dic Arquivos Brasileiros de Cardiologia Imagem cardiovascular Arq Bras Cardiol: Imagem cardiovasc 2675-312X Sociedade Brasileira de Cardiologia 10.47593/2675-312X/20223502eabc293 Systematic Review Article Role of Strain in the Early Diagnosis of Diabetic Cardiomyopathy SilvaThais Rossoni Weber da 1 SilvaRoberto Léo da 1 MartinsAdriana Ferraz 1 MarquesJefferson Luiz Brum 2 Department of CardiologyProf. Polydoro Ernani de São Thiago University HospitalFlorianópolisSCBrazil Department of Cardiology , Prof. Polydoro Ernani de São Thiago University Hospital , Florianópolis , SC , Brazil . Institute of Biomedical EngineeringFederal University of Santa CatarinaFlorianópolisSCBrazil Institute of Biomedical Engineering , Federal University of Santa Catarina , Florianópolis , SC , Brazil . Mailing Address: Thaís Rossoni Weber da Silva • Prof. Polydoro Ernani de São Thiago, Department of Cardiology, University Hospital R. Professora. Maria Flora Pausewang - Trinidad, Florianópolis, SC, Brazil 88036-800. E-mail: thaisrossoni@yahoo.com

Authors’ contributions

Research creation and design:: Silva TRW, Silva RL; Data acquisition: Silva TRW, Silva RL; Data analysis and interpretation: Silva TRW, Martins AF; Statistical analysis: Silva RL; Manuscript writing: Silva TRW, Silva RL, Martins AF; Critical revision of the manuscript for important intellectual content: Silva TRW, Silva RL, Martins A, Marques JLB.

Conflict of interest

The authors have declared that they have no conflict of interest.

 28 05 2022 2022 35 2 eabc293 282202210320221732022 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. AbstractBackground

Advanced echocardiography using two- and three-dimensional myocardial strain proposes to identify subclinical systolic dysfunction in different clinical conditions. Strain assessment plays an important role in the early diagnosis of diabetic cardiomyopathy in diabetes mellitus (DM). However, the findings of published articles are heterogeneous. Here we conducted a systematic review to analyze the current role of strain assessment in patients with DM.

Methods

This systematic review of five databases identified 19 studies that used two-dimensional strain and 8 studies that used three-dimensional strain.

Results

The studies of two-dimensional strain included 1,774 DM patients (mean age, 57.1 years; median age, 55 years; 47.5% women), while those of three-dimensional strain included 488 DM patients (mean age, 55.7 years; median age, 63 years; 51% women). Global longitudinal strain was the myocardial deformation marker that differed most frequently between the DM and control groups.

Conclusion

Myocardial strain imaging by two- and three-dimensional speckle tracking echocardiography allows the identification of subclinical systolic dysfunction in DM patients, and differences become more marked when associated with risk factors and ventricular remodeling.

 Diabetes MellitusEchocardiographyVentricular Function Introduction

Diabetes mellitus (DM), among the most prevalent diseases in the modern world, is a risk factor for heart failure that increases mortality, mainly from cardiovascular causes. 1 Cardiovascular complications are the leading cause of death in DM patients, 2 , 3 with diabetic cardiomyopathy being characterized by structural and functional cardiac changes without other known factors for the development of myocardial dysfunction, such as coronary heart disease, arterial hypertension, or significant valvular diseases. 4 Cardiac remodeling in diabetes results from cardiovascular autonomic neuropathy, renin-angiotensin-aldosterone system activation, interstitial myocardial fibrosis, microangiopathy, inflammatory cytokines, and metabolic changes such as hyperglycemia, 5 , 6 and its detection requires sensitive diagnostic methods. 7

The early diagnosis of diabetic cardiomyopathy is clinically relevant, as early lesions may be reversible 8 , 9 and therapy can be implemented to prevent cardiovascular disease progression. However, it remains little recognized by clinicians 1 due to the conflicting results of different populations 10 and the need for more sensitive and recently developed diagnostic tools. Left ventricular (LV) diastolic dysfunction was considered the initial sign on Doppler echocardiography. 11 , 12 Improved imaging methods such as speckle tracking echocardiography enabled the earlier detection of systolic myocardial dysfunction prior to diastolic dysfunction in asymptomatic subjects. 13 , 14

The incorporation of new techniques such as myocardial strain on echocardiography increased the diagnostic sensitivity of speckle tracking, especially of subclinical myocardial dysfunction, and was validated by magnetic resonance imaging with myocardial tagging and sonomicrometry. 15 The most commonly used parameter is global longitudinal strain (GLS), the mean strain of myocardial segments in the longitudinal direction, a technique that is more reproducible and can identify subclinical LV dysfunction, a better risk predictor than LV ejection fraction (LVEF). 16 Another recent concept is multilayer analysis, which introduced an anatomical aspect into myocardial deformation assessment in which the three LV myocardial layers (endocardium, mesocardium, and epicardium) contribute to more effective contractions in different directions. 17 In contrast, three-dimensional myocardial strain enables a more objective assessment of LV systolic dysfunction without requiring calculations to predict ventricular geometric shape, with the additional benefit of being more reproducible than two-dimensional strain for avoiding marker loss outside the analyzed plane despite requiring high-quality images. 18

Several studies aiming to assess cardiac function in DM patients using two- and three-dimensional strain reported worse myocardial deformation rates compared to controls. However, some such studies were small, heterogeneous, and presented several confounding factors. Thus, a review of the current evidence is necessary to understand knowledge gaps and revisit important issues. The present study aimed to identify whether advanced two- or three-dimensional speckle tracking echocardiography could demonstrate early cardiac lesions secondary to DM and define its current role for assessing DM patients. Thus, here we conducted a systematic review of the use of ventricular strain echocardiography in DM.

 Methods

This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the MEDLINE, EMBASE, SCOPUS, and WEB OF SCIENCE databases using the descriptors “ diabetic cardiomyopathy ” or “ speckle tracking ” or “ myocardial strain/dysfunction ” or “ ventricular function/dysfunction, ” “ deformation imaging/analysis, ” or “ cardiac mechanics/function ” and “ diabetes ” or “ diabetic. ” The search was limited to articles in humans; published in English, French, Spanish, or Portuguese; and published through January 31, 2022. The selection criteria for the articles were age older than 15 years, inclusion of control group without DM, no established heart disease, and speckle tracking description of the GLS value. Database references were gathered in the Mendeley ® application and duplicates were removed. Two researchers (TRWS and RLS) searched the articles separately and agreed on the eligibility of the final selections. First, a broad search identified articles related to the topic by title and abstract screening. The exclusion criteria were a different target population or no control group; the presence of coronary artery disease or other structural disease; use of another imaging method for measuring myocardial deformation such as magnetic resonance imaging or tissue Doppler; no description of the GLS value; and case report, conference presentation, review, and editorial articles.

The articles were subsequently subjected to full-text review to identify those that presented the necessary data and fit the previous requirements. In studies with multiple subgroups of patients or controls, the lowest-risk subgroup was selected ( Table 1 ). The studies were allocated to two- or three-dimensional speckle tracking groups for evaluation. The information extracted from the articles included author, year of publication, brand of equipment, study design, number of cases in the sample, age, sex, body mass index (BMI), blood pressure levels or diagnosis of hypertension, glycated hemoglobin (HbA1c) value, LVEF, GLS, global radial strain (GRS), and global circumferential strain (GCS) ( Table 2 ). Studies of three-dimensional strain also included global strain area (GSA) (Tables 3 and 4).

– Clinical and demographic data of studies that evaluated diabetic cardiomyopathy using two-dimensional speckle tracking strain.
Author N Control DM type HbA1c Control Age, years (DM) Age, years (Control) Women, % (DM) Women, % (Control) BMI (DM) BMI (Control) SBP (DM) SBP (Control)
Yamauchi et al. 7 192 81 DM2 8.5 Healthy 61 57 48 54 25 22 131 123
Weber et al. 10 40 40 DM1 8.0 Healthy 33 33 55 55 25 25 110 102
Tadic et al. 17 48 44 DM2 7.3 Healthy 55 52 48 50 27 26 131 127
Ringle et al. 18 66 26 DM1 7.7 Healthy 38 35 71 69 24 23 122 121
Ng et al. 20 397 104 DM2 7.3 Healthy 58 50 46 43.3 29 - 141 123
Yang et al. 21 47 27 DM2 6.1 Healthy 51 50 32 33 23 23 - -
Wang et al. 22 48 50 DM2 10.1 Healthy 54 50 52 50 23 23 127 122
Vukomanovic et al. 23 50 40 DM2 7.3 Healthy 55 50 48 45 29 24 131 129
Vukomanovic et al. 24 70 80 DM2 7.5 Healthy 52 49 44 43 28 26 126 124
Soufi Taleb Bendiab et al. 25 93 107 DM2 + SAH - SAH 61 62 63 53 30 29 158 142
Tadic et al. 26 50 55 DM2 + SAH 7.0 Healthy 56 51 48 47 27 26 145 128
Todo et al. 29 177 79 DM2 8.8 Healthy 61 58 47 57 25 22 131 125
Van Ryckeghem et al. 30 36 23 DM2 6.9 Healthy 62 57 14 48 28 26 149 140
Roberts et al. 31 34 17 DM1/DM2 7.8 Healthy 42 41 29 35 27 25 125 121
Li et al. 32 101 60 DM2 7.6 Healthy 52 54 53 53.3 24 23 123 123
Philouze et al. 33 44 35 DM2 7.2 Healthy 56 52 41 51 27 24 126 123
Mochizuki et al. 34 103 82 DM 8.6 Healthy 56 55 63 60 23 22 121 117
Jørgensen et al. 36 57 80 DM2 6.1 Healthy 65 65 44 35 26 24 126 123
Stevanovic et al. 39 121 40 DM2 8.2 Healthy 55 53 19 29 28 27 125 122

BMI, body mass index; DM, diabetes mellitus; DM1, type 1 DM; DM2, type 2 DM; HbA1c, glycated hemoglobin; N, number of patients with diabetes; SAH, systemic arterial hypertension; SBP, systolic blood pressure.

