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Patients with interatrial shunts (patient foramen ovale/atrial septal defect) are potentially at increased risk for paradoxical air embolism following computed tomography (CT) scans with intravenous (IV) contrast media injection. IV in-line filters aim to prevent such embolisms but are not compatible with power injection required for diagnostic CT.The purpose of this study was to determine whether the incidence of paradoxical embolism to the heart and brain in patients with an interatrial shunt is higher compared with controls within 48 hours following injection of IV contrast media without IV in-line filter.This is a retrospective cohort study conducted at a large tertiary academic center, which included a total of 2929 consecutive patients who underwent 8983 CT scans with IV contrast media injection between July 1, 2000 and April 30, 2018. Diagnosis of an interatrial shunt was confirmed by transthoracic or transesophageal echocardiography. Incidence and risk of cardiac embolic events (new troponin elevation,0.1 ng/mL) and neurological embolic events (new diagnosis of stroke/transient ischemic attacks) were evaluated.Among the 2929 patients analyzed (mean±SD age, 61±14 y), 475/2929 (16.2%) patients had an interatrial shunt. After applying the exclusion criteria, new elevated troponin was found in 8/329 (2.4%; 95% confidence interval [CI]: 1.1-4.7) patients with an interatrial shunt compared with 25/1687 (1.5%; 95% CI: 0.9-2.2) patients without an interatrial shunt. New diagnosis of stroke occurred in 2/169 (1%; 95% CI: 0.3-4.2) of patients with an interatrial shunt compared with 7/870 (0.8%; 95% CI: 0.4-1.7) without interatrial shunt.Among patients with echocardiographic evidence of an interatrial shunt, IV CT contrast administration without an in-line filter does not increase the incidence of cardiac or neurological events.

Background: Orthostatic hypotension (OH) is associated with cardiovascular disease, particularly in older adults. While standing transthoracic echocardiography (TTE) could identify changes in cardiac output to diagnose OH, no established protocols exist, and its feasibility is unknown. Objective: Determine the feasibility of standing TTE on adults in the outpatient setting. Methods: We recruited 72 adults scheduled for elective TTE. Consenting participants underwent recumbent TTE, followed by a focused standing TTE within 1-2 minutes of standing. The focused standing TTE used apical windows to measure left ventricular outflow tract velocity time integral, subsequently used to determine stroke volume and cardiac output. Standing blood pressure and heart rate were taken concurrently, and patients were monitored for symptoms. Results: Of the 72 enrolled participants, 60 (over 80%) completed the standing TTE. Mean age was 63 years (49% were ≥70 years), 49% were women, 42% had a BMI ≥30 kg/m 2 , and 18% had OH. The average duration of the study in the standing position was 127 seconds. Doppler quality was good-to-excellent in 87% of all our completing participants, 54% in those ≥70 years, and 86% in those with obesity. Only 5% of the participants experienced discomfort, and 9% experienced dizziness. There was no significant association between standing blood pressure and standing cardiac output. Conclusions: Standing focused TTE is safe, well-tolerated, and feasible in the ambulatory setting. While this clinical assessment is promising for identifying cardiogenic OH, further work is needed in larger at-risk cohorts to determine its clinical utility.

Introduction: High left ventricular ejection fraction (LVEF) has been associated with excess cardiovascular disease (CVD) morbidity and mortality among women with CVD. We sought to determine if high EF is associated with incident heart failure (HF) in a community-dwelling cohort of adults. Secondarily, we examined relationships between various adiposity measures and high EF, as obesity is associated with HF with preserved EF. Methods: 1794 participants aged 65±9y (53% women) of the Framingham Offspring cohort underwent cardiac MRI 2002-2006 to determine LV EF and mass (LVM). Anthropometric measures and clinical covariates were collected at the adjacent Offspring cycle 7 visit. Adiposity measures included body mass index (BMI) and waist circumference (WC). A healthy referent subset (no hypertension, diabetes, smoking, or history of CVD) was used to determine sex-specific upper 90 th percentile cutpoints (P90) for high EF. Cox proportional hazards regression models were used to assess event-free survival for the outcome of HF (adjudicated by 3 physician investigators). Multivariable-adjusted (MV) logistic regression analysis was used to determine clinical factors associated with high EF. Adiposity measures were considered categorically (as BMI≥30kg/m 2 and WC > 102 or 88 cm (men, women)) and as continuous variables. Results: P90 cutpoints for high EF were 72.5% (men) and 75.1% (women). Prevalence of high EF was 16.0% (men) and 14.7% (women). Over median 13.2 years of follow up there were 68 incident HF events. In MV-adjusted Cox models accounting for age, sex, hypertension, smoking, diabetes, and indexed LVM, the HF outcome was associated with greater age (hazard ratio, HR=3.13/10y, 95%CI 2.30 - 4.27), LVMi (HR=1.24/5g per m 2 , CI 1.12 - 1.36) and high EF (HR=2.26, CI 1.35 - 3.77). MV-adjusted logistic regression models showed high EF was associated with each measure of adiposity. High BMI (≥30) had odds ratio (OR) = 1.38 (CI 1.04 - 1.84), high WC (>102 or 88): OR=1.55 (1.12 - 2.09), continuous BMI: OR=1.03 (CI 1.01 - 1.06), continuous WC: OR=1.02 (1.01 - 1.03). In each of these models ORs for age ranged 1.52 to 1.54, hypertension 1.74 to 1.86. Conclusion: High EF was associated with greater hazard of incident heart failure in middle-aged and older adults. High EF was associated with increasing age, hypertension, and greater adiposity (measured by either BMI or WC). This work extends prior findings in women with CVD to a community-dwelling cohort of both sexes. Further work is needed to determine whether general or central measures of obesity are more strongly associated with high EF.

Introduction: The severity of an acute pulmonary embolism (PE) can be assessed using hemodynamics, right ventricular (RV) strain on imaging, and cardiac biomarkers. The spatial ventricular gradient (SVG) is a vectorcardiographic measurement acquired from a 12-lead ECG that reflects cardiac loading conditions via electromechanical coupling and could aid in risk stratification in acute PE. Hypothesis: SVG is correlated with RV strain, and predicts adverse events in patients with acute PE. Methods: Retrospective cohort study of patients with acute PE. ECG signs of RV strain (S1Q3T3, precordial T-wave inversions, RBBB); imaging (CT and TTE RV/LV ratios); and outcome data (30-day mortality, need for vasopressor or advanced therapy) were obtained. The SVG vector was regressed on degree of RV dysfunction. Odds of adverse outcome after PE were regressed on the SVG and covariates (imaging data, age, gender, ECG signs) using a logit model. Results: ECGs from 318 patients (48% male, age 62.2 ± 16.4 y) with acute PE were analyzed; 44 adverse events (13. 8%) were reported. Worse RV hypokinesis and decreasing tricuspid annular plane systolic excursion (TAPSE) were both associated with less positive X and Y, and a more positive SVG Z vector components (p Conclusion: The SVG vector is correlated with right heart dysfunction in acute PE. The SVG vector has a better prognostic value than traditional ECG markers, and may improve risk stratification in acute PE.

Background: Indexing mitral regurgitation (MR) regurgitation volume (RVol) for left ventricular (LV) cavity size accounts for concomitant LV remodeling, but whether it improves prognostication of mortality is uncertain. Methods: The ratio of RVol to LV end-diastolic diameter (LVDD) was measured in 399 individuals (mean age 70.1 ±16.4 years, 51.1% female) with any MR (mean RVol 49.2 ± 27.7 mL) undergoing echocardiography (TTE). Individuals with prior mitral valve interventions were excluded. The relationship between RVol/LVDD and all-cause mortality was examined. The incremental predictive value of RVol/LVDD was compared to RVol alone. Results: Over a median (interquartile range) of 8.8 (3.4-10.5) years follow-up, there were 101 deaths (25.3%). Amongst those treated medically (N = 348), a lower ratio was associated with higher mortality (HR per 1-mL/cm decrease, 1.04, 95% CI 1.01-1.10, p = 0.04), despite a lesser degree of MR (low vs. high RVol/LVDD group, mean RVol, 30.3 ± 11.7 mL vs. 68.1 ± 26.3 mL, p < 0.001), with an inflection for increased risk < 8.4 mL/cm ( Figure ). By contrast, amongst those treated surgically (N = 41), no association was observed (p = 0.69) between RVol/LVDD and mortality, though death was less frequent. This association with risk was observed only amongst individuals with a reduced LVEF and was independent of etiology of MR (e.g. secondary vs. primary). Compared to RVol alone, indexing for LV cavity size improved the prognostication of death (p < 0.001). Conclusions: Amongst patients with MR with a reduced LVEF, treated medically, survival was significantly worse amongst individuals with lower RVol/LVDD ratios. Furthermore, indexing for LV cavity size improved prediction of mortality compared to RVol alone. These results overall suggest that RVol should be routinely indexed for LV size to improve prognostication of risk. Moreover, they suggest a threshold may exist where LV size predominates risk in individuals with MR, treated medically.

