A case of atrial tachycardia treated with ivabradine as bridge to

ablation.

Ester Meles M.D., Claudio Carbone M.D., Stefano Maggiolini M.D., Paolo Moretti M.D.**,
Caterina C. De Carlini M.D., Gaetano Gentile M.D., Tomaso Gnecchi Ruscone M.D.

Division of Cardiology, Cardiovascular Department, S. Leopoldo Mandic Hospital, Merate, Italy,

** Division of Cardiology, Mater Domini Hospital, Castellanza, Italy.

Short title: Ivabradine in atrial tachycardia.

Correspondence:
Ester Meles, MD
e-mail: ester.meles@libero.it

Tel number: 039-039-5916521

FAX: 039-039-5916471

No disclosures.

This article has been accepted for publication and undergone full peer review but has not been through the
copyediting, typesetting, pagination and proofreading process, which may lead to differences between this
version and the Version of Record. Please cite this article as doi: 10.1111/jce.12636.

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Abstract

Ivabradine is indicated in cardiac failure and ischemia to reduce sinus rate by inhibition of the

pacemaker (If) current in sinoatrial node.

We report a case of a 18-year-old woman with left atrial tachyarrhythmia resistant to several

antiarrhytmic drugs and to electric cardioversion who responded only to ivabradine, which

significantly reduced heart rate without abolishing the arrhythmia itself.

An ectopic focus in the ostium of left pulmonary veins was found and the patient was successfully

ablated.

We suggest that ivabradine might be therefore useful in the treatment of supraventricular

tachyarrhytmias due to an enhanced automaticity.

Keywords: ivabradine; atrial tachycardia; heart rate; catheter ablation

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Case report

An 18-year-old woman was admitted to our department for a supraventricular tachycardia

(heart rate 160/minute). She had already suffered during the last year short episodes (20-30

min) of palpitations, characterized by rapid onset and regression that were not related to

efforts or emotions. The frequency of episodes had increased during the previous month,

becoming almost daily. No syncope was reported.

No history of hypertension, renal failure, diabetes, vascular disease, congenital heart disease

was present and she was taking no medication. Her blood examination tests were normal,

including serum electrolytes and thyroid function. The 12-lead electrocardiogram showed

supraventricular tachycardia with characteristics of left atrial tachycardia (LAT): i.e.,

negative P waves in leads I and aVL while positive in DII, DIII and aVF (Fig. 1).

Echocardiography showed a reduction in global myocardial function (EF 40%) with normal

valvular function and cardiac chambers dimensions.

Ineffective were both the carotid sinus massage and the administration of adenosine. The

Valsalva maneuver determined only one A-V block but no interruption of arrhythmia.

Intravenous verapamil (5 mg) caused a further increase in heart rate, while intravenous

flecainide (100 mg) reduced the heart rate, but caused hypotension and pathological QRS

enlargement. Amiodarone bolus (300 mg) caused symptomatic hypotension but no

regression of arrhythmia. An attempt of electrical cardioversion was also performed with

three DC shocks (70-70-100 Joules) without results. The patient was then treated with

atenolol (100 mg/day) for 5 days, obtaining a small heart rate reduction (down to

120/minute) but not interruption of arrhythmia or relief of symptoms.

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Thereafter, an attempt with ivabradine (5 mg x 2) was started after having fully explained the

effects of the drug to the patient. A significant reduction of heart rate arrhythmia to

100/minute was obtained in about 5 hours, with the lowest rate 75 bpm during the night (Fig.

2); the patient’s symptoms were also completely solved, and no side effects were observed.

Two days later she underwent an electrophysiological study that showed the origin of

arrhythmia in one atrial ectopic focus located in the inferior wall of the common ostium of

left pulmonary veins (PV) (Fig. 3), confirming an increased automaticity vs reentry

pathogenetic hypothesis. A normal H-V interval was also found. Radiofrequency ablation of

the focus was successfully performed.

