Alison Fenter, PA-S & Caroline Joseph, PA-S Comparing Nebivolol and Spironolactone in the Treatment of Heart Failure with a Preserved Ejection Fraction Alison Fenter, PA-S & Caroline Joseph, PA-S James Madison University, Harrisonburg, VA INTRODUCTION DISCUSSION RESULTS “Heart Failure with Preserved Ejection Fraction” (HFpEF) – inability to produce a cardiac output sufficient enough to perfuse and oxygenate vital organs and tissues while maintaining adequate and normal filling pressures in the heart. Present if signs and symptoms of heart failure are present, in addition to normal or near-normal left ventricular ejection fraction Left Ventricular Ejection Fraction (LVEF) <45% Left ventricular hypertrophy Left atrial enlargement Left ventricle not dilated Stiff ventricle with impaired relaxation Impaired diastolic filling Signs – pulmonary congestion (edema, crackles), elevated jugular venous pressure, hepatomegaly, ascites, displaced PMI (point of maximal impulse) Symptoms – dyspnea, orthopnea, paroxysmal nocturnal dyspnea , cough, peripheral edema (ankle swelling), fatigue, reduced exercise performance Study 1 Improvement in diastolic dysfunction as seen by a decreased in the E/e’ ratio in the spironolactone group with an increase in the placebo group. ( P < 0.001) No significant difference between study groups in peak VO2. Decrease in 6-minute walking distance for the spironolactone group. Improvement neuroendocrine activation, as seen by a decrease in NT-proBNP levels from base line. Study 2 Improvement in diastolic dysfunction, suggested by a decrease in the E/e’ ratio (P = 0.0001) No significant difference between study groups in the 6-minute walking distance. Improvement in BNP levels - not statistically significant (P = 0.074) PIIINP improvements in spironolactone compared to placebo (P = 0.035) Study 3 Mild difference between study groups in 6- minute walking distance (P = 0.094) No improvement of peak VO2 in the nebivolol study group and an increase in the placebo study group with (P = 0.63) No statistical difference between treatment groups for NT-ProBNP (P =0.878) OBJECTIVE Clinical Question  In adults with HFpEF (LVEF <45%) who are 40 years of age or older, does spironolactone as compared to nebivolol (selective B1 beta blocker) improve exercise capacity and reduce diastolic dysfunction, therefore improving diastolic filling and thus cardiac output. E/e’ Ratio – early mitral inflow velocity (E) to mitral annular early diastolic velocity (e’). E/A Ratio – early (E) and late (A) inflow to the left ventricle during diastolic filling. Peak VO2 – oxygen uptake; directly relates to peak exercise cardiac output/muscle blood flow; used to quantify exercise capacity. BNP (Brain Natriuretic Peptide) – pro-hormone released in ventricles in response to increased ventricular filling pressures. NT- proBNP (N-terminal pro b-type natriuretic peptide) – biologically inert 76 amino acid; byproduct of cleaved BNP. PIIINP (Procollagen type III amino-terminal peptide) – released during synthesis and deposition of the type III collagen; marker of collagen turnover; may be elevated in presence of left ventricular remodeling, with increased collagen deposition in the extracellular matrix [11] QD – every day, once a day METHODS CONCLUSION Initial search – September, 2016 (PubMed, JMU Library) Mesh Terms – Preserved ejection fraction, spironolactone, nebivolol, diastolic failure, beta blockers, and, mineralcorticoid receptor antagonists Results – 482 articles; removed duplicates = 375 remained; Exclusion criteria – No full-text, not in English, not using human subjects, articles published > 5 years ago Population age < 40, LVEF < 45%, study population with less than class II heart failure, based on the New York Heart Association (NYHA) classification system. Meta-analyses research articles Final – 91 articles left for qualitative synthesis For patients in heart failure with a preserved ejection fraction, the use of spironolactone, as compared to placebo, significantly improves diastolic dysfunction, as measured by E/e’ and E/A ratios as well as peak VO2 and NT-proBNP levels. There was no significant improvement in diastolic dysfunction for patients taking nebivolol as compared to placebo. There was no favorable improvement in exercise capacity with either spironolactone or nebivolol. ACKNOWLEDGEMENTS We would like to thank Dr. Kancler, Mrs. Carolyn Schubert, the JMU writing center, and the JMU communications center for all of the instruction and help we received. We appreciate each and every one of you. REFERENCES Conraads VM. Effects of the long-term administration of Nebivolol on the clinical symptoms, exercise capacity, and left ventricular function of patients with diastolic dysfunction: results of the ELANDD study. European Society of Cardiology . 2011;14:219-225. doi:10.1093/eurjhf/hfr161. Edelmann F, Wachter R. Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients with Heart Failure with Preserved Ejection Fraction . Journal of the American Medical Association (JAMA). 2013;309(8):781-791. doi:10.1001/jama.2013.905. Kurrelmeyer KM. Effects of Spironolactone Treatment in Elderly Women with Heart Failure and Preserved Left Ventricular Ejection Fraction . Journal of Cardiac Failure . 2014;20(8):560-567. doi:10.1016/j.cardfail.2014.05.010.