Heart failure worsens leg muscle strength and endurance in coexistence patients with COPD and heart failure reduced ejection fraction.

PURPOSE: Exercise intolerance and dyspnoea are clinical symptoms in both heart failure (HF) reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD), which are suggested to be associated with musculoskeletal dysfunction. We tested the hypothesis that HFrEF + COPD patients would present lower muscle strength and greater fatigue compared to compared to the COPD group. METHODS: We included 25 patients with HFrEF + COPD (100% male, age 67.8 ± 6.9) and 25 patients with COPD alone (100% male, age 66.1 ± 9.1). In both groups, COPD severity was determined as moderate-to-severe according to the GOLD classification (FEV1/FVC < 0.7 and predicted post-bronchodilator FEV1 between 30%-80%). Knee flexor-extensor muscle performance (torque, work, power and fatigue) were measured by isokinetic dynamometry in age and sex-matched patients with HFrEF + COPD and COPD alone; Functional capacity was assessed by the cardiopulmonary exercise test, the 6-min walk test (6MWT) and the four-minute step test. RESULTS: The COPD group exhibited reduced lung function compared to the HFrEF + COPD group, as evidenced by lower FEV1/FVC (58.0 ± 4.0 vs. 65.5 ± 13.9; p < 0.0001, respectively) and FEV1 (51.3 ± 17.0 vs. 62.5 ± 17.4; p = 0.026, respectively) values. Regarding musculoskeletal function, the HFrEF + COPD group showed a knee flexor muscles impairment, however this fact was not observed in the knee extensors muscles. Power peak of the knee flexor corrected by muscle mass was significantly correlated with the 6MWT (r = 0.40; p < 0.05), number of steps (r = 0.30; p < 0.05) and work ratepeak (r = 0.40; p < 0.05) in the HFrEF + COPD and COPD groups. CONCLUSION: The presence of HFrEF in patients with COPD worsens muscular weakness when compared to isolated COPD.

Exercise intolerance in comorbid COPD and heart failure: the role of impaired aerobic function.

Impaired aerobic function is a potential mechanism of exercise intolerance in patients with combined cardiorespiratory disease. We investigated the pathophysiological and sensory consequences of a low change in oxygen uptake (ΔV'O2 )/change in work rate (ΔWR) relationship during incremental exercise in patients with coexisting chronic obstructive pulmonary disease (COPD) and systolic heart failure (HF).After clinical stabilisation, 51 COPD-HF patients performed an incremental cardiopulmonary exercise test to symptom limitation. Cardiac output was non-invasively measured (impedance cardiography) in a subset of patients (n=18).27 patients presented with ΔV'O2 /ΔWR below the lower limit of normal. Despite similar forced expiratory volume in 1 s and ejection fraction, the low ΔV'O2 /ΔWR group showed higher end-diastolic volume, lower inspiratory capacity and lower transfer factor compared to their counterparts (p<0.05). Peak WR and peak V'O2 were ∼15% and ∼30% lower, respectively, in the former group: those findings were associated with greater symptom burden in daily life and at a given exercise intensity (leg discomfort and dyspnoea). The low ΔV'O2 /ΔWR group presented with other evidences of impaired aerobic function (sluggish V'O2 kinetics, earlier anaerobic threshold) and cardiocirculatory performance (lower oxygen pulse, lower stroke volume and cardiac output) (p<0.05). Despite similar exertional hypoxaemia, they showed worse ventilatory inefficiency and higher operating lung volumes, which led to greater mechanical inspiratory constraints (p<0.05).Impaired aerobic function due to negative cardiopulmonary-muscular interactions is an important determinant of exercise intolerance in patients with COPD-HF. Treatment strategies to improve oxygen delivery to and/or utilisation by the peripheral muscles might prove particularly beneficial to these patients.

Excess ventilation in COPD: Implications for dyspnoea and tolerance to interval exercise.

