Complex atrial tachycardias and respiratory syncytial virus infections in infants

Complex atrial tachycardias and respiratory syncytial virus infections in infants Richard L, Donnerstein, MD, Robert A, Berg, MD, Ziad Shehab, MD, a n d M a r c O v a d i a , MD From the Department of Pediatrics, Steele Memorial Children;s Research Center, Diamond Research Laboratory and University Heart Center, University of Arizona Health Sciences Center, Tucson Respiratory syncytial virus (RSV), a c o m m o n cause of respiratory infections in children, has only rarely been associated with a c q u i r e d heart disease. We rev i e w e d hospital charts, rhythm strips, and electrocardiograms of 8 infants with abnormal supraventricular t a c h y c a r d i a (SVT), >250 beats/min, associated with acute RSV infections. Cultures of n a s o p h a r y n g e a l specimens from six of eight infants grew RSV. Two infants with n e g a t i v e viral culture results had symptoms typical of an RSV infection during a d o c u m e n t e d RSV epidemic. Two infants had c o n g e n i t a l heart defects. Seven of the eight infants had an e c t o p i c atrial tachycardia, c h a o t i c atrial tachycardia, or atrial flutter, and five of eight had episodes of nonsustained w i d e - c o m p l e x SVT. One patient was initially treated with intravenously administered l i d o c a i n e for an incorrect diagnosis of ventricular tachycardia. SVT was unrelated to either ~'-agonist therapy or hypoxic episodes. SVT did not recur after discharge in any infant with a structurally normal heart. Both patients with structural heart disease had recurrences of SVT. We c o n c l u d e that RSV infections in infants may be associated with unusual atrial tachycardias and that the diagnosis may be c o m p l i c a t e d by episodes of nonsustained, w i d e - c o m p l e x tachycardias. In patients with RSV and structurally normal hearts, c h a o t i c and e c t o p i c atrial tachycardias are self-limited and do not require p r o l o n g e d drug therapy. (J PEDIATR1994;125:23-8)

Respiratory syncytial virus is the most common cause of lower respiratory tract infections in children. 13 Despite therapy with/%agonist agents and occasional hypoxemia, RSV infections have only rarely been associated with cardiac dysrhythmias. 47 Supraventricular tachycardia, the most common serious cardiac dysrhythmia in the pediatric age range, is generally caused by a reentrant mechanism, and the QRS complex is usually narrow. 8 Primary atrial tachycardias, such as Submitted for publication June 3, 1993; accepted Jan. 31, 1994. Reprint requests: Richard L. Donnerstein, MD, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, AZ 85724. Copyright ® 1994 by Mosby-Year Book, Inc. 0022-3476/94/$3.00 + 0 9/20/54859

ectopic atrial tachycardia, chaotic atrial tachycardia or atrial flutter, and wide-complex SVT, are unusual in children with structurally normal hearts. 8-11 In 1988 a child with an RSV infection was referred to us because of multiple short episodes of a wide-complex tachycardia that was unsuccessfully treated with a lidocaine RSV SVT

Respiratory syncytial virus Supraventricular tachycardia

infusion after a presumptive diagnosis of ventricular tachycardia. A review of electrocardiograms demonstrated that the dysrhythmia was an unusual atrial tachycardia. This patient and seven subsequent patients with SVT form the basis for this report. Seven of the eight patients had a primary atrial tachycardia (automatic ectopic atrial tachy-

23

24

Donnerstein et al.

The Journal of Pediatrics July 1994

Table. Patient characteristics

Patient No. Sex

Age

t3-Agonist before QRS Viral Heart Mechanical dysDysaberstudies defects ventilation rhythmia rhythmia rancy

1

M

4 wk

RSV*

-

+

-

2 3

F M

5 mo 7 wk

RSV NG

+ -

-

-

4 5

M M

1 mo 16 days

RSV RSV

-

+ -

+ +

6

F

7 wk

NG

-

+

+

7

M

11 mo

RSV

+

-

-

8

M

12 days

RSV

-

-

-

AAT vs CAT AAT AAT vs CAT PSVT AFI

AAT vs CAT AAT AAT vs CAT

+ + -

+ + +

Drug treatment Lidocaine, propranolol Propranolol Digoxin, propranolol Digoxin Digoxin, propranolol, quinidine Digoxin, propranolol Propranolol, procainamide -

