Exercise Oscillatory Ventilation (EOV) and a steep ventilatory efficiency (VE/VCO2) slope are features of ventilatory inefficiency on cardiopulmonary exercise testing (CPET), both associated with poor prognosis in patients with heart failure (HF). The prevalence in patients with co-existent atrial fibrillation (AF) and the impact of catheter ablation (CA) is unknown.

To characterize ventilatory inefficiency in patients with persistent AF and Left Ventricular Systolic Dysfunction (LVSD) and assess the impact of CA.

Patients with persistent AF and Left Ventricular Ejection Fraction (LVEF) < 50% undergoing first-time CA were prospectively enrolled. Echocardiography and CPET were performed at baseline and 6 months post-CA. EOV was defined using the Kremser-Corrà criteria, and VE/VCO2 slope gradient > 30 was considered abnormal.

A total of 53 participants were enrolled (mean LVEF of 34 ± 9%). A total of 10 (19.2%) exhibited EOV at baseline. These patients had larger indexed left atrial (41.6 ± 13.1 mL/m2 vs. 33.3 ± 9.3 mL/m2, p = 0.03) and ventricular volumes [65.7 mL/m2 (57.1, 89.0) vs. 46.7 mL/m2 (39.8, 61.4), p = 0.03]. The partial pressure of end-tidal carbon dioxide (PETCO2) at peak exercise increased (33.7 ± 6.1 mmHg to 41.2 ± 5.8 mmHg, p < 0.001) and correlated with improvement in HF symptoms (p = -0.003) and objective HF markers. A total of 25 (48.1%) had an abnormal VE/VCO2 gradient. The EOV pattern resolved in eight (80%) participants due to a reduction in EOV burden (71.1 ± 11.9% vs. 48.8 ± 14.8%, p = 0.006) and the component amplitude of minute ventilation cycles (2.6 L/min (2.5,3.2) vs 2.2 L/min (1.8,2.6), p = 0.028). Fewer patients had an abnormal VE/VCO2 gradient after CA [25 (48.1%) vs. 16 (34.0%), p = 0.004].

Ventilatory inefficiency is common in patients with AF and LVSD. CA improves both EOV and VE/VCO2 in AF-induced cardiomyopathy. Improvement in PETCO2 is also seen and correlates with HF symptom burden.

Exercise oscillatory ventilation (EOV) is a fascinating event that can be appreciated in the cardiopulmonary exercise test and is characterized by a cyclic fluctuation of minute ventilation, tidal volume, oxygen uptake, carbon dioxide production, and end-tidal pressure for oxygen and carbon dioxide. Its mechanisms stem from a dysregulation of the normal control feedback of ventilation involving one or more of its components, namely, chemoreflex delay, chemoreflex gain, plant delay, and plant gain. In this review, we intend to breakdown therapeutic targets according to pathophysiology and revise the prognostic value of exercise oscillatory ventilation in the setting of heart failure and other diagnoses.

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).

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.

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.

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.

Exercise oscillatory ventilation (EOV) is a strong prognostic marker in patients with heart failure (HF) and left ventricular (LV) dysfunction. This phenomenon can be explained through a single quantitative measurement of ventilatory instability, the loop gain. Therefore, we aimed to evaluate whether loop gain could be a better tool than subjective EOV evaluation to identify HF patients with a higher risk of major cardiovascular complications. This was a single-center retrospective study that included patients with left ventricular ejection fraction (LVEF) ≤ 50% consecutively referred for cardiopulmonary exercise testing (CPET) from 2016-2020. Loop gain was measured through computational evaluation of the minute ventilation graph. Of the 250 patients included, the 66 that presented EOV also had higher values of loop gain, when compared to patients without EOV. Those with both EOV and higher loop gain had more severe HF, with higher NT-proBNP and VE/VCO2 slope as well as lower peak VO2 and LVEF. On multivariable analysis, loop gain was strongly correlated with the composite endpoint of cardiovascular death, urgent heart transplantation, urgent left ventricular assist device implantation or HF hospitalization, even after correcting for peak VO2, LVEF, VE/VCO2 slope and NT-proBNP. Presence of EOV was not prognostically significant in this analysis. Loop gain is an objective parameter that quantifies ventilatory instability and showed to have a strong prognostic value in a cohort of patients with HF and LVEF ≤ 50%, outperforming the classification of EOV.

