Chest
Volume 126, Issue 1, Supplement, July 2004, Pages 14S-34S
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Screening, Early Detection, and Diagnosis of Pulmonary Arterial Hypertension: ACCP Evidence-Based Clinical Practice Guidelines

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Pulmonary arterial hypertension (PAH) occurs as an idiopathic process or as a component of a variety of disease processes, including chronic thromboembolic disease, connective tissue diseases, congenital heart disease, and exposure to exogenous factors including appetite suppressants or infectious agents such as HIV. This article reviews evidence for screening in susceptible patient groups and the approach to diagnosing PAH when it is suspected, and provides specific recommendations for applying this evidence to clinical practice.

Section snippets

Historical Perspective

The development of cardiac catheterization provided the first method to diagnose and confirm PAH, and was the pivotal diagnostic method for 3 decades after the first clinical description of idiopathic PAH (IPAH) in the early 1950s. Although cardiac catheterization is still necessary for disease confirmation in patients with suspected pulmonary hypertension (PH), in the current era it rarely reveals unsuspected new findings. The technical advances in noninvasive thoracic and cardiac imaging over

Evaluation of PAH

Assessment of PAH is based on a logical sequence of determining whether there is a risk of PAH being present, whether PAH is likely to be present based on initial, noninvasive evaluation, clarifying the underlying etiology of PAH in an individual patient, and delineating the specific hemodynamic profile, including the acute response to vasodilator testing. The schema for patient evaluation using this approach is provided in Figure 1, and is expanded in the text.

Genetic Screening for Mutations That Cause PAH

Mutations in the bone morphogenetic protein receptor II (BMPR2) gene have been identified in approximately 50% of patients with familial PAH (FPAH)12 and 25% of patients thought to have sporadic IPAH.3 Other FPAH families demonstrate linkage to the same chromosomal region, 2q32, where BMPR2 resides, but the responsible mutations have not been identified. Confirmation of linkage of any FPAH locus, other than 2q32, has not been reported to date. FPAH is inherited in an autosomal dominant manner

Echocardiographic Screening of Asymptomatic Subjects at Risk for PAH

Few reports have evaluated echocardiography for screening asymptomatic patients with PAH, since the incidence of disease is low and Bayesian analysis would predict a large number of false-positive test results. Furthermore, health insurers may not reimburse the expense of testing “asymptomatic” individuals. Finally, whether establishing an early diagnosis of PAH (such as in a presymptomatic phase of FPAH) improves outcome is unknown, although it unquestionably has important emotional and social

Presenting Symptoms

Patients with PAH generally present with a spectrum of symptoms attributable to impaired oxygen transport and reduced cardiac output. Although PAH may be asymptomatic, particularly in its early stages, exertional dyspnea is the most frequent presenting symptom, and was present in 60% of patients in the National Institutes of Health (NIH) prospective cohort study of patients with PPH.8 Dyspnea is eventually present in virtually all patients as the disease progresses. Fatigue, weakness, or

Physical Examination

Signs of PH on physical examination are subtle and often overlooked. Although no rigorous analysis of the sensitivity and specificity of findings on physical examination has been performed, experience suggests that the likelihood of PAH is increased when certain findings are present. For example, an accentuated pulmonary component of the second heart sound audible at the apex is noted in > 90% of patients with IPAH,8 reflecting increased force of pulmonary valve closure due to elevated

ECG

PAH results in right ventricular hypertrophy and right-heart dilation. Since these processes produce ECG abnormalities, the ECG may provide a signal of hemodynamically significant PH. Right ventricular hypertrophy and right-axis deviation on ECG are seen in 87% and 79%, respectively, of patients with IPAH.8 ECG findings suggestive of PAH are as follows: (1) right-axis deviation; (2) a tall R wave and small S wave with R/S ratio > 1 in lead V1; (3) qR complex in lead V1; (4) rSR' pattern in lead

Chest Radiography

The chest radiograph (CXR) may disclose abnormal anatomic features due to the presence of PAH. Although most patients with asymptomatic PAH have normal CXR findings, the accuracy of the CXR in detecting PAH is unknown. An index has been described based on the ratio of the summed horizontal measurements of the pulmonary arteries from midline to their first divisions divided by the transverse chest diameter.14 All 50 patients with a sPAP < 30 mm Hg, and 10 of 100 patients with a sPAP > 45 mm Hg

Diagnostic Strategies for IPAH

Once PAH is suspected based on the presenting features, screening examination, or incidental discovery during evaluation of apparently unrelated problems, further evaluation is intended to characterize the type of PH and establish its severity. The goal of this approach is to determine prognosis and establish an appropriate treatment strategy. As with assessment strategies for many diseases, this is a hierarchical process beginning with tests that are less invasive and complex but also less

Summary

A high level of suspicion is of paramount importance for the diagnosis of PAH, regardless of the underlying cause. Once suspected, a methodical workup using commonly employed diagnostic interventions allows both confirmation of the presence of PAH and elucidation of its etiology. Clarification of etiology is necessary to ensure that the proper therapeutic interventions are implemented. A diagnostic algorithm that is accepted among experienced centers (Fig 1) can guide the evaluation of PAH.

Summary of Recommendations

  • Genetic testing and professional genetic counseling should be offered to relatives of patients with FPAH. Level of evidence: expert opinion; benefit: intermediate; grade of recommendation: E/A.

  • 2.

    Patients with IPAH should be advised about the availability of genetic testing and counseling for their relatives. Level of evidence: expert opinion; benefit: intermediate; grade of recommendation: E/A.

  • 3.

    In patients with a suspicion of PAH, ECG should be performed to screen for a spectrum of cardiac

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