Takafumi Koji

Addition of Angiotensin II Receptor Antagonist to an ACE Inhibitor in Heart Failure Improves Cardiovascular Function by a Bradykinin-Mediated Mechanism

Whether cardiovascular responses to bradykinin are augmented by additional treatment with angiotensin II receptor antagonism (ATRA) to angiotensin-converting enzyme inhibition (ACEI) in congestive heart failure (CHF) is unknown. To clarify the level and functional effects of endogenous bradykinin in CHF with combined ATRA and ACEI, 35 dogs were assigned to the following treatment protocols: 1) rapid ventricular pacing (240 bpm), 2) concomitant ATRA (TCV116, 1.5 mg·kg−1·day−1) and rapid pacing, 3) concomitant ACEI (enalapril 1.9 mg·kg−1·day−1) and rapid pacing, 4) concomitant combined ATRA (TCV116, 0.75 mg·kg−1·day−1) and ACEI (enalapril 0.95 mg·kg−1·day−1) and rapid pacing, and 5) sham-operated control. Plasma bradykinin levels were increased and B2 receptors were synergistically upregulated in CHF groups treated with combined ATRA and ACEI compared with those treated with ATRA or ACEI alone. HOE-140 (0.3 mg/kg), a bradykinin B2 receptor antagonist, produced an increase in total systemic resistance and a decrease in left ventricular contractility in CHF with combined therapy compared with either monotherapy. Thus, endogenous bradykinin partially contributes to the synergistic improvement of cardiovascular function in CHF with additional treatment with ATRA to ACEI.

Candesartan prevents myocardial fibrosis during progression of congestive heart failure.

Background: The goal of this study was to determine whether an Angiotensin II receptor antagonist, candesartan, prevents myocardial fibrosis more effectively than enalapril in animals with a non-ACE pathway during the progression of congestive heart failure (CHF). Methods and Results: Dogs were randomly assigned to one of four groups: (1) rapid ventricular pacing (240 bpm); (2) concomitant candesartan cilexetil (1.5 mg/kg/d) and rapid pacing; (3) concomitant enalapril (1.9 mg/kg/d) and rapid pacing; (4) sham-operated control. The expression of collagen type I & III mRNA and the collagen volume fraction, which were significantly increased in the pacing-only group, were suppressed by both treatments; it was lower in the candesartan than the enalapril group. Although there were no differences in the LV stiffness coefficient (β) among all pacing groups, the absolute changes in β from the control values were smaller in the candesartan group, but not the enalapril group, compared with the rapid-pacing-only group. Conclusions: The present study demonstrates that in animals with a non-ACE pathway, candesartan suppressed myocardial fibrosis during the progression of CHF in comparison with enalapril. Furthermore, candesartan prevented an increase in LV stiffness. These findings imply potential clinical applications for candesartan in the management of CHF to prevent myocardial fibrosis. Further prospective evaluation and clinical study will be necessary before deciding on the net benefits of candesartan in comparison to enalapril.

An incomplete pacemaker lead fracture causing inappropriate pacing inhibition due to oversensing of the minute ventilation sensor pulses

Cardiac pacemakers using rate response technologies represent the effectiveness of increasing the heart rate and cardiac output during exercise. Minute ventilation (MV) sensors are popular and estimate rates using transthoracic impedance by emitting very low amperage short electrical current pulses between the pacemaker lead tip and pulse generator. We present a case of an incomplete pacemaker lead fracture developing inappropriate pacing inhibition due to oversensing caused by the electrical current emitted by the MV sensor. A permanent pacemaker replacement was performed, resulting in no further abnormal findings such as inappropriate pacing inhibition. <Learning objective: The minute ventilation (MV) sensor is estimated using the transthoracic impedance by emitting a very low amperage and short pulses of electrical current between the pacemaker lead tip and pulse generator. Therefore, if a fractured lead occurs, the voltage from the current pulses emitted for the MV sensor might be high enough to be oversensed as ventricular waves. We recommend that it is necessary to keep in mind the possibility of a fractured lead if oversensing of the thoracic impedance measurement current is observed.>.

The utility of atrial pacing for identifying the electrical breakthrough sites between the left atrium and pulmonary veins

Circumferential pulmonary vein (PV) isolation for atrial fibrillation (AF) is occasionally difficult to achieve because electrical breakthrough sites (EBSs) between the left atrium (LA) and PVs cannot be identified during ablation especially in the carina regions.