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

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

T1 Mapping and Extracellular Volume Fraction in Dilated Cardiomyopathy: A Prognosis Study

ObjectivesThe aim of this study is to examine the prognostic value of T1 mapping and the extracellular volume (ECV) fraction in patients with dilated cardiomyopathy (DCM).BackgroundPatients with DCM with functional left ventricular remodeling have poorer prognoses. Noninvasive assessment of myocardial fibrosis using T1 mapping and the ECV fraction may improve risk stratification of patients with DCM; however, this has not yet been systematically evaluated.MethodsA total of 659 consecutive patients with DCM (498 men; 45 ± 15 years) who underwent cardiac magnetic resonance with T1 mapping and late gadolinium enhancement (LGE) imaging with a 1.5-T magnetic resonance scanner were enrolled in this study. Primary endpoints were cardiac-related death and heart transplantation. Secondary endpoints were hospitalization for heart failure, ventricular arrhythmias, and implantable cardioverter-defibrillator or cardiac resynchronization therapy implantation. Survival estimates were calculated by Kaplan-Meier curves with the log-rank test.ResultsDuring a mean follow-up of 66.3 ± 20.9 months, 122 and 205 patients with DCM reached the primary and secondary endpoints, respectively. The presence of LGE had an association with both of the primary and secondary endpoints observed in the patients with DCM (both P < 0.001). The maximum native T1 (HR: 1.04; 95% CI: 1.02-1.09) and maximum ECV fraction (HR: 1.14; 95% CI: 1.08-1.21) had associations with the primary endpoints in the patients with positive LGE (both P < 0.001), whereas the mean native T1 (HR: 1.13; 95% CI: 1.10-1.36) and mean ECV fraction (HR: 1.32; 95% CI: 1.12-1.53) had the best associations in the patients with negative LGE (all P < 0.001).ConclusionsT1 mapping and the ECV fraction had prognostic value in patients with DCM and were particularly important in patients with DCM without LGE. Using a combination of T1 mapping, ECV fraction, and LGE provided optimal risk stratification for patients with DCM.     

Feature Tracking Myocardial Strain Incrementally Improves Prognostication in Myocarditis Beyond Traditional CMR Imaging Features

ObjectivesThis study investigated the association of cardiovascular cardiac magnetic resonance (CMR) feature tracking (FT) with outcome in a patient cohort with myocarditis and evaluated the possible incremental prognostic benefit beyond clinical features and traditional CMR features.BackgroundCMR is used to diagnose and risk stratify patients with myocarditis. CMR-FT allows quantitative strain analysis of myocardial function; however, its prognostic benefit in myocarditis is unknown.MethodsConsecutive patients with clinically suspected myocarditis and presence of midmyocardial or epicardial late gadolinium enhancement (LGE) and/or myocardial edema in CMR were included. Clinical and CMR features were analyzed with regard to major adverse cardiovascular events (MACE) (i.e., hospitalization for heart failure, sustained ventricular tachycardia, and all-cause mortality).ResultsOf 740 patients with clinically suspected myocarditis, 455 (61%) met our final diagnostic criteria based on CMR tissue characterization. At a median follow-up of 3.9 years, MACE occurred in 74 (16%) patients. In the univariable analysis, CMR-FT global longitudinal peak strain (GLS) was significantly associated with MACE. In a multivariable model adjusting for clinical variables (age, sex, body mass index, and acuteness of symptoms) and traditional CMR features (left ventricular ejection fraction [LVEF] and LGE extent), GLS remained independently associated with outcome (GLS hazard ratio: 1.21; 95% confidence interval: 1.08 to 1.36; p = 0.001) and incrementally improved prognostication (chi-square increases from 42.6 to 79.8 to 88.5; p < 0.001).ConclusionsMyocardial strain using CMR-FT provides independent and incremental prognostic value over clinical features, LVEF, and LGE in patients with myocarditis. CMR-FT may serve as a novel marker to improve risk stratification in myocarditis. (CMR Features in Patients With Suspected Myocarditis [CMRMyo]; NCT03470571)     

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

ObjectivesThis 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.BackgroundCMR is the reference tool for cardiac imaging but is time-consuming.MethodsA 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.ResultsThree-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.ConclusionsESSOS 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.     

