|Year : 2015 | Volume
| Issue : 3 | Page : 66-71
Screening of Chronic Obstructive Pulmonary Disease Patients for Pulmonary Arterial Hypertension Using Two-Dimensional Transthoracic Doppler Echocardiography in Tertiary Care Hospital in India
Vinay Mahishale, Bhagyashri Patil, Ankit Rathi, Avuthu Sindhuri, Ajith Eti
Department of Pulmonary Medicine, KLE University's J. N. Medical College, Belgaum, Karnataka, India
|Date of Web Publication||7-Sep-2015|
Dr. Vinay Mahishale
Department of Pulmonary Medicine, KLE University's J. N. Medical College, Belgaum, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Chronic obstructive pulmonary disease (COPD) and pulmonary arterial hypertension (PAH) are common and underdiagnosed medical conditions in India. Prevalence of these chronic diseases is high both in rural and urban areas. However, the exact prevalence of PAH in Indian COPD patients is unclear. Comorbid conditions like PAH have a great impact on the outcome of COPD in the form of severity, exacerbations, morbidity, and mortality. Right heart catheterization remains the gold standard test for diagnosis of PAH, but it is invasive and practically not feasible. Aims and objectives: The present study objective was to screen COPD patients for PAH using two-dimensional transthoracic Doppler echocardiography (ECHO) in Tertiary Care Hospital. Results: A total of 2040 patients with a confirmed diagnosis of COPD were enrolled in the study. Among these patients, 1509 were males (73.9%), 531 were females (23.06%), and 1428 were known or ex-smokers (70%). None of the females were smokers, but there was a history of biomass fuel exposure for >10 years. As per global initiative for chronic obstructive lung disease criteria, mild, moderate, severe, and very severe COPD was noted in 525,629,511, and 375 patients, respectively. When they were screened using ECHO, prevalence of PAH was 41.96% as 856 subjects had PAH. Prevalence of PAH among mild, moderate, severe, and very severe COPD was 23.8%, 34.81%, 48.53%, and 70.4%, respectively. There was a linear relationship between PAH and severity of COPD. Conclusion: PAH is very common in COPD patients in India. As the severity of COPD increased, the frequency and degree of PAH also increased. ECHO is an excellent tool for detection of PAH in COPD patients. All patients with severe to very severe COPD should be routinely screened by ECHO for PAH and with mild to moderate COPD, who have dyspnea out of proportion to their clinical condition should also be screened for PAH.
Keywords: Chronic obstructive pulmonary disease, pulmonary arterial hypertension, two-dimensional transthoracic doppler echocardiography
|How to cite this article:|
Mahishale V, Patil B, Rathi A, Sindhuri A, Eti A. Screening of Chronic Obstructive Pulmonary Disease Patients for Pulmonary Arterial Hypertension Using Two-Dimensional Transthoracic Doppler Echocardiography in Tertiary Care Hospital in India. Heart India 2015;3:66-71
|How to cite this URL:|
Mahishale V, Patil B, Rathi A, Sindhuri A, Eti A. Screening of Chronic Obstructive Pulmonary Disease Patients for Pulmonary Arterial Hypertension Using Two-Dimensional Transthoracic Doppler Echocardiography in Tertiary Care Hospital in India. Heart India [serial online] 2015 [cited 2019 Jun 25];3:66-71. Available from: http://www.heartindia.net/text.asp?2015/3/3/66/157277
| Introduction|| |
All the studies conducted agree in predicting that both morbidity and mortality burden of chronic obstructive pulmonary disease (COPD) is rising. COPD is a progressive, partially reversible airflow obstructive condition and is a growing public health problem globally. By 2020, COPD is projected to cause over 6 million deaths annually worldwide. In its advanced stage, the disease causes severe disabilities and poor quality-of-life. ,,, It was predicted that COPD will be the third leading cause of death worldwide by 2020 with Asian countries having 3 times the number of patients than the rest of the world. ,, If the mortality from co-morbid conditions like pulmonary arterial hypertension (PAH) associated with COPD is taken into account, then this disease poses an even greater impact on health outcomes.
Our general perceptive of the disease has greatly improved in last 10-15 years. Greater understanding of the pathophysiology of COPD, focused on the concept of systemic inflammation has also helped to explain the high frequency of major comorbidities mainly PAH. The development of PAH in COPD has both functional and prognostic implications. , PAH is a progressive disease of the pulmonary vasculature, characterized by elevated pulmonary arterial pressure (PAP), and pulmonary vascular resistance. The definitive diagnosis of PAH requires an elevated mean pulmonary arterial pressure (mPAP) of >25 mmHg at rest measured by right heart catheterization (RHC). Although, RHC "the gold standard test" is now a relatively safe procedure but is invasive, hence impractical to perform in all COPD patients for whom it is not clearly indicated.  Two-dimensional transthoracic Doppler echocardiography (ECHO) is one such tool and is widely available and can be safely used in COPD patients. In addition to its role in diagnosis, it can be used to screen for high-risk patient populations, to assess prognosis and to monitor disease stability and response to treatment. 
