Florian F. Hildenbrand

Reference values for the 6-minute walk test in healthy children and adolescents in Switzerland

BackgroundThe six-minute walk test (6MWT) is a simple, low tech, safe and well established, self-paced assessment tool to quantify functional exercise capacity in adults. The definition of normal 6MWT in children is especially demanding since not only parameters like height, weight and ethnical background influence the measurement, but may be as crucial as age and the developmental stage. The aim of this study is establishing reference values for the 6MWT in healthy children and adolescents in Switzerland and to investigate the influence of age, anthropometrics, heart rate, blood pressure and physical activity on the distance walked.MethodsChildren and adolescents between 5–17 years performed a 6MWT. Short questionnaire assessments about their health state and physical activities. anthropometrics and vitals were measured before and after a 6-minute walk test and were previously defined as secondary outcomes.ResultsAge, height, weight and the heart rate after the 6MWT all predicted the distance walked according to different regression models: age was the best single predictor and mostly influenced walk distance in younger age, anthropometrics were more important in adolescents and females. Heart rate after the 6MWT was an important distance predictor in addition to age and outreached anthropometrics in the majority of subgroups assessed.ConclusionsThe 6MWT in children and adolescents is feasible and practical. The 6MWT distance depends mainly on age; however, heart rate after the 6MWT, height and weight significantly add information and should be taken into account mainly in adolescents. Reference equations allow predicting 6-minute walk test distance and may help to better assess and compare outcomes in young patients with cardiovascular and respiratory diseases and are highly warranted for different populations.

Daytime measurements underestimate nocturnal oxygen desaturations in pulmonary arterial and chronic thromboembolic pulmonary hypertension.

Background: Nocturnal hypoxemia is important in precapillary pulmonary hypertension (pPH) as it worsens pulmonary hemodynamics. Whether daytime oxygen saturation (Sp<smlcap>o</smlcap>₂) predicts nocturnal hypoxemia in pPH patients has not been conclusively studied. Objectives: To investigate the prevalence of nocturnal hypoxemia in comparison to daytime Sp<smlcap>o</smlcap>₂ and disease severity in ambulatory patients with pulmonary hypertension. Methods: Consecutive patients diagnosed with pPH classified as either pulmonary arterial (PAH) or chronic thromboembolic pPH (CTEPH) had daytime resting and exercise Sp<smlcap>o</smlcap>₂ (at the end of a 6-min walk test); thereafter, they underwent overnight pulse oximetry at home. Functional class, pro-brain natriuretic peptide (pro-BNP) and the tricuspid pressure gradient were assessed. Results: Sixty-three patients [median (quartiles) age 62 (53; 71), 43 females] with PAH (n = 44) and CTEPH (n = 19) were included. The resting Sp<smlcap>o</smlcap>₂, exercise Sp<smlcap>o</smlcap>₂, and mean nocturnal Sp<smlcap>o</smlcap>₂ were 95% (92; 96), 88% (81; 95), and 89% (85; 92), respectively. Forty-nine patients (77%) spent >10% of the night with Sp<smlcap>o</smlcap>₂ <90% (desaturators), and 33 (52%) spent >50% of the night with Sp<smlcap>o</smlcap>₂ <90% (sustained desaturators). The positive predictive values of daytime Sp<smlcap>o</smlcap>₂ >90% for being a nocturnal nondesaturator or sustained nondesaturator were 25 and 53%, respectively. Nocturnal Sp<smlcap>o</smlcap>₂ was negatively correlated with the tricuspid pressure gradient, but not with functional class, 6-min walk test, or pro-BNP. Conclusions: Nocturnal hypoxemia is very common in PAH and CTEPH despite often normal daytime Sp<smlcap>o</smlcap>₂ and reflects disease severity. Nocturnal pulse oximetry should be considered in the routine evaluation of pPH patients and research should be directed toward the treatment of nocturnal desaturation in pPH.

Effect of nocturnal oxygen and acetazolamide on exercise performance in patients with pre-capillary pulmonary hypertension and sleep-disturbed breathing: randomized, double-blind, cross-over trial