Introduction: Afterload conferred by aortic stiffness contributes to heart failure (HF) pathogenesis. Hypothesis: Patients with HF have a greater rise in aortic stiffness with physical exertion compared to individuals without HF. Methods: Outpatients with HF (n=21) and without HF (n=26) underwent cardiovascular magnetic resonance (1.5T CMR) at rest and following submaximal supine bicycle ergometry. Short axis cine steady-state free precession (SSFP) images were obtained to quantify left ventricular volumes and ejection fraction. Cross-sectional aortic SSFP imaging at the level of the pulmonary artery bifurcation was obtained to measure descending aorta (DA) distensibility at rest and immediately after exercise. We compared least squares (LS) means of DA distensibility between HF and control groups, adjusting for age, sex, and metabolic equivalents (METs) achieved. Results: Characteristics of controls and HF patients are presented in the TABLE . There was no difference of DA distensibility between control and HF groups either at rest or after exercise (p=0.77 and p=0.13, respectively). However, compared to controls with no significant change in aortic stiffness with exercise, individuals with HF had a reduction in DA distensibility post-exercise in analyses adjusted for age, sex, and METs achieved ( TABLE ). In subgroup analyses, patients with HF with reduced ejection fraction (n=14) had lower post-exercise DA distensibility vs. rest (adjusted-LS means 3.06 x10 -3 mm Hg -1 , 95% CI 2.35x10 -3 —3.76x10 -3 mm Hg -1 , vs. 4.55 x10 -3 mm Hg -1 , 95% CI 3.84 x10 -3 —5.26 x10 -3 mm Hg - 1, respectively, p=0.020). DA distensibility at rest vs. exercise in patients with HF with preserved ejection fraction was similar (p=0.38). Conclusions: Patients with HF have exercise-induced aortic stiffness not seen in individuals without HF. This may result in less favorable ventricular-vascular coupling with exertion in HF patients. Character count: 1653 (limit=1700)

Background: Coronavirus disease 2019 (COVID-19) is associated with cardiac injury and overt myocardial dysfunction. However, whether COVID-19 is associated with subclinical myocardial dysfunction is unknown. Methods: We evaluated patients hospitalized for COVID-19 referred for transthoracic echocardiography (TTE), between March 17 and May 22, 2020, with a left ventricular ejection fraction (LVEF) ≥ 50%. Controls in a 1:1 ratio were selected from patients receiving TTE during the same month. Global longitudinal strain (GLS) was used to assess the association of COVID-19 and subclinical myocardial disease. Results: Among 99 patients (49 cases, 50 controls), average GLS was significantly reduced in cases vs. controls (mean ± SD, -14.8 ± 4.0% vs. -21.1 ± 4.0%, p < 0.0001). A total of 82.8% of cases vs. 7.1% of controls had an average GLS below normal (> 18%; p < 0.0001), which persisted despite multivariable adjustment ( Table ). Among COVID-19 patients with a prior TTE, absolute average GLS decreased 3.2% (p = 0.008) despite no change in LVEF (p = 0.41). Average GLS was reduced in non-survivors compared with survivors (p = 0.04), though only septal wall thickness (p = 0.03) was associated with in-hospital mortality on multivariable analysis. Conclusions: Among hospitalized patients receiving TTE, COVID-19 is independently associated with subclinical left ventricular systolic dysfunction in the vast majority of patients, and subclinical LV dysfunction is associated with survival. The clinical implications of these findings should be evaluated in future longitudinal multicenter studies.

Introduction: The association between baseline patient characteristics and the long-term utilization of transthoracic echocardiography (TTE) is unknown and may help focus value-based care initiatives. Methods: TTE reports from patients with ≥ 2 TTEs at our institution were linked to 100% Medicare Fee-for-service inpatient claims, 1/1/2000 – 12/31/2017. To avoid inclusion of individuals with short-interval follow-up, TTEs with < 1 year between studies were excluded. Validated claims algorithms were used to create 12 baseline cardiovascular comorbidities. Multivariable Poisson regression was used to estimate adjusted rates of TTE intensity according to baseline comorbidities. Results: Over a median (IQR) follow-up of 5.8 (3.1 – 9.5) years, 18,579 individuals (69.3 ± 12.8 years; 50.5% female) underwent a total of 59,759 TTEs (range 2 – 59). The median TTE intensity was 0.64 TTEs/patient/year (IQR 0.35 – 1.24; range 0.11 – 22.02). The top five contributors to TTE intensity were heart failure, chronic kidney disease, history of myocardial infarction, smoking, and hyperlipidemia ( Figure ). Female sex was associated with decreased TTE utilization (adjusted RR 0.95, 95% CI 0.94-0.96, p < 0.0001). Atrial fibrillation, hypertension, and history of ischemic stroke or transient ischemic attack were not significantly related to TTE intensity after multivariable adjustment (all p > 0.05). Conclusions: Among Medicare beneficiaries with ≥ 2 TTEs at our institution, the median TTE intensity was 0.64 TTEs/patient/year but varied widely. Heart failure, chronic kidney disease, and history of myocardial infarction were the strongest predictors of increased utilization. Female sex was associated with decreased utilization, reflecting broader disparities in utilization of cardiovascular procedures. Further research is needed to clarify reasons for this sex disparity and associations with cardiovascular outcomes.

Introduction: Pathophysiology of the aorta negatively impacts cardiovascular health. Hypothesis: Assessment of aortic anatomy facilitates population-based cardiovascular disease (CVD) risk stratification. Methods: Framingham Heart Study Offspring Cohort participants without prevalent CVD (n=1576, 64±9 years, 44% men) underwent 1.5T ECG-gated axial T2W black-blood CMR of the thoracoabdominal aorta (2002-2006). The diameters of the descending thoracic and proximal and distal abdominal aorta (infrarenal and aortic bifurcation) were measured ( Figure A ). Additionally, the maximum diameter and the total intravascular volume of the descending thoracic and abdominal aorta were calculated. Cox proportional hazards regression analyses adjusting for age, gender, systolic blood pressure, total cholesterol/HDL cholesterol ratio, diabetes mellitus, smoking, as well as treatment for hyperlipidemia, hypertension, and diabetes were undertaken to evaluate the association of aortic anatomy with incident CVD ( Figure ). Results: During follow-up (median 9.5 years, range 0 - 12.2 yrs), 163 incident CVD events occurred, of which 66 were major events (myocardial infarction, ischemic stroke, and CVD death). In multivariable-adjusted Cox regression models, each SD unit greater descending thoracic and maximum aortic diameter, as well as natural logarithmic transformed total aortic volume were associated with a >20% increased risk for incident CVD (per SD Unit hazard ratio [HR]: 1.21, 95% CI: 1.03-1.42, P=0.019; HR 1.22, 95% CI: 1.04-1.43, P=0.014; HR: 1.24, 95% CI: 1.10-1.39, PFigure B ). Abdominal aortic diameters were not associated with CVD. Conclusions: In this middle-aged community-dwelling Caucasian adult cohort followed over 10 years, greater thoracoabdominal aortic dimensions and volume, predicted incident CVD. Future investigations may determine the implications of aortic size modification on CVD outcomes.

Introduction: COVID-19 has significantly impacted hospital systems worldwide. The impact of statewide stay-at-home mandates on echocardiography volumes is unclear. Methods: We queried our institutional echocardiography database from 6/1/2018 to 6/13/2020 to examine rates of transthoracic (TTE), stress (SE), and transesophageal echocardiograms (TEE) prior to and following the COVID-19 Massachusetts stay-at-home order on March 15, 2020. Results: Among 36,377 total studies performed during the study period, mean weekly study volume dropped from 332 + 3 TTEs/week, 30 + 1 SEs/week, and 21 + 1 TEEs/week prior to the stay-at-home order (6/1/2018-3/15/2020) to 158 + 13 TTEs/week, 8 + 2 SEs/week, and 8 + 1 TEEs/week after (% change, -52%, -73%, and -62% respectively, all p < 0.001 when comparing volume prior to March 15 versus after). Weekly TTEs correlated strongly with hospital admissions throughout the study period (r = 0.93, 95% CI 0.89-0.95, p < 0.001) ( Figure ). Outpatient TTEs declined more than inpatient TTEs (% change, -74% vs. -39%, p Conclusions: Echocardiography volumes fell precipitously following the Massachusetts stay-at-home order, strongly paralleling declines in overall hospitalizations. Outpatient TTEs declined more than inpatient TTEs. Despite lifting of the order, echocardiography volumes remain substantially below pre-pandemic levels. The impact of the decreased use of echocardiographic services on patient outcomes remains to be determined.

