Correlation between pulmonary vascular performance and hemodynamics in patients with pulmonary arterial hypertension

ABSTRACT

Objective

To explore the correlation between pulmonary vascular performance and hemodynamics in patients with pulmonary arterial hypertension (PAH), using right heart catheterization (RHC) and intravascular ultrasound (IVUS).

Method

A total of 60 patients underwent RHC and IVUS examinations. Of these, 27 patients were diagnosed with PAH associated with connective tissue diseases (PAH-CTD group), 18 patients were diagnosed with other types of PAH (other-types-PAH group), and 15 patients were without PAH (control group). The hemodynamics and morphological parameters of pulmonary vessels in PAH patients were assessed using RHC and IVUS.

Results

There were statistically significant differences in right atrial pressure (RAP), pulmonary artery systolic pressure (sPAP), pulmonary artery diastolic pressure (dPAP), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) values between the PAH-CTD group, other-types-PAH group, and the control group (P < .05). No statistically significant difference was noticed in pulmonary artery wedge pressure (PAWP) and cardiac output (CO) values between these three groups (P > .05). The mean wall thickness (MWT), wall thickness percentage (WTP), pulmonary vascular compliance, dilation, elasticity modulus, stiffness index β, and other indicators were significantly different between these three groups (P < .05). Pairwise comparison showed that the average levels of pulmonary vascular compliance and dilation in PAH-CTD group and other-types-PAH group were lower than those in control group, while the average levels of elastic modulus and stiffness index β were higher than those in control group.

Conclusion

Pulmonary vascular performance deteriorates in PAH patients, and the performance is better in PAH-CTD patients than in other types of PAH.

KEYWORDS:

• Intravascular ultrasound
• pulmonary hypertension
• pulmonary vascular morphological changes
• pulmonary vascular performance change

Background

Pulmonary hypertension (PH) is a group of fatal diseases characterized by abnormally increased pulmonary arterial pressure (PAP) and continuous elevation of pulmonary vascular resistance (PVR) that eventually lead to right-sided heart failure and death. Of these, pulmonary arterial hypertension (PAH) is the most lethal type of PH (1, 2). At present, the median survival time of PAH patients under medication is only 7 years (3). PAH is a common complication in patients with connective tissue diseases. PAH associated with connective tissue diseases (PAH-CTD) mainly includes systemic lupus erythematosus (SLE)-associated PAH, scleroderma (SSc), mixed connective tissue disease (MCTD), rheumatoid arthritis (RA), Sjogren syndrome, etc (4).

The diagnosis and evaluation methods for pulmonary hypertension mainly include right heart catheterization (RHC), lung tissue biopsy, and pulmonary angiography. RHC remains the “gold standard” for the evaluation and diagnosis of PAH. However, it fails to detect abnormal pulmonary vascular performance or distinguish between slight changes in pulmonary vascular performance between different types of PAH (5). Lung tissue biopsy can be used to accurately assess pulmonary vascular lesions. Nevertheless, its clinical application is limited by the heterogeneity of pulmonary vascular lesions in PAH patients and the invasive procedure of biopsy. Intravascular ultrasound (IVUS) is a novel imaging technology combining non-invasive ultrasound with invasive cardiac catheterization, which is currently used in the study of coronary heart disease (6). However, Chinese and foreign studies have shown that IVUS can not only be used to assess the pulmonary vascular function, but also quantitatively and qualitatively analyze the functional changes of pulmonary vessels, thus playing an important role in evaluating the pulmonary vascular morphological changes and mechanical performance of pulmonary blood vessels in PAH patients (7–10). Pulmonary vascular remodeling presents with heterogeneity in pulmonary vessels. Such inhomogeneity not only refers to the vascular performance of the remodeling site, but the performance of the entire pulmonary blood vessels is abnormal. At present, most international studies on the use of IVUS to evaluate the pulmonary vascular performance in PAH patients emphasize the change in the remodeling site but overlook the overall abnormality. Therefore, IVUS has failed to accurately reflect the pulmonary vascular performance. The relationship between structural changes of the pulmonary vascular wall and hemodynamics remains unclear, and the clinical value of IVUS in pulmonary hypertension needs to be further evaluated. In this study, we aim to explore the relationship between pulmonary vascular mechanical performance and hemodynamics by the combined application of RHC and IVUS in PAH patients.

