Prolonged heart rate recovery time after 6-minute walk test is an independent risk factor for cardiac events in heart failure: a prospective cohort study

OBJECTIVES: To determine whether the time for peak exercise heart rate to return to resting heart rate after the 6-minute walk test (6MWT) can predict cardiac events in patients with heart failure (HF) within 2 years. DESIGN: Prospective cohort study. SETTING: HF outpatient facility at a tertiary teaching hospital. PARTICIPANTS: Seventy-six patients with HF, New York Heart Association functional classification II and III, and left ventricular ejection fraction <50% MAIN OUTCOME MEASURES: Patients used a heart rate monitor to measure the time for peak exercise heart rate to return to resting heart rate after the 6MWT. Data were analysed using Polar Pro-Trainer 5 software (Kempele, Finland). Patients were followed for >2 years for cardiac events (hospitalisations and death). RESULTS: Thirty-four patients had cardiac events during the 2-year follow-up period. There was a significant difference in time to return to resting heart rate between the groups with and without cardiac events {with 3.6 [standard deviation (SD) A] vs without 2.8 (SD B) minutes; mean difference C; 95% confidence interval (CI) of the difference D to E; P=0.003}. No significant differences between patients with and without cardiac events were found for mean walking distance, mean heart rate recovery at 1 minute and mean heart rate recovery at 2 minutes. The receiver operating curve discriminated between patients with and without cardiac events (área under the curve 0.71, 95% CI 0.61 to 0.81; P< 0.001). Using logistic regression analysis, prolonged time to return to resting heart rate (≥3 minutes) independently increased the risk for cardiac events 6.9-fold (95% CI 2.34 to 20.12; P< 0.001). The Kaplan­Meier curve showed more cardiac events in patients with prolonged time to return to resting heart rate (P=0.028). CONCLUSIONS: Prolonged time to return to resting heart rate (≥3 minutes) after the 6MWT was an independent predictor of cardiac events in patients with HF.

Prolonged heart rate recovery time after 6-minute walk test is an independent risk factor for cardiac events in heart failure: A prospective cohort study.

OBJECTIVES: To determine whether the time for peak exercise heart rate to return to resting heart rate after the 6-minute walk test (6MWT) can predict cardiac events in patients with heart failure (HF) within 2 years. DESIGN: Prospective cohort study. SETTING: HF outpatient facility at a tertiary teaching hospital. PARTICIPANTS: Seventy-six patients with HF, New York Heart Association functional classification II and III, and left ventricular ejection fraction <50%. MAIN OUTCOME MEASURES: Patients used a heart rate monitor to measure the time for peak exercise heart rate to return to resting heart rate after the 6MWT. Data were analysed using Polar Pro-Trainer 5 software (Kempele, Finland). Patients were followed for >2 years for cardiac events (hospitalisations and death). RESULTS: Thirty-four patients had cardiac events during the 2-year follow-up period. However, there was a significant difference in the time to return to resting heart rate between the groups with and without cardiac events {with 3.6 (SD 1.1) vs without 2.8 (SD 1.1) minutes; mean difference of 0.79 (95% confidence interval (CI) of the difference 0.28 to 1.28; P=0.003}. No significant differences between patients with and without cardiac events were found for mean walking distance, mean heart rate recovery at 1minute and mean heart rate recovery at 2minutes. The receiver operating curve discriminated between patients with and without cardiac events (área under the curve 0.71, 95% CI 0.61 to 0.81; P<0.001). Using logistic regression analysis, prolonged time to return to resting heart rate (≥3minutes) independently increased the risk for cardiac events 6.9-fold (95% CI 2.34 to 20.12; P<0.001). The Kaplan-Meier curve showed more cardiac events in patients with prolonged time to return to resting heart rate (P=0.028). CONCLUSIONS: Prolonged time to return to resting heart rate (≥3minutes) after the 6MWT was an independent predictor of cardiac events in patients with HF.

Tempo de recuperação da frequência cardíaca como marcador prognóstico de eventos cardíacos / Heart rate recovery time as a prognostic marker of cardiac events

