Early Relaxation Research Articles

Characterization of aging-associated cardiac diastolic dysfunction.

AimsDiastolic dysfunction is common in geriatric heart failure. A reliable parameter to predict myocardium stiffness and relaxation under similar end-diastolic pressure is being developed. We propose a material and mathematical model for calculating myocardium stiffness based on the concept of linear correlation between and wedge pressure.Methods and ResultsWe enrolled 919 patients (male: ). Compared with the younger population of controls (mean age: years; ; male: ), the elderly (mean age: ; ; male: ) had a greater prevalence of hypertension, diabetes mellitus, and coronary artery disease (all ). We collected their M-mode and 2-D echocardiographic volumetric parameters, intraventricular filling pressure, and speckle tracking images to establish a mathematical model. The feasibility of this model was validated. The average early diastolic velocity of the mitral annulus assessed using tissue Doppler imaging was significantly attenuated in the elderly (: vs. ; ) and corresponded to the higher estimated wedge () pressure ( vs. ; ) in that cohort. E (Young's modulus) was calculated to describe the tensile elasticity of the myocardium. With the same intraventricular filling pressure, E was significantly higher in the elderly, especially those with values . Compared with diastolic dysfunction parameters, E also presented sentinel characteristics more sensitive for detecting early myocardial relaxation impairment, which indicates stiffer myocardium in aging hearts.ConclusionOur material and geometric mathematical model successfully described the stiffer myocardium in aging hearts with higher intraventricular pressure. Additional studies that compare individual differences, especially in health status, are needed to validate its application for detecting diastolic heart failure.

Analysis of transthoracic echocardiographic data in major vascular surgery from a prospective randomised trial comparing sevoflurane and fentanyl with propofol and remifentanil anaesthesia

The aim of this study was to define pre-operative echocardiographic data and explore if postoperative indices of cardiac function after open abdominal aortic surgery were affected by the anaesthetic regimen. We hypothesised that volatile anaesthesia would improve indices of cardiac function compared with total intravenous anaesthesia. Transthoracic echocardiography was performed pre-operatively in 78 patients randomly assigned to volatile anaesthesia and 76 to total intravenous anaesthesia, and compared with postoperative data. Pre-operatively, 16 patients (10%) had left ventricular ejection fraction < 46%. In 138 patients with normal left ventricular ejection fraction, 5/8 (62%) with left ventricular dilatation and 41/130 (33%) without left ventricular dilatation had evidence of left ventricular diastolic dysfunction (p < 0.001). Compared with pre-operative findings, significant increases in left ventricular end-diastolic volume, left atrial maximal volume, cardiac output, velocity of early mitral flow and early myocardial relaxation occurred postoperatively (all p < 0.001). The ratio of the velocity of early mitral flow to early myocardial relaxation remained unchanged. There were no significant differences in postoperative echocardiographic findings between patients anaesthetised with volatile anaesthesia or total intravenous anaesthesia. Patients had an iatrogenic surplus of approximately 4.1 l of fluid volume by the first postoperative day. N-terminal prohormone of brain natriuretic peptide increased on the first postoperative day (p < 0.001) and remained elevated after 30 days (p < 0.001) in both groups. Although postoperative echocardiographic alterations were most likely to be related to increased preload due to a substantial iatrogenic surplus of fluid, a component of peri-operative myocardial ischaemia cannot be excluded. Our hypothesis that volatile anaesthesia improved indices of cardiac function compared with total intravenous anaesthesia could not be verified.

Effect of imatinib as add-on therapy on echocardiographic measures of right ventricular function in patients with significant pulmonary arterial hypertension

Imatinib mesylate, as add-on therapy in patients with pulmonary arterial hypertension (PAH) who remain inadequately treated despite receiving at least two PAH-specific drugs, improves exercise capacity and haemodynamics. We evaluated whether 24 weeks of add-on therapy with imatinib compared with placebo also improves right ventricular (RV) function assessed by echocardiography. Echocardiograms were obtained at baseline, 12 weeks, and 24 weeks in 74 patients randomized to imatinib or placebo in the Imatinib in Pulmonary arterial hypertension, a Randomized Efficacy Study (IMPRES) trial. Right ventricular function was assessed by tissue Doppler tricuspid annular peak systolic velocity (TA S'), tricuspid annular plane systolic excursion (TAPSE), RV Tei index, and RV fractional area change. Between-treatment-group differences in the changes from baseline to week-24 were assessed using an ANCOVA with the last observation carried forward. At week-24 patients randomized to imatinib demonstrated greater improvements in TA S' (1.6 ± 2.3 imatinib vs. 0.5 ± 2.4 cm/s placebo, P = 0.007) and RV Tei index (-0.11 ± 0.18 imatinib vs. 0.05 ± 0.18 placebo, P = 0.005) compared with placebo, but not in TAPSE (0.07 ± 0.44 imatinib vs. 0.03 ± 0.32 cm placebo, P = 0.08). Imatinib therapy was also associated with significant reduction in peak tricuspid regurgitation velocity, increase in LV size, and improvement in LV early diastolic relaxation velocity. Among patients with advanced PAH who remain symptomatic on at least two PAH-specific drugs, treatment with imatinib compared with placebo is associated with significant improvements in echocardiographic measures of RV function, in addition to LV size and LV early diastolic relaxation. NCT00902174 (Clinicaltrials.gov).

