Vascular endothelial growth factor inhibitor-induced cardiotoxicity: prospective multimodality assessment incorporating cardiovascular magnetic resonance imaging
Bibliographic record
Abstract
BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFIs) are effective anticancer agents, but are associated with cancer therapy-related cardiac dysfunction (CTRCD) and hypertension. The timing, frequency and magnitude of these toxicities are poorly defined. The objective of this study is therefore to investigate the incidence, time course and mechanisms of VEGFI-associated CTRCD and hypertension. METHODS: Patients commencing VEGFI underwent blood pressure (BP) monitoring, echocardiography and cardiac biomarker measurement at baseline and prospectively over 24 weeks. Serial adenosine stress perfusion cardiovascular MRI (CMR) was performed in a substudy. CTRCD was defined as left ventricular ejection fraction (LVEF) decline by ≥10 percentage points from baseline to a value <50%. RESULTS: 78 patients participated (68% men; age 63±11 years). 15 patients (19%) developed CTRCD, and it was evident at 4 weeks in 93% of cases. Overall, LVEF was 4.2% (95% CI: -6.2% to -2.3%, p<0.001) lower than baseline at 4 weeks. At 4 weeks, N-terminal pro-brain natriuretic peptide, but not troponin, was higher in patients with CTRCD. 62 (77%) patients developed hypertension. Home systolic and diastolic BP increased by 7.2 mm Hg (4.7-9.8, p<0.001) and 4.8 mm Hg (3.1-6.5, p<0.001), respectively, at 1 week. There was no association between change in LVEF and BP.CMR-derived LVEF, T1 relaxation times and resting myocardial blood flow (n=46) were 5.2% (-7.3% to -3.1%, p<0.001), 27 ms (-40 to -14, p<0.001) and 14.7 mL/100mL/min (-24.2 to -5.1, p=0.004), respectively, lower at 4 weeks. CONCLUSION: VEGFI-associated CTRCD is frequent and occurs early. This finding has implications for prioritising early cardiac imaging follow-up after commencing treatment. Underlying mechanisms include myocardial and microvascular effects that are at least partly independent of hypertension.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".