Neurological morbidity after fetal supraventricular tachyarrhythmia

Transcription

1 Ultrasound Obstet Gynecol 1999;13:43 47 Neurological morbidity after fetal supraventricular tachyarrhythmia R. P. Schade, P. Stoutenbeek*, L. S. de Vries and E. J. Meijboom Departments of Pediatric Cardiology, *Obstetrics and Neonatology, University Hospital/Wilhelmina Children s Hospital, Utrecht, The Netherlands Key words: ARRHYTHMIA, SUPRAVENTRICULAR TACHYCARDIA, ULTRASONOGRAPHY, FETAL, ENCEPHALOMALACIA ABSTRACT Background Fetal tachyarrhythmia is a well-documented entity which, in the absence of pharmacological intervention, may lead to congestive heart failure, fetal hydrops and eventually fetal demise. The success rate of the implemented treatment is generally measured by survival and achievement of control of the arrhythmia. We report on the occurrence of associated cerebral damage in three patients with fetal tachycardia. Methods We describe three patients with a history of fetal supraventricular tachyarrhythmia who developed cerebral complications in utero. Results Two patients had cerebral hypoxic ischemic lesions and one had hemorrhagic lesions present at birth. They had developed severe congestive heart failure and fetal hydrops secondary to fetal tachyarrhythmia, and there were no other obvious causes for the cerebral pathology. Two of these patients were referred to us antenatally. Therapy was instituted and resulted in control of the tachycardia and resolution of hydrops. The third patient was referred to our clinic shortly after birth because of severe circulatory problems secondary to fetal tachyarrhythmia. Conclusion From these observations, we believe that a fetus with tachyarrhythmia and subsequent hydrops is at increased risk for the development of cerebral complications, due to the circulatory disturbances and sudden changes in heart rate which may lead to fluctuations in cerebral perfusion. This would imply that it is of the utmost importance to aim at immediate and complete control of the heart rate in the treatment of fetal tachyarrhythmia. INTRODUCTION Since the advent of prenatal ultrasonographic diagnosis, fetal supraventricular tachyarrhythmia has become a welldescribed entity 1 4. It is accepted that sustained tachycardia in the fetus requires instant treatment, whether it is supraventricular tachycardia or atrial flutter. Without treatment these fetuses may develop congestive heart failure leading to fetal hydrops and eventually fetal demise 2. The success rate of the implemented pharmacological treatment is generally measured by survival and achievement of control of the arrhythmia, pre- and postnatally. This report focuses on the occurrence of associated cerebral damage in three neonates with a history of fetal supraventricular tachyarrhythmia. Two of these cases originated from our fetal cardiology program. The third was referred to our clinic shortly after birth because of severe circulatory problems secondary to fetal tachyarrhythmia. The case histories of these three patients are described in detail to illustrate the cerebral complications that may occur in association with fetal tachyarrhythmia. CASE REPORTS Case 1 A woman, gravida 5, para 3, was referred to our outpatient clinic at 25 1/7 weeks gestational age with fetal hydrops. The pregnancy had been uncomplicated and the woman had no history of prior disease. Fetal ultrasound examination showed extensive hydrops with hydrothorax and ascites, and normal intracardiac anatomy. M-mode echocardiography showed a paroxysmal supraventricular tachycardia of 245 beats/min (1 : 1 atrioventricular conduction), with intercurrent periods of bradycardia (60 beats/min) that gradually converted into sinus rhythm. Doppler flow measurements of the fetal heart were within the normal range. Pharmacological intervention was started with maternal therapy of flecainide mg. Two weeks later, when conversion to persistent sinus rhythm had not been achieved, the therapy was changed to sotalol (initially 3 80 mg, eventually mg), after a maternal electrocardiogram (ECG) proved normal. This converted the fetal heart rate to a sinus rhythm Correspondence: Dr E. J. Meijboom, Wilhelmina Children s Hospital, Department of Pediatric Cardiology, PO Box 18009, 3501 CA Utrecht, The Netherlands ORIGINAL PAPER 43 Received Revised Accepted

