Showing papers in "Circulation-cardiovascular Imaging in 2014"

Prognostic Value of Nonobstructive and Obstructive Coronary Artery Disease Detected by Coronary Computed Tomography Angiography to Identify Cardiovascular Events

Abstract: Background— The contribution of plaque extent to predict cardiovascular events among patients with nonobstructive and obstructive coronary artery disease (CAD) is not well defined. Our objective was to evaluate the prognostic value of plaque extent detected by coronary computed tomography angiography. Methods and Results— All consecutive patients without prior CAD referred for coronary computed tomography angiography to evaluate for CAD were included. Examination findings were classified as normal, nonobstructive ( 4 segments). The cohort included 3242 patients followed for the primary outcome of cardiovascular death or myocardial infarction for a median of 3.6 (2.1–5.0) years. In a multivariable analysis, the presence of extensive nonobstructive CAD (hazard ratio, 3.1; 95% confidence interval, 1.5–6.4), nonextensive obstructive (hazard ratio, 3.0; 95% confidence interval, 1.3–6.9), and extensive obstructive CAD (hazard ratio, 3.9; 95% confidence interval, 2.2–7.2) were associated with an increased rate of events, whereas nonextensive, nonobstructive CAD was not. The addition of plaque extent to a model that included clinical probability as well as the presence and severity of CAD improved risk prediction. Conclusions— Among patients with nonobstructive CAD, those with extensive plaque experienced a higher rate of cardiovascular death or myocardial infarction, comparable with those who have nonextensive disease. Even among patients with obstructive CAD, greater extent of nonobstructive plaque was associated with higher event rate. Our findings suggest that regardless of whether obstructive or nonobstructive disease is present, the extent of plaque detected by coronary computed tomography angiography enhances risk assessment.

Late gadolinium enhancement on cardiac magnetic resonance predicts adverse cardiovascular outcomes in nonischemic cardiomyopathy: a systematic review and meta-analysis.

Abstract: Background— Late gadolinium enhancement (LGE) by cardiac MR (CMR) is a predictor of adverse cardiovascular outcomes in patients with nonischemic cardiomyopathy (NICM). However, these findings are limited by single-center studies, small sample sizes, and low event rates. We performed a meta-analysis to evaluate the prognostic role of LGE by CMR (LGE-CMR) imaging in patients with NICM. Methods and Results— PubMed, Cochrane CENTRAL, and EMBASE were searched for studies looking at the prognostic value of LGE-CMR in patients with NICM. The primary end points included all-cause mortality, heart failure hospitalization, and a composite end point of sudden cardiac death (SCD) or aborted SCD. Pooling of odds ratios was performed using a random-effect model, and annualized event rates were assessed. Data were included from 9 studies with a total of 1488 patients and a mean follow-up of 30 months. Patients had a mean age of 52 years, 67% were men, and the average left ventricular ejection fraction was 37% on CMR. LGE was present in 38% of patients. Patients with LGE had increased overall mortality (odds ratio, 3.27; P <0.00001), heart failure hospitalization (odds ratio, 2.91; P =0.02), and SCD/aborted SCD (odds ratio, 5.32; P <0.00001) compared with those without LGE. The annualized event rates for mortality were 4.7% for LGE+ subjects versus 1.7% for LGE− subjects ( P =0.01), 5.03% versus 1.8% for heart failure hospitalization ( P =0.002), and 6.0% versus 1.2% for SCD/aborted SCD ( P <0.001). Conclusions— LGE in patients with NICM is associated with increased risk of all-cause mortality, heart failure hospitalization, and SCD. Detection of LGE by CMR has excellent prognostic characteristics and may help guide risk stratification and management in patients with NICM.

18F-sodium fluoride uptake is a marker of active calcification and disease progression in patients with aortic stenosis.

Abstract: Background— 18F-Sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) are promising novel biomarkers of disease activity in aortic stenosis. We compared 18F-NaF and 18F-FDG uptake with histological characterization of the aortic valve and assessed whether they predicted disease progression. Methods and Results— Thirty patients with aortic stenosis underwent combined positron emission and computed tomography using 18F-NaF and 18F-FDG radiotracers. In 12 patients undergoing aortic valve replacement surgery (10 for each tracer), radiotracer uptake (mean tissue/background ratio) was compared with CD68 (inflammation), alkaline phosphatase, and osteocalcin (calcification) immunohistochemistry of the excised valve. In 18 patients (6 aortic sclerosis, 5 mild, and 7 moderate), aortic valve computed tomography calcium scoring was performed at baseline and after 1 year. Aortic valve 18F-NaF uptake correlated with both alkaline phosphatase ( r =0.65; P =0.04) and osteocalcin ( r =0.68; P =0.03) immunohistochemistry. There was no significant correlation between 18F-FDG uptake and CD68 staining ( r =−0.43; P =0.22). After 1 year, aortic valve calcification increased from 314 (193–540) to 365 (207–934) AU ( P <0.01). Baseline 18F-NaF uptake correlated closely with the change in calcium score ( r =0.66; P <0.01), and this improved further ( r =0.75; P <0.01) when 18F-NaF uptake overlying computed tomography–defined macrocalcification was excluded. No significant correlation was noted between valvular 18F-FDG uptake and change in calcium score ( r =−0.11; P =0.66). Conclusions— 18F-NaF uptake identifies active tissue calcification and predicts disease progression in patients with calcific aortic stenosis. Clinical Trial Registration— URL: . Unique identifier: [NCT01358513][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01358513&atom=%2Fcirccvim%2F7%2F2%2F371.atom

Echocardiographic diagnosis of constrictive pericarditis: Mayo Clinic criteria.

