Left Ventricular End-diastolic Internal Dimension Research Articles

Exercise alleviates cardiac remodelling in diabetic cardiomyopathy via the miR-486a-5p-Mst1 pathway.

Objective(s):Physical exercise has emerged as an effective therapy to mitigate cardiac remodelling in diabetic cardiomyopathy (DCM). The results of our previous studies revealed mammalian sterile 20-like kinase 1 (Mst1) is a key regulator of the progression of DCM. However, the precise molecular mechanism of physical exercise-induced cardiac protection and its association with Mst1 inhibition remain unclear. Materials and Methods:Wildtype and Mst1 transgenic mice were challenged with streptozotocin (STZ) to induce experimental diabetes and were divided into sedentary and exercise groups. The DCM phenotype was evaluated by echocardiography, Masson’s trichrome staining, TUNEL and immunoblotting analyses. The exercise-regulated miRNAs targeting Mst1 were predicted by bioinformatic analysis and later confirmed by RT-qPCR, immunoblotting, and dual-luciferase reporter assays. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulate diabetes to elucidate the underlying mechanisms. Results:Compared to the sedentary diabetic control, physical exercise inhibited Mst1 and alleviated cardiac remodelling in mice with DCM, as evidenced by decreases in the left ventricular end-systolic internal dimension (LVESD) and left ventricular end-diastolic internal dimension (LVEDD), increases in the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), attenuation of collagen deposition, and the suppression of apoptosis. Bioinformatic analysis and apoptosis assessments revealed exercise exerted protective effects against DCM through miR-486a-5p release. Moreover, luciferase reporter assays confirmed miR-486a-5p directly suppressed the expression of Mst1, thereby inhibiting the apoptosis of cardiomyocytes subjected to high glucose treatment. Conclusion:Physical exercise inhibits cardiac remodelling in DCM, and the mechanism is associated with miR-486a-5p release-induced Mst1 inhibition.

Comparative study of cardiorespiratory adaptations in elite basketball players of different age groups.

Systematic training of basketball causes morphological cardiac and cardiorespiratory adaptations. Previous studies have mainly focused either on only cardiac or respiratory changes. However, the extent of these cardiac adaptations and their relationship with aerobic capacity remain unclear in basketball athletes of different ages. Eighty male basketball players participated in the experimental group and 80 healthy and sedentary male individuals served as controls. All participants underwent to athletic history, anthropometric measurements, 12-lead resting electrocardiogram (ECG), echocardiography, resting spirometry and cardiopulmonary exercise stress test. Left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular end-diastolic internal dimension (LVIDd), end-diastolic volume (EDV), stroke volume (SV) and interventricular septal thickness at diastole (IVSd) were significantly higher in all groups of athletes compared to controls (P<0.05). End-diastolic volume index (EDVI) was significantly higher only in adult players compared to controls (P<0.05). Posterior wall thickness at diastole (PWd) was significantly greater in groups of children and adult players compared to controls (P<0.05). Maximal oxygen uptake (V̇O<inf>2max</inf>) in relative values was higher in all groups of athletes compared to controls (P<0.05). The increased LVM is attributed to concentric hypertrophy. This is further supported by the finding that there was no relationship between V̇O<inf>2max</inf> and echo parameters. The results of the present study indicate that the cardiorespiratory adaptations caused by basketball training are mainly formed at the early age stages without further increase throughout the years of action.

COVID-19-Related Multisystem Inflammatory Syndrome in Children Affects Left Ventricular Function and Global Strain Compared with Kawasaki Disease

COVID-19-Related Multisystem Inflammatory Syndrome in Children Affects Left Ventricular Function and Global Strain Compared with Kawasaki Disease

P3434Galectin-3 identifies healthy subjects at risk of developing (pre-)diastolic dysfunction

