Abstract
Objective:
To determine the alterations in cardiac structure and function that occur in the months following spinal cord injury.
Study Design:
Cross-sectional
Setting:
Rehabilitation Hospital
Participants:
Twenty-nine (4F) volunteers 3 to 24 months post spinal cord injury.
Main Outcome Measures:
Transthoracic echocardiography was performed on each volunteer. The relationships of time since injury and neurological and sensory levels of injury to cardiac structure/function was assessed via multiple linear regression.
Results:
Time since injury was most strongly associated with reductions in left ventricular end-diastolic volume (r2 = 0.156, p = 0.034), end-systolic volume (r2 = 0.141, p = 0.045), and mass (r2 = 0.138, p = 0.047). These structural changes were paralleled by reduced stroke volume (r2 = 0.143 p = 0.043) and cardiac output (r2 = 0.317, p = 0.002, <0.001). The reductions in left ventricular structure and systolic function were not differentially affected by neurological or sensory levels of injury (p = 0.084–0.921).
Conclusions:
These results suggest progressive reductions in left ventricular structure and systolic function from 3 to 24 months following SCI that occur independent of neurological and sensory levels of injury.
Keywords: Spinal Cord Injury, Echocardiography, Atrophy
Smaller heart structures and reduced systolic and diastolic function have been documented cross-sectionally in individuals with spinal cord injury (SCI) compared with age/weight matched able bodied persons1–6. This includes lower left ventricular mass, enlarged septal and posterior wall thickness, and smaller end-diastolic and end-systolic volumes1–5,7 with reduced left ventricular filling velocity, stroke volume, and cardiac output1–4,6. These cross-sectional studies included individuals from 1 to 40 years after an SCI1,2,4–6 and therefore provide limited insight to the time course of cardiac remodeling early after injury. Although there are no direct longitudinal observations of cardiac atrophy or reduced function following SCI in humans, rodent models indicate that reductions in cardiac structure and function occur within days to weeks following spinal cord transection8. However, animal models do not approximate the effects of SCI in humans across all systems9,10. Therefore, the magnitude and time course of cardiac remodeling in the early months following SCI in humans remains largely unexamined.
Reductions in cardiac structure and function following SCI are suspected to be due to reduced physical activity, reduced venous return via loss of the muscle pump, and/or loss of supraspinal sympathetic influence11. Each of these factors would have greater influence on cardiac remodeling in those with higher level injuries as a result of more marked physical inactivity, lesser skeletal muscles engaged to augment venous return, and more impaired sympathetic function12. Individuals with cervical injuries are less likely to retain supraspinal cardiac sympathetic influence since these nerves originate between the upper thoracic (T1–T5) vertebra11. This may relate to the reduced baroreflex gain13 and lower systolic, diastolic, and mean arterial blood pressures compared to those with thoracic level injuries1,14,15. Therefore, cardiac changes in the months following injury could vary based on the level of spinal injury.
Characterizing the time frame of cardiac atrophy and physiological factors that influence it may provide insight to the increased cardiovascular disease risk in those with SCI and aid in the timing of interventions, such as exercise and weight control4,6. Therefore, the purpose of this research was to examine cardiac structure and function in individuals within the first 24 months after SCI. It was hypothesized that increasing time since injury would be associated with progressively smaller heart structures and lower indices of function and that those with high compared to low levels of injury would demonstrate a faster progression of these changes.
METHODS
Participants:
The study was approved by the Hospital Institutional Review Board and the study conforms to the Helsinki Declaration. Patients in the Hospital network who were 18 to 40 years of age with a spinal cord injury (American Spinal Injury Association A, B, C) within the previous 24 months were recruited for this cross-sectional study. Volunteers were required to be medically stable (no treatment for deep vein thrombosis, no orthostasis, no spinal precautions or weight-bearing precautions associated with a healing of a long-bone fracture) and be cleared for participation by their treating physician. Participants were excluded if they had hypertension (>140/90 mmHg), significant arrhythmias, coronary disease, diabetes, renal disease, cancer, epilepsy, any neurological disease, had regular tobacco use, autonomic dysreflexia, an implanted electronic cardiac device, or were participating in exercise beyond their standard of care.
Each volunteer gave written and informed consent prior to participation. Participants were instructed to refrain from caffeine, alcohol, and exercise 24 hrs prior to testing. All studies were conducted in the morning following a 12 hr overnight fast.
