Relationship of LVEF and Myocardial Scar to Long-Term Mortality Risk and Mode of Death in Patients With Nonischemic Cardiomyopathy.

BACKGROUND: Nonischemic cardiomyopathy is a leading cause of reduced left ventricular ejection fraction (LVEF) and is associated with high mortality risk from progressive heart failure and arrhythmias. Myocardial scar on cardiovascular magnetic resonance imaging is increasingly recognized as a risk marker for adverse outcomes; however, left ventricular dysfunction remains the basis for determining a patient's eligibility for primary prophylaxis with implantable cardioverter-defibrillator. We investigated the relationship of LVEF and scar with long-term mortality and mode of death in a large cohort of patients with nonischemic cardiomyopathy. METHODS: This study is a prospective, longitudinal outcomes registry of 1020 consecutive patients with nonischemic cardiomyopathy who underwent clinical cardiovascular magnetic resonance imaging for the assessment of LVEF and scar at 3 centers. RESULTS: During a median follow-up of 5.2 (interquartile range, 3.8, 6.6) years, 277 (27%) patients died. On survival analysis, LVEF ≤35% and scar were strongly associated with all-cause (log-rank test P=0.002 and P<0.001, respectively) and cardiac death (P=0.001 and P<0.001, respectively). Whereas scar was strongly related to sudden cardiac death (SCD; P=0.001), there was no significant association between LVEF ≤35% and SCD risk (P=0.57). On multivariable analysis including established clinical factors, LVEF and scar are independent risk markers of all-cause and cardiac death. The addition of LVEF provided incremental prognostic value but insignificant discrimination improvement by C-statistic for all-cause and cardiac death, but no incremental prognostic value for SCD. Conversely, scar extent demonstrated significant incremental prognostic value and discrimination improvement for all 3 end points. On net reclassification analysis, the addition of LVEF resulted in no significant improvement for all-cause death (11.0%; 95% CI, -6.2% to 25.9%), cardiac death (9.8%; 95% CI, -5.7% to 29.3%), or SCD (7.5%; 95% CI, -41.2% to 42.9%). Conversely, the addition of scar extent resulted in significant reclassification improvement of 25.5% (95% CI, 11.7% to 41.0%) for all-cause death, 27.0% (95% CI, 11.6% to 45.2%) for cardiac death, and 40.6% (95% CI, 10.5% to 71.8%) for SCD. CONCLUSIONS: Myocardial scar and LVEF are both risk markers for all-cause and cardiac death in patients with nonischemic cardiomyopathy. However, whereas myocardial scar has strong and incremental prognostic value for SCD risk stratification, LVEF has no incremental prognostic value over clinical measures. Scar assessment should be incorporated into patient selection criteria for primary prevention implantable cardioverter-defibrillator placement.

Impact of Cardiac Cycle on Thoracic Aortic Geometry-Morphometric Analysis of Ecg Gated Computed Tomography.

BACKGROUND: Understanding morphological changes of ascending aorta, aortic arch and descending aorta with cardiac and respiratory motion is critical for planning of endovascular repair of thoracic aorta. The aim of this study was to determine the impact of the cardiac cycle on thoracic aortic geometry. METHODS: In this retrospective study, electrocardiogram-gated cardiac computed tomography from 116 patients who were evaluated for transcatheter aortic valve replacement were reviewed. A protocol for measurements of maximal diameters and lengths of the thoracic aorta and supra-aortic vessels was established. Measurements were made in multiplanar views perpendicular to the semiautomatically created centerline on both systolic and diastolic phases. RESULTS: Mean age was 77 ± 11 years of our study cohort. Mean systolic and diastolic diameter were 31.6 ± 0.42 and 30.1 ± 4.4 mm at the sinotubular junction (STJ), 35.6 ± 4.8 and 34.8 ± 4.7 mm in the ascending aorta, 29.1 ± 3.3 and 28.5 ± 3.3 mm in the aortic arch (distal left common carotid artery), and 26.7 ± 5.4 and 25.8 ± 5.4 mm in the descending aorta. Mean diameter change was 1.5 ± 0.9 mm at the STJ, 0.8 ± 0.9 mm in the ascending aorta, 0.6 ± 0.8 mm in the aortic arch, and 0.9 ± 1.2 mm in the descending aorta. Mean arterial strain was 5.0 ± 3.2% at the level of the STJ, 2.4 ± 2.7% in the ascending aorta, 2.0 ± 2.9% in the aortic arch, and 3.9 ± 5.7% in the descending aorta. CONCLUSIONS: Our results demonstrated that small but significant circumferential and longitudinal strain was present at every aortic level. These findings may have implications for endovascular thoracic aortic repair and may provide reference values for future comparison.

