Table 2.
Reported risk factors for asymptomatic left ventricular systolic dysfunction
| 1st Author, year | Population | Outcome definition; (% abnormal) | Tested risk factors (reference category) | Tested categories (effect size; 95% confidence interval) | Model comments |
|---|---|---|---|---|---|
| Slieker, 2019 [13] |
n = 546 Last anthracycline dose + ≥ 3 years. Attained age < 18 years No stem cell transplant, congenital heart disease or familial cardiomyopathy |
GLS Z-score (continuous) | Attained age, years | β −0.086; −0.140– −0.031 | Includes 14% survivors 3-5 years since diagnosis |
| Age at diagnosis, years | n.m.a | ||||
| Female sex | n.m.a | ||||
| Body surface area per 0.1 m2 increment | β −0.065; −0.118– −0.013 | ||||
| Years since last anthracycline dose | n.m.a | ||||
| Heart RT exposure | n.m.a | ||||
| Anthracycline dose per 50 mg/m2 increment | n.m.a | ||||
| Dexrazoxane therapy | n.m.a | ||||
| Christiansen, 2016 [17] |
n = 231 Acute lymphoblastic leukaemia/lymphoma, diagnosis + ≥ 5 years, attained age ≥ 18 years |
GLS > − 18.3% (female) > − 17.2% (male) (32%) |
Age at diagnosis | OR 0.96; 0.90–1.03 | 23% had no anthracycline exposure |
| Attained age | OR 1.02; 0.98–1.06 | ||||
| Heart RT exposure | OR 5.2; 2.2–12 | ||||
| Anthracycline dose (< 300 mg/m2) | >300 (OR 4.8; 1.7–14) | ||||
| Armstrong, 2015 [18] |
n = 1807 any cancer, anthracycline or Heart RT, diagnosis + ≥ 10 years, attained age ≥ 18 years |
3D LVEF < 50% (5.8%) |
Ethnicity (non-Hispanic white) | Other (RR 1.53; 0.93–2.52) | 17% had no anthracycline exposure |
| Female sex | RR 0.54; 0.36–0.83 | ||||
| Age at diagnosis (≥ 15 years) | 0–4 (RR 0.66; 0.35–1.27), 5–9 (RR 0.67; 0.36–1.25), 10–14 (RR 1.02; 0.59–1.76) | ||||
| Attained age (18–30 years) | 31–40 (RR 1.38; 0.81– −2.35), > 40 (RR 0.98; 0.52–1.84) | ||||
| Heart RT dose (0 Gy) | 1-19 (RR 1.24; 0.70–2.22), 20–29 (RR 1.86; 1.00–3.45), ≥ 30 (RR 7.99; 3.88–16.48) | ||||
| Anthracycline dose (0 mg/m2) | 1–100 (RR 1.74; 0.66–4.61), 101-200 (RR 2.80; 1.24–6.31), 201-300 (RR 3.80; 1.59–9.10), 301-400 (RR 4.76; 2.16 – 10.50), > 400 (RR 7.71; 3.04 – 19.57) | ||||
| Metabolic syndrome (≥ 3 of the following) | RR 1.07; 0.74–1.53 | ||||
| Waist circumference > 102 (male) > 88 cm (female) | RR 1.34; 0.99-1.82 | ||||
| Triglycerides > 150 mg/dl | RR 1.01; 0.70–1.44 | ||||
| HDL < 40 (male) < 50 mg/dl (female) | RR 1.01; 0.74–1.38 | ||||
| Blood pressure ≥ 130/ and/or /85 mmHg or treated | RR 1.44; 1.22–1.70 | ||||
| Fasting glucose > 100 mg/dl or diabetes treatment | RR 1.02; 0.75–1.39 | ||||
|
GLS > age/sex norm (31.8%) |
Ethnicity (non-Hispanic white) | Other (RR 1.22; 1.03–1.46) | |||
| Female sex | RR 1.55; 1.34–1.79 | ||||
| Age at diagnosis (≥ 15 years) | 0–4 (RR 1.02; 0.82–1.27), 5–9 (RR 0.92; 0.74 – 1.15), 10–14 (RR 1.02; 0.83–1.24) | ||||
