Physiological and sensory consequences of exercise oscillatory ventilation in heart failure-COPD.

BACKGROUND: Exercise oscillatory ventilation (EOV) is associated with poor ventilatory efficiency and higher operating lung volumes in heart failure. These abnormalities may be particularly deleterious to dyspnea and exercise tolerance in mechanically-limited patients, e.g. those with coexistent COPD. METHODS: Ventilatory, gas exchange and sensory responses to incremental exercise were contrasted in 68 heart failure-COPD patients (12 EOV+). EOV was established by standard criteria. RESULTS: Compared to EOV-, EOV+ had lower exercise capacity, worse ventilatory inefficiency and higher peak dyspnea scores (p<0.05). Peak capillary PCO2 (PcCO2) was higher and end-tidal CO2 (PETCO2) was lower in EOV+. Thus, greater (i.e., more positive) P(c-ET)CO2 and dead space/tidal volume values were found in these patients compared to EOV- (p<0.05). Ventilatory inefficiency was related to increased dead space/tidal volume in EOV+ (r=0.74; p<0.01). Owing to higher operating lung volumes, inspiratory reserve volume (IRV) decreased to a greater extent in EOV+. Tidal volume oscillations consistently ceased when a "critical" IRV was reached (~0.3-0.5L); thereafter, PcCO2 stabilized or increased and dyspnea scores rose sharply. Exercise capacity was closely related to IRV decrements and peak dyspnea in EOV+ (r=-0.78 and 0.84, respectively; p<0.01). CONCLUSIONS: Dyspnea and exercise tolerance are negatively influenced by EOV in heart failure patients presenting with COPD as co-morbidity. Pharmacological and non-pharmacological interventions known to decrease EOV might prove particularly valuable to mitigate symptom burden and exercise intolerance in this specific heart failure group.

Exercise Ventilation in COPD: Influence of Systolic Heart Failure.

Systolic heart failure is a common and disabling co-morbidity of chronic obstructive pulmonary disease (COPD) which may increase exercise ventilation due to heightened neural drive and/or impaired pulmonary gas exchange efficiency. The influence of heart failure on exercise ventilation, however, remains poorly characterized in COPD. In a prospective study, 98 patients with moderate to very severe COPD [41 with coexisting heart failure; 'overlap' (left ventricular ejection fraction < 50%)] underwent an incremental cardiopulmonary exercise test (CPET). Compared to COPD, overlap had lower peak exercise capacity despite higher FEV1. Overlap showed lower operating lung volumes, greater ventilatory inefficiency and larger decrements in end-tidal CO2 (PETCO2) (P < 0.05). These results were consistent with those found in FEV1-matched patients. Larger areas under receiver operating characteristic curves to discriminate overlap from COPD were found for ventilation ([Formula: see text]E)-CO2 output [Formula: see text]CO2) intercept, [Formula: see text]E-[Formula: see text]CO2 slope, peak [Formula: see text]E/[Formula: see text]CO2 ratio and peak PETCO2. Multiple logistic regression analysis revealed that [Formula: see text]CO2 intercept ≤ 3.5 L/minute [odds ratios (95% CI) = 7.69 (2.61-22.65), P < 0.001] plus [Formula: see text]E-[Formula: see text]CO2 slope ≥ 34 [2.18 (0.73-6.50), P = 0.14] or peak [Formula: see text]E/[Formula: see text]CO2 ratio ≥ 37 [5.35 (1.96-14.59), P = 0.001] plus peak PETCO2 ≤ 31 mmHg [5.73 (1.42-23.15), P = 0.01] were indicative of overlapping. Heart failure increases the ventilatory response to metabolic demand in COPD. Variables reflecting excessive ventilation might prove useful to assist clinical interpretation of CPET responses in COPD patients presenting heart failure as co-morbidity.

Heart Failure Impairs Muscle Blood Flow and Endurance Exercise Tolerance in COPD.