2-D Echocardiography:
Transthoracic echocardiography (Vivid-Q; GE Healthcare, Milwaukee, WI) was performed on the participant while in a left lateral decubitus position. Participants rested for 10 min prior to echocardiographic examination. Imaging was performed by a single experienced cardiologist (AB) using contemporary clinical echocardiography guidelines16. Two-dimensional (2D), pulsed-Doppler, and color tissue Doppler imaging were performed from standard parasternal and apical transducer positions with 2D frame rates of 60 to 100 frames/s and tissue Doppler frame rates >100 frames/s. Recordings were stored in raw data format for subsequent off-line analysis (EchoPacPC version 7; GE Healthcare, Horton, Norway) which was performed by a single cardiologist (TKS) who was blinded to participant sex, SCI level, and time since injury.
Cardiac Structure:
Primary structural outcome variables included: thickness of the interventricular septum (IVS) and posterior wall (PWT), internal diameter of the left ventricle (LV) during systole (LVIDs) and diastole (LVIDd), left ventricle outflow track diameter (LVOTd), left atrial diameter (LAd), volume of the left ventricle during systole (LVESV) and diastole (LVEDV), and LV mass (LVM). LVM was calculated using the area-length method. Participants without complete visualization of endocardial borders in both apical 4 and 2 chamber views were excluded from data presentation and analysis involving LV volumes. Due to a strong positive association between LVM and body surface area17,18, mass measurements were adjusted to surface area using the method of Du Bois & Du Bois19.
Systolic Function:
Stroke volume (SV) was calculated from the difference between left ventricular diastolic and systolic volumes. Cardiac output (CO) was calculated from stroke volume multiplied by heart rate. Left ventricular ejection fraction (LVEF) was calculated from stroke volume as a percentage of the LVEDV.
Diastolic Function:
Blood flow velocity at the mitral valve leaflet tips was measured during the early (E-wave) and late (A-wave) phases of diastole using spectral Doppler imaging. Septal and lateral wall contraction velocity was measured during early (E′) and late diastole (A′). Tissue velocities were measured offline from 2D color-coded tissue Doppler images. All reported Doppler data represent the average of 3 consecutive cardiac cycles.
Heart rate and blood pressure:
Heart rate and blood pressures were assessed following 10 min of sedentary seated rest on a day separate from, but within 14 days of the echocardiography analysis. Measurements of heart rate and blood pressure were made simultaneously via standard lead II electrocardiogram and brachial oscillometric blood pressure monitor (Dash 5000 patient monitor, GE, Milwaukee, WI). Resting heart rate was also obtained via ECG during the echocardiography, values between the measurement times were not significantly different (p = 0.476) but only resting heart rate during blood pressure measures is presented.
Data and Statistical Analysis:
Cardiac structure and function measurements were converted to z-scores based on normative data16,18,20. Multiple linear regression analyses were performed to determine associations between cardiac structure and function and time since injury. To explore possible neurological influences on changes in cardiac structure and function, multiple analyses were run using the neurological or sensory level of injury as predictor variables. Neurological level of injury was analyzed as either a continuous (C1-S5) or a dichotomous variable (cervical vs thoracic) based on the level of injury. Sensory zone of partial preservation, as a proxy for autonomic level of injury, was analyzed as either a continuous (C1-S5) or a dichotomous variable (above or below T6). Tests were run using Stata V.16 (Stata Corp, College Station, Texas, USA). For all tests, significance was set at p < 0.05. All data are presented as means ± SD.
RESULTS
Participants:
Twenty-nine individuals (4F, 25M) volunteered for the study. Participant demographic and anthropometric characteristics are in Table 1. Participants had an American Spinal Injury Association Impairment Scale (AIS) A, B, or C injury, with neurological levels of injury from C1 to T10, a sensory zone of partial preservation from C4 to S4/5, and a time since injury of 10.6 ± 5.0 months (Range 3.3 – 23.8 mo). TSI was not normally distributed across the 24 months as the majority of participants (20/29) were examined <12 months post injury (p = 0.048). Neurological level of injury and the sensory zone of partial preservation ranged across subjects and approximately half (15/29) had a zone of partial preservation at least two levels lower than neurological level. For example, some subjects with cervical neurological level of injury displayed sacral sensory zone of partial preservation (n = 5). Fifteen subjects had a cervical neurological level injury and were similar to the fourteen individuals with thoracic level injuries in age, height, weight, time since injury, and body surface area (Table 1). The individuals 3–12 months post injury displayed cardiac structures and functions that were comparable to able-bodied reference values presented in the literature16,18,21, while those greater than 12 months post injury displayed cardiac structures and functions that are at the low end or below the reference ranges (Table 2).
