Heart, Lung and Circulation (2016) 25, 352 357 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2015.09.003 ORIGINAL ARTICLE Dextrocardia in Adults with Congenital Heart Disease Sophie Offen, MBBS a,b, Dan Jackson, BSc a, Carla Canniffe, MBBS, MRCPI a, Preeti Choudhary, MBBS a,b, David S. Celermajer, MBBS, DSc, FAA, FRACP a,b* a Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia b Sydney Medical School, University of Sydney, Sydney, Australia Received 25 June 2015; received in revised form 28 August 2015; accepted 5 September 2015; online published-ahead-of-print 9 October 2015 Background/ Objectives Dextrocardia is rare in the general population, and may be associated with significant additional cardiac malformations. We aimed to identify the prevalence and patterns of additional cardiac defects, as well as the associated long-term morbidity and mortality, in adult patients with dextrocardia, in a specialised Adult Congenital Heart Disease (ACHD) service. Methods A retrospective study of patients with dextrocardia managed by our tertiary ACHD service, since January 2000, was performed. Medical records were reviewed and the National Death Index was consulted to confirm survival status. Results Of 3698 adults in our ACHD Service, 19 (0.5%) had dextrocardia. Mean follow-up duration was 7 7.5 years. The mean age at last review was 36.8 10.5 years (range 20-63 years). Situs was solitus in 14 (74%) and inversus in five (26%). Eleven patients (58%) had functional single ventricles, of whom five had atrioventricular (AV)-ventriculoarterial (VA) discordance and two had VA discordance only. Four patients with two ventricles had AV-VA discordance. All patients had at least one additional cardiac malformation. Fourteen patients (74%) required surgical intervention. Eleven patients (58%) underwent a Fontan-type operation. Five patients (26%) required ablation procedures for arrhythmia. One patient had infective endocarditis and two deaths occurred, both in patients who also had AV-VA discordance. Conclusion Dextrocardia remains a rare finding in adults, even in a highly select group of patients with known congenital heart disease. Those with associated congenital heart abnormalities are likely to have complex lesions, which may require multiple surgical and medical interventions. Despite this, our series demonstrated that patients surviving to adulthood and then managed in an ACHD centre may have good mediumterm survival. Keywords Dextrocardia Adult congenital heart disease Mortality Introduction Dextrocardia refers to a right-sided location of the heart within the thoracic cavity, and is a primary manifestation of the abnormal lateralisation of the embryonic left-right axis during early development [1]. Whilst the precise signalling pathways involved in this aberrancy are not clear, it occurs in contrast to normal embryologic development, where the primitive heart tube first rotates to the right and subsequently moves to the left-side of the thoracic cavity to occupy a normal position (laevocardia). Dextrocardia is generally described as occurring in conjunction with one of three configurations of the asymmetric structures within an individual. The relationship between *Corresponding author at: Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia. Tel.: +61295157110, Email: david.celermajer@email.cs.nsw.gov.au 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
Dextrocardia in Adults with Congenital Heart Disease 353 these structures is commonly referred to as situs. Situs is primarily determined by the position of the atria, which maintain their laterality throughout development, and subsequently by the position of the tracheobronchial tree and abdominal viscera [2]. Most commonly associated with dextrocardia is situs inversus, where visceroatrial situs is a mirror image of normal. Dextrocardia may also occur with normal visceroatrial relationships (situs solitus), or in patients with heterotaxy (situs ambiguous), in whom visceroatrial relationships are inconsistent, often tending toward symmetric relationships of otherwise asymmetric structures (also known as isomerism ) [1 3]. In all its presentations, dextrocardia is a rare congenital abnormality, and while its true incidence remains largely unknown, estimates range from 1 in 8,000 to 25,000 live births [4]. It is commonly associated with additional cardiac malformations, the frequency of which vary considerably according to situs; 5% with situs inversus