Prevalence of Diastolic Dysfunction in Adult Survivors of Childhood Cancer: A Report From SJLIFE Cohort

Abstract

Background: The prevalence of diastolic dysfunction has not been systematically evaluated in a large population of survivors of childhood cancer using established guidelines and standards.

Objectives: This study sought to assess the prevalence and progression of diastolic dysfunction in adult survivors of childhood cancer exposed to cardiotoxic therapy.

Methods: Comprehensive, longitudinal echocardiographic examinations of adult survivors of childhood cancer ≥18 years of age and ≥10 years from diagnosis in SJLIFE (St. Jude Lifetime Cohort Study) were performed. Diastolic dysfunction was defined based on 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines.

Results: Among 3,342 survivors, the median (25th-75th percentiles [quartile (Q)1-Q3]) age at diagnosis was 8.1 years (Q1-Q3: 3.6-13.7 years), 30.1 years (Q1-Q3: 24.4-37.0 years) at the baseline echocardiography evaluation (Echo 1), and 36.6 years (Q1-Q3: 30.8-43.6 years) at the last follow-up echocardiography evaluation (1,435 survivors) (Echo 2). The proportion of diastolic dysfunction was 15.2% (95% CI: 14.0%-16.4%) at Echo 1 and 15.7% (95% CI: 13.9%-17.7%) at Echo 2, largely attributable to concurrent systolic dysfunction. Less than 5% of survivors with preserved ejection fraction had diastolic dysfunction (2.2% at Echo 1, 3.7% at Echo 2). Using global longitudinal strain assessment in adult survivors with preserved ejection fraction (defined with a cutpoint worse than -15.9%), the proportion of diastolic dysfunction increased to 9.2% at baseline and 9.0% at follow-up.

Conclusions: The prevalence of isolated diastolic dysfunction is low among adults who received cardiotoxic therapies for childhood cancer. The inclusion of left ventricular global longitudinal strain significantly increased the identification of diastolic dysfunction.

Keywords: adult survivors of childhood cancer; anthracycline chemotherapy; chest-directed radiotherapy; diastolic dysfunction; echocardiography.

Graphical abstract

Figure 1

Distribution of Echocardiographic Variables A violin plot illustrating the distribution of echocardiographic variables used to assess diastolic function over time. The shaded area describes probability density; the white box plot denotes the median and IQR. E/A = E velocity divided by A velocity; e’ = mitral annular e’ velocity; E/e’ = E velocity divided by mitral annular e’ velocity; LA = left atrial; TR = tricuspid regurgitation.

Figure 2

Distribution of Specific Echocardiographic Variables Stratified by Type of Cardiotoxic Therapy A violin plot demonstrating the distribution of specific echocardiographic variables used to assess diastolic function stratified by type of cardiotoxic therapy exposure at baseline echocardiography evaluation. The shaded area describes probability density; the white boxplot denotes the median and IQR. RT = therapy; other abbreviations as in Figure 1.

Figure 3

Changes in Left Ventricular Diastolic Function Over Time Following Childhood Cancer Therapies Septal velocity, average E/e’, and TR velocity significantly changed over time. Conversely, the E/A ratio, lateral e’ velocity, and LA volume index did not change. The P values are from the age-adjusted linear mixed-effects model. Echo 1 = baseline echocardiography evaluation; Echo 2 = follow-up echocardiography evaluation; other abbreviations as in Figure 1.

Central Illustration

Diastolic Dysfunction Distribution in St. Jude Lifetime Cohort Study Tier A displays adult survivors with preserved ejection fraction that could be assigned diastolic grading based on 4 key echocardiographic diastolic variables followed by global longitudinal strain worse than −15.9%. Tier B displays adult survivors with reduced ejection fraction that could be assigned diastolic grading. ASE = American Society of Echocardiography; EACVI = European Association of Cardiovascular Imaging; GLS = global longitudinal strain; LVEF = left ventricular ejection fraction; SJLIFE = St. Jude Lifetime Cohort Study.