Table I.
Subject Demographic and Anthropometric Descriptors
| All | Cervical | Thoracic | p-value | |
|---|---|---|---|---|
| Subjects | 29 (4F) | 15 (3F) | 14 (1F) | |
| ASIA | 21 A, 3 B, 5 C | 11 A, 1 B, 3 C | 10 A, 2 B, 2 C | |
| Age (yrs) | 29 ± 5 | 28 ± 6 | 29 ± 5 | 0.439 |
| Time Since Injury (mo) | 10.6 ± 5.0 | 10.7 ± 5.0 | 10.5 ± 5.2 | 0.885 |
| Height (m) | 1.78 ± 0.93 | 1.79 ± 0.78 | 1.76 ± 1.06 | 0.299 |
| Weight (kg) | 78.2 ± 11.3 | 78.7 ± 12.0 | 77.6 ± 10.9 | 0.810 |
| Body Surface Area (m2) | 1.95 ± 0.16 | 1.97 ± 0.16 | 1.93 ± 0.16 | 0.519 |
Values are Means ± Standard Deviation. ASIA = American Spinal Injury
Association impairment scale.
Table 2.
Cardiac structure and function values for all subjects, separated by those with TSI less than and greater than 12 mo and able-bodied reference values.
| n | All | TSI (mo) | AB Reference * | |||
|---|---|---|---|---|---|---|
| <12 | >12 | Male | Female | |||
| Dimensions | ||||||
| SWT (mm) | 29 | 9 ± 1 | 9 ± 1 | 9 ± 1 | 9 ± 2 | 8 ± 2 |
| PWT (mm) | 29 | 10 ± 1 | 10 ± 2 | 9 ± 1 | 9 ± 2 | 9 ± 2 |
| LVIDd (mm) | 29 | 47 ± 5 | 48 ± 5 | 44 ± 3 | 46 ± 5 | 43 ± 4 |
| LVIDs (mm) | 29 | 32± 4 | 33 ± 3 | 29 ± 2 | 31 ± 5 | 29 ± 4 |
| LVOTd (mm) | 29 | 21 ± 2 | 21 ± 2 | 20 ± 2 | 22 ± 2 | 19 ± 2 |
| LAd (mm) | 29 | 33 ± 5 | 33 ± 5 | 33 ± 5 | 35 ± 4 | 32 ± 4 |
| LVM (g) | 29 | 149 ± 35 | 158 ± 6 | 126 ± 19 | 146 ± 37 | 112 ± 31 |
| LVEDV (ml) | 26 | 109 ± 21 | 116 ± 20 | 94 ± 16 | 103 ± 29 | 83 ± 20 |
| LVESV (ml) | 26 | 44 ± 11 | 48 ± 11 | 37 ± 8 | 37 ± 12 | 29 ± 9 |
| Dimensions Normalized to BSA | ||||||
| LVM (g m−2) | 29 | 76 ± 18 | 80 ± 20 | 69 ± 10 | 74.8 ± 17.5 | 66.1 ± 16.4 |
| LVEDV (ml m−2) | 26 | 56 ± 10 | 58 ± 10 | 52 ± 10 | 55.1 ± 12.8 | 49.4 ± 11.7 |
| LVESV (ml m−2) | 26 | 23 ± 5 | 24 ± 5 | 22 ± 5 | 20.4 ± 5.8 | 17.8 ± 5.3 |
| Systolic Function | ||||||
| CO (L min−1) | 26 | 4.3 ± 1.1 | 4.6 ± 1.1 | 3.5 ± 0.7 | 4.3 ± 0.9 | 4.3 ± 0.9 |
| SV (ml) | 26 | 65 ± 14 | 68 ± 14 | 57 ± 9 | 64 ± 5 | 62 ± 5 |
| LVEF (%) | 26 | 59 ± 6 | 59 ± 7 | 61 ± 4 | 63.9 ± 5.5 | 64.8 ± 5.8 |
| Diastolic Function | ||||||
| E (cm s−1) | 29 | 71 ± 17 | 69.5 ± 18 | 75 ± 16 | 78 ± 11 | 78 ± 11 |
| A (cm s−1) | 29 | 49 ± 8 | 49 ± 9 | 47 ± 7 | 42 ± 7 | 42 ± 7 |
| E/A (cm s−1) | 29 | 1.5 ± 0.4 | 1.4 ± 0.4 | 1.6 ± 0.4 | 1.9 ± 0.4 | 1.9 ± 0.4 |
| E′S (cm s−1) | 29 | 11.8 ± 3.1 | 12.0 ± 3.2 | 11.4 ± 2.9 | 10.1 ± 1.9 | 10.1 ± 1.9 |