Abstract Background/Introduction Biomarkers might be useful to identify healthy subjects who are at risk of developing diastolic dysfunction. Cardiac remodeling, in particular fibrosis, is a hallmark of diastolic dysfunction. Previous (pre)clinical studies have linked galectin-3 to fibrogenesis. Therefore, we aimed to evaluate whether galectin-3 would be able to identify apparently healthy individuals who are at risk of developing pre-clinical diastolic dysfunction. Purpose To study whether galectin-3 is able to identify healthy subjects who are at risk of developing pre-clinical diastolic dysfunction over time. Methods We measured both galectin-3 and B-type natriuretic peptide (BNP) in 1.500 participants of the population study LifeLines. Based upon the biomarker profile, we selected 88 subjects with elevated galectin-3 (&gt;14.3 ng/mL; n=42) and with low galectin-3 (&lt;9.8 ng/mL; n=46) values, while all participants demonstrated low BNP. We matched these groups so other confounding variables like age, sex, kidney function (creatinine), body weight (BMI) and blood pressure were comparable between both groups. After approximately five years follow up, we invited those 88 participants to determine the level of diastolic dysfunction using echocardiography. Statistical analyses were performed in IBM SPSS Statistics 25 and StataMP 13. Results We included 88 participants at a median age of 50 years (standard deviation ± 11 years) in this case-control study. Besides the galectin-3 levels, all other variables were adequately matched and fully comparable between both groups. Obviously, galectin-3 levels (median, IQR) were markedly different between the groups (galectin-3 levels 7.35 ng/L (6.9 - 8.6) vs 16.4 ng/L (15.1- 17.8), P&lt;0.001). Subjects with elevated galectin-3 demonstrated signs of structural cardiac remodeling: enlarged left atrial diameter (35.3 mm vs. 37.3 mm P=0.034), and larger diastolic interventricular septum thickness (IVS) (9.4 mm vs. 10.1 mm P=0.038), and a smaller left ventricular end-diastolic internal dimension index (LVIDd Index) (2.3 cm/m2 vs. 2.2 cm/m2 P=0.026), a smaller left ventricular end diastolic volume (LVEDV) (98.9 mL vs. 89.9 mL P=0.025). In addition, they exhibited several indicators of worse diastolic function, such as a higher E/e' ratio (5.2 vs. 5.9, P=0.046), while there was no significant difference in the left ventricular ejection fraction (60.8% vs. 59.9%, P=0.110). Conclusion Elevated galectin-3, when fully matched for confounding factors, is associated with the development of preclinical-diastolic dysfunction before onset of clinical symptoms. Our data suggest that substantial elevations of galectin-3 in apparently healthy subjects hint towards preclinical cardiac dysfunction. Acknowledgement/Funding Dutch Heart Foundation 2015T034; NWO VIDI, grant 917.13.350; ERC CoG 818715, SECRETE-HF

Abstract P2003: Loss of Trpa1 in Mice Leads to Age-Related Dilated Cardiomyopathy

Activation of the transient receptor potential ankyrin 1 (TRPA1) channel, a mechanical and oxidative stress sensor, has been shown to slow down aging process and promote longevity in invertebrate animal models like Caenorhabditis elegans . Although physiologic sensory functions of TRPA1 are conservative across species, the role of TRPA1 in regulation of organ development and function in mammals in the aging process is unknown. The present study tests the hypothesis that TRPA1 ablation leads to cardiac dilation and cardiomyopathy in aging mice. Echocardiography was performed in male 12-week-old (young) and 52-week-old (older) Trpa1 gene knockout ( Trpa1 -/- ) mice and wild-type (WT) littermates on a mixed C57BL/6 x 129 genetic background. Echocardiogram data showed that, compared to young WT littermates, young Trpa1 -/- mice had similar cardiac dimensions and left ventricular function, as demonstrated by left ventricular end-diastolic internal dimension (LVIDd, WT 4.29±0.62 vs. Trpa1 -/- 4.50±0.41 mm, P&gt;0.05), left ventricular ejection fraction (LVEF, a parameter of systolic function, WT 66.73±9.50 vs. Trpa1 -/- 63.39±12.76 %, P&gt;0.05), and E/A ratio (a parameter of diastolic function, WT 1.23±0.03 vs. Trpa1 -/- 1.39±0.14, P&gt;0.05). In contrast, older Trpa1 -/- mice developed dilated cardiomyopathy with dilated left ventricle (LVIDd: WT 4.60±0.16 vs. Trpa1 -/- 5.00±0.37 mm, P&lt;0.05) and impaired left ventricular systolic function (LVEF: WT 58.04±9.27 vs. Trpa1 -/- 41.79±7.19 %, P&lt;0.05) when compared to older WT mice. In addition, older Trpa1 -/- mice had impaired left ventricular myocardial performance index (LV MPI, a parameter of ventricular systolic and diastolic function, WT 0.62±0.15 vs. Trpa1 -/- 0.89±0.18, P&lt;0.05) albeit left ventricular diastolic function was not different between old Trpa1 -/- and WT mice (E/A ratio: WT 1.53±0.22 vs. Trpa1 -/- 1.99±0.92, P&gt;0.05). These results show that genetic knockout of TRPA1 leads to age-related left ventricular dilation and systolic dysfunction. These findings suggest that TRPA1 activation protects against age-related dilated cardiomyopathy.

