[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 18.204.55.168. Please contact the publisher to request reinstatement.
[Skip to Content Landing]

Association of Mild Echocardiographic Pulmonary Hypertension With Mortality and Right Ventricular Function

Educational Objective
To describe the clinical and pathophysiologic implications of mild pulmonary hypertension found on echocardiography.
1 Credit CME
Key Points

Question  Do patients with mild echocardiographic pulmonary hypertension have worse right ventricular function and mortality than patients with pulmonary pressures in the normal range?

Findings  In this cohort study of 47 784 patients, those with mild echocardiographic pulmonary hypertension (right ventricular systolic pressure of 33 to 39 mm Hg) had higher mortality, reduced right ventricular function, and impaired right ventricular–pulmonary arterial coupling compared with patients with right ventricular systolic pressure less than 33 mm Hg.

Meaning  In a clinical referral population, mildly elevated pulmonary pressures were associated with adverse right ventricular compensation and increased adjusted mortality.

Abstract

Importance  Current guidelines recommend evaluation for echocardiographically estimated right ventricular systolic pressure (RVSP) greater than 40 mm Hg; however, this threshold does not capture all patients at risk.

Objectives  To determine if mild echocardiographic pulmonary hypertension (ePH) is associated with reduced right ventricular (RV) function and increased risk of mortality.

Design, Setting, and Participants  In this cohort study, electronic health record data of patients who were referred for echocardiography at Vanderbilt University Medical Center, Nashville, Tennessee, from March 1997 to February 2014 and had recorded estimates of RVSP values were studied. Data were analyzed from February 2017 to May 2019.

Exposures  Mild ePH was defined as an RVSP value of 33 to 39 mm Hg. Right ventricular function was assessed using tricuspid annular plane systolic excursion (TAPSE), and RV–pulmonary arterial coupling was measured using the ratio of TAPSE to RVSP.

Main Outcomes and Measures  Associations of mild ePH with mortality adjusted for relevant covariates were examined using Cox proportional hazard models with restricted cubic splines.

Results  Of the 47 784 included patients, 26 758 of 47 771 (56.0%) were female and 6040 of 44 763 (13.5%) were black, and the mean (SD) age was 59 (18) years. Patients with mild ePH had worse RV function compared with those with no ePH (mean [SD] TAPSE, 2.0 [0.6] cm vs 2.2 [0.5] cm; P < .001) and nearly double the prevalence of RV dysfunction (32.6% [92 of 282] vs 16.7% [170 of 1015]; P < .001). Compared with patients with RVSP less than 33 mm Hg, those with mild ePH also had reduced RV–pulmonary arterial coupling (mean [SD] ratio of TAPSE to RVSP, 0.55 [0.18] mm/mm Hg vs 0.93 [0.39] mm/mm Hg; P < .001). An increase in adjusted mortality began at an RVSP value of 27 mm Hg (hazard ratio, 1.32; 95% CI, 1.02-1.70). Female sex was associated with increased mortality risk at any given RVSP value.

Conclusions and Relevance  Mild ePH was associated with RV dysfunction and worse RV–pulmonary arterial coupling in a clinical population seeking care. Future studies are needed to identify patients with mild ePH who are susceptible to adverse outcomes.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Accepted for Publication: July 28, 2019.

Corresponding Author: Evan L. Brittain, MD, MSCI, Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, 2525 West End Ave, Ste 300-A, Nashville, TN 37203 (evan.brittain@vumc.org).

Published Online: September 18, 2019. doi:10.1001/jamacardio.2019.3345

Author Contributions: Dr Brittain had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Huston, Hemnes, Brittain.

Acquisition, analysis, or interpretation of data: Huston, Maron, French, Huang, Thayer, Farber-Eger, Wells, Choudhary, Brittain.

Drafting of the manuscript: Huston, Maron, Thayer, Brittain.

Critical revision of the manuscript for important intellectual content: Huston, French, Huang, Thayer, Farber-Eger, Wells, Choudhary, Hemnes, Brittain.

Statistical analysis: French, Huang, Thayer, Brittain.

Obtained funding: Brittain.

Administrative, technical, or material support: Huston, French, Thayer, Farber-Eger, Wells.