Efficient early global relaxation of asteroid Vesta

The asteroid Vesta is a differentiated planetesimal from the accretion phase of Solar System formation. Although its present-day shape is dominated by a non-hydrostatic fossil equatorial bulge and two large, mostly unrelaxed impact basins, Vesta may have been able to approach hydrostatic equilibrium during a brief early period of intense interior heating. We use a finite element viscoplastic flow model coupled to a 1D conductive cooling model to calculate the expected rate of relaxation throughout Vesta’s early history. We find that, given sufficient non-hydrostaticity, the early elastic lithosphere of Vesta experienced extensive brittle failure due to self-gravity, thereby allowing relaxation to a more hydrostatic figure. Soon after its accretion, Vesta reached a closely hydrostatic figure with <2km non-hydrostatic topography at degree-2, which, once scaled, is similar to the maximum disequilibrium of the hydrostatic asteroid Ceres. Vesta was able to support the modern observed amplitude of non-hydrostatic topography only >40–200My after formation, depending on the assumed depth of megaregolith. The Veneneia and Rheasilvia giant impacts, which generated most non-hydrostatic topography, must have therefore occurred >40–200My after formation. Based on crater retention ages, topography, and relation to known impact generated features, we identify a large region in the northern hemisphere that likely represents relic hydrostatic terrain from early Vesta. The long-wavelength figure of this terrain suggests that, before the two late giant impacts, Vesta had a rotation period of 5.02h (6.3% faster than present) while its spin axis was offset by 3.0° from that of the present. The evolution of Vesta’s figure shows that the hydrostaticity of small bodies depends strongly on its age and specific impact history and that a single body may embody both hydrostatic and non-hydrostatic terrains and epochs.

Thermodynamic feature of a Brownian heat engine operating between two heat baths

A generalized theory of nonequilibrium thermodynamics for a Brownian motor operating between two different heat baths is presented. Via a simple paradigmatic model, we not only explore the thermodynamic feature of the engine in the regime of the nonequilibrium steady state but also study the short time behavior of the system for either the isothermal case with load or, in general, the nonisothermal case with or without load. Many elegant thermodynamic theories can be checked via the present model. Furthermore the dependence of the velocity, the efficiency, and the performance of the refrigerator on time t is examined. Our study reveals a current reversal due to time t. In the early system relaxation period, the model works neither as a heat engine nor as a refrigerator and only after a certain period of time does the model start functioning as a heat engine or as a refrigerator. The performance of the engine also improves with time and at steady state the engine manifests a higher efficiency or performance as a refrigerator. Furthermore the effect of energy exchange via the kinetic energy on the performance of the heat engine is explored.

A cascade through spin states in the ultrafast haem relaxation of met-myoglobin

We report on a study of the early relaxation processes of met-Myoglobin in aqueous solution, using a combination of ultrafast broadband fluorescence detection and transient absorption with a broad UV-visible continuum probe at different pump energies. Reconstruction of the spectra of the transient species unravels the details of the haem photocycle in the absence of photolysis. Besides identifying a branching in the ultrafast relaxation of the haem, we show clear evidence for an electronic character of the intermediates, contrary to the commonly accepted idea that the early time relaxation of the haem is only due to cooling. The decay back to the ground state proceeds partially as a cascade through iron spin states, which seems to be a general characteristic of haem systems.

