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

6REFERENCES

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