Journal: JACC Cardiovasc Imaging

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Abstract

Cardiac Imaging in Carcinoid Heart Disease.

Baron T, Bergsten J, Albåge A, Lundin L, ... Öberg K, Flachskampf FA
Carcinoid disease is caused by neuroendocrine tumors, most often located in the gut, and leads in approximately 20% of cases to specific, severe heart disease, most prominently affecting right-sided valves. If cardiac disease occurs, it determines the patient\'s prognosis more than local growth of the tumor. Surgical treatment of carcinoid-induced valve disease has been found to improve survival in observational studies. Cardiac imaging is crucial for both diagnosis and management of carcinoid heart disease; in the past, imaging was accomplished largely by echocardiography, but more recently, imaging for carcinoid heart disease has increasingly become multimodal and warrants awareness of the particular diagnostic challenges of this disease. This paper reviews the pathophysiology and manifestations of carcinoid heart disease in light of the different imaging modalities.

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

JACC Cardiovasc Imaging: 08 Apr 2021; epub ahead of print
Baron T, Bergsten J, Albåge A, Lundin L, ... Öberg K, Flachskampf FA
JACC Cardiovasc Imaging: 08 Apr 2021; epub ahead of print | PMID: 33865761
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Abstract

Risk Stratification With the Use of Coronary Computed Tomographic Angiography in Patients With Nonobstructive Coronary Artery Disease.

Taron J, Foldyna B, Mayrhofer T, Osborne MT, ... Douglas PS, Hoffmann U
Objectives
The purpose of this study was to develop a risk prediction model for patients with nonobstructive CAD.
Background
Among stable chest pain patients, most cardiovascular (CV) events occur in those with nonobstructive coronary artery disease (CAD). Thus, developing tailored risk prediction approaches in this group of patients, including CV risk factors and CAD characteristics, is needed.
Methods
In Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) computed tomographic angiography patients, a core laboratory assessed prevalence of CAD (nonobstructive 1% to 49% left main or 1% to 69% stenosis any coronary artery), degree of stenosis (minimal: 1% to 29%; mild: 30% to 49%; or moderate: 50% to 69%), high-risk plaque (HRP) features (positive remodeling, low-attenuation plaque, and napkin-ring sign), segment involvement score (SIS), and coronary artery calcium (CAC). The primary end point was an adjudicated composite of unstable angina pectoris, nonfatal myocardial infarction, and death. Cox regression analysis determined independent predictors in nonobstructive CAD.
Results
Of 2,890 patients (age 61.7 years, 46% women) with any CAD, 90.4% (n = 2,614) had nonobstructive CAD (mean age 61.6 yrs, 46% women, atherosclerotic cardiovascular disease [ASCVD] risk 16.2%). Composite events were independently predicted by ASCVD risk (hazard ratio [HR]: 1.03; p = 0.001), degree of stenosis (30% to 69%; HR: 1.91; p = 0.011), and presence of ≥2 HRP features (HR: 2.40; p = 0.008). Addition of ≥2 HRP features to: 1) ASCVD and CAC; 2) ASCVD and SIS; or 3) ASCVD and degree of stenosis resulted in a statistically significant improvement in model fit (p = 0.0036; p = 0.0176; and p = 0.0318; respectively). Patients with ASCVD ≥7.5%, any HRP, and mild/moderate stenosis had significantly higher event rates than those who did not meet those criteria (3.0% vs. 6.2%; p = 0.007).
Conclusions
Advanced coronary plaque features have incremental value over total plaque burden for the discrimination of clinical events in low-risk stable chest pain patients with nonobstructive CAD. This may be a first step to improve prevention in this cohort with the highest absolute risk for CV events.

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

JACC Cardiovasc Imaging: 07 Apr 2021; epub ahead of print
Taron J, Foldyna B, Mayrhofer T, Osborne MT, ... Douglas PS, Hoffmann U
JACC Cardiovasc Imaging: 07 Apr 2021; epub ahead of print | PMID: 33865792
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Abstract

Are Training Programs Ready for the Rapid Adoption of CCTA?: CBME in CCTA.

Chow BJW, Yam Y, Alenazy A, Crean AM, ... Hossain A, Small GR
Objectives
This study sought to assess training volumes and its relationship to learning and identify potential new thresholds for determining expertise.
Background
Competency-based medical education (CBME) is being rapidly adopted and therefore training programs will need to adapt and identify new and novel methods of defining, measuring, and assessing clinical skills.
Methods
Consecutive cardiac computed tomography (CT) studies were interpreted independently by trainees and expert readers, and their interpretations (Agatston score, coronary artery disease severity, and Coronary Artery Disease Reporting and Data System) were collected. Kappa agreements were measured between trainees and experts for every 50 consecutive cases. Agreements between trainees and experts were tracked and compared with the agreement between expert readers.
Results
A total of 36 trainees interpreted 14,432 cardiac CT studies. Agreement between trainees and experts increased with CT case volumes, but trainees learned at different rates. Using a threshold for expertise, skill of measuring coronary calcification was achieved within 50 cases, but expertise for coronary CT angiography appeared to require a mean case volume of 750, comprising 400 abnormal cases.
Conclusions
Current volume-based training guidelines may be insufficient and higher case volumes may be required. We demonstrate that tracking cardiac CT learners is feasible and that CBME could be incorporated into CT training programs.

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Chow BJW, Yam Y, Alenazy A, Crean AM, ... Hossain A, Small GR
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865790
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Abstract

Myocardial Injury and Fibrosis From Acute Carbon Monoxide Poisoning: A Prospective Observational Study.

Cho DH, Ko SM, Son JW, Park EJ, Cha YS
Objectives
This study sought to evaluate the prevalence and patterns of late gadolinium enhancement (LGE) after carbon monoxide (CO) poisoning using cardiac magnetic resonance (CMR) imaging (CMRI) and transthoracic echocardiography (TTE).
Background
In acute CO poisoning, cardiac injury can predict mortality. However, it remains unclear why increased mortality and cardiovascular events occur despite normalization of CO-induced elevated troponin I (TnI) and cardiac dysfunction.
Methods
Patients with acute CO poisoning with elevated TnI were evaluated. CMRI was performed within 7 days of CO exposure and after 4 to 5 months. Patients were divided into LGE (n = 72; 69.2%) and no-LGE (n = 32; 30.8%) groups.
Results
In the LGE group, 39.4%, 4.8%, and 25.0% of patients exhibited midwall, subendocardial, and right ventricular insertion point injury, respectively. Diffuse injury was observed in 22.1% of patients, and 67.6% of the 37 patients who underwent follow-up CMRI showed no interval change. On TTE, baseline left ventricular ejection fraction and global longitudinal strain were significantly deteriorated in the LGE group; serial TTE within 7 days indicated that only left ventricular global longitudinal strain remained significantly deteriorated. Three cases of mortality occurred in the LGE group during the 1-year follow-up.
Conclusions
The LGE prevalence in patients with acute CO poisoning with elevated TnI levels, with no underlying cardiovascular diseases and eligible for CMRI, was 69.2%; this proportion primarily comprised patients with a midwall injury. Of the 37 patients who underwent follow-up CMRI, most chronic phase images showed no interval change. Myocardial fibrosis detected on CMR images was related to acute myocardial dysfunction and subacute deterioration of myocardial strain on TTE. (Cardiac Magnetic Resonance Image in Acute Carbon Monoxide Poisoning; NCT04419298).

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Cho DH, Ko SM, Son JW, Park EJ, Cha YS
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865788
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Abstract

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

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

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Schumann CL, Mathew RC, Dean JL, Yang Y, ... Kramer CM, Bourque JM
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865784
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Abstract

Early Comprehensive Cardiovascular Magnetic Resonance Imaging in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries.

Sörensson P, Ekenbäck C, Lundin M, Agewall S, ... Ugander M, Tornvall P
Objectives
The objective of the SMINC-2 (Stockholm Myocardial Infarction With Normal Coronaries 2) study was to determine if more than 70% of patients with myocardial infarction with nonobstructed coronary arteries (MINOCA), investigated early with comprehensive cardiovascular magnetic resonance (CMR), could receive a diagnosis entirely by imaging.
Background
The etiology of MINOCA is heterogeneous, including coronary, cardiac, and noncardiac causes. Patients with MINOCA, therefore, represent a diagnostic challenge where CMR is increasingly used.
Methods
The SMINC-2 study was a prospective study of 148 patients with MINOCA imaged with 1.5-T CMR with T1 and extracellular volume mapping early after hospital admission, compared to 150 patients with MINOCA imaged using 1.5-T CMR without mapping techniques from the SMINC-1 study as historic controls.
Results
CMR was performed at a median of 3 (SMINC-2) versus 12 (SMINC-1) days after hospital admission. In total, 77% of patients received a diagnosis with CMR imaging in the SMINC-2 study compared to 47% in the SMINC-1 study (p < 0.001). Compared to SMINC-1, CMR in SMINC-2 detected higher proportions of myocarditis (17% vs. 7%; p = 0.01) and takotsubo syndrome (35% vs. 19%; p = 0.002) but similar proportions of myocardial infarction (22% vs. 19%; p = 0.56) and other cardiomyopathies (3% vs. 2%; p = 0.46).
Conclusions
The results of the SMINC-2 study show that 77% of all patients with MINOCA received a diagnosis when imaged early with CMR, including advanced tissue characterization, which was a considerable improvement in comparison to the SMINC-1 study. This supports the use of early CMR imaging as a diagnostic tool in the investigation of patients with MINOCA. (Stockholm Myocardial Infarction With Normal Coronaries [SMINC]-2 Study on Diagnosis Made by Cardiac MRI [SCMINC-2]; NCT02318498).

