Sebastiaan Holverda

Cardiopulmonary Exercise Test Characteristics in Patients with Chronic Obstructive Pulmonary Disease and Associated Pulmonary Hypertension

Background: Pulmonary hypertension (PH) is a well-known complication of chronic obstructive pulmonary disease (COPD). It remains unclear whether exercise parameters can be used to discriminate between COPD patients with associated PH (COPD-PH) and COPD patients without associated PH (COPD-nonPH). Objective: To study whether the existence of pulmonary hypertension in COPD is related to characteristic findings in gas exchange and circulatory parameters during cardiopulmonary exercise testing (CPET). Methods: We retrospectively analyzed CPET data in 25 COPD patients in whom right heart catheterization had been performed. Differences were assessed between COPD-PH and COPD-nonPH patients in peak oxygen uptake (VO2 peak), ventilatory efficiency (VE/VCO2), oxygen pulse, maximal ventilation and pulse oximetry (SpO2). Results: PH was found in 10 of 25 patients (mPpa = 33 ± 7 mm Hg), in 15 patients mean pulmonary artery pressure (mPpa) was below 25 mm Hg (18 ± 3 mm Hg). CPET in COPD-PH was characterized by a higher VE/VCO2 at nadir, a higher VE/VCO2 slope, and a lower SpO2 at rest and during exercise, but values in both groups were overlapping considerably. In the whole group mPpa was associated with resting PaO2 (r = –0.70, p < 0.001), VE/VCO2 nadir (r = 0.43, p < 0.05), and inversely related to SpO2 at rest and during exercise (r = –0.58 and r = –0.64, p < 0.01, respectively). Conclusion: Although CPET characteristics showed a large overlap in both groups, the existence of PH in COPD is associated with a significantly reduced ventilatory efficiency during CPET. However, a low SpO2 at rest and a further decrease during exercise similarly suggest the presence of PH in COPD.

Ventilatory and Cardiocirculatory Exercise Profiles in COPD: The Role of Pulmonary Hypertension

BACKGROUND Pulmonary hypertension (PH) is a well-recognized complication of COPD. The impact of PH on exercise tolerance is largely unknown. We evaluated and compared the circulatory and ventilatory profiles during exercise in patients with COPD without PH, with moderate PH, and with severe PH. METHODS Forty-seven patients, GOLD (Global Initiative for Chronic Obstructive Lung Disease)stages II to IV, underwent cardiopulmonary exercise testing and right-sided heart catheterization at rest and during exercise. Patients were divided into three groups based on mean pulmonary artery pressure (mPAP) at rest: no PH (mPAP, < 25 mm Hg), moderate PH (mPAP, 25-39 mm Hg),and severe PH (mPAP, ≥ 40 mm Hg). Mixed venous oxygen saturation (S VO 2 ) was used for evaluating the circulatory reserve. Pa CO 2 and the calculated breathing reserve were used for evaluation of the ventilatory reserve. RESULTS Patients without PH (n = 24) had an end-exercise S VO 2 of 48%± 9%, an increasing Pa CO 2 with exercise, and a breathing reserve of 22% ± 20%. Patients with moderate PH (n = 14) had an exercise S VO 2 of 40% ± 8%, an increasing Pa CO 2 , and a breathing reserve of 26% ± 15%. Patients with severe PH (n =9) had a significantly lower end-exercise S VO 2 (30% ± 6%), a breathing reserve of 37% ± 11%, and an absence of Pa CO 2 accumulation. CONCLUSION Patients with severe PH showed an exhausted circulatory reserve at the end of exercise.A profile of circulatory reserve in combination with ventilatory impairments was found inpatients with COPD and moderate or no PH. The results suggest that pulmonary vasodilation might only improve exercise tolerance in patients with COPD and severe PH.

Acute effects of sildenafil on exercise pulmonary hemodynamics and capacity in patients with COPD.

BACKGROUND We investigated in chronic obstructive pulmonary disease (COPD) patients whether a single dose of sildenafil can attenuate the exercise-induced increase in pulmonary artery pressure, thereby allowing augmentation of stroke volume (SV), and improving maximal exercise capacity. METHODS Eighteen COPD patients (GOLD II-IV) underwent right heart catheterization at rest and submaximal exercise. Mean pulmonary artery pressure (mPpa) and cardiac output (CO) were assessed. Resting and exercise measurements were repeated 60 min after oral intake of 50mg sildenafil. Also, on different days, patients performed two maximal exercise tests (CPET) randomly, 1h after placebo and after 50mg sildenafil. RESULTS Five COPD patients had pulmonary hypertension (PH) at rest (mPpa >25 mmHg) and six developed PH during exercise (mPpa >30 mmHg). In all patients, mPpa increased from rest to submaximal exercise (23+/-10-35+/-14 mmHg). After sildenafil mPpa at rest was 20+/-10 mmHg, in exercise mPpa was increased less to 30+/-14 mmHg (p<0.01). The reduced augmentation in mPpa was not accompanied by an increased SV and CO. In COPD patients with PH the percentage increase in mPpa to submaximal exercise was 68% before, and 51% after oral intake of sildenafil (p=0.07). In COPD without PH, these values were 46% and 41% (ns), respectively. Maximal exercise capacity and CPET characteristics were unchanged after sildenafil. CONCLUSION Regardless of mPpa at rest, sildenafil attenuates the increase in mPpa during submaximal exercise in COPD. This attenuated increase is neither accompanied by enhanced SV and CO, nor by improved maximal exercise capacity.

