Download - Catalyst

Heterotaxy Syndrome:
considering malrotation
Isaac Chuang Stein
Seattle Children’s Hospital General Pediatric Surgery
Thursday August 13, 2015
Outline
• Intro to Heterotaxy
• Epidemiology
• Ways to stratify Heterotaxy patients
• Clinical Presentation
• Implications for intestinal malrotation
What is Heterotaxy?
• Internal thoraco-abdominal organs demonstrate
abnormal arrangement across the left-right axis of the
body; broad spectrum
• Results in an unusual degree of symmetry between the
right and left sides of the body
• Can involve the heart, liver, lungs, intestine, and spleen
• Associated with mutations of genes that encode proteins
that are components of the TGF-B pathway1
• NODAL, NKX2-5, CRELD1, LEFTY2, ZIC3, CRIPTC
Epidemiology
• HS occurs in 1 in 10,000-40,000 births2
• Equal distribution between male and female
• Equal risk across varying ethnic groups
• *Within the Heterotaxy population, 32-89% are
estimated to have intestinal rotation anomalies8
Ways to stratify patients
• Atrial appendage isomerism
• Right atrial isomerism vs. Left atrial isomerism
• Used to describe whether heart has two “right” atria or
two “left” atria
• Polysplenia syndrome vs. Asplenia syndrome
• Situs inversus
• Right/left asymmetry remains
• Mirror image of normal anatomy
• Will only have one spleen
Right Atrial Isomerism (RAI)
• “Two right sides”
• Heart with bilateral right atria and atrial appendages
• Absence of left-sided structures (such as coronary sinus)
• Consistent heart defects
•
•
•
•
Absent atrial septum3,4
Anomalous pulmonary venous drainage3,4
Pulmonary outflow tract obstruction3,4
Single ventricle physiology3,4
• Absent spleen
Left Atrial Isomerism (LAI)
• “Two left sides”
• Heart with bilateral left atria and atrial appendages
• Cardiac abnormalities
• *Interrupted IVC – characteristic (80%)5
• Highly variable atrial septal anatomy
• Commonly show polysplenia
Polysplenia vs. Asplenia
Polysplenia
Asplenia
• Spleen seen on left and right
sides of abdomen
• Spleen absent from
abdomen
• Indicative of left atrial
isomerism and its
associated abnormalities
• Indicative of right atrial
isomerism and its
associated abnormalities
How will they present?
• Antenatal
• Fetal complete heart block – consider LAI6
• AV canal defect with ventricular asymmetry – consider RAI
• Postnatal
• Cyanosis – due to right-to-left shunting secondary to
pulmonary artery outflow obstruction
• Respiratory distress – pulmonary congestion due to
obstructed pulmonary veins
• *Presentation of patients with RAI is much more severe
How will they present?
• Noncardiac presentations
• Sepsis – secondary to asplenia in RAI
• Jaundice – secondary to biliary atresia (10% of LAI)7
• Bilious vomiting – secondary to malrotation
Risk of malrotation
• Intestinal rotational anomalies have been reported in
32-89% of patients with Heterotaxy8
• Malrotation has been described in both RAI and
LAI
• May be asymptomatic; must always consider
malrotation in a patient with HS
• Evaluation and management of the asymptomatic
patient is controversial
Malrotation in RAI vs. LAI
• Hill et al. 2014, 38 patients with HS identified.
