defined based on surgical observation. During follow-up, primary endpoint was all-cause mortality and a secondary endpoint included cardiovascular death, heart failure hospitalizations, and cerebrovascular accidents.
Results
During a median follow-up of 6.4 (interquartile range: 3.6 to 10.4) years, 146 patients died (16 within 30 days after surgery), 46 patients were hospitalized for heart failure, and 13 patients had a cerebrovascular accident. Age (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.05 to 1.11; p < 0.001) and LV-GLS (HR: 1.13; 95% CI: 1.06 to 1.21; p < 0.001) were independently associated with all-cause mortality. Patients with LV-GLS >-20.6% (more impaired) showed significant worse survival than did patients with LV-GLS ≤-20.6%; of interest, patients with BD showed similar prognosis compared with FED and FF. In addition, previous atrial fibrillation (HR: 1.70; 95% CI: 1.01 to 2.86; p = 0.045) and LV-GLS (HR: 1.01; 95% CI: 1.01 to 1.15; p = 0.019) were independently associated with the secondary endpoint.
Conclusions
LV-GLS is independently associated with all-cause mortality and cardiovascular events after MV surgery for primary MR and might be helpful to guide surgical timing. Importantly, patients with BD showed similar prognosis when corrected for age, compared with patients with FED or FF.

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

JACC Cardiovasc Imaging: 11 Jun 2019; epub ahead of print
Hiemstra YL, Tomsic A, van Wijngaarden SE, Palmen M, ... Delgado V, Ajmone Marsan N
JACC Cardiovasc Imaging: 11 Jun 2019; epub ahead of print | PMID: 31202761
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Abstract

Prediction of Stroke Risk by Detection of Hemorrhage in Carotid Plaques: Meta-Analysis of Individual Patient Data.

Schindler A, Schinner R, Altaf N, Hosseini AA, ... Bonati LH, Saam T
Objectives
The goal of this study was to compare the risk of stroke between patients with carotid artery disease with and without the presence of intraplaque hemorrhage (IPH) on magnetic resonance imaging.
Background
IPH in carotid stenosis increases the risk of cerebrovascular events. Uncertainty remains whether risk of stroke alone is increased and whether stroke is predicted independently of known risk factors.
Methods
Data were pooled from 7 cohort studies including 560 patients with symptomatic carotid stenosis and 136 patients with asymptomatic carotid stenosis. Hazards of ipsilateral ischemic stroke (primary outcome) were compared between patients with and without IPH, adjusted for clinical risk factors.
Results
IPH was present in 51.6% of patients with symptomatic carotid stenosis and 29.4% of patients with asymptomatic carotid stenosis. During 1,121 observed person-years, 66 ipsilateral strokes occurred. Presence of IPH at baseline increased the risk of ipsilateral stroke both in symptomatic (hazard ratio [HR]: 10.2; 95% confidence interval [CI]: 4.6 to 22.5) and asymptomatic (HR: 7.9; 95% CI: 1.3 to 47.6) patients. Among patients with symptomatic carotid stenosis, annualized event rates of ipsilateral stroke in those with IPH versus those without IPH were 9.0% versus 0.7% (<50% stenosis), 18.1% versus 2.1% (50% to 69% stenosis), and 29.3% versus 1.5% (70% to 99% stenosis). Annualized event rates among patients with asymptomatic carotid stenosis were 5.4% in those with IPH versus 0.8% in those without IPH. Multivariate analysis identified IPH (HR: 11.0; 95% CI: 4.8 to 25.1) and severe degree of stenosis (HR: 3.3; 95% CI: 1.4 to 7.8) as independent predictors of ipsilateral stroke.
Conclusions
IPH is common in patients with symptomatic and asymptomatic carotid stenosis and is a stronger predictor of stroke than any known clinical risk factors. Magnetic resonance imaging might help identify patients with carotid disease who would benefit from revascularization.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print
Schindler A, Schinner R, Altaf N, Hosseini AA, ... Bonati LH, Saam T
JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print | PMID: 31202755
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Abstract

Value of Speckle Tracking-Based Deformation Analysis in Screening Relatives of Patients With Asymptomatic Dilated Cardiomyopathy.