Functional and Structural Myocardial Improvement after LVAD Therapy: The U-NOVA Reverse Remodeling Stages

Background The degree of left ventricular morphological and functional improvement following continuous flow left ventricular assist device (LVAD) implantation is variable. Objectives To evaluate the continuum of left ventricular reverse remodeling after LVAD implantation by serial echocardiographic imaging in an effort to define stages of reverse remodeling. Methods Consecutive patients with heart failure who required mechanical circulatory support with a durable LVAD were enrolled from two programs (UTAH consortium and Inova). Echocardiograms were performed within 1-month preceding LVAD implantation and then 1,2, 3, 6, 9, and 12 months after. Patients were categorized by the degree of morphologic and functional change after LVAD support. Results The study included 358 patients with baseline and at least 6-month follow up measurements. The mean duration of heart failure was 6.9 ± 6.7 years, baseline left ventricular ejection fraction (LVEF) was 19 ± 7%, with mean left ventricular end-diastolic internal dimension (LVIDd) 6.8 ± 1.0 cm. In the cohort, 34 patients (10%) experienced improvement of the LVEF ≥ 40% and LVIDd ≤ 6.0cm and were termed as responders. The remaining patients were categorized as non-responders, borderline responders and partial responders by an increase in LVEF during follow-up (∆) LVEF 10%, respectively. Most patients were non-responders (n=212, 59%), followed by borderline responders (n=55, 15%) and partial responders (n=57, 16%). Multivariable logistic regression identified smaller initial LVIDd (OR 1.77 per 1 cm decrease, 95% CI 1.15-2.3, p=0.009), use of an axial flow device (OR 2.57, 95% CI 1.08-6.12, p=0.033), and shorter heart failure duration (OR 1.10 per 1-year decrease, 95% CI 1.01-1.20, p=0.047) as predictors of response. Conclusions Reverse left ventricular remodeling associated with durable LVAD support is not an all or none phenomenon and as many other biological phenomena manifests as a continuous spectrum. Defining 4 stages across this continuum may have clinical management implications and may also facilitate advancing the field of myocardial plasticity by informing the study design of future investigations.

Left ventricular rotation and torsion in neonates and infants younger than three months with symptomatic ventricular septal defect: Acute effects from open heart surgery.

We evaluated ventricular rotation, torsion, and strain changes in infants using preoperative and postoperative M-mode echocardiography after early surgery for symptomatic ventricular septal defects (VSD). Thirty-five patients with VSD underwent vector velocity imaging echocardiography before and after open heart surgery. Their rotational variables were compared with 18 controls. All the patients (19 boys and 16 girls; median age: 44.4 days; range: 13-84 days) showed normal septal motion preoperatively; however, septal motion changed into flat septum or paradoxical septal motion after surgery. Left ventricular end-diastolic internal dimension and fractional shortening significantly decreased after surgery (P = .001 and P = .000). Patients showed significant postoperative reduction of peak systolic apical rotation and maximal torsion (P = .010 and P = .000). Peak systolic basal rotation decreased after surgery but it was not significantly (P = .106). No significant differences were found in longitudinal and circumferential systolic strains between patients and controls. Abnormal motion of the ventricular septum was confirmed by postoperative M-mode echocardiography. Decreased rotation/torsion variables may reflect postoperative changes of ventricular loading conditions. Because systolic strain was preserved, postoperative echocardiographic results should not be interpreted as abnormal or decreased ventricular function.

Renal denervation decreases susceptibility of the heart to ventricular fibrillation in a canine model of chronic kidney disease.

