Mineralocorticoid Receptor Antagonists (MRA) in Heart Failure (HF) and Loop Diuretic Resistance

The incidence and prevalence of heart failure (HF) is rising with more than 5 million Americans suffering from this syndrome. Hospitalization rates for acute decompensated heart failure (ADHF) are also remarkably high, exceeding more than 1 million admissions per year. Congestion is the main cause of hospitalization for ADHF. Loop diuretics as the main therapy for decongestion, often are not adequate since many patients with ADHF develop "loop diuretic resistance". These patients will require hospitalization for intravenous diuretic or other advanced decongestion therapies. Thus, novel decongestion therapies are needed to decrease hospital admission rates and subsequent complications of multiple hospitalizations. Hyperaldosteronism, not only is a pivotal pathogenic factor in HF, but also contributes to loop diuretic resistance. Attempts for normalization of circulatory aldosterone with mineralocorticoid receptor antagonists (MRAs), mainly spironolactone, have shown to decrease mortality in HF patients with reduced left ventricular ejection fraction (LVEF). Moreover, MRAs significantly decrease the rate of rehospitalization in both HF with preserved and reduced LVEF. The dose of spironolactone in these trials is 25mg daily. However, this dose does not increase natriuresis (urinary sodium excretion). Natriuresis is achieved with higher doses of MRAs. Therefore, the primary aim of this study is to examine the efficacy of 7-day 100mg daily of spironolactone on weight loss and resolution of signs and symptoms of congestion in patients aged 60 years with ADHF and loop diuretic resistance.

Inclusion criteria

• History of heart failure with either reduced or preserved ejection fraction for 3 months
• Patients with New York Heart Association (NYHA) class II- IV heart failure symptoms, with at least one worsening symptom (Dyspnea on exertion, shortness of breath, orthopnea, early satiety) and one sign of congestion (pulmonary rales, elevated jugular venous pressure10cmHg, peripheral edema and ascites)
• Decision by primary cardiologist or heart failure (HF) specialist to increase the home diuretic dose
• Stable treatment with beta-blockers for 1 month unless contraindicated (i.e. intolerance, bradycardia) as specified by primary cardiologist/HF provider
• Stable treatment with angiotensin converting enzyme-1 (ACE-1) or angiotensin receptor blocker (ARB) for 1 month
• Spironolactone dose 25mg or eplerenone 50mg per day
• Daily furosemide or furosemide equivalent dose of 80mg or greater
• Serum potassium concentration 4.5 mmol/L or 5.0 mmol/L if on potassium supplements
• Estimated Glomerular Filtration Rate (eGFR) by Modification of Diet in Renal Disease (MDRD) equation 40 ml/min/1.73

Exclusion criteria

• Inability to complete informed consent form
• Allergy or intolerance to spironolactone
• Systolic blood pressure <100 mmHg
• Patient in need of hospitalization per cardiologist decision
• Current inotrope dependency
• Current mechanical circulatory support
• Acute coronary syndromes or unstable angina within the past 4 weeks
• History of cardiac transplant
• Obstructive cardiac valvular disease
• Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy
• Significant ventricular arrhythmia necessitating defibrillator therapy within the past 14 days
• Atrioventricular conduction abnormality greater than first-degree block
• Primary liver disease resulted in cirrhosis or abnormal liver function tests (transaminases and alkaline phosphatase levels 3 times the upper limit of normal
• Acute malignancy
• Active infection requiring antimicrobial treatment (Suppression antimicrobial for chronic infections are exempt)