Verdonschot JAJ, Merken JJ, Brunner-La Rocca HP, Hazebroek MR, ... Krapels IPC, Knackstedt C
Objectives
This study sought to investigate the prevalence of systolic dysfunction using global longitudinal strain (GLS) and its prognostic value in relatives of dilated cardiomyopathy (DCM) patients that had normal left ventricular ejection fraction (LVEF).
Background
DCM relatives are advised to undergo cardiac assessment including echocardiography, irrespective of the genetic status of the index patient. Even though LVEF is normal, the question remains whether this indicates absence of disease or simply normal cardiac volumes. GLS may provide additional information regarding (sub)clinical cardiac abnormalities and thus allow earlier disease detection.
Methods
A total of 251 DCM relatives and 251 control subjects with a normal LVEF (≥55%) were screened. Automated software measured the GLS on echocardiographic 2-, 3-, and 4-chamber views. The cutoff value for abnormal strain was >-21.5. Median follow-up was 40 months (interquartile range: 5 to 80 months). Primary outcome was the combination of death and cardiac hospitalization.
Results
A total of 120 relatives and 83 control subjects showed abnormal GLS (48% vs. 33%, respectively; p < 0.001). Abnormal GLS was independently associated with DCM relatives and cardiovascular risk factors, rather than genetic mutations. Subjects with abnormal GLS had more frequent cardiac hospitalizations and a higher mortality as compared with subjects with normal GLS (hazard ratio: 3.29; 95% confidence interval: 1.58 to 6.87; p = 0.001). Additionally, follow-up LVEF was measured in a subset of relatives, and it decreased significantly in those with abnormal as compared with normal GLS (p = 0.006).
Conclusions
Relatives of DCM patients had a significantly higher prevalence of systolic dysfunction detected by GLS despite normal LVEF compared with control subjects, independent of age, sex, comorbidities, and genotype. Abnormal GLS was associated with LVEF deterioration, cardiac hospitalization, and death.

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

JACC Cardiovasc Imaging: 11 Jun 2019; epub ahead of print
Verdonschot JAJ, Merken JJ, Brunner-La Rocca HP, Hazebroek MR, ... Krapels IPC, Knackstedt C
JACC Cardiovasc Imaging: 11 Jun 2019; epub ahead of print | PMID: 31202754
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Abstract

CMR in the Evaluation of Diastolic Dysfunction and Phenotyping of HFpEF: Current Role and Future Perspectives.

Chamsi-Pasha MA, Zhan Y, Debs D, Shah DJ

Heart failure with preserved ejection fraction presents a challenging diagnosis given a heterogeneous patient population and limited therapeutic options. Diastolic function assessment using echocardiography has been a cornerstone in the work-up and is as important as systolic functional assessment. There has been increased awareness to the potential utility of cardiac magnetic resonance (CMR) imaging over the past decade as a promising, radiation-free, robust imaging modality providing an unrestricted field of view and high-resolution images for global and regional functional assessment. CMR provides early markers for detecting myocardial disease using tissue characterization imaging, which might prove useful to improve diagnosis and management. Over the years, several studies have examined CMR-derived diastolic functional indices, including transmitral and pulmonary venous velocities, left ventricular and left atrial strain using myocardial tagging, and, more recently, feature tracking. The relevance of imaging-based diastolic function indices and their clinical application across different modalities is increasingly recognized.

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

JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print
Chamsi-Pasha MA, Zhan Y, Debs D, Shah DJ
JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print | PMID: 31202753
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Abstract

Prognostic Value of Initial Left Ventricular Remodeling in Patients With Reperfused STEMI.

Rodriguez-Palomares JF, Gavara J, Ferreira-González I, Valente F, ... Bodí V, García-Dorado D
Objectives
This study sought to establish the best definition of left ventricular adverse remodeling (LVAR) to predict outcomes and determine whether its assessment adds prognostic information to that obtained by early cardiac magnetic resonance (CMR).
Background
LVAR, usually defined as an increase in left ventricular end-diastolic volume (LVEDV) is the main cause of heart failure after an ST-segment elevated myocardial infarction; however, the role of assessment of LVAR in predicting cardiovascular events remains controversial.
Methods
Patients with ST-segment elevated myocardial infarction who received percutaneous coronary intervention within 6 h of symptom onset were included (n = 498). CMR was performed during hospitalization (6.2 ± 2.6 days) and after 6 months (6.1 ± 1.8 months). The optimal threshold values of the LVEDV increase and the LV ejection fraction decrease associated with the primary endpoint were ascertained. Primary outcome was a composite of cardiovascular mortality, hospitalization for heart failure, or ventricular arrhythmia.
Results
The study was completed by 374 patients. Forty-nine patients presented the primary endpoint during follow-up (72.9 ± 42.8 months). Values that maximized the ability to identify patients with and without outcomes were a relative rise in LVEDV of 15% (hazard ratio [HR]: 2.1; p = 0.007) and a relative fall in LV ejection fraction of 3% (HR: 2.5; p = 0.001). However, the predictive model (using C-statistic analysis) failed to demonstrate that direct observation of LVAR at 6 months adds information to data from early CMR in predicting outcomes (C-statistic: 0.723 vs. 0.795).
Conclusions
The definition of LVAR that best predicts adverse cardiovascular events should consider both the increase in LVEDV and the reduction in LV ejection fraction. However, assessment of LVAR does not improve information provided by the early CMR.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print
Rodriguez-Palomares JF, Gavara J, Ferreira-González I, Valente F, ... Bodí V, García-Dorado D
JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print | PMID: 31202752
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Abstract

