Abstract
Background
Infantile-onset Pompe disease (IOPD) is a lethal disorder, but enzyme replacement therapy (ERT) has dramatically improved the prognosis of these patients.
Case Summary
An 18-year-old male patient, who had been diagnosed with IOPD based on decreased α-glucosidase activity in his infancy and received ERT, visited an emergency department at Kyoto University Hospital with poor complexion. An electrocardiogram showed extreme bradycardia and complete atrioventricular block (cAVB), and permanent pacemaker was implanted for cAVB.
Discussion
ERT has reduced the risk of death in patients with IOPD; on the other hand, severe cAVB in those patients needs to be recognized as a rare complication.
Take-Home Message
cAVB is a rare but critical complication in long-term survivors of IOPD and deserves attention.
Key Words: bradycardia, cardiac pacemaker, cardiomypathy
Graphical Abstract
History of Presentation
An 18-year-old male patient, who had been diagnosed with infantile-onset Pompe disease (IOPD) when he was 6 months old, visited the emergency department because he could not communicate with his family as usual. Although IOPD is a lethal disorder, he had survived for a long time because of enzyme replacement therapy (ERT). He could usually communicate with simple movements of his tongue and eyes because the muscle function of his tongue and eye movement had been preserved. However, when he visited the emergency department, he could not move his tongue and eyes. He also displayed peripheral perfusion disorder.
Take-Home Message
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•
Complete atrioventricular block is a rare complication in patients with infantile-onset Pompe disease who have been receiving enzyme replacement therapy for a long time.
Past Medical History
The patient was born at term (37 weeks of gestation) by vaginal delivery. He weighed 2,774 g, and his Apgar score was 8 and 9 at 1 and 5 minutes after birth, respectively. He exhibited hypotonia on physical examination, and blood examination revealed an elevated creatine kinase level. Although he had symptoms of specific muscle and nerve diseases, he could not be diagnosed during the neonatal period. At 6 months of age, he was diagnosed with IOPD based on decreased α-glucosidase activity. Simultaneously, cardiomegaly with left ventricular hypertrophy was noticed by radiography and cardiac echocardiography. The left ventricular mass index, as calculated, was over 150 g/m2, and ERT was initiated when he was 8 months old, and left ventricular hypertrophy subsequently improved remarkably in a time-dependent manner.1
Differential Diagnosis
Although left ventricular hypertrophy had improved on initiation of ERT, it was important to first rule out obstruction of the left ventricular outflow tract. The patient could not explain the distinctive symptoms of ischemia, so careful examinations were necessary. Moreover, an elongated QRS complex and a shortened PR interval were observed in his baseline electrocardiogram (ECG) (Figure 1). The wide QRS complex was partially due to left ventricular hypertrophy. It was important to consider Wolff-Parkinson-White syndrome based on the shortened PR interval because one of its complications, paroxysmal tachyarrhythmia, must be carefully managed until ECG examination was performed.
Figure 1.
Electrocardiogram in Usual Condition
Investigations
The ECG (Figure 2) showed atrial tachycardia at 120 beats/min, complete atrioventricular block (cAVB), and a slow narrow escape rhythm. Laboratory tests detected mildly increased aspartate aminotransferase and alanine aminotransferase levels. The creatine phosphokinase level was slightly elevated, but the myocardial band isozyme level was within the normal range. The N-terminal pro–B-type natriuretic peptide level was slightly elevated than usual (158 pg/mL). The most recent echocardiography did not show left ventricular outflow obstruction, and the left ventricular ejection fraction was 65% and wall motion was not reduced.
Figure 2.
Electrocardiogram in the Emergency Department Showing Atrial Tachycardia, Complete Atrioventricular Block, and a Narrow Complex Escape Rhythm of 22 beats/min
Management
Treatment was started with intravenous injection of atropine and isoproterenol, but bradycardia with cAVB did not improve. Temporary transvenous cardiac pacing was placed at the right ventricular apex via the femoral vein approach. On ventricular pacing, although he had remained hemodynamically stable, cardiomegaly slightly deteriorated because of dyssynchrony, and the B-type natriuretic peptide level was higher (75.1 pg/mL) than before. In chest radiograph examination, the cardiothoracic ratio was larger than before. Although biventricular pacing was considered preferable based on these findings, implantation of a permanent pacemaker in precordia would be at high risk for infection because tracheotomy had been performed. In addition, taking his low activities of daily living into account, it was determined that sufficient cardiac output could be maintained by VVI pacing, and implantation of a leadless pacemaker into the right ventricle was attempted. However, the 27-F sheath could not be inserted into his femoral vein due to the size of the blood vessel. Thus, implantation of a permanent pacemaker was considered and then successfully performed. The biventricular DDD pacing mode was selected and worked well. In case of rapid atrial tachycardia, the DDD pacing rate was set to 60 to 130. Cardiomegaly improved and the B-type natriuretic peptide level dramatically decreased to 11.5 pg/mL under pacemaker control.
Discussion
In patients with IOPD, symptoms start very early in life. These patients show generalized muscle weakness and heart failure in early infancy. Heart failure is a fatal condition, and these patients often do not survive beyond the first year of life. Hence, the treatment of IOPD was challenging until ERT, namely, recombinant human α-glucosidase, was developed. This dramatically improved the survival rate, and the U.S. Food and Drug Administration approved the use of Myozyme (alglucosidase alfa) for IOPD in 2006.2 ERT reduces the risk of death and use of invasive ventilation when it is initiated before 6 months of age.3 Even when ERT is initiated after the age of 6 months, it improves survival and prolongs invasive ventilation-free periods.4 In addition, 2 studies reported that ERT reduces the left ventricular mass.
In Pompe disease, ECG abnormalities are usually found. A shortened PR interval, increased QT dispersion, and large left ventricular voltages are hallmarks of this disease.5 It is speculated that the shortened PR interval is related to the enlargement of cells with accumulation of glycogen, thereby accelerating the conduction speed.6,7 Increased QT dispersion and large left ventricular voltages are associated with left ventricular hypertrophy. Although it is unclear whether these ECG abnormalities are associated with this disease, some patients show supraventricular tachyarrhythmia or premature ventricular contractions.8 However, life-threatening atrioventricular conduction delay has been rarely reported in Pompe disease. Sacconi et al9 reported 4 patients with severe atrioventricular block requiring pacemaker implantation among a cohort of 131 French late-onset Pompe disease patients. They concluded that ERT does not protect against the development of atrioventricular block because 3 of these 4 patients were receiving ERT before the onset of symptoms. Taking these findings into consideration, close cardiac follow-up, including Holter ECG monitoring, should be performed regularly in patients with IOPD.
Follow-Up
A pacemaker check has been performed biannually. The pacemaker works accurately for atrial sensing and ventricular pacing. A follow-up radiograph showed no re-worsening of cardiomegaly, and echocardiographic evaluation showed that the left ventricular ejection fraction was maintained at 60% to 70%. Laboratory tests showed that the B-type natriuretic peptide level was within the normal range. ERT has been continued every 2 weeks.
Conclusions
In patients with IOPD, although cAVB is rare, it sometimes occurs as a complication of this disease. With a long-term view, close cardiac follow-up, not only by echocardiography assessing cardiac function and ventricular hypertrophy but also by Holter ECG monitoring assessing arrhythmic problems, must be performed in patients with IOPD, even those who are receiving ERT.
Funding Support and Author Disclosures
This work was supported by Grant-in-Aid for Scientific Research(C) 24K11288. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
References
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