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Article

Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study

by
Paolo Basile
1,†,
Andrea Igoren Guaricci
1,*,†,
Giuseppina Piazzolla
2,
Sara Volpe
2,
Alfredo Vozza
2,
Marina Benedetto
3,
Maria Cristina Carella
1,
Daniela Santoro
1,
Francesco Monitillo
1,
Andrea Baggiano
4,
Saima Mushtaq
4,
Laura Fusini
4,
Fabio Fazzari
4,
Cinzia Forleo
1,
Nunziata Ribecco
3,
Gianluca Pontone
4,
Carlo Sabbà
2 and
Marco Matteo Ciccone
1
1
University Cardiology Unit, Interdisciplinary Department of Medicine, Policlinic University Hospital, 70121 Bari, Italy
2
Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy
3
Department of Economics and Finance, University of Bari—Aldo Moro, 70121 Bari, Italy
4
Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Clin. Med. 2023, 12(4), 1586; https://doi.org/10.3390/jcm12041586
Submission received: 22 January 2023 / Revised: 8 February 2023 / Accepted: 14 February 2023 / Published: 16 February 2023
(This article belongs to the Special Issue Cardiomyopathy: Clinical Diagnosis and Treatment)
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Review Reports Versions Notes

Abstract

:
(1) Background: Glucagone-Like Peptide-1 Receptor Agonists (GLP-1 RAs) (GLP-1 RAs) are incretine-based medications recommended in the treatment of type 2 Diabetes Mellitus (DM2) with atherosclerotic cardiovascular disease (ASCVD) or high or very high cardiovascular (CV) risk. However, knowledge of the direct mechanism of GLP-1 RAs on cardiac function is modest and not yet fully elucidated. Left ventricular (LV) Global Longitudinal Strain (GLS) with Speckle Tracking Echocardiography (STE) represents an innovative technique for the evaluation of myocardial contractility. (2) Methods: an observational, perspective, monocentric study was conducted in a cohort of 22 consecutive patients with DM2 and ASCVD or high/very high CV risk, enrolled between December 2019 and March 2020 and treated with GLP-1 RAs dulaglutide or semaglutide. The echocardiographic parameters of diastolic and systolic function were recorded at baseline and after six months of treatment. (3) Results: the mean age of the sample was 65 ± 10 years with a prevalence of the male sex (64%). A significant improvement in the LV GLS (mean difference: −1.4 ± 1.1%; p value < 0.001) was observed after six months of treatment with GLP-1 RAs dulaglutide or semaglutide. No relevant changes were seen in the other echocardiographic parameters. (4) Conclusions: six months of treatment with GLP-1 RAs dulaglutide or semaglutide leads to an improvement in the LV GLS in subjects with DM2 with and high/very high risk for ASCVD or with ASCVD. Further studies on larger populations and with a longer follow-up are warranted to confirm these preliminary results.

1. Introduction

According to the International Diabetes Federation (IDF), diabetic individuals comprise almost 9% of the entire world’s population [1]. Moreover, this percentage tends to increase over time in parallel with the average survival of the population. Over the past two decades, Diabetes Mellitus (DM) has been considered a “coronary risk equivalent” on the basis of diagnostic and prognostic studies [2,3,4,5,6,7,8]. With these assumptions, DM has been the target of maximal therapy aimed at lowering glycaemia and, at the same time, reducing cardiovascular complications.
Glucagone-Like Peptide-1 Receptor Agonists (GLP-1 RAs) (GLP-1RAs) are incretine-based glucose-lowering medications widely used in the treatment of Diabetes Mellitus type 2 (DM2) [9,10]. Beyond the effectiveness on the glycaemic control, these antidiabetic drugs demonstrated a reduction in major adverse cardiovascular events (MACE) in DM2 patients, such that recent European Society of Cardiology (ESC) guidelines strongly recommend their use [11,12,13,14,15,16,17,18]. In fact, GLP-1 RAs have demonstrated pleiotropic effects, reducing oxidative stress and inflammation, reversing cardiac remodelling and preserving renal function [19]. However, the understanding of the effects of GLP-1 RAs on the structures and function of the heart, mainly based on liraglutide and exenatide studies, is not yet fully elucidated [20]. The current analysis sought to explore the effect of GLP-1 RAs semaglutide and dulaglutide on myocardial contractility using the left ventricular (LV) Global Longitudinal Strain (GLS) Speckle Tracking Echocardiography (STE) technique. Left ventricle GLS-STE is an emerging diagnostic method for the evaluation of myocardial function [21,22]. It represents a very sensitive marker of myocardial function impairment, preceding the development of clinically relevant systolic dysfunction. Thus, its prompt recognition may allow for the prescription of treatment without delay, preventing severe cardiac complications [23].

2. Materials and Methods

2.1. Study Design

We conducted an observational, perspective, monocentric study in consecutive patients with DM2 to assess the effects of GLP1-RAs semaglutide and dulaglutide on cardiac function. The Inclusion criteria were: a diagnosis of DM2 and high or very high risk for cardiovascular (CV) disease or with an evident atherosclerotic cardiovascular disease (ASCVD); age ≥ 18 years; GLP-1 RAs naïve. The exclusion criteria were: contraindication for the prescription of GLP-1 Ras; previous treatment with anti-diabetic drugs or treatment with stable doses of metformin for at least 3 months; permanent atrial fibrillation or rhythm disorders; the presence of prosthetic valves; cancer cachexia; pregnancy and/or breastfeeding. Written informed consent was obtained from each participant before enrolment. The study was approved by the local ethics committee and conducted according to the principles of the revised Declaration of Helsinki.

2.2. Screening Protocol and Data Acquisition

A preliminary screening visit was performed at the Diabetology Clinic of the Internal Medicine Unit of our tertiary hospital to assess the eligibility of patients, according to the criteria previously provided, and to obtain the informed consent. The demographic and anthropometric data (age, sex, body mass index, body surface area, systolic and diastolic blood pressure, heart rate), the presence of CV risk factors (hypertension, dyslipidaemias, smoke habit, obesity, familiar history of CV disease), drugs assumption, comorbidity and laboratory data (renal function and serum electrolytes, hepatic function, plasma fasting glucose and glycated haemoglobin) were collected in a paper case report form. Then, the data were recorded in an electronic spreadsheet by two investigators. After the enrolment, subcutaneous dulaglutide (1.5 mg or 0.75 mg weekly) or semaglutide (0.5 or 1.0 mg weekly) was prescribed.

