Feasibility 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 diseasewith normal left ventricular ejection fraction (LVEF) > 50% and a previous RHCdemonstrating 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 PHthat is either persistent after pulmonary endarterectomy or inoperable due to distaldisease.

5. Symptomatic with current NYHA Functional Class II-IV

6. Biomarker and 2D echocardiogram evidence of RV dysfunction within 3 months:

7. NT-proBNP >300 ng/L and qualitative evidence of at least 'mild' RV dysfunctionon echocardiography OR NT-proBNP<300 ng/L and qualitative evidence of at leastmoderate RV dysfunction and/or dilatation on 2D echocardiogram AND

8. A quantitative 2D echocardiogram with evidence of RV dysfunction defined ashaving both of the following: i. TAPSE ≤18 mm ii. RV dilatation (RV diameter > 42 mm at the base).

9. Receiving loop diuretics or mineralocorticoid receptor antagonists for at least 4weeks.

10. 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 definitionfor 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 classIII 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