Variability analysis of discrete event series and wavefront patterns in surface electrocardiogram: contributions to psychophysiological and clinical research

The surface electrocardiogram (ECG) is an established diagnostic tool for the detection of abnormalities in the electrical activity of the heart. The interest of the ECG, however, extends beyond the diagnostic purpose. In recent years, studies in cognitive psychophysiology have related heart rate variability (HRV) to memory performance and mental workload. The aim of this thesis was to analyze the variability of surface ECG derived rhythms, at two different time scales: the discrete-event time scale, typical of beat-related features (Objective I), and the “continuous” time scale of separated sources in the ECG (Objective II), in selected scenarios relevant to psychophysiological and clinical research, respectively. Objective I) Joint time-frequency and non-linear analysis of HRV was carried out, with the goal of assessing psychophysiological workload (PPW) in response to working memory engaging tasks. Results from fourteen healthy young subjects suggest the potential use of the proposed indices in discriminating PPW levels in response to varying memory-search task difficulty. Objective II) A novel source-cancellation method based on morphology clustering was proposed for the estimation of the atrial wavefront in atrial fibrillation (AF) from body surface potential maps. Strong direct correlation between spectral concentration (SC) of atrial wavefront and temporal variability of the spectral distribution was shown in persistent AF patients, suggesting that with higher SC, shorter observation time is required to collect spectral distribution, from which the fibrillatory rate is estimated. This could be time and cost effective in clinical decision-making. The results held for reduced leads sets, suggesting that a simplified setup could also be considered, further reducing the costs. In designing the methods of this thesis, an online signal processing approach was kept, with the goal of contributing to real-world applicability. An algorithm for automatic assessment of ambulatory ECG quality, and an automatic ECG delineation algorithm were designed and validated.

Higher-order perturbative relativistic corrections to energies and properties

Relativistic effects need to be considered in quantum-chemical calculations on systems including heavy elements or when aiming at high accuracy for molecules containing only lighter elements. In the latter case, consideration of relativistic effects via perturbation theory is an attractive option. Among the available techniques, Direct Perturbation Theory (DPT) in its lowest order (DPT2) has become a standard tool for the calculation of relativistic corrections to energies and properties.In this work, the DPT treatment is extended to the next order (DPT4). It is demonstrated that the DPT4 correction can be obtained as a second derivative of the energy with respect to the relativistic perturbation parameter. Accordingly, differentiation of a suitable Lagrangian, thereby taking into account all constraints on the wave function, provides analytic expressions for the fourth-order energy corrections. The latter have been implemented at the Hartree-Fock level and within second-order Møller-Plesset perturbaton theory using standard analytic second-derivative techniques into the CFOUR program package. For closed-shell systems, the DPT4 corrections consist of higher-order scalar-relativistic effects as well as spin-orbit corrections with the latter appearing here for the first time in the DPT series.Relativistic corrections are reported for energies as well as for first-order electrical properties and compared to results from rigorous four-component benchmark calculations in order to judge the accuracy and convergence of the DPT expansion for both the scalar-relativistic as well as the spin-orbit contributions. Additionally, the importance of relativistic effects to the bromine and iodine quadrupole-coupling tensors is investigated in a joint experimental and theoretical study concerning the rotational spectra of CH2BrF, CHBrF2, and CH2FI.

Higher-order molecular properties and excitation energies in single-reference and multireference coupled-cluster theory

