Abstract
Purpose
To generate normal reference values for left ventricular mid-diastolic wall thickness (LV-MDWT) measured by using CT angiography.
Materials and Methods
LV-MDWT was measured in 2383 consecutive patients, without structural heart disease, undergoing prospective electrocardiographically (ECG) triggered mid-diastolic coronary CT angiography. LV-MDWT was manually measured on automatically segmented short-axis images according to the American Heart Association’s 17-segment model. Commercially available automatic software was used to calculate the left ventricular (LV) mass.
Results
Among the 2383 patients, average LV-MDWT was 7.24 mm ± 1.86 (standard deviation [SD]), with the basal anteroseptal segment being the thickest wall (8.71 mm ± 2.19) and the apical inferior segment being the thinnest wall (5.9 mm ± 1.58; P < .001). Over all LV segments, the maximum upper limit, as defined as 2 SD above the mean, was 13.6 mm for men (LV1) and 11.2 mm for women. For men, only the basal anterior segment was above 13 mm. There was a significant difference in average LV-MDWT between women and men with 6.47 mm ± 1.07 and 7.90 mm ± 1.24, respectively (P < .001). Significant differences in LV-MDWT were found in the subgroups aged less than 65 years and greater than or equal to 65 years (P < .001). There was a strong correlation between LV-MDWT and LV mass (P < .001).
Conclusion
Normal sex- and age-specific reference ranges for LV-MDWT in prospective ECG-triggered mid-diastolic coronary CT angiography have been provided. These benchmarks may expand the diagnostic and prognostic roles of CT angiography, beyond its role in the identification of coronary artery disease.
© RSNA, 2019
Summary
Normal sex- and age-specific reference ranges for left ventricular mid-diastolic wall thickness (LV-MDWT) at prospective electrocardiographically triggered mid-diastolic CT angiography were provided, and LV-MDWT was strongly correlated with myocardial mass.
Key Points
■ Normal sex- and age-specific reference ranges for left ventricular mid-diastolic wall thickness (LV-MDWT) at prospective electrocardiographically triggered mid-diastolic CT angiography studies were provided.
■ The upper limit of LV-MDWT for any segment was 13.6 mm for men and 11.2 mm for women.
■ There was a strong correlation between LV-MDWT and left ventricular mass.
Introduction
CT angiography is indicated in the assessment of coronary artery disease (CAD) in low-to-intermediate–risk patients (1,2). Prospective electrocardiographically (ECG) gated CT angiography acquisition is used routinely to lower patient radiation exposure in comparison with retrospective ECG-gated CT angiography acquisition protocol (3,4). Prospective gating implies that the entire cardiac cycle cannot be evaluated, and thus, the traditional assessment of left ventricular (LV) end-diastolic volume, LV end-diastolic wall thickness, and LV ejection fraction (EF) as performed with echocardiography and cardiac MRI (5) cannot be performed.
Quantification of LV EF, LV mass, and LV wall thickness provides diagnostic and prognostic information (6,7). Despite the limitations inherent to prospective ECG-gated mid-diastolic acquisition to measure these parameters, the assessment of LV mid-diastolic volume, LV mass, and LV mid-diastolic wall thickness (LV-MDWT) is feasible and strongly correlated with end-diastolic and end-systolic phases (8,9). Despite the fact that images from the entire cardiac cycle are not acquired, mid-diastolic images may allow the identification of an abnormally thick LV wall. However, there is no established upper limit of normal LV-MDWT that uses a large patient population, although postprocessing software readily enables LV wall thickness measurements.
Using CT angiography studies reconstructed in standard short-axis (SAX) planes and the 17-segment model of the American Heart Association, we measured LV wall thickness in mid-diastole and sought to define the upper bound of normal defined as 2 standard deviations (SD) above the mean wall thickness according to sex and age. We also evaluated the correlation between LV wall thickness and LV mass.
Materials and Methods
Study Population
The use of the University of Ottawa Heart Institute Cardiac CT Registry for this study was approved by the local research ethics board. We repurposed the 2383-patient study population from which normal reference values for LV mass and LV mid-diastolic volume were derived (10). The exclusion criteria were known CAD defined as prior myocardial infarction or prior revascularization, valvular heart disease, heart failure, congenital heart disease, heart transplant, and prior cardiac surgery. Diabetes mellitus (DM), hypertension, dyslipidemia, smoking, and obesity were not a part of the exclusion criteria.
