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Early detection of left atrial and bi-ventricular myocardial strain abnormalities by MRI feature tracking in normotensive or hypertensive T2DM patients with preserved LV function

BMC Cardiovascular Disorders volume 20, Article number: 196 (2020) Cite this article

Abstract

Background

Previous studies have found that impaired global myocardial systolic strain is associated with cardiovascular events in T2DM patients. However, the effect of hypertension (HT) on left atrial (LA), right ventricular (RV) and left ventricular (LV) myocardial deformation in hypertensive T2DM patients has not been fully studied by cardiac magnetic resonance feature tracking (CMR-FT). Our aim was to assess LA, RV and LV strain in T2DM patients with T2DM-HT and without hypertension using CMR-FT and to determine the underlying relationships with clinical parameters.

Methods

A total of 27 T2DM patients, 23 T2DM-HT patients and 31 controls were studied. LA, LV and RV strain was evaluated using CMR-FT. The clinical and biochemical parameters of the patients were collected.

Results

The T2DM patients had reduced LA global circumferential strain (LAGCS), radial strain (LAGRS), longitudinal strain (LAGLS) and right ventricular longitudinal strain (RVGLS) compared with the controls (LAGCS: 27.2 ± 2.1% vs 33.5 ± 2.4%; LAGRS: − 28.6 ± 1.1% vs − 31.9 ± 1.3%; LAGLS: 24.3 ± 1.3% vs 31.4 ± 1.5; RVGLS: − 21.4 ± 1.2% vs − 26.3 ± 1.1%, p < 0.05 for all). The T2DM-HT patients had greater LAGCS, LAGRS and LAGLS than the T2DM patients (LAGCS: 40.4 ± 3.8% vs 27.2 ± 2.1%; LAGRS: − 36.8 ± 2.0% vs − 28.6 ± 1.1%; LAGLS: 32.3 ± 2.4% vs 24.3 ± 1.3%, p < 0.05 for all). In the diabetic patients, LAGCS was associated with microalbuminuria levels (standardized ß = − 0.289, p = 0.021), and LAGCS, LAGRS and LAGLS were correlated with diuretic treatment (standardized ß =0.440, − 0.442, and 0.643, p < 0.05 for all).

Conclusions

CMR-FT may be considered a promising tool for the early detection of abnormal LA and RV myocardial strain. LA and RV strain values are impaired in T2DM patients. The amelioration of LA strain might be associated with hypertensive compensation or antihypertensive treatment, which requires to be confirmed in larger trials.

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Background

Cardiovascular disease (CVD) is the key cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM) [1]. Diabetic cardiomyopathy (DCM) is defined as abnormal cardiac structure and function that is independent of coronary artery disease (CAD) and hypertension and can lead to heart failure [2]. Hypertension (HT) is a common concomitant condition in the majority of T2DM patients, and its coexistence contributes to a four-fold increased risk of cardiovascular mortality compared with normal controls [3]. In addition, these two conditions are associated with structural and functional atrioventricular abnormalities. Consequently, in cases of left atrial (LA), left ventricular (LV) and right ventricular (RV) structure and function, early quantitative detection and timely intervention are crucial to the management of normotensive or hypertensive T2DM patients.

At present, cardiac MRI (CMR) is the most accurate noninvasive method for evaluating cardiac structure and function, although it has lower temporal resolution than echocardiography does [4]. Numerous studies on CMR imaging in T2DM patients have mainly focused on LV [5, 6]. Recently, a novel technique, cardiac magnetic resonance feature-tracking (CMR-FT), has been regarded as a more sensitive tool for measuring myocardial deformation as an indicator of subclinical myocardial dysfunction [7]. CMR-FT has been increasingly used for myocardial strain evaluation in various types of cardiomyopathy, such as cardiac amyloidosis [8], hypertrophic cardiomyopathy [9], and dilated cardiomyopathy [10], and the reproducibility of CMR-FT has been well demonstrated [11]. However, analyses of the role of LA and RV deformation in DCM by CMR-FT, especially with coexisting hypertension, have rarely been reported.

The identification of early systolic function derangements can be achieved with the use of myocardial deformation [12]. Consequently, the purpose of this study was to quantify MRI-derived LA, LV and RV strain alterations in normotensive or hypertensive T2DM patients and to investigate their association with clinical indicators.

Methods

Study population

From July 2017 to April 2018, 52 consecutive patients (27 T2DM patients and 25 T2DM-HT patients) were retrospectively recruited from the Department of Endocrinology at Wuhan Union Hospital. Additionally, 32 healthy volunteers matched for age, sex and BMI were recruited from the local population and served as control group. HT is defined as a history of hypertension or treatment with antihypertensive drugs or continuous blood pressure (BP) measurement > 140/90 mmHg [13]. For inclusion, T2DM patients were required to meet the World Health Organization standards [14]: age 30–70 years, no history of heart disease, and a normal physical examination and ECG. The inclusion criteria for the controls were no history of hyperlipidemia, hypertension, diabetes mellitus, or cardiovascular, peripheral vascular or cerebrovascular disease; normal findings on routine physical examination, including a normal ECG and echocardiogram; and no use of any cardioactive medications. The exclusion criteria included clinical evidence of coronary artery disease, myocardial infarction, dilated cardiomyopathy, valvular heart disease, renal failure (glomerular filtration rate (eGFR) < 30 ml/min), contraindications to MR imaging, the presence of abnormal cardiac dimensions and abnormal wall motion and cardiac insufficiency (LV ejection fraction (LVEF) < 50%). All subjects signed written informed consent forms in this study, which was approved by the ethics committee of our institution.

