Diastolic Dysfunction by Cardiac Magnetic Resonance Imaging in Patient’s with Sickle Cell Anemia

Background: Sickle Cell Anemia (SCA) is an autosomal hemoglobinopathy which causes anemia. Prolonged anemic states leads to a compensatory increase in plasma volume with an increase in cardiac output and eventual LV dilation with subsequent cardiac dysfunction. Diastolic dysfunction often precedes systolic dysfunction. Diastolic dysfunction has been associated with increase morbidity and mortality. CMR imaging can be used to measure peak filling rate (PFR) and time to peak filling rate (tPFR) which are both measurements of diastolic function. These measurements may give insight into early findings of diastolic dysfunction in this population.

Methods: Single institution retrospective study of SCA patients with CMR evaluation. Cine images were manually contoured across all phases of the cardiac cycle with removal of basal and apical slices without myocardium present (Figure 1). Diastolic filling curves were obtained using Medis. Demographic and clinical CMR data including indexed left ventricular end diastolic volume (LVEDVi), left ventricular mass (LVM), left ventricular cardiac index (LVCi) and systolic function by LVEF were collected. Statistical analysis was performed using Student’s T-test.

Results: 26 patients with SCA and 11 control patients were identified with complete CMR datasets. Table 1 shows the demographic and CMR findings. There were no differences in age between the two groups. Compared to the control group, patients with SCA had higher LVEDi, LV mass, and LVCi. There was no difference in EF between the two groups. For LV diastolic indices there was no difference in PFR or PFR/EDV between the two groups. When dichotomizing the SCA patients by mass (Table 2), patients with increased LVM had lower LV PFR/EDV (2.4 ± 0.9) compared to SCA patients with normal LVM (3.0 ± 0.7) with a p-value of .038. The tPFR was longer 118.4 ± 27.9 in patients with increase LVM compared to 98.2 ± 24.0 in SCA patients with normal LVM with a p-value of .031. The group with increase LVM was significantly older in age (18.3 ± 4.3) compared to the group with normal mass (9.7 ± 3.3), p-value < .001.

Conclusion: Patients with SCA have findings of LV dilation, increase LVM and increase cardiac output compared to the control group, although without evidence of diastolic dysfunction. Assuming increase LVM is a proxy for increase disease severity, the groups were divided into increase LVM and normal LVM. While both groups had diastolic indices within the normal range, the PFR/EDV was significantly decreased in the group with increased LVM and the tPFR was longer compared to those with normal LVM. It is notable that the group with increased LVM was older in age, which is consistent with prior studies showing increase prevalence of diastolic dysfunction in older patients with SCA. Thus, using CMR to evaluate filling curves and measure PFR, PFR/EDV and tPFR may show early subclinical evidence of diastolic dysfunction with potential for earlier intervention to decrease morbidity and mortality in these patients.

Table 1. Sickle Cell Anemia verse control demographics information and CMR indices

Parameters	Sickle Cell Anemia (N = 26)	Control (Nf11)</span>	SCA/Control P-value
Age (years)	14.3 ± 5.8	13.9 ± 3.4	.410
Body Surface Area (kg/m2)	1.4 ± 0.4	1.6 ± 0.4	.063
Male/Female	15/11	10/1	N/A
Hydroxyurea Therapy	15/26 (58%)
HR (beats per minute)	82.8 ± 16.8	70.3 ± 15.2	.020
Indexed LV end diastolic volume (mL/m2	111.0 ± 20.1	95.1 ± 7.2	.008
LV ejection fraction (%)	59.4 ± 6.1	59.6 ± 6.8	.459
LV mass (grams)	95.5 ± 33.2	56.5 ± 12.6	.0003
LVCi (L/min/m2)	5.4 ±1.5	3.9 ± 0.6	.002
LV Peak Filling Rate	391.6 ±143.6	394.3 ± 113.8	.478
LV Peak Filling Rate / End Diastolic Volume	2.7 ±.8	2.6 ± 0.4	.447
Time to Peak Filling rate	109.1 ± 27.7	129.9 ± 29.9	.024

Table 2. Sickle Cell Anemia demographics and CMR indices dichotomized by LV Mass

Parameters	Sickle Cell Anemia Normal Mass (N = 12)	Sickle Cell Anemia Increased Mass (Nf14)</span>	P-value
Age (years)	9.7 ± 3.3	18.3 ± 4.3	< .0001
Body Surface Area (kg/m2)	1.1 ± 0.2	1.7 ± 0.2	< .0001
Male/Female	6/6	9/5
Hydroxyurea Therapy	8/12 (66.6%)	7/14 (50%)
HR (beats per minute)	86.9 ± 20.9	79.4 ± 12.1	.131
Indexed LV end diastolic volume (mL/m2	108.0 ± 11.8	113.5 ± 25.4	.251
LV ejection fraction (%)	60.1 ± 5.4	58.8 ± 6.8	.304
LV mass (grams)	67.1 ± 15.2	119.9 ± 23.1	< .0001
LVCi (L/min/m2)	5.6 ±1.4	5.3 ± 1.7	.298
LV Peak Filling Rate	345.6 ±100.8	431.0 ± 165.7	.067
LV Peak Filling Rate / End Diastolic Volume	3.0 ± 0.7	2.4 ± 0.9	.038
Time to Peak Filling rate	98.2 ± 24.0	118.4 ± 27.9	.031

Figure 1. Contours across cardiac cycle