2.3. Echocardiographic Evaluation

Each patient underwent echocardiographic exams at baseline, before the initiation of GLP-1 RA, and in the follow-up, after 6 months of treatment. The echocardiographic examination was performed in a dedicated echocardiographic laboratory in the outpatient Cardiologic Clinic of the same hospital, using Canon Aplio i700 (Canon Medical System, Zoetermeer, The Netherlands) by a cardiologist trained in echocardiographic imaging (with at least 15 years of experience) and according to the recommendations stated by the American Society of Ecocardiography (ASE) and the European Society of Cardiovascular Imaging (EACVI) [24]. Before the echocardiographic evaluation, each patient was placed in the supine position for 5 min in a quiet room. Subsequently, we measured the brachial blood pressure and heart rate in the right arm with an automated digital oscillometric sphygmomanometer (A&D Medical Ltd, Tokyo, Japan). The values obtained are those included in the study and used for statistical analysis. The 2D-guided linear measurements were taken from a parasternal long axis (LV septum diameter, end-diastole LV diameter, LV posterior wall diameter, anteroposterior diameter of the left atrium) and short axis view (right ventricular outflow tract diameter) [25]. The LV mass was calculated by the linear method using the cube formula. From the apical four chamber view, the LV end diastolic volume, LV end systolic volume, left atrium volume, TAPSE (Tricuspid Annular Plane Systolic Excursion) and right ventricular inflow diameter were obtained. The left ventricular ejection fraction (LVEF) was obtained from the LV end-diastolic and end-systolic volumes using the biplane disk summation method. The right ventricular systolic function was also evaluated by the fractional area change (FAC), using the end-diastolic and end-systolic area of the right ventricle. A pulsed wave (PW) doppler at the mitral inflow and Tissue Doppler Imaging (TDI) at the mitral annular septal and lateral level in the four-chamber view were performed, then the E/A and the E/E’ ratios were calculated to assess the diastolic function of the left ventricle. A continuous wave (CW) doppler was used to assess the tricuspid regurgitation jet velocity in order to estimate the Systolic Pulmonary Artery Pressure (SPAP). Colour flow evaluation was used to define, in a semiquantitative way, the presence of valvular disease. The evaluation of the diameter of the inferior vena cava and collapse was performed in the subcostal view. The LV GLS-STE was calculated by a dedicated software from the apical four, two and three chamber view using an automated tracking algorithm to outline the myocardial borders throughout the cardiac cycle. If necessary, manual adjustments were performed to ensure the correct tracing of the endocardial border (Figure 1). A value around −20% was considered as a cut off for normality [24].

2.4. Study Endpoints

The endpoint of the study was to assess cardiac functional changes by echocardiography and, in particular, by GLS-STE, comparing the data at the baseline evaluation with the 6-month follow-up. Due to the explorative purpose of the study and the absence of previous data regarding the effects of dulaglutide and semaglutide on the endpoints analysed, a sample size determination was not performed.

2.5. Statistical Analysis

All of the statistical analyses were performed using the Statistical Package for Social Sciences version 25 (SPSS, Inc., Chicago, IL, USA). Continuous variables were expressed as mean and standard deviation (SD) or median and interquartile range (IQR), when appropriate. The normal distribution of each variable was evaluated with the Kolmogorov-Smirnov test with Lilliefors correction. Differences in the values of the explanatory variables were compared by a t-test for paired samples in cases of normally distributed data. For non-normal distributed variables, a Wilcoxon signed-rank test was used. Categorical variables were expressed as percentage values and compared by a X2 test or Fisher exact test, when appropriate. Furthermore, the association of the relevant baseline clinical variables with the mean difference of LV GLS after 6 months of GLP-1RAs treatment was explored. For continuous baseline variables, the Pearson’s or Spearman’s correlation coefficient was used, when appropriate. Baseline categorical variables were explored by point-biserial correlation A p value < 0.05 was set for statistical significance.

3. Results

Between December 2019 and March 2020, 22 patients were enrolled for a mean follow-up of 150 ± 41 days. The baseline characteristics of the study population are listed in Table 1. The mean age of the sample was 65 ± 10 years, with a small prevalence of male sex (64%). All of the patients were at high or very high risk of ASCVD, due to the presence of several CV risk factors, in addition to DM2. Indeed, the vast majority of the patients had arterial hypertension (100%), dyslipidaemia (95%), family history of CV disease (91%), obesity (86%) and a smoking habit (68%). Furthermore, two patients were affected by coronary artery disease (CAD), with a previous myocardial infarction (MI), leading to a moderate LV systolic dysfunction in one of them. Comorbidities are not rare in this setting of patients and were present in almost all of the patients (95%). Some of the patients were already taking oral antidiabetic drugs such as metformin, while none of them were taking insulin. The echocardiographic data are summarized in Table 2. A mild LV concentric hypertrophy was highly represented [median interventricular septum was 12 (IQR 1) mm and mean LV mass 154 ± 22 g]. The median LVEF was 59% (IQR 7), suggesting that systolic dysfunction was rare. The right heart was within the normal range in all of the patients, whilst the diastolic function was mildly impaired [median E/A 0.75 (IQR 0.28) and mean E/E’ 7 ± 2]. No one had valvular diseases, except for minimum/mild tricuspid and mitral regurgitation. The mean LV GLS was slightly under the normal range (−18.0 ± 1.8%). The association between the baseline clinical data and the LV GLS variations from baseline to the 6-month follow-up was explored, and the results are listed in Table 3. No significant interactions emerged from the analysis. After six months of treatment with semaglutide or dulaglutide, we observed a clinical and statistically significant (mean difference −1.4 ± 1.1%; p < 0.001) improvement in the LV GLS, with a mean value tending towards the normal range (19.5 ± 2.1%) (Figure 2). No relevant changes were seen in the other echocardiographic parameters, with the absence of considerable drug side effects during the follow-up period.

