Obesity and metabolic syndrome (MetS) are associated with high risk of cardiac dysfunction and heart failure. We assessed the effect of obesity and metabolic health status on left ventricular (LV) ...structure and function in subjects without overt heart disease.
In 789 subjects (58.8±13.0 years, 50.7% males) without overt heart disease, LV morphology and function were compared among 6 groups stratified by body mass index (BMI) (normal weight, overweight and obese) and metabolic health status (meeting ≤1 criterion of MetS excluding waist circumference defined as metabolically healthy; otherwise, metabolically unhealthy).
LV ejection fraction (LVEF) was not different among the 6 groups (P>0.05). However, high BMI and poor metabolic health were associated with poorer global longitudinal strain (GLS), higher LV mass index (LVMI) and higher E/e' (P<0.001). Poor metabolic health status was associated with greater adverse changes in LV structure and function than obesity, and among MetS components, high systolic blood pressure (SBP) showed the greatest impact. Higher SBP, BMI and triglycerides were independently associated with worse GLS, and higher SBP was also associated with worse LVMI and E/e´. GLS, LVMI and E/e´ worsened in proportion to the number of MetS criteria or continuous MetS scores. Adverse myocardial changes associated with obesity were significant in the metabolically healthy group, but not in the metabolically unhealthy group.
Obesity and poor metabolic health status were associated with subclinical decrement in LV systolic and diastolic function, and higher LV mass, but not with LVEF, in subjects without overt heart disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study examined the impact of septal flattening on left ventricular (LV) torsion in patients with precapillary pulmonary hypertension (PH). Fifty-two patients with proven precapillary PH and 13 ...healthy controls were included. Ventricular function was assessed including 4D-measurements, tissue velocity imaging, and speckle tracking analysis. Increased eccentricity index (1.39 vs. 1.08, p<0.001), systolic pulmonary artery pressure (64 vs. 29mmHg, p<0.001) and right ventricular Tei index (0.55 vs. 0.28, p = 0.007), and reduced tricuspid annular plane systolic excursion (19.0 vs. 26.5mm, p<0.001) were detected in PH patients as compared to controls. With increasing eccentricity of left ventricle, LV torsion was both decreased and delayed. Torsion rate paralleled this pattern of change during systole, but not during diastole. In conclusion, right ventricular pressure overload directly affects LV torsion mechanics. The echocardiographic methodology applied provides novel insights in the interrelation of right- and left ventricular function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Left ventricular (LV) hypertrophy and remodeling are frequently seen in hypertensive subjects and result from a complex interaction of several hemodynamic and non-hemodynamic variables. Although ...increased blood pressure is considered the major determinant of LV structural alterations, ethnicity, gender, environmental factors, such as salt intake, obesity and diabetes mellitus, as well as neurohumoral and genetic factors might influence LV mass and geometry. The conventional concept of hypertensive LV remodeling has been that hypertension leads to concentric hypertrophy, as an adaptive response to normalize wall stress, which is then followed by chamber dilation and heart failure. However, several lines of evidence have challenged this dogma. Concentric hypertrophy is not the most frequent geometric pattern and is less usually seen than eccentric hypertrophy in hypertensive subjects. In addition, data from recent studies suggested that transition from LV concentric hypertrophy to dilation and systolic dysfunction is not a common finding, especially in the absence of coronary heart disease. LV hypertrophy is also consistently associated with increased cardiovascular morbidity and mortality, raising doubts whether this phenotype is an adaptive response. Experimental evidence exists that a blunting of load-induced cardiomyocyte hypertrophy does not necessarily result in LV dysfunction or failure. Furthermore, the hypertrophic myocardium shows fibrosis, alterations in the coronary circulation and cardiomyocyte apoptosis, which may result in heart failure, myocardial ischemia and arrhythmias. Overall, this body of evidence suggests that LV hypertrophy is a complex phenotype that predicts adverse cardiovascular outcomes and may not be necessarily considered as an adaptive response to systemic hypertension.
