A case of right isomerism showing long survival without surgery.

Abstract: We report an autopsy case of right isomerism in a 42-year-old Japanese man. Although he had not undergone any surgical intervention, he was healthy and did not exhibit any symptoms of heart failure. The cardiac findings indicated right isomerism with complex and severe cardiac malformations, including a morphologically common atrium, common atrioventricular valve, double inlet right ventricle, total anomalous pulmonary venous drainage, pulmonary outflow obstruction, pulmonary atresia, and major aortopulmonary collaterals from the descending aorta. He had no spleen, and exhibited some gastrointestinal malformations. The absence of risk factors for mortality from right isomerism, such as pulmonary venous obstruction, AV valve regurgitation, sepsis or severe arrhythmia, might have contributed to the longevity of this patient. The presence of pulmonary outflow obstruction that is reported to confer a better prognosis might also have contributed to his longevity.

Key Words: right isomerism, long survival, nonoperated case, double inlet right ventricle, major aortopulmonary collaterals

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Right isomerism is a cardiac anomaly characterized by the bilateral presence of morphologically identical right atrial appendages. (1,2) Right isomerism is considered to result from a defect of lateralization, and is often associated with complex cardiac and vascular anomalies, pulmonary and bronchial symmetry, and abnormalities of abdominal organs, including asplenia. (2)

The complex congenital cardiac malformations associated with right isomerism are well documented, including common atrioventricular (AV) valve, ventricular hypoplasia or single ventricle, abnormal ventriculoarterial connections, pulmonary outflow obstruction, anomalous pulmonary venous drainage, and pulmonary vein obstruction. (3,4) Mortality due to right isomerism is dependent on the severity of the cardiac anomalies. The overall mortality rate is reported to be 69%, and many patients with right isomerism with cardiac anomalies die in the neonatal period. (3-5) Therefore, adult cases of right isomerism are extremely rare in comparison with the other congenital cardiac diseases. (1)

In this report, we describe a rare case of right isomerism in a 42-year-old male who had not undergone any surgical intervention. A postmortem examination revealed anomalies in the heart, lung, spleen, liver and gastrointestinal tract.

Case Report

Clinical History

The patient had been followed from childhood as an outpatient without medication because of cyanotic congenital heart disease. Although the cyanosis had persisted, he had lived a very healthy life. No interventions had been planned or instituted, and he had married and had two healthy children. He had been able to fulfill a normal daily work schedule without any symptoms of heart failure. At the age of 42 years, however, he was hospitalized because of acute hematemesis. During a diagnostic upper endoscopy examination, the patient developed sudden severe arrhythmia and dyspnea and died.

Autopsy Findings

The heart exhibited hypertrophy in the left hemithorax, and the atrial appendages were symmetrical in appearance. Pectinate muscles in both atrial appendages were observed to spill into the atrial chamber, resulting in left- and right-sided morphologic right atrium (mRA) (Fig. a). The atrial septum was hypoplastic and string-like. Both the superior and inferior caval veins drained into the left-sided atrial chamber. The pulmonary veins (PVs) were connected to the left side of the atrium through a common pulmonary channel (common PV). The position of a rudimentary and incomplete left ventricle was not clearly determined, and there was a functionally univentricular arrangement. The left- and right-sided mRA communicated with the morphologic right ventricle (mRV) via a common AV valve with three-leaflets (double inlet right ventricle; DIRV). The solitary aorta arose from the right-sided mRV (single outlet) with pulmonary atresia (Fig. b). The aortic arch was located to the left of the trachea. Four collateral arteries were noted between the descending aorta and the pulmonary artery (major aortopulmonary collaterals; MAPCAs), and one of them showed aneurysmal dilation (Fig. c, arrow). The right coronary artery arose from the posterior sinus, and the left coronary artery arose from the left sinus. The cardiac malformations found in the present case are schematized in Figure d.

The lungs were bilaterally trilobed and both main bronchi were symmetrically short. The spleen was absent, and the liver was positioned on the left (Fig. 1e). The ascending colon was not attached to the retroperitoneum, although malrotation of the bowel was not evident (Fig. e). In the upper lobe of the right lung, one abscess measuring 3.5 X 3.5 cm was observed. The mucosal surface of the small and large intestine was hemorrhagic and was covered by a pseudomembrane, suggesting ischemic enterocolitis.

