Software development to standardize the clinical diagnosis of exercise oscillatory ventilation in heart failure.

BACKGROUND: Exercise oscillatory ventilation (EOV) is characterized by periodic oscillations of minute ventilation during cardiopulmonary exercise testing (CPET). Despite its prognostic value in chronic heart failure (HF), its diagnosis is complex due to technical limitations. An easier and more accurate way of EOV identification can contribute to a better approach and clinical diagnosis. This study aims to describe a software development to standardize the EOV diagnosis from CPET's raw data in heart failure patients and test its reliability (intra- and inter-rater). METHODS: The software was developed in the "drag-and-drop" G-language using LabVIEW®. Five EOV definitions (Ben-Dov, Corrà, Kremser, Leite, and Sun definitions), two alternative approaches, one smoothing technique, and some basic statistics were incorporated into the interface to visualize four charts of the ventilatory response. EOV identification was based on a set of criteria verified from the interaction between amplitude, cycle length, and oscillation time. Two raters analyzed the datasets. In addition, repeated measurements were verified after six months using about 25% of the initial data. Cohen's kappa coefficient (κ) was used to investigate the reliability. RESULTS: Overall, 391 tests were analyzed in duplicate (inter-rater reliability) and 100 tests were randomized for new analysis (intra-rater reliability). High inter-rater (κ > 0.80) and intra-rater (κ > 0.80) reliability of the five EOV diagnoses were observed. CONCLUSION: The present study proposes novel semi-automated software to detect EOV in HF, with high inter and intra-rater agreements. The software project and its tutorial are freely available for download.

Effects of ß-blocker therapy on exercise oscillatory ventilation in reduced ejection fraction heart failure patients: A case series study.

BACKGROUND: Exercise oscillatory ventilation (EOV) is an abnormal breathing pattern that occurs in ~20% of patients with heart failure (HF) and is associated with poor prognosis and exercise intolerance. ß-blockers (ßb) are prescribed for most HF patients; however, their effect on EOV remains unclear. We evaluated the effect of ßb on EOV in HF patients with reduced ejection fraction (HFrEF). METHODS: Fifteen patients diagnosed with HF, ejection fraction < 45%, aged from 18 to 65 years, were included before starting ßb therapy. Patients underwent clinical evaluation, cardiopulmonary exercise testing, echocardiography, laboratory exams (norepinephrine levels, B type natriuretic peptide) at baseline and after ßb therapy optimized for six months. Presence of exercise oscillatory breathing was determined by two experienced observers who were blinded to the moment of the test (pre or post). RESULTS: Fifteen patients (1 female), aged 49.5 ± 2.5 years, with HFrEF, NYHA I-III enrolled in the study. The etiologies of the HFrEF were idiopathic (n = 8) and hypertensive (n = 7). LVEF increased after ßb therapy from 25.9 ± 2.5% to 33 ± 2.6%, P = 0.02; peak VO2 did not significantly change (21.8 ± 1.7 vs 24.7 ± 1.9, P = 0.4); VE/VCO2 slope changed from 32.1 ± 10.6-27.5 ± 9.1, P = 0.03. Before ßb initiation, nine patients (60%) had EOV, but only two (13%) did after optimized therapy. McNemar test was used to evaluate the significance of the association between the two moments (P = 0.02). CONCLUSION: In patients with HF, medical therapy with ßb can reverse EOV. This may explain why these patients experience symptom improvement after ßb therapy.

Sensitivity and specificity of different exercise oscillatory ventilation definitions to predict 2-year major adverse cardiovascular outcomes in chronic heart failure patients.

