Right heart failure medical therapy

Overview
Treatment of the underlying cause of right heart failure is the mainstay of therapy.

General Measures

 * Diuretics
 * Nitrates
 * Oxygen in some conditions

Pulmonary Embolism
In pulmonary embolism, thrombolysis (enzymatic dissolution of the blood clot) is advocated if there is dysfunction of the right ventricle.

Chronic Obstructive Pulmonary Disease
In Chronic Obstructive Pulmonary Disease (COPD), long-term oxygen therapy may improve cor pulmonale.

Pulmonary Arterial Hypertension
Treatment is determined by whether the PH is arterial, venous, hypoxic, thromboembolic, or miscellaneous. Since pulmonary venous hypertension is synonymous with congestive heart failure, the treatment is to optimize left ventricular function by the use of diuretics, beta blockers, ACE inhibitors, etc., or to repair/replace the mitral valve or aortic valve.

In PAH, lifestyle changes, digoxin, diuretics, oral anticoagulants, and oxygen therapy are considered conventional therapy, but have never been proven to be beneficial in a randomized, prospective manner.

High dose calcium channel blockers are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter. Unfortunately, calcium channel blockers have been largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality.

Vasoactive substances
Three major pathways are involved in the abnormal proliferation and contraction of the smooth-muscle cells of the pulmonary artery in patients with pulmonary arterial hypertension. These pathways correspond to important therapeutic targets in this condition and play a role in determining which of three classes of drugs — endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclin derivatives — will be used.

Prostaglandins
Prostacyclin (prostaglandin I2) is commonly considered the most effective treatment for PAH. Epoprostenol (synthetic prostacyclin, marketed as Flolan®) is given via continuous infusion that requires a semi-permanent central venous catheter. This delivery system can cause sepsis and thrombosis. Flolan® is unstable, and therefore has to be kept on ice during administration. Since it has a half-life of 3 to 5 minutes, the infusion has to be continuous (24/7), and interruption can be fatal. Other prostanoids have therefore been developed. Treprostinil (Remodulin®) can be given intravenously or subcutaneously, but the subcutaneous form can be very painful. Iloprost (Ilomedin®) is also used in Europe intravenously and has a longer half life. Iloprost (marketed as Ventavis®) is the only inhaled form of prostacyclin approved for use in the US and Europe. This form of administration has the advantage of selective deposition in the lungs with less systemic side effects.

Endothelin receptor antagonists
The dual (ETA and ETB) endothelin receptor antagonist bosentan (marketed as Tracleer®) was approved in 2001. Approved in June 2007, ambrisentan is marketed as Letairis® in U.S. by Gilead Sciences. Sitaxsentan has not been approved for marketing by the US FDA. A new trial is being planned to address FDA's concerns.

Phosphodiesterase type 5 inhibitors
Sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5), was approved for the treatment of PAH in 2005. It is marketed for PAH as Revatio®. Tadalafil (currently marketed as Cialis® for erectile dysfunction) is currently is Phase III clinical trials.

Other agents
Vasoactive intestinal peptide by inhalation should enter clinical trials for PAH in 2007. PRX-08066 is a serotonin antagonist currently being developed for hypoxic pulmonary hypertension.