Microscopic examination of the heart showed damaged cardiomyocytes, which were characterized by prominent contraction bands and coagulation necrosis, distributed around the apex, suggesting acute myocardial infarction confined to a small area. The pulmonary abscess in the right upper lobe contained colonized Gram negative bacteria, with infiltration of numerous polymorphoneutrophils. The arteries in almost all lung fields showed intimal thickening, indicating severe pulmonary hypertension. Thromboembolisms were found in the pulmonary arteries adjacent to the abscess. The arterial walls of the aorta and MAPCAs showed severe atherosclerosis. The mucosal wall of the intestinal tract showed marked ischemic changes.

[FIGURE OMITTED]

In summary, acute myocardial infarction, lung abscess, thromboembolism, pulmonary hypertension, and ischemic enterocolitis were observed, in addition to the complex anomalies of the heart, lung, spleen, liver and gastrointestinal tract.

Discussion

Many cardiac and extracardiac anomalies associated with right isomerism have been reported previously (Table). (3,4) Most of these common cardiac anomalies were observed in the present case, whereas pulmonary venous obstruction and systemic outflow obstruction, both of which are known to be less common in cases of right isomerism, were not evident. It has been reported that MAPCAs are found in only 3% of cases of right isomerism. (6) MAPCAs have been proposed to promote local pulmonary hypertension. (7) In the present case, although severe pulmonary hypertension was histologically disclosed, symptoms of heart failure were not observed during life, suggesting that the pulmonary hypertension does not appear to be a direct cause of death. On the other hand, some reports have stressed that in some patients with pulmonary atresia and ventricular septal defect (VSD), MAPCAs may contribute to maintain pulmonary blood flow. (8) Thus, we speculate that MAPCAs found in the present case might have facilitated a returning pulmonary arterial supply to the lungs. If this was indeed the case, then the MAPCAs observed in this patient might have contributed to his longevity.

The overall survival rates of patients with right isomerism have been reported to be 80% at one month, 65% at 1 year, 51% at 5 years, and 34% at 10 years. (4) The median age at death in children with anomalous pulmonary venous connection and pulmonary atresia is no more than 2.6 months. (9) It has been reported that, for the overwhelming majority, survival requires surgical intervention. (10) Despite advances made in surgical procedures, the overall survival of patients with right isomerism has not improved, and the long-term outcome still remains poor. (10,11) Therefore, the present case appears to be a very rare case, as the patient survived until the age of 42 years without any surgical treatment of his complex cardiac anomalies. (11) It has been reported that the presence of pulmonary vein obstruction, AV valve anomaly with regurgitation, or single ventricle is a significant detrimental prognostic factor for patients with right isomerism. (3,4) On the other hand, sepsis and arrhythmia are reported to be causes of late mortality. (4,12) Among possible risk factors for mortality, the present patient did not exhibit pulmonary venous obstruction, AV valve regurgitation, sepsis or severe arrhythmia, but did have pulmonary outflow obstruction, suggesting that the absence of these risk factors in the present case might have contributed to the patient's longevity. Furthermore, some reports have proposed that pulmonary outflow obstruction in patients with right isomerism may actually confer a prognostic advantage. (3) Therefore, pulmonary outflow obstruction found in this patient might have also contributed to his longevity.

References

1. Winer-Muram HT. Adult presentation of heterotaxic syndromes and related complexes. J Thorac Imaging 1995;10:43-57.

2. Anderson RH, Webb S, Brown NA. Defective lateralization in children with congenitally malformed hearts. Cardiol Young 1998;8:512-531.

3. Hashmi A, Abu-Sulaiman R, McCrindle BW, et al. Management and outcomes of right atrial isomerism: a 26-year experience. J Am Coll Cardiol 1998;31:1120-1126.

4. Cheung YF, Cheng VY, Chau AK, et al. Outcome of infants with right atrial isomerism: is prognosis better with normal pulmonary venous drainage? Heart 2002;87:146-152.

5. Phoon CK, Neill CA. Asplenia syndrome: insight into embryology through an analysis of cardiac and extracardiac anomalies. Am J Cardiol 1994;73:581-587.

