A Study on the Echocardiographic Assessment of Pulmonary Hypertension in Female Chronic Obstructive Pulmonary Disease Patients – A Cross-Sectional Study

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INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is an obstructive lung disease that causes recurrent airway inflow obstruction. The global prevalence of COPD is estimated to be 10.3%.^[1] COPD is more prevalent in men than in women. COPD is a disease of smokers. Recent studies have shed light on other causes such as air pollution, indoor pollution, occupational exposure, history of pulmonary tuberculosis, and poor socioeconomic status that can contribute to COPD.^[2] Hence, COPD is a polygenic disease. COPD can cause functional limitation in the form of breathlessness and easy fatiguability and can predispose to the most devastating complications like pulmonary hypertension (PH). This type of PH secondary to chronic lung disease has been grouped as Group 3 PH. Due to symptom overlap between lung disease and PH, there may be a delay in the diagnosis of PH. Once PH develops, the quality of life decreases and the mortality rate increases if not adequately controlled. According to the European Society of Cardiology (ESC)/European Respiratory Society (ERS) PH is diagnosed when the mean pulmonary arterial pressure is > 20 mm Hg using right heart catheterization.^[3] It is an invasive procedure, and non-invasive modalities like echocardiography can be used to diagnose PH.^[4] The large Indian PH registry, PROKERALA registry, used echocardiography to diagnose PH and follow up.^[4]

Group 3 PH includes PH due to COPD or interstitial lung disease (ILD) or hypoventilation syndromes.^[5] Patients with COPD often develop mild to moderate PH. Transthoracic echocardiographic findings such as pulmonary artery systolic pressure ≥45 mm Hg, or other abnormal RV findings can be used to diagnose PH.^[3] Major PH registries such as ASPIRE or REVEAL mainly focused on studying pulmonary arterial hypertension. PROKERALA registry, which studied the epidemiology pattern, showed that COPD-related PH is more prevalent than ILD-related PH.^[4] This study mainly focuses on identifying PH in female COPD patients using echocardiographic parameters. COPD is diagnosed with spirometry as per the Global Initiative for Chronic Obstructive Lung Disease, based on post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC).^[6]

Hence, this study was done on female COPD patients to study the prevalence and their clinical profile using echocardiography. All the patients were made to undergo a 6-min walk test to assess the functional capacity of these patients.

MATERIALS AND METHODS

It is a cross-sectional study conducted at the Government Stanley Medical College for a period of 3 months. The Institutional Ethics Committee has provided approval for the current study. Female patients diagnosed with COPD by spirometry, admitted under the department of general medicine and respiratory medicine, were included in this study. Patients with congenital or structural heart disease, left heart disease, were excluded based on echocardiographic findings. Patients with a previous history of coronary artery disease were excluded. Patients diagnosed with chronic pulmonary thromboembolism based on history/echocardiography/computed tomography pulmonary angiogram findings were excluded; connective tissue disorders, portal hypertension, and patients living with HIV/AIDS were excluded from this study. Patients are made to undergo echocardiography, and an assessment for PH was done. The following echocardiographic parameters were assessed for these patients, such as right atrial and right ventricle size from four-chamber view, flattened interventricular septum, and right atrial pressures which were calculated based on inferior vena cava size, pulmonary artery systolic pressures were calculated based on tricuspid regurgitation velocity and inferior vena cava size, diastolic pulmonary artery pressures were calculated based on end diastolic velocity of pulmonary regurgitation and inferior vena cava size, and mean pulmonary artery pressures were calculated based on peak early diastolic velocity of pulmonary regurgitation and Inferior vena cava size [Figure 1a, 1b and 1c]. Tricuspid annular plane systolic excursion (TAPSE) was measured from the tricuspid annulus in the four-chamber view, and pulmonary velocity acceleration time was measured from the right ventricular outflow tract (RVOT) in short-axis view [Figure 1d].^[3] They are made to undergo a 6-min walk test to assess their functional capacity.^[5] The sample size was estimated to be 36. The study period was from June 2024 to August 2024.

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Figure 1:

Echocardiographic features of pulmonary hypertension. (a) Apical four-chamber view showing dilated right atrium and right ventricle. (b) Apical four-chamber view showing tricuspid regurgitation. (c) Short-axis view at the aortic level showing pulmonary regurgitation. (d) Short-axis view at the aortic level showing pulmonary velocity acceleration time.

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RESULTS

Thirty-six female COPD patients diagnosed with spirometry were taken up for study over a period of 3 months from June 2024 to August 2024. Most of the females belonged to the age group of 61 - 70 years. Around 22% of females had enlarged right heart chamber size [Table 1 ] and 11% had elevated right heart pressures [Table 2]. They were in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 at the time of study [Table 3]. Around 69% of females belonged to the World Health Organization functional class 1 at the time of study. Around 80% of patients did not have echocardiographic features of PH; 11% of patients belonged to the severe PH category [Table 4]. Females with COPD duration of more than 10 years exhibited features of PH [Table 5]. All patients were made to undergo a 6-min walk test, and around 23 patients were able to complete the test. Four patients developed breathlessness and discontinued the test, and nine patients were not willing for this test. Patients who did not show any echocardiographic evidence of PH were able to complete the test [Table 6].