4. Discussion

To the best of our knowledge, this is the first clinical study that has sought to evaluate the effect of GLP-1RAs semaglutide and dulaglutide on cardiac function by employing echocardiography and, in particular, STE in a cohort of consecutive DM2 patients with ASCVD or high or very high CV risk. The main results of the current analysis are that myocardial contraction, as assessed by GLS-STE, significantly improved after six months of GLP-1RAs semaglutide and dulaglutide therapy.
Several CVOTs pointed out the cardioprotective role of these drugs [10,13,15,16,17]. The SUSTAIN-6, a preapproval safety CVOT, demonstrated a reduction in the rate of death from CV causes, non-fatal myocardial infarction and non-fatal stroke with semaglutide compared to the placebo after two years of follow-up [16]. In addition, the REWIND trial, which tested dulaglutide and the LEADER trial with liraglutide, showed a reduction in the MACE compared to the placebo [15,17]. According to this, the ESC guidelines recommend liraglutide, semaglutide or dulaglutide (class of recommendation I level of evidence A) in patients with DM2 and very high/high CV risk [18]. However, the exact cardioprotective mechanisms of GLP-1RAs still need to be clarified.
Although there is a lack of a universally accepted definition, diabetic cardiomyopathy (DCM) is defined as the presence of ventricular dysfunction in absence of hypertension, CAD, congenital or valvular heart disease and may evolve towards overt heart failure [26,27,28]. Diastolic dysfunction with a preserved LVEF is considered the first marker of DCM [29]; however, some studies have observed that it is preceded by an earliest reduction in LV GLS [30,31,32]. This subclinical LV dysfunction observed in asymptomatic DM2 patients is common and associated with a long-term worse outcome, with a high rate of mortality and hospitalization [23]. The development of these subtle alterations in the LV function, however, is multifactorial. One suggested mechanism consists of insulin resistance as a cause of impaired cardiac metabolic flexibility. The reduced uptake of glucose from the cardiomyocytes may lead to a substrate shift towards increased fatty acids oxidation, causing lipotoxicity, and, therefore, reduced cardiac efficiency, as well as an increase in myocardial oxygen consumption and the production of ROS (Reactive Oxygen Species). Furthermore, hyperglycaemia itself may promote the development of AGEs (Advanced Glycated End-Products) stimulating collagen expression and accumulation, leading to myocardial fibrosis with an increase in myocardial stiffness and reduced cardiac compliance [28,33,34,35]. High glucose levels also cause Ca2+ mishandling and mitochondrial dysfunction, which may play a crucial role in the earliest stages of DCM [36,37].
Several preclinical studies on animal models and clinical studies have demonstrated that GLP-1 and its analogues exert several beneficial actions on the cardiovascular system [14,38,39,40,41,42,43,44]. On cardiomyocytes, these are mainly indirect and manifest through better glycaemic control, weight loss and blood pressure lowering [14,45,46,47]. However, GLP-1 receptors are highly expressed in atrial and vascular cells; therefore, GLP-1 Ras could exert, at least partialy, a direct action on the cardiac tissue [45,48]. The reduction in insulin resistance induced by GLP1-RAs may restore cardiac metabolic flexibility through the improvement of the insulin receptor, increasing glucose uptake and utilization [45,49]. After the infusion of GLP-1, Sokol et al. highlighted an improvement in the systolic function and functional status of patients with chronic heart failure [40]. On ischemic myocardium, GLP-1 RAs may prevent cardiomyocyte apoptosis and improve cardiac function via the AMPK/phosphoinositide 3-kinase (PI3K)–protein kinase B (Akt) pathway [50]. This antiapoptotic effect may explain the reduction in the infarct size and myocardial stunning in an in vivo rabbit model of myocardial ischemia/reperfusion with a single dose of parenteral fusion protein GLP-1-Tf (transferrin) [51]. These results suggest that GLP1-RAs may play a pivotal role in preventing the development of DCM, particularly in those with an early subclinical LV dysfunction.
GLS-STE represents an innovative technique for the evaluation of myocardial function [21,22]. Numerous studies have shown its incremental diagnostic and prognostic value in multiple cardiovascular conditions, such as ischaemic heart disease [52] and cardiomyopathies [53]. Indeed, despite the normal values of LVEF, the evidence of the early impairment of LV GLS reveals a subclinical systolic dysfunction that may evolve towards clinically relevant systolic impairment and cardiac complications [23,54]. Previously, different echocardiographic techniques, including GLS-STE, were used for assessing the cardiac modifications derived by GLP1-RAs introduction. In fact, Lambadiari et al. found a modest increase in LV GLS after six months of therapy with liraglutide compared to metformin in subjects with newly diagnosed DM2 [55]. Our findings are in line with these preliminary results. However, as expected, the literature presents incongruent data on the topic. Bizino et al. pointed out, with the employment of cardiac magnetic resonance (CMR) in DM2 patients treated with liraglutide, a reduction in the LV filling pressure with a non-significant reduction in the systolic function after 26 weeks of treatment [56], and the same results were obtained by Yari et al. [57] The meta-analysis by Zhang et al. in a larger sample of 4790 subjects, highlights an increase in LVEF and a reduction in LVESV and E/e’ with GLP1-RAs compared to the placebo [20]. In the present study. we did not confirm these results because the LVEF remained nearly unchanged in the follow-up evaluation. Diastolic dysfunction with a preserved LVEF was considered another early sign of subclinical myocardial damage in diabetic patients [58]. Bizino et al. demonstrated in DM2 patients, with the use of CMR, that liraglutide reduces early LV diastolic filling and LV filling pressure, unloading the left ventricle, in a treatment interval of 26 weeks. Subsequently, these results were confirmed in a meta-analysis by Zhang et al., which highlighted a reduction in E/e’ after therapy [20]. Despite the fact that the positive effect on the diastolic function may be related to a direct improvement of GLP-1RAs treatment on LV cardiac remodelling, drug-induced weight loss may play a relevant role as an indirect mechanism [58]. Unexpectedly, in the present analysis, we did not find a relevant variation in the diastolic parameters; this was likely due to the small sample size.
In general, because of the heterogeneity of the study designs and the different pharmacological properties, any head-to-head comparison between different GLP-1 RA analogues should be interpreted cautiously. Therefore, further studies in larger populations and with a longer follow-up duration are needed to better elucidate the effect of these drugs on cardiac function.

Study Limitations

This study has some limitations. First, the reduced sample size led to weak statistical power. The identification of a difference between the baseline and after six months LV GLS requires further studies with a larger sample size to confirm these results. The second limitation is the absence of a control group and the lack of blinding, which may have led to bias in the evaluation of the echocardiographic parameters during the follow-up.

5. Conclusions

In the present study, we observed that six months of treatment with GLP-1 RAs dulaglutide or semaglutide leads to an improvement of LV GLS in subjects with DM2 with a high or very high risk for ASCVD or with ASCVD. Accordingly, these antidiabetic drugs should be preferred in this setting of subjects in order to prevent the development of DCM. Further studies on larger populations and with a longer duration of follow-up are warranted to confirm these preliminary results.