Abstract: Background— Constrictive pericarditis is a potentially reversible cause of heart failure that may be difficult to differentiate from restrictive myocardial disease and severe tricuspid regurgitation Echocardiography provides an important opportunity to evaluate for constrictive pericarditis, and definite diagnostic criteria are needed Methods and Results— Patients with surgically confirmed constrictive pericarditis (n=130) at Mayo Clinic (2008–2010) were compared with patients (n=36) diagnosed with restrictive myocardial disease or severe tricuspid regurgitation after constrictive pericarditis was considered but ruled out Comprehensive echocardiograms were reviewed in blinded fashion Five principal echocardiographic variables were selected based on prior studies and potential for clinical use: (1) respiration-related ventricular septal shift, (2) variation in mitral inflow E velocity, (3) medial mitral annular e' velocity, (4) ratio of medial mitral annular e' to lateral e', and (5) hepatic vein expiratory diastolic reversal ratio All 5 principal variables differed significantly between the groups In patients with atrial fibrillation or flutter (n=29), all but mitral inflow velocity remained significantly different Three variables were independently associated with constrictive pericarditis: (1) ventricular septal shift, (2) medial mitral e', and (3) hepatic vein expiratory diastolic reversal ratio The presence of ventricular septal shift in combination with either medial e'≥9 cm/s or hepatic vein expiratory diastolic reversal ratio ≥079 corresponded to a desirable combination of sensitivity (87%) and specificity (91%) The specificity increased to 97% when all 3 factors were present, but the sensitivity decreased to 64% Conclusions— Echocardiography allows differentiation of constrictive pericarditis from restrictive myocardial disease and severe tricuspid regurgitation Respiration-related ventricular septal shift, preserved or increased medial mitral annular e' velocity, and prominent hepatic vein expiratory diastolic flow reversals are independently associated with the diagnosis of constrictive pericarditis

Incremental prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis and preserved ejection fraction.

Abstract: Background— We sought to assess the utility of left ventricular global longitudinal strain (LV-GLS) in predicting mortality in moderate to severe and paradoxical severe aortic stenosis (AS) patients with preserved ejection fraction. Methods and Results— We studied 395 AS patients (70±14 years, 57% men) with aortic valve area <1.3 cm2 evaluated between January to June 2008 (excluding severe other valve disease and LV ejection fraction <50%). Clinical and echocardiographic data were recorded. LV-GLS was analyzed using Velocity Vector Imaging. AS patients were classified as (a) moderate–severe (n=93; aortic valve area, 1.1–1.3 cm2), (b) standard severe (n=161; aortic valve area, ≤1 cm2; mean gradient ≥40 mm Hg), and (c) paradoxical severe (n=141; aortic valve area, ≤1 cm2 and mean gradient <40 mm Hg). Additive Euroscore was 7±3. The association of LV-GLS with all-cause mortality was assessed after risk-adjustment using Cox proportional hazards models. Median LV-GLS was −14.8% (interquartile range, −17.2%, −12.1%). At 4.4±1.4 years, there were 92 (23%) deaths. On multivariable Cox analysis, additive Euroscore (hazard ratio, 1.19; 1.13–1.27; P <0.001), New York Heart Association class (hazard ratio, 1.44; 1.11–1.87; P <0.001), AV surgery with time-dependent covariate analysis (hazard ratio, 0.29; 0.19–0.45; P <0.001), and LV-GLS (hazard ratio, 1.05; 1.03–1.07; P <0.001) were independent predictors of mortality. LV-GLS <−12.1% (4th quartile) was associated with significantly reduced survival. Addition of LV-GLS to clinical parameters (additive Euroscore+New York Heart Association class) led to significant improvement in prediction of mortality (χ2 increased from 48 to 58; P <0.01). Conclusions— LV-GLS independently predicts mortality in moderate–severe and severe AS patients with preserved LV ejection fraction, providing incremental prognostic utility, in addition to standard clinical and echocardiographic parameters.

Myocardial strain analysis by 2-dimensional speckle tracking echocardiography improves diagnostics of coronary artery stenosis in stable angina pectoris.

Abstract: Background— Two-dimensional strain echocardiography detects early signs of left ventricular dysfunction; however, it is unknown whether myocardial strain analysis at rest in patients with suspected stable angina pectoris predicts the presence of coronary artery disease (CAD). Methods and Results— In total, 296 consecutive patients with clinically suspected stable angina pectoris, no previous cardiac history, and normal left ventricular ejection fraction were included. All patients were examined by 2-dimensional strain echocardiography, exercise ECG, and coronary angiography. Two-dimensional strain echocardiography was performed in the 3 apical projections. Peak regional longitudinal systolic strain was measured in 18 myocardial sites and averaged to provide global longitudinal peak systolic strain. Duke score, including ST-segment depression, chest pain, and exercise capacity, was used as the outcome of the exercise test. Patients with an area stenosis ≥70% in ≥1 epicardial coronary artery were categorized as having significant CAD (n=107). Global longitudinal peak systolic strain was significantly lower in patients with CAD compared with patients without (17.1±2.5% versus 18.8±2.6%; P <0.001) and remained an independent predictor of CAD after multivariable adjustment for baseline data, exercise test, and conventional echocardiography (odds ratio, 1.25 [ P =0.016] per 1% decrease). Area under receiver operating characteristic curve for exercise test and global longitudinal peak systolic strain in combination was significantly higher than that for exercise test alone (0.84 versus 0.78; P =0.007). Furthermore, impaired regional longitudinal systolic strain identifies which coronary artery is stenotic. Conclusions— In patients with suspected stable angina pectoris, global longitudinal peak systolic strain assessed at rest is an independent predictor of significant CAD and significantly improves the diagnostic performance of exercise test. Furthermore, 2-dimensional strain echocardiography seems capable of identifying high-risk patients.

Investigation of global and regional myocardial mechanics with 3-dimensional speckle tracking echocardiography and relations to hypertrophy and fibrosis in hypertrophic cardiomyopathy.