Heart failure, a prevalent and disabling co-morbidity of COPD, may impair cardiac output and muscle blood flow thereby contributing to exercise intolerance. To investigate the role of impaired central and peripheral hemodynamics in limiting exercise tolerance in COPD-heart failure overlap, cycle ergometer exercise tests at 20% and 80% peak work rate were performed by overlap (FEV1 = 56.9 ± 15.9% predicted, ejection fraction = 32.5 ± 6.9%; N = 16), FEV1-matched COPD (N = 16), ejection fraction-matched heart failure patients (N = 15) and controls (N = 12). Differences (Δ) in cardiac output (impedance cardiography) and vastus lateralis blood flow (indocyanine green) and deoxygenation (near-infrared spectroscopy) between work rates were expressed relative to concurrent changes in muscle metabolic demands (ΔO2 uptake). Overlap patients had approximately 30% lower endurance exercise tolerance than COPD and heart failure (p < 0.05). ΔBlood flow was closely proportional to Δcardiac output in all groups (r = 0.89-0.98; p < 0.01). Overlap showed the largest impairments in Δcardiac output/ΔO2 uptake and Δblood flow/ΔO2 uptake (p < 0.05). Systemic arterial oxygenation, however, was preserved in overlap compared to COPD. Blunted limb perfusion was related to greater muscle deoxygenation and lactate concentration in overlap (r = 0.78 and r = 0.73, respectively; p < 0.05). ΔBlood flow/ΔO2 uptake was related to time to exercise intolerance only in overlap and heart failure (p < 0.01). In conclusion, COPD and heart failure add to decrease exercising cardiac output and skeletal muscle perfusion to a greater extent than that expected by heart failure alone. Treatment strategies that increase muscle O2 delivery and/or decrease O2 demand may be particularly helpful to improve exercise tolerance in COPD patients presenting heart failure as co-morbidity.

Effects of heart failure on cerebral blood flow in COPD: Rest and exercise.

Cerebral blood flow (CBF) and oxygenation (COx) are generally well-preserved in COPD. It is unknown whether prevalent cardiovascular co-morbidities, such as heart failure, may impair CBF and COx responses to exertion. Eighteen males with moderate-to-severe COPD (8 with and 10 without overlapping heart failure) underwent a progressive exercise test with pre-frontal CBF and COx measurements (indocyanine green and near-infrared spectroscopy). Mean arterial pressure and cardiac output were lower from rest to exercise in overlap. Only COPD patients demonstrated an increase in arterialized PCO2 towards the end of progressive exercise. CBF index was consistently higher and increased further by ∼40% during exercise in COPD whereas a ∼10% reduction was observed in overlap. COx was lower in overlap despite preserved arterial oxygenation. In conclusion, heart failure introduces pronounced negative effects on CBF and COx in COPD which may be associated with clinically relevant outcomes, including dyspnea, exercise intolerance, cerebrovascular disease and cognitive impairment.

Exercise ventilation in COPD: influence of systolic heart failure

Systolic heart failure is a common and disabling co-morbidity of chronic obstructive pulmonary disease (COPD) which may increase exercise ventilation due to heightened neural drive and/or impaired pulmonary gas exchange efficiency. The influence of heart failure on exercise ventilation, however, remains poorly characterized in COPD. In a prospective study, 98 patients with moderate to very severe COPD [41 with coexisting heart failure; 'overlap' (left ventricular ejection fraction < 50%)] underwent an incremental cardiopulmonary exercise test (CPET). Compared to COPD, overlap had lower peak exercise capacity despite higher FEV1. Overlap showed lower operating lung volumes, greater ventilatory inefficiency and larger decrements in end-tidal CO2 (PETCO2) (P < 0.05). These results were consistent with those found in FEV1-matched patients. Larger areas under receiver operating characteristic curves to discriminate overlap from COPD were found for ventilation ([Formula: see text]E)-CO2 output [Formula: see text]CO2) intercept, [Formula: see text]E-[Formula: see text]CO2 slope, peak [Formula: see text]E/[Formula: see text]CO2 ratio and peak PETCO2. Multiple logistic regression analysis revealed that [Formula: see text]CO2 intercept ≤ 3.5 L/minute [odds ratios (95% CI) = 7.69 (2.61-22.65), P < 0.001] plus [Formula: see text]E-[Formula: see text]CO2 slope ≥ 34 [2.18 (0.73-6.50), P = 0.14] or peak [Formula: see text]E/[Formula: see text]CO2 ratio ≥ 37 [5.35 (1.96-14.59), P = 0.001] plus peak PETCO2 ≤ 31 mmHg [5.73 (1.42-23.15), P = 0.01] were indicative of overlapping...

