End-tidal Pressure Research Articles

The ventilatory efficiency parameters outperform peak oxygen consumption in monitoring the therapy effects in patients with hypertrophic cardiomyopathy

AimWe sought the cardiopulmonary exercise testing (CPET) parameter that most accurately reflected therapeutic efficacy in patients with hypertrophic cardiomyopathy (HCM). MethodsWell-being questionnaire, N-terminal brain natriuretic peptide measurements, echocardiography, and CPET were performed in patients with symptomatic non-obstructive HCM during phase II, randomized, open-label multicentre study, before and after 16 weeks of traditional or sacubitril/valsartan treatment. Patients were followed 36 months after the initial CPET. Primary endpoints were changes in: 1) peak oxygen consumption (VO2); 2) VO2 at anaerobic threshold (AT); 3) oxygen pulse; 4) minute ventilation (VE)/carbon-dioxide (CO2) production slope; 5) VE/VCO2 at AT (VE/VCO2_AT); 6) VE/VCO2 nadir; 7) VE/VCO2 intercept; and 8) partial end-tidal pressure of carbon-dioxide (PETCO2) change during CPET. ResultsOf 115 screened patients, 61 (52 ± 14 years, 43 % women) were included. Within subject therapy effects were detected only by the VE/VCO2 intercept and PETCO2 change, whereas the differences between medical regimens were detected by differences in VE/VCO2 nadir and VE/VCO2_AT changes after the treatment. The best predictors of the change in well-being were left ventricular outflow tract maximal gradient and VE/VCO2 intercept (B = 0.41,0.36; SE = 0.16,0.30; CI = 0.14–0.79, 0.15–1.14; p = 0.006,0.016, respectively). Adverse cardiac events were best predicted by the initial VE/VCO2 nadir. ConclusionVentilatory efficiency parameters outperform peak VO2 in gauging therapy effects in patients with HCM.

Standard versus individualised positive end-expiratory pressure (PEEP) compared by electrical impedance tomography in neurocritical care: a pilot prospective single centre study

BackgroundIndividualised bedside adjustment of mechanical ventilation is a standard strategy in acute coma neurocritical care patients. This involves customising positive end-expiratory pressure (PEEP), which could improve ventilation homogeneity and arterial oxygenation. This study aimed to determine whether PEEP titrated by electrical impedance tomography (EIT) results in different lung ventilation homogeneity when compared to standard PEEP of 5 cmH2O in mechanically ventilated patients with healthy lungs.MethodsIn this prospective single-centre study, we evaluated 55 acute adult neurocritical care patients starting controlled ventilation with PEEPs close to 5 cmH2O. Next, the optimal PEEP was identified by EIT-guided decremental PEEP titration, probing PEEP levels between 9 and 2 cmH2O and finding the minimal amount of collapse and overdistension. EIT-derived parameters of ventilation homogeneity were evaluated before and after the PEEP titration and after the adjustment of PEEP to its optimal value. Non-EIT-based parameters, such as peripheral capillary Hb saturation (SpO2) and end-tidal pressure of CO2, were recorded hourly and analysed before PEEP titration and after PEEP adjustment.ResultsThe mean PEEP value before titration was 4.75 ± 0.94 cmH2O (ranging from 3 to max 8 cmH2O), 4.29 ± 1.24 cmH2O after titration and before PEEP adjustment, and 4.26 ± 1.5 cmH2O after PEEP adjustment. No statistically significant differences in ventilation homogeneity were observed due to the adjustment of PEEP found by PEEP titration. We also found non-significant changes in non-EIT-based parameters following the PEEP titration and subsequent PEEP adjustment, except for the mean arterial pressure, which dropped statistically significantly (with a mean difference of 3.2 mmHg, 95% CI 0.45 to 6.0 cmH2O, p < 0.001).ConclusionAdjusting PEEP to values derived from PEEP titration guided by EIT does not provide any significant changes in ventilation homogeneity as assessed by EIT to ventilated patients with healthy lungs, provided the change in PEEP does not exceed three cmH2O. Thus, a reduction in PEEP determined through PEEP titration that is not greater than 3 cmH2O from an initial value of 5 cmH2O is unlikely to affect ventilation homogeneity significantly, which could benefit mechanically ventilated neurocritical care patients.

Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal data analysis 34 months post-discharge

BackgroundSARS-CoV-2 infection has raised concerns about long-term health repercussions. Exercise ventilatory inefficiency (EVin) has emerged as a notable long-term sequela, potentially impacting respiratory and cardiovascular health. This study aims to assess the long-term presence of EVin after 34 months and its association with cardiorespiratory health in post-COVID patients.MethodsIn a longitudinal study on 32 selected post-COVID subjects, we performed two cardiopulmonary exercise tests (CPETs) at 6 months (T0) and 34 months (T1) after hospital discharge. The study sought to explore the long-term persistence of EVin and its correlation with respiratory and cardiovascular responses during exercise. Measurements included also V̇O2peak, end-tidal pressure of CO2 (PETCO2) levels, oxygen uptake efficiency slope (OUES) and other cardiorespiratory parameters, with statistical significance set at p < 0.05. The presence of EVin at both T0 and T1 defines a persisting EVin (pEVin).ResultsOut of the cohort, five subjects (16%) have pEVin at 34 months. Subjects with pEVin, compared to those with ventilatory efficiency (Evef) have lower values of PETCO2 throughout exercise, showing hyperventilation. Evef subjects demonstrated selective improvements in DLCO and oxygen pulse, suggesting a recovery in cardiorespiratory function over time. In contrast, those with pEvin did not exhibit these improvements. Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse and OUES, indicating the potential prognostic value of OUES and Evin in post-COVID follow-ups.ConclusionsThe study highlights the clinical importance of long-term follow-up for post-COVID patients, as a significant group exhibit persistent EVin, which correlates with altered and potentially unfavorable cardiovascular responses to exercise. These findings advocate for the continued investigation into the long-term health impacts of COVID-19, especially regarding persistent ventilatory inefficiencies and their implications on patient health outcomes.

Effects of hyperventilation on repeated breath-holding while in a fasting state: do risks outweigh the benefits?

Breath-holding preceded by either an overnight fast or hyperventilation has been shown to potentiate the risk of a hypoxic blackout. However, no study has explored the combined effects of fasting and hyperventilation on apneic performance and associated physiological responses. Nine nondivers (8 males) attended the laboratory on two separate occasions (≥48 h apart), both after a 12-h overnight fast. During each visit, a hyperoxic rebreathing trial was performed followed by three repeated maximal static apneas preceded by either normal breathing (NORM) or a 30-s hyperventilation (HYPER). Splenic volume, hematology, cardiovascular, and respiratory variables were monitored. There were no interprotocol differences at rest or during hyperoxic rebreathing for any variable (P ≥ 0.09). On nine occasions (8 in HYPER), the subjects reached our safety threshold (oxygen saturation 65%) and were asked to abort their apneas, with the preponderance of these incidents (6 of 9) occurring during the third repetition. Across the sequential attempts, longer apneas were recorded in HYPER [median(range), 220(123-324) s vs. 185(78-296) s, P ≤ 0.001], with involuntary breathing movements occurring later [134(65-234) s vs. 97(42-200) s, P ≤ 0.001] and end-apneic partial end-tidal pressures of oxygen () being lower (P ≤ 0.02). During the final repetition, partial end-tidal pressure of carbon dioxide [(), 6.53 ± 0.46 kPa vs. 6.01 ± 0.45 kPa, P = 0.005] was lower in HYPER. Over the serial attempts, preapneic tidal volume was gradually elevated [from apnea 1 to 3, by 0.26 ± 0.24 L (HYPER) and 0.28 ± 0.30 L (NORM), P ≤ 0.025], with a correlation noted with preapneic (r = -0.57, P < 0.001) and (r = 0.76, P < 0.001), respectively. In a fasted state, preapnea hyperventilation compared with normal breathing leads to longer apneas but may increase the susceptibility to a hypoxic blackout.NEW & NOTEWORTHY This study shows that breath-holds (apneas) preceded by a 12-h overnight fast coupled with a 30-s hyperventilation as opposed to normal breathing may increase the likelihood of a hypoxic blackout through delaying the excitation of hypercapnic ventilatory sensory chemoreflexes. Evidently, this risk is exacerbated over a series of repeated maximal attempts, possibly due to a shift in preapneic gas tensions facilitated by an unintentional increase in tidal volume breathing.

Exercise oscillatory ventilation: the past, present, and future.

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.

Aortic stiffness and impairments in cerebrovascular function in cancer survivorship

