Sizing and mending of appendicular muscle mass for hydration during the 12-lead electrocardiogram: True incidence of sarcopenia in heart failure.

BACKGROUND: Our aim was to develop and evaluate a method for the measurement of muscle mass during the 12-channel electrocardiogram (ECG), to determine the incidence of sarcopenia in patients with overhydration and to correct it for congestion. METHODS: A 12-channel ECG that simultaneously provided multifrequency segmental impedance data was used to measure total body water (TBW), extracellular water (ECW), ECW/TBW ratio and appendicular muscle mass (AppMM), validated by whole-body dual-energy X-ray absorptiometry. The mean ECW/TBW ratio was 0.24 ± 0.018 (SD) and 0.25 ± 0.016 for young (age range 20-25 years) healthy males (n = 77) and females (n = 88), respectively. The deviation of the ECW/TBW ratio from this mean was used to correct AppMM for excess ECW ('dry AppMM') in 869 healthy controls and in 765 patients with chronic heart failure (CHF) New York Heart Association classes II-IV. The association of AppMM and dry AppMM with grip strength was also examined in 443 controls and patients. RESULTS: With increasing N-terminal pro-brain natriuretic peptide (NT-proBNP), a continuous decline of AppMM indices is observed, which is more pronounced for dry AppMM indices (for males with NT-proBNP < 125 pg/mL: AppMM index mean = 8.4 ± 1.05, AppMM index dry mean = 8.0 ± 1.46 [n = 201, P < 0.001]; for females with NT-proBNP < 150 pg/mL: AppMM index mean = 6.4 ± 1.0, AppMM index dry mean = 5.8 ± 1.18 [n = 198, P < 0.001]; for males with NT-proBNP > 1000 pg/mL: AppMM index mean = 7.6 ± 0.98, AppMM index dry mean = 6.2 ± 1.11 [n = 137, P < 0.001]; and for females with NT-proBNP > 1000 pg/mL: AppMM index mean = 5.9 ± 0.96, AppMM index dry mean = 4.8 ± 0.94 [n = 109, P < 0.001]). The correlation between AppMM and upper-body AppMM and grip strength (r-value) increased from 0.79 to 0.83 (P < 0.001) and from 0.80 to 0.84 (P < 0.001), respectively, after correction (n = 443). The decline of AppMM with age after correction for ECW is much steeper than appreciated, especially in males: In patients with CHF and sarcopenia, the incidence of sarcopenia may be up to 30% higher after correction for ECW excess according to the European (62% vs. 57%, for males, and 43% vs. 31%, for females) and Foundation for the National Institutes of Health (FNIH) (56% vs. 46%, for males, and 54% vs. 38%, for females) consensus guidelines. CONCLUSIONS: The incidence of sarcopenia in CHF as defined by the European Working Group on Sarcopenia and FNIH consensus may be up to 30% higher after correction for ECW excess. This correction improves the correlation between muscle mass and strength. The presented technology will facilitate, on a large scale, screening for sarcopenia, help identify mechanisms and improve understanding of clinical outcomes.

Abdominal Aortic Aneurysm Detection in Bioelectrical Impedance Cardiovascular Screenings-A Pilot Study.

Screening and diagnosing abdominal aortic aneurysms (AAA) are currently dependent on imaging studies such as ultrasound or computed tomography angiography. All imaging studies offer distinct advantages but also suffer from inherent limitations such as examiner dependency or ionizing radiation. Bioelectrical impedance analysis has previously been investigated with respect to its use in the detection of several cardiovascular and renal pathologies. The present pilot study assessed the feasibility of AAA detection based on bioimpedance analysis. In this single-center exploratory pilot study, measurements were conducted among three different cohorts: patients with AAA, end-stage renal disease patients without AAA, and healthy controls. The device used in the study, CombynECG, is an open-market accessible device for segmental bioelectrical impedance analysis. The data was preprocessed and used to train four different machine learning models on a randomized training sample (80% of the full dataset). Each model was then evaluated on a test set (20% of the full dataset). The total sample included 22 patients with AAA, 16 chronic kidney disease patients, and 23 healthy controls. All four models showed strong predictive performance in the test partitions. Specificity ranged from 71.4 to 100%, while sensitivity ranged from 66.7 to 100%. The best-performing model had 100% accuracy for classification when applied to the test sample. Additionally, an exploratory analysis to approximate the maximum AAA diameter was conducted. An association analysis revealed several impedance parameters that might possess predictive ability with respect to aneurysm size. AAA detection via bioelectrical impedance analysis is technically feasible and appears to be a promising technology for large-scale clinical studies and routine clinical screening assessments.