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Sörensson P, Ekenbäck C, Lundin M, Agewall S, ... Ugander M, Tornvall P
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865778
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Abstract

Myocardial Fibrosis and Inflammation by CMR Predict Cardiovascular Outcome in People Living With HIV.

de Leuw P, Arendt CT, Haberl AE, Froadinadl D, ... Nagel E, Puntmann VO
Objectives
The goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART).
Background
PLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared with the noninfected population. The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood.
Methods
This prospective observational longitudinal study included consecutive PLWH on long-term HAART undergoing cardiac magnetic resonance (CMR) examination for assessment of myocardial volumes and function, T1 and T2 mapping, perfusion, and scar. Time-to-event analysis was performed from the index CMR examination to the first single event per patient. The primary endpoint was an adjudicated adverse cardiovascular event (cardiovascular mortality, nonfatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization).
Results
A total of 156 participants (62% male; age [median, interquartile range]: 50 years [42 to 57 years]) were included. During a median follow-up of 13 months (9 to 19 months), 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 nonfatal acute myocardial infarction, 1 appropriate device discharge, and 16 HF hospitalizations). Patients with events had higher native T1 (median [interquartile range]: 1,149 ms [1,115 to 1,163 ms] vs. 1,110 ms [1,075 to 1,138 ms]); native T2 (40 ms [38 to 41 ms] vs. 37 ms [36 to 39 ms]); left ventricular (LV) mass index (65 g/m2 [49 to 77 g/m2] vs. 57 g/m2 [49 to 64 g/m2]), and N-terminal pro-B-type natriuretic peptide (109 pg/l [25 to 337 pg/l] vs. 48 pg/l [23 to 82 pg/l]) (all p < 0.05). In multivariable analyses, native T1 was independently predictive of adverse events (chi-square test, 15.9; p < 0.001; native T1 [10 ms] hazard ratio [95% confidence interval]: 1.20 [1.08 to 1.33]; p = 0.001), followed by a model that also included LV mass (chi-square test, 17.1; p < 0.001). Traditional cardiovascular risk scores were not predictive of the adverse events.
Conclusions
Our findings reveal important prognostic associations of diffuse myocardial fibrosis and LV remodeling in PLWH. These results may support development of personalized approaches to screening and early intervention to reduce the burden of HF in PLWH (International T1 Multicenter Outcome Study; NCT03749343).

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
de Leuw P, Arendt CT, Haberl AE, Froadinadl D, ... Nagel E, Puntmann VO
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865770
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Abstract

Role of Cardiac CT in Pre-Procedure Planning for Transcatheter Mitral Valve Replacement.

Ge Y, Gupta S, Fentanes E, Aghayev A, ... Shah P, Blankstein R
Objectives
This study sought to evaluate cardiac computed tomography (CCT) findings and their clinical impact among patients being considered for transcatheter mitral valve replacement (TMVR).
Background
CCT is used to evaluate whether patients are candidates for TMVR, but limited data exist on the yield of such tests.
Methods
Patients referred for pre-procedural CCT for TMVR planning in the context of failing mitral bioprosthetic valves, annuloplasty rings, and severe native valve disease with annular calcification were included in this study. CCT findings were analyzed to evaluate for suitability for TMVR. In the subset of patients who underwent TMVR, echocardiographic and procedural characteristics were recorded.
Results
Among 80 patients who underwent pre-procedural CCT, the mean age was 71.8 ± 11.4 years, 60% were women, and the mean Society of Thoracic Surgeon score was 9.4 ± 6.7. Most cases were referred for valve-in-native annular calcification planning (n = 43), followed by valve-in-valve (n = 29), and valve-in-ring procedures (n = 8). A total of 51 (64%) patients did not undergo TMVR, 37 of whom had high-risk features identified on CCT. The most common reason for exclusion was related to large annular size, followed by heightened risk of left ventricular outflow tract (LVOT) obstruction. Among 29 patients (36%) who underwent TMVR, the 30-day mortality rate was 17%. Five patients experienced LVOT obstruction, 4 of whom were predicted by CCT. Following TMVR, 5 patients had at least moderate peri-valvular regurgitation.
Conclusions
A minority of patients referred for TMVR planning ultimately undergo the procedure. CCT identifies unsuitable anatomy and leads to exclusion in a significant number of cases.

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Ge Y, Gupta S, Fentanes E, Aghayev A, ... Shah P, Blankstein R
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865768
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Abstract

A Strain-Based Staging Classification of Left Bundle Branch Block-Induced Cardiac Remodeling.

Calle S, Kamoen V, De Buyzere M, De Pooter J, Timmermans F
Objectives
This study speculated that longitudinal strain curves in left bundle branch block (LBBB) could be shaped by the degree of LBBB-induced cardiac remodeling.
Background
LBBB independently affects left ventricular (LV) structure and function, but large individual variability may exist in LBBB-induced adverse remodeling.
Methods
Consecutive patients with LBBB with septal flash (LBBB-SF) underwent thorough echocardiographic assessment, including speckle tracking-based strain analysis. Four major septal longitudinal strain patterns (LBBB-1 through LBBB-4) were discerned and staged on the basis of: 1) correlation analysis with echocardiographic indexes of cardiac remodeling, including the extent of SF; 2) strain pattern analysis in cardiac resynchronization therapy (CRT) super-responders; and 3) strain pattern analysis in patients with acute procedural-induced LBBB.
Results
The study enrolled 237 patients with LBBB-SF (mean age: 67 ± 13 years; 57% men). LBBB-1 was observed in 60 (26%), LBBB-2 in 118 (50%), LBBB-3 in 29 (12%), and LBBB-4 in 26 (11%) patients. Patients at higher LBBB stages had larger end-diastolic volumes, lower LV ejection fractions, longer QRS duration, increased mechanical dyssynchrony, and more prominent SF compared with less advanced stages (p < 0.001 for all). Among CRT super-responders (n = 30; mean age: 63 ± 10 years), an inverse transition from stages LBBB-3 and -4 (pre-implant) to stages LBBB-1 and -2 (pace-off, median follow-up of 66 months [interquartile range: 32 to 78 months]) was observed (p < 0.001). Patients with acute LBBB (n = 27; mean age: 83 ± 5.1 years) only presented with a stage LBBB-1 (72%) or -2 pattern (24%).
Conclusions
The proposed classification suggests a pathophysiological continuum of LBBB-induced LV remodeling and may be valuable to assess the attribution of LBBB to the extent of LV remodeling and dysfunction.

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Calle S, Kamoen V, De Buyzere M, De Pooter J, Timmermans F
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865764
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Abstract

Prognostic Implication of RV Coupling to Pulmonary Circulation for Successful Weaning From Extracorporeal Membrane Oxygenation.

Kim D, Park Y, Choi KH, Park TK, ... Jeon ES, Yang JH
Objectives
The aim of this study was to explore if right ventricular (RV) contractile function and its coupling to pulmonary circulation (PC) were associated with successful weaning from venoarterial-extracorporeal membrane oxygenation (VA-ECMO) at maintenance of pump flow.
Background
Limited data are available on predictors of successful weaning from VA-ECMO. under full cardiac support of VA-ECMO.
Methods
A total of 79 patients with cardiogenic shock underwent transthoracic echocardiography to evaluate weaning from ECMO and were prospectively enrolled between 2016 and 2019. The noninvasively measured RV-PC coupling index was acquired by indexing tricuspid annular S\' velocity, tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and RV free-wall longitudinal strain (FWLS) to right ventricular systolic pressure (RVSP).
Results
Transthoracic echocardiography was performed at a median 3.0 days (range 1 to 6 days) after ECMO initiation at a median ECMO flow of 3.2 l/min (range 3.0 to 3.6 l/min). The RV-PC coupling matrix, tricuspid annular S\'/RVSP, TAPSE/RVSP, and RV FWLS/RVSP exhibited satisfactory predictive performances for predicting successful weaning from ECMO. Using the best cutoff values derived from the area under the receiver-operator characteristic curve, tricuspid annular S\'/RVSP demonstrated a significantly better predictive performance than conventional echocardiographic parameters (left ventricular ejection fraction >20%, left ventricular outflow tract time-velocity integral ≥10 cm, and mitral annular S\' ≥6 cm/s).
Conclusions
Echocardiographic RV-PC coupling metrics exhibited a significantly better performance for predicting successful weaning from VA ECMO compared with conventional echocardiographic criteria at maintenance of pump flow.

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Kim D, Park Y, Choi KH, Park TK, ... Jeon ES, Yang JH
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865793
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Abstract

Coronary Microvascular Dysfunction Assessed by Pressure Wire and CMR After STEMI Predicts Long-Term Outcomes.