Study supervision: Huston, Hemnes, Brittain.

Conflict of Interest Disclosures: Dr Choudhary has received grants from Novartis. Dr Hemnes has received grants from the Cardiovascular Medical Research and Education Fund and the National Institutes of Health as well as personal fees from Actelion Pharmaceuticals, Bayer, Complexa, and United Therapeutics and has a patent issued for Annamometer. Dr Brittain has received personal fees from Bayer. No other disclosures were reported.

Funding/Support: This research was supported by grants U01 HL125212-01 (Dr Hemnes), K08HL111207-01A1 (Dr Maron), and R01HL146588 (Dr Brittain) from the National Institutes of Health, grants 13FTF16070002 (Dr Brittain) and 15GRNT25080016 (Dr Maron) from the American Heart Association, the Gilead Scholars Program in Pulmonary Arterial Hypertension (Dr Brittain), the Cardiovascular Medical Research and Education Foundation (Dr Maron), and the Klarman Foundation at Brigham and Women’s Hospital (Dr Maron). The datasets used for the analyses described were obtained from Vanderbilt University Medical Center’s Synthetic Derivative, which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the Clinical and Translational Science Award grant UL1TR000445 from the National Center for Advancing Translational Sciences and National Institutes of Health.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Abramson  SV, Burke  JF, Kelly  JJ  Jr,  et al.  Pulmonary hypertension predicts mortality and morbidity in patients with dilated cardiomyopathy.  Ann Intern Med. 1992;116(11):888-895. doi:10.7326/0003-4819-116-11-888PubMedGoogle ScholarCrossref
2.
Oswald-Mammosser  M, Weitzenblum  E, Quoix  E,  et al.  Prognostic factors in COPD patients receiving long-term oxygen therapy: importance of pulmonary artery pressure.  Chest. 1995;107(5):1193-1198. doi:10.1378/chest.107.5.1193PubMedGoogle ScholarCrossref
3.
Andersen  KH, Iversen  M, Kjaergaard  J,  et al.  Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease.  J Heart Lung Transplant. 2012;31(4):373-380. doi:10.1016/j.healun.2011.11.020PubMedGoogle ScholarCrossref
4.
McLaughlin  VV, Archer  SL, Badesch  DB,  et al; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association.  ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc; and the Pulmonary Hypertension Association.  J Am Coll Cardiol. 2009;53(17):1573-1619. doi:10.1016/j.jacc.2009.01.004PubMedGoogle ScholarCrossref
5.
Galiè  N, Hoeper  MM, Humbert  M,  et al; ESC Committee for Practice Guidelines (CPG).  Guidelines for the diagnosis and treatment of pulmonary hypertension: the 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 the International Society of Heart and Lung Transplantation (ISHLT).  Eur Heart J. 2009;30(20):2493-2537. doi:10.1093/eurheartj/ehp297PubMedGoogle ScholarCrossref
6.
Galiè  N, Humbert  M, Vachiery  JL,  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 Respir J. 2015;46(4):903-975. doi:10.1183/13993003.01032-2015PubMedGoogle ScholarCrossref
7.
McLaughlin  VV, Archer  SL, Badesch  DB,  et al; ACCF/AHA.  ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association.  Circulation. 2009;119(16):2250-2294. doi:10.1161/CIRCULATIONAHA.109.192230PubMedGoogle ScholarCrossref
8.
Assad  TR, Maron  BA, Robbins  IM,  et al.  Prognostic effect and longitudinal hemodynamic assessment of borderline pulmonary hypertension.  JAMA Cardiol. 2017;2(12):1361-1368. doi:10.1001/jamacardio.2017.3882PubMedGoogle ScholarCrossref
9.
