Echocardiographic Evaluation of Right Ventricular Function and its Role in the Prognosis of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with structural and mechanical changes in the pulmonary vascular bed that increase right ventricular (RV) afterload and subsequently right heart failure.
OBJECTIVES: The aim of the study was to elucidate RV dysfunction at rest by echocardiography in a cohort of COPD patients and to study its impact on prognosis.
METHODS: 84 patients of COPD and 40 matching healthy controls were evaluated at baseline. Evaluation included clinical examination, pulmonary function tests; 6 minutes walk test and echocardiography. Patient with COPD were again evaluated after 6 months.
RESULTS: All echocardiographic parameters of RV function were significantly impaired in COPD patients as compared to controls. Clinical deterioration in COPD group was much more in patients with baseline abnormal RV function (89%) and patients with RV systolic pressure ≥35 mmHg (P = 0.018). All the six patients who died had three or more abnormal RV systolic function parameters.
CONCLUSIONS: RV myocardial performance index and basal strain showed largest difference between controls and COPD cases. Clinical deterioration was more common in patients with abnormal RV function parameters and pulmonary hypertension. Copyright:

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by chronic obstruction of lung airflow that interferes with normal breathing and is not fully reversible. As per one of the World Health Organization's communications, COPD had a prevalence of ~251 million cases, and it accounted for 5% of all deaths globally in 2016.[1]

COPD is associated with structural and mechanical changes in the pulmonary vascular bed that increase right ventricular (RV) afterload and subsequently right heart failure, which is linked to worse outcomes with an increased risk of hospital re-admissions and mortality.[23]

The evaluation of RV function is clinically useful in patients with COPD because the presence of RV failure has prognostic implications.[45] The right heart enlargement or diastolic dysfunction is associated with limited exercise capacity and poor prognosis.[5] Invasive hemodynamic measurements of RV function by cardiac catheterization is the gold standard, but recently, a number of studies have focused on noninvasive evaluation of pulmonary hypertension (PH) and RV function by cardiac magnetic resonance (CMR) imaging. In one of such studies, RV mass index and pulmonary artery area change were used to estimate mean pulmonary artery pressure.[6] In another CMR study, pulmonary artery pulsatility and pulmonary acceleration time were found to be reduced in patients of COPD.[7] CMR has also been used to differentiate arrhythmogenic RV cardiomyopathy from RV changes in athletes heart.[8] Despite these interesting investigations, echocardiography has remained the standard and most commonly used clinical method to assess RV function noninvasively. Echocardiographic assessment of RV function has been often difficult using conventional methods because of the complex anatomy of the right ventricle. Newer techniques such as three-dimensional evaluation of RV ejection fraction (RVEF), tissue Doppler imaging (TDI) velocities, and strain have emerged and enable identification of impaired RV function at an earlier stage.[9] These parameters are well correlated with the RVEF measured with magnetic resonance imaging.[1011] However, as yet literature has been scarce with regard to the evaluation of these parameters in the prognostication of COPD patients.

Aim

The aim of the study was to elucidate RV dysfunction at rest by applying modern echocardiographic imaging in a cohort of patients with COPD and to study the impact of RV dysfunction on prognosis in these patients on a medium-term basis.

METHODS

Study design

Prospective, observational, comparative study conducted in the departments of cardiology and pulmonary medicine of our institute, from September 2014 to October 2016. A total of 84 stable COPD patients and 40 healthy controls were included in the study. Necessary permission and approval from the Hospital Administration and Ethics Committee prior to starting the study were taken. Informed consent from patients was obtained prior to the recruitment of the cases.

Study population

The study population consisted of 84 patients with stable COPD of varying severity and free of overt cardiovascular disease, which came to the department of pulmonary medicine. A random sample of forty matched (age and weight) cases of healthy controls was also taken for comparison [Table 1].

Table 1

Demographics, pulmonary function, and echocardiographic parameters in healthy controls and chronic obstructive pulmonary disease patients

Variable	Mean±SD		P
	Control (n=40)	COPD (n=84)
Age (years)	61.1±8.6	63.9±9.21	0.10
Weight (kg)	65.4±6.16	63.19±6.67	0.04
Height (cm)	163.1±4.1	164.2±4.88	0.17
BSA (m2)	1.71±0.09	1.69±0.1	0.30
Systolic BP (mmHg)	123.5±7.87	121.93±8.28	0.24
Diastolic BP (mmHg)	75.6±4.28	72.17±6.4	0.003
FEV1% predicted	100.92±12.49	60.1±23.84	<0.01
FVC % predicted	85.36±10.02	74.6±10.46	<0.01
FEV1/FVC	78.08±3.18	59.59±10.71	<0.01
GOLD Stage	0±0	2.14±1.03	<0.01
BODE Index	0±0	1.63±1.62	<0.01
6 MWD (m)	499.9±39.04	415.66±65.86	<0.01
RIMP	0.4±0.06	0.5±0.11	<0.01
TAPSE (mm)	19.7±2.78	18.05±3.64	<0.01
FAC%	44.34±6.28	38.47±9.36	<0.01
RV basal strain (%)	−26.5±2.36	−21.9±5.45	<0.01
TDI TASV (cm/s)	12.35±2.44	11.2±2.17	<.01
RV FWT (mm)	4.18±0.7	5.19±1.06	<0.01
TV E/A	1.14±0.3	1.06±0.32	<0.01
TV-E/E’	5.57±1.7	6.34±2.89	<0.01
RAA (cm2)	11±2.43	14.14±2.99	<0.0001
LVEF (%)	60.35±2.13	58.57±4.19	0.019
RVSP (mmHg)	21.4±5.68 (n=26)	32.72±9.94 (n=62)	<0.01

