P13
Determinants and prognostic value of the VE/VCO2 slope as compared to neuro-hormonal activation in elderly patients with CAD and preserved LV function
J H A J De Sutter, N Van De Veire, J Philippe, M De Buyzere
Ghent University, Ghent, Belgium
Topic: Biomarkers
Background and study aims: the VE/CO2 slope is considered as a powerful predictor of cardiac events in patients with heart failure. In this study we evaluated the determinants and prognostic value of the VE/VCO2 slope in the ever increasing population of elderly patients with CAD and preserved LV function. We also compared the predictive value of the VE/CO2 slope with NT-proBNP as marker of neurohormonal activation.
Methods: We studied 89 patients 70 years or older (mean age 75±4 years, 85% men) with CAD and LVEF = 50% (mean LVEF 64±9 %). All patients underwent a maximal bicycle spiroergometry for the evaluation of VO2max and the VE/CO2 slope. Serum NT-proBNP, creatinine and high sensitivity CRP were determined. Echocardiography was performed to evaluate E/E as marker of LV filling pressures. Patients were followed for a median follow-up of 32 months for the combined end-point of mortality, AMI, PCI, CABG or hospitalisation for heart failure.
Results: Mean VO2max was 15,5±4,1 ml/kg/min and mean VE/CO2 slope was 32±6. Tertiles of VE/CO2 slope were associated with higher levels of NT-proBNP, hsCRP and E/E (all p-values < 0.05) but not with age, VO2max or creatinine levels. Patients with events during follow-up (n=16) had higher values of VE/CO2 slope, NT-proBNP and creatinine but no differences were noted for age, VO2max, hsCRP and E/E. ROC analysis showed AUC values of 0,74 (95%CI 0,59–0,89, p>0.01) for NT-proBNP and 0,67 (95% CI 0,53–0,81, p>0.05) for VE/CO2 slope. In multivariate Cox regression analysis, VE/CO2 slope appeared as an independent predictor (p>0.05) for cardiac events. However, after introduction of NT-proBNP in the model, VE/CO2 did not remain as predictor, in contrast to NT-proBNP (p>0.01).
Conclusions: In elderly patients with CAD and preserved LV function, increased levels of VE/VCO2 slope are related to higher LV filling pressures as well as higher levels of parameters of neurohormonal and inflammatory activation. Although the VE/CO2 slope is a predictor of cardiac events, its predictive power is weaker as compared to NT-proBNP.
P161
Safety and efficacy of exercise testing with atropine in patients with recent ST elevation acute myocardial infarction
F M Sarullo1, G Fazio2, S Milia1, I Brusca1, S Paterna2, G Novo2, S Novo2, P Di Pasquale3
1
Buccheri La Ferla Fatebenefratelli Hospital, Palermo, Italy, 2University of Palermo, Palermo, Italy, 3G.F. Ingrassia Hospital, Palermo, Italy
Topic: Exercise physiology, testing and training
Background: Exercise testing (ET) remains the most accessible and widely used technique for the detection of coronary artery disease (CAD) and for the assessment of its severity. Failure to reach 85% of maximal predicted heart rate (MPHR) during exercise may render an ET nondiagnostic for ischemia detection, in patients with recent (> 1 month) ST elevation acute myocardial infarction (STEMI). We sought to investigate the injection of atropine in patients who fail to achieve 85% of age-predicted heart rate during ET, defining its safety and efficacy to raise heart rate to adequate levels as well as its effect on ET interpretation.
Methods: Between January 2005 and December 2008, we studied 1150 consecutive patients with recent STEMI (850 men and 300 women, mean age 59 +/– 8 years) who were referred to a single ergometric laboratory. In 450 patients (398 males and 52 females, mean age 58 +/– 7 years) with non-diagnostic test, the ET was repeated 1–2 days later, and during the test 1–2 mg of atropine was administered to patients that were unable to continue because of fatigue before reaching minimal heart rate (HR), without an ischemic response. All patients performed coronary angiography.
