Congenital cardiomyopathy associated with human parvovirus B19 infection

Volume 133, Number 1 American Heart Journal

Table

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I. Predictors of risk of recurrence of neonatal supraventricular tachycardia Predictive value

Delta wave (preexcitation) Congestive heart failure Recurrence during treatment Inducible at T-EPS Initial control (two medications) Congenital heart disease

Predictor present (n = 21)*

Recurrence

p Value

Positive

Negative

8 (38%) 7 (33%) 5 (33%) 8 (43%) 4 (19%) 3 (14%)

3 2 2 0 1 0

0.010"~ 0.186 0.060 N/A 0.496 0.445

38% 29% 40% 00% 25% 00%

100% 93% 94% 100% 88% 84%

T-EPS, Transesophageal electrophysiologicstudy. *Except n = 19 in T-EPS. tSiguificant p value.

an asymptomatic patient r e m a i n s unclear. 7, s We have shown t h a t the presence of an inducible tachycardia does not necessarily correspond to clinically relevant phenomena in our population. These patients m a y develop recurrences during long-term follow-up. T-EPS would t h e n be a successful predictor of late recurrence; however, this study is unable to answer t h a t question. This study demonstrates t h a t the presence of a delta wave on E C G is the only significant factor in predicting early recurrence of neonatal SVT. However, secondary to the low recurrence rate of SVT after an asymptomatic period, the positive predictive value of preexcitation r em ai n s <40%. Although T-EPS can accurately identify a ftmctional accessory pathway, its usefulness and practicality in this population is unsubstantiated. In our practice, all patients who fail to d em o n s t r a te a delta wave on E C G receive a trial discontinuation of medical t h e r a p y after 6 months without symptoms. Patients exhibiting a delta wave are more perplexing. This study does not identify the opportune time to discontinue medical t h e r a p y in this population. Therefore, because 38% of infants with Wolff-Parkinson-White syndrome will exhibit a recurrence after a 6-month asymptomatic period w h e n not t a k i n g drug therapy, we suggest t r e a t i n g these patients for an extended period, until the child is verbal and is developmentally able to express early symptoms (i.e., palpitations). REFERENCES

1. Southall DP, Johnson AM, Shinebourne EA, Johnston PG, Vulliamy DG. Frequency and outcome of disorders of cardiac rhythm and conduction in a population of newborn infants. Pediatrics 1981;68:5866. 2. LundbergA. Paroxysmal atrial tachycardia in infancy: long-term follow-up study of 49 subjects. Pediatrics 1982;70:638-42. 3. Benson DW Jr, Dunnigan A, Benditt DG, Pritzker MR. Transesophageal study, of infant supraventricular tachycardia: electrophysiologic characteristics. Am J Cardiol 1983;52:1002-6. 4. Schaffer MS, Gillette PC. Ventriculoatrial intervals during narrow complexreentrant tachycardia in children. Am Heart J 1991;121:1699702. 5. Deal BJ, Keane JF, Gillette PC, Garson A. Wolff-Parkinson-White syadrome and supraventricular tachycardia during infancy: management and followup. J Am Coll Cardiol 1985;5:130-5. 6. Perry JC, Garson A. Supraventricular tachycardia due to WolffParkinson-White syndrome in children: early disappearance and late recurrence. J Am Coll Cardiol 1990;16:1215-20. 7. RhodesLA,Walsh EP, Saul JP. Programmed atrial stimulation via the

esophagus for management ofsupraventricular arrhythmias in infants and children. Am J Cardiol 1994;74:353-6. 8. PongiglioneG, Saul JP, Dunnigan A, Strasburger JF, BensonDW. Role of transeophageal pacing in evaluation of palpitations in children and adolescents. Am J Cardiol 1988;62:566-70.

