Diffuse interstitial or replacement myocardial fibrosis is a common feature of a broad variety of cardiomyopathies. Myocardial fibrosis leads to impaired cardiac diastolic and systolic function and ...is related to adverse cardiovascular events. Cardiovascular magnetic resonance (CMR) may uniquely characterize the extent of replacement fibrosis and may have prognostic value in various cardiomyopathies. Myocardial longitudinal relaxation time mapping is an emerging technique that could improve CMR's diagnostic accuracy, especially for interstitial diffuse myocardial fibrosis. As such, CMR could be integrated in the monitoring and therapeutic management of a large number of patients. This review summarizes the advantages and limitations of CMR for the assessment of myocardial fibrosis.
Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation. Many rare genetic variants have been associated with DCM, but common variant ...studies of the disease have yielded few associated loci. As structural changes in the heart are a defining feature of DCM, we report a genome-wide association study of cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements in 36,041 UK Biobank participants, with replication in 2184 participants from the Multi-Ethnic Study of Atherosclerosis. We identify 45 previously unreported loci associated with cardiac structure and function, many near well-established genes for Mendelian cardiomyopathies. A polygenic score of MRI-derived left ventricular end systolic volume strongly associates with incident DCM in the general population. Even among carriers of TTN truncating mutations, this polygenic score influences the size and function of the human heart. These results further implicate common genetic polymorphisms in the pathogenesis of DCM.
We sought to define age-related geometric changes of the aortic arch and determine their relationship to central aortic stiffness and left ventricular (LV) remodeling.
The proximal aorta has been ...shown to thicken, enlarge in diameter, and lengthen with aging in humans. However, no systematic study has described age-related longitudinal and transversal remodeling of the aortic arch and their relationship with LV mass and remodeling.
We studied 100 subjects (55 women, 45 men, average age 46 ± 16 years) free of overt cardiovascular disease using magnetic resonance imaging to determine aortic arch geometry (length, diameters, height, width, and curvature), aortic arch function (local aortic distensibility and arch pulse wave velocity PWV), and LV volumes and mass. Radial tonometry was used to calculate central blood pressure.
Aortic diameters and arch length increased significantly with age. The ascending aorta length increased most, with age leading to aortic arch widening and decreased curvature. These geometric changes of the aortic arch were significantly related to decreased ascending aortic distensibility, increased aortic arch PWV (p < 0.001), and increased central blood pressures (p < 0.001). Increased ascending aortic diameter, lengthening, and decreased curvature of the aortic arch (unfolding) were all significantly associated with increased LV mass and concentric remodeling independently of age, sex, body size, and central blood pressure (p < 0.01).
Age-related unfolding of the aortic arch is related to increased proximal aortic stiffness in individuals without cardiovascular disease and associated with increased LV mass and mass-to-volume ratio independent of age, body size, central pressure, and cardiovascular risk factors.
Objectives The purpose of this study was to compare the coronary artery calcium (CAC) scores of metabolically-healthy obese (MHO) and metabolically healthy normal-weight individuals in a large sample ...of apparently healthy men and women. Background The risk of cardiovascular disease among obese individuals without obesity-related metabolic abnormalities, referred to as MHO, is controversial. Methods We conducted a cross-sectional study of 14,828 metabolically-healthy adults with no known cardiovascular disease who underwent a health checkup examination that included estimation of CAC scores by cardiac tomography. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. Results MHO individuals had a higher prevalence of coronary calcification than normal weight subjects. In multivariable-adjusted models, the CAC score ratio comparing MHO with normal-weight participants was 2.26 (95% confidence interval: 1.48 to 3.43). In mediation analyses, further adjustment for metabolic risk factors markedly attenuated this association, which was no longer statistically significant (CAC score ratio 1.24; 95% confidence interval: 0.79 to 1.96). These associations did not differ by clinically-relevant subgroups. Conclusions MHO participants had a higher prevalence of subclinical coronary atherosclerosis than metabolically-healthy normal-weight participants, which supports the idea that MHO is not a harmless condition. This association, however, was mediated by metabolic risk factors at levels below those considered abnormal, which suggests that the label of metabolically healthy for obese subjects may be an artifact of the cutoff levels used in the definition of metabolic health.