COPD=Chronic obstructive pulmonary disease, BSA=Body surface area, BP=Blood pressure, FVC=Forced vital capacity, FEV1=Forced expiratory volume in 1 s, 6 MWD=6-minute walk distance, TAPSE=Tricuspid Annular Plane Systolic Excursion, RIMP=Right index of myocardial performance, RV=Right ventricle, TDI=Tissue Doppler imaging, RVSP=Right ventricular systolic pressure, FAC=Fractional area change, TASV=Tricuspid annular systolic velocity, RV FWT=RV free wall thickness, LVEF=Left ventricular ejection fraction, SD=Standard deviation, RAA=Right atrial appendage

Exclusion criteria

Patients with coronary artery disease, valvular heart disease, hypertension, atrial fibrillation, and cardiomyopathies were excluded

Patients with other clinically obvious pulmonary pathologies such as bronchial asthma, bronchiectasis, existing tuberculosis, and interstitial lung disease were excluded

Patients with other clinically obvious causes of PH including pulmonary thromboembolism, sleep apnea syndrome, and connective tissue disorders were excluded

Patients with malignancy, hyperthyroidism, renal failure, and diabetes mellitus were excluded.

Methodology

Echocardiography, spirometry, and 6-min walk test (6 MWT) were performed according to the current guidelines.

A pulmonary function test (PFT) machine “Medisoft Exp Air 1.28” was used to perform spirometry. Ratio of forced expiratory volume in one second/forced vital capacity (FEV1/FVC), FEV1% predicted, and FVC% predicted were measured to diagnose and assess the degree of airflow limitation in COPD and classify patients according to GOLD guidelines.[12] 6MWT was performed both in control and COPD patients as per the American Thoracic Society guidelines,[13] and it was repeated after 6 months in COPD patients.

All patients and healthy controls were subjected to resting two-dimensional (2D) transthoracic Doppler echocardiography. Doppler echocardiography was performed on VIVID-7 ultrasound machine from (2007, GE (General electric company, Boston, USA)). The 3S sector transducer (probe) with a frequency of 1.5–3.6 MHz was used.

Assessment of RV function was carried out as per the guidelines of American Society of Echocardiography 2010.[14]

The recordings were performed from left parasternal long- and short-axis, subcostal views, and apical four-chamber views adjusted to acquire the RV-focused view. TDI was performed using a high frame rate (180 frames/s). The peak systolic longitudinal strain and peak TDI velocities were measured at RV-free wall basal segment and tricuspid annulus, respectively, as these are considered the most reliable imaging regions of the right ventricle. The various echocardiographic parameters included were RV basal and mid-level diameter, RV wall thickness, right atrial area, tricuspid annular peak systolic excursion (TAPSE), RV index of myocardial performance (RIMP), fractional area change (FAC), tricuspid lateral annular peak systolic velocity on TDI (tricuspid annular systolic velocity [TASV]), and basal RV strain. Tricuspid regurgitant flow was identified by color flow Doppler technique, and the maximum jet velocity was measured by continuous wave Doppler. RV systolic pressure (RVSP) was estimated based on the modified Bernoulli equation and was considered to be equal to the pulmonary artery systolic pressure in the absence of RV outflow obstruction. Right atrial pressure was estimated by evaluating inferior vena cava (IVC) diameter in subcostal view and its collapsibility with inspiration/sniffing. The following criteria were used:[14]

Normal IVC diameter (<2.1cm) and >50% collapsibility – 3 mmHg

Normal IVC diameter (<2.1cm) and <50% collapsibility – 8 mmHg

Dilated IVC (2.1cm or more) and >50% collapsibility – 8 mmHg

Dilated IVC (2.1cm or more) and <50% collapsibility – 15 mmHg.

Detailed methods of echocardiographic assessment of various RV parameters have been included in supplementary file.

RV dysfunction was indicated by the following echocardiographic parameters:[14]

RIMP >0.54 by tissue Doppler

TAPSE <17 mm

2D FAC <35%

TDI TASV (S') <9.5 cm/s

Basal RV strain > −20%.

The results were considered after taking the average of three measurements.

Left ventricular function (both systolic and diastolic) was also assessed in the control and COPD patients. Left ventricular systolic function was assessed by measuring left ventricular ejection fraction (LVEF). RV diastolic function was also assessed in both the control and COPD patients.

After 6 months, clinical evaluation, spirometery, 6MWT, and 2D echocardiography were done on follow-up in COPD group. Death from any cause, hospital admission, deterioration in the PFT of at least 1 grade as per GOLD classification, and reduction of at least 10% in 6 min walk distance (6MWD) were considered deterioration in status.[15]

Statistical analysis

Data were entered in MS EXCEL spreadsheet, and analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0 (IBM, USA). Quantitative variables were compared using unpaired t- test/Mann–Whitney test (when the data sets were not normally distributed) between the two groups and paired t-test/Wilcoxon rank sum test across follow-up. Qualitative variables were compared using Chi-square test/Fisher's exact test. Pearson's correlation coefficient/Spearman's rank correlation coefficient was used to assess the association of quantitative variables with each other. P < 0.05 was considered statistically significant.

RESULTS

Most of the studied population was in the age group of 51–70 years. Fifty-nine (70.2%) of COPD patients were chronic smokers, while there was no smoker among controls. Most of the COPD cases were in GOLD Stage 1 and 2. The mean FEV1/FVC % was 78% in the control group and 59.6% in the COPD group. The mean 6MWT distance was 499.9 m in the control group and 415.66 m in the COPD group [Table 2].

