Bart Boerrigter

Progressive Dilatation of the Main Pulmonary Artery Is a Characteristic of Pulmonary Arterial Hypertension and Is Not Related to Changes in Pressure

BACKGROUND Pulmonary artery (PA) dilatation is one of the consequences of pulmonary arterial hypertension (PAH) and is used for noninvasive detection. However, it is unclear how the size of the PA behaves over time and whether it is related to pressure changes. The aim of this study was to evaluate PA size during follow-up in treated patients with PAH and whether it reflects pulmonary vascular hemodynamics. METHODS Fifty-one patients with PAH who underwent at least two right-sided heart catheterizations (RHCs) together with cardiac MRI (CMR) were included in this study. Another 18 patients who had normal pressure at RHC were included for comparison at baseline. From RHC, we derived PA pressures and cardiac output. From the CMR images we derived PA diameter (PAD) and the ratio of the PAD and ascending aorta diameter. RESULTS The PAD was significantly larger in patients with PAH than in patients without PAH (P < .001). A ratio of the PAD and ascending aorta diameter > 1 had a positive predictive value of 92% for PAH. Mean follow-up time was 942 days, and there was a significant dilatation during this period (P < .001). The change of the PAD did not correlate with the changes in pressure or cardiac output. A moderate correlation with follow-up time was found (r = 0.56; P < .001). CONCLUSIONS A dilatated PA is useful for identifying patients with PAH. However, during patient follow-up, progressive dilatation of the PA is independent of the change in PA pressure and cardiac output and might become independent from hemodynamics.

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.

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.

Measuring central pulmonary pressures during exercise in COPD: how to cope with respiratory effects

Respiratory influences are major confounders when evaluating central haemodynamics during exercise. We studied four different methods to assess mean pulmonary artery pressure (mPAP) and pulmonary capillary wedge pressure (PCWP) in cases of respiratory swings. Central haemodynamics were measured simultaneously with oesophageal pressure during exercise in 30 chronic obstructive pulmonary disease (COPD) patients. mPAP and PCWP were assessed at the end of expiration, averaged over the respiratory cycle and corrected for the right atrial pressure (RAP) waveform estimated intrathoracic pressure, and compared with the transmural pressures. Bland–Altman analyses showed the best agreement of mPAP averaged over the respiratory cycle (bias (limits of agreement) 2.5 (-6.0–11.8) mmHg) and when corrected with the nadir of RAP (-3.6 (-11.2–3.9) mmHg). Measuring mPAP at the end of expiration (10.3 (0.5–20.3) mmHg) and mPAP corrected for the RAP swing (-9.3 (-19.8–2.1) mmHg) resulted in lower levels of agreement. The respiratory swings in mPAP and PCWP were similar (r2=0.82, slope±se 0.95±0.1). Central haemodynamics measured at the end of expiration leads to an overestimation of intravascular pressures in exercising COPD patients. Good measurement can be acquired even when oesopghageal pressure is omitted, by averaging pressures over the respiratory cycle or using the RAP waveform to correct for intrathoracic pressure. Assessment of the pulmonary gradient is unaffected by respiratory swings. Measurement of intravascular pressures in exercising COPD patients requires correction for intrathoracic pressure http://ow.ly/tVLlg

Right atrial pressure affects the interaction between lung mechanics and right ventricular function in spontaneously breathing COPD patients.

Introduction It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia. Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firmly established in spontaneously breathing patients at rest or during exercise, nor has it been determined whether these cardiopulmonary interactions are influenced by right atrial pressure. Methods Twenty-one patients with COPD underwent simultaneous measurements of intrathoracic, right atrial and pulmonary artery pressures during spontaneous breathing at rest and during exercise. Intrathoracic pressure and right atrial pressure were used to calculate right atrial filling pressure. Dynamic changes in pulmonary artery pulse pressure during expiration were examined to evaluate changes in right ventricular output. Results Pulmonary artery pulse pressure decreased up to 40% during expiration reflecting a decrease in stroke volume. The decline in pulse pressure was most prominent in patients with a low right atrial filling pressure. During exercise, a similar decline in pulmonary artery pressure was observed. This could be explained by similar increases in intrathoracic pressure and right atrial pressure during exercise, resulting in an unchanged right atrial filling pressure. Conclusions We show that in spontaneously breathing COPD patients the pulmonary artery pulse pressure decreases during expiration and that the magnitude of the decline in pulmonary artery pulse pressure is not just a function of intrathoracic pressure, but also depends on right atrial pressure.