Data and method

Participants and groups

The study participants were enrolled strictly in accordance with the inclusion and exclusion criteria, from December 2017 to December 2019, with a time period of 2 years. A total of 60 patients who were admitted to the People’s Hospital of Xinjiang Uygur Autonomous Region and highly suspected of PH based on medical history and echocardiography screening, were enrolled. RHC and IVUS were conducted on every patient after enrollment. Based on the RHC results, laboratory tests and the diagnosis by the Cardiology Department and Rheumatology and Immunology Department of the People’s Hospital of Xinjiang Uygur Autonomous Region, 27 patients were diagnosed with PAH-CTD (PAH-CTD group), 18 patients were diagnosed with other types of PAH (other-types-PAH group) (10 cases of idiopathic pulmonary hypertension, 4 cases of portopulmonary hypertension, 4 cases of pulmonary hypertension associated with congenital heart disease), and 15 patients were without PAH (control group). The study was approved by the Ethics Committee of the People’s Hospital of Xinjiang Uygur Autonomous Region (No. KY2019051567). Informed consent forms were obtained from all participants.

RHC and IVUS examination

According to the European Heart Journal’s guidelines for the diagnosis and treatment of pulmonary hypertension (11), RHC (8.5 F, Baxter Healthcare, Edwards Critical Care Division, Deerfield, IL, USA) was employed for examination of pulmonary artery hemodynamics. Examination indicators include: right atrial pressure (RAP), right ventricular pressure (RVP), pulmonary artery systolic pressure (sPAP), pulmonary artery diastolic pressure (dPAP), mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), cardiac output/cardiac index (CO/CI), etc. The calculation formula of PVR is: PVR = (mPAP-PAWP)/CO, while pulmonary artery pulse pressure difference (PPP) is calculated as PPP = sPAP-dPAP. Blood oxygen saturation in the vena cava, right atrium, right ventricles, pulmonary arteries, and systemic circulation were also measured.

After the RHC and pulmonary angiography (or acute pulmonary vasodilation test) were completed, IVUS was performed immediately after the restoration of pulmonary artery pressure. A 40 MHz US catheter (Boston Scientific, US) with an axial resolution of 43 μm was employed to detect the pulmonary artery of the lower lung: according to Bressollette et al. (12), typical pulmonary vascular performance abnormality usually occurs in the lower lungs, with similar degrees of abnormalities between the left and right lungs. Therefore, 2 lower segments of the left and right pulmonary arteries were measured in each patient, leading to a total of 4 lung segments detected. The average value was calculated for statistical analysis.

The US catheter was moved to the distal end of the pulmonary artery and returned to the proximal pulmonary artery at a rate of 0.5 mm/s. The image data was read using the iLab^TM system (Boston Scientific, USA) to ensure the good quality of all images (intact circumferential boundary between the intima-media and the medial wall of adventitia). The image data was recorded and saved on a Sony DVD.

Measurement and calculation of pulmonary vascular performance

Using the single blind method, the data was independently measured by two experienced operators using imap software (ImageJ Ver 1.44, NIH, USA) without knowing all clinical and hemodynamic data: all pulmonary vessels were divided into 2 segments. Those with a diameter of <5 mm were considered as the distal segments, while those with a diameter of >5 mm were considered as the proximal segments. A total of 480 pulmonary vascular segments were measured (216 in the PAH-CTD group, 144 in the other-types-PAH group, and 120 in the control group).

Since IVUS cannot distinguish the pulmonary vascular adventitia, the data of pulmonary vascular inner diameter (including pulmonary vascular intima and tunica media) during diastolic and systolic periods were studied, including total vascular area (pulmonary vascular intima and tunica media) (VAd and VAs), vascular diameter (VDd and VDs), luminal area (LAd and LAs), luminal diameter (LDd and LDs), and minimum luminal diameter (MLDd and MLDs), mean vascular diameter = (VDd+VDs)/2, mean wall thickness (MWT) = [(VDd+VDs)/2-(LDd+LDs)/2]/2, and mean wall thickness percentage (WTP) = (2× MWT)×100%/VD. If patients with PAH had higher WTP in the distal pulmonary artery segment than in the proximal part, they were included in the distal remodeling group (n = 21), or vice versa, the patients were included in the proximal remodeling group (n = 24).