Congenital cardiomyopathy associated with human parvovirus B19 infection Leslie L. Barton, MD, Daniela Lax, MD, Ziad M. Shehab, MD, and J e n n i f e r C. Keith, MD Tucson, Ariz. Parvovirus B19 is a known pathogen for the developing fetus. Affecting erythrocyte precursor cells, it m ay cause severe a n e m i a leading to hydrops fetalis and, rarely, death.1 Both immunochemical and histologic examinations of B19-infected fetal and other postmortem specimens h a v e demonstrated viral involvement of myocardial cells. 2, 3 Parvovirus B 19-associated myocarditis, however, has been documented only once previously, in a 1-year-old child. 3 We report a neonate born with a dilated cardiomyopathy in whom congenital infection with parvovirus B19 was documented by polymerase chain reaction (PCR). This case suggests t h a t parvovirus B19 infection should be considered in the differential diagnosis of perinatal cardiomyopathies. A 3165-gram, t e r m boy was born by spontaneous vaginal delivery to a 21-year-old w o m an (gravida 2, para 1). The m o t h e r h ad been i m m u n i z e d for rubella, was not reactive to rapid p l a s m a reagin (RPR), and apparently ha d an uncomplicated pregnancy. F a m i l y history was negative for cardiac disease. Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. At 2 hours of age, the infant was

From the Department of Pediatrics and The Steele Memorial Children's Research Center, The University of Arizona Health Sciences Center. Reprint requests: LeslieL. Barton, MD, SectionofPediatric InfectiousDiseases/3403, University ofArizonaHealth SciencesCenter, 1501 N. Campbell Ave., Tucson, AZ 85724-5073. Am Heart J 1997;133:131-3. Copyright © 1997 by Mosby-Year Book, Inc. 0002-8703/97/$5.00 + O 4/4/77021

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noted to be cyanotic and was given oxygen by hood. Progressive cyanosis and respiratory distress necessitated endotracheal intubation, mechanical ventilation, and umbilical artery catheterization. Chest radiographs showed marked cardiomegaly. The infant was transported on an emergency basis to University Medical Center. On admission, he had an oxygen saturation of 91% on 100% forced inspiratory oxygen; the respiratory rate was set at 40 breaths/min. The pulse was 140 beats/min, blood pressure (left upper extremity) was 80/64 mm Hg, and temperature was 98.0 ° F (36.7 ° C). Clear breath sounds were present bilaterally. He had normal first and second heart sounds and a grade 3/6 holosystolic murmur at the left lower sternal border. The liver was palpated 2 cm below the right costal margin. Peripheral pulses and perfusion in the upper and lower extremities were mildly diminished. No splenomegaly or hydrops fetalis was present. His initial arterial blood gases while receiving 100% forced inspiratory oxygen revealed a partial oxygen pressure of 42 mm Hg, pH of 7.28, partial carbon dioxide pressure of 56 mm Hg, and a bicarbonate level of 26 mmol/L. Hemoglobin was 17.6 gm/dl, hematocrit was 53%, the white blood cell count was 9900 cells/mm 3, and the platelet count was 196,000 cells/ram 3. Glucose was normal at 116 mg/dl, as was calcium at 8.7 mg/dl, alanine aminotransferase at <5 IU/L, and lactic dehydrogenase at 505 IU/L. Creatine phosphokinase was 626 IU/L (normal adult male 60 to 220 IU/L) with 2% MB fraction. Echocardiography demonstrated a dilated, poorly contractile left ventricle with severely reduced systolic function and a shortening fraction of 10%; severe tricuspid regurgitation with an estimated right ventricular pressure of 60 mm Hg indicating pulmonary hypertension; patent ductus arteriosus with a low-velocity left-to-right shunt confirming pulmonary hypertension; and a patent foramen ovale with a left-to-right shunt. The right atrium and right ventricle were enlarged and no evidence was present of left-sided obstructive lesions such as aortic stenosis or coarctation of the aorta. Coronary arteries originated normally. A possible thrombus was detected in the apex of the left ventricle. An electrocardiogram demonstrated normal sinus rhythm with right and left atrial enlargement. He received 10% dextrose with electrolytes, dopamine, dobutamine, heparin, sodium bicarbonate, and empiric Lcarnitine supplementation. He was weaned from the bicarbonate drip within 48 hours and from the inotropic support over a 7-day period. He began therapy with captopril, digoxin, furosemide, and coumadin and was successfully extubated on his ninth day of life. Additional laboratory data included blood and urine cultures (which were negative for bacteria and viruses); a negative toxoplasma IgM test; nonreactive RPR; normal serum insulin, thyroxine, thyroid stimulating hormone, and serum carnitine levels; cranial ultrasound; and ophthalmologic examination. PCR obtained on serum at 14 days of age detected parvovirus B19 deoxyribonucleic acid (DNA) (assay performed by Associated Regional and University Patholo-

