Effect of Acute β-blocker Withholding on Ventilatory Efficiency in Patients With Advanced Chronic Heart Failure

BackgroundThis is the first study to examine the effect of acute (24-hour) β-blocker withholding on ventilatory efficiency in patients with advanced chronic heart failure (CHF) during maximal incremental treadmill cardiopulmonary exercise test.Methods and ResultsSeventeen CHF patients were studied either 3 hours after administration of β-blocker (BB_ON) or 27 hours after the last β-blocker ingestion (BB_OFF). The ventilatory efficiency was measured via the slope of the linear relationship between ventilation (V′_E) and carbon dioxide production (V′CO₂) (ie, V′_E/V′CO₂ slope). Measurements were also made at rest, anaerobic threshold (AT), maximal end-tidal pressure for carbon dioxide (P_ETCO_2max), respiratory compensation point (RC), and peak exercise. Compared with BB_ON, the V′_E/V′CO₂ slope was significantly increased during BB_OFF (30.8 ± 7.4 vs. 29.1 ± 5.4, P = .04). At peak exercise, oxygen uptake (V′O₂, 16.0 ± 2.7 vs. 15.6 ± 2.8 mL·kg·min) and V′CO₂ (1458 ± 459 vs. 1414 ± 429 mL/min) were not different between the 2 conditions, whereas V′_E was higher during BB_OFF (49.5 ± 10.7 vs. 46.1 ± 9.6 L/min, P = .04). No differences were noted at AT and RC in V′O₂, V′CO₂, V′_E, V′_E/V′O₂, and V′_E/V′CO₂ ratios during the 2 conditions. At P_ETCO_2max, used to noninvasively estimate the CO₂ set point, V′_E was higher (33.9 ± 7.6 vs. 31.7 ± 7.3 L/min, P = .002) and P_ETCO₂ was lower (37.4 ± 4.8 vs. 38.5 ± 4.0 mm Hg, P = .03), whereas V′CO₂ was unchanged (1079 ± 340 vs. 1050 ± 322 mL/min) during BB_OFF.ConclusionAcute β-blocker withholding resulted in decreased ventilatory efficiency mostly from an increase of V′CO₂-independent regulation of V′_E and less likely from a change in ventilation/perfusion mismatching.     

Prognostic value of a new cardiopulmonary exercise testing parameter in chronic heart failure: oxygen uptake efficiency at peak exercise - comparison with oxygen uptake efficiency slope

IntroductionA growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O₂ consumption (VO₂) and minute ventilation (VE) in patients with chronic heart failure (CHF).ObjectiveTo evaluate the prognostic value of a new CPET parameter — peak oxygen uptake efficiency (POUE) — and to compare it with OUES in patients with CHF.MethodsWe prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy — 153 male, aged 53.3 ± 13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7 ± 8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone — who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverterdefibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up.Peak VO₂, percentage of predicted peak VO₂, VE/VCO₂ slope, OUES and POUE were analyzed. OUES was calculated using the formula VO₂ (l/min) = OUES (log₁₀VE) + b. POUE was calculated as pVO₂ (l/min) / log₁₀peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE.ResultspVO₂: 20.5 ± 5.9; percentage of predicted peak VO₂: 68.6 ± 18.2; VE/VCO₂ slope: 30.6 ± 8.3; OUES: 1.85 ± 0.61; POUE: 0.88 ± 0.27. During a mean follow-up of 33.1 ± 14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37).ConclusionPOUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF.     

Exercise Ventilatory Efficiency in Older and Younger Heart Failure Patients With Preserved Ejection Fraction

Background

Patients with heart failure with preserved ejection fraction (HFpEF) exhibit pulmonary abnormalities, but the studies to date have reported wide variability in the ventilatory equivalent for carbon dioxide (V?_E/V?CO₂) slope. It is possible that aging may contribute to that variability. We sought to compare ventilatory efficiency and its components in older and younger HFpEF patients during exercise.

Oxygen Uptake Efficiency Slope and Prediction of Post-operative Morbidity and Mortality in Patients with Lung Cancer

Objective

Peak oxygen consumption is a very valuable cardiopulmonary functional parameter in pre-operative evaluation of patients with lung cancer. However, it has several critical limitations for operability decision due to failure in achieving maximal level of exercise test for cases. The aim of this study was to reveal the importance of more accurate cardiopulmonary parameters that can be calculated from data of submaximal level test, such as oxygen uptake efficiency slope (OUES) and to determine whether it could be used in the operability decision phase for borderline cases by means of morbidity and mortality.

