Heart rate increment analysis is not effective for sleep-disordered breathing screening in patients with chronic heart failure

Frequency domain analysis of heart rate variation has been suggested as an effective screening tool for sleep-disordered breathing (SDB) in the general population. The aim of this study was to assess this method in patients with chronic congestive heart failure (CHF). We included prospectively 84 patients with stable CHF, left ventricular ejection fraction (LVEF) <45% and sinus rhythm. The patients underwent polygraphy to measure the apnoea/hypopnoea index (AHI) and simultaneous Holter electrocardiogram monitoring to measure the power spectral density of the very low frequency component of the heart rate increment, expressed as the percentage of total power spectral density [% very low frequency increment (%VLFI)]. %VLFI could be determined in 54 patients (mean age, 52.8 ± 12.3 years; LVEF, 33.5 ± 9.8%). SDB defined as AHI ≥15 h⁻¹ was diagnosed in 57.4% of patients. Percent VLFI was not correlated with AHI ( r  =   0.12). Receiver-operating characteristic curves constructed using various AHI cut-offs (5–30 h⁻¹) failed to identify a %VLFI cut-off associated with SDB. The 2.4% VLFI cut-off recommended for the general population of patients with suspected SDB had low specificity (35%) and low positive and negative predictive values (35% and 54%, respectively). Heart rate increment analysis has several limitations in CHF patients and cannot be recommended as an SDB screening tool in the CHF population.     

(.)VO(2) and EMG activity kinetics during moderate and severe constant work rate exercise in trained cyclists.

The purpose of this study was to compare O(2) uptake ((.)VO(2)) and muscle electromyography activity kinetics during moderate and severe exercise to test the hypothesis of progressive recruitment of fast-twitch fibers in the explanation of the VO(2) slow component. After an incremental test to exhaustion, 7 trained cyclists (mean +/- SD, 61.4 +/- 4.2 ml x min(-1) x kg(- 1)) performed several square-wave transitions for 6 min at moderate and severe intensities on a bicycle ergometer. The (.)VO(2) response and the electrical activity (i.e., median power frequency, MDF) of the quadriceps vastus lateralis and vastus medialis of both lower limbs were measured continuously during exercise. After 2 to 3 min of exercise onset, MDF values increased similarly during moderate and severe exercise for almost all muscles whereas a (.)VO(2) slow component occurred during severe exercise. There was no relationship between the increase of MDF values and the magnitude of the (.)VO(2) slow component during the severe exercise. These results suggest that the origin of the slow component may not be due to the progressive recruitment of fast-twitch fibers.     

Seasonal variation in work performance and heart rate response to exercise

Summary A near maximal bicycle exercise test in 1,835 presumably healthy Norwegian men indicated a seasonal variation in physical fitness. Thus, the total amount of work performed was significantly higher, and the work pulse on equivalent loads significantly lower during the summer than during the autumn. Although the differences were small, they may invalidate comparisons made between exercise tests in populations tested at different seasons of the year. In particular, there was a considerable and sudden change in the above mentioned parameters from June–August to September–October.     

Transient oxygen uptake response to exercise characterizes functional capacity of the cardiocirculatory system in patients with chronic heart failure: a random stimulus approach