– Clinical and demographic data from studies that evaluated diabetic cardiomyopathy by three-dimensional speckle tracking strain.
Author N Control DM HbA1c (%) Control Age, years (DM) Age, years (Control) Women, % (DM) Women, % (Control) BMI (DM) BMI (Control) SBP (DM) SBP (Control)
Wang et al. 41 40 40 DM2 - Healthy 66±7 68±8 50 50 24.6±2 23.5±3 128±7 123±9
Wang et al. 44 40 40 DM2 6.6±0.6 Healthy 68±8 68±7 50 55 24.9±3 24.4±3 128±9 126±10
Wang et al. 42 38 45 DM2 7.0±0.6 Healthy 61±8 62±7 45 50 24.5±3 24.7±2 127±10 126±7
Luo et al. 43 38 35 DM2 10.4±2.6 Healthy 59±7 58±76 32 32 24.9±2 24.3±2 128±9 107±6
Wang et al. 47 40 40 DM2 - Healthy 66±8 67±8 50 50 24.7±2 25.0±3 128±6 126±7
Wang et al. 45 34 40 DM2 - Healthy 65±7 64±8 50 50 24.0±2 24.5±3 125±8 125±7
Chen et al. 46 192 81 DM2 6.1±0.4 Healthy 52 ± 8 50±6 50 49 25.1 ± 2 24.3 ± 2 122 ±11 119 ±10
Ringle et al., 18 66 26 DM1 7.7±1.3 Healthy 37±9 35±7 71 69 24.0±3 23.0±3 121±12 122±9

BMI, body mass index; DM, diabetes mellitus; DM1, type 1 diabetes mellitus; DM2, type 2 diabetes mellitus; HbA1c, glycated hemoglobin; N, number of patients with diabetes; SAH, systemic arterial hypertension; SBP, systolic blood pressure.

– Systolic cardiac function evaluated by two-dimensional speckle tracking strain.
Author Equipment LVEF % (DM) LVEF % (Control) GLS (DM) GLS (Control) p (DM × Control) GCS (DM) GCS (Control) p GRS (DM) GRS (Control) p
Yamauchi et al. 7 GE Vivid E9 66±5 66±5 -17.6±3 -20.3±2 <0.0001 - - - - - -
Weber et al. 10 GE S6 72±5 71±5 -21.7±2 -21.0±2 0.21 - - - - - -
Tadic et al. 17 GE Vivid 7 64±4 65±4 -18.8±2 -20.8±2 <0.001 -19.2±2 -21.4±3 <0.001 41.6±8 43.2±8.3 0.001
Ringle et al. 18 Philips - IE33 60±8 61±3 -18.9±2 -20.5±2 0.0002 -25.4±3 -26.1±3 0.39 36.3±9 37.6±7 0.054
Ng et al. 20 GE Vivid 7/E9 60±5 58±4 -17.3±2 -20.5±2 - - - - - - -
Yang et al. 21 GE Vivid E9 58±3 59±2 -17.2±2 -20.2±3 0.04 -20.9±4 -22.1±3 0.06 37.4±12.6 40.3±11.8 0.45
Wang et al. 22 GE Vivid E9 66±4 62±5 -19.6±2 -22.5±3 <0.0001 - - - - - -
Vukomanovic et al. 23 GE Vivid 7 64±5 63±4 -18.5±2 -21.1±3 <0.001 -18.9±2 -21.9±3 <0.001 37.2±8.1 42.1±8.6 0.007
Vukomanovic et al. 24 GE Vivid 7 64±4 64±3 -18.4±2 -21.6±3 <0.001 -19.5±2.6 -22.0±3 <0.001 37.9±9.4 40.6±10.1 0.094
Soufi Taleb Bendiab et al. 25 GE S6 61±6 62±6 -16.4±3 -17.8±3 <0.0001 - - - - - -
Todo et al. 29 GE Vivid E9 66±5 66±5 -17.6±3 -20.5±2 <0.0001 - - - - - -
Van Ryckeghem et al. 30 GE Vivid E9 66±8 66±9 -17.0±3 -19.8±2 <0.001 - - - - - -
Tadic et al. 26 GE Vivid 7 62±3 63±3 -17.7±2 -21.3±3 <0.001 -18.3±2.3 -22.1±3 <0.001 38.5±9.3 41.8±10.1 0.247
Roberts et al. 31 GE Vivid E9 60±4 60±5 –18.6±2 –19.7±2 0.09 - - - - - -
Li et al. 32 GE Vivid E9 64±4 65±4 - 19.4±3 - 21.22±3 <0.001 - - - - - -
Philouze et al. 33 GE Vivid E95 64±8 64±7 -20.8±2 -20.2±3 NS - - - - - -
Mochizuki et al. 34 GE Vivid E9 67±4 66±5 -20.5±2 -20.5±2 <0.05 - - - - - -
Jørgensen et al. 36 GE Vivid E9 65 63 -15.3±2 -15.9±2 0.13 -18.7±5 -18.1±4 0.49 - - -
Stevanovic et al. 39 GE Vivid 7 62±4 62±5 -17.5±2 -24.4±2 <0.001 - - - - - -

DM, diabetes mellitus; GCS, global circumferential strain; GLS, global longitudinal strain; GRS, global radial strain; LVEF, left ventricular ejection fraction.

– Systolic cardiac function evaluated by three-dimensional speckle tracking strain.
Author Equipment LVEF % (DM) LVEF % (Control) GLS (DM) GLS (Control) p (DM × Control) GCS (DM) GCS (Control) p GRS (DM) GRS (Control) p GSA (DM) GSA (Control) p
Wang et al. 41 GE Vivid E9 61±6 61±5 -17.1±2.6 -18.4±3.0 <0.05 -17.8±2.7 -18.8±3.0 >0.05 49.0±8.9 51.0±9.0 >0.05 -29.1±4.0 -30.2±3.6 >0.05
Wang et al. 44 GE Vivid E9 60±7 61±7 -17.0±2.6 -18.9±2.5 <0.01 -17.4±2.5 -18.7±2.9 <0.05 47.7±8.5 51.5±8.9 >0.05 -30.1±3.6 -30.6±4.0 >0.05
Wang et al. 42 GE Vivid E9 58±6 58±6 -17.3±2.4 -19.9±2.6 <0.001 -17.2±2.7 -18.9±0.31 <0.05 47.7±7.9 53.2±10.0 <0.01 -30.2±3.4 -31.0±4.7 >0.05
Luo et al. 43 IE33 68±2 66±3 –17.2±3.0 –20.8±2.8 <0.01 -22.9±3.0 -25.9±3.4 <0.05 - - - - - -
Wang et al., 47 GE Vivid E9 60±7 60±6 -16.9±2.9 - 18.2±2.3 <0.05 -17.6±3.5 -18.1±2.2 >0.05 46.9±9.8 48.5±6.5 >0.05 -29.6±5.5 -30.0±3.2 >0.05
Wang et al. 45 GE Vivid E9 60±7 60±7 - 17.6±2.1 -18.8±2.7 <0.05 -17.9±2.7 -18.1±3.0 >0.05 49.1±7.9 50.2±9.3 >0.05 -30.7±3.2 -31.2±4.3 >0.05
Chen et al. 46 GE Vivid E9 65±8 67±4 -19.3±3.9 -20.1±3.2 >0.05 -19.7±4.9 -19.3±6.3 >0.05 45.4±7.0 45.7±7.5 >0.05 -30.3±5.5 -33.0±6.6 >0.05
Ringle et al., 18 IE33 60±8 61±3 -17.5±2.0 -19.0±2.0 >0.05 - - - - - - - - -

DM, diabetes mellitus; GSA, global strain area; GCS, global circumferential strain; GLS, global longitudinal strain; GRS, global radial strain; LVEF, left ventricular ejection fraction.