Coronary artery disease (CAD) is a major cause of cardiovascular morbidity and mortality in patients with diabetes mellitus, yet CAD often is asymptomatic prior to myocardial infarction (MI) and ...coronary death.
To assess whether routine screening for CAD by coronary computed tomography angiography (CCTA) in patients with type 1 or type 2 diabetes deemed to be at high cardiac risk followed by CCTA-directed therapy would reduce the risk of death and nonfatal coronary outcomes.
The FACTOR-64 study was a randomized clinical trial in which 900 patients with type 1 or type 2 diabetes of at least 3 to 5 years' duration and without symptoms of CAD were recruited from 45 clinics and practices of a single health system (Intermountain Healthcare, Utah), enrolled at a single-site coordinating center, and randomly assigned to CAD screening with CCTA (n = 452) or to standard national guidelines-based optimal diabetes care (n = 448) (targets: glycated hemoglobin level <7.0%, low-density lipoprotein cholesterol level <100 mg/dL, systolic blood pressure <130 mm Hg). All CCTA imaging was performed at the coordinating center. Standard therapy or aggressive therapy (targets: glycated hemoglobin level <6.0%, low-density lipoprotein cholesterol level <70 mg/dL, high-density lipoprotein cholesterol level >50 mg/dL women or >40 mg/dL men, triglycerides level <150 mg/dL, systolic blood pressure <120 mm Hg), or aggressive therapy with invasive coronary angiography, was recommended based on CCTA findings. Enrollment occurred between July 2007 and May 2013, and follow-up extended to August 2014.
The primary outcome was a composite of all-cause mortality, nonfatal MI, or unstable angina requiring hospitalization; the secondary outcome was ischemic major adverse cardiovascular events (composite of CAD death, nonfatal MI, or unstable angina).
At a mean follow-up time of 4.0 (SD, 1.7) years, the primary outcome event rates were not significantly different between the CCTA and the control groups (6.2% 28 events vs 7.6% 34 events; hazard ratio, 0.80 95% CI, 0.49-1.32; P = .38). The incidence of the composite secondary end point of ischemic major adverse cardiovascular events also did not differ between groups (4.4% 20 events vs 3.8% 17 events; hazard ratio, 1.15 95% CI, 0.60-2.19; P = .68).
Among asymptomatic patients with type 1 or type 2 diabetes, use of CCTA to screen for CAD did not reduce the composite rate of all-cause mortality, nonfatal MI, or unstable angina requiring hospitalization at 4 years. These findings do not support CCTA screening in this population.
clinicaltrials.gov Identifier: NCT00488033.
SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit(+) cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery ...bypass grafting (CABG). In the present study, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results.
A total of 33 patients (20 CSC-treated and 13 control subjects) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5 ± 1.6% to 35.1 ± 2.4% P=0.004, n=8 and 41.2 ± 4.5% P=0.013, n=5 at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: -6.9 ± 1.5 g -22.7% at 4 months P=0.002, n=9 and -9.8 ± 3.5 g -30.2% at 12 months P=0.039, n=6). LV nonviable mass decreased even more (-11.9 ± 2.5 g -49.7% at 4 months P=0.001 and -14.7 ± 3.9 g -58.6% at 12 months P=0.013), whereas LV viable mass increased (+11.6 ± 5.1 g at 4 months after CSC infusion P=0.055 and +31.5 ± 11.0 g at 12 months P=0.035).
Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue that persist at least 1 year and are consistent with cardiac regeneration.
This study is registered with clinicaltrials.gov, trial number NCT00474461.