CT Image Acquisition
CT images were acquired as described in a previous study (10). Patients without contraindications were premedicated with β blockers to achieve a target heart rate of 60 beats per minute. Sublingual nitroglycerin (0.8 mg) was administered before second-generation dual-source (Somatom Definition Flash; Siemens, Forchheim, Germany) imaging (gantry rotation of 280 msec, 128 sections × 0.6 mm). Prospective ECG-triggered images were acquired at mid-diastole (100-msec acquisition centered around 70% of the R-R interval with 5%–10% padding) at 80–120 kVp with an automated tube current (CARE dose 4D) (10). Intravenous contrast material (Omnipaque 350 or Omnipaque 300; GE Healthcare, Princeton, NJ) delivery was triphasic (100% contrast, 40% contrast and 60% saline, and 100% saline) and bolus tracking was used.
Measurements of LV Wall Thickness and LV Mass
The LV myocardial thickness measurements were obtained by two medical research assistants (3 years of experience) under the supervision of J.R.I. (cardiothoracic radiologist with 10 years of experience). For the first 100 cases of each reader, image snapshots of the measurements were saved and reviewed by J.R.I., and feedback was provided to adjust the placement of the calibers.
The measurement workflow was started by loading the best diastolic-phase (automatically selected by the CT vendor software) 0.6-mm reconstructed images from a picture archive and communication system (McKesson version 12.3) into a dedicated cardiac workstation (Aquarius iNtuition version 4.4.5.36.843; TeraRecon). LV long-axis, three-chamber, and SAX images were automatically reformatted. The LV was manually segmented into 17 segments according to the model of the American Heart Association by using standard anatomic landmarks (11). The apical segment was excluded from the analysis (segment no. 17), as no reliable SAX measurement can be made of this thin segment. The reader identified the basal, mid, and apical planes based on the identification of the papillary muscles on SAX images and by cross-referencing the SAX with LV long-axis planes. The 16 segments were identified on the SAX images by placement of guiding lines passing in the center of the LV and right ventricular hinge points and a third horizontal line (for basal and mid segments) dividing the myocardial segments into equal areas on each plane. Myocardial thickness was measured by using direct planimetry with manual calipers placed perpendicular to the myocardial wall. LV myocardial thickness was measured as the perpendicular distance between the endocardial and epicardial borders of the LV in each segment. LV endocardial trabeculations and papillary muscles were excluded from all measurements.
A dedicated measurement protocol was created in the TeraRecon workstation for standardization and reproducibility of the measurement process. The LV segments were measured manually, consecutively, and in sequence from basal to apical segments and labeled automatically from 1 to 16. Each LV segment started from segment 1, consecutively and in sequence from basal to apical segments. The myocardial thickness of 16 measurements was automatically captured and semiautomatically exported to an Excel sheet (Microsoft Office; Redmond, Wash) for each patient. This workflow avoided manual registration of measurement values and expedited data registration (Fig 1).
Figure 1a:
Images used for left ventricular (LV) mid-diastolic wall thickness and LV mass measurements. (a) Prospective electrocardiographically gated CT angiography study in mid-diastolic phase of the basal, mid, and apical (from left to right) short-axis (SAX) plane with LV wall thickness caliper measurements per myocardial segment according to the American Heart Association’s 17-segment model (TeraRecon software). The apical segment 17 was excluded. The 16 segments measured were identified on the SAX images by placement of guiding lines passing in the center of the LV and right ventricular hinge points and a third horizontal line (for basal and mid segments) dividing the myocardial segments in equal areas on each plane. LV myocardial thickness was measured as the perpendicular distance between the endocardial and epicardial borders of the LV in each segment. (b) Mid-diastolic SAX (left) and long-axis (right) planes with autocontouring of the endocardial (red) and epicardial (green) borders for automatic quantification of myocardial mass (Syngovia software).
Figure 1b:
Images used for left ventricular (LV) mid-diastolic wall thickness and LV mass measurements. (a) Prospective electrocardiographically gated CT angiography study in mid-diastolic phase of the basal, mid, and apical (from left to right) short-axis (SAX) plane with LV wall thickness caliper measurements per myocardial segment according to the American Heart Association’s 17-segment model (TeraRecon software). The apical segment 17 was excluded. The 16 segments measured were identified on the SAX images by placement of guiding lines passing in the center of the LV and right ventricular hinge points and a third horizontal line (for basal and mid segments) dividing the myocardial segments in equal areas on each plane. LV myocardial thickness was measured as the perpendicular distance between the endocardial and epicardial borders of the LV in each segment. (b) Mid-diastolic SAX (left) and long-axis (right) planes with autocontouring of the endocardial (red) and epicardial (green) borders for automatic quantification of myocardial mass (Syngovia software).
