Pulmonary Hypertension / Pulmonary Vascular Disease: 2012 Update (Review, AJRCCM)

Pulmonary Hypertension And Pulmonary Vascular Disease Review 2012
(More PulmCCM Topic Updates)

This document is periodically updated as new research findings are published. The published date reflects the most current update. Please suggest articles for inclusion in future versions of this document in the comments or by e-mail.

Chronic Thromboembolic Pulmonary Hypertension Update

The mechanism by which  chronic thromboembolic pulmonary hypertension (CTEPH) develops–incomplete resolution of pulmonary embolism with subsequent endothelial proliferation around residual thrombi, causing pulmonary arterial hypertension–remains unclear. It’s also unclear why some patients also develop proliferative disease in the small pulmonary vessels, with remodeling of the pulmonary vascular bed and progression of pulmonary arterial hypertension (PAH).

Haoming et al hypothesized that viral infection may play a role in this process, after finding that T cells’ virus killing ability is compromised in patients with CTEPH.

Pulmonary thromboendarterectomy in appropriately selected patients is life-saving and curative, and remains the standard of care when feasible. Success is dependent on surgical accessibility of thrombi (i.e., in the main, lobar, or segmental pulmonary arteries) and the degree to which this (removable) “clot burden” is causing whatever pulmonary vascular resistance is present, as opposed to to any more (non-removable) distal clot/vasculopathy.

Outcomes after surgery for CTEPH have steadily improved, and perioperative mortality has steadily declined: from 7% in the 1990s to ~4% in the late 2000s, and ~1% among lower-risk patients. Many of those that survive the surgery can expect to be cured, and long-term mortality from CTEPH after pulmonary thromboendarterectomy is probably about 5%. Much of this data comes from international registries; outcomes are at least as good (or better) at the primary U.S. center for pulmonary thromboendarterectomy at U. of California at San Diego.

Many patients are either not candidates for thromboendarterectomy, or continue to have pulmonary hypertension after surgery. Vasodilator drug therapies can delay progression of pulmonary hypertension in these patients, and/or can serve as a bridge therapy until surgery. Residual pulmonary hypertension after thromboendarterectomy caused dyspnea but did not reduce survival in one study with 5 year followup.

Sickle Cell Disease and Pulmonary Hypertension

Dessap et al showed that pulmonary artery thrombosis commonly occurs during acute chest syndrome in patients with sickle cell disease, but it is unclear whether the thrombosis represents a cause or an effect. In addition, they found pulmonary hypertension occurring during acute chest syndrome is a poor prognostic sign.

Although previous reports suggested that pulmonary hypertension is extremely common in patients with sickle cell disease (some studies suggesting a ~40% prevalence), a more rigorous study enrolling French patients with universal right heart catheterization suggested that the prevalence of PH is much lower than previously believed–only 6%–and that echocardiography is unreliable in this population for diagnosing PH.

Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis

Ley et al reported that the vast majority of patients with idiopathic pulmonary fibrosis (IPF) develop pulmonary hypertension during the course of their illness: 86% at the time of lung transplantation, compared to 39% at initial measurement. The development of pulmonary hypertension is a negative prognostic sign for people with IPF: one-year mortality of 28% in patients with PH versus 5.5% in those without PH, in their cohort. Treatment is lung transplantation for selected patients. Unfortunately, as the BUILD trials showed, vasodilator therapy (bosentan) appears ineffective and perhaps harmful in patients with PH due to IPF.

 Pulmonary Hypertension in Sarcoidosis

Baughman et al estimated that the prevalence of pulmonary hypertension in patients with sarcoidosis is probably around 10% overall, but the prevalence  of pulmonary hypertension may be greater than 50% in sarcoidosis patients with dyspnea or who are awaiting lung transplants.  It can be difficult or impossible to determine the reason for PH in patients with sarcoidosis–it can be from interstitial lung disease, compression of the pulmonary arteries by enlarged lymph nodes, lesions in the pulmonary vascular bed, and/or diastolic dysfunction of the left ventricle. Patients with sarcoidosis and PH who did not have diastolic dysfunction had a worse prognosis in their cohort.

There is limited evidence (Barnett et al’s Chest 2009 observational series at two centers) suggesting that some patients with sarcoidosis and PH do benefit from vasodilator therapy, with improved quality of life and reduced dyspnea. It’s not clear how best to identify the patients with sarcoidosis and PH who will respond to vasodilator therapy.

(More PulmCCM Topic Updates)

With gratitude to:

Hassoun PM, Adnot S. Update in Pulmonary Vascular Diseases 2011. AJRCCM 2012;185:1177-1182.

Fedullo P. Chronic thromboembolic pulmonary hypertension. Concise clinical review, AJRCCM 2011.

Piazza G, Goldhaber SZ. Chronic thromboembolic pulmonary hypertension. NEJM 2011;364:351-360.