Early Diagnosis of Right Ventricular Systolic Dysfunction by Tissue Doppler-Derived Isovolumic Myocardial Acceleration in Patients with Chronic Obstructive Pulmonary Disease

Objectives: The aim of the study was to assess validity of tissue Doppler imaging (TDI)-derived right ventricular (RV) myocardial systolic velocities in early detection of RV systolic dysfunction in chronic obstructive pulmonary disease (COPD). Methods: Ninety COPD patients (50 pure COPD and 40 with right heart failure [RHF]) and 40 controls were enrolled. Respiratory function tests, conventional echocardiographic parameters, and TDI-derived isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak velocity during systolic ejection (Sa) were measured. Results: All the TDI-derived RV systolic velocities were impaired in COPD (P = 0.0001) compared to controls. IVA was the only parameter that could distinguish the patients with pure COPD and COPD with RHF (P = 0.0001). IVA was found to be significantly correlated with FEV1 (r = 0.41, P = 0.0001), FEV1/FVC (r = 0.43, P = 0.0001), pulmonary artery pressure (r =−0.34, P = 0.001), pulmonary flow acceleration time (r = 0.48, P = 0.0001), and tricuspid annular systolic excursion (r =−0.41, P = 0.0001). In addition, IVA ≤ 2.7 m/sec² was able to predict COPD patients from controls with 81% sensitivity, 98% specificity and IVA ≤ 1.9 m/sec² predicted COPD patients accompanied by RHF with 82% sensitivity, 77% specificity from patients without RHF. Conclusions: TDI-derived RV IVA is a novel, noninvasive echocardiographic index which may be used in the assessment of subclinical RV dysfunction in patients with COPD.     

慢性支气管炎、COPD及肺心病患者BNP、肺功能和血气变化的研究

目的探讨慢性支气管炎(慢支)、COPD、慢性肺源性心脏病(肺心病)患者不同时期BNP(B型钠尿肽)、肺功能、动脉血气的变化。方法慢支、COPD、肺心病患者均空腹抽静脉血检测BNP;另抽动脉血检测血气;并行肺功能检测。三组间对比,并与正常组对照。结果由慢支发展到COPD、肺心病时BNP逐渐升高(P<0.05);慢支、COPD及肺心病各组FEV1/FVC、MMEF逐渐降低(P均<0.05),动脉血氧分压(PaO2)、PH值逐渐降低,二氧化碳分压(PaCO2)逐渐增高(P均<0.05)。BNP与PaO2、PH呈显著负相关(r=-0.69,-0.58,P均<0.01),而与PaCO2呈正相关(r=0.55,P<0.01)。BNP与FEV1/FVC、MMEF均呈显著负相关,P均<0.01)。结论血浆BNP水平与血气分析及肺功能变化关系密切,血浆BNP水平可以作为判断COPD病情严重程度的一个指标。     

超声心动图评价肺动脉高压患者右室功能的研究进展

肺动脉高压的发展会导致患者右室功能减低,对肺动脉高压患者右室功能的评价对其预后具有十分重要的临床意义。随着超声技术的不断发展,特别是新型超声技术的出现能敏感、准确地定量反映肺动脉高压患者的右室功能。现就目前超声心动图技术在评价肺动脉高压患者右室功能中的应用做一综述。     

肺动脉高压患者右室功能的多普勒超声评价与进展

肺动脉高压会导致患者右室功能减低,早诊断、早治疗肺动脉高压能明显改善患者的预后。近年来应用多普勒超声技术对肺动脉高压患者右室功能研究的新进展层出不穷,如双多普勒同步技术、Tei指数及三尖瓣环收缩期位移等,均为临床提供了全新的评价肺动脉高压及右室功能的新手段及新参数。     

Right Ventricular Function in Adult Patients with Eisenmenger Physiology: Insights from Quantitative Echocardiography

