The Prognosis and Management of Reclassified Systemic Lupus Erythematosus Associated Pulmonary Arterial Hypertension According to 2022 ESC/ERS Guidelines

doi:10.21203/rs.3.rs-3970011/v1

Download PDF

Research Article

The Prognosis and Management of Reclassified Systemic Lupus Erythematosus Associated Pulmonary Arterial Hypertension According to 2022 ESC/ERS Guidelines

https://doi.org/10.21203/rs.3.rs-3970011/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background and Aims:

The 2022 ESC/ERS guideline has recently revised the haemodynamic definition of pulmonary arterial hypertension. However, there is currently limited research on the prognosis and treatment of system lupus erythematosus associated pulmonary arterial hypertension (SLE-PAH) patients that reclassified by the new haemodynamic definition. This study aims to analyze the prognosis of newly reclassified SLE-PAH patients and provide recommendations for the management strategy.

Methods

This retrospective study analyze records of 236 SLE-PAH patients who visited Peking Union Medical College Hospital (PUMCH) from 2011 to 2023, among whom 22 patients were reclassified into mild SLE-PAH (fulfilling the criteria of 2022 ESC/ERS guideline [mean pulmonary arterial pressure (mPAP) ≥ 21mmHg and pulmonary vascular resistance (PVR) > 2WU] but not the previous haemodynamic criteria [mPAP ≥ 25mmHg and PVR > 3WU]) according to the guideline and 14 were defined as partially remitted patients (mPAP 21–24 mmHg and PVR < 2 WU). The prognosis were compared among mild SLE-PAH, partially remitted SLE-PAH and conventional SLE-PAH patients (mPAP ≥ 25mmHg and PVR > 3WU). Besides, the effectiveness of pulmonary arterial hypertension (PAH) targeted therapy was evaluated in mild SLE-PAH patients.

Results

Those mild SLE-PAH patients had significantly longer progression-free time than the conventional SLE-PAH patients, and the mild SLE-PAH patients had similar prognosis compared to partially remitted patients. Among the mild SLE-PAH patients, 4 did not receive PAH targeted therapy of PAH and had similar prognosis with patients not receiving targeted therapy. Besides, nearly all of the reclassified SLE-PAH patients received intensive immunosuppressive therapy (IIT).

Conclusions

This study supports the revised haemodynamic definition of SLE-PAH in the 2022 ESC/ERS guideline. Those reclassified mild and partially remitted SLE-PAH patients had better prognosis, demonstrating the possibility and significance of early diagnosis and intervention for SLE-PAH. This study also suggested that IIT against SLE might be sufficient for those reclassified SLE-PAH patients.

System lupus erythematosus associated pulmonary arterial hypertension

Haemodynamics

PAH is one of the most severe complications of SLE. PAH also has been demonstrated to be an important dead cause of SLE patients^1,2. Epidemiological research has revealed that SLE is the first predominant cause of connective tissue disease (CTD)-associated PAH in Asian nations^3–7.

Previous definition of pulmonary hypertension (PAH) was described as mPAP ≥ 25mmHg, PVR > 3WU and pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg ⁸. However, researches had proven that mildly elevated mPAP and PVR led to elevated mortality and worse prognosis^9–15. Therefore, the 2022 ESC/ERS guideline updated the definition of PAH to mPAP > 20 mmHg, PVR > 2WU and PAWP ≤ 15 mmHg ¹⁶. The change of the diagnostic criteria redefined those patients with mild PAH and contributed to the early diagnosis and detection. SLE-PAH patients dominate the Asian CTD-PAH patients and had a mortality rate exceeding 14%¹⁷. Early diagnosis and intervention are expected to improve their prognosis and prevent further disease progression. However, there is currently limited study focus on SLE-PAH and demonstrates how the revised haemodynamic definitions impacts the prognosis of SLE-PAH. Besides, the efficacy of targeted drugs against PAH has only been verified in patients fulfilling the conventional haemodynamic criteria, and no data is available to instruct the management of those reclassified SLE-PAH patients, which obstructs the implementation of the new guideline in clinical practice.¹⁶

The Chinese SLE Treatment and Research Group-PAH (CSTAR-PAH) is the largest national cohort that follows up SLE-PAH patients in China¹⁸. This study is a retrospective study basing on CSTAR-PAH cohort. The aims of this study are to (i) analyze the prognosis of those reclassified SLE-PAH patients and prove the impact of early diagnosis and detection; (ii) evaluate the effectiveness of targeted therapy in these patients and provide recommendations for their management.