Pulmonary vascular mechanical performance indicators include compliance, dilation, elastic modulus, and stiffness index β (13–16); the calculation methods of each index are as follows: compliance = (VAd-VAs)×100/PPP, dilation = (VAd-VAs)×100%/PPP×VAd, elastic modulus = PPP×VDd/(VDd-VDs), stiffness index β = Ln(sPAP/dPAP)/[(VDd-VDs)/VDd].

Statistical analysis

The data of this study were analyzed using SPSS 25.0, and the statistical graphs were drawn using GraphPad Prism software and R4.0.0 software with the tidyverse installation package. The measured data were expressed by mean ± standard deviation. One-way ANOVA was used for multi-group comparison, and LSD method was adopted for pairwise comparisons. χ2 test was employed for comparisons of enumeration data between groups. Nonlinear regression analysis was used to match the model and POWER exponentiation model was adopted to analyze the correlations between pulmonary vascular performance and hemodynamics. P < .05 (2-tailed) is considered as statistically significant difference.

Results

Patient characteristics at baseline

As shown in Table 1, there was no statistically significant difference in baseline data including age, sex, diabetes, hypertension, and coronary heart disease between the control group, PAH-CTD group, and other-types-PAH group. The baseline data of these three groups were comparable.

Table 1. Baseline data of patients in each group.

Indicators		Control group (n = 15)	PAH-CTD group (n = 27)	Other-types-PAH group (n = 18)	t/χ^2	P
Ages		45.4 ± 16.39	46.33 ± 16.12	43.72 ± 13.21	0.156	0.856
Gender	Male	9(60)	16(59.3)	11(61.1)	0.015	0.992
	Female	6(40)	11(40.7)	7(38.9)
Diabetes		2(13.3)	4(14.8)	3(16.7)	0.073	0.964
Hypertension		3(20.0)	7(25.9)	6(33.3)	0.760	0.684
Coronary heart disease		2(13.3)	6(22.2)	4(22.2)	0.594	0.743

Among the patients in the PAH-CTD group, 14 were diagnosed with systemic lupus erythematosus, 4 with systemic sclerosis, 2 with Sjogren’s syndrome, 1 with mixed connective tissue disease, and 1 with rheumatoid. Of these, the most common cause was SLE, accounting for 52% (14/27). Among the other-types-PAH patients, 10 were diagnosed with idiopathic pulmonary hypertension (IPAH), 4 with portopulmonary hypertension, and 4 with congenital heart disease-related pulmonary hypertension. Of these, IPAH patients were the majority, accounting for 67% (12/18). In the control group, all patients were diagnosed with connective tissue diseases except for 1 case of hepatopulmonary syndrome. See Table 1.

Hemodynamic results analysis of each group

There were no statistically significant differences in RAP values between the PAH-CTD group, other-types-PAH group, and the control group (P > .05), while the differences in RVP, sPAP, dPAP, mPAP, and PVR values were significant between these three groups (P < .05). Also, there was no statistically significant difference in PAWP and CO values between these three groups (P > .05). Pairwise comparison showed that the RVP, sPAP, dPAP, mPAP, and PVR values in the PAH-CTD group and other-types-PAH groups were higher than those in the control group, and the difference was statistically significant (P < .05). Moreover, there was no statistically significant difference in the RVP, sPAP, dPAP, mPAP, and PVR values between the PAH-CTD group and other-types-PAH groups (P > .05), as shown in Table 2.

Table 2. Detection results of hemodynamic indexes of patients in each group ($\bar{x}\pm s$).