The overall reported prevalence of PAH in COPD ranges between 20% and 43%. , It is difficult to define this prevalence exactly, as the diagnostic criteria used in the literature vary with differing RHC pressures and ECHO thresholds. Patient population also differ and run the spectrum from primary care-based community cohorts to patients being evaluated for either lung volume reduction surgery or lung transplantation. The prevalence of COPD in India according to various studies is 3.67% (4.46% among males and 2.86% in females). The estimated burden of COPD in India is about 15 million cases (males and females contributing to 9.02 and 5.75 million, respectively). These figures may however, underestimate the true burden since questionnaire-based prevalence rates tend to underestimate the true spirometry-based prevalence of COPD.  However, prevalence of PAH in COPD patients in India is unclear as it is practically impossible to subject all these patients to RHC. Hence, the present study was undertaken to find the prevalence of PAH in COPD patients, using ECHO in tertiary care hospital.
| Methodology|| |
Source of data
Patients visiting inpatient and Outpatient Departments of Pulmonary Medicine, Internal Medicine and Cardiology sections were selected by convenience sampling for the study at a Tertiary Care Hospital, Belgaum, Karnataka, India.
Patients known or newly diagnosed with COPD as per Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria 2013.
A cross-sectional study.
Primary data were collected from January 2013 to August 2014.
A total of 2040 COPD patients were screened for PAH (open-ended sample size).
- Both male and female patients known or newly diagnosed with COPD.
- Age >40 years.
Fallowing patients were excluded.
- History of chronic lung disease other than COPD
- Any congenital/acquired cardiac disease which can lead to the development of PAH
- Systemic diseases which can cause PAH
- Chronic thromboembolic diseases
- HIV infection
- On drugs which are known to cause PAH.
Patients with confirmed diagnosis of COPD as per GOLD criteria 2013, (post-bronchodilator forced expiratory volume in 1 s [FEV 1 ] ≤70% predicted) were enrolled in the study. After obtaining informed consent, all the enrolled patients were given a questionnaire concerning: Age, sex, level of education, self-reported height and weight, level of dyspnea (Medical Research Council range 0-4), smoking status (current or nonsmoker or ex-smoker), pack years, current treatment, previous medications, duration of illness, occupation, and number of exacerbations, that is, emergency hospital admissions or unscheduled hospital visits in last 1-year, dyspnea score (D), level of airflow obstruction (O), current smoking status (S), and exacerbations (E) (DOSE) score, socioeconomic status, and history of any other disease. The DOSE score is a useful scoring system comprising measurements such as the body mass index, airflow obstruction, dyspnea, and exercise capacity. The DOSE index is found to predict hospital admission, respiratory failure, and exacerbation risk.  Mortality has been found to be associated with patients with a DOSE index score >4. The patients were subjected to pulmonary function test and ECHO to stage the severity of COPD and to see the presence or absence of PAH, respectively.
Pulmonary function test
This was done in accordance with American Thoracic Society/European Respiratory Society guidelines using RMS Helios 401 spirometer (Recorders and Medicare systems private limited, MEDSPIROR, India). The following values were obtained from the test: FEV 1 , forced vital capacity (FVC), ratio of FEV 1 /FVC, slow vital capacity, and maximum voluntary ventilation. FEV 1 , FVC, and the ratio of FEV 1 /FVC were the main parameters used to stage the COPD patients according to GOLD guidelines. Postbronchodilator spirometry (salbutamol 2.5 mg by nebulization) was performed in all the patients. Subjects with post-bronchodilator FEV 1 /FVC <0.70 were enrolled in the study. Then staged as mild, moderate, severe, and very severe COPD as per GOLD criteria. 