Coupled-cluster (CC) theory is one of the most successful approaches in high-accuracy quantum chemistry. The present thesis makes a number of contributions to the determination of molecular properties and excitation energies within the CC framework. The multireference CC (MRCC) method proposed by Mukherjee and coworkers (Mk-MRCC) has been benchmarked within the singles and doubles approximation (Mk-MRCCSD) for molecular equilibrium structures. It is demonstrated that Mk-MRCCSD yields reliable results for multireference cases where single-reference CC methods fail. At the same time, the present work also illustrates that Mk-MRCC still suffers from a number of theoretical problems and sometimes gives rise to results of unsatisfactory accuracy. To determine polarizability tensors and excitation spectra in the MRCC framework, the Mk-MRCC linear-response function has been derived together with the corresponding linear-response equations. Pilot applications show that Mk-MRCC linear-response theory suffers from a severe problem when applied to the calculation of dynamic properties and excitation energies: The Mk-MRCC sufficiency conditions give rise to a redundancy in the Mk-MRCC Jacobian matrix, which entails an artificial splitting of certain excited states. This finding has established a new paradigm in MRCC theory, namely that a convincing method should not only yield accurate energies, but ought to allow for the reliable calculation of dynamic properties as well. In the context of single-reference CC theory, an analytic expression for the dipole Hessian matrix, a third-order quantity relevant to infrared spectroscopy, has been derived and implemented within the CC singles and doubles approximation. The advantages of analytic derivatives over numerical differentiation schemes are demonstrated in some pilot applications.

A triplet spike-timing–dependent plasticity model generalizes the Bienenstock–Cooper–Munro rule to higher-order spatiotemporal correlations

Synaptic strength depresses for low and potentiates for high activation of the postsynaptic neuron. This feature is a key property of the Bienenstock–Cooper–Munro (BCM) synaptic learning rule, which has been shown to maximize the selectivity of the postsynaptic neuron, and thereby offers a possible explanation for experience-dependent cortical plasticity such as orientation selectivity. However, the BCM framework is rate-based and a significant amount of recent work has shown that synaptic plasticity also depends on the precise timing of presynaptic and postsynaptic spikes. Here we consider a triplet model of spike-timing–dependent plasticity (STDP) that depends on the interactions of three precisely timed spikes. Triplet STDP has been shown to describe plasticity experiments that the classical STDP rule, based on pairs of spikes, has failed to capture. In the case of rate-based patterns, we show a tight correspondence between the triplet STDP rule and the BCM rule. We analytically demonstrate the selectivity property of the triplet STDP rule for orthogonal inputs and perform numerical simulations for nonorthogonal inputs. Moreover, in contrast to BCM, we show that triplet STDP can also induce selectivity for input patterns consisting of higher-order spatiotemporal correlations, which exist in natural stimuli and have been measured in the brain. We show that this sensitivity to higher-order correlations can be used to develop direction and speed selectivity.

Mild hypothermia during global cardiac ischemia opens a window of opportunity to develop heart donation after cardiac death

Although heart donation after cardiac death (DCD) could greatly improve graft availability, concerns regarding warm ischemic damage typically preclude transplantation. Improving tolerance to warm ischemia may thus open a window of opportunity for DCD hearts. We investigated the hypothesis that, compared with normothermia, mild hypothermia (32° C) initiated after ischemic onset improves cardiac functional recovery upon reperfusion. Isolated, working hearts from adult, male Wistar rats underwent global, no-flow ischemia, and reperfusion (n = 28). After ischemic onset, temperature was maintained at either 37° C for 20 or 30 min or reduced to 32° C for 40, 50, or 60 min. Recovery was measured after 60-min reperfusion. Following normothermic ischemia, recovery of rate-pressure product (RPP; per cent of preischemic value) was almost complete after 20-min ischemia (97 ± 9%), whereas no recovery was detectable after 30-min ischemia. After mildly hypothermic ischemia (32° C), RPP also recovered well after 40 min (86 ± 4%). Markers of metabolism and necrosis were similar in 37° C/20 min and 32° C/40 min groups. Simple reduction in cardiac temperature by a few degrees after the onset of global ischemia dramatically prolongs the interval during which the heart remains resistant to functional deterioration. Preservation of hemodynamic function is associated with improved metabolic recovery and reduced necrosis. The application of mild hypothermia may be a simple first step towards development of clinical protocols for DCD heart recovery.

QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up

We evaluated the association of QT interval corrected for heart rate (QT(c)) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes.