Indicators	Control group (n = 15)	PAH-CTD group (n = 27)	Other-types-PAH group (n = 18)	F	P
RAP(mmHg)	6.53 ± 1.25	8.30 ± 3.71	8.56 ± 3.24	2.040	0.139
RVP(mmHg)	11.00 ± 3.55	29.63 ± 6.48*	31.50 ± 10.9*	36.980	0.000
sPAP(mmHg)	20.60 ± 7.37	60.52 ± 10.83*	65.61 ± 15.56*	72.227	0.000
dPAP(mmHg)	11.13 ± 3.20	31.00 ± 9.80*	35.5 ± 11.25*	32.695	0.000
mPAP(mmHg)	14.29 ± 4.38	40.84 ± 9.48*	45.54 ± 12.09*	52.253	0.000
PAWP(mmHg)	10.67 ± 3.04	11.11 ± 4.21	13.33 ± 3.48	2.626	0.081
CO(L/min)	5.40 ± 1.12	4.96 ± 0.90	5.56 ± 1.38	1.703	0.191
PVR(Wood) unit	0.66 ± 0.34	6.23 ± 2.54*	6.02 ± 2.67*	33.341	0.000

Note: RAP: right atrial pressure, RVP: right ventricular pressure, sPAP: pulmonary artery systolic pressure, dPAP: pulmonary artery diastolic pressure, mPAP: mean pulmonary artery pressure, PAWP: pulmonary artery wedge pressure, CO: cardiac output, PVR: pulmonary vascular resistance. Compared with the control group, *P < 0.05

IVUS measurements

No complications were observed in all patients after IVUS examination. The average blood vessel diameter of patients in the PAH-CTD group, other-types-PAH group, and control group was basically identical at (4.38 ± 0.23) mm, (4.43 ± 0.16) mm, and (4.31 ± 0.42) mm, respectively, with no statistically significant difference (P > .05). This ensured the consistency in blood vessels and excluded the interference and deviation caused by the difference in pulmonary vascular diameter. The MWT and WTP values were significantly different between these three groups (P < .05). Pairwise comparison showed that the MWT and WTP values of patients in the PAH-CTD group and other-types-PAH group were higher than those in the control group, and the difference was statistically significant (P < .05). However, the difference in the MWT and WTP values between the PAH-CTD group and other-types-PAH group was not statistically significant (P > .05), as shown in Table 3. See Figure 1, Figure 2.

Figure 1. IVUS test results of patients in each group a: Vd; b: MWT; c: WTP; Group 1: PAH-CTD group; Group 2: the other types of PAH group; Group 3: control group.

Figure 2. IVUS of the PAH-CTD group (a), the other types of PAH group, (b) and the control group (c).

Table 3. IVUS test results of patients in each group ($\bar{x}\pm s$).

Indicators	Control group (n = 15)	PAH-CTD group (n = 27)	Other-types-PAH group (n = 18)	F	P
Vd (mm)	4.31 ± 0.42	4.35 ± 0.23	4.43 ± 0.16	0.872	0.423
MWT(mm)	0.24 ± 0.02	0.32 ± 0.02*	0.31 ± 0.03*	83.363	<0.001
WTP(%)	10.95 ± 1.05	14.68 ± 0.96*	13.9 ± 1.06*	67.390	<0.001

Note: Vd: vascular diameter, MWT: mean wall thickness, WTP: wall thickness percentage compared with the control group, *P < 0.05

Pulmonary vascular mechanical performance

There were statistically significant differences in pulmonary vascular compliance, dilation, elastic modulus, and stiffness index β between the PAH-CTD group, other-types-PAH group, and control group (P < .05). Pairwise comparison showed that the average levels of pulmonary vascular compliance and dilation in the PAH-CTD group and other-types-PAH group were lower than those in the control group, while the average levels of elastic modulus and stiffness index β were higher than those in the control group, which were significantly different (P < .05). Among them, the elastic modulus of patients in the PAH-CTD group was lower than that in other-types-PAH group, which was significantly different (P < .05). However, the differences in compliance, dilation, and stiffness index were not statistically significant between the PAH-CTD group and other-types-PAH group (P > .05). See Table 4 and Figure 3.

Figure 3. Pulmonary Vascular Mechanical Properties a: Compliance; b: Distensibility; c: Elasticity modulus; d: Stiffness index β; Group 1: PAH-CTD group; Group 2: the other types of PAH group; Group 3: control group.

Table 4. Hemodynamic measurements of patients in each group ($\bar{x}\pm s$).