Risk Factors for Hemoptysis in Idiopathic and Hereditary Pulmonary Arterial Hypertension

Introduction When hemoptysis complicates pulmonary arterial hypertension (PAH), it is assumed to result from bronchial artery hypertrophy. In heritable PAH, the most common mutation is in the BMPR2 gene, which regulates growth, differentiation and apoptosis of mesenchymal cells. The aim of this study is to determine the relationship in PAH between the occurrence of hemoptysis, and disease progression, bronchial artery hypertrophy, pulmonary artery dilation and BMPR2 mutations. Methods 129 IPAH patients underwent baseline pulmonary imaging (CT angio or MRI) and repeated right-sided heart catheterization. Gene mutations were assessed in a subset of patients. Results Hemoptysis was associated with a greater presence of hypertrophic bronchial arteries and more rapid hemodynamic deterioration. The presence of a BMPR2 mutation did not predispose to the development of hemoptysis, but was associated with a greater number of hypertrophic bronchial arteries and a worse baseline hemodynamic profile. Conclusion Hemoptysis in PAH is associated with bronchial artery hypertrophy and faster disease progression. Although the presence of a BMPR2 mutation did not correlate with a greater incidence of hemoptysis in our patient cohort, its association with worse hemodynamics and a trend of greater bronchial arterial hypertrophy may increase the risk of hemoptysis.

Pulmonary hypertension at exercise in COPD: does it matter?

Pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD). In these patients, the increase in pulmonary artery pressure (PAP) is usually mild, in the range of 20 to 30 mmHg mean PAP (mPAP) with little progression over the years, on average 0.4 mmHg per year, and is preventable and sometimes partially reversible with chronic oxygen therapy [1, 2]. Sharp increases in PAP may occur during sleep or episodes of acute respiratory failure, and also during exercise [1, 2]. Pulmonary hypertension in COPD is explained by the combined effects of hypoxia, inflammation, hyper-inflation of the lungs and an increase in left ventricular end-diastolic pressure [2, 3]. Increased PAP is associated with decreased survival, may be the cause of clinical right heart failure, particularly in hypoxaemic patients with associated salt and water retention, and is thought to limit exercise capacity [1, 2]. Right heart catheterisations to evaluate the pulmonary circulation used to be common practice in patients with advanced COPD. The procedure is nowadays limited to the work-up of lung transplantation or lung volume reduction surgery, or for the understanding of symptoms that appear out of proportion with the lung function impairment [2, 4]. Some rare patients with COPD, approximately 1% of those referred to expert centres, present with “out of proportion pulmonary hypertension”. This entity is defined by a particular combination of mPAP >35–40 mmHg, only moderate airflow obstruction, hypoxaemia and hypocapnia [2–5]. Whether “out of proportion pulmonary hypertension” actually represents a form of pulmonary arterial hypertension (PAH) triggered by altered blood gases or inflammation associated with COPD remains unclear [5]. But there has been no reported evidence until now that targeted therapies shown effective in the …

Sildenafil: a definitive NO in COPD

Several studies have shown that chronic obstructive pulmonary disease (COPD) patients have a low stroke volume at rest and an impaired stroke volume response during exercise [1, 2]. As a consequence, oxygen delivery to the tissues is impaired. Since oxygen delivery is critical for maintenance and growth of muscles, the systemic effects of COPD might, in part, be attributed to the lowered stroke volume. Therefore, restoring the stroke volume response would not only improve oxygen delivery capacity, but may also have beneficial effects at the muscle level. Improving muscle strength may, in turn, enhance exercise tolerance by reducing negative feedback from lower limb sensory muscle afferents and by reducing ventilatory responses and dyspnoea during exercise [3]. Since increased right ventricular afterload is considered the most likely explanation for the impaired stroke volume response, reducing pulmonary artery pressure is the key to restore stroke volume. Although pulmonary hypertension is present in 50% of the patients with severe COPD, pulmonary hypertension is usually mild-to-moderate [4]. However, exercise will induce a steep increase in pulmonary artery pressure in these patients [5, 6 …