The significance of the sympathetic nervous system in the pathophysiology of periodic leg movements in sleep

STUDY OBJECTIVES: Periodic leg movements in sleep (PLMS) are frequently accompanied by arousals and autonomic activation, but the pathophysiologic significance of these manifestations is unclear. DESIGN: Changes in heart rate variability (HRV), HRV spectra, and electroencephalogram (EEG) spectra associated with idiopathic PLMS were compared with changes associated with isolated leg movements and respiratory-related leg movements during sleep. Furthermore, correlations between electromyographic activity, HRV changes, and EEG changes were assessed. SETTING: Sleep laboratory. PATIENTS: Whole-night polysomnographic studies of 24 subjects fulfilling the criteria of either periodic leg movements disorder (n = 8), obstructive sleep apnea syndrome (n = 7), or normal polysomnography (n = 9) were used. MEASUREMENTS AND RESULTS: Spectral HRV changes started before all EEG changes and up to 6 seconds before the onset of all types of leg movements. An initial weak autonomic activation was followed by a sympathetic activation, an increase of EEG delta activity, and finally a progression to increased higher-frequency EEG rhythms. After movement onset, HRV indicated a vagal activation, and, the EEG, a decrease in spindle activity. Sympathetic activation, as measured by HRV spectra, was greater for PLMS than for all other movement types. In EEG, gamma synchronization began 1 to 2 seconds earlier for isolated leg movements and respiratory-related leg movements than for PLMS. Significant correlations were found between autonomic activations and electromyographic activity, as well as between autonomic activations and EEG delta activity, but not between higher-frequency EEG rhythms and EMG activity or HRV changes. CONCLUSIONS: These results suggest a primary role of the sympathetic nervous system in the generation of PLMS.

[Is resting heart rate a cardiovascular risk factor?]

During recent years, resting heart rate was not considered as a cardiovascular risk factor. However, new evidences have showed that resting heart rate is an important prognostic factor for sudden cardiac death and heart failure in the general population, and especially among patients with known cardiac disease. Interestingly, resting heart rate not only predicts cardiac mortality but also all-cause mortality. The most common pathophysiological explanation is related to the fact that increased heart rate increases myocardial oxygen consumption and in parallel reduces coronary blood flow (reduction in the diastolic duration).

Heart Rate Effects of Longboard Skateboarding

The longboard skateboard has a longer, and usually wider, deck than the standard skateboard to provide greater support for the rider during the higher speeds attained on this version of the skateboard. Fourteen volunteer subjects participated in downhill and uphill longboarding trials. Heart rates were monitored during both trials, and the downhill and uphill average heart rates were compared with resting heart rates and then compared with accepted intensity recommendations for health and fitness benefits. The study questions were: Does longboarding have an acute effect on heart rates? If so, will longboarding uphill and/or downhill cause heart rate changes to levels recommended to improve cardiorespiratory health and fitness? With these questions as guidance we developed four hypotheses. With beats/minute and average uphill heart rate of 167.8 beats/minute statistical analysis showed statistically significant p values < .0001 and each null hypothesis was rejected in favor of their respective research hypotheses. Based on average age and average resting heart rate, average age-predicted maximum heart rate was 193.2 beats/minute and heart rate reserve was 133.2 beats/minute. The average percentages of heart rate reserve for the downhill section (131.4 beats/minute) and uphill section )(167.8 beats/minute) were 54% and 81% respectively. Downhill heart rates are within moderate intensity levels, 40% to 60% of heart rate reserve, and uphill heart rates are within vigorous intensity levels, greater than 60% of heart rate reserve. These results indicate that longboarding can increase heart rate to suggested levels suggested by the American College of Sports Medicine for improving cardiovascular health and fitness.