Indicators	Control group (n = 15)	PAH-CTD group (n = 27)	Other-types-PAH group (n = 18)	F	P
Compliance(10^–2mm^2/mmHg)	39.06 ± 4.65	9.32 ± 0.58*	8.56 ± 0.44*	920.020	<0.001
Distensibility (%/mmHg)	4.25 ± 0.84	0.94 ± 0.13*	0.76 ± 0.08*	350.690	<0.001
Elasticity modulus(mmHg)	50.62 ± 7.16	182.61 ± 14.15*	213.84 ± 23.16*^▲	464.894	<0.001
Stiffness index β	2.25 ± 0.37	4.53 ± 0.34*	5.17 ± 0.56*	214.727	<0.001

Note: Compared with the control group, *P < 0.05, Compared with the PAH-CTD group, ^▲P < 0.05

Correlation between pulmonary vascular mechanical performance and hemodynamics

Nonlinear regression analysis was conducted on all patient data (Table 4). Results showed that there was significant power correlation between pulmonary vascular mechanical performance and pulmonary artery hemodynamics. Also, significant power correlations were noticed between the sPAP and compliance (R² = 0.402, P < .001), dilation (R² = 0.417, P < .001), elastic modulus (R² = 0.316, P < .001), and stiffness index β (R² = 0.301, P < .001), as well as between the mPAP and compliance (R² = 0.547, P < .001), dilation (R² = 0.499, P < .001), elastic modulus (R² = 0.418, P < .001), and stiffness index β (R² = 0.384, P < .001). Moreover, there were power correlations between PVR and compliance (R² = 0.314, P < .001), dilation (R² = 0.232, P < .001), elastic modulus (R² = 0.145, P < .001), and stiffness index β (R² = 0.248, P < .001). See Table 5 and Figure 4.

Figure 4. Correlation between IVUS data and hemodynamics. abc: Compliance; def: Distensibility; ghi: Elasticity modulus; jkl: Stiffness index β. Nonlinear regression analysis was conducted on all patient data. Results showed that there was significant power correlation between pulmonary vascular mechanical performance and pulmonary artery hemodynamics.

Table 5. The relationship between IVUS data and hemodynamic measurements.

Indicators	sPAP		mPAP		PVR
	R^2	P	R^2	P	R^2	P
Compliance	0.402	<0.001	0.547	<0.001	0.314	<0.001
Distensibility	0.417	<0.001	0.499	<0.001	0.232	<0.001
Elasticity modulus	0.316	<0.001	0.418	<0.001	0.145	0.010
Stiffness index β	0.301	<0.001	0.384	<0.001	0.248	<0.001

Discussion

Application of right heart catheterization in pulmonary hypertension

RHC is the only method to confirm the pulmonary hypertension diagnosis. According to different indicators such as pulmonary artery pressure and pulmonary capillary pressure measured using RHC, we could formulate hemodynamic classification to support clinical practice (17). Our results showed that there was no statistically significant difference in the average level of right atrial pressure, pulmonary artery wedge pressure, cardiac output, and other indicators between the PAH-CTD group and other-types-PAH (P > .05), while the average level of right ventricular pressure, pulmonary artery systolic pressure, pulmonary diastolic blood pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and other indicators in the PAH-CTD group were higher than those in the other-types-PAH group, with a statistically significant difference (P < .05). The above-mentioned indicators in the PAH-CTD group were lower than those in other-types-PAH groups. Pulmonary vascular remodeling due to immune response may be the direct cause of this difference. Early and persistent inflammatory immune responses in patients with PAH-CTD participate in the occurrence and development of PAH, among which abnormal inflammatory immunity, metabolic disorders, mitochondrial structure destruction and other factors may lead to the pulmonary vascular cells in a state of proliferative and apoptotic resistance, thus resulting in pulmonary vascular remodeling (18). Tamosiuniene et al. reported that T cells, especially regulatory T cells, play a protective role in reducing vascular damage during the formation of pulmonary hypertension (19). Shen JY et al. showed that although the hemodynamic changes were similar between the two groups of PAH patients, to some extent patients with PAH-CTD had better pulmonary vascular performance than patients with other types of PAH. This may be due to the higher levels of CD3⁺ T cell in PAH-CTD patients than that in other PAH patients (11). In addition, previous studies have shown that patients with lupus-associated PAH can significantly relieve PAH after anti-immunotherapy, which indirectly proves the close relationship between abnormal immune response and PAH (12). The above-mentioned indicators in the PAH-CTD group decreased as compared with those in other-types-PAH patients. These results varied. Given the limited number of patients in our study, there may be bias in the results. The findings need to be confirmed by more clinical studies, and studies with larger sample sizes may lead to more reliable conclusions.