The transient response of oxygen uptake (V˙O₂) to submaximal exercise, known to be abnormal in patients with cardiovascular disorders, can be useful in assessing the functional status of the cardiocirculatory system, however, a method for evaluating it accurately has not yet been established. As an alternative approach to the conventional test at constant exercise intensity, we applied a random stimulus technique that has been shown to provide relatively noise immune responses of system being investigated. In 27 patients with heart failure and 24 age-matched control subjects, we imposed cycle exercise at 50 W intermittently according to a pseudo-random binary (exercise-rest) sequence, while measuring breath-by-breath V˙O₂. After determining the transfer function relating exercise intensity (W˙) to V˙O₂ and attenuating the high frequency ranges (>6 exercise-rest cycles · min⁻¹), we computed the high resolution band-limited (0–6 cycles · min⁻¹) V˙O₂ response (0–120 s) to a hypothetical step exercise. The V˙O₂ response showed a longer time constant in the patients than in the control subjects [47 (SD 37) and 31 (SD 8) s, respectively, P < 0.05]. Furthermore, the amplitude of the V˙O₂ response after the initial response was shown to be significantly smaller in the patients than in the control subjects [176 (SD 50) and 267 (SD 54) ml · min⁻¹ at 120 s]. The average amplitude over 120 s correlated well with peak V˙O₂ (r = 0.73) and ΔV˙O₂/ΔW˙ (r = 0.70), both of which are well-established indexes of exercise tolerance. The data indicated that our band-limited V˙O₂ step response using random exercise was more markedly attenuated and delayed in the patients with heart failure than in the normal controls and that it could be useful in quantifying the overall functional status of the cardiocirculatory system. Accepted: 6 January 1998     

The off-transient pulmonary oxygen uptake (VO(2)) kinetics following attainment of a particular VO(2) during heavy-intensity exercise in humans

The oxygen uptake response to moderate-intensity exercise (i.e. < anaerobic threshold (an)) has been characterised with a gain (i.e. response amplitude per increment of work rate) and time constant that do not vary appreciably at different work rates or between the on- and off-transients. Above an, the response becomes more complex with an early component that typically projects to a value that has a gain similar to that of the < an response, but which is supplemented by the addition of a delayed slow kinetic component. We therefore established a constant target VO2 (VO21) for each subject such that with different imposed work rates the contribution to VO21 from the slow phase varied over a wide range. Work rates were chosen so that VO21 was attained at 2-24 min. Five subjects (aged 21-58 years) cycled at four to five different work rates. VO2 was measured breath-by-breath, at VO21 the work rate was abruptly reduced and the subject recovered by cycling unloaded for 15 min. Unlike the on-transient, for which the slow component shows a long delay, the off-transient was best fitted as two simultaneous exponential components. The slower off-transient component had a small amplitude and long time constant, but did not differ significantly among the various tests. The off-transient kinetics for VO2 therefore was independent of the magnitude of the contribution to the slow phase from the on-transient kinetics.     

Dynamics of chest wall volume regulation during constant work rate exercise in patients with chronic obstructive pulmonary disease

This study evaluated the dynamic behavior of total and compartmental chest wall volumes [(V_CW) = rib cage (V_RC) + abdomen (V_AB)] as measured breath-by-breath by optoelectronic plethysmography during constant-load exercise in patients with stable chronic obstructive pulmonary disease. Thirty males (GOLD stages II-III) underwent a cardiopulmonary exercise test to the limit of tolerance (Tlim) at 75% of peak work rate on an electronically braked cycle ergometer. Exercise-induced dynamic hyperinflation was considered to be present when end-expiratory (EE) V_CW increased in relation to resting values. There was a noticeable heterogeneity in the patterns of V_CW regulation as EEV_CW increased non-linearly in 17/30 “hyperinflators” and decreased in 13/30 “non-hyperinflators” (P < 0.05). EEV_AB decreased slightly in 8 of the “hyperinflators”, thereby reducing and slowing the rate of increase in end-inspiratory (EI) V_CW (P < 0.05). In contrast, decreases in EEV_CW in the “non-hyperinflators” were due to the combination of stable EEV_RC with marked reductions in EEV_AB. These patients showed lower EIV_CW and end-exercise dyspnea scores but longer Tlim than their counterparts (P < 0.05). Dyspnea increased and Tlim decreased non-linearly with a faster rate of increase in EIV_CW regardless of the presence or absence of dynamic hyperinflation (P < 0.001). However, no significant between-group differences were observed in metabolic, pulmonary gas exchange and cardiovascular responses to exercise. Chest wall volumes are continuously regulated during exercise in order to postpone (or even avoid) their migration to higher operating volumes in patients with COPD, a dynamic process that is strongly dependent on the behavior of the abdominal compartment.     