All patients were subjected to resting ECHO in the Department of Cardiology by experienced cardiologists. The machine used was Acuson SC 2000 cardiac ultrasound system using M4S multi-frequency probe with a range of 2-4.3 Mhz. Both 2D and M-Mode studies were done. ECHO was used to assess the pericardium, valvular anatomy, left and right-sided cardiac chambers, and cardiac functions. A carefully performed Doppler ECHO was able to identify and quantify Tricuspid regurgitant jet by color flow Doppler technique and the maximum jet velocity was measured by continuous wave Doppler without use of intravenous contrast. Right ventricular systolic pressure (RVSP) was estimated based on the modified Bernoulli equation and was considered to be equal to the systolic pulmonary arterial pressure (sPAP) in the absence of right ventricular outflow obstruction:
sPAP (mmHg) = RVSP = trans-tricuspid pressure gradient (TTPG) + right atrial pressure (RAP)
RVSP = 4Vmax 2 + RAP
where TTPG is 4Vmax 2 (V = peak velocity of tricuspid regurgitation (TR) in m/s). ,,
RAP is estimated on the basis of variation in size of IVC with inspiration as follows:
Complete collapse, RAP = 5 mm of Hg
Partial collapse, RAP = 10 mm of Hg
No collapse, RAP = 15 mm of Hg
Pulmonary arterial hypertension was defined in this study as sPAP ≥30 mmHg. This value was chosen according to the definition of PAH. PAH was classified into mild, moderate, and severe category as sPAP 30-50, 50-70, >70 mmHg, respectively. These values were chosen according to chemla formula; mPAP = 0.61 sPAP + 2 mmHg by putting value of mPAP for mild, moderate, and severe pulmonary hypertension as 25-35, 35-45, and >45 mmHg, respectively. ,
Mean ± standard deviation (SD) was calculated for normally distributed numerical outcomes. Mean ± SD of demographic characteristics among patients with and without PAH was done using Mann-Whitney test. Chi-square test was used to compare nonnumerical variables. Significance level was kept at P ≤ 0.05 level.
| Results|| |
A total of 2040 patients with a confirmed diagnosis of COPD were enrolled in the study after informed consent. Among these patients, 1509 were males (73.9%), 531 were females (23.06%), and 1428 were known or ex-smokers (70%). None of the females were smokers, but there was a history of biomass fuel exposure for >10 years. As per GOLD criteria, mild, moderate, severe, and very severe COPD was noted in 525, 629, 511, and 375 patients, respectively. When they were screened using ECHO, prevalence of PAH was 41.96% as 856 subjects had PAH. Prevalence of PAH among mild, moderate, severe, and very severe COPD was 23.8%, 34.81%, 48.53%, and 70.4%, respectively. There was a linear relationship between PAH and severity of COPD [Table 1]. PAH in COPD patients were found have correlation with age, smoking, duration of illness, DOSE score, annual exacerbations, severity of COPD, and hypoxia. The demographic data of patients with PAH and without PAH are demonstrated in [Table 2].
| Discussion|| |
Our perceptive of COPD has changed significantly over the past two decades. We have moved from an airflow limitation (FEV 1 )-centric view of the disease to the realization that COPD is a complex and heterogeneous condition. It is important to highlight that, "complex" means that COPD has a number of intrapulmonary and extrapulmonary components whose dynamic interactions along time are not linear, whereas "heterogeneous" indicates that not all of these components are present in all individuals at any given time point. 
Greater understanding of the pathophysiology of COPD has helped to explain the high frequency of major comorbidities (such as PAH, skeletal, and nutritional disorders) in addition to coexisting conditions that one would naturally expect due to the patients' advanced age and due to shared risk factors. Pulmonary artery remodeling is observed early in COPD and leads to PAH. This remodeling is the consequence of endothelial dysfunction and coagulopathy. The lung-specific mechanisms, such as hypoxic vasoconstriction, destruction of the pulmonary capillary bed by emphysema, smoking-induced inflammatory infiltration of the vascular wall, and shear stress due to redistribution of the blood flow significantly contribute to the development of PAH in COPD patients. 
The present study shows that the prevalence of PAH in COPD was significantly high in I COPD subjects (41.96%), when screened using ECHO. This study is in agreement with study by Gupta et al. done on a total of 40 patients of COPD where PAH was observed in 42.5% cases with prevalence of mild, moderate, and severe PAH being 25%, 10%, and 7.5%, respectively. The frequencies of PAH in mild, moderate, severe, and very severe COPD cases were 16.67%, 54.55%, 60.00%, and 83.33%, respectively.  Our analysis demonstrated that the frequency of PAH among mild, moderate, severe and very severe COPD was 23.8%, 34.81%, 48.53%, and 70.4% respectively. As the severity of COPD increased, prevalence, and severity of PAH also increased. PAH is associated with worse pre-bronchodilator FEV 1 and more severe hypoxemia.