Measurement of aortofemoral volume wave velocity during the routine 12-channel ECG: relation to age, physiological hemoglobin A 1C, triglycerides and SBP in healthy individuals.

OBJECTIVE: Measurements of pulse wave velocity are generally thought to be too impractical for clinical routine. This study aimed to develop a method that can be performed during routine 12-channel ECG. METHODS: A 12-channel ECG simultaneously supplies arterial impedance plethysmographic signals from the extremities beside segmental multifrequency impedance measurements for obtaining body composition. The origin of the plethysmographic signal (volume wave) at the arms and legs was determined at the level of the elbows and the knees. The volume wave velocity (VWV) at the aorta and femoral arteries was calculated from the time difference of the plethysmographic signals between arms and legs. RESULTS: Automated measurement of VWV was highly reproducible (r = 0.96). In 107 participants in perfect health, VWV in different models was positively related to age, physiological hemoglobin A 1C, triglycerides, normal standardized unattended blood pressure, but not to physiological low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol. Aortofemoral VWV was significantly higher in patients with established coronary artery disease than in healthy controls of the same age group (18.1 ±â€Š5.8 vs. 11.9 ±â€Š1.7 m/s, P < 0.001). VWV in study participants was higher than tonometrically determined pulse wave velocity as muscular arteries are included (13.2 ±â€Š5.81 vs. 8.8 ±â€Š2.98 m/s, n = 115, P < 0.001). CONCLUSION: These background arterial impedance plethysmographic measurements for the measurement of VWV made simultaneously during 12-channel ECG show promise for large-scale, routine clinical assessment of large artery function.

The Combyn™ ECG: Adding haemodynamic and fluid leads for the ECG. Part II: Prediction of total body water (TBW), extracellular fluid (ECF), ECF overload, fat mass (FM) and "dry" appendicular muscle mass (AppMM).

Simultaneous with a 12 channel ECG, body composition was analysed by segmental multi-frequency impedance analysis in 101 healthy subjects and in 118 patients with chronic heart failure (CHF, n= 40), chronic renal failure with haemodialysis (HD, n= 20), and miscellaneous internal diseases (n= 58). Whole body DXA and sodium bromide dilution were used as reference methods for total body water (TBW), extracellular fluid (ECF), appendicular muscle mass (AppMM) and fat mass (FM). Empirical prediction equations were developed in a randomized evaluation sample and then evaluated in unknowns. TBW, ECF, AppMM and FM could be predicted with regression coefficients of 0.96, 0.90, 0.95 and 0.93, respectively, all with p< 0.001. Only segmental impedances and height, but not age, sex, weight and BMI contributed to the prediction of water compartments. About half the patients with CHF and half of those on HD showed increased ECF/ICF ratio in relation to % FM at the legs but not at the thorax. The predicted AppMM was additionally corrected for increased ECF to determine "dry AppMM", which is markedly lower than the misleading reference DXA. This methodology shows promise as a combination of routine ECG with measurement of body composition, assessment of sarcopenia and detection of overhydration.

Adding "hemodynamic and fluid leads" to the ECG. Part I: the electrical estimation of BNP, chronic heart failure (CHF) and extracellular fluid (ECF) accumulation.