Materials and Methods

One hundred and twenty-five patients who were scheduled to undergo lung surgery due to lung cancer were included in the study. Peak oxygen uptake (pVO₂), heart rate at the anaerobic threshold, and oxygen consumption volume at anaerobic threshold values were obtained after performing the cardiopulmonary exercise test. The OUES value was calculated from the ratio of the peak VO₂ value and logarithmic equivalent of the ventilatory volume (VE). The following equation was used for determining OUES: VO₂/log₁₀ VE.

Results

The peak VO₂ mean value was 21.37?±?4.20 mL/min/kg in patients. However, OUES mean value was 12.44?±?2.11. When the metabolic parameters of the patients were compared, a significant correlation was determined between the peak VO₂ value and peak VE, OUES, and survival (p?<?0.01).

Conclusion

This study demonstrated that OUES is significantly correlated with peak VO₂ and it does not require the performance of maximal exercise and can be used together with peak VO₂ in this patient population when there is difficulty in making decision for surgery in patients with lung cancer.

     

Exercise training improves lipoprotein lipid profiles in patients with coronary artery disease

The effects of endurance exercise training on plasma lipoprotein lipids were determined in 10 men, ages 46 to 62 years, with coronary artery disease (CAD). Patients maintained body weight, health-related behaviors, and stable diets throughout the program. Training was at 50% to 85% of maximal oxygen consumption (V?O₂ max) for 40 to 60 minutes, 3 to 5 days/week for 29 ± 7 weeks. Training increased V?O₂ max (31 ± 19%, p < 0.001), reduced plasma cholesterol (C) (?8 ± 4%, p < 0.01), low-density lipoprotein-C (LDL-C) (?9 ± 9%, p < 0.01), and triglyceride (TG) (?13 ± 32%, p < 0.05) concentrations, and increased high-density lipoprotein-C (HDL-C) levels (11 ± 13%, p < 0.05) and $\text{HDL-C}\text{LDL-C}$ ratios (25 ± 20%, p < 0.01). Changes in LDL-C and V?O₂ max were correlated (r = ?0.73, p ± 0.01), while the changes in LDL-C and HDL-C each correlated inversely with pretraining lipoprotein levels (^rLDL-C = ?0.77, p < 0.01; ^rHDL-C = ?0.68, p < 0.05). Thus potentially “antiatherogenic” benefits of exercise seem to be due to a training effect, since they correlate best with changes in V?O₂ max and are maximal in patients with initially low V?O₂ max, high LDL-C, and low HDL-C levels.     

Alveolar Air and O2 Uptake During Exercise in Patients With Heart Failure

Background

Peak exercise pulmonary oxygen uptake (V?O₂) is a primary marker of prognosis in heart failure (HF). The pathophysiology of impaired peak V?O₂ is unclear in patients. To what extent alveolar airway function affects V?O₂ during cardiopulmonary exercise testing (CPET) has not been fully elucidated. This study aimed to describe how changes in alveolar ventilation (V?_A), volume (V_A), and related parameters couple with exercise V?O₂ in HF.

Association Between Physical Activity Measurements and Key Parameters of Cardiopulmonary Exercise Testing in Patients With Heart Failure

BackgroundA hallmark characteristic of heart failure (HF) is reduced physical activity (PA) patterns. The relationship between key cardiopulmonary exercise testing (CPX) variables and PA patterns has not been investigated. Therefore, we evaluated PA patterns in patients with ischemic HF and its relationship to peak oxygen consumption (VO₂), the minute ventilation/carbon dioxide production (VE/VCO₂) slope, and the oxygen uptake efficiency slope (OUES).Methods and ResultsSixteen patients with HF wore an accelerometer for six days to measure total steps/day as well as percentage of time at light, moderate, and vigorous PA. Symptom-limited CPX was performed on a treadmill using a ramping protocol. Total steps correlated with VO₂ (r = 0.64 P < .05), the VE/VCO₂ slope (r = ?0.72; P < .05), and the OUES (0.63; P < .05). The percentage of time at light-intensity PA correlated with the VE/VCO₂ slope (r = 0.58; P < .05) and the OUES (r = ?0.51; P < .05). The percentage of time at vigorous-intensity PA correlated with peak VO₂ (r = 0.55; P < .05) and the VE/VCO₂ slope (r = ?0.52; P < .05).ConclusionsPA assessed by accelerometer is significantly associated with key CPX variables in patients with HF.     