Author Contributions

Conceptualization, A.I.G., M.C.C. and P.B.; methodology, C.F., N.R. and G.P. (Giuseppina Piazzolla); software, M.B. and N.R.; validation, C.S., N.R. and M.M.C.; formal analysis, M.B., M.C.C. and N.R.; investigation, G.P. (Giuseppina Piazzolla), S.V. and A.V.; resources, G.P. (Gianluca Pontone), S.V. and A.V.; data curation, D.S. and F.M.; writing—original draft preparation, A.B., S.M., L.F. and F.F.; writing—review and editing, G.P. (Gianluca Pontone), A.I.G. and P.B.; visualization, N.R. and G.P. (Gianluca Pontone); supervision, C.F., A.I.G. and M.M.C.; project administration, C.S. and A.I.G.; funding acquisition, not applicable. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Chen, L.; Islam, R.M.; Wang, J.; Hird, T.R.; Pavkov, M.E.; Gregg, E.W.; Salim, A.; Tabesh, M.; Koye, D.N.; Harding, J.L.; et al. A systematic review of trends in all-cause mortality among people with diabetes. Diabetologia 2020, 63, 1718–1735. [Google Scholar] [CrossRef] [PubMed]
  2. Schramm, T.K.; Gislason, G.H.; Køber, L.; Rasmussen, S.; Rasmussen, J.N.; Abildstrøm, S.Z.; Hansen, M.L.; Folke, F.; Buch, P.; Madsen, M.; et al. Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: A population study of 3.3 million people. Circulation 2008, 117, 1945–1954. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Budoff, M.J.; Raggi, P.; Beller, G.A.; Berman, D.S.; Druz, R.S.; Malik, S.; Rigolin, V.H.; Weigold, W.G.; Soman, P. Noninvasive Cardiovascular Risk Assessment of the Asymptomatic Diabetic Patient: The Imaging Council of the American College of Cardiology. JACC Cardiovasc. Imaging 2016, 9, 176–192. [Google Scholar] [CrossRef] [PubMed]
  4. Haffner, S.M.; Lehto, S.; Rönnemaa, T.; Pyörälä, K.; Laakso, M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N. Engl. J. Med. 1998, 339, 229–234. [Google Scholar] [CrossRef] [PubMed]
  5. Maffei, E.; Seitun, S.; Nieman, K.; Martini, C.; Guaricci, A.I.; Tedeschi, C.; Weustink, A.C.; Mollet, N.R.; Berti, E.; Grilli, R.; et al. Assessment of coronary artery disease and calcified coronary plaque burden by computed tomography in patients with and without diabetes mellitus. Eur. Radiol. 2011, 21, 944–953. [Google Scholar] [CrossRef] [Green Version]
  6. Guaricci, A.I.; Lorenzoni, V.; Guglielmo, M.; Mushtaq, S.; Muscogiuri, G.; Cademartiri, F.; Rabbat, M.; Andreini, D.; Serviddio, G.; Gaibazzi, N.; et al. Prognostic relevance of subclinical coronary and carotid atherosclerosis in a diabetic and nondiabetic asymptomatic population. Clin. Cardiol. 2018, 41, 769–777. [Google Scholar] [CrossRef] [Green Version]
  7. Guaricci, A.I.; Pontone, G.; Fusini, L.; De Luca, M.; Cafarelli, F.P.; Guglielmo, M.; Baggiano, A.; Beltrama, V.; Muscogiuri, G.; Mushtaq, S.; et al. Additional value of inflammatory biomarkers and carotid artery disease in prediction of significant coronary artery disease as assessed by coronary computed tomography angiography. Eur. Heart J. Cardiovasc. Imaging 2017, 18, 1049–1056. [Google Scholar] [CrossRef]
  8. Esposito, A.; Francone, M.; Andreini, D.; Buffa, V.; Cademartiri, F.; Carbone, I.; Clemente, A.; Guaricci, A.I.; Guglielmo, M.; Indolfi, C.; et al. SIRM-SIC appropriateness criteria for the use of Cardiac Computed Tomography. Part 1: Congenital heart diseases, primary prevention, risk assessment before surgery, suspected CAD in symptomatic patients, plaque and epicardial adipose tissue characterization, and functional assessment of stenosis. Radiol. Med. 2021, 126, 1236–1248. [Google Scholar] [CrossRef]
  9. Htike, Z.Z.; Zaccardi, F.; Papamargaritis, D.; Webb, D.R.; Khunti, K.; Davies, M.J. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. Diabetes Obes. Metab. 2017, 19, 524–536. [Google Scholar] [CrossRef] [Green Version]
  10. Kim, G.S.; Park, J.H.; Won, J.C. The Role of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Reducing Cardiovascular Events in Patients with Type 2 Diabetes. Endocrinol. Metab. 2019, 34, 106–116. [Google Scholar] [CrossRef]
  11. Brunton, S.A.; Wysham, C.H. GLP-1 receptor agonists in the treatment of type 2 diabetes: Role and clinical experience to date. Postgrad. Med. 2020, 132, 3–14. [Google Scholar] [CrossRef]
  12. Zelniker, T.A.; Wiviott, S.D.; Raz, I.; Im, K.; Goodrich, E.L.; Furtado, R.H.M.; Bonaca, M.P.; Mosenzon, O.; Kato, E.T.; Cahn, A.; et al. Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus. Circulation 2019, 139, 2022–2031. [Google Scholar] [CrossRef]
  13. Sheahan, K.H.; Wahlberg, E.A.; Gilbert, M.P. An overview of GLP-1 agonists and recent cardiovascular outcomes trials. Postgrad. Med. J. 2020, 96, 156–161. [Google Scholar] [CrossRef] [Green Version]
  14. Nauck, M.A.; Meier, J.J.; Cavender, M.A.; Abd El Aziz, M.; Drucker, D.J. Cardiovascular Actions and Clinical Outcomes With Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors. Circulation 2017, 136, 849–870. [Google Scholar] [CrossRef]
  15. Marso, S.P.; Daniels, G.H.; Brown-Frandsen, K.; Kristensen, P.; Mann, J.F.; Nauck, M.A.; Nissen, S.E.; Pocock, S.; Poulter, N.R.; Ravn, L.S.; et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N. Engl. J. Med. 2016, 375, 311–322. [Google Scholar] [CrossRef] [Green Version]
