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This study sought to determine whether stress cardiac magnetic resonance (CMR) provides clinically relevant risk reclassification in patients with known coronary artery disease (CAD) in a multicenter setting in the United States.Despite improvements in medical therapy and coronary revascularization, patients with previous CAD account for a disproportionately large portion of CV events and pose a challenge for noninvasive stress testing.From the Stress Perfusion Imaging in the United States (SPINS) registry, we identified consecutive patients with documented CAD who were referred to stress CMR for evaluation of myocardial ischemia. The primary outcome was nonfatal myocardial infarction (MI) or cardiovascular (CV) death. Major adverse CV events (MACE) included MI/CV death, hospitalization for heart failure or unstable angina, and late unplanned coronary artery bypass graft. The prognostic association and net reclassification improvement by ischemia for MI/CV death were determined.Out of 755 patients (age 64 ± 11 years, 64% male), we observed 97 MI/CV deaths and 210 MACE over a median follow-up of 5.3 years. Presence of ischemia demonstrated a significant association with MI/CV death (HR: 2.30; 95% CI: 1.54-3.44; P 0.001) and MACE (HR: 2.24 ([95% CI: 1.69-2.95; P0.001). In a multivariate model adjusted for CV risk factors, ischemia maintained strong association with MI/CV death (HR: 1.84; 95% CI: 1.17-2.88; P = 0.008) and MACE (HR: 1.77; 95% CI: 1.31-2.40; P 0.001) and reclassified 95% of patients at intermediate pretest risk (62% to low risk, 33% to high risk) with corresponding changes in the observed event rates of 1.4% and 5.3% per year for low and high post-test risk, respectively.In a multicenter cohort of patients with known CAD, CMR-assessed ischemia was strongly associated with MI/CV death and reclassified patient risk beyond CV risk factors, especially in those considered to be at intermediate risk. Absence of ischemia was associated with a2% annual rate of MI/CV death. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891).

Stress cardiovascular magnetic resonance imaging (CMR) is a cost-effective, noninvasive test that accurately assesses myocardial ischemia, myocardial viability, and cardiac function without the need for ionizing radiation. There is a large body of literature, including randomized controlled trials, validating its diagnostic performance, risk stratification capabilities, and ability to guide appropriate use of coronary intervention. Specifically, stress CMR has shown higher diagnostic sensitivity than single-photon emission computed tomography imaging in detecting angiographically significant coronary artery disease. Stress CMR is particularly valuable for the evaluation of patients with moderate to high pretest probability of having stable ischemic heart disease and for patients known to have challenging imaging characteristics, including women, individuals with prior revascularization, and those with left ventricular dysfunction. This paper reviews the basics principles of stress CMR, the data supporting its clinical use, the added-value of myocardial blood flow quantification, and the assessment of myocardial function and viability routinely obtained during a stress CMR study.

Consensus Principles • Optimal patient care should be the priority for physicians and insurance providers. • Given equivalent diagnostic accuracy and appropriate use criteria, there is no clear jus...

Insulin resistance early after acute myocardial infarction is associated with increased heart failure and mortality. OMEGA-REMODEL was a prospective double-blind 1:1 randomized control trial of patients with AMI. We reported that 6-month treatment with omega-3 fatty acid (O-3FA) 4 g/day attenuated cardiac remodeling accompanied by reduction in inflammation. We hypothesized that insulin resistance modifies the therapeutic effect of O-3FA on post-MI cardiac remodeling. The OMEGA-REMODEL study group was dichotomized according to cohort- and gender-specific median cutoff value of leptin-to-adiponectin ratio (LAR) at baseline (LAR-Hi vs LAR-Lo). Mixed model regression analyses were used to evaluate effect modification of O-3FA on reduction of left ventricular end-systolic volume index (LVESVI) by LAR status. Baseline LAR was evaluated on 325 patients (59 ± 11 years, 81% male). A total of 168 patients were categorized in LAR-Lo, and 157 in LAR-Hi. O-3FA treatment resulted in significant LVESVI reduction in patients with LAR-Lo but not with LAR-Hi (p = 0.0002 vs 0.66, respectively). Mixed model regression analysis showed significant modification of LAR on O-3FA's treatment effect in attenuating LVESVI (p = 0.021). In conclusion, this post-hoc efficacy analysis suggests that LAR status significantly modified O-3FA's treatment effect in attenuating cardiac remodeling. During the convalescent phase of acute infarct healing, patients with lower insulin resistance estimated by LAR appear to derive more therapeutic response from O-3FA toward improvement of LVESVI.