| Attained age (18–30 years) | 31–40 (RR 1.25; 1.05–1.48), > 40 (RR 1.49; 1.20–1.85) | ||||
| Heart RT dose (0 Gy) | 1–19 (RR 1.38; 1.14–1.66), 20–29 (RR 1.65; 1.31– 2.08), ≥ 30 (RR 2.39; 1.79–3.18) | ||||
| Anthracycline dose (0 mg/m2) | 1–100 (RR 1.38; 1.05–1.82), 101–200 (RR 1.16; 0.89–1.50), 201–300 (RR 1.06; 0.78–1.45), 301–400 (RR 1.72; 1.31–2.26), > 400 (RR 1.73; 1.19–2.50) | ||||
| Metabolic syndrome (≥ 3 of the following) | RR 1.94; 1.66–2.28 | ||||
| Waist circumference > 102 (male) > 88 cm (female) | RR 1.73; 1.48–2.01 | ||||
| Triglycerides > 150 mg/dl | RR 1.65; 1.40–1.95 | ||||
| HDL < 40 (male) < 50 mg/dl (female) | RR 1.40; 1.23–1.59 | ||||
| Blood pressure ≥ 130/and/or /85 mmHg or treated | RR 1.48; 1.33–1.65 | ||||
| Fasting glucose > 100 mg/dl or diabetes treatment | RR 1.37; 1.19–1.59 | ||||
|
GCS > age/sex norm (23.1%) |
Ethnicity (non-Hispanic white) | Other (RR 0.84; 0.64–1.09) | |||
| Female sex | RR 1.01; 0.84–1.21 | ||||
| Age at diagnosis (≥ 15 years) | 0–4 (RR 1.24; 0.92–1.67), 5–9 (RR 1.01; 0.74–1.38), 10–14 (RR 1.11; 0.84–1.48) | ||||
| Attained age (18–30 years) | 31–40 (RR 0.85; 0.69–1.06), > 40 (RR 0.98; 0.73–1.33) | ||||
| Heart RT dose (0 Gy) | 1–19 (RR 0.86; 0.66–1.11), 20–29 (RR 1.14; 0.83–1.57), ≥ 30 (RR 1.64; 1.05–2.56) | ||||
| Anthracycline dose (0 mg/m2) | 1–100 (RR 0.99; 0.66–1.48), 101–200 (RR 1.24; 0.86–1.79), 201–300 (RR 1.36; 0.90 – 2.04), 301–400 (RR 1.61; 1.08–2.40), > 400 (RR 1.34; 0.78–2.31) | ||||
| Metabolic syndrome (≥ 3 of the following) | RR 1.02; 0.84–1.24 | ||||
| Waist circumference > 102 (male) > 88 cm (female) | RR 1.10; 0.92–1.32 | ||||
| Triglycerides > 150 mg/dl | RR 1.01; 0.82–1.13 | ||||
| HDL < 40 (male) < 50 mg/dl (female) | RR 0.92; 0.78–1.08 | ||||
| Blood pressure ≥ 130/ and/or /85 mmHg or treated | RR 1.04; 0.92–1.18 | ||||
| Fasting glucose > 100 mg/dl or diabetes treatment | RR 1.06; 0.89–1.25 | ||||
| van der Pal, 2010 [20] |
n = 525 any cancer, anthracycline/RT/high dose cyclo-/ifosfamide, diagnosis + ≥5 years, attained age ≥ 18 years |
FS (continuous) |
Male sex | β 0.77 (−0.27–1.80) | 31% had no anthracycline exposure |
| Age at diagnosis (>15 years) | 0–5 (β −3.55; −5.80– −1.30) > 5–10 (β −1.95; −4.03–0.12), > 10–15 (β −1.32; −3.21–0.58)b | ||||
| Time since diagnosis (5-10 years) | 10–15 (β 0.41; −1.25–2.08), 15–20 (β 1.71; −0.07–3.50), 20–25 (β 2.07; −0.08–4.22), > 25 years (β 4.86; 2.28–7.43)b | ||||
| Vincristine exposure | β −1.30; −2.88–0.27 | ||||
| Anthracycline dose (0–150 mg/m2) | 151–300 (β −1.93; −3.71− −0.15), 301–450 (β −4.24; -6.32− −2.16), > 450 (β −5.38; −7.98− −2.79)b | ||||
| Cyclophosphamide (≤ 10 g/m2) | No (β 0.38; -1.13–1.90), >10 (β -0.85; -2.91–1.22) | ||||
| Ifosfamide (≤ 10 g/m2) | No (β 0.54; −2.89–3.96), > 10 (β 0.66; −3.06–4.39) | ||||
