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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Imaging the right atrium in pulmonary hypertension: A systematic review and meta-analysis

Published:December 08, 2022DOI:https://doi.org/10.1016/j.healun.2022.11.007

      Background

      Right atrial (RA) imaging has emerged as a promising tool for the evaluation of patients with pulmonary hypertension (PH), albeit without systematic validation.

      Methods

      PubMed, Web of Science and the Cochrane library were searched for studies investigating the prognostic value of RA imaging assessment in patients with PH from 2000 to June 2021 (PROSPERO Identifier: CRD42020212850). An inverse variance-weighted meta-analysis of univariable hazard ratios (HRs) was performed using a random effects model.

      Results

      Thirty-five studies were included (3,476 patients with PH; 74% female, 86% pulmonary arterial hypertension). Risk of bias was low/moderate (Quality of Prognosis Studies checklist). RA area (HR 1.06; 95% confidence interval [CI] 1.04-1.08), RA indexed area (HR 1.09; 95% CI 1.04-1.14), RA peak longitudinal strain (PLS; HR 0.94; 95% CI 0.91-0.97) and RA total emptying fraction (HR 0.96; 95% CI 0.94-0.98) were significantly associated with combined end-points including death, clinical worsening and/or lung transplantation; RA volume and volume index showed marginal significant associations. RA area (HR 1.06; 95% CI 1.04-1.07), RA indexed area (HR 1.12; 95% CI 1.07-1.17) and RA PLS (HR 0.98; 95% CI 0.97-0.99) showed significant associations with mortality; RA total emptying fraction showed a marginal association.

      Conclusions

      Imaging-based RA assessment qualifies as a relevant prognostic marker in PH. RA area reliably predicts composite end-points and mortality, which underscores its clinical utility. RA PLS emerged as a promising imaging measure, but is currently limited by the number of studies and different acquisition methods.

      Graphic abstract

      KEYWORDS

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      References

        • Naeije R
        • Richter MJ
        • Rubin LJ
        The physiologic basis of pulmonary arterial hypertension.
        Eur Respir J. 2021; 59: 2102334https://doi.org/10.1183/13993003.02334-2021
        • Alenezi F
        • Rajagopal S
        • Kutty S
        Assessing right atrial function in pulmonary hypertension: window to the soul of the right heart?.
        Am J Physiol Heart Circulatory Physiol. 2020; 318: H154-H1H5
        • Alenezi F
        • Mandawat A
        • Il'Giovine ZJ
        • et al.
        Clinical utility and prognostic value of right atrial function in pulmonary hypertension.
        Circ Cardiovasc Imaging. 2018; 11e006984
        • Gaynor SL
        • Maniar HS
        • Bloch JB
        • Steendijk P
        • Moon MR
        Right atrial and ventricular adaptation to chronic right ventricular pressure overload.
        Circulation. 2005; 112: I212-I218
        • Wessels JN
        • Mouratoglou SA
        • van Wezenbeek J
        • et al.
        Right atrial function is associated with RV diastolic stiffness: RA-RV interaction in pulmonary arterial hypertension.
        Eur Respir J. 2021; 59: 2101454https://doi.org/10.1183/13993003.01454-2021
        • Alenezi F
        • Rajagopal S
        The right atrium, more than a storehouse.
        Int J Cardiol. 2021; 331: 329-330
      1. M. Humbert, G. Kovacs, M. M. Hoeper, R. Badagliacca, R. M. F. Berger, M. Brida, et al., ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension, Eur Respir J, 2022;43:3618–3731.