Background: The favorable outcomes of Eisenmenger syndrome (ES) relative to other forms of pulmonary arterial hypertension (PAH) have been partially attributed to a unique adaptation of the right ventricle (RV). However, conventional measures of RV function may not adequately express this adaptation. Methods: We studied 23 patients with ES (age 43 ± 17 years, 16 women, pulmonary artery systolic pressure [PASP] 93 ± 26 mmHg), 25 patients with PAH (age 44 ± 13 years, 17 women, PASP 92 ± 19 mmHg), and 25 subjects without known structural disease (age 45 ± 16 years, 17 women). We evaluated long‐ and short‐axis function of the RV with two‐dimensional strain and anatomical M‐mode echocardiography, respectively. Results: Long‐axis function of the RV was comparable between patients with ES and PAH although depressed relative to controls (global strain, ?15.6 ± 4.7, ?14.9 ± 4.3, and ?22.4 ± 2.8%, respectively, P < 0.001; global RV systolic strain rate, ?0.77 ± 0.26, ?0.84 ± 0.24, and ?1.11 ± 0.21 1/sec, respectively, P < 0.001). However, short‐axis RV function was significantly better in patients with ES versus those with PAH and preserved relative to controls (RV fractional shortening by anatomical M‐mode, median [interquartile range], 21%[14–33%], 14%[10–16%], and 26%[22–36%], respectively, P = 0.002 for ES vs. PAH, P = 0.09 for ES vs. controls). This differential was not reflected in conventional measures of RV function (fractional area change, 32 ± 10 vs. 29 ± 8% in ES and PAH, respectively, P = 0.26). Conclusion: In patients with ES, the RV is characterized by preserved short‐axis function, despite a depressed long‐axis function. Thus, conventional assessment of RV function might not be suitable for patients with ES. (Echocardiography 2010;27:937‐945)     

Echocardiographic Detection of Occult Cor Pulmonale During Exercise in Patients with Chronic Obstructive Pulmonary Disease

We tested the ability of cycle ergometer exercise echocardiography to detect cases of occult cor pulmonale among 25 patients with chronic obstructive pulmonary disease (COPD). The M-mode echocardiographic ventricular septal motion, left ventricular shape determined by short-axis two-dimensional (2-D) echocardiography, and right and left ventricular pressure curves were recorded at rest and during exercise and were compared between patients. The ventricular septal motion was normal at rest in all of the patients. In nine patients (dip group), there was marked downward ventricular septal motion in early diastole during exercise, indicating distortion of the left ventricular shape. There were no distinct changes in the remaining 16 patients (non-dip group). At rest, the cardiac index was significantly lower, and right ventricular systolic and mean pulmonary artery pressures were significantly higher in the dip group than in the non-dip group. However, no significant difference was noted in the right ventricular end-diastolic pressure between the two groups at rest. The right ventricular systolic and end-diastolic pressures were greater during exercise in the dip group than in the non-dip group. In all of the patients in the dip group, the right ventricular pressure exceeded the left ventricular pressure only in early diastole, coinciding with the early diastolic dip of the ventricular septum, during exercise. In conclusion, occult cor pulmonale can be diagnosed accurately by the appearance of an early diastolic dip of the ventricular septum and distorted left ventricular shape during exercise in patients with COPD.     

COPD患者肺部感染控制窗的影响因素分析

目的探讨COPD患者肺部感染控制窗（PIC窗）的影响因素及临床意义。方法对68例早出现PIC窗的患者和62例晚出现PIC窗的患者进行调查，判定PIC窗的影响因素。结果COPD患者的较早出现PIC窗组为（3．6±0．8）d，较晚出现PIC窗组为（7．8±0．6）d，两组差异有统计学意义（P〈0．001）；Logistic多因素回归分析结果为雾化吸入支气管舒张剂（P=0．006）和床旁支气管镜吸痰（P=0．001）是主要影响因素；结论雾化吸人支气管舒张剂和床旁支气管镜吸痰治疗有利于COPD患者PIC窗提早出现，把握好PIC窗，有助于危重症COPD急性加重期的治疗。     

Treatment of Chronic Obstructive Pulmonary Disease with Roflumilast,a New Phosphodiesterase 4 Inhibitor

ABSTRACT

Recent advances in chronic obstructive pulmonary disease (COPD) treatment offer symptom relief, but disease modification remains an unmet goal of pharmacotherapy. Reducing the frequency and severity of COPD exacerbations may help slow disease progression and reduce the morbidity, mortality, and costs associated with these major events. Other desirable characteristics for a COPD treatment include a once-daily dosing schedule, an oral formulation, and a low frequency of systemic side effects. Phosphodiesterase 4 inhibitors have been in clinical development for some years and roflumilast is currently the most advanced of these agents. In this review, the preclinical evidence, clinical safety, and efficacy of roflumilast available in published reports are considered. The data reviewed here suggest that the clinical efficacy of roflumilast occurs through a mechanism unrelated to bronchodilation and may be due to the suppression of lung inflammation. Lung function improved with roflumilast treatment and in some studies, the reduction in exacerbations was substantial and statistically significant. Notably, this effect appeared to be greatest in the subgroup of patients with more severe disease and more severe exacerbations. The evaluation of roflumilast safety largely centers on gastrointestinal adverse events, with diarrhea, nausea, and weight loss occurring more frequently with the drug than placebo. If approved for general use, we expect roflumilast to find its role initially as a substitute for inhaled corticosteroids in the maintenance treatment of severe and very severe disease, particularly in patients who have frequent acute exacerbations, and perhaps as a supplementary drug when symptoms are not adequately controlled by current conventional COPD therapy.     