Reproducibility of onset and recovery oxygen uptake kinetics in moderately impaired patients with chronic heart failure

Oxygen (O2) kinetics reflect the ability to adapt to or recover from exercise that is indicative of daily life. In patients with chronic heart failure (CHF), parameters of O2 kinetics have shown to be useful for clinical purposes like grading of functional impairment and assessment of prognosis. This study compared the goodness of fit and reproducibility of previously described methods to assess O2 kinetics in these patients. Nineteen CHF patients, New York Heart Association class II-III, performed two constant-load tests on a cycle ergometer at 50% of the maximum workload. Time constants of O2 onset- and recovery kinetics (tau) were calculated by mono-exponential modeling with four different sampling intervals (5 and 10 s, 5 and 8 breaths). The goodness of fit was expressed as the coefficient of determination (R2). Onset kinetics were also evaluated by the mean response time (MRT). Considering O2 onset kinetics, tau showed a significant inverse correlation with peak- VO2 (R = -0.88, using 10 s sampling intervals). The limits of agreement of both tau and MRT, however, were not clinically acceptable. O2 recovery kinetics yielded better reproducibility and goodness of fit. Using the most optimal sampling interval (5 breaths), a change of at least 13 s in tau is needed to exceed normal test-to-test variations. In conclusion, O2 recovery kinetics are more reproducible for clinical purposes than O2 onset kinetics in moderately impaired patients with CHF. It should be recognized that this observation cannot be assumed to be generalizable to more severely impaired CHF patients.     

Effect of work rate on the functional 'gain' of Phase II pulmonary O2 uptake response to exercise

It has recently been reported that the 'gain' of Phase II increase in pulmonary oxygen uptake (i.e. the 'fundamental' increase in V(O(2)) per unit increase in work rate; G(p)) does not attain the anticipated value of approximately 10 ml min(-1)W(-1) following the onset of high-intensity exercise. In the present study, we hypothesised that G(p) would fall significantly below 10 ml min(-1)W(-1) only when the work rate exceeded the so-called 'critical power' (CP). Seven healthy males completed several 'square-wave' transitions from 'unloaded' cycling to work rates requiring 60 and 90% of the gas exchange threshold (GET), 40 and 80% of the difference between the GET and V(O(2)) peak (i.e. below and above the CP, respectively), and 100, 110 and 120% of V(O(2)) peak. Pulmonary V(O(2)) was measured breath-by-breath and V(O(2)) kinetics were determined using non-linear regression techniques. The asymptotic G(p) was significantly lower at work rates above (7.2-8.6 ml min(-1)W(-1)) compared to work rates below (9.3-9.7 ml min(-1)W(-1)) the CP (P < 0.05). We conclude that the gain of Phase II increase in V(O(2)) becomes significantly reduced when the work rate exceeds the CP.     

The reliability of continuous measurement of mixed venous oxygen saturation during exercise in patients with chronic heart failure

Continuous assessment of mixed venous oxygen saturation (cSvO₂) during exercise using a fiber optic pulmonary artery catheter can provide valuable information on the physiological determinants of the exercise capacity in patients with chronic heart failure (CHF). Since its accuracy is not well established during exercise, this study evaluated the reliability of a fiber optic pulmonary artery catheter for measuring SvO₂ during exercise in CHF patients. Ten patients with stable CHF performed steady-state exercise tests at 30 and 80% of the ventilatory threshold and consequently a symptom-limited incremental exercise test. During the tests, SvO₂ was monitored continuously using a fiber optic pulmonary artery catheter (CCOmbo, Edwards Lifesciences, Irvine, CA, USA) and by oximetric analysis of mixed venous blood samples obtained at rest (n = 26), steady state (n = 17) and peak exercise (n = 8). There was a significant correlation between oximetrically determined SvO₂ and cSvO₂ values (r = 0.97). The bias between both methods was 0.6% with limits of agreement from −8 to 9%. The limits of agreement for SvO₂ values <30% (n = 16) were slightly wider than for SvO₂ values >30% (n = 35) (from −10 to 12% and from −7 to 8%, respectively). In conclusion, continuous measurement of SvO₂ during exercise using a fiber optic pulmonary catheter is reliable in patients with CHF, with somewhat less accurate measurements of SvO₂ below 30%.     

