There is conflicting evidence regarding the response to a fixed dose of regadenoson in patients with high body weight. The aim of this study was to evaluate the effectiveness of regadenoson in ...patients with varying body weights using novel quantitative CMR perfusion parameters in addition to standard clinical markers.
Consecutive patients with typical angina and/or risk factors for coronary artery disease (N=217) underwent regadenoson stress CMR perfusion imaging using a dual-sequence quantitative protocol with perfusion parameters generated from an artificial intelligence (AI) based algorithm. CMR was performed on 1.5T scanners using a standard 0.4mg injection of regadenoson. A cohort of consecutive patients undergoing adenosine stress perfusion (N=218) was used as a control group.
An inverse association of myocardial perfusion reserve and weight (mean decrease -0.05 per 10Kg increase, 95% CI -0.009/-0.0001, P=0.045) was noted in the regadenoson group but not in patients stressed with adenosine (P=0.77). Adjusted logistic regression analysis revealed a 10Kg increase resulted in 36% increased odds for inadequate stress response (OR= 1.36, 95% CI 1.10-1.69, P=0.005). Moreover, a significant interaction (OR=1.09, 95% CI 1.02-1.16, P=0.012) between stressor type (regadenoson vs adenosine) and weight was noted. This was also confirmed in the propensity matched subgroup (P=0.024) and was not attenuated after adjustment (P=0.041). BSA (P=0.006) but not BMI (P=0.055) was differentially associated with inadequate response conditional to the stressor used, and this association remained significant after adjustment for confounders (P=0.025). Patients in the highest quartile of weight (>93Kg) or BSA (>2.06m2) had substantially increased odds for inadequate response with regadenoson (OR=8.19, 95% CI 2.04-32.97, P=0.003 for increased weight and OR=7.75, 95% CI 1.93- 31.13, P=0.004 for increased BSA). Both weight and BSA had excellent discriminative ability for inadequate regadenoson response (ROC area under curve 0.84 and 0.83 respectively).
Using quantitative perfusion CMR in patients undergoing pharmacological stress with regadenoson, we found an inverse relationship between patient weight and both clinical response and myocardial perfusion parameters. A fixed-dose bolus approach may not be adequate to induce maximal hyperemia in patients with increased weight. Weight-adjusted stressors like adenosine may be considered instead in patients with body weight > 93Kg and BSA > 2.06m2.
Left-Dominant Arrhythmogenic Cardiomyopathy Sen-Chowdhry, Srijita, MBBS, MD (Cantab), MRCP; Syrris, Petros, PhD; Prasad, Sanjay K., MD, MRCP ...
Journal of the American College of Cardiology,
12/2008, Letnik:
52, Številka:
25
Journal Article
Recenzirano
Odprti dostop
Objectives We sought to investigate the clinical-genetic profile of left-dominant arrhythmogenic cardiomyopathy (LDAC). Background In the absence of coronary disease and left ventricular (LV) ...systolic dysfunction, lateral T-wave inversion and arrhythmia of LV origin are often considered benign. Similarly, chest pain with enzyme release might be attributed to viral myocarditis. We hypothesized that these abnormalities might be manifestations of the “left-dominant” subtype of arrhythmogenic right ventricular cardiomyopathy. Methods The 42-patient cohort was established through clinical evaluation of individuals with unexplained (infero)lateral T-wave inversion, arrhythmia of LV origin, and/or proven LDAC/idiopathic myocardial fibrosis in the family. Results Patients presented from adolescence to age >80 years with arrhythmia or chest pain but not heart failure. Desmosomal mutations were identified in 8 of 24 families (15 of 33 patients). Magnetic resonance findings included LV late-enhancement in a subepicardial/midwall distribution, corresponding to fibrofatty replacement and fibrosis on histopathology. Fifty percent had previously been misdiagnosed with viral myocarditis, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy, or idiopathic ventricular tachycardia. Arrhythmic events included presentation with ventricular fibrillatory arrest in 1 patient and 2 instances of sudden cardiac death during follow-up. Conclusions Arrhythmogenic cardiomyopathy is distinguished from DCM by a propensity towards arrhythmia exceeding the degree of ventricular dysfunction. The left-dominant subtype is under-recognized owing to misattribution to other disorders and lack of specific diagnostic criteria. Clinicians are alerted to the possibility of LDAC in patients of any age with unexplained arrhythmia of LV origin, (infero)lateral T-wave inversion, apparent DCM (with arrhythmic presentation), or myocarditis (chest pain and enzyme rise with unobstructed coronary arteries).