Electrocardiographic Characteristics of Patients with Chronic Obstructive Pulmonary Disease

Abstract

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease. Electrocardiography (ECG) carries information about cardiac disease and prognosis, but studies comparing ECG characteristics between patients with and without COPD are lacking. We related ECG characteristics of patients with COPD, to ECG characteristics of patients without COPD, and determined whether ECG abnormalities are related to COPD severity. A cross-sectional study was conducted within a cohort of 243 COPD patients, aged 65 years or older. All patients underwent extensive examinations, including resting 12-lead ECG and pulmonary function tests. The reference group (n = 293) was a sample from the general population, also aged 65 or older, without COPD. Abnormal ECGs were more prevalent in COPD patients (50%) than in patients without COPD (36%, p = 0.054). Conduction abnormalities were the most common ECG abnormality in COPD patients (28%) being significantly more prevalent than in patients without COPD (11%, p < 0.001). The mean heart rate was higher in COPD patients (72 bpm (SD 14)) compared to controls (65 bpm (SD 13), p < 0.001), and QTc prolongation was less frequent in COPD patients (9% versus 14%, p = 0.01). The prevalence of ECG abnormalities increased with severity of pulmonary obstruction. ECG abnormalities, especially conduction abnormalities are common in COPD patients, and the prevalence of ECG abnormalities increases with severity of COPD. This underlines the importance of an integrated-care approach for COPD patients, paying attention to early detection of unrecognized coexisting cardiac disorders.     

缺氧对肺心病患者肺动脉压力以及右心室结构与功能的影响

目的观察肺心病患者不同缺氧程度时肺动脉压力及右心室结构与功能的变化,同时取健康成人作对照,探讨缺氧对肺心病患者肺动脉压力及右心室结构与功能的影响。方法选择80例肺心病患者为病例组,并选取30名健康成人为对照组。测定治疗前以及病情缓解后血气分析、肺动脉压力(PAPS)、右心室前壁厚度(RVAW)、右心室舒张末期内径(EDRV)、右心室射血分数(EFRV)。结果治疗前,肺心病患者病情不同,缺氧程度不同,与健康成人比较,PAPS、RVAW、EDRV、EFRV均明显异常(P<0.01)。治疗后,与健康成人比较,肺心病患者PAPS、RVAW、EDRV、EFRV均明显异常(P<0.01)。缺氧程度不同的患者之间比较发现,PAPS、EDRV、EFRV等指标均有所异常(P<0.05或P<0.01)。结论缺氧对肺心病患者肺动脉压力以及右心室结构与功能有明显的负面影响,改善缺氧有利于降低肺动脉压力,改善右心功能。     

Doppler-Derived Myocardial Performance Index in Patients with Impaired Left Ventricular Relaxation and Preserved Systolic Function

Background: The Doppler-derived myocardial performance index (MPI) has been used in the evaluation of left ventricular (LV) function in several diseases. In patients with isolated diastolic dysfunction, the diagnostic utility of this index remains unclear. The aim of this study was to determine the diagnostic utility of MPI in patients with systemic hypertension, impaired LV relaxation, and normal ejection fraction. Methods: Thirty hypertensive patients with impaired LV relaxation were compared to 30 control subjects. MPI and its components, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), and the ejection time (ET), were measured from LV outflow and mitral inflow Doppler velocity profiles. Results: MPI was higher in patients than in control subjects (0.45 ± 0.13 vs 0.37 ± 0.07 P < 0.0029). The increase in MPI was due to the prolongation of IRT without significant change of ICT and ET. MPI cutoff value of ≥0.40 identified impaired LV relaxation with a sensitivity of 63% and specificity of 70% while an IRT >94 ms had a sensitivity of 67% and specificity of 80%. Multivariate analysis identified relative wall thickness, mitral early filling wave velocity (E), and systolic myocardial velocity (Sm) as independent predictors of MPI in patients with hypertension. Conclusions: MPI was increase in patients with hypertension, diastolic dysfunction, and normal ejection fraction but was not superior to IRT to detect impaired LV relaxation.     

