From the Guidelines
Treatment for pulmonary arterial hypertension (PAH) with marked cardiomegaly should initially include monotherapy with a phosphodiesterase-5 inhibitor, such as sildenafil 20mg three times daily or tadalafil 40mg once daily, or an endothelin receptor antagonist, such as ambrisentan 5-10mg daily, bosentan 62.5-125mg twice daily, or macitentan 10mg daily, as recommended by the Chest guideline and expert panel report 1. The choice of initial therapy should be based on disease severity and patient-specific factors.
- Phosphodiesterase-5 inhibitors, such as sildenafil and tadalafil, have been shown to improve 6-minute walk distance (6MWD) and delay time to clinical worsening in patients with PAH 1.
- Endothelin receptor antagonists, such as ambrisentan, bosentan, and macitentan, have also been shown to improve 6MWD and delay time to clinical worsening in patients with PAH 1. In addition to PAH-specific medications, diuretics like furosemide 20-80mg daily or spironolactone 25-100mg daily are essential to manage fluid overload contributing to cardiomegaly. Oxygen therapy should be provided to maintain oxygen saturation above 90%. The treatment approach should be guided by functional class assessment, with more advanced disease requiring more aggressive combination therapy. In patients who remain symptomatic on stable and appropriate doses of an endothelin receptor antagonist (ERA) or a phosphodiesterase-5 inhibitor (PDE5I), the addition of inhaled treprostinil may be considered to improve 6MWD, as suggested by the updated Chest guideline and expert panel report 1. Regular echocardiographic monitoring is necessary to assess treatment response and cardiac remodeling. In severe cases unresponsive to medical therapy, evaluation for lung transplantation may be necessary. Lifestyle modifications, including sodium restriction, moderate exercise as tolerated, and avoidance of pregnancy, are also important components of management.
From the FDA Drug Label
Treprostinil is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to -pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%)
The treatment for PAH with marked cardiomegaly is treprostinil (SQ), as it is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise.
- The initial dose for patients new to prostacyclin infusion therapy is 1.25 ng/kg/min.
- Dosage adjustments should be made to establish a dose at which PAH symptoms are improved, while minimizing excessive pharmacologic effects of treprostinil injection 2. Key considerations for treatment include:
- Avoiding abrupt cessation of infusion
- Restarting a treprostinil injection infusion within a few hours after an interruption can be done using the same dose rate
- Interruptions for longer periods may require the dose of treprostinil injection to be re-titrated 2.
From the Research
Treatment of PAH with Marked Cardiomegaly
- The treatment of pulmonary arterial hypertension (PAH) with marked cardiomegaly typically involves a combination of medications that target multiple biological pathways, such as the nitric oxide-cyclic guanosine monophosphate and endothelin pathways 3.
- Current guidelines recommend the use of two oral medications, including a phosphodiesterase type-5 inhibitor and an endothelin receptor antagonist, for low- and intermediate-risk patients 4.
- For patients with PAH and marked cardiomegaly, triple therapy including a parenteral prostacyclin may be considered in those at high or intermediate-high risk 4.
- The management of PAH is best performed in multidisciplinary teams located in experienced centers, and other core pillars of PAH management include supportive and adjunctive treatments such as oxygen, diuretics, rehabilitation, and anticoagulation in certain patients 4.
Medications Used in Treatment
- Endothelin receptor antagonists, such as bosentan and ambrisentan, are commonly used in the treatment of PAH 3, 5.
- Phosphodiesterase type-5 inhibitors, such as sildenafil and tadalafil, are also used to treat PAH 3, 4.
- Prostacyclin analogs, such as epoprostenol and treprostinil, are used to treat PAH, particularly in patients with severe disease 3, 6.
- Soluble guanylate cyclase stimulators, such as riociguat, are used to treat PAH and chronic thromboembolic pulmonary hypertension (CTEPH) 7, 6.