Management of Asymptomatic Severe Aortic Stenosis: Evolving Concepts in Timing of Valve Replacement.

Lindman BR, Dweck MR, Lancellotti P, Généreux P, ... O\'Gara PT, Bonow RO

New insights into the pathophysiology and natural history of patients with aortic stenosis, coupled with advances in diagnostic imaging and the dramatic evolution of transcatheter aortic valve replacement, are fueling intense interest in the management of asymptomatic patients with severe aortic stenosis. An intervention that is less invasive than surgery could conceivably justify pre-emptive transcatheter aortic valve replacement in subsets of patients, rather than waiting for the emergence of early symptoms to trigger valve intervention. Clinical experience has shown that symptoms can be challenging to ascertain in many sedentary, deconditioned, and/or elderly patients. Evolving data based on imaging and biomarker evidence of adverse ventricular remodeling, hypertrophy, inflammation, or fibrosis may radically transform existing clinical decision paradigms. Clinical trials currently enrolling asymptomatic patients have the potential to change practice patterns and lower the threshold for intervention.

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

JACC Cardiovasc Imaging: 06 Jun 2019; epub ahead of print
Lindman BR, Dweck MR, Lancellotti P, Généreux P, ... O'Gara PT, Bonow RO
JACC Cardiovasc Imaging: 06 Jun 2019; epub ahead of print | PMID: 31202751
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Abstract

Utility of Multimodality Intravascular Imaging and the Local Hemodynamic Forces to Predict Atherosclerotic Disease Progression.

Bourantas CV, Räber L, Sakellarios A, Ueki Y, ... Karagiannis A, Windecker S
Objectives
This study sought to examine the utility of multimodality intravascular imaging and of the endothelial shear stress (ESS) distribution to predict atherosclerotic evolution.
Background
There is robust evidence that intravascular ultrasound (IVUS)-derived plaque characteristics and ESS distribution can predict, with however limited accuracy, atherosclerotic evolution; nevertheless, it is yet unclear whether multimodality imaging and ESS mapping enable more accurate prediction of coronary plaque progression.
Methods
A total of 44 patients admitted with a myocardial infarction that had successful revascularization and 3-vessel IVUS and optical coherence tomography (OCT) imaging at baseline and 13-month follow-up were included in the study. The IVUS data acquired at baseline in the nonculprit vessels were fused with x-ray angiography to reconstruct coronary anatomy and in the obtained models blood flow simulation was performed and the ESS was estimated. The baseline plaque characteristics and ESS distribution were used to identify predictors of disease progression: defined as a lumen reduction and an increase in plaque burden at follow-up.
Results
Seventy-three vessels were included in the final analysis. Baseline ESS and the IVUS-derived but not the OCT-derived plaque characteristics were independently associated with a decrease in lumen area and an increase in plaque burden. Low ESS (odds ratio: 0.45; 95% confidence interval: 0.28 to 0.71; p < 0.001) and plaque burden (odds ratio: 0.73; 95% confidence interval: 0.54 to 0.97; p = 0.030) were the only independent predictors of disease progression at follow-up. The accuracy of the IVUS-derived plaque characteristics in predicting disease progression did not improve when ESS (AUC: 0.824 vs. 0.847; p = 0.127) or when OCT variables and ESS (AUC: 0.842; p = 0.611) were added into the model.
Conclusions
ESS and OCT-derived variables did not improve the efficacy of IVUS in predicting disease progression. Further research is required to investigate whether multimodality imaging combined with ESS mapping will allow more reliable vulnerable plaque detection. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416).