Association of left atrial volume index and all-cause mortality in patients referred for routine cardiovascular magnetic resonance: a multicenter study.

BACKGROUND: Routine cine cardiovascular magnetic resonance (CMR) allows for the measurement of left atrial (LA) volumes. Normal reference values for LA volumes have been published based on a group of European individuals without known cardiovascular disease (CVD) but not on one of similar United States (US) based volunteers. Furthermore, the association between grades of LA dilatation by CMR and outcomes has not been established. We aimed to assess the relationship between grades of LA dilatation measured on CMR based on US volunteers without known CVD and all-cause mortality in a large, multicenter cohort of patients referred for a clinically indicated CMR scan. METHOD: We identified 85 healthy US subjects to determine normal reference LA volumes using the biplane area-length method and indexed for body surface area (LAVi). Clinical CMR reports of patients with LA volume measures (n = 11,613) were obtained. Data analysis was performed on a cloud-based system for consecutive CMR exams performed at three geographically distinct US medical centers from August 2008 through August 2017. We identified 10,890 eligible cases. We categorized patients into 4 groups based on LAVi partitions derived from US normal reference values: Normal (21-52 ml/m2), Mild (52-62 ml/m2), Moderate (63-73 ml/m2) and Severe (> 73 ml/m2). Mortality data were ascertained for the patient group using electronic health records and social security death index. Cox proportional hazard risk models were used to derive hazard ratios for measuring association of LA enlargement and all-cause mortality. RESULTS: The distribution of LAVi from healthy subjects without known CVD was 36.3 ± 7.8 mL/m2. In clinical patients, enlarged LA was associated with older age, atrial fibrillation, hypertension, heart failure, inpatient status and biventricular dilatation. The median follow-up duration was 48.9 (IQR 32.1-71.2) months. On univariate analyses, mild [Hazard Ratio (HR) 1.35 (95% Confidence Interval [CI] 1.11 to 1.65], moderate [HR 1.51 (95% CI 1.22 to 1.88)] and severe LA enlargement [HR 2.14 (95% CI 1.81 to 2.53)] were significant predictors of death. After adjustment for significant covariates, moderate [HR 1.45 (95% CI 1.1 to 1.89)] and severe LA enlargement [HR 1.64 (95% CI 1.29 to 2.08)] remained independent predictors of death. CONCLUSION: LAVi determined on routine cine-CMR is independently associated with all-cause mortality in patients undergoing a clinically indicated CMR.

Postprandial effects on arterial stiffness parameters in healthy young adults.

Postprandial lipemia has been associated with acute endothelial dysfunction. Endothelial dysfunction, in turn, is associated with increased arterial stiffness. However, the relationship between postprandial lipemia and acute changes in arterial stiffness has not been extensively investigated. Therefore, we conducted a pilot study on the effects of postprandial lipemia on arterial stiffness in 19 healthy young adults before and after consumption of a high-fat mixed meal. Arterial stiffness was assessed locally with echo-tracking carotid arterial strain (CAS) and globally with carotid-femoral pulse wave velocity (PWV). As assessed by these two benchmark parameters, arterial stiffness did not differ significantly postprandially. However, the arterial distension period (ADP) was significantly lower 2 hours after mixed meal ingestion. In addition, slopes of carotid artery area (CAA) curves were significantly steeper postprandially. Therefore, we concluded that ADP may be a more sensitive marker of arterial stiffness in healthy young adults when compared to PWV and CAS.

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

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

Longitudinal Magnetic Resonance Imaging-Based Superficial Femoral Artery Velocity Measurements in Diabetic and Nondiabetic Patients With Peripheral Artery Disease.

