for Specialists

1. HOW DO I DIAGNOSE PAH EARLY?

1HOW DO I DIAGNOSE PAH EARLY?

What Can Be Done To Clinically Diagnose Pulmonary Arterial Hypertension Early?

Pulmonary arterial hypertension (PAH) is slow to diagnose because the symptoms of the disease mimic those of more common diseases and may be mild to nonexistent in the early stages of the disease.1,2,3

  • Since the symptoms may be common, patients may fail to seek medical attention or physicians may delay pursuing diagnosis4
  • Other tests can be used to help in aiding the early diagnosis of PAH5
  • While several tests help to diagnose PAH and rule out other diseases, right heart catheterization (RHC) is the only definitive test to confirm PAH5,6

Clinical Presentation6

  • Syncope
  • Angina
  • Dyspnea
  • Edema

Potential Causes

  • Hemodynamic: Systemic vasodilation (exertion, orthostatic, vasodepressor) and low-fixed cardiac output (CO) due to high pulmonary resistance
  • Arrhythmic: Benign arrhythmias (atrial fibrillation) result in loss of atrial contribution to CO; Malignant arrhythmias provoked by wall stretch, ischemia
  • Many symptoms are non-descript7
  • Consistent monitoring of potential causes of symptoms that mimic those of more common disease could contribute to earlier diagnosis of PAH2,3,7

Referring Patients With Suspected PAH

Diagnosis

Additional Tests

The Role of RHC in the Diagnosis of PAH

2 WHY IS EARLY DIAGNOSIS KEY?

Early Diagnosis is Key in Pulmonary Arterial Hypertension Management

PAH is a progressive, potentially life-threatening disease that affects the lungs and subsequently the heart.5,15

  • Historically, the majority of undiagnosed and untreated patients progress to the New York Heart Association functional class (NYHA FC) III before they are diagnosed with advanced abnormalities that are detected by physical examination, laboratory tests, or hemodynamic assessments of the pulmonary circulation4*
  • Despite the availability of multiple treatments, mortality after 5 years remains high in newly and previously diagnosed patients who are classified as NYHA FC III16 (see figure below for previously diagnosed patients)
  • There is often a delay of approximately 2.8 years from symptom onset to a formal diagnosis17

5-Year Survival Rate in Previously Diagnosed NYHA FC III Patients at Enrollment in the REVEAL Registry16†

*Data are from the Patient Registry for the Characterization of Primary Pulmonary Hypertension, initiated by the National Institute of Health in 1981. This multicenter, prospective registry included 32 medical centers in the United States with 187 patients with primary pulmonary hypertension enrolled from July 1981 to September 1985. Limitations include lack of standardized follow-up assessments; prospective studies are needed to validate findings.


†Data are from the Registry to Evaluate Early and Long-term PAH disease management (REVEAL Registry), a large, multicenter, prospective cohort registry that included 54 centers in the United States. 2,967 patients were enrolled between March 2006 and September 2007, all with newly or previously diagnosed World Health Organization group I PAH and pre-specified hemodynamic criteria by right-heart catheterization test. Limitations include lack of standardized follow-up assessments; prospective studies are needed to validate findings.

The Negative Impact of Delayed Diagnosis and Treatment

How Sick Is Your PAH Patient?

Importance of Functional Class Status

Impact of Risk Factor Severity on Long-term Survival in Newly Diagnosed PAH Patients

3WHAT IS THE RISK ASSESSMENT STRATEGY?

Implementing an Effective Risk Assessment Strategy in Pulmonary Arterial Hypertension

What Is Essential for Risk Assessment in PAH?

Low-Risk as a Goal of Treatment in PAH

What Variables Define Low-Risk in PAH?

Ensuring Utilization of the 6-Minute Walk Test

Impact of Change in Functional Class

Moving From Intermediate to Low-Risk

Clinical Deterioration and Risk Assessment in PAH

4WHAT IS THE THERAPEUTIC MANAGEMENT?

What Are the Pharmacologic Approaches for PAH Management?

There are multiple pathophysiologic pathways that have been implicated in the pathogenesis of PAH with current therapies focusing on the imbalance of vasoconstriction and vasodilation (prostacyclin deficiency).27

  • Three primary pharmacologic pathways are leveraged for managing PAH: the nitric oxide, prostacyclin, and endothelin pathways (see figure below)7
  • These pathways correspond to important therapeutic targets in PAH and play a role in determining which class of drugs should be selected28

The Three Primary Treatment Pathways14,29

Nitric oxide pathway

PDE-5 inhibitors increase cGMP, while soluble guanylate cyclase stimulators enhance cGMP production.
Both induce vasodilation

Prostacyclin pathway

Prostacyclin-class therapies result in vasodilation and inhibition of platelet aggregation and smooth muscle cell proliferation

Endothelin pathway

Endothelin receptor antagonists prevent vasoconstrictive and endothelium proliferative effects

cGMP=cyclic guanosine monophosphate; PDE-5=phosphodiesterase type 5.