Assessment of Right Ventricular Function by Tissue Doppler, Strain and Strain Rate Imaging in Patients with Left-Sided Valvular Heart Disease and Pulmonary Hypertension

Background: Pulmonary artery hypertension is the presentation of various types of cardiovascular and systematic diseases. There are different kinds of noninvasive methods to determine right ventricular function, pulmonary artery pressure, and effect of pulmonary hypertension on right ventricular function. These methods include the tissue Doppler imaging (TDI) of the tricuspid annulus and the longitudinal deformation indices of the right ventricular free wall. Objectives: In some patients, the echocardiogram cannot help estimate pulmonary artery pressure. In this study, we evaluated the effect of pulmonary hypertension on the TDI of the tricuspid annulus and the longitudinal strain and strain rate of the basal segment of the right ventricular free wall in patients with left-sided valvular heart disease and pulmonary hypertension. Indeed, we sought to investigate whether we can guess the presence of pulmonary hypertension through the measurement of the TDI of the tricuspid annulus and the deformity indices of the basal segment of the right ventricular free wall. Patients and Methods: Eighty consecutive patients with left-sided valvular disease and pulmonary artery hypertension (V/PH Group) and 80 healthy matched controls (H Group) were enrolled in this research. The TDI parameters were obtained in the tissue velocity imaging mode during systole (S, S VTI), early relaxation (E), atrial systole (A), and isovolemic relaxation time (IVRT). The deformation indices included peak systolic longitudinal strain and strain rate measured from the basal segment of the right ventricular free wall and were calculated as the relative magnitude of segmental deformation. Results: S, E, and S VTI were reduced significantly in the V/PH Group, and there was a significant negative correlation between S velocity, S VTI with pulmonary artery systolic pressure (PASP), and right ventricular diameter (RVD). According to the ROC curve, S velocity 40 ms had 78% sensitivity and 67% specificity for the prediction of pulmonary hypertension. In comparison with the H Group, RV longitudinal peak systolic strain (-14/35 ± 4%) and strain rate (-0.65 ± 0.12) at the basal segment of the right ventricular free wall were significantly lower in the V/PH Group (P < 0.001 and P < 0.001). Conclusions: We observed a significant reduction in S, E velocity, and S VTI of the tricuspid annulus. Moreover, the strain/strain rate of the basal segment of the right ventricular free wall had a marked decrease in the V/PH Group in comparison with the healthy subjects.

Early stage chronic kidney disease: a paradigm for diffuse fibrosis and clinical progression

Background Early stage chronic kidney disease (CKD) is an under recognised, highly prevalent cardiovascular (CV) risk factor. Despite a clustering of conventional atherosclerotic risk factors, there is a disproportionate rate of sudden cardiac death, heart failure and stroke rather than myocardial infarction. It is hypothesised that non-atherosclerotic processes, including left ventricular (LV) hypertrophy and fibrosis account for most of the excess CV risk. Methods In total, 30 patients (mean age 57 +/- 8 years) with CKD stage 2-4 (mean GFR 58 ± 22 ml/min/1.73 m2) with no history of cardiovascular disease (mean BP 129 mmHg ± 13/70 mmHg ± 11) or diabetes were compared with age and gender matched controls. All subjects underwent cardiac MRI (1.5T Siemens Avanto) for assessment of LV volumes, myocardial deformation (SPAMM tagging) and aortic distensibility. Late gadolinium enhancement (LE) and T1-mapping using a modified look-locker inversion recovery sequence (MOLLI) before and 15 minutes post gadolinium (0.1 mmol/Kg) for myocardial extracellular volume (ECV) were performed. Global ECV was the average measure from basal and mid short axis slices excluding LGE indicative of infarcted myocardium. Results Global ECV was increased in CKD (0.30 ± 0.05 vs. 0.27 ± 0.03, p < 0.05) with associated reductions in long axis systolic deformation (strain 14.8% ± 2 vs. 17.1% ± 2, p < 0.05), early relaxation (SR e’ 0.50 ± 0.2 vs. 0.67 ± 0.2, p < 0.05) and MAPSE (13 mm ± 2 vs. 17 mm ± 3, p < 0.05). Aortic distensibility was reduced in CKD (Table 1).

Inhibition of the NA+/CA2+ Exchanger (Ncx) Improves Cardiomyocyte Contractile Dysfunction in a Rat Model with Compensated Renal Failure and Heart Failure with Preserved Ejection Fraction