Patients

All of the enrolled patients visited the Peking Union Medical College Hospital (PUMCH) and fulfilled the 1997 SLE classification criteria revised by the American College of Rheumatology (ACR) or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE^19,20. Besides, they were all diagnosed of PAH basing on right heart catheterization (RHC) from 2011 to 2023 were included. The haemodynamic criteria included mPAP ≥ 21mmHg, PVR>2 WU and pulmonary arterial wedge pressure (PAWP) ≤ 15mmHg. Patients who met the new diagnosis criteria did not fulfill the previous hameodynamic definition (mPAP ≥ 25mmHg and PVR > 3WU) were reclassified to mild SLE-PAH according to the 2022 ESC/ERS guideline. Patients with mPAP of 21–24 mmHg and PVR < 2 were reclassified as partially remitted SLE-PAH. Patients lost follow-up or had insufficient follow-up time were excluded. Patients with other CTD such as SSc (systemic sclerosis) were excluded. Patients with other types of PH (pulmonary hypertension) revealed by PAWP > 15mmg, diffusing capacity of the lung for carbon monoxide (DLCO) < 60% or pulmonary embolism diagnosed by ventilation perfusion scintigraphy or computed tomographic pulmonary angiography (CTPA). Patients with a follow-up time shorter than 6 months were also excluded. The flow chart of the research process is shown in Fig. 1. The Peking Union Medical College Hospital Institutional Review Board and Ethical Board approved this study (ethic number JS-2038). All patients gave written informed permissions.

The process of this study was demonstrated in the Figure. 293 patients diagnosed as SLE-PAH were included in this study and classified to three groups according to their RHC result. Prognosis of three groups were compared and the effect of targeted therapy was evaluated.

Data collection and risk assessment

The baseline of the study was defined as the time of the first RHC for conventional SLE-PAH patients. The baseline for reclassified SLE-PAH patients were defined as the first RHC in which their haemodynamic features fulfilled the reclassifying criteria mentioned above. The demographic features, clinical evaluation, laboratory results, medical treatment, transthoracic echocardiography (TTE) and RHC parameters were recorded at baseline. All the patients had at least one follow-up evaluation 6 months at a minimum after the baseline.

IIT was defined as using one or more of cyclophosphamide (CTX), mycophenolate mofetil (MMF), cyclosporin A (CsA), azathioprine (AZA) and tacrolimus (FK506).

The progression of PAH was defined as (i) all cause death; or (ii) Hospitalization for more than 24 hours due to deterioration of PAH; or (iii) additional PAH targeted therapy compared to baseline; or (iv) decrease in 6-minute walk distance (6MWD) more than 15%; or (v) deterioration of World Health Organization functional class (WHO-FC) to level III or IV²¹.

The COMPERA 2.0 four-strata risk assessment tool and three-strata model published in the 2022 ESC/ERS guideline were applied to was applied to evaluate the baseline condition of SLE-PAH patients.^16,22

Statistical analysis

Quantitative variables were described as means and standard deviations. Non-quantitative data were presented as counts and percentages. Kaplan–Meier estimation was used to calculate cumulative survival probabilities and log-rank test was used to compare the survival rates between different groups. Elevation of risk strata of one or more variables or additional utilization of targeted drugs compared to baseline was defined as endpoint events as mentioned above. The survival time was calculated from the baseline time and the upper limit was set as 5 years. The values of p < 0.05 were considered as statistically significant. R software was used to perform the statistical analysis (R 4.3.1).