Interval exercise delays critical mechanical-ventilatory constraints with positive consequences on Dyspnoea and exercise tolerance in COPD. We hypothesized that those advantages of interval exercise would be partially off-set in patients showing excessive ventilation (V˙E) to metabolic demand (V˙CO2). Sixteen men (FEV1 = 42.3 ±â€¯8.9%) performed, on different days, 30 s and 60 s bouts at 100% peak (on) interspersed by moderate exercise at 40% (off). Nine patients did not sustain exercise for 30 min irrespective of on duration. They presented with higher V˙E/V˙CO2 nadir (35 ±â€¯3 vs. 30 ±â€¯5) and dead space/tidal volume (0.39 ±â€¯0.05 vs. 0.34 ±â€¯0.06) compared to their counterparts (p < 0.05). [Lactate], operating lung volumes and symptom burden (dyspnoea and leg effort) were also higher (p < 0.05). Unloading off decreased the metabolic-ventilatory demands, thereby allowing 7/9 patients to exercise for 30 min. Increased wasted ventilation accelerates the rate at which critical mechanical constraints and limiting dyspnoea are reached during interval exercise in patients with COPD.

Are heart rate dynamics in the transition from rest to submaximal exercise related to maximal cardiorespiratory responses in COPD?

BACKGROUND: Poor exercise capacity is an important negative prognostic marker in patients with chronic obstructive pulmonary disease (COPD). Heart rate variability (HRV) responses can indicate alterations in cardiac autonomic control. Nevertheless, it remains unclear whether these abnormalities are related to cardiorespiratory responses to exercise in these patients. OBJECTIVE: To evaluate whether HRV at rest and submaximal exercise are related to impaired cardiopulmonary responses to exercise in COPD patients. METHODS: Fifteen men (66.2±8.7 years) with COPD (FEV1: 55.1±19.2%) were assessed. The R-R interval (RRi) data collection was performed at rest (stand position) and during the six-minute walk test (6MWT). All patients performed a symptom-limited cardiopulmonary exercise test on a cycle ergometer. The HRV changes from rest to submaximal exercise (Δ rest-6MWT) were calculated. RESULTS: We found significant correlations between low frequency (LF) and high frequency (HF) Δ rest-6MWT with Δ oxyhemoglobin saturation by pulse oximetry (r=-0.64 and r=0.65, respectively; p<0.05), minute ventilation/carbon dioxide output relationship from beginning to peak exercise (r=-0.52 and r=0.53, p<0.05), and exercise ventilatory power (r=0.52 and r=-0.53, p<0.05). Interestingly, there was a strong positive correlation (r=0.82, p<0.05) between six-minute walk distance (6MWD) and Δ LF/HF from rest to exercise. CONCLUSION: HRV analysis in the transition from rest to submaximal exercise is associated with exercise ventilatory and hemodynamic abnormalities in COPD patients. Rehabilitative strategies to improve HRV responses may provide an important tool to clinical practice in these patients.

Influence of heart failure on resting lung volumes in patients with COPD.