Background Dilated cardiomyopathy (DCM) is increasingly recognized as a heterogenous disease with distinct phenotypes on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging. While mid-wall striae (MWS) fibrosis is a widely recognized phenotypic risk marker, other fibrosis patterns are prevalent but poorly defined. Right ventricular (RV) insertion (RVI) site fibrosis is commonly seen, but without objective criteria has been considered a non-specific finding. In this study we developed objective criteria for RVI fibrosis and studied its clinical relevance in a large cohort of patients with DCM. Methods We prospectively enrolled 645 DCM patients referred for LGE-CMR. All underwent standardized imaging protocols and baseline health evaluations. LGE images were blindly scored using objective criteria, inclusive of RVI site and MWS fibrosis. Associations between LGE patterns and CMR-based markers of adverse chamber remodeling were evaluated. Independent associations of LGE fibrosis patterns with the primary composite clinical outcome of heart failure admission or death were determined by multivariable analysis. Results The mean age was 56 ± 14 (28% female) with a mean left ventricular (LV) ejection fraction (LVEF) of 37%. At a median of 1061 days, 129 patients (20%) experienced the primary outcome. Any abnormal LGE was present in 306 patients (47%), inclusive of 274 (42%) meeting criteria for RVI site fibrosis and 167 (26%) for MWS fibrosis. All with MWS fibrosis showed RVI site fibrosis. Solitary RVI site fibrosis was associated with higher bi-ventricular volumes [LV end-systolic volume index (78 ± 39 vs. 66 ± 33 ml/m2, p = 0.01), RV end-diastolic volume index (94 ± 28 vs. 84 ± 22 ml/m2 (p 2, p Conclusions RVI site fibrosis in the absence of MWS fibrosis is associated with bi-ventricular remodelling and intermediate risk of heart failure admission or death. Our study findings suggest RVI site fibrosis to be pre-requisite for the incremental development of MWS fibrosis, a more advanced phenotype associated with greater LV remodeling and risk of clinical events.

In this study we aimed to investigate left atrial (LA) function, measured from routine cine cardiovascular magnetic resonance imaging, to determine its value for the prediction of sudden cardiac death (SCD) or appropriate implantable cardioverter defibrillator (ICD) shock in patients who received primary prevention ICD implantation.We studied 203 patients with ischemic or idiopathic nonischemic dilated cardiomyopathy who underwent cardiovascular magnetic resonance imaging before primary prevention ICD implantation. LA volumes were measured at end-diastole and end-systole from 4- and 2-chamber cine images, and LA emptying function (LAEF) calculated. Patients were followed for the primary composite end point of SCD or appropriate ICD shock.Mean age was 61 ± 12 years with a mean left ventricular ejection fraction of 24 ± 7%. The mean LAEF was 27 ± 15% (range, 0.9%-73%). At a median follow-up of 1639 days, 35 patients (17%) experienced the primary composite outcome. LAEF was strongly associated with the primary outcome (P = 0.001); patients with an LAEF ≤ 30% experienced a cumulative event rate of 26.1% vs 5.7% (hazard ratio, 5.5; P0.001) in patients above this cutoff. This finding was maintained in multivariable analysis (hazard ratio, 4.7; P = 0.002) and was consistently shown in the ischemic and nonischemic dilated cardiomyopathy subgroups.LAEF is a simple, powerful, and independent predictor of SCD in patients being referred for primary prevention ICD implantation.

