Uncovering Silent Acquired Long QT Syndrome Using Exercise Testing In Long-Term Pediatric ALL Survivors
Bibliographic record
Abstract
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
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".