Cardiac Magnetic Resonance Assessment of Response to Cardiac Resynchronization Therapy and Programming Strategies

ObjectivesThe objective was to determine the feasibility and effectiveness of cardiac magnetic resonance (CMR) cine and strain imaging before and after cardiac resynchronization therapy (CRT) for assessment of response and the optimal resynchronization pacing strategy.BackgroundCMR with cardiac implantable electronic devices can safely provide high-quality right ventricular/left ventricular (LV) ejection fraction (RVEF/LVEF) assessments and strain.MethodsCMR with cine imaging, displacement encoding with stimulated echoes for the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) dyssynchrony parameter, and scar assessment was performed before and after CRT. Whereas the pre-CRT scan constituted a single “imaging set” with complete volumetric, strain, and scar imaging, multiple imaging sets with complete strain and volumetric data were obtained during the post-CRT scan for biventricular pacing (BIVP), LV pacing (LVP), and asynchronous atrial pacing modes by reprogramming the device outside the scanner between imaging sets.Results100 CMRs with a total of 162 imaging sets were performed in 50 patients (median age 70 years [IQR: 50-86 years]; 48% female). Reduction in LV end-diastolic volumes (P = 0.002) independent of CRT pacing were more prominent than corresponding reductions in right ventricular end-diastolic volumes (P = 0.16). A clear dependence of the optimal CRT pacing mode (BIVP vs LVP) on the PR interval (P = 0.0006) was demonstrated. The LVEF and RVEF improved more with BIVP than LVP with PR intervals ≥240 milliseconds (P = 0.025 and P = 0.002, respectively); the optimal mode (BIVP vs LVP) was variable with PR intervals <240 milliseconds. A lower pre-CRT displacement encoding with stimulated echoes (DENSE) CURE-SVD was associated with greater improvements in the post-CRT CURE-SVD (r = −0.69; P < 0.001), LV end-systolic volume (r = −0.58; P < 0.001), and LVEF (r = −0.52; P < 0.001).ConclusionsCMR evaluation with assessment of multiple pacing modes during a single scan after CRT is feasible and provides useful information for patient care with respect to response and the optimal pacing strategy.     

Diagnostic and Prognostic Value of Myocardial Work Indices for Identification of Cancer Therapy–Related Cardiotoxicity

BackgroundEchocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment–related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation.ObjectivesThis work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD.MethodsIn this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3 months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regression tree analysis was used to explore the combined use of GLS and MW for the diagnostic/prognostic assessment of CTRCD.ResultsBaseline left ventricular ejection fraction (LVEF) was 63.2 ± 4.0%. Thirty-seven (27.2%) patients developed CTRCD. An absolute change in GLS (standardized odds ratio [sOR]: 1.97 [95% CI: 1.07-3.66]; P = 0.031) and GWI (sOR: 1.73 [95% CI: 1.04-2.85]; P = 0.033) were associated with concurrent CTRCD. An absolute change in GLS (sOR: 1.79 [95% CI: 1.22-2.62]; P = 0.003), GWI (sOR: 1.67 [95% CI: 1.20-2.32]; P = 0.003), and GCW (sOR: 1.65 [95% CI: 1.17-2.34]; P = 0.005) were associated with subsequent CTRCD. Change in GWI and GCW demonstrated incremental value over GLS and clinical factors for the diagnosis of concurrent CTRCD. In a small group with a GLS change <3.3% (absolute), and a >21 mm Hg reduction in systolic blood pressure, worsening of GWI identified patients with higher probability of concurrent CTRCD (24.0% vs 5.2%). MWIs did not improve identification of subsequent CTRCD beyond knowledge of GLS change.ConclusionsGLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538)     

Prognostic Value of Stress CMR in Symptomatic Patients With Coronary Stenosis on CCTA