to 90% with situs solitus [2,5,6]. There remains a paucity of literature describing the phenotypes of patients with dextrocardia who survive into adulthood. The aim of this study is therefore to describe the range of cardiac abnormalities, complications and surgical interventions, in an adult population with dextrocardia. Methods The study was approved by our Institutional Ethics Committee. Study Population Patients with a diagnosis of dextrocardia were identified from an existing database at our tertiary referral centre for ACHD. All those 16 years old who had been reviewed at least once in our ACHD clinic since January 2000 were included. Our database identified three patients who had undergone transthoracic echocardiography (TTE) at our institute and had a diagnosis of dextrocardia with no associated congenital heart defects and so were never reviewed at our ACHD clinic; these were not included in our study. Between 2012-2014, a comprehensive search of all medical records was conducted. This included reviewing clinic records, cardiac imaging reports, catheterisation reports, operation reports and hospital medical records. Vital status was obtained for all dextrocardia patients from the Australian National Death Index, with the ascertainment date being the end of 2013. For the purposes of this study, dextrocardia was defined as a rightward facing apex secondary to an intrinsic defect of normal lateralisation. Those with dextroposition, a displacement of the heart to the right secondary to extra-cardiac abnormalities (such as right lung hypoplasia) were excluded from this study. (Five of our patients had dextroposition, all of whom also had situs solitus. Of these, two had structurally normal hearts, and three had septal defects, of whom one had VA discordance.) Normal visceroatrial arrangement, where the morphologic right atrium was to the right of the morphologic left atrium, with a right-sided liver and left-sided stomach and spleen, was termed situs solitus. A mirror-image of this arrangement was termed situs inversus, and otherwise disordered visceroatrial relationships was termed situs ambiguous. We chose to define the relationships of the atria, ventricles and great vessels anatomically in order to avoid any confusion that could arise with relation to abnormal situs. Statistics Analysis was performed using SPSS version 20 (IBM, Armonk, New York). Data for categorical variables are reported as frequency and percentage (%) and data for continuous variables are summarised using mean standard deviation. Continuous variables that were not normally distributed were reported as median and range (minimum and maximum). Results Patient Demographics From our database of 3698 patients, we identified 19 (0.5%) patients with a diagnosis of dextrocardia. Eleven (58%) were male. Average follow-up since first visit to our centre was 7 7.5 years. Mean age of the patients at last review was 36.8 SD 10.5 years (range 20-63 years). Cardiac Position and Situs Situs was solitus in 14 (74%) and inversus in five (26%). There were no patients with situs ambiguous (Table 1). Table 1 Dextrocardia in relation to situs and atrioventricular/ ventriculoarterial connections All (n= 19) AV-VA discordance (n=9) VA discordance only (n=3) Concordance (n=10) Situs Solitus 14 7 2 5 Situs Inversus 5 2 1 2 AV-VA - atrio-ventricular and ventriculo-arterial; VA - ventriculo-arterial.
354 S. Offen et al. Table 2 Dextrocardia and associated cardiac abnormalities Cardiac Defect; type and total number Situs Solitus (n=14) Single Ventricles (n=11) 9 2 DILV (n=4) 4 - DORV (n=2) 1 1 ASD (n=5) 3 2 VSD (n=7) 5 2 PA (n=5) 4 1 PS (n=4) 3 1 TA (n=1) 1 - Double Ventricles (n=8) 5 3 DORV (n=2) 2 - ASD (n=1) - 1 VSD (n=3) 3 - AVSD (n=1) - 1 AoC (n=1) - 1 Associated Cardiac Malformations Situs Inversus (n=5) DILV = double inlet left ventricle, DORV = double outlet right ventricle, ASD = atrial septal defect, VSD = ventricular septal defect, PA = pulmonary atresia, PS = pulmonary stenosis, TA = tricuspid atresia, AVSD = atrioventricular septal defect, AoC = coarctation of aorta. All patients had at least one additional congenital cardiac abnormality. Nine (47%) had atrioventricular (AV) and ventriculoarterial (VA) discordance. Three (16%) had VA discordance only. The types of associated cardiac abnormalities are listed in Tables 2 and 3. Those with situs solitus were more likely to have a univentricular system (p=0.19) and more complex cardiac abnormalities (p=0.18) compared to those with situs inversus. Single Ventricles Eleven patients (58%) had functional single ventricles (SV), of whom nine were situs solitus and two situs inversus. Five (45%) of those with single ventricles had atrioventricular (AV) and ventriculoarterial (VA) discordance, two (18%) had VA discordance only, and the remaining four patients (36%) had normal AV-VA concordance. All patients with a SV had at least one additional abnormality of their cardiac anatomy. Additional anatomical abnormalities included a double-inlet left ventricle (n=4) including one patient with AV-VA discordance, one with VA discordance and two with normal AV-VA concordance, double-outlet right ventricle (n=2), including one with AV-VA discordance and the other with normal AV-VA concordance. Seven patients had an associated VSD, six had pulmonary atresia, four had pulmonary stenosis and one had tricuspid atresia, which was associated with both PA and a VSD. Presence of a ventricular septal defect (VSD), atrial septal defect (ASD), or both was documented in nine patients (82%). Two Ventricles The remaining eight patients in the cohort had two functional ventricles. Situs was solitus in five and inversus in three. Of all those with two functional ventricles, 50% had AV-VA discordance, one (13%) had VA-discordance only and three (38%) had normal AV-VA concordance. Two of these patients (25%) had double outlet (DO)RV, of which both were situs solitus and had a co-existing VSD. Six patients (75%) were documented as having either an ASD or VSD or both. Two patients (25%) with two ventricles had abnormalities of the aorta, one of which was accompanied by an AVSD and the other an isolated coarctation of the aorta. Extra-cardiac Anomalies Eleven per cent of the cohort (n=2) demonstrated extra-cardiac anomalies or syndromes. One patient with situs solitus had a complex congenital syndrome CHARGE syndrome, which includes coloboma of the eye, choanal atresia, retardation of growth and of mental development, genital and ear anomalies. One patient, with situs inversus, had Kartagener s Syndrome, an inherited ciliary disorder associated with sinusitis, bronchiectasis and situs inversus. Surgical Interventions Fourteen patients (74%) required some form of surgical intervention, with over half (57%) of the cohort requiring more than one surgical intervention. A Fontan-type operation was performed in 10 patients (71%). Six of the Fontan procedures performed involved an anastomosis between the SVC/IVC and pulmonary artery (cavopulmonary connection), and four with an anastomosis between the right atrium and pulmonary artery (atriopulmonary connection). Two patients underwent Rastelli operations. One patient underwent AVSD repair and one had aortoplasty repair of an aortic coarctation. Surgical revisions were required in three patients - one required replacement of the RV to PA conduit, two shunt revisions. Two patients underwent additional surgery, one had mitral valve replacement in the context of a prior AV canal defect and the second underwent resection of an aortic aneurysm. Electrophysiology Procedures Five patients (26%), all diagnosed with a form of supraventricular tachycardia, required an electrophysiology study (EPS). Four of these patients underwent an ablation procedure at the time of the study. One patient had an insertion of a dual chamber pacemaker. Complications The most common complication diagnosed in this cohort was supraventricular tachycardia. Five (45%) patients with a single ventricle and three (27%) patients with two ventricles had had a diagnosis of atrial flutter, atrial fibrillation or another form of supraventricular tachycardia.
Dextrocardia in Adults with Congenital Heart Disease 355 Table 3 Characteristics and associated cardiac malformations in patients with dextrocardia Age at F/U (yrs) Gender Situs Diagnosis and associated lesions Complications EP Surgery Single Ventricle (SV) 27 M S AVdVAd, PA, VSD - - S; F(C) 30 M S AVdVAd, Abn TV/RV, VSD, PS AFl EPS + ABL F(A) 62 M S AVdVAd, TA, VSD, PA/PS CVA - S; F(A) 26 F S AVdVAd, DILV, ASD, PS - - F(A) 31 M S AVdVAd, DORV, PS paf, SVT - S; F(A) 27 M I AVcVAd, HypoRV/TV, AF/AFl E PS + ABL S; F(C) VSD/ASD, PS 46 F S AVcVAd, DILV, VSD, ASD, PA AF, CVA - S; F(C) 39 M I DORV, PA, VSD/ASD CVA - S; F(C) 19 F S PA, VSD - - S; F(C) 29 F S DILV, ASD - - F (A) 23 M S DILV, PA - - S; F(C) Two Ventricles (TV) 38 F S AVdVAd - - - 61 F I AVdVAd CCF PPM insertion - (DDDR) 