Anthropometric and biochemistry evaluations

The sex, age, height, body weight, and BP of all subjects were collected. Blood samples were obtained under fasting conditions before the MRI examination. Laboratory tests, including tests for glycosylated hemoglobin (HbA1c), microalbuminuria (MA), medications, serum glucose, fasting blood samples, creatinine, triglycerides (TG), total cholesterol (TC), blood urea nitrogen (BUN), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were performed for all patients within 1 week of this study. Low-density likpoprotein (LDL) cholesterol was calculated according to the Friedewald equation.

CMR scanning protocol

All subjects underwent a standard CMR examination with a 1.5 T scanner (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany). A balanced steady-state free procession (b-SSFP) sequence was used to obtain cine images, including the acquisition of three long-axis (two-, three-, and four-chamber) and short-axis (coverage from the base to the apex segment) slices. The cine image parameters were as follows: repetition time (TR)/echo time (TE), 2.9/1.2 ms; slice thickness, 6 mm; flip angle, 80°; FOV, 360 × 270 mm2; matrix, 144 × 256 pixels; voxel size, 1.3 × 1.3 × 8.0 mm3; and scanning time, the duration of 11 heartbeats.

Assessment of cardiac volume and function

Argus software (Syngo MMWP VE30A workstation, Siemens) was used to analyze cardiac structure and function. The LV function parameters, LV end-diastolic (LVEDV), end-systolic volume (LVESV), stroke volume (SV), ejection fraction (LVEF) and mass (LVM) were measured by manually tracing the endocardial and epicardial contours on all contiguous short-axis cine images. Furthermore, the LA volume (LAV) was calculated using the biplane area-length method (LAV = [0.85 × (2-chamber area) × (4-chamber area)]/L, where L was the shortest dimension from the back wall to the line across the hinge points of the mitral valve between the above two chambers above it). The LA appendage and the pulmonary veins were excluded from the measurements. All parameters were indexed to the body surface area.

CMR feature tracking analysis

Data were analyzed and processed using commercial cardiovascular postprocessing software (Medis 3.0, Netherlands) to obtain global measurements of LA, LV and RV strain. Two-, three-, and four-chamber long-axis images were imported into the software. At the end of diastole, the left ventricular endocardial and epicardial contours were manually delineated on the short axis and the long axis, respectively. The trabecular and papillary muscles were included within the endocardium (Fig. 1a–c, e–g). The LA endocardium was delineated in the 2-and 4-chamber views of the LA (Fig. 1i, j). The endocardium of the RV was outlined in 4-chamber view (Fig. 1l). LV global longitudinal strain (LVGLS), LV global circumferential strain (LVGCS), left atrial global radial strain (LAGRS) and right ventricular global longitudinal strain (RVGLS) were automatically extracted from the corresponding strain curves (Fig. 1d, h, k, and m).

Fig. 1
figure 1

Representative images of a healthy volunteer in long axis (a–c) and short axis (e–g) directions and strain curves. Representative contour of the endocardium and endocardium of the left ventricular in the 2-, 3-, 4-chamber (a、b、c) and corresponding LV MyoGLS (d). Endocardial and epicardial borders in base, mid, apical short axis views were presented (e-g) and corresponding LV MyoGCS (h). Left atrial endocardial boundaries were represented in 2-, and 4-chamber (i-j) corresponding LA endoGLS (k). Right ventricular endocardial boundaries were represented in 4-chamber (l) and corresponding RV endoGLS (m)

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LAGLS, left atrial global circumferential strain (LAGCS), and left atrial global circumferential strain (LAGRS) were measured in both two- and four-chamber views, although pulmonary vein confluence and LA appendages were not included. The LVGRS and LVGCS were measured in the short axial field of view. LVGLS measurements were obtained in 2-, 3-, 4-chamber views. The global RVGLS was obtained in the 4-chamber view [15, 16].

Reproducibility

To determine the reproducibility of the myocardial strain measurements, LA, LV and RV global deformation parameters in 25 random cases (9 T2DM patients, 9 T2DM-HT patients and 7 normal controls) were measured twice at 2-week intervals by a radiologist. Then, another independent investigator who was blinded to the first investigator’s measurements again measured the same images from the 25 randomly selected individuals. Finally, based on the results of the two investigators, the interobserver variability was evaluated.

Statistical analysis

All data were statistically analyzed using standard statistical software (SPSS 21.0 for Windows, IBM, Chicago, IL, USA). The Kolmogorov–Smirnov test was used to check the normality of all continuous data. Normally distributed data and categorical variables are presented as the means ± standard deviations and frequencies (percentages). Differences in continuous variables between two groups were compared using an independent-sample Student’s t test, and the chi-square test was used to test for differences between categorical variables. Analysis of variance (ANOVA) was used to assess the differences among the three groups. After adjusting for BMI, SBP, DBP or treatment with medication, atrial-ventricular strain and other myocardial function measures were compared using analysis of covariance (ANCOVA). Pearson’s correlation analysis was used for normally distributed variables. Multiple linear regression analyses were used to identify determinants of LA strain in T2DM patients with and without hypertension.

