Maaike G. J. Gademan

Exercise training increases oxygen uptake efficiency slope in chronic heart failure.

Background and aim The oxygen uptake efficiency slope (OUES) is a novel measure of cardiopulmonary reserve. OUES is measured during an exercise test, but it is independent of the maximally achieved exercise intensity. It has a higher prognostic value in chronic heart failure (CHF) than other exercise test-derived variables such as V . O 2 peak or V . E / V . CO 2 slope. Exercise training improves V . O 2 peak and V . E / V . CO 2 in CHF patients. We hypothesized that exercise training also improves OUES. Methods and results We studied 34 New York Heart Association (NYHA) class II–III CHF patients who constituted an exercise training group T (N = 20; 19 men/1 woman; age 60 ± 9 years; left ventricular ejection fraction 34 ± 5%) and a control group C (N = 14; 13 men/one woman; age 63 ± 10 years; left ventricular ejection fraction 34 ± 7%). A symptom-limited exercise test was performed at baseline and repeated after 4 weeks (C) or after completion of the training program (T). Exercise training increased NYHA class from 2.6 to 2.0 (P [ 0.05), V . O 2 peak by 14% [P(TvsC)[0.01], and OUES by 19% [P(TvsC) [ 0.01]. Exercise training decreased V . E / V . CO 2 by 14% [P(TvsC) [ 0.05]. Conclusion Exercise training improved NYHA class, V . O 2 peak , V . E / V . CO 2 and also OUES. This finding is of great potential interest as OUES is insensitive for peak load. Follow-up studies are needed to demonstrate whether OUES improvements induced by exercise training are associated with improved prognosis.

Maternal Prepregnancy Body Mass Index and Their Children’s Blood Pressure and Resting Cardiac Autonomic Balance at Age 5 to 6 Years

Adverse intrauterine conditions can program hypertension. Because one of the underlying mechanisms is thought to be cardiac autonomic balance, we investigated the association between prepregnancy body mass index (BMI) and blood pressure and indicators of the autonomic balance in the child at age 5 to 6 years. Also investigated was whether these associations were mediated by standardized birth weight and child BMI. Pregnant women (n=3074) participating in the Amsterdam Born Children and their Development study completed a questionnaire at gestational week 14. At age 5 to 6 years, offspring’s sympathetic drive (pre-ejection period), parasympathetic drive (respiratory sinus arrhythmia), and heart rate were measured by electrocardiography and impedance cardiography at rest. Blood pressure was assessed simultaneously. After adjusting for possible maternal/offspring confounders, prepregnancy BMI was positively linearly associated with diastolic blood pressure (&bgr;=0.11 mm Hg; 95% confidence interval, 0.05–0.17), systolic blood pressure (&bgr;=0.14 mm Hg; 95% confidence interval, 0.07–0.21), but not with heart rate, sympathetic or parasympathetic drive. After adding birth weight and child BMI to the model, the independent effect size of prepregnancy body mass index on systolic blood pressure (&bgr;=0.07 mm Hg; 95% confidence interval, 0.00–0.14) and diastolic blood pressure (&bgr;=0.07 mm Hg; 95% confidence interval, 0.01–0.13) decreased by ≈50%. Birth weight did not mediate these relationships, but was independently and negatively associated with blood pressure. Child BMI was positively associated with blood pressure and partly mediated the association between prepregnancy BMI and blood pressure. In conclusion, higher prepregnancy BMI is associated with higher blood pressure in the child (aged 5–6 years) but does not seem to be attributable to early alterations in resting cardiac autonomic balance. Child BMI, but not birth weight, mediated the association between prepregnancy BMI and blood pressure.