Abstract: Background— In hypertrophic cardiomyopathy (HCM), heterogeneous myocardial hypertrophy and fibrosis are responsible for abnormalities of left ventricular (LV) function. We aimed to characterize LV global and regional myocardial mechanics in HCM, according to segmental hypertrophy and fibrosis. Methods and Results— Fifty-nine patients with HCM underwent standard echocardiography, 3-dimensional speckle tracking echocardiography, and cardiac magnetic resonance with late gadolinium enhancement (LGE); all 3 tests were <24 hours apart. Longitudinal, circumferential, and area strains were investigated according to the extent of LGE (no LGE, LGE<10%, and LGE≥10%), segmental thickness (≥15 versus <15 mm), and segmental LGE (LGE versus non-LGE). Attenuated global longitudinal strain showed association with extent of hypertrophy (indexed LV mass, r =0.32, P =0.01; maximum LV wall thickness, r =0.34, P =0.009; number of segments ≥15 mm, r =0.44, P <0.001), whereas enhanced global circumferential strain was correlated to LV global functional parameters (indexed end-systolic volume, r =0.47, P <0.001; ejection fraction, r =−0.75, P <0.001). Parameters of global myocardial mechanics showed no association with the extent of LGE; in contrast, the extent of LGE was associated with the extent of hypertrophy. All 3 deformation parameters were attenuated both in segments ≥15 mm in thickness and in those with LGE; adjusted analysis demonstrated that segmental presence of LGE was associated with additional attenuation in myocardial deformation. Conclusions— Both hypertrophy and fibrosis contribute to regional impairment of myocardial shortening in HCM. The extent of hypertrophy is the primary factor altering global myocardial mechanics. Circumferential myocardial shortening seems to be directly involved in preservation of LV systolic performance in HCM.

Complex Left Atrial Appendage Morphology and Left Atrial Appendage Thrombus Formation in Patients With Atrial Fibrillation

Abstract: Background—In patients with atrial fibrillation (AF), most thrombus forms in the left atrial appendage (LAA). However, the relation of LAA morphology with LAA thrombus is unknown. Methods and Resul...

Aortic annular sizing using a novel 3-dimensional echocardiographic method: use and comparison with cardiac computed tomography.

Abstract: Background— Previous studies have shown cross-sectional 3-dimensional (3D) transesophageal echocardiographic (TEE) measurements to severely underestimate multidetector row computed tomographic (MDCT) measurements for the assessment of aortic annulus before transcatheter aortic valve replacement. This study compares annulus measurements from 3D-TEE using off-label use of commercially available software with MDCT measurements and assesses their ability to predict paravalvular regurgitation. Methods and Results— One hundred patients with severe, symptomatic aortic stenosis who had both contrast MDCT and 3D-TEE for annulus assessment before balloon-expandable transcatheter aortic valve replacement were analyzed. Annulus area, perimeter, and orthogonal maximum and minimum diameters were measured. Receiver operating characteristic analysis was performed with mild or greater paravalvular regurgitation as the classification variable. Three-dimensional TEE and MDCT cross-sectional perimeter and area measurements were strongly correlated ( r =0.93–0.94; P <0.0001); however, the small differences (≤1%) were statistically significant ( P =0.0002 and 0.0074, respectively). Discriminatory ability for ≥ mild paravalvular regurgitation was good for both MDCT (area under the curve for perimeter and area cover index=0.715 and 0.709, respectively) and 3D-TEE (area under the curve for perimeter and area cover index=0.709 and 0.694, respectively). Differences in receiver operating characteristic analysis between MDCT and 3D-TEE perimeter and area cover indexes were not statistically significant ( P =0.15 and 0.35, respectively). Conclusions— Annulus measurements using a new method for analyzing 3D-TEE images closely approximate those of MDCT. Annulus measurements from both modalities predict mild or greater paravalvular regurgitation with equivalent accuracy.

Changes in Right Ventricular Function Measured by Cardiac Magnetic Resonance Imaging in Patients Receiving Pulmonary Arterial Hypertension-Targeted Therapy The EURO-MR Study

Abstract: Background— Most measures that predict survival in pulmonary hypertension (PH) relate directly to, or correlate with, right ventricular (RV) function. Direct assessment of RV function using noninvasive techniques such as cardiac MRI may therefore be an appropriate way of determining response to therapy and monitoring disease progression in PH. Methods and Results— In this pan-European study, 91 patients with PH (mean pulmonary arterial pressure 46±15 mm Hg) underwent clinical and cardiac MRI assessments at baseline and after 12 months of disease-targeted therapy (predominantly endothelin receptor antagonists [47.3%] or phosphodiesterase type-5 inhibitors [25.3%]). At month 12, functional class had improved in 21 patients, was unchanged in 63 patients, and had deteriorated in 7 patients. Significant improvements were achieved in RV and left ventricular ejection fraction ( P P =0.0007, respectively), RV stroke volume index ( P P =0.0015). Increases in 6-minute walk distance were significant ( P P =0.01 and r=0.26, P =0.02, respectively). Conclusions— On-treatment changes in cardiac MRI–derived variables from left and right sides of the heart reflected changes in functional class and survival in patients with PH. Direct measurement of RV function using cardiac MRI can fully assess potential benefits of treatment in PH.

Increased benefit of interleukin-1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis.