© 2019 International Society for Magnetic Resonance in Medicine Background: Characterization of left atrial (LA) hemodynamics in paroxysmal atrial fibrillation (PAF) may provide valuable insights for thromboembolic risk. Purpose: To evaluate LA vortex formation and velocity distributions by 4D flow MRI and identify associations with age, LA/LV (left ventricle) function, and established risk scores. Study Type: Prospective clinical. Population: Patients with PAF (n = 45, 46 ± 14 years) and healthy controls (n = 15, 54 ± 9 years) were enrolled. MRI Sequences: 3T standardized cardiac MRI protocol inclusive of 4D flow MRI. Assessment: Flow analysis planes were prescribed at each pulmonary vein. Velocity distribution analysis and vortex size quantification by the Lambda2 (λ2) method were performed in the LA. Statistics: Pearson or Spearman's correlation coefficients, r, were calculated to identify relationships between 4D flow-derived LA parameters and age, LA/LV function, and CHA2DS2-VASc stroke risk score. Univariate and multivariate determinants of stroke risk were assessed using linear regressions. To compare parameters within multiple groups, one-way analysis of variance or Kruskal–Wallis was used. Results: LA vortice sizes were observed in all subjects using λ2 showing inverse correlations with peak pulmonary vein inflow velocities (P < 0.05), and positive correlations with LA volume (P < 0.05). Vortex size was elevated in PAF at all phases of the cardiac cycle, being most prominent at end early diastole (3.98 ± 1.84 cm3 vs. 6.93 ± 3.11 cm3, P = 0.001). Velocity distribution analysis showed a greater incidence of flow stasis among patients with PAF (P < 0.05). In univariate regression, vortex size was associated with the CHA2DS2-VASc risk score at peak systole (0.457 ± 0.038, P ≤ 0.001). However, in multivariate regression age was the dominant determinant of stroke risk (0.348 ± 0.012, P = 0.006). Data Conclusion: This study demonstrated that LA vortex size is increased among low-risk patients with PAF and is associated with the CHA2DS2-VASc risk score. Age remained the dominant determinant of stroke risk. Level of Evidence: 2. Technical Efficacy: Stage 3. J. Magn. Reson. Imaging 2020;51:871–884.

Background: There is increasing evidence that right ventricular ejection fraction (RVEF) may provide incremental value to left ventricular (LV) ejection fraction for the prediction of major adverse cardiovascular events. To date, generalizable utility for RVEF quantification in patients with cardiovascular disease has not been established. Using a large prospective clinical outcomes registry, we investigated the prognostic value of RVEF for the prediction of major adverse cardiovascular events- and heart failure-related outcomes. Methods: Seven thousand one hundred thirty-one consecutive patients with known or suspected cardiovascular disease undergoing cardiovascular magnetic resonance imaging were prospectively enrolled. Multichamber volumetric quantification was performed by standardized operational procedures. Patients were followed for the primary composite outcome of all-cause death, survived cardiac arrest, admission for heart failure, need for transplantation or LV assist device, acute coronary syndrome, need for revascularization, stroke, or transient ischemic attack. A secondary, heart failure focused outcome of heart failure admission, need for transplantation/LV assist device or death was also studied. Results: Mean age was 54±15 years. The mean LV ejection fraction was 55±14% (range 6%–90%) with a mean RVEF of 54±10% (range 9%–87%). At a median follow-up of 908 days, 870 (12%) patients experienced the primary composite outcome and 524 (7%) the secondary outcome. Each 10% drop in RVEF was associated with a 1.3-fold increased risk of the primary outcome ( P P P Conclusions: RVEF is a powerful and independent predictor of major adverse cardiac events with broad generalizability across patients with known or suspected cardiovascular disease. These findings support migration towards biventricular phenotyping for the classification of risk in clinical practice. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04367220.

A 62-year-old female with COVID-19 developed acute respiratory failure and cardiogenic shock in the setting of a systemic hyper-inflammatory state and apparent ST-elevation myocardial infarction. Cardiac magnetic resonance (CMR) imaging showed fulminant acute myocarditis with severe left ventricular dysfunction. Treatment with the recombinant interleukin-1 (IL-1) receptor antagonist anakinra and dexamethasone resulted in rapid clinical improvement, reduction in serum inflammatory markers and a marked recovery in CMR-based markers of inflammation and contractile dysfunction. The patient was subsequently discharged from hospital. Emerging evidence supports use of anti-inflammatory therapies, including anakinra and dexamethasone, in severe COVID-19., A 62-year-old female with COVID-19 developed cardiogenic shock and apparent ST-elevation myocardial infarction. Cardiac magnetic resonance (CMR) imaging showed fulminant acute myocarditis with severe left ventricular dysfunction. Treatment with anakinra and dexamethasone resulted in rapid clinical improvement and marked recovery in CMR-based markers of inflammation and contractile dysfunction.