Table 2

Pulmonary function and echocardiographic parameters of right ventricle in chronic obstructive pulmonary disease group at baseline and 6 months of follow-up

Variable	Mean±SD		P<0.0001
	Baseline (n=84)	6 months (n=67)
FEV1%	60.1±23.8	59.5±21.4	<0.01
FVC%	74.6±10.5	74.27±8.9	<0.01
FEV1/FVC	59.6±10.7	58.0±9.6	<0.01
GOLD Stage	2.14±1.03	2.09±1.07	0.01
BODE Index	1.63±1.62	1.52±1.49	<0.01
6 MWD (m)	415.66±65.86	410.75±69.79	<0.01
RIMP	0.5±0.11	0.52±0.08	<.01
TAPSE (mm)	18.05±3.64	17.92±3.39	>0.05
FAC%	38.47±9.36	37.72±8.6	<0.01
RV basal strain %	−21.9±5.45	−21.62±5.55	<0.01
TDI TASV (cm/s)	11.2±2.17	10.71±1.82	>0.05
RV FWT (mm)	5.19±1.06	5.34±1.04	<0.01
TV E/A	1.06±0.32	1.01±0.32	>0.05
TV-E/E’	6.34±2.89	6.32±3.09	>0.05
RAA (cm2)	14.14±2.99	13.91±2.98	>0.05
RVSP (mmHg)	32.72±9.94 (n=62)	32.47±11.25 (n=62)	>0.05

FVC=Forced vital capacity, FEV1=Forced expiratory volume in 1 s, 6 MWD=6-minute walk distance, TAPSE=Tricuspid Annular Plane Systolic Excursion, RIMP=Right index of myocardial performance, RV=Right ventricle, TDI=Tissue Doppler imaging, RVSP=Right ventricular systolic pressure, FAC=Fractional area change, TASV=Tricuspid annular systolic velocity, RV FWT=RV free wall thickness, LVEF=Left ventricular ejection fraction, SD=Standard deviation, RAA=Right atrial appendage

Tricuspid regurgitation and pulmonary hypertension

Fourteen (35%) controls and 22 (26.2%) COPD cases had no tricuspid regurgitation (TR) jet. Mild TR was seen in 24 (60%) controls and 51 (60.7%) COPD cases. Moderate TR was present in two (5%) controls and nine (10.7%) COPD cases and severe TR in two (2.4%) COPD cases. On the basis of Doppler peak regurgitation gradient, the patients were divided into two groups: those with RVSP <35 mmHg and the rest with RVSP >35 mmHg. Presence of RVSP >35 mmHg was considered to have PH. The mean RVSP in the COPD group was 32.72 mmHg as compared to 21.4 mmHg in the control group. The majority (34/62) of COPD patients with TR had RVSP <35 mmHg. Only one such patient had RVSP >50 mmHg.

Parameters of right ventricular function

Out of 84 patients with COPD, 28 had no abnormal parameter of RV dysfunction at baseline, while 1, 2, 3, 4, and 5 parameters were abnormal in 11, 12, 17, 11, and 5 patients, respectively. RIMP and all echocardiographic parameters of RV systolic function were significantly impaired in COPD patients (with and without PH) as compared to controls. Seventeen (20.24%) of COPD cases had abnormal TASV on TDI (<9.5 cm/s). Thirty-three (39.3%) COPD cases and six (15%) controls had abnormal TAPSE (<17 mm). Two (5%) cases among the control group and 26 (30.9%) among COPD group had low FAC (<35%). Out of the 84 COPD patients, 41 (48.8%) had abnormal RIMP (>0.54), while 43 (51.2%) had normal RIMP (≤0.54); all the cases in the control group had normal RIMP. Forty-eight (57.1%) COPD patients had abnormal RV basal strain (>−20%), whereas in the control group all cases had normal RV basal strain (≤−20%). RIMP and the RV basal strain showed the largest differences between controls and COPD. These indices were significantly impaired, as compared to controls, even in those COPD cases where RVSP was <35 mmHg.

Right ventricular wall thickness and right ventricular diameter

RV free wall thickness (RV-FWT) was significantly increased in COPD cases. Forty-four (52.4%) COPD patients has RV FWT >5 mm. Twenty-five patients with increased wall thickness had RVSP >35 mmHg (P < 0.0001). A statistically significant correlation was observed between RV-FWT and RVSP (r = 0.46, P = 0.002). Seven (8.3%) patients of COPD group had RV dilatation with basal diameter more than 4.2 cm in apical four-chamber view.

Right ventricular diastolic dysfunction and left ventricular function

Forty-eight (57.1%) COPD patients and 18 (45%) controls had RV diastolic dysfunction. The majority of the study population (41.67% COPD cases % and 32.5% control group) had type II diastolic dysfunction.

The mean LVEF in COPD was 58.5%, whereas in the control group, it was 60.35%. Seventy-five percent of the control group and 44% of the COPD patients had normal left ventricular diastolic function. Nearly 34.5% of COPD cases and 22.5% of controls had Grade I LV diastolic dysfunction. Grade II diastolic dysfunction was seen in 20.24% of COPD cases and 2.5% of controls. Grade III LV diastolic dysfunction was present in 1.2% of COPD cases.

Correlation between severity of chronic obstructive pulmonary disease and right ventricular function

There was a strong negative correlation of RIMP (r = −0.343, r = −0.071), RV basal strain (r = −0.448, r = −0.270), RVSP (r = −0.545, r = −0.502), and RV-FWT (r = −0.436, r = −0.357) with FEV1% and FEV1/FVC and a strong positive correlation of TAPSE (r = 0.393, r = 0.322) and FAC (r = 0.435, r = 0.330) with FEV1% and FEV1/FVC. There was a positive correlation of RIMP, RV basal strain, RVSP, RV FWT with GOLD stage, and BODE index and a negative correlation of TAPSE, FAC, and TDI TASV (S') with GOLD stage and BODE index [Figures 1 and 2, Supplementary File].

