Selective Heart Rate Reduction With Ivabradine Unloads the Left Ventricle in Heart Failure Patients

• Published in: Journal of the American College of Cardiology Vol. 62; no. 21; pp. 1977 - 1985
• Main Authors: Reil, Jan-Christian, MD, Tardif, Jean-Claude, MD, Ford, Ian, MD, Lloyd, Suzanne M., MSc, O'Meara, Eileen, MD, Komajda, Michel, MD, Borer, Jeffrey S., MD, Tavazzi, Luigi, MD, Swedberg, Karl, MD, Böhm, Michael, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 19.11.2013; Elsevier; Elsevier Limited
• Subjects: Antiarythmic agents; Biological and medical sciences; Blood pressure; Cardiology; Cardiology. Vascular system; Cardiovascular; Cardiovascular Agents - therapeutic use; Cardiovascular system; Clinical Medicine; Compliance; Drug therapy; Heart; Heart attacks; Heart failure; Heart Failure - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart rate; Heart Rate - physiology; heart rate reduction; Heart Ventricles - physiopathology; Humans; Internal Medicine; Klinisk medicin; Medical sciences; Pharmacology. Drug treatments; Studies; systolic heart failure; ventricular-arterial coupling; end-systolic pressure–volume relationship; PP; heart rate reduction; ejection fraction; PV; HR; LV; LVOT; cardiac output; effective arterial elastance; total arterial compliance; EDV; TPR; end-diastolic volume; left ventricular; EF; heart failure; pulse pressure; heart rate; pressure-volume; SV; systolic heart failure; mean arterial pressure; left ventricular outflow tract; CO; ESPVR; end-systolic pressure; stroke volume; Ees; ventricular-arterial coupling; TAC; end-systolic elastance; total peripheral resistance; Ea; MAP; HF; Pes; Human; Heart failure; Cardiac frequency; Ivabradine; Patient; Cardiovascular disease; Antiarrhythmic agent; Left ventricle; Heart rate; Left heart; Reduction; Heart disease; Circulatory system; Cardiology
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2013.07.027

Objectives The study aimed to determine whether isolated heart rate (HR) reduction with ivabradine reduces afterload of patients with systolic heart failure. Background The effective arterial elastance (Ea) represents resistive and pulsatile afterload of the heart derived from the pressure volume relation. HR modulates Ea, and, therefore, afterload burden. Methods Among the patients with systolic heart failure (ejection fraction ≤35%) randomized to either placebo or ivabradine in the SHIFT (Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial), 275 patients (n = 132, placebo; n = 143, ivabradine 7.5 mg twice a day) were included in the echocardiographic substudy. Ea, total arterial compliance (TAC), and end-systolic elastance (Ees) were calculated at baseline and after 8 months of treatment. Blood pressure was measured by arm cuff; stroke volume (SV), ejection fraction, and end-diastolic volume were assessed by echocardiography. Results At baseline Ea, TAC, HR, and Ees did not differ significantly between ivabradine- and placebo-treated patients. After 8 months of treatment, HR was significantly reduced in the ivabradine group (p < 0.0001) and was accompanied by marked reduction in Ea (p < 0.0001) and improved TAC (p = 0.004) compared with placebo. Although contractility remained unchanged, ventricular-arterial coupling was markedly improved (p = 0.002), resulting in a higher SV (p < 0.0001) in the ivabradine-treated patients. Conclusions Isolated HR reduction by ivabradine improves TAC, thus reducing Ea. Because Ees is unaltered, improved ventricular-arterial coupling is responsible for increased SV. Therefore, unloading of the heart may contribute to the beneficial effect of isolated HR reduction in patients with systolic heart failure. (Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial [SHIFT]; ISRCTN70429960 )