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Arterial blood gas profile at rest and during exercise in 85 patients with or without pulmonary hypertension 

Arterial blood gas profile at rest and during exercise in 85 patients with or without pulmonary hypertension 

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Introduction: Few data are available in regards to the prevalence of pulmonary hypertension (PH) in the broad spectrum of COPD. This study was aimed at assessing the prevalence of PH in a cohort of COPD patients across the severity of airflow limitation, and reporting the hemodynamic characteristics at rest and during exercise. Methods: We perfo...

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... 2 , respectively; P=0.001) ( Figure 2). Patients with associated PH had, as compared with patients without PH, lower PaO 2 and higher PaCO 2 both at rest and during exercise ( Table 5). ...

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... Airway obstruction and loss of functional pulmonary parenchyma are important features of chronic obstructive pulmonary disease (COPD), leading to impaired exercise capacity and survival [1]. In addition, pulmonary hypertension (PH) may complicate the course of COPD and contribute to poor prognosis [2][3][4][5]. The overall prevalence of a mean PAP ≥ 25 mmHg in COPD is estimated to be around 10% [6]. ...
... Although severe PH is rare, mild to moderate forms of pulmonary vascular disease (PVD) are quite frequent [7,8]. Despite normal or mildly elevated pulmonary arterial pressures at rest, hemodynamic response to exercise may be abnormal in these patients, which could substantially contribute to their symptoms and impaired exercise capacity [5,9,10]. In recent years, our understanding of pulmonary hemodynamics during exercise improved and prognostically relevant variables have been identi ed. ...
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Background Pulmonary hypertension (PH) is a frequent complication in COPD and it is associated with decreased exercise capacity and poor prognosis. We hypothesized that even in COPD patients without significant PH at rest, abnormal pulmonary hemodynamics during exercise affect exercise capacity. Methods Consecutive COPD patients with clinically indicated right heart catheterization and resting mean pulmonary arterial pressure (mPAP) < 25mmHg and age- and sex-matched controls without chronic lung disease who underwent clinical work-up including invasive hemodynamic assessment during exercise were retrospectively analyzed. Chi-square tests were used to evaluate differences between groups for categorical data and Fisher’s exact test or Mann-Whitney-U-tests for continuous variables. Associations were analyzed with Spearman rank correlation tests. Results We included n=26 COPD patients (female/male: 16/10, 66±11yr, FEV1: 56±25 %predicted) and n=26 matched controls (FEV1: 96±22 %predicted). At rest, COPD patients presented with slightly increased mPAP (21 (18-23) vs. 17 (14-20) mmHg, p=0.022), and pulmonary vascular resistance (PVR) (2.5 (1.9-3.0) vs. 1.9 (1.5-2.4) WU, p=0.020) as compared to controls. During exercise, COPD patients reached significantly higher mPAP (47 (40-52) vs. 38 (32-44) mmHg, p=0.015) and PVR (3.1 (2.2-3.7) vs. 1.7 (1.1-2.9) WU, p=0.028) values despite lower peak exercise level (50 (50-75) vs. 100 (75-125) Watt, p=0.002). The mPAP/cardiac output slope was increased in COPD vs. controls (6.9 (5.5-10.9) vs. 3.7 (2.4-7.4) mmHg/L/min, p=0.007) and negatively correlated with both peak oxygen uptake (r=-0.46, p=0.007) and 6-minute walk distance (r=-0.46, p=0.001). Conclusion Even in the absence of significant PH at rest, COPD patients reveal characteristic abnormalities in pulmonary hemodynamics during exercise, which may represent an important exercise-limiting factor.
... This proposed definition has later been used in the largest currently available study on the prognostic relevance of exercise PH in patients with dyspnea, confirming its prognostic relevance 15 . The mPAP/CO slope may be calculated either from multipoint mPAP/CO relationships or from two-point measurements including resting and peak exercise values, only 16,17 . In direct comparison, both methods showed high diagnostic accuracy for exercise PH 18 . ...
... In two cohorts of patients with severe COPD, the mean mPAP was 26 mmHg 9, 10 . The prevalence of an mPAP of > 20 mmHg in COPD patients was found to be between 18% and 91% in the whole spectrum of severity of the airway obstruction [10][11][12] . Severe PH is not frequently encountered in patients with COPD 5 and in a large cohort of 998 patients with COPD, the mean mPAP was 20.8 mmHg and only 5.8% of the patients presented with an mPAP of ≥ 35 mmHg 13 . ...
