Cardiopulmonary exercise testing in patients with CACNA1C-associated LQTS

Background Type 8 long QT syndrome (LQT8) is characterised by prolonged QT interval and a high burden of ventricular repolarisation abnormalities including sudden cardiac death. Purpose Patients and clinicians face uncertainties about the daily risk of cardiac arrest, particularly during physical performance. Therefore, we aim to establish a risk assessment based on systematically collected data. Methods We analysed eight patients genetically confirmed to carry CACNA1C variants, of whom three had cardiac arrests in early childhood, while others were discovered incidentally. One patient met criteria for cardiac-only Timothy syndrome. All patients performed cardiopulmonary exercise testing (CPET) with several having multiple studies over time, resulting in a total of 19 CPETs. Echocardiograms were available for all patients, and Holter monitor results for all but one patient. All CPETs were conducted on beta-blockade. Results On resting ECG the average heart rate was 66.5 ± 10.7 beats per minute (bpm). Average QT at diagnosis was 476.8 ± 47.8 ms, with a corrected QTc of 487.9 ± 37.2 ms. Two patients had sinus arrhythmia and three were atrially paced at rest. No ventricular arrhythmias were observed at rest. On initial CPET, average peak oxygen uptake was 29.3 ± 8.5 ml/kg/min (82 ± 25% predicted) at a peak heart rate of 141.6 ± 24.3 bpm (73 ± 13% predicted). Peak respiratory exchange ratio averaged 1.09 ± 0.13. On initial CPET, four patients developed premature ventricular contractions (PVCs), but only in one patient were more than 5 per minute detected. That patient had a high PVC burden with multiple runs of non-sustained ventricular tachycardia. There were no episodes of syncope or cardiac arrest across all 19 CPETs. Conclusions Our cases demonstrate the safety and utility of exercise testing in CACNA1C-related disease. Longitudinal follow-up revealed diverse electrophysiological findings, including QT prolongation and reduced chronotropic response. From our data it is suggested that CPET is safe to perform on appropriate therapy and exercise should be encouraged.