Study Population and Baseline Characteristics

In this study, a total of 236 SLE-PAH patients were finally included, among whom 36 patients met the reclassifying criteria as previously stated. 22 reclassified patients were defined as mild SLE-PAH and 14 were defined as partially remitted SLE-PAH. Baseline characteristics of patients are displayed in Table 1. There is no significant disparity in the demographic characteristics between the three groups with different haemodynamic profiles. The majority of enrolled patients were females (97.5%) and the mean age when they were recruited was around 35. The disease activity and manifestation of SLE also showed no statistically significant difference. The mean SLE disease activity index (SLEDAI) also showed similarity between different groups²³. The three groups showed significant differences in indicators related to PAH risk assessment, and such results were reasonable. There were only 14.3% of the mild patients in WHO FC (World Health Organization functional class) III while 27% of conventional patients were in WHO FC III or IV. The reclassified SLE-PAH patients also had higher mean 6MWD (511.6 m for mild patients and 586 m for partially remitted patients ) than those conventional ones (496.6 m). Meanwhile, the overall risk strata of mild SLE-PAH patients and partially remitted patients were significantly lower than that of conventional patients. All the results above indicate that those reclassified SLE-PAH patients had milder cardiopulmonary involvement than conventional SLE-PAH patients, while they had similar characteristics related to SLE and demography.

Prognosis of reclassified SLE-PAH patients

The endpoint event is set as disease progression to evaluate the prognosis of SLE-PAH patients. Detailed definition of disease progression is shown above. Overall, 5 mild, 1 partially remitted and 102 conventional SLE-PAH patients progressed during the follow-up. The log-rank test demonstrates that the mild group and partially remitted group had significantly better prognosis than the conventional group (Fig. 2), while the two groups of reclassified SLE-PAH showed similar prognosis (Figure S1). The analysis showed a trend towards better prognosis in patients of partial remission compared to the mild group, but the difference in prognosis between the two groups was not statistically significant. This might be due to the small sample size. This result supports the 2022 ESC/ERS guideline and confirm the significance of early diagnosis and intervention of SLE-PAH.

The prognosis was evaluated by disease progression rate of conventional SLE-PAH (green), mild SLE-PAH (blue) and partially remitted SLE-PAH (red) groups. The log-rank test p value was shown in the figure.

Efficacy of targeted therapy for mild SLE-PAH patients

The 36 reclassified SLE-PAH patients are extracted for further analysis to study the impact of targeted therapy on their prognosis. The comparation of baseline characteristics for 22 mild SLE-PAH patients, whom were grouped according to the utilization of targeted therapy, was shown in the Table 2. The baseline characteristics of patients with or without targeted therapy showed no significant disparity. Among the mild SLE-PAH patients, 4 patients did not receive targeted therapy at baseline and none of them progressed during the follow-up. As shown in Table S1, there were no significant difference between the prognosis of patients with or without targeted therapy. It was also shown in Table 1 that half of the partially remitted patients did not receive targeted therapy while they had similar prognosis with mild SLE-PAH. All the 5 progressed patients were defined as progression due to receiving additional targeted therapy to prevent further deterioration. It is worth noting that almost all reclassified patients, no matter mild or partially remitted, received IIT. In general, the results support that IIT against SLE might be sufficient for those reclassified SLE-PAH patients, but targeted therapy is still needed when disease progression is detected.

To our knowledge, this is the first study focusing on the SLE patients that newly classified as SLE-PAH according to the 2022 ESC/ERS guideline¹⁶. In the CSTAR cohort, 22 patients (15.3%) from PUMCH center were reclassified to mild SLE-PAH and 14 to partially remitted SLE-PAH according to the new haemodynamic definition of PAH. Their prognosis was compared with those conventional SLE-PAH patients⁸. Considering the current lack of evidence-based data to instruct the treatment of such mild SLE-PAH patients, we analyze the impact of targeted therapy on the prognosis of them.