Background: The effect of mitral regurgitation (MR) severity on heart failure (HF) hospitalization and mortality in individuals with a preserved ejection fraction (LVEF) and no prior HF history is uncertain. Methods: Transthoracic echocardiogram (TTE) reports from patients with an LVEF > 50% at our institution were linked to complete Medicare inpatient claims, 2003-2017. Patients with HF hospitalization within the 12 months prior to TTE were excluded. We evaluated the relationship of baseline MR severity and time to the composite of all-cause mortality or HF hospitalization using the Kaplan-Meier technique. Secondary outcomes included the individual components of all-cause mortality and HF hospitalization, adjusting for the competing risk of death with Fine-Gray methods. Results: A total of 18,315 individuals met inclusion criteria (77.6 ±7.7 years, 54.3% female). Over a median follow-up time of 6.5 (IQR 3.0 to 10.2) years, the primary endpoint occurred in 7566 individuals (50.6%) of whom 6,927 (37.8%) died and 1703 (13.9%) were admitted for HF at a median of 1.4 (IQR 0.2 to 4.3) years and 1.6 (IQR 0.2 to 4.3) years respectively ( Figure ). After multivariable adjustment, MR severity was not associated with the primary or secondary outcome at 1-, 3-, 5-, or 10-years after TTE (p > 0.05 for all). Mitral valve prolapse (MVP) was associated with decreased risk of the primary outcome at 1-year and 3-years (interaction p-value = 0.04 for both). Jet eccentricity did not impact the observed relationship (interaction p-value > 0.05). Conclusions: In this large, single institution echocardiographic study of individuals with preserved ejection fraction and no prior history of HF, MR severity was not associated with an increased risk of all-cause mortality or HF hospitalization. Presence of MVP was associated with decreased risk of the primary outcome with increasing MR severity.

Introduction: Training in the acquisition and interpretation of echocardiograms is integral to cardiovascular disease fellowship training. The American Society of Echocardiography recommends 150 transthoracic echo (TTE) scans and 300 interpretations for level 2 training. Hypothesis: The COVID-19 pandemic led to the temporary restructuring of many fellowship programs. At our institution, fellows not involved in essential clinical rotations served in a backup capacity or were re-assigned with the onset of the Massachusetts stay-at-home advisory on March 15, 2020. A one-hour mid-day Zoom TTE reading session was offered when fellows were available. We hypothesized that these restrictions would impact fellow education in TTE scanning and interpretation volumes. Methods: We examined the number of TTE performed or interpreted by F1 and F2 fellows between July 2017 and June 2020 as recorded in our echo lab electronic database. Results: In the 21 months prior to the onset of the COVID-19 pandemic, 45 + 1 TTE scans/wk were performed by fellows which was reduced to 9 + 3 scans/wk (-80%, p Conclusions: By recognizing that there has already been an impact on echo education, fellowship programs will need to optimize fellow exposure and instruction in echocardiography so as to maintain adequate training volumes.

Background In patients with nonischemic cardiomyopathy, nonischemic fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance is related to adverse cardiovascular outcomes. However, its relationship with left ventricular (LV) mechanical deformation parameters remains unclear. We sought to investigate the association between LV mechanics and the presence, location, and extent of fibrosis in patients with nonischemic cardiomyopathy. Methods and Results We retrospectively identified 239 patients with nonischemic cardiomyopathy (67% male; 55±14 years) referred for a clinical cardiovascular magnetic resonance. LGE was present in 109 patients (46%), most commonly (n=52; 22%) in the septum. LV deformation parameters did not differentiate between LGE‐positive and LGE‐negative groups. Global longitudinal, radial, and circumferential strains, twist and torsion showed no association with extent of fibrosis. Patients with septal fibrosis had a more depressed LV ejection fraction (30±12% versus 35±14%; P =0.032) and more impaired global circumferential strain (−7.9±3.5% versus −9.7±4.4%; P =0.045) and global radial strain (10.7±5.2% versus 13.3±7.7%; P =0.023) than patients without septal LGE. Global longitudinal strain was similar in both groups. While patients with septal‐only LGE (n=28) and free wall–only LGE (n=32) had similar fibrosis burden, the septal‐only LGE group had more impaired LV ejection fraction and global circumferential, longitudinal, and radial strains (all P Conclusions There is no association between LV mechanical deformation parameters and presence or extent of fibrosis in patients with nonischemic cardiomyopathy. Septal LGE was associated with poor global LV function, more impaired global circumferential and radial strains, and more impaired global strain rates.

Introduction: Greater left ventricular (LV) sphericity, a more globular shape, is associated with poor outcomes. Two measures of sphericity are commonly used: Linear sphericity (LinS) is the ratio of LV end-diastolic diameter (EDD) to 4-chamber length (4cL); volumetric sphericity (VolS) is the ratio of end-diastolic volume (EDV) to the volume of a sphere with diameter=4cL. We sought to compare LinS to VolS and to determine: 1) whether LinS and VolS differ with sex and age group; 2) normal values for LinS and VolS, 3) whether LinS and VolS are concordant in how they stratify individuals. Methods: 1794 adults (age 65±9y, 47.1% men) in the Framingham Offspring cohort underwent CMR imaging; LV EDD, EDV and 4cL were measured. A referent group (340M, 512W) free of clinical cardiovascular disease, hypertension, diabetes and smoking was identified. Among these, we compared LinS and VolS between sexes and across age groups (th percentile (P90) cutpoints for LinS and VolS were determined and applied to the entire cohort (N=1794) to stratify each individual as having or not having high sphericity. Concordance between LinS and VolS was assessed using kappa coefficient and McNemar’s test. Methods: LinS was greater than VolS for each sex, but there was robust, positive linear (Pearson) correlation between LinS and VolS for men (r=0.864) and women (r=0.855), p0.27) for either sex. Conclusion: Linear and volumetric measures of LV sphericity are concordant in how they rank and stratify adults in a community dwelling cohort, but the measures are not directly comparable, as mean LinS is markedly greater than VolS. Neither measure of sphericity varies with age among healthy adults.

Background: Conduction velocity (CV) is an important property that contributes to the arrhythmogenicity of the tissue substrate. The aim of this study was to investigate the association between local CV versus late gadolinium enhancement (LGE) and myocardial wall thickness in a swine model of healed left ventricular infarction. Methods: Six swine with healed myocardial infarction underwent cardiovascular magnetic resonance imaging and electroanatomic mapping. Two healthy controls (one treated with amiodarone and one unmedicated) underwent electroanatomic mapping with identical protocols to establish the baseline CV. CV was estimated using a triangulation technique. LGE+ regions were defined as signal intensity >2 SD than the mean of remote regions, wall thinning+ as those with wall thickness Results: Significantly slower CV was observed in LGE+ (0.33±0.25 versus 0.54±0.36 m/s; P P P P Conclusions: Slower CV is observed in the presence of LGE, myocardial wall thinning, high LGE heterogeneity, and a high wall thickness gradient. Cardiovascular magnetic resonance may offer a valuable imaging surrogate for estimating CV, which may support noninvasive identification of the arrhythmogenic substrate.

Introduction: Atherosclerotic abdominal aortic plaque (AAP) is often seen incidentally on magnetic resonance (MR) scans. Prevalence and burden of AAP are associated with cardiovascular disease (CVD) risk factors, but the relationship between AAP and all-cause mortality (“Death”) is not well characterized. We sought to determine whether AAP predicts Death among community-dwelling adults initially without clinically overt CVD. Methods: 318 Framingham Offspring cohort members (age 60±9 yrs, 51% women) underwent noncontrast abdominal MR at 1.5 Tesla in 1998-1999. Participants were recruited from equal strata of age, sex and quintile of Framingham Risk Score (FRS), with double sampling of the top quintile. MR used ECG-triggered black-blood T2W turbo spin-echo with 1.03 x 0.64 x 5-mm 3 voxels. AAP was hand-traced and comprised discrete protrusions of ≥1mm into the aortic lumen. Participants were stratified into three levels of AAP: zero (AAP0); then among those with nonzero-AAP, subdivided into below median (AAP1) and above median (AAP2). FRS was calculated for each participant (using age, sex, systolic blood pressure, total and HDL cholesterol, diabetes, smoking); A Cox proportional hazards model adjusted for standardized, log-transformed FRS (zFRS) was used to determine hazard ratio (HR) for Death with AAP0 as the referent. The log-rank test was used to compare event-free survival. Results: AAP by MR was present in 40.4% of women and 42.1% of men. Over a median 14.8 years of follow up, there were 52 Deaths (5 CVD, 22 cancer, 25 other causes). AAP2 had HR=2.08 (95% CI 1.07 - 4.08, p=0.03); AAP1 was HR=1.37 (CI=0.65 - 2.92, p=0.4). The figure shows the Kaplan-Meier plot for survival; log-rank p=0.034. Conclusions: Among adults initially free of clinically overt CVD, above median burden of AAP was associated with 2-fold greater hazard of all-cause mortality. Although the majority of deaths were not principally due to CVD, excess AAP was a predictor of mortality over nearly 15 year follow up.