OBJECTIVE:: To evaluate the influence of chronic heart failure (CHF) on resting lung volumes in patients with COPD, i.e., inspiratory fraction-inspiratory capacity (IC)/TLC-and relative inspiratory reserve-[1 - (end-inspiratory lung volume/TLC)]. METHODS:: This was a prospective study involving 56 patients with COPD-24 (23 males/1 female) with COPD+CHF and 32 (28 males/4 females) with COPD only-who, after careful clinical stabilization, underwent spirometry (with forced and slow maneuvers) and whole-body plethysmography. RESULTS:: Although FEV1, as well as the FEV1/FVC and FEV1/slow vital capacity ratios, were higher in the COPD+CHF group than in the COPD group, all major "static" volumes-RV, functional residual capacity (FRC), and TLC-were lower in the former group (p < 0.05). There was a greater reduction in FRC than in RV, resulting in the expiratory reserve volume being lower in the COPD+CHF group than in the COPD group. There were relatively proportional reductions in FRC and TLC in the two groups; therefore, IC was also comparable. Consequently, the inspiratory fraction was higher in the COPD+CHF group than in the COPD group (0.42 ± 0.10 vs. 0.36 ± 0.10; p < 0.05). Although the tidal volume/IC ratio was higher in the COPD+CHF group, the relative inspiratory reserve was remarkably similar between the two groups (0.35 ± 0.09 vs. 0.44 ± 0.14; p < 0.05). CONCLUSIONS:: Despite the restrictive effects of CHF, patients with COPD+CHF have relatively higher inspiratory limits (a greater inspiratory fraction). However, those patients use only a part of those limits, probably in order to avoid critical reductions in inspiratory reserve and increases in elastic recoil. OBJETIVO:: Avaliar a influência da insuficiência cardíaca crônica (ICC) nos volumes pulmonares de repouso em pacientes com DPOC, ou seja, fração inspiratória -capacidade inspiratória (CI)/CPT - e reserva inspiratória relativa - [1 - (volume pulmonar inspiratório final/CPT)]. MÉTODOS:: Após cuidadosa estabilização clínica, 56 pacientes com DPOC (24 alocados no grupo DPOC+ICC; 23 homens/1 mulher) e 32 (28 homens/4 mulheres) com DPOC isolada foram submetidos à espirometria forçada e lenta e pletismografia de corpo inteiro. RESULTADOS:: Os pacientes do grupo DPOC+ICC apresentaram maior VEF1, VEF1/CVF e VEF1/capacidade vital lenta; porém, todos os principais volumes "estáticos" - VR, capacidade residual funcional (CRF) e CPT - foram menores que aqueles do grupo DPOC (p < 0,05). A CRF diminuiu mais do que o VR, determinando assim menor volume de reserva expiratória no grupo DPOC+ICC que no grupo DPOC. Houve redução relativamente proporcional da CRF e da CPT nos dois grupos; logo, a CI também foi similar. Consequentemente, a fração inspiratória no grupo DPOC+ICC foi maior que no grupo DPOC (0,42 ± 0,10 vs. 0,36 ± 0,10; p < 0,05). Embora a razão volume corrente/CI fosse maior no grupo DPOC+ICC, a reserva inspiratória relativa foi notadamente similar entre os grupos (0,35 ± 0,09 vs. 0,44 ± 0,14; p < 0,05). CONCLUSÕES:: Apesar dos efeitos restritivos da ICC, pacientes com DPOC+ICC apresentam elevações relativas dos limites inspiratórios (maior fração inspiratória). Entretanto, esses pacientes utilizam apenas parte desses limites, com o provável intuito de evitar reduções críticas da reserva inspiratória e maior trabalho elástico.

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.

Influence of heart failure on resting lung volumes in patients with COPD / Influência da insuficiência cardíaca nos volumes pulmonares de repouso em pacientes com DPOC

ABSTRACT Objective: To evaluate the influence of chronic heart failure (CHF) on resting lung volumes in patients with COPD, i.e., inspiratory fraction-inspiratory capacity (IC)/TLC-and relative inspiratory reserve-[1 − (end-inspiratory lung volume/TLC)]. Methods: This was a prospective study involving 56 patients with COPD-24 (23 males/1 female) with COPD+CHF and 32 (28 males/4 females) with COPD only-who, after careful clinical stabilization, underwent spirometry (with forced and slow maneuvers) and whole-body plethysmography. Results: Although FEV1, as well as the FEV1/FVC and FEV1/slow vital capacity ratios, were higher in the COPD+CHF group than in the COPD group, all major "static" volumes-RV, functional residual capacity (FRC), and TLC-were lower in the former group (p < 0.05). There was a greater reduction in FRC than in RV, resulting in the expiratory reserve volume being lower in the COPD+CHF group than in the COPD group. There were relatively proportional reductions in FRC and TLC in the two groups; therefore, IC was also comparable. Consequently, the inspiratory fraction was higher in the COPD+CHF group than in the COPD group (0.42 ± 0.10 vs. 0.36 ± 0.10; p < 0.05). Although the tidal volume/IC ratio was higher in the COPD+CHF group, the relative inspiratory reserve was remarkably similar between the two groups (0.35 ± 0.09 vs. 0.44 ± 0.14; p < 0.05). Conclusions: Despite the restrictive effects of CHF, patients with COPD+CHF have relatively higher inspiratory limits (a greater inspiratory fraction). However, those patients use only a part of those limits, probably in order to avoid critical reductions in inspiratory reserve and increases in elastic recoil.