Effects of heart failure on cerebral blood flow in COPD: Rest and exercise

Cerebral blood flow (CBF) and oxygenation (COx) are generally well-preservedin COPD. It is unknown whether prevalent cardiovascular co-morbidities, suchas heart failure, may impair CBF and COx responses to exertion. Eighteen maleswith moderate-to-severe COPD (8 with and 10 without overlapping heart failure)underwent a progressive exercise test with pre-frontal CBF and COxmeasurements (indocyanine green and near-infrared spectroscopy). Meanarterial pressure and cardiac output were lower from rest to exercise in overlap. Only COPD patients demonstrated an increase in arterialized PCO2 towards theend of progressive exercise. CBF index was consistently higher and increasedfurther by ~40% during exercise in COPD whereas a ~10% reduction wasobserved in overlap. COx was lower in overlap despite preserved arterialoxygenation. In conclusion, heart failure introduces pronounced negative effectson CBF and COx in COPD which may be associated with clinically relevantoutcomes, including dyspnea, exercise intolerance, cerebrovascular disease and cognition...

Heart Failure Impairs Muscle Blood Flow and Endurance Exercise Tolerance in COPD

Heart failure, a prevalent and disabling co-morbidity of COPD, may impair cardiac output and muscle blood flow there by contributing to exercise intolerance. To investigate the role of impaired central and peripheral hemodynamics in limiting exercise tolerance in COPD-heart failure overlap, cycle ergometer exercise tests at20% and 80% peak work rate were performed by overlap (FEV1 = 56.9 ± 15.9% predicted, ejection fraction =32.5 ± 6.9%; N = 16), FEV1-matched COPD (N = 16), ejection fraction-matched heart failure patients (N =15) and controls (N = 12). Differences () in cardiac output (impedance cardiography) and vastus lateralis blood flow (indocyanine green) and deoxygenation (near-infrared spectroscopy) between work rates were expressed relative to concurrent changes in muscle metabolic demands (O2 uptake). Overlap patientshad approximately 30% lower endurance exercise tolerance than COPD and heart failure (p < 0.05). Blood flow was closely proportional to cardiac output in all groups (r = 0.89–0.98; p < 0.01). Overlap showedthe largest impairments in cardiac output/O2 uptake and blood flow/O2 uptake (p < 0.05). Systemicarterial oxygenation, however, was preserved in overlap compared to COPD. Blunted limb perfusion wasrelated to greater muscle deoxygenation and lactate concentration in overlap (r = 0.78 and r = 0.73, respectively;p < 0.05). Blood flow/O2 uptake was related to time to exercise intolerance only in overlap andheart failure (p < 0.01). In conclusion, COPD and heart failure add to decrease exercising cardiac output andskeletal muscle perfusion to a greater extent than that expected by heart failure alone. Treatment strategiesthat increase muscle O2 delivery and/or decrease O2 demand may be particularly helpful to improveexercise tolerance in COPD patients presenting heart failure as co-morbidity...

Does exercise ventilatory inefficiency predict poor outcome in heart failure patients with COPD?

To investigate whether the opposite effects of heart failure (HF) and chronic obstructive pulmonary disease (COPD) on exercise ventilatory inefficiency (minute ventilation [(Equation is included in full-text article.)E]-carbon dioxide output [(Equation is included in full-text article.)CO2] relationship) would negatively impact its prognostic relevance. METHODS: After treatment optimization and an incremental cardiopulmonary exercise test, 30 male patients with HF-COPD (forced expiratory volume in 1 second [FEV1] = 57% ± 17% predicted, ejection fraction = 35% ± 6%) were prospectively followed up during 412 ± 261 days for major cardiac events.RESULTS:Fourteen patients (46%) had a negative outcome. Patients who had an event had lower echocardiographically determined right ventricular fractional area change (RVFAC), greater ventilatory inefficiency (higher (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir), and lower end-tidal CO2 (PETCO2) (all P 36, ΔPETCO2(PEAK-REST)≥2 mm Hg, and PETCO2PEAK≤33 mm Hg added prognostic value to RVFAC≤45%. Kaplan-Meyer analyses showed that although 18% of patients with RVFAC>45% had a major cardiac event after 1 year, no patient with RVFAC>45% and (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir ≤36 (or PETCO2PEAK>33 mm Hg) had a negative event. Conversely, although 69% of patients with RVFAC≤45% had a major cardiac event after 1 year, all patients with RVFAC≤45% and ΔPETCO2(PEAK-REST)≥2 mm Hg had a negative event...