Follow-up Follow-up dysinterval rhythmia (¥r) -

5.5

AF1 -

0.3t 1.0:~

-

2.7 2.6

-

2.6

AAT

1.8

-

1.7

AAT, Automatic ectopic atrial tachycardia; AFI, atrial flutter; CAT, chaotic atrial tachycardia; NG, no growth of viral cultures; PSVT, paroxysmal supraventricular tachycardia. *Virus grown from viral cultures. ?Died :~Lost to follow-up.

cardia, chaotic atrial tachycardia, or atrial flutter), and five had multiple episodes of a nonsustained wide-complex SVT. All patients had episodes of SVT unrelated to hypoxemia or /3-agonist therapy. METHODS Hospital charts and electrocardiograms were reviewed for all eight subjects. For each patient the following information was obtained" (1) age, (2) sex, (3) length and weight, (4) clinical characteristics of illness, (5) results of viral and bacterial cultures, (6) history of cardiovascular disease, (7) medications taken before onset of tachydysrhythmia, (8) evidence of hypoxia before onset of tachydysrhytbmia, (9) type of dysrhythmia, (10) medications used to treat tachydysrhythmia, (11) interpretation of electrocardiogram during sinus rhythm, (12) length of time between onset of illness and the most recent episode of tachydysrhythmia, and (13) follow-up interval. All patients were followed by a pediatric cardiologist after discharge from the hospital. Heart rhythm analysis. For the purposes of this study, supraventricular tachycardia is defined as an abnormal tachycardia (>250 beats/rain or paroxysms of tachycardia) resulting from an abnormality proximal to the bundle of His. Surface electrocardiograms obtained during SVT were evaluated for maximal heart rate, duration of SVT, presence or absence of P waves, morphologic features of P waves, coupling of initial P wave of the tachycardia to the previous sinus P wave, maximal P R interval, variation of

P-P, PR, and R - R intervals, initial decrement of tachycardia cycle length ("warm-up"), Q R S duration and morphologic features, atrioventricular block, and echo beats. Standard 12-lead electrocardiograms obtained during sinus rhythm were evaluated for heart rate, P-wave and Q R S morphologic characteristics, intervals (PR, QT, and Q R S ) , axes (P, QRS, and T waves), delta waves, and echo beats. At least five of the following criteria were required for the diagnosis of automatic ectopic atrial tachycardia: (1) visible P waves of a single morphologic feature (but not flutter waves) during tachycardia, (2) variability in coupling between the initial P wave of the SVT and the preceding sinus P wave, (3) decreasing P-P interval during the start of the tachycardia ("warm-up"), (4) variability of P R interval during tachycardia, (5) variability of R - R interval with time, and (6) absence of evidence of atrioventricular node reentry or atrioventricular reciprocating tachycardia. 9 A diagnosis of chaotic atrial tachycardia was considered if there were (1) at least three different P wave morphologic features, (2) varying P-P, PR, and R - R intervals, and (3) a discrete isoelectric baseline between P waves) °, tl Diagnosis of RSV infection. The diagnosis of RSV infection was confirmed by culture and antigen detection techniques described previously. 2 Specimens obtained by nasopharyngeal and throat swabs were cultured and tested for respiratory viral antigens by direct and indirect immunofluorescence. 12

The Journal of Pediatrics Volume 125, Number 1

RESULTS Clinical data are summarized in the Table. Examples of dysrhythmias are shown in Figs. 1 to 3. Patient population. Patients consisted of six boys and two girls with ages ranging from 12 days to 11 months (mean, 2.5 months). RSV infection was established in six infants by detection of RSV in cultures, viral antigen detection by immunofluorescence, or both. Two additional infants with negative findings in viral studies (patients 3 and 6) were included because they had bronchiolitis during a well-established RSV epidemic and did not have any other respiratory viral pathogen identified. Six patients had no prior history of cardiovascular disease; two had congenital heart disease, including an atrioventricular canal (patient 2) and an anomalous left coronary artery (patient 7). Respiratory therapy. All patients were monitored by pulse oximetry. Three patients required mechanical ventilation for severe respiratory distress. Oxygen saturation by pulse oximetry was <50% for approximately 1 minute in patient 6 immediately before endotracheal intubation. Oxygen saturation remained >90% in all other patients. All three patients requiring endotracheal intubation continued to have episodes of SVT despite >24 hours of mechanical ventilation with oxygen saturation >90%. Three patients received albuterol aerosol therapy before their initial episode of SVT. In two patients the initial episode of SVT occurred 2 hours (patient 4) and 14 hours (patient 5) after their most recent aerosol treatments with 0,1 mg/kg of albuterol. Patient 6 had received continuous albuterol aerosol treatment immediately before endotracheal intubation. All three patients receiving albuterol aerosols continued to have episodes of SVT more than 24 hours after this therapy was discontinued. Dysrhythmias. All patients had SVT with heart rates of at least 250 beats/rain. Examples of tachycardias are shown in Figs. 1 to 3. As noted in the Table, seven patients had primary atrial tachycardias. The P waves could not be seen well enough in four patients to differentiate between automatic ectopic atrial tachycardia and chaotic atrial tachycardia; however, the presence of atrioventricular block suggested that these patients had a primary atrial tachycardia. Five patients had nonsustained wide-complex SVT caused by aberrant ventricular conduction (Fig. I). In all patients with wide-complex SVT, the QRS complex became narrow if the tachycardia lasted a sufficient time. Vagal maneuvers terminated the dysrhythmia in only one patient (patient 4); his dysrhythmia was consistent with atrioventricular node reentrant tachycardia or atrioventricular reciprocating tachycardia. Antiarrhythmie therapy. One of our patients with a nonsustained wide-complex SVT was initially treated with lidocaine (patient I). Six patients received propranolol, 4