BACKGROUND: Longitudinal associations of noninvasive 2-dimensional phase-contrast magnetic resonance imaging (2D-PC-MRI) velocity markers of the superficial femoral artery (SFA) were analyzed along with the characteristics of peripheral artery disease (PAD). We hypothesized that the 2-year differences in MRI-based measures of SFA velocity were associated with longitudinal changes in markers of PAD. METHODS: A total of 33 (11 diabetic, 22 nondiabetic) patients with PAD with baseline and 2-year follow-up MRI scans were included in this secondary analysis of the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically gated 2D-PC-MRI was performed at a proximal and a distal location of the distal SFA territory. SFA lumen, wall, and total vessel volumes and the normalized wall index (NWI) were analyzed. RESULTS: Baseline characteristics did not differ between diabetic and nondiabetic PAD patients. Maximum proximal and distal SFA velocity measures did not differ between baseline and 2 years (41.98 interquartile range (IQR) (23.58-72.6) cm/s vs. 40.31 IQR (26.69-61.29) cm/s; P = 0.30). Pooled analysis (N = 33) showed that the 24-month change in the NWI was inversely associated with the 24-month change in the proximal maximal SFA velocity (beta = -168.36, R2 = 0.150, P value = 0.03). The 24-month change of the maximum velocity differences between the proximal and distal SFA locations was inversely associated with the 24-month changes in peak walking distance (beta = -0.003, R2 = 0.360, P value = 0.011). CONCLUSION: The 2-year change of SFA plaque burden is inversely associated with the 2-year change of proximal peak SFA blood flow velocity. 2D-PC-MRI measured SFA velocity may be of interest in assessing PAD longitudinally.

Carotid arterial wall characteristics are associated with incident ischemic stroke but not coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: Ultrasound measurements of arterial stiffness are associated with atherosclerosis risk factors, but limited data exist on their association with incident cardiovascular events. We evaluated the association of carotid ultrasound-derived arterial stiffness measures with incident coronary heart disease (CHD) and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: Carotid arterial strain and compliance, distensibility and stiffness indices, pressure-strain, and Young elastic moduli were measured in 10 407 individuals using ultrasound. Hazard ratios for incident CHD (myocardial infarction, fatal CHD, coronary revascularization) and stroke in minimally adjusted (age, sex, center, race) and fully adjusted models (minimally adjusted model+diabetes, height, weight, total cholesterol, high-density lipoprotein cholesterol, tobacco use, systolic blood pressure, antihypertensive medication use, and carotid intima-media thickness) were calculated. RESULTS: The mean age was 55.3 years. Over a mean follow-up of 13.8 years, 1267 incident CHD and 383 ischemic stroke events occurred. After full adjustment for risk factors and carotid intima-media thickness, all arterial stiffness parameters (carotid arterial strain hazard ratio [HR], 1.14 [95% CI, 1.02-1.28]; arterial distensibility HR, 1.19 [1.02-1.39]; stiffness indices HR, 1.14 [1.04-1.25]; pressure-strain HR, 1.17 [1.06-1.28]; Young elastic moduli HR, 1.13 [1.03-1.24]), except arterial compliance (HR, 1.02 [0.90-1.16], were significantly associated with incident stroke but not with CHD. CONCLUSIONS: After adjusting for cardiovascular risk factors, ultrasound measures of carotid arterial stiffness are associated with incident ischemic stroke but not incident CHD events despite that the 2 outcomes sharing similar risk factors. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00005131.

Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.

Drug-induced liver injury is the most common cause of market withdrawal of pharmaceuticals, and thus, there is considerable need for better prediction models for DILI early in drug discovery. We present a study involving 223 marketed drugs (51% associated with clinical hepatotoxicity; 49% non-hepatotoxic) to assess the concordance of in vitro bioactivation data with clinical hepatotoxicity and have used these data to develop a decision tree to help reduce late-stage candidate attrition. Data to assess P450 metabolism-dependent inhibition (MDI) for all common drug-metabolizing P450 enzymes were generated for 179 of these compounds, GSH adduct data generated for 190 compounds, covalent binding data obtained for 53 compounds, and clinical dose data obtained for all compounds. Individual data for all 223 compounds are presented here and interrogated to determine what level of an alert to consider termination of a compound. The analysis showed that 76% of drugs with a daily dose of <100 mg were non-hepatotoxic (p < 0.0001). Drugs with a daily dose of ≥100 mg or with GSH adduct formation, marked P450 MDI, or covalent binding ≥200 pmol eq/mg protein tended to be hepatotoxic (∼ 65% in each case). Combining dose with each bioactivation assay increased this association significantly (80-100%, p < 0.0001). These analyses were then used to develop the decision tree and the tree tested using 196 of the compounds with sufficient data (49% hepatotoxic; 51% non-hepatotoxic). The results of these outcome analyses demonstrated the utility of the tree in selectively terminating hepatotoxic compounds early; 45% of the hepatotoxic compounds evaluated using the tree were recommended for termination before candidate selection, whereas only 10% of the non-hepatotoxic compounds were recommended for termination. An independent set of 10 GSK compounds with known clinical hepatotoxicity status were also assessed using the tree, with similar results.

