Late effects of pediatric hematopoietic stem cell transplantation on left ventricular function, aortic stiffness and myocardial tissue characteristics

Abstract

Background: Pediatric hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of cardiovascular disease later in life. As HSCT survival has significantly improved, with a growing number of HSCT indications, tailored screening strategies for HSCT-related late effects are warranted. Little is known regarding the value of cardiovascular magnetic resonance (CMR) for early identification of high-risk patients after HSCT, before symptomatic cardiovascular disease manifests. This study aimed to assess CMR-derived left ventricular (LV) systolic and diastolic function, aortic stiffness and myocardial tissue characteristics in young adults who received HSCT during childhood.

Methods: Sixteen patients (22.1 ± 1.5 years) treated with HSCT during childhood and 16 healthy controls (22.1 ± 1.8 years) underwent 3 T CMR. LV systolic and diastolic function were measured as LV ejection fraction (LVEF), the ratio of transmitral early and late peak filling rate (E/A), the estimated LV filling pressure (E/Ea) and global longitudinal and circumferential systolic strain and diastolic strain rates, using balanced steady-state free precession cine CMR and 2D velocity-encoded CMR over the mitral valve. Aortic stiffness, myocardial fibrosis and steatosis were assessed with 2D velocity-encoded CMR, native T1 mapping and proton CMR spectroscopy (¹H-CMRS), respectively.

Results: In the patient compared to the control group, E/Ea (9.92 ± 3.42 vs. 7.24 ± 2.29, P = 0.004) was higher, LVEF (54 ± 6% vs. 58 ± 5%, P = 0.055) and global longitudinal strain (GLS) ( -20.7 ± 3.5% vs. -22.9 ± 3.0%, P = 0.063) tended to be lower, while aortic pulse wave velocity (4.40 ± 0.26 vs. 4.29 ± 0.29 m/s, P = 0.29), native T1 (1211 ± 36 vs. 1227 ± 28 ms, P = 0.16) and myocardial triglyceride content (0.47 ± 0.18 vs. 0.50 ± 0.13%, P = 0.202) were comparable. There were no differences between patients and controls in E/A (2.76 ± 0.92 vs. 2.97 ± 0.91, P = 0.60) and diastolic strain rates.

Conclusion: In young adults who received HSCT during childhood, LV diastolic function was decreased (higher estimated LV filling pressure) and LV systolic function (LVEF and GLS) tended to be reduced as compared to healthy controls, whereas no concomitant differences were found in aortic stiffness and myocardial tissue characteristics. When using CMR, assessment of LV diastolic function in particular is important for early detection of patients at risk of HSCT-related cardiovascular disease, which may warrant closer surveillance.

Keywords: Aortic stiffness; Cardiovascular magnetic resonance; Diffuse fibrosis; Hematopoietic stem cell transplantation; Myocardial steatosis; Pediatric; Systolic and diastolic function; T1 mapping.

Fig. 1

A 22-year-old man, who was transplanted for a non-malignant bone marrow failure disorder at the age of 8 years. a the transmitral E/A ratio (early peak filling rate/late peak filling rate) was measured using 2D velocity-encoded CMR (left panel) and Ea (early peak diastolic mitral septal tissue velocity) was derived from the four-chamber long-axis relaxation (right panel). LV filling pressure was estimated by the ratio of the transmitral early peak maximum velocity and the early peak diastolic mitral septal tissue velocity. b From two, three- and four-chamber and mid-ventricular short-axis cine CMR (left panel), the longitudinal and circumferential strain and strain rate curves were extracted (right panel). The myocardial features at the endocardial borders (red dots), which were automatically tracked throughout the cardiac cycle (green lines), were manually annotated in the end-diastolic and end-systolic phase. GLS: global longitudinal strain; GCS: global circumferential strain; GLSR-S: global longitudinal peak systolic strain rate; GCSR-E: global circumferential early peak diastolic strain rate

Fig. 2

The same patient as in Fig. 1 is presented. a Aortic pulse wave velocity was calculated from through-plane 2D velocity-encoded CMR transecting the ascending aorta (red) and the abdominal aorta, above the aortic bifurcation (green) (left panel), according to: aortic pulse wave velocity = ∆x/∆t, with ∆x: the distance between the ascending and abdominal aorta (yellow dotted line) and ∆t: transit time of the onset of the systolic velocity wave front (black arrow) (right panel). b Proton-cardioavascular magnetic resonance spectroscopy (¹H-CMRS) was used to measure the myocardial triglyceride content. The voxel of interest was placed in the mid-ventricular septum (yellow box) (left panel). Myocardial triglyceride content was calculated as Tg-(CH₂)ⁿ and Tg-CH₃ relative to the sum of the triglyceride and the unsuppressed water signal (not shown). Triglycerides were measured using the water-suppressed spectrum (right panel). c Native T1 was measured in the mid-ventricular septal segments in short-axis view (black, dotted region of interest)

Fig. 3

CMR measurements with means and 95% confidence intervals and median and interquartile ranges for normally and non-normally distributed data, respectively. Despite a non-significantly lower left ventricular (LV) systolic function (a-c) and lower LV diastolic function (d-e) as indicated by the increased estimated LV filling pressure, the CMR parameters for aortic stiffness (f) and LV structure (g) and myocardial tissue characteristics (h-i) were comparable for the patients who received HSCT and the healthy controls. Abbreviations as in Table 4