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.

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.

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).

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.

I) to evaluate the impact of exertional oscillatory ventilation (EOV) in patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) during cardiopulmonary exercise testing (CPET) compared with patients without EOV (N-EOV); II) to identify the influence of EOV persistence (P-EOV) and EOV disappearance (D-EOV) during CPET on the outcomes of mortality and hospitalization in HFrEF patients; and III) to identify further predictors of mortality and hospitalization in patients with P-EOV.

315 stable HFrEF patients underwent CPET and were followed for 35 months. We identified 202 patients N-EOV and 113 patients with EOV. Patients with EOV presented more symptoms (NYHA III: 35% vs. N-EOV 20%, p < 0.05), worse cardiac function (LVEF: 28 ± 6 vs. N-EOV 39 ± 1, p < 0.05), higher minute ventilation/carbon dioxide production (V̇E/V̇CO2 slope: 41 ± 11 vs. N-EOV 37 ± 8, p < 0.05) and a higher rate of deaths (26% vs. N-EOV 6%, p < 0.05) and hospitalization (29% vs. N-EOV 9%, p < 0.05). P-EOV patients had more severe HFrEF (NYHA IV: 23% vs D-EOV: 9%, p < 0.05), had worse cardiac function (LVEF: 24 ± 5 vs. D-EOV: 34 ± 3, p < 0.05) and had lower peak oxygen consumption (V̇O2) (12.0 ± 3.0 vs D-EOV: 13.3 ± 3.0 mlO2.kg-1.min-1, p < 0.05). Among P-EOV, other independent predictors of mortality were V̇E/V̇CO2 slope ≥36 and V̇O2 peak ≤12 mlO2.kg-1.min-1; a V̇E/V̇CO2 slope≥34 was a significant predictor of hospitalization. Kaplan-Meier survival analysis showed that, HFrEF patients with P-EOV had a higher risk of mortality and higher risk of hospitalization (p < 0.05) than patients with D-EOV and N-EOV.

In HFrEF patients, EOV persistence during exercise had a strong prognostic role. In P-EOV patients V̇E/V̇CO2 ≥36 and V̇O2 peak ≤12 mlO2.kg-1.min-1, had a further additive negative prognostic role.

To study the relationship between the indicators of dynamic capnography and pulse oximetry with the indicators of the 6-minute walk test (6MWT) in patients with chronic obstructive pulmonary disease (COPD).

67 patients of both sexes were examined: 45 patients with COPD (age 60.02.74 years) and 25 patients of the control group (age 47.603.46 years). The study of the functional capabilities of the patients respiratory system was carried out before, during and after the 6MWT on the equipment LifeSense LS1-9R capnograph-pulse oximeter (MedAir AB).

In the comparison group, the parameters of dyspnea at rest were higher than the control group (p0.05), the spirometry indices were significantly lower (p0.05). Shortness of breath as a reason for stopping/slowing down the pace during the 6MWT was noted by patients of both groups (p0.05). When analyzing the PETCO2 trend graphs, periodic breathing (PВ) was revealed. In the group of patients with COPD, signs of PВ in the analysis of the PETCO2 trend were found in 80.95% (p0.05). Regression analysis of Cox proportional risks of mortality in patients with COPD revealed the prognostic value of the following parameters of a comprehensive assessment of the patient: body mass index (BMI), BODE index, dyspnea index on the mMRS scale, Borg, forced expiratory volume in 1 second (FEV1), index Tiffno, signs of PВ, distance 6MWT, signs of PВ and desaturation during 6MWT. At the same time, the total contribution of these indicators to the risk of a lethal event was assessed (p=0.003).