AIM Sleep-disturbed breathing (SDB) is common in pre-capillary pulmonary hypertension (PH) and impairs daytime performance. In lack of proven effective treatments, we tested whether nocturnal oxygen therapy (NOT) or acetazolamide improve exercise performance and quality of life in patients with pre-capillary PH and SDB. METHODS This was a randomized, placebo-controlled, double-blind, three period cross-over trial. Participants received NOT (3 L/min), acetazolamide tablets (2 × 250 mg), and sham-NOT/placebo tablets each during 1 week with 1-week washout between treatment periods. Twenty-three patients, 16 with pulmonary arterial PH, 7 with chronic thromboembolic PH, and with SDB defined as mean nocturnal oxygen saturation <90% or oxygen saturation dips >10 h(-1) with daytime PaO2 ≥7.3 kPa participated. Assessments at the end of the treatment periods included a 6 min walk distance (MWD), SF-36 quality of life, polysomnography, and echocardiography. RESULTS Medians (quartiles) of the 6 MWD after NOT, acetazolamide, and placebo were 480 m (390;528), 440 m (368;468), and 454 m (367;510), respectively, mean differences: NOT vs. placebo +25 m (95% CI 3-46, P= 0.027), acetazolamide vs. placebo -9 m (-34-17, P = 0.223), and NOT vs. acetazolamide +33 (12-45, P < 0.001). SF-36 quality of life was similar with all treatments. Nocturnal oxygen saturation significantly improved with both NOT and acetazolamide. Right ventricular fractional area change was greater on NOT compared with placebo (P = 0.042) and acetazolamide (P = 0.027). CONCLUSIONS In patients with pre-capillary PH and SDB on optimized pharmacological therapy, NOT improved the 6 MWD compared with placebo already after 1 week along with improvements in SDB and haemodynamics. CLINICALTRIALSGOV NTC01427192.

A low resting heart rate at diagnosis predicts favourable long-term outcome in pulmonary arterial and chronic thromboembolic pulmonary hypertension. A prospective observational study

BackgroundA low resting heart rate (HR) is prognostically favourable in healthy individuals and in patients with left heart disease. In this study we investigated the impact of HR at diagnosis on long-term outcome in patients with differently classified precapillary pulmonary hypertension (pPH).MethodspPH patients diagnosed as pulmonary arterial (PAH) or inoperable chronic thromboembolic pulmonary hypertension (CTEPH) were registered and regularly followed at our centre Baseline characteristics and events defined as either death or lung transplantation were noted. The prognostic value of HR was analysed using Kaplan Meier estimates, live tables and Cox regression.Results206 patients with PAH (148) and inoperable CTEPH (58) were included. The median HR was 82 bpm. pPH with a HR below 82 bpm had a significantly longer overall event-free survival (2409 vs.1332 days, p = .000). This advantage was similarly found if PAH and CTEPH were analysed separately. Although a lower HR was associated with a better hemodynamic and functional class, HR was a strong and independent prognostic marker for transplant free survival even if corrected for age, sex, hemodynamics and functional status.ConclusionWe show that resting HR at diagnosis is a strong and independent long-term prognostic marker in PAH and CTEPH. Whether reducing HR by pharmacological agents would improve outcome in pPH has to be assessed by future trials with high attention to safety.

Tobacco Smoke Exposure in Pulmonary Arterial and Thromboembolic Pulmonary Hypertension

Background: Animal studies and data from a single-center study suggest that tobacco smoke exposure may be a risk factor for precapillary pulmonary hypertension (PH). Objective: We aimed to survey tobacco smoke exposure in a large PH collective and to compare it with epidemiological data from healthy subjects. Methods: This is an international, multicenter, case-control study including patients with pulmonary arterial and chronic thromboembolic PH. All patients were asked specific questions about tobacco smoke exposure. Healthy controls were retrieved from the Swiss Health Survey (n = 18,747). Results: Overall (n = 472), 49% of PH patients were smokers and there was a clear sex difference (women 37%, men 71%). Significantly more PH men were smokers compared with healthy controls, whereas less PH women were ever active smokers. However, 50% of the non-smoking PH women were exposed to secondhand smoke, leading to a significantly higher number of tobacco smoke-exposed individuals compared to healthy controls. PH smokers were significantly younger compared to those not exposed. Conclusion: Active and environmental tobacco smoke exposure is common in PH. The higher prevalence of male PH smokers, the higher exposure to environmental tobacco smoke in PH women compared to healthy controls and the lower age at PH diagnosis in smokers may indicate a pathogenic role of tobacco smoke exposure in PH.

Effect of oxygen and acetazolamide on nocturnal cardiac conduction, repolarization, and arrhythmias in precapillary pulmonary hypertension and sleep-disturbed breathing.