伊伐布雷定对慢性阻塞性肺疾病所致慢性肺源性心脏病失代偿期患者心肺功能的影响

目的:观察伊伐布雷定对COPD所致慢性肺源性心脏病失代偿期患者心肺功能的影响。方法：62例COPD所致慢性肺源性心脏病患者随机分为常规治疗组及伊伐布雷定组,进行常规抗心衰治疗或联合伊伐布雷定治疗3个月,记录治疗前后NT-proBNP、hs-CRP、PCT、肺功能、COPD评估测试(CAT)、6分钟步行实验距离、心脏彩超(LVEF、SV、RVD)、24小时平均心率等治疗。结果：两组患者治疗前一般情况一致,无统计学差异。治疗后,伊伐布雷定组患者6分钟步行实验距离、CAT评分均改善,NT-proBNP较常规治疗组明显降低,24小时平均心率明显下降,两组差异具有统计学意义。hs-CRP、PCT、肺功能指标(PEF、FEV1%pred、FEV1/FVC％)、LVEF、SV、RVD改变无统计学差异。结论:在COPD所致肺心病患者中应用伊伐布雷定3个月,可改善患者心功能,提高运动耐量及生活质量,但对患者肺功能及心脏改变无影响。     

Paraoxonase 1 Activity in Patients with Chronic Obstructive Pulmonary Disease

Introduction: Paraoxonase 1 (PON1) is an antioxidative enzyme manly associated with high density lipoproteins (HDL) in the peripheral blood. The aim of this study was to determine the PON1 paraoxonase and arylesterase activities in patients with chronic obstructive pulmonary disease (COPD). We also aimed to determine the concentration of reduced thiol groups as a marker of protein oxidation. Materials and methods: The study included 105 patients with stable COPD and 44 healthy controls. PON1 activities and thiols concentration were assayed in sera by spectrophotometry. Results: PON1 basal (POX) and salt-stimulated paraoxonase activity (POX1) as well as arylesterase activity (ARE) were significantly reduced in COPD patients. In addition, concentration of reduced thiol groups was significantly decreased in COPD group. PON1 activities were similar in patients with different disease severity (GOLD stages). However, a significant reduction in POX, POX1 and ARE was observed already in GOLD II stage when compared to controls. POX and POX1 showed modest while ARE yielded very good power for discrimination between healthy subjects and COPD patients. Univariate and multivariate logistic regression analysis indicated that ARE is a good COPD predictor. Conclusion: Reduction of PON1 activity observed in COPD patients could be partly caused by oxidative environment. Lower concentrations of reduced thiol groups in COPD patients suggest that a decrease in PON1 activity could reflect oxidative changes of enzyme free cysteine residues. Furthermore, decreased PON1 arylesterase activity might indicate a down-regulation of PON1 concentration. Our results suggest that ARE could be considered as potential biomarker for COPD diagnosis.     

慢阻肺病人肺功能与精神障碍的相关性研究

目的探讨慢性阻塞性肺疾病患者肺功能和精神障碍的相关性。方法入选慢性阻塞性肺疾病患者120例,按照精神状态分为精神障碍组48例和精神正常组72例,分析并比较其肺功能状态。结果和精神正常组相比,精神障碍组肺功能损害程度较重,以重度和极重度者居多,两组之间的差异具有统计学意义（P〈0.01）。结论慢性阻塞性肺疾病患者合并精神障碍者肺功能损害更为严重,对这类患者的临床诊治,更应考虑其肺功能特点,制定科学完善的方案。     

Right Ventricular Function Predicts Clinical Response to Specific Vasodilator Therapy in Patients with Pulmonary Hypertension

Introduction: We followed patients with pulmonary arterial hypertension (PAH) receiving specific vasodilator therapy and tested for predictors of clinical outcome. Methods: Thirty‐two patients (mean age 39 ± 15 years, 22 women, diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with inoperable chronic thromboembolic PH received therapy with either bosentan, sildenafil, or both and were evaluated with clinical parameters, biomarkers (B‐type natriuretic peptide values), and echocardiography before receiving specific medication and every 3 months thereafter. A right heart catheterization was performed at baseline. A composite endpoint of death, worsening of functional class, or the need of a second vasodilator agent was used to define the clinical nonresponders. Results: Patients were followed for 14 months (7.5–21). The endpoint was reached by 15 patients: four patients died (two idiopathic PAH and two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional class worsening, and four patients needed to be switched to combination therapy. Patients who remained clinically stable or improved had at baseline a better cardiac output with a less remodeled right ventricle (RV) and better functioning RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV global strain value higher than ?13.4% predict with 87% sensitivity and 83% specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC 84.2%, P = 0.003), respectively, patients who will deteriorate clinically under specific vasodilator therapy. A multivariate model showed RVFAC to be the only independent predictor of the endpoint with a HR of 0.87 (0.8–0.96), P = 0.007. Conclusions: Over an average period of 1 year, almost half of patients showed signs of clinical deterioration despite specific vasodilator therapy. Parameters of right ventricular morphology and function had prognostic value in these patients.