Pulmonary Arterial Hypertension
Section snippets
Classification and Epidemiology
The term primary pulmonary hypertension (PPH) was first coined in 1951 after Dresdale et al1 reported data on 39 patients with unexplained pulmonary hypertension. A sudden rise in incidence of pulmonary hypertension (PH) in Europe attributed to the diet pill, aminorex, prompted the World Health Organization (WHO) in 1973 to propose a classification scheme for PH, consisting of 2 categories: PPH or secondary PH. Since this time, the classification of PH has evolved, with the first major revision
Pathophysiology
The pulmonary vasculature is a low-pressure system with approximately one-tenth the resistance to flow observed in the systemic circulation. PH refers to a hemodynamic state in which the pulmonary artery pressure is abnormally high and is clinically defined as an mPAP greater than 25 mm Hg. PAH also requires that the pulmonary capillary wedge pressure (PCWP) be normal. A “multiple-hit” theory, similar to that of cancer and atherosclerosis development, has been generated to explain the natural
Symptoms
A detailed history, careful physical examination, and a high index of suspicion can be invaluable in the diagnosis of PAH. In the National Institutes of Health (NIH) registry, the average time from symptom onset to diagnosis was 2 years,28 and this delay may be attributed to the rarity of the disease, patients' reluctance to endorse the severity of their symptoms, and physicians' reluctance to assign a diagnosis with grave implications. Unfortunately, the time from onset of symptoms to
Diagnostic Evaluation
If PAH is suspected by the patient's symptoms, physical examination, or risk factors, a structured and methodical evaluation is recommended. The diagnostic algorithm is summarized in Fig 1.
Treatment
Treatment of PAH has evolved considerably over the past decade due in part to advances in knowledge of the disease and the availability of agents that target known derangements in the pathobiologic processes. Treatment algorithms have been formulated by the American College of Chest Physicians, the European Society of Cardiology/and European Respiratory Society, the ACCF/AHA, and a panel of experts who convened at the fourth World Symposium on PH held in Dana Point, California in 2008.64, 77, 78
Prognosis
The natural history of PAH was well documented by the NIH registry, where 194 patients with IPAH were enrolled in a multicenter observational study from 1981 through 1985.112 The median survival was 2.8 years with 1-, 3-, and 5-year survival rates of 68%, 48%, and 34%, respectively. Studies from other countries, including Japan, India, and Mexico, have shown similar results, with a median survival estimate of 2-3 years. More recently, 2 large registries have shed light on the prognosis of
Pulmonary Hypertension in Left-Sided Heart Disease
PH resulting from elevated left-sided pressures is much more frequently encountered than PAH and likely represents the most common form of disease in clinical settings. Any disease state that elevates left-sided pressures can result in secondary elevations in pulmonary artery pressure, such as congestive heart failure with or without systolic dysfunction and valvular heart disease. Chronic left ventricular dysfunction with elevated PCWP leads to secondary increases in pulmonary vascular
Pulmonary Hypertension with Lung Disease
Hypoxemic pulmonary diseases that result in pulmonary hypertension are classified as WHO group 3. Chronic obstructive pulmonary disease, interstitial lung disease, sleep-disordered breathing, and obesity hypoventilation syndrome are common examples. Restrictive ventilatory defects caused by thoracic cage deformities or neuromuscular diseases, and chronic hypoventilation syndromes, such as high altitude exposure, can also cause PH.
Hypoxemic lung disease involves alveolar hypoxia, acidemia, and
Chronic Thromboembolic Pulmonary Hypertension
Chronic thromboembolic pulmonary hypertension (CTEPH), classified as WHO group 4 pulmonary hypertension, is frequently underdiagnosed. Among patients presenting with acute pulmonary embolism (PE) but no other history of venous thromboembolism, the estimated cumulative incidence of CTEPH is 1% after 6 months, 3.1% after 1 year, and 3.8% after 2 years.132 Even if patients do not relate a history of deep vein thrombosis or PE, CTEPH may be present. In 1 series, 63% of patients with CTEPH had no
Future Directions
Although our understanding of the pathogenesis of and treatment for PAH has advanced substantially over the recent decades, we still have a long way to go. The basic understanding of the pathobiology often relies on animal models that do not accurately reflect human disease. In hopes of advancing translational science, the Pulmonary Hypertension Breakthrough Initiative is a project that harvests explanted lungs of PAH patients at the time of lung transplantation. Making human tissue available
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Vallerie McLaughlin has received grant/research support from Actelion, Novartis, United Therapeutics; is consultant to Actelion, BMS, Mondo Biotech, Gilead, United Therapeutics; serves on the Speaker's Bureau for Actelion, Gilead, United Therapeutics. Melinda Davis and William Cornwell have no conflicts of interest to disclose.