Observational StudyFeasibility Trial for a Right Ventricular Failure Platform Trial

Inclusion Criteria:

1. Age ≥ 18 years.
2. Able to provide informed consent.
3. Able to comply with all study procedures.
4. 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.
5. Symptomatic with current NYHA Functional Class II-IV
6. Biomarker and 2D echocardiogram evidence of RV dysfunction within 3 months:

1. 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
2. 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).
7. Receiving loop diuretics or mineralocorticoid receptor antagonists for at least 4 weeks.
8. Access to an iOS or android smart phone or tablet.

Exclusion Criteria:

1. Estimated glomerular filtration rate (eGFR) <30 ml/min.
2. LVEF < 50%
3. Normal RV size and function
4. Severe aortic or mitral valvular disease
5. Moderate or severe hepatic dysfunction (Child-Pugh Class B or C)
6. Participants requiring augmentation of diuretics or otherwise not meeting definition for clinical stability
7. Pregnancy or lactation
8. Unable to provide consent and comply with follow-up visits
9. Listed for lung, heart or heart/lung transplantation
10. Myocardial infarction or acute coronary syndrome within 90 days of screening
11. Enrolled in another interventional trial
12. Planned cardiac or thoracic surgical intervention in the next 6 months.
13. Known hypersensitivity to empagliflozin or ranolazine.
14. 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)

15. Congenital long QT syndrome or a QTc interval >500 ms