25 M I AVdVAd, ASD TR (systemic - ASD repair AV-valve) 35 M S AVdVAd, DORV, VSD, ASD AF, HF - SAVVR; LV to PA conduit 44 F S AVcVAd, DORV, VSD, PS SVT, paf EPS + ABL S; Rastelli 47 F S VSD, ASD AFl, ES EPS + ABL x3 36 M S AVSD, LPA stenosis, SubAoStenosis - - AVSD repair MVR 35 M I AoC AA - Aortoplasty Situs: S = Situs Solitus, I = Situs Inversus. AV and VA connection (concordant unless otherwise noted): AVdVAd (cctga) = Atrioventricular (AV) and Ventriuloarterial discordance, AVcVAd = Ventriculoarterial discordance only. Diagnosis: ASD = Atrial Septal Defect, AVSD = Atrioventricular Septal Defect, DILV = Double Inlet Left Ventricle, DIRV = Double Inlet Right Ventricle, DORV = Double Outlet Right Ventricle, PA = Pulmonary Atresia, RVH = Right Ventricular Hypertrophy, TA = Tricuspid Atresia, VSD = Ventricular Septal Defect. Complications: AF = Atrial Fibrillation, AFl = Atrial Flutter, ES = Eisenmenger s, IE = Infective Endocarditis, HF = Heart Failure, AA = Aortic aneurysm. EP: EPS = Electrophysiology Study, ABL = EP Ablation procedure. Surgery: S = Shunt, F(A) = Fontan Procedure with atriopulmonary connection, F(C) = Fontan s with cavopulmonary connection, SAVVR = Systemic atrioventricular valve replacement. Three patients, all with single ventricles, had an embolic stroke. All of these patients had undergone previous Fontan procedures. One of these patients had complete AV-VA discordance, associated with both tricuspid and pulmonary atresia, one VA-discordance only associated with pulmonary atresia only, and the third had DORV associated with pulmonary atresia. There was one case of Eisenmenger s syndrome in a patient with situs solitus, two ventricles and a large VSD. Mortality There were two deaths in the cohort, both with a diagnosis of AV and VA discordance. The first was a 61-year-old female who had a history of pacemaker insertion at the age of 53 years. She was referred for transplantation at the age of 61 and died shortly thereafter due to organ rejection. The second patient was a 31-year-old male who had sudden cardiac death less than six months after a review which documented sinus rhythm with ventricular bigeminy, good subjective exercise capacity and mild to moderate right ventricular dysfunction on the transthoracic echocardiogram. Discussion The diagnosis of dextrocardia by foetal echocardiogram has estimated an overall incidence of between 0.22% [8] and
356 S. Offen et al. 0.84% [7] in pregnant women referred for pre-natal cardiac ultrasound. A large proportion of these foetuses have associated CHD [8]. The prevalence of dextrocardia in an adult population is unknown. With the advancement of new surgical techniques to correct previously fatal cardiac abnormalities, patients with dextrocardia and CHD surviving to birth are increasingly surviving into adulthood. Associations with cardiac abnormalities and outcomes have not been well described in adults with dextrocardia surviving into adulthood. In our series of adult patients attending a specialist ACHD centre, we recorded a prevalence of dextrocardia of 0.5%, the majority of whom also had associated cardiac, or extra-cardiac, abnormalities. Cardiac and Extra-cardiac Associations All patients in our series had at least one additional congenital heart abnormality. We found that those with situs solitus were also more likely to have a complex or univentricular type abnormality, compared to those with situs inversus. This has been recognised by previous series looking at foetal and neonatal diagnoses of dextrocardia. Bohun et al. found that in their cohort, with a median age of 5.5 years, 96% of those with situs solitus had associated CHD, compared to only 23% of their situs inversus group [10]. In a retrospective study of foetal echocardiograms, Walmsley et al. found that their entire cohort with situs solitus had an additional cardiac malformation, and these malformations were frequently complex in nature [7]. Sixty-four per cent of our patients had situs solitus. This differs from previous series, which have reported situs inversus as being more common than situs solitus in those with dextrocardia [1,2]. This discrepancy may be explained by the strong association of situs solitus with other complex congenital heart disease, making these patients more likely to be referred to specialised ACHD centres such as our own. Two of our patients also had extra-cardiac anomalies. One patient with situs solitus had a complex congenital malformation