Significance of intravascular ultrasound in evaluating pulmonary vascular performance in patients with pulmonary hypertension

Pathological changes in pulmonary hypertension are characterized by pulmonary vascular remodeling, which are manifested by pulmonary intima hyperplasia, tunica media hypertrophy, and fibrosis and adventitia thickening, accompanied by vascular inflammatory infiltration, plexiform lesions, and thrombosis (18, 19). There are many ways to detect or quantify these pathological changes. There is no doubt that pulmonary artery biopsy can accurately confirm pulmonary vascular remodeling. However, its application in clinical practice is limited due to its severe invasiveness. The thickness of blood vessel wall, total blood vessel area, blood vessel diameter, etc., can be directly observed by IVUS. The mean wall thickness (MWT) and the wall thickness percentage (WTP) can be indirectly calculated. The compliance, dilation, elastic modulus, stiffness index β, and other indicators of pulmonary vascular mechanical performance can also be calculated (7, 11, 12). Based on our experience with IVUS, we sought to explore its role in the evaluation and treatment of patients with PAH.

Our results suggest that the IVUS examination showed a statistically significant difference in the mean wall thickness, wall thickness percentage, pulmonary vascular compliance, dilation, elastic modulus, and stiffness index β between the PAH-CTD group, other-types-PAH group, and control group (P < .05). Pairwise comparison showed that the MWT and WTP values of patients in the PAH-CTD group and other-types-PAH group were higher than those in the control group, while the average levels of pulmonary vascular compliance and dilation were lower than those of the control group. Moreover, the average levels of elastic modulus and stiffness index β were higher than those in the control group, and the difference was statistically significant (P < .05). Among them, the elastic modulus of patients in the PAH-CTD group was lower than that in the other-types-PAH group, while no obvious difference was noticed in the mean wall thickness, wall thickness percentage, compliance, dilation, and stiffness index between the PAH-CTD group and other-types-PAH group (P > .05). The results suggest that the pulmonary vascular stiffness in patients with all types of PAH in this study was greater than that of the control group, while the elasticity was less than that of the control group. Moreover, there was no statistically significant difference in pulmonary vascular stiffness and elasticity between the PAH-CTD group and other-types-PAH group. Our results are in line with relevant foreign studies.

Our data also demonstrated the important role of IVUS in the evaluation of pulmonary vascular performance, which causes minimal trauma and can be used to directly observe blood vessel wall thickness. Consistent with previous studies, pulmonary vascular remodeling is evident in patients with PH. IVUS examination in this study showed that the pulmonary vascular mechanical performance significantly decreased in patients with PAH. Mechanical performance changes may be induced by pulmonary vascular remodeling, which is commonly observed in inflammatory immune abnormalities, metabolic disorders, mitochondrial structure destruction, and other factors (13). Pulmonary vascular remodeling presents with a proliferative status and apoptotic resistance of vascular cells. Early and persistent inflammatory immune response is involved in the development of PAH, especially in patients with PAH-CTD. Hemodynamic changes are similar in patients with PAH. However, patients with PAH-CTD have better pulmonary vascular performance than other-types-PAH to some extent, which may be related to inflammatory immune abnormalities, and deserve in-depth study.