Stroke volume response during exercise measured by acetylene uptake and MRI

The intra-breath technique to measure acetylene absorption offers the possibility to determine augmentation of the pulmonary blood flow per heart beat (Q(C)) as an estimate of the stroke volume response during exercise. However, this method has not been compared with a validated test until now. Therefore, the aim of this study was to compare Q(C) with stroke volume (SV(MRI)) determined by magnetic resonance imaging (MRI) at rest and during exercise in healthy subjects and patients. For this purpose, ten healthy subjects and ten patients with idiopathic pulmonary arterial hypertension (iPAH) with expected impaired stoke volume response during exercise were measured by both methods. Exercise-induced changes in Q(C) and SV(MRI) were correlated in healthy controls (r = 0.75, p < 0.05). Compared to healthy controls, Q(C) increased less during exercise in iPAH patients (11 +/- 17 ml versus 33 +/- 12 ml, p < 0.05). A similar difference in stroke volume response to exercise between the two groups was measured by MRI (-0.6 +/- 8 ml versus 23 +/- 12 ml, p < 0.05, respectively). Hence, intra-breath and MRI measurements showed similar differences in exercise-induced changes in stroke volume between controls and patients. From these results it can be concluded that the intra-breath measurement of acetylene absorption might be of value as a non-invasive tool to estimate stroke volume augmentation during exercise and can detect differences in stroke volume responses between iPAH patients and healthy subjects.

Original ResearchPulmonary Vascular DiseaseVentilatory and Cardiocirculatory Exercise Profiles in COPD: The Role of Pulmonary Hypertension

BACKGROUND Pulmonary hypertension (PH) is a well-recognized complication of COPD. The impact of PH on exercise tolerance is largely unknown. We evaluated and compared the circulatory and ventilatory profiles during exercise in patients with COPD without PH, with moderate PH, and with severe PH. METHODS Forty-seven patients, GOLD (Global Initiative for Chronic Obstructive Lung Disease)stages II to IV, underwent cardiopulmonary exercise testing and right-sided heart catheterization at rest and during exercise. Patients were divided into three groups based on mean pulmonary artery pressure (mPAP) at rest: no PH (mPAP, < 25 mm Hg), moderate PH (mPAP, 25-39 mm Hg),and severe PH (mPAP, ≥ 40 mm Hg). Mixed venous oxygen saturation (S VO 2 ) was used for evaluating the circulatory reserve. Pa CO 2 and the calculated breathing reserve were used for evaluation of the ventilatory reserve. RESULTS Patients without PH (n = 24) had an end-exercise S VO 2 of 48%± 9%, an increasing Pa CO 2 with exercise, and a breathing reserve of 22% ± 20%. Patients with moderate PH (n = 14) had an exercise S VO 2 of 40% ± 8%, an increasing Pa CO 2 , and a breathing reserve of 26% ± 15%. Patients with severe PH (n =9) had a significantly lower end-exercise S VO 2 (30% ± 6%), a breathing reserve of 37% ± 11%, and an absence of Pa CO 2 accumulation. CONCLUSION Patients with severe PH showed an exhausted circulatory reserve at the end of exercise.A profile of circulatory reserve in combination with ventilatory impairments was found inpatients with COPD and moderate or no PH. The results suggest that pulmonary vasodilation might only improve exercise tolerance in patients with COPD and severe PH.

Compression of the Pulmonary Vein After Right-Sided Pneumonectomy

Six years after right pneumonectomy, a 67-year-old man had progressive dyspnea during exercise. He was admitted to the hospital because of severe dyspnea after some exercise. The chest radiograph showed signs of pulmonary edema, which improved rapidly after furosemide and oxygen therapy. There were no signs of tumor recurrence or airway obstruction on computed tomography. Pulmonary function tests were not changed compared with the years before (forced expiratory volume in 1 second, 2.1 L/s; diffusion capacity for carbon monoxide, 70% of predicted). …