Peak Oxygen Uptake on Cardiopulmonary Exercise Test Is a Predictor for Severe Arrhythmic Events during Three-Year Follow-Up in Patients with Complex Congenital Heart Disease.

Peak Oxygen Uptake on Cardiopulmonary Exercise Test Is a Predictor for Severe Arrhythmic Events during Three-Year Follow-Up in Patients with Complex Congenital Heart Disease.

Von Sanden F, Ptushkina S, Hock J, Fritz C, Hörer J, Hessling G, Ewert P, Hager A, Wolf CM.J Cardiovasc Dev Dis. 2022 Jul 4;9(7):215. doi: 10.3390/jcdd9070215.PMID: 35877577


 Take Home Points:

  • Risk stratification for sudden cardiac death (SCD) and primary prevention ICD therapy in patients with complex congenital heart disease is challenging.
  • This single-centre retrospective study of 1194 patients with complex CHD evaluated the ability of a range of measurements collected during routine cardiopulmonary exercise testing (CPET) to aid in the risk assessment of SCD over a three-year follow up period.
  • Severe arrhythmia was documented in 97 patients (8.1 %/3 years), with independent risk factors being older age and low peak oxygen uptake (VO2peak) on multivariate analysis.
  • The authors thus suggest considering age and VO2peak in the risk stratification of SCD and the individualized decision for primary prevention ICD implantation in patients with complex CHD.
  • The data from this study has a number of limitations and will not result in a significant change in clinical practice, however it does endorse the large body of literature supporting the use of CPET in the overall risk stratification of patients with CHD.

Dr Timothy Roberts


Commentary by Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch:

 Patients with complex CHD carry a life-time elevated risk for severe arrhythmia and sudden cardiac death (SCD), with up to 26 % of CHD deaths attributed to SCD. International guidelines specific to CHD patients and indications for primary prevention ICD are limited, and improving the risk stratification process is desperately needed.

Cardiopulmonary exercise testing (CPET) provides a well-established marker of cardiopulmonary function in children and adults with CHD and has not been mentioned in 2015 and 2020 guidelines as a tool for SCD risk stratification. The aim of this study was to evaluate measurements obtained during CPET as predictors for the occurrence of severe arrhythmias during a three-year follow-up.

The study design was that of a single-centre retrospective analysis of patients with complex CHD (univentricular heart, Ebstein’s anomaly, tetralogy of Fallot, truncus arteriosus communis, and transposition of the great arteries post arterial switch operation or Senning/Mustard procedure) undergoing CPET between 2009 and 2014. A symptom-limited customized ramped upright bicycle CPET protocol was used until exhaustion (respiratory exchange ratio > 1.0). The highest 30-second interval of oxygen uptake during exercise was defined as peak oxygen uptake (VO2peak). Data collected on the date of CPET were demographics (age, gender, body mass index), VO2peak, anaerobic threshold (VO2at), ventilatory efficiency (VE/VCO2 slope), respiratory exchange ratio at peak exercise, and pulse oximetric saturation at peak exercise (SpO2max). Medical charts and available Holter recordings, ICD-, pacemaker- and event-recorder readings were reviewed within a follow-up time of three years after CPET. Systemic ventricular function by transthoracic echocardiography was added to the analysis if assessed within 12 months of the index CPET.  Primary endpoint was survival without severe arrhythmia events (SAE), chiefly SCD, aborted SCD, appropriate ICD discharge, ICD anti-tachycardia pacing for VT, hospital admission for acute ventricular arrhythmia, cardiac syncope caused by ventricular arrhythmia, and the occurrence of non-sustained VT on Holter, event-recorder, pacemaker, or ICD recordings. Data analyses were performed using SPSS with appropriate statistical considerations. Univariate and backwards stepwise multivariable logistic regression models were used to identify parameters associated with SAE within three years. Time-to-event analysis was conducted via univariable and backwards stepwise multivariable Cox regression analysis. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic ability of VO2peak to predict SAE.

In total, 1194 patients (663 male) were included in the study. Median age was 25.9 years (IQR 17.4–34.6 years), median BMI was 22.4 (IQR 19.8–25.6) kg/m2. Underlying diagnosis was:

  • Univentricular heart (UVH) in 205
  • Ebstein’s anomaly (EBS) in 135
  • Tetralogy of Fallot (TOF) in 469
  • Truncus arteriosus communis (TAC) in 51
  • Transposition of the great arteries, arterial switch operation (TGA ASO) in 149
  • Transposition of the great arteries, Senning/Mustard procedure (TGA SM) in 185.

Transthoracic echocardiogram was available in 1148 patients. Peak performance was reached by 1075 patients during CPET. Three years of follow-up were completed in 1101 patients (92.2 %). Holter recordings were available in 445 patients (38.1 %). During follow-up, ICD’s were present in 42 patients, 145 patients had a pacemaker, and event-recorders were used in three patients; of these totals, 27 pacemakers and 17 ICDs were implanted during follow-up, including five ICD-upgrades to preexisting pacemakers.

Twenty-seven patients (2.3 %) died during follow-up:

  • SCD diagnosed in 2 patients
  • Non-SCD in 16
  • Unclear cause of death in 9.

Severe arrhythmic events occurred in 97 of 1194 patients (8.1 %), with no statistically significant differences found between the distinct anatomical groups. Non-sustained VT was the most frequent SAE, while sustained VT was documented in eight patients  (Table 2, below):

Clinical variables associated with SAE in multivariable analysis were age at CPET (OR, 1.029; 95 % CI, 1.00901.049; p=0.004) and VO2peak (OR, 0.951; 95 % CI, 0.921-0.982; p=0.002). VE/VCO2 slope, RERmax, SpO2max, gender, and type of CHD did not correlate significantly in the logistic regression model.

ROC curve analysis identified VO2peak (AUC, 0.687; 95 % CI, 0.631-0.743; p < 0.001) and age (AUC, 0.659; 95 % CI, 0.602-0.715; p < 0.001) as independent predictors for SAE in CHD patients, with potential cut-off values for VO2peak at 24.9 ml/min/mg (Youden’s Index, 0.318; sensitivity 0.702; specificity 0.616) and age at 26.2 years (YI, 0.242; sensitivity 0.711; specificity 0.531). Lower VO2peak values in the second and first quartiles were associated with a decrease in SAE-free survival (90.7% and 82.2%). Patients with VO2peak above the cut-off value of 24.9 ml/min/kg presented with more frequent 3-year survival without SAE than patients with lower VO2peak than cut-off (95.8% vs. 85.1%). Age above the cutoff value of 26.2 years led to less frequent 3-year survival without SAE (87.4% vs. 95.1%).