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. 2023 May 8;28(4):e13064. doi: 10.1111/anec.13064

Ivabradine in the treatment of non‐paroxysmal junctional tachycardia with interference atrioventricular dissociation: A case report

Shuo Ying 1, Jing Zhang 1, Nai‐kuan Fu 1, Peng Zhang 1,✉
PMCID: PMC10335621  PMID: 37157886

Abstract

Ivabradine reduces the heart rate by selectively inhibiting the I f current of the sinoatrial node, mainly for the treatment of chronic heart failure with decreased left ventricular systolic function and inappropriate sinus tachycardia, but the inhibitory effect on the atrioventricular node is rarely reported. The patient was admitted to hospital mainly because of intermittent chest pain for 7 years, which worsened for 10 days. Admission electrocardiogram (ECG) considered sinus tachycardia, with QS wave and T wave inversion in II, III, aVF, V3R‐V5R, V4–V9 leads, and non‐paroxysmal junctional tachycardia (NPJT) with interference atrioventricular dissociation. After treatment with ivabradine the ECG returned to normal conduction sequence. NPJT with interference atrioventricular dissociation is a fairly rare electrocardiographic phenomenon. This case reports for the first time that ivabradine is used in the treatment of NPJT with interference atrioventricular dissociation. It is speculated that ivabradine has a potential inhibitory effect on the atrioventricular node.

Keywords: acute myocardial infarction, atrioventricular node, interference atrioventricular dissociation, ivabradine, non‐paroxysmal junctional tachycardia

Non‐paroxysmal junctional tachycardia (NPJT) with interference atrioventricular dissociation was found in an old patient with acute myocardial infarction after first failed percutaneous coronary intervention. The electrocardiograph (ECG) was showed sinus rhythm, first‐degree atrioventricular block after treatment with Ivabradine.

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1. INTRODUCTION

Non‐paroxysmal junctional tachycardia (NPJT) is also known as accelerated junctional tachycardia (AJT). The concept of this electrocardiographic phenomenon was first proposed by Pick and Dominguez (1957). Non‐paroxysmal junctional tachycardia is a burst of arrhythmias caused by abnormal conduction or activation in the atrioventricular junctional area. Overdose of digitalis preparations, rheumatic fever, acute myocardial infarction, and cardiac surgery are the most common causes of this arrhythmia (Chen, 2009). Three or more consecutive sinus or atrial activation and junctional or ventricular activation in the atrioventricular junction with absolute interference dissociation is known as interference atrioventricular dissociation (Lu, 2012). Ivabradine selectively inhibits the current (I f) in the sinoatrial nodal that reduces the heart rate without affecting myocardial contractility and cardiac conduction. At present, guidelines recommend ivabradine for the combined treatment of chronic heart failure (Ponikowski et al., 2016; Yancy et al., 2017), stable coronary heart disease (Knuuti et al., 2020), and inappropriate sinus tachycardia (Brugada et al., 2020; Sheldon et al., 2015). This article reports a case of acute myocardial infarction related to NPJT with interference atrioventricular dissociation treated with ivabradine.

2. CASE PRESENTATION

Twelve days before admission, a 68‐year‐old man went to the emergency department of our hospital due to chest discomfort. The electrocardiogram was as follows (Figure 1). Since there was no abnormality in myocardial enzymes and troponin, the patient went home with aspirin, clopidogrel, and rosuvastatin. Ten days ago, the patient was admitted to the gastroenterology department of another hospital for diarrhea. At that night, he experienced crushing chest pain with ST‐segment elevation of 1–6 mm in leads II, III, aVF, V4–V6, V3R–V5R, complete atrioventricular block on the electrocardiogram (ECG; Figure 2). Bedside echocardiography found decreased left ventricular systolic function (Left ventricular ejection fraction 39%). Emergency coronary angiography showed total occlusion in the middle of the right coronary artery. The blood flow was not recovered by thrombus aspiration, intracoronary antithrombotic therapy, and balloon dilation. Dopamine and norepinephrine were used to increase blood pressure and heart rates. He returned to the ward after temporary cardiac pacing and intra‐aortic balloon pump in the lower limbs. Aspirin, clopidogrel, metoprolol, isosorbide mononitrate, sacubitril‐valsartan, dapagliflozin, furosemide, and spironolactone were applicated when the condition stabilized. The ECG after the operation was as follows (Figure 3). He improved after 10 days of medication and came to our department for further treatment. He underwent coronary stenting 7 years earlier for acute inferior myocardial infarction accompanied by type 2 diabetes for 20 years and a 30‐year history of smoking.

FIGURE 1.

FIGURE 1

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12 days before admission, the emergency electrocardiogram (ECG) in our hospital: sinus rhythm, first‐degree atrioventricular block (PR interval 205 ms), QS type in leads III and aVF, heart rate 79 beats/min.

FIGURE 2.

FIGURE 2

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Electrocardiogram (ECG) during myocardial infarction in another hospital: ST‐segment elevation of 1–6 mm in leads II, III, aVF, V4–V6, complete atrioventricular block.