2 of 130 beats/min and was followed by a gradual partial resolution of the hydrops. At 34 2/7 weeks, the mother felt reduced fetal movement; the cardiotocogram (CTG) showed signs of fetal distress, and an emergency Cesarean section was therefore performed. A 2.64-kg, moderately hydropic male infant was delivered with Apgar scores of 3, 7 and 9 at 1, 5 and 10 min, respectively. The first (capillary) blood gas analysis at 1 h showed a ph of 7.28 and a base excess of 0.9 mmol/l. Despite a loading dose of digoxin, the infant experienced several periods of supraventricular re-entry tachycardia (Wolff Parkinson White type) with a heart rate of more than 220 beats/min in the first 36 h of life. These periods caused minor circulatory deterioration and could be converted to sinus rhythm only with intravenous adenosine. During the first 15 days of life, short periods of tachycardia (of less than 1 min) continued to occur without hemodynamic consequences. Sotalol was added, and this controlled the heart rate permanently. On cranial ultrasound examination, performed within the first hours of life, multiple areas of increased echogenicity in the periventricular white matter were seen. These did not develop into cystic lesions, but a repeat ultrasound scan at 11 months of age showed mild ventricular dilatation with widening of the interhemispheric fissure suggestive of atrophy, occurring following grade I periventricular leukomalacia. The infant was last seen at 16 months of age and showed a global developmental delay with a developmental quotient of 63 out of 100 at a corrected age of 16 months on the Griffiths developmental assessment scale. Case 2 During routine obstetric examination at 28 5/7 weeks gestational age, a woman, gravida 2, para 1, was seen with acute onset of fetal hydrops in an otherwise uncomplicated pregnancy. After referral to our outpatient clinic, fetal ultrasound examination showed hydrothorax and ascites, and normal intracardiac anatomy. Extensive serological investigation ruled out maternal and immunological causes for the hydrops, and M-mode echocardiography showed no irregularities. On re-examination 3 days later, M-mode echocardiography showed a paroxysmal supraventricular tachycardia of 360 beats/min (1 : 1 atrioventricular conduction), with Doppler flow measurements within the normal range. Pharmacological intervention was started with maternal therapy of sotalol 3 80 mg after the maternal ECG proved normal. Short recurrent periods of paroxysmal supraventricular tachycardia required an increase of the sotalol regime to, eventually, mg. Only after the addition of digoxin mg did the hydrops resolve. At 32 6/7 weeks, labor started spontaneously and a non-hydropic male was delivered. Birth weight was 2.14 kg and Apgar scores were 8 and 8, at 1 and 5 min, respectively. The first (capillary) blood gas analysis at 1 h showed a ph of 7.32 and a base excess of 1.4 mmol/l. The infant experienced three periods of supraventricular re-entry tachycardia (Wolff Parkinson White type) with heart rates of 280 beats/min in the first 15 days of life. These episodes could be converted to sinus rhythm with intravenous adenosine. Sotalol was added, after which permanent control of the heart rate was achieved. Cranial ultrasound examination, performed within the first hours of life, showed a left-sided porencephalic cyst with a resolving clot in the left ventricle (Figure 1). The ventricular size did not increase initially, but a repeat ultrasound study 7 weeks after birth showed an increase in size of the left ventricle and a porencephalic cyst with a shift of the midline, suggestive of an obstruction at the level of the foramen of Monro. These findings were confirmed on magnetic resonance imaging (MRI). The size of the left ventricle continued to increase and therefore a ventriculoperitoneal drain was inserted in the left ventricle. The infant was last seen at 20 months of age. His developmental quotient was 99 out of 100 when uncorrected for prematurity, and 107 when corrected. He is able to use both hands, but has mild hemiplegia. Case 3 A woman, gravida 2, para 1, had an uncomplicated pregnancy until the development of a large-for-gestational-age uterus at 27 weeks. Ultrasound examination at another hospital showed polyhydramnios, but otherwise there was no significant morbidity. Normal heart sounds were reported and no attempts at further investigation or referral for a level-3 ultrasound examination were Figure 1 Case 2: sequential cranial ultrasound scans during the first hours of life, showing a left-sided porencephalic cyst and resolving clot in the (increased) left ventricle 44 Ultrasound in Obstetrics and Gynecology

3 undertaken. A CTG performed at 37 weeks showed very irregular tracings. Spontaneous labor occurred at 37 2/7 weeks and a massively hydropic female was born with a birth weight of 3.75 kg. The patient was severely hypotonic and had absent heart sounds, therefore requiring immediate resuscitation. The first (capillary) blood gas analysis at 15 min showed a ph of 6.5 and a base excess of 15 mmol/l. The patient was intubated and ventilated, but the heart rate remained very irregular. Capillary blood gas analysis at 2 h revealed a ph of 7.01 and base excess of 11 mmol/l. On transfer to our hospital, 2.5 h after birth, a severely irregular heart rate and poor circulatory status were noted, with an atrial flutter of beats/min and variable atrioventricular block. Echocardiography showed normal cardiac anatomy with an enlarged right atrium. Sinus rhythm could not be achieved by