Background— The age cutoff to define elderly is controversial in cardiac surgery, empirically ranging from ≥65 to ≥80 years. Beyond semantics, this has important implications as a starting point for clinical care pathways and inclusion in trials. We sought to characterize the relationship between age and adverse outcomes in patients undergoing cardiac surgery and to derive and validate prognosis-based age cutoffs. Methods and Results— Six thousand five hundred seventy one consecutive adult patients undergoing cardiac surgery at 3 hospitals in the United States and Canada were included in the cohort. Logistic regression models and generalized additive models with thin-plate splines were fit to the data. The age distribution was 50 to 59 years in 1244 (18.9%), 60 to 69 years in 2144 (32.6%), 70 to 79 years in 2000 (30.4%), ≥80 years in 1183 (18.0%) patients. After controlling for sex and type of operation, the relationship between age and 30-day operative mortality was found to be nonlinear. Receiver operating characteristic analysis showed that the optimal cutoffs to identify older patients at higher risk of operative mortality were greater than 74, 78, and 75 years for isolated coronary bypass, isolated valve surgery, and coronary bypass plus valve surgery, respectively. These age cutoffs were validated in an independent cohort. Conclusions— The relationship between age and operative mortality is not linear, manifesting a steeper rise after age 75 for coronary bypass and approaching octogenarian age for isolated valve surgery. Rather than using arbitrary age cutoffs to define elderly, the outcomes-based cutoff of ≥75 years should be used to identify the population of older adults that has higher risk and may benefit from preoperative geriatric evaluation and optimization.

BACKGROUND AND IMPORTANCE: Alcohol dependence is related to dysfunctional brain processes, in which a genetic background and environmental factors shape brain mechanisms involved with alcohol consumption. Craving, a major component determining relapses in alcohol abuse, has been linked to abnormal brain activity. CLINICAL PRESENTATION: We report the results of a treatment-intractable, alcohol-addicted patient with associated agoraphobia and anxiety. Functional imaging studies consisting of functional magnetic resonance imaging and resting-state electroencephalogram were performed as a means to localize craving-related brain activation and for identification of a target for repetitive transcranial magnetic stimulation and implant insertion. Repetitive transcranial magnetic stimulation of the dorsal anterior cingulate cortex with a double-cone coil transiently suppressed his very severe alcohol craving for up to 6 weeks. For ongoing stimulation, 2 "back-to-back" paddle electrodes were implanted with functional magnetic resonance imaging neuronavigation guidance for bilateral dorsal anterior cingulate cortex stimulation. Using a recently developed novel stimulation design, burst stimulation, a quick improvement was obtained on craving, agoraphobia, and associated anxiety without the expected withdrawal symptoms. The patient has remained free of alcohol intake and relieved of agoraphobia and anxiety for over 18 months, associated with normalization of his alpha and beta activity on electroencephalogram in the stimulated area. He perceives a mental freedom by not being constantly focused on alcohol. CONCLUSION: This case report proposes a new pathophysiology-based target for the surgical treatment of alcohol dependence and suggests that larger studies are warranted to explore this potentially promising avenue for the treatment of intractable alcohol dependence with or without anxiety and agoraphobia. ABBREVIATIONS: ACC, anterior cingulate cortexBOLD, blood oxygen level dependentdACC, dorsal anterior cingulate cortexDBS, deep brain stimulationEEG, electroencephalogramfMRI, functional magnetic resonance imagingrTMS, repetitive transcranial magnetic stimulationSMA, supplementary motor areaTMS, transcranial magnetic stimulation. Language: en

Background: Cross-sectional studies demonstrate that women are often under-represented in key-leadership roles. We sought to examine the proportion of women in cardiology leadership positions and to compare the findings with the disparity prevalent in the overall cardiology faculty. Furthermore, we aspired to compare the proportion of women in leadership positions to the proportion in which they entered the cardiology field. Methods: Cardiology fellowship training programs of all teaching hospitals of the United States were identified from Fellowship and Residency Electronic Interactive Database (AMA FREIDA). Program directors and division chiefs were identified from the institutions’ websites, and their research statistics and years of graduation were extracted from Scopus and Doximity. Results: Data of all (n=512) cardiology fellowship program directors, as well as 69% (n=140) of cardiology division chiefs were collected. A lower percentage of women held the role of division chief (5% vs. 95%) or program director (14% vs. 86%). However, when compared to the proportion of women in the 1992 fellowship cohort, women were significantly overrepresented in the role of program directors, with no significant difference in representation at the level of division chief. When compared to the overall cardiology faculty, program directors had significantly more publications and were more likely to have an academic rank of full professor (40% vs. 28%) or associate professor (37% vs. 23%). Male program directors had a significantly higher number of research publications, H-index and academic rank than their female counterparts; however, such difference was not seen at the level of division chief. Conclusion: Gender disparity is present in both cardiology program director and division chief roles. However, when compared to the historical cohort, significant overrepresentation of women was seen in the program director position, while proportionate representation was seen in the division chief role.

Introduction: Increased left ventricular mass (LVM) predicts excess cardiovascular morbidity and mortality. LVM is often indexed to height (HT) or body surface area (BSA). HT-indexation ignores weight and thus obesity. The relationship of indexed LVM with weight, obesity, and adiposity is unclear. We investigated the association of LVM with total-body mass (TBM, i.e. weight) and fat-free mass (FFM), hypothesizing that LVM scales better to FFM than TBM. Methods: From the 1794 members of Framingham Offspring cohort who underwent cardiac magnetic resonance (CMR), we identified 845 (aged 65±9y) without any history of hypertension, myocardial infarction, heart failure, or CMR wall-motion abnormality. LVM was measured from cine bSSFP images and indexed to HT, BSA, TBM and FFM (by DEXA). Participants were stratified by sex and body mass index (BMI) category (NL=BMI 18.5 - 24.9; OW=25.0 - 29.9; OB=30.0+ kg/m 2 ). We used sex-specific ANCOVA to test for linear trend across BMI categories, and determined sex-specific Pearson correlation coefficients of LVM with BMI; both sets of analyses were adjusted for age and systolic blood pressure. Data are summarized as mean ± SD. Results: The Table shows that LVM and LVM/HT increase with greater BMI-category in both sexes. LVM/BSA was similar across BMI-categories, while LVM/TBM decreased. There was no linear trend across BMI-categories for LVM/FFM in either sex. On a continuous basis, LVM and LVM/HT were positively correlated with BMI in both sexes (r=0.20 to 0.35, p Conclusion: LVM as a proportion of TBM (weight) actually decreases with greater BMI, while LVM/FFM is not associated with BMI. Whether LVM is better scaled to FFM vs HT, BSA or TBM for risk stratification purposes remains to be determined.

Background— Cross-sectional epidemiological and clinical research suggests that lower cardiac index is associated with abnormal brain aging, including smaller brain volumes, increased white matter hyperintensities, and worse cognitive performances. Lower systemic blood flow may have implications for dementia among older adults. Methods and Results— A total of 1039 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, and dementia formed our sample (age, 69±6 years; 53% women). Multivariable-adjusted proportional hazard models adjusting for Framingham Stroke Risk Profile score (age, sex, systolic blood pressure, antihypertensive medication, diabetes mellitus, cigarette smoking, cardiovascular disease history, atrial fibrillation), education, and apolipoprotein E4 status related cardiac magnetic resonance imaging–assessed cardiac index (cardiac output divided by body surface area) to incident all-cause dementia and Alzheimer disease (AD). Over the median 7.7-year follow-up period, 32 participants developed dementia, including 26 cases of AD. Each 1-SD unit decrease in cardiac index increased the relative risk of both dementia (hazard ratio [HR]=1.66; 95% confidence interval [CI], 1.11–2.47; P =0.013) and AD (HR=1.65; 95% CI, 1.07–2.54; P =0.022). Compared with individuals with normal cardiac index, individuals with clinically low cardiac index had a higher relative risk of dementia (HR=2.07; 95% CI, 1.02–4.19; P =0.044). If participants with clinically prevalent cardiovascular disease and atrial fibrillation were excluded (n=184), individuals with clinically low cardiac index had a higher relative risk of both dementia (HR=2.92; 95% CI, 1.34–6.36; P =0.007) and AD (HR=2.87; 95% CI, 1.21–6.80; P =0.016) compared with individuals with normal cardiac index. Conclusion— Lower cardiac index is associated with an increased risk for the development of dementia and AD.