Results

We recruited subjects (52 patients and 32 controls) for this study and acquired CMR imaging data for all subjects. However, the data from one subject had to be excluded due to poor image quality (severe motion artifacts in one control), and data from two patients were excluded because of abnormal MRI findings (abnormal wall motion in two T2DM-HT patients). Thus, the final study cohort comprised 27 T2DM patients, 23 T2DM-HT patients and 31 healthy controls. The general characteristics of the study subjects are summarized in Table 1. The T2DM-HT group had significantly greater SBP and DBP than the control group (131.7 ± 9.8 vs. 123.9 ± 9.1, p < 0.001; 84.2 ± 8.6 vs. 74.9 ± 8.0; p < 0.001, respectively). No significant differences in HbA1c, microalbuminuria (MA), medications, serum glucose, fasting blood samples, diabetes duration, creatinine, TG, TC, BUN, HDL-C or LDL-C were observed.

Table 1 Clinical characteristics of study subjects
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Table 2 shows comparisons of various parameters of MRI characteristics among subjects. LV myocardial strain was not significantly different among the three groups. LAGCS was significantly greater in the T2DM-HT group than in the control group (LAGCS: 39.4 ± 12.7% vs 33.9 ± 8.7%, p < 0.05). LAGCS, LAGRS and LAGLS were significantly lower in the T2DM group than in the control group (LAGCS: 27.6 ± 3.6% vs 33.9 ± 8.7%; LAGRS: − 29.2 ± 4.7% vs − 32.9 ± 3.9%; LAGLS: 23.8 ± 5.5% vs 30.9 ± 6.0, p < 0.05 for all). LAGCS, LAGRS and LAGLS were significantly greater in the T2DM-HT group than in the T2DM group (LAGCS: 39.4 ± 12.7% vs 27.6 ± 3.6%; LAGRS: − 34.8 ± 7.3% vs − 29.2 ± 4.7%; LAGLS: 33.5 ± 6.7% vs 23.8 ± 5.5%, p < 0.05 for all). RVGLS was significantly lower in the T2DM and T2DM-HT groups than in the control group (RVGLS: − 22.0 ± 3.4% vs − 26.0 ± 7.4%, − 21.1 ± 5.5% vs − 26.0 ± 7.4%; p < 0.05, respectively).

Table 2 MRI characteristics of study population
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Table 3 shows comparisons of various parameters of MRI characteristics among subjects; the comparisons are adjusted for BMI, SBP, and DBP. LV myocardial strain was not significantly different among the three groups. LAGCS was significantly greater in the T2DM-HT group than in the control group (LAGCS: 41.2 ± 2.1% vs 33.0 ± 1.6%; p < 0.001) (Fig. 2a). LAGCS, LAGRS and LAGLS were significantly lower in the T2DM group than in the control group (LAGCS: 27.1 ± 1.7% vs. 33.0 ± 1.6%; LAGRS: − 29. 2 ± 1.0% vs. -32.3 ± 0.9%; LAGLS: 23.8 ± 1.2% vs. 30.5 ± 1.1%; p < 0.05 for all). LAGCS, LAGRS and LAGLS were significantly higher in the T2DM-HT group than in the T2DM group (LAGCS: 41.2 ± 2.1% vs. 27.1 ± 1.7%; LAGRS: − 35.5 ± 1.2% vs. -29.2 ± 1.0%; LAGLS: 34.1 ± 1.4% vs. 23.8 ± 1.2%, p < 0.05 for all) (Fig. 2a-c). RVGLS was significantly lower in the T2DM and T2DM-HT groups than in the control group (RVGLS: − 22.0 ± 1.2% vs. -25.9 ± 1.1%, − 21.4 ± 1.4% vs. -25.9 ± 1.1%, p < 0.05, respectively) (Fig. 2d). In the diabetic patients, LAGCS showed a significant negative correlation with MA levels (r = − 0.344, p = 0.014) (Table 4) (Fig. 3a). The improvement of LAGCS, LAGLS and LAGRS might be associated with diuretic treatment (r = 0.451, p = 0.001; r = 0.686, p < 0.001; r = − 0.459, p = 0.001, respectively) (Table 4) (Fig. 3b-d).

Table 3 MRI characteristics of study population adjusted for BMI, SBP, DBP
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Fig. 2
figure 2

Comparison of LAGCS (a), LAGRS (b), LAGLS (c) and RVGLS (d) values among the healthy controls, T2DM and T2DM-HT group. RVGLS, right ventricle global longitudinal strain. LAGCS, left atrial global circumferential strain (GCS); T2DM, type 2 diabetes mellitus; T2DM-HT, type 2 diabetes mellitus with hypertension

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Table 4 Univariate regression analysis for LAGLS, LAGCS, LAGRS and RVGLS in normotensive or hypertensive T2DM patients
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Fig. 3
figure 3

The relationship between LAGCS value and MA level in diabetic patients (a); The relationship between LAGCS value and diuretic treatment in diabetic patients (b); The relationship between LAGLS value and diuretic treatment in diabetic patients (c); The relationship between LAGRS value and diuretic treatment in diabetic patients (d); LAGCS, left atrial global circumferential strain; MA, microalbuminuria; LAGLS, left atrial global longitudinal strain; LAGRS, left atrial global radial strain