  16. Marso, S.P.; Bain, S.C.; Consoli, A.; Eliaschewitz, F.G.; Jódar, E.; Leiter, L.A.; Lingvay, I.; Rosenstock, J.; Seufert, J.; Warren, M.L.; et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N. Engl. J. Med. 2016, 375, 1834–1844. [Google Scholar] [CrossRef] [Green Version]
  17. Gerstein, H.C.; Colhoun, H.M.; Dagenais, G.R.; Diaz, R.; Lakshmanan, M.; Pais, P.; Probstfield, J.; Riesmeyer, J.S.; Riddle, M.C.; Rydén, L.; et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): A double-blind, randomised placebo-controlled trial. Lancet 2019, 394, 121–130. [Google Scholar] [CrossRef]
  18. Cosentino, F.; Grant, P.J.; Aboyans, V.; Bailey, C.J.; Ceriello, A.; Delgado, V.; Federici, M.; Filippatos, G.; Grobbee, D.E.; Hansen, T.B.; et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur. Heart J. 2020, 41, 255–323. [Google Scholar] [CrossRef] [Green Version]
  19. Ma, X.; Liu, Z.; Ilyas, I.; Little, P.J.; Kamato, D.; Sahebka, A.; Chen, Z.; Luo, S.; Zheng, X.; Weng, J.; et al. GLP-1 receptor agonists (GLP-1RAs): Cardiovascular actions and therapeutic potential. Int. J. Biol. Sci. 2021, 17, 2050–2068. [Google Scholar] [CrossRef]
  20. Zhang, D.P.; Xu, L.; Wang, L.F.; Wang, H.J.; Jiang, F. Effects of antidiabetic drugs on left ventricular function/dysfunction: A systematic review and network meta-analysis. Cardiovasc. Diabetol. 2020, 19, 10. [Google Scholar] [CrossRef]
  21. Voigt, J.U.; Pedrizzetti, G.; Lysyansky, P.; Marwick, T.H.; Houle, H.; Baumann, R.; Pedri, S.; Ito, Y.; Abe, Y.; Metz, S.; et al. Definitions for a common standard for 2D speckle tracking echocardiography: Consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. Eur. Heart J. Cardiovasc. Imaging 2015, 16, 1–11. [Google Scholar] [CrossRef] [PubMed]
  22. Potter, E.; Marwick, T.H. Assessment of Left Ventricular Function by Echocardiography: The Case for Routinely Adding Global Longitudinal Strain to Ejection Fraction. JACC Cardiovasc. Imaging 2018, 11, 260–274. [Google Scholar] [CrossRef] [PubMed]
  23. Holland, D.J.; Marwick, T.H.; Haluska, B.A.; Leano, R.; Hordern, M.D.; Hare, J.L.; Fang, Z.Y.; Prins, J.B.; Stanton, T. Subclinical LV dysfunction and 10-year outcomes in type 2 diabetes mellitus. Heart 2015, 101, 1061–1066. [Google Scholar] [CrossRef] [PubMed]
  24. Lang, R.M.; Badano, L.P.; Mor-Avi, V.; Afilalo, J.; Armstrong, A.; Ernande, L.; Flachskampf, F.A.; Foster, E.; Goldstein, S.A.; Kuznetsova, T.; et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J. Am. Soc. Echocardiogr. 2015, 28, 1–39.e14. [Google Scholar] [CrossRef] [Green Version]
  25. Merlo, M.; Porcari, A.; Pagura, L.; Cameli, M.; Vergaro, G.; Musumeci, B.; Biagini, E.; Canepa, M.; Crotti, L.; Imazio, M.; et al. A national survey on prevalence of possible echocardiographic red flags of amyloid cardiomyopathy in consecutive patients undergoing routine echocardiography: Study design and patients characterization-the first insight from the AC-TIVE Study. Eur. J. Prev. Cardiol. 2021, 29, e173–e177. [Google Scholar] [CrossRef]
  26. Minciună, I.-A.; Hilda Orășan, O.; Minciună, I.; Lazar, A.-L.; Sitar-Tăut, A.V.; Oltean, M.; Tomoaia, R.; Puiu, M.; Sitar-Tăut, D.-A.; Pop, D.; et al. Assessment of subclinical diabetic cardiomyopathy by speckle-tracking imaging. Eur. J. Clin. Investig. 2021, 51, e13475. [Google Scholar] [CrossRef]
  27. Lorenzo-Almorós, A.; Cepeda-Rodrigo, J.M.; Lorenzo, Ó. Diabetic cardiomyopathy. Rev. Clin. Esp. 2022, 222, 100–111. [Google Scholar] [CrossRef]
  28. Paolillo, S.; Marsico, F.; Prastaro, M.; Renga, F.; Esposito, L.; De Martino, F.; Di Napoli, P.; Esposito, I.; Ambrosio, A.; Ianniruberto, M.; et al. Diabetic Cardiomyopathy: Definition, Diagnosis, and Therapeutic Implications. Heart Fail. Clin. 2019, 15, 341–347. [Google Scholar] [CrossRef]
  29. Cosson, S.; Kevorkian, J.P. Left ventricular diastolic dysfunction: An early sign of diabetic cardiomyopathy? Diabetes Metab. 2003, 29, 455–466. [Google Scholar] [CrossRef]
  30. Ng, A.C.; Delgado, V.; Bertini, M.; van der Meer, R.W.; Rijzewijk, L.J.; Shanks, M.; Nucifora, G.; Smit, J.W.; Diamant, M.; Romijn, J.A.; et al. Findings from left ventricular strain and strain rate imaging in asymptomatic patients with type 2 diabetes mellitus. Am. J. Cardiol. 2009, 104, 1398–1401. [Google Scholar] [CrossRef]
  31. Karagöz, A.; Bezgin, T.; Kutlutürk, I.; Külahçıoğlu, S.; Tanboğa, I.H.; Güler, A.; Karabay, C.Y.; Oduncu, V.; Aksoy, H.; Kırma, C. Subclinical left ventricular systolic dysfunction in diabetic patients and its association with retinopathy: A 2D speckle tracking echocardiography study. Herz 2015, 40 (Suppl. 3), 240–246. [Google Scholar] [CrossRef]
  32. Zoroufian, A.; Razmi, T.; Taghavi-Shavazi, M.; Lotfi-Tokaldany, M.; Jalali, A. Evaluation of subclinical left ventricular dysfunction in diabetic patients: Longitudinal strain velocities and left ventricular dyssynchrony by two-dimensional speckle tracking echocardiography study. Echocardiography 2014, 31, 456–463. [Google Scholar] [CrossRef]
  33. Fang, Z.Y.; Prins, J.B.; Marwick, T.H. Diabetic cardiomyopathy: Evidence, mechanisms, and therapeutic implications. Endocr. Rev. 2004, 25, 543–567. [Google Scholar] [CrossRef]