OBJECTIVES: In primary care the diagnosis of CHF and ECF accumulation is no triviality. We aimed to predict plasma BNP, CHF and ECF accumulation with segmental impedance spectroscopy while using and extending the electrodes of the conventional electrocardiography. METHODS: Three combined multiple electrodes were added to the 15 lead ECG for segmental impedance spectroscopy and for measuring the maximal rate of segmental fluid volume change with heart action at the thorax and the legs. The obtained signals were analyzed by partial correlation analyses in comparison with plasma BNP, CHF classes, ejection fraction by echocardiography and cardiac index by double gas re-breathing. 119 subjects (34 healthy volunteers, 50 patients with CHF, NYHA classes II to IV and 35 patients without CHF) were investigated. RESULTS: The maximal rate of volume change with heart action at the thorax and at the legs, as well as the ECF/ICF ratio at the legs contribute equally and independently to the prediction of BNP and heart failure in an unknown test sample of 49 patients (multiple r=0.88, p<0.001). The ROC-curve for the predicted plasma BNP>400 pg/ml gave an AUC=0.93. The absence or the presence of heart failure could be predicted correctly by a binomial logistic regression in 92.9 and 87.5% of cases, respectively. CONCLUSION: The methodology, which is based on inverse coupling of BNP release and of maximal blood acceleration and on sensitive detection of ECF overload, could enable the diagnosis of CHF with useful sensitivity and specificity while writing a routine-ECG.

A critical analysis of whole body bioimpedance spectroscopy (BIS) for the estimation of body compartments in health and disease.

Aim of the study was to assess the accuracy and precision of a BIS device and the relative contribution of BIS beyond the anthropometric parameters. The output of the Impedimed device (SFB7) and the relative contribution of height, weight, age, sex and resistance values at zero and infinite frequency (Rzero and Rinf respectively) to the prediction of total body water (TBWd, deuterium space), of extracellular fluid (ECFbr, sodium bromide space) and of fat mass (FMDXA) were assessed in 116 subjects (32 healthy subjects and 84 patients with disorders of body composition). Using a repeated randomization procedure, new equations for TBW, ECF and FM were derived. The SFB7 gave measures of determination similar to those obtained with equations that included only anthropometric data. The SFB7, but not the newly derived regression equations, underestimated TBW and ECF by 3.82±3.37 (mean±SD) and by 0.93±2.62l and overestimated FM by 6.55±3.86kg. Nine of 16 patients with ECF overload as detected by ECFbr were also detected by BIS. BIS measurements contribute marginally but not significantly beyond anthropometric data to the prediction of TBW, ECF and FM, either in healthy subjects or in patients with disturbed body composition.

Proto-dialytic cardiac function relates to intra-dialytic morbid events.

BACKGROUND: Intra-dialytic morbid events (IDME) such as intra-dialytic hypotension (IDH) and muscle cramps frequently complicate haemodialysis (HD). Cardiac dysfunction is highly prevalent in HD patients. We investigated the relationship between proto-dialytic (i.e. early intra-dialytic) cardiac function and IDME in HD patients. METHODS: Heart rate, beat-to-beat blood pressure (BP) and cardiac output were continuously measured during the first 30 min of dialysis treatment using the Task Force™ Monitor. Total peripheral resistance index (TPRI) was calculated from cardiac index (CI) and BP. Univariate, multivariate and logistic regression analyses were employed to relate IDME to haemodynamic predictors; Kaplan-Meier method was employed for time-to-event analysis. RESULTS: Fourteen HD patients (age 67 ± 15 years; 7 females) were studied. Dialysis treatment was complicated by IDH and muscle cramps in 4 and 8 out of 30 sessions, respectively. CI was higher in patients without IDME (2.6 ± 0.5 L/min/m(2)) as compared to those with muscle cramps (2.0 ± 0.3 L/min/m(2)) or IDH (1.8 ± 0.2 L/min/m(2); all P < 0.05). CI and TPRI at baseline independently predicted IDME in a multivariate regression analysis (odds ratio: 0.043 per unit of CI, 95% confidence interval: 0.003-0.611; odds ratio: 1.124 per unit of TPRI, 95% confidence interval: 1.25-1.01). Patients were stratified by tertiles of CI. IDME occurred in the two lower tertiles, whereas patients in the upper tertile were event free (log-rank test, P < 0.002). CONCLUSIONS: Low CI and high TPRI in the first 30 min of HD are associated with an increased risk of IDME.

Prevalence of chronic kidney disease in patients with suspected sleep apnoea.