When analyzing the correlation dependence, it was revealed that the presence of PВ was a prognostically unfavorable sign in patients with COPD. Predictors of an unfavorable course of COPD were BMI (23.0 kg/m2), BODE index, dyspnea indices on the mMRS, Borg, FEV1 scales, Tiffnos index, signs of PH, distance 6MST, signs of PD and desaturation during 6MST (reliability of the model coefficient p=0.003) in terms of forecast.

Background: The prognostic value of cardiopulmonary exercise testing (CPET) variables for major cardiovascular events in patients with heart failure (HF) is widely established. However, the prognostic value of these variables as predictors of appropriate implantable cardioverter-defibrillator (ICD) therapies has not been sufficiently well addressed. This study aimed to evaluate CPET variables such as peak oxygen uptake (VO₂ peak), relationship between change in minute ventilation (VE) and carbon dioxide output (VCO₂) during incremental exercise (VE/VCO₂ slope) and exercise-related periodic breathing (EPB) as appropriate ICD therapy predictors in HF patients.Methods: We retrospectively assessed 61 HF patients who underwent CPET and had ICD implanted for primary prevention. Patients were followed for 767 ± 601 days. Primary outcome was appropriate ICD-delivered therapy, either anti-tachycardia pacing (ATP) or shock.Results: The sample consisted mostly of male patients (65.6%), with severe ventricular dysfunction (mean left ventricular ejection fraction (LVEF) 27 ± 6%). The primary outcome occurred in 20 patients (32%). There were no significant differences in VO₂ peak (17.7 ± 4.1 and 16.9 ± 4.5 mL/kg/min), VE/VCO₂ slope (39.7 ± 8.4 and 39.6 ± 10.2) or EPB prevalence (20% and 19.5%) in patients with or without appropriate ICD therapy. According to Cox regression analysis, none of the CPET variables were significant predictors of appropriate ICD therapy.Conclusions: In this cohort study of HF patients, CPET variables did not predict appropriate ICD therapies. Further studies with large number of patients are warranted to address this issue.

Aim: Variation of exercise ventilation confers poor prognosis in heart failure. Sedentary men have higher exercise ventilatory variability than athletes. However, the impact of lifestyle intervention on exercise ventilatory variability in sedentary people is unknown and this is the aim of this study. Materials & methods: Prospective controlled single-blinded interventional study that randomly assigned healthy sedentary individuals to diet and exercise (intervention group, n = 12) or no intervention (control group, n = 12) for 12 weeks. Exercise ventilatory variability was accessed before and after intervention. Results: Despite similar values at baseline, there was a 15% reduction in respiratory rate variability (root mean square of the successive differences/n) in intervention group. Conclusion: Diet and exercise training reduced exercise ventilatory variability.

Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction (<40%, HFrEF) and with HF with preserved ejection fraction (>50%, HFpEF), but no data are available for patients with HF with mid-range ejection fraction (40-49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients.

We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2-year follow-up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF, respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV- patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV- patients. Kaplan-Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV- of the same ejection fraction groups. EOV-associated survival differences in HFmrEF patients started after 18 months of follow-up.

Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow-up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV- patients diverged only after 18 months.

Determination of exercise oscillatory ventilation (EOV) is subjective, and the interreviewer agreement has not been reported. The purposes of this study were, among patients with heart failure (HF), as follows: 1) to determine the interreviewer agreement for EOV and 2) to describe a novel, objective, and quantifiable measure of EOV.

This was a secondary analysis of the HEART Camp: Promoting Adherence to Exercise in Patients with Heart Failure study. EOV was determined through a blinded review by six individuals on the basis of their interpretation of the EOV literature. Interreviewer agreement was assessed using Fleiss kappa (κ). Final determination of EOV was based on agreement by four of the six reviewers. A new measure (ventilation dispersion index; VDI) was calculated for each test, and its ability to predict EOV was assessed with the receiver operator characteristics curve.