... Pulmonary hypertension (PH) is a complication of chronic obstructive pulmonary disease (COPD) [1] associated with increased morbidity [2,3] and mortality [4 && , 5,6]. Prevalence, reported to be up to 90% [7][8][9], varies widely according to the different study populations (mild COPD to pretransplant stages) and different definitions of PH (including postcapillary PH and diverse thresholds for PH diagnosis) [9,10]. The threshold to define PH in lung disease has been lowered [1] to define mild-moderate PH as mean pulmonary artery pressure (mPAP) 21 mmHg in the presence of increased pulmonary vascular resistance (PVR 3 wood units, WU) or mPAP 25 mmHg, and severe PH as mPAP 35 mmHg or mPAP 25 mmHg with cardiac index (CI) <2 L/min/m 2 . ...
... The threshold to define PH in lung disease has been lowered [1] to define mild-moderate PH as mean pulmonary artery pressure (mPAP) 21 mmHg in the presence of increased pulmonary vascular resistance (PVR 3 wood units, WU) or mPAP 25 mmHg, and severe PH as mPAP 35 mmHg or mPAP 25 mmHg with cardiac index (CI) <2 L/min/m 2 . PH is usually mild to moderate in COPD but is severe in 1-5% of cases [8,11], representing a distinct subgroup with markedly worse prognosis and predominant vascular impairment associated with relatively mild obstructive disease [6,12], which has been described as a 'pulmonary vascular phenotype' (PVP) [13]. A paradigm shift is taking place in PH research, aimed at the analysis of phenotypic heterogeneity and ultimately precision medicine [14,15]. ...
... PH can take many forms in COPD (Fig. 1), partly explaining its variable prevalence [8][9][10][72][73][74]. All COPD patients, regardless of hemodynamic status, should be treated according to guidelines including oxygen (if in respiratory failure), physiotherapy and optimal medical therapy. ...
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Purpose of review: Pulmonary hypertension (PH) is a common complication of chronic obstructive lung disease (COPD), but clinical presentation is variable and not always 'proportional' to the severity of the obstructive disease. This review aims to analyze heterogeneity in clinical features of PH-COPD, providing a guide for diagnosis and management according to phenotypes. Recent findings: Recent works have focused on severe PH in COPD, providing insights into the characteristics of patients with predominantly vascular disease. The recently recognized 'pulmonary vascular phenotype', characterized by severe PH and mild airflow obstruction with severe hypoxemia, has markedly worse prognosis and may be a candidate for large trials with pulmonary vasodilators. In severe PH, which might be best described by a pulmonary vascular resistance threshold, there may also be a need to distinguish patients with mild COPD (pulmonary vascular phenotype) from those with severe COPD ('Severe COPD-Severe PH' phenotype). Summary: Correct phenotyping is key to appropriate management of PH associated with COPD. The lack of evidence regarding the use of pulmonary vasodilators in PH-COPD may be due to the existence of previously unrecognized phenotypes with different responses to therapy. This review offers the clinician caring for patients with COPD and PH a phenotype-focused approach to diagnosis and management, aimed at personalized care.
... We defined exercise pulmonary hypertension as a change in the mPAP from rest to peak exercise divided by the change in CO (ΔmPAP/ΔCO) >3 mm Hg/L per minute. [19][20][21][22] To differentiate exercise pulmonary hypertension related to left heart disease from precapillary forms of pulmonary hypertension, we defined exercise-induced postcapillary pulmonary hypertension as a change in the mean PAWP from rest to peak exercise divided by the change in CO (ΔPAWP/ΔCO) >2 mm Hg/L per minute. 23 Since there is no consensus definition of pulmonary hypertension during exercise, we also assessed 2 other proposed definitions as secondary assessment of exercise-induced postcapillary pulmonary hypertension: (1) PAWP at exercise ≥25 mm Hg and (2) mPAP >30 mm Hg, total pulmonary resistance >3 Wood, and PAWP ≥20 mm Hg. [24][25][26] Total pulmonary resistance was calculated as mPAP at exercise divided by the CO at exercise. ...