BACKGROUND: Little is known about the epidemiology of chronic kidney disease (CKD) in patients with suspected sleep apnoea (SA). METHODS: Glomerular filtration rate (eGFR) was calculated in consecutive patients referred for full-night observed in-hospital polysomnography. SA was defined as the respiratory disturbance index (RDI) > 5. RESULTS: One hundred and fifty-eight patients were studied. The age (mean +/- SD) was 61.2 +/- 12.7 years, body mass index 29.5 +/- 5.9 kg/m(2) and eGFR 86.1 +/- 21.7 mL/min/1.73 m(2). SA was present in 133 patients (85%). The eGFR was 94.6 7 mL/min/1.73 m(2) in patients without SA and 84.5 7 mL/min/1.73 m(2) in patients with SA [mean difference (95% confidence interval) 10.0 (0.6-19.4) mL/min/1.73 m(2); P = 0.037]. Seventy patients had eGFR > or = 90 mL/min/1.73 m(2) (group 1), and 70 patients had between 60 and 89 mL/min/1.73 m(2) (group 2), and 18 patients had 30-59 mL/min/1.73 m(2) (CKD 3). Although the prevalence of SA did not differ among the groups (group 1: 80%; group 2: 86%; CKD 3: 94%), the number of central sleep apnoeas (CSA) per hour was 5.9 +/- 12.2 in CKD 3, six times greater compared to patients with eGFR > or = 60 mL/min/1.73 m(2) (1.0 +/- 2.1; P = 0.01). The prevalence of obstructive SA did not differ between the groups. After adjustment for age, gender, BMI, hypertension, diabetes mellitus and smoking status, CKD 3 (P = 0.0004) and New York Heart Association class > or =3 (P = 0.0001) remained predictive of CSA events per hour. CONCLUSIONS: eGFR is reduced in patients with SA, particularly in those with episodes of CSA.

Sympathetic reserve, serum potassium, and orthostatic intolerance after endurance exercise and implications for neurocardiogenic syncope.

AIMS: To elucidate the mechanisms of orthostatic intolerance (OI) after endurance exercise which are incompletely understood. METHODS AND RESULTS: We investigated beat-to-beat haemodynamic and autonomic parameters in 51 male athletes during supine rest and after active standing the day before and 2 h after a marathon run. None of the subjects before the marathon [non-orthostatic intolerance (Non-OI)], but 14 after the marathon [orthostatic intolerance (OI)] exhibited with pre-syncope. There were no differences between OI and Non-OI before the marathon. After the marathon, only Non-OI was able to increase sympathetic modulation to resistance vessels from already increased basal levels in response to standing; OI could not. OI instead exhibited a decrease in total peripheral resistance and a paradoxical increase in parasympathetic sinus node modulation. We observed a significant correlation between serum potassium before the race and the maximally achieved sympathetic drive after the marathon (r = 0.55, P = 0.001). CONCLUSION: Post-exercise OI is associated with a 'high basal sympathetic modulation of vasomotor tone in combination with a diminished orthostatic sympathetic response' to resistance vessels. This situation may mimic the OI in some clinical conditions, which are also known to be associated with increased 'basal' sympathetic tone. The role of serum potassium deserves further study.

Noninvasive measurement of cardiac output in hemodialysis patients by task force monitor: a comparison with the Transonic System.

Cardiovascular disease is the leading cause of morbidity and mortality in maintenance hemodialysis (MHD) patients. The Transonic (TRS; Transonic Systems, Ithaca, NY) device is frequently used for determination of cardiac output (CO) by an indicator dilution technique. The Task Force Monitor (TFM; CN Systems, Graz, Austria) has gained attention as noninvasive tool for continuous beat-to-beat assessment of cardiovascular variables, including CO by impedance cardiography. Despite its use in cardiology and intensive care settings, the TFM has yet not been validated in dialysis patients. This study compares CO measurements in 12 MHD patients by TFM and TRS. Bland-Altman and regression analysis were used. CO was measured simultaneously by TRS and TFM. Average CO was 5.4 L/min by TRS and 5.0 L/min by TFM, respectively. Bland-Altman analysis revealed no significant systematic differences between the two methods (mean difference: 0.4 L/min; SD: 0.6; p > 0.05). Linear regression analysis showed significant correlation between both techniques (r = 0.802, p = 0.002). The SD of mean individual CO values was 1.1 L/min with TRS and 0.8 L/min with TFM, respectively.CO measured by TFM and TRS does not differ significantly, thus making the TFM an attractive noninvasive tool for the continuous beat-to-beat assessment of CO in MHD patients.