DISCUSSION

Chronic obstructive pulmonary disease is one of the three major causes of death globally.^[7] It is a major cause of morbidity and mortality and causes a significant social and economic burden to the world.^[7] Smoking was long considered to be a main risk factor for COPD.^[8] However, several risk factors were studied to cause PH, such as genetic and environmental interactions. The prevalence of COPD is higher even in less populated areas and this calls for studying other factors causing COPD.

The prevalence of COPD is higher in males than in females.^[9,10] Women often develop COPD at a much younger age when compared to men because women are more exposed to indoor pollution.^[9,10] COPD is common in females who are non-smokers or who smoke less when compared to men.

Patients with COPD often present with breathlessness, chronic cough, or sputum production. COPD is diagnosed with spirometry, presence of post bronchodilator FEV1/FVC < 0.7 is necessary to establish the diagnosis of COPD.

PH is a dreaded complication of COPD. The main pathogenesis behind PH due to lung disease is chronic hypoxia. Chronic hypoxia causes changes in the pulmonary vasculature such as intimal thickening, smooth muscle hyperplasia of the tunica media of the pulmonary arterioles and arteries. There is also increased production of pulmonary vasoconstrictors such as endothelin-1 and decreased expression of vasodilators such as endothelial nitric oxide synthase and prostacyclin synthase in COPD patients, that causes significant narrowing of pulmonary vasculature, leading to PH.^[11] The diagnosis of PH is made by right heart catheterization showing MPAP > 20 mm Hg.^[12,13] PH can be classified into five types such as pulmonary arterial hypertension, PH due to mitral or aortic disease, PH due to lung disease, PH due to chronic pulmonary thromboembolism, and multifactorial mechanisms causing PH.^[12,14] PH due to left heart disease forms the major cause of PH worldwide followed by PH associated with lung disease.

Echocardiography is the most widely used non-invasive investigative modality to diagnose PH.^[13] ESC/ERS guidelines on transthoracic echocardiographic parameters such as enlarged right ventricle and right atrium [Figure 2], flattened interventricular septum, dilated inferior vena cava, reduced right ventricle fractional area change, RVOT acceleration time of < 105 ms [Figure 1d], decreased TAPSE < 18 mm, elevated systolic pulmonary artery pressure, and [Figure 3] presence of pericardial effusion can be used to diagnose PH.^[13]

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Figure 2:

Right heart chamber size frequency distribution.

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Figure 3:

Pulmonary artery systolic pressure (PASP), diastolic pulmonary artery pressure (DPAP), and mean pulmonary artery pressure frequency (MPAP). (X axis represents PASP, DPAP and MPAP and Y axis represents pressure in mmhg)

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This study uses echocardiography as an investigative modality of choice to diagnose PH. As PROKERALA registry, the largest multicenter PH registry in India^[4] stated that patients with COPD develop mild-to-moderate PH [Figure 4]; in this study, the majority of patients did not have any echocardiographic evidence of PH. Patients with COPD duration of more than 10 years exhibited features of PH such [Figures 5 and 6] as enlarged right atrium and right ventricle, PASP of more than 70 mm Hg, DPAP of more than 36 mm Hg, MPAP of more than 50 mm Hg, TAPSE <18 mm, and pulmonary velocity acceleration time of <105 ms.

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Figure 4:

Stage of chronic obstructive pulmonary disease frequency distribution.

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Figure 5:

Grades of pulmonary hypertension frequency distribution.

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Figure 6:

Comparison between chronic obstructive pulmonary disease (COPD) duration and grades of pulmonary hypertension (PH). (The X-axis represents grades of PH and Y-axis represents the duration of COPD).

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Patients with PH did not complete a 6-min walk test. Patients without PH were able to complete a 6-min walk test [Figure 7].^[5] This study shows that there is a significant correlation between the duration of COPD and the development of PH. Prompt management of COPD and early diagnosis will improve morbidity and reduce mortality.

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Figure 7:

The comparison table between grades of pulmonary hypertension (PH) and 6-min walk test. (The X-axis represents the grades of PH and the Y-axis represents the number of female chronic obstructive pulmonary disease patients.)

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CONCLUSION

This study used echocardiography to identify PH in COPD patients and found a significant corelation between duration of COPD and PH. In this study, around 80% of female COPD patients did not show any echocardiographic evidence of PH. Patients with COPD duration of more than 10 years exhibited echocardiographic evidence of PH. Patients without PH were able to complete the 6-min walk test. This study calls for early diagnosis of PH using echocardiography and prompts management to improve the quality of life of such patients.