BackgroundNoninvasive functional imaging is often performed in patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA). However, the prognostic value of stress cardiac magnetic resonance (CMR) is unknown in patients with coronary stenosis of unknown significance on coronary CTA.ObjectivesThis study assessed the prognostic value of stress CMR in symptomatic patients with obstructive CAD of unknown significance on coronary CTA.MethodsBetween 2008 and 2020, consecutive symptomatic patients without known CAD referred for coronary CTA were screened. Patients with obstructive CAD (at least 1 ≥50% stenosis on coronary CTA) were further referred for stress CMR and followed for the occurrence of major adverse cardiovascular events (MACEs), defined as cardiovascular death or nonfatal myocardial infarction.ResultsOf 2,210 patients who completed CMR, 2,038 (46.5% men; mean age 69.8 ± 12.2 years) completed follow-up (median 6.8 years; IQR: 5.9-9.2 years); 281 experienced a MACE (13.8%). Inducible ischemia and late gadolinium enhancement (LGE) were significantly associated with MACEs (HR: 4.51 [95% CI: 3.55-5.74], and HR: 3.32 [95% CI: 2.55-4.32], respectively; P < 0.001). In multivariable Cox regression, the number of segments with >70% stenosis, with noncalcified plaques and the number of vessels with obstructive CAD were prognosticators (P < 0.001). The presence of inducible ischemia and LGE were independent predictors of MACEs (HR: 3.97 [95% CI: 3.43-5.13]; HR: 2.30 [95% CI: 1.52-3.33]; P < 0.001). After adjustment, stress CMR showed the best improvement in model discrimination and reclassification above traditional risk factors and coronary CTA (C-statistic improvement: 0.04; net reclassification improvement = 0.421; integrative discrimination index = 0.047).ConclusionsIn symptomatic patients with obstructive CAD of unknown significance on coronary CTA, stress CMR had incremental prognostic value to predict MACEs.     

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

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

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

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

Improving the Characterization of Stage A and B Heart Failure by Adding Global Longitudinal Strain

BackgroundCurrent guidelines distinguish stage B heart failure (SBHF) (asymptomatic left ventricular [LV] dysfunction) from stage A heart failure (SAHF) (asymptomatic with heart failure [HF] risk factors) on the basis of myocardial infarction, LV remodeling (hypertrophy or reduced ejection fraction [EF]) or valvular disease. However, subclinical HF with preserved EF may not be identified with these criteria.ObjectivesThe purpose of this study was to assess the prediction of incident HF with global longitudinal strain (GLS) in patients with SAHF and SBHF.MethodsThe authors analyzed echocardiograms (including GLS) in 447 patients (age 65 ± 11 years; 77% male) enrolled in a prospective study of HF in individuals at risk of incident HF, with normal or mildly impaired EF (≥40%). Long-term follow-up was obtained via data linkage. Analysis was performed using a competing risks model.ResultsAfter a median of 9 years of follow-up, 50 (10%) of the 447 patients had new HF admissions, and 87 (18%) died. In multivariable analysis, all imaging variables were independent predictors of HF admissions, including left ventricular ejection fraction (LVEF) (HR: 0.97 [95% CI: 0.94-0.99]), LV mass index (HR: 1.01 [95% CI: 1.00-1.02]), left atrial volume index (HR: 1.02 [95% CI: 1.00-1.05]), and E/e′ (HR: 1.05 [95% CI: 1.01-1.24]), incremental to clinical variables (age and Charlson comorbidity score). However, the addition of GLS provided value incremental to both clinical and other echocardiographic parameters (P = 0.004). Impaired GLS (<18%) (HR: 4.09 [95% CI: 1.87-8.92]) was independent and incremental to all clinical and other echocardiographic variables in predicting HF, and impaired LVEF, left ventricular hypertrophy, left atrial enlargement, high E/e′, or SBHF were not predictive.ConclusionsThe inclusion of GLS as a criterion for SBHF would add independent and incremental information to standard markers of SBHF for the prediction of subsequent HF admissions.     

