EXPLANATION


Heterotaxy is a disorder in which the usual arrangement of thoracic and abdominal organs is absent. It is also described with the term right or left atrial isomerism, which is determined by the anatomy of the atrial appendages. Right atrial isomerism or bilateral right-sidedness refers to bilateral atria with anatomic features of a right atrium. Left atrial isomerism or bilateral left-sidedness refers to bilateral atria with anatomic features of a left atrium. Fifty to ninety percent of patients with heterotaxy will also have complex congenital heart disease. Any combination of congenital heart defects may occur in patients with heterotaxy. However, certain combinations of defects appear to be more common in each type of atrial isomerism, which are listed below.


Right atrial isomerism (RAI) is associated with the following defects:
• Single ventricle physiology
• Bilateral superior vena cava (right-sided structure)
• Atrial septal defect
• Absent coronary sinus (left-sided structure)
• Dual sinoatrial nodes
• Abnormalities of pulmonary veins (i.e. anomalous pulmonary venous return, hypoplastic pulmonary veins)
• Malposed great arteries (frequency of 95%)
• Double-outlet right ventricle (frequency of 5%)
• Pulmonary valve obstruction (i.e. pulmonary stenosis/atresia, frequency > 90%)
• Common atrioventricular valve
• Bilateral trilobed lungs
• Eparterial bronchi
• Asplenia


Left atrial isomerism (LAI) is associated with the following defects:
• Interrupted inferior vena cava (absence of the intrahepatic portion of the inferior vena cava with venous continuation via the azygos vein)
• Absent sinoatrial and atrioventricular nodes
• Left-sided obstructive defects (i.e. mitral stenosis, aortic stenosis, aortic coarctation)
• Common atrioventricular valve
• Bilateral bilobed lungs
• Hyparterial bronchi
• Polysplenia
• Biliary atresia
• Absent/hypoplastic gallbladder



Patients with RAI often have dual sinoatrial and atrioventricular nodes, predisposing them to tachyarrhythmias (i.e. supraventricular tachycardia, junctional tachycardia, ectopic atrial tachycardia, and atrial flutter/fibrillation). Although patients with LAI often have tachyarrhythmias as well, they are more prone to bradyarrythmias (i.e. sinoatrial node dysfunction, atrioventricular block) due to absence of sinoatrial and atrioventricular nodes. Atrial suture lines from previous/repeat surgical procedures and physiologic derangements may also contribuate to the development of arrhythmias in heterotaxy.


A single-center, retrospective review by Niu et al. of 337 patients with heterotaxy from 1980 to 2012, over a median seven-year follow-up period, demonstrated that 38% of all heterotaxy patients had been diagnosed with an arrhythmia. Twenty-two percent experienced tachyarrhythmias, while 9% had bradyarrhythmias, and 7% had both. Age, pulmonary venous obstruction, and outflow tract obstruction significantly contributed to the development of arrhythmias. Multivariate analysis revealed that tachyarrhythmias were associated with pulmonary venous obstruction at a hazard ratio (HZ) of 2.33 (95% CI 1.45-3.76), moderate atrioventricular valve regurgitation at a HR of 1.66 (95% C.I. 1.11-2.5), and single ventricle anatomy at a HR of 2.3 (95% CI 1.09-4.85). Ectopic atrial tachycardia (EAT) tended to occur in infants during a perioperative period. Of the patients with perioperative EAT, 50% were weaned from anti-arrhythmic medications over a twelve month period without recurrence. Atrial fibrillation and/or atrial flutter were more frequent in older patients with a median age of fifteen years.


Bradyarrhythmias occurred in 54 (16% total) patients. Thirty-two had symptomatic sinus bradycardia necessitating pacemaker placement. Twenty-two had a high grade or complete atrioventricular block (AVB). LAI was associated with a higher risk for bradyarrhythmias with a HR of 7.12 (95% CI 3.01-16.9) as compared to RAI. The increased risk persisted when LAI was compared to the mixed or indeterminate subtype of heterotaxy (HR 2.63, (95% CI 1.34-5.16)). Fifty-one patients in the entire cohort (54) required pacemaker placement. Forty-one percent had high-grade atrioventricular block or complete congenital atrioventricular block. Fifty-nine percent had symptomatic sinoatrial bradycardia. In this cohort, the presence of a tachyarrhythmia was associated with an increased risk for death and heart transplantation with a HR of 2.24 (95% CI 1.45-3.46). In contrast, presence of a bradyarrhythmia was not associated with an increased risk of death or need for heart transplantation.


A smaller, single-center retrospective study by Ozawa et al., demonstrated that of 40 patients with heterotaxy (40% with LAI and 60% with RAI), 21 experienced arrhythmias during a mean follow-up duration of 5.4 years. Of those with arrhythmias, 87% had LAI and 29% had RAI. Of the LAI patients, ten had sinoatrial node dysfunction, three had atrioventricular block and one had supraventricular tachycardia (SVT). In the RAI group, there were five patients with SVT, two with EAT, one with junctional tachycardia and one with AVB. Two patients with AVB in the LAI group received pacemakers. Interestingly this study was conducted in Japan where cilostazol, an anti-platelet medication with antiphosphodiesterase type 3 activity, is used to increase the heart rate in patients. Five patients with LAI and sinus node dysfunction received cilostazol and none required pacemaker placement.


In summary, heterotaxy patients with LAI are more likely to exhibit bradyarrhythmias (i.e. AV block) and later require pacemaker placement. Patients with RAI are predisposed to tacharrhythmias, making the need for pacemaker implantation less common.


REFERENCES


Agarwal R, Varghese R, Jesudian V, Moses J. The heterotaxy syndrome: associated congenital heart defects and management. Indian J Thorac Cardiovasc Surg. 2021;37:67-81.


Ozawa Y, Asakai H, Shiraga K, et al. Cardiac Rhythm Disturbances in Heterotaxy Syndrome. Pediatr Cardiol. 2019;40(5):909-913. doi:10.1007/s00246-019-02087-2


Niu MC, Dickerson HA, Moore JA, et al. Heterotaxy syndrome and associated arrhythmias in pediatric patients. Heart Rhythm. 2018;15(4):548-554. doi:10.1016/j.hrthm.2017.11.013