Feasibility Trial for a Right Ventricular Failure Platform Trial

Inclusion criteria

• Age ≥ 18 years.
• Able to provide informed consent.
• Able to comply with all study procedures.
• History of RV dysfunction or RHF secondary to any of:
• a. Group 1 PH, pulmonary arterial hypertension b. Group 2 PH, left heart disease with normal left ventricular ejection fraction (LVEF) \> 50% and a previous RHC demonstrating combined pre and post-capillary PH, defined as: i. mPAP \>20 mmHg ii. PAWP \> 15 mmHg iii. PVR\> 2 WU c. Group 3 PH d. Group 4 PH, chronic thromboembolic PH that is either persistent after pulmonary endarterectomy or inoperable due to distal disease.
• Symptomatic with current NYHA Functional Class II-IV
• Biomarker and 2D echocardiogram evidence of RV dysfunction within 3 months:
• NT-proBNP \>300 ng/L and qualitative evidence of at least 'mild' RV dysfunction on echocardiography OR NT-proBNP\<300 ng/L and qualitative evidence of at least moderate RV dysfunction and/or dilatation on 2D echocardiogram AND
• A quantitative 2D echocardiogram with evidence of RV dysfunction defined as having both of the following:
• i. TAPSE ≤18 mm ii. RV dilatation (RV diameter \> 42 mm at the base).
• Receiving loop diuretics or mineralocorticoid receptor antagonists for at least 4 weeks.
• Access to an iOS or android smart phone or tablet.

Exclusion criteria

• Estimated glomerular filtration rate (eGFR) \<30 ml/min.
• LVEF \< 50%
• Normal RV size and function
• Severe aortic or mitral valvular disease
• Moderate or severe hepatic dysfunction (Child-Pugh Class B or C)
• Participants requiring augmentation of diuretics or otherwise not meeting definition for clinical stability
• Pregnancy or lactation
• Unable to provide consent and comply with follow-up visits
• Listed for lung, heart or heart/lung transplantation
• Myocardial infarction or acute coronary syndrome within 90 days of screening
• Enrolled in another interventional trial
• Planned cardiac or thoracic surgical intervention in the next 6 months.
• Known hypersensitivity to empagliflozin or ranolazine.
• Concurrent treatment with:
• strong inhibitors of Cytochrome P450 3A4 (CYP 3A4), (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, nelfinavir, ritonavir, indinavir, saquinavir and grapefruit juice)
• class IA antiarrhythmics (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmics (e.g., sotalol, ibutilide, amiodarone, dronedarone)
• inducers of CYP 3A4 (e.g., rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John's wort)
• Congenital long QT syndrome or a QTc interval \>500 ms