What is the central question of this study? Renal denervation (RDN) has been shown to be effective and safe, resulting in better control of blood pressure and an improvement in left ventricular hypertrophy in chronic kidney disease (CKD) patients. Ventricular arrhythmias and sudden cardiac death are common causes of death in CKD patients, but previous studies pay almost no attention to the effects of RDN on the risk of ventricular fibrillation associated with CKD. What is the main finding and its importance? Renal denervation could decrease susceptibility of the heart to ventricular fibrillation in a canine CKD model. Improvement of left ventricular hypertrophy, sympathetic activation and inflammation by RDN may be responsible for its beneficial effects. Renal denervation (RDN) has been shown to have therapeutic value in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether RDN could decrease the susceptibility of the heart to ventricular fibrillation in a canine model of CKD. Twenty-one dogs were used. Chronic kidney disease was produced by subtotal nephrectomy in 16 dogs with RDN treatment (CKD+RDN group, n=8) or sham RDN (CKD group, n=8). Another five dogs underwent sham operation and sham RDN to serve as controls (CTR group). Parameters of renal function, blood pressure, echocardiography, ECG, noradrenaline and inflammation were measured at baseline and 6weeks after the surgical procedure. The ventricular fibrillation threshold (VFT) was determined at the end of the study. Subtotal nephrectomy successfully induced a canine CKD model. When compared with the CTR group, subtotal nephrectomy in the CKD group significantly elevated blood pressure; increased the left ventricular mass, end-diastolic left ventricular internal dimension, left ventricular end-diastolic posterior wall thickness and end-diastolic interventricular septum thickness; prolonged the QT interval, corrected QT interval, the interval from the peak to the end of the T wave (Tp-e) and the corrected Tp-e interval; and increased the QT dispersion and the Tp-e/QT ratio; decreased the VFT; and increased the serum concentrations of noradrenaline, C-reactive protein and interleukin-6. Renal denervation significantly attenuated these changes induced by CKD. The study demonstrated that RDN could decrease the susceptibility of the heart to ventricular fibrillation in this CKD model. Improvement of left ventricular hypertrophy, sympathetic activation and inflammation by RDN may be responsible for its beneficial effects.

Clinical characteristics, target organ damage and associate risk factors of resistant hypertension determined by ambulatory blood pressure monitoring in patients aged ≥ 80 years.

ObjectivesTo investigate clinical characteristics, target organ damage, and the associated risk factors of the patients aged ≥ 80 years with true resistant hypertension (RH).MethodsPatients aged ≥ 80 years with hypertension (n = 1163) were included in this study. The included participants attended a structured clinical examination and an evaluation of RH was carried out. The prevalence, clinical characteristics and target organ damage of patients with RH were assessed. The associated clinical risk factors were analyzed by using logistic regression.ResultsThe prevalence of RH diagnosis by 24-h ambulatory blood pressure monitoring assessment was 21.15%. End-diastolic left ventricular internal dimension, left ventricular mass index as well as prevalence of left ventricular hypertrophy were significantly greater in patients with RH than in control group. The common carotid artery intimal media thickness, carotid walls thickness, common carotid artery diameter and relative wall thickness were significant greater in RH group than in control. A relatively higher level of creatinine, estimated glomerular filtration rate, microalbuminuria and retinal changes was found in RH group than in control. A multivariate analysis showed that patients with a history of diabetes, higher body mass index (BMI) and lipid profiles were independent risk factors of RH.ConclusionsThe prevalence of RH in patients aged ≥ 80 years was within the range of reported rates of the general population. Subjects with RH diagnosis showed a higher occurrence of target organ damage than patients with well controlled blood pressure. Patients with diabetes, higher BMI and serum lipid profiles were independent risk factors for RH in patients aged ≥ 80 years.