        • Page MJ
        • McKenzie JE
        • Bossuyt PM
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        J Clin Epidemiol. 2021; 134: 178-189
        • Simonneau G
        • Robbins IM
        • Beghetti M
        • et al.
        Updated clinical classification of pulmonary hypertension.
        J Am Coll Cardiol. 2009; 54: S43-S54
        • Greenland S
        Quantitative methods in the review of epidemiologic literature.
        Epidemiol Rev. 1987; 9: 1-30
        • Ouzzani M
        • Hammady H
        • Fedorowicz Z
        • Elmagarmid A
        Rayyan-a web and mobile app for systematic reviews.
        Syst Rev. 2016; 5: 210
        • Hayden JA
        • van der Windt DA
        • Cartwright JL
        • Cote P
        • Bombardier C
        Assessing bias in studies of prognostic factors.
        Ann Intern Med. 2013; 158: 280-286
        • Riley RD
        • Higgins JP
        • Deeks JJ
        Interpretation of random effects meta-analyses.
        BMJ. 2011; 342: d549
        • Higgins JP
        • Thompson SG
        • Deeks JJ
        • Altman DG
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Amsallem M
        • Sweatt AJ
        • Aymami MC
        • et al.
        Right heart end-systolic remodeling index strongly predicts outcomes in pulmonary arterial hypertension: comparison with validated models.
        Circ Cardiovasc Imaging. 2017; 10: e005771https://doi.org/10.1161/CIRCIMAGING.116.005771
        • Badagliacca R
        • Pezzuto B
        • Papa S
        • et al.
        Right ventricular strain curve morphology and outcome in idiopathic pulmonary arterial hypertension.
        JACC Cardiovasc imaging. 2021; 14: 162-172
        • Badagliacca R
        • Papa S
        • Valli G
        • et al.
        Echocardiography combined with cardiopulmonary exercise testing for the prediction of outcome in idiopathic pulmonary arterial hypertension.
        Chest. 2016; 150: 1313-1322
        • Bai Y
        • Yang J
        • Liu J
        • Ning H
        • Zhang R
        Right atrial function for the prediction of prognosis in connective tissue disease-associated pulmonary arterial hypertension: a study with two-dimensional speckle tracking.
        Int J Cardiovasc Imaging. 2019; 35: 1637-1649
        • Bredfelt A
        • Radegran G
        • Hesselstrand R
        • Arheden H
        • Ostenfeld E
        Increased right atrial volume measured with cardiac magnetic resonance is associated with worse clinical outcome in patients with pre-capillary pulmonary hypertension.
        ESC Heart Fail. 2018; 5: 864-875
        • Brunner NW
        • Haddad F
        • Kobayashi Y
        • et al.
        Prognostic utility of right atrial emptying fractions in pulmonary arterial hypertension.
        Pulmonary circulation. 2015; 5: 473-480
        • D'Alto M
        • D'Andrea A
        • Di Salvo G
        • et al.
        Right atrial function and prognosis in idiopathic pulmonary arterial hypertension.
        Int J Cardiol. 2017; 248: 320-325
        • Darsaklis K
        • Dickson ME
        • Cornwell 3rd, W
        • et al.
        Right atrial emptying fraction non-invasively predicts mortality in pulmonary hypertension.
        Int J Cardiovasc Imaging. 2016; 32: 1121-1130
        • Forfia PR
        • Fisher MR
        • Mathai SC
        • et al.
        Tricuspid annular displacement predicts survival in pulmonary hypertension.
        Am J Respir Crit Care Med. 2006; 174: 1034-1041
        • Freed BH
        • Gomberg-Maitland M
        • Chandra S
        • et al.
        Late gadolinium enhancement cardiovascular magnetic resonance predicts clinical worsening in patients with pulmonary hypertension.
        J Cardiovasc Magn Reson. 2012; 14: 11
        • Ghio S
        • Mercurio V
        • Fortuni F
        • et al.
        A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension.
        Eur Respir J. 2020; 56: 2000513https://doi.org/10.1183/13993003.00513-2020
        • Grunig E
        • Tiede H
        • Enyimayew EO
        • et al.
        Assessment and prognostic relevance of right ventricular contractile reserve in patients with severe pulmonary hypertension.
        Circulation. 2013; 128: 2005-2015
        • Guo X
        • Lai J
        • Wang H
        • et al.
        Predictive value of non-invasive right ventricle to pulmonary circulation coupling in systemic lupus erythematosus patients with pulmonary arterial hypertension.
