Selective heart rate reduction with ivabradine unloads the left ventricle in heart failure patients.
OBJECTIVE
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.
Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. Electronic address: jan.reil@uks.eu.
Jan-Christian
JC
Reil
Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
Jean-Claude
JC
Tardif
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
Ian
I
Ford
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
Suzanne M
SM
Lloyd
Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
Eileen
E
O'Meara
Department of Cardiology, University Pierre et Marie Curie Paris VI, La Pitié-Salpétrière Hospital, Paris, France.
Michel
M
Komajda
Division of Cardiovascular Medicine and the Howard Gilman Institute for Heart Valve Disease, State University of New York Downstate Medical Center, Brooklyn and New York, New York.
Jeffrey S
JS
Borer
Maria Cecilia Hospital, GVM Care and Research, Ettore Sansavini Health Science Foundation, Cotignola, Italy.
Luigi
L
Tavazzi
Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Karl
K
Swedberg
Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Michael
M
Böhm
D002317:Cardiovascular Agents / Q000627:therapeutic use*; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology*; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans
D002317:Cardiovascular Agents
CO; EDV; EF; ESPVR; Ea; Ees; HF; HR; LV; LVOT; MAP; PP; PV; Pes; SV; TAC; TPR; cardiac output; effective arterial elastance; ejection fraction; end-diastolic volume; end-systolic elastance; end-systolic pressure; end-systolic pressure–volume relationship; heart failure; heart rate; heart rate reduction; left ventricular; left ventricular outflow tract; mean arterial pressure; pressure-volume; pulse pressure; stroke volume; systolic heart failure; total arterial compliance; total peripheral resistance; ventricular-arterial coupling