Maternal Prepregancy BMI and Lipid Profile during Early Pregnancy Are Independently Associated with Offspring's Body Composition at Age 5-6 Years: The ABCD Study

Background There is growing evidence that disturbances in maternal metabolism and, subsequently, intrauterine conditions affect foetal metabolism. Whether this has metabolic consequences in offspring later in life is not fully elucidated. We investigated whether maternal pre-pregnancy body mass index (pBMI) is associated with offsprings adiposity at age 5–6 years and whether this association is mediated by the mothers lipid profile during early pregnancy. Methods Data were derived from a multi-ethnic birth cohort, the Amsterdam Born Children and their Development (ABCD) study (inclusion 2003–2004). During early gestation mothers completed a questionnaire during pregnancy (pBMI) and random non-fasting blood samples were analysed for total cholesterol (TC), triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total free fatty acids (FFA) in early gestation. At age 5–6 years, childs BMI, waist-to-height-ratio (WHtR) and fat% were assessed. Results Only non-diabetic mothers with at term-born children were included(n = 1727). Of all women, 15.1% were overweight(BMI: 25–29.9 kg/m2) and 4.3% were obese(BMI≥30 kg/m2). After adjustments for confounders, every unit increase in pBMI was linearly associated with various offspring variables: BMI(β 0.10; 95% CI 0.08–0.12), WHtR*100(β 0.13; 95% CI 0.09–0.17), fat%(β 0.21; 95% CI 0.13–0.29) and increased risk for overweight(OR:1.15; 95% CI 1.10–1.20). No convincing proof for mediation by maternal lipid profile during early gestation was found. Moreover, maternal FFA was associated with the childs fat percentage, BMI and risk for overweight. Maternal ApoB and TC were positively associated with the offsprings fat percentage and maternal TG was positively associated with their childrens WHtR. Conclusions Both pBMI and maternal lipids during early pregnancy are independently related to offspring adiposity.

Biventricular pacing in chronic heart failure acutely facilitates the arterial baroreflex

Metabolic and mechanical stress in the failing heart activates the cardiac sympathetic afferent reflex (CSAR). It has been demonstrated that cardiac resynchronization therapy (CRT) acutely reduces MSNA in clinical responders. Mechanistically, this beneficial effect might be explained by acute deactivation of the CSAR. In addition to sympathoexcitation, CSAR inhibits the arterial baroreflex at the level of the nucleus tractus solitarii. Hence, in responders, CRT is likely to remove/reduce this inhibition. Therefore, we hypothesized that CRT acutely facilitates the arterial baroreflex. One day after implantation of a CRT device in 32 patients with chronic heart failure (LVEF; 27 +/- 6%), we measured noninvasive baroreflex sensitivity (BRS) and heart rate variability (HRV) in two conditions: CRT device switched on and switched off (on/off order randomized). BRS changes were correlated with the difference in unpaced/paced LVEF, a measure of acute mechanical response to CRT. CRT increased BRS by 35% from 2.96 to 3.79 ms/mmHg (P < 0.02) and increased HRV (standard deviation of the intervals between normal beats) from 18.5 to 24.0 ms (P < 0.01). The CRT-induced relative change in BRS correlated with the change in LVEF (r = 0.44; P < 0.01). In conclusion, CRT acutely increases BRS and HRV. This favorable response of the autonomic nervous system might be caused by CRT-induced CSAR deactivation. Follow-up studies should verify the mechanism of the acute response and the possible predictive value of an acute positive BRS response.

Rehabilitation: Periodic somatosensory stimulation increases arterial baroreflex sensitivity in chronic heart failure patients

