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hyperkinesia following relief of pain was in accordance with observations previously made in the canine heart.6 In the experimental setting, transient postischemic hyperki- nesia is abolished if reactive hyperemia is restricted to the preocclusive value of coronary artery flo~.~ Therefore, exaggerated wall motion should not be expected following ischemia due to significant fixed stenosis. Since echocar- diography is a potential noninvasive diagnostic tool for demonstrating myocardial ischemia, we encourage more systematic studies of wall motion following hyperventila- tion in PVA, in Heberden’s angina, and in normal sub- jects.

REFERENCES

1. Widlansky S, McHenry PL, Corya BC, et al: Coronary angiographic, echocardiographic, and electrocardiographic studies on a patient with variant angina due to coronary artery spasm. AM HEART J 90:631, 1975.

2. Gerson MC, Noble RJ, Wann LS, et al: Non-invasive docu- mentation of Prinzmetal’s angina. Am J Cardiol 43:329, 1979.

3. Heupler FA: Provocative testing for coronary arterial spasm: Risk, method, and rationale. Am J Cardiol 46:335, 1980.

4. Pujadas G, Tamashiro A, Baptista G et al: Coronary vaso- spasm elicited by the cold-hyperventilation test. Proceedings of the VIII European Congress of Cardiology, Abstract 1458, 1980.

5. Mortensen SA, Vilhelmsen R, Sand@ E: Prinzmetal’s variant angina. Circadian variation’in response to hyperventilation. Acta Med Stand [Suppl] 644:38, 1981.

6. Pagani M, Vatner SF, Baig H et al: Initial myocardial adjustments to brief periods of ischemia and reperfusion in the conscious dog. Circ Res 43:83, 1978.

lnfradiaphragmatic total anomalous pulmonary venous connection in siblings

Peter Baron, M.D., Howard Gutgesell, M.D., Edith Hawkins, M.D., and Dan McNamara, M.D. Houston, Texas

Total anomalous pulmonary venous connection (TAPVC) is a rare form of congenital heart disease in which all the pulmonary veins connect anomalously to the right atrium or to one of its venous tributaries. TAPVC accounts for approximately 1.3% of patients with congenital heart disease.’ Infradiaphragmatic TAPVC occurs in 18% to

24% of cases,‘,’ the anomalous trunk most commonly joining the portal vein and less often the ductus venosus, one of the hepatic veins, or the inferior vena cava. In this

From the Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine; and the Department of Pathology, Texas Children’s Hospital.

Supported in part by Grant HL-07190 from the National Institutes of Health, United States Public Health Service; and by Grant RR-99188 from General Clinical Research Branch, National Institutes of Health.

Received for publication June 16, 1982; accepted July 1, 1982.

Reprint requests: Howard Gutgesell, M.D., Pediatric Cardiology, Texas Children’s Hospital, 6621 Fannin St., Houston, TX 77030.

Fig. 1. Case No. 1. Posterior view of abdominal and thoracic organs. Right and left common pulmonary veins (RC and LC) connect with a common pulmonary vein (CPV) which in turn connects with the inferior vena cava (ZVC) via a right-angle channel (arrow).

report we describe the rare occurence of infradiaphrag- matic TAPVC in siblings.

Case 1. This male infant was born at term to a 20-year-old Latin American mother following an uncom- plicated pregnancy. This was the mother’s third pregnan- cy, the first having terminated in a spontaneous abortion. There was no family history of congenital heart disease. Labor and delivery were normal and birth weight was 3.6

kg. He was noted to be cyanotic and tachypneic shortly after birth. Physical examination revealed a left paraster- nal lift and a split second heart sound with accentuation of the pulmonary component. No murmur was audible. The liver edge was palpable 4 cm below the right costal margin. Chest x-ray examination showed a normal-size heart with a diffuse granular appearance to both lung fields. The ECG was normal for age. Echocardiography demonstrated abnormal septal motion and an enlarged right ventricle. Cardiac catheterization performed at 33 hours demon- strated TAPVC to the inferior vena cava, a small atrial septal defect, and a patent ductus arteriosus. During surgery performed at 36 hours of age, the anomalous venous trunk was ligated distally with anastomosis of the descending vein to the left atrium. The atrial septal defect was closed by primary suture closure and the patent ductus arteriosus was ligated. The patient remained hypo- tensive with low cardiac output and died at 42 hours of age.

At autopsy the infant was found to have an adequate surgical repair of the anomalous pulmonary venous return, atria1 septal defect, and patent ductus arteriosus (Fig. 1). He had generalized edema of the internal organs as well as pleural effusions and ascites. There was evi- dence of disseminated intravascular coagulation with

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1108 Brief Communications November, 1982

American Heart Journal

Fig. 2. Case No. 2. Posterior view of thoracic and abdom- inal organs. The right lower pulmonary vein (RL) passes anterior to the left main bronchus and connects with an intrapulmonary venous trunk (Ip) in the left lung. The latter descends below the diaphragm as a common pulmo- nary vein (CPV) and connects with the inferior vena cava (IVC) via a right-angle channel (arrow).

platelet thrombi in the lungs and petechial hemorrhages in the lungs, pleura, spleen and kidneys, and a mediastinal hematoma. In addition, he had localized intracranial hemorrhages.

