Impact of borderline pulmonary hypertension due to left heart failure on mortality in a multicenter registry study: A 3-year survivorship analysis

Yangyi Lin, Lingpin Pang, Shian Huang, Jieyan Shen, Weifeng Wu, Fangming Tang, Weiqing Su, Xiulong Zhu, Jingzhi Sun, Ruilin Quan, Tao Yang, Huijun Han, Jianguo He, Yangyi Lin, Lingpin Pang, Shian Huang, Jieyan Shen, Weifeng Wu, Fangming Tang, Weiqing Su, Xiulong Zhu, Jingzhi Sun, Ruilin Quan, Tao Yang, Huijun Han, Jianguo He

Abstract

Background: Patients with left heart failure (LHF) are often associated with the development of pulmonary hypertension (PH) which leads to an increased risk of death. Recently, the diagnostic standard for PH has changed from mean pulmonary arterial pressure (mPAP) ≥25 mmHg to >20 mmHg. Nonetheless, the effect of borderline PH (mPAP: 21-24 mmHg) on the prognosis of LHF patients is unclear. This study aimed to investigate the relationship between borderline PH and 3-year clinical outcomes in LHF patients.

Methods: A retrospective analysis of a prospective cohort study was done for LHF patients who underwent right heart catheterization (RHC) between January 2013 and November 2016. The primary outcome was all-cause mortality; the secondary outcome was rehospitalization.

Results: Among 344 patients, 62.5% were identified with a proportion of PH (mPAP ≥ 25), 10.8% with borderline PH (21-24), and 26.7% with non-PH (≤20), respectively. Multivariable Cox analysis revealed that borderline PH patients had a higher adjusted mortality risk (HR = 3.822; 95% CI: 1.043-13.999; p = 0.043) than non-PH patients. When mPAP was treated as a continuous variable, the hazard ratio for death increased progressively with increasing mPAP starting at 20 mmHg (HR = 1.006; 95% CI: 1.001-1.012). There was no statistically significant difference in adjusted rehospitalization between borderline PH and non-PH patients (HR = 1.599; 95% CI: 0.833-3.067; p = 0.158).

Conclusions: Borderline PH is independently related to increased 3-year mortality in LHF patients. Future research is needed to evaluate whether more close monitoring, and managing with an intensifier improves clinical outcomes in borderline PH caused by LHF.

Clinical trials registration: www.clinicaltrials.gov NCT02164526.

Keywords: borderline pulmonary hypertension; left heart failure; mean pulmonary artery pressure (mPAP); mortality; right heart catheterization (RHC).

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor JQ declared a shared affiliation with the author(s) JSh at the time of review.

Copyright © 2022 Lin, Pang, Huang, Shen, Wu, Tang, Su, Zhu, Sun, Quan, Yang, Han and He.

Figures

Figure 1
Figure 1
The study design and flowchart for the selection of patients. LHF, left heart failure; RHC, right heart catheterization; PH, pulmonary hypertension.
Figure 2
Figure 2
3-year survival and hospitalization-free survival for without pulmonary hypertension (PH) (mPAP ≤ 20 mmHg), borderline PH (21–24 mmHg), and traditionally defined PH (≥25 mmHg) patients, and Kaplan-Meier analysis of the probability of all-cause mortality (A) (Log-rank, p < 0.001) and rehospitalization (B) (Log-rank, p < 0.001) was performed.
Figure 3
Figure 3
(A) The adjusted hazard ratio for mortality according to mean pulmonary artery pressure (mPAP). (B) Receiver operator characteristic (ROC) curves with associated area under the curve (AUC) of mPAP to predict mortality at 1-, 2-, and 3-year.

