Article Figures & Data
Figures
- FIGURE 1.
Dose-dependent doxorubicin effect on LV MRGlu. (A) Axial and sagittal planes of small-animal PET studies on mice before and after treatment with saline or with 5 or 7.5 mg/kg dose of doxorubicin. (B) Doxorubicin administration was followed by significant increase in LV MRGlu, as opposed to stable values in untreated mice. Moreover, dose-dependent nature of doxorubicin metabolic effect was confirmed by significant difference between posttherapy scans in animals treated with standard or high doses. (C) Doxorubicin administration did not affect SM MRGlu. *P < 0.05 vs. after treatment. **P < 0.01 vs. after treatment. DXR = doxorubicin.
- FIGURE 2.
Myocardial and SM divergent metabolic pattern in HD population. (A) Distribution of baseline LV SUV was similar between 69 enrolled subjects, excluded patients, and controls. (B) In HD patients, LV SUV progressively increased from PET1 to PET3, remaining relatively stable at PET4. By contrast, it remained unchanged in controls. (C) Divergent nature of SM doxorubicin effect can be appreciable at PET4. (D) LV SUV/SM SUV ratio at the 4 time points. *P < 0.05 vs. control.
- FIGURE 3.
Individual and average values of LV ejection fraction in 2 subgroups of patients with normal and abnormal cardiac follow-up. ns = not statistically significant.
- FIGURE 4.
(A and B) Divergent myocardial metabolic pattern between example HD patients with abnormal (A) and normal (B) cardiac follow-up. (C) 18F-FDG uptake on 4 PET/CT scans in 2 subgroups shows that baseline LV SUV was markedly lower in patients with late cardiac abnormalities than in remaining 25 patients (*P < 0.01). (D) 18F-FDG uptake significantly and progressively increased in 11 patients with late cardiac abnormalities. (E) This trend persisted even after doxorubicin discontinuation, as opposed to remaining 25 subjects.
Tables
Characteristic HD Control P Age (y) 39 ± 13 (range, 19–58) 41 ± 8 (range, 20–72) NS Male sex 37/69 (53%) 35/69 (50%) NS Weight (kg) 67.1 ± 12 76.5 ± 7 <0.05 Glycemia at 18F-FDG injection (mg/dL) 79 ± 7 (range, 61–101) 83 ± 11 (range, 62–94) NS Cardiovascular risk profile Hypertension 6/69 (8%) 15/69 (21%) <0.01 Tobacco use 19/69 (27%) 30/69 (43%) <0.05 Total cholesterol 183.7 ± 30 188 ± 53 NS Low-density lipoprotein 114.5 ± 32 120 ± 25 NS Triglycerides 121.3 ± 49 129.7 ± 57 NS Creatinine 0.8 ± 0.1 0.85 ± 0.2 NS Family history of CAD 7/69 (10%) 5/69 (7%) NS Time intervals between PET studies PET1–PET2 (d) 73.7 ± 21 99 ± 90 <0.05 PET2–PET3 (d) 148 ± 70 167 ± 98 NS PET3–PET4 (d) 195 ± 92 229 ± 100 NS Overall PET1–PET4 (d) 427 ± 198 448 ± 141 NS Baseline Ann-Arbor staging I stage 7/69 (10%) — — II stage 42/69 (60%) — — III stage 8/69 (12%) — — IV stage 12/69 (17%) — — B symptoms 10/69 (14%) — — Mediastinal radiotherapy 35/69 (55%) — — Total administered doxorubicin dose (mg) 456.6 ± 103 — — NS = not statistically significant; CAD = coronary artery disease.
Qualitative data are expressed as numbers followed by percentages in parentheses; continuous data are expressed as mean ± SD.
- TABLE 2
Demographic and Clinical Data of HD Patients with Normal Follow-up Findings with Respect to Those with Abnormal Follow-up Findings
Characteristic Normal follow-up (n = 25) Abnormal follow-up (n = 11) P Age (y) 36.8 ± 12 44.5 ± 17 NS Male sex 14 (56%) 7 (63%) NS Weight (kg) 68.9 ± 13 70.7 ± 12 NS Glycemia at PET1 (mg/dL) 79.2 ± 5 82.4 ± 4 NS Cardiovascular risk profile Hypertension 2 (8%) 1 (9%) NS Tobacco use 5 (20%) 2 (18%) NS Total cholesterol 186 ± 28 181 ± 33 NS Low-density lipoprotein 119.6 ± 28 113.3 ± 31 NS Triglycerides 117.2 ± 56 122.9 ± 49 NS Creatinine 0.8 ± 0.1 0.7 ± 0.1 NS Family history of CAD 2 (8%) 1 (9%) NS Baseline Ann Arbor staging I stage 3 (12%) 2 (18%) NS II stage 15 (60%) 5 (45%) NS III stage 3 (12%) 2 (18%) NS IV stage 4 (16%) 2 (18%) NS B symptoms 5 (20%) 2 (18%) NS Mediastinal radiotherapy 13(52%) 5 (45%) NS Total administered doxorubicin dose (mg) 430.9 ± 109 421.3 ± 107 NS Clinical follow-up duration (d) 1,121 ± 874 860 ± 665 NS Follow-up clinical data Chest pain — — - Dyspnea — 2 (18%) - Syncope — — - Palpitations — 2 (18%) - Follow-up ECG abnormalities — 3 (27%)* - Baseline echocardiography End-diastolic diameter (mm) 49.1 ± 2 48 ± 3 NS End-systolic diameter (mm) 29 ± 3 31 ± 2 NS Fractional shortening (%) 44% ± 4% 46% ± 3% NS LV ejection fraction 59.8 ± 2.1 59.3 ± 1.7 NS Diastolic dysfunction 0 (0%) 0 (0%) NS Follow-up echocardiography End-diastolic diameter (mm) 49.2 ± 1 49.3 ± 5 NS End-systolic diameter (mm) 27.2 ± 3 33.6 ± 11 NS Fractional shortening (%) 44% ± 4% 38% ± 5%† <0.05 LV ejection fraction 60.3 ± 2 55 ± 7† <0.05 Diastolic dysfunction 0 (0%) 5 (45%) <0.01 ↵* 1 patient developed atrial fibrillation; 2 patients developed negative T waves in anterior leads.
↵† P < 0.05 with respect to corresponding baseline.
NS = not statistically significant; ECG = electrocardiographic; CAD = coronary artery disease.
Qualitative data are expressed as numbers followed by percentages in parentheses; continuous data are expressed as mean ± SD.
Univariate analysis Multivariate analysis Characteristic df P OR 95% CI P OR 95% CI Sex 1 0.760 0.8 0.19–3.35 0.142 * Age (y) 1 0.140 1.04 0.99–1.09 0.339 * Anne Arbor stage 1 0.882 0.94 0.41–2.12 0.694 * Mediastinal radiotherapy 1 0.718 1.30 0.31–5.39 0.711 * Cumulative doxorubicin dose (mg) 1 0.963 1.00 0.99–1.01 0.486 * Baseline LV SUV 1 0.030 0.18 0.03–0.85 <0.001 0.065 0.006–0.74 Follow-up time (d) 1 0.364 1.00 0.99–1.001 0.408 * ↵* Excluded from final model.
df = degrees of freedom; OR = odds ratio; CI = confidence limit.
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