3-Dimensional Strain Analysis of Hypertrophic Cardiomyopathy: Insights From the NHLBI International HCM Registry

BackgroundAbnormal global longitudinal strain (GLS) has been independently associated with adverse cardiac outcomes in both obstructive and nonobstructive hypertrophic cardiomyopathy.ObjectivesThe goal of this study was to understand predictors of abnormal GLS from baseline data from the National Heart, Lung, and Blood Institute (NHLBI) Hypertrophic Cardiomyopathy Registry (HCMR).MethodsThe study evaluated comprehensive 3-dimensional left ventricular myocardial strain from cine cardiac magnetic resonance in 2,311 patients from HCMR using in-house validated feature-tracking software. These data were correlated with other imaging markers, serum biomarkers, and demographic variables.ResultsAbnormal median GLS (> –11.0%) was associated with higher left ventricular (LV) mass index (93.8 ± 29.2 g/m² vs 75.1 ± 19.7 g/m²; P < 0.0001) and maximal wall thickness (21.7 ± 5.2 mm vs 19.3 ± 4.1 mm; P < 0.0001), lower left (62% ± 9% vs 66% ± 7%; P < 0.0001) and right (68% ± 11% vs 69% ± 10%; P < 0.01) ventricular ejection fractions, lower left atrial emptying functions (P < 0.0001 for all), and higher presence and myocardial extent of late gadolinium enhancement (6 SD and visual quantification; P < 0.0001 for both). Elastic net regression showed that adjusted predictors of GLS included female sex, Black race, history of syncope, presence of systolic anterior motion of the mitral valve, reverse curvature and apical morphologies, LV ejection fraction, LV mass index, and both presence/extent of late gadolinium enhancement and baseline N-terminal pro–B-type natriuretic peptide and troponin levels.ConclusionsAbnormal strain in hypertrophic cardiomyopathy is associated with other imaging and serum biomarkers of increased risk. Further follow-up of the HCMR cohort is needed to understand the independent relationship between LV strain and adverse cardiac outcomes in hypertrophic cardiomyopathy.     

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

ObjectivesThe prognostic value of echocardiographic atrial and ventricular strain imaging in patients with biopsy-proven cardiac amyloidosis was assessed.BackgroundAlthough 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.MethodsOne 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).ResultsStrain 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).ConclusionsStrain 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.     

Relation of Left Ventricular Diastolic Function to Global Fibrosis Burden: Implications for Heart Failure Risk Stratification

BackgroundLeft ventricular (LV) diastolic function is primarily assessed by means of echocardiography, which has limited utility in detecting fibrosis. Cardiac magnetic resonance (CMR) readily detects and quantifies fibrosis.ObjectivesIn this study, the authors sought to determine the association of LV diastolic function by echocardiography with CMR-determined global fibrosis burden and the incremental value of fibrosis with diastolic function grade in prediction of total mortality and heart failure hospitalizations.MethodsA total of 549 patients underwent comprehensive echocardiography and CMR within 30 days. Echocardiography was used to assess LV diastolic function, and CMR was used to determine LV volumes, mass, ejection fraction, replacement fibrosis, and percentage extracellular volume fraction (ECV).ResultsNormal diastolic function was present in 142 patients; the rest had diastolic dysfunction grades I to III, except for 18 (3.3%) with indeterminate results. The event rate was higher in patients with diastolic dysfunction compared with patients with normal diastolic function (33.4% vs 15.5; P < 0.001). The model including LV diastolic function grades II and III predicted composite outcome (C-statistic: 0.71; 95% CI: 0.67-0.76), which increased by adding global fibrosis burden (C-statistic: 0.74, 95% CI: 0.70-0.78; P = 0.02). For heart failure hospitalizations, the competing risk model with LV diastolic function grades II and III was good (C-statistic: 0.78; 95% CI: 0.74-0.83) and increased significantly with the addition of global fibrosis burden (C-statistic: 0.80; 95% CI: 0.76-0.85; P = 0.03).ConclusionsHigher grades of diastolic dysfunction are seen in patients with replacement fibrosis and increased ECV. Fibrosis burden as determined with the use of CMR provides incremental prognostic information to echocardiographic evaluation of LV diastolic function.     