6. Uemura H, Ho SY, Anderson RH, et al. Ventricular morphology and coronary arterial anatomy in hearts with isometric atrial appendages. Ann Thorac Surg 1999;67:1403-1411.

7. Norgaard MA, Alphonso N, Cochrane AD, et al. Major aorto-pulmonary collateral arteries of patients with pulmonary atresia and ventricular septal defect are dilated bronchial arteries. Eur J Cardiothorac Surg 2006;29:653-658.

8. Schulze-Neick I, Ho SY, Bush A, et al. Severe airflow limitation after the unifocalization procedure: clinical and morphological correlates. Circulation 2000;102(suppl III):III-142-III-147.

9. Wolfe MW, Vacek JL, Kinard RE, et al. Prolonged and functional survival with the asplenia syndrome. Am J Med 1986;81:1089-1091.

10. Freedom RM, Jaeggi ET, Lim JS, et al. Hearts with isomerism of the right atrial appendages: one of the worst forms of disease in 2005. Cardiol Young 2005;15:554-567.

11. Ichikawa H, Sawa Y, Fukushima N, et al. Late assessment after biventricular repair for isomerism heart. Ann Thorac Surg 2005;80:50-55.

12. Raman R, Al-Ali SY, Poole CA, et al. Isomerism of the right atrial appendages: clinical, anatomical, and microscopic study of a long-surviving case with asplenia and ciliary abnormalities. Clin Anal 2003;16:269-276.

It is by surmounting difficulties, not by sinking under them, that we
discover our fortitude.
--Hannah Webster Foster

Keiko Matsuura, MD, PhD, Shinichiro Akizuki, MD, PhD, Natsuki Nakamura, MD, PhD, Hatsue Ishibashi-Ueda, MD, PhD, and Masatsugu Moriyama, MD, PhD

From the Department of Molecular Pathology, Faculty of Medicine, Oita University, Yufu-city, Oita, Japan; the Departments of Pathology and Internal Medicine, Shin-beppu Hospital, Beppu-city, Oita, Japan; and the Department of Pathology, National Cardiovascular Center, Osaka, Japan.

Reprint requests to Keiko Matsuura, MD, PhD, Department of Molecular Pathology, Faculty of Medicine, Oita University, Yufu-city, Oita 879-5593, Japan. Email: [e-mail]

Accepted July 5, 2006.

RELATED ARTICLE: Key Points

* Right isomerism is defined as a cardiac anomaly with bilateral, morphologically identical right atrial appendages, often associated with complex and severe cardiac anomalies.

* The long-term outcome of patients with right isomerism is poor. Therefore, adult cases of right isomerism with complex cardiac anomalies untreated by surgery are extremely rare.

* It is considered that the absence of pulmonary venous obstruction and significant atrioventricular valve regurgitation and the presence of pulmonary outflow obstruction might have contributed to the present patient's longevity.

Table. Cardiac and extracardiac anomalies in right isomerism

                               Hashmi        Cheung
                               et al         et al          Present
                               (n = 91) (a)  (n = 111) (a)  case

Cardiac anomalies
Common atrium                  76 (84%)       68 (59%)      +
Common atrioventricular        74 (81%)      107 (92%)      +
  (AV) valve
Ventricular hypoplasia or      66 (73%)       96 (83%)      +
  single ventricle
Abnormal ventriculoarterial    87 (96%)      115 (99%)      +
  connection
Pulmonary outflow obstruction  76 (84%)       96 (83%)      +
Pulmonary atresia              23 (25%)       42 (44%)      +
Anomalous pulmonary venous     77 (87%)       60 (52%)      +
  connection
Pulmonary vein obstruction     25 (30%)       15 (13%)      -
Systemic outflow obstruction   11 (12%)        4 (3%)       -
MAPCA                          ND            ND             +

Extracardiac anomalies
Asplenia                       87 (94%)      ND             +
Anomaly of liver position
  Midline liver position       66 (77%)      ND             -
  Left-sided liver              7 (8%)       ND             +
Gastrointestinal anomalies     29 (34%)      ND             +
  Malrotation of the bowel     16 (19%)      ND             -
Genitourinary anomalies         7 (9%)       ND             -

(a) Number of cases.
ND, not described; MAPCAs, major aortopulmonary collaterals.