Results

We identified 819 references in the electronic databases in the previous five years, excluding 123 duplicates. Of the remaining 696 studies, we obtained 75 full articles for analysis after title and abstract screenings. Another 49 studies were excluded ( Figure 1 ). The review included 26 articles for qualitative analysis, which were classified into two main categories: two-dimensional strain (n = 19; Table 1 ) and three-dimensional strain (n = 8; Table 2 ). Only studies with a control group were included. The articles were mostly published in English, followed by French and Portuguese. Three 18 were prospective studies and the others were case-control studies.

– Flowchart of search and selection of studies evaluating diabetic cardiomyopathy through bidimensional and three-dimensional strain. TDI: Tissue Doppler Imaging; CAD: Coronary Artery Disease; 3D: three-dimensional; 2D: two-dimensional. In the qualitative synthesis, one study was included in 2D and 3D strain.

The studies using two-dimensional strain resulted in a sample of 1,774 DM patients (mean age, 57.1 years; median age, 55 years; 47.5% women). A GE Vivid E9 ultrasound machine was most often used in these studies. The studies using three-dimensional strain resulted in a sample of 488 DM patients (mean age, 55.7 years; median age, 63 years; 51% women). All studies used the GE Vivid E9 device except for two that used an Philips iE33 ultrasound system.

Of the 19 analyzed studies, less than half excluded hypertensive patients from the DM group, 10 , 18 , 21 most involved type 2 DM (DM2) patients, and only three analyzed type 1 DM (DM1) cases. In one study, 25 the control group consisted of hypertensive patients without diabetes. Some studies evaluated DM patients with versus without hypertension, with versus without associated microvascular complications, or even subgroups in which uncontrolled risk factors were quantified. Another study presented a DM population prior to hospitalization with changed glycemic levels (HbA1c > 10%). 22

Different assessments were studied in this population, such as myocardial work index, 26 , 27 myocardial torsion by speckle tracking, 28 right ventricular systolic dysfunction by speckle tracking, 29 cardiac function during physical activity and exercise capacity, 24 , 30 , 31 dispersion value between systolic strain peaks, 32 heart rate effect, 7 cardiac function during dobutamine stress echocardiography, 33 heart rate variability, 23 diastolic dysfunction progression, 34 and multilayer speckle tracking analysis. 17 , 23

The echocardiographic characteristics of interest here are shown in Tables 3 and 4.

 Discussion

The use of new imaging techniques for diagnosing diabetic cardiomyopathy has increased our knowledge through the identification of earlier lesions. Although LV diastolic dysfunction has traditionally been believed to precede systolic dysfunction, subclinical systolic dysfunction detected by GLS may be the first sign of diabetic cardiomyopathy. 14

GLS is the myocardial deformation marker that most frequently differs between DM and control groups. Some studies established a specific GLS value for the diagnosis of subclinical ventricular dysfunction based on the statistical analysis of the values obtained in the sample. In these studies, the incidence of subclinical ventricular dysfunction was 40–45% in the diabetic population. 20 , 35 The fewer studies that used other parameters, such as GCS 17 , 23 , 24 , 26 or GRS 23 , identified myocardial function differences using two-dimensional strain. These differences were not detected using LVEF. Tadic et al. 17 showed a GRS difference only in a DM and hypertension group. Likewise, Jørgensen et al. reported a GCS difference among subgroups of DM patients with more risk factors. 36

Multilayer speckle tracking analysis can show differences between DM and control groups. 17 , 23 , 24 , 37 Despite being a new technology that requires further validation, this tool locates myocardial lesions and detects possible changes early. 38 Tadic et al. studied healthy controls, DM2 patients, and/or patients with systemic arterial hypertension (SAH) and reported multidirectional strain change; hypertension as a factor for LV mechanical deterioration; involvement of all myocardial layers due to DM and SAH; and a correlation between glycemic control (fasting glucose and HbA1c), GLS, and LV layer–specific strain.

In the previous five years, only three studies followed the participants. Studies including DM2 patients had larger sample sizes. Stevanovic et al. and Ng et al. followed up more than 100 subjects and demonstrated that GLS was a strong predictor of cardiovascular events in multivariate analysis. 20 , 39 Ringle et al. evaluated a group of DM1 patients a mean 37 years of age without cardiovascular risk factors who presented an absolute strain value lower than the control population and a significantly decreased absolute strain value during follow-up; however, no events were observed in the follow-up period. This study showed no correlation between GLS and metabolic status in terms of glycemic control, diabetes duration, or coexisting microvascular complications. 18

Of the 19 articles analyzed, only four 10 , 31 , 33 , 36 identified no GLS differences and demonstrated subclinical myocardial function reduction attributable to diabetes. These studies analyzed DM1 and/or DM2 patients but with clearly fewer risk factors, such as SAH, overweight and obesity, dyslipidemia, renal function measured by creatinine clearance, lower glycemic levels (HbA1c < 8%), which, when present, were controlled in addition to showing no or smaller differences in LV structural parameters such as ventricular mass index and relative wall thickness. This information is useful for predicting a better prognosis for these patients and encouraging good control of comorbidities.

Several authors studied possible contributors to worsen systolic function in patients with diabetes. Yang et al. studied the relationship between microvascular complications and LV systolic function and reported decreased GLS in the group without complications that was even greater in the group with microvascular complications. 21 Soufi et al. studied hypertensive patients with and without diabetes and showed that the association of SAH and DM further decreases ventricular systolic function when evaluated by strain and that the two independent variables for this decreased absolute GLS value were DM2 and relative posterior wall thickness. 25 Jørgensen et al. designed a study to assess the influence of risk factors in DM patients and reported an association between systolic blood pressure, BMI, HbA1c, and LV structure and function. Thus, risk factors should be weighed when analyzing studies that assess diabetic cardiomyopathy to avoid confounding factors. Regardless, this population has a high prevalence of comorbidities, and poor metabolic control can interfere with cardiac function.

As for glycemic control, Lind et al. analyzed 20,985 DM1 patients and concluded that even after adjusting for other cardiovascular risk factors, the risk of heart failure was still four-fold higher in patients with poor glycemic control than in those with excellent glycemic control and that each 1% increase in HbA1c corresponded to a 30% increase in the risk of developing heart failure. 40 Li et al. explored the relationship between glycemic control and LV dysfunction in DM2 patients through HbA1c 32 and found that LVEF showed no difference; however, ventricular mass index and mitral E-wave velocity differed between the DM and control groups, with a greater difference in the group with worse glycemic control. In addition, there was no GLS difference between the group with good glycemic control and the control group. This study showed a correlation between HbA1c, ventricular mass index, and E/e' ratio, and GLS. Wang et al. 22 showed an intergroup difference in GLS; however, there was already an LVEF difference. This study highlights the poor glycemic control in the DM2 group prior to hospitalization, with an HbA1c value around 10%.

Contrary evidence was reported by studies that showed no difference between DM and control groups with populations with better-controlled risk factors. 10 , 18 , 31 , 36 Three-dimensional speckle tracking analysis identified a lower absolute GLS value in subjects with diabetes versus controls. 18 , 41 Depending on the associated risk factor, other parameters also showed differences, such as GCS 42 and GRS. 42 , 47 Chen et al. concluded that three-dimensional speckle tracking strain detects LV dysfunction in DM patients with poor glycemic control and that myocardial dysfunction is associated with DM duration and HbA1c. 46 Wang et al. demonstrated that fasting glucose, dyslipidemia, and BMI were significant risk factors for LV remodeling in DM2 patients. Those with normal ventricular geometry showed differences in only GLS compared to controls, while DM patients with LV remodeling showed lower absolute GLS, GCS, GSA, and GRS values. 44 Hepatic steatosis is another condition highly prevalent in DM2, being associated with LV remodeling and subclinical ventricular dysfunction; of the three-dimensional strain parameters, GLS presented the most evident change. 42 Finally, intensive treatment with an insulin pump improved LV systolic function, proving a sensitive and accurate diagnostic technique that could even provide data on the therapeutic effect. 43

As previously reported, 18 , 48 image acquisition and the analysis of myocardial deformation by three-dimensional speckle tracking was faster than that by two-dimensional speckle tracking; however, high-quality images are required to ensure an accurate strain analysis.

 Conclusion

Myocardial strain imaging by two- and three-dimensional speckle tracking echocardiography enables the identification of subclinical systolic dysfunction in DM patients that becomes more marked when associated with risk factors and ventricular remodeling. The introduction of tools like the layer-specific method allows for a broader understanding of myocardial involvement in DM. Despite few prospective studies assessing clinical outcomes, there is evidence of an association between GLS and cardiovascular events in DM patients.