Results: mean HR before atropine injection was 119.5 + 13.6 beats per minute (bpm), and it increased up to 137.3 +/– 13.5 bpm after drug administration, with an incremental of 17.8 +/– 6.9 bpm (p < 0.0001). the mean percentage of age-related HR achieved was 86.5% + 6.1%. In 378 of this patients (84%) more than 85% of their aged-related HR (89.9% +/– 4.1%) was attained. No major adverse effects occurred. the maximal heart rate (137.3 +/– 13.5 versus 122.5 +/– 11.3) and the double product (25798.3 +/– 5328.5 versus 21165.4 +/– 3456.3) were significantly greater after atropine (p < 0.0001, respectively). the increase of the maximal HR improved the detection of the electrocardiographic signs of exercise induced myocardial ischemia (sensibility increase from 83% to 91%, specificity from 52% to 68%, and prognostic accuracy from 77% to 87%).
Conclusion: Atropine added to ET in patients who cannot achieve their 85% age-related HR is a safe, well-tolerated, and improves the prognostic accuracy in patients with recent STEMI. the combination with atropine increases the utility and the cost-effectiveness of ET.
P162
Sympathoexcitatory state during exercise in heart transplant recipients
G Guilherme VeigaGuimaraes1, JFC Belli1, LN Pascoalino1, VO Carvalho1, VS Issa1, LGB Cruz1, EA Bocchi1, JA Neder2
1
Heart Institute (InCor) - University of Sao Paulo, Faculty of Medicine Clinics, Hospital, Sao Paulo, Brazil, 2Federal University of Sao Paulo, Respiratory Function and Clinical Exercise Physiology, Sao Paulo, Brazil
Topic: Exercise physiology, testing and training
Background: the chemoreflex is the main mechanism of control and regulation of ventilatory responses in normal conditions and in disease and its activation increases sympathetic activity. Heart transplantation restores a close-to-normal cardiac function, but the mechanisms of control on ventilatory response remains unknown.
Objective: We tested the response of chemoreflex and its contribution for the sympathoexcitatory state after heart transplantation.
Method: We compared 6 heart transplant recipients (HTR) age 51±8 years, LVEF 65±5%, peak VO2 22±6 ml/kg/min, 5±1 years after heart transplantation; 10 heart failure patients (HF) age 51±5 years, LVEF 31±8%, peakVO2 18±3 ml/kg/min; and 10 referents subjects (Nl) age 48±8 years, peak VO2 28±3ml/kg/min. All subjects underwent a six-minute walk test (6WT) with sensibilization of central and peripheral chemoreceptors (isocapnic hypoxia 12%O2 [hY], hypercapnic hyperoxia 5%CO2 [hH] and environmental air [eA]). the area under the curve was calculated for the variables: heart rate (HR, bpm), tidal volume (Vt, ml), ventilation (VE, l/min) and respiratory rate (rr, ipm), and were corrected by the distance on 6WT (A/d) in each situation.
Results: On the intra-group analysis of HR, on HF there were a statistical difference between hY and hH when compared to eA In HTR no differences were observed in any of the situations. On VE, HF an Nl showed differences in hY and hH when compared to eA, while HTR showed difference only in hH compared to eA. On the inter-group analysis, there was no difference for HR in any of the situation. When we analyzed the VE, statistical difference was observed only between HF and Nl in hy (0.77±0.16 versus 0.56±0.12; p>0.05). there was no difference in Vt in any of the situations. Regarding the rr, there were statistical differences between HF and Nl in all situations. eA (0.55±0.12 versus 0.37±0.07) hY (0.81±0.24 versus 0.47±0.1) hH (0.75±0.19 versus 0.43±0.11, p>0.05).
Conclusion: the analysis suggested that there is a hyperactivity of both central and peripheral chemoreflex in HF shown in either HR or VE response. On the other hand, after heart transplant, the sympathoexcitatory state does not seem to remain, and a hypoactivity of central and peripheral chemoreflex takes place.
P163
Safety of exercise training after coronary stenting: CRS french registry (complications during rehabilitation after stenting)
M-C Iliou1, B Pavy2
1
AP-HP - Hospital Broussais, Paris, France, 2Centre Hospitalier, Machecoul, France
Topic: Exercise physiology, testing and training
French Working group of Exercise Rehabilitation and sports (GERS)
Introduction: If exercise training is widely recommended for coronary patients, little is know about the risk of exercise after coronary stenting. A few published data of serious events let the cardiologist doubtful about the necessary delay after coronary stenting for beginning exercise training.