Scarsini R, Shanmuganathan M, De Maria GL, Borlotti A, ... Banning AP, OxAMI Study Investigators
Objectives
This study sought to evaluate the long-term prognostic implications of coronary microvascular dysfunction (CMD) when assessed with both cardiovascular magnetic resonance (CMR) and index of microcirculatory resistance (IMR) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).
Background
Post-ischemic CMD can be assessed using the pressure-wire based IMR and/or by the presence of microvascular obstruction (MVO) on CMR.
Methods
A total of 198 patients with STEMI underwent IMR and MVO assessment. Patients were classified as follows: Group 1, no significant CMD (low IMR [≤40 U] and no MVO); Group 2, CMD with either high IMR (>40 U) or MVO; Group 3, CMD with both IMR >40 U and MVO. The primary endpoint was the composite of all-cause mortality, diagnosis of new heart failure, cardiac arrest, sustained ventricular tachycardia/fibrillation, and cardioverter defibrillator implantation.
Results
CMD with both high IMR and MVO was present in 23.7% of the cases (Group 3) and CMD with either high IMR or MVO was observed in 40.9% of cases (Group 2). At a median follow-up of 40.1 months, the primary endpoint occurred in 34 (17%) cases. At 1 year of follow-up, Group 3 (hazard ratio [HR]: 12.6; 95% confidence interval [CI]: 1.6 to 100.6; p = 0.017) but not Group 2 (HR: 7.2; 95% CI: 0.9 to 57.9; p = 0.062) had worse clinical outcomes compared with those with no significant CMD in Group 1. However, in the long-term, patients in Group 2 (HR: 4.2; 95% CI: 1.4 to 12.5; p = 0.009) and those in Group 3 (HR: 5.2; 95% CI: 1.7 to 16.2; p = 0.004) showed similar adverse outcomes, mainly driven by the occurrence of heart failure.
Conclusions
Post-ischemic CMD predicts a more than 4-fold increase in long-term risk of adverse outcomes, mainly driven by the occurrence of heart failure. Defining CMD by either invasive IMR >40 U or by CMR-assessed MVO showed similar risk of adverse outcomes.

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Scarsini R, Shanmuganathan M, De Maria GL, Borlotti A, ... Banning AP, OxAMI Study Investigators
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865789
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Abstract

Clinical Validation of a 3-Dimensional Ultrafast Cardiac Magnetic Resonance Protocol Including Single Breath-Hold 3-Dimensional Sequences.

Gómez-Talavera S, Fernandez-Jimenez R, Fuster V, Nothnagel ND, ... Ibáñez B, Sánchez-González J
Objectives
This study sought to clinically validate a novel 3-dimensional (3D) ultrafast cardiac magnetic resonance (CMR) protocol including cine (anatomy and function) and late gadolinium enhancement (LGE), each in a single breath-hold.
Background
CMR is the reference tool for cardiac imaging but is time-consuming.
Methods
A protocol comprising isotropic 3D cine (Enhanced sensitivity encoding [SENSE] by Static Outer volume Subtraction [ESSOS]) and isotropic 3D LGE sequences was compared with a standard cine+LGE protocol in a prospective study of 107 patients (age 58 ± 11 years; 24% female). Left ventricular (LV) mass, volumes, and LV and right ventricular (RV) ejection fraction (LVEF, RVEF) were assessed by 3D ESSOS and 2D cine CMR. LGE (% LV) was assessed using 3D and 2D sequences.
Results
Three-dimensional and LGE acquisitions lasted 24 and 22 s, respectively. Three-dimensional and LGE images were of good quality and allowed quantification in all cases. Mean LVEF by 3D and 2D CMR were 51 ± 12% and 52 ± 12%, respectively, with excellent intermethod agreement (intraclass correlation coefficient [ICC]: 0.96; 95% confidence interval [CI]: 0.94 to 0.97) and insignificant bias. Mean RVEF 3D and 2D CMR were 60.4 ± 5.4% and 59.7 ± 5.2%, respectively, with acceptable intermethod agreement (ICC: 0.73; 95% CI: 0.63 to 0.81) and insignificant bias. Both 2D and 3D LGE showed excellent agreement, and intraobserver and interobserver agreement were excellent for 3D LGE.
Conclusions
ESSOS single breath-hold 3D CMR allows accurate assessment of heart anatomy and function. Combining ESSOS with 3D LGE allows complete cardiac examination in <1 min of acquisition time. This protocol expands the indication for CMR, reduces costs, and increases patient comfort.

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Gómez-Talavera S, Fernandez-Jimenez R, Fuster V, Nothnagel ND, ... Ibáñez B, Sánchez-González J
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865783
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Abstract

Sex-Specific Computed Tomography Coronary Plaque Characterization and Risk of Myocardial Infarction.

Williams MC, Kwiecinski J, Doris M, McElhinney P, ... Dweck MR, Dey D
Objectives
This study was designed to investigate whether coronary computed tomography angiography assessments of coronary plaque might explain differences in the prognosis of men and women presenting with chest pain.
Background
Important sex differences exist in coronary artery disease. Women presenting with chest pain have different risk factors, symptoms, prevalence of coronary artery disease and prognosis compared to men.
Methods
Within a multicenter randomized controlled trial, we explored sex differences in stenosis, adverse plaque characteristics (positive remodeling, low-attenuation plaque, spotty calcification, or napkin ring sign) and quantitative assessment of total, calcified, noncalcified and low-attenuation plaque burden.
Results
Of the 1,769 participants who underwent coronary computed tomography angiography, 772 (43%) were female. Women were more likely to have normal coronary arteries and less likely to have adverse plaque characteristics (p < 0.001 for all). They had lower total, calcified, noncalcified, and low-attenuation plaque burdens (p < 0.001 for all) and were less likely to have a low-attenuation plaque burden >4% (41% vs. 59%; p < 0.001). Over a median follow-up of 4.7 years, myocardial infarction (MI) occurred in 11 women (1.4%) and 30 men (3%). In those who had MI, women had similar total, noncalcified, and low-attenuation plaque burdens as men, but men had higher calcified plaque burden. Low-attenuation plaque burden predicted MI (hazard ratio: 1.60; 95% confidence interval: 1.10 to 2.34; p = 0.015), independent of calcium score, obstructive disease, cardiovascular risk score, and sex.
Conclusions
Women presenting with stable chest pain have less atherosclerotic plaque of all subtypes compared to men and a lower risk of subsequent MI. However, quantitative low-attenuation plaque is as strong a predictor of subsequent MI in women as in men. (Scottish Computed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Williams MC, Kwiecinski J, Doris M, McElhinney P, ... Dweck MR, Dey D
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865779
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Abstract

Hyperventilation/Breath-Hold Maneuver to Detect Myocardial Ischemia by Strain-Encoded CMR: Diagnostic Accuracy of a Needle-Free Stress Protocol.

Ochs MM, Kajzar I, Salatzki J, Ochs AT, ... Katus HA, Friedrich MG
Objectives
The purpose of this study was to evaluate the diagnostic accuracy of a fast, needle-free test for myocardial ischemia using fast Strain-ENCoded (fSENC) cardiovascular MR (CMR) after a hyperventilation/breath-hold maneuver (HVBH).
Background
Myocardial stress testing is one of the most frequent diagnostic tests performed. Recent data indicate that CMR first-pass perfusion outperforms other modalities. Its use, however, is limited by the need for both, a vasodilatory stress and the intravenous application of gadolinium. Both are associated with added cost, safety concerns, and patient inconvenience. The combination of 2 novel CMR approaches, fSENC, an ultrafast technique to visualize myocardial strain, and HVBH, a physiological vasodilator, may overcome these limitations.
Methods
Patients referred for CMR stress testing underwent an extended protocol to evaluate 3 different tests: 1) adenosine-perfusion; 2) adenosine-strain; and 3) HVBH-strain. Diagnostic accuracy was assessed using quantitative coronary angiography as reference.
Results
A total of 122 patients (age 66 ± 11years; 80% men) suspected of obstructive coronary artery disease were enrolled. All participants completed the protocol without significant adverse events. Adenosine-strain and HVBH-strain provided significantly better diagnostic accuracy than adenosine-perfusion, both on a patient level (adenosine-strain: sensitivity 82%, specificity 83%; HVBH-strain: sensitivity 81%, specificity 86% vs. adenosine-perfusion: sensitivity 67%, specificity 92%; p < 0.05) and territory level (adenosine-strain: sensitivity 67%, specificity 93%; HVBH-strain: sensitivity 63%, specificity 95% vs. adenosine-perfusion: sensitivity 49%, specificity 96%; p < 0.05). However, these differences in diagnostic accuracy disappear by excluding patients with history of coronary artery bypass graft or previous myocardial infarction. The response of longitudinal strain differs significantly between ischemic and nonischemic segments to adenosine (ΔLSischemic = 0.6 ± 5.4%, ΔLSnonischemic = -0.9 ± 2.7%; p < 0.05) and HVBH (ΔLSischemic = 1.3% ± 3.8%, ΔLSnonischemic = -0.3 ± 1.8%; p = 0.002). Test duration of HVBH-strain (t = 64 ± 2 s) was significantly shorter compared with adenosine-strain (t = 184 ± 59 s; p < 0.0001) and adenosine-perfusion (t = adenosine-perfusion: 172 ± 59 s; p < 0.0001).
Conclusions
HVBH-strain has a high diagnostic accuracy in detecting significant coronary artery stenosis. It is not only significantly faster than any other method but also neither requires contrast agents nor pharmacological stressors.

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Ochs MM, Kajzar I, Salatzki J, Ochs AT, ... Katus HA, Friedrich MG
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865775
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Abstract

Prognostic Value of Feature-Tracking Right Ventricular Longitudinal Strain in Severe Functional Tricuspid Regurgitation: A Multicenter Study.