An established consequence of anti-cancer treatment is increased aortic stiffness, which impairs the aortic damping of cardiac-generated pulsatile pressure and blood flow. These increased pulsations may result in vascular injury in the microcirculation of target end organs like the brain. The aim of the present study was to determine the ramifications of elevated aortic stiffness on cerebral macro- and microvascular pulsatility and autoregulatory function in cancer survivors. We hypothesized that cerebrovascular pulsatility would be enhanced, and cerebrovascular reactivity (CVR) to elevations in arterial CO 2 would be impaired, both in the large and small cerebral vessels in patients with a history of cancer and anti-cancer treatment versus healthy age- and sex-matched non-cancer controls. Aortic arch pulse wave velocity (aaPWV), a regional measure of stiffness in the proximal aorta, was calculated from echocardiographic views of the aortic valve and the descending aortic arch. Subjects then breathed room air for 60s followed by ~2 minutes of rebreathing with simultaneous collection of end-tidal pressure of CO 2 (P ET CO 2 ). Middle cerebral artery blood flow velocity (MCAv) was assessed using transcranial doppler. Oxygenated (oxy-[Hb]) and deoxygenated (deoxy-[Hb]) cerebral microvascular hemoglobin concentrations were monitored using two near-infrared spectroscopy probes placed over the prefrontal cortices. Pulsatility was assessed at baseline using Gosling’s Pulsatility Index (PI) for both the microvasculature and MCA. To account for changes in perfusion pressure, MAP was collected via finger plethysmography and cerebrovascular conductance indices were calculated for both oxy-[Hb] (CVCi oxy ) and MCAv (CVCi MCA ). CVR was calculated as the slope of CVCi oxy and CVCi MCA over P ET CO 2 during rebreathing. Six women were recruited (n = 3/group). Age was similar between the healthy non-cancer controls (HC) and patients with a history of cancer and anti-cancer treatment (CS) (31.0 ± 7 vs. 32.7 ± 13 years). Baseline ventilatory (P ET CO 2 ), central and cerebral hemodynamics were also similar (all p &gt; 0.05). aaPWV was significantly elevated in CS compared to HC (5.3 ± 0.6 vs. 3.1 ± 1.1 m/s, p = 0.04). Cerebral microcirculation PI in CS was significantly elevated (0.04 ± 0.01 vs. 0.02 ± 0.01, p = 0.02), but MCA PI was not different (p &gt; 0.05). CVR-CVCi oxy was impaired in CS (-3.6 ± 2.8 vs. 1.5 ± 0.5 nM·mmHg -1 /mmHg, p = 0.03), and CVR-CVCi MCA was similarly reduced (-0.05 ± 0.06 vs. 0.15 ± 0.01 mm/sec·mmHg -1 /mmHg, p &lt; 0.01). The increase in MAP during hypercapnia was similar between groups. Consistent with our hypothesis, both CVR-CVCi oxy and CVR-CVCi MCA were attenuated in patients with a history of anti-cancer treatment. Additionally, the microvascular pulsatility was greater in CS. This suggests an impaired cerebrovascular function, possibly related to increased transmission of pulsatility into the brain, in the years following cancer diagnoses and treatment. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of greater erythroid Cl-/HCO3- transporter (band 3) expression on ventilation and gas exchange during exhaustive exercise.

Band 3 protein is a Cl-/[Formula: see text] transporter on the red blood cell (RBC) surface with an important role in CO2 excretion. Greater band 3 expression by roughly 20% is found in people with the GP.Mur blood type. Intriguingly, a disproportional percentage of those with GP.Mur excel in field-and-track sports. Could higher band 3 activity benefit an individual's physical performance? This study explored the impact of GP.Mur/higher band 3 expression on ventilation and gas exchange during exhaustive exercise. We recruited 36 nonsmoking, elite male athletes (36.1% GP.Mur) from top sports universities to perform incremental exhaustive treadmill cardiopulmonary exercise testing (CPET). We analyzed CPET data with respect to absolute running time and to individual's %running time and %maximal O2 uptake. We found persistently higher respiratory frequencies and slightly lower tidal volume in GP.Mur athletes, resulting in a slightly larger increase of ventilation as the workload intensified. The expiratory duty cycle (Te/Ttot) was persistently longer and inspiratory duty cycle (Ti/Ttot) was persistently shorter for GP.Mur subjects throughout the run. Consequently, end-tidal pressure of carbon dioxide ([Formula: see text], a surrogate marker for alveolar and arterial CO2 tension-[Formula: see text] and [Formula: see text]) was lower in the GP.Mur athletes during the early stages of exercise. In conclusion, athletes with GP.Mur and higher band 3 expression hyperventilate more during exercise in a pattern that uses a greater fraction of time for expiration than inspiration to increase the rate of CO2 excretion than increased tidal volume. This greater ventilation response reduced Pco2 and may help to extend exercise capacity in high-level sports.NEW & NOTEWORTHY Higher expression of the Cl-/[Formula: see text] transporter band 3 anion exchanger-1 (AE1) on the red blood cell membrane, as in people with the GP.Mur blood type, increases the rate of CO2 excretion during exercise.

Validation of Noninvasive Assessment of Pulmonary Gas Exchange in Patients with Chronic Obstructive Pulmonary Disease during Initial Exposure to High Altitude.