Abstract: Background— We investigated the effects of anakinra, an interleukin-1 receptor antagonist, on coronary and left ventricular function in coronary artery disease (CAD) patients with rheumatoid arthritis. Methods and Results— In a double-blind crossover trial, 80 patients with rheumatoid arthritis (60 with CAD and 20 without) were randomized to a single injection of anakinra or placebo and after 48 hours to the alternative treatment. At baseline and 3 hours after treatment, we assessed (1) flow-mediated dilation of brachial artery; (2) coronary flow reserve, ejection fraction, systemic arterial compliance, and resistance by echocardiography; (3) left ventricular global longitudinal and circumferential strain, peak twisting, untwisting velocity by speckle tracking; and (4) interleukin-1β, nitrotyrosine, malondialdehyde, protein carbonyl, and Fas/Fas ligand levels. At baseline, patients with CAD had 3-fold higher interleukin-1β, protein carbonyl, higher nitrotyrosine, malondialdehyde, and Fas/Fas ligand than non-CAD ( P <0.05). After anakinra, there was a greater improvement of flow-mediated dilation (57±4% versus 47±5%), coronary flow reserve (37±4% versus 29±2%), arterial compliance (20±18% versus 2±17%), resistance (−11±19% versus 9±21%), longitudinal strain (33±5% versus 18±2%), circumferential strain (22±5% versus 13±5%), peak twisting (30±5% versus 12±5%), untwisting velocity (23±5% versus 13±5%), ejection fraction (12±5% versus 0.5±5%), apoptotic and oxidative markers, and, in particular, of protein carbonyl (35±20% versus 14±9%) in CAD than in non-CAD patients ( P <0.01). No changes in the examined markers were observed after placebo. Conclusions— Interleukin-1 inhibition causes a greater improvement in endothelial, coronary aortic function in addition to left ventricular myocardial deformation and twisting in rheumatoid arthritis patients with CAD than in those without. Clinical Trial Registration— URL: . Unique identifier: [NCT01566201][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01566201&atom=%2Fcirccvim%2F7%2F4%2F619.atom

Reference ranges of blood flow in the major vessels of the normal human fetal circulation at term by phase-contrast magnetic resonance imaging.

Abstract: Background— Phase-contrast MRI with metric-optimized gating is a promising new technique for studying the distribution of the fetal circulation. However, mean and reference ranges for blood flow measurements made in the major fetal vessels using this technique are yet to be established. Methods and Results— We measured flow in the major vessels of the fetal circulation in 40 late-gestation normal human fetuses using phase-contrast MRI (mean gestational age, 37 [SD=1.1] weeks). Flows were indexed to the fetal weight, which was estimated from the fetal volume calculated by MRI segmentation. The following mean flows (in mL/min per kilogram; ±2SD) were obtained: combined ventricular output, 465 (351, 579); main pulmonary artery, 261 (169, 353); ascending aorta, 191 (121, 261); superior vena cava, 137 (77, 197); ductus arteriosus, 187 (109, 265); descending aorta, 252 (160, 344); pulmonary blood flow, 77 (0, 160); umbilical vein, 134 (62, 206); and foramen ovale, 135 (37, 233). Expressed as percentages of the combined ventricular output, the mean flows±2 SD were as follows: main pulmonary artery, 56 (44, 68); ascending aorta, 41 (29, 53); superior vena cava, 29 (15, 43); ductus arteriosus, 41 (25, 57); descending aorta, 55 (35, 75); pulmonary blood flow, 16 (0, 34); umbilical vein, 29 (11, 47); and foramen ovale, 29 (7, 51). A strong inverse relationship between foramen ovale shunt and pulmonary blood flow was noted ( r =−0.64; P <0.0001). Conclusions— Although too small a sample size to provide normal ranges, these results are in keeping with those predicted in humans based on measurements made in fetal lambs using radioactive microspheres and provide preliminary reference ranges for the late-gestation human fetuses. The wide range we found in foramen ovale shunting suggests a degree of variability in the way blood is streamed through the fetal circulation.

How to Image Cardiac Amyloidosis

Abstract: A 74-year-old man presented with decreasing exercise tolerance and mild ankle edema. He was previously fit but was now breathless on climbing 2 flights of stairs. He had no history of angina, orthopnea, or paroxysmal nocturnal dyspnea. His medical history included non–insulin-dependent diabetes mellitus treated for 10 years and mild hypertension. Six years earlier he had been diagnosed with a monoclonal gammopathy of unknown significance. At that time, a bone marrow biopsy showed 30% overall cellularity with 5% to 10% plasmacytosis (normal <4%) and immunoglobulin light-chain restriction. Approximately 3 years ago, he developed deep vein thrombosis and was treated with low-molecular-weight heparin. A year later, leg swelling occurred and was attributed to venous insufficiency. The following year, he developed progressive fatigue on exertion, and an abnormal ECG (Figure 1) led to a treadmill test that was considered normal. An echocardiogram showed concentric wall thickening (Movie 1 in the Data Supplement), and the possibility of cardiac amyloidosis was raised. A fat pad biopsy was negative for amyloid deposits. The bone marrow biopsy performed in 2005 (when his monoclonal gammopathy of unknown significance was diagnosed) was restained and was negative for amyloid. At that time, serum-free λ light chains were 108.9 mg/L (normal range, 5.7–26.3) with κ light chains of 13 mg/L (normal, 3.3–19) and an abnormal ratio of 0.12 (normal, 0.26–1.65). His brain natriuretic peptide measured 275 pcg/mL. He was treated with oral diuretics, which improved leg swelling, but because of persistent symptoms, he sought medical care at our institution. On review of symptoms, he denied jaw claudication, symptoms of postural hypotension, easy bruising, or tongue swelling. He did give a history suggestive of neuropathy with a leathery feeling in his feet but no numbness in his hands. Medications included metformin 500 mg twice a day, aspirin 80 mg daily, lisinopril …

Sildenafil improves exercise hemodynamics in Fontan patients.