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Background Optimal timing of aortic valve replacement remains difficult in patients with asymptomatic, severe aortic stenosis (AS). More accurate diagnostic methods are warranted for the detection of subtle ventricular impairment. We aimed to evaluate diastolic function in asymptomatic patients with severe AS. Methods In this cross-sectional study, patients with asymptomatic, severe AS were evaluated with right heart catheterization at rest and during moderate exercise. The patients also underwent cardiopulmonary exercise testing to objectify functional capacity and confirm the absence of symptoms. Results Between February 2019 and May 2021, we included 50 patients aged 70±12 years. The patients had severe AS with peak velocity 4.4±0.4 m/s, mean gradient 46±9 mm Hg, and an indexed valve area of 0.47±0.08 cm ² at rest. All patients were asymptomatic and had normal left ventricular ejection fraction. Five patients had postcapillary pulmonary hypertension at rest. During exercise, 44 patients (88%) had an increase in the mean pulmonary artery pressure per increase in cardiac output of >3 mm Hg/L per minute, of whom 93% had a concomitant increase in the pulmonary artery wedge pressure per increase in cardiac output >2 mm Hg/L per minute, suggesting exercise-induced pulmonary hypertension due to left heart disease. Female gender and increasing age were associated with a higher increase in the pulmonary artery wedge pressure per increase in cardiac output ratio. The catheterization was well tolerated, and there were no adverse events. Conclusions A large proportion of asymptomatic patients with severe, degenerative AS have exercise-induced postcapillary pulmonary hypertension.
... Some studies using cardiac catheterization have shown a prevalence of PH in non-severe COPD patients lower than 7%. 8 Using transthoracic echocardiography (TTE), prior studies have found that the prevalence of PH in patients with mild airflow limitation ranges from 0% to 25%. 5,9,10 Although the development of PH in COPD patients is multifactorial, hypoxic pulmonary vasoconstriction (HPV) seems to be one central mechanism. ...
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Background Pulmonary hypertension (PH) is associated with poor prognosis for patients with chronic obstructive pulmonary disease (COPD). Most of the knowledge about PH in COPD has been generated at sea level, with limited information associated with high altitude (HA). Objectives To assess the prevalence and severity of PH in COPD patients living in a HA city (2,640 m). Methods Cross-sectional study in COPD patients with forced expiratory volume in the first second / forced vital capacity ratio (FEV1/FVC) post-bronchodilator <0,7. Transthoracic echocardiography (TTE), spirometry, carbon monoxide diffusing capacity, and arterial blood gasses tests were performed. Patients were classified according to the severity of airflow limitation. PH was defined by TTE as an estimated systolic pulmonary artery pressure (sPAP) > 36 mmHg or indirect PH signs; severe PH as sPAP > 60 mmHg; and disproportionate PH as an sPAP > 60 mmHg with non-severe airflow limitation (FEV1 > 50% predicted). Results We included 176 COPD patients. The overall estimated prevalence of PH was 56.3% and the likelihood of having PH increased according to airflow-limitation severity: mild (31.6%), moderate (54.9%), severe (59.6%) and very severe (77.8%) (p = 0.038). The PH was severe in 7.3% and disproportionate in 3.4% of patients. Conclusions The estimated prevalence of PH in patients with COPD at HA is high, particularly in patients with mild to moderate airflow limitation, and greater than that described for COPD patients at low altitude. These results suggest a higher risk of developing PH for COPD patients living at HA compared to COPD patients with similar airflow limitation living at low altitude.
... Many of the prior studies investigating the clinical characteristics of COPD-PH patients were relatively small and/or limited to hospitalized subjects, which reduces generalization to more stable patients. [4][5][6][7][8][9][10][11][12]25 Second, this study is performed using the definitions developed at the last World Symposium on Pulmonary Hypertension, defining PH as an mPAP greater than 20 mmHg. Third, we included individuals with COPD and without PH on RHC as a reference group. ...
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Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Little is known about the prevalence and clinical profiles of patients with COPD-PH. We report the clinical characteristics, hemodynamic profiles, and prognosis in a large population of patients with COPD referred for right heart catheterization (RHC). We extracted data from all patients referred for RHC between 1997 and 2017 in Vanderbilt's deidentified medical record. PH was defined as mean pulmonary artery pressure >20 mmHg. Pre- and postcapillary PH were defined according to contemporary guidelines. COPD was identified using a validated rules-based algorithm requiring international classification of diseases codes relevant to COPD. We identified 6065 patients referred for RHC, of whom 1509 (24.9%) had COPD and 1213 had COPD and PH. Patients with COPD-PH had a higher prevalence of diabetes, atrial fibrillation, and heart failure compared with COPD without PH. Approximately 55% of patients with COPD-PH had elevated left ventricle (LV) filling pressure. Pulmonary function testing data from individuals with COPD-PH revealed subtype differences, with precapillary COPD-PH having lower diffusion capacity of the lungs for carbon monoxide (DLCO) values than the other COPD-PH subtypes. Patients with COPD-PH had significantly increased mortality compared with COPD alone (hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.28–2.26) with the highest mortality among the combined pre- and postcapillary COPD-PH subgroup (HR: 2.39; 95% CI: 1.64–3.47). PH is common among patients with COPD referred for RHC. The etiology of PH in patients with COPD is often mixed due to multimorbidity and is associated with high mortality, which may have implications for risk factor management.