Figure 1

Correlation between forced expiratory volume 1% and right ventricular index of myocardial performance

Figure 2

Correlation between forced expiratory volume 1 % and right ventricular basal strain

Right ventricular function at 6-month follow-up and clinical deterioration

After 6 months, out of 84 COPD cases, 11 (13.1%) were lost to follow-up, 67 (79.7%) were alive, and 6 (7.1%) died. On follow-up, 11 (16.4%) COPD patients had deterioration in PFT and 6MWD. There was deterioration of RV function in 27 (32%) patients, which include 18 patients with abnormal baseline RV function and nine patients with normal baseline RV function. This was more common in patients with RVSP ≥35 mmHg (P < 0.001). Out of 27 patients with deterioration in RV function at 6 months, only 9 had worsening of PFT (P ≤ 0.0001). Out of 28 COPD patients with normal baseline RV function, 9 developed new RV dysfunction over a period of 6 months. New RV dysfunction was seen even in patients with RVSP of <35 mmHg.

A total of twenty patients developed clinical deterioration, out of which six had deterioration in PFT in the form of change in GOLD staging, six subjects died, and eight patients had hospital admission in the form of acute exacerbation of COPD (five patients) and right heart failure (three patients). Out of the eight patients who got admitted, five had worsening of PFT in the form of change in GOLD staging. Clinical deterioration was much more in patients with baseline abnormal RV function (89%) and patients with RVSP ≥35 mmHg (P = 0.018). All the six patients who died had three or more abnormal RV systolic function parameters. Out of the eight patients, who got admitted during follow-up, six had an abnormal RV systolic function at baseline. Three out of seven patients of COPD with RV dilatation at baseline developed clinical right heart failure.

DISCUSSION

The perceptive of COPD has changed significantly over the past two decades. We have moved from an airflow limitation (FEV1)-centric view of the disease to the realization that COPD is a complex and heterogeneous condition.[16] Pulmonary artery remodeling is observed early in COPD and leads to pulmonary artery hypertension (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.[17]

The presence of PAH is suggestive of a poor prognosis in COPD patients, as several studies correlate elevated PAP with worsening survival.[18] For long, while looking at cardiac ultrasound, the interest of pulmonologists as well as of cardiologists was restricted to the evaluation of RVSP in COPD patients. Therefore, in this study, we tried to look beyond RVSP and evaluated the correlation of various parameters of RV systolic function with severity of COPD as well as with the medium-term outcome.

We found that more than 50% COPD patients have RV dysfunction when newer echocardiographic methods such as RV basal strain and RIMP were used as compared to conventional echo parameters such as TAPSE or FAC (which were present in only 25%–30% cases). These newer methods were specific to COPD with or without PH. RIMP and RV basal strain showed the largest differences between controls and COPD cases [Table 1]. These indices were significantly impaired as compared with controls even in the absence of PH. These findings are consistent with the study by Hilde et al.[9] Vitarelli et al. have also demonstrated that systolic strain and strain rate were reduced in patients with RVSP <35 mmHg.[19]

The present study showed that abnormal RV systolic function and RV hypertrophy were present even in patients with COPD who did not have PH. These findings suggest that cardiac complications on the right side start early in the course of the pulmonary vascular disease, are incremental, and lead to RV impairment even at subclinical levels of elevated pulmonary artery pressures.

Majority of COPD patients (34/62 [~55%]) had RVSP <35 mmHg. Only one out of 62 COPD patients with TR had RVSP >50 mmHg. In one of the previous studies, PH was observed in 63% cases with the majority (58.8%) having mild PH.[20] This again indicates that RV dysfunction sets in before clinically recognizable PH.

Echocardiographic parameters of RV function had a strong correlation with disease severity as judged by pulmonary function testing as well as clinical classification. There was a strong negative correlation of RIMP, RV basal strain, RVSP, and RV FWT and a strong positive correlation of TAPSE, FAC, and TDI TASV with FEV1% and FEV1/FVC. There was a positive correlation of RIMP, RV basal strain, RVSP, RV FWT with GOLD stage, and BODE index and a negative correlation of TAPSE, FAC, and TDI TASV (S') with GOLD stage and BODE index [Figures 1 and 2, Supplementary File]. This emphasizes the fact that harmful effects of COPD on RV function progress in a continuous fashion.

The study provided some important insights regarding medium-term prognostication with the help of echocardiography. The majority of patients (89%) who develop clinical deterioration at 6 months had at least one abnormal parameter of the RV function at baseline. All the six patients who died had three or more abnormal RV systolic function parameters. Out of eight patients, who got admitted during follow-up, six (75%) had at least one abnormal parameter of RV systolic function at baseline. Forty-three percent of COPD patients who had RV dilatation at baseline subsequently develop clinical RV failure. RV end-diastolic diameter index was found to be one of the strongest prognostic markers in chronic pulmonary disease in one of the early studies.[5] These findings suggest an important role of echocardiographic parameters of RV function in COPD prognosis. Though this study was relatively small in size, this correlation between COPD prognosis and RV function on echocardiography has not been studied extensively in the past. Echocardiography is relatively cheaper and noninvasive modality which is readily available and can immensely help in prognostication of these patients. There is a need of larger future studies in this direction.