Among 243 patients with HF (age, 60 ± 12 yr; 45% women), the interreviewer agreement for EOV was fair (κ = 0.303) with 10-s discrete data averages and significantly better, but only moderate (κ = 0.429) with 30-s rolling data averages. Prevalence rates of positive and indeterminate EOVs were 18% and 30% with the 10-s discrete averages and 14% and 13% with the 30-s rolling averages, respectively. VDI was strongly associated with EOV, with areas under the receiver operator characteristics curve of 0.852 to 0.890.

Interreviewer agreement for EOV in patients with HF is fair to moderate, which can negatively affect risk stratification. VDI has strong predictive validity with EOV; as such, it might be a useful measure of prognosis in patients with HF.

Heart failure with reduced ejection fraction (HFrEF) is common in the developed world and results in significant morbidity and mortality. Accurate risk assessment methods and prognostic variables are therefore needed to guide clinical decision making for medical therapy and surgical interventions with the ultimate goal of decreasing risk and improving health outcomes. The purpose of this review is to examine the role of cardiopulmonary exercise testing (CPET) and its most commonly used ventilatory gas exchange variables for the purpose of risk stratification and management of HFrEF. We evaluated five widely studied gas exchange variables from CPET in HFrEF patients based on nine previously used systematic criteria for biomarkers. This paper provides clinicians with a comprehensive and critical overview, class recommendations and evidence levels. Although some CPET variables met more criteria than others, evidence supporting the clinical assessment of variables beyond peak V̇O₂ is well-established. A multi-variable approach also including the V̇_E-V̇CO₂ slope and EOV is therefore recommended.

Periodic breathing during incremental cardiopulmonary exercise testing is a regularly recurring waxing and waning of tidal volume due to oscillations in central respiratory drive. Periodic breathing is a sign of respiratory control system instability, which may occur at rest or during exercise. The possible mechanisms responsible for exertional periodic breathing might be related to any instability of the ventilatory regulation caused by: (1) increased circulatory delay (i.e., circulation time from the lung to the brain and chemoreceptors due to reduced cardiac index leading to delay in information transfer), (2) increase in controller gain (i.e., increased central and peripheral chemoreceptor sensitivity to arterial partial pressure of oxygen and of carbon dioxide), or (3) reduction in system damping (i.e., baroreflex impairment). Periodic breathing during exercise is observed in several cardiovascular disease populations, but it is a particularly frequent phenomenon in heart failure due to systolic dysfunction. The detection of exertional periodic breathing is linked to outcome and heralds worse prognosis in heart failure, independently of the criteria adopted for its definition. In small heart failure cohorts, exertional periodic breathing has been abolished with several dedicated interventions, but results have not yet been confirmed. Accordingly, further studies are needed to define the role of visceral feedbacks in determining periodic breathing during exercise as well as to look for specific tools for preventing/treating its occurrence in heart failure.

The occurrence of minute-ventilation oscillations during exercise, named periodic breathing, exhibits important prognostic information in heart failure. Considering that exercise training could influence the fluctuation of ventilatory components during exercise, we hypothesized that ventilatory variability during exercise would be greater in sedentary men than athletes.

To compare time-domain variability of ventilatory components of sedentary healthy men and athletes during a progressive maximal exercise test, evaluating their relationship to other variables usually obtained during a cardiopulmonary exercise test.

Analysis of time-domain variability (SD/n and RMSSD/n) of minute-ventilation (Ve), respiratory rate (RR) and tidal volume (Vt) during a maximal cardiopulmonary exercise test of 9 athletes and 9 sedentary men was performed. Data was compared by two-tailed Student T test and Pearson´s correlations test.