Mixed venous blood temperature response to exercise in heart failure patients treated with short-term vasodilators

Deep-body or core temperature decreases during exercise in patients with heart failure, primarily due to the circulatory inadequacies associated with the pathophysiology of this condition. Vasodilators are commonly used to treat patients suffering from heart failure because these drugs improve total cardiac output and blood-flow to the regional circulations. In heart failure patients, the core temperature response to exercise should also be affected if the circulation is improved by vasodilators. Patients with severe heart failure were studied at rest and during upright bicycle exercise before, and after, short-term treatment with vasodilators (2-minoxidil, 3-hydralazine, 5-captopril). Their heart rate increased significantly (P less than 0.05) from rest to exercise before (87 +/- 15 109 +/- 14 beats/min), and after 89 +/- 13- 112 +/- 15 beats/min) vasodilators, but there was no drug-related affect on these changes. Mean arterial and pulmonary capillary wedge pressures were significantly (P less than 0.05) decreased at rest and after the administration of vasodilators (mean arterial pressure 88 +/- 7 mmHg before; 77 +/- 8 mmHg after; pulmonary capillary wedge pressure 25 +/- 8 mmHg before, 19 +/- 9 mmHg after). During exercise, the increases in mean arterial and pulmonary capillary wedge pressures were not significantly different from the before vasodilator values (mean arterial pressure 92 +/- 14 mmHg before, 87 +/- 14 mmHg after; pulmonary capillary wedge pressure 31 +/- 11 mmHg before, 29 +/- 11 mmHg after). Vasodilators increased cardiac output significantly (P less than 0.05) at rest (3.1 +/- 0.6 litre/min to 4.1 +/- 1.1 litre/m) and during exercise (4.8 +/- .2 litre/min-5.6 +/- 1.7 litre/min). The core temperature (mixed venous blood temperature) decreased significantly (P less than 0.05) during exercise from 37.04 +/- 0.62 degrees C to 36.65 +/- 0.65 degrees C, before treatment with vasodilators. After administration of vasodilators, resting core temperature was not significantly different (36.95 +/- 0.54 degrees C) and still decreased significantly (P less than 0.05) during exercise to 36.73 +/- 0.53 degrees C. This decrease was significantly (P less than 0.05) different from the core temperature response before the administration of vasodilators. We conclude that heart failure patients, treated with short-term vasodilators, have an attenuation of the core temperature response that typically occurs during exercise. This change in the core temperature response is the result of the vasodilator-induced improvement in circulation.     

Reduced ambulatory heart rate response to physical work and complaints of fatigue among hypertensive males treated with beta-blockers

Treatment with beta-blockers affects oxygen metabolism and lipolysis during physical exertion. Together with possible central nervous system effects, this may impair the work capacity of treated hypertensive subjects. In a study of 1619 male employees, aged 45–64 years, mean resting and ambulatory heart rate (HR) and complaints of fatigue were compared between hypertensive workers treated with beta-blockers and untreated hypertensives and normotensives under low and high workload conditions. Treated hypertensives had lower mean resting HRs compared with normotensives and untreated hypertensives. Their change from resting to ambulatory HR during low and high workload was also lower than normotensives and untreated hypertensives, and they had higher fatigue scores than their untreated counterparts at both workload levels. The highest fatigue score was reported by treated subjects under high workload. These findings demonstrate a reduced HR response to physical work accompanied by more symptoms of fatigue during treatment with beta-blockers. When hypertensives are engaged in physically demanding work, other classes of antihypertensive therapy should be considered.This study was supported by the Committee for Preventive Action and Research in Occupational Health, The Ministry of Labor and Social Affairs, Jerusalem, Israel.     

