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National Institute for
Health Research
NIHR Leeds Clinical Research Facility
The acute effects of Ivabradine
on left ventricular size and function in heart failure
Maria F Paton, BSc, MSc, John Gierula, BSc, Haqeel A Jamil, PhD, Roo Byrom, BSc, Judith E Lowry, MSc,
Richard M Cubbon, PhD, David A Cairns, PhD, Mark T Kearney, MD, Klaus K Witte, MD.
WHAT WE LEARNED
Improvements in left ventricular function associated with
ivabradine are not exclusively dependent on a change in
heart rate.
Ivabradine is associated with improvements in left
ventricular size and global function from just 2 hours
post administration.
BACKGROUND
Chronic heart failure (HF) affects approximately 2-3% of the population in
many Western countries.(1) Treatments have substantially improved in
recent years, but prognosis remains poor.(2) Advances in therapeutic
approaches and knowledge surrounding disease mechanisms are crucial.
Ivabradine is a heart rate (HR) lowering agent. It has been shown to
reduce cardiovascular death and hospitalisation in HF patients.(3) The
precise mechanism of its effects are unknown.
Global longitudinal strain, a promising method for left ventricular (LV)
assessment, is superior to existing methods in predicting outcomes in HF
patients.(4)
OBJECTIVES
To determine if ivabradine is associated with acute changes in cardiac
size and function related to heart rate changes.
Figure 1. Processing and Presentation of 2D strain(5)
Figure 2. Ivabradine vs. Placebo Effects on Cardiac Variables
80
Placebo
60
Ivabradine
40
20
0
HR
-20
LVEF
LVESVi
Biplane GLS
-40
RESULTS
• Patients in the sub-study (8 male) were 74 ± 9 years old with a mean
LVEF of 40 ± 10%. Sub-study patients did not differ significantly in
baseline variable to those in the overall study sample
• Mean resting HR was non-significantly lower following Ivabradine than
placebo (p=0.2) Ivabradine was associated with lower LVESVi (p=0.009),
an improved LVEF (p=0.003), and GLS (p=0.02) vs. placebo (Figure 2).
• Non-significant correlation between heart rate reduction and change in
GLS (P 0.49) (Figure 3).
IMPLICATIONS
Ivabradine may be applicable to patients with acute decompensated
heart failure, but requires further investigation.
Global longitudinal strain is a reliable method of left ventricular function
in heart failure patients.
Figure 3. Correlation between Change in HR and Change in
Global Longitudinal Strain
METHODS
Change in HR (bpm)
• 26 patients with systolic HF enrolled in a randomised, double-blind,
cross-over placebo-controlled study on the effects of chronotropic
incompetence on exercise capacity; allocated ivabradine (7.5mg) or
placebo 1 week apart 2 hours prior to undergoing a cardiopulmonary
exercise test.
• 9 sub-study patients underwent 2D transthoracic echocardiography at
both visits and were included in this analysis.
• Measurements of size:
Left ventricular end diastolic volume (LVEDV)
Left ventricular end systolic volume (LVESV)
Left ventricular end systolic volume index (LVESVi)
Measurements of function:
Ejection fraction (EF)
Global longitudinal strain (GLS) (Figure 1) were taken.
• Continuous variables were statistically analysed using T-test,
categorical variables were analysed with chi-squared techniques.
A linear correlation was performed to asses the relationship between
heart rate change and left ventricular function.
20
Correlation
between Change
in HR and Change
in Global
Longitudinal
Strain
15
10
5
0
-15
-10
-5
-5
-10
-15
0
5
Linear
(Correlation
between Change
in HR and Change
in Global
Longitudinal
Strain)
Change in GLS (%)
References:
1. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
2008.Eur J Heart Fail 2008; 10: 933–89.
2. Jhund PS, Macintyre K, Simpson CR, et al. Long-term trends in fi rst hospitalization for heart failure and subsequent survival between
1986 and 2003: a population study of 5.1 million people. Circulation 2009; 119:515–23.
3. Swedberg K, Komajda M, Bohm M, et al.Ivabradine and outcomes in chronic heart failure(SHIFT): a randomised placebo-controlled
study.Lancet 2010;376:875–85.
4. Reisner S. A., Lysyansky P., Agmon Y., Mutlak D., Lessick J., Friedman Z. Global longitudinal strain: a novel index of left ventricular
systolic function. Journal of the American Society of Echocardiography.2004;17(6):630–633
5. Marwick TH, Leano RL, Brown J, et al. Myocardial Strain Measurement With 2-Dimensional Speckle-Tracking Echocardiography:
Definition of Normal Range. J Am Coll Cardiol Img. 2009;2(1):80-84.