  34. Mandavia, C.H.; Aroor, A.R.; Demarco, V.G.; Sowers, J.R. Molecular and metabolic mechanisms of cardiac dysfunction in diabetes. Life Sci. 2013, 92, 601–608. [Google Scholar] [CrossRef] [Green Version]
  35. Liu, Q.; Wang, S.; Cai, L. Diabetic cardiomyopathy and its mechanisms: Role of oxidative stress and damage. J. Diabetes Investig. 2014, 5, 623–634. [Google Scholar] [CrossRef]
  36. Dia, M.; Gomez, L.; Thibault, H.; Tessier, N.; Leon, C.; Chouabe, C.; Ducreux, S.; Gallo-Bona, N.; Tubbs, E.; Bendridi, N.; et al. Reduced reticulum-mitochondria Ca(2+) transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy. Basic Res. Cardiol. 2020, 115, 74. [Google Scholar] [CrossRef]
  37. Jaquenod De Giusti, C.; Palomeque, J.; Mattiazzi, A. Ca(2+) mishandling and mitochondrial dysfunction: A converging road to prediabetic and diabetic cardiomyopathy. Pflügers Arch. 2022, 474, 33–61. [Google Scholar] [CrossRef]
  38. DeNicola, M.; Du, J.; Wang, Z.; Yano, N.; Zhang, L.; Wang, Y.; Qin, G.; Zhuang, S.; Zhao, T.C. Stimulation of glucagon-like peptide-1 receptor through exendin-4 preserves myocardial performance and prevents cardiac remodeling in infarcted myocardium. Am. J. Physiol. Endocrinol. Metab. 2014, 307, E630–E643. [Google Scholar] [CrossRef] [Green Version]
  39. Huang, D.D.; Huang, H.F.; Yang, Q.; Chen, X.Q. Liraglutide improves myocardial fibrosis after myocardial infarction through inhibition of CTGF by activating cAMP in mice. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 4648–4656. [Google Scholar] [CrossRef]
  40. Sokos, G.G.; Nikolaidis, L.A.; Mankad, S.; Elahi, D.; Shannon, R.P. Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J. Card. Fail. 2006, 12, 694–699. [Google Scholar] [CrossRef]
  41. Chen, W.R.; Chen, Y.D.; Tian, F.; Yang, N.; Cheng, L.Q.; Hu, S.Y.; Wang, J.; Yang, J.J.; Wang, S.F.; Gu, X.F. Effects of Liraglutide on Reperfusion Injury in Patients With ST-Segment-Elevation Myocardial Infarction. Circ. Cardiovasc. Imaging 2016, 9, e005146. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  42. Arturi, F.; Succurro, E.; Miceli, S.; Cloro, C.; Ruffo, M.; Maio, R.; Perticone, M.; Sesti, G.; Perticone, F. Liraglutide improves cardiac function in patients with type 2 diabetes and chronic heart failure. Endocrine 2017, 57, 464–473. [Google Scholar] [CrossRef] [PubMed]
  43. Nathanson, D.; Frick, M.; Ullman, B.; Nystrom, T. Exenatide infusion decreases atrial natriuretic peptide levels by reducing cardiac filling pressures in type 2 diabetes patients with decompensated congestive heart failure. Diabetol. Metab. Syndr. 2016, 8, 5. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Lonborg, J.; Kelbaek, H.; Vejlstrup, N.; Botker, H.E.; Kim, W.Y.; Holmvang, L.; Jorgensen, E.; Helqvist, S.; Saunamaki, K.; Terkelsen, C.J.; et al. Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia. Circ. Cardiovasc. Interv. 2012, 5, 288–295. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Ussher, J.R.; Drucker, D.J. Cardiovascular actions of incretin-based therapies. Circ. Res. 2014, 114, 1788–1803. [Google Scholar] [CrossRef] [Green Version]
  46. Wang, B.; Zhong, J.; Lin, H.; Zhao, Z.; Yan, Z.; He, H.; Ni, Y.; Liu, D.; Zhu, Z. Blood pressure-lowering effects of GLP-1 receptor agonists exenatide and liraglutide: A meta-analysis of clinical trials. Diabetes Obes. Metab. 2013, 15, 737–749. [Google Scholar] [CrossRef]
  47. Nauck, M.A.; Quast, D.R.; Wefers, J.; Meier, J.J. GLP-1 receptor agonists in the treatment of type 2 diabetes—State-of-the-art. Mol. Metab. 2021, 46, 101102. [Google Scholar] [CrossRef]
  48. Helmstädter, J.; Keppeler, K.; Küster, L.; Münzel, T.; Daiber, A.; Steven, S. Glucagon-like peptide-1 (GLP-1) receptor agonists and their cardiovascular benefits-The role of the GLP-1 receptor. Br. J. Pharmacol. 2022, 179, 659–676. [Google Scholar] [CrossRef]
  49. Song, R.; Qian, H.; Wang, Y.; Li, Q.; Li, D.; Chen, J.; Yang, J.; Zhong, J.; Yang, H.; Min, X.; et al. Research Progress on the Cardiovascular Protective Effect of Glucagon-Like Peptide-1 Receptor Agonists. J. Diabetes Res. 2022, 2022, 4554996. [Google Scholar] [CrossRef]
  50. Ravassa, S.; Zudaire, A.; Carr, R.D.; Diez, J. Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 2011, 300, H1361–H1372. [Google Scholar] [CrossRef] [Green Version]
  51. Matsubara, M.; Kanemoto, S.; Leshnower, B.G.; Albone, E.F.; Hinmon, R.; Plappert, T.; Gorman, J.H., 3rd; Gorman, R.C. Single dose GLP-1-Tf ameliorates myocardial ischemia/reperfusion injury. J. Surg. Res. 2011, 165, 38–45. [Google Scholar] [CrossRef] [Green Version]
  52. Guaricci, A.I.; Chiarello, G.; Gherbesi, E.; Fusini, L.; Soldato, N.; Siena, P.; Ursi, R.; Ruggieri, R.; Guglielmo, M.; Muscogiuri, G.; et al. Coronary-specific quantification of myocardial deformation by strain echocardiography may disclose the culprit vessel in patients with non-ST-segment elevation acute coronary syndrome. Eur. Heart J. Open 2022, 2, oeac010. [Google Scholar] [CrossRef]
  53. Phelan, D.; Collier, P.; Thavendiranathan, P.; Popović, Z.B.; Hanna, M.; Plana, J.C.; Marwick, T.H.; Thomas, J.D. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart 2012, 98, 1442–1448. [Google Scholar] [CrossRef]