Case 2. This female infant was born 18 months after her brother (Case No. 1). The pregnancy, labor, and delivery were uncomplicated. Birthweight was 3.3 kg. Within 1 hour of birth she was noted to be cyanotic with mild respiratory distress. Her condition deteriorated with the development of severe hypoxemia and metabolic acidosis, requiring mechanical ventilation at 20 hours of age. On examination at that time, she had poor pulses with poor peripheral perfusion, there was a left parasternal lift, the second heart sound was single and accentuated, and no murmur was audible. Rales were present throughout both lung fields and the liver edge was palpable 4 cm below the right costal margin. Chest x-ray examination showed a normal-size heart with increased pulmonary vascular markings. The ECG was normal. Echocardiography dem-

onstrated an enlarged right ventricle and a linear echo in the left atrium suggesting the presence of a posterior chamber. Cardiac catheterization performed at 24 hours of age demonstrated infradiaphragmatic TAPVC, an atri- al septal defect, and a patent ductus arteriosus. During the procedure, the infant had several episodes of bradycardia requiring resuscitative measures. At the conclusion of the procedure she sustained a cardiorespiratory arrest and could not be resuscitated.

Postmortem examination revealed TAPVC. The right lower pulmonary vein drained into the left upper pulmo- nary vein with a large intrapulmonary venous trunk in the left lung descending below the diaphragm and connecting with the inferior vena cava via a narrow right angle channel within the liver (Fig. 2). The two right upper pulmonary veins drained separately into the right superior vena cava. A secundum atria1 septal defect and a patent ductus arteriosus were present. The lungs showed pulmo- nary venous congestion and there was congestive hepato- megaly.

It is not possible to make a confident statement about the pattern of inheritance of this rare anomaly in these siblings. When considering congenital heart disease in general, it appears that about 8% of cases are predomi- nately genetic (3% single mutant gene, 5% chromosomal anomalies) and about 2 % are predominately environmen- tal in etiology.3 In the remaining 90% there is an impor- tant genetic-environmental interaction (multifactorial inheritance). Although examples of TAPVC have occa- sionally been reported with known single gene disorders (Holt-Oram syndrome, Noonan syndrome, Ivemark syn- drome) and chromosomal aberrations (22 partial triso- my),3 in the majority of cases there are insufficient data to draw conclusions about hereditary predisposition. Unusu- ally large clusters of cases of TAPVC have been encoun- tered, but a common etiologic basis has not been identi- fied.4 In an extensive review of the world literature we found two previous reports of infradiaphragmatic TAPVC in siblings. The first report5 described the occurrence of infradiaphragmatic TAPVC in a brother and sister, the first and second children born to a young couple in France. Both infants died in the seventh week of life and the diagnosis was confirmed by postmortem examination in both. Two male siblings with infradiaphragmatic TAPVC were subsequently reported from Australia.6 One died before investigation was possible and the other survived corrective surgery. The parents were of Italian descent and there was no family history of congenital heart disease.

Few instances of familial occurrence of TAPVC of other types have been described. Gatham and Nadas (1970)7 encountered two sibships in which TAPVC occurred among 75 cases of proven TAPVC treated at Children’s Hospital Medical Center in Boston between January, 1950, and June, 1968. The type of TAPVC was not mentioned. In a subsequent report on 91 autopsied cases of TAPVC from the same medical center, Delise et al. ( 1976)2 described a 11/z month old white male infant with TAPVC to the coronary sinus whose sibling had died 2

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years previously at 15 days of age from infradiaphragmatic TAPVC. They also described TAPVC in two sets of identical twins where the lesion was present in only one of each pair. Paz and Castilla (1971)8 from Argentina re- ported the occurrence of three male infants dying from TAPVC within a single family. Two of them were brothers and the third child was a first cousin, the son of a paternal aunt of the first two children. The brothers both had supracardiac TAPVC while the cousin had TAPVC to the portal vein. The parents were not affected, no consanguin- ity was detected, and chromosome studies were normal. Kaufman et al. ( 1972)Q reported the occurrence of TAPVC in two sisters and their female maternal first cousin. The second sibling had TAPVC to the coronary sinus, whereas the first sibling and cousin had the supracardiac form of defect. Milner et al. (1977)” encountered TAPVC in two brothers, the younger being one of nonidentical twins. One had the supracardiac form of the lesion while in the other the anomalous pulmonary veins drained into both the common vertical vein and the coronary sinus (mixed type).