cardioversion, but, after a loading dose of intravenous digoxin, the heart rate converted to a sinus rhythm during the following day. Cranial ultrasound examination, performed within the first hours of life, showed extensive subcortical echogenicity suggestive of severe leukomalacia (Figure 2). Electroencephalography showed a severely abnormal background pattern, the sensory-evoked potential was normal, the visual-evoked potential was delayed and the auditory brain reflex could not be obtained at 90 db. On the basis of these results (evidence of severe cerebral ischemia), further therapeutic support was withdrawn and the patient died at 2 days of age. Postmortem examination On postmortem examination, there were multiple signs of generalized ischemia secondary to cardiac failure. The cerebrum showed widespread ischemic damage, predominantly periventricular leukomalacia. There were no structural organ malformations. DISCUSSION The presentation of fetal supraventricular tachyarrhythmias has a wide range of severity. At one end of the spectrum there are frequently occurring but relatively benign premature atrial contractions. More serious are the patients with paroxysmal tachycardia. Although most of these tachycardias are not immediately threatening to the condition of the fetus, treatment is usually instituted. The fetuses showing sustained tachycardia, either atrial flutter or reentry tachycardia, represent the most severe end of the spectrum. The arrythmia-induced circulatory failure in these fetuses can lead to fetal hydrops and thus constitute a significant threat to the patient. It is therefore generally agreed that therapeutic intervention should be undertaken, either directly in the fetus, or in the mother. Various types of therapy with different success rates have been described 4 8. Generally, success is measured by the achievement of a normal sinus rhythm, creation of a partial block resulting in a more or less adequate ventricular rate, disappearance of fetal hydrops and survival of the fetus resulting in a healthy live-born infant. The neurological condition of the treated children, however, has received little attention. We carefully reviewed the literature and found six cases of fetal tachycardia in whom cerebral complications were diagnosed in utero or shortly after birth These cases all concerned patients with a history of fetal tachyarrhythmia and subsequent congestive heart failure and fetal hydrops. In the three patients with fetal tachyarrhythmia that we describe in this report, the cerebral lesions were present at birth which clearly indicates that the pathological events causing these lesions must have taken place in utero. In Case 1, cranial ultrasonography showed extensive periventricular echogenicity, indicating an intrauterine cerebral hypoxic ischemic event. In Case 2, the presence of a porencephalic cyst at birth indicated that periventricular hemorrhage had occurred in utero. In Case 3, the extensive periventricular and subcortical echogenicity seen at birth indicated a sustained period of cerebral ischemia in utero. All three patients had developed congestive heart failure and fetal hydrops secondary to periods of fetal supraventricular tachyarrhythmia and had no other obvious causes for the intrauterine onset of cerebral damage. Fetal tachycardia was documented in the first two cases and seems likely in the third. This case shares the postnatal features including non-immune hydrops and atrial flutter, and is Figure 2 Case 3: sequential cranial ultrasound scans during the first hours of life, showing extensive subcortical echogenicity suggestive of severe subcortical leukomalacia Ultrasound in Obstetrics and Gynecology 45

4 included in our report with the assumption that the fetal atrial flutter was responsible for the poor circulatory condition of the patient at birth. Irregular tracings of the CTG, which showed an irregular fetal ventricular rate, and absence of other obvious causes for the non-immune hydrops make it very likely that the postnatal atrial flutter with variable atrioventricular block was already present antenatally. Of primary importance in the etiology of both hypoxic ischemic and hemorrhagic cerebral lesions is the disturbance of the maintenance of adequate cerebral perfusion. In adults as well as unstressed newborns, this maintenance is provided by an autoregulatory mechanism of arteriolar vasoconstriction/vasodilatation which maintains a constant cerebral blood flow over a broad range of perfusion pressures 14. Loss of this cerebrovascular autoregulation will result in a pressure-passive phenomenon, whereby a reduction or increase in mean arterial blood pressure is accompanied by a concomitant reduction or increase in cerebral blood flow. In the distressed newborn, cerebral autoregulation is lost, exposing the brain to ischemia in even moderate hypotension and to an increased pressure gradient across the capillary wall in even moderate