Is the Increased Septal Perfusion the Signal of Asymmetrical Septal Hypertrophy?

In this study, we have compared scintigraphic and echocardiographic data in order to investigate whether increased septal perfusion represents asymmetrical septal hypertrophy (ASH), which is a symptom followed in the scintigraphy of myocardial perfusion. The study consists of a total of 186 patients (120 females and 66 males with an average age of 59.45 ± 11.54 years) who had normal myocardial perfusion scintigraphy and echocardiography examinations. Statistical comparison of septal wall thickness measurements obtained from echocardiography and septal-to-lateral wall ratios (S/L ratio) was performed scintigraphically. Left ventricular mass values were obtained as both scintigraphic and echocardiographic data and their correlations were evaluated in order to assess the presence of left ventricular hypertrophy (LVH). In statistical analyses, the values of interventricular septal thickness in diastole (IVSd), left ventricle posterior wall thickness in diastole (LVPWd), left ventricle mass (LVM), and left ventricle mass index (LVMI) were found to be significantly higher in group 2 (S/L ratio >1) compared to group 1 (S/L ratio <1). In addition, S/L ratio is significantly correlated with echocardiographic IVSd, LVPWd, LVM, LVMI, and scintigraphic LVM (rest) values. Furthermore, echocardiographic LVM and LVMI values were significantly correlated with LVM and LVMI values obtained from scintigraphy. It should be known that increased S/L ratio that can be monitored during scintigraphic studies can be an indicator of septal hypertrophy and/or LVH, however, further examination and close follow-ups should be performed in necessary cases.

Introduction

Asymmetrical septal hypertrophy (ASH) is defined as abnormal ventricular muscle thickening of the interventricular septal wall, and it is often seen in patients with hypertension.[123] ASH usually develops during the initial phase of left ventricular hypertrophy (LVH) seen in hypertensive (HT) patients. It is also considered as a type of HT LVH.[456] Even though LVH is observed in some disorders and diseases, such as valve disease, congenital heart disease, hypertrophic cardiomyopathy (HCM) and obesity, the most common reason that causes LVH is hypertension.[789] Increased septal perfusion is a finding that may be encountered during perfusion scans, and it can be evaluated visually as well as quantitatively (S/L ratio). Although clinical meaning of increased septal perfusion is not fully understood, it is thought that it points to hypertension cases and hypertrophic cardiomyopathy. Therefore, in the present study, it has been aimed to investigate whether increased septal perfusion represents asymmetric septal hypertrophy by evaluating increased septal perfusion, which is commonly encountered in routine nuclear medicine, with echocardiographic data. We have also aimed to investigate whether the size of the left ventricle and dimensions obtained from echocardiography are correlated with each other.

Materials and Methods

Patient population

A total of 323 patients with normal perfusion were retrospectively selected as population of the study among cases who were waiting for myocardial perfusion gated single-photon emission computed tomography (SPECT) examinations between January 2012 and November 2014. However, only 186 (120 women and 66 men, with a mean age of 59.45 ± 11.54 years) of these patients with echocardiography examination were included in the study. Standard 12 lead electrocardiograms (ECGs) data and gated myocardial perfusion gated SPECT image findings in addition to the records of patients' histories were reviewed prior to the study. Demographic characteristics and risk factors for coronary artery disease of all patients were also noted.

We have obtained written informed consent from all patients.

Myocardial perfusion gated SPECT imaging protocol

All patients included in the study received as same-day rest-stress technetium (Tc)-99m sestamibi gated SPECT myocardial perfusion imaging protocol. Rest images were taken 30 min to 1 h after injection of 296-370 MBq Tc 99mmethoxy-isobutyl-isonitrile (sestaMIBI). On the other hand, stress images are taken 3–4 h after taking the rest images. 925-1,110 MBq of Tc 99msestamibi was injected at peak exercise for stress studies and imaging was done 15 min to 1 h after the injection. Treadmill (Bruce protocol) exercise and dipyridamole (0.142 mg/kg/min IV) was used for myocardial perfusion gated SPECT. A dual head gamma camera (Infinia, General Electric Medical Systems, Milwaukee, Wisconsin, USA) was used to perform SPECT imaging. The data obtained were analyzed using automatic-processing software for quantitative gated SPECT (QGS), Cedars Cinai Quantitative Perfusion SPECT (QPS), and Emory Cardiac Toolbox (ECTb). Two nuclear medicine specialists analyzed the scintigraphic images visually and quantitatively.