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After further adjustment for medication (Table 5), the LV myocardial strain was not significantly different among the three groups. LAGCS was significantly greater in the T2DM-HT group than in the control group (LAGCS: 40.4 ± 3.8% vs 33.5 ± 2.4%, p < 0.05). LAGCS, LAGRS and LAGLS were significantly lower in the T2DM group than in the control group (LAGCS: 27.2 ± 2.1% vs 33.5 ± 2.4%; LAGRS: − 28.6 ± 1.1% vs − 31.9 ± 1.3%; LAGLS: 24.3 ± 1.3% vs 31.4 ± 1.5, p < 0.05 for all). LAGCS, LAGRS and LAGLS were significantly greater in the T2DM-HT group than in the T2DM group (LAGCS: 40.4 ± 3.8% vs 27.2 ± 2.1%; LAGRS: − 36.8 ± 2.0% vs − 28.6 ± 1.1%; LAGLS: 32.3 ± 2.4% vs 24.3 ± 1.3%, p < 0.05 for all). RVGLS was significantly lower in the T2DM and T2DM-HT groups than in the control group (RVGLS: − 21.4 ± 1.2% vs − 26.3 ± 1.1%, − 21.4 ± 1.4% vs − 26.3 ± 1.1%; p < 0.05, respectively). In the univariate analysis, the HbA1c level was negatively correlated with LAGLS, but in the multivariate analysis, there was no correlation. In the multivariable stepwise analysis, the independent determinant of LAGLS was diuretic treatment (β = 0.643, p < 0.001) (model R2 = 0.464), the independent determinants of LAGCS were MA (β = − 0.289, p = 0.021) and diuretic treatment (β =0.440, p = 0.001) (model R2 = 0.341), and the independent determinant of LAGRS was diuretics (β = − 0.442, p = 0.001) (model R2 = 0.345) (Table 6).

Table 5 MRI characteristics of study population adjusted for BMI, SBP, DBP and medicine treatment
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Table 6 multivariate regression analysis for LAGLS, LAGCS and LAGRS in normotensive or hypertensive T2DM patients
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Intra-observer and inter-observer reproducibility

The intraclass correlation coefficient (ICC) values in the intraobserver analysis were 0.987, 0.810, 0.981, 0.985, 0.923, 0.916 and 0.877 for LVGRS, LVGCS, LVGLS, LAGLS, LAGCS, LAGRS, and RVGLS, respectively. The ICC values in the interobserver analysis were 0.973, 0.706, 0.983, 0.952, 0.955, 0.872 and 0.809 for LVGRS, LVGCS, LVGLS, LAGLS, LAGCS, LAGRS, and RVGLS, respectively.

Discussion

Our findings suggest that (1) compared to the control group, the T2DM group had significantly deteriorated LA and RV strain, and the amelioration of LA strain in the T2DM-HT group compared with the T2DM group; (2) the MA level was negatively related to the LAGCS value; and (3) the improvement of LAGCS, LAGRS, and LAGLS might be associated with diuretic treatment.

DM is a strong risk factor for atrial fibrillation (AF) rate [17], and likely promotes structural and functional alterations of the LA. Previous studies have indicated that T2DM patients showed a reduction in LA strain indices compared with controls [18, 19], and our study yielded the same finding. There are two possible mechanisms that explain why LA global strain in the T2DM group was significantly lower than that in the control group. First, T2DM can lead to LA fibrosis [20], and a subsequent decrease in LA compliance [21]. Impaired LA compliance results in reduced LA strain [19]. Second, myocardial inflammation occurs in T2DM patients [22] and may cause atrial remodelling [4, 23]. In the T2DM-HT group, the LA strain was significantly greater than that in the T2DM group. One possible explanation for this difference is the effect of hypertension on the myocardium. Hypertension increased LV stiffness, blood flow from the LA into the LV was affected, and LA showed an increase in preload in a certain range. Within certain limits, contraction of the LA also follows the Frank–Starling mechanism, which means that the work of LA contraction depends on the volume before its active contraction preload. Thus, LA deformation may be compensatorily enhanced when the LA preload increases within a certain range [24, 25]. Another possible explanation for this difference is the confounding effect of some antihypertensive treatments used by T2DM patients with coexisting hypertension. In a previous experimental study, renin-angiotensin system (RAS) inhibition effects were found to prevent angiotensin II concentration, phosphorylated ERK expression, caspase-3 activity and increased apoptosis, suggesting a beneficial effect on atrial myocardium [26]. Renin-angiotensin system inhibitors (ACEI) can improve LA strain in patients with hypertension [27]. Furthermore, longitudinal dysfunction might be reversed by diuretic treatment in hypertensive patients [28]. However, a prior study [18] indicated that the coexistence of T2DM and hypertension further depressed LA strain in an additive way. The above diferences in the LA strain measurements may be due to diferences in the study populations and diferent strain acquisition methods. Specifcally, the mean age was 64.7 years in T2DM-HT patients in Mondillo’s study, whereas the mean age in our T2DM-HT patients was relatively young, approximately 56.8 years. The literature reports increasing age is independently associated with deteriorated left atrial systolic strain [29]. Second, our strain acquisition method was MR-derived tissue tracking technology, whereas Mondillo’s study employed ultrasound speckle tracking. However, to our knowledge, there are few studies on LA strain changes in T2DM patients, especially those with coexisting hypertension. Whether amelioration of LA strain in T2DM-HT patients can be ascribed to the true effect of HT or to a confounding effect of some antihypertensive treatment still requires further study.