BACKGROUND One of the beneficial effects of exercise training in chronic heart failure (CHF) is an improvement in baroreflex sensitivity (BRS), a prognostic index in CHF. In our hypothesis-generating study we propose that at least part of this effect is mediated by neural afferent information, and more specifically, by exercise-induced somatosensory nerve traffic. OBJECTIVE To compare the effects of periodic electrical somatosensory stimulation on BRS in patients with CHF with the effects of exercise training and with usual care. METHODS We compared in stable CHF patients the effect of transcutaneous electrical nerve stimulation (TENS, N = 23, LVEF 30 ± 9%) with the effects of bicycle exercise training (EXTR, N = 20, LVEF 32 ± 7%). To mimic exercise-associated somatosensory ergoreceptor stimulation, we applied periodic (2/s, marching pace) burst TENS to both feet. TENS and EXTR sessions were held during two successive days. RESULTS BRS, measured prior to the first intervention session and one day after the second intervention session, increased by 28% from 3.07 ± 2.06 to 4.24 ± 2.61 ms/mmHg in the TENS group, but did not change in the EXTR group (baseline: 3.37 ± 2.53 ms/mmHg; effect: 3.26 ± 2.54 ms/mmHg) (P(TENS vs EXTR) = 0.02). Heart rate and systolic blood pressure did not change in either group. CONCLUSIONS We demonstrated that periodic somatosensory input alone is sufficient and efficient in increasing BRS in CHF patients. This concept constitutes a basis for studies towards more effective exercise training regimens in the diseased/impaired, in whom training aimed at BRS improvement should possibly focus more on the somatosensory aspect.

Indication criteria for total hip or knee arthroplasty in osteoarthritis: a state-of-the-science overview

BackgroundThis systematic review gives an overview of guidelines and original publications as well as the evidence on which the currently proposed indication criteria are based. Until now such a state-of-the-science overview was lacking.MethodsWebsites of orthopaedic and arthritis organizations (English/Dutch language) were independently searched by two authors for THA/TKA guidelines for OA. Furthermore, a systematic search strategy in several databases through August 2014 was performed. Quality of the guidelines was assessed with the AGREE II instrument, which consists of 6 domains (maximum summed score of 6 indicating high quality). Also, the level of evidence of all included studies was assessed.ResultsWe found 6 guidelines and 18 papers, out of 3065 references. The quality of the guidelines summed across 6 domains ranged from 0.46 to 4.78. In total, 12 THA, 10 TKA and 2 THA/TKA indication sets were found. Four studies stated that no evidence-based indication criteria are available. Indication criteria concerning THA/TKA consisted of the following domains: pain (in respectively 11 and 10 sets), function (12 and 7 sets), radiological changes (10 and 9 sets), failed conservative therapy (8 and 4 sets) and other indications (6 and 7 sets). Specific cut-off values or ranges were often not stated and the level of evidence was low.ConclusionThe indication criteria for THA/TKA are based on limited evidence. Empirical research is needed, especially regarding domain specific cut-off values or ranges at which the best postoperative outcomes are achieved for patients, taking into account the limited lifespan of a prosthesis.

Validation of the SQUASH physical activity questionnaire in a multi-ethnic population: the HELIUS study

Purpose To investigate the reliability and validity of the SQUASH physical activity (PA) questionnaire in a multi-ethnic population living in the Netherlands. Methods We included participants from the HELIUS study, a population-based cohort study. In this study we included Dutch (n = 114), Turkish (n = 88), Moroccan (n = 74), South-Asian Surinamese (n = 98) and African Surinamese (n = 91) adults, aged 18–70 years. The SQUASH was self-administered twice to assess test-re-test reliability (mean interval 6–7 weeks) and participants wore an accelerometer and heart rate monitor (Actiheart) to enable assessment of construct validity. Results We observed low test-re-test reliability; Intra class correlation coefficients ranged from low (0.05 for moderate/high intensity PA in African Surinamese women) to acceptable (0.78 for light intensity PA in Moroccan women). The discrepancy between self-reported and measured PA differed on the basis of the intensity of activity: self-reported light intensity PA was lower than measured but self-reported moderate/high intensity PA was higher than measured, with wide limits of agreement. The discrepancy between questionnaire and Actiheart measures of moderate intensity PA did not differ between ethnic minority and Dutch participants with correction for relevant confounders. Additionally, the SQUASH overestimated the number of participants meeting the Dutch PA norm; Cohen’s kappas for the agreement were poor, the highest being 0.30 in Dutch women. Conclusion We found considerable variation in the test-re-test reliability and validity of self-reported PA with no consistency based on ethnic origin. Our findings imply that the SQUASH does not provide a valid basis for comparison of PA between ethnic groups.