| A′S (cm s−1) | 29 | 8.9 ± 2.0 | 9.0 ± 2.2 | 8.6 ± 1.7 | 6.1 ± 1.1 | 6.1 ± 1.1 |
| E′L (cm s−1) | 29 | 17.1 ± 3.7 | 17.0 ± 4.0 | 17.3 ± 3.1 | ||
| A′L (cm s−1) | 29 | 8.8 ± 2.2 | 8.6 ± 1.9 | 9.2 ± 2.8 | ||
| Hemodynamics | ||||||
| MAP (mmHg) | 29 | 84 ± 10 | 87 ± 9 | 77 ± 7 | 84 ± 4 | 84 ± 4 |
| SBP (mmHg) | 29 | 116 ±11 | 118 ± 11 | 108 ± 9 | 128 ± 11 | 128 ± 11 |
| DBP (mmHg) | 29 | 68 ± 10 | 71 ± 9 | 60 ± 8 | 62 ± 6 | 62 ± 6 |
| HR (bpm) | 29 | 65 ± 12 | 68 ± 13 | 59 ±9 | 57 ± 10 | 57 ± 10 |
Values are Means ± Standard Deviation. SWT = Septal wall thickness, PWT = Posterior wall thickness, LVIDd = left ventricular internal diameter during diastole, LVIDs = left ventricular internal diameter during systole, LVOTd = left ventricular outflow track diameter, LAd = left atrial diameter, LVM = left ventricular mass, CO = cardiac output, SV = stroke volume, LVEF = left ventricular ejection fraction, E = early transmitral filling velocity, A = late transmitral filling velocity, E’S = early diastolic septal wall velocity, A’S = late diastolic septal wall velocity, E′L = early lateral wall velocity, A′L = late lateral wall velocity, MAP = mean arterial pressure, SBP = systolic blood pressure, DBP = diastolic blood pressure, HR = heart rate, TSI = time since injury, mo = months.
reference values from Kou at al 2014, Mitchell 2019, Lang 2015.
Time since injury and cardiac structure:
Increasing time since injury correlated significantly with smaller LVIDd, LVIDs, LVEDV, LVESV, and LV mass (Figure 1). Increased time since injury showed similar trends with smaller LVEDV, LVESV, and LV mass indexed for BSA but failed to reach significance (Table 3). In contrast, IVS, PWT, and LAd were unrelated to time since injury during the 3 to 24 month observation period. Neither neurological nor sensory level of injury significantly influenced to these relationships.
FIGURE 1.
The relationship between time since injury and cardiac structure. Males are represented with circles (○●) and females with triangles (▲Δ). Open shapes depict individuals with cervical injuries while filled shapes depict individuals with thoracic injuries. The line represents the linear regression of best fit with the surrounding 95% confidence interval in grey. Dotted lines represent +/− 2 SD. LV Left Ventricular; TSI Time Since Injury; mo Months.
Table 3.