New haemodynamic definition helps patients achieve better prognosis

As PAH is one of the primary causes of mortality in SLE patients^1,2, it is crucial to predict the occurrence and recurrence of PAH in SLE patients, diagnose it timely and intervene promptly. Gene variants underlying idiopathic pulmonary arterial hypertension (IPAH) have been widely studied basing on genome sequencing data^24,25. The prediction of susceptibility to IPAH basing on genetic markers has also been widely accepted in the field, reflecting the demand in clinical practice for early prediction and intervention of PAH. As for CTD-PAH, previous research mainly focused on systemic sclerosis associated PAH (SSc-PAH), since SSc-PAH dominates the patient population in Europe and America^26–28. Efficacy of early detection of SSc-PAH with algorithm according to new definition has been validated²⁹. Basing on CSTAR-PAH cohort, the efficacy of PAH risk assessment tools has been verified in SLE-PAH patients³⁰. Prediction model for risk of PAH in SLE patients were also developed³¹. Furthermore, genetic risk factors for SLE-PAH such as HLA-DQA1*03:02 have been discovered basing on CSTAR-PAH cohort, which contributed to the prediction of SLE-PAH susceptibility³². With further insight into the progression and susceptibility of SLE-PAH, the conventional haemodynamic criteria appeared overly conservative and unable to meet the needs of clinical practice. The revision of haemodynamic definition in 2022 ESC/ERS guideline benefited early diagnosis and intervention for SLE-PAH. In this study, the prognosis of reclassified SLE-PAH patients was proved to be better, demonstrating the significance of timely intervention for SLE-PAH. With further advancement in the research of molecular mechanisms and genetic markers of SLE-PAH, it is expectable that more accurate and comprehensive prediction models, such as polygenic risk score (PRS), will be constructed in the future, which will enable the early diagnosis and treatment of SLE-PAH, thereby improving patient prognosis.

Treatment strategy of mild SLE-PAH patients

Treatment of CTD-PAH can be divided into specific drugs against PAH and immunosuppressive therapy against CTD. Given the fact that CTD-PAH was included in most randomized controlled trials (RCTs) for regulatory approval of PAH targeted therapy, the targeted therapy for IPAH was recommended to treat CTD-PAH adhering to nearly the same algorithm¹⁶. When it comes to the other part of the treatment, rituximab has been proven to be an efficient and safe drug to treat SSc-PAH by depleting B cells³³, which strongly support the opinion that SSc-PAH patients can benefit from immunosuppressive therapy. Cyclophosphamide, in combination with glucocorticoids, was reported to be beneficial for the PAH of SLE-PAH patients³⁴. Besides, IIT in combination with targeted therapy for PAH was proved to improve the prognosis of SLE-PAH patients³⁵. The efficacy of immunosuppressive therapy was attributed to the significant role played by the inflammatory response of CTD in the pathogenesis of CTD-PAH, which has been demonstrated in both patients and animal models^36,37. The study of treatment in SLE involving other organs, such as immunosuppressive therapy for lupus nephritis, could also provide some clues^38,39. With these evidences, our team proposed the concept of “dual treat-to-target” for SLE-PAH and other type of CTD-PAH patients, attaching importance equally to CTD related immunosuppressive therapy and PAH related targeted therapy⁴⁰. As for patients reclassified into SLE-PAH according to the new guideline, their mild cardiopulmonary involvement suggested that the application of immunosuppressive therapy alone might potentially control their disease. In this study, 22 mild SLE-PAH patients with follow-up time longer than 6 months are grouped basing on whether they received targeted therapy and analyze the prognosis of different groups. The result shows that the two groups had similar prognosis. Besides, the partially remitted patients had similar or even better prognosis compared to those mild patients, while only half of them received targeted therapy. It was remarkable that among the 36 reclassified SLE-PAH patients, nearly all patients received IIT. Basing on all the results, we recommend that for those reclassified SLE-PAH patients with mild elevation of haemodynamic parameters measured by RHC, IIT is potentially sufficient. It is notable that once their cardiopulmonary condition deteriorates, targeted therapy in combination with immunosuppressants are still recommended as the first-line treatment.