CONCLUSIONS

This study on clinically stable patients with COPD with a wide range of severity of airways disease provides evidence of subclinical RV dysfunction and suggests that cardiovascular comorbidities may begin early in COPD and are often occult. RIMP and RV basal strain showed largest difference between controls and COPD cases irrespective of the presence or absence of PH. Clinical deterioration was more common in patients with abnormal RV function parameters and in patients with RVSP ≥35 mmHg. RV hypertrophy was significantly present in COPD and has a significant positive correlation with RVSP. Left ventricular as well as RV diastolic dysfunction is present in majority of COPD patients even in patients with RVSP <35 mmHg.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Correlation between right ventricular index of myocardial performance and right ventricular systolic pressure

Correlation between right ventricular basal strain and right ventricular systolic pressure

Table 1

Comparison of echocardiographic parameters of right ventricle function in chronic obstructive pulmonary disease at baseline and follow up

Echocardiographic parameters of RV	COPD		P
	Baseline (n=84), n (%)	6 months (n=67), n (%)
RIMP
≤0.54	43 (51.19)	34 (50.75)	<0.0001
>0.54	41 (48.81)	33 (49.25)
TAPSE (mm)
<17	33 (39.29)	27 (40.30)	0.026
≥17	51 (60.71)	40 (59.70)
FAC%
<35	26 (30.95)	24 (35.82)	0.003
≥35	58 (69.05)	43 (64.18)
RV basal strain
>−20%	48 (57.14)	40 (59.70)	0.008
≤−20%	36 (42.86)	27 (40.30)
TDI TASV(S’) cm/s
<9.5	17 (20.24)	16 (23.88)	0.02
≥9.5	67 (79.76)	51 (76.12)
Abnormal RV parameters
0	28 (33)	23 (34.3)
1	12 (14.2)	5 (7.4)
2	11 (13.1)	8 (11.9)
3	27 (32.1)	15 (22.3)
4	11 (13.1)	10 (14.9)
5	5 (5.9)	6 (8.9)
RVOT free wall thickness
≤5	40 (47.62)	32 (47.76)	<0.0001
>5	44 (52.38)	35 (52.24)
RV basal diameter D1 (cm)
≤4.2	77 (91.67)	60 (89.55)	0.004
>4.2	7 (8.33)	7 (10.45)
RV mid diameter 2 (cm)
≤3.5	80 (95.24)	63 (94.03)	<0.0001
>3.5	4 (4.76)	4 (5.97)
Tricuspid regurgitation
Nil	22 (26.19)	17 (25.76)
Mild	51 (60.71)	42 (63.64)
Moderate	9 (10.71)	5 (7.58)
Severe	2 (2.38)	2 (3.03)
RV diastolic function
Normal	36 (42.86)	27 (40.30)	<0.0001
Type I DD	13 (15.48)	8 (11.94)
Type II DD	35 (41.67)	32 (47.76)

COPD=Chronic obstructive pulmonary disease, FVC=Forced vital capacity, FEV1=Forced expiratory volume in 1 s, TAPSE=Tricuspid Annular Plane Systolic Excursion, RIMP=Right index of myocardial performance, RV=Right ventricle, TDI=Tissue Doppler imaging, FAC=Fractional area change, TASV=Tricuspid annular systolic velocity, RVOT=Right ventricular outflow tract, DD=Diastolic dysfunction

