restrictive physiology is a major predictor of poor outcomes in children with hypertrophic...
TRANSCRIPT
Restrictive Physiology is a Major Predictor of Poor Outcomes in Children
with Hypertrophic Cardiomyopathy
Shiraz A Maskatia MD, Jamie A Decker MD, Joseph A Spinner BA, Jeffrey J Kim MD, Jack F Price MD, John L Jefferies MD, William J Dreyer MD, E O’Brian Smith PhD, Joseph W Rossano MD, Susan W Denfield MD
Background• Hypertrophic cardiomyopathy (HCM) is associated
with an increased risk of sudden and heart failure deaths in children 1,2
• Previously identified risk factors for death or heart transplant (HT) in children include abnormal BP response to exercise and left ventricular hypertrophy 2
• A subgroup of patients with restrictive physiology (RP) with worse outcomes has been described, but data in children is limited 3,4
1. Nugent et al Circulation 20052. Decker et al J Am Coll Cardiol 2009
3. Colan et al Circulation 20074. Webber et al Circulation (S2) 2008
Hypothesis
• The presence of restrictive physiology is a major predictor of hospitalization, death or transplant in children with HCM
Methods
• Retrospective review of patients followed for HCM at Texas Children’s Hospital
• Inclusion criteria: – Age < 18 years at the time of diagnosis– Follow up time ≥ 1 year– Echocardiogram (echo) evidence of HCM without
secondary cause• Outcomes analysis included Poisson and Cox
regression
Methods• RP on echo defined as > 1 echo with one of the
following: – Left atrial enlargement without left ventricular dilation– Mitral inflow E/A ratio ≥ 3– Mitral E/E’ ratio ≥ 10
• RP on catheterization (cath) defined as: – Systolic pulmonary artery pressure ≥ 35 mmHg– Left or right ventricular end diastolic pressure ≥ 15 mmHg– Pulmonary vascular resistance index ≥ 4 woods units
Results• 444 patients with HCM treated at our institution from
1/1/1985 to 1/1/2010• 119 patients met inclusion criteria• RP by echo was present in 49 (41%) patients– Left atrial enlargement was present in 43 (88%) patients– E/E’ ratio ≥ 10 present in 27 (55%) patients
– E/A ratio ≥ 3 present in 9 (18%) patients
• 17 (14%) patients underwent cath– RP by cath present in 11 (65%) patients– Of the 11 patients with RP by cath, 10 (91%) had RP by
echo
• No evidence of RP present in 69 (58%) patients• One patient had RP by cath, and not by echo
Results
Patient Characteristics
All patients (n=119)
Non-restrictive
(n=69)
Restrictive by Echo (n=49)
Restrictive by Cath (n=11)
Age at diagnosis (years) 10.2 ± 5.5 11.2 ± 5.5 9.2 ± 5.3 9.4 ± 5.5
Male (%) 86 (72%) 51 (74%) 29 (59%) 4 (36%)
Symptoms at presentation (%) 31 (26%) 16 (23%) 12 (24%) 7 (64%)
FH of HCM (%) 47 (40%) 22 (32%) 22 (45%) 6 (55%)
Ventricular arrhythmias (%) 9 (7.6%) 2 (3%) 7 (14%) 1 (9%)
IVS (z-score) 5.7 ± 4.8 4.8 ± 4.7 6.8 ± 4.7 4.5 ± 2.6
Abn BP response (%) 35 (29%) 13 (19%) 19 (39%) 3 (27%)
Results
• Patients with RP by echo – higher ventricular septal z-scores (p=0.03) – more likely to have ventricular arrhythmias (p=0.02
OR=5.6 CI=1.1-28.2) – more likely to have an abnormal blood pressure
response to exercise (p=0.01 OR=3.9 CI=1.4-11.4)
• Patients with RP by cath had higher left ventricular free wall z-scores (p=0.03)
• 7 patients died; 6 (86%) had RP• 3 pts underwent HT; all 3 had RP• Aborted sudden cardiac death (aSCD)
occurred in 9 pts; 6 (67%) had RP• RP by echo or cath had a positive predictive
value of 17% and a negative predictive value of 98% for death or HT
Results
Risk Factor Hazard Ratio (95% Conf Int) P-valueHospitalization
Restrictive by Echo 3.5 (1.3-9.3) 0.01
Restrictive by Cath 11.5 (3.0-43.5) <0.01
Restrictive on presentation 7.4 (1.4-38.5) 0.02Female 4.8 (2.1-10.8) <0.01Age at presentation (years) 1.1 (1.1-1.2) 0.05
Symptoms at presentation 1.7 (0.77-3.8) 0.19
Abnormal BP response 2.1 (0.73-5.9) 0.17
Septal wall thickness z-score 1.02 (0.94-1.1) 0.63
Death or Aborted Sudden Cardiac DeathRestrictive by Echo 3.8 (1.2-11.9) 0.02
Restrictive by Cath 4.7 (1.1-22.7) 0.05
Restrictive on presentation 9.0 (1.1-76.9) 0.05Female 1.5 (0.54-4.4) 0.43Age at presentation (years) 1.02 (0.93-1.1) 0.70
Symptoms at presentation 6.5 (1.9-22.7) <0.01
Septal wall thickness z-score 1.03 (0.89-1.2) 0.67
Death or Heart TransplantRestrictive by Echo 5.7 (1.05-31) 0.04
Restrictive by Cath 89 (4.9-1000) <0.01
Restrictive on presentation 22 (1.05-500) 0.04Female 1.33 (0.32-5.6) 0.69Age at presentation (years) 0.93 (0.80-1.1) 0.37
Symptoms at presentation 8.0 (1.66-38) <0.01
Septal wall thickness z-score 0.98 (0.82-1.15) 0.98
Limitations
• Retrospective analysis• Determination of left atrial volume was
subjective• Only 14% of patients in the study underwent
cath – may result in selection bias.
Conclusions• Children with hypertrophic cardiomyopathy without
restrictive physiology have a good prognosis • Children with hypertrophic cardiomyopathy and
restrictive physiology accounted for the majority of poor outcomes
• Patients with evidence of restrictive physiology on echocardiogram and symptoms should undergo further hemodynamic assessment by cardiac catheterization