hypertension, with increased risk of intracranial hemorrhage 15. Experimental studies in the fetal lamb have shown that this certainly applies to the distressed fetus in utero: a period of intrauterine distress causes abolition of cerebral autoregulation leading to severe impairment of the maintenance of constant cerebral perfusion 16,17. A fetus presenting with hemodynamic compromise and hydrops secondary to fetal tachyarrhythmia is therefore at increased risk for development of a pressure-passive cerebral circulation and the cerebral complications that may result from this. In the group of 18 patients diagnosed with fetal supraventricular tachyarrhythmia at our fetal cardiology clinic between 1990 and 1997 (Table 1), seven patients had developed non-immune hydrops secondary to the arrhythmia, and two of these seven developed cerebral complications in utero (Cases 1 and 2). Neurological evaluation including cranial ultrasonography showed no abnormalities in the other 16 patients. Gestational age is likely to be another important factor in the intrauterine onset of cerebral morbidity. Early in gestation, the autoregulatory range of systemic blood pressures is narrow and, as cerebral autoregulation matures with increasing gestational age, maintenance of constant cerebral blood flow is provided over a larger range of arterial pressures 15,17. This suggests that the margin of safety for circulatory events secondary to fetal tachycardia Table 1 Patients with fetal supraventricular tachyarrhythmia at our fetal cardiology clinic between 1990 and 1997 Prenatal history Number of patients No fetal hydrops, no treatment 3 No fetal hydrops, pharmacological treatment 8 Fetal hydrops, no treatment 1 Fetal hydrops, pharmacological treatment 6 Total 18 is small in the immature fetus, and is more likely to lead to disturbance of constant cerebral perfusion than in the older fetus. In the seven patients with fetal tachyarrhythmia and hydrops whom we have encountered between 1990 and 1997, the mean gestational age of presentation was lower in the patients who developed cerebral complications than in those who did not: 26.9 weeks (range weeks) vs weeks (range weeks). Unfortunately, our group of patients is too small for us to draw definite conclusions about gestational age as a risk factor. We assume that the short recurrences of tachycardia occurring with incomplete control of the fetal heart rate are also of significance in the etiology of cerebral complications. The sudden changes in heart rate occurring when a fetus switches back and forth from sinus rhythm to tachycardia may have serious consequences for the maintenance of constant cerebral perfusion when autoregulation is impaired. Fluctuations in arterial blood pressure will then lead to similar changes in cerebral blood flow, and these fluctuations predispose the fetal brain to periventricular ischemic lesions and periventricular hemorrhage 15,18. The three patients whom we describe were exposed to rapidly changing heart rates in utero. In the first two cases, periods of paroxysmal tachycardia had been present for at least 1 week before therapy was started, and frequent relapses from sinus rhythm into tachycardia and back to sinus rhythm were registered in both cases before the instituted therapy permanently controlled the heart rate. In the third patient, control of the heart rate was not achieved, exposing the fetal brain to the effects of the rapidly fluctuating heart rates of the atrial flutter. We believe that in these patients the repeated and prolonged intrauterine periods of tachycardia with subsequent hemodynamic decompensation and fetal hydrops resulted in hypoxic ischemic and hemorrhagic damage of the fetal brain. The severe circulatory disturbances that occur in fetal tachyarrhythmia 19,20 may have provoked a pressure-passive cerebral circulation, and the sudden changes in heart rate may have consequently led to similar fluctuations in cerebral perfusion and thus formed the determining factor in the development of cerebral damage. The observations in this report suggest in our opinion that rapid and persistent control of the fetal heart rate could be of primary importance in the prevention of cerebral complications of fetal tachycardia. A fetus with hemodynamic compromise secondary to tachyarrhythmia should therefore be treated resolutely with high doses of a drug that passes the placental barrier quickly. Some authors have advocated the use of direct fetal therapy 8,21. Although we have not used this method, it may be useful and could be considered when transplacental therapy fails to control the heart rate completely. CONCLUSION The observations in this report indicate that patients with fetal tachycardia may develop cerebral complications in utero. We believe that a fetus with tachyarrhythmia and subsequent hydrops is at increased risk for the 46 Ultrasound in Obstetrics and Gynecology

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