Visual interpretation

The images of sagittal, coronal, and transaxial slices obtained from rest and stress studies were evaluated. According to these evaluations, it has been concluded that all patients included in the study had normal myocardial perfusion.

Quantitative interpretation of perfusion wall motion and thickening with QPS and QGS programs

The global summed thickening score (STS), left ventricular ejection fractions (LVEFs), and global summed motion score (SMS) were obtained from stress studies automated QGS program. Summed rest score (SRS), summed stress score (SSS), and summed difference score (SDS) were automatically calculated by using QPS software.

Gated myocardial perfusion with ECTb program

Left ventricular mass values were automatically obtained from this program.

Echocardiographic measurements

According to the current recommendations of the European Society of Echocardiography, a 3.5-MHz transducer (Vivid 7 GE USA) was used to perform the transthoracic echocardiographic examination.[10] Left ventricular posterior wall thickness in diastole (LVPWd), left ventricular diameter in diastole (LVDd), and interventricular septal thickness in diastole (IVSd) were also recorded.

Left ventricle mass (LVM) was calculated by using the adjusted formula of Devereux as follows: LVM = 0.8 × 1.04× [(LVDd + LVPWTd + IVSTd) 3 – LVDd3] +0.6 g.[11]

Left ventricle mass index (LVMI) was calculated by dividing body surface area (LVM/BSA, g/m2) into LVM. BSA was calculated using the formula as follows: BSA = 0.6 × height (m) +0.0128 × weight (kg) – 0.1529.[12]

Quantitative Definition of S/L ratio

Segment maps of Bull's eye created from stress images are used to calculate S/L ratio values. S/L ratios were obtained for each patient by calculating average perfusion ratios in the segments corresponding to septum and lateral wall. Patients with S/L ratio values smaller than 1 were identified as group 1 and those with S/L values higher than 1 were identified as group 2, respectively.

Statistical analysis

Statistical Package for the Social Sciences version 19.0 computer program (SPSS-Inc., Chicago, US) was used to perform all statistical analyses, and continuous data were given as mean ± SD. t-Test was used for samples in order to test the significance level of mean values. Pearson's Chi-square tests were used to compare the distribution of variables and Mann–Whitney U-test and Student's t-test were used to test the differences between two groups in terms of categorical factors. In addition, Kruskal–Wallis test was used to compare continuous values after analyzing the normality. Finally, Spearman's correlation analysis was employed to analyze the changes occurred in the variables.

Results

A total of 186 patients with normal perfusion scintigraphy findings were included in these analyses. Table 1 presents the clinical characteristics of the cohort. According to the results of analyses, there were no significant differences between two groups in terms of clinical characteristics such as smoking habits, diabetes mellitus, hyperlipidemia, age, body mass index, and family history of coronary artery disease. Systolic and diastolic arterial blood pressures measured during scintigraphy of the patients before the test were found to be higher in the patients of group 2 compared to group 1 (systolic pressure P < 0.001, diastolic pressure P = 0.012).

Table 1

Some demographic-clinical parameters results in the presented patients

According to comparison of electrocardiographic parameters, there was statistically significant difference between the heart rate parameters (P = 0.014). However, no significant differences were found in corrected QT (QTc), PR interval, and electrocardiographic parameter of QRS [Table 1].

When echocardiographic and scintigraphic data were compared between the groups; it has been seen that values of echocardiographic parameters such as LVPW, IVS, LVM, and LVMI were found to be higher in group 2 compared to group 1, respectively. There was no difference between groups in terms of LVD values. However, while only LVM (rest) parameters showed differences (P = 0.043) between groups among index parameters LVM and LVMI obtained from both rest and stress scintigraphy, there was no differences between groups in terms of other parameters. Furthermore, there were significant differences between groups in terms of septal-to-lateral wall values that are used as grouping criteria. Examples of patients with S/L ratio >1 and S/L ratio <1 were given in Figure 1a and b, respectively. All these findings are consistent with correlation tests performed between echocardiographic and scintigraphic parameters and S/L ratios [Table 2].

