Complex Pathophysiology of Pulmonary Hypertension Associated with Systemic Sclerosis: Potential Unfavorable Effects of Vasodilators

Therapeutic advance by pulmonary vasodilators has provided huge impacts on prognosis in patients with pulmonary arterial hypertension (PAH), but outcomes of systemic sclerosis (SSc)-associated PAH still remain unsatisfactory. One of the major reasons is a series of potential unfavorable effects triggered by pulmonary vasodilators, which result from the complex pathophysiology of SSc-PAH. We herein present and discuss five representative conditions potentially induced by pulmonary vasodilators, including (i) emergence of latent pulmonary veno-occlusive disease, (ii) emergence of latent left-heart disease, (iii) worsening of pulmonary gas change in the presence of interstitial lung disease, (iv) ischemic limb gangrene by stealing of blood flow, and (v) uncontrolled hemorrhage from gastrointestinal telangiectasia. The former three conditions are common causes for worsening of dyspnea or oxygenation during treatment with pulmonary vasodilators, whereas the latter two are rare, but have significant negative impacts on patients’ quality of life and survival. These unfavorable conditions are pitfalls in clinical practice, and interfere with optimizing therapies in patients with SSc-PAH. Therefore, pre-assessment of pathophysiology of pulmonary hypertension and cautious monitoring during the treatment are necessary to achieve better outcomes in patients with SSc-PAH.