January 1997 American Heart Journal

gists, Inc.). The PCR assay used detects 30 to 300 parvovirus B19 genome copies per milliliter of a 171-base pair segment in the VPI structural protein gene region. Parvovirus B19 IgM antibody was absent at 22 days of age. No other viruses were sought by PCR. The infant was discharged at 2 weeks of age taking oral captopril, digoxin, furosemide, coumadin, and L-carnitine. At 6 weeks of age, a repeat echocardiogram showed persistent left ventricular dysfunction with shortening fraction of 20%. The previously patent ductus arteriosus and foramen ovale had closed, and trace tricuspid regurgitation was present. L-Carnitine supplementation was discontinued because of the normal serum carnitine level. At 4 months of age, his precordium was quiet; normal first and second heart sounds were auscultated and a grade I/VI holosystolic murmur was heard at the left lower sternal border. Peripheral pulses were normal. At 6 months of age, B19 IgM antibody remained undetectable and repeat serum carnitine level measurements were normal. At 1 year of age, his cardiac examination was unchanged. Echocardiogram showed improved, but still mildly decreased, left ventricular function with a shortening fraction of 28%. Trace tricuspid regurgitation was present, predicting a right ventricular pressure of 30 mm Hg. A density near the left ventricu!ar apex was again seen and was unchanged from previous studies; this most likely represented apical myocardium rather than clot. Captopril and digoxin were continued; furosemide and coumadin were discontinued. Cardiac catheterization showed normal coronary arteries. Serum lactate and pyruvate levels were normal.

DISCUSSION Parvovirus B 19, the only known pathogenic human parvovirus, causes a variety of clinical syndromes in children and adults. In the normal host B19 infection may be asymptomatic or associated with erythema infectiosum (fifth disease), arthropathies, and, rarely, purpura. 3, 4 Patients with chronic hemolytic anemias may develop acute red blood cell aplasia. 1 Immunocompromised hosts may become chronically anemic. 4 Fetal infection has ranged from asymptomatic and self-limited, to chronic and, rarely, fatalfl 2 Severe anemia has been associated with nonimmune hydrops (NIH). Both fetuses and live-born infants with NIH may demonstrate intrauterine growth retardation. Canine parvovirus infection has been associated with fatal myocarditis in puppies, but this virus is not transmitted to humans. However, cardiomegaly is often detected in B 19-infected fetuses and newborns, both with and without anemia. 1, 2 Furthermore, fetuses with NIH and cardiac dysfunction may demonstrate spontaneous resolution of their disease 5 or improve with therapy such as digitalization. 2 The latter observations in concert with previous clinical, 1, 2 histocytochemical,1 and pathophysiologi c4 data suggest that infection with B19 may be associated with previously unexplained neonatal cardiac disease. Parvovirus B19 binds to the P antigen present on

Volume 133, Number 1 American Heart Journal

erythrocytes, megakaryocytes, and heart cells. 4 Thus B19 infection could result in anemia, thrombocytopenia, and myocarditis. B19 DNA has been detected in vitro in myocardial cells. 6 Round cell myocardial infiltrates I and intranuclear viral particles typical of B19 have been seen on light and electron microscopic examination, respectively, of fetal cardiac tissue obtained after death. SaintMartin et al.3 recently reported a 1-year-old child with fatal myocarditis associated with serologic evidence of acute B19 infection. B19 DNA was also detected in postmortem myocardial tissue. Ours is the first report of a newborn with cardiomyopathy associated with documented B19 infection. This case also illustrates the relative insensitivity of the anti-B 19 IgM antibody determination for the serodiagnosis of fetal and neonatal B19 infection. 2 In our case, and in others previously reported, 2 viral DNA, but not anti-B19 IgM antibody, was detected in the neonatal period. Dilated cardiomyopathy may be familial or associated with a number of toxins, nutritional deficiencies, carnitine deficiency, ischemia, Kawasaki syndrome, hyperthyroidism and hypothyroidism, and hypoparathyroidism. 7 These causes were all excluded in our patient. Infectious myocarditis, predominantly ascribed to enteroviruses, is the most common putative cause, although many cases remain unexplained. 7 To our knowledge, however, dilated cardiomyopathy associated with B19 infection has not been previously reported in a live-born infant. We speculate that a spectrum of cardiac abnormalities may be associated with intrauterine B 19 infection, in part determined by viral inoculum, fetal gestational age, and immunocompetence. These disease manifestations in the neonate may include, but are not limited to, self-limited or chronic myocarditis, endocardial fibroelastosis, and congenital cardiomyopathy. The prevalence of B19 infection in myocardial disease awaits further investigation. We thank Ms. Amy Sites for technical assistance.