Abstract: Background— Patients with Fontan circulation have reduced exercise capacity. The absence of a presystemic pump may limit flow through the pulmonary circulation, restricting ventricular filling and cardiac output. We evaluated exercise hemodynamics and the effect of sildenafil on exercise hemodynamics in Fontan patients. Methods and Results— Ten Fontan patients (6 men, 20±4 years) underwent cardiac magnetic resonance imaging at rest and during supine bicycle exercise before and after sildenafil. Systemic ventricular volumes were obtained at rest and during low- (34±15 W), moderate- (69±29 W), and high-intensity (97±36 W) exercise using an ungated, free-breathing cardiac magnetic resonance sequence and analyzed correcting for cardiac phase and respiratory translation. Radial and pulmonary artery pressures and cGMP were measured. Before sildenafil, cardiac index increased throughout exercise (4.0±0.9, 5.9±1.1, 7.0±1.6, 7.4±1.7 L/(min·m2); P <0.0001) with 106±49% increase in heart rate. Stroke volume index ( P =0.015) and end-diastolic volume index ( P =0.001) decreased during exercise. End-systolic volume index remained unchanged ( P =0.8). Total pulmonary resistance index ( P =0.005) increased, whereas systemic vascular resistance index decreased during exercise ( P <0.0001). Sildenafil increased cardiac index ( P <0.0001) and stroke volume index ( P =0.003), especially at high-intensity exercise (interaction P =0.004 and P =0.003, respectively). Systemic vascular resistance index was reduced ( P <0.0001–interaction P =0.1), whereas total pulmonary resistance index was reduced at rest and reduced further during exercise ( P =0.008–interaction P =0.029). cGMP remained unchanged before sildenafil ( P =0.9), whereas it increased significantly after sildenafil ( P =0.019). Conclusions— In Fontan patients, sildenafil improved cardiac index during exercise with a decrease in total pulmonary resistance index and an increase in stroke volume index. This implies that pulmonary vasculature represents a physiological limitation, which can be attenuated by sildenafil, the clinical significance of which warrants further study.

Rationale and design of a multicenter echocardiographic study to assess the relationship between cardiac structure and function and heart failure risk in a biracial cohort of community-dwelling elderly persons: the Atherosclerosis Risk in Communities study.

Abstract: Background— Heart failure is an important public health concern, particularly among persons >65 years of age. Women and blacks are critically understudied populations that carry a sizeable portion of the heart failure burden. Limited normative and prognostic data exist on measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community. Methods and Results— The Atherosclerosis Risk in Communities (ARIC) study is a large, predominantly biracial, National Heart, Lung, and Blood Institute–sponsored epidemiological cohort study. Between 2011 and 2013, ≈6000 surviving participants, now in their seventh to ninth decade of life, are expected to return for a fifth study visit during which comprehensive 2-dimensional, Doppler, tissue Doppler, and speckle-tracking echocardiography will be performed uniformly in all cohort clinic visit participants. The following objectives will be addressed: (1) to characterize cardiac structural and functional abnormalities among the elderly and to determine how they differ by sex and race/ethnicity, (2) to determine the relationship between ventricular and vascular abnormalities, and (3) to prospectively examine the extent to which these noninvasive measures associate with incident heart failure. Conclusions— We describe the design, imaging acquisition and analysis methods, and quality assurance metrics for echocardiography in visit 5 of the ARIC cohort. A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen our understanding of the pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies.

Cardiac magnetic resonance parameters predict transplantation-free survival in patients with fontan circulation.

Abstract: Background— Several clinical risk factors for death and heart transplantation have been identified in patients with Fontan circulation. It is unknown whether cardiac magnetic resonance (CMR) measurements of ventricular size and function are independently associated with these outcomes and further improve risk stratification. Methods and Results— Data on patients with Fontan circulation who had a CMR study from January 2002 to January 2011 were retrospectively reviewed. The end point was time to death or listing for heart transplantation after the CMR study. The median age of the 215 patients was 18.3 years (25th, 75th percentiles: 14, 26) with a median age at Fontan of 3.6 years (2.3, 7.1). During a median post-CMR follow-up period of 4.1 years (2.6, 6.2), 24 patients (11%) reached the end point: 20 deaths, 3 transplantations, and 1 transplantation listing. In a multivariable Cox regression model with clinical parameters only, protein-losing enteropathy was associated with transplantation-free survival. A multivariable model, including clinical and CMR parameters, showed that in addition to protein-losing enteropathy, ventricular indexed end-diastolic volume >125 mL/body surface area raised to the 1.3 power was associated with transplantation-free survival. A likelihood-ratio test comparing the 2 models showed that the addition of indexed end-diastolic volume resulted in a significantly improved end point prediction ( P <0.001)— C -index increased from 0.63 to 0.79. Conclusions— CMR-derived ventricular indexed end-diastolic volume is an independent predictor of transplantation-free survival in patients late after the Fontan operation and adds incremental value over clinical symptoms alone for risk stratification.

Metabolic Activity of the Spleen and Bone Marrow in Patients With Acute Myocardial Infarction Evaluated by 18F-Fluorodeoxyglucose Positron Emission Tomograpic Imaging

Abstract: Background— Atherosclerosis is considered to be an inflammatory disease associated with the activation of hematopoietic and immune-related organs such as the bone marrow (BM) and spleen. We evaluated the metabolic activity of those organs and of the carotid artery with 18F-fluorodeoxyglucose positron emission tomography in patients with coronary artery disease, including acute myocardial infarction. Methods and Results— Whole-body combined 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 32 patients with acute myocardial infarction, 33 patients with chronic stable angina, and 25 control subjects. The mean standard uptake value was calculated in the regions of interest in the spleen and the BM of lumbar vertebrae. The target-to-background ratio of the standard uptake values of the carotid artery and jugular vein was also calculated. In patients with acute myocardial infarction, the standard uptake values of the BM (1.67±0.16) and spleen (2.57±0.39), as well as the target-to-background ratio of the carotid artery (2.13±0.42), were significantly higher than the corresponding values of patients with angina (1.22±0.62; 2.03±0.35; 1.36±0.37; all P <0.001) and controls (0.80±0.44; 1.54±0.26; 1.22±0.22; all P <0.001), independent of traditional cardiovascular risk factors and high-sensitivity C-reactive protein. In all groups combined, the target-to-background ratio of the carotid artery was significantly associated with the standard uptake values of the BM ( r =0.535; P <0.001), spleen ( r =0.663; P <0.001), and high-sensitivity C-reactive protein ( r =0.465; P <0.001). Conclusions— The metabolic activity of the BM and spleen, as well as of the carotid artery, was highest in patients with acute myocardial infarction, intermediate in patients with angina, and lowest in control subjects. The activation of the BM and spleen was significantly associated with inflammatory activity of the carotid artery.