Romano S, Dell\'atti D, Judd RM, Kim RJ, ... Hahn RT, Farzaneh-Far A
Objectives
This study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR) feature-tracking-derived right ventricular (RV) free wall longitudinal strain (RVFWLS) in a large multicenter population of patients with severe functional tricuspid regurgitation.
Background
Tricuspid regurgitation imposes a volume overload on the RV that can lead to progressive RV dilation and dysfunction. Overt RV dysfunction is associated with poor prognosis and increased operative risk. Abnormalities of myocardial strain may provide the earliest evidence of ventricular dysfunction. CMR feature-tracking techniques now allow assessment of strain from routine cine images, without specialized pulse sequences. Whether abnormalities of RV strain measured using CMR feature tracking have prognostic value in patients with tricuspid regurgitation is unknown.
Methods
Consecutive patients with severe functional tricuspid regurgitation undergoing CMR at 4 U.S. medical centers were included in this study. Feature-tracking RVFWLS was calculated from 4-chamber cine views. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between RVFWLS and death. The incremental prognostic value of RVFWLS was assessed in nested models.
Results
Of the 544 patients in this study, 128 died during a median follow-up of 6 years. By Kaplan-Meier analysis, patients with RVFWLS ≥median (-16%) had significantly reduced event-free survival compared with those with RVFWLS <median (log-rank p < 0.001). By Cox multivariable regression modeling, RVFWLS was associated with increased risk-of-death after adjustment for clinical and imaging risk factors, including RV size and ejection fraction (hazard ratio: 1.14 per %; p < 0.001). Addition of RVFWLS in this model resulted in significant improvement in the global chi-square (31 to 78; p < 0.001).
Conclusions
CMR feature-tracking-derived RVFWLS is an independent predictor of mortality in patients with severe functional tricuspid regurgitation, incremental to common clinical and imaging risk factors.

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

JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print
Romano S, Dell'atti D, Judd RM, Kim RJ, ... Hahn RT, Farzaneh-Far A
JACC Cardiovasc Imaging: 06 Apr 2021; epub ahead of print | PMID: 33865769
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Abstract

Regurgitant Volume/Left Ventricular End-Diastolic Volume Ratio: Prognostic Value in Patients With Secondary Mitral Regurgitation.

Namazi F, van der Bijl P, Fortuni F, Mertens BJA, ... Delgado V, Bax JJ
Objectives
The purpose of this study was to investigate the prognostic implications of the ratio of mitral regurgitant volume (RVol) to left ventricular (LV) end-diastolic volume (EDV) in patients with significant secondary mitral regurgitation (MR).
Background
Quantification of secondary MR remains challenging, and its severity can be over- or underestimated when using the proximal isovelocity surface area method, which does not take LV volume into account. This limitation can be addressed by normalizing mitral RVol to LVEDV.
Methods
A total of 379 patients (mean age 67 ± 11 years; 63% male) with significant (moderate and severe) secondary MR were divided into 2 groups according to the RVol/EDV ratio: RVol/EDV ≥20% (greater MR/smaller EDV) and <20% (smaller MR/larger EDV). The primary endpoint was all-cause mortality.
Results
During median (interquartile range) follow-up of 50 (26 to 94) months, 199 (52.5%) patients died. When considering patients receiving medical therapy only, patients with RVol/EDV ratio ≥20% tended to have higher mortality rates than those with RVol/EDV ratio <20% (5-year estimated rates 24.1% vs. 18.4%, respectively; p = 0.077). Conversely, when considering the entire follow-up period including mitral valve interventions, patients with a higher RVol/EDV ratio (≥20%) had lower rates of all-cause mortality compared with patients with RVol/EDV ratio <20% (5-year estimated rates 39.0% vs. 44.8%, respectively; p = 0.018). On multivariable analysis, higher RVol/EDV ratio (per 5% increment as a continuous variable) was independently associated with lower all-cause mortality (0.93; p = 0.023).
Conclusions
In patients with significant secondary MR treated medically, survival tended to be lower in those with a higher RVol/EDV ratio. Conversely, a higher RVol/EDV ratio was independently associated with reduced all-cause mortality. when mitral valve interventions were taken into consideration.

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:730-739
Namazi F, van der Bijl P, Fortuni F, Mertens BJA, ... Delgado V, Bax JJ
JACC Cardiovasc Imaging: 30 Mar 2021; 14:730-739 | PMID: 32828778
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Abstract

Impact of Proportionality of Secondary Mitral Regurgitation on Outcome After Transcatheter Mitral Valve Repair.

Orban M, Karam N, Lubos E, Kalbacher D, ... Hausleiter J, EuroSMR Investigators
Objectives
The purpose of this paper was to evaluate the impact of proportionality of secondary mitral regurgitation (SMR) in a large real-world registry of transcatheter edge-to-edge mitral valve repair (TMVr) BACKGROUND: Differences in the outcomes of recent randomized trials of TMVr for SMR may be explained by the proportionality of SMR severity to left ventricular (LV) volume.
Methods
The ratio of pre-procedural effective regurgitant orifice area (EROA) to LV end-diastolic volume (LVEDV) was retrospectively assessed in patients undergoing TMVr for severe SMR between 2008 and 2019 from the EuroSMR registry. A recently proposed SMR proportionality scheme was adapted to stratify patients according to EROA/LVEDV ratio in 3 groups: MR-dominant (MD), MR-LV-co-dominant (MLCD), and LV-dominant (LD). All-cause mortality was assessed as a primary outcome, secondary heart failure (HF) outcomes included hospitalization for HF (HHF), New York Heart Association (NYHA) functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-min-walk distance, quality of life and MR grade.
Results
A total of 1,016 patients with an EROA/LVEDV ratio were followed for 22 months after TMVr. MR was reduced to grade ≤2+ in 92%, 96%, and 94% of patients (for MD, MLCD, and LD, respectively; p = 0.18). After adjustment for covariates including age, sex, diabetes, kidney function, body surface area, LV ejection fraction, and procedural MR reduction (grade ≤2+), adjusted rates of 2-year mortality in MD patients did not differ from those for MLCD patients (17% vs. 18%, respectively), whereas it was higher in LD patients (23%; p = 0.02 for comparison vs. MD+MLCD). The adjusted first HHF rate differed between groups (44% in MD, 56% in MLCD, 29% in LD; p = 0.01) as did the adjusted time for first death or HHF rate (66% in MD, 82% in MLCD, 68% in LD; p = 0.02). Improvement of NYHA functional class was seen in all groups (p < 0.001). Values for 6-min-walk distances, quality of life and NT-proBNP improved in most patients.
Conclusions
MD and MLCD patients had a comparable, adjusted 2-year mortality rate after TMVr which was slightly better than that of LD patients. Patients treated with TMVr had symptomatic improvement regardless of EROA/LVEDV ratio.

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:715-725
Orban M, Karam N, Lubos E, Kalbacher D, ... Hausleiter J, EuroSMR Investigators
JACC Cardiovasc Imaging: 30 Mar 2021; 14:715-725 | PMID: 32861652
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Abstract

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

Messika-Zeitoun D, Iung B, Armoiry X, Trochu JN, ... Boutitie F, Obadia JF
Objectives
This study aimed to identify a subset of patients based on echocardiographic parameters who might have benefited from transcatheter correction using the MitraClip system in the MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial.
Background
It has been suggested that differences in the degree of mitral regurgitation (MR) and left ventricular (LV) remodeling may explain the conflicting results between the MITRA-FR and the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trials.
Methods
In a post hoc analysis, we evaluated the interaction between the intervention and subsets of patients defined based on MR severity (effective regurgitant orifice [ERO], regurgitant volume [RVOL] and regurgitant fraction [RF]), LV remodeling (end-diastolic and end-systolic diameters and volumes) and combination of these parameters with respect to the composite of death from any cause or unplanned hospitalization for heart failure at 24 months.
Results
We observed a neutral impact of the intervention in subsets with the highest MR degree (ERO ≥30 mm2, RVOL ≥45 ml or RF ≥50%) as in patients with milder MR degree. The same was seen in subsets with the milder LV remodeling using either diastolic or systolic diameters or volumes. When parameters of MR severity and LV remodeling were combined, there was still no benefit of the intervention including in the subset of patients with an ERO/end-diastolic volume ratio ≥ 0.15 despite similar ERO and LV end-diastolic volume compared with COAPT patients.
Conclusions
In the MITRA-FR trial, we could not identify a subset of patients defined based on the degree of the regurgitation, LV remodeling or on their combination, including those deemed as having disproportionate MR, that might have benefited from transcatheter correction using the MitraClip system. (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation [MITRA-FR]; NCT01920698).