Relation of heart rate recovery to psychological distress and quality of life in patients with chronic heart failure

BACKGROUND: Psychological distress, poor disease-specific quality of life (QoL), and reduction in vagally mediated early heart rate recovery (HRR) after exercise, all previously predicted morbidity and mortality in patients with chronic heart failure (CHF). We hypothesized lower HRR with greater psychological distress and poorer QoL in CHF. DESIGN: All assessments were made at the beginning of a comprehensive cardiac outpatient rehabilitation intervention program. METHODS: Fifty-six CHF patients (mean 58+/-12 years, 84% men) completed the Hospital Anxiety and Depression Scale and the Minnesota Living With Heart Failure Questionnaire. HRR was determined as the difference between HR at the end of exercise and 1 min after exercise termination (HRR-1). RESULTS: Elevated levels of anxiety symptoms (P=0.005) as well as decreased levels of the Minnesota Living With Heart Failure Questionnaire total (P = 0.025), physical (P=0.026), and emotional (P=0.017) QoL were independently associated with blunted HRR-1. Anxiety, total, physical, and emotional QoL explained 11.4, 8, 7.8, and 9.0%, respectively, of the variance after controlling for covariates. Depressed mood was not associated with HRR-1 (P=0.20). CONCLUSION: Increased psychological distress with regard to elevated anxiety symptoms and impaired QoL were independent correlates of reduced HRR-1 in patients with CHF. Reduced vagal tone might explain part of the adverse clinical outcome previously observed in CHF patients in relation to psychological distress and poor disease-specific QoL.

Heart rate response determines long term exercise capacity after heart transplantation

BACKGROUND: Exercise capacity after heart transplantation (HTx) remains limited despite normal left ventricular systolic function of the allograft. Various clinical and haemodynamic parameters are predictive of exercise capacity following HTx. However, the predictive significance of chronotropic competence has not been demonstrated unequivocally despite its immediate relevance for cardiac output. AIMS: This study assesses the predictive value of various clinical and haemodynamic parameters for exercise capacity in HTx recipients with complete chronotropic competence evolving within the first 6 postoperative months. METHODS: 51 patients were enrolled in this exercise study. Patients were included when at least >6 months after HTx and without negative chronotropic medication or factors limiting exercise capacity such as significant transplant vasculopathy or allograft rejection. Clinical parameters were obtained by chart review, haemodynamic parameters from current cardiac catheterisation, and exercise capacity was assessed by treadmill stress testing. A stepwise multiple regression model analysed the proportion of the variance explained by the predictive parameters. RESULTS: The mean age of these 51 HTx recipients was 55.4 +/- 13.2 yrs on inclusion, 42 pts were male and the mean time interval after cardiac transplantation was 5.1 +/- 2.8 yrs. Five independent predictors explained 47.5% of the variance observed for peak exercise capacity (adjusted R2 = 0.475). In detail, heart rate response explained 31.6%, male gender 5.2%, age 4.1%, pulmonary vascular resistance 3.7%, and body-mass index 2.9%. CONCLUSION: Heart rate response is one of the most important predictors of exercise capacity in HTx recipients with complete chronotropic competence and without relevant transplant vasculopathy or acute allograft rejection.

Plasma NGAL and glomerular filtration rate in cardiac transplant recipients treated with standard or reduced calcineurin inhibitor levels.

AIM Predictors of renal recovery following conversion from calcineurin inhibitor- to proliferation signal inhibitor-based therapy are lacking. We hypothesized that plasma NGAL (P-NGAL) could predict improvement in glomerular filtration rate (GFR) after conversion to everolimus. PATIENTS & METHODS P-NGAL was measured in 88 cardiac transplantation patients (median 5 years post-transplant) with renal dysfunction randomized to continuation of conventional calcineurin inhibitor-based immunosuppression or switching to an everolimus-based regimen. RESULTS P-NGAL correlated with measured GFR (mGFR) at baseline (R(2) = 0.21; p < 0.001). Randomization to everolimus improved mGFR after 1 year (median [25-75 % percentiles]: ΔmGFR 5.5 [-0.5-11.5] vs -1 [-7-4] ml/min/1.73 m(2); p = 0.006). Baseline P-NGAL predicted mGFR after 1 year (R(2) = 0.18; p < 0.001), but this association disappeared after controlling for baseline mGFR. CONCLUSION P-NGAL and GFR correlate with renal dysfunction in long-term heart transplantation recipients. P-NGAL did not predict improvement of renal function after conversion to everolimus-based immunosuppression.