Strengths and limitations

This is the first study focuses on the prognosis of reclassified SLE-PAH patients according to the new haemodynamic definition based on the CSTAR-PAH cohort in China¹⁶. This study also pioneers the updating of management strategy of those reclassified SLE-PAH patients. The proposal that IIT is sufficient for those mild SLE-PAH patients contributes to the development of more economical and efficient treatment strategy.

However, this study has several limitations. First, this is not a randomized clinical trial to evaluate the efficacy of targeted therapy, the detailed treatment plans and baseline condition of different patients varied. Further standardized study is needed. Second, though our cohort is the currently the largest SLE-PAH cohorts in China, the sample size is still small, which restricted us from conducting more detailed studies. Further study with larger sample size is called in the future.

This study supports the revised haemodynamic definition of SLE-PAH in the 2022 ESC/ERS guideline. Those reclassified SLE-PAH patients had better prognosis compared to conventional SLE-PAH patients, while within the reclassified group, mild patients showed similar prognosis with partially remitted patients. It demonstrates the significance of early diagnosis and intervention of SLE-PAH. This study also discovered that targeted therapy did not generate significant impact on prognosis among the mild SLE-PAH patients. Though half of the partially remitted patients were not treated with targeted therapy, they gained similar or even better prognosis compared to mild SLE-PAH patients. The results give us a clue that IIT against SLE may be sufficient for those patients.

ACR American College of Rheumatology

AZA Azathioprine

CsA Cyclosporin A

CSTAR-PAH Chinese SLE Treatment and Research Group-Pulmonary Arterial Hypertension

CTD Connective tissue disease

CTD-PAH Connective tissue disease associated pulmonary arterial hypertension

CTPA Computed tomographic pulmonary angiography

CTX Cyclophosphamide

DLCO Diffusing capacity of the lung for carbon monoxide

FK506 Tacrolimus

IIT Intensive immunosuppressive therapy

IPAH Idiopathic pulmonary arterial hypertension

MMF Mycophenolate mofetil

PAH Pulmonary arterial hypertension

PAWP Pulmonary arterial wedge pressure

PH Pulmonary hypertension

PRS Polygenic risk score

PUMCH Peking Union Medical College Hospital

PVR Pulmonary vascular resistance

RCT Randomized controlled trials

RHC Right heart catheterization

SLEDAI System lupus erythematosus disease activity index

SLE-PAH System lupus erythematosus associated pulmonary arterial hypertension

SLICC Systemic Lupus International Collaborating Clinics

SSc Systemic sclerosis

SSc-PAH Systemic sclerosis associated pulmonary arterial hypertension

TTE Transthoracic echocardiography

WHO-FC World Health Organization functional class

6MWD 6-minute walk distance

Ethics approval and consent to participate

This study was approved by the Peking Union Medical College Hospital Institutional Review

Board and Ethical Board (Ethical number: JS-2038). Written informed consent was obtained from each enrolled patient.

Consent for publication

Not applicable.

Availability of data and material

Data from CSTAR-PAH cohort in this work will be shared on reasonable request

Competing interests

All the authors declared no potential conflicts of interest with respect to the research, publication and authorship of this article.

Funding

This work was supported by the Chinese National Key Research R&D Program (grant nos: 2021YFC25013015, 2017YFC0907601, 2017YFC0907602, 2017YFC0907603, and 2008BAI59B02), the Chinese National High Technology Research and Development Program, Ministry of Science and Technology (grant no: 2012AA02A513), ‘13th Five-Year’ National Science and Technology Major Project for New Drugs of the Ministry of Science and Technology of China (grant no: 2019ZX09734001-002-004), Medical and health science and technology innovation project of Chinese Academy of Medical Sciences (grant no: 2019-I2M-2-008), and Youth Program of National Natural Science Foundation of China (grant no: 81900054).

Acknowledgements

We appreciate every physician, research nurse, and coordinator involved in the CSTAR-PAH cohort study. We also sincerely thank all patients who were enrolled in this study.