Introduction: Greater burden of pericardial fat is associated with increased body mass index (BMI). Obesity is associated with unfavorable metabolic characteristics such as hypertension, dyslipidemia, and glucose intolerance. We sought to determine whether increased pericardial fat thickness (PFT) was associated with unfavorable metabolic profile alone, in the absence of excess BMI. Methods: From the 1,794 Framingham Offspring cohort adults who underwent cardiac magnetic resonance (CMR), we identified 446 free of non-skin cancer and prevalent clinical cardiovascular disease (CVD) who had 18.5≤BMI2 and complete covariates. We calculated a metabolic score (MS) based on ATPIII criteria where 1 point was assigned for each of: a) fasting plasma glucose≥100 mg/dL or diabetes; b) SBP≥130 or DBP≥85 mm Hg or antihypertensive treatment; c) triglycerides≥150 mg/dL; d) HDL cholesterol Results: PFT increased with worsening metabolic score (see Table) at the fixed locations of the apical and mid-level RV, as well as at maximal PFT. On pairwise comparisons, only the MS3+ group had PFT that was consistently significantly greater than that of MS0 (all p Conclusions: In a community-dwelling cohort, among participants who were free of cancer and clinical CVD and had normal-range or “healthy” BMI, worsening metabolic profile was associated with increased pericardial fat thickness.

Background and Purpose— Thromboembolism in paroxysmal atrial fibrillation (AF) has often been attributed to occult AF. We hypothesized that the surface ECG may not always reflect left atrial appendage (LAA) mechanical function. Methods— Transesophageal echocardiographic images from 201 consecutive patients undergoing transesophageal echocardiography by a single operator were reviewed. LAA pulse wave Doppler phenotype, ECG rhythm, and mitral valve motion for rhythm of the body of the left atrium and the electronic medical record were reviewed by 3 blinded, independent observers. Results— Of 201 patients (63.4±15 years; 61% men) undergoing transesophageal echocardiography, 15 (7.5%) demonstrated LA–LAA discordance including 7 (3.5%) with a sinus rhythm ECG/mitral valve motion and an AF LAA pulse wave Doppler phenotype. Of 24 patients with a clinical history of AF but sinus rhythm ECG, 25% demonstrated a discordant AF LAA pulse wave Doppler phenotype. Compared with concordant AF, the AF discordant group had greater CHA2DS2-VASc (CHADS2, vascular disease, age, sex category; P =0.008) and lower LAA ejection velocity ( P =0.02). Conclusions— A quarter of patients with paroxysmal AF demonstrate a prothrombotic AF LAA pulse wave Doppler phenotype, despite concurrent sinus rhythm ECG. These findings provide a novel explanation for ongoing thromboembolism in the paroxysmal AF population, despite apparent ECG maintenance of sinus rhythm.

This observer performance study assessed lesion detection in the computed tomography attenuation correction image, as would be produced for myocardial perfusion imaging over a tube current (mA) range. A static anthropomorphic chest phantom containing simulated pulmonary lesions was scanned using the four available mA values (1, 1.5, 2 and 2.5) on a GE Infinia Hawkeye 4. All other computed tomography acquisition parameters remained constant throughout. Twenty-seven cases showing zero to four lesions were produced for a free-response receiver-operating characteristic method. Image observations were completed using our novel web-based ROCView software under controlled conditions. The Jackknife alternative free-response receiver-operating characteristic (JAFROC) figure of merit was used for significance testing, wherein a difference in lesion detection performance was considered significant at P values less than 0.05. Twenty readers with varying computed tomography experience (0–24 years) evaluated 108 images using an ordinal scale to score confidence. The JAFROC analysis showed that there was no statistically significant difference in performance between mA values (P =0.439) for this sample of observers. In conclusion, no significant difference in lesion detection performance was seen between the mA values. This suggests that there is no value in using anything other than the lowest mA value for the investigation of incidental extracardiac findings.

Atrial fibrillation (AF) is the most common sustained arrhythmia, afflicting >5 million people in the United States alone1 and associated with considerable morbidity because of migration of left atrial (LA) and specifically left atrial appendage (LAA) thrombi. A combination of LA anatomic, inflammatory, and metabolic changes results in abnormalities in both flow characteristics, endothelial function, and blood constituents. Thus, AF creates an hypercoagulable state in the LA by virtue of fulfilling Virchow’s triad of thrombogenesis.2 Although the CHADS2 and CHA2DS2-VASc risk scores are clinically useful for identifying AF patients who are at high risk for thromboembolism,3 they are imperfect (C statistics 0.60–0.69).4,5 They concentrate on the clinical substrate and do not consider local physiological factors such as LA/LAA flow, which are likely to offer higher fidelity discrimination of those at highest risk for thrombus formation. See Article by Markl et al The essence of cardiology is blood flow, but noninvasive tools to comprehensively characterize intracavitary blood flow dynamics have been lacking. Cardiovascular magnetic resonance (CMR) is already recognized as the noninvasive clinical gold standard for the assessment of cardiac volumes, regional/global systolic function, fibrosis, and inflammation.6,7 More recently, 2D phase-contrast CMR has been shown to be clinically important for assessment of mitral regurgitation.8 Advancement in flow visualization have now provided us with more powerful tools for in vivo multidirectional blood flow assessment using either phase-contrast CMR, echocardiography particle imaging velocimetry, and echocardiography vector flow mapping.9 These novel tools enable us to verify and continue Leonardo Da Vinci’s quest to study intracavitary flow dynamics10 and provide new insights regarding intracardiac flow—revealing asymmetrical spiral flow in the heart chambers and great arteries that have pivotal importance in physiological and pathological conditions.11 The use of …

Introduction: Persons with normal-range body mass index (BMI) but adverse metabolic characteristics associated with obesity have been described as metabolically-obese normal weight (MONW). We sought to determine whether adverse metabolic profile is associated with alterations in left ventricular (LV) structure or function among adults with normal BMI. Methods: From the 1794 Framingham Offspring cohort adults who underwent cardiac magnetic resonance (CMR), we identified 446 free of non-skin cancer and prevalent clinical cardiovascular disease (CVD) who had 18.5≤BMI Results: LV concentricity increased with worsening metabolic status (see Table); this was driven by lower LV EDV, not increased LVM. LVM did not differ across (trend) or between MS-groups. LVEDV decreased across groups but only MS2 differed significantly from MS0. LVEF increased slightly but significantly across MS-groups. Conclusions: In a community-dwelling cohort, among participants who were free of cancer and clinical CVD and had normal BMI, worsening metabolic profile was associated with adverse remodeling of the left ventricle, reflected by greater LV concentricity.

Background— Cardiac magnetic resonance is uniquely well suited for noninvasive imaging of the right ventricle. We sought to define normal cardiac magnetic resonance reference values and to identify the main determinants of right ventricular (RV) volumes and systolic function using a modern imaging sequence in a community-dwelling, longitudinally followed cohort free of clinical cardiovascular and pulmonary disease. Methods and Results— The Framingham Heart Study Offspring cohort has been followed since 1971. We scanned 1794 Offspring cohort members using steady-state free precession cardiac magnetic resonance and identified a reference group of 1336 adults (64±9 years, 576 men) free of prevalent cardiovascular and pulmonary disease. RV trabeculations and papillary muscles were considered cavity volume. Men had greater RV volumes and cardiac output before and after indexation to body size (all P P Conclusions— We report sex-specific normative values for RV measurements among principally middle-aged and older adults. RV ejection fraction is greater in women. RV volumes increase with body size, are greater in men, and are smaller in older people. Body surface area seems to be appropriate for indexation of cardiac magnetic resonance–derived RV volumes.