The minute ventilation/carbon dioxide production slope is prognostically superior to the oxygen uptake efficiency slope

BackgroundVentilatory efficiency, commonly assessed by the minute ventilation (VE)-carbon dioxide production (VCO₂) slope, has proven to be a strong prognostic marker in the heart failure (HF) population. Recently, the oxygen uptake efficiency slope (OUES) has demonstrated prognostic value, but additional comparisons to established cardiopulmonary exercise test (CPET) variables are required.Methods and ResultsA total of 341 subjects were diagnosed with HF participated in this analysis. The VE/VCO₂ slope and the OUES were calculated using 50% (VE/VCO₂ slope₅₀ or OUES₅₀) and 100% (VE/VCO₂ slope₁₀₀ or OUES₁₀₀) of the exercise data. Peak oxygen consumption (VO₂) was also determined. There were 47 major cardiac-related events during the 3-year tracking period. Receiver operating characteristic (ROC) curve analysis demonstrated the classification schemes for both VE/VCO₂ slope and OUES calculations as well as peak VO₂ were statistically significant (all areas under the ROC curve: ≥0.74, P < .001). Area under the ROC curve for the VE/VCO₂ slope₁₀₀ was, however, significantly greater than OUES₅₀, OUES₁₀₀, and peak VO₂ (P < .05).ConclusionsAlthough the OUES was a significant predictor of mortality, the VE/VCO₂ slope maintained optimal prognostic value. An elevated VE/VCO₂ slope may be the single best indicator of increased risk for adverse events.     

Oxygen uptake efficiency slope, a new submaximal parameter in evaluating exercise capacity in chronic heart failure patients

Background

The oxygen uptake efficiency slope (OUES) is a new submaximal parameter which objectively predicts the maximal exercise capacity in children and healthy subjects. However, the usefulness of OUES in adult patients with and without advanced heart failure remains undetermined. The present study investigates the stability and the usefulness of OUES in adult cardiac patients with and without heart failure.

Methods

Forty-five patients with advanced heart failure (group A) and 35 patients with ischemic heart disease but normal left ventricular ejection fraction (group B) performed a maximal exercise test. PeakVO₂ and percentage of predicted peakVO₂ were markers of maximal exercise capacity, whereas OUES, ventilatory anaerobic threshold (VAT), and slope VE/VCO₂ were calculated as parameters of submaximal exercise.

Results

Group A patients had lower peakVO₂ (P < .001), lower percentage of predicted peakVO₂ (P = .001), lower VAT (P < .05), steeper slope VE/VCO₂ (P < .001), and lower OUES (P < .02). Within group A, significant differences were found for VAT, slope VE/VCO₂, and OUES (all P < .01) between patients with peakVO₂ above and below 14 mL O₂/kg/min. Of all the submaximal parameters, VAT correlated best with peakVO₂ (r =.814, P < .01) followed by OUES/kg (r = .781, P < .01), and slope VE/VCO₂ (r = −.492, P < .001). However, VAT could not be determined in 18 (23%) patients.

Conclusions

OUES remains stable over the entire exercise duration and is significantly correlated with peakVO₂ in adult cardiac patients with and without impaired LVEF. Therefore, OUES could be helpful to assess exercise performance in advanced heart failure patients unable to perform a maximal exercise test. Further studies are needed to confirm our hypothesis.     

Acetazolamide and Inhaled Carbon Dioxide Reduce Periodic Breathing During Exercise in Patients With Chronic Heart Failure

