Maria Clara Alencar

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. Exercise ventilatory inefficiency relates to dyspnoea and exercise intolerance across whole COPD severity spectrum http://ow.ly/CpWLj

A randomized trial of the effects of exercise training in Chagas cardiomyopathy

The effects of exercise training in chronic heart failure are well established, however, they have not been evaluated in Chagas cardiomyopathy (ChC). We sought to determine the effects of exercise training on functional capacity, health‐related quality of life (HQoL), and brain natriuretic peptide (BNP) levels in patients with ChC.

Impact of chronic obstructive pulmonary disease on exercise ventilatory efficiency in heart failure

BACKGROUND Heart failure (HF) and chronic obstructive pulmonary disease (COPD) coexistence increases morbidity and mortality. The intercept of ventilation (VEint) on the VE vs. carbon dioxide production (VCO2) relationship during exercise has been found to vary in proportion with dead space (VD) in HF. Considering that increased VD is the key pathophysiological abnormality in COPD but a secondary finding in HF we hypothesized that a high VEint would be useful in suggesting COPD as HF co-morbidity. Our aim was to assess whether an elevated VEint suggests the presence of COPD in HF. METHODS In a multicenter retrospective study, the VE-VCO2 relationship was analyzed both as slope and intercept in HF (n = 108), HF-COPD (n = 106) and COPD (n = 95). Patients with pulmonary arterial hypertension (PAH) (n = 85) and healthy subjects (HF) (n = 56) served as positive and negative controls relative to VE-VCO2 abnormalities, respectively. RESULTS Slope and VEint varied in opposite directions in all groups (p < 0.05) being VE-VCO2 slope highest and lowest in PAH and healthy subjects, respectively. No slope differences were observed among HF, HF-COPD and COPD (32 ± 7, 31 ± 7, and 31 ± 6, respectively). VEint was higher in HF-COPD and COPD compared to HF, PAH and controls (4.8 ± 2.4 L/min, 5.9 ± 3.0 L/min, 3.0 ± 2.6L/min, 2.3 ± 3.3 L/min and 3.9 ± 2.5L/min, respectively; p < 0.01). A VEint ≥ 4.07 L/min identified patients with high probability of having COPD or HF-COPD (sensitivity of 71.6% and specificity of 72.0%). CONCLUSION These data provide novel evidence that a high VEint (≥ 4.07 L/min) should be valued to suggest coexistent COPD in HF patients.

Left Ventricular Diastolic Function and Exercise Capacity in Patients with Chagas Cardiomyopathy

Parameters of diastolic function have been shown to correlate with exercise capacity (EC) in individuals with impaired left ventricular (LV) systolic function. However, the role of LV diastolic function in predicting EC in Chagas cardiomyopathy has not been reported. Objectives: This study aimed to determine the relationship between LV diastolic parameters assessed by echocardiography and EC in patients with Chagas cardiomyopathy. Methods: We studied 40 patients (23 men; 49 ± 8 years), with diagnosis of Chagas disease and dilated cardiomyopathy. Medical therapy was individually adjusted according to standardized guidelines. Methods of acquiring two‐dimensional Doppler, tissue Doppler imaging (TDI), and their measurements were described. Exercise testing was performed by a Bruce protocol. Brain natriuretic peptide (BNP) levels were also determined. Results: Most patients (63%) were in NYHA functional class I. Mean peak oxygen consumption estimated (peakVO2) was 31.7 ± 10.2 mL/kg per minute, and mean left ventricular ejection fraction (LVEF) was 36.3 ± 7.8%. Univariate analysis showed that various echocardiographic parameters of diastolic function were correlated with peakVO2. There was no correlation between BNP levels or LVEF and EC. Multivariate analysis, after adjustment for age and gender, revealed that E/E′ ratio and left atrial volume (LAV), emerged as independent predictors of EC, as demonstrated in the model: peakVO2= 60.825 + (0.439 × LAV) − (1.620 × E/E′ ratio) − (0.483 × age) − (4.821 × female gender). The R2 of this model was 0.52. Conclusions: Functional capacity assessed by peakVO2 was related to increase LV filling pressures, independently on systolic function in patients with Chagas cardiomyopathy. (Echocardiography 2010;27:519‐524)

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.