Inorganic arsenic (iAs) is a ubiquitous element present in the groundwater worldwide. Cardiovascular effects related to iAs exposure have been studied extensively in adult populations. Few ...epidemiological studies have been focused on iAs exposure-related cardiovascular disease in children.
In this study we investigated the association between iAs exposure, blood pressure (BP), and functional and anatomical echocardiographic parameters in children.
A cross-sectional study of 161 children between 3 and 8 years was conducted in Central Mexico. The total concentration of arsenic (As) species in urine (U-tAs) was determined by hydride generation-cryotrapping-atomic absorption spectrometry and lifetime iAs exposure was estimated by multiplying As concentrations measured in drinking water by the duration of water consumption in years (LAsE). BP was measured by standard protocols, and M-mode echocardiographic parameters were determined by ultrasonography.
U-tAs concentration and LAsE were significantly associated with diastolic (DBP) and systolic blood pressure (SBP) in multivariable linear regression models: DBP and SBP were 0.013 (95% CI: 0.002, 0.024) and 0.021 (95% CI: 0.004, 0.037) mmHg higher in association with each 1-ng/mL increase in U-tAs (p < 0.025), respectively. Left ventricular mass (LVM) was significantly associated with LAsE 5.5 g higher (95% CI: 0.65, 10.26) in children with LAsE > 620 compared with < 382 μg/L-year; p = 0.03 in an adjusted multivariable model. The systolic function parameters left ventricular ejection fraction (EF) and shortening fraction were 3.67% (95% CI: -7.14, -0.20) and 3.41% (95% CI: -6.44, -0.37) lower, respectively, in children with U-tAs > 70 ng/mL compared with < 35 ng/mL.
Early-life exposure to iAs was significantly associated with higher BP and LVM and with lower EF in our study population of Mexican children.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Recently there has been considerable interest in LV torsion and its relationship with symptomatic and pre-symptomatic disease processes. Torsion gives useful additional information about myocardial ...tissue performance in both systolic and diastolic function. CMR assessment of LV torsion is simply and efficiently performed. However, there is currently a wide variation in the reporting of torsional motion and the procedures used for its calculation. For example, torsion has been presented as twist (degrees), twist per length (degrees/mm), shear angle (degrees), and shear strain (dimensionless). This paper reviews current clinical applications and shows how torsion can give insights into LV mechanics and the influence of LV geometry and myocyte fiber architecture on cardiac function. Finally, it provides recommendations for CMR measurement protocols, attempts to stimulate standardization of torsion calculation, and suggests areas of useful future research.
This study aimed to optimise techniques for whole transcriptome and small RNA analyses on clinical tissue samples from patients with cardiovascular disease. Clinical samples often represent a ...particular challenge to extracting RNA of sufficient quality for robust RNA sequencing analysis, and due to availability, it is rarely possible to optimise techniques on the samples themselves. Therefore, we have used equivalent samples from pigs undergoing cardiopulmonary bypass surgery to test different protocols for optimal RNA extraction, and then validated the protocols in human samples. Here we present an assessment of the quality and quantity of RNA obtained using a variety of commercially-available RNA extraction kits on both left ventricular biopsies and blood plasma. RNA extraction from these samples presents different difficulties; left ventricular biopsies are small and fibrous, while blood plasma has a low RNA content. We have validated our optimised extraction techniques on human clinical samples collected as part of the ARCADIA (Association of non-coding RNAs with Coronary Artery Disease and type 2 Diabetes) cohort study, resulting in successful whole transcriptome and small RNA sequencing of human left ventricular tissue.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pulmonary arterial hypertension (PAH) is a lethal disease and improved therapeutic strategies are needed. Increased pulmonary arterial pressure, due to vasoconstriction and vascular remodeling, ...causes right ventricle (RV) failure and death in patients. The treatment of Sprague-Dawley rats with SU5416 injection and exposure to chronic hypoxia for three weeks followed by maintenance in normoxia promote progressive and severe PAH with pathologic features that resemble human PAH. At 5-17 weeks after the SU5416 injection, PAH is developed with pulmonary vascular remodeling as well as RV hypertrophy and fibrosis. The present study investigated subsequent events that occur in these PAH animals.