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

JACC Cardiovasc Imaging: 11 Jun 2019; epub ahead of print
Bourantas CV, Räber L, Sakellarios A, Ueki Y, ... Karagiannis A, Windecker S
JACC Cardiovasc Imaging: 11 Jun 2019; epub ahead of print | PMID: 31202749
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Abstract

Should We Test for Diastolic Dysfunction? How and How Often?

Litwin SE, Zile MR

Symptoms of heart failure (HF) are due in large part to elevation of left and/or right ventricular filling pressures. Although abnormal diastolic function is difficult to define, it contributes to the elevation of filling pressures. Tests that characterize aspects of diastolic function or structural changes associated with diastolic dysfunction, may help in establishing a diagnosis of HF, assessing prognosis, and guiding treatments. Individual echocardiographic parameters correlate weakly with LV (LV) filling pressures measured directly. However, a combination of multiple parameters improves accuracy for detection of elevated filling pressures. Serum natriuretic peptide levels are related to ventricular filling pressures and, when elevated, are a key diagnostic criterion for HF. Currently available evidence is not adequate to recommend serial echocardiographic studies or natriuretic peptide level measurements to assess changes in filling pressures or to guide HF therapy. Measurements of inferior vena cava size and dynamics have potential for identifying inadequate decongestion during episodes of acute decompensated HF but have not yet demonstrated utility in improving HF outcomes. Direct measurement of LV filling pressures using implanted pressure sensors is the only \"diastolic assessment\" thus far that has proven efficacy in reducing HF hospitalization rates.

Published by Elsevier Inc.

JACC Cardiovasc Imaging: 06 Jun 2019; epub ahead of print
Litwin SE, Zile MR
JACC Cardiovasc Imaging: 06 Jun 2019; epub ahead of print | PMID: 31202743
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Abstract

5-Year Prognostic Value of Quantitative Versus Visual MPI in Subtle Perfusion Defects: Results From REFINE SPECT.

Otaki Y, Betancur J, Sharir T, Hu LH, ... Berman DS, Slomka PJ
Objectives
This study compared the ability of automated myocardial perfusion imaging analysis to predict major adverse cardiac events (MACE) to that of visual analysis.
Background
Quantitative analysis has not been compared with clinical visual analysis in prognostic studies.
Methods
A total of 19,495 patients from the multicenter REFINE SPECT (REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT) study (64 ± 12 years of age, 56% males) undergoing stress Tc-99m-labeled single-photon emission computed tomography (SPECT) myocardial perfusion imaging were followed for 4.5 ± 1.7 years for MACE. Perfusion abnormalities were assessed visually and categorized as normal, probably normal, equivocal, or abnormal. Stress total perfusion deficit (TPD), quantified automatically, was categorized as TPD = 0%, TPD >0% to <1%, ≤1% to <3%, ≤3% to <5%, ≤5% to ≤10%, or TPD >10%. MACE consisted of death, nonfatal myocardial infarction, unstable angina, or late revascularization (>90 days). Kaplan-Meier and Cox proportional hazards analyses were performed to test the performance of visual and quantitative assessments in predicting MACE.
Results
During follow-up examinations, 2,760 (14.2%) MACE occurred. MACE rates increased with worsening of visual assessments, that is, the rate for normal MACE was 2.0%, 3.2% for probably normal, 4.2% for equivocal, and 7.4% for abnormal (all p < 0.001). MACE rates increased with increasing stress TPD from 1.3% for the TPD category of 0% to 7.8% for the TPD category of >10% (p < 0.0001). The adjusted hazard ratio (HR) for MACE increased even in equivocal assessment (HR: 1.56; 95% confidence interval [CI]: 1.37 to 1.78) and in the TPD category of ≤3% to <5% (HR: 1.74; 95% CI: 1.41 to 2.14; all p < 0.001). The rate of MACE in patients visually assessed as normal still increased from 1.3% (TPD = 0%) to 3.4% (TPD ≥5%) (p < 0.0001).
Conclusions
Quantitative analysis allows precise granular risk stratification in comparison to visual reading, even for cases with normal clinical reading.

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

JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print
Otaki Y, Betancur J, Sharir T, Hu LH, ... Berman DS, Slomka PJ
JACC Cardiovasc Imaging: 07 Jun 2019; epub ahead of print | PMID: 31202740
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Abstract

Vascular Positron Emission Tomography and Restenosis in Symptomatic Peripheral Arterial Disease: A Prospective Clinical Study.