After 6 months, the patient remained asymptomatic and in sinus rhythm; echocardiography

showed full recovery of myocardial function.

Discussion

Atrial tachycardia is an arrhythmia that is often difficult to treat. In our case, we followed the

international guidelines (1) for treatment of supraventricular tachycardia using the

recommended antiarrhythmic drugs and electric cardioversion without obtaining either the

interruption of arrhythmia or a significant rate reduction.

Ivabradine is a drug currently used for the management of patients with stable angina pectoris

(2) or with heart failure (3), and has been proposed in patients with postural orthostatic

tachycardia syndrome (4). With the exception of inappropriate sinus tachycardia (5)

ivabradine is not actually indicated in the management of cardiac arrhythmias.

Ivabradine inhibits the I(f) ion current, one of the most important currents in regulating
pacemaker activity, selectively and in a dose dependent way, slowing the heart rate with no

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effect on myocardial contractility, relaxation, intraventricular conduction or action potential
duration (6).

I(f) is carried by hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. Four

different isoforms of the HCN family have been identified (7,8), and HCN4 is the main

subtype present in the human sinoatrial and in the AV nodes.

Interestingly, the I(f) channels are highly expressed not only in the sinoatrial (9) and AV
nodes

(10), but different isoforms are also present in non pacemaker cardiac cells in atria (11) and

in pulmonary veins (PV) (6,12) where a mixture of pacemaker cells and working
myocardium

cells exist and may potentially induce atrial arrhytmias (12). Ivabradine has been shown to

decrease the spontaneous activity in PV cardiomyocytes (6).

Although we cannot exclude a role for ivabradine for slowing down the tachycardia by

affecting the HCN4 channels present in the AV node ( 13 ), as it happens in atrial fibrillation

in the experimental model (14), in our patient the P-R interval (172 msec) was not prolonged

after ivabradine treatment.

We therefore hypothesize an increased automaticity mechanism in the pathogenesis of the

arrhytmia in our patient.

Our spontaneous LAT case adds to two recent reports:

The first deals with a 15-year-old girl (15) where a focal LAT resulted as a complication of

PV isolation occurring in a failed first ablative treatment for atrial fibrillation. Similarly to

our case, the tachycardia was successfully treated with ivabradine to control heart rate

allowing a later and successful second ablation to be performed. The second also based on an

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increased automaticity mechanism, an incessant junctional ectopic tachycardia in a 2-year-old

girl where ivabradine both acutely and chronically allowed to postpone an ablation procedure

(16).

We do not know if our case can be a model for the treatment of all focal atrial tachycardia,

but due to the presence of I(f) channels in PV and in atrium we can suppose that the

reduction of heart frequency could occur in other forms of arrhythmia generated by an

ectopic atrial focus. Finally, our case, together with the other presented cases, suggests the

use of ivabradine for at least three reasons: first because ivabradine gives symptomatic relief

by reducing the automatic focus discharge; second, it allows to probe the possible automatic

based vs reentrant pathogenic mechanism; and last, it can be useful as a bridge to a

subsequent electrophysiological study.

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Fig. 1

Twelve–lead electrocardiogram showing atrial tachycardia (P waves negative in leads I and

aVL and positive in DII, DIII and aVF) before treatment with ivabradine.

FIG 1

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Fig. 2

Twelve–lead electrocardiogram of atrial tachycardia after treatment with ivabradine, showing

the same morphology of P wave but lessened heart rate.

FIG 2

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Fig. 3

Intracardiac recording during atrial tachycardia with mapping catheter in the inferior wall of the
common ostium of left pulmonary veins showing earliest atrial activation to coronary sinus (40 msec.)
with unipolar negative. CS=coronary sinus; HBEp=His bundle electrogram proximal; HBEd=His
bundle electrogram distal; SITEp= mapping catheter proximal; SITEd= mapping catheter distal;
Uni=unipolar catheter.

FIG 3

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