Although a confident statement about the pattern of inheritance in the family presented cannot be made, multifactorial inheritance with a low trigger threshold is probable. Assuming a multifactorial mode inheritance, the theoretic recurrence risk in a sibling of an individual with TAPVC would be approximately 1% (square root of the population frequency).4 One of the implications of the multifactorial threshold model is that the recurrence risk increases sharply with the number of affected first-degree relatives. If there are two affected first-degree relatives, the recurrence risk for the next child becomes two to three times as great as compared to one affected first-degree relative. In the family described, the risk of recurrence in a subsequent pregnancy would therefore be in the order of 2% to 3%. If there are three affected first-degree rela- tives, a risk comparable to or greater than Mendelian risks is found.

Although there are many isolated case reports regarding recurrence of rare cardiovascular defects, available data appear to support the concept that uncommon lesions rarely recur. With the exception of endocardial fibroelas- tosis and hypoplastic left heart syndrome, there does not appear to be an increase in risk of congenital heart disease above the general population risk of about 1% .4 There are at present insufficient genetic data to project confident recurrence risks for individuals with TAPVC.

REFERENCES

1. Rowe RD: Anomalies of venous return. In Keith JD, Rowe RD. Vlad P. editors: Heart disease in infancv and childhood. New York, i978, Macmillan Publishing CO,~ 558.

2. Delisle G, Ando M, Calder AL, Zuberbuhler JR, Rochen- macher S, Alday LE, Mangini 0, Van Praagh S, Van Praagh R: Total anomalous pulmonary venous connection: Report of 93 autopsied cases with emphasis on diagnostic and surgical considerations. AM HEART J 91:99, 1976.

3. Nora JJ: Update on the etiology of congenital heart disease and gentic counseling. In Van Praagh R, Takao A, editors: Etiology and morphogenesis of congenital heart disease. New York, 1980, Futura Publishing Co, p 21.

4.

5.

6.

7.

8.

9.

10.

Nora JJ, Nora AH: Congenital heart disease: Multifactorial inheritance. In Nora JJ, Nora AH, editors: Genetics and counseling in cardiovascular diseases. Springfield, 1979, Charles C?Thomas, p 155. Vinh LT, Van Due T, Aicardi J, Thieffry S: Retour veineux pulmonaire anormal total infradiaphragmatique familial. Arch Fr Pediatr 25:1141, 1968. Clark CP, Edis BD, Danks DM: Familial total anomalous aulmonarv venous return. Aust NZ J Med 3:629. 1973. bathman”GE, Nadas AS: Total anomalous pulmonary venous connection. Clinical and physiologic observations of 75 pedi- atric patients. Circulation 42:143, 1970. Paz JE, Castilla EE: Familial total anomalous pulmonary venous return. J Med Genet 8:312, 1971. Kaufman RL, Boynton RC, Hartmann AF, Morgan BC, McAlister WH: Familial studies in congenital heart disease. III. Total anomalous pulmonary venous connection in two sisters and their female maternal first cousin. In Birth defects: Original article series. Baltimore, 1972, The Williams & Wilkins Co, p 88. Milner S, Levin SE, Marchand PE, Hitchcock F: Total anomalous pulmonary venous drainage in sibs. Arch Dis Child 52:984, 1977.

Sequential intracoronary streptokinase and transluminal angioplasty in unstable angina with evolving myocardial infarction

Richard S. Meltzer, M.D., Marcel van den Brand, M.D., Patrick W. Serruys, M.D., Paolo Fioretti, M.D., and Paul G. Hugenholtz, M.D. Rotterdam, The Netherlands

Salvage of ischemic myocardium in the setting of impend- ing myocardial infarction is an important current concept in cardiology. One of the most dramatic interventions to recover ischemic myocardium is relieving the obstruction of the nutrient coronary artery by intracoronary strepto- kinase in the first hours after onset of myocardial infarc- tion.1.2 This approach is currently undergoing randomized trials in our institution as well ae others. In addition, transluminal coronary angioplasty has been performed increasingly over the past several years to relieve proximal coronary obstruction nonoperatively.3l4 In general, trans- luminal angioplasty has been applied to patients with stable coronary disease. We report here a patient with impending myocardial infarction clinically in whom a very satisfactory result was achieved and operation averted by the use of intracoronary streptokinase followed by trans- luminal coronary angioplasty.

A 55-year-old woman was transferred from another hospital for unstable angina pectoris refractory to maxi- mal medical treatment. She had been entirely well until 2

From the Thoraxcenter, Erasmus University and University Hospital.

Dr. Mel&r is a Clinician-Scientist Awardee of the American Heart Association.

Received for publication Oct. 1, 1981; accepted Oct. 14, 1981.

Reprint requests: Richard S. Meltzer, M.D., Director, Noninvasive Labo- ratory, Cardiology Division, Mt. Sinai Medical Center, New York, NY 10029.

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