INTRODUÇÃO: O teste de caminhada de 6 minutos (TC6M) é um teste funcional amplamente utilizado em pacientes com insuficiência cardíaca crônica (IC). A distância percorrida no teste, bem como o delta de frequência cardíaca entre o repouso e a recuperação no 1° minuto (HRR1) e o delta de frequência cardíaca entre o repouso e a recuperação no 2° minuto (HRR2) têm sido propostos como marcadores prognósticos de eventos cardíacos em pacientes com IC. Nós hipotetizamos que a variação do tempo em minutos (denominado THRR) entre o pico da frequência cardíaca e o retorno à frequência cardíaca no repouso possa ser um marcador simples e de fácil obtenção no contexto clínico para estimar eventos cardíacos em pacientes com IC. OBJETIVOS: Nós investigamos se o THRR pode ser usado para estimar hospitalizações e morte ao longo de 2 anos de acompanhamento em pacientes com IC. MÉTODOS: Setenta e seis pacientes (média de idade 57 anos, NYHA II e III, IMC 25.5kg/m2, média FEVE de 33%) foram incluídos nesse estudo e divididos em Com eventos e Sem eventos. RESULTADOS: Trinta e quatro pacientes do grupo Com eventos e 42 pacientes do grupo Sem eventos tiveram, respectivamente as seguintes médias: THRR= 3.6 vs 2.8 min (p=0,003), distância percorrida= 463 vs 465 metros (p=0,930), HRR1=12 bpm para ambos grupos (p=0,952) e HRR2= 23 vs 22 bpm (p=0,723). A área sob a curva ROC para discriminar eventos e não eventos foi de 0,70 (IC95%: 0,58-0,82 e p=0,001). Usando a análise de regressão logística, o THRR ≥ 3 minutos dobrou o risco para eventos cardíacos (p=0,003). CONCLUSÃO: A variação de tempo entre o pico do exercício no TC6M e a recuperação da frequência cardíaca de repouso ≥ 3 minutos é um eficiente marcador clínico preditor de hospitalizações e morte em 2 anos para pacientes com IC. (AU)

Atypical visual and somatosensory adaptation in schizophrenia-spectrum disorders.

Neurophysiological investigations in patients with schizophrenia consistently show early sensory processing deficits in the visual system. Importantly, comparable sensory deficits have also been established in healthy first-degree biological relatives of patients with schizophrenia and in first-episode drug-naive patients. The clear implication is that these measures are endophenotypic, related to the underlying genetic liability for schizophrenia. However, there is significant overlap between patient response distributions and those of healthy individuals without affected first-degree relatives. Here we sought to develop more sensitive measures of sensory dysfunction in this population, with an eye to establishing endophenotypic markers with better predictive capabilities. We used a sensory adaptation paradigm in which electrophysiological responses to basic visual and somatosensory stimuli presented at different rates (ranging from 250 to 2550 ms interstimulus intervals, in blocked presentations) were compared. Our main hypothesis was that adaptation would be substantially diminished in schizophrenia, and that this would be especially prevalent in the visual system. High-density event-related potential recordings showed amplitude reductions in sensory adaptation in patients with schizophrenia (N=15 Experiment 1, N=12 Experiment 2) compared with age-matched healthy controls (N=15 Experiment 1, N=12 Experiment 2), and this was seen for both sensory modalities. At the individual participant level, reduced adaptation was more robust for visual compared with somatosensory stimulation. These results point to significant impairments in short-term sensory plasticity across sensory modalities in schizophrenia. These simple-to-execute measures may prove valuable as candidate endophenotypes and will bear follow-up in future work.

The six-minute walk test and body weight-walk distance product in healthy Brazilian subjects

We assessed the 6-min walk distance (6MWD) and body weight x distance product (6MWw) in healthy Brazilian subjects and compared measured 6MWD with values predicted in five reference equations developed for other populations. Anthropometry, spirometry, reported physical activity, and two walk tests in a 30-m corridor were evaluated in 134 subjects (73 females, 13-84 years). Mean 6MWD and 6MWw were significantly greater in males than in females (622 ± 80 m, 46,322 ± 10,539 kg.m vs 551 ± 71 m, 36,356 ± 8,289 kg.m, P < 0.05). Four equations significantly overestimated measured 6MWD (range, 32 ± 71 to 137 ± 74 m; P < 0.001), and one significantly underestimated it (-36 ± 86 m; P < 0.001). 6MWD significantly correlated with age (r = -0.39), height (r = 0.44), body mass index (r = -0.24), and reported physical activity (r = 0.25). 6MWw significantly correlated with age (r = -0.21), height (r = 0.66) and reported physical activity (r = 0.25). The reference equation devised for walk distance was 6MWDm = 622.461 - (1.846 x Ageyears) + (61.503 x Gendermales = 1; females = 0); r2 = 0.300. In an additional group of 85 subjects prospectively studied, the difference between measured and the 6MWD predicted with the equation proposed here was not significant (-3 ± 68 m; P = 0.938). The measured 6MWD represented 99.6 ± 11.9 percent of the predicted value. We conclude that 6MWD and 6MWw variances were adequately explained by demographic and anthropometric attributes. This reference equation is probably most appropriate for evaluating the exercise capacity of Brazilian patients with chronic diseases.

The six-minute walk test and body weight-walk distance product in healthy Brazilian subjects.

