Significant Changes In Systolic Function Research Articles

Long-term atorvastatin or the combination of atorvastatin and nicotinamide ameliorate insulin resistance and left ventricular diastolic dysfunction in a murine model of obesity

Current studies aimed at investigating the association between atorvastatin therapy and insulin resistance (IR) appear to be controversial. IR is considered to be an important contributor to inducing cardiac dysfunction through multiple signals. The paradoxical cardiotoxicity of atorvastatin reported under different conditions suggests that the association between atorvastatin treatment, insulin resistance and cardiac function should be clarified further. In this study, C57BL/6 J male mice were fed a high-fat diet (HD) or standard chow diet (SD) for 12 weeks and subsequently randomly divided into four groups: the SD-Control (SD-C) and HD-Control (HD-C) groups treated with saline for 10 months and the HD-A and HD-A + N groups treated with atorvastatin (20 mg/kg/day) alone or atorvastatin combined with nicotinamide (NAM, 1 g/kg/day) for 10 months. Although no significant changes in systolic function and structure were observed between the four groups of mice at an age of 46 or 58 weeks, respectively, long-term treatment with atorvastatin alone or atorvastatin and NAM combination significantly retarded the HD-induced IR and diastolic dysfunction and attenuated both cardiac and hepatic fibrosis in obese mice possibly by regulating the cleavage of osteopontin and then controlling profibrotic activity. Changes in cardiac function and structure were similar between the HD-A and HD-A + N groups; however, mice in the HD-A + N group exhibited better glucose control and marked reduction in body weight and hepatic lipid accumulation. Thus, these results suggest that long-term treatment with atorvastatin or the combination of atorvastatin and nicotinamide may be alternative therapies due to their beneficial effects on IR and diastolic function.

Effect of Sodium-Glucose Cotransporter-2 Inhibitors versus Dipeptidyl Peptidase 4 Inhibitors on Cardiovascular Function in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease.

BackgroundRandomized controlled trials demonstrated lowering risks of cardiovascular events with sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk. We analyzed the effects of cardiovascular function on SGLT2 inhibitors compared with dipeptidyl peptidase-4 (DPP4) inhibitors in T2DM with atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF).MethodsThis is a retrospective, observational, single center study. Data from 89 patients with ASCVD or HF from January 2015 to February 2018 were analyzed regarding the effect of SGLT2 inhibitors and DPP4 inhibitors. Cardiovascular function was assessed by 2-D echocardiography and N-terminal prohormone of brain natriuretic peptide (NT-pro BNP).ResultsA total of 89 patients with T2DM were considered in two groups of SGLT2 inhibitors (n=41) and DPP4 inhibitors (n=48). The mean follow-up period was 2 years, with a total of 89 patient-years. Despite no significant change in systolic function, SGLT2 inhibitors improved cardiovascular function, as demonstrated by a reduced left ventricular ejection fraction less than 40%, ratio of mitral peak velocity of early filling velocity to early diastolic mitral annular velocity, ratio of early to late ventricular filling velocities, and NT-pro BNP compared with the DPP4 inhibitor group.ConclusionSGLT2 inhibitors improve cardiovascular function in T2DM with coronary artery disease compared to DPP4 inhibitors.

Abstract 13060: Abrogation of miR-195 Improves Function in Aged Heart by Preventing Telomere Shortening and Mitochondrial Dysfunction