The Role of Prostacyclin in PAH

2015 ESC/ERS Guidelines Recommendations

Evidence-Based Treatment Algorithm

5ADDITIONAL RESOURCES

6REFERENCES

  1. Elliot CA, Kiely DG. Pulmonary hypertension. Contin Educ Anesth Crit Care Pain. 2006;6(1):17-22.
  2. Palevksy HI. The early diagnosis of pulmonary arterial hypertension: can we do better? Chest. 2011;140(1):4-6.
  3. Brown LM, Chen H, Halpern S, et al. Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry. Chest. 2011;140(1):19-26.
  4. Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. 1987;107(2):216-223.
  5. Ross CA. Pulmonary arterial hypertension: early recognition and treatment can make a lifetime difference for your patient. J Nurse Pract. 2007;3(6):404-409.
  6. McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation. 2006;114(13):1417-1431.
  7. Galiè N, Humbert M, Vachiery JL, et al; ESC Scientific Document Group. 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(1):67-119.
  8. Galiè N, Torbicki A, Barst R, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. Eur Heart J. 2004;25(24):2243-2278.
  9. Mandras SA, Ventura HO, Corris PA. Breaking down the barriers: why the delay in referral for pulmonary arterial hypertension? Ochsner Journal. 2016;16(3):257-262.
  10. Sweiss NJ, Hushaw L, Thenappan T, et al. Diagnosis and management of pulmonary arterial hypertension in systemic sclerosis. Curr Rheumatol Rep. 2010;12(1):8-18.
  11. Rich JD, Rich S. Clinical diagnosis of pulmonary hypertension. Circulation. 2014;130(20):1820-1830.
  12. Pulmonary Hypertension RN website. Blood Tests. http://pulmonaryhypertensionrn.com/blood-tests/. Updated January 2018. Accessed November 26, 2018.
  13. Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(suppl 25):D42-D50.
  14. 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.
  15. Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376-387.
  16. Farber HW, Miller DP, Poms AD, et al. Five-year outcomes of patients enrolled in the REVEAL Registry. Chest. 2015;148(4):1043-1054.
  17. Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376-387.
  18. Farber HW, Miller DP, Meltzer LA, et al. Treatment of patients with pulmonary arterial hypertension at the time of death or deterioration to functional class IV: insights from the REVEAL Registry. J Heart Lung Transplant. 2013;32(11):1114-1122.
  19. Barst RJ, Chung L, Zamanian RT, et al. Functional class improvement and 3-year survival outcomes in patients with pulmonary arterial hypertension in the REVEAL Registry. Chest. 2013;144(1):160-168.
  20. Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017;50(2):1-10
  21. 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 Heart J. 2015;46(4):903-975.
  22. Crapo RO, Casaburi R, Coates AL, et al. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166(1):111-117.
  23. Barnett CT, Jackman JS, Moore NC, et al. The effect of walking path configuration on six-minute walk test performance and gait variability: a pilot study. Gait & Posture. 2015;42(3):S54.
  24. Farber HW, Miller DP, McGoon MD, et al. Predicting outcomes in pulmonary arterial hypertension based on the 6-minute walk distance. J Heart Lung Transplant. 2015;34(3):362-368.
  25. Nickel N, Golpon H, Greer M, et al. The prognostic impact of follow-up assessments in patients with idiopathic pulmonary arterial hypertension. Eur Respir J. 2012;39(3):589-596.
  26. Kylhammar D, Kjellström B, Hjalmarsson C, et al. A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension [published online ahead of print June 1, 2017]. Eur Heart J. doi:10.1093/eurheartj/ehx257.
  27. Christman BW, McPherson CD, Newman JH, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. 1992;327(2):70-75.
  28. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351(14):1425-1436.
  29. Sitbon O, Morrell N. Pathways in pulmonary arterial hypertension: the future is here. Eur Respir Rev. 2012;21(126):321-327.
  30. Galiè N, Barbera JA, Frost AE, et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373(9):834-844.
  31. Galiè N, Corris PA, Frost A, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(suppl 25):D60-D72.
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This MPR/PulmonologyAdvisor Fact Pack is produced as a basic reminder of important information for healthcare professionals. Readers are advised to consult manufacturers and specialists if questions arise about specific products, treatments, or diseases. The publisher and editors do not assume liability for any errors or omissions. MPR, PulmonologyAdvisor, and Fact Pack are registered trademarks of Haymarket Media, Inc.

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