Linear regression coefficients and significance for z-score changes in cardiac structure and function and time since injury over the 24 months following injury
|
Dimensions |
Time Since Injury | |||
|---|---|---|---|---|
| R-Squared | Coefficient | Standard Error | P-value | |
| Septal Wall Thickness | 0.002 | −0.006 | 0.026 | 0.828 |
| Posterior Wall Thickness | 0.041 | −0.027 | 0.025 | 0.294 |
| LVIDd | 0.129 | −0.063 | 0.313 | 0.050 |
| LVIDs | 0.338 | −0.086 | 0.023 | 0.001 |
| LVOTd | 0.045 | −0.033 | 0.029 | 0.270 |
| LAd | 0.009 | −0.022 | 0.046 | 0.627 |
| LVM | 0.138 | −0.060 | 0.029 | 0.047 |
| LVEDV | 0.156 | −0.054 | 0.024 | 0.034 |
| LVESV | 0.141 | −0.069 | 0.033 | 0.045 |
| Dimensions Normalized to BSA | ||||
| LVM | 0.079 | −0.054 | 0.036 | 0.141 |
| LVEDV | 0.098 | −0.048 | 0.029 | 0.120 |
| LVESV | 0.075 | −0.056 | 0.034 | 0.094 |
| Systolic Function | ||||
| CO | 0.317 | −0.128 | 0.036 | 0.001 |
| SV | 0.143 | −0.193 | 0.091 | 0.043 |
| LVEF | 0.002 | 0.022 | 0.141 | 0.842 |
| Diastolic Function | ||||
| E | 0.025 | 0.049 | 0.059 | 0.412 |
| A | 0.000 | −0.001 | 0.044 | 0.979 |
| E/A | 0.020 | 0.029 | 0.039 | 0.465 |
| E′S | 0.003 | −0.012 | 0.064 | 0.776 |
| A′S | 0.016 | −0.046 | 0.070 | 0.515 |
SCI (n = 29). LVIDd = left ventricular internal diameter during diastole, LVIDs = left ventricular internal diameter during systole, LVOTd = left ventricular outflow track diameter, LAd = left atrial diameter, LVM = left ventricular mass, Q = cardiac output, SV = stroke volume, LVEF = left ventricular ejection fraction, E = early transmitral filling velocity, A = late transmitral filling velocity, E’S = early diastolic septal wall velocity, A’S = late diastolic septal wall velocity, E′L = early lateral wall velocity, A′L = late lateral wall velocity.
Time since injury and cardiac systolic & diastolic function.
Smaller SV and CO were associated with increased time since injury (Figure 2) while LVEF was not associated with time since injury (p = 0.842) (Table 3). Neither neurological nor sensory level of injury differentially affected the relationship of smaller stroke volume and cardiac output with time since injury.
FIGURE 2.
The relationship between time since injury and systolic function. Males are represented with circles (○●) and females with triangles (▲Δ). Open shapes depict individuals with cervical injuries while filled shapes depict individuals with thoracic injuries. The line represents the linear regression of best fit with the surrounding 95% confidence interval in grey. Dotted lines represent +/− 2 SD. TSI Time Since Injury; mo Months.
There were no relationships between velocity of blood flow past the mitral value leaflet tips during the early (E-wave; p = 0.413) or late phases (A-wave; p = 0.978) of diastole and time since injury. Additionally, neither the E- to A-wave ratio (E/A) (p = 0.465) nor the early (E′S; p = 0.775) or late (A′S; p = 0.515) peak diastolic septal wall velocities were related to the time since injury. There was no relationship in early (E′L; p = 0.374) or late (A′L; p = 0.281) lateral wall velocities and time since injury (Table 3).
Time since injury, heart rate, and blood pressure.
Lower heart rate was associated with longer time since injury (p = 0.050, Figure 3). There was a trend (p = 0.066–0.168) for lower systolic, diastolic, and mean arterial pressures with increased time since injury. These relationships were not affected by neurological or sensory level of injury.
FIGURE 3.
The relationship between time since injury, heart rate and blood pressures. Males are represented with circles (○●) and females with triangles (▲Δ). Open shapes depict individuals with cervical injuries while filled shapes depict individuals with thoracic injuries. The line represents the linear regression of best fit with the surrounding 95% confidence interval in grey. SBP Systolic Blood Pressure; DBP Diastolic Blood Pressure; MAP Mean Arterial Blood Pressure; TSI Time Since Injury; mo Months.
DISCUSSION
Our cross-sectional results show that increased time since injury relates to a smaller cardiac structure, most notably smaller left ventricular mass, internal diameters, and volumes. There were also significant associations between increased time since injury and reduced systolic function, including reduced stroke volume and cardiac output. Interestingly, there were no associated changes in sepal and posterior wall thickness, diastolic function, or blood pressure within 3 to 24 months since injury. The early post-injury assessment of cardiac structure and function is novel and important in that associations between a longer time since injury and smaller heart structures and reduced systolic function are noted although measures are similar to reference range of able-bodied individuals but larger than those reported in individuals with chronic injuries4–6. Finally, counter to our hypothesis, we found that neither neurological nor sensory level of spinal injury had an effect on these time-related declines.
