Long-term risk of heart failure in adult cancer survivors: a systematic review and meta-analysis

Abstract

Background: Cancer survivors are at increased risk of heart failure (HF). While cardiotoxicity is commonly sought at the time of cancer chemotherapy, HF develops as a result of multiple 'hits' over time, and there is limited evidence regarding the frequency and causes of HF during survivorship.

Objectives: This systematic review sought to investigate the relationship between cardiotoxic cancer therapies and HF during survivorship.

Methods: We searched the EMBASE, MEDLINE and CINAHL databases for studies reporting HF in adult survivors (≥50 years old), who were ≥5 years postpotential cardiotoxic cancer therapy. A random effects model was used to examine the associations of HF.

Results: Thirteen papers were included, comprising 190 259 participants (mean age 53.5 years, 93% women). The risk of HF was increased (overall RR 1.47 (95% CI (1.17 to 1.86)). Cardiotoxic treatment, compared with cancer alone, provided a similar risk (RR of 1.46 (95% CI 0.98 to 2.16)). The overall HF incidence rate was 2.1% compared with 1.7% in the control arm-an absolute risk difference of 0.4%. In the breast cancer population ratio (11 studies), the overall HF RR was 2.57 (95% CI 1.35 to 4.90)). Although heterogeneity was significant (I²=77.2), this was explained by differences in patient characteristics; once multivariable analysis accounted for follow-up duration (OR 0.99, 95% CI (0.97 to 0.99), p=0.047), age (OR 1.14, 95% CI (1.04 to 1.25), p=0.003) and hypertension (OR 0.95, 95% CI (0.92 to 0.98), p<0.001), residual heterogeneity was low (I²=28.7).

Conclusions: HF is increased in adult cancer survivors, associated with cardiotoxic cancer therapy and standard risk factors. However, the small absolute risk difference between survivors and controls suggests that universal screening of survivors is unjustifiable. A risk model based on age, cardiotoxic cancer therapy and standard risk factors may facilitate a selective screening process in this at-risk population.

Keywords: Cardiomyopathy, Dilated; Cardiovascular Diseases; Risk Factors.

Figure 1

Study selection process.

Figure 2

Association of cancer survivorship with reduction of left ventricular ejection fraction (LVEF).

Figure 3

Association of cancer survivorship with incident HF; (A) incident HF in all cancer survivors, (B) incident HF in subgroups of cancer survivors. HF, heart failure; REML, random effect restricted maximum likelihood.

Figure 4

Association of exposure to potentially cardiotoxic therapy with incident HF, independent of other risk factors. BMI, body mass index; CVD, cardiovascular disease; HF, heart failure; REML, random effect restricted maximum likelihood.

Figure 5

Annualised HF risk in cancer survivors. HF, heart failure; REML, random effect restricted maximum likelihood.