Myocardial infarction leads to changes in the geometry (remodeling) of the left ventricle (LV) of the heart. The degree and type of remodeling provides important diagnostic information for the ...therapeutic management of ischemic heart disease. In this paper, we present a novel analysis framework for characterizing remodeling after myocardial infarction, using LV shape descriptors derived from atlas-based shape models. Cardiac magnetic resonance images from 300 patients with myocardial infarction and 1991 asymptomatic volunteers were obtained from the Cardiac Atlas Project. Finite element models were customized to the spatio-temporal shape and function of each case using guide-point modeling. Principal component analysis was applied to the shape models to derive modes of shape variation across all cases. A logistic regression analysis was performed to determine the modes of shape variation most associated with myocardial infarction. Goodness of fit results obtained from end-diastolic and end-systolic shapes were compared against the traditional clinical indices of remodeling: end-diastolic volume, end-systolic volume and LV mass. The combination of end-diastolic and end-systolic shape parameter analysis achieved the lowest deviance, Akaike information criterion and Bayesian information criterion, and the highest area under the receiver operating characteristic curve. Therefore, our framework quantitatively characterized remodeling features associated with myocardial infarction, better than current measures. These features enable quantification of the amount of remodeling, the progression of disease over time, and the effect of treatments designed to reverse remodeling effects.
The aorta stiffens with aging, a process that is accelerated by arterial hypertension. Decreased arterial compliance is one of the earliest detectable manifestations of adverse structural and ...functional changes within the vessel wall. The use of different imaging techniques optimized for assessment of vascular elasticity and quantification of luminal and vessel wall parameters allows for a comprehensive and detailed view of the vascular system. In addition, several studies have also documented the prognostic importance of arterial stiffness (AS) in various populations as an independent predictor of cardiovascular morbidity and all-cause mortality. Measurement of AS by applanation tonometry with pulse-wave velocity has been the gold-standard method and is well-validated in large populations as a strong predictor of adverse cardiovascular outcomes. Because aortic stiffness depends on the prevailing blood pressure, effective antihypertensive treatment is expected to reduce it in proportion to the blood pressure reduction. Nevertheless, drugs lowering blood pressure might differ in their effects on structure and function of the arterial walls. This review paper not only will discuss the current understanding and clinical significance of AS but also will review the effects of various pharmacological and nonpharmacological interventions that can be used to preserve the favorable profile of a more compliant and less stiff aorta.
Arterial stiffness predicts cardiovascular events beyond traditional risk factors. However, the relationship with aging of novel noninvasive measures of aortic function by MRI and their ...interrelationship with established markers of vascular stiffness remain unclear and currently limit their potential impact. Our aim was to compare age-related changes of central measures of aortic function with carotid distensibility, global carotid-femoral pulse wave velocity, and wave reflections. We determined aortic strain, distensibility, and aortic arch pulse wave velocity by MRI, carotid distensibility by ultrasound, and carotid-femoral pulse wave velocity by tonometry in 111 asymptomatic subjects (54 men, age range: 20 to 84 years). Central pressures were used to calculate aortic distensibility. Peripheral and central pulse pressure, augmentation index, and carotid-femoral pulse wave velocity increased with age, but aortic strain and aortic arch PWV were most closely and specifically related to aging. Ascending aortic (AA) strain and distensibility decreased, respectively, by 5.3+/-0.5% (R(2)=0.54, P<0.0001) and 13.6+/-1 kPa(-1)x10(-3) (R(2)=0.62, P<0.0001), and aortic arch pulse wave velocity increased by 1.6+/-0.13 m/sec (R(2)=0.60, P<0.0001) for each decade of age after adjustment for gender, body size, and heart rate. We demonstrate in this study a dramatic decrease in AA distensibility before the fifth decade of life in individuals with diverse prevalence of risk factors free of overt cardiovascular disease. In particular, compared with other measures of aortic function, the best markers of subclinical large artery stiffening, were AA distensibility in younger and aortic arch pulse wave velocity in older individuals.
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