Maron  BA, Hess  E, Maddox  TM,  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(13):1240-1248. doi:10.1161/CIRCULATIONAHA.115.020207PubMedGoogle ScholarCrossref
10.
Douschan  P, Kovacs  G, Avian  A,  et al.  Mild elevation of pulmonary arterial pressure as a predictor of mortality.  Am J Respir Crit Care Med. 2018;197(4):509-516. doi:10.1164/rccm.201706-1215OCPubMedGoogle ScholarCrossref
11.
Kjaergaard  J, Akkan  D, Iversen  KK,  et al.  Prognostic importance of pulmonary hypertension in patients with heart failure.  Am J Cardiol. 2007;99(8):1146-1150. doi:10.1016/j.amjcard.2006.11.052PubMedGoogle ScholarCrossref
12.
Tello  K, Axmann  J, Ghofrani  HA,  et al.  Relevance of the TAPSE/PASP ratio in pulmonary arterial hypertension.  Int J Cardiol. 2018;266:229-235. doi:10.1016/j.ijcard.2018.01.053PubMedGoogle ScholarCrossref
13.
Guazzi  M, Dixon  D, Labate  V,  et al.  RV contractile function and its coupling to pulmonary circulation in heart failure with preserved ejection fraction: stratification of clinical phenotypes and outcomes.  JACC Cardiovasc Imaging. 2017;10(10, pt B):1211-1221. doi:10.1016/j.jcmg.2016.12.024PubMedGoogle ScholarCrossref
14.
Hussain  I, Mohammed  SF, Forfia  PR,  et al.  Impaired right ventricular-pulmonary arterial coupling and effect of sildenafil in heart failure with preserved ejection fraction: an ancillary analysis from the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (RELAX) trial.  Circ Heart Fail. 2016;9(4):e002729. doi:10.1161/CIRCHEARTFAILURE.115.002729PubMedGoogle Scholar
15.
Sultan  I, Cardounel  A, Abdelkarim  I,  et al.  Right ventricle to pulmonary artery coupling in patients undergoing transcatheter aortic valve implantation.  Heart. 2019;105(2):117-121. doi:10.1136/heartjnl-2018-313385PubMedGoogle ScholarCrossref
16.
Prins  KW, Archer  SL, Pritzker  M,  et al.  Interleukin-6 is independently associated with right ventricular function in pulmonary arterial hypertension.  J Heart Lung Transplant. 2018;37(3):376-384. doi:10.1016/j.healun.2017.08.011PubMedGoogle ScholarCrossref
17.
Gerges  M, Gerges  C, Pistritto  AM,  et al.  Pulmonary hypertension in heart failure. epidemiology, right ventricular function, and survival.  Am J Respir Crit Care Med. 2015;192(10):1234-1246. doi:10.1164/rccm.201503-0529OCPubMedGoogle ScholarCrossref
18.
Guazzi  M, Naeije  R, Arena  R,  et al.  Echocardiography of right ventriculoarterial coupling combined with cardiopulmonary exercise testing to predict outcome in heart failure.  Chest. 2015;148(1):226-234. doi:10.1378/chest.14-2065PubMedGoogle ScholarCrossref
19.
Roden  DM, Pulley  JM, Basford  MA,  et al.  Development of a large-scale de-identified DNA biobank to enable personalized medicine.  Clin Pharmacol Ther. 2008;84(3):362-369. doi:10.1038/clpt.2008.89PubMedGoogle ScholarCrossref
20.
Pulley  J, Clayton  E, Bernard  GR, Roden  DM, Masys  DR.  Principles of human subjects protections applied in an opt-out, de-identified biobank.  Clin Transl Sci. 2010;3(1):42-48. doi:10.1111/j.1752-8062.2010.00175.xPubMedGoogle ScholarCrossref
21.
Wells  QS, Farber-Eger  E, Crawford  DC.  Extraction of echocardiographic data from the electronic medical record is a rapid and efficient method for study of cardiac structure and function.  J Clin Bioinforma. 2014;4:12. doi:10.1186/2043-9113-4-12PubMedGoogle ScholarCrossref
22.
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(7):685-713, 786-788. doi:10.1016/j.echo.2010.05.010PubMedGoogle ScholarCrossref
23.