Background: Heart failure with preserved ejection fraction (HFPEF) and renal impairment are often associated but the underlying pathomechanisms are largely unknown. We investigated tissue fibrosis and cardiomyocyte contractile function in a rat model with HFPEF and compensated renal failure.Methods: Seventy young male Wistar rats were subjected to subtotal nephrectomy (NXT) or sham operation (SOP). Blood/urine samples, echocardiography, pressure-volume loops were performed after 8 and 24 weeks. Left ventricular (LV) hypertrophy, fibrosis (picosirius-red-staining) and NCX protein expression (Western blot) were determined after sacrification. Cardiomyocyte function (Ca2+ transients, cell shortening) was quantified in isolated cardiomyocytes without and with the NCX inhibitor SEA0400 (300nM).Results: NXT rats showed stable renal impairment with preserved urine excretion and elevated arterial pressure (148±8 and 154±7 vs. 105±3 and 109±2 mmHg, p<0.01) at 8 and 24 weeks, respectively. LV in NXT were significantly hypertrophied at 8 and 24 weeks, but LV systolic function (EF, dP/dt) were preserved. LVEDP, LA size and lung weight were significantly increased indicating HFPEF with pulmonary congestion. Fibrosis was increased in LV from NXT. LV cardiomyocytes showed significantly prolonged time for early (50%) relaxation and decay of the Ca2+ transient. Time constant of the caffeine-induced Ca2+ transient (TAU) was significantly prolonged indicating reduced NCX forward mode activity, while NCX protein expression was upregulated. Acute treatment with SEA0400 (300nM) significantly accelerated early relaxation in cardiomyocytes from NXT (8 weeks).Conclusion: In this model of compensated renal failure and HFPEF cardiomyocyte relaxation was prolonged already at an early stage. Our results suggest increased NCX activity may contribute to contractile dysfunction, likely through reverse mode Ca2+ influx. NCX represents a potential target to treat cardiomyocyte dysfunction in HFPEF.

PREDICTION OF CORONARY ARTERY DISEASE BY DETECTION OF POSITIVE ISOVOLUMIC RELAXATION VELOCITY IN PATIENTS WITH NORMAL RESTING WALL MOTIONS "A Tissue Doppler Echocardiographic Study"

Background: Diagnosis of coronary artery disease (CAD) is of importance in the contemporary society of ever-increasing CAD (1,2). Isovolumic relaxation velocity (VIR), Postsystolic motion or postsystolic shortening (PSS) is a delayed ejection motion of the myocardium occurring after the aortic valve closure during a generally prolonged isovolumic relaxation time, which is related with myocardial ischemia in human(3,4) and in experimental studies(5). Spectral tissue Doppler imaging (TDI) is a simple echocardiographic technique that can provide velocity measurement of the myocardial segments(6). A positive myocardial velocity during isovolumic relaxation phase (VIR) detected by TDI, which corresponds to postsystolic motion or PSS, has been shown to indicate severely ischemic myocardium(8). So, detection of positive VIR by spectral TDI may be used as a noninvasive, nonprovocative method to predict possible CAD; specially for those with coexisting morbidities, such as peripheral artery disease in the lower limb, orthopedic diseases. Aim of the work: Diagnostic value of positive myocardial velocity during isovolumic relaxation phase (VIR) by spectral TDI in prediction of CAD in patients with typical ischemic chest pain and normal resting wall motions. Patients and methods: This study was done in Cardiology department, Zagazig University on 80 patients; 41 females (51%) & 39 males (49%)) with typical ischemic chest pain and no regional wall motion abnormalities detected by resting echocardiography. Patients were divided into 2 groups according to presence of significant coronary artery lesion by coronary angiography; group A (patients with CAD) and group B (patients without CAD). All the following parameters were measured by TDI; 5 peak velocities during; Isovolumic contraction phase (VIC), Systolic ejection phase (S'), Early diastolic relaxation phase (Em), Atrial contraction phase (Am) and Isovolumic relaxation phase (VIR) if present and VIR time. Then coronary angiography was done for all patients. Results: As regard to presence of VIR velocity, there was significant difference (<0.05) between group A and group B at mid septal and anterior walls, highly significant difference (<0.001) at basal septal and anterior walls. There was highly significant difference between group A and B at mid and basal lateral and inferior walls. There was highly significant correlation between coronary angiography and VIR velocity regarding detection of positive and negative cases and also there was highly significant correlation between previous 2 tests by Kappa test p value (<0.001). Conclusion: Positive VIR detected by spectral tissue Doppler imaging is a useful indicator of CAD in patients with apparently normal left ventricular contraction and chest pain. Key words: TDI, VIR velocity, coronary angiofraphy, coronary artery disease.

Structural and functional left ventricular impairment in subjects with chronic spinal cord injury and no overt cardiovascular disease

