The aim of this study is to assess the efficacy of Ivabradine therapy in patients with congestive heart failure using the cardiac biomarkers NT-Pro BNP and Neopterin.

• Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy, Damanhour University
• All participants have agreed to take part in this clinical study and provide informed consent
• A 3 months, prospective interventional study.
• Sixty ambulatory, clinically stable symptomatic patients with systolic chronic HF (≥ 4 weeks), on optimized standard medical therapy were consecutively included and randomly allocated to the ivabradine group (n=30) and non-ivabradine group (n=30).
• The baseline evaluation comprised physical examination, NYHA class, 12-lead electrocardi¬ography (ECG), Echocardiography, blood sampling for laboratory measurements, including NT-Pro BNP and Neopterin.
• Patients in the Ivabradine group were administered Ivabradine 5 mg twice daily and doses (2.5, 5, 7.5 mg) were to be adjusted upwards or downwards at every visit according to HR at rest and tolerability.
• Patients were followed up after 1 week of initiation of ivabradine therapy then monthly till the end of the study.
• Peripheral venous blood samples were drawn between 8 and 9 am after a 30-min rest in the supine position. Serum samples were frozen at -80°C until assay.
• Levels of NT-Pro BNP and Neopterin were detected using ELISA kits as prescribed by manufacturer.
• Statistical tests appropriate to the study will be conducted to evaluate significance of results
• Results, conclusion, discussion and recommendations will be given

Inclusion Criteria:

• Patients with chronic HF, on optimized medical therapy according to European Society of Cardiol¬ogy guidelines, with LV ejection fraction (LVEF) < 35% according to the Simpson method, New York Heart Association (NYHA) class II-III, and sinus rhythm and resting HR > 70/min were eligible for inclusion in the study.

Exclusion Criteria:

• acute decompen¬sation (acute coronary syndromes and acute HF);
• hemodynamically significant valve disease;
• cer¬ebrovascular events during the previous 6 months;
• dysfunctional prosthetic heart valve;
• obstructive or non-obstructive cardiomyopathy; uncorrected congenital heart disease; active myocarditis;
• a his¬tory of resuscitation from sudden death; an absence of stable sinus rhythm, severe arrhythmias; HR < 60 bpm; sick sinus syndrome; second-degree and third-degree atrioventricular block;
• severe obesity (body mass index > 36 kg/m²);
• established or sus¬pected pulmonary diseases (vital capacity < 80% or forced expiratory volume in 1 s < 80% of age spe¬cific and sex-specific reference values);
• hemoglobin ≤ 11 g/dL;
• treatment with non-dihydropyridine calcium-channel blockers, class I antiarrhythmic agents, strong inhibitors of cytochrome P450-3A4, or QT interval-prolonging medications;
• acute and chronic kidney failure;
• pregnancy; hypo- and hy¬perthyroidism or acute infections.

double-blind study