Detection of haemorrhagic shock: Are vital signs obsolete? A commentary by Dr M. Luginbühl

The ATLS program by the American college of surgeons is probably the most important globally active training organization dedicated to improve trauma management. Detection of acute haemorrhagic shock belongs to the key issues in clinical practice and thus also in medical teaching. (In this issue of the journal William Schulz and Ian McConachrie critically review the ATLS shock classification Table 1), which has been criticized after several attempts of validation have failed [1]. The main problem is that distinct ranges of heart rate are related to ranges of uncompensated blood loss and that the heart rate decrease observed in severe haemorrhagic shock is ignored [2]. Table 1. Estimated blood loos based on patient's initial presentation (ATLS Students Course Manual, 9th Edition, American College of Surgeons 2012). Class I Class II Class III Class IV Blood loss ml Up to 750 750–1500 1500–2000 >2000 Blood loss (% blood volume) Up to 15% 15–30% 30–40% >40% Pulse rate (BPM) <100 100–120 120–140 >140 Systolic blood pressure Normal Normal Decreased Decreased Pulse pressure Normal or ↑ Decreased Decreased Decreased Respiratory rate 14–20 20–30 30–40 >35 Urine output (ml/h) >30 20–30 5–15 negligible CNS/mental status Slightly anxious Mildly anxious Anxious, confused Confused, lethargic Initial fluid replacement Crystalloid Crystalloid Crystalloid and blood Crystalloid and blood Table options In a retrospective evaluation of the Trauma Audit and Research Network (TARN) database blood loss was estimated according to the injuries in nearly 165,000 adult trauma patients and each patient was allocated to one of the four ATLS shock classes [3]. Although heart rate increased and systolic blood pressure decreased from class I to class IV, respiratory rate and GCS were similar. The median heart rate in class IV patients was substantially lower than the value of 140 min−1 postulated by ATLS. Moreover deterioration of the different parameters does not necessarily go parallel as suggested in the ATLS shock classification [4] and [5]. In all these studies injury severity score (ISS) and mortality increased with in increasing shock class [3] and with increasing heart rate and decreasing blood pressure [4] and [5]. This supports the general concept that the higher heart rate and the lower blood pressure, the sicker is the patient. A prospective study attempted to validate a shock classification derived from the ATLS shock classes [6]. The authors used a combination of heart rate, blood pressure, clinically estimated blood loss and response to fluid resuscitation to classify trauma patients (Table 2) [6]. In their initial assessment of 715 predominantly blunt trauma patients 78% were classified as normal (Class 0), 14% as Class I, 6% as Class II and only 1% as Class III and Class IV respectively. This corresponds to the results from the previous retrospective studies [4] and [5]. The main endpoint used in the prospective study was therefore presence or absence of significant haemorrhage, defined as chest tube drainage >500 ml, evidence of >500 ml of blood loss in peritoneum, retroperitoneum or pelvic cavity on CT scan or requirement of any blood transfusion >2000 ml of crystalloid. Because of the low prevalence of class II or higher grades statistical evaluation was limited to a comparison between Class 0 and Class I–IV combined. As in the retrospective studies, Lawton did not find a statistical difference of heart rate and blood pressure among the five groups either, although there was a tendency to a higher heart rate in Class II patients. Apparently classification during primary survey did not rely on vital signs but considered the rather soft criterion of “clinical estimation of blood loss” and requirement of fluid substitution. This suggests that allocation of an individual patient to a shock classification was probably more an intuitive decision than an objective calculation the shock classification. Nevertheless it was a significant predictor of ISS [6]. Table 2. Shock grade categories in prospective validation study (Lawton, 2014) [6]. Normal No haemorrhage Class I Mild Class II Moderate Class III Severe Class IV Moribund Vitals Normal Normal HR > 100 with SBP >90 mmHg SBP < 90 mmHg SBP < 90 mmHg or imminent arrest Response to fluid bolus (1000 ml) NA Yes, no further fluid required Yes, no further fluid required Requires repeated fluid boluses Declining SBP despite fluid boluses Estimated blood loss (ml) None Up to 750 750–1500 1500–2000 >2000 Table options What does this mean for clinical practice and medical teaching? All these studies illustrate the difficulty to validate a useful and accepted physiologic general concept of the response of the organism to fluid loss: Decrease of cardiac output, increase of heart rate, decrease of pulse pressure occurring first and hypotension and bradycardia occurring only later. Increasing heart rate, increasing diastolic blood pressure or decreasing systolic blood pressure should make any clinician consider hypovolaemia first, because it is treatable and deterioration of the patient is preventable. This is true for the patient on the ward, the sedated patient in the intensive care unit or the anesthetized patients in the OR. We will therefore continue to teach this typical pattern but will continue to mention the exceptions and pitfalls on a second stage. The shock classification of ATLS is primarily used to illustrate the typical pattern of acute haemorrhagic shock (tachycardia and hypotension) as opposed to the Cushing reflex (bradycardia and hypertension) in severe head injury and intracranial hypertension or to the neurogenic shock in acute tetraplegia or high paraplegia (relative bradycardia and hypotension). Schulz and McConachrie nicely summarize the various confounders and exceptions from the general pattern and explain why in clinical reality patients often do not present with the “typical” pictures of our textbooks [1]. ATLS refers to the pitfalls in the signs of acute haemorrhage as well: Advanced age, athletes, pregnancy, medications and pace makers and explicitly state that individual subjects may not follow the general pattern. Obviously the ATLS shock classification which is the basis for a number of questions in the written test of the ATLS students course and which has been used for decades probably needs modification and cannot be literally applied in clinical practice. The European Trauma Course, another important Trauma training program uses the same parameters to estimate blood loss together with clinical exam and laboratory findings (e.g. base deficit and lactate) but does not use a shock classification related to absolute values. In conclusion the typical physiologic response to haemorrhage as illustrated by the ATLS shock classes remains an important issue in clinical practice and in teaching. The estimation of the severity haemorrhage in the initial assessment trauma patients is (and was never) solely based on vital signs only but includes the pattern of injuries, the requirement of fluid substitution and potential confounders. Vital signs are not obsolete especially in the course of treatment but must be interpreted in view of the clinical context. Conflict of interest None declared. Member of Swiss national ATLS core faculty.