Time since injury and cardiac structure.
Previous cross-sectional comparisons found reduced left ventricle diameters (7–15%), volumes (10–20%), mass (10–20%), as well as an increased septal and posterior wall thicknesses in individuals 1 to 40 years post SCI compared to able-bodied controls1,3–5. The present results show a negative linear relationship, from 3 to 24 months post injury, between smaller heart structures and increased time since injury. The relationship suggests that cardiac remodeling occurs relatively soon after injury and proceeds without a distinctive plateau over 24 months (Figure 1). This suggests cardiac structure atrophy is proceeding up to 3% per month (Table 3), implying that cardiac remodeling may continue up to 60 months post injury in order to reach the reductions documented in individuals 3 to 40 years post injury in previous studies1,3–6.
Time since injury and cardiac systolic & diastolic function.
Similar to previous reports3,6, the individuals with SCI in the current investigation displayed reduced systolic function (Figure 2). Prior cross-sectional studies demonstrated a 20% reduction in cardiac output and 23% reduction in stroke volume in individuals with SCI compared to able-bodied individuals3,4. The reductions in cardiac function occurred concurrently with the reductions in cardiac structure (Figure 1) and the loss of function did not plateau in the 24 months following injury (Figure 2). Despite the reduced stroke volume (Figure 2) there are parallel reductions in left-ventricular end diastolic and systolic volumes that account for the preserved ejection fraction (Figure 1), similar to previous findings1.
The present study did not detect any reductions in diastolic function (Table 3). Previous studies that noted reduced diastolic function had examined individuals more than 6 years post injury5,6. Hence, changes in cardiac structure and systolic function may occur early and longer-term declines result in reduced diastolic function (Table 3).
Time since injury, blood pressure, and heart rate.
There was a negative relationship between seated resting heart rate and time since injury with a trend for declines in blood pressure (Figure 3). This suggest that 3 to 24 months after injury, arterial pressures are maintained despite reductions in cardiac structure, systolic function, and heart rate. Previous research shows that systolic, diastolic, and mean arterial pressures are reduced long term (3–10 years) after SCI3 which indicates that pressure changes may require longer to fully manifest after cardiac remodeling and systolic functional adjustments.
Neurological and sensory level of injury.
We hypothesized that the effect of time since injury on cardiac structure/function would be greater in those with high neurological and sensory levels of SCI. This was based on previous observations of larger heart structures and higher systolic function in those with neurological injuries in the thoracic compared to cervical regions, as well as preserved baroreflex gain13 and attenuated reductions in blood pressure and heart rate4,13. Additionally, those with cervical injuries would likely retain less sympathetic innervation to the heart and vasculature below the level of injury leading to lower blood pressures and result in accelerated cardiac atrophy. Contrary to this hypothesis, no measure of cardiac structure or function differed between individuals with high and low neurological or sensory levels of injury. It is possible that neither neurological nor sensory level of injury influenced the rate of cardiac decline or that divergent rates of cardiac remodeling are not apparent in the relatively short period of 24 months after injury. Therefore, differences in cardiac structure and function between high and low level injuries may only be apparent when differences in arterial pressures manifest, which seem to occur more than 24 months following injury6.
Cause of cardiac remodeling and function loss.
The human heart, similar to skeletal muscle, has the ability to remodel itself in proportion to the stressed placed upon it5,22. For example, the ventricles expand in size and increase either stroke volume or wall thickness after endurance and resistance training programs, respectively17,23,24. Conversely, the human heart decreases in size following reductions in physical activity and periods of inactivity, such as bed rest22,25. It has been speculated that the reduction in cardiac structures and decrement of function following SCI result from several synergistic mechanisms including reduced physical activity, reduced venous return due to a loss of the muscle pump, reduced blood volume, reduced systemic (or arterial) blood pressure, and/or reduction of sympathetic innervation11. We hypothesized that individuals with cervical level injuries would present greater reductions in cardiac structure/function with time since injury compared to individuals with thoracic level injuries as they would likely have greater reductions in physical activity, venous return, blood pressure via loss of splanchnic and renal vascular resistance, and supraspinal cardiac sympathetic influence. The lack of effect of injury level suggest that these variables may not differentially impact the associations between reductions in cardiac structure/function and time since injury. Although the present study was not designed to clarify causal mechanisms, these results suggest that reductions in sympathetic supraspinal influence may not have a large affect on cardiac changes in structure or function in the first 24 months after injury.