Background: Cancer Therapeutics-related Cardiac Dysfunction (CTRCD) is defined by an interval drop in contractile performance to below reference lower limits of normal. This definition assumes healthy reference data appropriately represent referral populations with active cancer. However, the influence of active cancer on cardiac chamber volumes and contractile performance has not been established. Using cardiac magnetic resonance (CMR), we studied chamber volume- and deformation-based markers in ~400 cancer patients with comparison to ~100 healthy controls. Methods: 394 active cancer patients referred for first-time anthracycline-based chemotherapy and 102 healthy volunteers (HV) were recruited. Both underwent identical CMR protocols with quantification of chamber volumes and ejection fraction (EF). Left ventricular (LV) mechanics were also assessed by 3D myocardial deformation analysis (3D-MDA), providing global longitudinal, circumferential, radial and principal peak-systolic strain amplitude and rate. Results: The mean age was 53.8±13 years (78% female), with 64% having breast cancer and 36% lymphoma. Table 1 summarizes CMR findings of cancer patients versus HV, stratified by sex. Chamber volumes were significantly smaller while LV mass was significantly greater versus HV. LV EF and global longitudinal (GLS) were similar. However, cancer patients demonstrated significantly higher radial, circumferential and maximal principal strain amplitude. Peak-systolic strain rates were also consistently elevated. Conclusion: Chemotherapy-naïve cancer patients have smaller chamber volumes, greater LV mass, and higher radial, circumferential, and maximal principal strain versus healthy subjects. LV EF and peak GLS remain similar, and therefore are most appropriate to define CTRCD. However, an altered state of cardiac health is apparent by all other CMR-based markers, reflecting a unique cardiac phenotype of patients with active cancer.

Introduction: Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere genes that alter myocardial contractility and relaxation. Three-dimensional myocardial deformation analysis (3D-MDA) may elucidate left ventricular (LV) abnormalities associated with sarcomere genotype status. Hypothesis: We hypothesize that HCM patients with sarcomere mutations have changes in myocardial contractility profiles that are associated with adverse LV architectural changes. Methods: 3D-MDA was measured using validated feature-tracking software applied to 2D cine cardiac MRI studies in 2,221 genotyped patients within the NHLBI HCM Registry. Results: Baseline, cardiac MRI, and 3D MDA-derived strain characteristics stratified by sarcomere status are shown in Table 1. Sarcomere positive patients were younger, had less LV outflow tract obstruction and lower indexed LV mass, but similar LVEF and trend towards higher serum NT-proBNP levels. Maximal wall thickness, measures of diffuse myocardial fibrosis (native T1, extracellular volume fraction) were elevated with corresponding reduction in global radial strain. Global minimum principal and epicardial layer conventional strain values were higher in sarcomere positive patients. Epicardial minimum principal strain was highly correlated with indexed LV mass (r=0.42, P Conclusions: Sarcomere positive HCM patients had differences in myocardial deformation strain profiles that were correlated to LV architectural changes and NT-proBNP levels despite lower indexed LV mass. More sensitive measures of contractile dysfunction may help elucidate pathophysiological mechanisms by which sarcomere mutations cause disease progression and adverse clinical outcomes in HCM.

Background Cardiovascular diseases remain the leading cause of morbidity worldwide and impose the highest economic burden among noncommunicable diseases. Much of these costs are related to hospitalizations for adverse cardiovascular events, which may be reduced by targeted management of high-risk patients. Cardiac markers derived from CMR imaging have been shown to be strong independent predictors of prognosis within specific cohorts. However, its capacity to broadly contribute to risk models aimed at predicting incident cardiac hospitalization has not been demonstrated. Purpose Using a large clinical outcomes registry of patients clinically referred for CMR, develop and validate a nomogram for prediction of cardiovascular hospital admission. Methods A total of 7127 consecutive patients were prospectively recruited between 02/2015 and 07/2019. All patients completed standardized health questionnaires and CMR imaging protocols. A nomogram was developed for prediction of cardiovascular hospitalization, inclusive of admission for heart failure, MI, cardiac arrest, heart transplant, LVAD implantation, or stroke. The risk model was derived from 80% (n=5702) of the cohort using Cox modelling that included CMR, medication, laboratory, and patient-reported health variables. Model validation was assessed by discrimination and calibration procedures applied to the remaining 20% of patients (n=1425). A minimum follow-up of six months was mandated. Results The derivation cohort was comprised of 38% females with a median age of 56 (IQR 44–65) years. During a median follow-up of 934 days, 514 (9.0%) events occurred. The validation cohort was similarly comprised of 37% females with a median age of 57 (IQR 44–66) years. During a median follow-up of 970 days, 142 (10.0%) events occurred. Numerous CMR parameters were significantly different between those experiencing versus not experiencing the primary composite outcome, including: LVEF (44% vs 59%, p Conclusion Using data available at time of CMR imaging, we derived and validated a Cox-based nomogram that offers robust prediction of future cardiovascular admissions. This tool may provide value for the identification of patients who may benefit from targeted surveillance and management strategies, and may offer a foundation for improved patient-specific cost modelling. Figure 1 Funding Acknowledgement Type of funding source: None

