Reply to the Editor

Abstract

We thank Dr Martucci and her colleagues for their supportive letter, which emphasizes the general point that the presence of genetic syndromes may significantly affect the perioperative management of patients with a congenital heart defect. Specifically for patients with heterotaxy, we agree that these complex patients require “cardiac and extracardiac preoperative assessment to recognize risk factors and to reduce the operative mortality and postoperative complications.” Extrapolating beyond the phenotype–genotype–prognosis paradigm of their cited reference,1Formigari R. Michielon G. Digilio M.C. Piacentini G. Carotti A. Giardini A. et al.Genetic syndromes and congenital heart defects: how is surgical management affected?.Eur J Cardiothorac Surg. 2009; 35: 606-614Crossref PubMed Scopus (77) Google Scholar we suggest adding “therapy” to the paradigm. Patients in our study with heterotaxy and congenital heart disease (CHD) showed high postoperative morbidity/mortality, with some having respiratory complications.2Swisher M. Jonas R. Tian X. Lee E.S. Lo C.W. Leatherbury L. Increased postoperative and respiratory complications in patients with congenital heart disease associated with heterotaxy.J Thorac Cardiovasc Surg. 2011; 141: 637-644Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar Although this respiratory phenotype is often attributed to the CHD, airway mucus clearance and left-right patterning, abnormal in heterotaxy syndrome, both require motile ciliary function. Thus airway ciliary dysfunction (CD) similar to that of primary ciliary dyskinesia (PCD) may have relevance for increased respiratory complications seen in patients with heterotaxy. To better characterize the phenotype of a broad spectrum of patients with heterotaxy, 43 patients with CHD were assessed for airway CD. We used videomicroscopy to look for abnormal ciliary motion in nasal tissue and nasal nitric oxide noninvasive testing (typically low with PCD) to assess for CD. A remarkable 42% (18/43) of patients exhibited CD, with one third in the severe PCD range. Patients greater than 6 years old with CD showed increased respiratory disease similar to that seen in PCD.3Nakhleh N. Swisher M. Francis R. Giese R. Chatterjee B. Connelly P. et al.Low nasal nitric oxide and ciilary dysmotility in patients with congenital heart disease and heterotaxy.Am J Respir Crit Care Med. 2009; 179: A1223Google Scholar Our studies suggest patients with CHD who have heterotaxy have substantial risk of CD and respiratory disease that complicates their prognosis. The phenotype–genotype–prognosis correlation is also important in that further research may allow future patients and families to correlate gene mutations with phenotype and prognosis. Now families face the very high recurrence risk ratio of 79.1 for heterotaxia (95% confidence interval, 32.9-190).4Oyen N. Poulsen G. Boyd H.A. Wohlfahrt J. Jensen P.K.A. Melbye M. Recurrence of congenital heart defects in families.Circulation. 2009; 120: 295-301Crossref PubMed Scopus (240) Google Scholar Further study of our patients with heterotaxy who have CD through next-generation sequencing of all 14 known PCD genes in 13 heterotaxy patients with CD identified 10 novel coding variants in 6 PCD genes. Recently, some CD gene mutations have become commercially available. The paradigm of phenotype–genotype–prognosis is beneficial to promote translational research to the patient, family, and medical care team. Our research suggests that patients with CHD and heterotaxy will be at higher perioperative risk if they have CD.3Nakhleh N. Swisher M. Francis R. Giese R. Chatterjee B. Connelly P. et al.Low nasal nitric oxide and ciilary dysmotility in patients with congenital heart disease and heterotaxy.Am J Respir Crit Care Med. 2009; 179: A1223Google Scholar These findings indicate that patients with CHD and heterotaxy may benefit from preoperative screening for CD. Recognition of specific surgical risks factors in genetic syndromes is leading to specific diagnostic protocols that improve phenotyping or predictive genotyping.1Formigari R. Michielon G. Digilio M.C. Piacentini G. Carotti A. Giardini A. et al.Genetic syndromes and congenital heart defects: how is surgical management affected?.Eur J Cardiothorac Surg. 2009; 35: 606-614Crossref PubMed Scopus (77) Google Scholar To add “therapy” to the paradigm, further studies are needed to evaluate whether perioperative protocols improving airway ciliary motility and enhancing mucus clearance may reduce respiratory complications and improve postoperative outcome for patients with CHD who have heterotaxy and CD. Respiratory complications in patients with heterotaxy syndromeThe Journal of Thoracic and Cardiovascular SurgeryVol. 143Issue 3PreviewWe read the interesting paper by Swisher and associates1 on the respiratory complications after cardiac surgery in patients with heterotaxy syndrome. The authors compared the postoperative course of children with heterotaxy syndrome with that of patients with cardiac defects and similar surgical complexities following the Risk Adjustment in Congenital Heart Surgery.1,2 Full-Text PDF