REFERENCES

1. Morey AL, Keeling JW, Porter HJ, Fleming KA. Clinical and histopathological features of parvovirus B19 infection in the human fetus. B J Obstet Gynaecol 1992;99:566-74. 2. Weiner CP, Naides SJ. Fetal survival after human parvovirns B19 infection: spectrum of intrauterine response in a twin gestation. Am J Perinatol 1992;9:66-8. 3. Saint-Martin J, Bonnaud E, Morinet F, Choulot JJ, Mensire A. Myocardite aign~ h parvovirus d'6volution 16tale. P4diatrie 1991;46:59799. 4. Brown KE, Hibbs JR, GallineUa G, Anderson SM, Lehman ED, McCarthy P, et al. Resistance to parvovirus B19 infection due to lack of virus receptor (erythrocyto P antigen). N Engl J Med 1994;330: 1192-6. 5. Pryde PG, Nugent CE, Pridjian G, Barr M Jr, Faix RG. Spontaneous resolution of nonimmune hydrops fetalis secondary to human parvovirus B19 infection. Obstet Gynecol 1992;79:859-61. 6. Porter HJ, Quantrill AM, Fleming KA. B19 parvovirus infection of myocardial cells. Lancet 1988;1:535-6. 7. Dec GW, Fuster V. Idiopathic dilated cardiomyopathy. N Engl J Med 1994;331:1564-75.

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Aneurysm of saphenous vein bypass graft detected by first-pass radionuclide ventriculography Boaz Benari, MD, Jacob Erel, MD, Howard N. Allen, MD, John Friedman, MD, Hosen Kiat, MD, Jeffrey M. Silverman, MD, Alfredo Trento, MD, and Daniel Berman, MD

Los Angeles, Calif.

Since the introduction of saphenous vein aortocoronary bypass graft surgery by Favaloro in 1967, several million of this procedure have been performed. However, aneurysms and pseudoaneurysms of saphenous vein coronary artery bypass grafts (SVCABG) are rarely reported. We present a case report of an SVCABG aneurysm that was demonstrated in three noninvasive imaging modalities: echocardiography, magnetic resonance imaging (MRI), and first-pass radionuclide ventriculography (FPRNV). By retrospective analysis, only FPRNV with its unique feature of sequential chamber visualization led to the correct diagnosis of aneurysm or pseudoaneurysm of the graft. The final diagnosis was made by coronary angiography. To the best of our knowledge, this is the first publication in the English literature of SVCABG aneurysm demonstrated by FPRNV. A 75-year-old man with a history of coronary artery disease underwent CABG surgery in 1975, during which time he had a single-vein graft sequentially placed to the left anterior descending diagonal, circumflex marginal, and right coronary arteries and the posterolateral branches. He did well for about 18 years, until he began having exertional dyspnea. An office stress echocardiogram showed him to have a mass close to the right atrium. Further investigation by transthoracic echocardiography (Fig. 1) and MRI (Fig. 2) showed it to be a right atrial pseudoaneurysm filled mostly with clot; a jet of flowing blood was seen to enter this mass, presumably from the right atrium. FPRNV performed as part of an exercise radionuclide perfusion test demonstrated alate appearance (only in the levophase) of the technetium 99m sestamibi tracer in the area of the right ventricle (Fig. 3). The absence of a left-to-right shunt was verified by normal analysis of the pulmonary tracer dynamics; this unusual phenomenon was characteristic of

From the Division of Cardiology, Department of Medicine, and the Division of Nuclear Medicine and Magnetic Resonance Imaging, Cedars-Sinai Medical Center; and University of California Los Angeles School of Medicine. Dr. Benari is a recipient of a research fellowship grant from the Save A Heart Foundation, Los Angeles, and the American Physician Fellowship for Medicine in Israel, Brookline, Mass. Reprint requests: Daniel Berman, MD, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048. Am Heart J 1997;133:133-6. Copyright © 1997 by Mosby-Year Book, Inc. 0002-8703/97/$5.00 + 0 4/4/71376