  54. Oikonomou, E.K.; Kokkinidis, D.G.; Kampaktsis, P.N.; Amir, E.A.; Marwick, T.H.; Gupta, D.; Thavendiranathan, P. Assessment of Prognostic Value of Left Ventricular Global Longitudinal Strain for Early Prediction of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-analysis. JAMA Cardiol. 2019, 4, 1007–1018. [Google Scholar] [CrossRef]
  55. Lambadiari, V.; Pavlidis, G.; Kousathana, F.; Varoudi, M.; Vlastos, D.; Maratou, E.; Georgiou, D.; Andreadou, I.; Parissis, J.; Triantafyllidi, H.; et al. Effects of 6-month treatment with the glucagon like peptide-1 analogue liraglutide on arterial stiffness, left ventricular myocardial deformation and oxidative stress in subjects with newly diagnosed type 2 diabetes. Cardiovasc. Diabetol. 2018, 17, 8. [Google Scholar] [CrossRef] [Green Version]
  56. Bizino, M.B.; Jazet, I.M.; Westenberg, J.J.M.; van Eyk, H.J.; Paiman, E.H.M.; Smit, J.W.A.; Lamb, H.J. Effect of liraglutide on cardiac function in patients with type 2 diabetes mellitus: Randomized placebo-controlled trial. Cardiovasc. Diabetol. 2019, 18, 55, Correction in Cardiovasc. Diabetol. 2019, 18, 101. [Google Scholar] [CrossRef] [Green Version]
  57. Yagi, K.; Imamura, T.; Tada, H.; Chujo, D.; Liu, J.; Shima, Y.; Ohbatake, A.; Miyamoto, Y.; Okazaki, S.; Ito, N.; et al. Diastolic Cardiac Function Improvement by Liraglutide Is Mainly Body Weight Reduction Dependent but Independently Contributes to B-Type Natriuretic Peptide Reduction in Patients with Type 2 Diabetes with Preserved Ejection Fraction. J. Diabetes Res. 2021, 2021, 8838026. [Google Scholar] [CrossRef]
  58. Raev, D.C. Which left ventricular function is impaired earlier in the evolution of diabetic cardiomyopathy? An echocardiographic study of young type I diabetic patients. Diabetes Care 1994, 17, 633–639. [Google Scholar] [CrossRef]
Jcm 12 01586 g001 550
Figure 1. Left Ventricular Global Longitudinal Strain (LV GLS) with speckle tracking echocardiography (STE) is a helpful tool able to find out a subclinical LV dysfunction in an otherwise normal heart, which may evolve towards diabetic cardiomyopathy. Peak GLS is a negative number and a value in the range of −20% is considered normal.
Figure 1. Left Ventricular Global Longitudinal Strain (LV GLS) with speckle tracking echocardiography (STE) is a helpful tool able to find out a subclinical LV dysfunction in an otherwise normal heart, which may evolve towards diabetic cardiomyopathy. Peak GLS is a negative number and a value in the range of −20% is considered normal.
Jcm 12 01586 g001
Jcm 12 01586 g002 550
Figure 2. Peak Left Ventricular Global Longitudinal Strain (LV GLS) at baseline and after 6 months of treatment. The boxplots and the lines graph show a statistically significant (p < 0.001) improvement of LV GLS after 6 months of treatment with GLP1-RAs.
Figure 2. Peak Left Ventricular Global Longitudinal Strain (LV GLS) at baseline and after 6 months of treatment. The boxplots and the lines graph show a statistically significant (p < 0.001) improvement of LV GLS after 6 months of treatment with GLP1-RAs.
Jcm 12 01586 g002
Table
Table 1. Baseline characteristics of the study population. BSA: Body Surface Area; BMI: Body Mass Index; SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; CAD: Coronary Artery Disease; MI: Myocardial Infarction; COPD: Chronic Obstructive Pulmonary Disease; CKD: Chronic Kidney Disease; PAD: Peripheral Artery Disease; eGFR: estimated Glomerular Filtration Rate; ALT: Alanine-amino Transferase.
Table 1. Baseline characteristics of the study population. BSA: Body Surface Area; BMI: Body Mass Index; SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; CAD: Coronary Artery Disease; MI: Myocardial Infarction; COPD: Chronic Obstructive Pulmonary Disease; CKD: Chronic Kidney Disease; PAD: Peripheral Artery Disease; eGFR: estimated Glomerular Filtration Rate; ALT: Alanine-amino Transferase.
VariableAll Patients (n = 22)
Demographic and anthropometric data
Age, years, mean ± SD65 ± 10
Sex, male, n (%)14 (64)
BSA, m2, mean ± sd2.03 ± 0.21
BMI, m2/Kg33.9 ± 5.1
Clinical data
SBP, mmHg, mean ± sd133 ± 13
DBP, mmHg, mean ± sd79 ± 10
Heart rate, bpm71 ± 10
Cardiovascular risk factors other than DMT2
Hypertension, yes, n (%)22 (100)
Dyslipidaemia, yes, n (%)21 (95)
Smoking habit, yes, n (%)15 (68)
Obesity, yes, n (%)19 (86)
Family history of cardiovascular disease, yes, n (%)20 (91)
Comorbidities
CAD, yes, n (%)2 (9)
Previous IM, yes, n (%)2 (9)
COPD, yes, n (%)7 (32)
CKD, yes, n (%)2 (9)
PAD, yes, n (%)3 (14)
Thyroid disorders, yes, n (%)4 (18)
Medical therapy
ACE-I/ARB, yes, n (%)18 (82)
Beta-blockers, yes, n (%)10 (45)
Diuretics, yes, n (%)8 (36)
Anticoagulant therapy, yes, n (%)2 (9)
Anti-thrombotic agents, yes, n (%)11 (50)
Statins, yes, n (%)15 (68)
Metformin, yes, n (%)21 (95)
Insulin, yes, n (%)0 (0)
Laboratory testing
Creatinine, mg/dL, median [IQR]0.87 [0,31]
eGFR, mL/min/1.73 m2, median [IQR]83 [26]
Uric acid, mg/dL, median [IQR]5.6 [2,9]
Plasma sodium, mEq/L, mean ± sd139.5 ± 1.8
Plasma potassium, mEq/L, median [IQR]4.2 [0,4]