Comparison of Longitudinal Skeletal Thigh Muscle Findings With Magnetic Resonance Imaging in Patients With Peripheral Artery Disease With-Versus-Without Diabetes Mellitus.

The aim of this secondary analysis of ELIMIT (The Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial) was to determine longitudinal changes over 24 months in skeletal thigh muscle volumes and individual muscle compartments in patients with peripheral artery disease (PAD) with and without diabetes. A total of 48 patients with available magnetic resonance imaging of the distal superficial femoral artery at baseline and 2 years were included in this analysis. Muscle volumes and superficial femoral artery wall, lumen, and total vessel volumes were quantified. Intrareader reproducibility of muscle tracings was assessed with the intraclass correlation coefficient using a 2-way model. Baseline characteristics were similar between patients with PAD with and without diabetes, except for smoking history (p = 0.049), cholesterol levels (p <0.050), and calf walking pain (p = 0.049). Interobserver reproducibility of the muscle volume tracings was excellent for all muscle groups (all intraclass correlation coefficients >0.86, confidence interval 0.69 to 0.94). Total muscle and total leg volumes increased significantly between baseline and 24 months among patients with PAD without diabetes (31 ± 6.4 cm3 vs 32 ± 7.0 cm3, p <0.001; 18 ± 4.4 cm3 vs 19 ± 4.8 cm3, p = 0.045), whereas there was no change in patients with PAD and diabetes. Total muscle volume was inversely associated with age and body mass index in patients with PAD both with and without diabetes (p <0.05). In conclusion, magnetic resonance imaging-quantified thigh muscle volumes are highly reproducible and may be of interest in assessing PAD patients with and without diabetes.

Magnetic resonance imaging based superficial femoral artery velocity measurements in peripheral artery disease.

Peripheral artery disease (PAD) causes lower extremity dysfunction and is associated with an increased risk of cardiovascular mortality and morbidity. In this study, we analyzed how non-invasive 2-dimensional-phase-contrast magnetic resonance imaging (2D-PC-MRI) measured velocity markers of the distal superficial femoral artery (SFA) are associated with clinical and functional characteristics of PAD. A total of 70 (27 diabetic and 43 non-diabetic) PAD patients were included in this secondary analysis of data collected from the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically (ECG)-gated 2D-PC-MRI was performed at a proximal and a distal imaging location of the distal SFA. Baseline characteristics did not differ between diabetic and non-diabetic PAD patients. Claudication onset time (COT) was shorter in diabetic PAD patients compared to non-diabetics (0.56 (inter quartile range (IQR): 0.3, 2.04) minutes vs. 1.30 (IQR: 1.13, 2.15) minutes, p = 0.025). In a pooled analysis of all 70 PAD patients, maximum velocity was significantly higher in the proximal compared with the distal SFA segment (43.97 (interquartile range (IQR): 20.4, 65.2) cm/s; vs. 34.9 (IQR: 16.87, 51.71) cm/s; p < 0.001). The maximum velocities in both the proximal and distal SFA segments were significantly higher in diabetic PAD patients compared with non-diabetics (proximal: 53.6 (IQR: 38.73, 89.43) cm/s vs. 41.49 (IQR: 60.75, 15.9) cm/s, p = 0.033; distal: 40.8 (IQR: 23.7, 71.90) cm/s vs. 27.4 (IQR: 41.67, 12.54) cm/s, p = 0.012). Intra-observer variability, as assessed by intraclass correlation (ICC) analysis, was excellent for SFA mean and maximum velocities (0.996 (confidence interval [CI]: 0.996, 0.997); 0.999 (CI: 0.999, 0.999)). In conclusion, 2D-PC-MRI SFA velocity measures are reproducible and may be of interest in assessing diabetic and non-diabetic PAD patients.

Ultrasound imaging of carotid intima-media thickness: an office-based tool to assist physicians in cardiovascular risk assessment.