Automated software (Syngovia, Siemens) was used to calculate the LV mass. The epicardial and endocardial borders and the contours were manually edited as needed. Papillary muscles were included in blood volume measurement (10).
Statistical Analysis
Continuous variables are presented as mean ± SD, and categorical variables are presented as frequencies. Continuous variables were compared by using Student t test (two tailed), and statistical significance was defined as P < .05. When a variable comprising more than two subgroups (eg, weight categories: normal weight, overweight, and obese) was tested for differences in average LV-MDWT between the subgroups, the P value of one-way analysis of variance was reported, without further multiple comparison adjustments. All analyses were performed in SPSS version 24 (IBM; Armonk, NY).
Upper limits of normal LV-MDWT were defined as the upper bound of the 97.5% confidence interval (mean + 2 SD) of the cohort. Normal values for both sexes and different age groups were established. Univariable and multivariable analyses were performed with average LV-MDWT as the dependent variable, and age, sex, DM, hypertension, body mass index (BMI), dyslipidemia, and smoking as independent variables.
Three cardiac phase groups (R-R% interval) were defined to test the potential influence of the chosen mid-diastolic phase to assess LV-MDWT: 65%–71%, 72%–74%, and 75%–80%.
The correlation between the average LV wall thickness and LV mass was assessed by calculating the Pearson correlation coefficient.
To evaluate interreader and intrareader variability of LV-MDWT measurements, interclass and intraclass correlation with 95% confidence interval was calculated.
Results
The mean age of the male population was 56.0 years ± 10.6 (range, 19–89 years), and the mean age of the female population was 59.5 years ± 10.4 (range, 23–90 years). Diabetes was present in 344 of 2383 (14.4%) patients, and 1127 of 2383 patients (47.3%) had hypertension.
There was a significant difference in average LV-MDWT in women and men with 6.47 mm ± 1.07 and 7.90 mm ± 1.24, respectively (P < .001) (Table 1).
Table 1:
Reference Values for Normal Left Ventricular Mid-Diastolic Wall Thickness
When the study population was grouped by age (< 65 years vs ≥ 65 years), a small difference was found with mean LV-MDWT of 7.28 mm ± 1.38 and 7.13 mm ± 1.33, respectively (P < .001).
When the myocardium was divided into basal (segments 1–6), mid (segments 7–12), and distal (segments 13–16) walls, significant differences were found in average LV-MDWT, with the basal wall being the thickest and the apical wall, the thinnest.
Patients with type 2 DM had higher average LV-MDWT (7.61 mm ± 1.37) than those without diabetes (7.18 mm ± 1.36; P < .001). The average LV-MDWT of normotensive (7.00 mm ± 1.29) versus hypertensive (7.51 mm ± 1.4) patients was small but statistically significant (P < .001). Table 2 summarizes the effects of clinical variables on the average LV-MDWT.
Table 2:
Average Left Ventricular Mid-Diastolic Wall Thickness in Subgroups
Table 2 lists the average LV-MDWT for different ethnic groups. When the patients were grouped by ethnicity, no statistically significant differences were found in average LV-MDWT (P = .607).
Considering all segment measurements, the upper bound of normal as defined by 2 SD above the mean was 13.6 mm for men and 11.2 mm for women. For men, only the basal anterior segment was above 13 mm.
Table 3 lists the results of the univariable analysis with parameter estimates, standard errors of the estimate, R2 values, and P values with LV-MDWT as the dependent variable (P = .01 for age; P < .001 for sex, type 2 DM, BMI, hypertension, smoking, and dyslipidemia). Table 4 lists the results of the multivariable analysis (R for the model = 0.618). Age, sex, BMI, hypertension, and smoking had an independent relation to LV-MDWT. When BMI was excluded from the model, the multivariable analysis was also significant for type 2 DM (P < .001).
Table 3:
Univariable Analysis
Table 4:
Multivariable Analysis
The median R-R interval was 71% for the whole study acquired in mid-diastole, and the average was 71.3% ± 1.9. The mean LV-MDWT for the three cardiac phase groups (65%–71%, 7.27 mm ± 1.36; 72%–74%, 7.17 mm ± 1.30; 75%–80%, 7.07 mm ± 1.21) did not show a significant difference for early versus mid phase (P = .086), for early versus late phase (P = .109), and for mid versus late phase (P = .302) (Table 2).