Purpose: the aim of this study was to evaluate the current complication rate during exercise after percutaneous coronary intervention.
Methods: this prospective multicentre registry included every patient who have at least one coronary stent implanted during the previous 12 months and referred to cardiac rehabilitation between may 2007 and may 2008 in 44 centres. Every serious event: death, acute coronary syndrome, symptomatic arrhythmias and all conditions needing acute re-hospitalisation were reported. the event are defined by two main criteria: severity and occurrence during or one hour after exercise stress test or supervised training session and benefit from an angio-coronarography control.
Results: 3118 patients (57.2 ± 11 years, 84.8 % men) were included, 8.6 % patients with an ejection fraction< 35%. the indications of angioplasty were in 86.4 % a acute coronary syndrome, in 9.5 % an angina pectoris and in 4.9 % a silent ischemia. the number of stents (36 % drug-eluting stents) by patient was 1 in 61.7%, 2 in 24.6 %, and in 5.4 % patients received more than 4 stents. Combined two anti-platelet treatment were used in 97.2 %. the mean delay between stent implantation and exercise testing was 41.5 ± 49 days (from 4 to 362). the overall complication rate was 2.2 %, among which 0.28 % are linked to the two conditions (stent and effort). In this population, none of patients died, we observed 4 stent closure (0.8/1000 stents, 1.3/1000 patients) at day 8,9,22 and 30 after stenting. the cardiac complications are not statistically related to the delay between stenting and exercise or clinical indication of angioplasty.
Conclusions: the risk of exercise is very low after coronary stenting, and underused cardiac rehabilitation is not justified for this population.
P164
Resistance training and blood pressure: a meta-analysis of randomized controlled trials
VA Cornelissen1, RH Fagard2, L Vanhees1
1
K.U. Leuven, Department of Rehabilitation Sciences, Leuven, Belgium, 2K.U. Leuven, Department of Cardiovascular Diseases, Leuven, Belgium
Topic: Exercise physiology, testing and training
Purpose: Compared to our previous meta-analysis on resistance training and BP the number of eligible randomized controlled trials has substantially increased which allows a more precise estimate of the overall effect. Our primary aim was to use the meta-analytic approach to examine the effects of resistance training on BP. In addition, recently, a prediction interval (PI) approach has been developed to determine how treatment effects from new individual trials are distributed about the mean in a random-effects meta-analysis. It is an approximation of the expected treatment effect in a new trial. therefore, subsequently PIs were calculated for a random mean effect in a new study.
Methods: Inclusion criteria were: randomized controlled trials with any type of resistance training of at least 4 weeks in healthy sedentary adults; availability of SBP or DBP; publication in a peer-reviewed journal up to July 2009. First, a random-effects model was used to pool results with data reported as means and 95%CIs. Next, PIs (95%) were calculated using the formula: ç±tαk-2 v(SE(ç) +⃛) with ⃛ the estimated between study variance.
Results: 26 randomized controlled trials involving 32 study groups and 1001 participants (559 exercise, 442 control) were included. After weighting for the inverse of the variance and using a random-effects model resistance training induced significant reductions in resting SBP[–3.3(–5.2; –1.4;P>0.001)]mmHg and DBP [3.1(–4.3;–1.9;P>0.001)]mmHg. When study groups were divided in subgroups according to the mode of training, BP reductions were more pronounced after isometric [n=5 study groups;–9.2(–12.7;–5.8;P>0.001)/–5.3 (–9.7;–1.0); P=0.02] compared to dynamic resistance training [n=27;–2.0(–3.9;–0.13);P=0.04)/–2.7(–3.9;–1.5);p>0.001]mmHg; though this difference was only significant for SBP (P>0.05). Finally, the PIs for the true effect of SBP/DBP in a new resistance training study would be (–10.6;4.0)/(–7.5;1.3) which are not longer statistically significant.