RESUMO Objetivo: Avaliar a influência da insuficiência cardíaca crônica (ICC) nos volumes pulmonares de repouso em pacientes com DPOC, ou seja, fração inspiratória -capacidade inspiratória (CI)/CPT - e reserva inspiratória relativa - [1 − (volume pulmonar inspiratório final/CPT)]. Métodos: Após cuidadosa estabilização clínica, 56 pacientes com DPOC (24 alocados no grupo DPOC+ICC; 23 homens/1 mulher) e 32 (28 homens/4 mulheres) com DPOC isolada foram submetidos à espirometria forçada e lenta e pletismografia de corpo inteiro. Resultados: Os pacientes do grupo DPOC+ICC apresentaram maior VEF1, VEF1/CVF e VEF1/capacidade vital lenta; porém, todos os principais volumes "estáticos" - VR, capacidade residual funcional (CRF) e CPT - foram menores que aqueles do grupo DPOC (p < 0,05). A CRF diminuiu mais do que o VR, determinando assim menor volume de reserva expiratória no grupo DPOC+ICC que no grupo DPOC. Houve redução relativamente proporcional da CRF e da CPT nos dois grupos; logo, a CI também foi similar. Consequentemente, a fração inspiratória no grupo DPOC+ICC foi maior que no grupo DPOC (0,42 ± 0,10 vs. 0,36 ± 0,10; p < 0,05). Embora a razão volume corrente/CI fosse maior no grupo DPOC+ICC, a reserva inspiratória relativa foi notadamente similar entre os grupos (0,35 ± 0,09 vs. 0,44 ± 0,14; p < 0,05). Conclusões: Apesar dos efeitos restritivos da ICC, pacientes com DPOC+ICC apresentam elevações relativas dos limites inspiratórios (maior fração inspiratória). Entretanto, esses pacientes utilizam apenas parte desses limites, com o provável intuito de evitar reduções críticas da reserva inspiratória e maior trabalho elástico.

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.

Using the Human Activity Profile to Assess Functional Performance in Heart Failure.

PURPOSE: To investigate (1) the validity of using the Human Activity Profile (HAP) in patients with heart failure (HF) to estimate functional capacity; (2) the association between the HAP and 6-Minute Walk Test (6MWT) distance; and (3) the ability of the HAP to differentiate between New York Heart Association (NYHA) functional classes. METHODS: In a cross-sectional study, we evaluated 62 clinically stable patients with HF (mean age, 47.98 years; NYHA class I-III). Variables included maximal functional capacity as measured by peak oxygen uptake ((Equation is included in full-text article.)O2) using a cardiopulmonary exercise test (CPET), peak (Equation is included in full-text article.)O2 as estimated by the HAP, and exercise capacity as measured by the 6MWT. RESULTS: The difference between the measured (CPET) and estimated (HAP) peak (Equation is included in full-text article.)O2 against the average values showed a bias of 2.18 mL/kg/min (P = .007). No agreement was seen between these measures when applying the Bland-Altman method. Peak (Equation is included in full-text article.)O2 in the HAP showed a moderate association with the 6MWT distance (r = 0.62; P < .0001). Peak (Equation is included in full-text article.)O2 in the HAP was able to statistically differentiate NYHA functional classes I, II, and III (P < .05). CONCLUSIONS: The estimated peak (Equation is included in full-text article.)O2 using the HAP was not concordant with the gold standard CPET measure. On the contrary, the HAP was able to differentiate NYHA functional class associated with the 6MWT distance; therefore, the HAP is a useful tool for assessing functional performance in patients with HF.

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...

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...

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...