Impact of ocean acidification and warming on respiration, heart rate and acid-base status of Mytilus edulis from the North Sea

Anthropogenic climate change confronts marine organisms with rapid trends of concomitant warming and CO2 induced ocean acidification. The survival and distribution of species partly depend on their ability to exploit their physiological plasticity during acclimatization. Therefore, in laboratory studies the effects of simulated future ocean acidification on thermal tolerance, energy metabolism and acid-base regulation capacity of the North Sea population of the blue mussel Mytilus edulis were examined. Following one month of pre-acclimation to 10 °C and control CO2 levels, mussels were exposed for two weeks to control and projected oceanic CO2 levels (390, 750 and 1120 µatm) before being subjected to a stepwise warming protocol between 10 °C and 31 °C (+ 3 °C each night). Oxygen consumption and heart rates, anaerobic metabolite levels and haemolymph acid-base status were determined at each temperature. CO2 exposure left oxygen consumption rate unchanged at acclimation temperature but caused a somewhat stronger increase during acute warming and thus mildly higher Q10-values than seen in controls. Interestingly, the thermally induced limitation of oxygen consumption rate set in earlier in normocapnic than in hypercapnic (1120 µatm CO2) mussels (25.2 °C vs. 28.8 °C), likely due to an onset of metabolic depression in the control group following warming. However, the temperature induced increase in heart rate became limited above 25 °C in both groups indicating an unchanged pejus temperature regardless of CO2 treatment. An upper critical temperature was reached above 28 °C in both treatments indicated by the accumulation of anaerobic metabolites in the mantle tissue, paralleled by a strong increase in haemolymph PCO2 at 31 °C. Ocean acidification caused a decrease in haemolymph pH. The extracellular acidosis remained largely uncompensated despite some bicarbonate accumulation. In all treatments animals developed a progressive warming-induced extracellular acidosis. A stronger pH drop at around 25 °C was followed by stagnating heart rates. However, normocapnic mussels enhanced bicarbonate accumulation at the critical limit, a strategy no longer available to hypercapnic mussels. In conclusion, CO2 has small effects on the response patterns of mussels to warming, leaving thermal thresholds largely unaffected. High resilience of adult North Sea mussels to future ocean acidification indicates that sensitivity to thermal stress is more relevant in shaping the response to future climate change.