Introduction: Aortic plaque can be seen on noncontrast cardiovascular magnetic resonance (CMR) imaging. We sought to determine the prevalence, distribution and burden, or quantitative amount, of CMR-detected thoracic (TAP) and abdominal (AAP) aortic plaque in a community-dwelling cohort of adults. Methods: 1794 Framingham Offspring cohort members underwent ECG-gated, fat-suppressed, T2-weighted TSE black blood aortic CMR at 1.5T: 1.03 x 0.64-mm pixels, 5-mm slice thickness. We obtained 12 thoracic (above diaphragm, 1-cm interslice gap) slices and 24 abdominal (below diaphragm/above aortic bifurcation, 5-mm gap) slices. Plaque protruding ≥1mm into the lumen was traced on each slice and summed to determine AAP and TAP burdens. Participants were stratified by sex and 10-year age groups. We tabulated number of persons with prevalent (i.e. >0) AAP and TAP and tested for trend (Cochrane-Armitage) across age groups. Among those with plaque>0, we determined upper 90th percentile (P90) plaque burden, if the sex/age-group had ≥20 persons with prevalent plaque (we felt calculations based on N Results: Complete aortic studies were available on 1726 adults aged 65±9y (47% men). AAP was more prevalent than TAP: 359/806 (44.5%) men and 430/920 (46.7%) women had AAP, p=0.26; 72/806 (8.9%) men and 65/920 (7.1%) women had TAP, p=0.15. The Table shows sex-specific distributions and burdens of plaque by age-group, where +AAP (+TAP) indicates abdominal (thoracic) aortic plaque is present. Prevalence of both AAP and TAP increased monotonically with age (p Conclusions: Among middle-aged and older community dwelling adults, AAP is seen on noncontrast CMR in 45.7%, while TAP is less prevalent at 7.9%. Prevalence of aortic plaque did not differ between men and women and increases with age in both sexes. Burden (amount) of AAP also increases with greater age.

Background— In hypertrophic cardiomyopathy (HCM), the arrhythmic potential associated with a variety of left ventricular myocardial signal intensities evident on contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is unresolved. Methods and Results— In 145 HCM patients (43±15 years old), visually identified areas of LGE in left ventricle were analyzed quantitatively for intermediate (≥4 but P =0.003 to P =0.02–0.003) than patients without these arrhythmias. In HCM patients with either nonsustained ventricular tachycardia, couplets, or premature ventricular contractions, the extent of intermediate LGE-SI exceeded that of high LGE-SI (17±7 versus 15±6 g, 16±10 versus 14±9 g, and 13±8 versus 12±7 g, respectively; P =0.01–0.04). In addition, the receiver operating characteristic area under the curve established intermediate LGE-SI as a better discriminator of patients with nonsustained ventricular tachycardia than was high LGE-SI, with 7 additional patients with this arrhythmia identified. Conclusions— In patients with HCM, intermediate LGE-SI is a better predictor of ventricular tachyarrhythmias (including nonsustained ventricular tachycardia, a risk factor for sudden death) than is high LGE-SI. Longitudinal studies in larger HCM cohorts are justified to define the independent prognostic impact of intermediate LGE-SI.

Background— Whether morphological abnormalities of the mitral valve represent part of the hypertrophic cardiomyopathy (HCM) disease process is unresolved. Therefore, we applied cardiovascular magnetic resonance to characterize mitral valve morphology in a large HCM cohort. Methods and Results— Cine cardiac magnetic resonance images were obtained in 172 HCM patients (age, 42±18 years; 62% men) and 172 control subjects. In addition, 15 HCM gene-positive/phenotype-negative relatives were studied. Anterior mitral leaflet (AML) and posterior mitral leaflet lengths were greater in HCM patients than in control subjects (26±5 versus 19±5 mm, P P 2 SDs above controls). Leaflet length was increased compared with controls in virtually all HCM age groups, including young patients 15 to 20 years of age (AML, 26±5 versus 21±4 mm; P =0.0002) and those ≥60 years of age (AML, 26±4 versus 19±2 mm; P P =0.09 and P =0.16, respectively). A ratio of AML length to LV outflow tract diameter of >2.0 was associated with subaortic obstruction ( P =0.001). In addition, AML length in 15 genotype-positive relatives without LV hypertrophy exceeded that of matched control subjects (21±3 versus 18±3 mm; P Conclusions— In HCM, mitral valve leaflets are elongated independently of other disease variables, likely constituting a primary phenotypic expression of this heterogeneous disease, and are an important morphological abnormality responsible for LV outflow obstruction in combination with small outflow tract dimension. These findings suggest a novel role for cardiac magnetic resonance in the assessment of HCM.

Reduced heart rate variability (HRV) reflects autonomic dysfunction and can triage patients better than routine trauma criteria or vital signs. However, there is questionable specificity and no consensus measurement technique. The purpose of this study was to analyze whether factors that alter autonomic function affect the specificity of HRV for assessing traumatic injury.We evaluated 216 hemodynamically stable adults (3:1 M:F; 97:3 blunt:penetrating; age 49 years ± 1 year, mean ± standard error) undergoing computed axial tomography (CT) scan to rule out traumatic brain injury (TBI). All were prospectively instrumented with a Mars Holter system (GE Healthcare, Milwaukee, WI). HRV was determined offline using time domain (standard deviation of normal-normal intervals, root-mean-square successive difference) and frequency domain (very low frequency [VLF], LF, wideband frequency, high frequency [HF], low to HF index ratio) calculations from 15-minute electrocardiogram and correlated with routine vital signs, mortality, TBI, morbidity, length of stay (LOS), and comorbidities. Significance (p ≤ 0.05) was determined using nonparametric analysis, Student's t test, analysis of variance, or multiple logistic regression.VLF alone predicted survival, severity of TBI, intensive care unit LOS, and hospital LOS (all p0.05). Beta-blockers or diabetes had no effect, whereas age, sedation, mechanical ventilation, spinal cord injury, and intoxication influenced one or more of the variables with age being the most powerful confounder (all p0.05). Except for the Glasgow Coma Scale, no other routine trauma or hemodynamic criteria correlated with any of these outcomes.Decreased VLF is an independent predictor of mortality and morbidity in hemodynamically stable trauma patients. Other time and other frequency domain variables correlated with some, but not all, outcomes. All were heavily influenced by factors that alter autonomic function, especially patient age.

Background— Data regarding the relationships of diabetes, insulin resistance, and subclinical hyperinsulinemia/hyperglycemia with cardiac structure and function are conflicting. We sought to apply volumetric cardiovascular magnetic resonance (CMR) in a free-living cohort to potentially clarify these associations. Methods and Results— A total of 1603 Framingham Heart Study Offspring participants (age, 64�9 years; 55% women) underwent CMR to determine left ventricular mass (LVM), LVM to end-diastolic volume ratio (LVM/LVEDV), relative wall thickness (RWT), ejection fraction, cardiac output, and left atrial size. Data regarding insulin resistance (homeostasis model, HOMA-IR) and glycemia categories (normal, impaired insulinemia or glycemia, prediabetes, and diabetes) were determined. In a subgroup (253 men, 290 women) that underwent oral glucose tolerance testing, we related 2-hour insulin and glucose with CMR measures. In both men and women, all age-adjusted CMR measures increased across HOMA-IR quartiles, but multivariable-adjusted trends were significant only for LVM/ht 2.7 and LVM/LVEDV. LVM/LVEDV and RWT were higher in participants with prediabetes and diabetes (in both sexes) in age-adjusted models, but these associations remained significant after multivariable adjustment only in men. LVM/LVEDV was significantly associated with 2-hour insulin in men only, and RWT was significantly associated with 2-hour glucose in women only. In multivariable stepwise selection analyses, the inclusion of body mass index led to a loss in statistical significance. Conclusions— Although insulin and glucose indices are associated with abnormalities in cardiac structure, insulin resistance and worsening glycemia are consistently and independently associated with LVM/LVEDV. These data implicate hyperglycemia and insulin resistance in concentric LV remodeling.