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Myocardial work in hypertensive patients with and without diabetes: An echocardiographic study. J Clin Hypertens. 2020;22(11):2121-7. doi: https://doi.org/10.1111/jch.14053 TadicMCuspidiCPencicBGrassiGCelicVMyocardial work in hypertensive patients with and without diabetes: An echocardiographic studyJ Clin Hypertens2020221121212127https://doi.org/10.1111/jch.14053 . Wang T, Li L, Huang J, Fan L. Assessment of subclinical left ventricle myocardial dysfunction using global myocardial work in type 2 diabetes mellitus patients with preserved left ventricle ejection fraction. Diabetol Metab Syndr. 2022;14(1):17. doi: https://doi.org/10.1186/s13098-021-00781-x WangTLiLHuangJFanLAssessment of subclinical left ventricle myocardial dysfunction using global myocardial work in type 2 diabetes mellitus patients with preserved left ventricle ejection fractionDiabetol Metab Syndr202214117https://doi.org/10.1186/s13098-021-00781-x . Yang QM, Fang JX, Chen XY, Lv H, Kang CS. The systolic and diastolic cardiac function of patients with type 2 diabetes mellitus: an evaluation of left ventricular strain and torsion using conventional and speckle tracking echocardiography. Front Physiol. 2022;12. doi: https://doi.org/10.3389/fphys.2021.726719 YangQMFangJXChenXYLvHKangCSThe systolic and diastolic cardiac function of patients with type 2 diabetes mellitus: an evaluation of left ventricular strain and torsion using conventional and speckle tracking echocardiographyFront Physiol202212https://doi.org/10.3389/fphys.2021.726719 . Todo S, Tanaka H, Yamauchi Y, Yokota S, Mochizuki Y, Shiraki H, et al. Association of left ventricular longitudinal myocardial function with subclinical right ventricular dysfunction in type 2 Diabetes mellitus. Cardiovasc Diabetol. 2021;20(1):212. doi: https://doi.org/10.1186/s12933-021-01404-5 TodoSTanakaHYamauchiYYokotaSMochizukiYShirakiHet alAssociation of left ventricular longitudinal myocardial function with subclinical right ventricular dysfunction in type 2 Diabetes mellitusCardiovasc Diabetol2021201212https://doi.org/10.1186/s12933-021-01404-5 . Van Ryckeghem L, Keytsman C, Verbaanderd E, Frederix I, Bakelants E, Petit T, et al. Asymptomatic type 2 diabetes mellitus display a reduced myocardial deformation but adequate response during exercise. Eur J Appl Physiol. 2021;121(3):929-40. doi: https://doi.org/10.1007/s00421-020-04557-5 Van RyckeghemLKeytsmanCVerbaanderdEFrederixIBakelantsEPetitTet alAsymptomatic type 2 diabetes mellitus display a reduced myocardial deformation but adequate response during exerciseEur J Appl Physiol20211213929940https://doi.org/10.1007/s00421-020-04557-5 . Roberts TJ, Barros-Murphy JF, Burns AT, MacIsaac RJ, MacIsaac AI, Prior DL, et al. Reduced exercise capacity in diabetes mellitus is not associated with impaired deformation or twist. J Am Soc Echocardiogr. 2020;33(4):481-9. doi: https://doi.org/10.1016/j.echo.2019.11.012 RobertsTJBarros-MurphyJFBurnsATMacIsaacRJMacIsaacAIPriorDLet alReduced exercise capacity in diabetes mellitus is not associated with impaired deformation or twistJ Am Soc Echocardiogr2020334481489https://doi.org/10.1016/j.echo.2019.11.012 . Li C, Yuan M, Li K, Bai W, Rao L. Value of peak strain dispersion in discovering left ventricular dysfunction in diabetes mellitus. Sci Rep. 2020;10(1). doi: https://doi.org/10.1038/s41598-020-78621-7 LiCYuanMLiKBaiWRaoLValue of peak strain dispersion in discovering left ventricular dysfunction in diabetes mellitusSci Rep2020101https://doi.org/10.1038/s41598-020-78621-7 . Philouze C, Obert P, Nottin S, Benamor A, Barthez O, Aboukhoudir F. Dobutamine stress echocardiography unmasks early left ventricular dysfunction in asymptomatic patients with uncomplicated type 2 diabetes: a comprehensive two-dimensional speckle-tracking imaging study. J Am Soc Echocardiogr. 2018;31(5):587-97. doi: https://doi.org/10.1016/j.echo.2017.12.006 PhilouzeCObertPNottinSBenamorABarthezOAboukhoudirFDobutamine stress echocardiography unmasks early left ventricular dysfunction in asymptomatic patients with uncomplicated type 2 diabetes: a comprehensive two-dimensional speckle-tracking imaging studyJ Am Soc Echocardiogr2018315587597https://doi.org/10.1016/j.echo.2017.12.006 . Mochizuki Y, Tanaka H, Matsumoto K, Sano H, Shimoura H, Ooka J, et al. Impact of left ventricular longitudinal functional mechanics on the progression of diastolic function in diabetes mellitus. Int J Cardiovasc Imaging. 2017;33(12):1905-14. doi: https://doi.org/10.1007/s10554-017-1198-8 MochizukiYTanakaHMatsumotoKSanoHShimouraHOokaJet alImpact of left ventricular longitudinal functional mechanics on the progression of diastolic function in diabetes mellitusInt J Cardiovasc Imaging2017331219051914https://doi.org/10.1007/s10554-017-1198-8 . Stevanovic A, Dekleva M. The importance of subclinical left ventricular dysfunction and blood pressure pattern in asymptomatic type-2 diabetic patients: the diagnostic and prognostic significance of Tissue Doppler parameters, left ventricular global longitudinal strain, and night. J Diabetes Complications. 2018;32(1):41-7. doi: https://doi.org/10.1016/j.jdiacomp.2017.07.022 StevanovicADeklevaMThe importance of subclinical left ventricular dysfunction and blood pressure pattern in asymptomatic type-2 diabetic patients: the diagnostic and prognostic significance of Tissue Doppler parameters, left ventricular global longitudinal strain, and nightJ Diabetes Complications20183214147https://doi.org/10.1016/j.jdiacomp.2017.07.022 . Jørgensen PG, Jensen MT, Biering-Sørensen T, Mogelvang R, Fritz-Hansen T, Vilsbøll T, et al. Burden of uncontrolled metabolic risk factors and left ventricular structure and function in patients with type 2 diabetes mellitus. J Am Heart Assoc. 2018;7(19):e008856. doi: https://doi.org/10.1161/JAHA.118.008856 JørgensenPGJensenMTBiering-SørensenTMogelvangRFritz-HansenTVilsbøllTet alBurden of uncontrolled metabolic risk factors and left ventricular structure and function in patients with type 2 diabetes mellitusJ Am Heart Assoc2018719e008856https://doi.org/10.1161/JAHA.118.008856 . Berceanu M, Mirea O, Donoiu I, Militaru C, Saftoiu A, Istratoaie O. Myocardial function assessed by multi-layered two-dimensional speckle tracking analysis in asymptomatic young subjects with diabetes mellitus type 1. Cardiology. 2020;145(2):80-7. doi: https://doi.org/10.1159/000504532 BerceanuMMireaODonoiuIMilitaruCSaftoiuAIstratoaieOMyocardial function assessed by multi-layered two-dimensional speckle tracking analysis in asymptomatic young subjects with diabetes mellitus type 1Cardiology202014528087https://doi.org/10.1159/000504532 . Ananthapadmanabhan S, Vo G, Nguyen T, Dimitri H, Otton J. Direct comparison of multilayer left ventricular global longitudinal strain using CMR feature tracking and speckle tracking echocardiography. BMC Cardiovasc Disord. 2021;21(1):1-10. doi: https://doi.org/10.1186/s12872-021-01916-8 AnanthapadmanabhanSVoGNguyenTDimitriHOttonJDirect comparison of multilayer left ventricular global longitudinal strain using CMR feature tracking and speckle tracking echocardiographyBMC Cardiovasc Disord2021211110https://doi.org/10.1186/s12872-021-01916-8 . Stevanovic A, Dekleva M. The importance of subclinical left ventricular dysfunction and blood pressure pattern in asymptomatic type-2 diabetic patients: the diagnostic and prognostic significance of Tissue Doppler parameters, left ventricular global longitudinal strain, and night. J Diabetes Complications. 2018;32(1):41-7. doi: https://doi.org/10.1016/j.jdiacomp.2017.07.022 StevanovicADeklevaMThe importance of subclinical left ventricular dysfunction and blood pressure pattern in asymptomatic type-2 diabetic patients: the diagnostic and prognostic significance of Tissue Doppler parameters, left ventricular global longitudinal strain, and nightJ Diabetes Complications20183214147https://doi.org/10.1016/j.jdiacomp.2017.07.022 . Lind M, Bounias I, Olsson M, Gudbjörnsdottir S, Svensson AM, Rosengren A. Glycaemic control and incidence of heart failure in 20 985 patients with type 1 diabetes: An observational study. Lancet. 2011;378(9786):140-6. doi:10.1016/S0140-6736(11)60471-6LindMBouniasIOlssonMGudbjörnsdottirSSvenssonAMRosengrenAGlycaemic control and incidence of heart failure in 20 985 patients with type 1 diabetes: An observational studyLancet2011378978614014610.1016/S0140-6736(11)60471-6 . Wang Q, Tan K, Xia H, Gao Y. Association of pulse pressure with left ventricular geometry and function in elderly nonhypertensive patients with diabetes: A 3D speckle tracking echocardiography study. J Clin Ultrasound. 2017;45(7):416-25. doi: https://doi.org/10.1002/jcu.22484 WangQTanKXiaHGaoYAssociation of pulse pressure with left ventricular geometry and function in elderly nonhypertensive patients with diabetes: A 3D speckle tracking echocardiography studyJ Clin Ultrasound2017457416425https://doi.org/10.1002/jcu.22484 . Wang Q, Ma W, Xia J. Nonalcoholic fatty liver is associated with further left ventricular abnormalities in patients with type 2 diabetes mellitus: a 3-dimensional speckle-tracking study. J ULTRASOUND Med. 2018;37(8):1899-911. doi: https://doi.org/10.1002/jum.14536 WangQMaWXiaJNonalcoholic fatty liver is associated with further left ventricular abnormalities in patients with type 2 diabetes mellitus: a 3-dimensional speckle-tracking studyJ ULTRASOUND Med201837818991911https://doi.org/10.1002/jum.14536 . Luo HX, Zhou XL, Kou HJ, XW, Wu Q, Zou CP, et al. Improvement of continuous subcutaneous insulin infusion on patients with type 2 diabetes mellitus by 3-dimensional speckle tracking echocardiography. Int J Cardiovasc Imaging. 2018;34(3):379-84. doi: https://doi.org/10.1007/s10554-017-1245-5 LuoHXZhouXLKouHJXWWuQZouCPet alImprovement of continuous subcutaneous insulin infusion on patients with type 2 diabetes mellitus by 3-dimensional speckle tracking echocardiographyInt J Cardiovasc Imaging2018343379384https://doi.org/10.1007/s10554-017-1245-5 . Wang Q, Tan K, Xia H, Gao Y. Left ventricular structural alterations are accompanied by subclinical systolic dysfunction in type 2 diabetes mellitus patients with concomitant hyperlipidemia: An analysis based on 3D speckle tracking echocardiography. Echocardiography. 2018;35(7):965-74. doi: https://doi.org/10.1111/echo.13858 WangQTanKXiaHGaoYLeft ventricular structural alterations are accompanied by subclinical systolic dysfunction in type 2 diabetes mellitus patients with concomitant hyperlipidemia: An analysis based on 3D speckle tracking echocardiographyEchocardiography2018357965974https://doi.org/10.1111/echo.13858 . Wang Q, Tan K, Xia H, Gao Y. Left ventricular metabolic remodeling and accompanied dysfunction in type 2 diabetic patients: A 3D speckle tracking analysis. Echocardiography. 2019;36(3):486-94. doi: https://doi.org/10.1111/echo.14248 WangQTanKXiaHGaoYLeft ventricular metabolic remodeling and accompanied dysfunction in type 2 diabetic patients: A 3D speckle tracking analysisEchocardiography2019363486494https://doi.org/10.1111/echo.14248 . Chen X, Guo H, Yang Q, Fang J, Kang X. Quantitative evaluation of subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus by three-dimensional echocardiography. Int J Cardiovasc Imaging. 2020;36(7):1311-9. doi: https://doi.org/10.1007/s10554-020-01833-5 ChenXGuoHYangQFangJKangXQuantitative evaluation of subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus by three-dimensional echocardiographyInt J Cardiovasc Imaging202036713111319https://doi.org/10.1007/s10554-020-01833-5 . Wang Q, Tan K, Xia H, Gao Y. The further negative effect of hyperuricemia on left ventricular structure and function in patients with type 2 diabetes mellitus: a transthoracic 3d speckle tracking imaging study. Metab Syndr Relat Disord. 2019;17(9):436-43. doi: https://doi.org/10.1089/met.2019.0048 WangQTanKXiaHGaoYThe further negative effect of hyperuricemia on left ventricular structure and function in patients with type 2 diabetes mellitus: a transthoracic 3d speckle tracking imaging studyMetab Syndr Relat Disord2019179436443https://doi.org/10.1089/met.2019.0048 . Reant P, Barbot L, Touche C, Dijos M, Arsac F, Pillois X, et al. Evaluation of global left ventricular systolic function using three-dimensional echocardiography speckle-tracking strain parameters. J Am Soc Echocardiogr. 2012;25(1):68-79. doi: https://doi.org/10.1016/j.echo.2011.10.009 ReantPBarbotLToucheCDijosMArsacFPilloisXet alEvaluation of global left ventricular systolic function using three-dimensional echocardiography speckle-tracking strain parametersJ Am Soc Echocardiogr2012251):6879https://doi.org/10.1016/j.echo.2011.10.009 Artigo de Revisão Sistemática Papel do Strain no Diagnóstico Precoce da Cardiomiopatia Diabética SilvaThais Rossoni Weber da 1 SilvaRoberto Léo da 1 MartinsAdriana Ferraz 1 MarquesJefferson Luiz Brum 2 Departmento de Cardiologia, Hospital Universitário Prof. Polydoro Ernani de São Thiago, Florianópolis, SC, Brasil BrasilInstituto de Engenharia Biomédica, Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil . Correspondência: Thaís Rossoni Weber da Silva • Hospital Universitário Prof. Polydoro Ernani de São Thiago/ Setor de Cardiologia – Rua Professora Maria Flora Pausewang – Trindade – CEP: 88036-800 –Florianópolis, SC, Brasil. E-mail: thaisrossoni@yahoo.com