There does appear to be an influence of age and sex on the predisposition for PAH in COPD. PAH is more commonly described in patients with advanced age, but whether this association is attributable to age alone, or other comorbidities contributing to PAH in the elderly, is unclear.  Our study was in line with this hypothesis. In the present study, the mean age of the subjects with PAH was higher than those without (67.46 ± 11.30 vs. 63.15 ± 10.64). Sertogullarindan et al. found PAH to be more common in females exposed to smoke from biomass fuels,  which was evident in our study also. Many women who had COPD were not smokers, but were exposed to the biomass fuel. Exposure to biomass fuel remains an important risk factor for the development of airflow limitation in Indian women, as tobacco smoking among women is regarded socially unacceptable in this country, and the number of women smokers is negligible compared to Nepal and other Western countries. ,
Interestingly in our study, on comparison of PAH within COPD groups, it was observed that there was no significant difference in PAPs between mild and moderate COPD. It has been demonstrated by Weitzenblum et al. by serial right heart catheterizations that annual increment in PAPs is minimal (1.47 ± 2.3 mm of Hg).  Kessler et al. confirmed that the evolution of PAH in patients with a moderate degree of airway obstruction was slow.  Similarly, a study by Renzetti et al. concluded that marked increase in PAP is only observed when FEV 1 is <1 l, which corresponds to FEV 1 <50% of predicted. 
Another important observation in our study was that 19 patients with mild to moderate COPD had severe PAH. It is important to note that PAH associated with COPD tends to be mostly mild to moderate in severity. However, PAH "out of proportion" to the severity of airflow obstruction is increasingly noted and may represent a distinct clinical entity that could potentially be amenable to vasoactive therapy.  The mechanisms responsible for "out-of-proportion" PAH in COPD are inadequately understood. It is uncertain whether it represents a severe variant of COPD-associated PAH caused by the same mechanisms or a distinct clinical entity. One theory is that these patients are "high responders" to acute hypoxemia, perhaps due to a genetic predisposition. Another possibility is that out-of-proportion PAH is a separate disease similar to idiopathic PAH.  Given the current uncertainty and poor prognosis associated with this clinical variant, it is imperative that clinicians identify such patients at the earliest which provides a window of opportunity to study them better by enrolling them in clinical trials.
The presence of PAH is suggestive of a poor prognosis in COPD patients, as several studies correlate elevated PAP with worsened survival. ,, In addition to its association with mortality, the presence of PAH also has a significant morbidity implication. PAH is associated with an exercise-induced desaturation and reduced exercise performance. Even mild elevations in the mPAP (18 mmHg) have been associated with an increased risk of COPD exacerbations and hospitalization.  In the current study also, the DOSE score which is a measure of severity of COPD and exacerbations were significantly higher in the patients with PAH (3.72 ± 2.19 vs. 2.41 ± 1.52).
Higham et al. concluded that the presence and degree of PAH is readily and reliably determined by ECHO in the majority of COPD patients and in view of the adverse effects of PAH on morbidity and mortality, routine ECHO in patients with severe disease may be warranted.  Similar conclusions were made in an Indian study by Gupta et al.  and in a Nepalese study by Shrestha et al.  who recommended that ECHO was found to be very useful in early detection of PAH in COPD cases.
Given the prevalence of PAH in COPD and its effect on outcomes there is value in screening for its presence. RHC cannot be used as a screening tool given its invasive nature and expense. Hence, ECHO is reliable, noninvasive, cost-effective, readily available, and time-saving tool to identify COPD patients with PAH. In addition to this, there is a wealth of additional information that can be revealed by ECHO as it can assess TR, right ventricular systolic function, septal defects, and left ventricular systolic and diastolic functions.
It is evident from current study as well as studies discussed above, failure or delayed diagnosis of PAH in COPD patients have greater impact on the outcome of COPD in the form of severity, quality-of-life, exacerbations, hospital stay, health care costs, and death. Active screening by ECHO for PAH in these subjects should lead to earlier detection of PAH and timely initiation of PAH specific treatment would lead to a good outcome.
The strength of the current study was active screening of large number of COPD patients for PAH using ECHO in Indian population which routinely not done. Other causes of PAH in patients were carefully excluded. However, this was a prospective study and carried out at a single center. Further studies with multiple centers and at different geographic population can be recommended to know the prevalence of PAH in Indian COPD subjects.
| Conclusion|| |
Pulmonary arterial hypertension is very common in COPD patients in India. As the severity of COPD increased, the frequency and degree of PAH also increased. ECHO is an excellent tool for detection of PAH in COPD patients. All patients with severe to very severe COPD should be routinely screened by ECHO for PAH and with mild to moderate COPD, who have dyspnea out of proportion to their clinical condition should also be screened for PAH.
| Acknowledgment|| |
Department of Cardiology KLES DR. Prabhakar Kore Hospital and Medical Research Centre, Belgaum, India.
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[Table 1], [Table 2]