DISCUSSION
The present case shows the favorable hemodynamic effect of ivabradine in
a patient with decompensated HF related to CHIC, refractory to
conventional medical therapy.
It is reported that the incidence of CHIC due to anthracycline is 9%,
with 98% of the cases developing within 1 year. Anthracycline-induced
myocardial damage is irreversible 9, and the 2-year
survival rate has been reported to be 50% or less when anthracyclines
are the of cause HF. The treatment
is often difficult in such cases, where HF is advanced and refractory to
inotropes 1. The use of ivabradine in
decompensated HF is off-label.
However, due to its unique mechanism of reduction of HR without
influencing myocardial contraction, ivabradine does not cause the
undesired effect of hypotension, which is a major problem on
up-titration of beta-blockers, and might have favorable effects on
hemodynamics even in decompensated HF due to CHIC. In some patients in
advanced HF or cardiogenic shock, ivabradine was safely used to reduce
HR and increase SV without impairing their hemodynamic status5 7.
Though the reason ivabradine increases SV in decompensated HF is not
fully understood, the mechanisms are suggested to be as follows (Figure
5). Ivabradine causes prolongation of diastolic time, which leads to an
increase of LV diastolic filling
along with an increase of coronary perfusion, increasing SV via the
Franck-Starling mechanism 5, 10,11, 12. Moreover, ivabradine has a
positive inotropic effect primarily due to increased
sarcoplasmic/endoplasmic reticulum calcium ATPase 2a activity, and does
not have a negative inotropic effect, unlike β-blockers13. Afterload reduction based on the reciprocal
interaction between HR and effective arterial elastance (Ea) has also
been reported 10, 5, 12. Ventricular arterial coupling
was improved because of the decrease in Ea, resulting in higher SV in
patients treated with ivabradine 12.
How much should the heart rate be reduced by ivabradine? From the
viewpoint of echocardiography, monitoring the degree of overlap between
the E- and A-waves might be useful as a way to optimize HR (Figure 6).
The overlap between E- and A-waves observed at higher sinus HR suggests
that LV relaxation is interfered with by atrial systole. And that could
result in reduced LV filling volume. Izumida et al. propose a novel
formula to estimate ideal HR in patients with HF using echocardiographic
parameters, the overlap between the E- and A-waves, and deceleration
time 14.
In the present case, the HR lowering effect of ivabradine could increase
SV, with its attendant favorable hemodynamic consequences.
Though medical therapy is often
difficult in advanced HF related to CHIC, ivabradine might be effective
as a complementary medical option in these cases. Also, assessing
the degree of overlap between the
E- and A-waves facilitates
estimation of the effects of ivabradine.
In conclusion, the administration of ivabradine could lead to
improvement of hemodynamic status in decompensated HF related to CHIC
via the increase of SV. Assessment of the overlap between the E- and
A-waves facilitates receiving the benefits of ivabradine in such cases.
Further large-sample verification will be needed to confirm these
findings.