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:742-752
Messika-Zeitoun D, Iung B, Armoiry X, Trochu JN, ... Boutitie F, Obadia JF
JACC Cardiovasc Imaging: 30 Mar 2021; 14:742-752 | PMID: 32950444
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Abstract

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

Hirasawa K, Namazi F, Milhorini Pio S, Vo NM, ... Bax JJ, Delgado V
Objectives
The purpose of this study was to determine whether the mitral valve (MV) total leaflet area (TLA)-to-mitral annular area (MAA) (TLA/MAA) ratio measured using 3-dimensional (3D) transesophageal echocardiography (TEE) was associated with residual mitral regurgitation (MR) after MitraClip implantation in patients with secondary MR.
Background
The factors influencing the results of MitraClip implantation for secondary MR are controversial. This study hypothesized that insufficient remodeling of the mitral leaflets relative to the annular dilation may be associated with significant MR after MitraClip implantation.
Methods
This study included patients with secondary MR treated with MitraClips. Using 3D TEE dataset, the TLA in diastole and MAA in systole were measured with dedicated software.
Results
In a total cohort of 119 patients (mean age 74 ± 9 years; 61% male), significant residual MR (≥2+) was present in 43 patients (36%). In patients with significant residual MR, MAA was greater than in patients without residual MR (10.7 ± 2.4 cm2 vs. 9.0 ± 2.1 cm2; p < 0.001) whereas no significant difference was observed in TLA (12.2 ± 2.6 cm2 vs. 12.0 ± 2.9 cm2; p = 0.836). TLA/MAA ratio was lower in patients with significant residual MR as compared to their counterparts (1.14 ± 0.15 vs. 1.34 ± 0.16; p < 0.001), suggesting insufficient leaflet remodeling relative to annular dilation. On receiver-operating characteristic curve analysis, the TLA/MAA ratio had better discriminative power to identify patients who will have significant residual MR compared to MAA alone (area under the curve [AUC]: 0.830 vs. 0.723; p = 0.049).
Conclusions
In patients with secondary MR, insufficient mitral leaflet remodeling relative to the annulus dilation, as reflected by a lower TLA/MAA ratio, is associated with significant residual MR after MitraClip implantation.

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:756-765
Hirasawa K, Namazi F, Milhorini Pio S, Vo NM, ... Bax JJ, Delgado V
JACC Cardiovasc Imaging: 30 Mar 2021; 14:756-765 | PMID: 33129743
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Abstract

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

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

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:854-866
Reid A, Ben Zekry S, Turaga M, Tarazi S, ... Blanke P, Leipsic J
JACC Cardiovasc Imaging: 30 Mar 2021; 14:854-866 | PMID: 33248959
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Abstract

Impact of Myocardial Scar on Prognostic Implication of Secondary Mitral Regurgitation in Heart Failure.

Tayal B, Debs D, Nabi F, Malahfji M, ... Kleiman N, Shah DJ
Objectives
The objective of the present study was to use cardiovascular magnetic resonance (CMR) to examine the natural history of secondary MR severity and the implication of left ventricular (LV) scar on its prognostic significance.
Background
There is a need for further understanding of the prognostic implication of secondary mitral regurgitation (MR) given the heterogeneous findings of the 2 recent randomized trials on percutaneous mitral intervention in patients with secondary MR.
Methods
Patients with heart failure were enrolled into a prospective observational registry between 2008 and 2019. Outcomes were a composite of all-cause death, heart transplantation, or LV assist device implantation at follow-up. CMR was used to quantify the mitral regurgitation volume and mitral regurgitation fraction (MRF) along with scar burden utilizing late gadolinium enhancement. Patients were categorized into 4 subgroups based on presence and tertiles of scar extent: no scar, limited scar (scar burden 1% to 4%), intermediate scar (scar burden 5% to 20%), and extensive scar (scar burden >20%).
Results
Among patients (n = 441) included in the study (age 59 ± 14 years, 43% with ischemic etiology), 85 (19%) experienced an adverse event. MRF ≥30% was associated with increased risk of events among the study group (hazard ratio: 1.74; 95% confidence interval: 1.10 to 2.76; p = 0.02). When stratified by presence or absence of scar, MRF ≥30% was associated with events only among patients with scar (hazard ratio: 1.67; 95% confidence interval: 1.02 to 2.76; p = 0.04) but not among patients without scar. On further classification of patients with scar, the prognostic significance of secondary MR was observed primarily among patients with intermediate scar burden.
Conclusions
The natural history of secondary MR is complex, and outcomes are affected by severity of MR and vary depending upon the extent of scar. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823).

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:812-822
Tayal B, Debs D, Nabi F, Malahfji M, ... Kleiman N, Shah DJ
JACC Cardiovasc Imaging: 30 Mar 2021; 14:812-822 | PMID: 33341417
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Abstract

Basic Principles of the Echocardiographic Evaluation of Mitral Regurgitation.

Grayburn PA, Thomas JD
Mitral regurgitation (MR) is a common form of valvular heart disease that is associated with significant morbidity and mortality. Treatment decisions are completely dependent on accurate diagnosis of both mechanism and severity of MR, which can be challenging and is often done incorrectly. Transthoracic echocardiography is the most commonly used imaging test for MR; transesophageal echocardiography is often needed to better define morphology and MR severity, and is essential for guiding transcatheter therapies for MR. Multidetector computed tomography has become the standard to assess whether transcatheter valve replacement is an option because of its ability to assess valve sizing, access, and potential left ventricular outflow tract obstruction. Finally, cine cardiac magnetic resonance has been recommended by recent guidelines to quantify MR severity when the distinction between moderate and severe MR is indeterminate by echocardiography. This paper focuses on the main questions to be answered by imaging techniques and illustrates some common tips, tricks, and pitfalls in the assessment of MR.

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:843-853
Grayburn PA, Thomas JD
JACC Cardiovasc Imaging: 30 Mar 2021; 14:843-853 | PMID: 33454273
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Impact:
Abstract

Importance of Myocardial Fibrosis in Functional Mitral Regurgitation: From Outcomes to Decision-Making.

Lopes BBC, Kwon DH, Shah DJ, Lesser JR, ... Sorajja P, Cavalcante JL
Functional mitral regurgitation (FMR) is a common and complex valve disease, in which severity and risk stratification is still a conundrum. Although risk increases with FMR severity, it is modulated by subjacent left ventricular (LV) disease. The extent of LV remodeling and dysfunction is traditionally evaluated by echocardiography, but a growing body of evidence shows that myocardial fibrosis (MF) assessment by cardiac magnetic resonance (CMR) may complement risk stratification and inform treatment decisions. This review summarizes the current knowledge on the comprehensive evaluation that CMR can provide for patients with FMR, in particular for the assessment of MF and its potential impact in clinical decision-making.

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:867-878
Lopes BBC, Kwon DH, Shah DJ, Lesser JR, ... Sorajja P, Cavalcante JL
JACC Cardiovasc Imaging: 30 Mar 2021; 14:867-878 | PMID: 33582069
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Abstract

Impact of Right Ventricular Dysfunction on Outcomes After Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

Karam N, Stolz L, Orban M, Deseive S, ... Lurz P, Hausleiter J
Objectives
This study sought to assess the impact of right ventricular dysfunction (RVD) as defined by impaired right ventricular-to-pulmonary artery (RV-PA) coupling, on survival after edge-to-edge transcatheter mitral valve repair (TMVR) for severe secondary mitral regurgitation (SMR).
Background
Conflicting data exist regarding the benefit of TMVR in severe SMR. A possible explanation could be differences in RVD.
Methods
Using data from the EuroSMR (European Registry on Outcomes in Secondary Mitral Regurgitation) registry, this study compared the characteristics and outcomes of SMR patients undergoing TMVR, according to their RV-PA coupling, assessed by tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure (TAPSE/sPAP) ratio.
Results
Overall, 817 patients with severe SMR and available RV-PA coupling assessment underwent TMVR in the participating centers. RVD was present in 211 patients (25.8% with a TAPSE/sPAP ratio <0.274 mm/mm Hg). Although all patients demonstrated significant improvement in their New York Heart Association (NYHA) functional class, there was a trend toward a lower rate of NYHA functional class I or II among patients with RVD (56.5% vs. 65.5%, respectively; p = 0.086) after TMVR. Survival rates at 1 and 2 years were lower among patients with RVD (70.2% vs. 84.0%, respectively; p < 0.001; and 53.4% vs. 73.1%, respectively; p < 0.001). On multivariate analysis, a reduced TAPSE/sPAP ratio was a strong predictor of mortality (odds ratio: 1.62; 95% confidence interval: 1.14 to 2.31; p = 0.007).
Conclusions
RVD, as shown by impairment of RV-PA coupling, is a major predictor of adverse outcome in patients undergoing TMVR for severe SMR. The often neglected functional and anatomic RV parameters should be systematically assessed when planning TMVR procedures for patients with severe SMR.

Copyright © 2021. Published by Elsevier Inc.

JACC Cardiovasc Imaging: 30 Mar 2021; 14:768-778
Karam N, Stolz L, Orban M, Deseive S, ... Lurz P, Hausleiter J
JACC Cardiovasc Imaging: 30 Mar 2021; 14:768-778 | PMID: 33582067
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Impact:
Abstract

Ischemia-Mediated Dysfunction in Subpapillary Myocardium as a Marker of Functional Mitral Regurgitation.

Kochav JD, Kim J, Judd R, Kim HW, ... Kim R, Weinsaft JW
Objectives
The goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR.
Background
FMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain.
Methods
Vasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia.
Results
A total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p < 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p < 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p < 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p < 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia.
Conclusions
Ischemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:826-839
Kochav JD, Kim J, Judd R, Kim HW, ... Kim R, Weinsaft JW
JACC Cardiovasc Imaging: 30 Mar 2021; 14:826-839 | PMID: 33744130
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Impact:
Abstract

Severe Atrial Functional Mitral Regurgitation: Clinical and Echocardiographic Characteristics, Management and Outcomes.