Background Whether baseline cardiovascular health status significantly influences the risk of Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD) in patients receiving de-novo chemotherapy exposure is an important clinical question for both surveillance and management decisions. The reference standard technique for the serial monitoring of left ventricular (LV) volumes and ejection fraction (EF) is cardiovascular magnetic resonance (CMR). Using this technique, we sought to prospectively evaluate baseline clinical risk factors and CMR-based pre-exposure characteristics for their influence on the incident occurrence of CTRCD. Methods We prospectively enrolled 371 cancer patients referred for baseline (pre-chemotherapy) followed by surveillance CMR imaging as part of the Cardiotoxicity Prevention Research Initiative (CAPRI). We also recruited 62 healthy volunteers to evaluate for referral population differences in CMR-based markers. Study subjects and healthy volunteers underwent identical CMR imaging protocols inclusive of cine imaging, T1 and T2 mapping. CTRCD was defined according to surveillance CMR imaging with criteria established as a drop in LVEF by >5% (meaningful detectable difference for CMR technique) to a value ≤56% (lower limit of normal) at any time point during chemotherapy surveillance. A total of 1474 CMR studies were performed over a median surveillance period of 12.5 months (range 2.3 to 68.9 months). Results The majority of patients were female (77%), being referred for breast cancer (64%) or lymphoma (36%), with a mean age of 54.0±14 years. The baseline prevalence of hypertension, diabetes, hyperlipidemia, and current smoking were 32%, 11%, 46%, and 13%, respectively. Compared to healthy volunteers, cancer patients at baseline showed smaller indexed LV and RV volumes, higher indexed LV mass, and higher native T1 values (mean difference +33 msec; p Conclusion Using the reference standard of serial CMR imaging we identified that of all baseline (pre-chemotherapy) clinical and CMR-based markers of cardiovascular health, only indexed LV end-doastolic volume (EDV) was independently associated with future occurrence of CTRCD following adjustment for chemotherapy regimen. We did not observe significant associations with conventional cardiac risk factors in our study population. The observed risk for indexed LVEDV was clinically meaningful (2.3-fold risk per 10 ml/m2) and warrants further investigation as a relevant baseline marker of risk in this referral population. Figure 1. Forest plot of predictors of CTRCD Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Alberta Innovates/Genome Alberta: CAPRI

Over the past 2 decades, cardiac magnetic resonance (CMR) has become an essential component of cardiovascular clinical care and contributed to imaging-guided diagnosis and management of coronary artery disease, cardiomyopathy, congenital heart disease, cardio-oncology, valvular, and vascular disease, amongst others. The widespread availability, safety, and capability of CMR to provide corresponding anatomical, physiological, and functional data in 1 imaging session can improve the design and conduct of clinical trials through both a reduction of sample size and provision of important mechanistic data that may augment clinical trial findings. Moreover, prospective imaging-guided strategies using CMR can enhance safety, efficacy, and cost-effectiveness of cardiovascular pathways in clinical practice around the world. As the future of large-scale clinical trial design evolves to integrate personalized medicine, cost-effectiveness, and mechanistic insights of novel therapies, the integration of CMR will continue to play a critical role. In this document, the attributes, limitations, and challenges of CMR's integration into the future design and conduct of clinical trials will also be covered, and recommendations for trialists will be explored. Several prominent examples of clinical trials that test the efficacy of CMR-imaging guided pathways will also be discussed.

Aims Left ventricular hypertrophy (LVH) is the most common form of myocardial remodelling and predicts adverse outcomes in patients with coronary artery disease (CAD). However, sex-specific prevalence and prognostic significance of LVH patterns are poorly understood. We investigated the sex-specific influence of LVH pattern on clinical outcomes in patients undergoing cardiovascular magnetic resonance (CMR) and coronary angiography following adjustment for co-morbidities including CAD burden. Methods and results Patients undergoing CMR and coronary angiography between 2005 and 2013 were included. Volumetric measurements of left ventricular (LV) mass with classification of concentric vs. eccentric remodelling patterns were determined from CMR cine images. Multivariable Cox analysis was performed to assess independent associations with the primary outcome of all-cause mortality. In total, 3754 patients were studied (mean age 59.3 ± 13.1 years), including 1039 (27.7%) women. Women were more likely to have concentric remodelling (8.1% vs. 2.1%, P Conclusion Patterns of LV remodelling differ by sex and LVH and provides prognostic information in both men and women. Our findings support the presence of sex-specific factors influencing LV remodelling.