ContextCardiovascular disease (CVD) is the leading cause of morbidity and mortality in subjects with long-term spinal cord injury (SCI). More specific recommendations for CVD prevention in this population are needed.MethodsOne hundred thirty male subjects (47 subjects with SCI and 83 able-bodied persons (ABPs), mean age 43.89 ± 1.9 and 45.44 ± 12.2 years; P = 0.48) underwent transthoracic echocardiography (TTE). The effects of age, weight, mean arterial pressure (MAP) and level of physical training on cardiac adaptations were evaluated through multiple regression analysis.ResultsIn subjects with SCI, TTE revealed increased wall thickness (P < 0.05), lower E wave, E/A ratio and early diastolic myocardial relaxation velocity on Tissue Doppler Imaging (TDI) (P < 0.05) and higher systolic myocardial contraction velocity on TDI (0.10 ± 0.02 vs. 0.09 ± 0.02 m/seconds, P = 0.002) and peak systolic pressure to end-systolic volume ratio (3.62 ± 1.39 vs. 2.82 ± 0.90, P < 0.001) compared with ABPs. Aortic diameters were larger in subjects with SCI than ABPs. Differences remained statistically significant even after adjustment for age, weight, MAP, and level of physical training. Weight and age were found to be independent variables that substantially affected left ventricular structure and function in subjects with SCI.ConclusionsSubjects with post-traumatic chronic SCI and no overt cardiovascular risk factors, exhibit initial left ventricular remodeling (as assessed by TTE) compared with ABPs. Lifestyle modifications, including regular physical exercise and weight control, should be implemented in all subjects with SCI, even at a very early stage, in order to reduce cardiovascular risk and prevent the development of CVD.

Experimental and Computational Approaches to Study Myofilament Structure-Function in Normal and Diseased Muscle

We use a combination of site-directed mutagenesis, protein biochemistry, multi-scale mechanical analysis and computational modeling to study the regulation of normal muscle myofibril contraction and how this is altered in diseases of the sarcomere. This interdisciplinary approach allows us to do detailed structure-function analysis. Mutations in cardiac troponin C (cTnC) that increase Ca2+ binding affinity also increase its affinity for cardiac troponin I (cTnI) and when these cTnC mutants are exchanged into myofibrils or skinned trabeculae, they increase the magnitude and rate of force generation at sub-maximal, but not maximal levels of activation, and can slow the early phase of relaxation. In contrast, cTnC mutations that reduce Ca2+ binding affinity have either no effect or reduce interaction with cTnI, reduce the magnitude and rate of force generation at all levels of Ca2+ and speed relaxation. Molecular Dynamics (MD) simulations show positive correlation between Ca2+ binding affinity and stability of both 1) interaction of Ca2+ with coordinating side chains in site II and 2) the hydrophobic patch of cTnC. Together the data suggest that native cTnC may operate just at the edge of maximal effectiveness. Mutations in cTnI associated with hypertrophic cardiomyopathy increase its affinity for cTnC and also Ca2+ binding affinity of cTnI. Interestingly, they also blunt the ability of cTnI Ser 23/24 phosphorylation to reduce its affinity for cTnC and increase the rate of early phase relaxation. MD simulation studies of whole cTn suggest Ser 23/24 phosphorylation leads to the formation of the intra-subunit interaction between the N-terminus and the inhibitory peptide region of cTnI. We are studying how this, and other intra-molecular interactions may be affected by HCM associated mutations and the contraction and relaxation properties of cardiac muscle. HL65497, HL11197 (MR), 8P41GM103426 (AM).

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Introduction: Right ventricular (RV) dysfunction can occur after cardiac surgery. Although the exact mechanism is not well understood, it has been suggested to be associated with pericardial incision as well as other factors related to cardiac surgery. Speckle Tracking Echocardiography was performed to assess RV systolic and diastolic function before and after cardiac surgery. Methods: RV speckle tracking was performed by transthoracic echocardiography before (mean 20.4hrs ±27) and after surgery (mean 47hrs ±33) in 50 patients (mean age 67.2 years ±12, 64% male) undergoing a variety of cardiac operations: 3 coronary artery bypass grafts, 12 aortic valve replacement, 3 mitral or aortic valve mass removal, 16 open and 16 robotic-assisted minimally-invasive mitral valve repair. The following strain parameters were measured: systolic function parameters include RV free wall longitudinal strain (RV LS) and strain rate (RV LSR), and diastolic function parameter RV free wall longitudinal early strain rate relaxation (RV LSRe). Results: RV systolic function assessed by speckle tracking was significantly reduced after cardiac surgery: RV longitudinal strain -25.3% to -15.5% (p<0.001), RV longitudinal strain rate -1.5 to -0.94 (p<0.001). RV diastolic function assessed by speckle tracking was similarly reduced: RV longitudinal strain rate early relaxation 1.4 to 0.92 (p<0.001). Conventional assessment methods of RV function also showed significant reductions: TAPSE 24.7mm to 13.4mm (p<0.001), Tricuspid valve S’ 0.14m/s to 0.08m/s (p<0.001), RIMP 0.39 to 0.54 (p<0.001), RV E:e’ 4.3 to 7.2 (p<0.001). RV fractional area change, E:A ratio and RV systolic pressure estimation did not significantly change. There was no significant association for the reduction in RV systolic or diastolic function assessed by speckle tracking (RV LS, RV LSR, RV LSRe) with echo-based RV peak systolic pulmonary artery pressures, cross clamp or bypass time, time to extubation, vasoactive requirement or number of days in hospital. The association between the reduction in RV longitudinal strain and whether surgery was minimally invasive approached significance (p=0.055), with minimally invasive surgery having a smaller reduction in strain values. Conclusions: RV systolic and diastolic function decreases significantly after cardiac surgery. This reduction is independent of echo-based RV peak systolic artery pressure estimation, cross-clamp or bypass time, vasoactive requirements, intubation time or number of days in hospital. RV longitudinal strain reduction may be smaller if surgery is minimally invasive supporting the concept that RV dysfunction is associated with the size of pericardial incision. Larger studies are warranted to extend this finding.