In our study, CMR-derived LV strains were similar among the three groups regardless of the presence of coexisting hypertension. We did not observe that a significantly decreased GLS in T2DM patients compared with normal subjects [30]. The above difference may lie in the duration of diabetes in the study populations. Specifically, the mean duration of diabetes in the longer-term T2DM group was approximately 11 years in Liu’s study [30], whereas the duration in our study was relatively short at only approximately 8 years. In this study, we also found that the LA strain changed significantly, indicating that LA deformation-related impairment could appear even earlier than the LV strain in the early stages of DCM, a finding that is consistent with Cameli’s study [31]. This finding revealed that LV strain did not represent the most accurate parameter for detecting early damage in those patients. A possible explanation may be related to anatomy: the LA is a very thin, single-layer wall that is very sensitive to even subtle stimuli [31]. Therefore, LA strain, as an early parameter, may have been more sensitive than LV strain for the detection of early DCM in our study.

Recently, RV function has received increasing attention and has been deemed to be clinically and prognostically significant in various diseases [32, 33]. RV impairment might be a component of DCM [34, 35]. The present study also confirmed this point: RVGLS was significantly reduced in the T2DM group compared with the control group, which is in agreement with Ng’s study [36]. One possible mechanism is that myocardial triglyceride content is increased in T2DM [37], and the intracellular surplus of triglyceride itself is likely to contribute to myocardial steatosis, which may contribute to significantly greater impairment of RVGLS [36]. Furthermore, a recent animal study also indicated that therapeutic interventions aimed at reducing myocardial triglyceride accumulation have shown beneficial myocardial effects [38]. When coexisting hypertension was present, no significant difference in the RV strain parameter was observed. Recently, Hwang et al. also showed that cardiovascular risk factors, such as hypertension, and RV strain parameter values were similar between individuals with risk factors and those without risk factors [39]. A possible explanation is that T2DM is likely related to subclinical RV systolic and diastolic dysfunction, regardless of coexisting hypertension [40].

The recommended treatment for diabetes is usually a combination of drugs [41], which may include diuretics. Our findings demonstrated that diuretic treatment was significantly related to greater LA global strain. A previous study demonstrated that longitudinal dysfunction might be reversed by diuretic treatment in hypertensive patients [28]. These results and the results of our study suggest that diuretic treatment exerts a protective effect on or reverses LA myocardial strain. Nonetheless, whether diuretics can prevent, delay, or reverse the impairment of LA strain requires further study, and additional information is needed to determine whether there are correlations among the duration of diuretic treatment, the order of diuretic treatment and T2DM diagnosis, and LA strain values. Furthermore, it is well known that DCM is associated with diabetic complications, such as diabetic nephropathy. Previous studies have supported an association between myocardial dysfunction and diabetic nephropathy [42]. In our study, we found that the LAGCS value was correlated with MA level in T2DM. Similarly, Jensen et al. [43] also demonstrated that the degeneration of systolic myocardial function is mainly related to the presence of MA in T1DM. A previous study noted [44] that circumferential strain is mainly generated by subepicardial myofiber contraction. Thus, LAGCS increased after the MA level decreased, which means that LA subepicardial myofiber contraction improved. Thus, the reduction of MA levels is necessary for diabetic patients. MA has traditionally been identified as the earliest marker of diabetic nephropathy. The presence of MA indicates the occurrence of proteinuria, which plays a key role in the progression of early renal dysfunction to end-stage renal disease [45]. However, MA may be temporary and does not always represent permanent kidney damage [46]. Stehouwer’s [47] study showed that diuretics can decrease albuminuria, which may provide effective theoretical guidance for clinical intervention in the treatment of diabetic complications.

In this study, several limitations should be considered. First, our sample size was relatively small, which greatly reduced the power of the study and did not allow us to draw generalized conclusions. We will continue to recruit participants and expand our sample size in our future studies on this topic. Second, several software programs can be used to analyze LA and biventricular deformation, and data on LA and biventricular strain quantification using CMR-FT are insufficient. Thus, reference values for those strains should be determined. Third, other biochemical indices (renal function, microalbuminuria, cholesterol, fasting plasma glucose and hemoglobin A1C levels, etc.) of the controls were not measured at the time of CMR. However, we obtained a detailed medical history for the controls and checked their medical examination reports within 6 months of enrollment to guarantee that our controls met the inclusion criteria. Fourth, the lack of sufficient prospective trials validating the use of left trial indices, such as LAGLS, in evaluating patients for cardiomyopathy is very limiting. Therefore, the use of LA indices to evaluate patients for cardiomyopathy requires further study. Fifth, in our study, CMR-FT was applied to cine SSFP sequences featuring 25 phases per cardiac cycle. Therefore, the temporal resolution was lower than that of speckle tracking echocardiography, and this difference is likely to be relevant, especially in the use of strain to evaluate diastolic function.

Conclusions

T2DM patients with preserved LV function demonstrated impaired LAGRS, LAGLS, LAGCS and RVGLS compared with controls. The amelioration of LA strain might be associated with hypertensive compensation or antihypertensive treatment. LA strain impairment may appear even earlier than LV myocardial strain in the early stage of DCM. Future follow-up studies are needed to assess the potential prognostic significance of LA and biventricular deformation in diabetic and hypertensive patients.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CVD:

Cardiovascular disease

DCM:

Diabetic cardiomyopathy

CAD:

Coronary artery disease

HT:

Hypertension

LA:

Left atrial

RV:

Right ventricle

LV:

Left ventricle

T2DM:

Type 2 diabetes mellitus

T2DM-HT:

Type 2 diabetes mellitus with hypertension

CMR-FT:

Cardiovascular magnetic resonance feature tracking

LVEDV:

Left ventricular end-diastolic volume

LVESV:

Left ventricular end-systolic volume

SV:

Stroke volume

LVEF:

Left ventricular ejection fraction

LVM:

Left ventricular mass

LAV:

Left atrial volume

LVGRS:

Left ventricular global radial strain

LVGCS:

Left ventricular global circumferential strain

LVGLS:

Left ventricular global longitudinal strain

LAGRS:

Left atrial global radial strain

LAGCS:

Left atrial global circumferential strain

LAGLS:

Left atrial global longitudinal strain

RVGLS:

Right ventricular global longitudinal strain

HbA1c:

Hemoglobin A1c

MA:

Microalbuminuria

TG:

Triglycerides

TC:

Total cholesterol

BUN:

Urea nitrogen

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

ACEI:

Angiotensin-converting enzyme inhibitor

RAS:

Renin-angiotensin system

ICC:

Intra-class correlation coefficient

References

  1. Jia G, Whaley-Connell A, Sowers JR. Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease. Diabetologia. 2018;61(1):21–8.