Traditional coronary heart disease risk prediction schemes such as the Framingham Risk Score, although useful, do not adequately identify all individuals who experience an adverse coronary heart disease event. Therefore, additional tools, including biomarkers, genetic markers, and imaging markers, are being evaluated for their value in improving cardiovascular risk assessment. Of the two accepted imaging markers of atherosclerosis, namely coronary artery calcium score (CACS) measured by CT scan and carotid intima-media thickness (CIMT) measured by ultrasound, CIMT has the potential to be widely adopted as a clinical tool for physician offices. Ultrasound-based CIMT measurement is safe but has several challenges, including reproducibility and operator-dependency. We review and present data with respect to the added value of CIMT and information about plaque presence or absence in improving coronary heart disease risk prediction and further provide information related to adequate scanning protocols. New developments in the area of automated CIMT measurement, three-dimensional, ultrasound-based plaque volume estimation are promising and have the potential to create a quantum leap in our ability to measure, characterize, and monitor carotid atherosclerosis and in turn prediction of cardiovascular disease risk.

Isolated coronary artery bypass grafting in obese individuals: a propensity matched analysis of outcomes.

BACKGROUND: There is conflicting data regarding the impact of obesity on morbidity and mortality in patients undergoing isolated coronary artery bypass grafting (CABG). METHODS AND RESULTS: Retrospective cohort analysis of patients who underwent CABG from January 1, 1995, through July 31, 2010 was performed. Patients were classified as obese or non-obese (body mass index ≥ 30.0 kg/m(2) and <30.0 kg/m(2), respectively). The primary outcome was in-hospital mortality. Secondary outcomes included postoperative respiratory failure, postoperative stroke, postoperative myocardial infarction, sternal and leg wound infections, postoperative atrial fibrillation, postoperative ventricular tachycardia, postoperative renal failure and length of hospital stay. Propensity-matched stepwise multivariable logistic regression was performed. Of 13,115 patients, 4,619 (35.2%) were obese. In the propensity-matched logistic regression models (n = 8,442), obesity was not associated with postoperative mortality (odds ratio = 1.13, 95% confidence interval 0.86-1.48). However, obesity was associated with postoperative respiratory failure, postoperative renal insufficiency, sternal wound infection, and leg wound infection. Obesity was also associated with a decreased risk of postoperative bleeding and re-operation from bleeding. CONCLUSIONS: Obesity was associated with an increased risk of postoperative respiratory failure, postoperative renal failure, and surgical site infections. However, obesity was not associated with in-hospital mortality in patients undergoing CABG.

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

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

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

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

Extracellular Volume in Primary Mitral Regurgitation.

OBJECTIVES: This study used cardiovascular magnetic resonance (CMR) to evaluate whether elevated extracellular volume (ECV) was associated with mitral valve prolapse (MVP) or if elevated ECV was a consequence of remodeling independent of primary mitral regurgitation (MR) etiology. BACKGROUND: Replacement fibrosis in primary MR is more prevalent in MVP; however, data on ECV as a surrogate for diffuse interstitial fibrosis in primary MR are limited. METHODS: Patients with chronic primary MR underwent comprehensive CMR phenotyping and were stratified into an MVP cohort (>2 mm leaflet displacement on a 3-chamber cine CMR) and a non-MVP cohort. Factors associated with ECV and replacement fibrosis were assessed. The association of ECV and symptoms related to MR and clinical events (mitral surgery and cardiovascular death) was ascertained. RESULTS: A total of 424 patients with primary MR (229 with MVP and 195 non-MVP) were enrolled. Replacement fibrosis was more prevalent in the MVP cohort (34.1% vs. 6.7%; p < 0.001), with bi-leaflet MVP having the strongest association with replacement fibrosis (odds ratio: 10.5; p < 0.001). ECV increased with MR severity in a similar fashion for both MVP and non-MVP cohorts and was associated with MR severity but not MVP on multivariable analysis. Elevated ECV was independently associated with symptoms related to MR and clinical events. CONCLUSIONS: Although replacement fibrosis was more prevalent in MVP, diffuse interstitial fibrosis as inferred by ECV was associated with MR severity, regardless of primary MR etiology. ECV was independently associated with symptoms related to MR and clinical events. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823).

Cardiac Magnetic Resonance in Nonischemic Cardiomyopathies.

Cardiovascular magnetic resonance (CMR) has emerged as a key modality to assess nonischemic cardiomyopathies. Its ability to detect cardiac morphology and function with fast cine imaging, myocardial edema with T2-based techniques, and fibrosis with late gadolinium enhancement techniques has enabled noninvasive characterization of cardiac tissue, thus helping clinicians assess cardiovascular risk and determine the most effective management strategy. Active investigations into parametric imaging techniques will further expand the potential clinical applications of CMR for cardiac tissue characterization. This review discusses the use of CMR techniques in characterizing the major morphofunctional phenotypes of nonischemic cardiomyopathies.