Haplotypes of the beta-2 adrenergic receptor associate with high diastolic blood pressure in the Caerphilly prospective study.

OBJECTIVES: Current evidence demonstrates that both genetic and environmental factors influence blood pressure. The sympathetic nervous system is a key player in blood pressure control and functional genetic variants of the beta-2 adrenergic receptor (B2AR) have been identified and implicated in the pathogenesis of hypertension. The present study aimed to determine the effects of common haplotypes of the B2AR gene upon blood pressure in the Caerphilly Prospective Study. DESIGN: Two thousand five hundred and twelve men (aged 45-59 years) participated in the study. We selected individuals in the upper (n = 347) and lower (n = 279) quintiles of the diastolic blood pressure distribution fixed at two time points [phase 2 (1984-88) or phase 3 (1989-93)] as cases and controls. METHODS: We analysed two functional polymorphisms (Arg16Gly and Gln27Glu) of B2AR and their haplotypes. RESULTS: We found a higher risk of hypertension in individuals homozygous for the Gln27 compared to those individuals homozygous for Glu27 [odds ratio (OR) = 1.94; 95% confidence interval (CI) = 1.34-2.81; P = 0.001]. Three haplotypes (Gly16Gln27, Gly16Glu27 and Arg16Gln27) were present in both quintile groups. Logistic regression analysis showed that haplotypes with a Gln27 allele (Gly16Gln27 and Arg16Gln27) conferred a significantly higher risk for hypertension than the Gly16Glu27 haplotype (OR = 1.55; 95% CI = 1.11-2.17, OR = 1.37; 95% CI = 1.04-1.81; P = 0.009 and P = 0.027, respectively). However, there was no evidence to support a statistically significant difference in odds ratios for the Gly16Gln27 and Arg16Gln27 haplotypes (P = 0.477), suggesting that it is the Gln27 allele alone, rather than any haplotype, which best explains the association. CONCLUSIONS: In a prospectively studied Caucasian male cohort, high diastolic blood pressure was associated with B2AR haplotypes containing the pro-downregulatory Gln27 variant.

Multi-site-frequency electromechanocardiography for the prediction of ejection fraction and stroke volume in heart failure.

BACKGROUND: Methods for stroke volume (SV) and ejection fraction (EF) measurements require the presence of qualified physicians and are not suited for continuous monitoring. AIM: To develop an automated non-invasive method for the measurement and continuous monitoring of SV and EF. METHODS: We have designed a method for the measurement of EF and SV using multiple-site-impedance (z0) measurements, applying multiple frequencies of 5, 40 and 200 kHz whereby various segments of the human body, including volume changes within these segments, could be defined electrically. The obtained variables were used to train neuronal nets and related by multiple regression analyses to cardiac output (CO) as measured by a partial rebreathing Fick method (CO(r-fick)) or EF as measured by echocardiography (EF(echo)), respectively. A total of 129 subjects (48 with normal heart function and 81 with CHF, NYHA I-IV) were investigated. RESULTS: The multiply derived values of z0 and of change of impedance (dz/dt) were shown, by multiple regression analysis, to be significantly related to CO(r-fick) and to EF(echo), (total r=0.77, n=35, p<0.001, and r=0.81, n=47, p<0.001, respectively.). By training a neuronal net with the electrical data of 67 (out of 94) subjects, EF(echo) could be predicted in the remaining 27 subjects which were unknown to the neuronal net with a combined r=0.71 (p<0.001,n=27). In contrast, conventional impedance cardiography (ICG) was unable to predict either CO(r-fick) or EF(echo). CONCLUSION: The new method, which we call multi-site-frequency electromechanocardiography (msf-ELMC) appears promising for the automated electrical measurement of the mechanical heart action in patients with normal and reduced cardiac function.

Hemodynamic and autonomic changes induced by Ironman: prediction of competition time by blood pressure variability.