Sedentary men exhibited greater Vt (SD/n: 1.6 ± 0.3 vs. 0.9 ± 0.3 mL/breaths; p < 0.001) and Ve (SD/n: 97.5 ± 23.1 vs. 71.6 ± 4.8 mL/min x breaths; p = 0.038) variabilities than athletes. VE/VCO2 correlated to Vt variability (RMSSD/n) in both groups.

Time-domain variability of Vt and Ve during exercise is greater in sedentary than athletes, with a positive relationship between VE/VCO2 pointing to a possible influence of ventilation-perfusion ratio on ventilatory variability during exercise in healthy volunteers.

The variable "exercise oscillatory ventilation" (EOV), assessed during cardiopulmonary exercise test (CPET), recently became a fundamental prognostic parameter in patients with heart failure. In literature, various definitions are suggested, but an uniformly accepted description to identify EOV still lacks. We performed a systematic review of the literature in order to determine the different definitions and diagnostic techniques to assess EOV. A systematic search strategy was established and executed in seven databases (PubMed, Google Scholar, Cochrane Clinical Trials, Science Direct, Pedro, Web Of Science library and Medline (Ovid)) resulting in 605 citations after de-duplication. Full-text articles (n=124) were assessed for eligibility, resulting in 75 citations. The review accounted 17,440 patients of whom 4,638 subjects presented EOV. Seven studies described EOV in a non-heart failure population accounting 168 EOV subjects. The definitions could be categorized in nine subdivisions of which four (n=43) referred to an original description. The other subdivisions were combinations of the original definitions (n=11), quantifications (n=4), computational (n=3), vaguely described (n=8) or not defined (n=6). Symptom limited maximal exercise tests were conducted to assess EOV, however the modes, protocols, software and data sampling were divers. Heterogeneity in the numerous definitions to identify EOV and the vaguely described assessment methods are hindering the evolution to a standardized uniformly accepted definition and technique to identify this abnormal breathing pattern. Unity in definition and international adopted assessment is warranted to strengthen its validity as a prognostic marker and could promote communication. It may facilitate clinical trials on pathophysiology and origin of EOV.

The advent of microprocessed "metabolic carts" and rapidly incremental protocols greatly expanded the clinical applications of cardiopulmonary exercise testing (CPET). The response normalcy to CPET is more commonly appreciated at discrete time points, for example, at the estimated lactate threshold and at peak exercise. Analysis of the response profiles of cardiopulmonary responses at submaximal exercise and recovery, however, might show abnormal physiologic functioning which would not be otherwise unraveled. Although this approach has long been advocated as a key element of the investigational strategy, it remains largely neglected in practice. The purpose of this paper, therefore, is to highlight the usefulness of selected submaximal metabolic, ventilatory, and cardiovascular variables in different clinical scenarios and patient populations. Special care is taken to physiologically justify their use to answer pertinent clinical questions and to the technical aspects that should be observed to improve responses' reproducibility and reliability. The most recent evidence in favor of (and against) these variables for diagnosis, impairment evaluation, and prognosis in systemic diseases is also critically discussed.

Cardiopulmonary exercise testing (CPX) is a relatively old technology, but has sustained relevance for many primary care clinical scenarios in which it is, ironically, rarely considered. Advancing computer technology has made CPX easier to administer and interpret at a time when our aging population is more prone to comorbidities and higher prevalence of nonspecific symptoms of exercise intolerance and dyspnea, for which CPX is particularly useful diagnostically and prognostically. These discrepancies in application are compounded by patterns in which CPX is often administered and interpreted by cardiology, pulmonary, or exercise specialists who limit their assessments to the priorities of their own discipline, thereby missing opportunities to distinguish symptom origins. When used properly, CPX enables the physician to assess fitness and uncover cardiopulmonary issues at earlier phases of work-up, which would therefore be especially useful for primary care physicians. In this article, we provide an overview of CPX principles and testing logistics, as well as some of the clinical contexts in which it can enhance patient care.