A raised metabolic rate slows pulmonary O(2) uptake kinetics on transition to moderate-intensity exercise in humans independently of work rate

During exercise below the lactate threshold (LT), the rate of adjustment (τ) of pulmonary VO(2) uptake (τ) is slowed when initiated from a raised work rate. Whether this is consequent to the intrinsic properties of newly recruited muscle fibres, slowed circulatory dynamics or the effects of a raised metabolism is not clear. We aimed to determine the influence of these factors on τV(O(2)) using combined in vivo and in silico approaches. Fifteen healthy men performed repeated 6 min bouts on a cycle ergometer with work rates residing between 20 W and 90% LT, consisting of the following: (1) two step increments in work rate (S1 and S2), one followed immediately by the other, equally bisecting 20 W to 90% LT; (2) two 20 W to 90% LT bouts separated by 30 s at 20 W to raise muscle oxygenation and pretransition metabolism (R1 and R2); and (3) two 20 W to 90% LT bouts separated by 12 min at 20 W allowing full recovery (F1 and F2). Pulmonary O(2) uptake was measured breath by breath by mass spectrometry and turbinometry, and quadriceps oxygenation using near-infrared spectroscopy. The influence of circulatory dynamics on the coupling of muscle and τV(O(2)) lung was assessed by computer simulations. The τV(O(2)) in R2 (32 ± 9 s) was not different (P > 0.05) from S2 (30 ± 10 s), but both were greater (P < 0.05) than S1 (20 ± 10 s) and the F control bouts (26 ± 10 s). The slowed V(O(2)) kinetics in R2 occurred despite muscle oxygenation being raised throughout, and could not be explained by slowed circulatory dynamics (τV(O(2)) predicted by simulations: S1 = R2 < S2). These data therefore suggest that the dynamics of muscle O(2) consumption are slowed when exercise is initiated from a less favourable energetic state.     

Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure

BACKGROUND: The benefits of angiotensin-converting-enzyme inhibitors and beta-blockers may be smaller in black patients than in patients of other races, but it is unknown whether race influences the response to carvedilol in patients with chronic heart failure. METHODS: In the U.S. Carvedilol Heart Failure Trials Program, 217 black and 877 nonblack patients (in New York Heart Association class II, III, or IV and with a left ventricular ejection fraction of no more than 0.35) were randomly assigned to receive placebo or carvedilol (at doses of 6.25 to 50 mg twice daily) for up to 15 months. The effects of carvedilol on ejection fraction, clinical status, and major clinical events were retrospectively compared between black and nonblack patients. RESULTS: As compared with placebo, carvedilol lowered the risk of death from any cause or hospitalization for any reason by 48 percent in black patients and by 30 percent in nonblack patients. Carvedilol reduced the risk of worsening heart failure (heart failure leading to death, hospitalization, or a sustained increase in medication) by 54 percent in black patients and by 51 percent in nonblack patients. The ratios of the relative risks associated with carvedilol for these two outcome variables in black as compared with nonblack patients were 0.74 (95 percent confidence interval, 0.42 to 1.34) and 0.94 (95 percent confidence interval, 0.43 to 2.05), respectively. Carvedilol also improved functional class, ejection fraction, and the patients' and physicians' global assessments in both the black patients and the nonblack patients. For all these measures of outcome and clinical status, carvedilol was superior to placebo within each racial cohort (P<0.05 in all analyses), and there was no significant interaction between race and treatment (P> 0.05 in all analyses). CONCLUSIONS: The benefit of carvedilol was apparent and of similar magnitude in both black and nonblack patients with heart failure.     