Contribuição dos autores

Concepção e desenho da pesquisa: Silva TRW, Silva RL; Obtenção de dados: Silva TRW, Silva RL; Análise e interpretação dos dados: Silva TRW, Martins AF; Análise estatística: Silva RL; Redação do manuscrito: Silva TRW, Silva RL, Martins AF; Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Silva TRW, Silva RL, Martins A, Marques JLB.

Conflito de interesses

Os autores declaram não terem conflitos de interesse.

 ResumoFundamento

A ecocardiografia avançada com utilização de strain miocárdico bi e tridimensional propõe identificar a disfunção sistólica subclínica em diversas condições clínicas. No diabetes mellitus , seu papel é de grande interesse para diagnóstico precoce de cardiomiopatia diabética. Contudo, há grande heterogeneidade nos artigos publicados.

Objetivo

Realizar uma revisão sistemática, para avaliar o papel atual da avaliação com strain nos pacientes com diabetes mellitus .

Métodos

Após revisão sistemática em cinco bancos de dados, 19 estudos que utilizaram strain bidimensional e oito estudos que utilizaram strain tridimensional foram incluídos.

Resultados

Na avaliação por strain bidimensional, a amostra totalizou 1.774 indivíduos com diabetes mellitus , com idade média de 57,1 anos e mediana de 55 anos, com equilíbrio em relação ao sexo dos participantes (47,5% do sexo feminino). Nos estudos que utilizaram strain tridimensional, foram incluídos 488 indivíduos com diabetes, com idade média de 55,7 anos e mediana de 63 anos, também com equilíbrio entre o sexo dos pacientes (51% do sexo feminino). O strain global longitudinal foi o marcador de deformação miocárdica que mais frequentemente conseguiu demonstrar diferença entre grupos com indivíduos diabéticos e controles.

Conclusão

O strain miocárdico por speckle tracking bi e tridimensional permite identificar disfunção sistólica subclínica em pacientes diabéticos, o que se torna mais marcante nos pacientes com mais fatores de risco associados e com remodelamento ventricular.

 Diabetes MellitusEcocardiografiaFunção Ventricular Introdução

O diabetes mellitus (DM) é uma das doenças mais prevalentes no mundo moderno. Consiste em um fator de risco para insuficiência cardíaca e contribui para o aumento de mortalidade, principalmente cardiovascular. 1 As complicações cardiovasculares são a principal causa de morte nos indivíduos com diabetes. 2 , 3 Dentre elas, encontra-se a cardiomiopatia diabética, que se caracteriza por alterações estruturais e funcionais cardíacas, na ausência de outros fatores conhecidos para o desenvolvimento de disfunção miocárdica, como doença coronariana, hipertensão arterial ou doenças valvares significativas. 4 O remodelamento cardíaco no diabetes resulta de mecanismos como neuropatia autonômica cardiovascular, ativação do sistema renina-angiotensina-aldosterona, fibrose miocárdica intersticial, microangiopatia, citocinas inflamatórias e alterações metabólicas, como a hiperglicemia, 5 , 6 e a detecção do remodelamento neste contexto requer métodos sensíveis de diagnóstico. 7

O diagnóstico precoce da cardiomiopatia diabética é clinicamente relevante, pois as lesões iniciais podem ser reversíveis, 8 , 9 e uma estratégia terapêutica pode ser instituída, a fim de prevenir a progressão de doenças cardiovasculares. No entanto, ainda é uma condição pouco reconhecida pelos clínicos, 1 tendo em vista os resultados conflitantes descritos na literatura, provenientes de diferentes populações estudadas, 10 assim como a necessidade de ferramentas mais sensíveis para esse diagnóstico, que foram recentemente desenvolvidas. A disfunção diastólica do ventrículo esquerdo (VE) era tida como a manifestação inicial evidenciada na ecocardiografia com o uso do Doppler. 11 , 12 Com o aperfeiçoamento dos métodos de imagem, permitiu-se detecção mais precoce de disfunção miocárdica sistólica previamente à disfunção diastólica em indivíduos assintomáticos por meio do strain por speckle tracking. 13 , 14