Background: Recently, we discovered a distinct microRNAs profile in young and old MSCs by microarray which led us to hypothesize that senescence-associated microRNA(miR)-195 plays a critical role in stem cell aging through telomerase reverse transcriptase (tert) deactivation and determined whether direct inhibition of miR-195 in aged myocardium restores juvenile characteristics and improves cardiac function. Methods and Results: To examine the mechanistic participation of miR-195 in cardiac aging and function, we directly injected lentivral miR-195 inhibitor into the normal mice heart through open chest surgery. Interestingly, we observed a significant telomere re-lengthening in myocardium injected with anti-miR-195 as examined by Q-FISH analysis. In addition, heart tissues treated with miR-195 inhibitor markedly restored the expression of anti-aging factors such as Tert, telomeric repeat-binding factor 2 (Trf2) and Sirt1, whereas expression of pro-aging markers including p53 and p16 were reduced. Additionally, we found that mitochondrial activity was significantly improved in miR-195 knocked down heart as examined by cytochrome c oxidase activity assay. To investigate whether abrogation of miR-195 in myocardium improves cardiac function, we performed echocardiography at 4 weeks after injection. The cardiac function was markedly improved in miR-195 knocked down myocardium as evaluated by cardiac performance index, a useful marker for heart failure (0.24±0.05 vs 0.44±0.13, p<0.05, n=6), whereas there was no significant change in systolic function . Furthermore, histological analysis showed that transfection of miR-195 inhibitor markedly reduced fibrosis as well as expression of connective tissue growth factor (CTGF), a fibrogenic master switch, in the aged myocardium as compared to scramble transfected heart. Conclusions: These results demonstrate that abrogation of miR-195 improves cardiac function through restoration of anti-aging factors as well as amelioration of mitochondrial dysfunction. Suppression of miR-195 in aging myocardium is a novel therapeutic strategy for treatment against age-dependent cardiovascular diseases.

Short-term changes in serum sex steroid levels and cardiac function in healthy young men

Introduction: Male obesity is associated with an increase in estradiol (E2) and a decrease in testosterone (T). And, although sex steroids are associated with cardiovascular disease, direct effects on cardiac structure and function are hardly investigated in humans. Methodology: Twenty healthy men aged 20–40 years were randomized into two groups. One group was given an aromatase inhibitor (letrozole) only, thus obtaining a high testosterone and low E2 (group T). The other group received an aromatase inhibitor plus an E2 patch (dermestril), reaching a low testosterone and high E2 (group E). Serum levels of both testosterone and E2 remained within the normal reference range. The men underwent an echocardiography by a single cardiologist before the start of the intervention and after 7 days. Results: Total and free E2 serum levels were positively associated with ejection fraction (r=0.7, P=0.002 and r=0.6, P=0.007 respectively) at baseline in the whole group. In group E global circumferential strain decreased significantly from −25.3%±3.9 to −19.6%±2.5 after 1 week as compared to baseline (P=0.01). No significant changes in systolic function were observed in group T. Cardiac structure remained unaltered. Conclusion: In young healthy men, an increase in E2 and decrease in testosterone levels significantly decreased circumferential strain. The finding justifies larger studies of longer duration to discover the exact nature of the impact of changed sex steroids on cardiac function and remodelling in obesity.

Myocardial function in children after fetal chemotherapy exposure. A tissue Doppler and myocardial deformation imaging study

Chemotherapy and particularly anthracycline exposure are associated with acute and chronic cardiotoxicity. Few data exist on the effect of cardiac function after in utero exposure to maternal chemotherapy. Our recently published multicenter prospective study showed no significant changes in systolic function using conventional echocardiographic parameters. The purpose of this study was to further investigate whether early functional changes can be detected using tissue Doppler imaging (TDI) and two-dimensional (2D) speckle tracking echocardiography (STE). Sixty-two children (median/range age 1.7 (1-9.8) years) exposed to chemotherapy during fetal life were enrolled and compared to 62 age- and gender-matched controls. TDI velocities were measured at the basal interventricular septum (IVS) and right and left ventricular (LV) free walls. LV global longitudinal and circumferential systolic strains were derived using 2D STE. We found small but significant differences between the groups (patients versus controls) in LV fractional shortening [35 (29-46)% versus 39 (28-53)%, p < 0.001], LV ejection fraction [66 (57-79)% versus 70 (57-83)%, p < 0.001], LV posterior wall thickness z score [-0.15 (-2.32-1.81) versus -0.10 (-1.9-2.0), p < 0.001], and IVS thickness z score [-1.06 (-2.6-1.3) versus -0.5 (-2.1-1.7), p < 0.001]. No significant differences in TDI velocities or LV global strains were observed. Within the patient group, the cardiac functional parameters did not correlate to the number of cycles of anthracycline or the cumulative anthracycline dose. Children exposed to fetal chemotherapy have a lower normal fractional shortening and mildly lower left ventricular wall thickness. Tissue Doppler and strain measurements are within normal range and not statistically different from normal controls. The long-term implications of these findings will be further studied in this prospective cohort study.