Mesi O, Gad MM, Crane AD, Ramchand J, ... Kapadia SR, Harb SC
Objectives
This study was designed to compare the clinical and echocardiographic characteristics, management, and outcomes of severe atrial functional mitral regurgitation (AFMR) to primary mitral regurgitation (PMR).
Background
AFMR remains poorly defined clinically.
Methods
Consecutive patients who underwent transesophageal echocardiography at our institution between 2011 and 2018 for severe mitral regurgitation with preserved left ventricular function were screened. We excluded patients with endocarditis, any form of cardiomyopathy, or prior mitral intervention. The absence of leaflet pathology defined AFMR. Outcomes included death and heart failure hospitalizations.
Results
A total of 283 patients were included (AFMR = 14%, PMR = 86%). Compared to PMR, patients with AFMR had more comorbidities, including hypertension (94.9% vs. 76.2%; p = 0.015), diabetes mellitus (46.2% vs. 18.4%; p < 0.001), long-standing atrial fibrillation (28.2% vs. 13.1%; p = 0.015), prior nonmitral cardiac surgery (25.6% vs. 9.8%; p = 0.004), and pacemaker placement (33.3% vs. 13.5%; p = 0.002). They also had higher average E/e\' (median [interquartile range]:16.04 [13.1 to 22.46] vs. 14.1 [10.89 to 19]; p = 0.036) and worse longitudinal left atrial strain peak positive value (16.86 ± 12.15% vs. 23.67 ± 14.09%; p = 0.002) compared to PMR. During follow-up (median: 22 months), patients with AFMR had worse survival (log-rank p = 0.009) and more heart failure hospitalizations (log-rank p = 0.002). They were also less likely to undergo mitral valve intervention (59.0% vs. 83.6%; p = 0.001), although surgery was associated with improved survival (log-rank p = 0.021). On multivariable regression analysis, AFMR was independently associated with mortality [adjusted odds ratio: 2.61, 95% confidence interval: 1.17 to 5.83; p = 0.02].
Conclusions
AFMR constitutes an under-recognized high-risk group, with significant comorbidities, limited therapeutic options, and poor outcomes.

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:797-808
Mesi O, Gad MM, Crane AD, Ramchand J, ... Kapadia SR, Harb SC
JACC Cardiovasc Imaging: 30 Mar 2021; 14:797-808 | PMID: 33832663
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Impact:
Abstract

Mitral Valve Remodeling and Strain in Secondary Mitral Regurgitation: Comparison With Primary Regurgitation and Normal Valves.

El-Tallawi KC, Zhang P, Azencott R, He J, ... Lawrie GM, Zoghbi WA
Objectives
The aim of this study was to assess mitral valve (MV) remodeling and strain in patients with secondary mitral regurgitation (SMR) compared with primary MR (PMR) and normal valves.
Background
A paucity of data exists on MV strain during the cardiac cycle in humans. Real-time 3-dimensional (3D) echocardiography allows for dynamic MV imaging, enabling computerized modeling of MV function in normal and disease states.
Methods
Three-dimensional transesophageal echocardiography (TEE) was performed in a total of 106 subjects: 36 with SMR, 38 with PMR, and 32 with normal valves; MR severity was at least moderate in both MR groups. Valve geometric parameters were quantitated and patient-specific 3D MV models generated in systole using a dedicated software. Global and regional peak systolic MV strain was computed using a proprietary software.
Results
MV annular area was larger in both the SMR and PMR groups (12.7 ± 0.7 and 13.3 ± 0.7 cm2, respectively) compared with normal subjects (9.9 ± 0.3 cm2; p < 0.05). The leaflets also had significant remodeling, with total MV leaflet area larger in both SMR (16.2 ± 0.9 cm2) and PMR (15.6 ± 0.8 cm2) versus normal subjects (11.6 ± 0.4 cm2). Leaflets in SMR were thicker than those in normal subjects but slightly less than those with PMR posteriorly. Posterior leaflet strain was significantly higher than anterior leaflet strain in all 3 groups. Despite MV remodeling, strain in SMR (8.8 ± 0.3%) was overall similar to normal subjects (8.5 ± 0.2%), and both were lower than in PMR (12 ± 0.4%; p < 0.0001). Valve thickness, severity of MR, and primary etiology of MR were correlates of strain, with leaflet thickness being the multivariable parameter significantly associated with MV strain. In patients with less severe MR, anterior leaflet strain in SMR was lower than normal, whereas strain in PMR remained higher than normal.
Conclusions
The MV in secondary MR remodels significantly and similarly to PMR with a resultant larger annular area, leaflet surface area, and leaflet thickness compared with that of normal subjects. Despite these changes, MV strain remains close to or in some instances lower than normal and is significantly lower than that of PMR. Strain determination has the potential to improve characterization of MV mechano-biologic properties in humans and to evaluate its prognostic impact in patients with MR, with or without valve interventions.

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

JACC Cardiovasc Imaging: 30 Mar 2021; 14:782-793
El-Tallawi KC, Zhang P, Azencott R, He J, ... Lawrie GM, Zoghbi WA
JACC Cardiovasc Imaging: 30 Mar 2021; 14:782-793 | PMID: 33832661
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Impact:
Abstract

Myocardial Flow Reserve and Coronary Calcification in Prognosis of Patients With Suspected Coronary Artery Disease.

Aljizeeri A, Ahmed AI, Alfaris MA, Ahmed D, ... Alsaileek A, Al-Mallah MH
Objectives
The aim of this analysis is to examine the incremental prognostic value of coronary artery calcium (CAC) score and myocardial flow reserve (MFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI).
Background
Advances in cardiac PET and computed tomography imaging enabled the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD.
Methods
Consecutive patients who underwent PET MPI and CAC score calculation at King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia, between May 2011 and May 2018 were included in the study. MPI and CAC images were obtained in the same setting. The primary endpoint of the study was a composite of cardiac death and nonfatal myocardial infarction. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and MFR by sequentially adding the variables to a model that included clinical and PET variables.
Results
A total of 4,008 patients (mean age 59.7 ± 11.6 years, 55% women) were included in the analysis. Risk factors were prevalent (77.6% hypertension, 58.1% diabetes). In total, 35.9% of the cohort had CAC of 0, 16.5% had CAC ≥400, and 43.9% had MFR <2. Over a median follow up of 1.9 years, 130 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CAC and MFR score added incremental prognostic value over clinical and perfusion variables (base model: c-index 0.8137; Akaike information criterion [AIC]: 1,865.877; p = 0.0011; CAC model: c-index = 0.8330; AIC: 1,850.810; p = 0.045 vs. base model; MFR model: c-index = 0.8279; AIC: 1,859.235; p = 0.024). Combining CAC and MFR did not enhance risk prediction (c-index = 0.8435; AIC: 1,846.334; p = 0.074 vs. MFR model; p = 0.21 vs. CAC model.)
Conclusions:
In this large cohort of patients referred for PET MPI, both CAC and MFR independently added incremental prognostic value over clinical and MPI variables. Although combining both may have synergetic prognostic effect, this relation was not shown in multivariable model of this analysis.

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

JACC Cardiovasc Imaging: 10 Mar 2021; epub ahead of print
Aljizeeri A, Ahmed AI, Alfaris MA, Ahmed D, ... Alsaileek A, Al-Mallah MH
JACC Cardiovasc Imaging: 10 Mar 2021; epub ahead of print | PMID: 33744156
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Abstract

Computed Tomography-Derived 3D Modeling to Guide Sizing and Planning of Transcatheter Mitral Valve Interventions.

Ooms JF, Wang DD, Rajani R, Redwood S, ... O\'Neill W, Van Mieghem NM
A plethora of catheter-based strategies have been developed to treat mitral valve disease. Evolving 3-dimensional (3D) multidetector computed tomography (MDCT) technology can accurately reconstruct the mitral valve by means of 3-dimensional computational modeling (3DCM) to allow virtual implantation of catheter-based devices. 3D printing complements computational modeling and offers implanting physician teams the opportunity to evaluate devices in life-size replicas of patient-specific cardiac anatomy. MDCT-derived 3D computational and 3D-printed modeling provides unprecedented insights to facilitate hands-on procedural planning, device training, and retrospective procedural evaluation. This overview summarizes current concepts and provides insight into the application of MDCT-derived 3DCM and 3D printing for the planning of transcatheter mitral valve replacement and closure of paravalvular leaks. Additionally, future directions in the development of 3DCM will be discussed.

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

JACC Cardiovasc Imaging: 10 Mar 2021; epub ahead of print
Ooms JF, Wang DD, Rajani R, Redwood S, ... O'Neill W, Van Mieghem NM
JACC Cardiovasc Imaging: 10 Mar 2021; epub ahead of print | PMID: 33744155
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Abstract

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

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

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

JACC Cardiovasc Imaging: 10 Mar 2021; epub ahead of print
Yang LT, Boler A, Medina-Inojosa JR, Scott CG, ... Tribouilloy C, Michelena HI
JACC Cardiovasc Imaging: 10 Mar 2021; epub ahead of print | PMID: 33744153
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Impact:
Abstract

Tricuspid Annulus Disjunction: Novel Findings by Cardiac Magnetic Resonance in Patients With Mitral Annulus Disjunction.

