Peak oxygen uptake, ventilatory efficiency and QRS-duration predict event free survival in patients late after surgical repair of tetralogy of Fallot

Abstract

Objective

Patients with repaired tetralogy of Fallot (ToF) have an increased long-term risk of cardiovascular morbidity and mortality. Risk stratification in this population is difficult. Initial evidence suggests that cardiopulmonary exercise testing (CPET) may be helpful to risk-stratify patients with repaired ToF.

Methods and results

We studied 875 patients after surgical repair for ToF (358 females, age 25.5 ± 11.7 year, range 7–75 years) who underwent CPET between 1999 and 2009. During a mean follow-up of 4.1 ± 2.6 years after CPET, 30 patients (3.4%) died or had sustained ventricular tachycardia (VT). 225 patients (25.7%) had other cardiac related events (emergency admission, surgery, or catheter interventions). On multivariable Cox regression-analysis, %predicted peak oxygen uptake ($\dot{\mathrm{V}}\mathrm{O}2$ %) (p = 0.001), resting QRS duration (p = 0.030) and age (p < 0.001) emerged as independent predictors of mortality or sustained VT. Patients with a peak $\dot{\mathrm{V}}\mathrm{O}2$ ≤ 65% of predicted and a resting QRS duration ≥ 170 ms had a 11.4-fold risk of death or sustained VT.

Ventilatory efficiency expressed as $\dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{C}\mathrm{O}2$ slope (p < 0.001), peak $\dot{\mathrm{V}}\mathrm{O}2$ % (p = .001), QRS duration (p = .001) and age (p = 0.046) independently predicted event free survival. $\dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{C}\mathrm{O}2$ slope ≥ 31.0, peak $\dot{\mathrm{V}}\mathrm{O}2$ % ≤ 65% and QRS duration ≥ 170 ms were the cut-off points with best sensitivity and specificity to detect an unfavorable outcome.

Conclusions

CPET is an important predictive tool that may assist in the risk stratification of patients with ToF. Subjects with a poor exercise capacity in addition to a prolonged QRS duration have a substantially increased risk for death or sustained ventricular tachycardia, as well as for cardiac-related hospitalizations.

Introduction

Tetralogy of Fallot (ToF) is the most common cyanotic heart defect at birth. Surgical improvements over the past decades have led to an excellent long term outcome [1]. Nevertheless, adults with repaired ToF continue to have residual or recurrent lesions as well as an increased risk for right and left heart failure and sudden cardiac death. The exact mechanisms for late sudden death are incompletely defined but are probably related to both, the residual hemodynamic and electrophysiological substrates that act in concert [2], [3]. Pulmonary valve replacement may be required in patients with significant pulmonary regurgitation to avoid progressive right ventricular dilation and to preserve right ventricular function [3], [4], [5], [6], [7] with the ultimate aim of improving long-term survival.

In patients with congenital heart disease (CHD), cardiopulmonary exercise testing (CPET) is generally used to quantify the degree of exercise intolerance [8], [9], [10], [11]. Beyond this application, increasing interest had been devoted at understanding the prognostic value of CPET in CHD [5], [8], [12], [13], [14]. However, the identification of patients at higher risk for death or cardiac-related morbidity is challenging. In patients with repaired ToF, Gatzoulis et al. [3] demonstrated a relationship between prolonged QRS duration and sudden cardiac death. whereas Giardini et al. [5] demonstrated in a small cohort that peak oxygen uptake $\left(\dot{\mathrm{V}}\mathrm{O}2\right)$ and ventilatory efficiency could be helpful to stratify patients regarding their risk of death and hospitalization during follow-up. Recent studies [15], [16] confirmed the predictive value of hemodynamic and cardiopulmonary parameters in patients with ToF.

Both QRS prolongation and reduced exercise tolerance are thought to be related to some of the same underlying hemodynamic abnormalities. So far, there is no information on whether exercise variables provide any additional prognostic information over QRS duration, and how the information provided by the two tests might integrate to provide a better risk stratification tool for patients with repaired ToF.

Hence, the objective of the present study was to assess the potential value of CPET variables to predict survival, as well as morbidity-free survival both independently of and in combination with QRS-duration and demographic variables in a large cohort of patients after surgical ToF repair.