Altered left ventricular longitudinal diastolic function correlates with reduced systolic function immediately after anthracycline chemotherapy

The benefits from anthracycline chemotherapy are undermined by potentially life-threatening cardiotoxicity. Transthoracic echocardiography is the most commonly used method for monitoring cardiotoxicity, and centres on the measurement of left ventricular systolic function. The aim of this study was to utilize two-dimensional speckle tracking echocardiography (2DSTE) at baseline and immediately after anthracycline chemotherapy to investigate whether patients with significant changes in systolic function after anthracycline therapy would also develop alterations in diastolic parameters. Fifty-two women with histologically confirmed breast cancer were prospectively recruited. Echocardiograms were performed 1 week prior to and 1 week following chemotherapy (always before adjuvant trastuzumab or thoracic radiotherapy). Conventional Doppler, tissue velocity imaging (TVI), and 2DSTE were used to measure diastolic function. 2DSTE measurements included longitudinal diastolic strain, early (E-Sr), and late (A-Sr) myocardial strain rate. 2DSTE and left ventricular ejection fraction (LVEF) were used to measure longitudinal systolic function. Altered LV diastolic function (including E-Sr) was observed in the entire cohort after chemotherapy, with a differential reduction in participants with a post therapy LVEF <55%. Pre-chemotherapy systolic strain was found to predict reduced E-Sr post therapy (P = 0.04). Univariate predictors of E-Sr were LVEF post therapy (P = 0.049) and systolic strain post-therapy (P = 0.01). In a multivariate analysis, systolic strain after chemotherapy was the strongest independent predictor (P = 0.001). Altered LV diastolic function was observed immediately after the administration of therapeutic doses of anthracycline chemotherapy. Furthermore, our analysis indicates that the changes in diastolic function are associated with reduced systolic function.

Diastolic dysfunction in volume-overload hypertrophy is associated with abnormal shearing of myolaminar sheets

Diastolic dysfunction in volume-overload hypertrophy by aortocaval fistula is characterized by increased passive stiffness of the left ventricle (LV). We hypothesized that changes in passive properties are associated with abnormal myolaminar sheet mechanics during diastolic filling. We determined three-dimensional finite deformation of myofiber and myolaminar sheets in the LV free wall of six dogs with cineradiography of implanted markers during development of volume-overload hypertrophy by aortocaval fistula. After 9 +/- 2 wk of volume overload, all dogs developed edema of extremities, pulmonary congestion, elevated LV end-diastolic pressure (5 +/- 2 vs. 21 +/- 4 mmHg, P < 0.05), and increased LV volume. There was no significant change in systolic function [dP/dt(max): 2,476 +/- 203 vs. 2,330 +/- 216 mmHg/s, P = not significant (NS)]. Diastolic relaxation was significantly reduced (dP/dt(min): -2,466 +/- 190 vs. -2,076 +/- 166 mmHg/s, P < 0.05; time constant of LV pressure decline: 32 +/- 2 vs. 43 +/- 1 ms, P < 0.05), whereas duration of diastolic filling was unchanged (304 +/- 33 vs. 244 +/- 42 ms, P = NS). Fiber stretch and sheet shear occur predominantly in the first third of diastolic filling, and chronic volume overload induced remodeling in lengthening of the fiber and reorientation of the laminar sheet architecture. Sheet shear was significantly increased and delayed at the subendocardial layer (P < 0.05), whereas magnitude of fiber stretch was not altered in volume overload (P = NS). These findings indicate that enhanced filling in volume-overload hypertrophy is achieved by enhanced sheet shear early in diastole. These results provide the first evidence that changes in motion of radially oriented laminar sheets may play an important functional role in pathology of diastolic dysfunction in this model.