Coronary artery disease detected by coronary computed tomographic angiography is associated with intensification of preventive medical therapy and lower low-density lipoprotein cholesterol

Abstract: Background—Coronary computed tomographic angiography (CCTA) is an accurate test for the identification of coronary artery disease (CAD), yet the impact of CCTA results on subsequent medical therapy...

Quantification of left ventricular interstitial fibrosis in asymptomatic chronic primary degenerative mitral regurgitation.

Abstract: Background— The optimum timing of surgery in asymptomatic patients with chronic severe primary degenerative mitral regurgitation (MR) remains controversial, and further markers are needed to improve decision-making. There are limited data that wall stress is increased in MR and may result in ventricular fibrosis. We investigated the hypothesis that chronic volume overload in MR is a stimulus for myocardial fibrosis using T1-mapping cardiac MRI. Methods and Results— A cross-sectional study of 35 patients (age 60±14 years) with asymptomatic moderate and severe primary degenerative MR (mean effective regurgitant orifice area, 0.45±0.25 cm)[2][1] with no class I indication for surgery were compared with age and sex controls. Subjects were studied with cardiopulmonary exercise testing, echocardiography, and cardiac MRI. Longitudinal and circumferential myocardial deformation was reduced with MR when left ventricular ejection fraction (67%±10%) and N-terminal pro B Natriuretic peptide (126 [76–428] ng/L) were within the normal range. Myocardial extracellular volume was increased (0.32±0.07 versus 0.25±0.02, P <0.01) and was associated with increased left ventricular end-systolic volume index ( r =0.62, P <0.01), left atrial volume index ( r =0.41, P <0.05) but lower left ventricular ejection fraction ( r =−0.60, P <0.01), longitudinal function (mitral annular plane systolic excursion, r =−0.46, P <0.01), and peak VO2 max ( r =−0.51, P <0.05). In a multivariable regression model, left ventricular end-systolic volume index and left atrial volume index were independent predictors of extracellular volume ( r 2=0.42, P <0.01). Conclusions— Patients with asymptomatic MR demonstrate a spectrum of myocardial fibrosis associated with reduced myocardial deformation and reduced exercise capacity. Future work is warranted to investigate whether left ventricle fibrosis affects clinical outcomes. [1]: #ref-2

Novel imaging of coronary artery anomalies to assess their prevalence, the causes of clinical symptoms, and the risk of sudden cardiac death.

Abstract: In a fundamental 1974 article, Cheitlin et al1 of the Armed Forces Institute of Pathology emphasized the special role of anomalous aortic origin of the coronary arteries and differentiated this condition from the other coronary artery anomalies (CAAs) as being associated with an increased frequency of sudden cardiac death (SCD) in young persons, especially during strenuous exertion. More recently, CAAs have also been considered possible causes of clinically disabling symptoms, including dyspnea, angina pectoris, and syncope, especially in young adults.2–5 Clinicians and epidemiologists have identified the need to prevent not only SCD in young persons, especially athletes or military recruits, but also other CAA-related symptoms in persons of any age.6–12 Much of the available information concerning the incidence of SCD in carriers of CAAs is lacking a denominator (measure of the carriers at risk). The most notable study of SCD incidence is a classic 2004 article by Eckart et al,7 who reported the mortality rate (>25 years) that US military recruits experienced during a 2-month-long boot-camp training period. All the recruits were involved in strenuous exercise and had undergone routine screening based on a history and physical examination performed by general practitioners. Of the 23 million recruits, 64 died of SCD (0.28 per 100 000 per 2 months, or 1.68 per 100 000 per year). Of these deaths, 21 (33%) were attributed to CAAs, specifically anomalous origin of the left coronary artery from the right sinus of Valsalva with an interarterial course. To establish a solid theory and a preventive policy in this field, we must understand the pathophysiology of CAAs, identify the prevalence of individuals living with different kinds of CAAs (the denominator), clarify the individual severity of each case, study the influence of different types of exertion, and identify the …

Is there a role for coronary artery calcium scoring for management of asymptomatic patients at risk for coronary artery disease?: Clinical risk scores are not sufficient to define primary prevention treatment strategies among asymptomatic patients.

Abstract: Although risk factors have proven to be useful therapeutic targets, they are poor predictors of risk. Traditional risk scores are moderately successful in predicting future CHD events and can be a starting place for general risk categorization. However, there is substantial heterogeneity between traditional risk and actual atherosclerosis burden, with event rates predominantly driven by burden of atherosclerosis. Serum biomarkers have yet to show any clinically significant incremental value to the FRS and even when combined cannot match the predictive value of atherosclerosis imaging. As clinicians, are we willing to base therapy decisions on risk models that lack optimum-achievable accuracy and limit personalization? The decision to treat a patient in primary prevention must be a careful one because the benefit of therapy in an asymptomatic patient must clearly outweigh the potential risk. CAC, in particular, provides a personalized assessment of risk and may identify patients who will be expected to derive the most, and the least, net absolute benefit from treatment. Emerging evidence hints that CAC may also promote long-term adherence to aspirin, exercise, diet, and statin therapy. When potentially lifelong treatment decisions are on the line, clinicians must arm their patients with the most accurate risk prediction tools, and subclinical atherosclerosis testing with CAC is, at the present time, superior to any combination of risk factors and serum biomarkers.