We assessed the 6-min walk distance (6MWD) and body weight x distance product (6MWw) in healthy Brazilian subjects and compared measured 6MWD with values predicted in five reference equations developed for other populations. Anthropometry, spirometry, reported physical activity, and two walk tests in a 30-m corridor were evaluated in 134 subjects (73 females, 13-84 years). Mean 6MWD and 6MWw were significantly greater in males than in females (622 +/- 80 m, 46,322 +/- 10,539 kg.m vs 551 +/- 71 m, 36,356 +/- 8,289 kg.m, P < 0.05). Four equations significantly overestimated measured 6MWD (range, 32 +/- 71 to 137 +/- 74 m; P < 0.001), and one significantly underestimated it (-36 +/- 86 m; P < 0.001). 6MWD significantly correlated with age (r = -0.39), height (r = 0.44), body mass index (r = -0.24), and reported physical activity (r = 0.25). 6MWw significantly correlated with age (r = -0.21), height (r = 0.66) and reported physical activity (r = 0.25). The reference equation devised for walk distance was 6MWDm = 622.461 - (1.846 x Ageyears) + (61.503 x Gendermales = 1; females = 0); r2 = 0.300. In an additional group of 85 subjects prospectively studied, the difference between measured and the 6MWD predicted with the equation proposed here was not significant (-3 +/- 68 m; P = 0.938). The measured 6MWD represented 99.6 +/- 11.9% of the predicted value. We conclude that 6MWD and 6MWw variances were adequately explained by demographic and anthropometric attributes. This reference equation is probably most appropriate for evaluating the exercise capacity of Brazilian patients with chronic diseases.

Assessment of menstrual blood loss in Brazilian users of the frameless copper-releasing IUD with copper surface area of 330 mm2 and the frameless levonorgestrel-releasing intrauterine system.

OBJECTIVE: This study was conducted to evaluate the effect of two types of IUDs on the amount of menstrual blood loss (MBL): the frameless copper-releasing intrauterine device (IUD) with copper surface area of 330 mm2 (GyneFix; Contrel Research, Ghent, Belgium) and the frameless levonorgestrel (LNG)-releasing intrauterine system (IUS) releasing 14 microg per day (FibroPlant-LNG; Contrel Research). Heavy and abnormal MBL is the main reason for discontinuation of intrauterine devices. METHODS: In 20 Brazilian women using GyneFix 330 and 32 using FibroPlant-LNG, respectively, MBL was measured by the quantitative alkaline hematin technique. In addition, ferritin levels were measured in GyneFix 330 and FibroPlant-LNG users. RESULTS: MBL with GyneFix 330, measured over a 24-month period, increased but was less when compared with TCu380A. Ferritin levels with GyneFix 330 were not affected in contrast with TCu380A. In FibroPlant-LNG users, mean MBL decreased by about 90% and ferritin levels increased significantly. CONCLUSIONS: The authors confirm earlier reports that, especially for women with low body iron stores and heavy menstrual bleeding, there is an order of preference for IUD use to minimize MBL. The choice should first be a progestin-releasing IUS, then a copper IUD, which has the least effect on menstrual bleeding, such as the frameless GyneFix IUD.

Effect of orally administered misoprostol and cimetidine on the steady state pharmacokinetics of diazepam and nordiazepam in human volunteers.

The effects of misoprostol and cimetidine on diazepam pharmacokinetics were evaluated in order to determine whether the kinetic variables for diazepam and nordiazepam alone differ with the repeated oral administration of misoprostol and cimetidine to healthy adult volunteers. The trial was conducted as an open crossover study in 12 normal subjects, divided into two groups with all subjects receiving both regimens. Total study duration was 5 weeks. An initial clinical assessment, including blood biochemistry and assessment of subject oxidation status was carried out on study day 1. On this day, subjects began taking diazepam (10 mg) orally for one week, with pharmacokinetic studies performed at day 8, when steady state levels of diazepam were reached. This was followed by one week with active drug, misoprostol to Group I and cimetidine to Group II, with pharmacokinetic studies performed at the end of a 1-week treatment. After a 2-week wash-out period, both groups took for one week, the alternate drug, i.e. cimetidine plus diazepam to Group I and misoprostol plus diazepam to Group II. On days 8, 15 and 36, subjects were admitted to the hospital for 12 h, during which time a clinical examination was carried out and blood samples were taken at time zero and at 4, 8, 12, 24, and 36 h post-dosing for the measurement of serum diazepam and nordiazepam. The main parameters measured and evaluated were diazepam and nordiazepam pharmacokinetics at steady state (days 8, 15 and 36). These were areas under the curve in the dose intervals (AUC0-24h), maximum plasma concentrations (Cmax), time to peak concentrations (Tmax), elimination half-life (t1/2), elimination constant (Kel), distribution volume (Vd), total body clearance (ClB) and clearance after oral administration (Cloral). The results demonstrated that plasma diazepam and nordiazepam concentrations had a significant increase after steady states have been reached with the simultaneous administration of 800 mg of cimetidine daily for one week. The simultaneous administration of 800 micrograms of misoprostol did not cause any significant change in diazepam and nordiazepam plasma levels after steady states had been reached. Comparing the pharmacokinetic parameters of Groups A and B as well as within groups on days 8, 15 and 36, a significant increase in plasma diazepam and nordiazepam levels was detected. This was due to a cimetidine-induced impairment in microsomal oxidation of diazepam and nordiazepam, which caused a decrease in total metabolic clearance and increased mean steady state plasma concentrations. A more prolonged half-life was observed for both groups taking cimetidine as well as an increase of mean maximum plasma concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)