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