Cerebral microvascular blood flow and CO2 reactivity in pulmonary arterial hypertension

Hypocapnia and endothelial dysfunction might impair microvascular cerebral blood flow (CBFmicr) and cerebrovascular reactivity to CO2 (CVRCO2). Pulmonary arterial hypertension (PAH) is characteristical lyassociated with chronic alveolar hyperventilation and microvascular endothelial dysfunction. We therefore determined CBFmicr (pre-frontal blood flow index (BFI) by the indocyanine green-near infrared spectroscopy methodology) during hypocapnia and hypercapnia in 25 PAH patients and 10 gender- andage-matched controls. Cerebral BFI was lower in patients than controls at similar transcutaneous PCO2(PtcCO2) levels in both testing conditions. In fact, while BFI increased from hypocapnia to hypercapnia inall controls, itfailed to increase in 17/25 (68%) patients. Thus, BFI increased to a lesser extentfrom hypo tohypercapnia (“”) in patients, i.e., they showed lower BFI/ PtcCO2 ratios than controls. In conclusion,CBFmicr and CVRCO2 are lessened in clinically stable, mildly-impaired patients with PAH. These abnormalities might be associated with relevant clinical outcomes (hyperventilation and dyspnea, cognition,cerebrovascular disease) being potentially amenable to pharmacological treatment...

Relationship between linear and nonlinear dynamics of heart rate and impairment of lung function in COPD patients.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), functional and structural impairment of lung function can negatively impact heart rate variability (HRV); however, it is unknown if static lung volumes and lung diffusion capacity negatively impacts HRV responses. We investigated whether impairment of static lung volumes and lung diffusion capacity could be related to HRV indices in patients with moderate to severe COPD. METHODS: Sixteen sedentary males with COPD were enrolled in this study. Resting blood gases, static lung volumes, and lung diffusion capacity for carbon monoxide (DLCO) were measured. The RR interval (RRi) was registered in the supine, standing, and seated positions (10 minutes each) and during 4 minutes of a respiratory sinus arrhythmia maneuver (M-RSA). Delta changes (Δsupine-standing and Δsupine-M-RSA) of the standard deviation of normal RRi, low frequency (LF, normalized units [nu]) and high frequency (HF [nu]), SD1, SD2, alpha1, alpha2, and approximate entropy (ApEn) indices were calculated. RESULTS: HF, LF, SD1, SD2, and alpha1 deltas significantly correlated with forced expiratory volume in 1 second, DLCO, airway resistance, residual volume, inspiratory capacity/total lung capacity ratio, and residual volume/total lung capacity ratio. Significant and moderate associations were also observed between LF/HF ratio versus total gas volume (%), r=0.53; LF/HF ratio versus residual volume, %, r=0.52; and HF versus total gas volume (%), r=-0.53 (P<0.05). Linear regression analysis revealed that ΔRRi supine-M-RSA was independently related to DLCO (r=-0.77, r (2)=0.43, P<0.05). CONCLUSION: Responses of HRV indices were more prominent during M-RSA in moderate to severe COPD. Moreover, greater lung function impairment was related to poorer heart rate dynamics. Finally, impaired lung diffusion capacity was related to an altered parasympathetic response in these patients.

Exercise ventilatory inefficiency in mild to end-stage COPD.

Ventilatory inefficiency during exercise is a key pathophysiological feature of chronic obstructive pulmonary disease. Currently, it is unknown how this physiological marker relates to clinically relevant outcomes as resting ventilatory impairment progresses across disease stages. Slope and intercept of the linear region of the ventilation-carbon dioxide output relationship and the ratio between these variables, at the lowest point (nadir), were contrasted in 316 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-4 (forced expiratory volume in 1 s, ranging from 148% pred to 12% pred) and 69 aged- and gender-matched controls, Compared to controls, slope and intercept were higher in GOLD stages 1 and 2, leading to higher nadirs (p<0.05). Despite even larger intercepts in GOLD stages 3 and 4, slopes diminished as disease evolved (from mean±sd 35±6 in GOLD stage 1 to 24±5 in GOLD stage 3, p<0.05). As a result, there were no significant differences in nadirs among patient groups. Higher intercepts, across all stages (p<0.01), and to a lesser extent lower slopes in GOLD stages 2-4 (p<0.05), were related to greater mechanical constraints, worsening pulmonary gas exchange, higher dyspnoea scores, and poorer exercise capacity. Increases in the ventilation intercept best indicate the progression of exercise ventilatory inefficiency across the whole spectrum of chronic obstructive pulmonary disease severity.