OP.8A.01] EXERCISE-INDUCED HYPERTENSION AND CARDIAC HYPERTROPHY IN EPINEPHRINE-DEFICIENT MICE

Objective: Phenylethanolamine-N-methyltransferase (Pnmt) is required for the conversion of norepinephrine to epinephrine. Bao et al (2007) described that Pnmt-knockout (Pnmt-KO) mice have an increased ratio of left ventricular (LV) posterior wall thickness to internal dimensions (LVPW/LVID) but not overall cardiac hypertrophy. Pnmt-KO mice showed normal resting blood pressure (BP) but became hypertensive during treadmill exercise. The aim of this study was to evaluate cardiac morphological and functional alterations after chronic exercise in Pnmt-KO mice. Design and method: PCR-based genotyping was performed at the Pnmt locus of 10-week-old Pnmt-KO (Pnmt-/-) and WT mice (129x1/SvJ). Epinephrine and norepinephrine were quantified by RP-HPLC-ED in adrenal glands. Animals were submitted to a 6-week exercise training program. BP was measured by a photoelectric pulse detector. Mice were anesthetized (sevoflurane, 8%) and cardiac morphology and function were evaluated by echocardiography followed by morphometric analysis. Results: Epinephrine levels were vestigial in Pnmt-KO compared with WT mice. There were no differences in systolic and diastolic BP between untrained Pnmt-KO and WT mice. However, trained Pnmt-KO mice showed a significant increase in systolic BP when compared to trained WT mice. Our findings also showed that the ratios between heart weight (HW/BW) and LV weight (LVW/BW) and body weight (BW) were significantly increased in trained compared to untrained Pnmt-KO mice. Trained Pnmt-KO mice presented higher HW/BW than trained WT mice. Untrained Pnmt-KO mice display echocardiographic results similar to those reported by Bao et al (2007) while LVPW and IVS thicknesses, LV end-diastolic internal dimension (LVIDd) and LV mass indexed for body surface area (LVMi) were significantly increased in trained Pnmt-KO mice, indicating overall LV hypertrophic changes. Indexed LV end-diastolic volume (LVEDVi), indexed stroke volume (SVi) and cardiac index (CI) were significantly higher in trained Pnmt-KO than untrained Pnmt-KO mice. Conclusions: In conclusion, the increased BP in Pnmt-KO mice in response to exercise appears to be associated with an increase in LV wall thickness and chamber volume suggesting hypertrophic remodelling of the LV in Pnmt-KO mice. Epinephrine appears to be essential for maintaining normal BP, probably through β2-adrenoceptors-induced vessel relaxation, and preventing LV hypertrophy in chronic exercise.

The effects of long-term aerobic exercise on cardiac structure, stroke volume of the left ventricle, and cardiac output.

The purpose of this study is to investigate the effect of the long-term aerobic exercises on cardiac structure, left ventricular stroke volume, and cardiac output. To achieve the purpose of the study, a total of 22 volunteers—including 10 people who have continued regular exercises and 12 people as the control group—were selected as subjects. With regard to data processing, the IBM SPSS Statistics ver. 21.0 was used to calculate the mean and standard deviation, and the difference of the means between the groups was verified through an independent t-test. As a result, there were significant differences between groups in the left ventricular end-diastolic internal dimension, left ventricular end-systolic internal dimension, left ventricular end-diastolic septum thickness. There were significant differences between groups in left ventricular end-diastolic volume, left ventricular mass, and left ventricular mass index per body surface area. However, in cardiac function, only left ventricular stroke volume showed a significant difference between groups.

Proof of concept study: Improvement of echocardiographic parameters after renal sympathetic denervation in CKD refractory hypertensive patients

AimEvaluation of the effectiveness of the renal sympathetic denervation (RSD) in reducing lesions of target organs such as the heart and kidneys, in resistant hypertensive CKD patients. Methods and resultsForty-five patients were included and treated with an ablation catheter with open irrigated tip. RSD was performed by a single operator following the standard technique. Patients included with CKD were on stages 2 (n=22), 3 (n=16), and 4 (n=7). Data were obtained at baseline and monthly until the 6th month of follow-up. Twenty-six out of the 45 patients had LVH and nineteen did not present LVH. The LV mass index decreased from 123.70±38.44g/m2 at baseline to 106.50±31.88g/m2 at the 6th month after RSD, P<0.0001. The end-diastolic left ventricular internal dimension (LVIDd) reduced from 53.02±6.59mm at baseline to 51.11±5.85mm 6months post procedure, P<0.0001. The left ventricular end-diastolic posterior wall thickness (PWTd) showed a reduction from 10.58±1.39mm at baseline to 9.82±1.15mm at the 6th month of follow-up, P<0.0001. The end-diastolic interventricular septum thickness (IVSTd) also decreased from 10.58±1.39mm at baseline to 9.82±1.15mm 6months post procedure, P<0.0001. The left ventricular ejection fraction (LVEF) improved from 58.90±10.48% at baseline to 62.24±10.50% at the 6th month of follow-up, P<0.0001. When the ∆ between baseline and the 6th month post RSD in LVH patients and non LVH patients were compared to the same parameters no significant difference was found. ConclusionsThe RSD seemed to be feasible, effective, and safe resulting in an improvement of echocardiographic parameters in LVH and non LVH CKD refractory hypertensive patients.