The role of fitness on VO2 and VCO2 kinetics in response to proportional step increases in work rate

Summary The purpose of this study was to determine the effect of fitness and work level on the O₂ uptake and CO₂ output kinetics when the increase in work rate step is adjusted to the subject's maximum work capacity. Nine normal male subjects performed progressive incremental cycle ergometer exercise tests in 3-min steps to their maximum tolerance. The work rate step size was selected so that the symptom-limited maximum work rate would be reached in four steps at 12 min in all subjects. Oxygen consumption (VCO₂) and carbon dioxide production VCO₂ were calculated breath by breath. For the group, the time (mean, SEM) to reach 75% of the 3-min response (T _0.75) for VO₂ increased significantly (P<0.01) at progressively higher work rate steps, being 53.3 (5.5) s, 63.5 (4.6) s, 79.5 (5.0) s, and 94.5 (5.8) s, respectively. In contrast, T _0.75 for VCO₂ did not change significantly [74.9 (7.4) s,. 75.6 (5.0) s, 85.1 (5.3) s, and 89.4 (6.3) s, respectively]. VCO₂ kinetics were slower than VO₂ kinetics at the low fractions of the subjects' work capacities but were the same of faster at the high fractions because of the slowing of VO₂ kinetics. The first step showed the fastest rise in VO₂. While VO₂ kinetics slowed at each step, they were faster at each fraction of the work capacity in the fitter subjects. The step pattern in VO₂ disappeared at high work rates for the less fit subjects. The heart rate response paralleled that of VO₂. We conclude that VO₂ and VCO₂ kinetics are slower in the less fit subjects but only VO₂ kinetics are significantly attenuated in response to proportional step increases in work rate.     

Nonlinear dynamics of heart rate variability in response to orthostatism and hemodialysis in chronic renal failure patients: Recurrence analysis approach

We studied the response of heart rate variability to hemodialysis and orthostatism using traditional linear indexes and 9 recurrence quantification analysis indexes to reveal changes in the heart rate dynamics. Twenty healthy subjects and 19 chronic renal failure patients treated with hemodialysis thrice a week were included. Five-minute heart rate variability time series were obtained during supine position (clinostatism) and orthostatism from each participant; recordings in renal patients were repeated after hemodialysis. Linear indexes were consistent with sympathetic predominance in response to orthostatism in the control group. Renal patients before hemodialysis showed increased sympathetic predominance in clinostatism, with further increase in orthostatism and hemodialysis. In response to orthostatism, 4 recurrence indexes changed in the control group, while in renal patients any of them changed before hemodialysis and 1 changed after hemodialysis. In clinostatism, renal patients (both before and after hemodialysis) had higher laminarity, trapping time, and recurrence time than the control group. Recurrence indexes showed that the heart rate dynamics in renal patients are different from healthy subjects, suggesting loss of access to some regulatory conditions. These findings are consistent with reports of sympathetic stimulation induced by hemodialysis and active standing.     

Decrease in peak heart rate with acute hypoxia in relation to sea level VO(2max)

The aim of this study was to evaluate the influence of arterial oxygen saturation (SaO₂) on maximal heart rate during maximal exercise under conditions of acute hypoxia compared with normoxia. Forty-six males were divided into three groups depending on their sea level maximal oxygen consumption (O_2max): high [GH, O_2max=64.2 (3.3) ml.min^–1.kg^–1], medium [GM, 50.8 (3.9) ml.min^–1.kg^–1] and low [GL, 41.0 (1.9) ml.min^–1.kg^–1]. All subjects performed a maximal exercise test in two conditions of inspired oxygen tension (PIO₂, (149 mmHg and 70 mmHg). Among the GM group, seven subjects performed five supplementary incremental exercise tests at PIO₂ 136, 118, 104, 92, and 80 mmHg. Measurements of O_2max and SaO₂ using an ear-oxymeter were carried out at all levels of PIO₂. The decrease in SaO₂ and peak heart rate (HR_peak) with PIO₂ became significant from 104 and 92 mmHg. SaO₂ correlated with the decrease in HR_peak. For PIO₂=70 mmHg, the decrease in O_2max, SaO₂ and HR_peak was, respectively, 44%, 62%, and 17.0 bpm for GH, 38%, 68%, and 14.7 bpm for GM, and 34%, 68%, and 11.8 bpm for GL. During maximal exercise in hypoxia, SaO₂ was lower for GH than GM and GL (p<0.01). Among subjects in GH, five presented exercise-induced hypoxemia (EIH) when exercising in normoxia. The EIH group exhibited a greater decrement in HR_peak than the non-EIH group at maximal hypoxic exercise (21.2 bpm vs. 15.0 bpm; p<0.05). When subjects are exposed to acute hypoxia, the lower SaO₂, due either to lower PIO₂ or to training status, is associated with lower HR_peak.     