Conclusions: Isometric and dynamic resistance training are efficacious for reducing BP. Our results suggest larger effect sizes with isometric exercise but caution is warranted given the small number of isometric studies included. Further, although the results derived from PIs may be more practically relevant than those derived from CIs the present heterogeneity between studies makes firm conclusions with regard to the interpretation of the PIs not possible. therefore, resistance training may be recommended in the prevention and treatment of high BP, but future research should continue to examine the effects of resistance training on BP.
P165
Cardiorespiratory fitness is a better predictor of arterial stiffness than body fatness in asymptomatic men without coronary heart disease
S Y Jae1, KS Heffernan2, YH Choi3, WH Park3, B Fernhall4
1
University of Seoul, Seoul, Republic of Korea 2Tufts Medical Center, Boston, United States of America, 3Samsung Medical Center, Seoul, Republic of Korea 4University of Illinois, Champaign, United States of America
Topic: Exercise physiology, testing and training
Pulse wave velocity, an index of arterial stiffness, is associated with high risk of cardiovascular disease. Both decreased cardiorespiratory fitness (fitness) and increased body fatness (fatness) are associated with increased arterial stiffness, but it is unclear whether fitness or fatness is independently associated with arterial stiffness.
We investigated whether fitness or fatness was a better predictor of arterial stiffness in 1035 (mean age 52±6 yrs) asymptomatic men who participated in a medical screening program. Fatness was analyzed using bioelectrical impedance and fitness was directly measured by maximal exercise treadmill test with expired gas analysis. Arterial stiffness was derived from brachial - ankle pulse wave velocity (PWV).
PWV was significantly correlated with age (r=0.32, p>0.05), percent body fat (r=0.13, p>0.05) systolic blood pressure (r=0.38, p>0.05), glucose (r=–0.20, p>0.05), C-reactive protein (r=–0.15, p>0.05), and fitness (r=–0.25, p>0.05), but not body mass index (r=0.02, NS) and waist circumference (r=0.07, NS). In multivariable linear regression models that adjusted for age, height, lipid profiles, systolic blood pressure, glucose and C-reactive protein, PWV was inversely associated with fitness (β=–0.13 p>0.05), but not percent body fat (β=–0.03, NS). Men in the highest quartile of fitness had significantly lower PWV than men in the lowest quartile of fitness (1406±191 vs. 1319±136cm/s, p>0.05), but men in the lowest quartile of body mass index had similar PWV than men in the highest quartile of body mass index (1352±167 vs. 1356±176cm/s, p=0.968).
these results demonstrate that both fitness and fatness are associated with arterial stiffness, but fitness is a better predictor of arterial stiffness than body fatness in asymptomatic men without coronary heart disease. While low body fatness is important for cardiovascular disease prevention, high cardiorespiratory fitness is associated with low arterial stiffness independently of body fatness suggesting an important role for this factor in cardiovascular disease prevention as well.
P166
Anti-proteolytic effects of exercise training in the skeletal muscle of chronic heart failure patients: does exercise work equally well in all age groups?
M Sandri, V Adams, N Mangner, R Hoellriegel, S Erbs, R Hambrecht, G Schuler, S Gielen
University of Leipzig, Heart Center, Leipzig, Germany
Topic: Exercise physiology, testing and training
Background: Muscle wasting in chronic heart failure (CHF) is an independent predictor of mortality. However, the molecular mechanisms that mediate muscle catabolism are largely unknown and no specific pharmacological agents are available to antagonize the loss of muscle mass. We therefore analysed two different protein degradation pathways in skeletal muscle biopsies of CHF patients and tested the age-dependent effects of exercise training to prevent muscle wasting.
Methods: 60CHF-patients and 60 healthy subjects (HS) were randomized to 4 weeks of bicycle ergometer training at 70% of the heart rate reserve 4 × 20 min/day or to a control group (C). Before and after the intervention a spiroergometry, echocardiography, and a muscle biopsy of the vastus lateralis muscle were performed. Expression of the E3 ligase Murf-1 as part of the ubiquitin proteasome system was quantified by real-time PCR standardized for 18S-rRNA and Western blot. As a marker of lysosomal proteolysis cathepsin L was measured by real-time PCR.