A incorporação de novas técnicas, como o strain miocárdico na ecocardiografia, tem por objetivo aumentar a sensibilidade diagnóstica do método, principalmente para disfunção miocárdica subclínica, validado por ressonância magnética (com tagging miocárdico) e a sonomicrometria. 15 O parâmetro mais utilizado é o strain global longitudinal (SGL), que se refere à média do strain dos segmentos miocárdicos no sentido longitudinal, mais reprodutível, capaz de identificar disfunção subclínica do VE, considerado melhor preditor de risco do que a fração de ejeção do VE (FEVE). 16 Outro conceito mais recente é a análise por multilayer que introduziu na avaliação da deformação miocárdica um aspecto anatômico, em que três camadas miocárdicas do VE (endocárdio, mesocárdio e epicárdio) em diferentes orientações contribuem para uma contração mais efetiva. 17 Já o strain miocárdico tridimensional permite avaliar de forma mais objetiva a disfunção sistólica do VE, sem necessitar de cálculos para predizer a forma geométrica ventricular, com o benefício adicional de ser mais reprodutível que o strain bidimensional, por evitar a perda de marcadores que fiquem fora do plano analisado, apesar de requerer imagens de alta qualidade. 18

Diversos estudos objetivaram a avaliação precoce da função cardíaca em indivíduos com DM usando o strain bi e tridimensional, mostrando piores índices de deformação miocárdica nos indivíduos com DM, quando comparados com controles normais. Contudo, alguns desses estudos são pequenos, heterogêneos e com inúmeros fatores de confusão. Rever as evidências atuais torna-se necessário para entender as lacunas de conhecimento e revisitar questões importantes.

O presente estudo teve como objetivo identificar se a ecocardiografia avançada com strain por speckle tracking bi ou tridimensional tem a capacidade de demonstrar lesões cardíacas precoces secundárias ao DM e seu papel atual na avaliação de indivíduos com DM. Para isso, conduziu-se uma revisão sistemática sobre a utilização das técnicas de strain ventricular por ecocardiografia no DM.

 Métodos

Este estudo é uma revisão sistemática de acordo com Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Realizou-se busca de artigos nas bases de dados MEDLINE®, Embase, Scopus e Web of Science , com os descritores “ diabetic cardiomyopathy ” ou “ speckle tracking ” ou “ myocardial strain/dysfunction ” ou “ ventricular function/dysfunction ”, “ deformation imaging/analysis ” ou “ cardiac mechanics/function ” e “ diabetes ” ou “ diabetic ”. A busca foi limitada a artigos em seres humanos, com idiomas em inglês, francês, espanhol e português, e finalizada no dia 31 de janeiro de 2022. Os critérios de seleção dos artigos foram: faixa etária acima de 15 anos, grupo controle sem DM, ausência de cardiopatia estabelecida e descrição do valor do SGL por speckle tracking . As referências das bases de dados foram reunidas no aplicativo Mendeley®, e aquelas duplicadas foram removidas. Dois pesquisadores realizaram busca dos artigos separadamente e acordaram quanto à elegibilidade da seleção final. Primeiramente, uma busca ampla reuniu artigos relacionados ao tema. Foram descartados aqueles que utilizaram uma população-alvo diferente ou sem grupo controle, presença de doença arterial coronariana ou outra doença estrutural, outro método de imagem para aferição da deformação miocárdica como ressonância magnética ou Doppler tecidual, ausência de descrição do valor do SGL, assim como relatos de caso, apresentação em congressos, revisões e editoriais, por meio da análise de título e resumo. Posteriormente, os artigos foram acessados na íntegra, confirmando aqueles que apresentavam os dados necessários e se encaixavam nos quesitos anteriores. Nos estudos com múltiplos subgrupos de pacientes ou controles, o subgrupo de menor risco foi selecionado, e os dados referentes a esse subgrupo foram descritos nas tabelas. Os estudos foram alocados em avaliação bi ou tridimensional por speckle tracking . As informações extraídas dos artigos foram: autor e ano de publicação, marca do equipamento, desenho do estudo, número de casos da amostra, idade, sexo, índice de massa corporal, níveis pressóricos ou diagnóstico de hipertensão, valor de hemoglobina glicada (HbA1c), FEVE, strain global longitudinal, radial e circunferencial. No caso dos estudos que avaliaram strain tridimensional, a área global do strain também foi incluída (Tabelas 3 e 4).

– Avaliação da função cardíaca sistólica por strain bidimensional por <italic>speckle tracking</italic> .
Autor Equipamento FEVE % (DM) FEVE % (controle) SGL (DM) SGL (controle) Valor de p (DM versus controle) SGC (DM) SGC (controle) Valor de p SGR (DM) SGR (controle) Valor de p
Yamauchi et al. 7 GE Vivid E9 66±5 66±5 -17,6±3 -20,3±2 <0,0001 - - - - - -
Weber et al. 10 GE S6 72±5 71±5 -21,7±2 -21,0±2 0,21 - - - - - -
Tadic et al. 17 GE Vivid 7 64±4 65±4 -18,8±2 -20,8±2 <0,001 -19,2±2 -21,4±3 <0,001 41,6±8 43,2±8,3 0,001
Ringle et al. 18 Philips - IE33 60±8 61±3 -18,9±2 -20,5±2 0,0002 -25,4±3 -26,1±3 0,39 36,3±9 37,6±7 0.054
Ng et al. 20 GE Vivid 7/E9 60±5 58±4 -17,3±2 -20,5±2 - - - - - - -
Yang et al. 21 GE Vivid E9 58±3 59±2 -17,2±2 -20,2±3 0,04 -20,9±4 -22,1±3 0,06 37,4±12,6 40,3±11,8 0,45
Wang et al. 22 GE Vivid E9 66±4 62±5 -19,6±2 -22,5±3 <0,0001 - - - - - -
Vukomanovic et al. 23 GE Vivid 7 64±5 63±4 -18,5±2 -21,1±3 <0,001 -18,9±2 -21,9±3 <0,001 37,2±8,1 42,1±8,6 0,007
Vukomanovic et al. 24 GE Vivid 7 64±4 64±3 -18,4±2 -21,6±3 <0,001 -19,5±2,6 -22,0±3 <0,001 37,9±9,4 40,6±10,1 0,094
Soufi Taleb Bendiab et al. 25 GE S6 61±6 62±6 -16,4±3 -17,8±3 <0,0001 - - - - - -
Todo et al. 29 GE Vivid E9 66±5 66±5 -17,6±3 -20,5±2 <0,0001 - - - - - -
Van Ryckeghem et al. 30 GE Vivid E9 66±8 66±9 -17,0±3 -19,8±2 <0,001 - - - - - -
Tadic et al. 26 GE Vivid 7 62±3 63±3 -17,7±2 -21,3±3 <0,001 -18,3±2,3 -22,1±3 <0,001 38,5±9,3 41.8±10,1 0,247
Roberts et al. 31 GE Vivid E9 60±4 60±5 –18,6±2 –19,7±2 0,09 - - - - - -
Li et al. 32 GE Vivid E9 64±4 65±4 - 19,4±3 - 21,22±3 <0,001 - - - - - -
Philouze et al. 33 GE Vivid E95 64±8 64±7 -20,8±2 -20,2±3 NS - - - - - -
Mochizuki et al. 34 GE Vivid E9 67±4 66±5 -20,5±2 -20,5±2 <0,05 - - - - - -
Jørgensen et al. 36 GE Vivid E9 65 63 -15,3±2 -15,9±2 0,13 -18,7±5 -18,1±4 0,49 - - -
Stevanovic et al. 39 GE Vivid 7 62±4 62±5 -17,5±2 -24,4±2 <0,001 - - - - - -

FEVE: fração de ejeção do ventrículo esquerdo; DM: diabetes mellitus; SGL: strain global longitudinal; SGC: strain global circunferencial; SGR: strain global radial.

