Tanshinone IIA Improves Ventricular Remodeling following Cardiac Infarction by Regulating miR-205-3p

Objective. To illustrate the role of tanshinone IIA (TSN) in regulating cardiac structure and function following myocardial infarction (MI) and the involvement of miR-205-3p in TSN-induced antifibrosis effect on ventricular remodeling. Patients and Methods. One hundred MI patients were randomly assigned into two groups, and they were treated with TSN (TSN group, n = 50 ) or conventional therapy (control group, n = 50 ). Plasma levels of miR-205-3p and TGF-β1 were detected in each patient. Echocardiography was conducted in each patient at post-MI 1 day, 2 weeks, and 4 weeks, respectively, for recording LVIDd (left ventricular internal-diastolic diameter), LVIDs (left ventricular internal-systolic diameter), and LVEF (left ventricular ejection fraction). The interaction between miR-205-3p and TGF-β1 was examined by the RNA-Binding Protein Immunoprecipitation (RIP) assay. After induction of TGF-β1 and/or 10 μL of TSN in cardiac fibroblasts, relative levels of miR-205-3p, Col1a1, and Col3a1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results. Compared with the control group, miR-205-3p and TGF-β1 were downregulated in plasma of MI patients in the TSN group. In the TSN group, LVIDd and LVIDs were reduced, and EF was enhanced at 2 weeks and 4 weeks compared with that at post-MI 1 day. miR-205-3p could negatively interact with TGF-β1. TSN induction abolished the regulatory effects of TGF-β1 on downregulating miR-205-3p and upregulating Col1a1 and Col3a1 in cardiac fibroblasts. Conclusions. Through upregulating miR-205-3p and downregulating TGF-β1, TSN alleviates cardiac fibrosis and improves ventricular remodeling following MI.

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Antihypertrophic Memory after Regression of Exercise-induced Physiological Myocardial Hypertrophy is Mediated by the Long Noncoding RNA Mhrt779

Circulation ◽

10.1161/circulationaha.120.047000 ◽

2021 ◽

Author(s):

Hairuo Lin ◽

Yingqi Zhu ◽

Cankun Zheng ◽

Donghong Hu ◽

Siyuan Ma ◽

...

Keyword(s):

Western Blot ◽

Noncoding Rna ◽

Rna Binding ◽

Myocardial Hypertrophy ◽

Quantitative Polymerase Chain Reaction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Sham Operation ◽

Ventricular Ejection Fraction

Background: Exercise can induce physiological myocardial hypertrophy (PMH), and former athletes can live 5-6 years longer than nonathletic controls, suggesting a benefit after regression of PMH. We previously reported that regression of pathological myocardial hypertrophy has antihypertrophic effects. Accordingly, we hypothesized that antihypertrophic memory exists even after PMH has regressed, increasing myocardial resistance to subsequent pathological hypertrophic stress. Methods: C57BL/6 mice were submitted to 21 days of swimming training to develop PMH. After termination of exercise, PMH regressed within 1 week. PMH regression mice (exercise hypertrophic preconditioning group, EHP) and sedentary mice (control group) then underwent transverse aortic constriction (TAC) or a sham operation for 4 weeks. Cardiac remodeling and function were evaluated using echocardiography, invasive left ventricular hemodynamic measurement and histological analysis. LncRNA sequencing, chromatin immunoprecipitation assay (ChIP), and comprehensive identification of RNA-binding proteins by mass spectrometry (CHIRP-MS) and Western blot were used to investigate the role of Mhrt779 involved in the anti-hypertrophy effect induced by EHP. Results: At 1 and 4 weeks after TAC, the EHP group showed less increase in myocardial hypertrophy and lower expression of the Nppa and Myh7 genes than the sedentary group. At 4 weeks after TAC, EHP mice had less pulmonary congestion, smaller left ventricular dimensions and end-diastolic pressure, and a larger left ventricular ejection fraction and maximum pressure change rate than sedentary mice. Quantitative polymerase chain reaction (qPCR) revealed that the long noncoding myosin heavy chain associated RNA transcript Mhrt779 was one of the markedly upregulated long noncoding RNAs in the EHP group. Silencing of Mhrt779 attenuated the antihypertrophic effect of EHP in mice with TAC and in cultured cardiomyocytes treated with angiotensin II, and overexpression enhanced the antihypertrophic effect. By ChIP and qPCR, we found that EHP increased histone 3 trimethylation (H3K4me3 and H3K36me3) at the a4 promoter of Mhrt779 . CHIRP-MS and Western blot showed that Mhrt779 can bind Brg1 to inhibit the activation of Hdac2/Akt/GSK3β pathway induced by pressure overload. Conclusions: Myocardial hypertrophy preconditioning evoked by exercise increases resistance to pathological stress via an antihypertrophic effect mediated by a signal pathway of Mhrt779 /Brg1/Hdac2/p-Akt/p-GSK3β.