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

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

Prognostic Value of Right Ventricular Function in Patients With Suspected Myocarditis Undergoing Cardiac Magnetic Resonance

BackgroundRisk-stratification of myocarditis is based on functional parameters and tissue characterization of the left ventricle (LV), whereas right ventricular (RV) involvement remains mostly unrecognized.ObjectivesIn this study, the authors sought to analyze the prognostic value of RV involvement in myocarditis by cardiac magnetic resonance (CMR).MethodsPatients meeting the recommended clinical criteria for suspected myocarditis were enrolled at 2 centers. Exclusion criteria were the evidence of coronary artery disease, pulmonary artery hypertension or structural cardiomyopathy. Biventricular ejection fraction, edema according to T2-weighted images, and late gadolinium enhancement (LGE) were linked to a composite end point of major adverse cardiovascular events (MACE), including heart failure hospitalization, ventricular arrhythmia, recurrent myocarditis, and death.ResultsAmong 1,125 consecutive patients, 736 (mean age: 47.8 ± 16.1 years) met the clinical diagnosis of suspected myocarditis and were followed for 3.7 years. Signs of RV involvement (abnormal right ventricular ejection fraction [RVEF], RV edema, and RV-LGE) were present in 188 (25.6%), 158 (21.5%), and 92 (12.5%) patients, respectively. MACE occurred in 122 patients (16.6%) and was univariably associated with left ventricular ejection fraction (LVEF), LV edema, LV-LGE, RV-LGE, RV edema, and RVEF. In a series of nesting multivariable Cox regression models, the addition of RVEF (HR_adj: 0.974 [95% CI: 0.956-0.993]; P = 0.006) improved prognostication (chi-square test = 89.5; P = 0.001 vs model 1; P = 0.006 vs model 2) compared with model 1 including only clinical variables (chi-square test = 28.54) and model 2 based on clinical parameters, LVEF, and LV-LGE extent (chi-square test = 78.93).ConclusionsThis study emphasizes the role of RV involvement in myocarditis and demonstrates the independent and incremental prognostic value of RVEF beyond clinical variables, CMR tissue characterization, and LV function. (Inflammatory Cardiomyopathy Bern Registry [FlamBER]; NCT04774549; CMR Features in Patients With Suspected Myocarditis [CMRMyo]; NCT03470571)     

Improved Risk Stratification for Ventricular Arrhythmias and Sudden Death in Patients With Nonischemic Dilated Cardiomyopathy

BackgroundRisk stratification for ventricular arrhythmias (VA) and sudden death in nonischemic dilated cardiomyopathy (DCM) remains suboptimal.ObjectivesThe goal of this study was to provide an improved risk stratification algorithm for VA and sudden death in DCM.MethodsThis was a retrospective cohort study of consecutive patients with DCM who underwent cardiac magnetic resonance with late gadolinium enhancement (LGE) at 2 tertiary referral centers. The combined arrhythmic endpoint included appropriate implantable cardioverter-defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, and sudden death.ResultsIn 1,165 patients with a median follow-up of 36 months, LGE was an independent and strong predictor of the arrhythmic endpoint (hazard ratio: 9.7; p < 0.001). This association was consistent across all strata of left ventricular ejection fraction (LVEF). Epicardial LGE, transmural LGE, and combined septal and free-wall LGE were all associated with heightened risk. A simple algorithm combining LGE and 3 LVEF strata (i.e., ≤20%, 21% to 35%, >35%) was significantly superior to LVEF with the 35% cutoff (Harrell’s C statistic: 0.8 vs. 0.69; area under the curve: 0.82 vs. 0.7; p < 0.001) and reclassified the arrhythmic risk of 34% of patients with DCM. LGE-negative patients with LVEF 21% to 35% had low risk (annual event rate 0.7%), whereas those with high-risk LGE distributions and LVEF >35% had significantly higher risk (annual event rate 3%; p = 0.007).ConclusionsIn a large cohort of patients with DCM, LGE was found to be a significant, consistent, and strong predictor of VA or sudden death. Specific high-risk LGE distributions were identified. A new clinical algorithm integrating LGE and LVEF significantly improved the risk stratification for VA and sudden death, with relevant implications for implantable cardioverter-defibrillator allocation.     

Prognostic Value of RV Abnormalities on CMR in Patients With Known or Suspected Cardiac Sarcoidosis

BackgroundLeft ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.ObjectivesThis study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.MethodsThis study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95% CIs were weighted and summarized.ResultsEight studies including a total of 899 patients with a mean follow-up duration of 3.2 ± 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95% CI: 1.7-5.5; P < 0.01) for composite events and 3.0 (95% CI: 1.3-7.0; P < 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95% CI: 2.4-9.6]; P < 0.01) and a higher risk for SCD (RR: 9.5 [95% CI: 4.4-20.5]; P < 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95% CI: 0.8-0.9), 69% (95% CI: 50%-84%), and 90% (95% CI: 70%-97%), respectively.ConclusionsIn patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.     