Investigation of pulmonary gas exchange efficacy usually requires arterial blood gas analysis (aBGA) to determine arterial partial pressure of oxygen (mPaO2) and compute the Riley alveolar-to-arterial oxygen difference (A-aDO2); that is a demanding and invasive procedure. A noninvasive approach (AGM100), allowing the calculation of PaO2 (cPaO2) derived from pulse oximetry (SpO2), has been developed, but this has not been validated in a large cohort of chronic obstructive pulmonary disease (COPD) patients. Our aim was to conduct a validation study of the AG100 in hypoxemic moderate-to-severe COPD. Concurrent measurements of cPaO2 (AGM100) and mPaO2 (EPOC, portable aBGA device) were performed in 131 moderate-to-severe COPD patients (mean ±SD FEV1: 60 ± 10% of predicted value) and low-altitude residents, becoming hypoxemic (i.e., SpO2 < 94%) during a short stay at 3100 m (Too-Ashu, Kyrgyzstan). Agreements between cPaO2 (AGM100) and mPaO2 (EPOC) and between the O2-deficit (calculated as the difference between end-tidal pressure of O2 and cPaO2 by the AGM100) and Riley A-aDO2 were assessed. Mean bias (±SD) between cPaO2 and mPaO2 was 2.0 ± 4.6 mmHg (95% Confidence Interval (CI): 1.2 to 2.8 mmHg) with 95% limits of agreement (LoA): -7.1 to 11.1 mmHg. In multivariable analysis, larger body mass index (p = 0.046), an increase in SpO2 (p < 0.001), and an increase in PaCO2-PETCO2 difference (p < 0.001) were associated with imprecision (i.e., the discrepancy between cPaO2 and mPaO2). The positive predictive value of cPaO2 to detect severe hypoxemia (i.e., PaO2 ≤ 55 mmHg) was 0.94 (95% CI: 0.87 to 0.98) with a positive likelihood ratio of 3.77 (95% CI: 1.71 to 8.33). The mean bias between O2-deficit and A-aDO2 was 6.2 ± 5.5 mmHg (95% CI: 5.3 to 7.2 mmHg; 95%LoA: -4.5 to 17.0 mmHg). AGM100 provided an accurate estimate of PaO2 in hypoxemic patients with COPD, but the precision for individual values was modest. This device is promising for noninvasive assessment of pulmonary gas exchange efficacy in COPD patients.

An Impairment in Resting and Exertional Breathing Pattern May Occur in Long-COVID Patients with Normal Spirometry and Unexplained Dyspnoea.

Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (TI) during the tidal volume (VT) to the total breath duration (TI/TTOT) and by the VT/TI ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed TI/TTOT and VT/TI at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O2 uptake (VO2peak) and workload, compared to 40 HS (22 females) (p < 0.05). LC patients also showed significantly higher values of TI/TTOT at rest and at peak, and lower values in VT/TI at peak (p < 0.05). In LC patients, values of TI/TTOT at peak were significantly related to ∆PETCO2, i.e., the end-tidal pressure of CO2 at peak minus the one at rest (p < 0.05). When LC patients were categorized by the TI/TTOT 0.38 cut-off value, patients with TI/TTOT > 0.38 showed lower values in VO2peak and maximal workload, and greater values in the ventilation/CO2 linear relationship slope than patients with TI/TTOT ≤ 0.38 (p < 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.

Abstract 11461: The Hemodynamic Gain Index is an Independent Predictor of Adverse Outcomes, and Comparable to Peak Oxygen Consumption in Patients With Chronic Heart Failure With Reduced Ejection Fraction

Introduction: The hemodynamic gain index (HGI) is a novel simple parameter calculated from resting and peak systolic BP (SBP) and heart rate (HR) during exercise testing. It is a predictor of mortality in population-based cohorts. However, the prognostic significance of the HGI in chronic HFrEF has not been well studied. Hypothesis: The HGI is independently associated with adverse outcomes, and is comparable to other cardiopulmonary exercise testing (CPET) parameters. Methods: Medical records of 1,067 consecutive HFrEF patients (EF ≤ 40%) undergoing CPET for symptom evaluation from 12/2012 to 9/2020 were reviewed. HGI was calculated using the formula, [(SBP peak x HR peak )-(SBP rest x HR rest )]/(SBP rest x HR rest ). Patients with missing vital signs, hypotensive or bradycardic response to exercise were excluded. Primary outcome was the composite endpoint of all-cause mortality, LVAD implantation, and heart transplantation. Multivariable Cox proportional hazard models were used with subgroup analyses based on median age, sex, BMI of 35 kg/m 2 , respiratory exchange ratio (RER) of 1.05, and beta-blocker use. ROC curves with AUCs were used to compare HGI, peak VO 2 , VE/VCO 2 slope and peak end-tidal pressure of CO 2 (PEtCO 2 ). Results: We included 954 HFrEF patients (mean age was 56.3 ± 12.0 years, 72% men, 17% with BMI ≥ 35 kg/m 2 , 86% on beta-blockers, and 73% with RER &gt; 1.05). During a median follow up time of 946 days, the incidence of the composite outcome was 331 (34.7%). After adjustment for age, sex, BMI, comorbidities, and EF, higher HGI was independently associated with lower risk of the adverse outcomes in the main cohort (hazard ratio per unit increase 0.46, 95%CI 0.35 to 0.59, p &lt; 0.001), and all subgroups, except for patients with BMI ≥ 35 kg/m 2 ( Figure 1A ). The HGI was also comparable to peak VO 2 , and outperformed VE/VCO 2 slope and PEtCO 2 ( Figure 1B ). Conclusions: The HGI is an independent predictor of adverse outcomes, and comparable to peak VO 2 in patients with chronic HFrEF.