    Article  CAS  PubMed  Google Scholar 

  2. Kurian GA, Rajagopal R, Vedantham S, Rajesh M. The role of oxidative stress in myocardial ischemia and reperfusion injury and remodeling: revisited. Oxidative Med Cell Longev. 2016;2016:1656450.

    Article  CAS  Google Scholar 

  3. Pavlou DI, Paschou SA, Anagnostis P, Spartalis M, Spartalis E, Vryonidou A, Tentolouris N, Siasos G. Hypertension in patients with type 2 diabetes mellitus: targets and management. Maturitas. 2018;112:71–7.

    Article  PubMed  Google Scholar 

  4. Markman TM, Habibi M, Venkatesh BA, Zareian M, Wu C, Heckbert SR, Bluemke DA, Lima JAC. Association of left atrial structure and function and incident cardiovascular disease in patients with diabetes mellitus: results from multi-ethnic study of atherosclerosis (MESA). Eur Heart J Cardiovasc Imaging. 2017;18(10):1138–44.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Shang Y, Zhang X, Chen L, Leng W, Lei X, Yang Q, Liang Z, Wang J. Assessment of left ventricular structural Remodelling in patients with diabetic cardiomyopathy by cardiovascular magnetic resonance. J Diabetes Res. 2016;2016:4786925.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Burgmaier M, Frick M, Liberman A, Battermann S, Hellmich M, Lehmacher W, Jaskolka A, Marx N, Reith S. Plaque vulnerability of coronary artery lesions is related to left ventricular dilatation as determined by optical coherence tomography and cardiac magnetic resonance imaging in patients with type 2 diabetes. Cardiovasc Diabetol. 2013;12:102.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pedrizzetti G, Claus P, Kilner PJ, Nagel E. Principles of cardiovascular magnetic resonance feature tracking and echocardiographic speckle tracking for informed clinical use. J Cardiovasc Magn Reson. 2016;18(1):51.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Williams LK, Forero JF, Popovic ZB, Phelan D, Delgado D, Rakowski H, Wintersperger BJ, Thavendiranathan P. Patterns of CMR measured longitudinal strain and its association with late gadolinium enhancement in patients with cardiac amyloidosis and its mimics. J Cardiovasc Magn Reson. 2017;19(1):61.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Smith BM, Dorfman AL, Yu S, Russell MW, Agarwal PP, Ghadimi Mahani M, Lu JC. Relation of strain by feature tracking and clinical outcome in children, adolescents, and young adults with hypertrophic cardiomyopathy. Am J Cardiol. 2014;114(8):1275–80.

    Article  PubMed  Google Scholar 

  10. Buss SJ, Breuninger K, Lehrke S, Voss A, Galuschky C, Lossnitzer D, Andre F, Ehlermann P, Franke J, Taeger T, et al. Assessment of myocardial deformation with cardiac magnetic resonance strain imaging improves risk stratification in patients with dilated cardiomyopathy. Eur Heart J Cardiovasc Imaging. 2015;16(3):307–15.

    Article  PubMed  Google Scholar 

  11. Dobrovie M, Barreiro-Perez M, Curione D, Symons R, Claus P, Voigt JU, Bogaert J. Inter-vendor reproducibility and accuracy of segmental left ventricular strain measurements using CMR feature tracking. Eur Radiol. 2019;29(12):6846-57.

  12. Kosmala W, Sanders P, Marwick TH. Subclinical myocardial impairment in metabolic diseases. J Am Coll Cardiol Img. 2017;10(6):692–703.

    Article  Google Scholar 

  13. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34(28):2159–219.

    Article  PubMed  Google Scholar 

  14. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15(7):539–53.

    Article  CAS  PubMed  Google Scholar 

  15. Peng J, Zhao X, Zhao L, Fan Z, Wang Z, Chen H, Leng S, Allen J, Tan RS, Koh AS, et al. Normal values of myocardial deformation assessed by cardiovascular magnetic resonance feature tracking in a healthy Chinese population: a multicenter study. Front Physiol. 2018;9:1181.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Heermann P, Fritsch H, Koopmann M, Sporns P, Paul M, Heindel W, Schulze-Bahr E, Schulke C. Biventricular myocardial strain analysis using cardiac magnetic resonance feature tracking (CMR-FT) in patients with distinct types of right ventricular diseases comparing arrhythmogenic right ventricular cardiomyopathy (ARVC), right ventricular outflow-tract tachycardia (RVOT-VT), and Brugada syndrome (BrS). Clin Res Cardiol. 2019;108(10):1147-62.

  17. Ostgren CJ, Merlo J, Rastam L, Lindblad U. Atrial fibrillation and its association with type 2 diabetes and hypertension in a Swedish community. Diabetes Obes Metab. 2004;6(5):367–74.