Despite substantial declines in mortality following myocardial infarction (MI), subsequent left ventricular remodeling (LVRm) remains a significant long-term complication. Extracellular small non-coding RNAs (exRNAs) have been associated with cardiac inflammation and fibrosis and we hypothesized that they are associated with post-MI LVRm phenotypes. RNA sequencing of exRNAs was performed on plasma samples from patients with “beneficial” (decrease LVESVI ≥ 20%, n = 11) and “adverse” (increase LVESVI ≥ 15%, n = 11) LVRm. Selected differentially expressed exRNAs were validated by RT-qPCR (n = 331) and analyzed for their association with LVRm determined by cardiac MRI. Principal components of exRNAs were associated with LVRm phenotypes post-MI; specifically, LV mass, LV ejection fraction, LV end systolic volume index, and fibrosis. We then investigated the temporal regulation and cellular origin of exRNAs in murine and cell models and found that: 1) plasma and tissue miRNA expression was temporally regulated; 2) the majority of the miRNAs were increased acutely in tissue and at sub-acute or chronic time-points in plasma; 3) miRNA expression was cell-specific; and 4) cardiomyocytes release a subset of the identified miRNAs packaged in exosomes into culture media in response to hypoxia/reoxygenation. In conclusion, we find that plasma exRNAs are temporally regulated and are associated with measures of post-MI LVRm., Highlights • Plasma exRNA signatures were associated with post-MI remodeling as assessed by cardiac MRI. • Candidate exRNAs originated from different cell types, and were dynamically regulated in experimental models of ischemia. • Candidate exRNAs were predicted to regulate pathways of inflammation and fibrosis by bioinformatics analysis. Plasma RNA signatures are associated with heart remodeling following a myocardial infarction, and are predicted to regulate inflammation pathways. These extracellular RNAs are derived from different types of cells in the heart and are altered in the heart tissue as well as plasma in a mouse model of myocardial infarction, reflecting the complex and dynamic process of heart remodeling after myocardial infarction.

Two-dimensional (2D) strain analysis is constrained by geometry-dependent reference directions of deformation (i.e. radial, circumferential, and longitudinal) following the assumption of cylindrical chamber architecture. Three-dimensional (3D) principal strain analysis may overcome such limitations by referencing intrinsic (i.e. principal) directions of deformation. This study aimed to demonstrate clinical feasibility of 3D principal strain analysis from routine 2D cine MRI with validation to strain from 2D tagged cine analysis and 3D speckle tracking echocardiography. Thirty-one patients undergoing cardiac MRI were studied. 3D strain was measured from routine, multi-planar 2D cine SSFP images using custom software designed to apply 4D deformation fields to 3D cardiac models to derive principal strain. Comparisons of strain estimates versus those by 2D tagged cine, 2D non-tagged cine (feature tracking), and 3D speckle tracking echocardiography (STE) were performed. Mean age was 51 ± 14 (36% female). Mean LV ejection fraction was 66 ± 10% (range 37–80%). 3D principal strain analysis was feasible in all subjects and showed high inter- and intra-observer reproducibility (ICC range 0.83–0.97 and 0.83–0.98, respectively—p

The influence of complex bicuspid aortic valve (BAV) flow patterns on net intraluminal aortic pressure, both among patients with and without significant aortic stenosis, is unknown. Pressure drop (PD), as estimated by 4D Flow MRI, can quantify pre- vs post-valvular pressure at multiple levels simultaneously.In this prospective clinical study, 32 patients with BAV with varying degrees of aortic stenosis and regurgitation and 11 healthy subjects were enrolled. 4D flow MRI was processed and analyzed at 9 pre-defined thoracic aortic levels. PD was calculated at each plane relative to a reference located within the left ventricular outflow tract. Conventional 2D phase-contrast imaging was used as reference of hemodynamic obstruction. PD was compared between healthy subjects versus BAV patients using Kruskal-Wallis H test and Mann-Whitney U. Correlation studies were conducted using Spearman's rank-order correlation.Both BAV patients and healthy subjects showed progressive elevation in PD from the aortic root to the distal descending thoracic aorta. However, BAV patients showed higher PD than healthy subjects (p ≤ 0.01) at all analysis planes. Patients with moderate-severe aortic stenosis (n = 5) by 2D phase-contrast (peak PG 40 mm Hg) showed higher PD than those without in the descending aortic segments (p ≤ 0.005). A correlation (r = 0.88, p 0.05) was observed between PD at the distal descending thoracic aorta and peak trans-valvular velocity measured by 2D phase-contrast MRI.We demonstrated that PD with 4D flow MRI is clinically feasible in BAV patients and provides an additional physiologic description of valve-related hemodynamic obstruction.