– Avaliação da função cardíaca sistólica por strain tridimensional por <italic>speckle tracking</italic> .
Autor Equipamento FEVE % (DM) FEVE % (controle) SGL (DM) SGL (controle) Valor de p (DM versus controle) SGC (DM) SGC (controle) Valor de p SGR (DM) SGR (controle) Valor de p AGS (DM) AGS (controle) Valor de p
Wang et al. 41 GE Vivid E9 61±6 61±5 -17,1±2,6 -18,4±3,0 <0,05 -17,8±2,7 -18,8±3,0 >0,05 49,0±8,9 51,0±9,0 >0,05 -29,1±4,0 -30,2±3,6 >0.05
Wang et al. 44 GE Vivid E9 60±7 61±7 -17,0±2,6 -18,9±2,5 <0,01 -17,4±2,5 -18,7±2,9 <0,05 47,7±8,5 51,5±8,9 >0,05 -30.1±3,6 -30,6±4,0 >0,05
Wang et al. 42 GE Vivid E9 58±6 58±6 -17,3±2,4 -19,9±2,6 <0,001 -17,2±2,7 -18,9±0,31 <0,05 47,7±7,9 53,2±10,0 <0,01 -30,2±3,4 -31,0±4,7 >0,05
Luo et al. 43 IE33 68±2 66±3 –17,2±3,0 –20,8±2,8 <0,01 -22,9±3,0 -25,9±3,4 <0,05 - - - - - -
Wang et al., 47 GE Vivid E9 60±7 60±6 -16,9±2,9 - 18,2±2,3 <0,05 -17,6±3,5 -18.1±2,2 >0,05 46,9±9,8 48,5±6,5 >0,05 -29,6±5,5 -30,0±3,2 >0,05
Wang et al. 45 GE Vivid E9 60±7 60±7 - 17,6±2,1 -18,8±2,7 <0,05 -17,9±2,7 -18,1±3,0 >0,05 49,1±7,9 50,2±9,3 >0,05 -30,7±3.2 -31,2±4,3 >0.05
Chen et al. 46 GE Vivid E9 65±8 67±4 -19,3±3,9 -20,1±3,2 >0,05 -19,7±4,9 -19,3±6,3 >0,05 45,4±7,0 45,7±7,5 >0,05 -30,3±5,5 -33,0±6,6 >0,05
Ringle et al., 18 IE33 60±8 61±3 -17,5±2,0 -19,0±2,0 >0.05 - - - - - - - - -

FEVE: fração de ejeção do ventrículo esquerdo; DM: diabetes mellitus; SGL: strain global longitudinal; SGC: strain global circunferencial; SGR: strain global radial; AGS; área global do strain.

Resultados

Foram identificadas 819 referências em buscas em bases de dados eletrônicas nos últimos 5 anos, sendo descartadas 123 duplicatas. Dos 696 estudos restantes, foram obtidos 75 artigos na íntegra para análise após triagem de títulos e resumos. Foram excluídos adicionalmente 49 estudos, conforme Figura 1 . Restaram 26 artigos para análise qualitativa desta revisão, sendo classificados em duas categorias principais: strain bidimensional (n=١٩; Tabela 1 ) e strain tridimensional (n=8; Tabela 2 ). Somente foram incluídos estudos com grupo controle. Os artigos foram publicados majoritariamente em inglês, mas também em francês e português. Três artigos 18 - 20 realizaram acompanhamento dos pacientes (coortes prospectivas), e os demais eram estudos de caso-controle.

– Fluxograma de busca e seleção de estudos que avaliaram cardiomiopatia diabética através de strain bi e tridimensional. TDI: tissue doppler imaging; DAC: doença arterial coronariana;3D: tridimensão; 2D: bidimensão. Na síntese qualitativa, um estudo foi incluído em Strain por 2D e 3D.

– Dados clínicos e demográficos dos estudos que avaliaram cardiomiopatia diabética com strain tridimensional por <italic>speckle tracking</italic> .
Autor n Controle Tipo de DM HbA1c Controle Idade, anos (DM) Idade, anos (controle) Sexo feminino % (DM) Sexo feminino % (controle) IMC (DM) IMC (controle) PAS (DM) PAS (controle)
Yamauchi et al. 7 192 81 DM2 8,5 Saudável 61 57 48 54 25 22 131 123
Weber et al. 10 40 40 DM1 8,0 Saudável 33 33 55 55 25 25 110 102
Tadic et al. 17 48 44 DM2 7,3 Saudável 55 52 48 50 27 26 131 127
Ringle et al. 18 66 26 DM1 7,7 Saudável 38 35 71 69 24 23 122 121
Ng et al. 20 397 104 DM2 7,3 Saudável 58 50 46 43.3 29 - 141 123
Yang et al. 21 47 27 DM2 6,1 Saudável 51 50 32 33 23 23 - -
Wang et al. 22 48 50 DM2 10,1 Saudável 54 50 52 50 23 23 127 122
Vukomanovic et al. 23 50 40 DM2 7,3 Saudável 55 50 48 45 29 24 131 129
Vukomanovic et al. 24 70 80 DM2 7,5 Saudável 52 49 44 43 28 26 126 124
Soufi Taleb Bendiab et al. 25 93 107 DM2 + HAS - HAS 61 62 63 53 30 29 158 142
Tadic et al. 26 50 55 DM2 + HAS 7,0 Saudável 56 51 48 47 27 26 145 128
Todo et al. 29 177 79 DM2 8,8 Saudável 61 58 47 57 25 22 131 125
Van Ryckeghem et al. 30 36 23 DM2 6,9 Saudável 62 57 14 48 28 26 149 140
Roberts et al. 31 34 17 DM1/DM2 7,8 Saudável 42 41 29 35 27 25 125 121
Li et al. 32 101 60 DM2 7,6 Saudável 52 54 53 53.3 24 23 123 123
Philouze et al. 33 44 35 DM2 7,2 Saudável 56 52 41 51 27 24 126 123
Mochizuki et al. 34 103 82 DM 8,6 Saudável 56 55 63 60 23 22 121 117
Jørgensen et al. 36 57 80 DM2 6,1 Saudável 65 65 44 35 26 24 126 123
Stevanovic et al. 39 121 40 DM2 8,2 Saudável 55 53 19 29 28 27 125 122

DM: diabetes mellitus; HbA1c: hemoglobina glicada; IMC: índice de massa corporal; PAS: pressão arterial sistólica; DM1: diabetes mellitus tipo 1; DM2: diabetes mellitus tipo 2; HAS: hipertensão arterial sistêmica.

– Dados clínicos e demográficos dos estudos que avaliaram cardiomiopatia diabética com strain bidimensional por <italic>speckle tracking</italic> .
Autor n Controle DM HbA1c (%) Controle Idade, anos (DM) Idade, anos (controle) Sexo Feminino % (DM) Sexo Feminino % (controle) IMC (DM) IMC (Controle) PAS (DM) PAS (Controle)
Wang et al. 41 40 40 DM2 - Saudável 66±7 68±8 50 50 24,6±2 23,5±3 128±7 123±9
Wang et al. 44 40 40 DM2 6,6±0,6 Saudável 68±8 68±7 50 55 24,9±3 24,4±3 128±9 126±10
Wang et al. 42 38 45 DM2 7,0±0,6 Saudável 61±8 62±7 45 50 24,5±3 24,7±2 127±10 126±7
Luo et al. 43 38 35 DM2 10,4±2,6 Saudável 59±7 58±76 32 32 24,9±2 24,3±2 128±9 107±6
Wang et al. 47 40 40 DM2 - Saudável 66±8 67±8 50 50 24,7±2 25,0±3 128±6 126±7
Wang et al. 45 34 40 DM2 - Saudável 65±7 64±8 50 50 24,0±2 24,5±3 125±8 125±7
Chen et al. 46 192 81 DM2 6,1±0,4 Saudável 52 ± 8 50±6 50 49 25,1 ± 2 24,3 ± 2 122 ±11 119 ±10
Ringle et al., 18 66 26 DM1 7,7±1,3 Saudável 37±9 35±7 71 69 24,0±3 23,0±3 121±12 122±9

DM: diabetes mellitus; HbA1c: hemoglobina glicada; IMC: índice de massa corporal; PAS: pressão arterial sistólica; DM1: diabetes mellitus tipo 1; DM2: diabetes mellitus tipo 2.

Ao todo, uma população de 1.774 diabéticos foi incluída nos estudos que utilizaram a técnica speckle tracking para avaliação do strain bidimensional, com idade média de 57,1 anos e mediana de 55 anos, com equilíbrio em relação ao sexo dos participantes (47,5% do sexo feminino). O equipamento mais utilizado nestes estudos foi o GE Vivid E9.

Nos estudos que utilizaram strain tridimensional, foram incluídos 488 pacientes com diabetes, com idade média de 55,7 anos e mediana de 63 anos, também com equilíbrio entre o sexo dos pacientes (51% sexo feminino). Quase a totalidade dos estudos foi realizada com o aparelho GE Vivid E9, com somente dois estudos utilizando o aparelho Philips IE33.

Dos 19 estudos analisados, menos da metade excluiu hipertensos do grupo com diabetes 10 , 18 , 21 - 24 – a maior parte envolvendo indivíduos com DM2 – , e apenas três estudos estudaram indivíduos com DM1. Em um estudo, 25 o grupo controle era constituído de hipertensos sem diabetes. Alguns estudos avaliaram grupos de diabéticos com e sem hipertensão, grupos de diabéticos com e sem complicação microvascular associada, ou ainda subgrupos em que se quantificaram os fatores de risco não controlados. Outro estudo apresentou população diabética previamente à hospitalização com níveis glicêmicos alterados (HbA1c >10%). 22

Diferentes avaliações também foram estudadas nessa população, como: índice de trabalho miocárdico, 26 , 27 torsão miocárdica por speckle tracking , 28 disfunção sistólica do ventrículo direito por speckle tracking , 29 função cardíaca durante atividade física e capacidade ao exercício, 24 , 30 , 31 valor de dispersão entre picos sistólicos do strain , 32 efeito da frequência cardíaca, 7 função cardíaca durante ecocardiografia por estresse com dobutamina, 33 variabilidade da frequência cardíaca, 23 progressão da disfunção diastólica 34 e análise multilayer por speckle tracking. 17 , 23

As características ecocardiográficas de interesse para esta revisão estão apresentadas nas tabelas 3 e 4.