BACKGROUND: Exercise oscillatory ventilation (EOV) shows a four-fold greater risk of adverse events. This study aims to analyze the sensitivity and specificity of three EOV diagnostic definitions to predict adverse outcomes at a 2-year follow-up and to compare its EOV prevalence and relations with the patient's profile. METHODS: Cardiopulmonary exercise tests from 233 heart failure patients were analyzed. Two blinded reviewers used a semiautomated software to identify EOV cases pattern according to the definitions of Ben-Dov, Corrà, and Leite. Data were grouped in EOV-positive or EOV-negative according to each definition. Baseline characteristics, EOV prevalence, relative risk, sensitivity, and specificity to predict 2-years of major adverse cardiovascular outcomes were analyzed. RESULTS: The Corrà definition led to the best prediction of 2-year major cardiovascular adverse outcomes (HR 2.46 [1.16 to 5.25]; p = 0.019, AUC = 0.618; p = 0.007). EOV prevalence was 17.2%, 17.2%, and 9.4% applying Ben-Dov, Corrà, and Leite definition, respectively. The main clinical differences between EOV-positive and EOV-negative patients were: MECKI score and VE/VCO2 slope (all definitions), and BNP levels (Ben-Dov and Leite). BNP levels were correlated with amplitude (rho = 0.255; p = 0.033) and cycle length (rho = 0.388; p = 0.002). CONCLUSION: Corrà definition was the only one that exhibited the capacity to predict major adverse cardiovascular outcomes at a 2-year follow-up. Regardless of its definition, EOV was more often prevalent in patients with a greater MECKI score and VE/VCO2 slope values.

Apnea central del sueño y respiración periódica / Central Sleep Apnea and Periodic Breathing

La apnea central del sueño es causada por una falla temporal del centro ponto-medular que es el responsable de generar una respiración rítmica. Puede ser un hallazgo fisiológico durante la transición vigilia-sueño o estar presente por múltiples causas. La enfermedad cardiovascular o cerebro-vascular, el síndrome de apneas e hipopneas obstructivas durante el sueño, el uso de opioides y el tratamiento con CPAP son las más frecuentes en la práctica clínica, mientras que en sujetos sanos las apneas centrales se relacionan con la altura durante la exposición recreacional. Este trabajo revisa la fisiopatología de las apneas centrales, su clasificación, las normas para su identificación en los estudios de sueño y un enfoque práctico sobre las opciones terapéuticas disponibles.

Central sleep apnea is caused by a temporary failure of the ponto-medullary center that is responsible for generating rhythmic breathing. It can be a physiological finding during the sleep-wake transition or be present for multiple causes. Cardiovascular or cerebrovascular disease, obstructive sleep apnea/hypopnea syndrome, use of opioids and treatment with CPAP (Continuous Positive Airway Pressure) are the most frequent in clinical practice, while in healthy subjects central apneas are related to high altitude during recreational exposure. This study reviews the physiopathology of central apneas, their classification, the current rules for their identification in sleep studies and a practical approach to the therapeutic options available.

Oxygen saturation increases over the course of the night in mountaineers at high altitude (3050-6354 m).

BACKGROUND: Blood oxygen saturation (SpO 2 ) is frequently measured to determine acclimatization status in high-altitude travellers. However, little is known about nocturnal time course of SpO 2 (SpO 2N ), but alterations in SpO 2N might be practically relevant as well. To this end, we describe the time-course of SpO 2N in mountaineers at high altitude. METHODS: SpO 2N was continuously measured in ten male mountaineers during a three-week expedition in Peru (3,050-6,354m). Average SpO 2N of the first (SpO 2N1 ) and second half (SpO 2N2 ) of an individual's sleep duration was calculated from 2h intervals of uninterrupted sleep. Heart rate oscillations and sleep dairies were used to exclude periods of wakefulness. SpO 2 was also measured at rest in the morning. RESULTS: SpO 2N significantly increased from SpO 2N1 to SpO 2N2 . The magnitude of this increase (ΔSpO 2 ) was reduced with time spent at altitude. On night 1 (3,050m) SpO 2 increased from 83.4% (N1) to 86.3% (N2). At the same location on night 21, SpO 2 increased from 88.3% to 90.1%, which is a relative change of 4.7% and 2.0%, respectively. This pattern of increase in SpO 2N was perturbed when individual acclimatization was poor or altitude was extreme (5630m). SpO 2N was significantly lower than SpO 2 at rest in the morning. CONCLUSIONS: This study is the first to demonstrate an increase of SpO 2 during the night in mountaineers at high altitude (3,050-6,354m) with high consistency between and within subjects. The magnitude of ΔSpO 2N decreased as acclimatization improved, suggesting that these changes in ΔSpO 2 between nights might be a valuable indicator of individual acclimatization. In addition, the failure of any increase in SpO 2N during the night might indicate insufficient acclimatization. Even though underlying mechanisms for the nocturnal increase remain unclear, the timing of SpO 2N measurement is obviously of utmost importance for its interpretation. Finally our study illustrates the detailed effects of ventilatory acclimatization over several weeks.

