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Depressed Systemic Arterial Compliance and Impaired Left Czestkowska et al. Cardiovasc Diabetol (2019) 18:92 https://doi.org/10.1186/s12933-019-0894-1 Cardiovascular Diabetology ORIGINAL INVESTIGATION Open Access Depressed systemic arterial compliance and impaired left ventricular midwall performance in aortic stenosis with concomitant type 2 diabetes: a retrospective cross-sectional study Ewa Czestkowska1†, Agnieszka Rożanowska1†, Dorota Długosz1, Klaudiusz Bolt1, Jolanta Świerszcz2, Olga Kruszelnicka3‡, Bernadeta Chyrchel4‡ and Andrzej Surdacki4*‡ Abstract Background: Degenerative aortic stenosis (AS), a disease of the elderly, frequently coexists with concomitant dis- eases, including type 2 diabetes (T2DM) which amplifes the cardiovascular (CV) risk. T2DM afects left ventricular (LV) structure and function via hemodynamic and metabolic factors. In concentric LV geometry, typical for AS, indices of LV midwall mechanics are better estimates of LV function than ejection fraction (EF). Efects of T2DM coexisting with AS on circumferential LV midwall systolic function and large artery properties have not been reported so far. Our aim was to compare characteristics of AS patients with and without T2DM, with a focus on LV midwall systolic function and arterial compliance. Methods: Medical records of 130 electively hospitalized patients with moderate or severe isolated degenerative AS were retrospectively analyzed. Exclusion criteria included clinical instability, atrial fbrillation, coronary artery disease and relevant non-cardiac diseases. From in-hospital echocardiography and blood pressure, we calculated LV midwall fractional shortening (mwFS), circumferential end-systolic LV wall stress (cESS) and valvulo-arterial impedance (Zva), estimates of LV afterload, as well as systemic arterial compliance. Results: Patients with (n 50) and without T2DM (n 80) did not difer in age, AS severity, LV mass and LV dias- tolic diameter. T2DM patients= exhibited elevated cESS= (247 105 vs. 209 84 hPa, p 0.025) and Zva (5.8 2.2 vs. 5.1 1.8 mmHg per mL/m2, p 0.04), and lower stroke volume± index (33± 10 vs. 38 = 12 mL/m2, p 0.01)± and systemic± arterial compliance (0.53= 0.16 vs. 0.62 0.22 mL/m2 per mmHg,± p 0.01). ±mwFS (11.9 3.9= vs. 14.1 3.7%, p 0.001), but not EF (51 14 vs. 54± 13%, p n.s.),± was reduced in T2DM. mwFS= and cESS were± inversely inter±- related= in patients both with± (r 0.59,± p < 0.001)= and without T2DM (r 0.53, p < 0.001) By multiple regression, higher cESS (p < 0.001) and T2DM=− (p 0.02) were independent predictors= of− depressed mwFS. = *Correspondence: [email protected] †Ewa Czestkowska and Agnieszka Rożanowska contributed equally to this work and are shared frst authors ‡Olga Kruszelnicka, Bernadeta Chyrchel and Andrzej Surdacki are joint senior authors on this work 4 Second Department of Cardiology, Jagiellonian University Medical College, 17 Kopernika Street, PL31-501 Cracow, Poland Full list of author information is available at the end of the article © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Czestkowska et al. Cardiovasc Diabetol (2019) 18:92 Page 2 of 9 Conclusions: In AS, coexistent T2DM appears associated with reduced systemic arterial compliance and LV dysfunc- tion at the midwall level, corresponding to slightly depressed myocardial contractility. Keywords: Aortic stenosis, Arterial compliance, Left ventricular systolic function, Type 2 diabetes mellitus Background characteristics of AS patients with and without T2DM, Degenerative aortic stenosis (AS), a disease of the elderly, with a focus on LV systolic function at the midwall level frequently coexists with concomitant diseases includ- and systemic arterial compliance. ing type 2 diabetes (T2DM) which amplifes the risk of adverse cardiovascular (CV) events in asymptomatic Methods patients [1] and after surgical aortic valve replacement Patients [2]. Regardless of associations with coronary artery dis- We retrospectively analyzed medical records of clini- ease (CAD) and hypertension, T2DM per se is a risk cally stable