 Discussão

O uso de novas técnicas de imagem para diagnóstico de cardiomiopatia diabética tem propiciado a construção de um maior conhecimento, pela identificação de lesões mais precoces. Apesar de tradicionalmente se acreditar que a disfunção diastólica do VE precede a disfunção sistólica, sugere-se que a disfunção sistólica subclínica detectada pelo strain global longitudinal pode ser o primeiro sinal de cardiomiopatia diabética. 14

O strain global longitudinal foi o marcador de deformação miocárdica que mais frequentemente conseguiu demonstrar diferença entre grupos com indivíduos diabéticos e controles nos estudos aqui listados. Alguns estudos estabeleceram um determinado valor de SGL para diagnóstico de disfunção ventricular subclínica, baseado em análise estatística dos próprios valores obtidos na amostra. Nesses estudos, a incidência de disfunção ventricular subclínica variou de 40 a 45% na população diabética. 20 , 35

Um menor número de estudos que utilizou outros parâmetros, como o strain global circunferencial (SGC) 17 , 23 , 24 , 26 e o strain global radial (SGR), 23 conseguiu identificar diferenças na função miocárdica por meio do strain bidimensional. Essas diferenças não foram detectadas pela FEVE. No estudo de Tadic et al., 17 houve diferença no strain radial global apenas no grupo de diabéticos e hipertensos. Da mesma forma, Jorgensen et al. relataram diferença no SGC nos subgrupos de diabéticos com mais fatores de risco. 36

Outra ferramenta disponível, a análise multilayer por speckle tracking , demonstrou diferenças entre grupos de diabéticos e de controle. 17 , 23 , 24 , 37 Apesar de ser uma nova tecnologia e ainda requerer mais estudos, pretendem-se localizar a lesão no miocárdio e detectar precocemente possíveis alterações. 38 Em estudo envolvendo controles saudáveis, Tadic et al. revelaram indivíduos com DM2 e/ou hipertensão arterial sistêmica (HAS) os seguintes achados: alteração multidirecional no strain ; hipertensão como fator para deterioração da mecânica do VE; acometimento de todas as camadas miocárdicas pelo DM e HAS; e, por fim, correlação entre controle glicêmico (glicemia de jejum e HbA1c) com SGL e strain layer-specific do VE.

Nos últimos 5 anos, apenas três estudos realizaram acompanhamento dos participantes. Naqueles envolvendo indivíduos com DM2, uma amostra maior de participantes foi obtida. Stevanovic et al. e Ng et al. acompanharam mais de cem indivíduos e demostraram que o SGL foi um forte preditor de eventos cardiovasculares em análise multivariada. 20 , 39 Ringle et al. avaliaram um grupo de indivíduos com DM1, com idade em torno de 37 anos, sem fatores de risco cardiovasculares, que apresentaram valor absoluto de strain inferior à população controle e, no acompanhamento, houve redução significativa do valor absoluto do strain , no entanto, não se observaram eventos no período de acompanhamento. Neste estudo, não houve correlação entre SGL e o status metabólico, seja controle glicêmico, duração do diabetes ou coexistência de complicações microvasculares. 18

Dos 19 artigos analisados, em apenas quatro estudos 10 , 31 , 33 , 36 não foi possível identificar diferença no valor do SGL e demonstrar redução da função miocárdica atribuível ao diabetes de maneira subclínica. Esses estudos envolveram indivíduos com DM1 e/ou DM2, porém claramente com menos fatores de risco que, quando presentes, estavam controlados, como HAS, sobrepeso e obesidade, dislipidemia, função renal aferida por clearance de creatinina, níveis glicêmicos menores (HbA١c <8%), além de não apresentar diferença ou esta ser menor nos parâmetros estruturais do VE, como índice de massa ventricular e espessura relativa de parede. Essa informação torna-se útil, pois pode revelar um melhor prognóstico a esses pacientes e incentivar o bom controle de comorbidades.

Vários autores estudaram possíveis contribuintes para a piora da função sistólica nos indivíduos diabéticos. Yang et al. estudaram a relação entre complicações microvasculares e função sistólica do VE e observaram redução do SGL no grupo sem complicações e ainda maior no grupo com complicações microvasculares. 21 Soufi et al. demonstraram, em um estudo com indivíduos hipertensos, com e sem diabetes, que a associação HAS e DM reduz ainda mais a função sistólica ventricular, quando avaliada por strain , e as duas variáveis independentes para o declínio do valor absoluto de SGL foram DM2 e a espessura relativa da parede posterior. 25 Jørgensen et al. desenharam um estudo para avaliar a influência dos fatores de risco em pacientes diabéticos e relataram associação entre pressão arterial sistólica, índice de massa corporal, HbA1c com estrutura e função do VE. Dessa forma, ao se analisarem os estudos que avaliam cardiomiopatia diabética, devem-se pesar os fatores de risco, buscando evitar fatores de confusão. Independentemente, entende-se que essa população apresenta alta prevalência de comorbidades, e o mau controle metabólico pode interferir na função cardíaca.

Em relação especificamente ao controle glicêmico, Lind et al., em estudo com 20.985 indivíduos com DM1, concluíram que, mesmo após o ajuste de outros fatores de risco cardiovascular, o risco de insuficiência cardíaca ainda foi quatro vezes maior em pacientes com mau controle glicêmico comparados aos com ótimo controle glicêmico, e cada 1% de aumento na HbA1c correspondeu a um aumento de 30% no risco de desenvolver insuficiência cardíaca. 40 Li et al. exploraram a relação entre controle glicêmico e disfunção ventricular esquerda em indivíduos com DM2 por meio do valor de HbA1c; 32 não houve diferença na FEVE, entretanto, havia diferença entre o índice de massa ventricular e a velocidade de onda E mitral entre os grupos com DM versus controle, sendo maior a diferença no grupo com pior controle glicêmico. Além disso, não se observou diferença do SGL entre o grupo com bom controle glicêmico e o grupo controle. Nesse estudo, houve correlação entre HbA1c, índice de massa ventricular e relação E/e’ com o SGL. No estudo realizado por Wang et al., 22 houve diferença no valor do SGL entre os grupos, no entanto, já com diferença na FEVE. Destaca-se, nesse estudo, o mau controle glicêmico do grupo DM2, previamente à hospitalização, com valor de HbA1c em torno de 10%. A evidência contrária também se apresenta nos trabalhos que não demonstraram diferença entre grupo diabético e controle, com populações com melhor controle dos fatores de risco. 10 , 18 , 31 , 36 A avaliação por speckle tracking tridimensional identificou menor valor absoluto de SGL em indivíduos com diabetes em relação aos controles. 18 , 41 - 46 Dependendo do fator de risco associado, outros parâmetros também demonstraram diferenças, como o SGC 42 - 46 e SGR. 42 , 47 Chen et al. concluíram que o strain por speckle tracking tridimensional permite detectar disfunção ventricular esquerda em indivíduos diabéticos com mau controle glicêmico e a disfunção miocárdica está associada à duração do DM e à HbA1c. 46 Wang et al. demonstraram que glicemia de jejum, dislipidemia e índice de massa corporal foram fatores de risco significativos para o remodelamento ventricular esquerdo em indivíduos com DM2; naqueles com geometria ventricular normal, houve apenas diferença no SGL em relação aos controles, enquanto nos indivíduos com remodelamento ventricular esquerdo, houve diferença com menor valor absoluto de SGL, SGC, SAG e SGR nos diabéticos. 44 A esteatose hepática é outra condição com alta prevalência no DM2 e também foi associada ao remodelamento ventricular esquerdo e à disfunção ventricular subclínica, sendo que, dentre os parâmetros da avaliação tridimensional por strain , o SGL apresentou alteração mais evidente. 42 Por fim, observou-se que o tratamento intensivo com bomba de insulina melhorou a função sistólica ventricular esquerda, demonstrando ser uma técnica diagnóstica sensível e acurada, que poderia inclusive fornecer dados sobre efeito terapêutico. 43

Como previamente relatado, 18 , 48 a aquisição da imagem e a análise da deformação miocárdica pelo speckle tracking tridimensional foram mais rápidas em relação ao speckle tracking bidimensional; no entanto, imagens de alta qualidade são necessárias para análise acurada do strain.

 Conclusão

O strain miocárdico por speckle tracking bi e tridimensional permite identificar disfunção sistólica subclínica em pacientes diabéticos, o que se torna mais marcante nos pacientes com mais fatores de risco associados e com remodelamento ventricular. A introdução de ferramentas como layer-specific ao método possibilita um entendimento mais amplo do acometimento miocárdico no diabetes mellitus . Apesar de poucos estudos prospectivos para avaliação de desfechos clínicos, encontra-se evidência de associação do strain global longitudinal com eventos cardiovasculares nos indivíduos com diabetes.