The purpose of this study is to evaluate the safety, tolerability and mechanistic effects of spironolactone, an aldosterone receptor antagonist, on sympathetic nervous system activity and right heart function and remodeling in patients with chronic right heart failure.

This study is a phase 4, single center, randomized, double blind, placebo-controlled trial evaluating the safety, tolerability and mechanistic effects of spironolactone, an aldosterone antagonist, on neurohormonal activity and remodeling in patients with chronic right heart failure (RHF).

RHF is one of the most important predictors of prognosis in many cardiac disease states including pulmonary hypertension (PH), and left heart failure. Sympathetic nervous system activation plays an important role in the development and progression of heart failure. It remains to be determined whether there is a role for neurohormonal therapy in chronic right HF, but evidence points to the role of sympathetic nervous system stimulation and activation of the renin-angiotensin and aldosterone system as a contributor to progressive right heart failure.

The study will determine if treatment with spironolactone is associated with reduction in right ventricular wall stress. In addition, the study aims to evaluate the effects of spironolactone on cardiac sympathetic activity assessed by HED(11 C-hydroxy-ephedrine) retention on PET(positron emission tomography) imaging, and global autonomic function assessed by heart rate variability.

Approximately 30 patients with RHF will be randomized to receive either spironolactone daily or placebo.

Inclusion Criteria:

• Provide a personally signed and dated inform consent form.

• Male or female ≥ 18 years.

• Able to comply with all study procedures.

• History of right heart failure (RHF) secondary to either:

  i) WHO, group 1 pulmonary arterial hypertension PAH OR ii) WHO group II PH with normal LV systolic function OR iii) WHO group III or IV PH OR iv) primary RV cardiomyopathy.

• Current NYHA II-IV

• RV dysfunction as measured by 2D echocardiogram:

  i)defined as a tricuspid annular plane systolic excursion (TAPSE) <16 mm ii) and /or a two dimensional fractional area change <35% on screening echo plus

• NT-proBNP>400 pg/ml

• Chronic use of diuretics

• Clinical stability: defined as no need for increased diuretics, hospitalization or emergency room visit 3 months prior to enrollment

Exclusion Criteria:

• Patients on chronic MRA therapy or other potassium sparing diuretics.
• Baseline serum potassium>5 ummol/l.
• Estimated glomerular filtration rate <30 ml/min.
• LV ejection fraction <45%,
• Moderate or severe LV diastolic function,
• Moderate or severe aortic or valvular disease.
• Patients requiring augmentation of diuretics or otherwise not meeting definition for clinical stability.
• Severe Liver Failure (Child-Pugh Class C)
• Claustrophobia or inability lie still in a supine position
• Patients with contraindications to either PET or CMR imaging
• Pregnancy or lactation.
• Unable to provide consent and comply with follow up visits.

There is no plan to share individual participant data with researchers outside of Dr. Mielniczuk's research team.

Patients will be blinded to study treatment for the duration of the study. Clinicians will also be blinded to study drug assignment. Evaluation of all study results will be done blinded to treatment randomization. Because of the double-blind design, safety laboratory tests, and monitoring of potential side effects will be performed for each participant for the duration of the trial, regardless of the treatment arm.