FIGURE 3.

FIGURE 3

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Postoperative Electrocardiogram (ECG) in another hospital: sinus rhythm (red arrows), QS type, and T wave inversion in leads II, III, and aVF, qRs type in leads V4–V6, nonparoxysmal junctional tachycardia (NPJT) with complete interference atrioventricular dissociation, heart rate 96 bpm.

The admission ECG was as follows (Figure 4a). The ventricular rate was slightly lower after ivabradine (5 mg bid) was combined with metoprolol (Figure 4b). NPJT with interference atrioventricular dissociation terminated after the dose of ivabradine increased to 7.5 mg bid (Figure 4c). NPJT with interference atrioventricular dissociation did not recur 2 days later (Figure 4d). The patient successfully underwent coronary intervention 4 days later (Figure 5). The postoperative ECG was as follows (Figure 4e). Due to the progressive prolongation of the PR interval, metoprolol was discontinued (Figure 4f). The patient recovered and was discharged 3 days after the operation. The patient took aspirin, clopidogrel, ivabradine, sacubitril‐valsartan, dapagliflozin, furosemide, and spironolactone all the time after discharge without complaining of discomfort.

FIGURE 4.

FIGURE 4

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Electrocardiogram (ECG) in our hospital: (a) sinus rhythm (red arrows), QS type in leads II, III, aVF, T wave inversion, NPJT with complete interference atrioventricular dissociation, heart rate 105 bpm; (b) sinus rhythm (red arrows), QS type in leads II, III, aVF, T wave inversion, NPJT with complete interference atrioventricular dissociation, heart rate 94 bpm; (c) sinus rhythm (red arrows), first‐degree atrioventricular block, heart rate 83 bpm, PR interval 211 ms; (d) sinus rhythm (red arrows), first‐degree atrioventricular block, heart rate 79 bpm, PR interval 218 ms; (e) sinus rhythm (red arrows), first‐degree atrioventricular block, heart rate 75 bpm, PR interval 227 ms; (f) sinus rhythm (red arrows), first‐degree atrioventricular block, heart rate 78 bpm, PR interval 241 ms.

FIGURE 5.

FIGURE 5

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Coronary angiography and interventional treatment in our hospital: (a) Occlusion in the middle of right coronary; (b) Angiography after right coronary revascularization.

3. DISCUSSION AND CONCLUSION

Non‐paroxysmal junctional tachycardia was first reported by Pick and Dominguez (1957). This arrhythmia is caused by abnormal conduction or activation in the junctional area. The ECG characteristics are as follows: (1) The rate of NPJT is generally between 70 and 130 bpm, most of which is 70–100 bpm, and its rhythm has nothing to do with sinoatrial node rhythm. (2) At the time of the attack, the ectopic rhythm point in the junction area is caused by increased automaticity. The QRS complex is basically the same as that in sinus rhythm. Sinus P waves or retrograde P waves should be determined. (3) When the sinus rhythm is close to the non‐paroxysmal junctional rhythm, activation of the ventricle is sometimes controlled by the sinus node, and sometimes by the junctional rhythm. (4) Various forms of atrial fusion waves can be seen on the electrocardiogram, and the QRS wave is regular (Chen, 2009). Overdose of digitalis preparations (Jr & Sahar, 1987), rheumatic fever (Ceviz et al., 2014), acute myocardial infarction (Fishenfeld et al., 1973), and cardiac surgery (Arvind et al., 2021) are the most common causes of this arrhythmia (Chen, 2009). In patients with posterior myocardial infarction, although NPJT has resulted in death in individual patients, this arrhythmia cannot simply be considered a predictor of poor clinical outcomes. In fact, a modest increase in ventricular rate may reduce symptoms caused by bradycardia after myocardial infarction (Pick & Dominguez, 1957). Knoebel et al. (1975) observed ECG changes in 30 patients with acute myocardial infarction and found that the incidence of NPJT was very high (accounting for 40%) within the first 24 h after hospitalization. Although the study found that patients with NPJT had higher mortality, it may be related to the larger myocardial infarction size. There was no significant difference between with and without NPJT in the incidence of acute heart failure. Wang et al. (1982) analyzed the ECG and etiology of 135 patients with NPJT. Enrolled cases were divided into two groups according to whether they had atrioventricular dissociation or not. The results found that NPJT without atrioventricular dissociation was mainly seen in healthy people (accounting for 38.1% of this group). The vast majority of NPJT with atrioventricular dissociation was found in patients with organic heart disease and systemic disease (accounting for 97.2% of this group). The study noted that NPJT had no effect on clinical outcomes. The study also pointed out that inflammation, ischemia, trauma, and systemic toxins, metabolic, and electrolyte disturbances involving the junctional area can increase the diastolic depolarization velocity of pacemaker cells in the junctional area, resulting in tachycardia.

The interference phenomenon refers to the cardiac rhythm point which is in the refractory period and cannot be activated by other rhythm points. The dissociation phenomenon refers to two independent rhythm points with similar frequencies which occur in three or more consecutive complete interference (Lu, 2012).