Figure 1

(a) An example of Bull's eye segments of the patient with S/L ratio >1 in myocardial perfusion scintigraphy. The values obtained from echocardiography were as follows: IVSd = 13 mm, LVPWd = 12 mm. (b) An example of Bull's eye segments of patient with S/L ratio <1 in myocardial perfusion scintigraphy. The values obtained from echocardiography were as follows: IVSd = 10 mm, LVPWd = 9 mm

Table 2

Spearman's correlation coefficients of S/L wall ratio and echocardiographic, sintigraphics parameters

Considering LVM and LVMI values obtained from scintigraphy, the values obtained in both rest and stress tests obtained from scintigraphy were found to be lower than LVM and LVMI values. However, there was a strong correlation between these values obtained from echocardiography and scintigraphy [Table 3].

Table 3

Spearman's correlation coefficients of echocardiographic and sintigraphic lef ventricular mass parameters

Discussion

The lateral wall thickness of a normal left ventricle is greater than septum. Accordingly, in myocardial perfusion scintigraphy, it is expected to see more radiopharmaceutical uptake expected in lateral wall since its thickness is greater than thickness of septum. However, during myocardial perfusion scintigraphy scanning, some cases are observed where radiopharmaceutical uptake is visually or/and quantitatively more in the septal wall compared to the lateral wall. However, this situation is not fully understood in clinical terms yet. In order to present the clinical meaning of this case more clearly, we have selected patients with normal perfusion findings and compared their S/L ratios. According to these comparisons, it has been seen that these ratios are correlated with echocardiographic left ventricular size indexes. In addition, since a strong correlation was found between echocardiographic and scintigraphic measurements of LVM and LVMI values; it can be concluded that scintigraphic LVM and LVMI values can provide important clues in daily nuclear medicine practices.

As it is known, hypertension is a widely encountered disease that can be associated with LVH. Left ventricular hypertrophy may be asymptomatic until developing unexpected sudden death or congestive heart failure. So it is important to detect the presence of left ventricular hypertrophy and ASH, which are an early symptoms of left ventricular hypertrophy.[13141516]

In the literature, it is reported that asymmetric septal hypertrophy can be seen in both HT patients and HCM cases. According to a study conducted by Shimizu et al., the wall thickness was significantly greater in both the HT and HCM groups than in the control group, whereas there were no differences in these indices between the HT and HCM groups. Furthermore, they have suggested that ASH is a type of HT LV hypertrophy in HT patients.[1]

Amano et al. have conducted a study in order to evaluate the relationship between global and regional cardiac abnormalities in case of HCM with ASH, and delayed hyper-enhancement of the myocardium by using magnetic resonance imaging (MRI).[17] According to the results of this study, it has been reported that delayed hyper-enhancement of the myocardium with extensive extent may reflect the hypokinesia and severe regional hypertrophy in HCM with ASH if it is higher than 50%.

According to a case presented by Raymond Ching-Chiew Wong et al., it has been reported that a young man with heart failure and obesity cardiomyopathy presented with asymmetric septal hypertrophy, marked LV hypertrophy, and endomyocardial biopsy (EMB) defeated genetic HCM.[18] Nevertheless, some studies suggest that obesity may be associated with larger LVMI, increased myocardial wall thickness, and diastolic dysfunction.[1920] However, in the present study, no significant difference was found between two groups in terms of body mass index values.

Although echocardiography is a more frequent method because of it is safe, rapid, reliable, and cost-effective for the evaluation of left ventricle size and functions, yet it may be inadequate especially in cases with limited echocardiographic window.[2122] However, echocardiographic images can change with the change in probe angle and measurements because they are operator-dependent.[23] These situations are important for determining asymmetric septal hypertrophy in HT patients.

LVM should be accurately calculated but it may be difficult because of the heart angle, movement, and limited image. Therefore, it may require multimodal screening techniques. In our study, left ventricular wall thickness and mass in myocardial perfusion scintigraphy (MPS) were correlated with echocardiographic measurements. MPS also can be use for determining of left ventricle volumes and functions as well as myocardial perfusion. In this context, MPS has a complementary value in clinical practice. Enhanced septal activity should be reported and investigated in terms of hypertrophy.

The small population size is the major limitation of our study. Secondly because of the retrospective design of the study, echocardiographic evaluations were performed only by a two-dimensional technique. Three-dimensional echocardiographic measurements could better correlate with MPS.

Conclusion

Results of our study suggest that increased S/L ratio can be an indicator of asymmetric septal hypertrophy and/or LVH. Therefore, it should be noted that increased S/L ratio that can be monitored during myocardial perfusion scintigraphy can be an indicator of septal hypertrophy or/and LVH, however, further examination and close follow-ups should be performed in necessary cases.

Financial support and sponsorship

Nil

Conflicts of interest

There are no conflicts of intrest.