Examining the Relationship and Prognostic Implication of Diabetic Status and Extracellular Matrix Expansion by Cardiac Magnetic Resonance.

BACKGROUND: Although not fully understood, diabetes mellitus is thought to be associated with cardiac fibrosis and stiffness due to alteration of myocardial extracellular matrix. Newer cardiac magnetic resonance techniques may be able to identify extracellular matrix expansion by measuring extracellular volume fraction (ECV). We used cardiac magnetic resonance to evaluate the association of alteration in the extracellular matrix with diabetic status and its implications on incident heart failure events and all-cause mortality. METHODS: We studied 442 patients who underwent comprehensive contrast cardiac magnetic resonance to assess cardiac morphology and function, left ventricular replacement fibrosis, and pre-post contrast T1 mapping to quantify ECV. The cohort did not have coexisting pathologies associated with ECV alteration. We categorized our final cohort based on diabetic status using criteria from the American Diabetic Association. Subsequent heart failure hospitalization and all-cause death were ascertained. RESULTS: Our patients were predominantly white with a median age of 57 with 48% being men. Compared with nondiabetes mellitus, diabetes mellitus was significantly associated with elevated ECV after adjusting for clinical and imaging covariates: ß coefficient 1.33 (95% CI, 0.22-2.44); P=0.02. Over a median follow-up of 24.5 (interquartile range, 14.8-33.4) months, 52 deaths and 24 heart failure events occurred. Patients with diabetes mellitus and elevated ECV had the worst outcomes compared with patients with diabetes mellitus and normal ECV or nondiabetics. Elevated ECV remained an independent predictor of outcomes (hazard ratio, 3.31 [95% CI, 1.93-5.67]; P<0.001) after adjusting for covariates. CONCLUSIONS: Elevated ECV is an independent predictor of mortality among patients with diabetes mellitus and may have an additive effect with diabetes mellitus on outcomes. ECV may represent a novel noninvasive biomarker to evaluate severity of diabetic heart disease.

Relationship of extracellular volume assessed on cardiac magnetic resonance and serum cardiac troponins and natriuretic peptides with heart failure outcomes.

Measures of serum cardiac troponins and natriuretic peptides have become established as prognostic heart failure risk markers. In addition to detecting myocardial fibrosis through late gadolinium enhancement (LGE), extracellular volume fraction (ECV) measures by cardiac magnetic resonance (CMR) have emerged as a phenotypic imaging risk marker for incident heart failure outcomes. We sought to examine the relationship between cardiac troponins, natriuretic peptides, ECV and their associations with incident heart failure events in a CMR referral base. Mid short axis T1 maps were divided into 6 cardiac segments, each classified as LGE absent or present. Global ECV was derived from T1 maps using the area-weighted average of only LGE-absent segments. ECV was considered elevated if measured >30%, the upper 95% bounds of a reference healthy group without known cardiac disease (n = 28). Patients were dichotomized by presence of elevated ECV. High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal B-type natriuretic peptide (NT-proBNP) were measured using serum samples acquired and stored at time of CMR scan, and patients were categorized into 3 groups for each blood marker based on recommended cutoff values. Subsequent heart failure admission and any death were ascertained. Relationships with ECV, hs-cTnT, and NT-proBNP were examined separately and as a composite with Cox proportional hazard models. Of 1,604 serial patients referred for a clinical CMR with myocardial T1 maps, 331 were eligible after exclusions and had blood available and were followed over a median 25.0 [interquartile range 21.8, 31.7] months. After adjustments for age (mean 57.3 [standard deviation (SD) 15.1 years), gender (61% male), and ethnicity (12.7% black), elevated ECV remained a predictor of a first composite heart failure outcome for patients with high levels of hs-cTnT (≥14 ng/L; hazard ratio [HR] 2.42 [95% confidence interval (CI) 1.17, 5.03]; p = 0.02) and NT-proBNP (≥300 pg/mL; HR 2.28 [95% CI 1.24, 4.29]; p = 0.01). Similar trends were seen for lower category levels of blood markers, but did not persist with minimal covariate adjustments. Elevated measures of ECV by CMR are associated with incident heart failure outcomes in patients with high hs-cTnT and NT-proBNP levels. This imaging marker may have a role for additional heart failure risk stratification.