Haemoglobin, g/dL, mean ± sd13.6 ± 1.4
Glycated haemoglobin, mMol/Mol, median [IQR]49 [16]
Fasting plasma glucose, mg/dL, median [IQR]109 [25]
Total bilirubin, mg/dL, median [IQR]0.6 [0,2]
ALT, mg/dL, median [IQR]25 [14]
Table
Table 2. Echocardiographic data at baseline and after 6 months of GLP-1RA treatment. LV: Left Ventricle; PW: Posterior Wall; EDD: End Diastolic Diameter; EDV: End Diastolic Volume; EF: Ejection Fraction; ESV: End Systolic Volume; TAPSE: Tricuspid Annular Plane Systolic Excursion; LA: Left Atrium; APD: Antero-posterior Diameter; RVOT: Right Ventricle Outflow Tract; RV: Right Ventricle; EDA: End Diastolic Area; ESA: End Systolic Area; FAC: Fractional Area Change; DT: Deceleration Time; SPAP: Systolic Pulmonary Artery Pressure; IVC: Inferior Vena Cava; GLS: Global Longitudinal Strain.
Table 2. Echocardiographic data at baseline and after 6 months of GLP-1RA treatment. LV: Left Ventricle; PW: Posterior Wall; EDD: End Diastolic Diameter; EDV: End Diastolic Volume; EF: Ejection Fraction; ESV: End Systolic Volume; TAPSE: Tricuspid Annular Plane Systolic Excursion; LA: Left Atrium; APD: Antero-posterior Diameter; RVOT: Right Ventricle Outflow Tract; RV: Right Ventricle; EDA: End Diastolic Area; ESA: End Systolic Area; FAC: Fractional Area Change; DT: Deceleration Time; SPAP: Systolic Pulmonary Artery Pressure; IVC: Inferior Vena Cava; GLS: Global Longitudinal Strain.
VariableBaseline (n = 22)After 6 Months (n = 22)Difference (n = 22)p Value
LV septum, mm, median [IQR]12 [1]12 [1]0 [0]0.257
LV PW, mm, median [IQR]11 [1]11 [1]0 [0]0.206
LV EDD, mm, mean ± sd47 ± 546 ± 51 ± 30.158
LV Mass, g, mean ± sd154 ± 22153 ± 211 ± 20.560
LV EDV, mL, median [IQR]98 [24]98 [23]0 [11]0.835
LV ESV, mL, median [IQR]40 [19]41 [16]0 [6]0.615
LV EF, %, median [IQR]59 [7]58 [8]1 [6]0.776
LA APD, mm, median [IQR]41 [3]40 [3]0 [2]0.273
LA Area, cm2, median [IQR]17 [5]17 [4]1 [2]0.024
LA Volume, mL, mean ± sd50 ± 1348 ± 132 ± 70.278
RVOT, mm, mean ± sd31 ± 432 ± 3−1 ± 100.294
RV basal, median [IQR]35 [4]36 [4]−1 [2]0.059
RV EDA, cm2, mean ± sd15 ± 215 ± 20 ±20.102
RV ESA, cm2, mean ± sd8 ± 17 ± 11 ± 10.005
RV FAC, %, mean ± sd46 ± 648 ± 8−2 ± 80.172
E wave, cm/s, mean ± sd64 ± 1364 ± 130 ± 160.863
A wave, cm/s, mean ± sd85 ± 1883 ± 142 ± 130.545
E/A, median [IQR]0.75 [0,28]0.78 [0,19]−0.02 [0,15]0.433
DT, msec, mean ± sd175 ± 45166 ± 399 ± 340.236
S’ septal, cm/s, mean ± sd8 ± 28 ± 10 ± 20.390
E’ septal, cm/s, mean ± sd9 ± 28 ± 21 ± 20.280
A’ septal, cm/s, mean ± sd 10 ± 211 ± 2−1 ± 20.196
S’ mitral, cm/s, mean ± sd9 ± 29 ± 20 ± 20.853
E’ mitral, cm/s, mean ± sd10 ± 310 ± 30 ± 20.741
A’ mitral, cm/s, mean ± sd11 ± 311 ± 30 ± 20.343
E/E’, mean ± sd7 ± 27 ± 20 ± 20.589
S’ tricuspid, cm/s, median [IQR]12 [2]12 [3]0 [2]0.751
E’ tricuspid, cm/s, median [IQR]11 [2]11 [2]0 [1]0.842
A’ tricuspid, cm/s, median [IQR]9 [5]13 [6]−1 [5]0.003
TAPSE, mm, mean ± sd21 ± 222 ± 2−1 ± 20.392
SPAP, mmHg, median [IQR]26 [10]26 [9]0 [4]0.362
IVC diameter, mm, median [IQR]18 [2]18 [3]0 [1]0.361
IVC collapse, no, n (%)22 (100)21 (95)-nv
LV GLS, %, mean ± sd−18.0 ± 1.8−19.5 ± 2.1−1.4 ± 1.1<0.001
Table
Table 3. Correlations between baseline clinical data and variation of LV GLS after 6-months of treatment. BMI: Body Mass Index; SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure.
Table 3. Correlations between baseline clinical data and variation of LV GLS after 6-months of treatment. BMI: Body Mass Index; SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure.
VariabileCoefficientp Value
Age0.2390.285
Sex−0.0450.843
BMI0.3640.096
Smoking habit−0.4310.045
SBP0.0590.796
DBP−0.2370.287
Heart Rate0.0540.817
Therapy with metformin−0.2090.351
Gylicated haemoglobin0.0190.933
Fasting plasma glucose−0.0070.975
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Basile, P.; Guaricci, A.I.; Piazzolla, G.; Volpe, S.; Vozza, A.; Benedetto, M.; Carella, M.C.; Santoro, D.; Monitillo, F.; Baggiano, A.; et al. Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study. J. Clin. Med. 2023, 12, 1586. https://doi.org/10.3390/jcm12041586

AMA Style

Basile P, Guaricci AI, Piazzolla G, Volpe S, Vozza A, Benedetto M, Carella MC, Santoro D, Monitillo F, Baggiano A, et al. Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study. Journal of Clinical Medicine. 2023; 12(4):1586. https://doi.org/10.3390/jcm12041586

Chicago/Turabian Style

Basile, Paolo, Andrea Igoren Guaricci, Giuseppina Piazzolla, Sara Volpe, Alfredo Vozza, Marina Benedetto, Maria Cristina Carella, Daniela Santoro, Francesco Monitillo, Andrea Baggiano, and et al. 2023. "Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study" Journal of Clinical Medicine 12, no. 4: 1586. https://doi.org/10.3390/jcm12041586

APA Style

Basile, P., Guaricci, A. I., Piazzolla, G., Volpe, S., Vozza, A., Benedetto, M., Carella, M. C., Santoro, D., Monitillo, F., Baggiano, A., Mushtaq, S., Fusini, L., Fazzari, F., Forleo, C., Ribecco, N., Pontone, G., Sabbà, C., & Ciccone, M. M. (2023). Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study. Journal of Clinical Medicine, 12(4), 1586. https://doi.org/10.3390/jcm12041586

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