The correlation between the mean LV-MDWT and semiautomated LV mass (Pearson correlation = 0.739, P < .001) is shown in Figure 2.
Figure 2:
The plot shows the correlation between average left ventricular mid-diastolic wall thickness (LV-MDWT; y-axis) and LV mass (x-axis). Pearson correlation = 0.739, P < .001. Red line denotes best-fit line (linear method).
Inter- and intrareader analyses were performed on 15 patients equaling 240 segment measurements analyzed. Interclass variability was 0.777 (95% confidence interval: 0.713, 0.827), and intrareader variability was 0.827 (95% confidence interval: 0.775, 0.867).
Discussion
In this study, the upper cutoff of 13.6 mm for men and 11.2 mm for women for mid-diastole CT-derived LV wall thickness in any segment has been established, and a strong correlation between LV-MDWT and LV mass has been demonstrated.
LV mass independently predicts adverse cardiac outcomes (12). Although the pathophysiologic mechanism for higher cardiovascular mortality in the setting of LV hypertrophy is not completely understood, American College of Cardiology Foundation and the American Heart Association Guidelines for Assessment of Cardiovascular Risk in Asymptomatic Adults (12) recommend the use of echocardiography (13) to measure LV mass and LV wall thickness to assess cardiovascular risk. With the validation of reference values of LV-MDWT, it becomes feasible to identify increased LV wall thickness in routine cardiac CT studies with a simple operational measurement. By demonstrating a strong correlation between LV-MDWT and LV mass, we note that measuring LV-MDWT provides an opportunity to expand the diagnostic and prognostic roles of CT angiography beyond its role in the identification of CAD.
Sex, age, BMI, and hypertension demonstrated expected differences in average LV-MDWT (Table 2), as these variations are also found in previous studies providing reference values for LV mass or LV wall thickness among different imaging modalities (10,14–16).
The literature on normal values of LV-MDWT measured by using cardiac CT in the mid-diastolic phase is limited. To the best of our knowledge, only one study of 568 adults, free of cardiovascular disease, using a 320-detector CT for CT angiography examination, reported normal reference values for LV-MDWT by using semiautomated software. This study found that the LV was thickest in the basal septum (segment 3) with a mean thickness of 8.3 mm and 7.2 mm and thinnest in the midventricular anterior wall (segment 7) with 5.6 mm and 4.5 mm for men and women, respectively (16). Our study confirmed the difference in wall thickness between these segments, and small but statistically significant differences in LV-MDWT of the basal, mid, and distal walls, with decreasing wall thickness from the base of the LV to the apex.
Stolzmann et al investigated end-diastolic septal wall thickness and posterior wall thickness using retrospective ECG-gated CT and reported a mean thickness of 9 mm in both regions (17). Our results are comparable with this study if we consider the corresponding segments that were measured. We measured all 17 segments in a large data set and thus can provide slightly different cutoffs and averages of LVWT, which may be attributable to measuring LV-MDWT in different diastolic phases.
Albeit a small difference in LV-MDWT was expected according to the R-R interval of mid-diastolic phase of CT acquisition, the mean LV-MDWT for the three cardiac phase groups (65%–71%, 7.27 mm ± 1.36; 72%–74%, 7.17 mm ± 1.30; 75%–80%, 7.07 mm ± 1.21) did not show a significant difference between groups. There was a difference of approximately 2 mm in LV-MDWT between the 65%–71% and 75%–80% groups, but this falls within the expected measurement error.
Compared with cardiac MRI and echocardiography, cardiac CT has the highest spatial resolution, which offers an opportunity for the accurate assessment of myocardial anatomy and function. The administration of intravenous contrast material to visualize the coronary artery lumen also provides exquisite delineation of the LV cavity and the LV wall. These properties make this technique suitable for assessment of LV wall thickness, mass, dimensions, and function and comparable with the standard of reference of cardiac MRI (18).
Previous studies comparing LV wall thickness measured by using cardiac CT and cardiac MRI with echocardiography have systematically demonstrated small but significant differences between imaging modalities (17,19). Echocardiography tends to overestimate LV wall thickness compared with CT, partially because the delineation of the LV wall from the LV cavity in echocardiography is more difficult. A study comparing LV wall thickness assessed by using echocardiography, contrast-enhanced echocardiography, and cardiac MRI found that the LV wall thickness measured by using contrast-enhanced echocardiography was closer to that measured by using cardiac MRI than conventional echocardiography (20).