Myocardial Extracellular Volume Expansion and the Risk of Recurrent Atrial Fibrillation After Pulmonary Vein Isolation

This study tested whether myocardial extracellular volume (ECV) is increased in patients with hypertension and atrial fibrillation (AF) undergoing pulmonary vein isolation and whether there is an association between ECV and post-procedural recurrence of AF. Hypertension is associated with myocardial fibrosis, an increase in ECV, and AF. Data linking these findings are limited. T1 measurements pre-contrast and post-contrast in a cardiac magnetic resonance (CMR) study provide a method for quantification of ECV. Consecutive patients with hypertension and recurrent AF referred for pulmonary vein isolation underwent a contrast CMR study with measurement of ECV and were followed up prospectively for a median of 18 months. The endpoint of interest was late recurrence of AF. Patients had elevated left ventricular (LV) volumes, LV mass, left atrial volumes, and increased ECV (patients with AF, 0.34 ± 0.03; healthy control patients, 0.29 ± 0.03; p < 0.001). There were positive associations between ECV and left atrial volume (r= 0.46, p < 0.01) and LV mass and a negative association between ECV and diastolic function (early mitral annular relaxation [E'], r=-0.55, p<0.001). In the best overall multivariable model, ECV was the strongest predictor of theprimary outcome of recurrent AF (hazard ratio: 1.29; 95% confidence interval: 1.15 to 1.44; p<0.0001) and the secondary composite outcome of recurrent AF, heart failure admission, and death (hazard ratio: 1.35; 95% confidence interval: 1.21 to 1.51; p < 0.0001). Each 10% increase in ECV was associated with a 29% increased risk of recurrent AF. In patients with AF and hypertension, expansion of ECV is associated with diastolicfunction and left atrial remodeling and is a strong independent predictor of recurrent AF post-pulmonary vein isolation.

Abstract 18278: Anabolic-Androgenic Steroid Use is Associated With Systolic and Diastolic Left Ventricular Dysfunction

Background: Illicit anabolic-androgenic steroid (AAS) abuse is a worldwide public health problem. While several small recent human studies suggest that AAS abuse leads to left ventricular (LV) dysfunction, this association remains incompletely explored. We therefore examined LV function in long-term AAS users (≥2 years of lifetime AAS) and age-matched, non-user comparison men. Methods: All participants underwent a structured clinical interview to obtain a detailed medical history, prior use of AAS and other illicit drugs, and exercise exposure followed by standard 2-dimensional transthoracic echocardiography. LV systolic function was assessed by LV ejection fraction (bi-plane method) and LV diastolic function was assessed using early LV relaxation velocity (E’). Groups were compared by linear regression with adjustment for traditional cardiovascular risk factors and lifetime use of other drugs. Results: We evaluated 33 weightlifting current AAS users (mean [SD] age 44.0 [5.7] years), 18 weightlifting prior AAS users with &gt; 3 months of abstinence (42.4 [4.2] years), 19 non-AAS-using weightlifters (43.2 [5.2] years), and 18 non-AAS-using non-weightlifting men (42.4 [5.2] years). Current AAS users had significantly lower LV ejection fractions than non-AAS-using weightlifters and non-weightlifting men (Table). Similarly, current AAS users showed impaired diastolic function compared to non-AAS-using weightlifters and non-weightlifting men (Table). Of note, prior AAS users showed no significant difference from the two non-AAS comparison groups, and were significantly better than current users on both indices of LV function. Conclusions: Current AAS use is associated with statistically and clinically significant impairment of LV function. Although further confirmatory study is required, these findings suggest that AAS-induced LV dysfunction is a serious but potentially reversible pathology that regresses with AAS abstinence.

Exercise-induced changes in cardiovascular function after stroke: a randomized controlled trial.