References

    1. Hoeper MM, Humbert M, Souza R, Idrees M, Kawut SM, Sliwa-Hahnle K, et al. . A global view of pulmonary hypertension. Lancet Respir Med. (2016) 4:306–22. 10.1016/S2213-2600(15)00543-3
    1. Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, 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. (2016) 37:67–119. 10.1093/eurheartj/ehv317
    1. Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, et al. . Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. (2013) 62:D42–50. 10.1016/j.jacc.2013.10.032
    1. Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, et al. . Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. (2019) 53:1801913. 10.1183/13993003.01913-2018
    1. Brusca SB, Zou Y Elinoff JM. How low should we go? Potential benefits and ramifications of the pulmonary hypertension hemodynamic definitions proposed by the 6th World Symposium. Curr Opin Pulm Med. (2020) 26:384–90. 10.1097/MCP.0000000000000699
    1. Gibbs JSR, Torbicki A. Proposed new pulmonary hypertension definition: is 4 mm(Hg) worth re-writing medical textbooks? Eur Respir J. (2019) 53:1900197. 10.1183/13993003.00197-2019
    1. Hoeper MM, Humbert M. The new haemodynamic definition of pulmonary hypertension: evidence prevails, finally! Eur Respir J. (2019) 53:1900038. 10.1183/13993003.00038-2019
    1. Vachiery JL, Tedford RJ, Rosenkranz S, Palazzini M, Lang I, Guazzi M, et al. . Pulmonary hypertension due to left heart disease. Eur Respir J. (2019) 53:1801897. 10.1183/13993003.01897-2018
    1. Cappola TP, Felker GM, Kao WH, Hare JM, Baughman KL, Kasper EK. Pulmonary hypertension and risk of death in cardiomyopathy: patients with myocarditis are at higher risk. Circulation. (2002) 105:1663–8. 10.1161/01.CIR.0000013771.30198.82
    1. Assad TR, Maron BA, Robbins IM, Xu M, Huang S, Harrell FE, et al. . Prognostic effect and longitudinal hemodynamic assessment of borderline pulmonary hypertension. JAMA Cardiol. (2017) 2:1361–8. 10.1001/jamacardio.2017.3882
    1. Maron BA, Hess E, Maddox TM, Opotowsky AR, Tedford RJ, Lahm T, 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. (2016) 133:1240–8. 10.1161/CIRCULATIONAHA.115.020207
    1. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, et al. . ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European society of cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. (2012) 33:1787–847. 10.1093/eurheartj/ehs104
    1. Hatano S, Strasser T. Primary Pulmonary Hypertension: Report on a WHO Meeting, Geneva, 15–17 (1975).
    1. Badesch DB, Champion HC, Gomez Sanchez MA, Hoeper MM, Loyd JE, Manes A, et al. . Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. (2009) 54:S55–66. 10.1016/j.jacc.2009.04.011
    1. Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. (2009) 34:888–94. 10.1183/09031936.00145608
    1. Kovacs G, Avian A, Tscherner M, Foris V, Bachmaier G, Olschewski A, et al. . Characterization of patients with borderline pulmonary arterial pressure. Chest. (2014) 146:1486–93. 10.1378/chest.14-0194
    1. Douschan P, Kovacs G, Avian A, Foris V, Gruber F, Olschewski A, et al. . Mild elevation of pulmonary arterial pressure as a predictor of mortality. Am J Respir Crit Care Med. (2018) 197:509–16. 10.1164/rccm.201706-1215OC
    1. Nemoto K, Oh-Ishi S, Akiyama T, Yabuuchi Y, Goto H, Nonaka M, et al. . Borderline pulmonary hypertension is associated with exercise intolerance and increased risk for acute exacerbation in patients with interstitial lung disease. BMC Pulm Med. (2019) 19:167. 10.1186/s12890-019-0932-5
    1. Lamia B, Muir JF, Molano LC, Viacroze C, Benichou J, Bonnet P, et al. . Altered synchrony of right ventricular contraction in borderline pulmonary hypertension. Int J Cardiovasc Imaging. (2017) 33:1331–9. 10.1007/s10554-017-1110-6
    1. Pagnamenta A, Dewachter C, McEntee K, Fesler P, Brimioulle S, Naeije R. Early right ventriculo-arterial uncoupling in borderline pulmonary hypertension on experimental heart failure. J Appl Physiol. (1985) 109:1080–5. 10.1152/japplphysiol.00467.2010
    1. Aschauer S, Zotter-Tufaro C, Duca F, Kammerlander A, Dalos D, Mascherbauer J, et al. . Modes of death in patients with heart failure and preserved ejection fraction. Int J Cardiol. (2017) 228:422–6. 10.1016/j.ijcard.2016.11.154
    1. Kjaergaard J, Akkan D, Iversen KK, Kober L, Torp-Pedersen C, Hassager C. Right ventricular dysfunction as an independent predictor of short- and long-term mortality in patients with heart failure. Eur J Heart Fail. (2007) 9:610–6. 10.1016/j.ejheart.2007.03.001
    1. Meluzin J, Spinarova L, Hude P, Krejci J, Dusek L, Vitovec J, et al. . Combined right ventricular systolic and diastolic dysfunction represents a strong determinant of poor prognosis in patients with symptomatic heart failure. Int J Cardiol. (2005) 105:164–73. 10.1016/j.ijcard.2004.12.031
    1. Rosenkranz S, Gibbs JS, Wachter R, De Marco T, Vonk-Noordegraaf A, Vachiery JL. Left ventricular heart failure and pulmonary hypertension. Eur Heart J. (2016) 37:942–54. 10.1093/eurheartj/ehv512

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