Circulating thrombospondin-2 in patients with moderate-to-severe chronic heart failure due to coronary artery disease

Chronic heart failure (CHF) remains a leading cause of morbidity and mortality. In the current study, we aimed to evaluate the predictive value of circulating thrombospondin-2 (TSP-2) for cumulative survival in patients with ischemic CHF due to coronary artery disease (CAD). The results showed that during a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repeatedly. The median circulating levels of TSP-2 in patients who survived and those who died were 0.63 ng/mL (95%CI = 0.55-0.64 ng/mL) and 1.03 ng/mL (95% CI = 0.97-1.07 ng/mL) (P<0.001). Circulating TSP-2 independently predicted all-cause mortality (OR = 1.27; 95%CI = 1.08–1.59; P = 0.002), CHF-related death (OR = 1.16; 95%CI = 1.02–1.50; P<0.001), and also CHF-related rehospitalization (OR = 1.12; 95%CI = 1.07–1.25; P<0.001). In conclusion, among CAD patients with symptomatic CHF, increased circulating TSP-2 is correlated with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization.     

Effects of angiotensin II type 1 receptor antagonist, losartan, on ventilatory response to exercise and neurohormonal profiles in patients with chronic heart failure

Chronic heart failure (CHF) is associated with abnormal neurohormonal profiles and increased ventilatory response to exercise. This study determined if treatment with angiotensin II type 1 receptor antagonist, losartan, improves ventilatory efficiency and neurohormonal factors in patients with CHF. Symptom-limited cardiopulmonary exercise testing was performed after a 2-week placebo period (baseline) and after 16 weeks of treatment with losartan (40 +/- 4 mg/day) in 10 patients with CHF (age 57.7 +/- 3.7 years). Echocardiogram, daily physical activity (by the specific activity scale), and neurohormones were evaluated. Treatment with losartan increased left ventricular ejection fraction (baseline vs. losartan: 31 +/- 3 vs. 39 +/- 3%, p<0.01) and specific activity scale score (5.3 +/- 0.5 vs. 6.4 +/- 0.4 METS, p<0.05). Losartan decreased the ventilatory response to carbon dioxide production during exercise (VE/VCO2 slope: 34.6 +/- 2.4 vs. 32.0 +/- 2.2, p<0.05). Plasma brain natriuretic peptide concentrations were decreased after therapy (301 +/- 79 vs. 176 +/- 53 pg/ml, p<0.05). In summary, the results of this open-label, uncontrolled study suggest that chronic treatment with losartan may improve ventilatory efficiency and decrease plasma brain natriuretic peptide concentrations with the improvement of physical activity and left ventricular systolic function in patients with CHF.     

Genetic damage in chronic renal failure patients is associated with the glomerular filtration rate index

Chronic renal failure (CRF) patients are considered to present genomic instability and, as a consequence, elevated levels of genetic damage. An open question is whether this damage is related to the stage of the pathology. To determine the background levels of genetic damage, a large population of 258 Caucasian adults (201 CRF patients and 57 controls) was analysed using the micronucleus (MN) assay. The frequency of MN in CRF patients was significantly higher than in controls and correlated with the progression of the disease, according to the glomerular filtration rate. In addition, a significant association was observed between genetic damage and serum creatinine levels. Genetic damage, measured as frequency of MN, increases when renal function decreases. The fact that an increased level of MN is already observed in patients' Stage 2 seems to indicate a genetic predisposition on these patients. Nevertheless, part of the observed damage can be attributed to the uraemic state itself.