Ranolazine and Pulmonary Hypertension
Condition: Angina; Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Angina Pectoris
Intervention: Ranolazine
Intervention description: ranolazine 1000 mg PO BID for 3 months
Intervention MeSH terms: Ranolazine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Angina; Right Ventricular Ischemia; Pulmonary Arterial Hypertension; Pulmonary Hypertension

Summary:

      The purpose of the study is to determine if the medication, ranolazine (study drug), can help
      improve blood flow to your heart, increase your exercise capacity and improve your quality of
      life (QOL). For this study, you will be asked to perform several tests in order to determine
      if your heart function, exercise capacity, chest pain and QOL have improved after 3 months of
      treatment with ranolazine. Ranolazine is approved by the U.S. Food and Drug Administration
      (FDA) for the treatment of angina.
    

Eligibility criteria:

        Inclusion criteria:

          1. World Health Organization (WHO) Group 1 PAH, defined as a pulmonary hypertension with
             mean pulmonary artery pressure > 25 mmHg, pulmonary capillary wedge pressure < 15
             mmHg, and pulmonary vascular resistance > 3 Wood units.

          2. Right ventricular dysfunction, defined as RV fractional area change < 32% or RV
             tricuspid annular plane systolic excursion (TAPSE) < 15 mm.

          3. Symptoms of angina or angina equivalent (exertional dyspnea, exertional epigastric
             pain, exertional nausea).

          4. New York Heart Association functional class II or III symptoms.

          5. Stable doses of pulmonary vasodilators (prostacyclins, endothelin receptor
             antagonists, phosphodiesterase inhibitors), with no new therapy initiation or dose
             escalation > 50% in the 4 weeks prior to randomization.

          6. Age 18-80 years.

        Exclusion criteria:

          1. Acute coronary syndrome or coronary revascularization within the prior 3 months.

          2. Patients with unstable angina.

          3. Patients with Class IV congestive heart failure.

          4. Planned revascularization, pacemaker or defibrillator placement during the study
             period.

          5. Changes in antianginal medical therapy likely to occur during the study period.

          6. Corrected QT interval measurement >500 ms.

          7. Patients with pre-existing QT prolongation (including congenital long QT syndrome) or
             receiving other QT prolonging drugs (including Class Ia-e.g., quinidine, Class
             III-e.g., dofetilide, sotalol, antiarrhythmics; antipsychotics (e.g., thioridazine,
             ziprasidone), or known history of complex ventricular arrhythmias requiring
             antiarrhythmic medications or ICD implantation.

          8. Patients with known history of hepatic dysfunction.

          9. Current use of strong CYP3A inhibitors, including ketoconazole, itraconazole,
             clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir and
             diltizaem.

         10. Patients with pacemakers, cochlear implants, aneurysm clips, who have worked with
             metal.

         11. Patients with metallic hardware, implants, or prostheses will consult with the
             radiologist/cardiologist prior to the study.

         12. Patients with severe or end stage renal disease (an estimated GFR < 30 mL/min/1.73 m).

         13. Women who are pregnant or lactating

         14. Any contraindications for the use of a right heart catheter including, but not limited
             to:

               -  Pulmonic or tricuspid valve stenosis

               -  Prosthetic pulmonic or tricuspid valve

               -  Right atrial or ventricular masses

               -  Previous pneumonectomy

               -  Risk of severe arrhythmias, including left bundle branch block (LBBB)

         15. Subjects unable to perform cardiopulmonary exercise testing will be excluded (i.e.
             extensive musculoskeletal disease)