Comparing Nebivolol and Spironolactone in the Treatment of Heart
Failure with a Preserved Ejection Fraction
INTRODUCTION
“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
Alison Fenter, PA-S & Caroline Joseph,
PA-S
James Madison University, Harrisonburg,
RESULTS
VA
DISCUSSION
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)
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
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.
METHODS
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. NTproBNP (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
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)
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
1.
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.
2.
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.
3.
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.