To compare 3 different flow targeted magnetization preparation strategies for coronary MR angiography (cMRA), which allow selective visualization of the vessel lumen.The right coronary artery of 10 healthy subjects was investigated on a 1.5 Tesla MR system (Gyroscan ACS-NT, Philips Healthcare, Best, NL). A navigator-gated and ECG-triggered 3D radial steady-state free-precession (SSFP) cMRA sequence with 3 different magnetization preparation schemes was performed referred to as projection SSFP (selective labeling of the aorta, subtraction of 2 data sets), LoReIn SSFP (double-inversion preparation, selective labeling of the aorta, 1 data set), and inflow SSFP (inversion preparation, selective labeling of the coronary artery, 1 data set). Signal-to-noise ratio (SNR) of the coronary artery and aorta, contrast-to-noise ratio (CNR) between the coronary artery and epicardial fat, vessel length and vessel sharpness were analyzed.All cMRA sequences were successfully obtained in all subjects. Both projection SSFP and LoReIn SSFP allowed for selective visualization of the coronary arteries with excellent background suppression. Scan time was doubled in projection SSFP because of the need for subtraction of 2 data sets. In inflow SSFP, background suppression was limited to the tissue included in the inversion volume. Projection SSFP (SNR(coro): 25.6 +/- 12.1; SNR(ao): 26.1 +/- 16.8; CNR(coro-fat): 22.0 +/- 11.7) and inflow SSFP (SNR(coro): 27.9 +/- 5.4; SNR(ao): 37.4 +/- 9.2; CNR(coro-fat): 24.9 +/- 4.8) yielded significantly increased SNR and CNR compared with LoReIn SSFP (SNR(coro): 12.3 +/- 5.4; SNR(ao): 11.8 +/- 5.8; CNR(coro-fat): 9.8 +/- 5.5; P0.05 for both). Longest visible vessel length was found with projection SSFP (79.5 mm +/- 18.9; P0.05 vs. LoReIn) whereas vessel sharpness was best in inflow SSFP (68.2% +/- 4.5%; P0.05 vs. LoReIn). Consistently good image quality was achieved using inflow SSFP likely because of the simple planning procedure and short scanning time.Three flow targeted cMRA approaches are presented, which provide selective visualization of the coronary vessel lumen and in addition blood flow information without the need of contrast agent administration. Inflow SSFP yielded highest SNR, CNR and vessel sharpness and may prove useful as a fast and efficient approach for assessing proximal and mid vessel coronary blood flow, whereas requiring less planning skills than projection SSFP or LoReIn SSFP.

Background— Pericardial fat has been implicated in the pathogenesis of obesity-related cardiovascular disease. Whether the associations of pericardial fat and measures of cardiac structure and function are independent of the systemic effects of obesity and visceral adiposity has not been fully explored. Methods and Results— Participants from the Framingham Heart Study (n=997; 54.4% women) underwent chest and abdominal computed tomography and cardiovascular magnetic resonance imaging between 2002 and 2005. Pericardial fat, intrathoracic fat, and visceral adipose tissue quantified from multidetector computed tomography, along with body mass index and waist circumference, were examined in relation to cardiovascular magnetic resonance measures of left ventricular (LV) mass, LV end-diastolic volume, and left atrial dimension. In women, pericardial fat ( r =0.20 to 0.35, P r =0.25 to 0.37, P r =0.24 to 0.45, P r =0.36 to 0.53, P r =0.30 to 0.48, P r =0.19 to 0.37, P r =0.17 to 0.31, P r =0.19 to 0.36, P r =0.32 to 0.44, P r =0.34 to 0.44, P Conclusions— Pericardial fat is correlated with cardiovascular magnetic resonance measures, but the association is not independent of or stronger than other ectopic fat stores or proxy measures of visceral adiposity. An important exception is left atrial dimension in men. These results suggest that the systemic effects of obesity on cardiac structure and function may outweigh the local pathogenic effects of pericardial fat.

Objective— The scavenger receptors SR-A and CD36 have been implicated in macrophage foam cell formation during atherogenesis and in the regulation of inflammatory signaling pathways, including those leading to lesional macrophage apoptosis and plaque necrosis. To test the impact of deleting these receptors, we generated Apoe −/− mice lacking both SR-A and CD36 and fed them a Western diet for 12 weeks. Methods and Results— We analyzed atheroma in mice, assessing lesion size, foam cell formation, inflammatory gene expression, apoptosis, and necrotic core formation. Aortic root atherosclerosis in Apoe −/− Cd36 −/− Msr1 −/− mice, as assessed by morphometry, electron microscopy, and immunohistochemistry, showed no decrease in lesion area or in vivo foam cell formation when compared to Apoe −/− mice. However, Apoe −/− Cd36 −/− Msr1 −/− lesions showed reduced expression of inflammatory genes and morphological analysis revealed a ≈30% decrease in macrophage apoptosis and a striking ≈50% decrease in plaque necrosis in aortic root lesions of these mice. Conclusions— Although targeted deletion of SR-A and CD36 does not abrogate macrophage foam cell formation or substantially reduce atherosclerotic lesion area in Apoe −/− mice, loss of these pathways does reduce progression to more advanced necrotic lesions. These data suggest that targeted inhibition of these pathways in vivo may reduce lesional inflammation and promote plaque stability.

Background— Contrast-enhanced cardiovascular magnetic resonance with delayed enhancement (DE) can provide in vivo assessment of myocardial fibrosis. However, the clinical significance of DE in hypertrophic cardiomyopathy (HCM) remains unresolved. Methods and Results— Cine and cardiovascular magnetic resonance with DE were performed in 202 HCM patients (mean age, 42�17 years; 71% male), DE was compared with clinical and demographic variables, and patients were followed up for 681�249 days for adverse disease events. DE was identified in 111 (55%) HCM patients, occupying 9%�11% of left ventricular myocardial volume, including >25% DE in 10% of patients. The presence of DE was related to occurrence of heart failure symptoms ( P =0.05) and left ventricular systolic dysfunction ( P =0.001). DE was present in all patients with ejection fraction ≤50% but also in 53% (102/192) of patients with preserved ejection fraction ( P r =−0.3; P r =−0.4; P P =0.5). Conclusions— In a large HCM cohort, DE was an independent predictor of systolic dysfunction but with only a modest relationship to heart failure symptoms. These data suggest an important role for myocardial fibrosis in the clinical course of HCM patients but are not sufficient at this time to consider DE as an independent risk factor for adverse prognosis.

Advances in magnetic resonance (MR) imaging over the past 2 decades have led to MR becoming an increasingly attractive imaging modality. With the growing number of patients treated with permanent implanted or temporary cardiovascular devices, it is becoming ever more important to clarify safety issues in regard to the performance of MR examinations in patients with these devices. Extensive, although not complete, ex vivo, animal, and clinical data are available from which to generate recommendations regarding the safe performance of MR examination in patients with cardiovascular devices, as well as to ascertain caveats and contraindications regarding MR examination for such patients. Safe MR imaging involves a careful initial patient screening, accurate determination of the permanent implanted or temporary cardiovascular device and its properties, a thoughtful analysis of the risks and benefits of performing the examination at that time, and, when indicated, appropriate physician management and supervision. This scientific statement is intended to summarize and clarify issues regarding the safety of MR imaging in patients with cardiovascular devices.

Background— Patients with type 1 diabetes and nephropathy maintain an excess cardiovascular mortality compared with diabetic patients with normoalbuminuria. We sought to evaluate coronary and aortic atherosclerosis in a cohort of asymptomatic type 1 diabetic patients with and without diabetic nephropathy using cardiovascular magnetic resonance imaging. Methods and Results— In a cross-sectional study, 136 subjects with long-standing type 1 diabetes without symptoms or history of cardiovascular disease, including 63 patients (46%) with nephropathy and 73 patients with normoalbuminuria, underwent cardiovascular magnetic resonance imaging. All subjects underwent cardiac exercise testing and noninvasive tests for peripheral artery disease and autonomic neuropathy. Coronary artery stenoses were identified in 10% of subjects with nephropathy (versus 0% with normoalbuminuria; P =0.007). Coronary plaque burden, expressed as right coronary artery mean wall thickness (1.7±0.3 versus 1.3±0.2 mm; P P P =0.28) and abdominal aortic plaque (22% versus 16%; P =0.7) was similar in both groups. Subjects with and without abdominal aortic plaques had similar coronary plaque burden. Conclusions— In asymptomatic type 1 diabetes, cardiovascular magnetic resonance imaging reveals greater coronary plaque burden in subjects with nephropathy compared with those with normoalbuminuria.

Intensive care unit (ICU) patients comprise a small proportion of patients in the hospital but consume a disproportionate amount of hospital resources. In our cost-conscious environment, it becomes necessary to address the overall performance of our ICUs. This study was designed to analyze survival among trauma ICU (TICU) patients with a length of stay (LOS)1 month.We retrospectively reviewed the prospectively collected Trauma Registry Database between January 1, 1995, and January 1, 2005, in an adult TICU from a Level I trauma center. Data on demographics, mechanism of injury, Injury Severity Score (ISS), LOS, and in-hospital survival was collected. Descriptive statistics were calculated and student's t test and comparison of proportions were performed where appropriate. Logistic regression was performed to analyze independent predictors of mortality with significance when p0.05.The initial cohort consisted of 3,556 patients with a mean LOS of 9.8 days (range, 0-274 days). Sixty-nine percent were men, mean age was 44.3 years (range, 0-104 years), and mean ISS was 18 (range, 0-75). The mechanism of injury was blunt trauma in 75%, burns in 15%, and penetrating trauma in 10%. Overall survival was 87%. A total of 339 patients had a LOS1 month. There was no difference in survival between patients with a LOS1 month and those with a LOS1 month (87.1% versus 86.7%). Patients50 years old (n = 1,251) had a longer LOS (12.5 versus 8.4 days; p0.001) and increased mortality (22.1% versus 8.0%; p0.001). Age remained an independent predictor of mortality when controlling for ISS.In our TICU population, extended LOS did not preclude a significant chance of survival. Patients50 years old had longer LOS and increased mortality. This suggests that the utilization of resources in patients with a prolonged LOS is reasonable and justified.