BackgroundPeriodic breathing (PB) during sleep and exercise in heart failure (HF) is related to respiratory acid-base status, CO₂ chemosensitivity, and temporal dynamics of CO₂ and O₂ sensing. We studied inhaled CO₂ and acetazolamide to alter these factors and reduce PB.Methods and ResultsWe measured expired and arterial gases and PB amplitude and duration in 20 HF patients during exercise before and after acetazolamide given acutely (500 mg intravenously) and prolonged (24 hours, 2 g orally), and we performed overnight polysomnography. We studied CO₂ inhalation (1%–2%) during constant workload exercise. PB disappeared in 19/20 and 2/7 patients during 2% and 1% CO₂. No changes in cardiorespiratory parameters were observed after acute acetazolamide. With prolonged acetazolamide at rest: ventilation +2.04 ± 4.0 L/min (P = .001), tidal volume +0.11 ± 1.13 L (P = .003), respiratory rate +1.24 ± 4.63 breaths/min (NS), end-tidal PO₂ +4.62 ± 2.43 mm Hg (P = .001), and end-tidal PCO₂ −2.59 ± 9.7 mm Hg (P < .001). At maximum exercise: Watts −10% (P < .02), VO₂ −61 ± 109 mL/min (P = .04) and VCO₂ 101 ± 151 mL/min (P < .02). Among 20 patients, PB disappeared in 1 and 7 subjects after acute and prolonged acetazolamide, respectively. PB was present 80% ± 26, 65% ± 28, and 43% ± 39 of exercise time before and after acute and prolonged acetazolamide, respectively. Overnight apnea/hypopnea index decreased from 30.8 ± 83.8 to 21.1 ± 16.9 (P = .003).ConclusionsIn HF, inhaled CO₂ and acetazolamide reduce exercise PB with additional benefits of acetazolamide on sleep PB.     

The validation of oxygen uptake efficiency slope in patients with stroke

To evaluate the real aerobic capacity is difficult due to impaired limbs function in stroke patients. Oxygen uptake efficiency slope (OUES) could represent the aerobic capacity in submaximal exercise test. Hence, we designed this observational study to investigate the application of the OUES for evaluating aerobic capacity in these patients.Thirty-seven stroke patients were classified into 2 groups according to their Brunnstrom stage of affected lower limbs. Patients underwent cardiopulmonary exercise testing to assess cardiorespiratory fitness. Minute ventilation and oxygen consumption were measured, and OUES was calculated, compared with healthy reference values, and correlated with the peak oxygen consumption. The predictive validity of submaximal OUES was derived.Study participants’ OUES (median 566.2 [IQR, 470.0-711.6]) was 60% of healthy reference values and correlated positively with the peak oxygen consumption (r = 0.835) (P < .01). The predictive validity of oxygen uptake efficiency slope at 50% of maximal exercise duration (OUES₅₀) and oxygen uptake efficiency slope at 75% of maximal exercise duration (OUES₇₅) for oxygen uptake efficiency slope at 100% of maximal exercise duration (OUES₁₀₀) was 0.877 and 0.973, respectively (P < .01). The OUES₅₀, OUES₇₅, and OUES₁₀₀ groups were not significantly different; agreement of submaximal and maximal OUES values was strong.OUES is a valuable submaximal index for evaluating cardiorespiratory fitness in stroke patients. Moderate-to-high concurrent validity of this parameter with peak oxygen consumption and the high predictive validity of OUES₅₀ and OUES₇₅ for OUES₁₀₀ suggest maximal exercise testing in stroke patients who cannot reach maximal exercise is unnecessary.     

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.     

Determinants of Cardiorespiratory Fitness After Bariatric Surgery: Insights From a Randomised Controlled Trial of a Supervised Training Program

BackgroundSeverely obese patients have decreased cardiorespiratory fitness (CRF) and poor functional capacity. Bariatric surgery–induced weight loss improves CRF, but the determinants of this improvement are not well known. We aimed to assess the determinants of CRF before and after bariatric surgery and the impact of an exercise training program on CRF after bariatric surgery.MethodsFifty-eight severely obese patients (46.1 ± 6.1 kg/m², 78% women) were randomly assigned to either an exercise group (n = 39) or usual care (n = 19). Exercise training was conducted from the 3rd to the 6th months after surgery. Anthropometric measurements, abdominal and mid-thigh computed tomographic scans, resting echocardiography, and maximal cardiopulmonary exercise testing was performed before bariatric surgery and 3 and 6 months after surgery.ResultsWeight, fat mass, and fat-free mass were reduced significantly at 3 and 6 months, without any additive impact of exercise training in the exercise group. From 3 to 6 months, peak aerobic power (V?O_2peak) increased significantly (P < 0.0001) in both groups but more importantly in the exercise group (exercise group: from 18.6 ± 4.2 to 23.2 ± 5.7 mL/kg/min; control group: from 17.4 ± 2.3 to 19.7 ± 2.4 mL/kg/min; P value, group × time = 0.01). In the exercise group, determinants of absolute V?O_2peak (L/min) were peak exercise ventilation, oxygen pulse, and heart rate reserve (r² = 0.92; P < 0.0001), whereas determinants of V?O_2peak indexed to body mass (mL/kg/min) were peak exercise ventilation and early-to-late filling velocity ratio (r² = 0.70; P < 0.0001).ConclusionsA 12-week supervised training program has an additive benefit on cardiorespiratory fitness for patients who undergo bariatric surgery.     