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Novel antisense therapy targeting microRNA-132 in patients with heart failure

European Heart Journal ◽

10.1093/eurheartj/ehab724.0920 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

J Taubel ◽

W Hauke ◽

S Rump ◽

J Viereck ◽

S Batkai ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Fibrosis ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Private Company ◽

Ventricular Ejection Fraction ◽

Pharmacodynamic Effects ◽

Amino Terminal ◽

Patients With Heart Failure

Abstract Background Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. Purpose The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study. Methods Patients had left ventricular ejection fraction between ≥30% and <50% or amino terminal fragment of pro-brain natriuretic peptide (NT-proBNP) >125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. Results CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed median 23.3% NT-proBNP reduction, vs. 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and positive trends for cardiac fibrosis biomarkers. Conclusions This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. The indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Cardior Pharmaceuticals GmbH

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Prognostic role of results of dynamic capnography in integral assessment of parameters of respiratory system in 6-minute walk test in patients with chronic heart failure

I P Pavlov Russian Medical Biological Herald ◽

10.23888/pavlovj2020283290-299 ◽

2020 ◽

Vol 28 (3) ◽

pp. 290-299

Author(s):

Kira A. Ageeva ◽

Evgenii V. Filippov

Keyword(s):

Respiratory System ◽

Prognostic Significance ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Walk Test ◽

Ventricular Ejection Fraction ◽

6Mwt Distance ◽

6 Minute Walk Test ◽

Minute Walk

Aim. To study the prognostic value of the results of dynamic capnography in the complex assessment of parameters of the respiratory system in 6-minute walk test in patients with chronic heart failure (CHF). Materials and Methods. 73 Patients were examined: the group of study included 48 patients with IIA or IIB stage CHF (mean age 57.94.6 years, 23 men), the control group included 25 practically healthy volunteers (mean age 47.63.5 years, 9 men). The patients were conducted complex determination of parameters of the respiratory system: clinical scaling before and after 6-minute walk test (6MWT), instrumental examinations including spirometry, capnography and pulse oximetry before, during and after physical activity. The analysis of survival was conducted on the basis of the dynamic follow-up of patients within 5 years (60 months). Results. In the analysis of parameters of dyspnea at rest, all the parameters were higher in the group of patients with CHF (р0.05). The distance walked by the patients with CHF in 6 minutes was 488.2390.84 m, which was significantly less than in the control group (815.6053.89 m, р=0.009). Dyspnea as the cause of stoppage/slowing down of walking in 6MWT, was also more often recorded in patients with CHF (93.83.0% and 48.05.1%, р=0.049). Besides, in 6MWT the patients noted: weakness in legs (50.15.0% in the group of CHF and 40.05.0% in the control group, р=0.014), palpitation (29.04.6% and 20.04.1%, respectively, р=0.004). Worsening of dyspnea parameters in 6MWT was more evident in patients with CHF than in the control group (р0.01). In the CHF group, hypocapnic type of ventilation was revealed in 6MWT, analysis of РЕТСО2 trend graphs revealed a wave-like increase in the parameters, the so called periodic breathing (PB). CO2 trend was recorded in CHF group in 58.31.0% of cases (the difference with the control group with р=0.046), the trend of heart rate in 18.80.3% of cases (р=0.027). Cox proportional hazards regression analysis of mortality in patients with CHF showed a prognostic significance of a complex model comprising the following parameters of a patient: body mass index (р=0.005), left ventricular end-diastolic dimension (р=0.034), left ventricular end-systolic dimension (р=0.002), left ventricular ejection fraction (р=0.041), 6MWT distance (р=0.004), desaturation (р=0.009), and the presence of signs of PB during 6MWT (р=0.005). Model coefficients were statistically significant at р0.0001. Conclusions. Dynamic capnography and pulse oximetry allow to identify signs of PB in patients with CHF during 6MWT which may deepen a complex assessment of parameters of the cardio-respiratory system in patients with CHF in order to determine tolerance to physical exercise as well as the effectiveness of the conducted treatment. Complex assessment of survival of patients with CHF showed prognostic significance of the following parameters of a patient: body mass index, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, 6MWT distance, desaturation, PB during 6MWT.