At 35 weeks after the SU5416 injection, rats still maintained high RV pressure, but pulmonary vascular remodeling was significantly reduced. Metabolomics analysis revealed that lungs of normal rats and rats from the 35-week time point had different metabolomics profiles. Despite the maintenance of high RV pressure, fibrosis was resolved at 35-weeks. Masson's trichrome stain and Western blotting monitoring collagen 1 determined 12% fibrosis in the RV at 17-weeks, and this was decreased to 5% at 35-weeks. The level of myofibroblasts was elevated at 17-weeks and normalized at 35-weeks.
These results suggest that biological systems possess natural ways to resolve pulmonary and RV remodeling. The resolution of RV fibrosis appears to involve the reduction of myofibroblast-dependent collagen synthesis. Understanding these endogenous mechanisms should help improve therapeutic strategies to treat PAH and RV failure.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive method for determining left ventricular (LV) mass and volume but has not been used previously to characterise the LV ...remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR.
Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ≥ 13 mm and >1.5-fold the thickness of the opposing myocardial segment.
Ninety-one patients (61 ± 21 years; 57 male) with aortic stenosis (aortic valve area 0.93 ± 0.32 cm2) were recruited. The severity of aortic stenosis was unrelated to the degree (r2=0.012, P=0.43) and pattern (P=0.22) of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02). Six patterns of LV adaption were observed: normal ventricular geometry (n=11), concentric remodeling (n=11), asymmetric remodeling (n=11), concentric hypertrophy (n=34), asymmetric hypertrophy (n=14) and LV decompensation (n=10). Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17 ± 2mm) with hypertrophic cardiomyopathy.
We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common.
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death ...(SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background/Aims: The alterations in myocyte autophagy after myocardial infarction (MI) and the underlying mechanisms have not been fully understood. In this study, we investigated the temporal ...changes of myocyte autophagy in the remote non-infarcted myocardium in rabbits after MI and the relationships between alterations of myocyte autophagy and left ventricular (LV) remodeling and myocardial oxidative stress. Methods: Rabbits were assigned to MI or sham operation. Rabbits with MI or sham were randomly assigned to receive chloroquine, an autophagy inhibitor, antioxidant vitamins C and E or placebo for 4 weeks. H9C2 cardiomyocytes were subjected to hypoxia or hydrogen peroxide (H2O2) treatment. Results: MI rabbits exhibited progressive increases of LV end-diastolic dimension (EDD), and decreases of LV fractional shortening (FS) and dP/dt over 8 weeks. Myocyte autophagy assessed by the scores of LC3 and Beclin1 expression was progressively decreased at 1, 4 and 8 weeks after MI. The ratio of LC3 II/I and Beclin1 and Atg5 proteins were also decreased at 4 weeks after MI. There was a negative correlation between autophagy and LV EDD and a positive correlation between autophagy and LV FS and dP/dt. The autophagy inhibitor chloroquine worsened LV remodeling after MI. Decreased myocyte autophagy was associated with increased myocardial 4-hydroxynonenal. Antioxidant vitamins C and E prevented the decrease in myocyte autophagy after MI. In cultured H9C2 cardiomyocytes, the LC3 II/I ratio was decreased at 4 and 8 h after exposure to hypoxia, and the change was associated with increased 8-hydroxy-2-deoxyguanosine. A low concentration of H2O2 decreased the LC3 II/I ratio. Conclusion: Progressive reduction in myocyte autophagy in the remote non-infarcted myocardium was associated with myocardial oxidative stress and LV remodeling after MI. Antioxidants prevented the reduction in myocyte autophagy after MI, suggesting that oxidative stress mediates reduction in myocyte autophagy that contributes to post-MI remodeling.
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