Table 2

Correlation of pulmonary function test with echocardiography parameters

Variable	FEV1 (%)	FEV1% (6 M)	FVC%	FVC% (6 M)	FEV1/FVC	FEV1/FVC (6 M)	GOLD	GOLD (6 M)	BODE	BODE (6 M)	RVSP	RVSP (6 M)
FEV1%
Correlation coefficient	1.000	0.973**	0.729**	0.457**	0.599**	0.480**	−0.952**	−0.872**	−0.856**	−0.713**	−0.545**	−0.544**
P		<0.0001	<0.0001	0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.0001
n	84	67	84	67	84	67	84	67	84	67	62	49
FEV1% (6 M)
Correlation coefficient	0.973**	1.000	0.621**	0.501**	0.609**	0.551**	−0.944**	−0.900**	−0.815**	−0.734**	−0.532**	−0.545**
P	<.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.0001	0.0001
n	67	67	67	67	67	67	67	67	67	67	48	49
FVC%
Correlation coefficient	0.729**	0.621**	10.000	0.673**	0.401**	0.347**	−0.765**	−0.682**	−0.597**	−0.434**	−0.510**	−0.557**
P	<0.0001	<0.0001		<0.0001	0.0002	0.004	<0.0001	<0.0001	<0.0001	0.0002	<0.0001	<0.0001
n	84	67	84	67	84	67	84	67	84	67	62	49
FVC%(6 M)
Correlation coefficient	0.457**	0.501**	0.673**	1.000	0.335**	0.371**	−0.512**	−0.584**	−0.406**	−0.493**	−0.563**	−0.618**
P	0.0001	<0.0001	<0.0001		0.006	0.002	<0.0001	<0.0001	0.001	<0.0001	<0.0001	<0.0001
n	67	67	67	67	67	67	67	67	67	67	48	49
FEV1/FVC
Correlation coefficient	0.599**	0.609**	0.401**	0.335**	1.000	0.764**	−0.584**	−0.643**	−0.632**	−0.680**	−0.502**	−0.586**
P	<0.0001	<0.0001	0.0002	0.006		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
n	84	67	84	67	84	67	84	67	84	67	62	49
FEV1/FVC (6 M)
Correlation coefficient	0.480**	0.551**	0.347**	0.371**	0.764**	1.000	−0.508**	−0.623**	−0.463**	−0.555**	−0.533**	−0.470**
P	<0.0001	<0.0001	0.004	0.002	<0.0001		<0.0001	<0.0001	0.0001	<0.0001	0.0001	0.001
n	67	67	67	67	67	67	67	67	67	67	48	49
GOLD
Correlation coefficient	−0.952**	−0.944**	−0.765**	−0.512**	−0.584**	−0.508**	1.000	0.910**	0.851**	0.678**	0.509**	0.509**
P	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	0.0002
n	84	67	84	67	84	67	84	67	84	67	62	49
GOLD (6 M)
Correlation coefficient	−0.872**	−0.900**	−0.682**	−0.584**	−0.643**	−0.623**	0.910**	1.000	0.757**	0.761**	0.580**	0.638**
P	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001
n	67	67	67	67	67	67	67	67	67	67	48	49
BODE
Correlation coefficient	−0.856**	−0.815**	−0.597**	−0.406**	−0.632**	−0.463**	0.851**	0.757**	1.000	0.896**	0.590**	0.547**
P	<0.0001	<0.0001	<0.0001	0.001	<0.0001	0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001
n	84	67	84	67	84	67	84	67	84	67	62	49
BODE (6 M)
Correlation coefficient	−0.713**	−0.734**	−0.434**	−0.493**	−0.680**	−0.555**	0.678**	0.761**	0.896**	1.000	0.618**	0.651**
P	<0.0001	<0.0001	0.0002	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001
n	67	67	67	67	67	67	67	67	67	67	48	49
6MWD
Correlation coefficient	0.685**	0.610**	0.676**	0.472**	0.656**	0.616**	−0.732**	−0.709**	−0.626**	−0.558**	−0.429**	−0.421**
P	<0.0001	<0.0001	<0.0001	0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.001	0.003
n	84	67	84	67	84	67	84	67	84	67	62	49
6 MWD (6 M)
Correlation coefficient	0.555**	0.607**	0.588**	0.605**	0.634**	0.720**	−0.628**	−0.751**	−0.504**	−0.631**	−0.479**	−0.514**
P	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.001	0.0002
n	67	67	67	67	67	67	67	67	67	67	48	49
RIMP
Correlation coefficient	−0.343**	−0.241*	−0.447**	−0.180	−0.071	−0.035	0.327**	0.167	0.390**	0.165	0.448**	0.244
P	0.001	0.050	<0.0001	0.144	0.518	0.781	0.002	0.177	0.0002	0.182	0.0003	0.091
n	84	67	84	67	84	67	84	67	84	67	62	49
RIMP (6 M)
Correlation coefficient	−0.240	−0.238	−0.302*	−0.198	−0.256*	−0.167	0.218	0.249*	0.323**	0.315**	0.488**	0.433**
P	0.050	0.052	0.013	0.108	0.037	0.177	0.076	0.042	0.008	0.009	0.0004	0.002
n	67	67	67	67	67	67	67	67	67	67	48	49
TAPSE
Correlation coefficient	0.393**	0.407**	0.508**	0.417**	0.322**	0.286*	−0.468**	−0.423**	−0.345**	−0.368**	−0.479**	−0.370**
P	0.001	0.001	<0.0001	0.0005	0.008	0.019	0.0001	0.0004	0.004	0.002	0.0001	0.009
n	67	67	67	67	67	67	67	67	67	67	62	49
TAPSE (6 M)
Correlation coefficient	0.411**	0.429**	0.523**	0.394**	0.233	0.260*	−0.469**	−0.426**	−0.313**	−0.329**	−0.349*	−0.306*
P	0.001	0.0003	<0.0001	0.001	0.057	0.034	0.0001	0.0003	0.010	0.007	0.015	0.033
n	67	67	67	67	67	67	67	67	67	67	48	49
FAC%
Correlation coefficient	0.435**	0.315**	0.289**	0.133	0.330**	0.080	−0.407**	−0.246*	−0.525**	−0.400**	−0.603**	−0.534**
P	<0.0001	0.009	0.008	0.282	0.002	0.520	0.0001	0.045	<0.0001	0.001	<0.0001	0.0001
n	84	67	84	67	84	67	84	67	84	67	62	49
FAC%(6 M)