Vascular Adhesion Protein-1, a Novel Molecule, in Kidney and Heart Allograft Recipients

BackgroundVAP-1 (vascular adhesion protein-1) is a copper-containing SSAO (semicarbazide-sensitive amine oxidase) secreted by vascular smooth muscle cells, adipocytes, and endothelial cells. Elevation of SSAO activity is observed in atherosclerosis, diabetes mellitus, and obesity. The aim of the study was to assess VAP-1 in prevalent heart and kidney allograft recipients. MethodsComplete blood count, urea, serum lipids, fasting glucose, and creatinine were studied by standard laboratory methods. VAP-1, N-terminal pro brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP) were estimated using commercially available assays. ResultsHealthy volunteers showed higher hemoglobin and estimated glomerular filtration rate (eGFR) but lower creatinine, NT-proBNP, hsCRP and VAP-1 relative to heart and kidney transplantation (OHT) (KTx). Among heart transplant recipients, VAP-1 correlated with age, presence of diabetes, insulin therapy, ejection fraction, estimated glomerular filtration rate by MDRD (Modification of Diet in Renal Disease), eGFR by CKD-EPI (Chronic Kidney Disease-Epidemiological Collaboration), use of tacrolimus, LVIDd (left ventricular internal end-diastolic dimension), New York Heart Association class and NT-proBNP. VAP-1 was significantly lower among patients treated with tacrolimus than cyclosporine. Diabetic patients versus nondiabetic subjects as well as patients with eGFR below 60 versus ≥ 60 mL/min showed higher serum VAP-1 in OHT and KTx populations. Multiple regression analysis revealed VAP-1 to be predicted in 25% by LVIDd, and use of tacrolimus in OHT. In kidney transplant recipients, VAP-1 correlated only with time after transplantation and serum glucose. ConcludingVAP-1 elevations in heart transplant recipients were predominantly dependent on left ventricular diameter and use of tacrolimus; however, the precise associations with the immunosuppressive regimen warrant further studies. VAP-1 elevations in kidney transplant recipients may relate to glucose control.

Mathematically engineered stromal cell–derived factor-1α stem cell cytokine analog enhances mechanical properties of infarcted myocardium

The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell-derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction. Male rats (n=54) underwent either sham surgery (n=17) with no coronary artery ligation or ligation of the left anterior descending artery (n=37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n=18) or ESA (6 μg/kg, n=19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB. Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P=.0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P=.04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P=.05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P=.04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle. Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart.

Effects of high thoracic epidural sympathetic blockade for the treatment of severe chronic heart failure due to dilated cardiomyopathy

Objective Beta blockers and angiotensin-converting enzyme inhibitors are known to attenuate the remodelling process in chronic heart failure, but the high mortality after heart failure must be resolved. We aimed to evaluate the eff ects of using high thoracic epidural sympathetic blockade (HTESB) as an adjunctive treatment to conventional therapy on the regression of left ventricular remodelling in chronic heart failure due to dilated cardiomyopathy.Methods We studied 40 patients with severe chronic heart failure due to dilated cardiomyopathy. These patients were randomly divided into two groups with equal size, and treated either by conventional therapy or HTESB as an adjunctive therapy (HTESB therapy) for 30 days. Echocardiography was performed before and after treatment.Results HTESB therapy was found to reduce left ventricular end-diastolic internal dimension by 5.3 mm, left atrial dimension by 7.6 mm, right ventricular dimension by 5.0 mm and right atrial dimension by 10.5 mm (P < 0.01). No discernable changes were observed in patients treated by conventional therapy. Moreover, HTESB therapy produced a greater increase in ejection fraction (11.2% vs. 2.2%) and more signifi cant improvement to NYHA class than conventional therapy (P < 0.05).Conclusions These data demonstrate that the use of HTESB as an adjunctive therapy to conventional therapy in severe chronic heart failure due to dilated cardiomyopathy was associated with reduction in cardiac chamber dimension and increase in left ventricular systolic function. These benefi cial eff ects on remodelling may lead to better prognosis.