Observational Study of Neural Respiratory Drive During Sleep at High Altitude.

Steier, Joerg, Nic Cade, Ben Walker, John Moxham, and Caroline Jolley. Observational study of neural respiratory drive during sleep at high altitude. High Alt Med Biol. 18:242-248, 2017. AIMS: Ventilation at altitude changes due to altered levels of pO2, pCO2 and the effect on blood pH. Nocturnal ventilation is particularly exposed to these changes. We hypothesized that an increasing neural respiratory drive (NRD) is associated with the severity of sleep-disordered breathing at altitude. METHODS: Mountaineers were studied at sea level (London, United Kingdom), and at altitude at the Aconcagua (Andes, Argentina). NRD was measured as electromyogram of the diaphragm (EMGdi) overnight by a transesophageal multi-electrode catheter; results were reported for sea level, 3,380 m, 4,370 m, and 5,570 m. RESULTS: Four healthy subjects (3 men, age 31(3)years, body mass index 23.6(0.9)kg/m2, neck circumference 37.0(2.7)cm, forced expiratory volume in 1 second 111.8(5.1)%predicted, and forced vital capacity 115.5(6.3)%predicted) were studied. No subject had significant sleep abnormalities at sea level. Time to ascent to 3,380 m was 1 day, to 4,370 m was 5 days, and the total nights at altitude were 21 days. The oxygen desaturation index (4% oxygen desaturation index [ODI] 0.8(0.4), 22.0 (7.2), 61.4 (26.9), 144.9/hour, respectively) and the EMGdi (5.2 (1.9), 12.8 (5.1), 14.1 (3.4), 18.5%, respectively) increased with the development of periodic breathing at altitude, whereas the average SpO2 declined (97.5 (1.3), 84.8 (0.5), 81.0 (4.1), 68.5%, respectively). The average EMGdi correlated well with the 4%ODI (r = 0.968, p = 0.032). CONCLUSION: NRD sleep increases at altitude in relation to the severity of periodic breathing.

Periodic breathing and oxygen supplementation in Chilean miners at high altitude (4200m).

Our objective was to determine the nocturnal ventilatory pattern and characterize the effect of oxygen enrichment on nocturnal ventilatory pattern and sleep quality in miners exposed to intermittent hypobaric hypoxia at 4200m. A total of 16 acclimatized miners were studied. Nocturnal ventilatory pattern (plethysmographic inductance), arterial oxygen saturation and heart rate (pulse oximetry) were performed in 9/16 subjects. Sleep quality at high altitude was assessed by self-questionnaires in 16/16 subjects. All measurements were performed during at least 7h of sleep. Subjects were studied while sleeping at high altitude without (control, C) and with oxygen supplementation (FiO2=0.25, treated, T). Periodic breathing (%) C: 25±18 vs T: 6.6±5.6 (p<0.05), apneas index (no./h) C: 34.9±24.1 vs T: 8.5±6.8 (p<0.05); and sleep quality C: 17.8±3.4 vs T: 12.1±2.2 (p<0.0001) were evaluated. In conclusion, periodic breathing with apneas was present in miners exposed to high altitude for 1 to 4 years and was reduced by treatment with supplementary oxygen.