Aabel EW, Chivulescu M, Dejgaard LA, Ribe M, ... Lie ØH, Haugaa KH
Objectives
This study aimed to assess whether patients with MAD also have disjunction of the tricuspid annulus.
Background
Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral annulus. Whether the disjunction extends to the right side of the heart is not known.
Methods
In a cohort of patients with MAD, we assessed the presence of tricuspid annulus disjunction (TAD) with the use of cardiac magnetic resonance. We explored the associations between TAD and MAD characteristics and the relationship to ventricular arrhythmias (nonsustained/sustained ventricular tachycardias and aborted cardiac arrest).
Results
We included 84 patients (mean age: 48 ± 16 years; 63% female). We observed TAD in 42 (50%). Patients with TAD were older (age 52 ± 16 years vs. 43 ± 15 years; p = 0.02), had greater circumferential extent of MAD (164 ± 57° vs. 115 ± 58°; p = 0.002), greater maximum longitudinal MAD distance (9.4 ± 2.9 mm vs. 6.2 ± 2.8 mm; p < 0.001), and more frequent mitral valve prolapse (39 patients [92%] vs. 24 patients [57%]; p < 0.001). Ventricular arrhythmias had occurred in 34 patients (41%), who were younger (age 39 ± 14 years vs. 54 ± 14 years; p < 0.001) and had lower prevalence of TAD (22 patients [29%] vs. 12 patients [52%]; p = 0.03). TAD was not associated with ventricular arrhythmias when adjusted for age (odds ratio adjusted for age: 0.54; 95% confidence interval: 0.20 to 1.45; p = 0.22).
Conclusions
We report for the first time the existence of right-sided annulus disjunction as a common finding in patients with MAD. TAD was associated with more severe left-sided annulus disjunction and mitral valve prolapse, but not with ventricular arrhythmias.

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

JACC Cardiovasc Imaging: 10 Mar 2021; epub ahead of print
Aabel EW, Chivulescu M, Dejgaard LA, Ribe M, ... Lie ØH, Haugaa KH
JACC Cardiovasc Imaging: 10 Mar 2021; epub ahead of print | PMID: 33744128
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Abstract

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

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

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

JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print
Sen J, Huynh Q, Stub D, Neil C, Marwick TH
JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print | PMID: 33744157
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Abstract

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

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

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

JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print
Tian F, Zhang L, Xie Y, Zhang Y, ... Li Y, Xie M
JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print | PMID: 33744147
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Impact:
Abstract

Prognostic Utility of Echocardiographic Atrial and Ventricular Strain Imaging in Patients With Cardiac Amyloidosis.

Huntjens PR, Zhang KW, Soyama Y, Karmpalioti M, Lenihan DJ, Gorcsan J
Objectives
The prognostic value of echocardiographic atrial and ventricular strain imaging in patients with biopsy-proven cardiac amyloidosis was assessed.
Background
Although left ventricular global longitudinal strain (GLS) is known to be predictive of outcome, the additive prognostic value of left (LA), right atrial (RA), and right ventricular (RV) strain is unclear.
Methods
One hundred thirty-six patients with cardiac amyloidosis and available follow-up data were studied by endomyocardial biopsy, noncardiac biopsy with supportive cardiac imaging, or autopsy confirmation. One hundred nine patients (80%) had light-chain, 23 (17%) had transthyretin, and 4 (3%) had amyloid A type cardiac amyloidosis. GLS, RV free wall strain, peak longitudinal LA strain, and peak longitudinal RA strain were measured from apical views. Clinical and routine echocardiographic data were compared. All-cause mortality was followed (median 5 years).
Results
Strain data were feasible for GLS in 127 (93%), LA strain in 119 (88%), RA strain in 117 (86%), and RV strain in 102 (75%). Strain values from all 4 chambers were significantly associated with survival. Hazard ratio (HR) and 95% confidence interval (CI) for low median strain values were as follows: GLS, HR: 2.3; 95% CI: 1.3 to 3.8 (p < 0.01); LA strain, HR: 7.5; 95% CI: 3.8 to 14.7 (p < 0.001); RA strain, HR: 3.5; 95% CI: 2.0 to 6.2 (p < 0.001); and RV free wall strain, HR: 2.8; 95% CI: 1.5 to 5.1 (p < 0.001). Peak longitudinal LA strain and RV strain remained independently associated with survival in multivariable analysis. Peak LA strain had the strongest association with survival (p < 0.001), and LA strain combined with GLS and RV free wall strain had the highest prognostic value (p < 0.001).
Conclusions
Strain data from all 4 chambers had important prognostic associations with survival in patients with biopsy-confirmed cardiac amyloidosis. Peak longitudinal LA strain was particularly associated with prognosis. Atrial and ventricular strain have promise for clinical utility.

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

JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print
Huntjens PR, Zhang KW, Soyama Y, Karmpalioti M, Lenihan DJ, Gorcsan J
JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print | PMID: 33744146
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Impact:
Abstract

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

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

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

JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print
Saijo Y, Isaza N, Conic JZ, Desai MY, ... Griffin BP, Popović ZB
JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print | PMID: 33744141
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Impact:
Abstract

Proposal for a Standard Echocardiographic Tricuspid Valve Nomenclature.

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

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

JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print
Hahn RT, Weckbach LT, Noack T, Hamid N, ... Hausleiter J, Nabauer M
JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print | PMID: 33744134
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Impact:
Abstract

Impaired Coronary Vasodilator Reserve and Adverse Prognosis in Patients With Systemic Inflammatory Disorders.

Weber BN, Stevens E, Perez-Chada LM, Brown JM, ... Liao K, Di Carli MF
Objectives
The purpose of this study was to evaluate the prognostic value of quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR), reflecting the integrated effects of diffuse atherosclerosis and microvascular dysfunction in patients with systemic inflammatory disorders.
Background
Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis (PsO) are common inflammatory conditions with excess cardiovascular (CV) risk compared to the general population. Systemic inflammation perturbs endothelial function and has been linked to coronary vasomotor dysfunction. However, the prognostic significance of this vascular dysfunction is not known.
Methods
This was a retrospective study of patients with RA, SLE, and PsO undergoing clinically indicated rest and stress myocardial perfusion positron emission tomography (PET). Patients with an abnormal myocardial perfusion study or left ventricular dysfunction were excluded. MFR was calculated as the ratio of myocardial blood flow (MBF, ml/min/g) at peak stress compared to that at rest.
Results
Among the 198 patients (median age: 65 years; 80% female), 20.7% had SLE, 31.8% had PsO, and 47.5% had RA. There were no differences in mean MFR between these conditions. Over a median follow-up of 7.8 years, there were 51 deaths and 63 major adverse cardiovascular events (MACE). Patients in the lowest tertile (MFR <1.65) had higher all-cause mortality than the highest tertile, which remained significant after adjusting for age, sex, and the pre-test clinical risk score (hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.05 to 5.4; p = 0.038). Similarly, compared to the highest MFR tertile, those in the lowest tertile had a lower MACE-free survival after adjusting for age, sex, and the pre-test clinical risk score (HR: 3.6; 95% CI: 1.7 to 7.6; p = 0.001).
Conclusions
In patients with systemic inflammatory disorders, impaired coronary vasodilator reserve was associated with worse cardiovascular outcomes and all-cause mortality.

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

JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print
Weber BN, Stevens E, Perez-Chada LM, Brown JM, ... Liao K, Di Carli MF
JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print | PMID: 33744132
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Impact:
Abstract

Deep Learning to Estimate Biological Age From Chest Radiographs.

Raghu VK, Weiss J, Hoffmann U, Aerts HJWL, Lu MT
Objectives
The goal of this study was to assess whether a deep learning estimate of age from a chest radiograph image (CXR-Age) can predict longevity beyond chronological age.
Background
Chronological age is an imperfect measure of longevity. Biological age, a measure of overall health, may improve personalized care. This paper proposes a new way to estimate biological age using a convolutional neural network that takes as input a CXR image and outputs a chest x-ray age (in years) as a measure of long-term mortality risk.
Methods
CXR-Age was developed using CXR from 116,035 individuals and validated in 2 held-out testing sets: 1) 75% of the CXR arm of PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) (N = 40,967); and 2) the CXR arm of NLST (National Lung Screening Trial) (N = 5,414). CXR-Age was compared to chronological age and a multivariable regression model of chronological age, risk factors, and radiograph findings to predict all-cause and cardiovascular mortality with a maximum 23 years and 13 years of follow-up, respectively. The primary outcome was observed mortality; results are provided for the testing datasets only.
Results
In the PLCO testing dataset, a 5-year increase in CXR-Age carried a higher risk of all-cause mortality than a 5-year increase in chronological age (CXR-Age hazard ratio [HR]: 2.26 [95% confidence interval (CI): 2.24 to 2.29] vs. chronological age HR: 1.77 [95% CI: 1.75 to 1.78]; p < 0.001). A similar pattern was found for cardiovascular mortality (CXR-Age cause-specific HR: 2.45 per 5 years [95% CI: 2.34 to 2.56] vs. chronological age HR: 1.82 per 5 years [95% CI: 1.74 to 1.90]). Similar results were seen for both outcomes in the NLST external testing dataset. Adding CXR-Age to the multivariable model resulted in significant improvements for predicting both outcomes in both testing datasets (p < 0.001 for all comparisons).
Conclusions
Based on a CXR image, CXR-Age predicted long-term all-cause and cardiovascular mortality.

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

JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print
Raghu VK, Weiss J, Hoffmann U, Aerts HJWL, Lu MT
JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print | PMID: 33744131
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Impact:
Abstract

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

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

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

JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print
El-Tallawi KC, Zhang P, Azencott R, He J, ... Lawrie GM, Zoghbi WA
JACC Cardiovasc Imaging: 09 Mar 2021; epub ahead of print | PMID: 33744129
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Abstract

Impact of Early Revascularization on Major Adverse Cardiovascular Events in Relation to Automatically Quantified Ischemia.

