Uncovering Silent Acquired Long QT Syndrome Using Exercise Testing In Long-Term Pediatric ALL Survivors

Doxorubicin is a key treatment for acute lymphoblastic leukemia (ALL). However, it leads to a significant burden of acute and delayed chemotherapy-induced cardiotoxicity in survivors. An example is acquired long QT syndrome (aLQTS), which may cause serious yet preventable life-threatening consequences. PURPOSE: To identify and characterize childhood ALL survivors with aLQTS using maximal exercise testing. METHODS: In this cross-sectional study with exploratory analysis, a total of 250 childhood ALL survivors were evaluated for abnormal QT interval prolongation using the McMaster cycle exercise test. QT intervals were corrected for heart rate using Bazett's formula (QTc). RESULTS: A total of 198 survivors (102 males; 96 females), having reached their VO2peak (mean 32.1 ± 8.4 mL/kg/min; range 15.5-57.8 mL/kg/min), were included in our analyses. Two survivors were excluded for possible congenital LQTS. The QTc of borderline (n = 37) and long QT survivors (n = 20) was significantly longer than normal survivors (n = 141) at rest, exercise, and recovery (see Table 2). Out of 57 survivors presenting an abnormal QTc prolongation, 40 survivors (70%) presented no QT interval anomalies at rest but developed various anomalies during exercise. No significant differences were found between the groups for any of the measured clinical characteristics or cardiac parameters. CONCLUSION: This is the first study to identify and characterize long-term childhood ALL survivors with silent aLQTS using exercise testing. The standardization of exercise testing in the regular follow-up of oncology patients is necessary for appropriate cardiac prevention and surveillance to enhance the health and quality of life of the ever-increasing number of cancer survivors. Table 2. - QTc values (using the Bazett formula) throughout rest, exercise, and recovery stages of the CPET Stage of CPET Total QTcB (ms) Borderline QTc (ms) Long QTc (ms)* Normal QTc (ms) p-value** p-value*** Supine rest 396.6 ± 35.9 402.3 ± 32.1 429.8 ± 44.9 390.4 ± 32.8 <0.0001 <0.0001a,c Seated rest 391.1 ± 30.2 399.0 ± 34.9 408.4 ± 29.1 386.8 ± 28.1 0.003 0.008c Standing rest 400.0 ± 34.8 411.4 ± 32.8 425.2 ± 57.3 393.3 ± 29.1 <0.0001 <0.0001b,c Exercise stage 1 400.2 ± 31.3 405.7 ± 37.4 424.8 ± 35.7 395.1 ± 27.4 0.001 <0.0001c Exercise stage 2 401.4 ± 38.5 414.5 ± 36.9 434.6 ± 52.5 393.2 ± 33.3 <0.0001 <0.0001b,c Exercise stage 3 402.3 ± 36.0 420.9 ± 28.9 432.4 ± 54.2 393.5 ± 31.0 <0.0001 <0.0001b,c Exercise stage 4 396.1 ± 33.4 409.6 ± 30.2 400.8 ± 67.9 391.7 ± 27.5 0.006 0.017b Exercise stage 5 400.0 ± 29.7 404.0 ± 35.4 425.8 ± 38.6 394.6 ± 23.4 0.002 <0.0001a,c Exercise stage 6 398.7 ± 25.5 409.4 ± 26.8 420.8 ± 33.0 392.2 ± 21.1 0.001 0.002b,c Exercise stage 7 382.3 ± 26.1 414.3 ± 17.8 358.0 ± 27.5 378.6 ± 20.3 0.347 0.005a,b Exercise stage 8 379.1 ± 23.2 - - 379.1 ± 23.2 - - Exercise stage 9 370.4 ± 12.2 - - 370.4 ± 12.2 - - Active pedaling recovery 1-min 399.5 ± 29.8 412.7 ± 29.3 427.9 ± 38.7 391.7 ± 24.7 <0.0001 <0.0001b,c Active pedaling recovery 3-min 401.4 ± 34.3 426.3 ± 31.9 417.7 ± 46.4 392.7 ± 29.2 <0.0001 <0.0001b,c Passive seated recovery 5-min 408.0 ± 30.4 431.2 ± 24.6 432.9 ± 32.1 397.5 ± 25.0 <0.0001 <0.0001b,c a significant difference between borderline QT and long QT b borderline QT and normal QT c long QT and normal QT