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

INTRODUCTIONPart 1

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

METHODOLOGYPart 2

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)

RESULTSPart 3

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 detailsVariable %

SubtypeClassicalToF-PA, ToF absent pulmonary valve, ToF-AVSDUnknown

93.64.11.3

Palliative shunt01>1

65.429.05.6

RepairInfundibular resectionTransannular patchVSD closure and pulmonary homograftUnknown

19.130.15.945.0

Overall survival lower than general population

Log rank test p <0.001

Tetralogy cohortControl 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 0.003

*Univariate mode only

Quality of life

• NYHA class– I: 87.5%, – 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 0.226p = 0.013

Reintervention

Procedure N

PVR 166

Surgical 147123

110143

Percutaneous 1912

171

Early revision 24

AVR/root replacement 2

Tricuspid valve 8

Balloon pulmonary angioplasties 24

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 0.001

Older age at repair 0.96 0.92 – 1.00 0.008

PVR only

Transannular patch 1.79 1.26 – 2.56 0.001

Nonclassical ToF 4.22 2.16 – 8.25 <0.001

Older age at repair 0.92 0.87 – 0.96 <0.001

PVR and survival

Log rank test p = 0.539

PVR groupSevere PR group

The effect of PVR on RV size and function

Indexed RVEDV ml/m2 RV ejection fraction %

P = 0.154P < 0.001

N=17

The effect of PVR on exercise performance

Peak VO2 as % predicted VE/VCO2 slope

P = 0.050P = 0.623

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

SUMMARYPart 4

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

QUESTIONSPart 4