Ivabradine selectively inhibits If channels to reduce heart rate by blocking hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels which are mainly expressed in sinoatrial node cells (Amstetter et al., 2021). However, the exploration of the application scope of ivabradine has not stopped. For many years, some scholars have discovered I f channels from isolated rabbit, rat, mouse, and pig atrioventricular node cells (Dobrzynski et al., 2003; Munk et al., 1996). Verrier et al. (2014) found that ivabradine reduced the ventricular rate in atrial fibrillation by prolonging the AH interval in guinea pig hearts, and this effect was frequency‐dependent. In 2015, an animal trial of ivabradine combined with ranolazine to reduce the ventricular rate of atrial fibrillation found that the combination of the two drugs could increase the PR and AH intervals in atrial fibrillation, and ranolazine enhanced the effect of low‐dose ivabradine. The combination was more than twice as effective as high‐dose ivabradine alone, but the combination did not prolong the QT interval and decreased myocardial contractility (Verrier et al., 2015). In 2017, a case report described a 60‐year‐old male with a previous mitral valve replacement for rheumatic heart disease who had permanent atrial fibrillation with complete left bundle branch block and severe left ventricular insufficiency. He underwent cardiac resynchronization therapy in the local hospital. After the maximum tolerated dose of bisoprolol, the patient's ventricular rate was still poorly controlled, and the rate of biventricular pacing was only 74%. Due to histories of digitalis poisoning and renal failure, atrioventricular node ablation was planned. But after preoperative combined application of ivabradine 5 mg q12h, the proportion of biventricular pacing increased to 95% and increased to 96% after 1 month follow‐up, so atrioventricular node ablation was not performed (Fontenla et al., 2017).

This patient was an elderly male suffering from recurrent acute myocardial infarction with a history of inferior wall myocardial infarction. The ECG changed from third‐degree atrioventricular block to NPJT with interference atrioventricular dissociation after unsuccessful reperfusion therapy. After treatment with metoprolol, there was no significant improvement. During hospitalization in our department, the same dose of metoprolol was used in combination with ivabradine. With an increasing dose of ivabradine, the rate of the sinoatrial node and ventricle were decreased, and cardiac electrical activity returned to normal conduction sequence, while PR interval was gradually prolonged. ECG turned to first‐degree atrioventricular block, and NPJT with interference atrioventricular dissociation did not occur again. Interestingly, PR interval did not shorten after right coronary revascularization and discontinuation of metoprolol. In Figure 4a, the PP intervals were 600 ms, the RR intervals were 570 ms, and the PP intervals in Figure 4e were equal to the RR intervals of 800 ms. Since the combined use of ivabradine (5 mg bid increased to 7.5 mg bid), the PP intervals had increased by 200 ms and the RR intervals had increased by 230 ms. It was speculated that the inhibitory effect of ivabradine on the atrioventricular node is stronger than the sinoatrial node in this patient. This patient has continued to take ivabradine since he was discharged from the hospital. This is due to two reasons. One is to prevent the recurrence of NPJT with interference atriovascular dissociation. On the other hand, Heart failure with reduced ejection fraction is one of the indications for ivabradine (Swedberg et al., 2010).

Over the past 30 years, Chinese and foreign literatures have analyzed the epidemiological characteristics and mechanism of NPJT with interference atrioventricular dissociation, but this phenomenon is rare. This is the first time that ivabradine is used to treat NPJT with interference atrioventricular dissociation. This may be helpful for the indication expansion of ivabradine, but further verification is required in future large‐scale randomized controlled studies.

AUTHOR CONTRIBUTION

YS discovered and explained the phenomenon of non‐paroxysmal junctional tachycardia with interference atrioventricular dissociation and was major contributors in writing the manuscript. ZJ and FNK performed coronary intervention for this patient. ZP proofreaded this manuscript and was the corresponding author. All authors read and approved the final manuscript.

FUNDING INFORMATION

This work was supported by Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK‐055B) and Tianjin Municipal Health Commission Tianjin Municipal Administration of Traditional Chinese Medicine Research Project of Integrated Traditional Chinese and Western Medicine (2021205) in case collection, literature summarization, manuscript writing and page charges.

CONFLICT OF INTEREST STATEMENT

No competing interests.

ETHICAL APPROVAL

The study was approved by the ethics committee of Tianjin Chest Hospital.

CONSENT TO PARTICIPATE

The patient had written consent to participate in the study.

CONSENT FOR PUBLICATION

Written informed consent for publication was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal.

ACKNOWLEDGMENTS

The authors are very grateful to this patient for his active cooperation.

Ying, S. , Zhang, J. , Fu, N.‐k. , & Zhang, P. (2023). Ivabradine in the treatment of non‐paroxysmal junctional tachycardia with interference atrioventricular dissociation: A case report. Annals of Noninvasive Electrocardiology, 28, e13064. 10.1111/anec.13064

DATA AVAILABILITY STATEMENT

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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Associated Data

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Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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