Recumbent Ergometer vs Treadmill Cardiopulmonary Exercise Test in HFpEF: Implications for Chronotropic Response and Exercise Capacity

Cardiopulmonary exercise testing (CPET) can identify mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF), but exercise modalities with differing body positions (eg, recumbent ergometer, treadmill) are broadly used. In this study, we aimed to determine whether body position affects CPET parameters in patients with HFpEF. Subjects with stable HFpEF (n = 23) underwent noninvasive treadmill CPET, followed by an invasive recumbent-cycle ergometer CPET within 3 months. A comparison group undergoing similar studies included healthy subjects (n = 5) and subjects with pulmonary arterial hypertension (n = 6). The peak oxygen consumption (VO2peak) and peak heart rate were significantly lower in the recumbent vs the upright position (10.1 vs 13.1 mL/kg/min [Δ-3 mL/kg/min]; P < 0.001; and 95 vs 113 bpm [Δ-18 bpm]; P < 0.001, respectively). No significant differences were found in the minute ventilation to carbon dioxide production ratio, end-tidal pressure of carbon dioxide or respiratory exchange ratio. A similar pattern was observed in the comparison groups. Compared to recumbent ergometer, treadmill CPET revealed higher VO2peak and peak heart rate response. When determining chronotropic incompetence to adjust beta-blocker administration in HFpEF, body position should be taken into account.

Correlation of Hemodynamic and Respiratory Parameters in Invasive Cardiopulmonary Exercise Testing (iCPET).

Background: Invasive cardiopulmonary exercise testing (iCPET) is an integral part in the advanced diagnostic workup of pulmonary hypertension (PH). Our study evaluated the relation between hemodynamic and respiratory parameters at two different resting conditions and two defined low exercise levels with a close synchronization of measurements in a broad variety of dyspnea patients. Subjects and methods: We included 146 patients (median age 69 years, range 22 to 85 years, n = 72 female) with dyspnea of uncertain origin. Invasive hemodynamic and gas exchange parameters were measured at rest, 45° upright position, unloaded cycling, 25 and 50 W exercise. All measurements were performed in a single RHC procedure. Results: Oxygen uptake (VO/body mass) correlated significantly with cardiac index (all p ≤ 0.002) at every resting and exercise level and with every method of cardiac output measurement (thermodilution, method of Fick). Mean pulmonary arterial pressure (PAPmean) correlated with all respiratory parameters (respiratory rate, partial end-tidal pressures of oxygen and carbon dioxide [petCO and petO], ventilation/carbon dioxide resp. oxygen ratio [VE/VCO, VE/VO], and minute ventilation [VE], all p < 0.05). These correlations improved with increasing exercise levels from rest via unloaded cycling to 25 W. There was no correlation with right atrial or pulmonary arterial wedge pressure. Summary: In dyspnea patients of different etiologies, the cardiac index is closely linked to VO at every level of rest and submaximal exercise. PAPmean is the only pressure that correlates with different respiratory parameters, but this correlation is highly significant and stable at rest, unloaded cycling and at 25 W.

Mild-to-moderate COVID-19 impact on the cardiorespiratory fitness in young and middle-aged populations.

The goal of the present study was to compare pulmonary function test (PFT) and cardiopulmonary exercise test (CPET) performance in COVID-19 survivors with a control group (CG). This was a cross-sectional study. Patients diagnosed with COVID-19, without severe signs and symptoms, were evaluated one month after the infection. Healthy volunteers matched for sex and age constituted the control group. All volunteers underwent the following assessments: i) clinical evaluation, ii) PTF; and iii) CPET on a cycle ergometer. Metabolic variables were measured by the CareFusion Oxycon Mobile device. In addition, heart rate responses, peak systolic and diastolic blood pressure, and perceived exertion were recorded. Twenty-nine patients with COVID-19 and 18 healthy control subjects were evaluated. Surviving patients of COVID-19 had a mean age of 40 years and had higher body mass index and persistent symptoms compared to the CG (P<0.05), but patients with COVID-19 had more comorbidities, number of medications, and greater impairment of lung function (P<0.05). Regarding CPET, patients surviving COVID-19 had reduced peak workload, oxygen uptake (V̇O2), carbon dioxide output (V̇CO2), circulatory power (CP), and end-tidal pressure for carbon dioxide (P ETCO2) (P<0.05). Additionally, survivors had depressed chronotropic and ventilatory responses, low peak oxygen saturation, and greater muscle fatigue (P<0.05) compared to CG. Despite not showing signs and symptoms of severe disease during infection, adult survivors had losses of lung function and cardiorespiratory capacity one month after recovery from COVID-19. In addition, cardiovascular, ventilatory, and lower limb fatigue responses were the main exercise limitations.

Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post–Coronavirus Disease

ObjectivesThe authors used cardiopulmonary exercise testing (CPET) to define unexplained dyspnea in patients with post-acute sequelae of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (PASC). We assessed participants for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). BackgroundApproximately 20% of patients who recover from coronavirus disease (COVID) remain symptomatic. This syndrome is named PASC. Its etiology is unclear. Dyspnea is a frequent symptom. MethodsThe authors performed CPET and symptom assessment for ME/CFS in 41 patients with PASC 8.9 ± 3.3 months after COVID. All patients had normal pulmonary function tests, chest X-ray, and chest computed tomography scans. Peak oxygen consumption (peak VO2), slope of minute ventilation to CO2 production (VE/VCO2 slope), and end tidal pressure of CO2 (PetCO2) were measured. Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing. ResultsEighteen men and 23 women (average age: 45 ± 13 years) were studied. Left ventricular ejection fraction was 59% ± 9%. Peak VO2 averaged 20.3 ± 7 mL/kg/min (77% ± 21% predicted VO2). VE/VCO2 slope was 30 ± 7. PetCO2 at rest was 33.5 ± 4.5 mm Hg. Twenty-four patients (58.5%) had a peak VO2 <80% predicted. All patients with peak VO2 <80% had a circulatory limitation to exercise. Fifteen of 17 patients with normal peak VO2 had ventilatory abnormalities including peak respiratory rate >55 (n = 3) or dysfunctional breathing (n = 12). For the whole cohort, 88% of patients (n = 36) had ventilatory abnormalities with dysfunctional breathing (n = 26), increased VE/VCO2 (n = 17), and/or hypocapnia PetCO2 <35 (n = 25). Nineteen patients (46%) met criteria for ME/CFS. ConclusionsCirculatory impairment, abnormal ventilatory pattern, and ME/CFS are common in patients with PASC. The dysfunctional breathing, resting hypocapnia, and ME/CFS may contribute to symptoms. CPET is a valuable tool to assess these patients.

The stability of cerebrovascular CO2 reactivity following attainment of physiological steady-state.

What is the central question of this study? During a steady-state cerebrovascular CO2 reactivity test, do different data extraction time points change the outcome for cerebrovascular CO2 reactivity? What is the main finding and its importance? Once steady-state end-tidal pressure of CO2 and haemodynamics were achieved, cerebral blood flow was stable, and so cerebrovascular CO2 reactivity values remained unchanged regardless of data extraction length (30 vs. 60s) and time point (at 2-5min). This study assessed cerebrovascular CO2 reactivity (CVR) and examined data extraction time points and durations with the hypotheses that: (1) there would be no difference in CVR values when calculated with cerebral blood flow (CBF) measures at different time points following the attainment of physiological steady-state, (2) once steady-state was achieved there would be no difference in CVR values derived from 60 to 30s extracted means, and (3) that changes in would not be associated with any changes in CVR. We conducted a single step iso-oxic hypercapnic CVR test using dynamic end-tidal forcing (end-tidal , +9.4 ± 0.7mmHg), and transcranial Doppler and Duplex ultrasound of middle cerebral artery (MCA) and internal carotid artery (ICA), respectively. From the second minute of hypercapnia onwards, physiological steady-state was apparent, with no subsequent changes in end-tidal , or mean arterial pressure. Therefore, CVR measured in the ICA and MCA was stable following the second minute of hypercapnia onwards. Data extraction durations of 30 or 60s did not give statistically different CVR values. No differences in CVR were detected following the second minute of hypercapnia after accounting for mean arterial pressure via calculated conductance or covariation of mean arterial pressure. These findings demonstrate that, provided the stimulus remains in a steady-state, data extracted from any minute of a CVR test during physiological steady-state conditions produce equivalent CVR values; any change in the CVR value would represent a failure of CVR mechanisms, a change in the magnitude of the stimulus, or measurement error.

