Peak oxygen uptake, ventilatory efficiency and QRS-duration predict event free survival in patients late after surgical repair of tetralogy of Fallot
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 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.
Section snippets
Study design and study subjects
This study was designed as a multicenter retrospective investigation. In seven European tertiary institutions all consecutive patients with tetralogy of Fallot or Fallot-type morphology (double outlet right ventricle with sub-aortic ventricular septal defect and pulmonary atresia with ventricular septal defect after bi-ventricular repair) who were referred for a CPET as part of their routine clinical follow-up evaluation between 1999 and 2009 were included in the study. The study was approved
Results
Baseline characteristics of the 875 patients studied are presented in Table 1. All CPETs were performed until maximum exhaustion resulting in a mean respiratory exchange ratio of 1.11 ± 0.16 and a mean peak of 27.7 ± 8.6 ml/kg/min, representing 76.6 ± 19.7% predicted (Fig. 1). No patient was cyanotic at rest or during peak exercise. Follow-up was completed for all patients.
Discussion
This study showed that CPET is a valuable prognostic tool in patients with repaired tetralogy of Fallot and its prognostic value is complementary to that provided by more traditional risk factors, like QRS duration. Indeed, patients who have both a predicted peak of ≤ 65% and a resting QRS duration of ≥ 170 ms have a 11.4-fold increased risk of dying or having a sustained VT during follow-up. We also showed that significant cardiac morbidity could be predicted by a peak of ≤ 65%, a
Limitations
All patients were followed up at tertiary centers and a referral bias towards more advanced forms of the disease with more symptomatic patients cannot be excluded. However, at the institutions involved, it is established clinical practice to test every patient with repaired ToF with CPET. Therefore, we believe that the results of our study can be generalized to the whole ToF patient population.
Cardiac MRI is the gold standard for the assessment of cardiovascular hemodynamics after repair of ToF
Conclusion
Cardiopulmonary exercise testing is a valuable tool in the long-term follow-up of patients with tetralogy of Fallot. It has independent, additional prognostic value on top of the established risk factor of QRS duration. Exercise testing should be used in the clinical risk stratification of patients with repaired ToF.
Acknowledgment
No funding. No conflict of interest.
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