Is MRI the Preferred Method for Evaluating Right Ventricular Size and Function in Patients With Congenital Heart Disease? MRI Is the Preferred Method for Evaluating Right Ventricular Size and Function in Patients With Congenital Heart Disease

Abstract: In contrast to adult patients with acquired heart disease, abnormalities of the right ventricle (RV) are ubiquitous in children and adults with congenital heart disease (CHD). The RV is exposed to volume overload in shunt lesions (eg, atrial septal defect, anomalous pulmonary venous connections), as well as congenital or acquired tricuspid and pulmonary valve regurgitation. RV pressure overload characterizes numerous congenital anomalies, including pulmonary valve stenosis or atresia, large ventricular septal defect, single ventricle, tetralogy of Fallot (TOF), truncus arteriosus, and transposition of the great arteries, to name a few. Importantly, many surgical and transcatheter treatments of CHD result in persistent or acquired volume and pressure overload of the RV. In some patients with CHD, the RV functions as the systemic ventricle (eg, palliated hypoplastic left heart syndrome, physiologically corrected transposition of the great arteries, and D-loop transposition of the great arteries after atrial switch procedure). Furthermore, exposure to cyanosis and surgical procedures in the RV often leads to myocardial abnormalities, including scar tissue and diffuse fibrosis. Response by Yeh and Foster see p 197 Given the frequent involvement of the RV in CHD, it is not surprising that the assessment of RV size and function is key for guiding clinical decisions in these patients.1 Among the diagnostic imaging tools available to clinicians for RV imaging, cardiac magnetic resonance (CMR) has emerged as the reference standard. In the following sections, I will review the evidence supporting this contention, highlight how CMR data are used to guide clinical decisions, and discuss the strengths and weaknesses of CMR in comparison with other modalities, including echocardiography, computed tomography, conventional x-ray angiography, and nuclear scintigraphy. CMR is ideally suited for the assessment of the RV because it allows comprehensive assessment of cardiovascular morphology and physiology without most of the limitations that hinder alternative …

Near-Infrared II Fluorescence for Imaging Hindlimb Vessel Regeneration With Dynamic Tissue Perfusion Measurement

Abstract: Background—Real-time vascular imaging that provides both anatomic and hemodynamic information could greatly facilitate the diagnosis of vascular diseases and provide accurate assessment of therapeu...

Morphological and Functional Adaptation of Left and Right Atria Induced by Training in Highly Trained Female Athletes

Abstract: Background— Exercise is able to induce atrial remodeling in top-level athletes. However, evidence is mainly limited to men and based on cross-sectional studies. The aim of this prospective, longitudinal study was to investigate whether exercise is able to influence left and right atrial morphology and function also in female athletes. Methods and Results— Two-dimensional echocardiography was performed before season and after 16 weeks of intensive training in 24 top-level female athletes. Left and right atrial myocardial deformation was assessed by two-dimensional speckle-tracking echocardiography. Left atrial volume index (24.0±3.6 versus 26.7±6.9 mL/m2; P <0.001) and right atrial volume index (15.66±3.09 versus 20.47±4.82 mL/m2; P <0.001) significantly increased after training in female athletes. Left atrial global peak atrial longitudinal strain and peak atrial contraction strain significantly decreased after training in female athletes (43.9±9.5% versus 39.8±6.5%; P <0.05 and 15.5±4.0% versus 13.9±4.0%; P <0.05, respectively). Right atrial peak atrial longitudinal strain and peak atrial contraction strain showed a similar, although non-significant decrease (42.8±10.6% versus 39.3±8.3%; 15.6±5.6% versus 13.1±6.1%, respectively). Neither biventricular E / e ′ ratio nor biatrial stiffness changed after training, suggesting that biatrial remodeling occurs in a model of volume rather than pressure overload. Conclusions— Exercise is able to induce biatrial morphological and functional changes in female athletes. Biatrial enlargement, with normal filling pressures and low atrial stiffness, is a typical feature of the heart of female athletes. These findings should be interpreted as physiological adaptations to exercise and should be considered in the differential diagnosis with cardiomyopathies.

Endothelial shear stress and coronary plaque characteristics in humans: combined frequency-domain optical coherence tomography and computational fluid dynamics study.

Abstract: Background— Despite the exposure of the entire vasculature to the atherogenic effects of systemic risk factors, atherosclerotic plaques preferentially develop at sites with disturbed flow. This study aimed at exploring in vivo the relationship between local endothelial shear stress (ESS) and coronary plaque characteristics in humans using computational fluid dynamics and frequency-domain optical coherence tomography. Methods and Results— Three-dimensional coronary artery reconstruction was performed in 21 patients (24 arteries) presenting with acute coronary syndrome using frequency-domain optical coherence tomography and coronary angiography. Each coronary artery was divided into sequential 3-mm segments and analyzed for the assessment of local ESS and plaque characteristics. A total of 146 nonculprit segments were evaluated. Compared with segments with higher ESS [≥1 Pascal (Pa)], those with low ESS (<1 Pa) showed higher prevalence of lipid-rich plaques (37.5% versus 20.0%; P =0.019) and thin-cap fibroatheroma (12.5% versus 2.0%; P =0.037). Overall, lipid plaques in segments with low ESS had thinner fibrous cap (115 μm [63–166] versus 170 μm [107–219]; P =0.004) and higher macrophage density (normalized standard deviation: 8.4% [4.8–12.6] versus 6.2% [4.2–8.8]; P =0.017). Segments with low ESS showed more superficial calcifications (minimum calcification depth: 93 μm [50–140] versus 152 μm [105–258]; P =0.049) and tended to have higher prevalence of spotty calcifications (26.0% versus 12.0%; P =0.076). Conclusions— Coronary regions exposed to low ESS are associated with larger lipid burden, thinner fibrous cap, and higher prevalence of thin-cap fibroatheroma in humans. Frequency-domain optical coherence tomography–based assessment of ESS and wall characteristics may be useful in identifying vulnerable coronary regions. Clinical Trial Registration— URL: . Unique identifier: [NCT01110538][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01110538&atom=%2Fcirccvim%2F7%2F6%2F905.atom

Noninvasive assessment of hypoxia in rabbit advanced atherosclerosis using ¹⁸F-fluoromisonidazole positron emission tomographic imaging.