Fei, Y. et al. Death causes and pathogens analysis of systemic lupus erythematosus during the past 26 years. Clin. Rheumatol. 33, 57–63 (2014).
Wang, Z. et al. Long-term survival and death causes of systemic lupus erythematosus in China: a systemic review of observational studies. Medicine (Baltimore) 94, e794 (2015).
Hao, Y.-J. et al. Connective tissue disease-associated pulmonary arterial hypertension in Chinese patients. Eur. Respir. J. 44, 963–972 (2014).
Lin, C.-Y., Ko, C.-H., Hsu, C.-Y. & Chen, H.-A. Epidemiology and mortality of connective tissue disease-associated pulmonary arterial hypertension: A national cohort study in taiwan. Semin. Arthritis Rheum. 50, 957–962 (2020).
Jeon, C. H. et al. Pulmonary hypertension associated with rheumatic diseases: baseline characteristics from the Korean registry. Int. J. Rheum. Dis. 15, e80-89 (2012).
Li, M. et al. Chinese SLE Treatment and Research Group (CSTAR) Registry 2009-2019: Major Clinical Characteristics of Chinese Patients with Systemic Lupus Erythematosus. Rheumatol. Immunol. Res. 2, 43–47 (2021).
Wang, Z. et al. Long-term Outcomes of Patients with Systemic Lupus Erythematosus: A Multicenter Cohort Study from CSTAR Registry. Rheumatol. Immunol. Res. 2, 195–202 (2021).
Galiè, N. et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur. Heart J. 37, 67–119 (2016).
Kovacs, G., Berghold, A., Scheidl, S. & Olschewski, H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur. Respir. J. 34, 888–894 (2009).
Assad, T. R. et al. Prognostic Effect and Longitudinal Hemodynamic Assessment of Borderline Pulmonary Hypertension. JAMA Cardiol. 2, 1361–1368 (2017).
Xue, L. et al. Mildly Elevated Pulmonary Arterial Pressure Is Associated With a High Risk of Progression to Pulmonary Hypertension and Increased Mortality: A Systematic Review and Meta-Analysis. J. Am. Heart Assoc. 10, e018374 (2021).
Jaafar, S. et al. Impact of the revised haemodynamic definition on the diagnosis of pulmonary hypertension in patients with systemic sclerosis. Eur. Respir. J. 54, 1900586 (2019).
Xanthouli, P. et al. Haemodynamic phenotypes and survival in patients with systemic sclerosis: the impact of the new definition of pulmonary arterial hypertension. Ann. Rheum. Dis. 79, 370–378 (2020).
Kolte, D. et al. Mild Pulmonary Hypertension Is Associated With Increased Mortality: A Systematic Review and Meta-Analysis. J. Am. Heart Assoc. 7, e009729 (2018).
Maron, B. A. et al. Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. Circulation 133, 1240–1248 (2016).
Humbert, M. et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur. Respir. J. 61, 2200879 (2023).
Qian, J. et al. Long-term prognosis of patients with systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study. Eur. Respir. J. 53, 1800081 (2019).
Tian, X., Li, M., Wang, Q., Zhao, J. & Zeng, X. The Challenges and Future Perspective for the Management of Systemic Lupus Erythematosus in China: A Concise Annual Report of 2020. Rheumatol. Immunol. Res. 3, 38–44 (2022).
Hochberg, M. C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 40, 1725 (1997).
Petri, M. et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 64, 2677–2686 (2012).
Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC) et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur. Respir. J. 34, 1219–1263 (2009).
Hoeper, M. M. et al. COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension. Eur. Respir. J. 60, 2102311 (2022).
Gladman, D. D., Ibañez, D. & Urowitz, M. B. Systemic lupus erythematosus disease activity index 2000. J. Rheumatol. 29, 288–291 (2002).
Hemnes, A. R. et al. Critical Genomic Networks and Vasoreactive Variants in Idiopathic Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med. 194, 464–475 (2016).
de Jesus Perez, V. A. et al. Whole-exome sequencing reveals TopBP1 as a novel gene in idiopathic pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 189, 1260–1272 (2014).
Condliffe, R. et al. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am. J. Respir. Crit. Care Med. 179, 151–157 (2009).
Thenappan, T., Shah, S. J., Rich, S. & Gomberg-Maitland, M. A USA-based registry for pulmonary arterial hypertension: 1982-2006. Eur. Respir. J. 30, 1103–1110 (2007).
Humbert, M. et al. Pulmonary arterial hypertension in France: results from a national registry. Am. J. Respir. Crit. Care Med. 173, 1023–1030 (2006).
Distler, O. et al. Performance of DETECT PAH algorithm according to the hemodynamic definition of pulmonary arterial hypertension (PAH) in the 2022 ESC/ERS guidelines: Early detection of pulmonary arterial hypertension in systemic sclerosis patients. Arthritis Rheumatol. Hoboken NJ (2023) doi:10.1002/art.42791.
Wang, Q. et al. Risk assessment in systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study. Ther. Adv. Chronic Dis. 13, 20406223221112528 (2022).
Qu, J. et al. Predicting the Risk of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: A Chinese Systemic Lupus Erythematosus Treatment and Research Group Cohort Study. Arthritis Rheumatol. Hoboken NJ 73, 1847–1855 (2021).
Qian, J. et al. Association Study Identified HLA-DQA1 as a Novel Genetic Risk of Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension. Arthritis Rheumatol. Hoboken NJ 75, 2207–2215 (2023).
Zamanian, R. T. et al. Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis-associated Pulmonary Arterial Hypertension: A Multicenter, Double-Blind, Randomized, Placebo-controlled Trial. Am. J. Respir. Crit. Care Med. 204, 209–221 (2021).
Jais, X. et al. Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. Arthritis Rheum. 58, 521–531 (2008).
Kommireddy, S. et al. Pulmonary arterial hypertension in systemic lupus erythematosus may benefit by addition of immunosuppression to vasodilator therapy: an observational study. Rheumatol. Oxf. Engl. 54, 1673–1679 (2015).
Zanatta, E. et al. Pulmonary arterial hypertension in connective tissue disorders: Pathophysiology and treatment. Exp. Biol. Med. Maywood NJ 244, 120–131 (2019).
Yeh, F.-C. et al. TLR7/8 activation induces autoimmune vasculopathy and causes severe pulmonary arterial hypertension. Eur. Respir. J. 62, 2300204 (2023).
Fanouriakis, A. et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann. Rheum. Dis. 79, 713–723 (2020).
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 100, S1–S276 (2021).
Zhao, J. et al. The treatment strategy of connective tissue disease associated pulmonary arterial hypertension: Evolving into the future. Pharmacol. Ther. 239, 108192 (2022).