Cardiovascular co-morbidities are prevalent after stroke, with heart disease, hypertension and impaired glucose tolerance present in the majority of cases. Exercise has the potential to mediate cardiovascular risk factors commonly present in people with stroke. This single-blinded randomized controlled trial compared the effects of high versus low intensity exercise on fitness, cardiovascular risk factors, and cardiac function after stroke. Fifty participants (age 50-80 y, >1 y post-stroke) were randomized to a high-intensity Aerobic Exercise (AE) or low-intensity non-aerobic Balance/Flexibility (BF) program (6 months, 3 60-min sessions/week). Outcomes assessed by VO2 peak (primary outcome), arterial stiffness, ambulatory capacity, hemodynamics and cardiac function using echocardiography, and lipid, glucose and homocysteine levels. Assessors were blinded to group allocation. Twenty-three (92%) of 25 AE group participants (withdrawals unrelated to the intervention) and all BF group participants completed the program. One BF group participant experienced 2 non-injurious falls during class. No other adverse events occurred. There were no changes in VO2 peak in either group (AE 16·9±7 to 17·4±7 ml●kg(-1) ●min(-1) vs. BF 16·9±6 to 16·6±5 ml●kg(-1) ●min(-1) , P=0·45), but AE group demonstrated greater improvement in right atrial emptying fraction (AE 30±22 to 37±22% vs. BF 35±20 to 31±20%, P=0·04). Both groups demonstrated improvements in lipid profiles, glucose and homocysteine levels, and ambulatory capacity (P<0·04). This was the first study to examine the effects of aerobic exercise after stroke on cardiovascular hemodynamics. High-intensity exercise improved right-sided function and early myocardial relaxation. Low-intensity exercise may also benefit plasma lipid, glucose and inflammatory markers, and ambulatory capacity. This study is an important step towards understanding mechanisms by which exercise may reduce cardiovascular risk and function.

Bedside assessment of right atrial pressure in critically ill septic patients using tissue Doppler ultrasonography

PurposeRight atrial pressure (RAP) is considered a surrogate for right ventricular filling pressure or cardiac preload. It is an important parameter for fluid management in patients with septic shock. It is commonly approximated by the central venous pressure (CVP) either invasively using a catheter placed in the superior vena cava or by bedside ultrasound, in which the size and respiratory variations of the inferior vena cava (IVC) are measured from the subcostal view. Doppler imaging of the tricuspid valve from the apical 4-chamber view has been proposed as an alternative approach for the estimation of RAP. The tricuspid E/Ea ratio is measured, where E is the peak velocity of the early diastolic tricuspid inflow and Ea is the peak velocity of the early diastolic relaxation of the lateral tricuspid annulus. We hypothesized that the tricuspid E/Ea ratio may represent an alternative to IVC metrics, using invasive CVP as the criterion standard, for the assessment of RAP in critically ill septic patients. Materials and methodsA convenience sample of 30 septic patients, both mechanically ventilated and non–mechanically ventilated, was enrolled. Using a portable ultrasound system, maximum velocity of tricuspid E and Ea was measured from the apical 4-chamber view; and IVC diameter and degree of collapse were measured from the subcostal view. Decision tree induction was used to determine the performance of each model compared with invasive CVP. ResultsOur results suggest that a tricuspid E/Ea ratio of greater than 4.7 can predict a CVP greater than 10 mm Hg in septic patients with sensitivity greater than 85% and specificity greater than 90%. ConclusionsIn this pilot study, Doppler imaging of the tricuspid valve provided a valuable alternative for noninvasive bedside estimation of RAP in septic patients.

Cellular mechanisms of contractile dysfunction in a rat model with compensated renal failure and heart failure with preserved ejection fraction