The Impact of Prolonged Rotary Ventricular Assist Device Support upon Ventricular Geometry and Flow Kinetics

The aim of this study was to determine the impact of prolonged left ventricular assist device (VAD) support on cardiac ventricular geometry and VAD flow kinetics. Nineteen patients with end-stage heart failure underwent the implantation of HeartMate II rotary flow VADs. Left and right ventricular geometry and VAD flow kinetics were assessed by transthoracic echocardiography early (7 ± 1 days) and late (113 ± 21 days) after VAD implantation. Left ventricular end-diastolic internal dimension decreased by 21% and 35%, respectively, early and late after VAD implantation (n = 19; P < .001 vs before VAD implantation). Right ventricular end-diastolic internal dimension did not decrease at either time. Hemodynamic trends were similar. VAD inflow obstruction by myocardium was observed in eight patients, seven of whom demonstrated significantly increased variation of VAD inflow during the cardiac cycle ("pulsatility") detected by Doppler studies. Medical or surgical intervention returned VAD flow patterns toward baseline in seven of eight patients with VAD obstructions. Prolonged rotary VAD support unloads the left ventricle, with modest effects on the right ventricle. These changes are often associated with alterations of VAD flow kinetics, requiring therapeutic intervention. These findings indicate the usefulness of echocardiographic surveillance in patients undergoing prolonged VAD support.

Apelin and Cardiac Function in Hemodialyzed Patients: Possible Relations?

Background: Apelin, a newly discovered adipocytokine, is produced by white adipose tissue and is also expressed in the kidney and heart. Increasing evidence suggests a role for apelin in the pathology of the cardiovascular system. Cardiovascular disease is a major contributor to the mortality and morbidity in patients with chronic renal failure. The aim of this study was to assess associations between apelin, coronary artery disease (CAD) and echocardiographic parameters in hemodialyzed patients. Patients and Methods: We investigated plasma apelin levels (using commercially available kits) in 81 nondiabetic, clinically stable hemodialyzed patients (38 females, 43 males) with and without CAD. Results: Patients with CAD were significantly older, with significantly increased left ventricular internal end-diastolic dimension (LVIDd), left ventricular internal end-systolic dimension (LVISd), right ventricle (RV), left atrium (LA), interventricular septum in diastole, left ventricle posterior wall in diastole (LVPW), aorta, pulmonary artery, significantly lower ejection fraction and apelin than patients without CAD. We observed statistically significant correlations between apelin and echocardiographic parameters: LVIDd, LVISd, RV, LA, right atrium, LVPW, aorta, and serum lipids: cholesterol, LDL, triglycerides. In multiple logistic regression analysis, the only associate of apelin was LVIDd. Conclusions: Apelin level was significantly lower in dialyzed patients with CAD and it was associated with cardiac function. Apelin might be involved in the pathophysiology of cardiovascular disease in chronic renal failure. Since apelin is an inotrope in normal and failing hearts, this finding may have clinical implications for future use of apelin as a novel inotropic agent also for patients with uremic cardiomyopathy.

Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilation and clinical status in patients without structural heart disease