        Eur Heart J Cardiovasc Imaging. 2021; 22: 111-118
        • Hasselberg NE
        • Kagiyama N
        • Soyama Y
        • et al.
        The prognostic value of right atrial strain imaging in patients with precapillary pulmonary hypertension.
        J Am Soc Echocardiograp. 2021; 34: 851-861.e1
        • Hulshof HG
        • van Dijk AP
        • Hopman MTE
        • et al.
        5-Year prognostic value of the right ventricular strain-area loop in patients with pulmonary hypertension.
        Eur Heart J Cardiovasc Imaging. 2021; 22: 188-195
        • Kawamukai M
        • Hashimoto A
        • Koyama M
        • et al.
        Risk classification of pulmonary arterial hypertension by echocardiographic combined assessment of pulmonary vascular resistance and right ventricular function.
        Heart Vessels. 2019; 34: 1789-1800
        • Kishiki K
        • Singh A
        • Narang A
        • et al.
        Impact of severe pulmonary arterial hypertension on the left heart and prognostic implications.
        J Am Soc Echocardiogr. 2019; 32: 1128-1137
        • Leng S
        • Dong Y
        • Wu Y
        • et al.
        Impaired cardiovascular magnetic resonance-derived rapid semiautomated right atrial longitudinal strain is associated with decompensated hemodynamics in pulmonary arterial hypertension.
        Circ Cardiovasc Imaging. 2019; 12e008582
        • Mathai SC
        • Sibley CT
        • Forfia PR
        • et al.
        Tricuspid annular plane systolic excursion is a robust outcome measure in systemic sclerosis-associated pulmonary arterial hypertension.
        J Rheumatol. 2011; 38: 2410-2418
        • Moceri P
        • Duchateau N
        • Baudouy D
        • et al.
        Three-dimensional right-ventricular regional deformation and survival in pulmonary hypertension.
        Eur Heart J Cardiovasc Imaging. 2018; 19: 450-458
        • Mouratoglou SA
        • Dimopoulos K
        • Kamperidis V
        • et al.
        Right atrial function predicts clinical outcome in patients with precapillary pulmonary hypertension.
        J Am Soc Echocardiogr. 2018; 31: 1137-1145
        • Mouratoglou SA
        • Kallifatidis A
        • Pitsiou G
        • et al.
        Duration of interventricular septal shift toward the left ventricle is associated with poor clinical outcome in precapillary pulmonary hypertension: A cardiac magnetic resonance study.
        Hellenic J Cardiol. 2020; 61: 112-117
        • Murata M
        • Tsugu T
        • Kawakami T
        • et al.
        Prognostic value of three-dimensional echocardiographic right ventricular ejection fraction in patients with pulmonary arterial hypertension.
        Oncotarget. 2016; 7: 86781-86790
        • Murata M
        • Tsugu T
        • Kawakami T
        • et al.
        Right ventricular dyssynchrony predicts clinical outcomes in patients with pulmonary hypertension.
        Int J Cardiol. 2017; 228: 912-918
        • Mysore MM
        • Bilchick KC
        • Ababio P
        • et al.
        Right atrial to left atrial volume index ratio is associated with increased mortality in patients with pulmonary hypertension.
        Echocardiography. 2018; 35: 1729-1735
        • Park JH
        • Park MM
        • Farha S
        • et al.
        Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension.
        J Cardiovasc Ultrasound. 2015; 23: 91-99
        • Radchenko GD
        • Zhyvylo IO
        • Sirenko YM
        Analysis of pulmonary hypertension patient survival after treatment in referral center (data of first Ukrainian register).
        Pulmonary Circ. 2019; 92045894019845604
        • Raymond RJ
        • Hinderliter AL
        • Willis PW
        • et al.
        Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension.
        J Am Coll Cardiol. 2002; 39: 1214-1219
        • Richter MJ
        • Fortuni F
        • Wiegand MA
        • et al.
        Association of right atrial conduit phase with right ventricular lusitropic function in pulmonary hypertension.
        Int J Cardiovasc Imaging. 2020; 36: 633-642
        • Sato T
        • Tsujino I
        • Ohira H
        • et al.
        Right atrial volume and reservoir function are novel independent predictors of clinical worsening in patients with pulmonary hypertension.
        J Heart and Lung Transplant. 2015; 34: 414-423
        • Shelburne NJ
        • Parikh KS
        • Chiswell K
        • et al.
