See 2013 HF guideline.9 Participation in investigational studies is also appropriate for stage C, NYHA class II and III HF. ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor-blocker; ARNI, angiotensin receptor-neprilysin inhibitor; BP, blood pressure; bpm, beats per minute; C/I, contraindication; COR, Class of Recommendation; CrCl, creatinine clearance; CRT-D, cardiac resynchronization therapy device; Dx, diagnosis; GDMT, guideline-directed management and therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; ICD, implantable cardioverter-defibrillator; ISDN/HYD, isosorbide dinitrate hydral-nitrates; K+, potassium; LBBB, left bundle-branch block; LVAD, left ventricular assist device; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NSR, normal sinus rhythm; and NYHA, New York Heart Association. 2017 ACC/AHA/HFSA Heart Failure Focused Update CLINICAL STATEMENTS AND GUIDELINES IIb B-R In appropriately selected patients with HFpEF (with EF 45%, elevated BNP levels or HF admission within 1 year, estimated glomerular filtration rate >30 mL/min, creatinine <2.5 mg/dL, potassium <5.0 mEq/L), aldosterone receptor antagonists might be considered to decrease NEW: Current recommendation reflects new RCT data. See Online Data Supplement C. Mechanistic studies have suggested that mineralocorticoid receptor antagonists can improve measures of diastolic function in patients with HFpEF, possibly by a similar effect on remodeling.83,168 The TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial166 investigated the effects of spironolactone on a combined endpoint of death, aborted cardiac death, and HF hospitalization in patients with HFpEF. A small reduction (HR=0.89) in this composite endpoint did not reach statistical significance, although HF hospitalization was reduced (HR=0.83); known side effects of hyperkalemia and rising creatinine were seen more commonly in the treatment group.166 An unusual amount of regional variation was seen in this trial, prompting a post-hoc analysis167 that showed that rates of the primary endpoint were 4-fold lower in Russia/Georgia than in North America and South America (the Americas). 