Correlation coefficient	0.248*	0.282*	0.104	0.305*	0.325**	0.228	−0.244*	−0.299*	−0.373**	−0.456**	−0.525**	−0.537**
P	0.043	0.021	0.405	0.012	0.007	0.063	0.047	0.014	0.002	0.0001	0.0001	0.0001
n	67	67	67	67	67	67	67	67	67	67	48	49
STRAIN %
Correlation coefficient	−0.448**	−0.327**	−0.410**	−0.005	−0.270*	−0.098	0.404**	0.296*	0.494**	0.332**	0.348**	0.257
P	<0.0001	0.007	0.0001	0.971	0.013	0.430	0.0001	0.015	<0.0001	0.006	0.006	0.075
n	84	67	84	67	84	67	84	67	84	67	62	49
STRAIN (6 M)
Correlation coefficient	−0.313**	−0.313**	−0.310*	−0.193	−0.309*	−0.244*	0.298*	0.297*	0.444**	0.406**	0.405**	0.369**
P	0.010	0.010	0.011	0.118	0.011	0.046	0.014	0.015	0.0002	0.001	0.004	0.009
n	67	67	67	67	67	67	67	67	67	67	48	49
TDI TASV(S’)cm/s
Correlation coefficient	0.213	0.080	0.184	−0.080	0.128	−0.110	−0.134	−0.055	−0.354**	−0.231	−0.399**	−0.286*
P	0.052	0.522	0.094	0.520	0.246	0.374	0.224	0.656	0.001	0.060	0.001	0.046
n	84	67	84	67	84	67	84	67	84	67	62	49
TDI TASV(S’) (6 M)
Correlation coefficient	0.125	0.133	0.148	0.097	0.150	0.275*	−0.085	−0.132	−0.315**	−0.418**	−0.467**	−0.414**
P	0.315	0.282	0.231	0.433	0.225	0.024	0.495	0.287	0.009	0.0004	0.001	0.003
n	67	67	67	67	67	67	67	67	67	67	48	49
RVFWT
Correlation coefficient	−0.436**	−0.276*	−0.472**	−0.138	−0.357**	−0.160	0.433**	0.330**	0.564**	0.463**	0.462**	0.413**
P	<0.0001	0.024	<0.0001	0.265	0.001	0.196	<0.0001	0.006	<0.0001	0.0001	0.0002	0.003
n	84	67	84	67	84	67	84	67	84	67	62	49
RV FWT (6 M)
Correlation coefficient	−0.280*	−0.267*	−0.339**	−0.195	−0.452**	−0.295*	0.259*	0.317**	0.457**	0.499**	0.608**	0.559**
P	0.022	0.029	0.005	0.114	0.0001	0.015	0.034	0.009	0.0001	<0.0001	<0.0001	<0.0001
n	67	67	67	67	67	67	67	67	67	67	48	49
PRVOT
Correlation coefficient	−0.172	−0.104	−0.192	−0.100	−0.197	−0.102	0.227*	0.228	0.225*	0.260*	0.589**	0.473**
P	0.118	0.401	0.081	0.420	0.072	0.413	0.038	0.063	0.039	0.034	<0.0001	0.001
n	84	67	84	67	84	67	84	67	84	67	62	49
PRVOT (6 M)
Correlation coefficient	−0.085	−0.120	−0.149	−0.191	−0.162	−0.090	0.135	0.218	0.053	0.205	0.504**	0.448**
P	0.496	0.334	0.229	0.121	0.191	0.468	0.275	0.077	0.672	0.096	0.0003	0.001
n	67	67	67	67	67	67	67	67	67	67	48	49
RV BASAL D1 (cm/m2)
Correlation coefficient	−0.549**	−0.540**	−0.331**	−0.178	−0.536**	−0.377**	0.537**	0.505**	0.569**	0.539**	0.570**	0.532**
P	<0.0001	<0.0001	0.002	0.149	<0.0001	0.002	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.0001
n	84	67	84	67	84	67	84	67	84	67	62	49
RV BASAL D1 cm/m2 (6 M)
Correlation coefficient	−0.484**	−0.518**	−0.216	−0.164	−0.571**	−0.440**	0.422**	0.495**	0.452**	0.516**	0.570**	0.547**
P	<0.0001	<0.0001	0.079	0.184	<0.0001	0.0002	0.0004	<0.0001	0.0001	<0.0001	<0.0001	<0.0001
n	67	67	67	67	67	67	67	67	67	67	48	49
RV BASAL D1 (cm)
Correlation coefficient	−0.585**	−0.581**	−0.388**	−0.186	−0.467**	−0.333**	0.546**	0.488**	0.539**	0.478**	0.505**	0.466**
P	<0.0001	<0.0001	0.0003	0.133	<0.0001	0.006	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.001
n	84	67	84	67	84	67	84	67	84	67	62	49
RV BASAL D1 cm (6 M)
Correlation coefficient	−0.497**	−0.519**	−0.310*	−0.170	−0.509**	−0.410**	0.429**	0.476**	0.431**	0.480**	0.599**	0.569**
P	<0.0001	<0.0001	0.011	0.170	<0.0001	0.001	0.0003	<0.0001	0.0003	<0.0001	<0.0001	<0.0001
n	67	67	67	67	67	67	67	67	67	67	48	49
RV MID D2 (cm/m2)
Correlation coefficient	−0.467**	−0.417**	−0.476**	−0.247*	−0.381**	−0.218	0.537**	0.494**	0.508**	0.429**	0.550**	0.539**
P	<0.0001	0.0004	<0.0001	0.044	0.0003	0.076	<0.0001	<0.0001	<0.0001	0.0003	<0.0001	0.0001
n	84	67	84	67	84	67	84	67	84	67	62	49
RV MID D2 cm/m2 (6 M)
Correlation coefficient	−0.413**	−0.415**	−0.411**	−0.220	−0.463**	−0.307*	0.441**	0.494**	0.364**	0.430**	0.540**	0.568**
P	0.001	0.0005	0.001	0.074	0.0001	0.011	0.0002	<0.0001	0.002	0.0003	0.0001	<0.0001
n	67	67	67	67	67	67	67	67	67	67	48	49
RV MID D2 (cm)
Correlation coefficient	−0.507**	−0.441**	−0.561**	−0.294*	−0.284**	−0.180	0.560**	0.493**	0.514**	0.394**	0.531**	0.552**
P	<0.0001	0.0002	<0.0001	0.016	0.009	0.146	<0.0001	<0.0001	<0.0001	0.001	<0.0001	<0.0001
n	84	67	84	67	84	67	84	67	84	67	62	49
RV MID D2 cm (6 M)
Correlation coefficient	−0.413**	−0.415**	−0.411**	−0.220	−0.463**	−0.307*	0.441**	0.494**	0.364**	0.430**	0.540**	0.568**
P	0.001	0.0005	0.001	0.074	0.0001	0.011	0.0002	<0.0001	0.002	0.0003	0.0001	<0.0001
n	67	67	67	67	67	67	67	67	67	67	48	49
RVSP
Correlation coefficient	−0.545**	−0.532**	−0.510**	−0.563**	−0.502**	−0.533**	0.509**	0.580**	0.590**	0.618**	1.000	0.956**