Azadani PN, Miller RJH, Sharir T, Diniz MA, ... Berman DS, Slomka PJ
Objectives
Using a contemporary, multicenter international single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) registry, this study characterized the potential major adverse cardiovascular event(s) (MACE) benefit of early revascularization based on automatic quantification of ischemia.
Background
Prior single-center data reported an association between moderate to severe ischemia SPECT-MPI and reduced cardiac death with early revascularization.
Methods
Consecutive patients from a multicenter, international registry who underwent 99mTc SPECT-MPI between 2009 and 2014 with solid-state scanners were included. Ischemia was quantified automatically as ischemic total perfusion deficit (TPD). Early revascularization was defined as within 90 days. The primary outcome was MACE (death, myocardial infarction, and unstable angina). A propensity score was developed to adjust for nonrandomization of revascularization; then, multivariable Cox modeling adjusted for propensity score and demographics was used to predict MACE.
Results
In total, 19,088 patients were included, with a mean follow-up of 4.7 ± 1.6 years, during which MACE occurred in 1,836 (9.6%) patients. There was a significant interaction between ischemic TPD modeled as a continuous variable and early revascularization (interaction p value: 0.012). In this model, there was a trend toward reduced MACE in patients with >5.4% ischemic TPD and a significant association with reduced MACE in patients with >10.2% ischemic TPD.
Conclusions
In this large, international, multicenter study reflecting contemporary cardiology practice, early revascularization of patients with >10.2% ischemia on SPECT-MPI, quantified automatically, was associated with reduced MACE.

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

JACC Cardiovasc Imaging: 27 Feb 2021; 14:644-653
Azadani PN, Miller RJH, Sharir T, Diniz MA, ... Berman DS, Slomka PJ
JACC Cardiovasc Imaging: 27 Feb 2021; 14:644-653 | PMID: 32828784
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Abstract

Worldwide Diagnostic Reference Levels for Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging: Findings From INCAPS.

Hirschfeld CB, Dondi M, Pascual TNB, Mercuri M, ... Einstein AJ, INCAPS Investigators Group
Objectives
This study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).
Background
Reference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset.
Methods
Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data.
Results
The aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m-labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions.
Conclusions
This study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs.

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

JACC Cardiovasc Imaging: 27 Feb 2021; 14:657-665
Hirschfeld CB, Dondi M, Pascual TNB, Mercuri M, ... Einstein AJ, INCAPS Investigators Group
JACC Cardiovasc Imaging: 27 Feb 2021; 14:657-665 | PMID: 32828783
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Abstract

Cardiac Imaging for Coronary Heart Disease Risk Stratification in Chronic Kidney Disease.

Dilsizian V, Gewirtz H, Marwick TH, Kwong RY, ... Al-Mallah MH, Herzog CA
Chronic kidney disease (CKD), defined as dysfunction of the glomerular filtration apparatus, is an independent risk factor for the development of coronary artery disease (CAD). Patients with CKD are at a substantially higher risk of cardiovascular mortality compared with the age- and sex-adjusted general population with normal kidney function. The risk of CAD and mortality in patients with CKD is correlated with the degree of renal dysfunction including presence of microalbuminuria. A greater cardiovascular risk, albeit lower than for patients receiving dialysis, persists even after kidney transplantation. Congestive heart failure, commonly caused by CAD, also accounts for a significant portion of the cardiovascular-related events observed in CKD. The optimal strategy for the evaluation of CAD in patients with CKD, particularly before renal transplantation, remains a topic of contention spanning over several decades. Although the evaluation of coexisting cardiac disease in patients with CKD is desirable, severe renal dysfunction limits the use of radiographic and magnetic resonance contrast agents due to concerns regarding contrast-induced nephropathy and nephrogenic systemic sclerosis, respectively. In addition, many patients with CKD have extensive and premature (often medial) calcification disproportionate to the severity of obstructive CAD, thereby limiting the diagnostic value of computed tomography angiography. As such, echocardiography, non-contrast-enhanced magnetic resonance, nuclear myocardial perfusion, and metabolic imaging offer a variety of approaches to assess obstructive CAD and cardiomyopathy of advanced CKD without the need for nephrotoxic contrast agents.

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

JACC Cardiovasc Imaging: 27 Feb 2021; 14:669-682
Dilsizian V, Gewirtz H, Marwick TH, Kwong RY, ... Al-Mallah MH, Herzog CA
JACC Cardiovasc Imaging: 27 Feb 2021; 14:669-682 | PMID: 32828780
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Abstract

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

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

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

JACC Cardiovasc Imaging: 27 Feb 2021; 14:615-625
Nakanishi R, Slomka PJ, Rios R, Betancur J, ... Budoff MJ, Berman DS
JACC Cardiovasc Imaging: 27 Feb 2021; 14:615-625 | PMID: 33129741
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Abstract

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

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

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

JACC Cardiovasc Imaging: 27 Feb 2021; 14:573-584
El-Tallawi KC, Kitkungvan D, Xu J, Cristini V, ... Zoghbi WA, Shah DJ
JACC Cardiovasc Imaging: 27 Feb 2021; 14:573-584 | PMID: 33129724
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Abstract

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

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

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

JACC Cardiovasc Imaging: 27 Feb 2021; 14:525-536
Slimani A, Roy C, de Meester C, Bouzin C, ... Gerber BL, Vanoverschelde JL
JACC Cardiovasc Imaging: 27 Feb 2021; 14:525-536 | PMID: 33221240
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Abstract

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

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

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

JACC Cardiovasc Imaging: 27 Feb 2021; 14:588-598
Dabbagh GS, Ghannam M, Siontis KC, Attili A, ... Morady F, Bogun F
JACC Cardiovasc Imaging: 27 Feb 2021; 14:588-598 | PMID: 33248970
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Impact:
Abstract

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

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

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

JACC Cardiovasc Imaging: 27 Feb 2021; 14:602-611
Zhou W, Lee JCY, Leung ST, Lai A, ... Pennell DJ, Ng MY
JACC Cardiovasc Imaging: 27 Feb 2021; 14:602-611 | PMID: 33248966
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Abstract

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

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

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

JACC Cardiovasc Imaging: 27 Feb 2021; 14:629-641
Yang S, Koo BK, Hoshino M, Lee JM, ... Kakuta T, Narula J
JACC Cardiovasc Imaging: 27 Feb 2021; 14:629-641 | PMID: 33248965
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Abstract

A Novel Assessment Using Projected Transmitral Gradient Improves Diagnostic Yield of Doppler Hemodynamics in Rheumatic and Calcific Mitral Stenosis.

Kato N, Pislaru SV, Padang R, Pislaru C, ... Nkomo VT, Pellikka PA
Objectives
The aims of this study were to: 1) develop a formula for projected transmitral gradient (TMG), expected gradient under normal heart rate (HR), and stroke volume (SV); and 2) assess the prognostic value of projected TMG.
Background
In mitral stenosis (MS), TMG is highly dependent on hemodynamics, often leading to discordance between TMG and mitral valve area.
Methods
All patients with suspected MS based on echocardiography from 2001 to 2017 were analyzed. Data were randomly split (2:1); projected TMG was modeled in the derivation cohort, then tested in the validation cohort. The composite endpoint was death or mitral valve intervention.
Results
Of 4,973 patients with suspected MS, severe and moderate MS, defined as mitral valve area ≤1.5 and >1.5 to 2.0 cm2, were present in 437 (9%) and 936 (19%), respectively. In the derivation cohort (n = 3,315; age 73 ± 12 years; 34% male), corresponding gradients were TMG ≥6 and 4 to <6 mm Hg, respectively, under normal hemodynamics. Based on the impact of hemodynamics on TMG, the formula was projected TMG = TMG - 0.07 (HR - 70) - 0.03 (SV - 97) in men and projected TMG = TMG - 0.08 (HR - 72) - 0.04 (SV - 84) in women. In the validation cohort (n = 1,658), projected TMG had better agreement with MS severity than TMG (kappa 0.61 vs. 0.28). Among 281 patients with TMG ≥6 mm Hg, projected TMG ≥6 mm Hg, present in 171 patients (61%), was associated with higher probability of the endpoint versus projected TMG <6 mm Hg (adjusted hazard ratio: 1.8; 95% confidence interval: 1.2 to 2.6; p < 0.01).
Conclusions
The novel concept of projected TMG, constructed using the observed impact of HR and SV on TMG, significantly improved the concordance of gradient and valve area in MS and provided better risk stratification than TMG.

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

JACC Cardiovasc Imaging: 27 Feb 2021; 14:559-570
Kato N, Pislaru SV, Padang R, Pislaru C, ... Nkomo VT, Pellikka PA
JACC Cardiovasc Imaging: 27 Feb 2021; 14:559-570 | PMID: 33582068
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Impact:
Abstract

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

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

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

JACC Cardiovasc Imaging: 02 Feb 2021; epub ahead of print
Kirkels FP, Lie ØH, Cramer MJ, Chivulescu M, ... Teske AJ, Haugaa KH
JACC Cardiovasc Imaging: 02 Feb 2021; epub ahead of print | PMID: 33582062
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Impact:

This program is still in alpha version.