    Article  CAS  PubMed  Google Scholar 

  18. Mondillo S, Cameli M, Caputo ML, Lisi M, Palmerini E, Padeletti M, Ballo P. Early detection of left atrial strain abnormalities by speckle-tracking in hypertensive and diabetic patients with normal left atrial size. J Am Soc Echocardiogr. 2011;24(8):898–908.

    Article  PubMed  Google Scholar 

  19. Kadappu KK, Boyd A, Eshoo S, Haluska B, Yeo AE, Marwick TH, Thomas L. Changes in left atrial volume in diabetes mellitus: more than diastolic dysfunction? Eur Heart J Cardiovasc Imaging. 2012;13(12):1016–23.

    Article  PubMed  Google Scholar 

  20. Liu Y, Wang K, Su D, Cong T, Cheng Y, Zhang Y, Wu J, Sun Y, Shang Z, Liu J, et al. Noninvasive assessment of left atrial phasic function in patients with hypertension and diabetes using two-dimensional speckle tracking and volumetric parameters. Echocardiography. 2014;31(6):727–35.

    Article  PubMed  Google Scholar 

  21. Asbun J, Villarreal FJ. The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy. J Am Coll Cardiol. 2006;47(4):693–700.

    Article  CAS  PubMed  Google Scholar 

  22. Zhao CT, Wang M, Siu CW, Hou YL, Wang T, Tse HF, Yiu KH. Myocardial dysfunction in patients with type 2 diabetes mellitus: role of endothelial progenitor cells and oxidative stress. Cardiovasc Diabetol. 2012;11:147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Imai M, Ambale Venkatesh B, Samiei S, Donekal S, Habibi M, Armstrong AC, Heckbert SR, Wu CO, Bluemke DA, Lima JA. Multi-ethnic study of atherosclerosis: association between left atrial function using tissue tracking from cine MR imaging and myocardial fibrosis. Radiology. 2014;273(3):703–13.

    Article  PubMed  Google Scholar 

  24. Cui Q, Wang H, Zhang W, Wang H, Sun X, Zhang Y, Yang H. Enhanced left atrial reservoir, increased conduit, and weakened booster pump function in hypertensive patients with paroxysmal atrial fibrillation. Hypertens Res. 2008;31(3):395–400.

    Article  PubMed  Google Scholar 

  25. Stefanadis C, Dernellis J, Toutouzas P. A clinical appraisal of left atrial function. Eur Heart J. 2001;22(1):22–36.

    Article  CAS  PubMed  Google Scholar 

  26. Cardin S, Li D, Thorin-Trescases N, Leung TK, Thorin E, Nattel S. Evolution of the atrial fibrillation substrate in experimental congestive heart failure: angiotensin-dependent and -independent pathways. Cardiovasc Res. 2003;60(2):315–25.

    Article  CAS  PubMed  Google Scholar 

  27. Dimitroula H, Damvopoulou E, Giannakoulas G, Dalamanga E, Dimitroulas T, Sarafidis PA, Styliadis H, Hatzitolios A, Karvounis H, Parcharidis G. Effects of renin-angiotensin system inhibition on left atrial function of hypertensive patients: an echocardiographic tissue deformation imaging study. Am J Hypertens. 2010;23(5):556–61.

    Article  CAS  PubMed  Google Scholar 

  28. Mottram PM, Haluska B, Leano R, Cowley D, Stowasser M, Marwick TH. Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure. Circulation. 2004;110(5):558–65.

    Article  CAS  PubMed  Google Scholar 

  29. Liao JN, Chao TF, Kuo JY, Sung KT, Tsai JP, Lo CI, Lai YH, Su CH, Hung CL, Yeh HI, et al. Age, Sex, and Blood Pressure-Related Influences on Reference Values of Left Atrial Deformation and Mechanics From a Large-Scale Asian Population. Circ Cardiovasc Imaging. 2017;10(10).

  30. Liu X, Yang ZG, Gao Y, Xie LJ, Jiang L, Hu BY, Diao KY, Shi K, Xu HY, Shen MT, et al. Left ventricular subclinical myocardial dysfunction in uncomplicated type 2 diabetes mellitus is associated with impaired myocardial perfusion: a contrast-enhanced cardiovascular magnetic resonance study. Cardiovasc Diabetol. 2018;17(1):139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cameli M, Mandoli GE, Lisi E, Ibrahim A, Incampo E, Buccoliero G, Rizzo C, Devito F, Ciccone MM, Mondillo S. Left atrial, ventricular and atrio-ventricular strain in patients with subclinical heart dysfunction. Int J Cardiovasc Imaging. 2019;35(2):249–58.

    Article  PubMed  Google Scholar 

  32. Inoue YY, Alissa A, Khurram IM, Fukumoto K, Habibi M, Venkatesh BA, Zimmerman SL, Nazarian S, Berger RD, Calkins H, et al. Quantitative tissue-tracking cardiac magnetic resonance (CMR) of left atrial deformation and the risk of stroke in patients with atrial fibrillation. J Am Heart Assoc. 2015;4(4).