• 18/38 underwent diagnostic laparoscopy or
laparotomy based on upper GI findings or clinical
symptoms worrisome for malrotation (bilious
emesis, abdominal distension, bloody BM)
• Malrotation identified in 8/18 patients (44%) who
underwent surgery
• Presence of abdominal symptoms predictive of
identifying malrotation (80%)
LAI vs. RAI
• Likelihood of malrotation in LAI is significantly
lower than in RAI (15% vs 72%)10
• Especially in an asymptomatic patient with LAI
Hill et al. 2014
Management of the
asymptomatic patient
• Risks vs. benefits of surgery must be weighed heavily
in his patient population
• Avoid overtreating, especially in these patients with
cardiac anomalies
•
Papillon et al. in 2013
• 30 asymptomatic HS patients with upper GI findings
indicative of malrotation
• 0% had true malrotation or a narrow mesentery at time
of exploration
Treatment algorithm
Hill et al. (2014)
Alternative approach
• Yu et al. 2009 retrospective review over 1997-2007
(Boston Children’s)
• 31 HS patients compared to 51 non-HS patients
undergoing Ladd’s
• No significant difference found in…
• Rates of SBO
• Hospital stay
• Hospital mortality
• Routine screening and elective Ladd’s procedure to any
patient with HS with positive upper GI given possible
catastrophic outcome of volvulus
Multicenter Analysis
• Salavitabar et al. 2015 (NYPB, Columbia)
• Inclusion criteria: HS, IRA shown on upper GI,
asymptomatic
• 325 patients at 41 tertiary care children’s hospitals
(Pediatric Health Information System database)
• 2004-2011
• Primary outcome: major morbidity or mortality on
admissions subsequent to the initial hospitalization
• Obstruction including volvulus, gut ischemia, intestinal
resection, any subsequent admission.
Multicenter Analysis
• 188/325 (58%) underwent Ladd’s
• Remainder managed with observation
• Ladd’s procedure on initial hospitalization was
associated with a 2.2x increase in odds of major
morbidity or mortality (p=0.007)
• Suggest that in an asymptomatic patient with HS,
even with IRA seen on upper GI, cautious
observation is safest.
The asymptomatic patient
• Multidisciplinary approach with cardiology, cardiac
surgery, GI, etc…
• Consider patient’s overall health/ability to undergo
surgery
• Ability to follow-up/social support
• Consider isomerism if present
• Comfort level of surgeon with Ladd’s procedure
References
1.
Kosaki K, Bassi MT, Kosaki R, et al. Characterization and mutation analysis of human LEFTYA and LEFTYB, homologues of murine genese implicated
in left-right axis development. Am J Hum Genet 1999; 64: 712.
2.
Lim JS, McCrindle BW, Smallhorn JF, et al. Clinial features, management, and outcome of children with fetal and postnatal diagnoses of isomerism
syndromes. Circulation 2005; 112: 2454.
3.
Sapire DW, Ho SY, Anderson RH, Rigby ML. Diagnosis and significance of atrial isomerism. Am J Cardiol 1986; 58: 342.
4.
Stranger P, Rudolph AM, Edwards JE. Cardiac malpositions. An overview based on study of sixty-five necropsy specimens. Circulation 1977; 56: 159
5.
Sharma S, Devine W, Anderson RH, Zuberbuhler JR. Identification and analysis of left atrial isomerism. Am J Cardiol 1987; 60: 1157.
6.
Ho SY, Fagg N, Anderson RH, et al. Disposition of the atrioventricular conduction tissues in the heart with isomerism of the atrial appendages: its relation
to congenital complete heart block. J Am Coll Cardiol 1992; 20: 904.
7.
Tanano H, Hasegawa T, Kawahara H, et al. Biliary atresia associated with congenital structural anomalies. J Pediatr Surg 1999; 34: 1687.
8.
Strouse PJ. Disorders of intestinal rotation and fixation (“malrotation”). Pedatr Radiol 2004; 34(11): 837-51.
9.
Ferdman B, States L, Gaynor JL, et al. Abnormalities of intestinal rotation in patients with congeniral heart disease and the heterotaxy syndrome. Congenit
Heart Dis 2007; 2(1): 12-8.
10.
Hill SJ, Heiss KF, Mittal R, et al. Heterotoxy syndrome and malrotation: Does isomerism influence risk and decision to treat. J Pedatr Surg 2014; 49: 934937.
11.
Papillon S, Goodhue CJ, Zmora O, et al. Congenital heart disease and heterotaxy; upper gastrointestinal fluoroscopy can be misleading and surgery in an
asymptomatic patient is not beneficial. J Pedatr Surg 2013; 48: 164-9.
12.
Yu DC, Thiagarajan RR, Laussen PC, et al. Outcomes after the Ladd procedure in patients with heterotaxy syndrome, congenital heart disease, and
intestinal malrotation. J Pediatr Surg 2009; 44: 1089-95.
13.
Salavitabar A, Anderson B, Aspelund G, et al. Heterotaxy syndrome and intestinal rotational anomalies: Impact of the Ladd procedure. J Pediatr Surg 2015;
In press.