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STUDY THE CHANGES IN MORPHOLOGY AND LEFT VENTRICULAR FUNCTION IN OVERWEIGHT-OBESE CHILDREN 5-15 YEARS OLD WHO VISITED CHILDREN'S HOSPITAL IN CAN THO

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2011.6.4 ◽

2011 ◽

pp. 36-42

Author(s):

Hung Viet Bui ◽

Thi Cu Nguyen

Keyword(s):

Left Ventricular Function ◽

Ventricular Function ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Obese Children ◽

Ventricular Ejection Fraction ◽

Children's Hospital ◽

Number Of Patients ◽

Children’S Hospital

Objective: In Vietnam, obesity is increasing particularly in many large cities. Adult cardiovascular diseases are often derived from cardiovascular disorders during the children period. The implementation of early measures to prevent atherosclerosis, such as weight control, better lipid control will reduce the cardiovascular complications, such as hypertension (HTA), coronary heart diseases and some other diseases. Materials and Methods: Overweight - obese children from 5 to 15 years old who visited the Children's Hospital in Can Tho from May 2009 to May 2010. Total number of patients were chosen as 50 children. Method: Descriptive cross-sectional. Children in the study underwent Doppler ultrasound exam to evaluate cardiac morphology and cardiac function. Results: There were increases in left ventricular systolic diameter, left ventricular diastolic diameter, LV mass in overweight-obese children in the study compared with controls at all ages (p <0.05 ). Left ventricular ejection fraction in overweight-obese children in the study was lower than the control group at all ages (p> 0.05). The average rate of left ventricular shortening of overweight-obese children in the study was 34.8 ± 4.5(%). There was no difference in the rate of shortening of the left ventricle in overweight-obese children in the study compared with controls (p>0.05). There was no relationship between variation in morphology and left ventricular function with the degree of overweight-obesity in this study. Conclusion: The study showed that disturbances in morphology and left ventricular function in overweight-obese children but did not find a strong association with the disorder degree of overweight-obesity.

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Review of Irish patients meeting ST elevation criteria during the COVID-19 pandemic

Open Heart ◽

10.1136/openhrt-2021-001716 ◽

2021 ◽

Vol 8 (2) ◽

pp. e001716

Author(s):

Luke Byrne ◽

Roisin Gardiner ◽

Patrick Devitt ◽

Caleb Powell ◽

Richard Armstrong ◽

...

Keyword(s):

Public Health ◽

Public Perception ◽

Coronary Intervention ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Ventricular Ejection Fraction ◽