Correlation between pulmonary vascular mechanical performance and hemodynamics

Currently, the hemodynamic examination of patients with pulmonary hypertension mainly relies on right heart catheterization, and the main indicators include pulmonary artery systolic pressure, pulmonary artery diastolic pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, pulmonary vascular resistance, etc. Studies have shown that morphological changes detected using IVUS have significant correlation with pulmonary hemodynamics in patients with pulmonary hypertension. Ploegstra et al. (10) found that the size of the low echo zone in pulmonary arteries intima-media detected by IVUS in children with pulmonary hypertension is linearly correlated to pulmonary vascular resistance. The same results have been confirmed for adults in other studies (9, 14, 15). Nevertheless, Guazzi M et al. (16) found that this correlation is less pronounced in patients with secondary pulmonary hypertension. Nakamoto et al. (7) also demonstrated that the structural changes detected by IVUS in patients with primary pulmonary hypertension are closely related to hemodynamics. Their results showed that there was a statistically significant correlation between average echo intensity detected by IVUS and the average pulmonary artery pressure measured at the same time in patients with primary pulmonary hypertension. Furthermore, the average echo intensity of pulmonary arteries in patients with primary pulmonary hypertension significantly increased as compared with that of ordinary people. Bressollette et al. (11) showed that for the pulmonary artery wall of the lower lobe, morphological indicators including the mean wall thickness (mWT), wall area (WA), and percentage of wall thickness (WT%) are closely related to pulmonary artery systolic pressure. Moreover, mWT is associated with pulmonary vascular resistance. However, these correlations between morphological indicators and hemodynamics are not observed in the upper lobe.

Our data demonstrates a strong power correlation between pulmonary vascular performance and hemodynamics. According to the trend of the data, when the hemodynamic value is at a low level or critical point, tiny variations can cause changes in pulmonary vascular performance. In contrast, when hemodynamics deteriorates severely, the morphological changes in pulmonary blood vessels can hardly improve even if the hemodynamics is significantly ameliorated. It is suggested that interventions are given at the early stages of PAH (when both mPAP and PVR are at low levels) to significantly improve pulmonary vascular performance. In addition, as compared to the hemodynamic changes found using RHC, IVUS can better detect changes in pulmonary vascular performance at an early stage. However, due to the limitation of diagnostic techniques, most patients with PAH have progressed to the end stage by the time they are diagnosed with RHC. Severe deterioration of hemodynamics makes it difficult to reverse the performance of pulmonary vessels. It is suggested that early intervention and treatment of PAH should be emphasized. Timely prevention and intervention in the patients’ hemodynamics will likely reverse the deterioration of pulmonary vascular performance, while early lesions can be detected using IVUS.

It is known that due to the limitation of diagnostic techniques, PAH patients are often at end stage when the diagnosis is confirmed by RHC. By then, the hemodynamics have seriously deteriorated. Treatment provided at that time can better improve the hemodynamics, but the reversal of pulmonary vascular performance is basically minimal. In this study, we statistically analyzed the relationship between pulmonary vascular performance and hemodynamics, and a significant power correlation was found. When the hemodynamic value is at a low level or critical point, tiny variations can cause changes in pulmonary vascular performance. These findings suggest that pulmonary vascular performance may be unexpectedly improved when intervention therapy is given at the early stage of PAH. In addition, compared to the hemodynamic changes detected by RHC, changes in pulmonary vascular performance can be better determined at an early stage with IVUS. To sum up, more attention should be paid to the early intervention and treatment of PAH. Early and timely prevention and treatment are expected to significantly improve hemodynamics, and even reverse the deterioration of pulmonary vascular performance.

In summary, the results of this study suggest that pulmonary vascular hemodynamic and morphological indicators are significantly worse in patients with PAH than in the control group, while patients with PAH-CTD had better hemodynamic and pulmonary vascular morphological changes compared with other-types-PAH patients. IVUS is of much importance in the evaluation of pulmonary vascular performance in pulmonary hypertension. In combination with the hemodynamic changes found using RHC, IVUS can better detect changes in pulmonary vascular performance. Also, there is a strong power correlation between pulmonary vascular morphological changes and hemodynamics. The pulmonary vascular performance is poor in patients with PAH. However, patients with PAH-CTD have slightly better pulmonary vascular performance than those with other types of PAH. Future studies should focus on whether pulmonary vascular performance is reversible in patients with PAH after targeted drug therapy.

This study also had several limitations. First, the small sample size may weaken the generalizability of the results. Second, this study lacked a control group of healthy individuals. Third, the mechanism at the cellular and molecular level was not studied in this study. Thus, all results need to be verified by prospective studies with large sample size.

Ethics approval and consent to participate

This study was conducted with approval from the Ethics Committee of People’s Hospital of Xinjiang Uygur Autonomous Region (No. KY2019051567). This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants.

Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Natural Science Foundation of Xinjiang Autonomous Region (No.2019D01C155).