Pulmonary Hypertension: Diagnosis and Management

Abstract

Pulmonary arterial hypertension is a progressive, symptomatic, and ultimately fatal disorder for which substantial advances in treatment have been made during the past decade. Effective management requires timely recognition and accurate diagnosis of the disorder and appropriate selection among therapeutic alternatives. Despite progress in treatment, obstacles remain that impede the achievement of optimal outcomes. The current article provides an overview of the pathobiologic mechanisms of pulmonary arterial hypertension, including genetic substrates and molecular and cellular mechanisms, and describes the clinical manifestations and classification of pulmonary arterial hypertension. The article also reviews established approaches to evaluation and treatment, with emphasis on the appropriate application of calcium channel blockers, prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. In addition, the authors discuss unresolved issues that may complicate patient management, such as the clinical importance of mild or exercise-related pulmonary arterial hypertension, and they identify avenues by which treatment may advance in the future through the use of combination treatment, outcomes assessment, and exploration of alternative pharmacologic strategies. Mayo Clin Proc. 2009;84(2):191-2075-HTT = 5-hydroxytryptamine transporter; BMPR2 = bone morphogenetic protein receptor, type II; FDA = Food and Drug Administration; IPAH = idiopathic pulmonary arterial hypertension; mPAP = mean pulmonary arterial pressure; PAH = pulmonary arterial hypertension; PASP = pulmonary arterial systolic pressure; PCWP = pulmonary capillary wedge pressure; PDE5 = phosphodiesterase 5; PH = pulmonary hypertension; TGF-β β β β β = transforming growth factor β β β β β; WHO = World Health Organization T he diagnosis, management, and pathobiologic mechanisms of pulmonary arterial hypertension (PAH) have been of intense interest during the past decade, in large part because of the development of effective treatments that have enhanced the outcome for patients. In the absence of effective treatments, patients with PAH had a median life expectancy of only 2.8 years. Current approaches to the evaluation and management of PAH and to the understanding of the underlying pathophysiologic mechanisms of this condition have been well outlined in recent reviews.

Support Experienced by Patients Living with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension

“…These patients have to plan for possible hospital visits at the place of stay and maybe even arrange with a physician if an oxygen supply is necessary during the flight, which is not uncommon [25]. Moreover, it is ultimately a matter for each responsible airline captain to give permission to use oxygen during a flight, although a physician can provide information and certificates on request from the airline company.…”

Physicians’ and patients’ expectations of therapies for pulmonary arterial hypertension: where do they meet?

“…For example, some patients may find intravenous therapies too intrusive, even decreasing their quality of life [26]. However, as in the case of patient B, patients should be closely monitored to review their goals and ensure that they are being met [27]. Improvements in these regimens and their monitoring should improve HRQoL for patients.…”

The Effects of a Novel Endothelin Receptor Antagonist, Macitentan, on Right Ventricular Substrate Utilization and Function in a Sugen5416/Hypoxia Rat Model of Severe Pulmonary Artery Hypertension

“…The developmental hemodynamic elevations exhibited in this model are also representative of clinical presentation of PAH (Steele et al, 2010). PAH is diagnosed by the presence of mPAP greater than 25 mmHg in a patient's hemodynamic profile and is commonly the first test for evaluation of the disease (McGoon et al, 2009). SuHx proves to be a relevant model of severe PAH because of the achievement of high persisting pressures, which progress even upon re-exposure to normoxia (TarasevicieneSewart et al, 2001).…”