  33. Heermann P, Hedderich DM, Paul M, Schulke C, Kroeger JR, Baessler B, Wichter T, Maintz D, Waltenberger J, Heindel W, et al. Biventricular myocardial strain analysis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) using cardiovascular magnetic resonance feature tracking. J Cardiovasc Magn Reson. 2014;16:75.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Widya RL, van der Meer RW, Smit JW, Rijzewijk LJ, Diamant M, Bax JJ, de Roos A, Lamb HJ. Right ventricular involvement in diabetic cardiomyopathy. Diabetes Care. 2013;36(2):457–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Movahed MR, Milne N. Presence of biventricular dysfunction in patients with type II diabetes mellitus. Congest Heart Fail. 2007;13(2):78–80.

    Article  PubMed  Google Scholar 

  36. Ng AC, Delgado V, Bertini M, van der Meer RW, Rijzewijk LJ, Hooi Ewe S, Siebelink HM, Smit JW, Diamant M, Romijn JA, et al. Myocardial steatosis and biventricular strain and strain rate imaging in patients with type 2 diabetes mellitus. Circulation. 2010;122(24):2538–44.

    Article  PubMed  Google Scholar 

  37. Rijzewijk LJ, van der Meer RW, Smit JW, Diamant M, Bax JJ, Hammer S, Romijn JA, de Roos A, Lamb HJ. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol. 2008;52(22):1793–9.

    Article  PubMed  Google Scholar 

  38. Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, Orci L, Unger RH. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000;97(4):1784–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hwang JW, Cha MJ, Kim SM, Kim Y, Choe YH. Relationship between cardiovascular risk factors and myocardial strain values of both ventricles in asymptomatic Asian subjects: measurement using cardiovascular magnetic resonance tissue tracking. Int J Cardiovasc Imaging. 2018;34(12):1949–57.

    Article  PubMed  Google Scholar 

  40. Kosmala W, Przewlocka-Kosmala M, Mazurek W. Subclinical right ventricular dysfunction in diabetes mellitus--an ultrasonic strain/strain rate study. Diabet Med. 2007;24(6):656–63.

    Article  CAS  PubMed  Google Scholar 

  41. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281–357.

    Article  CAS  PubMed  Google Scholar 

  42. Falcao-Pires I, Leite-Moreira AF. Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment. Heart Fail Rev. 2012;17(3):325–44.

    Article  CAS  PubMed  Google Scholar 

  43. Jensen MT, Sogaard P, Andersen HU, Bech J, Fritz Hansen T, Biering-Sorensen T, Jorgensen PG, Galatius S, Madsen JK, Rossing P, et al. Global longitudinal strain is not impaired in type 1 diabetes patients without albuminuria: the thousand & 1 study. J Am Coll Cardiol Img. 2015;8(4):400–10.

    Article  Google Scholar 

  44. Stanton T, Marwick TH. Assessment of subendocardial structure and function. J Am Coll Cardiol Img. 2010;3(8):867–75.

    Article  Google Scholar 

  45. Williams ME. Diabetic nephropathy: the proteinuria hypothesis. Am J Nephrol. 2005;25(2):77–94.

    Article  PubMed  Google Scholar 

  46. Hohenadel D, Bode H, van der Woude FJ. Regression of microalbuminuria in type 1 diabetes. N Engl J Med. 2003;349(9):906–8 author reply 906-908.

    Article  PubMed  Google Scholar 

  47. Stehouwer CD, Henry RM, Dekker JM, Nijpels G, Heine RJ, Bouter LM. Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: further evidence for a link between microalbuminuria and endothelial dysfunction--the Hoorn study. Kidney Int Suppl. 2004;92:S42–4.

    Article  Google Scholar 

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Acknowledgements

We would like to thank all colleagues for helping us during the current study. We are also very grateful for all selfless volunteers who participated in the study.

Funding

This study was funded by Hubei Province Key Laboratory of Molecular Imaging (02.03.2018–90) and Union Hospital, Huazhong University of Science and Technology (02.03.2019–101). The funders only provide funding and have no influence on study design, data collection, data analysis, data interpretation, decision to publish, or writing the manuscript.

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Author notes

  1. Guozhu Shao and Yukun Cao contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Guozhu Shao, Yukun Cao, Yue Cui, Xiaoyu Han, Jia Liu, Yumin Li, Na Li, Tong Liu, Jie Yu & Heshui Shi

  2. Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, P.R. China

    Guozhu Shao, Yukun Cao, Yue Cui, Xiaoyu Han, Jia Liu, Yumin Li, Na Li, Tong Liu, Jie Yu & Heshui Shi

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  1. Guozhu Shao
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  9. Jie Yu
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Contributions

Study designing: JY, H-SS, G-ZS and Y-KC; data search G-ZS, Y-KC; data extraction: G-ZS, Y-KC, YC, X-YH, JL, Y-ML, NL and TL; data analysis and interpretation: G-ZS, Y-KC, JY, H-SS; Manuscript drafting: G-ZS, Y-KC, JY and H-SS; manuscript critical intellectual content revision: G-ZS, Y-KC, JY, H-SS. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Jie Yu or Heshui Shi.

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Ethics approval and consent to participate

This study was approved by ethics committee of Tongji Medical College of Huazhong University of Science and Technology and in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All subjects provided written informed consent.

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Not Applicable.

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All authors declared that: there is no conflict of interest existing in the submission of this manuscript, and all authors approved the article for publication.

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Shao, G., Cao, Y., Cui, Y. et al. Early detection of left atrial and bi-ventricular myocardial strain abnormalities by MRI feature tracking in normotensive or hypertensive T2DM patients with preserved LV function. BMC Cardiovasc Disord 20, 196 (2020). https://doi.org/10.1186/s12872-020-01469-2

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Keywords

BMC Cardiovascular Disorders

ISSN: 1471-2261

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