... The slope utilizes multiple mPAP-CO ratios during exercise (4-5 points), and a slope > 3 mmHg·min·L −1 is defined as exercise-induced PH [31]. Third, the two-point mPAP/CO slope is used: this slope is calculated as the change in mPAP from rest to peak exercise divided by the change in CO from rest to peak exercise, and a slope > 3 mmHg·min·L −1 is considered abnormal [40]. ...
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The right ventricle (RV) is more sensitive to an increase in afterload than the left ventricle (LV), and RV afterload during exercise increases more easily than LV afterload. Pulmonary arterial hypertension (PAH)-specific therapy has improved pulmonary hemodynamics at rest; however, the pulmonary hemodynamic response to exercise is still abnormal in most patients with PAH. In these patients, RV afterload during exercise could be higher, resulting in a greater increase in RV wall stress. Recently, an increasing number of studies have indicated the short-term efficacy of exercise training. However, considering the potential risk of promoting myocardial maladaptive remodeling, even low-intensity repetitive exercise training could lead to long-term clinical deterioration. Further studies investigating the long-term effects on the RV and pulmonary vasculature are warranted. Although the indications for exercise training for patients with PAH have been expanding, exercise training may be associated with various risks. Training programs along with risk stratification based on the pulmonary hemodynamic response to exercise may enhance the safety of patients with PAH.
... Pulmonary hypertension (PH) is a frequent complication in patients with COPD [1,2], and it is associated with increased risk for hospitalisation, worse clinical course and increased mortality [3,4]. The prevalence of PH in patients with COPD is not negligible; it has been reported to range between 23% and 91%, depending on the diagnostic criteria used to define it and the severity of the disease [5][6][7]. In most cases, the severity of PH is usually moderate, and right ventricular function is not impacted. ...
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Background Pulmonary hypertension (PH) is a frequent complication in patients with COPD. Objective To determine if, in patients with COPD, the presence of PH decreases exercise tolerance. Methods We included studies that analysed exercise tolerance using a cardiopulmonary exercise test (CPET) in patients with COPD with PH (COPD-PH) and without PH (COPD-nonPH). Two independent reviewers analysed the studies, extracted the data and assessed the quality of the evidence. Results Of the 4915 articles initially identified, seven reported 257 patients with COPD-PH and 404 patients with COPD-nonPH. The COPD-PH group showed differences in peak oxygen consumption ( V ′ O 2peak ), −3.09 mL·kg ⁻¹ ·min ⁻¹ (95% CI −4.74 to −1.43, p=0.0003); maximum workload (W max ), −20.5 W (95% CI −34.4 to −6.5, p=0.004); and oxygen pulse (O 2 pulse), −1.24 mL·beat ⁻¹ (95% CI −2.40 to −0.09, p=0.03), in comparison to the group with COPD-nonPH. If we excluded studies with lung transplant candidates, the sensitivity analyses showed even bigger differences: V ′ O 2 , −4.26 mL·min ⁻¹ ·kg ⁻¹ (95% CI −5.50 to −3.02 mL·kg ⁻¹ ·min ⁻¹ , p<0.00001); W max , −26.6 W (95% CI −32.1 to −21.1 W, p<0.00001); and O 2 pulse, −2.04 mL·beat ⁻¹ (95% CI −2.92 to −1.15 mL·beat ⁻¹ , p<0.0001). Conclusion Exercise tolerance was significantly lower in patients with COPD-PH than in patients with COPD-nonPH, particularly in nontransplant candidates.
... Other criteria include a linearized slope of multiple mPAP and CO determinations > 3 WU 26,28 and a change in peak minus resting mPAP over the respective change in CO > 3 WU, but these are less sensitive. 28,29 The diagnosis of WHO group 2 PH related to occult HFpEF is supported by a PCWP ≥ 15 mm Hg at rest or an increase in PCWP to ≥ 25 mm Hg at peak physical activity, ideally along with ∆PCWP/∆CO slope > 2 mm Hg/L/min ( Table 3, Figure 3). The pathophysiology is due to decreased LV compliance resulting in an increase in PCWP. ...
... This is valuable for identifying occult HFpEF in high-risk patients (eg, those with obesity or scleroderma) and accurately classifying patients with ambiguous phenotypic characteristics that overlap between WHO group 1 and group 2 PH. 29 Additionally, a saline-loading fluid challenge is widely available, inexpensive, and easily administered, with 500 mL of 0.9% sodium chloride infused intravenously over 5 minutes. Slow infusion should be avoided since it would enable fluid redistribution in the interstitial space and, therefore, a false negative result. ...