Ultra long term outcomes in adult survivors of tetralogy of Fallot and the effect of pulmonary valve replacement Dobson R1,2, Danton M2, Walker N2, Tzemos, N1,Walker H2 1Institute of Cardiovascular and Medical Sciences, University of Glasgow 2Scottish Adult Congenital Cardiac Service, Golden Jubilee National Hospital

Part 1 Introduction

The problem Survival to adulthood of infants with tetralogy of Fallot (ToF) now exceeds 90% in modern cohorts1,2 Form a significant proportion of the workload of adult CHD services The ability of post-ToF repair interventions to modify the long term prognosis for these patients has not been fully defined 1Ide et al 2009, 2Park et al 2010

Objective To define the long term outcomes of adult survivors of ToF with respect to Survival, functional capacity and adverse events The effect of pulmonary valve replacement on clinical and functional outcome

Part 2 METHODOLOGY

Data collection National centralized model for ACHD care in Scotland Computerised database Electronic records were where possible corroborated with op notes and medical certificate of cause of death

Methods Overall survival analysis; KM curve compared to age and gender matched controls Morbidity outcomes Ventricular arrhythmia Atrial arrhythmia Device (pacemaker or ICD) Reintervention and PVR Current functional status (clinical / CPET / CMR data)

Part 3 RESULTS

Baseline characteristics 376 patients (male:female 59:41) post ToF repair who survived to at least age 16 Mean age at repair 5.2 years (SD 7.3); median 3 years Mean follow-up from repair 28.3 years (SD 9.4)

Era of repair

Temporal trends in median age at repair* *Excluded 1950s and 2000s as too few patients in each category

ToF subtypes and repair details Variable % Subtype Classical ToF-PA, ToF absent pulmonary valve, ToF-AVSD Unknown 93.6 4.1 1.3 Palliative shunt 1 >1 65.4 29.0 5.6 Repair Infundibular resection Transannular patch VSD closure and pulmonary homograft 19.1 30.1 5.9 45.0

Overall survival lower than general population Log rank test p <0.001 Tetralogy cohort Control group

Deaths 15 patients died at a mean age of 49 +/- SD 13.7 years Cause of death Heart failure (5) Postoperative – PVR (3)* Sepsis (3) Sudden (2) Stroke (1) Malignancy (1) *From 166 PVR procedures

Multivariate analysis for death Variable HR 95% CI P-value Older age at repair 1.11 1.04 – 1.19 0.003 Male gender 5.64 1.08 – 29.49 0.041 Nonclassical ToF 13.43 2.51 – 71.92 0.002 QRS duration* 1.07 1.02 – 1.11 *Univariate mode only

Quality of life NYHA class Median peak VO2 69.5% predicted II: 5.3% III: 0.5% Median peak VO2 69.5% predicted Social deprivation score = 4.1 Scottish population mean 4; p=0.51 Total Fertility Rate 0.18 (1.61 for national data 2013)

MRI n=181 RV volumes RV ejection fraction

CPET n=169 % predicted VO2max VE/VCO2 slope

RVEF versus peak VO2 Spearman’s rho 0.226 p = 0.013

Reintervention Procedure N PVR 166 Surgical 147 Percutaneous 19 2 3 110 14 Percutaneous 19 17 Early revision 24 AVR/root replacement Tricuspid valve 8 Balloon pulmonary angioplasties

Historical trends in repeat intervention

Freedom from repeat intervention Total reintervention PVR

Multivariate analysis for reintervention Variable HR 95% CI P-value Any reintervention Transannular patch 1.72 1.23 – 2.39 0.001 Nonclassical ToF 2.95 1.57 – 5.54 Older age at repair 0.96 0.92 – 1.00 0.008 PVR only 1.79 1.26 – 2.56 4.22 2.16 – 8.25 <0.001 0.92 0.87 – 0.96

PVR and survival Log rank test p = 0.539 PVR group Severe PR group

The effect of PVR on RV size and function Indexed RVEDV ml/m2 RV ejection fraction % P < 0.001 P = 0.154 N=17

The effect of PVR on exercise performance Peak VO2 as % predicted VE/VCO2 slope P = 0.623 P = 0.050 N=16

Prevalence of arrhythmia Atrial arrhythmia in 13.3%, ventricular arrhythmia in 3.4% Therapy 12.8% on regular antiarrhythmics 5.1% ICD 2.1% had radiofrequency ablation

Freedom from arrhythmia

Multivariate analysis for arrhythmia Atrial arrhythmia Older age at repair conferred hazard ratio of 1.10 (95% CI 1.07 – 1.13) p = <0.001 No significant variables identified for ventricular arrhythmia

Device insertion (pacemaker or ICD) 9% of patients overall Device type Pacemaker in 4% (VVI 0.8% and DDD in 3.2%) ICD in 4.8% CRT-D in 0.3%

Freedom from device insertion

Part 4 SUMMARY

Mortality Long term (>30 years) survival remains excellent For patients who survive to age >16 Heart failure is the main cause of death Older age at repair, non-classical forms of ToF, and male gender confer increased risk

Morbidity Arrhythmia is common High rates of repeat intervention, mainly PVR, performed with low mortality PVR reduces RV volumes but does not improve exercise capacity

Limitations and future directions Single center retrospective cohort Functional data is cross-sectional for a heterogenous group Historical loss of follow-up – patients geographically remote from surgical center may still be under the radar Creation of an international registry will enable far more powerful and robust analysis of prognosis and intervention

Part 4 QUESTIONS