A Study on Mediation by Offspring BMI in the Association between Maternal Obesity and Child Respiratory Outcomes in the Amsterdam Born and Their Development Study Cohort

Background A causal relationship between maternal obesity and offspring asthma is hypothesized to begin during early development, but no underlying mechanism for the found association is identified. We quantitatively examined mediation by offspring body mass index (BMI) in the association of maternal pre-pregnancy BMI on risk of asthma and wheezing during the first 7–8 years of life in a large Amsterdam born birth cohort. Methods For 3185 mother-child pairs, mothers reported maternal pre-pregnancy BMI and offspring outcomes “ever being diagnosed with asthma” and “wheezing in the past 12 months” on questionnaires. We measured offspring height and weight at age 5–6 years. We performed a multivariate log linear regression comparing outcomes in offspring of mothers with different BMI categories. For each category we quantified and tested mediation by offspring BMI and also investigated interaction by parental asthma. Results At the age of 7–8 years, 8% of the offspring ever had asthma and 7% had current wheezing. Maternal pre-pregnancy obesity was associated with higher risks of asthma (adjusted RR 2.32 (95% CI: 1.49–3.61) and wheezing (adjusted RR 2.16 (95% CI: 1.28–3.64). Offspring BMI was a mediator in the association between maternal BMI and offspring wheezing, but not for asthma. There was no interaction by parental asthma. Conclusions Maternal pre-pregnancy obesity was associated with higher risks of offspring asthma and wheezing. The association between maternal obesity and offspring wheezing was both direct and indirect (mediated) through the child’s own BMI.

Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children: The ABCD Study

Background In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5–6 years. Methods Cross-sectional data from an apparently healthy population (within the ABCD study) were collected at age 5–6 years in 1540 children. Heart rate (HR), respiratory sinus arrhythmia (RSA; parasympathetic activity) and pre-ejection period (PEP; sympathetic activity) were assessed during rest. Metabolic components were waist-height ratio (WHtR), systolic blood pressure (SBP), fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed. Results In analysis adjusted for child’s physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01), higher SBP (p<0.001) and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01). Lower PEP was only associated with higher SBP (p <0.05). Of all children, 5.6% had 3 or more (out of 5) adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001). Conclusions This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5–6 years.

Biventricular pacing-induced acute response in baroreflex sensitivity has predictive value for midterm response to cardiac resynchronization therapy

In a previous study we demonstrated that the institution of biventricular pacing in chronic heart failure (CHF) acutely facilitates the arterial baroreflex. The arterial baroreflex has important prognostic value in CHF. We hypothesized that the acute response in baroreflex sensitivity (BRS) after the institution of cardiac resynchronization therapy (CRT) has predictive value for midterm response. One day after implantation of a CRT device in 33 CHF patients (27 male/6 female; age, 66.5 +/- 9.5 yr; left ventricular ejection fraction, 28 +/- 7%) we measured noninvasive BRS and heart rate variability (HRV) in two conditions: CRT device switched on and switched off (on/off order randomized). Echocardiography was performed before implantation (baseline) and 6 mo after implantation (follow-up). CRT responders were defined as patients in whom left ventricular end-systolic volume at follow-up had decreased by > or =15%. Responders (69.7%) and nonresponders (30.3%) had similar baseline characteristics. In responders, CRT increased BRS by 30% (P = 0.03); this differed significantly (P = 0.02) from the average BRS change (-2%) in the nonresponders. CRT also increased HRV by 30% in responders (P = 0.02), but there was no significant difference found compared with the increase in HRV (8%) in the nonresponders. Receiver-operating characteristic curve analysis revealed that the percent BRS increase had predictive value for the discrimination of responders and nonresponders (area under the curve, 0.69; 95% confidence interval, 0.51-0.87; maximal accuracy, 0.70). Our study demonstrates that a CRT-induced acute BRS increase has predictive value for the echocardiographic response to CRT. This finding suggests that the autonomic nervous system is actively involved in CRT-related reverse remodeling.