Long-Term Prognostic Value of Stress CMR in Patients With Heart Failure and Preserved Ejection Fraction

ObjectivesThe objectives of this study were to investigate the long-term prognostic value of inducible myocardial ischemia assessed by vasodilator stress cardiovascular magnetic resonance (CMR) in patients with HFpEF.BackgroundSome studies suggest that ischemia could play a key role in HF in patients with preserved ejection fraction (HFpEF).MethodsBetween 2008 and 2019, consecutive patients prospectively referred for stress CMR with HFpEF as defined by current guidelines, without known coronary artery disease (CAD), were followed for the occurrence of major adverse cardiovascular events (MACE), as defined by cardiovascular mortality or nonfatal myocardial infarction (MI). Secondary composite outcomes included cardiovascular mortality or hospitalization for acute HF. Cox regression analysis was performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR.ResultsAmong the 1,203 patients with HFpEF (73 ± 13 years of age; 29% males) who underwent stress CMR and completed follow-up (6.9 years interquartile range [IQR]: 6.7 to 7.7 years]), 108 experienced a MACE (9%). Kaplan-Meier analysis showed inducible ischemia and LGE were significantly associated with MACE (HR: 6.63; 95% confidence interval [CI]: 4.54 to 9.69; and HR: 2.56; 95% CI: 1.60 to 4.09, respectively; both p < 0.001) and secondary outcomes (HR: 8.40; 95% CI: 6.31 to 11.20; p < 0.001; and HR: 1.87; 95% CI: 1.27 to 2.76, respectively; p = 0.002). In multivariate analysis, inducible ischemia and LGE were independent predictors of MACE (HR: 6.10; 95% CI: 4.14 to 9.00; p < 0.001 and HR: 1.62; 95% CI: 1.06 to 2.49; p = 0.039; respectively).ConclusionsStress CMR-inducible myocardial ischemia and LGE have accurate discriminative long-term prognostic value in HFpEF patients without known CAD to predict the occurrence of MACE.     

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

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

Comprehensive Phenotypic Characterization of Late Gadolinium Enhancement Predicts Sudden Cardiac Death in Coronary Artery Disease

BackgroundLate gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) offers the potential to noninvasively characterize the phenotypic substrate for sudden cardiac death (SCD).ObjectivesThe authors assessed the utility of infarct characterization by CMR, including scar microstructure analysis, to predict SCD in patients with coronary artery disease (CAD).MethodsPatients with stable CAD were prospectively recruited into a CMR registry. LGE quantification of core infarction and the peri-infarct zone (PIZ) was performed alongside computational image analysis to extract morphologic and texture scar microstructure features. The primary outcome was SCD or aborted SCD.ResultsOf 437 patients (mean age: 64 years; mean left ventricular ejection fraction [LVEF]: 47%) followed for a median of 6.3 years, 49 patients (11.2%) experienced the primary outcome. On multivariable analysis, PIZ mass and core infarct mass were independently associated with the primary outcome (per gram: HR: 1.07 [95% CI: 1.02-1.12]; P = 0.002 and HR: 1.03 [95% CI: 1.01-1.05]; P = 0.01, respectively), and the addition of both parameters improved discrimination of the model (Harrell’s C-statistic: 0.64-0.79). PIZ mass, however, did not provide incremental prognostic value over core infarct mass based on Harrell’s C-statistic or risk reclassification analysis. Severely reduced LVEF did not predict the primary endpoint after adjustment for scar mass. On scar microstructure analysis, the number of LGE islands in addition to scar transmurality, radiality, interface area, and entropy were all associated with the primary outcome after adjustment for severely reduced LVEF and New York Heart Association functional class of >1. No scar microstructure feature remained associated with the primary endpoint when PIZ mass and core infarct mass were added to the regression models.ConclusionsComprehensive LGE characterization independently predicted SCD risk beyond conventional predictors used in implantable cardioverter-defibrillator (ICD) insertion guidelines. These results signify the potential for a more personalized approach to determining ICD candidacy in CAD.