Chowdhury MM, Tarkin JM, Albaghdadi MS, Evans NR, ... Rudd JHF, Coughlin PA
Objectives
This study determined whether in vivo positron emission tomography (PET) of arterial inflammation (F-fluorodeoxyglucose [F-FDG]) or microcalcification (F-sodium fluoride [F-NaF]) could predict restenosis following PTA.
Background
Restenosis following lower limb percutaneous transluminal angioplasty (PTA) is common, unpredictable, and challenging to treat. Currently, it is impossible to predict which patient will suffer from restenosis following angioplasty.
Methods
In this prospective observational cohort study, 50 patients with symptomatic peripheral arterial disease underwent F-FDG and F-NaF PET/computed tomography (CT) imaging of the superficial femoral artery before and 6 weeks after angioplasty. The primary outcome was arterial restenosis at 12 months.
Results
Forty subjects completed the study protocol with 14 patients (35%) reaching the primary outcome of restenosis. The baseline activities of femoral arterial inflammation (F-FDG tissue-to-background ratio [TBR] 2.43 [interquartile range (IQR): 2.29 to 2.61] vs. 1.63 [IQR: 1.52 to 1.78]; p < 0.001) and microcalcification (F-NaF TBR 2.61 [IQR: 2.50 to 2.77] vs. 1.69 [IQR: 1.54 to 1.77]; p < 0.001) were higher in patients who developed restenosis. The predictive value of both F-FDG (cut-off TBR value of 1.98) and F-NaF (cut-off TBR value of 2.11) uptake demonstrated excellent discrimination in predicting 1-year restenosis (Kaplan Meier estimator, log-rank p < 0.001).
Conclusions
Baseline and persistent femoral arterial inflammation and micro-calcification are associated with restenosis following lower limb PTA. For the first time, we describe a method of identifying complex metabolically active plaques and patients at risk of restenosis that has the potential to select patients for intervention and to serve as a biomarker to test novel interventions to prevent restenosis.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 11 Jun 2019; epub ahead of print
Chowdhury MM, Tarkin JM, Albaghdadi MS, Evans NR, ... Rudd JHF, Coughlin PA
JACC Cardiovasc Imaging: 11 Jun 2019; epub ahead of print | PMID: 31202739
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Abstract

The Association of Coronary Artery Calcification With Subsequent Incidence of Cardiovascular Disease in Type 1 Diabetes: The DCCT/EDIC Trials.

Budoff M, Backlund JC, Bluemke DA, Polak J, ... Lachin JM,
Objectives
This study sought to determine the relationship between coronary artery calcium (CAC) scores and subsequent cardiovascular disease (CVD) events in DCCT (Diabetes Control and Complications Trial)/EDIC (Epidemiology of Diabetes Interventions and Complications) participants.
Background
The CAC score has been validated for improved risk stratification in general populations; however, this association has not been well studied in type 1 diabetes (T1DM).
Methods
Computed tomography (CT) to measure CAC was performed in 1,205 DCCT/EDIC participants at a mean of 42.8 years of age during EDIC years 7 to 9, after the end of DCCT. This study analyzed the association between CAC and time to the first subsequent CVD event or to the first major adverse cardiac event (MACE), a follow-up of 10 to 13 years. CAC was categorized as: 0, >0 to 100, >100 to 300, or >300 Agatston units.
Results
Of 1,156 participants at risk for subsequent CVD, 105 had an initial CVD event (8.5 per 1,000 patient-years); and of 1,187 participants at risk for MACE, 51 had an initial MACE event (3.9 per 1,000 patient-years). Event rates among those with scores of zero (n = 817 [70.7%]) were very low for CVD (5.6 per 1,000 patient years). CAC scores >100 to 300 (hazard ratio [HR]: 4.17, 5.40) and >300 (HR: 6.06, 6.91) were associated with higher risks of CVD and MACE, respectively, compared to CAC of 0 (p < 0.0001). CAC scores >0 to 100 were nominally associated with CVD (HR: 1.71; p = 0.0415) but not with MACE (HR: 1.11; p = 0.8134). Similar results were observed when also adjusted for mean HbA and conventional CVD risk factors. The increment in the AUC due to CAC was modest.
Conclusions
CAC scores >100 Agatston units were significantly associated with an increased risk of the subsequent occurrence of CVD and MACE in DCCT/EDIC cohort. (Diabetes Control and Complications Trial [DCCT]; NCT00360815; Epidemiology of Diabetes Interventions and Complications [EDIC]; NCT00360893).

