Sargento L, Satendra M, Longo S, et al.
Clin Cardiol. 2013 Aug 8. doi: 10.1002/clc.22183.

Background

In the treatment of systolic heart failure (HF) with angiotensin-converting enzyme inhibitors, angiotensin receptor II blockers, and spironolactone, left ventricle remodelling can be accompanied by a decrease of natriuretic peptide levels [1-4]. Bèta-blockers have a variable effect [2,5]. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) predict chronic HF prognosis [6].
The decreased stroke volume in patients with left ventricle systolic dysfunction may be compensated for by increased heart rate (HR). Aggressive HR control could however attenuate that response and have negative inotropic effects.
Ivabradine is a selective and specific inhibitor of the sinus node If current. HR lowering with ivabradine improves left ventricle filling by prolonging diastolic time and increasing stroke volume. This study evaluates the short-term (3 months) effect of ivabradine on NT-proBNP in 25 stable outpatients with systolic HF.

Main results

• After 3 months, a significant decrease of NT-proBNP was seen as compared to baseline (median absolute decrease: 964 pg/mL, 44.5% decrease, P=0.002).
• Resting HR was decreased by 10.0+10.4 bpm (P<0.001), corresponding to 12.4+12.5% decrease. There were no significant changes in blood pressure and renal function.
• NYHA class decreased significantly (2.1+0.3 vs. 2.5+0.5 at baseline). 40% improved the NYHA class and 56% had a better patient-reported self-assessment, while 40% experienced no change.
• 88% of patients took bèta-blockers. In a subgroup of patients achieving 50% of the bèta-blocker target dose, baseline HR, final HR and baseline NT-proBNP were not significantly different from those who reached <50% target dose.
• Baseline HR correlated significantly with baseline NT-proBNP (Spearman’s rho: 0.411, P=0.041), as well as the absolute and percent HR decrease (Spearman’s rho: 0.442, P=0.027 and Spearman’s rho: 0.395, P=0.05).
• The absolute and percent HR decrease correlated with the patient-reported self-assessment (Spearman’s rho: 0.451, P=0.024 and rho=0.481, P=0.15). Patients who moved to a lower NYHA class had lower values of the final HR (75.6+9.7 vs. 64.0+8.0, P=0.004).

Conclusion

Outpatients with systolic HF on optimised medical therapy, including ivabradine, and resting HR>70/min showed lower NT-proBNP levels after 3 months, which was related to the decrease in HR. These changes in HR and NT-proBNP were not dependent on the achieved bèta-blocker dose.

References

1. Troughton RW, Richards AM, Yandle TG, et al. The effects of medications on circulating levels of cardiac natriuretic peptides. Ann Med. 2007;39:242–260.
2. Rosenberg J, Gustafsson F, Remme WJ, et al. Effect of betablockade and ACE inhibition on B-type natriuretic peptides in stable patients with systolic heart failure. Cardiovasc Drugs Ther. 2008;22:305–311.
3. White M, Rouleau JL, Afzal R, et al. Effects of enalapril, candersartran or both on neurohormonal activation and LV volumes and function in patients with heart failure not treated with beta-blocker. Ther Adv Cardiovasc Dis. 2009;3:113–121.
4. Berry C, Murphy NF, De Vito G, et al. Effects of aldosterone receptor blockage in patients with mild-moderate heart failure taking a beta-blocker. Eur J Heart Fail. 2007;9:429–434.
5. Hartmann F, Packer M, Coats AJ, et al. Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. Circulation. 2004;110:1780–1786.
6. Masson S, Latini R, Anand IS, et al. Prognostic value of changes in N-terminal pro-brain natriuretic peptide in Vaal-HeFT (Valsartran Heart Failure Trial). J Am Coll Cardiol. 2008;52: 997–1003.

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