Brittain  EL, Duncan  MS, Chang  J,  et al.  Increased echocardiographic pulmonary pressure in HIV-infected and -uninfected individuals in the Veterans Aging Cohort study.  Am J Respir Crit Care Med. 2018;197(7):923-932. doi:10.1164/rccm.201708-1555OCPubMedGoogle ScholarCrossref
24.
Simonneau  G, Montani  D, Celermajer  DS,  et al.  Haemodynamic definitions and updated clinical classification of pulmonary hypertension.  Eur Respir J. 2019;53(1):1801913. doi:10.1183/13993003.01913-2018PubMedGoogle Scholar
25.
Chemla  D, Castelain  V, Humbert  M,  et al.  New formula for predicting mean pulmonary artery pressure using systolic pulmonary artery pressure.  Chest. 2004;126(4):1313-1317. doi:10.1378/chest.126.4.1313PubMedGoogle ScholarCrossref
26.
Badesch  DB, Champion  HC, Sanchez  MA,  et al.  Diagnosis and assessment of pulmonary arterial hypertension.  J Am Coll Cardiol. 2009;54(1, suppl):S55-S66. doi:10.1016/j.jacc.2009.04.011PubMedGoogle ScholarCrossref
27.
Heresi  GA, Minai  OA, Tonelli  AR,  et al.  Clinical characterization and survival of patients with borderline elevation in pulmonary artery pressure.  Pulm Circ. 2013;3(4):916-925. doi:10.1086/674756PubMedGoogle ScholarCrossref
28.
Guazzi  M, Bandera  F, Pelissero  G,  et al.  Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis.  Am J Physiol Heart Circ Physiol. 2013;305(9):H1373-H1381. doi:10.1152/ajpheart.00157.2013PubMedGoogle ScholarCrossref
29.
Kolte  D, Lakshmanan  S, Jankowich  MD, Brittain  EL, Maron  BA, Choudhary  G.  Mild pulmonary hypertension is associated with increased mortality: a systematic review and meta-analysis.  J Am Heart Assoc. 2018;7(18):e009729. doi:10.1161/JAHA.118.009729PubMedGoogle Scholar
30.
Gladwin  MT, Sachdev  V, Jison  ML,  et al.  Pulmonary hypertension as a risk factor for death in patients with sickle cell disease.  N Engl J Med. 2004;350(9):886-895. doi:10.1056/NEJMoa035477PubMedGoogle ScholarCrossref
31.
Bursi  F, McNallan  SM, Redfield  MM,  et al.  Pulmonary pressures and death in heart failure: a community study.  J Am Coll Cardiol. 2012;59(3):222-231. doi:10.1016/j.jacc.2011.06.076PubMedGoogle ScholarCrossref
32.
Szwejkowski  BR, Elder  DH, Shearer  F,  et al.  Pulmonary hypertension predicts all-cause mortality in patients with heart failure: a retrospective cohort study.  Eur J Heart Fail. 2012;14(2):162-167. doi:10.1093/eurjhf/hfr159PubMedGoogle ScholarCrossref
33.
Lam  CS, Borlaug  BA, Kane  GC, Enders  FT, Rodeheffer  RJ, Redfield  MM.  Age-associated increases in pulmonary artery systolic pressure in the general population.  Circulation. 2009;119(20):2663-2670. doi:10.1161/CIRCULATIONAHA.108.838698PubMedGoogle ScholarCrossref
34.
Lam  CS, Roger  VL, Rodeheffer  RJ, Borlaug  BA, Enders  FT, Redfield  MM.  Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study.  J Am Coll Cardiol. 2009;53(13):1119-1126. doi:10.1016/j.jacc.2008.11.051PubMedGoogle ScholarCrossref
35.
United States Census Bureau. Quick facts: race and Hispanic origin. https://www.census.gov/quickfacts/fact/table/US/PST045217. Accessed May 13, 2019.
36.
Marra  AM, Halank  M, Benjamin  N,  et al.  Right ventricular size and function under riociguat in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (the RIVER study).  Respir Res. 2018;19(1):258. doi:10.1186/s12931-018-0957-yPubMedGoogle ScholarCrossref
37.
Strange  G, Stewart  S, Celermajer  DS,  et al; NEDA Contributing Sites.  Threshold of pulmonary hypertension associated with increased mortality.  J Am Coll Cardiol. 2019;73(21):2660-2672. doi:10.1016/j.jacc.2019.03.482PubMedGoogle ScholarCrossref
38.