Donnerstein et al.

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received digoxin, 1 received procainamide, 1 received quinidine, and 1 received no antiarrhythmic medication. No patient with a primary atrial tachyeardia responded adequately to digoxin alone. Propranolol provided satisfactory control of chaotic or automatic ectopic atrial tachycardias in 5 patients, and procainamide was used in 1 patient. Patient follow-up. Both patients with congenital heart

26

Donnerstein et al.

The Journal of Pediatrics July 1994

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defects continued to have primary atrial dysrhythmias after their acute episodes. Patient 2 died after cardiac surgery. None of the six patients without heart defects have had a recurrence of their SVT. Patient 3 was lost to follow-up after 1 year, and the remaining five have been followed from 1.7 to 5.5 years (mean, 3.0 years). DISCUSSION Our recognition of SVT in infants with RSV infection was facilitated by the current common practice of contin-

uous cardiorespiratory monitoring of all hospitalized children with respiratory distress or a diagnosis of RSV infection. This series of patients suggests an association between RSV and unusual supraventricular tachycardias: chaotic atrial tachycardia, automatic ectopie atrial tachycardia, atrial flutter, and nonsustained wide-complex SVT. These dysrhythmias may cause significant diagnostic and therapeutic problems. Dysrhythmias, including ectopic beats,19 various degrees of heart block, 14 and SVT, 15' 16 have been associated with

The Journal o f Pediatrics Volume 125, Number 1

viral infections. In a report by Ming et al., 1° the majority of 22 infants with chaotic atrial tachycardias had respiratory disease. However, only isolated case reports have suggested an association of RSV with dysrhythmias, including three cases with complete heart block4-6 and one with SVT. 7 In two of the three reported cases, complete heart block did not resolve after the patients recovered from their infections. 46 Menahem 7 described a single case of a 7-week-old infant who had a chaotic atrial tachycardia in association with an RSV infection. The patient responded to digoxin and had no further episodes of SVT after hospital discharge. These cases suggest that RSV, through invasive, inflammatory, or toxic effects, can cause acute or chronic rhythm disturbances. Atrioventricular node reentrant tachycardia and atrioventricular reciprocating tachycardia (such as Wolff-Parkinson-White syndrome) are the usual mechanisms of abnormal SVT in children; atrial flutter, chaotic atrial tachycardia, and automatic ectopic atrial tachycardia are relatively unusual, s Six of our eight patients had an automatic ectopic atrial tachycardia or chaotic atrial tachycardia similar to that described by Menahem 7 in his patient. One patient had atrial flutter, which also suggests focal disease at the atrial level. Only one patient had a dysrhythmia consistent with an atrioventricular node reentrant tachycardia or atrioventricular reciprocating tachycardia. None of our six patients with a structurally normal heart had documented recurrence of SVT more than 1 month after hospital discharge or after discontinuation of antiarrhythmic medications. Sustained wide-complex tachycardias in children are usually due to ventricular tachycardia. 8 However, most of our patients had multiple nonsustained episodes of SVT beginning with aberrancy, and a diagnosis of ventricular tachycardia was frequently considered. Misdiagnosis of the dysrhythmia as ventricular tachycardia in one patient resulted in unnecessary, potentially harmful therapy with lidocaine. Although most of our patients with chaotic and automatic ectopic atrial tachycardias responded well to propranolol, fl-blockers should be used cautiously in patients with obstructive airway disease. We included two patients with preexisting heart disease because both of these patients with documented RSV infection had tachydysrhythmias similar to those of our patients without structural heart defects. Neither of these patients had ectopic atrial tachycardia before the illness with RSV. Both patients with structural heart disease had persistent atrial dysrhythmias. It is possible that the acute systemic illness precipitated an atrial tachycardia at the site of underlying atrial disease and resulted in a chronic cardiac abnormality. Although it is possible that some of the dysrhythmic ep-

Donnerstein et al.