CT and cardiac MRI studies comparing LV wall thickness have shown to correlate better with each other than with echocardiography (21–23), and this has a clinical impact as cardiac CT has become widely available.
Interestingly, we found a small but significant increase in LV-MDWT in patients with diabetes compared with those without diabetes. However, the multivariable analysis model with age, sex, type 2 DM, hypertension, and BMI no longer demonstrated a significant relation between type 2 DM and average LV-MDWT. The suggested difference raises the hypothesis that CT can detect subclinical structural myocardial changes. This was possible owing to the very large population studied and may represent an additional way in which the high spatial resolution of CT can help in the assessment of myocardial structure. Further studies will be required to investigate the potential clinical relevance of this finding.
Our study had two important limitations that need to be discussed. First, several risk factors for CAD were not considered as part of the exclusion criteria for this study, and thus our study population may not represent a truly normal population, leading to uncertainty about the “normality” of the LV wall thickness values. The univariable and multivariable analyses demonstrated a small but statistically significant effect of several factors on average LV-MDWT, although the small differences that were found are probably clinically irrelevant differences. Hypertension was present in 43.7% of the study population, allowing an evaluation of the effect of hypertension on LV-MDWT. It is worth noting that of all the cardiovascular risk factors in the multivariable analysis, hypertension had the highest β estimation after sex. Compared with normotensive patients, the average LV-MDWT in hypertensive patients was 0.5 mm larger (Table 2), not influencing the main study result that a LV-MDWT of less than 14 mm is always within the normal reference range. Furthermore, compared with hypertension, sex has a more profound effect on average LV-MDWT with a difference of 1.5 mm between male and female patients. These differences are small and within the measurement error. To minimize potential bias, we used well-defined exclusion criteria to avoid inclusion of patients with overt heart disease. Therefore, it can be assumed that the normal values reported in this large study population reflect a clinical, meaningful population of typical CT angiography studies, where the detection of abnormal myocardial thickness may have a clinical and prognostic impact.
Second, the LV wall thickness of the myocardial segments was obtained from the SAX views. Several studies evaluating the comparison of LV wall thickness measured by different imaging modalities emphasize the need for adequate standardization of image planes (23). For cardiac MRI and echocardiography, three-chamber measurements have better agreement than the basal SAX plane. We aimed to describe normal myocardial thickness in all standard myocardial segments, and therefore, we used basal, mid, and apical SAX planes. The data sets available from CT studies provide full volumetric heart coverage, with an isotropic resolution of about 0.6 mm, and circumvent the limitations of echocardiography and cardiac MRI, in which a selected, limited number of planes are available for analysis and which suffer from lower spatial resolution. We used simultaneously reformatted images of the LV long-axis, three-chamber, and the SAX planes with 0.6-mm thickness, providing accurate selection of the correct SAX plane and all anatomic landmarks, including RV insertion points, identification of LV trabeculations, and mitral valve subvalvular apparatus structures for the accurate measurement of myocardial thickness.
In conclusion, by using a large population of patients clinically referred for CT angiography, this study provides normal sex- and age-specific reference ranges for LV-MDWT in prospective mid-diastolic ECG-triggered CT angiography. LV-MDWT is strongly correlated with myocardial mass. The upper limit of LV-MDWT for any segment is 13.6 mm for men and 11.2 mm for women.
By demonstrating a strong correlation between LV-MDWT and LV mass, we note that measuring LV-MDWT provides an opportunity to identify left ventricular hypertrophy in routine CT angiography studies, expanding the diagnostic role of CT angiography beyond its role in the identification of CAD and in increasing risk stratification.
Disclosures of Conflicts of Interest: J.W. disclosed no relevant relationships. D.J. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: consults for AbbVie. Other relationships: disclosed no relevant relationships. S.M. disclosed no relevant relationships. G.D. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: has received payments from Astra Zeneca and Amgen from service on speaker bureaus. Other relationships: disclosed no relevant relationships. F.J.R. disclosed no relevant relationships. B.J.W.C. Activities related to the present article: received grant from TeraRecon. Activities not related to the present article: holds stock in GE. Other relationships: disclosed no relevant relationships. J.R.I. disclosed no relevant relationships.
Abbreviations:
- BMI
- body mass index
- CAD
- coronary artery disease
- DM
- diabetes mellitus
- ECG
- electrocardiography
- EF
- ejection fraction
- LV-MDWT
- left ventricular mid-diastolic wall thickness
- LV
- left ventricular
- SAX
- short axis
- SD
- standard deviation
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