Shapiro  S, Traiger  GL, Turner  M, McGoon  MD, Wason  P, Barst  RJ.  Sex differences in the diagnosis, treatment, and outcome of patients with pulmonary arterial hypertension enrolled in the registry to evaluate early and long-term pulmonary arterial hypertension disease management.  Chest. 2012;141(2):363-373. doi:10.1378/chest.10-3114PubMedGoogle ScholarCrossref
39.
Assad  TR, Hemnes  AR, Larkin  EK,  et al.  Clinical and biological insights into combined post- and pre-capillary pulmonary hypertension.  J Am Coll Cardiol. 2016;68(23):2525-2536. doi:10.1016/j.jacc.2016.09.942PubMedGoogle ScholarCrossref
40.
Yang  BQ, Assad  TR, O’Leary  JM,  et al.  Racial differences in patients referred for right heart catheterization and risk of pulmonary hypertension.  Pulm Circ. 2018;8(2):2045894018764273. doi:10.1177/2045894018764273PubMedGoogle Scholar
41.
Farber  HW, Foreman  AJ, Miller  DP, McGoon  MD.  REVEAL registry: correlation of right heart catheterization and echocardiography in patients with pulmonary arterial hypertension.  Congest Heart Fail. 2011;17(2):56-64. doi:10.1111/j.1751-7133.2010.00202.xPubMedGoogle ScholarCrossref
42.
Fisher  MR, Forfia  PR, Chamera  E,  et al.  Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension.  Am J Respir Crit Care Med. 2009;179(7):615-621. doi:10.1164/rccm.200811-1691OCPubMedGoogle ScholarCrossref
43.
Rich  JD, Shah  SJ, Swamy  RS, Kamp  A, Rich  S.  Inaccuracy of Doppler echocardiographic estimates of pulmonary artery pressures in patients with pulmonary hypertension: implications for clinical practice.  Chest. 2011;139(5):988-993. doi:10.1378/chest.10-1269PubMedGoogle ScholarCrossref
44.
Vanderpool  RR, Pinsky  MR, Naeije  R,  et al.  RV-pulmonary arterial coupling predicts outcome in patients referred for pulmonary hypertension.  Heart. 2015;101(1):37-43. doi:10.1136/heartjnl-2014-306142PubMedGoogle ScholarCrossref
45.
French  S, Amsallem  M, Ouazani  N,  et al.  Non-invasive right ventricular load adaptability indices in patients with scleroderma-associated pulmonary arterial hypertension.  Pulm Circ. 2018;8(3):2045894018788268. doi:10.1177/2045894018788268PubMedGoogle Scholar
46.
Lamia  B, Muir  JF, Molano  LC,  et al.  Altered synchrony of right ventricular contraction in borderline pulmonary hypertension.  Int J Cardiovasc Imaging. 2017;33(9):1331-1339. doi:10.1007/s10554-017-1110-6PubMedGoogle ScholarCrossref
47.
Herman  C.  What makes a screening exam “good”?  Virtual Mentor. 2006;8(1):34-37.PubMedGoogle Scholar
48.
Herman  CR, Gill  HK, Eng  J, Fajardo  LL.  Screening for preclinical disease: test and disease characteristics.  AJR Am J Roentgenol. 2002;179(4):825-831. doi:10.2214/ajr.179.4.1790825PubMedGoogle ScholarCrossref
49.
Greiner  S, Jud  A, Aurich  M,  et al.  Reliability of noninvasive assessment of systolic pulmonary artery pressure by Doppler echocardiography compared to right heart catheterization: analysis in a large patient population.  J Am Heart Assoc. 2014;3(4):e001103. doi:10.1161/JAHA.114.001103PubMedGoogle Scholar
50.
Janda  S, Shahidi  N, Gin  K, Swiston  J.  Diagnostic accuracy of echocardiography for pulmonary hypertension: a systematic review and meta-analysis.  Heart. 2011;97(8):612-622. doi:10.1136/hrt.2010.212084PubMedGoogle ScholarCrossref
51.
Navar  AM, Peterson  ED, Steen  DL,  et al.  Evaluation of mortality data from the Social Security Administration Death Master File for clinical research.  JAMA Cardiol. 2019;4(4):375-379. doi:10.1001/jamacardio.2019.0198PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close