St Elevation ◽

The Impact ◽

Transfer Times

IntroductionThe COVID-19 pandemic has seen the introduction of important public health measures to minimise the spread of the virus. We aim to identify the impact government restrictions and hospital-based infection control procedures on ST elevation myocardial infarction (STEMI) care during the COVID-19 pandemic.MethodsPatients meeting ST elevation criteria and undergoing primary percutaneous coronary intervention from 27 March 2020, the day initial national lockdown measures were announced in Ireland, were included in the study. Patients presenting after the lockdown period, from 18 May to 31 June 2020, were also examined. Time from symptom onset to first medical contact (FMC), transfer time and time of wire cross was noted. Additionally, patient characteristics, left ventricular ejection fraction, mortality and biochemical parameters were documented. Outcomes and characteristics were compared against a control group of patients meeting ST elevation criteria during the month of January.ResultsA total of 42 patients presented with STEMI during the lockdown period. A significant increase in total ischaemic time (TIT) was noted versus controls (8.81 hours (±16.4) vs 2.99 hours (±1.39), p=0.03), with increases driven largely by delays in seeking FMC (7.13 hours (±16.4) vs 1.98 hours (±1.46), p=0.049). TIT remained significantly elevated during the postlockdown period (6.1 hours (±5.3), p=0.05), however, an improvement in patient delays was seen versus the control group (3.99 hours (±4.5), p=0.06). There was no difference seen in transfer times and door to wire cross time during lockdown, however, a significant increase in transfer times was seen postlockdown versus controls (1.81 hours (±1.0) vs 1.1 hours (±0.87), p=0.004).ConclusionA significant increase in TIT was seen during the lockdown period driven mainly by patient factors highlighting the significance of public health messages on public perception. Additionally, a significant delay in transfer times to our centre was seen postlockdown.

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Evaluation of Galectin-3 Plasma Concentration in Adolescents with Ventricular Arrhythmia

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052410 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2410

Author(s):

Radosław Pietrzak ◽

Tomasz M. Książczyk ◽

Elżbieta Górska ◽

Łukasz A. Małek ◽

Bożena Werner

Keyword(s):

Plasma Concentration ◽

Ventricular Arrhythmia ◽

Linear Regression Analysis ◽

Holter Monitoring ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Healthy Children ◽

Ventricular Ejection Fraction ◽

Galectin 3

Galectin-3 (G3) is a biomarker known as an inflammatory state exponent. The aim of this paper was to analyze the G3 in adolescents with ventricular arrhythmia (VES) in order to evaluate its impact on myocardial tissue preservation. The study group (SG) consisted of 25 VES adolescents. The control group (CG) was 21 healthy children. G3 was assessed in the SG and CG. In the SG electrocardiography, Holter monitoring, echocardiography and CMR were performed. The G3 in SG was 13.45 ± 11.4 ng/mL and in CG 7.2 ± 2.0 ng/mL, p < 0.001. Moderate positive correlation between the G3 and z-score of the left ventricular diameter (r = 0.47, p = 0.041) and moderate negative correlation between the G3 and the left ventricular ejection fraction in cardiac magnetic resonance (CMR EF) (−0.49, p = 0.032) were found. According to the multiple linear regression analysis, CMR EF and VES were independent predictors for G3 elevation. Conclusion: Galectin-3 plasma concentration is elevated and correlates with the chosen left ventricular dysfunction parameters in adolescents suffering from ventricular arrhythmia. Further investigation is necessary to establish if elevated G3 is a useful biomarker for screening young individuals with ventricular arrhythmia who are at risk of structural cardiovascular pathology.

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Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST)

Netherlands Heart Journal ◽

10.1007/s12471-021-01584-5 ◽

2021 ◽

Author(s):

W. P. te Rijdt ◽

E. T. Hoorntje ◽

R. de Brouwer ◽

A. Oomen ◽

A. Amin ◽

...

Keyword(s):

Disease Progression ◽

Cardiac Fibrosis ◽

Intervention Study ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Probe Design ◽

Mineralocorticoid Receptor Antagonist ◽

Ventricular Ejection Fraction ◽

Increased Risk ◽

Overt Disease

Abstract Background The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. Aims The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. Methods iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. Baseline results A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and < 2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021. Conclusion iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856).

