The Evolving Management and Treatment Options for Patients with Pulmonary Hypertension: Current Evidence and Challenges

Abstract

Pulmonary hypertension may develop as a disease process specific to pulmonary arteries with no identifiable cause or may occur in relation to other cardiopulmonary and systemic illnesses. The World Health Organization (WHO) classifies pulmonary hypertensive diseases on the basis of primary mechanisms causing increased pulmonary vascular resistance. Effective management of pulmonary hypertension begins with accurately diagnosing and classifying the disease in order to determine appropriate treatment. Pulmonary arterial hypertension (PAH) is a particularly challenging form of pulmonary hypertension as it involves a progressive, hyperproliferative arterial process that leads to right heart failure and death if untreated. Over the last two decades, our understanding of the pathobiology and genetics behind PAH has evolved and led to the development of several targeted disease modifiers that ameliorate hemodynamics and quality of life. Effective risk management strategies and more aggressive treatment protocols have also allowed better outcomes for patients with PAH. For those patients who experience progressive PAH with medical therapy, lung transplantation remains a life-saving option. More recent work has been directed at developing effective treatment strategies for other forms of pulmonary hypertension, such as chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary hypertension due to other lung or heart diseases. The discovery of new disease pathways and modifiers affecting the pulmonary circulation is an ongoing area of intense investigation.

Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension

“…New treatments directly targeting the crucial pathological determinants of RV failure and arrhythmogenesis are still emerging. Moreover, the discovery of novel disease pathways and modifiers affecting the pulmonary circulation requires intense investigation [ 185 ].…”

Classification, Diagnosis, and Medical Treatment of Pulmonary Hypertension

“…Two tyrosine kinase inhibitors, imatinib, and sorafenib have received significant attention as adjunct therapy in patients resistant to more traditional drug combinations targeting the nitric oxide, endothelin, and prostacyclin pathways. The IMPRES (Imatinib in Pulmonary Arterial Hypertension, a Randomized, Efficacy Study) trial demonstrated significant improvement in 6-minute walking distance and PVR in patients receiving two or traditional PAH therapies [55]. Meanwhile, sorafenib has been connected to improvements in functional class and mPAP and is being further investigated for refractory PAH [55].…”

“…The IMPRES (Imatinib in Pulmonary Arterial Hypertension, a Randomized, Efficacy Study) trial demonstrated significant improvement in 6-minute walking distance and PVR in patients receiving two or traditional PAH therapies [55]. Meanwhile, sorafenib has been connected to improvements in functional class and mPAP and is being further investigated for refractory PAH [55].…”

“…Rodatristat ethyl, which inhibits tryptophan hydroxylase and blocks the synthesis of serotonin from tryptophan, is also under investigation. It is believed that excessive serotonin could contribute to vasoconstriction and vascular remodeling seen in PAH [55]. As the first dedicated hemodynamic study comparing two drugs versus one alone, the A DUE trial (Macitentan/Tadalafil Fixed-Dose Combination in Pulmonary Arterial Hypertension) showed that use of a combination pill containing fixed doses of macitentan and tadalafil led to a two-fold greater reduction in PVR compared to either drug alone.…”

Pulmonary Hypertension in Women

“…1 Pulmonary hypertension was first classified in 1973 at the 1st World Symposium on Pulmonary Hypertension, and since then the classification system has been revised multiple times. 2 Recently, the definition of PH was expanded to include a mean pulmonary artery pressure (mPAP) > 20 mm Hg on supine right heart catheterization (RHC) to aid in early detection of disease. 1,3 PH is divided into five different groups, where Group 1 (those with pulmonary arterial hypertension, or PAH) is known to predominantly affect women.…”