27

isodes may have resulted from medications (e.g., j3-agonists), it is unlikely that this was the sole cause because dysrhythmias continued long after these medications were discontinued. Moreover, in all our patients dysrhythmias occurred either before initiation of ~3-agonist therapy or long after their effects should have dissipated. Although potentially beneficial for some children with RSV bronchiolitis, B-agonist therapy should be used cautiously in patients with SVTs. It is unlikely that significant hypoxemia contributed to the development of the tachydysrhythmias. All patients were monitored by pulse oximetry and, if necessary, received oxygen therapy or mechanical ventilation to maintain oxygen saturation at more than 90%. Although three patients required mechanical ventilation for respiratory distress, each later had multiple episodes of SVT unrelated to hypoxemia. The presentation of our patients suggests that their dysrhythmias were caused by direct invasion of the heart (myocarditis), myocardial irritation from adjacent pneumonitis, or toxic effects from RSV. Myocarditis in human beings has been associated with multiple viruses 17 but rarely with RSV. 6 All six of our patients without congenital heart disease underwent echocardiography during their acute illness. Four of these patients had normal systolic function and 2 (patients 3 and 6) had mildly decreased left ventricular function that later resolved. We did not obtain tissue diagnosis for any of our patients and therefore cannot determine with certainty whether focal myocarditis or cardiac injury contributed to the dysrhythmias. In this study, all patients were either less than 2 months of age or had preexisting structural heart disease. These findings may have resulted from the inability of young infants or children with abnormal hearts to tolerate the excess stress caused by an RS V infection. On the other hand, the characteristics of our patients may simply reflect those patients with RSV who are most commonly admitted to the hospital. Signs of viral respiratory infections are present in 60% to 75% of all cases of sudden infant death syndrome. 18 Postmortem examinations do not reveal life-threatening acute pulmonary abnormalities, t8 The association of SVT with RSV infections raises the possibility that some children with RSV infections may incur more severe fatal dysrhythmias, and thereby be considered to have had sudden infant death syndrome. Further investigation of this issue is warranted. We conclude that there is an association between unusual supraventricular tachycardias and RSV infections in infants. These observations underscore the importance of careful electrocardiographic monitoring of hospitalized childi~l with RSV infections.

28

Donnerstein et al.

REFERENCES

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The Journal of Pediatrics July 1994

10. Ming-yi W, Zhi-fang W, Xiu-yu C. Chaotic atrial tachycardia in 22 infants. Chin Med J (Engl) 1984;97:500~3. 11. Porter CJ. Premature atrial contractions and atrial tachyarrhythmias. In: Gillette PC, Garson A Jr, eds. Pediatric arrhythmias: electrophysiology and pacing. Philadelphia: WB Saunders, 1990:330-3. 12. Ray CG, Minnich LL. Efficiency of immunofluorescence for rapid detection of common respiratory viruses. J Clin Microbiol 1987;25:355-7. 13. Nathenson G, Spigland I, Eisenberg R. Benign neonatal arrhythmias and Coxsackie B virus infection [Letter]. J PEDIATR 1975;86:152-3. 14. Bergen D, Grossman H. Complete heart block in viral myocarditis [Letter]. J PEDIATR 1975;87:831-2. 15. Spencer MJ, Cherry JD, Adams FH, Byatt PH. Supraventricular tachycardia in an infant associated with a rhinoviral infection [Letter]. J PEDIATR 1975;86:811-2. 16. Cherry JD, Jahn CL, Meyer TC. Paroxysmal atrial tachycardia associated with echo 9 virus infection. Am Heart J 1967; 73:681-6. 17. Karjalainen J, Heikkila J, Nieminen MS, et al. Etiology of mild acute infectious myocarditis. Acta Med Scand 1983; 213:65-73. 18, MarfinezFD. Sudden infant death syndrome and small airway occlusion: facts and a hypothesis. Pediatrics 1991;87:190-8.