Introduction: In hypertrophic cardiomyopathy (HCM), there are significant variations in left ventricular (LV) wall thickness and fibrosis, which necessitates a volumetric coverage. Slice-interleaved T1 (STONE) mapping sequence allows for the assessment of native T1 time with complete coverage of LV myocardium. Hypothesis: We hypothesized that STONE sequence is useful for the assessment of regional native T1 time abnormality in HCM patients. Methods: Twenty-four septal HCM patients (56±16 years) and 10 healthy adult control subjects (57±15 years) were studied. Native T1 mapping was performed using STONE sequence which enables acquisition of 5 slices in the short-axis plane within a 90 sec free-breathing scan. We measured LV native T1 time and maximum LV wall thickness in each 16 segments from 3 slices (basal-, mid- and apical-slice) and evaluated the relationship between LV native T1 time and wall thickness. Late gadolinium enhanced (LGE) MRI was acquired to assess presence of myocardial enhancement. Results: In HCM patients, LV native T1 time was significantly elevated compared to healthy controls, regardless of presence or absence of LGE (mean native T1 time; LGE (+) segments (n=27), 1139±55 msec; LGE (-) segments (n=351), 1118±55 msec; healthy control (n=160),1065±35 msec; p Conclusions: In HCM, substantial number of segments without LGE showed elevated native T1 time, and native T1 time was correlated with LV wall thickness. Multi-slice T1 mapping by using STONE sequence could be advantageous to overcome limited cardiac coverage of conventional single-slice T1 mapping technique and to accurately detect the diffuse myocardial fibrosis in HCM patients.

Background Elevated left ventricular mass index ( LVMI ) and concentric left ventricular ( LV ) remodeling are related to adverse cardiovascular disease ( CVD ) events. The predictive utility of LV concentric remodeling and LV mass in the prediction of CVD events is not well characterized. Methods and Results Framingham Heart Study Offspring Cohort members without prevalent CVD (n=1715, 50% men, aged 65±9 years) underwent cardiovascular magnetic resonance for LVMI and geometry (2002–2006) and were prospectively followed for incident CVD (myocardial infarction, coronary insufficiency, heart failure, stroke) or CVD death. Over 13 808 person‐years of follow‐up (median 8.4, range 0.0 to 10.5 years), 85 CVD events occurred. In multivariable‐adjusted proportional hazards regression models, each 10‐g/m 2 increment in LVMI and each 0.1 unit in relative wall thickness was associated with 33% and 59% increased risk for CVD , respectively ( P =0.004 and P =0.009, respectively). The association between LV mass/ LV end‐diastolic volume and incident CVD was borderline significant ( P =0.053). Multivariable‐adjusted risk reclassification models showed a modest improvement in CVD risk prediction with the incorporation of cardiovascular magnetic resonance LVMI and measures of LV concentricity (C‐statistic 0.71 [95% CI 0.65 to 0.78] for the model with traditional risk factors only, improved to 0.74 [95% CI 0.68 to 0.80] for the risk factor model additionally including LVMI and relative wall thickness). Conclusions Among adults free of prevalent CVD in the community, greater LVMI and LV concentric hypertrophy are associated with a marked increase in adverse incident CVD events. The potential benefit of aggressive primary prevention to modify LV mass and geometry in these adults requires further investigation.

Over the past decade, coronary magnetic resonance imaging has been transformed from a scientific curiosity to a clinically useful imaging tool for patients with known or suspected anomalous coronary arteries or coronary artery aneurysms and for assessment of coronary artery bypass graft patency. Coronary magnetic resonance imaging also appears to be of clinical value for assessment of native vessel integrity in selected patients, especially those patients with suspected left main/multivessel disease. Among patients referred for X-ray angiography, a normal coronary magnetic resonance imaging strongly suggests the absence of severe multivessel disease. Technical and methodological advances in motion suppression, along with increasing clinical experience will no doubt facilitate improved visualization of the distal and branch vessel.

Background— The detection and differentiation of intracardiac masses is still challenging and may include neoplasms and thrombi. The aim of this study was the investigation of a targeted, fibrin-specific contrast agent (EP-2104R) for molecular targeted magnetic resonance imaging (MRI) of left atrial clots. Methods and Results— Chronic human thrombi were surgically implanted in the left atrial appendage of 5 swine. Molecular MRI was performed with a navigator-gated, free-breathing, cardiac-triggered 3D inversion-recovery, black-blood, gradient-echo sequence before and after systemic administration of 4 μmol/kg EP-2104R. MR images were analyzed by 2 investigators, and the contrast-to-noise ratio was calculated. Location of clots was confirmed by autopsy, and the gadolinium concentration in the clots was assessed. Before contrast agent administration, thrombi were not visible on black-blood MR images. After contrast administration, all atrial clots (n=5) were selectively visualized as white spots with a high contrast-to-noise ratio (clot/blood, 29.7±8.0). The gadolinium concentration in the clots averaged 74±45 μmol/L. Conclusions— The fibrin-specific MR contrast agent EP-2104R allows for selective and high-contrast visualization of left atrial clots by means of molecular targeted MRI.

Background Aspirin has a significant effect on hemostasis, so it is often recommended that patients taking aspirin discontinue treatment before elective surgery. While off aspirin, these patients may be at risk of thrombosis. The optimum period of time that aspirin should be withheld is controversial. The aim of this study was to establish the duration of the antihemostatic effect of prolonged aspirin therapy. Study design In a prospective study, 51 healthy volunteers were randomly assigned into 3 groups, each receiving an identical tablet for 14 days. One group received a placebo tablet; individuals in the other two groups received either 75 mg or 300 mg of aspirin once a day. Template bleeding times and specific platelet function testing (using the PFA-100; Dade Behring) were carried out on subjects before therapy and again after its completion until they returned to baseline. Results Thirty-eight volunteers complied sufficiently with the protocol to provide useful results. All bleeding times normalized within 96 hours and all platelet function tests within 144 hours after stopping aspirin. There was no demonstrable hemostatic defect in any volunteer persisting by or beyond the sixth day after treatment cessation. There was no apparent difference in duration of effect between those taking either 75 mg or 300 mg of aspirin. Conclusions This study uses sensitive measures of platelet function to demonstrate the duration of increased bleeding tendency after withdrawal of aspirin therapy. It supports discontinuation of aspirin therapy 5 days before elective surgery (with the operation being performed on the sixth day).

Background— The advent of fibrin-binding molecular magnetic resonance (MR) contrast agents and advances in coronary MRI techniques offers the potential for direct imaging of coronary thrombosis. We tested the feasibility of this approach using a gadolinium (Gd)-based fibrin-binding contrast agent, EP-2104R (EPIX Medical Inc), in a swine model of coronary thrombus and in-stent thrombosis. Methods and Results— Ex vivo and in vivo sensitivity of coronary MR thrombus imaging was tested by use of intracoronarily delivered Gd-DTPA–labeled fibrinogen thrombi (n=6). After successful demonstration, in-stent coronary thrombosis was induced by x-ray–guided placement of thrombogenic-coated, MR-lucent stents (n=5). After stent placement, 60 μmol of EP-2104R was injected via the left main coronary artery. Free-breathing, navigator-gated 3D coronary MR angiography and thrombus imaging were performed (1) before and after stent placement and (2) before and after EP-2104R. Thrombi were confirmed by x-ray angiography and autopsy. Fibrinogen thrombi: 5 of 6 intracoronarily delivered Gd-labeled fibrinogen clots (≈250 μmol/L Gd) were visible on MRI and subsequently confirmed by x-ray angiography. In-stent thrombi: in-stent thrombosis was observed in all stents after EP-2104R. Four of 5 thrombi were confirmed by x-ray angiography. Chemical analysis of 2 thrombi demonstrated 99 to 147 μmol/L Gd. Conclusions— We demonstrate the feasibility of MRI of coronary thrombus and in-stent thrombosis using a novel fibrin-binding molecular MR contrast agent. Potential applications include detection of coronary in-stent thrombosis or thrombus burden in patients with acute coronary syndromes.