The present study evaluated clinical benefits of radiofrequency catheter ablation (RFA) for premature ventricular complexes from right ventricular outflow tract (RVOT-PVC) in patients without structural heart disease. It is unknown whether PVC causes left ventricular (LV) dilation, which is a well-recognized precursor of LV dysfunction and heart failure, and whether eliminating PVC by RFA produces clinical benefits in patients with RVOT-PVC. Frequency of PVC per total heart beats by 24-h Holter monitoring, left ventricular ejection fraction (LVEF), left ventricular end-diastolic internal dimension (LVDd), mitral regurgitation (MR) by echocardiogram, cardiothoracic ratio (CTR) by chest radiogram, and New York Heart Association (NYHA) functional class of 40 patients with RVOT-PVC without structural heart disease were evaluated before and 6 to 12 months after RFA. Before RFA, a subgroup of patients with frequent (>20%) PVC demonstrated significantly enlarged LVDd and CTR, reduced LVEF, increased MR, and deteriorated NYHA functional class as compared to the subgroup with rare (<20%) PVC (54 +/- 1 mm vs. 45 +/- 1 mm, 52 +/- 2% vs. 46 +/- 1%, 66 +/- 2% vs. 73 +/- 2%, 1.2 +/- 0.2 degree vs. 0.4 +/- 0.1 degree, and 1.8 +/- 0.2 vs. 1.3 +/- 0.1, respectively; p < 0.05). Furthermore, ablating RVOT-PVC readily produced the improvement of all these abnormalities (47 +/- 1 mm, 41 +/- 1%, 72 +/- 2%, 0.3 +/- 0.1 degree, and 1.0 +/- 0.0, respectively; p < 0.05 compared with before RFA). These findings suggest that frequent (>20%) RVOT-PVC may be a possible cause of LV dysfunction and/or heart failure, and RFA produces clinical benefits in these patients.

Pressure Overload Induces Cardiac Dysfunction and Dilation in Signal Transducer and Activator of Transcription 6–Deficient Mice

Signal transducer and activator of transcription (STAT) proteins constitute a family of transcription factors that mediate many cytokine-induced responses. STAT6 is activated by angiotensin II and in rat hypertrophied hearts and in human hearts with dilated cardiomyopathy. This suggests that STAT6 may be involved in the pathogenesis of cardiac hypertrophy and heart failure. For this study we used STAT6-deficient (STAT6-/-) mice to examine the in vivo role of STAT6. STAT6-/- hearts showed no morphological, histological, or functional defects. We examined left ventricular structural and functional remodeling 1 week after thoracic transverse aortic constriction (TAC). Western blot and immunohistochemical analyses showed increased STAT6 activity after TAC in the heart of wild-type mice. STAT6-/- mice showed a significant increase in end-diastolic left ventricular internal dimension accompanied by impaired contractility compared with wild-type mice but no differences in hypertrophic parameters. The number of terminal deoxynucleotidyl transferase-mediated biotin dUTP nick-end labeling-positive myocytes after TAC had increased in STAT6-/- compared with wild-type mice. Prolonged induction of tumor necrosis factor-alpha (TNF-alpha) mRNA was observed in STAT6-/- hearts, whereas TNF-alpha mRNA was only transiently induced in wild-type mice. Tristetraprolin was induced after TAC in wild-type mice but not in STAT6-/- mice. Tristetraprolin reporter assay with the use of isolated neonatal cardiomyocyte indicated that the promoter was significantly activated by endothelin-1 in wild-type but not in STAT6-/- cardiomyocytes. The lack of promoter activation by endothelin-1 in STAT6-/- cardiomyocytes was rescued by forced expression of STAT6. STAT6 plays a protective role against hemodynamic stress in hearts.

Time-dependent systolic and diastolic function in mice overexpressing calcineurin.

Echocardiograms have been assessed only at 56 days in mice overexpressing calcineurin (CN mice). Age-dependent echocardiographic changes were evaluated because the development of sudden death is time dependent. Because cyclosporin A (CsA) reverses hypertrophy in CN mice, its effects on the time course of the development of sudden death and cardiac dysfunction were assessed. In wild-type (WT) mice, the left ventricular (LV) internal end-diastolic dimension (LVIDd) increased and the LV mass index (LVMI) decreased with age. In CN mice, two distinct phases of pathophysiology were found. After 14 days, in CN mice, the LVIDd and LVMI were significantly increased, but sudden death had not occurred. After 28 days, in CN mice, relative dilation of the left ventricle occurred, whereas the LVMI decreased. Sudden death developed during progressive dilation associated with systolic and diastolic dysfunction. CsA treatment reversed hypertrophy in CN mice but did not reverse systolic and diastolic dysfunction and exaggerated sudden death. Sudden cardiac death was associated with systolic and diastolic dysfunction but was not related to isolated cardiac hypertrophy in CN mice.