Why Levosimendan Improves the Clinical Condition of Patients With Advanced Heart Failure: A Holistic Approach

BackgroundIn advanced heart failure (HF), levosimendan increases peak oxygen uptake (VO2). We investigated whether peak VO2 increase is linked to cardiovascular, respiratory, or muscular performance changes. Methods and ResultsTwenty patients hospitalized for advanced HF underwent, before and shortly after levosimendan infusion, 2 different cardiopulmonary exercise tests: (a) a personalized ramp protocol with repeated arterial blood gas analysis and standard spirometry including alveolar–capillary gas diffusion measurements at rest and at peak exercise, and (b) a step incremental workload cardiopulmonary exercise testing with continuous near-infrared spectroscopy analysis and cardiac output assessment by bioelectrical impedance analysis.Levosimendan significantly decreased natriuretic peptides, improved peak VO2 (11.3 [interquartile range 10.1–12.8] to 12.6 [10.2–14.4] mL/kg/min, P < .01) and decreased minute ventilation to carbon dioxide production relationship slope (47.7 ± 10.7 to 43.4 ± 8.1, P < .01). In parallel, spirometry showed only a minor increase in forced expiratory volume, whereas the peak exercise dead space ventilation was unchanged. However, during exercise, a smaller edema formation was observed after levosimendan infusion, as inferable from the changes in diffusion components, that is, the membrane diffusion and capillary volume. The end-tidal pressure of CO2 during the isocapnic buffering period increased after levosimendan (from 28 ± 3 mm Hg to 31 ± 2 mm Hg, P < .01). During exercise, cardiac output increased in parallel with VO2. After levosimendan, the total and oxygenated tissue hemoglobin, but not deoxygenated hemoglobin, increased in all exercise phases. ConclusionsIn advanced HF, levosimendan increases peak VO2, decreases the formation of exercise-induced lung edema, increases ventilation efficiency owing to a decrease of reflex hyperventilation, and increases cardiac output and muscular oxygen delivery and extraction.

Second-generation laryngeal mask airway as an alternative to endotracheal tube in prolonged laparoscopic abdominal surgery: a comparative analysis of intraoperative gas exchanges.

Laryngeal mask airway (LMA), which is used in difficult airway maintenance conditions during emergencies, is rarely used in prolonged surgery despite its advantages over endotracheal tube (ETT). In this study, we conducted a comparative analysis of intraoperative gas exchanges between second-generation LMA and ETT during prolonged laparoscopic abdominal surgery. Prolonged surgery was defined as a surgery lasting more than 2 h. In total, 394 patients who underwent laparoscopic liver resection via either second-generation LMA or ETT were retrospectively analysed. The following parameters were compared between the two groups of patients: end-tidal pressure of carbon dioxide (ETCO2), tidal volume (TV), respiratory rate (RR), peak inspiratory pressure (PIP), arterial partial pressure of carbon dioxide (PaCO2), pH and ratio of arterial partial pressure of oxygen to fractional inspired oxygen (PFR) during surgery. In addition, the incidence of postoperative pulmonary complications (PPCs), including pulmonary aspiration, was compared. The values of ETCO2, TV, RR and PIP during pneumoperitoneum were comparable between the two groups. Although PaCO2 at 2 h after induction was higher in patients in the LMA group (40.5 vs. 38.5 mmHg, P < 0.001), the pH and PFR values of the two groups were comparable. The incidence of PPC was similar. During prolonged laparoscopic abdominal surgery, second-generation LMA facilitates adequate intraoperative gas exchange and may serve as an alternative to ETT.

New volumetric capnography-derived parameter: a potentially valuable tool for detecting hyperventilation during cardiopulmonary resuscitation in a porcine model.

BackgroundVolumetric capnography is increasingly being applied in cardiopulmonary resuscitation. However, during cardiopulmonary resuscitation, the abnormal ventilation state affects the monitoring effect of the most commonly used capnography-derived parameter, the partial carbon dioxide end-tidal pressure (PetCO2). In this study, we evaluated the ability of a new volumetric capnography-derived parameter, the ratio between the PetCO2 and the volume of carbon dioxide (CO2) eliminated per min and per kilogram of body weight, for detecting hyperventilation during cardiopulmonary resuscitation.MethodsWe used 12 porcine models of primary ventricular fibrillation-induced cardiac arrest. Ventricular fibrillation was induced and left untreated for 4 min. Standardized chest compressions were performed throughout the experiment using mechanical cardiopulmonary resuscitation. Following 5 min of normal ventilation as a washout period, each animal underwent 4 types of ventilation. The main outcome measures were the PetCO2, the ratio between the PetCO2 and the volume of CO2 eliminated per min and per kilogram of body weight with each ventilation type.ResultsDifferent ventilation types had a significant effect on the volumetric capnography-derived parameters. The PetCO2 and ratio between the PetCO2 and the volume of CO2 eliminated per min and per kilogram of body weight values during cardiopulmonary resuscitation was significantly higher in non-hyperventilating than in hyperventilating animals. The ratio reflected hyperventilation accurately and immediately, with an area under the curve (AUC) of 0.98. The optimal cut-off point of the ratio for discriminating hyperventilation from non-hyperventilation was 6.36, with a sensitivity and specificity of 0.99 and 0.89, respectively.ConclusionsThe ratio between the PetCO2 and the volume of CO2 eliminated per min and per kilogram of body weight showed good performance in discriminating hyperventilation from non-hyperventilation and was sensitive to changes in ventilation status. This ratio may be a valuable clinical indicator for monitoring the ventilation status during cardiopulmonary resuscitation.