syndrome and one patient with situs inversus had Kartagener s syndrome. Previous series report a higher prevalence of extra-cardiac anomalies associated with dextrocardia, however these series are largely reporting on those diagnosed with Kartagener s syndrome in foetal and early paediatric life. Bohun et al. reported that 42% of their cohort had associated extra-cardiac manifestations [10]. This may reflect the fact that those with dextrocardia and more severe forms of congenital syndromes may not survive into adulthood. In paediatric series of patients with dextrocardia, situs ambiguous and pulmonary venous anomalies have been reported; we did not observe these abnormalities, in the current reported series [8,10]. Surgical Interventions and Complications Seventy-four per cent of our cohort underwent some form of cardiac surgery. The commonest form of cardiac surgery performed was a Fontan-type procedure, accounting for 71% of all surgical procedures performed. Fifty-seven per cent of our cohort had more than one cardiac surgery performed. This reflects the complexity of the cardiac malformations that are found in patients with dextrocardia. Other series have reported similarly high rates of cardiac surgery in those with dextrocardia. Bohun et al. reported that 68% of their cohort underwent surgical intervention, with 65% of these requiring 2 cardiac surgeries [10]. The morbidity of patients in our cohort was predominantly related to complications of the complex cardiac and extracardiac anomalies associated with dextrocardia. Fifty-five per cent of our cohort had experienced complications related to their underlying congenital heart disease, the commonest of which was a supraventricular tachycardia or embolic stroke. Limitations The selection of patients by referral to a specialised ACHD centre is subject to notable bias, likely selecting for patients with significant cardiac abnormalities in addition to dextrocardia. Thus our observations may not be generalisable to a wider group of patients with isolated dextrocardia, not seen in specialist centres. However, with an increasing number of such centres around the world, we believe that this remains a representative sample of what is a very select group of patients, with significant additional cardiac abnormalities associated with dextrocardia. Our series also has the limitations of a single centre retrospective study, with a small number of patients included. Larger collaborative studies across multiple tertiary ACHD centres would further help define the characteristics and outcomes of patients with dextrocardia. Conclusion Dextrocardia remains a rare finding in adults, even in a highly select group of patients with known congenital heart disease. All patients in our series had at least one additional congenital heart abnormality, many of whom had complex lesions requiring multiple surgical and medical interventions. The morbidity of patients in our cohort was predominantly related to complications of these complex cardiac and extra-cardiac anomalies associated with dextrocardia. Despite this, our series demonstrated that patients surviving to adulthood and then managed in an ACHD centre have good medium-term survival. References [1] Perloff JK, Marelli AJ. Perloff s Clinical Recognition of Congenital Heart Disease, 6th Edition, Philadelphia, PA: Saunders: Elselvier; 2012, 15 30. [2] Maldjian PD, Saric M. Approach to Dextrocardia in Adults: Review. AJR 2007;188:S39 49. [3] Perloff JK. The Cardiac Malpositions. Am J Cardiol 2011;108:1352 61. [4] Casey B. Two rights make a wrong: human left right malformations. Human Molecular Genetics 1998;1565 71. [5] Solzbach U, Beuter M, Hartig B, Haas H. Isolated Dextrocardia with Situs Solitus (Dextroversion). Herz 2010;35:207 10.
Dextrocardia in Adults with Congenital Heart Disease 357 [6] Buxton A, Morganroth J, Josephson M, Perloff J, Shelburne J. Isolated dextroversion of the heart with asymmetric septal hypertrophy. Am Heart Journal 1976;92:785 90. [7] Walmsley R, Hishitani T, Sandor GG, Lim K, Duncan W, Tessier F, et al. Diagnosis and outcome of dextrocardia diagnosed in the fetus. Am J Cardiol 2004;94:141 3. [8] Bernasconi A, Azancot A, Simpson JM, Jones A, Sharland GK. Fetal dextrocardia: diagnosis and outcome in two tertiary centres. Heart 2005;91(12):1590 4. [10] Bohun C, Potts J, Casey B, Sandor G. A Population-Based Study of Cardiac Malformations and Outcomes Associated with Dextrocardia. AJC 2007;100:305 9.