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Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction

Cardiology ◽

10.1159/000446639 ◽

2016 ◽

Vol 135 (4) ◽

pp. 221-227 ◽

Cited By ~ 2

Author(s):

Shao-Ling Yang ◽

Ke-Qiang Tang ◽

Jun-Jia Tao ◽

Ai-Hong Wan ◽

Yan-Duan Lin ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Function ◽

Rabbit Model ◽

Physiological Saline ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Therapeutic Effects ◽

Ventricular Ejection Fraction ◽

Cluster Of Differentiation

Objectives: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). Methods: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. Results: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. Conclusion: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

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A Randomized Controlled Trial to Study the Effect of Yoga Therapy on Cardiac Function and N Terminal Pro BNP in Heart Failure

Integrative Medicine Insights ◽

10.4137/imi.s13939 ◽

2014 ◽

Vol 9 ◽

pp. IMI.S13939 ◽

Cited By ~ 12

Author(s):

Bandi Hari Krishna ◽

Pravati Pal ◽

G. K. Pal ◽

J. Balachander ◽

E. Jayasettiaseelon ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Medical Therapy ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Tei Index ◽

Ventricular Ejection Fraction ◽

Yoga Therapy ◽

Standard Medical Therapy

Aims The purpose of this study was to evaluate whether yoga training in addition to standard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF). Methods 130 patients were recruited and randomized into two groups: Control Group (CG) ( n = 65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the study. Cardiac function using left ventricular ejection fraction (LVEF), myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was assessed at baseline and after 12 weeks. Result Improvement in LVEF, Tei index, and NT pro BNP were statistically significant in both the groups. Furthermore, when the changes in before and after 12 weeks were in percentage, LVEF increased 36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and 2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG. The between group comparisons from pre to post 12 weeks were significant for YG improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01). Conclusion These results indicate that the addition of yoga therapy to standard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF.

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Abstract 3791: Improved Ventricular-Arterial Coupling After 4 Weeks of Exercise Training in Patients with Chronic Heart Failure

Circulation ◽

10.1161/circ.116.suppl_16.ii_862-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Marcus Sandri ◽

Stephan Gielen ◽

Norman Mangner ◽

Volker Adams ◽

Sandra Erbs ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Exercise Training ◽

Endothelial Function ◽

Training Group ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Lv Function ◽

Ventricular Ejection Fraction

Background: The concept of ventricular-arterial coupling implies that LV-function is determined by the three factors left ventricular diastolic, left ventricular systolic and arterial elastance. We have previously documented an improvement in endothelial function and systolic LV-function in patients with chronic heart failure (CHF) after 6 months of exercise training (ET). It remains, however, unclear, how shorter ET periods may affect endothelial, systolic and diastolic ventricular function as echocardiographic parameters related to ventricular arterial coupling in patients with CHF. METHODS: In this ongoing study we randomised 43 patients with stable CHF (age 60.3 ± 2.9 years, EF 27.4 ± 1.7%, VO 2 max 14.7 ± 4.3ml/kg*min) to a training or a control group (C). Patients in the training group exercised 4 times daily at 70% of the individual heart rate reserve for 4 weeks under supervision. At baseline and after 4 weeks the E/A ratio and septal/lateral E’/A’ velocities were determined by echocardiography with tissue Doppler. Exercise capacity was measured by ergospirometry and flow-mediated dilatation (FMD) was assessed by high-resolution radial ultrasound. RESULTS: After only 4 weeks of ET oxygen uptake at peak exercise increased from 14.9 ± 3.3 to 18.1 ± 4.7 ml/min/kg, (p<0.01 vs. C) in training subjects. Left ventricular ejection fraction improved from 26.8 ± 4.6 to 33.1 ± 5.5% (p<0.05 vs. C) in patients of the training group while it remained unchanged in the control group. E/A-ratio mended from 0.63 ± 0.12 to 0.81 ± 0.22 (p<0.01 vs. C) in training patients. Septal E’ velocities increased from 5.5 ± 0.5 to 7.8 ± 1.4 cm/s in training patients (p<0.05 vs. C). FMD of the radial artery improved from 8.2 ± 2.1 to 15.2 ± 3.8% (p<0.01 vs. C) as a result of ET. CONCLUSIONS: Only 4 weeks of endurance training are highly effective with significantly improved FMD accompanied by an emended systolic and diastolic LV-function. We hypothesise that the improvement in LV-EF in training patients may be caused by a corrected ventricular-arterial coupling: ventricular diastolic relaxation and effective endothelial function are ameliorated resulting in an augmentation of stroke volume.

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