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

JACC Cardiovasc Imaging: 29 Jun 2019; 12:1341-1349
Budoff M, Backlund JC, Bluemke DA, Polak J, ... Lachin JM,
JACC Cardiovasc Imaging: 29 Jun 2019; 12:1341-1349 | PMID: 30878435
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Abstract

Multiparametric Cardiac Magnetic Resonance Imaging Can Detect Acute Cardiac Allograft Rejection After Heart Transplantation.

Dolan RS, Rahsepar AA, Blaisdell J, Suwa K, ... Carr JC, Markl M
Objectives
The purpose of this study was to evaluate the sensitivity of multiparametric cardiac magnetic resonance imaging (CMR) for the detection of acute cardiac allograft rejection (ACAR).
Background
ACAR is currently diagnosed by endomyocardial biopsy, but CMR may be a noninvasive alternative because of its capacity for regional myocardial structure and function characterization.
Methods
Fifty-eight transplant recipients (mean age 47.0 ± 14.7 years) and 14 control subjects (mean age 47.7 ± 16.7 years) were prospectively recruited from August 2014 to May 2017 and underwent 97 CMR studies (83 transplant recipients, 14 control subjects) for assessment of global left ventricular function and myocardial T2, T1, and extracellular volume fraction (ECV). CMR studies were divided into 4 groups on the basis of biopsy grade: control subjects (n = 14), patients with no ACAR (no history of ACAR; n = 36), patients with past ACAR (history of ACAR; n = 24), and ACAR+ patients (active grade ≥1R ACAR; n = 23).
Results
Myocardial T2 was significantly higher in patients with past ACAR compared with those with no ACAR (51.0 ± 3.8 ms vs. 49.2 ± 4.0 ms; p = 0.02) and in patients with no ACAR compared with control subjects (49.2 ± 4.0 ms vs. 45.2 ± 2.3 ms; p < 0.01). ACAR+ patients demonstrated increased T2 compared with the no ACAR group (52.4 ± 4.7 ms vs. 49.2 ± 4.0 ms, p < 0.01) but not compared with the past ACAR group. In contrast, ECV was significantly elevated in ACAR+ patients compared with transplant recipients without ACAR regardless of history of ACAR (no ACAR: 31.5 ± 3.9% vs. 26.8 ± 3.3% [p < 0.01]; past ACAR: 31.5 ± 3.9% vs. 26.8 ± 4.0% [p < 0.01]). Receiver operating characteristic curve analysis revealed that a combined model of age at CMR, global T2, and global ECV was predictive of ACAR (area under the curve = 0.84).
Conclusions
The combination of CMR-derived myocardial T2 and ECV has potential as a noninvasive tissue biomarker for ACAR. Larger studies during acute ACAR are needed for continued development of multiparametric CMR for transplant recipient surveillance.

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

JACC Cardiovasc Imaging: 30 Jul 2019; 12:1632-1641
Dolan RS, Rahsepar AA, Blaisdell J, Suwa K, ... Carr JC, Markl M
JACC Cardiovasc Imaging: 30 Jul 2019; 12:1632-1641 | PMID: 30878427
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Abstract

Native T Mapping in the Diagnosis of Cardiac Allograft Rejection: A Prospective Histologically Validated Study.

Imran M, Wang L, McCrohon J, Yu C, ... Macdonald P, Jabbour A
Objectives
This study aimed to determine the role of T mapping in identifying cardiac allograft rejection.
Background
Endomyocardial biopsy (EMBx), the current gold standard to diagnose cardiac allograft rejection, is associated with potentially serious complications. Cardiac magnetic resonance (CMR)-based T mapping detects interstitial edema and fibrosis, which are important markers of acute and chronic rejection. Therefore, T mapping can potentially diagnose cardiac allograft rejection noninvasively.
Methods
Patients underwent CMR within 24 h of EMBx. T maps were acquired at 1.5-T. EMBx-determined rejection was graded according to International Society of Heart and Lung Transplant (ISHLT) criteria.
Results
Of 112 biopsies with simultaneous CMR, 60 were classified as group 0 (ISHLT grade 0), 35 as group 1 (ISHLT grade 1R), and 17 as group 2 (2R, 3R, clinically diagnosed rejection, antibody-mediated rejection). Native T values in patients with grade 0 biopsies and left ventricular ejection fraction >60% (983 ± 42 ms; 95% confidence interval: 972 to 994 ms) were comparable to values in nontransplant healthy control subjects (974 ± 45 ms; 95% confidence interval: 962 to 987 ms). T values were significantly higher in group 2 (1,066 ± 78 ms) versus group 0 (984 ± 42 ms; p = 0.0001) and versus group 1 (1,001 ± 54 ms; p = 0.001). After excluding patients with an estimated glomerular filtration rate <50 ml/min/m, there was a moderate correlation of log-transformed native T with high-sensitivity troponin T (r = 0.54, p < 0.0001) and pro-B-type natriuretic peptide (r = 0.67, p < 0.0001). Using a T cutoff value of 1,029 ms, the sensitivity, specificity, and negative predictive value were 93%, 79%, and 99%, respectively.
Conclusions
Myocardial tissue characterization with T mapping displays excellent negative predictive capacity for the noninvasive detection of cardiac allograft rejection and holds promise to reduce substantially the EMBx requirement in cardiac transplant rejection surveillance.