Abstract Background Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may ...enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. Objectives This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM. Methods In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients. Results In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001). Conclusions Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans.
Abstract
Context
“Accelerated aging,” assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether ...epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age.
Design
DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA; preserved across cell types) and extrinsic (EEAA; dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development.
Results
In 995 participants (49.6% female; age, 17.3 ± 0.6 years), EEAA (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ–inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age and a 3% increase, after adjustment for conventional risk factors.
Conclusions
Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle age CVD. Irrespective of whether this is cause or effect, assessing epigenetic age might refine disease prediction.
An estimate of biological age determined from peripheral blood DNA from ∼1000 adolescents may refine prediction of cardiovascular risk above and beyond traditional risk factors.
Coronary angiography has been the gold standard for determining the severity, extent and prognosis of coronary atheromatous disease for the past 15–20 years. However, established non-invasive testing ...(such as myocardial perfusion scintigraphy and stress echocardiography) and newer imaging modalities (multi-detector x ray computed tomography and cardiovascular magnetic resonance) now need to be considered increasingly as a challenge to coronary angiography in contemporary practice. An important consideration is the degree to which appropriate use of such techniques impacts on the need for coronary angiography over the next 10–15 years. This review aims to determine the role of the various investigation techniques in the management of coronary artery disease and their resource implications, and should help determine future service provision, accepting that we are in a period of significant technological change.
Background and aims
Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in ...such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks.
Approach and results
We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal
p
value < 0.007. EWAS identified dmCpGs related to three genes (
ANK1, MIR10a
,
PTPRN2
) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (
ANK1 n
= 6,
MIR10a n
= 7,
PTPRN2 n
= 3), three dmCpGs in
ANK1
and two in
MIR10a
were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in
ANK1
remained significant. These
ANK1
CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted
p
< 2.3 × 10
–3
).
Conclusions
We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.
Graphical abstract
There were 116 articles published in the Journal of Cardiovascular Magnetic Resonance (JCMR) in 2015, which is a 14 % increase on the 102 articles published in 2014. The quality of the submissions ...continues to increase. The 2015 JCMR Impact Factor (which is published in June 2016) rose to 5.75 from 4.72 for 2014 (as published in June 2015), which is the highest impact factor ever recorded for JCMR. The 2015 impact factor means that the JCMR papers that were published in 2013 and 2014 were cited on average 5.75 times in 2015. The impact factor undergoes natural variation according to citation rates of papers in the 2 years following publication, and is significantly influenced by highly cited papers such as official reports. However, the progress of the journal's impact over the last 5 years has been impressive. Our acceptance rate is <25 % and has been falling because the number of articles being submitted has been increasing. In accordance with Open-Access publishing, the JCMR articles go on-line as they are accepted with no collating of the articles into sections or special thematic issues. For this reason, the Editors have felt that it is useful once per calendar year to summarize the papers for the readership into broad areas of interest or theme, so that areas of interest can be reviewed in a single article in relation to each other and other recent JCMR articles. The papers are presented in broad themes and set in context with related literature and previously published JCMR papers to guide continuity of thought in the journal. We hope that you find the open-access system increases wider reading and citation of your papers, and that you will continue to send your quality papers to JCMR for publication.
There is a high incidence of anomalous coronary arteries in subjects with congenital heart disease. These abnormalities can be responsible for myocardial ischemia and sudden death or be damaged ...during surgical intervention. It can be difficult to define the proximal course of anomalous coronary arteries with the use of conventional x-ray coronary angiography. Magnetic resonance coronary angiography (MRCA) has been shown to be useful in the assessment of the 3-dimensional relationship between the coronary arteries and the great vessels in subjects with normal cardiac morphology but has not been used in patients with congenital heart disease.