A meta-analysis of the prognostic significance of cardiopulmonary exercise testing in patients with heart failure

The objective of the study is to assess the role of cardiopulmonary exercise testing (CPX) variables, including peak oxygen consumption (VO₂), which is the most recognized CPX variable, the minute ventilation/carbon dioxide production (VE/VCO₂) slope, the oxygen uptake efficiency slope (OUES), and exercise oscillatory ventilation (EOV) in a current meta-analysis investigating the prognostic value of a broader list of CPX-derived variables for major adverse cardiovascular events in patients with HF. A search for relevant CPX articles was performed using standard meta-analysis methods. Of the initial 890 articles found, 30 met our inclusion criteria and were included in the final analysis. The total subject populations included were as follows: peak VO₂ (7,319), VE/VCO₂ slope (5,044), EOV (1,617), and OUES (584). Peak VO₂, the VE/VCO₂ slope and EOV were all highly significant prognostic markers (diagnostic odds ratios ≥ 4.10). The OUES also demonstrated promise as a prognostic marker (diagnostic odds ratio = 8.08) but only in a limited number of studies (n = 2). No other independent variables (including age, ejection fraction, and beta-blockade) had a significant effect on the meta-analysis results for peak VO₂ and the VE/VCO₂ slope. CPX is an important component in the prognostic assessment of patients with HF. The results of this meta-analysis strongly confirm this and support a multivariate approach to the application of CPX in this patient population.     

Left ventricular diastolic performance at rest is essential for exercise capacity in patients with non-complicated myocardial infarction

IntroductionIn patients with recent myocardial infarction (MI) limited exercise capacity during physical activity is an important symptom and the base for future treatment. The myocardial injury after MI leads to both systolic and diastolic left ventricular (LV) dysfunction.ObjectiveThe aim of this study was to assess the relevance of systolic and diastolic LV function for cardiopulmonary exercise capacity in patients with prior MI.MethodsSixty-five consecutive patients after first MI without signs and symptoms of heart failure, aged 52 ± 6 years, were included in the study. The following echo parameters were evaluated: LV ejection fraction (LVEF), peak early and late diastolic velocities (E, A), deceleration time of E wave (dec t E), ratio of early trans-mitral to early annular diastolic velocities (E/e′), velocity propagation of early filling (Vp), and diameters and volumes of LV and left atrium (LA). CPET variables included: oxygen uptake at peak exercise (peak VO₂), oxygen pulse (VO₂ HR), VE/VCO₂ slope, circulatory power (CP) and recovery half time (T1/2).ResultsSignificant correlations were demonstrated between peak VO₂ and E/e’ (p < 0.001), peak VO₂ and dec t E (p < 0.001), VO₂ HR and E/e′ (p = 0.002) and between VE/VCO₂ and E/e′ (p < 0.001). Twenty patients with elevated LV filling pressure achieved significantly lower peak VO₂ (1624 vs. 1932 ml, p = 0.027) VO₂ HR (11.70 vs. 14.05, p = 0.011) and CP (287,073 vs. 361,719, p = 0.014). By using multivariate regression model we found that only E/e′ (p = 0.001) and dec t E (p = 0.008) significantly contributed to peak VO₂.ConclusionsDiastolic dysfunction, particularly LV filling pressure, determine exercise capacity, despite differences in LV ejection fraction in patients with prior MI.     

Gas Exchange and Ventilatory Efficiency During Exercise in Pulmonary Vascular Diseases