Background: Renal impairment and heart failure with preserved ejection fraction (HFPEF) are often associated but the underlying mechanisms are largely unresolved. Therefore we investigated cardiomyocyte function in a rat model with compensated renal failure and diastolic dysfunction. Methods: Fifty-six young male Wistar rats were subjected to subtotal nephrectomy (NXT) or sham operation (SOP) and observed up to 24 weeks. Urine and blood samples for calculating the glomerular filtration rate (GFR) and echocardiography were performed during disease progression. Invasive hemodynamics (P/V-loops), morphometry, protein expression analysis and Ca2+ transients (confocal and ratiometric) as well as cell shortening (CS) were studied in isolated left ventricle (LV) cardiomyocytes in final experiments at 8 and 24 weeks. Results: Following NXT rats develop compensated renal failure (GFR 22±2 and 16±2 vs. 32±2 and 28±3 ml/min/m2 at 8 and 24 weeks, resp. p<0.01) with preserved urinary excretion and unchanged electrolytes. Arterial pressure is significantly increased in NXT at 8 and 24 weeks (148±8 and 154±7 vs. 105±3 and 109±2 mmHg, p<0.01) which is associated with pronounced LV hypertrophy in NXT (LV mass 708±21 and 866±34 vs. 637±12 and 660±7 mg, resp. p<0.05). Increased LV end-diastolic pressure (10.4±0.8 vs. 5.1±0.4 mmHg, p<0.01), left atrial enlargement (39±2 vs. 30±1 mg, p<0.01) and increased lung weight (1816±92 vs. 1414±39 mg, p<0.01) in NXT after 24 weeks reflect diastolic dysfunction with congestion indicating HFPEF (EF 50±5 vs. 56±4%). LV cardiomyocytes isolated from NXT compared to SOP showed no significant differences in cell shortening amplitude at 1 Hz (4.3±0.7 vs. 5.1±1.1%; n≥10) while time for early (50%) relaxation was significantly prolonged in NXT (CS RT50 42±3 vs. 34±1 ms; n≥10; p< 0.05) at 24 weeks. Cytosolic Ca2+ transients had similar amplitude (F/FO 4.2±0.1 vs. 4.1±0.1, n≥20). Sarcoplasmatic reticulum (SR) Ca2+ content was significantly reduced in NXT at 24 weeks (F/F0 5.3±0.2 vs. 6.0±0.2; n≥20; p<0.01) while it was unchanged after 8 weeks (F/F0 4.7±0.2 vs. 4.8±0.3; n≥10). Time constant of the caffeine-induced Ca2+ transient (TAU) was significantly prolonged in NXT after 24 weeks (1.77±0.07 vs. 1.22±0.06; n≥20; p< 0.01). NCX protein expression was unchanged in NXT, suggesting functional impairment of NCX1 activity. Conclusion: Subtotal nephrectomy in rats lead to compensated renal failure and an in vivo phenotype of HFPEF. Our in vitro results suggest early impairment of intracellular Ca2+ transients in HFPEF in NXT, leading to contractile dysfunction of the cardiac myocyte.

Photoexcitation and Charge-Transfer-to-Solvent Relaxation Dynamics of the I–(CH3CN) Complex

Photoexcitation of iodide-acetonitrile clusters, I(-)(CH3CN)n, to the charge-transfer-to-solvent (CTTS) state and subsequent cluster relaxation could result in the possible formation of cluster analogues of the bulk solvated electron. In this work, the relaxation process of the CTTS excited iodide-acetonitrile binary complex, [I(-)(CH3CN)]*, is investigated using rigorous ab initio quantum chemistry calculations and direct-dynamics simulations to gain insight into the role and motion of iodine and acetonitrile in the relaxation of CTTS excited I(-)(CH3CN)n. Computed potential energy curves and profiles of the excited electron vertical detachment energy for [I(-)(CH3CN)]* along the iodine-acetonitrile distance coordinate reveal for the first time significant dispersion effects between iodine and the excited electron, which can have a significant stabilizing effect on the latter. Results of direct-dynamics simulations demonstrate that [I(-)(CH3CN)]* undergoes dissociation to iodine and acetonitrile fragments, resulting in decreased stability of the excited electron. The present work provides strong evidence of solvent translational motion and iodine ejection as key aspects of the early time relaxation of CTTS excited I(-)(CH3CN)n that can also have a substantial impact on the subsequent electron solvation processes and further demonstrates that intricate details of the relaxation process of CTTS excited iodide-polar solvent molecule clusters make it heavily solvent-dependent.

Megalobrama amblycephala cardiac troponin T variants: Molecular cloning, expression and response to nitrite

Cardiac troponin T (TNNT2), as a member of troponin superfamily, plays important roles during early cardiogenesis, and contraction and relaxation of myocardial cells. In this study, two alternatively spliced variants of Megalobrama amblycephala TNNT2 were identified showing a difference of 19 amino acids in the N-terminal hypervariable region. The longer cDNA (TNNT2-1) was 1118bp, encoding 284 amino acid residues, contained conserved central tropomyosin-binding region, cardiac specific signal and C-terminal segments except the N-terminal hypervariable region. The TNNT2 transcripts first appeared at 16hours post-fertilization (hpf) peaking at 28hpf (onset of heartbeat). In addition, strong expression of TNNT2 was found in the cardiac muscle. After nitrite exposure, the increased TNNT2 expression levels in the heart indicated that nitrite might induce cardiac injury. Results of semi-quantitative RT-PCR indicated that the two alternatively spliced variants existed in early development stages since their first appearance at 16hpf and heart, spleen, headkiney of M. amblycephala. The shorter transcript (TNNT2-2) was proved to be dominant in the embryos and heart of M. amblycephala, furthermore, the increase of TNNT2 expression level in the heart after nitrite exposure was mainly caused by TNNT2-2.