Sildenafil improves skeletal muscle oxygenation during exercise in men with intermittent claudication.

Endothelial dysfunction caused by defective nitric oxide (NO) signaling plays a pivotal role in the pathogenesis of intermittent claudication (IC). In the present study, we evaluated the acute effects of sildenafil, a phosphodiesterase type 5 inhibitor that acts by prolonging NO-mediated cGMP signaling in vascular smooth muscle, on blood pressure (BP), skeletal muscle oxygenation, and walking tolerance in patients with IC. A randomized, double-blind, crossover study was conducted in which 12 men with stable IC received two consecutive doses of 50 mg of sildenafil or matching placebo and underwent a symptom-limited exercise test on the treadmill. Changes in gastrocnemius deoxy-hemoglobin by near-infrared spectroscopy estimated peripheral muscle O2 delivery-to-utilization matching. Systolic BP was significantly lower during the sildenafil trial relative to placebo during supine rest (∼15 mmHg), submaximal exercise (∼14 mmHg), and throughout recovery (∼18 mmHg) (P < 0.05). Diastolic BP was also lower after sildenafil during upright rest (∼6 mmHg) and during recovery from exercise (∼7 mmHg) (P < 0.05). Gastrocnemius deoxygenation was consistently reduced during submaximal exercise (∼41%) and at peak exercise (∼34%) following sildenafil compared with placebo (P < 0.05). However, pain-free walking time (placebo: 335 ± 42 s vs. sildenafil: 294 ± 35 s) and maximal walking time (placebo: 701 ± 58 s vs. sildenafil: 716 ± 62 s) did not differ between trials. Acute administration of sildenafil lowers BP and improves skeletal muscle oxygenation during exercise but does not enhance walking tolerance in patients with IC. Whether the beneficial effects of sildenafil on muscle oxygenation can be sustained over time and translated into positive clinical outcomes deserve further consideration in this patient population.

Does impaired O2 delivery during exercise accentuate central and peripheral fatigue in patients with coexistent COPD-CHF?

Impairment in oxygen (O2) delivery to the central nervous system ("brain") and skeletal locomotor muscle during exercise has been associated with central and peripheral neuromuscular fatigue in healthy humans. From a clinical perspective, impaired tissue O2 transport is a key pathophysiological mechanism shared by cardiopulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). In addition to arterial hypoxemic conditions in COPD, there is growing evidence that cerebral and muscle blood flow and oxygenation can be reduced during exercise in both isolated COPD and CHF. Compromised cardiac output due to impaired cardiopulmonary function/interactions and blood flow redistribution to the overloaded respiratory muscles (i.e., ↑work of breathing) may underpin these abnormalities. Unfortunately, COPD and CHF coexist in almost a third of elderly patients making these mechanisms potentially more relevant to exercise intolerance. In this context, it remains unknown whether decreased O2 delivery accentuates neuromuscular manifestations of central and peripheral fatigue in coexistent COPD-CHF. If this holds true, it is conceivable that delivering a low-density gas mixture (heliox) through non-invasive positive pressure ventilation could ameliorate cardiopulmonary function/interactions and reduce the work of breathing during exercise in these patients. The major consequence would be increased O2 delivery to the brain and active muscles with potential benefits to exercise capacity (i.e., ↓central and peripheral neuromuscular fatigue, respectively). We therefore hypothesize that patients with coexistent COPD-CHF stop exercising prematurely due to impaired central motor drive and muscle contractility as the cardiorespiratory system fails to deliver sufficient O2 to simultaneously attend the metabolic demands of the brain and the active limb muscles.