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.