Cardiac shunt in COPD as a cause of severe hypoxaemia: probably not so uncommon after all

To the Editors: Hypoxaemia is a common finding in chronic obstructive pulmonary disease (COPD) and may be aggravated during exercise. The main mechanism is perfusion through areas that are not well ventilated: a ventilation–perfusion mismatch. True shunting, defined as venous blood mixing directly with end-capillary blood at the arterial side of the circulation, is not a usual cause of hypoxaemia in COPD 1, 2. The amount of shunting related to ventilation–perfusion mismatch is usually made by the calculation of the shunt fraction while the patient is inhaling 100% oxygen. We present two cases of severe hypoxaemia in patients with COPD to show that a cardiac shunt can contribute to hypoxaemia, and that this shunt can be missed if the 100% oxygen method is used to quantify shunt. Patient A was a 68-yr-old man, referred from another hospital to our clinic for evaluation of severe dyspnoea and hypoxaemia. Patient complaints were rapidly progressive dyspnoea and severe impaired exercise tolerance with blue discoloration of the fingers and lips for 3 months. There were no complaints of coughing, sputum production or fever. Patient A ceased smoking 12 yrs previously after 60 pack-yrs. Physical examination revealed peripheral and central cyanosis, and a little ankle oedema. Arterial blood gas analysis revealed a hypoxaemia at rest, with an arterial oxygen tension ( P a,O2) of 42 mmHg and an arterial oxygen saturation ( S a,O2) of 77%. Pulmonary function tests showed moderate obstruction (forced expiratory volume in 1 s (FEV1) of 67% predicted and FEV1/synchronised vital capacity (SVC) ratio of 65% pred). Initiation of exercise resulted in immediate oxygen desaturation to 71%, preventing any further exercise. Radiological analysis by means of high-resolution computed tomography (CT), pulmonary angiography and ventilation–perfusion scan revealed only signs of emphysema. Transthoracic …

Spirometry in chronic obstructive pulmonary disease: a hemodynamic roller coaster?

A 70-year-old female patient with very severe chronic obstructive pulmonary disease (COPD) (FEV1/VC: 46%; FEV1: 0.62 L, 29% of predicted). The patient gave informed and written consent to participate in a larger, institutional review board–approved study of the effects of airflow limitation and hyperinflation on the central hemodynamics (Medical Ethical Review Committee, VU University Medical Center, registration number: NL30766.029.10). Some of the results of this study have been previously reported in the form of an abstract (1). The patient performed a forced expiratory flow maneuver with simultaneous central hemodynamic measurements using a pulmonary artery catheter and measurement of pleural pressure using an esophageal balloon. At the onset of the forced expiration, the increase in pleural pressure forces blood into the left heart, leading to a (pulse) pressure increase in the radial artery (Figure 1, section A). However, at the same time, venous return is impaired, indicated by the low transmural pressure of the right atrium (Figure 1, section B). As a consequence, right ventricular output decreases, reflected by a decrease in pulmonary artery pulse pressure (Figure 1, section C). The decline in right ventricular output is followed by a decrease of left ventricular output, leading to a marked decrease in (pulse) pressure in the radial artery (Figure 1, section D). Overall, a drop Figure 1. Simultaneous recording of pressures in (from top to bottom) the pulmonary artery, right ventricle, radial artery, right atrium, and esophagus, and the calculated transmural pressure of the right atrium (right atrial minus esophageal pressure) during a forced expiration in a patient with very severe COPD. See text for explanation of the panels. 4 C /F P O