| RT exposure (none) | Thorax (β − 3.67; − 5.54 − − 1.79), Abdomen (β − 3.54; -5.87− − 1.20), Spine (β − − 0.79; − 2.92–1.24), total body (β − 0.53; − 4.01–2.94) | ||||
|
FS < 30% (27%) |
Male sex | OR 0.73; 0.47–1.13 | |||
| Age at diagnosis (> 15 years) | 0–5 (OR 2.94; 1.08–8.02), > 5–10 (OR 1.64; 0.67– 4.01), > 10–15 (OR 1.45; 0.64–3.28)b | ||||
| Time since diagnosis (5–10 years) | 10–15 (OR 0.80; 0.41–1.54), 15–20 (OR 0.40; 0.18–0.86), 20–25 (OR 0.48; 0.19–1.23), > 25 (OR 0.11; 0.03–0.42)b | ||||
| Vincristine exposure | OR 1.47; 0.71–3.05 | ||||
| Anthracycline dose (0–150 mg/m2) | 151–300 (OR 3.98; 1.58–10.01), 301–450 (OR 7.77; 2.85–21.22), > 450 (OR 10.58; 3.35–33.40)b | ||||
| Cyclophosphamide (≤ 10 g/m2) | No (OR 1.01; 0.52–1.99), > 10 (OR 1.01; 0.45–2.26) | ||||
| Ifosfamide (≤ 10 g/m2) | No (OR 1.25; 0.23–6.67), > 10 (OR 1.50; 0.26–8.82) | ||||
| RT exposure (none) | Thorax (OR 3.49; 1.60–7.61), Abdomen (OR 2.66; 1.00–7.05), Spine (OR 0.64; 0.23–1.74), total body (OR 0.53; 0.10–2.87) | ||||
| Hudson, 2007 [21] |
n = 278 various cancers, no congenital heart disease/congestive heart failure/chronic illness/trisomy21/anaemia |
FS (continuous) |
Age at diagnosis | < 5 years (mean 35%), ≥ 5 years (mean 32%) | 22% had no anthracycline exposure |
| Diagnosis group | Leukaemia (mean 36%), Sarcoma (mean 32%), Lymphoma (mean 33%), Embryonal (mean 34%) | ||||
| QTc time | Normal (mean 34%), prolonged (mean 29%) | ||||
| Years off therapy per 5-year increment | β −.004 | ||||
| Anthracycline dose per 50 mg/m2 increment | β −.008 | ||||
|
FS < 28% (14%) |
Age at diagnosis (< 5 years) | ≥ 5 (OR 2.41; 0.91–6.40) | |||
| Diagnosis group (leukaemia) | Sarcoma (OR 5.09; 1.30–19.89), Lymphoma (OR 2.04; 0.47–8.94), Embryonal (OR 1.70; 0.36–8.04) | ||||
| Years off therapy per 5-year increment | OR 1.08; 0.52–2.27 | ||||
| Anthracycline dose per 50 mg/m2 increment | OR 1.19; 1.01–1.39 | ||||
| Pein, 2004 [22] |
n = 205 any cancer, anthracycline, diagnosis + ≥ 15 years |
FS (continuous) |
Anthracycline dose | ≤ 150 mg/m2 (mean 35%), 151–250 (mean 34%), 251–400 (mean 33%), > 400 (mean 30%)b | |
|
Teich LVEF (continuous) |
Anthracycline dose | ≤ 150 mg/m2 (mean 64%), 151–250 (mean 62%), 251–400 (mean 61%), > 400 (mean 57%)b |
Bolded values indicate statistical significance in multivariable analysis that at least included sex, age at diagnosis and either attained age or follow-up time since cancer diagnosis. aIncluded, but no effect size reported for multivariable model; bsignificant trend
FS, fractional shortening; GCS, global circumferential strain; GLS, global longitudinal strain; LVEF, left ventricular ejection fraction; OR, odds ratio; Heart RT, radiotherapy involving the heart region; RR, risk ratio; n.m., not mentioned