Implication:
Exercise training has been investigated as an intervention to improve both cardiac structure and function in those with SCI2,26. FES-cycle training for 6 months has been shown to increase myocardial mass and increase ventricular internal diameters26. A pilot study consisting of 5 individuals suggested that eight weeks of FES-rowing can increase cardiac dimensions and improve function in individuals with chronic spinal cord injuries2. Given the rapidity which cardiac atrophy and loss of function appears to occur, the current results suggest that implementing training programs within the first 24 months following injury may be needed to attenuate or reverse cardiac mal-adaptations.
Limitations:
A limitation of the current study is that heart size and function were unknown prior to the date of injury and the majority of subjects, twenty, were within 12 months of injury and nine were between 12- and 24-months post injury. Additionally, the conclusions of this study are based on a cross-sectional comparison of individuals 3 to 24 months post-injury, therefore predictions beyond this period should be made with caution. Longitudinal assessment of cardiac structure and function following SCI is needed to clarify the temporal relationship between SCI and adverse cardiac remodeling. Due to difficulty of scheduling and transport of the subjects between laboratories, echocardiographs and blood pressure measures were taken up to 14 days apart. Therefore, blood pressure associations with cardiac structure/function should be interpreted with caution. Additionally, volunteers blood pressures were unknown in the first three months after injury. It is possible that blood pressures were immediately lowered due to the injury with larger reductions occurring in those with cervical compared to thoracic injuries, and any further reductions were not apparent in the 3 to 24 month time frame. Another potential limitation of the analysis was the use of sensory level as an index of remaining autonomic innervation. This method of estimating remaining autonomic function is not a direct measure and others noted that sacral sparing may not be indicative of full autonomic function27,28. Lastly, we had an insufficient number of females to examine the role of sex in cardiac remodeling. Females, in general, have smaller heart structures than males21 though this may not be a major confounder in the overall interpretation of our findings given the small number of females (n = 4) and conversion to z-score. Removal of the 4 females from the analysis did not change the associations between time since injury and cardiac structure/function. Nonetheless, future investigations should explore the impact of sex on these declines.
CONCLUSION
Three to twenty-four months after a spinal cord injury, reductions in cardiac structure and systolic function were related to increased time since injury. This relationship was not influenced by neurological or sensory level of spinal cord injury. The apparent cardiac atrophy and loss of function appear to precede changes in diastolic disfunction or systemic arterial pressures and suggest that peripheral factors must compensate to maintain arterial pressure.
Importantly, cardiac atrophy is linked to breathlessness, lethargy, reduced exercise tolerance, congestive heart failure, and increased mortality. Therefore, clinicians should consider implementing interventions to prevent cardiac atrophy and the associated loss of systolic function within months of spinal cord injury.
Supplementary Material
Acknowledgments:
We would like to thank all our volunteers for their participation.
Funding: This work was supported by NIH R01 HL117037 and NIDILRR - Spinal Cord Injury Model Systems Program 90S15021-01-00.
Abbreviations
- A′S
septal wall contraction velocity during late diastole
- A-wave
blood flow velocity at the mitral valve during the late diastole
- CO
cardiac output
- E-wave
blood flow velocity at the mitral valve during the early diastole
- E′S
septal wall contraction velocity during early diastole
- g
gram
- hr
hour
- IVS
interventricular septum thickness
- L
liter
- LV
left ventricle
- LAd
left atrial diameter
- LVEF
left ventricular ejection fraction
- LVEDV
volume of the left ventricle during diastole
- LVESV
volume of the left ventricle during systole
- LVIDs
internal diameter of the left ventricle during systole
- LVIDd
internal diameter of the left ventricle during diastole
- LVM
LV mass
- LVOTd
left ventricle outflow track diameter
- min
minute
- ml
milliliter
- mo
month
- PWT
posterior wall thickness
- SCI
spinal cord injury
- SV
stroke volume
Footnotes
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Competing interests: The authors declare that they have no conflict of interest.
Data availability statement: Data are available on reasonable request. All data relevant to the study are included in the manuscript. All provided data in the manuscript can not be traced back to individuals that participated in the study.
Clinical Trial Identifier: NCT02139436
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