BACKGROUND Sleep-disturbed breathing (SDB) is common in patients with precapillary pulmonary hypertension (PH). Nocturnal oxygen therapy (NOT) and acetazolamide improve SDB in patients with PH, and NOT improves exercise capacity. We investigated the effect of NOT and acetazolamide on nocturnal cardiac conduction, repolarization, and arrhythmias in patients with PH and SDB. METHODS In a randomized, placebo-controlled, double-blind, crossover trial, 23 patients with arterial (n = 16) or chronic thromboembolic PH (n = 7) and SDB defined as a mean nocturnal oxygen saturation < 90% or dips (> 3%) > 10/h with daytime Pao2 ≥ 7.3 kPa were studied. Participants received NOT (3 L/min), acetazolamide tablets (2 × 250 mg), and sham-NOT/placebo each during 1 week separated by a 1-week washout period. Three-lead ECG was recorded during overnight polysomnography at the end of each treatment period. Repolarization indices were averaged over three cardiac cycles at late evening and at early morning, and nocturnal arrhythmias were counted. RESULTS NOT was associated with a lower overnight (68 ± 10 beats/min vs 72 ± 9 beats/min, P = .010) and early morning heart rate compared with placebo. At late evening, the heart rate-adjusted PQ time was increased under acetazolamide compared with placebo (mean difference, 10 milliseconds; 95% CI, 0-20 milliseconds; P = .042). In the morning under NOT, the heart rate-adjusted QT (QTc) interval was decreased compared with placebo (mean difference, -25 milliseconds; 95% CI, -45 to -6 milliseconds; P = .007), and the interval between the peak and the end of the T wave on the ECG was shorter compared with acetazolamide (mean difference, -11 milliseconds; 95% CI, -21 to -1 milliseconds; P = .028). Arrhythmias were rare and similar with all treatments. CONCLUSIONS In patients with PH with SDB, NOT reduces nocturnal heart rate and QTc in the morning, thus, favorably modifying prognostic markers. TRIAL REGISTRY ClinicalTrials.gov; No.: NTC-01427192; URL: www.clinicaltrials.gov.

CME: Bakterielle Meningitis bei Erwachsenen

Zusammenfassung. Die akute bakterielle Meningitis ist ein seltenes Krankheitsbild in der hausarztlichen Praxis mit jedoch hoher Mortalitat. Deshalb ist die rasche Diagnose, unmittelbare Hospitalisierung und Einleitung einer empirischen Antibiotikatherapie eine grosse Herausforderung. Die klassische klinische Trias bestehend aus Fieber, Meningismus und Bewusstseinsveranderung ist unspezifisch, und oft sind erste Symptome bei einer Grippe oder einem gastrointestinalen Infekt sehr ahnlich. Bereits bei geringem Verdacht sollte eine Liquorpunktion erfolgen, wobei diese die erste Gabe von Ceftriaxon i.v. nicht verzogern darf. In der empirischen Therapie mussen Meningokokken, Pneumokokken und je nach Risikoprofil auch Listerien sowie mogliche resistente Keime abgedeckt werden.

Disease-Targeted Treatment Improves Cognitive Function in Patients with Precapillary Pulmonary Hypertension

Background: Patients with pulmonary hypertension (PH) may suffer from cognitive deficits that potentially relate to reduced oxygen delivery and cerebral tissue oxygenation (CTO). Objective: To evaluate the hypothesis that cognitive function improves with therapy, along with improved CTO. Methods: Twenty incident patients with arterial or chronic thromboembolic PH had CTO monitoring by near-infrared spectroscopy during diagnostic right heart catheterization. Cognitive tests [Trail Making Tests (TMTs), Victoria Stroop tests and the Five-Point Test (5PT)], the 6-min walk distance (6MWD) test, New York Heart Association (NYHA) class and health-related quality of life (HRQoL) were assessed and repeated after 3 months of disease-targeted medication. Results: At baseline, 45% of PH patients had cognitive deficits. At 3 months, the patients had improved on the TMT A and the Stroop 2 test [37 s (27; 55) versus 30 s (24; 42), p < 0.05, and 18 s (16; 22) versus 16 s (15; 20), p < 0.01], whereas CTO remained unchanged. Arterial oxygen saturation, NYHA class, 6MWD and HRQoL had also improved. Baseline CTO was the strongest predictor of cognitive function, even in multivariate analysis including age, 6MWD and HRQoL. Improvements in cognitive function were not associated with changes in CTO. Conclusions: In patients with PH, 3 months of disease-targeted medication resulted in better cognitive function. Although CTO was the strongest predictor of cognitive function at baseline, it did not change during target therapy. The results of this pilot study should be confirmed in an adequately powered controlled trial.

Contents Vol. 84, 2012

J. Hammer, Basel F.J.F. Herth, Heidelberg J. Johnston, Vancouver, B.C. C. Kroegel, Jena F. Kummer, Vienna P.N. Mathur, Indianapolis, Ind. M. Miravitlles, Barcelona J. Müller-Quernheim, Freiburg L.P. Nicod, Lausanne M. Noppen, Brussels D. Olivieri, Parma C. Page, London W. Randerath, Solingen S. Siddiqui, Leicester T. Terashima, Ichikawa O.S. Usmani, London S. van Eeden, Vancouver, B.C. K. Yasufuku, Toronto, Ont. Official Journal of