Cardiovascular magnetic resonance (CMR) imaging is commonly used to diagnose acute myocarditis. However, the natural history of CMR-based tissue markers and their association with left ventricular recovery is poorly explored. We prospectively investigated the natural history of CMR-based myocardial injury and chamber remodeling over 12 months in patients with suspected acute myocarditis.One hundred patients with suspected acute myocarditis were enrolled. All underwent CMR evaluations at baseline and 12 months, inclusive of T2 and late gadolinium enhancement. Blinded quantitative analyses compared left ventricular chamber volumes, function, myocardial edema, and necrosis at each time point using predefined criteria. The predefined primary outcomes were improvement in left ventricular ejection fraction ≥10% and improvement in the indexed left ventricular end diastolic volume ≥10% at 12 months.The mean age was 39.9±14.5 years (82 male) with baseline left ventricular ejection fraction of 57.1±11.2%. A total of 72 patients (72%) showed late gadolinium enhancement at baseline with 57 (57%) having any T2 signal elevation. Left ventricular volumes and EF improved significantly at 12 months. Global late gadolinium enhancement extent dropped from 8.5±9.2% of left ventricular mass to 3.0±5.2% ( P=0.0001) with prevalence of any late gadolinium enhancement dropping to 48%. Reductions in global T2 signal ratio occurred at 12 months (1.85±0.3 to 1.56±0.2; P=0.0001) with prevalence of T2 ratio ≥2.0 dropping to 7%. Neither marker provided associations with the primary outcomes.In clinically suspected acute myocarditis, significant reductions in tissue injury markers occur during the first 12 months of convalescence. Neither the presence nor extent of the investigated CMR-based tissue injury markers were predictive of our pre-defined function or remodeling outcomes at 12 months in this referral population.

Background: Cardiovascular magnetic resonance (CMR) imaging is commonly used to diagnose acute myocarditis. However, the natural history of CMR-based tissue markers and their association with left ventricular recovery is poorly explored. We prospectively investigated the natural history of CMR-based myocardial injury and chamber remodeling over 12 months in patients with suspected acute myocarditis. Methods: One hundred patients with suspected acute myocarditis were enrolled. All underwent CMR evaluations at baseline and 12 months, inclusive of T2 and late gadolinium enhancement. Blinded quantitative analyses compared left ventricular chamber volumes, function, myocardial edema, and necrosis at each time point using predefined criteria. The predefined primary outcomes were improvement in left ventricular ejection fraction ≥10% and improvement in the indexed left ventricular end diastolic volume ≥10% at 12 months. Results: The mean age was 39.9±14.5 years (82 male) with baseline left ventricular ejection fraction of 57.1±11.2%. A total of 72 patients (72%) showed late gadolinium enhancement at baseline with 57 (57%) having any T2 signal elevation. Left ventricular volumes and EF improved significantly at 12 months. Global late gadolinium enhancement extent dropped from 8.5±9.2% of left ventricular mass to 3.0±5.2% ( P =0.0001) with prevalence of any late gadolinium enhancement dropping to 48%. Reductions in global T2 signal ratio occurred at 12 months (1.85±0.3 to 1.56±0.2; P =0.0001) with prevalence of T2 ratio ≥2.0 dropping to 7%. Neither marker provided associations with the primary outcomes. Conclusions: In clinically suspected acute myocarditis, significant reductions in tissue injury markers occur during the first 12 months of convalescence. Neither the presence nor extent of the investigated CMR-based tissue injury markers were predictive of our pre-defined function or remodeling outcomes at 12 months in this referral population.