WS06: Fetal echocardiography WS06‐01Human fetal cardiac function during the first trimester of pregnancy

IntroductionThe hypothesis was tested whether the improvement in the human fetal cardiac diastolic and systolic functions are associated with changes in the cardiac volume blood flow, inflow blood velocity waveform characteristics, systemic venous blood flow parameters, umbilical artery velocimetry and fetal nuchal translucency. By a longitudinal study protocol the inflow and outflow blood velocity waveforms were obtained in 16 uncomplicated pregnancies at 6, 7, 8, 9 and 10 weeks.ResultsThe proportion of isovolumetric relaxation time decreased and the proportions of filling and ejection times of the cardiac cycle increased significantly from 6 to 7 weeks. The proportion of isovolumetric contraction decreased between 8 and 9 weeks. Every inflow waveform was monophasic before 9 weeks but it was biphasic in all cases at 10 weeks. Mean velocity of inflow and outflow increased between 6 and 7 weeks and Vmean of inflow increased further after 8 weeks. At 9 and 10 weeks, atrioventriculu valve recurgitation (AVVR) was present in 4 and 7 fetuses, respectively. Nuchal translucency was greater in fetuses with AVVR present at 10 weeks compared with non‐AVVR cases.ConclusionImprovement in the diastolic function of fetal heart between 6 and 7 weeks is accompanied by simultaneous increase in the mean velocities across inflow and outflow tracts. Appearance of biphasic inflow pattern is associated with significant change in systolic function between 8 and 9 weeks. AVVR is a common finding at 10 weeks of gestation.

Iatrogenic Myocardial Edema: Increased Diastolic Compliance and Time Course of Resolution in Vivo

Perfusion-induced edema reduces diastolic compliance in isolated hearts, but this effect and the time for edema to resolve after blood reperfusion have not been defined in large animals. Edema was induced by coronary perfusion with Plegisol (750 mL, 289 mOsm/L) during a 1-minute aortic occlusion in 6 pigs. This was followed by whole blood reperfusion, inotropic support, and circulatory assistance until sinus rhythm and contractile function were restored. A control group (n = 6) was treated similarly, with 1 minute of electrically induced ventricular fibrillation and no coronary perfusion. Recorded data included electrocardiogram, left ventricular pressure and conductance, aortic flow, and two-dimensional echocardiography. Preload reduction by vena caval occlusion was used to define systolic and diastolic properties. Data were recorded at baseline and at 15-minute intervals for 90 minutes after reperfusion. In the edema group, average left ventricular mass (132 +/- 7 [standard error of the mean] versus 106 +/- 4 g) and ventricular stiffness constant (0.15 +/- 0.02 versus 0.05 +/- 0.01) increased after Plegisol versus baseline (p < 0.05), returning to normal after 45 minutes of reperfusion. In controls, mass (118 +/- 6 versus 116 +/- 4 g) and ventricular stiffness (0.06 +/- 0.01 versus 0.05 +/- 0.01) did not change significantly. There was no significant change in systolic function. Myocardial water content at the end of the study was not different for the two groups. Crystalloid-induced edema and diastolic stiffness resolve after 45 minutes in pigs. This suggests that edema caused solely by cardioplegia during cardiac operations should not cause significant perioperative ventricular dysfunction.

Prospective study of left ventricular function after radiofrequency ablation of atrioventricular junction in patients with atrial fibrillation.

In patients with drug resistant incessant supraventricular tachycardia, radiofrequency induced ablation of the atrioventricular junction and pacemaker implantation have hitherto been considered a treatment of last resort. To assess the short and long term effects of ablation of the atrioventricular junction on systolic and diastolic left ventricular function in patients with atrial fibrillation with and without impaired left ventricular function. 29 patients (19 men; mean age 65 (SD 7) years (range 50-76)) undergoing ablation of the atrioventricular junction for drug refractory atrial fibrillation were examined a mean of 2, 65, and 216 days after ablation of the bundle of His. Left ventricular ejection fraction and early filling deceleration times (Edec) were assessed by Doppler echocardiography after 1 to 2 hours of ventricular pacing at a rate of 80 beats/minute. In 14 patients with a left ventricular ejection fraction < 50% left ventricular ejection fraction increased significantly from 32% (11%) to 39% (11%) (65 days) and 45% (11%) (216 days) (P < 0.001); Edec increased from 142 (46) ms to 169 (57) ms (65 days) and 167 (56) ms (216 days) (P < 0.05). In 15 patients with an ejection fraction > or = 50% at the initial examination no significant change in systolic function was observed. In patients with left ventricular dysfunction long term improvement of systolic and diastolic left ventricular function was seen after ablation of the atrioventricular junction for rate control of atrial fibrillation. This procedure had no adverse effects on normal left ventricular function.