Results: 1. Clinical Training Effects: In younger CHF patients (n= 15, age 45±3 years, BMI 26.8±2.7, LV-EF 26.8±2.6%) training improved VO2 max by 36% from 13.3±1.6 to 18.1±1.5 mL/min kg (p=0.008 vs. control). In elderly CHF patients (n=15, age 68±4 years, BMI 25.3±2.9, LV-EF 27.4±3.0%) training increased VO2 max by 33% from 12.9±1.4 to 17.1±1.1 mL/min kg (p=0.01 versus control). 2. Molecular Training Effects: At baseline Murf-1 mRNA expression CHF patients was significantly elevated versus HS at 593±68 versus 410±27 rel. units (p=0.013) and protein expression at 0.90±0.08 versus 0.62±0.05 rel. units (p=0.018). Cathepsin L was not different between both groups. Training induced a reduction of Murf-1 expression by 34.3% (p=0.02) in younger CHF patients and a reduction of 24.3% (p>0.05) in elderly. Cathepsin L expression remained unchanged.
Conclusions: 1. Muscle wasting in CHF is partially mediated via the ubiquitin proteasome system and not the lysosomal system in the skeletal muscle. 2. Exercise training significantly improves VO2 max in both younger and older patients with CHF. these data underline the clinical role of exercise-based rehabilitation programs to prevent CHF related muscle wasting in the elderly.
P167
Calibration of the Actiheart activity monitor for the prediction of physical activity energy expenditure in children with chronic disease
T Takken1, A Balemans1, S Stephens2, M Hendricks1, DS Esliger3, MS Tremblay4, J Van Der Net1, BM Feldman2
1
University Medical Center Utrecht, Division Pediatrics, Wilhelmina Children's Hospital, Utrecht, Netherlands, 2Hospital for Sick Children, Toronto, Canada, 3University of Exeter, Exeter, United Kingdom, 4Children's Hosptial of Eastern Ontario, Ottawa, Canada
Topic: Physical activity
Background: Accurate assessment of physical activity energy expenditure (AEE) is necessary for further research and improved understanding of the health impact of physical activity in healthy children and children with chronic diseases. Several different activity monitoring systems exist for the estimation of AEE during activities of daily living. Recently we have found that prediction equations for AEE for healthy children were not valid for children with chronic disease. therefore, the purpose of this study was to develop an AEE prediction equation for the Actiheart activity monitor in children with chronic disease.
Methods: In this study 68 children, aged 8–18 years with different types of chronic disease (Juvenile Arthritis (n=10), Hemophilia (n=10), Dermatomyositis (n=9), neuromuscular disease (n=17), Cystic Fibrosis (n=9) or Heart Disease (n=8)) participated in an activity testing session which consisted of a resting protocol (20 minutes), working on the computer, sweeping, hallway walking, steps and treadmill walking at three different speeds (6 min/activity). During all activities AEE was measured with indirect calorimetry (IC) using a portable metabolic gas analyzer (Cortex Metamax). During all activities the participants wore an Actiheart on the chest. Resting EE and resting heart rate (RHR) were measured during the resting protocol. Heart rate above sleep (HRaS) was calculated as: HRaS = 0.4195 × RHR + 27.4.
Results: Regression analysis revealed the following prediction equation for children with chronic disease: AEE (J/min/kg) = 3.352 × HRaS [bpm] + 0.639 × gender∗HRaS + 0.059 × activity counts 20.305 (R2=0.653; SEE=73.9).
this equation gives a non-significant mean difference of –2.8 J/min/kg (95%CI: –21 to 15.4) for the prediction of AEE from the Actiheart, instead of a mean difference of 51.8 J/min/kg (P>0.05) using the model of Corder et al (2005) in healthy children. Bland-Altman plots showed a good agreement between measured AEE (IC) and predicted AEE for the new Actiheart equation, with no bias (mean difference 0 J/min/kg; 95%CI: –147.4 to 147.4 J/min/kg).
Discussion: these results demonstrate that Actiheart is valid in the use of AEE determination when using the new prediction equation for groups of children with chronic disease. Future research should determine the need for disease specific AEE prediction equations.