Background and ObjectiveVentilatory inefficiency (high V′_E/V′CO₂) and resting hypocapnia are common in pulmonary vascular disease and are associated with poor prognosis. Low resting PaCO₂ suggests increased chemosensitivity or an altered PaCO₂ set-point. We aimed to determine the relationships between exercise gas exchange variables reflecting the PaCO₂ set-point, exercise capacity, hemodynamics and V′_E/V′CO₂.MethodsPulmonary arterial hypertension (n = 34), chronic thromboembolic pulmonary hypertension (CTEPH, n = 19) and pulmonary veno-occlusive disease (PVOD, n = 6) patients underwent rest and peak exercise arterial blood gas measurements during cardiopulmonary exercise testing. Patients were grouped according to resting PaCO₂: hypocapnic (PaCO₂ ≤34 mmHg) or normocapnic (PaCO₂ 35–45 mmHg). The PaCO₂ set-point was estimated by the maximal value of end-tidal PCO₂ (maximal P_ETCO₂) between the anaerobic threshold and respiratory compensation point.ResultsThe hypocapnic group (n = 39) had lower resting cardiac index (3.1 ±0.8 vs. 3.7 ±0.7 L/min/m², p < 0.01), lower peak V′O₂ (15.8 ± 3.5 vs. 20.7 ± 4.3 mL/kg/min, p < 0.01), and higher V′_E/V′CO₂ slope (60.6 ± 17.6 vs. 38.2 ± 8.0, p < 0.01). At peak exercise, hypocapic patients had lower PaO₂, higher V_D/V_T and higher P_(a-ET)CO₂. Maximal P_ETCO₂ (r = 0.59) and V_D/V_T (r = −0.59) were more related to cardiac index than PaO₂ or PaCO₂ at rest or peak exercise. Maximal P_ETCO₂ was the strongest correlate of V′_E/V′CO₂ slope (r = −0.86), peak V′O₂ (r = 0.64) and peak work rate (r = 0.49).ConclusionsResting hypocapnia is associated with worse cardiac function, more ventilatory inefficiency and reduced exercise capacity. This could be explained by elevated chemosensitivity and lower PaCO₂ set-point. Maximal P_ETCO₂ may be a useful non-invasive marker of PaCO₂ setpoint and disease severity even with submaximal effort.     

Hemodynamic determinants of the abnormal cardiopulmonary exercise response in heart failure with preserved left ventricular ejection fraction

BackgroundThe cardiopulmonary exercise testing (CPET) response in heart failure with preserved left ventricular ejection fraction (HFPEF) is incompletely understood. We aimed to describe the CPET response in HFPEF and to assess its invasive hemodynamic determinants.Methods and ResultsTen patients with HFPEF and 8 asymptomatic controls underwent resting and exercise right heart catheterization and maximal symptom-limited CPET. The slope of the minute ventilation/carbon dioxide production relationship (VE/VCO₂ slope; 34.3 ± 5.4 vs. 28.4 ± 3.4; P = .02) was steeper, peak oxygen consumption (peak VO₂; 15.1 ± 4.9 vs. 26.6 ± 12.5 mL1kg^-11min^-1; P = .02) was lower, and heart rate recovery 1 minute after exercise termination (HRR-1; 10 ± 5 vs. 27 ± 10 beats/min; P < .001) was slower in HFPEF compared to controls. A steeper VE/VCO₂ slope (r = 0.67, P = .002), lower peak VO₂ (r = ?0.48, P = .04), and slower HRR-1 (r = ?0.58, P = .02) were significantly related to a higher ratio of the change in pulmonary capillary wedge pressure per change in work rate as a measure of the left ventricular pressure volume relationship.ConclusionsIn HFPEF patients, fundamental alterations in the CPET profile occur and these may, in part, result from the rapid rise in left ventricular filling pressures which accompanies exercise in these patients.     

Resting Physiological Correlates of Reduced Exercise Capacity in Smokers with Mild Airway Obstruction