Coronary heart disease is a leading cause of death. Tissue remodeling and fibrosis results in cardiac pump dysfunction and ischemic heart failure. Cardiac fibroblasts may rebuild damaged tissues when prompted by suitable environmental cues. Here, we use acellular biologic extracellular matrix scaffolds (bioscaffolds) to stimulate pathways of muscle repair and restore tissue function. We show that acellular bioscaffolds with bioinductive properties can redirect cardiac fibroblasts to rebuild microvascular networks and avoid tissue fibrosis. Specifically, when human cardiac fibroblasts are combined with bioactive scaffolds, gene expression is upregulated and paracrine mediators are released that promote vasculogenesis and prevent scarring. We assess these properties in rodents with myocardial infarction and observe bioscaffolds to redirect fibroblasts, reduce tissue fibrosis and prevent maladaptive structural remodeling. Our preclinical data confirms that acellular bioscaffold therapy provides an appropriate microenvironment to stimulate pathways of functional repair. We translate our observations to patients with coronary heart disease by conducting a first-in-human observational cohort study. We show that bioscaffold therapy is associated with improved perfusion of infarcted myocardium, reduced myocardial scar burden, and reverse structural remodeling. We establish that clinical use of acellular bioscaffolds is feasible and offers a new frontier to enhance surgical revascularization of ischemic heart muscle.

BackgroundThe double-blind OMEGA-REMODEL placebo-controlled randomized trial of high-dose omega-3 fatty acids (O-3FA) post-acute myocardial infarction (AMI) reported improved cardiac remodeling and attenuation of non-infarct myocardial fibrosis. Fatty acid desaturase 2 (FADS2) gene cluster encodes key enzymes in the conversion of essential omega-3 and omega-6 fatty acids into active arachidonic (ArA) and eicosapentaenoic acids (EPA), which influence cardiovascular outcomes.Methods and resultsWe tested the hypothesis that the genotypic status of FADS2 (rs1535) modifies therapeutic response of O-3FA in post-AMI cardiac remodeling in 312 patients. Consistent with known genetic polymorphism of FADS2, patients in our cohort with the guanine-guanine (GG) genotype had the lowest FADS2 activity assessed by arachidonic acid/linoleic acid (ArA/LA) ratio, compared with patients with the adenine-adenine (AA) and adenine-guanine (AG) genotypes (GG:1.62±0.35 vs. AA: 2.01±0.36, pConclusionGenetic profiling using FADS2 genotype can predict the therapeutic benefits of O-3FA treatment against adverse cardiac remodeling during the convalescent phase of AMI.Clinical trial registration informationclinicaltrials.gov Identifier: NCT00729430.

BACKGROUND Supplemental long-chain omega-3 (n-3) fatty acids (EPA and DHA) raise erythrocyte EPA + DHA [omega-3 index (O3I)] concentrations, but the magnitude or variability of this effect is unclear. OBJECTIVE The purpose of this study was to model the effects of supplemental EPA + DHA on the O3I. METHODS Deidentified data from 1422 individuals from 14 published n-3 intervention trials were included. Variables considered included dose, baseline O3I, sex, age, weight, height, chemical form [ethyl ester (EE) compared with triglyceride (TG)], and duration of treatment. The O3I was measured by the same method in all included studies. Variables were selected by stepwise regression using the Bayesian information criterion. RESULTS Individuals supplemented with EPA + DHA (n = 846) took a mean ± SD of 1983 ± 1297 mg/d, and the placebo controls (n = 576) took none. The mean duration of supplementation was 13.6 ± 6.0 wk. The O3I increased from 4.9% ± 1.7% to 8.1% ± 2.7% in the supplemented individuals ( P

Characterization of left atrial (LA) hemodynamics in paroxysmal atrial fibrillation (PAF) may provide valuable insights for thromboembolic risk.To evaluate LA vortex formation and velocity distributions by 4D flow MRI and identify associations with age, LA/LV (left ventricle) function, and established risk scores.Prospective clinical.Patients with PAF (n = 45, 46 ± 14 years) and healthy controls (n = 15, 54 ± 9 years) were enrolled.3T standardized cardiac MRI protocol inclusive of 4D flow MRI.Flow analysis planes were prescribed at each pulmonary vein. Velocity distribution analysis and vortex size quantification by the Lambda2 (λPearson or Spearman's correlation coefficients, r, were calculated to identify relationships between 4D flow-derived LA parameters and age, LA/LV function, and CHALA vortice sizes were observed in all subjects using λThis study demonstrated that LA vortex size is increased among low-risk patients with PAF and is associated with the CHA2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:871-884.