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

JACC Cardiovasc Imaging: 30 Jul 2019; 12:1618-1628
Imran M, Wang L, McCrohon J, Yu C, ... Macdonald P, Jabbour A
JACC Cardiovasc Imaging: 30 Jul 2019; 12:1618-1628 | PMID: 30660547
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Impact:
Abstract

Microvascular Dysfunction in Dilated Cardiomyopathy: A Quantitative Stress Perfusion Cardiovascular Magnetic Resonance Study.

Gulati A, Ismail TF, Ali A, Hsu LY, ... Arai AE, Prasad SK
Objectives
This study sought to quantify myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) in dilated cardiomyopathy (DCM) and examine the relationship between myocardial perfusion and adverse left ventricular (LV) remodeling.
Background
Although regarded as a nonischemic condition, DCM has been associated with microvascular dysfunction, which is postulated to play a role in its pathogenesis. However, the relationship of the resulting perfusion abnormalities to myocardial fibrosis and the degree of LV remodeling is unclear.
Methods
A total of 65 patients and 35 healthy control subjects underwent adenosine (140 μg/kg/min) stress perfusion cardiovascular magnetic resonance with late gadolinium enhancement imaging. Stress and rest MBF and MPR were derived using a modified Fermi-constrained deconvolution algorithm.
Results
Patients had significantly higher global rest MBF compared with control subjects (1.73 ± 0.42 ml/g/min vs. 1.14 ± 0.42 ml/g/min; p < 0.001). In contrast, global stress MBF was significantly lower versus control subjects (3.07 ± 1.02 ml/g/min vs. 3.53 ± 0.79 ml/g/min; p = 0.02), resulting in impaired MPR in the DCM group (1.83 ± 0.58 vs. 3.50 ± 1.45; p < 0.001). Global stress MBF (2.70 ± 0.89 ml/g/min vs. 3.44 ± 1.03 ml/g/min; p = 0.017) and global MPR (1.67 ± 0.61 vs. 1.99 ± 0.50; p = 0.047) were significantly reduced in patients with DCM with LV ejection fraction ≤35% compared with those with LV ejection fraction >35%. Segments with fibrosis had lower rest MBF (mean difference: -0.12 ml/g/min; 95% confidence interval: -0.23 to -0.01 ml/g/min; p = 0.035) and lower stress MBF (mean difference: -0.15 ml/g/min; 95% confidence interval: -0.28 to -0.03 ml/g/min; p = 0.013).
Conclusions
Patients with DCM exhibit microvascular dysfunction, the severity of which is associated with the degree of LV impairment. However, rest MBF is elevated rather than reduced in DCM. If microvascular dysfunction contributes to the pathogenesis of DCM, then the underlying mechanism is more likely to involve stress-induced repetitive stunning rather than chronic myocardial hypoperfusion.

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Jul 2019; 12:1699-1708
Gulati A, Ismail TF, Ali A, Hsu LY, ... Arai AE, Prasad SK
JACC Cardiovasc Imaging: 30 Jul 2019; 12:1699-1708 | PMID: 30660522
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Impact:
Abstract

Selective Referral Using CCTA Versus Direct Referral for Individuals Referred to Invasive Coronary Angiography for Suspected CAD: A Randomized, Controlled, Open-Label Trial.