Smokers with minor spirometric abnormalities can experience persistent activity-related dyspnea and exercise intolerance. Additional resting tests can expose heterogeneous physiological abnormalities, but their relevance and association with clinical outcomes remain uncertain. Subjects included sixty-two smokers (≥20 pack-years), with cough and/or dyspnea and minor airway obstruction [forced expiratory volume in one-second (FEV₁) ≥80% predicted and >5th percentile lower limit of normal (LLN) (i.e., z-score >?1.64) using the 2012-Global Lung Function Initiative equations]. They underwent spirometry, plethysmography, oscillometry, single-breath nitrogen washout, and symptom-limited incremental cycle exercise tests. Thirty-two age-matched nonsmoking controls were also studied. Thirty-three (53%) of smokers had chronic obstructive pulmonary disease by LLN criteria. In smokers [n = 62; age 65 ± 11 years; smoking history 43 ± 19 pack-years; post-bronchodilator FEV₁ z-score ?0.60 ± 0.72 and FEV₁/FVC z-score ?1.56 ± 0.87 (mean ± SD)] versus controls, peak oxygen uptake (?VO₂) was 21 ± 7 vs. 32 ± 9 ml/kg/min, and dyspnea/?VO₂ slopes were elevated (both p < 0.0001). Smokers had evidence of peripheral airway dysfunction and maldistribution of ventilation when compared to controls. In smokers versus controls: lung diffusing capacity for carbon monoxide (D_LCO) was 85 ± 22 vs. 105 ± 17% predicted, and residual volume (RV)/total lung capacity (TLC) was 36 ± 8 vs. 31 ± 6% (both p < 0.01). The strongest correlates of peak ?VO₂ were D_LCO% predicted (r = 0.487, p < 0.0005) and RV/TLC% (r = ?0.389, p = 0.002). D_LCO% predicted was also the strongest correlate of dyspnea/?VO₂ slope (r = ?0.352, p = 0.005). In smokers with mild airway obstruction, associations between resting tests of mechanics and pulmonary gas exchange and exercise performance parameters were weak, albeit consistent. Among these, DLCO showed the strongest association with important outcomes such as dyspnea and exercise intolerance measured during standardized incremental exercise tests.     

Measures of exercise capacity in adults with congenital heart disease

Background

Exercise capacity in grown-ups with congenital heart disease (GUCH) is mostly reported by peak oxygen consumption (peak VO₂). Our aim was to evaluate the maximal character of exercise tests, and to investigate submaximal measures of exercise capacity.

Methods

Adults with Coarctation of the Aorta (COA, n = 155), Tetralogy of Fallot (TOF, n = 98), dextro-Transposition of the Great Arteries (dTGA, n = 68) and Univentricular Heart (UVH, n = 10), and 122 healthy adults performed cardiopulmonary exercise testing until exhaustion. Gas exchange was measured breath by breath. The maximal performance of the test was evaluated by respiratory exchange ratio (RER), ventilatory equivalent for oxygen and Borg scale. Oxygen uptake efficiency slope (OUES), VE/VCO₂ slope and VO₂/WR slope were calculated and ventilatory anaerobic threshold (VAT) was defined. Correlations of these measures with peak VO₂ were calculated.

Results

GUCH showed significantly lower peak VO₂ than controls (p < 0.001), declining from 80% in COA, 74% in TOF, 64% in dTGA, to 55% in UVH. Compared to suggested criteria, mean peak RER and median Borg scale indicated a maximal effort in GUCH, however these results were significantly lower than controls (p < 0.05). OUES, VO₂/WR slope and VAT were significantly lower in patients compared to controls. OUES (r = 0.853) and VAT (r = 0.840) correlated best with peak VO₂; VO₂/WR slope (r = 0.551) and VE/VCO₂ slope (r = −0.421) correlated to a lesser degree (p < 0.001).

Conclusion

The investigated GUCH show reduced exercise tolerance compared to controls, related to the underlying heart defect. Different expressions of exercise tolerance clearly reveal the same differences in exercise capacity across groups of GUCH.     

A comparison of finger and forehead pulse oximeters in heart failure patients during maximal exercise

BackgroundPulse oximeters, clinically used to measure oxygen saturation (SpO₂), rely on adequate perfusion of the tissues over which they are placed. Heart failure (HF) patients can have impaired peripheral perfusion which may compromise the accuracy of a peripherally placed pulse oximeter. This decrease in peripheral perfusion may be especially apparent during exercise. The objective of this study was to determine if pulse oximeter accuracy is dependent on location in heart failure patients during peak exercise.Methods20 participants with HF (7F, age 64.±11 yr) and 9 participants with coronary artery disease as controls (CAD: 3F, age 66±5 yr) performed a maximal exertion treadmill exercise stress test while wearing both finger and forehead pulse oximeters.ResultsAt peak exercise, the two pulse oximeters measurements of SpO₂ differed from each other by 3.8 ± 3.3% in the HF group (p<0.01) and 2.0 ± 1.4% in the CAD group (p = 0.065). The difference between the pulse rate from the pulse oximeters and the heart rate from the 12-lead ECG in the HF group was 12±20 BPM (p<0.01) for the finger pulse oximeter, and 2 ± 3 BPM (p = 0.162) for the forehead pulse oximeter.ConclusionsForehead pulse oximeters may be more reliable compared to finger pulse oximeters in obtaining SpO₂ measurements in HF patients during a treadmill maximal exercise test.