Predictive Value of Cardiopulmonary Exercise Testing Parameters in Ambulatory Advanced Heart Failure

ObjectivesThis study sought to determine cardiopulmonary exercise (CPX) predictors of the combined outcome of durable mechanical circulatory support (MCS), transplantation, or death at 1 year among patients with ambulatory advanced heart failure (HF). BackgroundOptimal CPX predictors of outcomes in contemporary ambulatory advanced HF patients are unclear. MethodsREVIVAL (Registry Evaluation of Vital Information for ventricular assist devices [VADs] in Ambulatory Life) enrolled 400 systolic HF patients, INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles 4-7. CPX was performed by 273 subjects 2 ± 1 months after study enrollment. Discriminative power of maximal (peak oxygen consumption [peak VO2]; VO2 pulse, circulatory power [CP]; peak systolic blood pressure • peak VO2], peak end-tidal pressure CO2 [PEtCO2], and peak Borg scale score) and submaximal CPX parameters (ventilatory efficiency [VE/VCO2 slope]; VO2 at anaerobic threshold [VO2AT]; and oxygen uptake efficiency slope [OUES]) to predict the composite outcome were assessed by univariate and multivariate Cox regression and Harrell’s concordance statistic. ResultsAt 1 year, there were 39 events (6 transplants, 15 deaths, 18 MCS implantations). Peak VO2, VO2AT, OUES, peak PEtCO2, and CP were higher in the no-event group (all p < 0.001), whereas VE/VCO2 slope was lower (p < 0.0001); respiratory exchange ratio was not different. CP (hazard ratio [HR]: 0.89; p = 0.001), VE/VCO2 slope (HR: 1.05; p = 0.001), and peak Borg scale score (HR: 1.20; p = 0.005) were significant predictors on multivariate analysis (model C-statistic: 0.80). ConclusionsAmong patients with ambulatory advanced HF, the strongest maximal and submaximal CPX predictor of MCS implantation, transplantation, or death at 1 year were CP and VE/VCO2, respectively. The patient-reported measure of exercise effort (Borg scale score) contributed substantially to the prediction of outcomes, a surprising and novel finding that warrants further investigation. (Registry Evaluation of Vital Information for VADs in Ambulatory Life [REVIVAL]; NCT01369407)

Breath-hold task induces temporal heterogeneity in electroencephalographic regional field power in healthy subjects.

We demonstrated that changes in CO2 values cause oscillations in the cortical activity in δ-and α-bands. The analysis of the regional field power (RFP) showed evidence that different cortical areas respond with different time delays to CO2 challenges. An opposite behavior was found for the end-tidal O2. We suppose that the different cortical time delays likely expresse specific ascending pathways to the cortex, generated by chemoreceptor nuclei in the brain stem. Although the brain stem is in charge of the automatic control of ventilation, the cortex is involved in the voluntary control of breathing but also receives inputs from the brain stem, which influences the perception of breathing, the arousal state and sleep architecture in conditions of hypoxia/hypercapnia. We evaluated in 11 healthy subjects the effects of breath hold (BH; 30 s of apneas and 30 s of normal breathing) and BH-related CO2/O2 changes on electroencephalogram (EEG) global field power (GFP) and RFP in nine different areas (3 rostrocaudal sections: anterior, central, and posterior; and 3 sagittal sections: left, middle, and right) in the δ- and α-bands by cross correlation analysis. No significant differences were observed in GFP or RFP when comparing free breathing (FB) with the BH task. Within the BH task, the shift from apnea to normal ventilation was accompanied by an increase in the δ-power and a decrease in the α-power. The end-tidal pressure of CO2 ([Formula: see text]) was positively correlated with the δ-band and negatively with the α- band with a positive time shift, whereas an opposite behavior was found for the end-tidal pressure of O2 ([Formula: see text]). Notably, the time shift between [Formula: see text] / [Formula: see text] signals and cortical activity at RFP was heterogenous and seemed to follow a hierarchical activation, with the δ-band responding earlier than the α-band. Overall, these findings suggest that the effect of BH on the cortex may follow specific ascending pathways from the brain stem and be related to chemoreflex stimulation.NEW & NOTEWORTHY We demonstrated that the end tidal CO2 oscillation causes oscillations of delta and alpha bands. The analysis of the regional field power showed that different cortical areas respond with different time delays to CO2 challenges. An opposite behavior was found for the end-tidal O2. We can suppose that the different cortical time delay response likely expresses specific ascending pathways to the cortex generated by chemoreceptor nuclei in the brainstem.