P	<0.0001	0.0001	<0.0001	<0.0001	<0.0001	0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001
n	62	48	62	48	62	48	62	48	62	48	62	46
RVSP (6 M)
Correlation coefficient	−0.544**	−0.545**	−0.557**	−0.618**	−0.586**	−0.470**	0.509**	0.638**	0.547**	0.651**	0.956**	1.000
P	0.0001	0.0001	<0.0001	<0.0001	<0.0001	0.001	0.0002	<0.0001	<0.0001	<0.0001	<0.0001
n	49	49	49	49	49	49	49	49	49	49	46	49
TV-E
Correlation coefficient	−0.146	−0.055	−0.129	−0.175	−0.171	−0.089	0.205	0.033	0.146	−0.046	0.194	0.031
P	0.186	0.660	0.241	0.156	0.120	0.476	0.061	0.792	0.186	0.713	0.132	0.834
n	84	67	84	67	84	67	84	67	84	67	62	49
TV-E (6 M)
Correlation coefficient	0.046	0.015	0.079	−0.025	−0.153	−0.049	0.079	−0.038	0.073	0.003	0.074	0.074
P	0.714	0.904	0.525	0.841	0.216	0.693	0.528	0.760	0.558	0.981	0.616	0.615
n	67	67	67	67	67	67	67	67	67	67	48	49
TV-A
Correlation coefficient	−0.046	0.099	−0.033	0.093	−0.085	0.145	0.091	−0.137	0.139	−0.026	0.166	−0.002
P	0.679	0.426	0.767	0.453	0.441	0.243	0.410	0.268	0.209	0.835	0.198	0.990
n	84	67	84	67	84	67	84	67	84	67	62	49
TV-A (6 M)
Correlation coefficient	0.151	0.189	0.004	0.128	−0.046	0.159	−0.076	−0.203	−0.028	−0.157	0.042	−0.018
P	0.221	0.125	0.977	0.301	0.711	0.199	0.543	0.099	0.822	0.204	0.775	0.903
n	67	67	67	67	67	67	67	67	67	67	48	49
TVE/A
Correlation coefficient	−0.140	−0.133	−0.173	−0.292*	0.004	−0.127	0.168	0.138	0.017	−0.065	0.042	−0.011
P	0.203	0.283	0.116	0.017	0.973	0.306	0.127	0.265	0.879	0.602	0.744	0.942
n	84	67	84	67	84	67	84	67	84	67	62	49
TVE/A (6 M)
Correlation coefficient	−0.206	−0.282*	0.027	−0.213	−0.099	−0.271*	0.209	0.264*	0.068	0.172	0.023	0.042
P	0.094	0.021	0.826	0.083	0.425	0.026	0.090	0.031	0.586	0.163	0.876	0.777
n	67	67	67	67	67	67	67	67	67	67	48	49
TV E’
Correlation coefficient	0.151	0.140	0.129	−0.192	−0.057	0.048	−0.164	−0.107	−0.038	0.073	0.171	0.241
P	0.171	0.258	0.242	0.120	0.605	0.699	0.136	0.389	0.729	0.558	0.185	0.095
n	84	67	84	67	84	67	84	67	84	67	62	49
TV E’ (6 M)
Correlation coefficient	0.156	0.095	0.272*	−0.119	−0.127	−0.036	−0.267*	−0.136	−0.015	0.099	0.341*	0.259
P	0.207	0.443	0.026	0.337	0.306	0.770	0.029	0.271	0.906	0.427	0.018	0.072
n	67	67	67	67	67	67	67	67	67	67	48	49
TV E/E’
Correlation coefficient	−0.191	−0.139	−0.181	0.007	−0.015	−0.083	0.265*	0.138	0.141	−0.033	−0.006	−0.116
P	0.082	0.261	0.100	0.958	0.889	0.504	0.015	0.266	0.201	0.790	0.960	0.429
n	84	67	84	67	84	67	84	67	84	67	62	49
TV E/E’ (6 M)
Correlation coefficient	−0.108	−0.066	−0.165	0.103	0.080	0.028	0.255*	0.089	0.039	−0.104	−0.238	−0.163
P	0.386	0.594	0.181	0.405	0.522	0.824	0.037	0.474	0.751	0.403	0.103	0.264
n	67	67	67	67	67	67	67	67	67	67	48	49
TV DT
Correlation coefficient	0.069	0.042	0.105	−0.050	−0.130	−0.043	−0.135	−0.104	0.011	0.063	−0.058	−0.153
P	0.535	0.734	0.340	0.690	0.239	0.730	0.220	0.403	0.923	0.612	0.653	0.293
n	84	67	84	67	84	67	84	67	84	67	62	49
TVDT (6 M)
Correlation coefficient	−0.079	−0.063	0.153	0.138	−0.379**	−0.351**	−0.057	−0.036	−0.004	0.031	0.003	−0.177
P	0.524	0.612	0.217	0.265	0.002	0.004	0.648	0.775	0.972	0.803	0.982	0.223
n	67	67	67	67	67	67	67	67	67	67	48	49
RAA
Correlation coefficient	−0.399**	−0.305*	−0.173	0.101	−0.290**	−0.153	0.385**	0.310*	0.410**	0.383**	0.267*	0.270
P	0.0002	0.012	0.115	0.415	0.008	0.216	0.0003	0.011	0.0001	0.001	0.036	0.061
n	84	67	84	67	84	67	84	67	84	67	62	49
RAA (6 M)
Correlation coefficient	−0.307*	−0.296*	−0.092	−0.037	−0.237	−0.076	0.278*	0.265*	0.273*	0.362**	0.190	0.274
P	0.012	0.015	0.459	0.766	0.054	0.540	0.023	0.030	0.026	0.003	0.195	0.056
n	67	67	67	67	67	67	67	67	67	67	48	49
LVEF
Correlation coefficient	0.114	0.161	0.175	0.087	0.201	0.204	−0.182	−0.243*	−0.054	−0.148	−0.019	−0.124
P	0.302	0.194	0.110	0.482	0.066	0.097	0.098	0.048	0.627	0.232	0.881	0.394
n	84	67	84	67	84	67	84	67	84	67	62	49

*Correlation is significant at 0.05 level. **Correlation is significant at 0.01 level. FVC=Forced vital capacity, FEV1=Forced expiratory volume in 1 s, 6 MWD=6-minute walk distance, TAPSE=Tricuspid Annular Plane Systolic Excursion, RIMP=Right index of myocardial performance, RV=Right ventricle, TDI=Tissue Doppler imaging, RVSP=Right ventricular systolic pressure, FAC=Fractional area change, TASV=Tricuspid annular systolic velocity, RV FWT=RV free wall thickness, LVEF=Left ventricular ejection fraction, SD=Standard deviation, RAA=Right atrial appendage, PRVOT=Proximal right ventricular outflow tract. MID