Physiological and clinical relevance of exercise ventilatory efficiency in COPD

Exercise ventilation (V′E) relative to carbon dioxide output (V′CO2) is particularly relevant to patients limited by the respiratory system, e.g. those with chronic obstructive pulmonary disease (COPD). High V′E−V′CO2 (poor ventilatory efficiency) has been found to be a key physiological abnormality in symptomatic patients with largely preserved forced expiratory volume in 1 s (FEV1). Establishing an association between high V′E−V′CO2 and exertional dyspnoea in mild COPD provides evidence that exercise intolerance is not a mere consequence of detraining. As the disease evolves, poor ventilatory efficiency might help explaining “out-of-proportion” breathlessness (to FEV1 impairment). Regardless, disease severity, cardiocirculatory co-morbidities such as heart failure and pulmonary hypertension have been found to increase V′E−V′CO2. In fact, a high V′E−V′CO2 has been found to be a powerful predictor of poor outcome in lung resection surgery. Moreover, a high V′E−V′CO2 has added value to resting lung hyperinflation in predicting all-cause and respiratory mortality across the spectrum of COPD severity. Documenting improved ventilatory efficiency after lung transplantation and lung volume reduction surgery provides objective evidence of treatment efficacy. Considering the usefulness of exercise ventilatory efficiency in different clinical scenarios, the V′E−V′CO2 relationship should be valued in the interpretation of cardiopulmonary exercise tests in patients with mild-to-end-stage COPD. Ventilatory efficiency is a key measurement for the interpretation of cardiopulmonary exercise testing in COPD http://ow.ly/1nsY307pbz8

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.

Carotid intimal-medial thickening and endothelial function in coronary artery disease

OBJECTIVE To investigate the correlation between the endothelial function and the carotid intimal-medial thickening (IMT) in a population of patients with coronary artery disease, as well as that between the endothelial function and carotid IMT with the severity of the coronary lesions. METHODS Forty-three patients aged 60.5+/-9.2 years, (67.4% males) with coronary artery disease at the coronariography were studied. Endothelial function was assessed using the brachial artery reactivity test (BART), which measured the percentage of flow-mediated dilatation (%FMD). The carotid IMT was evaluated through vascular ultrasound. RESULTS The mean %FDM was 4.7 +/- 3.6 and the mean carotid IMT was 1.08 +/- 0.23 mm. The carotid MIT and %FMD measurements showed a statistically significant correlation, with Spearmans coefficient of 0.315, p= 0.042, demonstrating that lower %FMD values corresponded to an increased carotid IMT (r = -0.315, p = 0.042). There was no correlation between %FMD or IMT and the severity of coronary lesions. CONCLUSIONS The presence of a correlation between carotid IMT and %FMD demonstrates a concomitance of anatomical and functional vascular alterations in coronary artery disease, regardless of the severity of the atherosclerotic lesions.

Exercise oxygen uptake efficiency slope independently predicts poor outcome in pulmonary arterial hypertension.

To the Editor: Pulmonary arterial hypertension (PAH) remains a disabling and frequently lethal disease despite remarkable advances in treatment. Cardiopulmonary exercise testing (CPET) has proved a valuable tool to objectively quantify disease severity and estimate prognosis in these patients [1–3]. Exercise intolerance is characteristically multifactorial in PAH. Among its potential contributing mechanisms, increased ventilatory response, deranged pulmonary mechanics, peripheral muscle impairment and reduced oxygen delivery have been more widely investigated [1–5]. In this context, a CPET-derived variable that conflates the effects of increased ventilation and poor O2 transfer and/or peripheral O2 utilisation is the O2 uptake efficiency slope (OUES) [6]. OUES is the slope of the linear relationship between O2 uptake ( V ′O2) and the logarithmic transformation of minute ventilation ( V ′E) during rapidly incremental exercise, i.e. it aims to reflect how effectively O2 is extracted from the atmosphere and taken into the body as exercise progresses. We recently found that a combination of increased sub-maximal exercise V ′E as a function of carbon dioxide output ( V ′CO2) and reduced O2 delivery/utilisation (as suggested by shallow V ′O2–work rate relationship) were independent predictors of negative outcome in PAH of mixed aetiology [7]. These findings prompted the hypothesis that OUES would combine the prognostic information provided separately by those variables, thereby being the single predictor of poor outcome in our cohort. In order to address this question, we revisited our dataset and contrasted OUES prognostic relevance with that of a range of resting and cardiopulmonary exercise responses to ramp-incremental cycle ergometry. In the previous report [7], we described results from a group of 84 patients in whom 16 PAH-related deaths and two …

Exercise Ventilation in COPD: Influence of Systolic Heart Failure

ABSTRACT 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 (E)-CO2 output CO2) intercept, E-CO2 slope, peak E/CO2 ratio and peak PETCO2. Multiple logistic regression analysis revealed that CO2 intercept ≤ 3.5 L/minute [odds ratios (95% CI) = 7.69 (2.61–22.65), P < 0.001] plus E-CO2 slope ≥ 34 [2.18 (0.73–6.50), P = 0.14] or peak E/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.