Chang HJ, Lin FY, Gebow D, An HY, ... Shaw LJ, Min JK
Objectives
This study compared the safety and diagnostic yield of a selective referral strategy using coronary computed tomographic angiography (CCTA) compared with a direct referral strategy using invasive coronary angiography (ICA) as the index procedure.
Background
Among patients presenting with signs and symptoms suggestive of coronary artery disease (CAD), a sizeable proportion who are referred to ICA do not have a significant, obstructive stenosis.
Methods
In a multinational, randomized clinical trial of patients referred to ICA for nonemergent indications, a selective referral strategy was compared with a direct referral strategy. The primary endpoint was noninferiority with a multiplicative margin of 1.33 of composite major adverse cardiovascular events (blindly adjudicated death, myocardial infarction, unstable angina, stroke, urgent and/or emergent coronary revascularization or cardiac hospitalization) at a median follow-up of 1-year.
Results
At 22 sites, 823 subjects were randomized to a selective referral and 808 to a direct referral strategy. At 1 year, selective referral met the noninferiority margin of 1.33 (p = 0.026) with a similar event rate between the randomized arms of the trial (4.6% vs. 4.6%; hazard ratio: 0.99; 95% confidence interval: 0.66 to 1.47). Following CCTA, only 23% of the selective referral arm went on to ICA, which was a rate lower than that of the direct referral strategy. Coronary revascularization occurred less often in the selective referral group compared with the direct referral to ICA (13% vs. 18%; p < 0.001). Rates of normal ICA were 24.6% in the selective referral arm compared with 61.1% in the direct referral arm of the trial (p < 0.001).
Conclusions
In stable patients with suspected CAD who are eligible for ICA, the comparable 1-year major adverse cardiovascular events rates following a selective referral and direct referral strategy suggests that both diagnostic approaches are similarly effective. In the selective referral strategy, the reduced use of ICA was associated with a greater diagnostic yield, which supported the usefulness of CCTA as an efficient and accurate method to guide decisions of ICA performance. (Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization [CONSERVE]; NCT01810198).

Published by Elsevier Inc.

JACC Cardiovasc Imaging: 29 Jun 2019; 12:1303-1312
Chang HJ, Lin FY, Gebow D, An HY, ... Shaw LJ, Min JK
JACC Cardiovasc Imaging: 29 Jun 2019; 12:1303-1312 | PMID: 30553687
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Abstract

Changes in Coronary Plaque Composition in Patients With Acute Myocardial Infarction Treated With High-Intensity Statin Therapy (IBIS-4): A Serial Optical Coherence Tomography Study.

Räber L, Koskinas KC, Yamaji K, Taniwaki M, ... Radu MD, Windecker S
Objectives
This study assessed changes in optical coherence tomography (OCT)-defined plaque composition in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin treatment.
Background
OCT is a high-resolution modality capable of measuring plaque characteristics including fibrous cap thickness (FCT) and macrophage infiltration. There is limited in vivo evidence regarding the effects of statins on OCT-defined coronary atheroma composition and no evidence in the context of STEMI.
Methods
In the IBIS-4 (Integrated Biomarker Imaging Study-4), 103 patients underwent intravascular ultrasonography and OCT of 2 noninfarct-related coronary arteries in the acute phase of STEMI. Patients were treated with high-dose rosuvastatin for 13 months. Serial OCT imaging was available in 153 arteries from 83 patients. We measured FCT by using a semi-automated method. Co-primary endpoints consisted of the change in minimum FCT (measured in fibroatheromas) and change in macrophage line arc.
Results
At 13 months, median low-density lipoprotein cholesterol had decreased from 128 mg/dl to 73.6 mg/dl. Minimum FCT, measured in 31 lesions from 27 patients, increased from 64.9 ± 19.9 μm to 87.9 ± 38.1 μm (p = 0.008). Macrophage line arc decreased from 9.6° ± 12.8° to 6.4° ± 9.6° (p < 0.0001). The secondary endpoint, mean lipid arc, decreased from 55.9° ± 37° to 43.5° ± 33.5°. In lesion-level analyses (n = 191), 9 of 13 thin-cap fibroatheromata (TCFAs) at baseline (69.2%) regressed to non-TCFA morphology, whereas 2 of 178 non-TCFA lesions (1.1%) progressed to TCFAs.
Conclusions
In this observational study, we found significant increase in minimum FCT, reduction in macrophage accumulation, and frequent regression of TCFAs to other plaque phenotypes in nonculprit lesions of patients with STEMI treated with high-intensity statin therapy.

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

JACC Cardiovasc Imaging: 30 Jul 2019; 12:1518-1528
Räber L, Koskinas KC, Yamaji K, Taniwaki M, ... Radu MD, Windecker S
JACC Cardiovasc Imaging: 30 Jul 2019; 12:1518-1528 | PMID: 30553686
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This program is still in alpha version.