Abstract: Background— Hypoxia is an important microenvironmental factor influencing atherosclerosis progression by inducing foam-cell formation, metabolic adaptation of infiltrated macrophages, and plaque neovascularization. Therefore, imaging plaque hypoxia could serve as a marker of lesions at risk. Methods and Results— Advanced aortic atherosclerosis was induced in 18 rabbits by atherogenic diet and double balloon endothelial denudation. Animals underwent 18F-fluoromisonidazole positron emission tomographic and 18F-fluorodeoxyglucose positron emission tomographic imaging after 6 to 8 months (atherosclerosis induction) and 12 to 16 months (progression) of diet initiation. Four rabbits fed standard chow served as controls. Radiotracer uptake of the abdominal aorta was measured using standardized uptake values. After imaging, plaque hypoxia (pimonidazole), macrophages (RAM-11), neovessels (CD31), and hypoxia-inducible factor-1α were assessed by immunohistochemistry.18F-fluoromisonidazole uptake increased with time on diet (standardized uptake value mean, 0.10±0.01 in nonatherosclerotic animals versus 0.20±0.03 [ P =0.002] at induction and 0.25±0.03 [ P <0.001] at progression). Ex vivo positron emission tomographic imaging corroborated the 18F-fluoromisonidazole uptake by the aorta of atherosclerotic rabbits. 18F-fluorodeoxyglucose uptake also augmented in atherosclerotic animals, with an standardized uptake value mean of 0.43±0.02 at induction versus 0.35±0.02 in nonatherosclerotic animals ( P =0.031) and no further increase at progression. By immunohistochemistry, hypoxia was mainly located in the macrophage-rich areas within the atheromatous core, whereas the macrophages close to the lumen were hypoxia-negative. Intraplaque neovessels were found predominantly in macrophage-rich hypoxic regions (pimonidazole+/hypoxia-inducible factor-1α+/RAM-11+). Conclusions— Plaque hypoxia increases with disease progression and is present in macrophage-rich areas associated with neovascularization. 18F-fluoromisonidazole positron emission tomographic imaging emerges as a new tool for the detection of atherosclerotic lesions.

Four-Group Classification of Left Ventricular Hypertrophy Based on Ventricular Concentricity and Dilatation Identifies a Low-Risk Subset of Eccentric Hypertrophy in Hypertensive Patients

Abstract: Background-Left ventricular hypertrophy (LVH; high LV mass [LVM]) is traditionally classified as concentric or eccentric based on LV relative wall thickness. We evaluated the prediction of subseque ...

Prognostic Value of Rubidium-82 Positron Emission Tomography in Patients After Heart Transplant

Abstract: Background— Cardiac allograft vasculopathy is a key prognostic determinant after heart transplant. Detection and risk stratification of patients with cardiac allograft vasculopathy are problematic. Positron emission tomography using rubidium-82 allows quantification of absolute myocardial blood flow and may have utility for risk stratification in this population. Methods and Results— Patients with a history of heart transplant undergoing dipyridamole rubidium-82 positron emission tomography were prospectively enrolled. Myocardial perfusion and left ventricular ejection fraction were recorded. Absolute flow quantification at rest and after dipyridamole stress as well as the ratio of mean global flow at stress and at rest, termed myocardial flow reserve, were calculated. Patients were followed for all-cause death, acute coronary syndrome, and heart failure hospitalization. A total of 140 patients (81% men; median age, 62 years; median follow-up, 18.2 months) were included. There were 14 events during follow-up (9 deaths, 1 acute coronary syndrome, and 4 heart failure admissions). In addition to baseline clinical variables (estimated glomerular filtration rate, previously documented cardiac allograft vasculopathy), relative perfusion defects, mean myocardial flow reserve, and mean stress myocardial blood flow were significant predictors of adverse outcome. Conclusions— Abnormalities on rubidium-82 positron emission tomography were predictors of adverse events in heart transplant patients. Larger prospective studies are required to confirm these findings.

Ectopic fat depots and left ventricular function in nondiabetic men with nonalcoholic fatty liver disease.

Abstract: Background— Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease. Methods and Results— Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function. Conclusions— Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study.

Prognostic Value of Cardiovascular Magnetic Resonance Imaging Measurements Corrected for Age and Sex in Idiopathic Pulmonary Arterial Hypertension

Abstract: Background— There are limited data on the prognostic value of cardiovascular magnetic resonance measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of cardiovascular magnetic resonance indices for age and sex on prognostic value. Methods and Results— Consecutive patients with idiopathic pulmonary arterial hypertension underwent cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession cardiac volumes and mass measurements were corrected for age, sex, and body surface area according to reference data and prognostic significance assessed. A total of 80 patients with idiopathic pulmonary arterial hypertension were identified, and 23 patients died during the mean follow-up of 32±14 months. Corrected for age, sex, and body surface area, right ventricular end-systolic volume ( P =0.004) strongly predicted mortality, independent of World Health Organization functional class, mean right atrial pressure, cardiac index, and mixed venous oxygen saturations. Conclusions— Consideration should be given to correcting cardiovascular magnetic resonance measures for age, sex, and body surface area, particularly given the changing demographics of patients with idiopathic pulmonary arterial hypertension. Corrected right ventricular end-systolic volume is a strong prognostic marker in idiopathic pulmonary arterial hypertension, independent of invasively derived measurements, mean right atrial pressure cardiac index, and mixed venous oxygen saturations.