        Echocardiographic assessment of right ventricular function and response to therapy in pulmonary arterial hypertension.
        Am J Cardiol. 2019; 124: 1298-1304
        • Stepnowska E
        • Lewicka E
        • Dabrowska-Kugacka A
        • et al.
        Predictors of poor outcome in patients with pulmonary arterial hypertension: A single center study.
        PLoS One. 2018; 13e0193245
        • Stolfo D
        • Albani S
        • Biondi F
        • et al.
        Global right heart assessment with speckle-tracking imaging improves the risk prediction of a validated scoring system in pulmonary arterial hypertension.
        J Am Soc Echocardiogr. 2020; 33: 1334-1344.e2
        • Wright L
        • Dwyer N
        • Wahi S
        • Marwick TH
        Relative importance of baseline and longitudinal evaluation in the follow-up of vasodilator therapy in pulmonary arterial hypertension.
        JACC Cardiovasc imaging. 2019; 12: 2103-2111
        • Rudski LG
        • Lai WW
        • Afilalo J
        • et al.
        Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography.
        J Am Soc Echocardiogr. 2010; 23 (quiz 86-8): 685-713
        • Lang RM
        • Badano LP
        • Mor-Avi V
        • et al.
        Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the american society of echocardiography and the European association of cardiovascular imaging.
        J Am Soc Echocardiogr. 2015; 28: 1-39.e14
        • Lang RM
        • Bierig M
        • Devereux RB
        • et al.
        Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.
        J Am Soc Echocardiogr. 2005; 18: 1440-1463
        • Kiely DG
        • Levin D
        • Hassoun P
        • et al.
        EXPRESS: Statement on imaging and pulmonary hypertension from the Pulmonary Vascular Research Institute (PVRI).
        Pulmonary Circ. 2019; 2045894019841990
        • Grapsa J
        • Pereira Nunes MC
        • Tan TC
        • et al.
        Echocardiographic and hemodynamic predictors of survival in precapillary pulmonary hypertension: seven-year follow-up.
        Circ Cardiovasc Imaging. 2015; 8
        • Haddad F
        • Spruijt OA
        • Denault AY
        • et al.
        Right heart score for predicting outcome in idiopathic, familial, or drug- and toxin-associated pulmonary arterial hypertension.
        JACC Cardiovasc imaging. 2015; 8: 627-638
        • Grunig E
        • Henn P
        • D'Andrea A
        • et al.
        Reference values for and determinants of right atrial area in healthy adults by 2-dimensional echocardiography.
        Circ Cardiovasc Imaging. 2013; 6: 117-124
        • Hoeper MM
        • Pausch C
        • Olsson KM
        • et al.
        COMPERA 2.0: A refined 4-strata risk assessment model for pulmonary arterial hypertension.
        Eur Respir J. 2022; 60: 2102311https://doi.org/10.1183/13993003.02311-2021
        • Tello K
        • Dalmer A
        • Vanderpool R
        • et al.
        Right ventricular function correlates of right atrial strain in pulmonary hypertension: a combined cardiac magnetic resonance and conductance catheter study.
        Am J Physiol Heart Circ Physiol. 2020; 318: H156-HH64
        • Il'Giovine ZJ
        • Mulder H
        • Chiswell K
        • et al.
        Right ventricular longitudinal strain reproducibility using vendor-dependent and vendor-independent software.
        J Am Soc Echocardiogr. 2018; 31: 721-732.e5
        • Petersen SE
        • Aung N
        • Sanghvi MM
        • et al.
        Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (CMR) in Caucasians from the UK Biobank population cohort.
        J Cardiovasc Magn Reson. 2017; 19: 18
        • Soulat-Dufour L
        • Addetia K
        • Miyoshi T
        • et al.
        Normal values of right atrial size and function according to age, sex, and ethnicity: results of the world alliance societies of echocardiography study.
        J Am Soc Echocardiogr. 2021; 34: 286-300
        • Grapsa J
        • Gibbs JS
        • Cabrita IZ
        • et al.
        The association of clinical outcome with right atrial and ventricular remodelling in patients with pulmonary arterial hypertension: study with real-time three-dimensional echocardiography.
        Eur Heart J Cardiovasc Imaging. 2012; 13: 666-672
        • Marra AM
        • Benjamin N
        • Cittadini A
        • Bossone E
        • Grunig E
        When pulmonary hypertension complicates heart failure.
        Cardiol Clin. 2022; 40: 191-198