Table 1 and 2 are available in the Supplementary Files section.

No competing interests reported.

Download PDF

Editorial decision: Revision requested
27 Mar, 2024
Reviews received at journal
22 Mar, 2024
Reviewers agreed at journal
20 Mar, 2024
Reviews received at journal
29 Feb, 2024
Reviewers agreed at journal
27 Feb, 2024
Reviewers agreed at journal
27 Feb, 2024
Reviewers invited by journal
27 Feb, 2024
Editor assigned by journal
21 Feb, 2024
Submission checks completed at journal
20 Feb, 2024
First submitted to journal
19 Feb, 2024

You are reading this latest preprint version

The Prognosis and Management of Reclassified Systemic Lupus Erythematosus Associated Pulmonary Arterial Hypertension According to 2022 ESC/ERS Guidelines

Status:

Version 1

Abstract

Background and Aims:

Methods

Results

Conclusions

Figures

Introduction

Methods

Patients

Data collection and risk assessment

Statistical analysis

Results

Study Population and Baseline Characteristics

Prognosis of reclassified SLE-PAH patients

Efficacy of targeted therapy for mild SLE-PAH patients

Discussion

New haemodynamic definition helps patients achieve better prognosis

Treatment strategy of mild SLE-PAH patients

Strengths and limitations

Conclusion

Abbreviations

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1