Filtro respiratório reduz efeitos cardiovasculares associados à poluição: estudo randomizado, duplo-cego, controlado e cruzado em pacientes com insuficiência cardíaca (FILTER-HF trial)

Introdução A poluição do ar é um fator de risco associado com descompensação e mortalidade em pacientes com insuficiência cardíaca (IC). Objetivo Avaliar o impacto de um filtro de polipropileno sobre desfechos cardiovasculares em pacientes com IC e voluntários saudáveis durante exposição controlada à poluição. Métodos Ensaio clínico duplocego, controlado e cruzado, incluindo 26 pacientes com IC e 15 voluntários saudáveis, expostos a três protocolos diferentes de inalação randomizados por ordem: Ar Limpo; Exposição à Partículas de Exaustão do Diesel (ED); e ED filtrada. Os desfechos estudados foram função endotelial por índice de hiperemia reativa (RHi) e índice de aumento (Aix), biomarcadores séricos, variáveis de teste cardiopulmonar submáximo (caminhada de seis-minutos [tc6m]; consumo de oxigênio [VO2]; equivalente ventilatório de gás carbônico [VE/VCO2 slope]; consumo de O2 por batida [PulsoO2]) e variabilidade da frequência cardíaca (VFC). Resultados No grupo IC, a ED piorou o RHi [de 2,17 (IQR: 1,8-2,5) para 1,72 (IQR: 1,5-2,2); p=0,002], reduziu o VO2 [de 11.0 ± 3.9 para 8.4±2.8ml/Kg/min; p < 0.001], o tc6m [de 243,3±13 para 220,8 ± 14m; p=0,030] e o PulsoO2 [de 8.9 ± 1.0 para 7.8±0.7ml/bpm; p < 0.001]; e aumentou o BNP [de 47,0pg/ml (IQR: 17,3-118,0) para 66,5pg/ml (IQR: 26,5-155,5); p=0,004]. O filtro foi capaz de reduzir a concentração de poluição de 325±31 para 25±6?g/m3 (p < 0,001 vs. ED). No grupo IC, o filtro foi associado com melhora no RHi [2,06 (IQR: 1,5-2,6); p=0,019 vs. ED); aumento no VO2 (10.4 ± 3.8ml/Kg/min; p < 0.001 vs. ED) e PulsoO2 (9.7±1.1ml/bpm; p < 0.001 vs. ED); e redução no BNP [44,0pg/ml (IQR: 20,0-110,0); p=0,015 vs. ED]. Em ambos os grupos, a ED reduziu o Aix, sem efeito do filtro. O uso do filtro foi associado com maior ventilação e reinalação de CO2. Outras variáveis pesquisadas como VE/VCO2 slope e VFC não sofreram influências entre os protocolos. Conclusão A poluição do ar afetou adversamente o desempenho cardiovascular de pacientes com IC. Este é o primeiro ensaio clínico demonstrando que um simples filtrorespiratório pode prevenir a disfunção endotelial, a intolerância ao exercício e o aumento do BNP associados à poluição em pacientes com IC. O uso de máscaras com filtro tem o potencial de reduzir a morbidade associada à IC. Identificador ClinicalTrials.gov: NCT01960920