We hypothesized that the extreme endurance exercise of an Ironman competition would lead to long-standing hemodynamic and autonomic changes. We investigated also the possibility of predicting competition performance from baseline hemodynamic and autonomic parameters. We have investigated 27 male athletes before competition, 1 h after, and then for the following week after the competition. The Task Force monitor was used to measure beat-to-beat hemodynamic and autonomic parameters during supine rest and active standing. Heart rate (P < 0.001) was increased, and stroke index (P = 0.011), systolic blood pressure (P = 0.004), diastolic blood pressure (P < 0.001), total peripheral resistance index (P < 0.001), and baroreceptor reflex sensitivity (P < 0.001) were decreased after the competition. The 0.05- to 0.17-Hz band of heart rate and blood pressure variability was increased (P < 0.001 and P < 0.001, respectively), the 0.17- to 0.40-Hz band of heart rate interval variability was decreased after the competition (P < 0.001). All parameters returned to baseline values 3 days after the competition. After the competition, the autonomic response to orthostasis was significantly impaired. The 0.05- to 0.17-Hz band of diastolic blood pressure variability before competition and weekly net exercise training, but not the other hemodynamic and autonomic parameters, were related to competition time in multivariate regression analysis (multiple r = 0.70, P < 0.001). The marked hemodynamic and autonomic changes after an ultraendurance race, which are compatible with myocardial depression in the face of sympathetic activation and reduction of afterload, return to baseline after only 1-3 days. Because the 0.05- to 0.17-Hz band of diastolic blood pressure variability contributes to the prediction of competition time, the analysis of blood pressure variability in the frequency domain deserves further study for the prediction of endurance capacity.

[Arterial elasticity, arterial hypertension and antihypertensive therapy]. / Gefässelastizität, Hochdruck und Hochdrucktherapie.

Semi-automated methods for pulse wave analysis enable the early diagnosis of changes in the elasticity of large and small blood vessels. Currently two methods are in routine use: a) The augmentation index and b) the compliance of the large and the small blood vessels (C1, C2). It has been shown that both measurements are able to predict cardiovascular mortality independent of other established risk factors. It remains to be shown whether antihypertensive therapy with drugs which improve compliance, in addition to lowering blood pressure, are superior to drugs which only lower blood pressure without affecting compliance. An increase of pulse pressure represents a later stage in the development of atherosclerosis and is therefore less sensitive than the above named elasticity measurements. Changes in elasticity occur very early in the development of atherosclerosis therefore these methods should prove very useful in preventive medicine. It is to be hoped that these methods will be increasingly used for detecting incipient atherosclerosis.

Autonomic dysfunction and hemodynamics in vitamin B12 deficiency.

Orthostatic hypotension in patients with cobalamin (Cbl) deficiency has been reported previously in isolated cases but we are not aware of detailed systematic studies of hemodynamic and autonomic nervous system function in patients with cobalamin deficiency. We investigated hemodynamic and autonomic responses to 60 degrees passive head up tilt (HUT) in 21 patients with vitamin B12 deficiency, 21 healthy age-matched control subjects and 9 age-matched patients with diabetes mellitus (DM) and established diabetic neuropathy. To systematically assess hemodynamic and autonomic nervous system function, we performed measurements of heart rate, beat-to-beat systolic and diastolic blood pressure, stroke index, cardiac index, total peripheral resistance index, total power, low (LF) and high (HF) frequency oscillatory component of heart rate variability, LF/HF ratio and spontaneous baroreflex sensitivity. As compared to controls, we found a significant fall of systolic blood pressure during 60 consecutive beats directly after head up tilt; furthermore, a significantly blunted fall of stroke index, cardiac index and a lack of increase of total peripheral resistance index for the duration of tilt in patients with diabetes mellitus and in patients with vitamin B12 deficiency. As compared to controls, we observed an altered response of spectral indices of sympathetic activation and vagal withdrawal and an impaired modulation of baroreflex sensitivity during head up tilt suggestive of a complex modification in the neural control activities in patients with cobalamin deficiency, which was comparable to that observed in patients with diabetes mellitus and established autonomic neuropathy. The results suggest that vitamin B12 deficiency causes autonomic dysfunction with similar hemodynamic consequences and patterns of autonomic failure as seen in diabetic autonomic neuropathy. Defective sympathetic activation may be the cause for orthostatic hypotension, which is occasionally seen in patients with vitamin B12 deficiency. It is concluded that patients with orthostatic hypotension should be screened for cobalamin deficiency.