Twenty-five adults with various congenital heart abnormalities were studied. X-ray coronary angiography and respiratory-gated MRCA were performed in all subjects. Coronary artery origin and proximal course were assessed for each imaging modality by separate, blinded investigators. Images were then compared, and a consensus diagnosis was reached. With the consensus readings for both magnetic resonance and x-ray coronary angiography, it was possible to identify the origin and course of the proximal coronary arteries in all 25 subjects: 16 with coronary anomalies and 9 with normal coronary arteries. Respiratory-gated MRCA had an accuracy of 92%, a sensitivity of 88%, and a specificity of 100% for the detection of abnormal coronary arteries. The MRCA results were more likely to agree with the consensus for definition of the proximal course of the coronary arteries (P<0.02).
For the assessment of anomalous coronary artery anatomy in patients with congenital heart disease, the use of the combination of MRCA with x-ray coronary angiography improves the definition of the proximal coronary artery course. MRCA provides correct spatial relationships, whereas x-ray angiography provides a view of the entire coronary length and its peripheral run-off. Furthermore, respiratory-gated MRCA can be performed without breath holding and with only limited subject cooperation.
Development of left ventricular hypertrophy in aortic stenosis (AS) is accompanied by coronary microcirculatory dysfunction, demonstrated by an impaired coronary vasodilator reserve (CVR). However, ...evidence for regional abnormalities in myocardial blood flow (MBF) and the potential mechanisms is limited. The aims of this study were to quantitatively demonstrate differences in subendocardial and subepicardial microcirculation and to investigate the relative contribution of myocyte hypertrophy, hemodynamic load, severity of AS, and coronary perfusion to impairment in microcirculatory function.
Twenty patients with isolated moderate to severe AS were studied using echocardiography to assess severity of AS, cardiovascular magnetic resonance to measure left ventricular mass (LVM), and PET to quantify resting and hyperemic (dipyridamole 0.56 mg/kg) MBF and CVR in both the subendocardium and subepicardium. In the patients with most severe AS (n=15), the subendocardial to subepicardial MBF ratio decreased from 1.14+/-7 at rest to 0.92+/-7 during hyperemia (P<0.005), and subendocardial CVR (1.43+/-3) was lower than subepicardial CVR (1.78+/-35; P=0.01). Resting total LV blood flow was linearly related to LVM, whereas CVR was not. Increase of total LV blood flow during hyperemia (mean value, 89.6+/-6%; range, 17% to 233%) was linearly related to aortic valve area. The decrease in CVR was related to severity of AS, increase in hemodynamic load, and reduction in diastolic perfusion time, particularly in the subendocardium.
CVR was more severely impaired in the subendocardium in patients with LVH attributable to severe AS. Severity of impairment was related to aortic valve area, hemodynamic load imposed, and diastolic perfusion rather than to LVM.
In cardiac syndrome X (a syndrome characterized by typical angina, abnormal exercise-test results, and normal coronary arteries), conventional investigations have not found that chest pain is due to ...myocardial ischemia. Magnetic resonance techniques have higher resolution and therefore may be more sensitive.
We performed myocardial-perfusion cardiovascular magnetic resonance imaging in 20 patients with syndrome X and 10 matched controls, both at rest and during an infusion of adenosine. Quantitative perfusion analysis was performed by using the normalized upslope of myocardial signal enhancement to derive the myocardial perfusion index and the myocardial-perfusion reserve index (defined as the ratio of the myocardial perfusion index during stress to the index at rest).
In the controls, the myocardial perfusion index increased in both myocardial layers with adenosine (in the subendocardium, from a mean +/-SD of 0.12+/-0.03 to 0.16+/-0.03 P=0.02; in the subepicardium, from 0.11+/-0.02 to 0.17+/-0.05 P=0.002); in patients with syndrome X, the myocardial perfusion index did not change significantly in the subendocardium (0.13+/-0.02 vs. 0.14+/-0.03, P=0.11; P=0.09 as compared with controls) but increased in the subepicardium (from 0.11+/-0.02 to 0.20+/-0.04, P<0.001; P=0.11 for the comparison with controls). Adenosine provoked chest pain in 95 percent of patients with syndrome X and 40 percent of controls (P<0.001).
In patients with syndrome X, cardiovascular magnetic resonance imaging demonstrates subendocardial hypoperfusion during the intravenous administration of adenosine, which is associated with intense chest pain. These data support the notion that the chest pain may have an ischemic cause.
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