patients hospitalized on an elective basis in factor for heart failure (HF) [3–6], infuencing left ven- our center during 2013–2018 with a fnal diagnosis of tricular (LV) structure and function via multiple path- isolated moderate or severe degenerative AS-defned as 2 ways, including large artery stifening and direct efects aortic valve area ≤ 1.5 cm (by the continuity equation), on the myocardium with consequent enhanced LV supported by additional measures (mean aortic pressure hypertrophy and LV dysfunction [7–11]. gradient, aortic valve area index and maximal aortic jet Although a restrictive, not dilated, phenotype of dia- velocity) in case of any doubts with regard to AS severity, betic cardiomyopathy predominates in T2DM without i.e. in accordance with an integrative approach to grading CV disease [10, 12, 13], slight impairment of LV systolic AS [21, 22]. Exclusion criteria included: more than mild function despite normal ejection fraction (EF) appears aortic regurgitation or disease of another valve, atrial also frequent, with combined systolic and diastolic dys- fbrillation, a history of myocardial infarction or coronary function in 10–25% of T2DM patients without overt revascularization, diameter narrowings of ≥ 50% in major cardiac disease [14–16]. Of note, subclinical circumfer- epicardial artery segments on coronary angiography, esti- ential and/or longitudinal LV systolic dysfunction was mated glomerular fltration rate < 30 mL/min per 1.73 m2 reported in over one-half of T2DM patients free of CV (by the CKD-EPI formula), other relevant non-cardiac disease [16]. Additionally, impaired stress-corrected coexistent diseases except for T2DM and well-controlled LV midwall fractional shortening (mwFS), detected hypertension, and the use of sodium-glucose co-trans- in almost 40% of T2DM subjects without CV disease, porter 2 (SGLT-2) inhibitors or glucagon-like peptide 1 independently predicted CV mortality [17]. Moreover, receptor agonists. depressed mwFS predisposed to adverse ischemic and On the basis of the exclusion criteria, out of 335 pre- aortic valve-related CV events in asymptomatic AS with screened subjects, 130 AS patients in sinus rhythm with a preserved EF [18]. an adequate echocardiographic image quality and com- To the best of our knowledge, efects of T2DM coex- plete data (50 with previously diagnosed T2DM and 80 isting with AS on circumferential LV systolic function without diabetes) entered the fnal analysis. at the midwall level, a better estimate of LV func- tion than EF at concentric LV geometry, typical for Data extraction and additional calculations AS, have not been reported so far. As compared to In-hospital echocardiography was performed on an non-diabetic patients with severe AS, in diabetic AS ultrasound device (Vivid 8; GE Healthcare, Chicago, IL, subjects Lindman et al. [19] found reduced conven- USA) by a recognized sonographer. From routine in-hos- tional EF (i.e., at the endocardial level) and depressed pital echocardiographic records we extracted EF, calcu- longitudinal LV systolic function by strain-rate imag- lated from recorded 2D-images by means of the modifed ing using the speckle tracking method, a trend toward Simpson’s rule and validated by one of the senior authors, impaired LV diastolic function by tissue Doppler, and while LV mass was derived by the Devereux formula, similar systemic arterial compliance. On the other in accordance with the current practice guidelines [23]. hand, Falcão-Pires et al. [20] described signifcantly Additionally, from echocardiography and mean in-hospi- lower LV end-diastolic distensibility, enhanced inter- tal blood pressure (computed from all in-hospital blood stitial myocardial fbrosis and reduced cardiomyocyte pressure measurements), we calculated valvulo-arterial passive stifness in AS patients with versus without impedance (Zva)—an index of the sum of valvular and T2DM, undergoing perioperative LV biopsies, however arterial components of LV afterload, and systemic arterial the subgroups had similar EF. Our aim was to compare compliance, as previously proposed [24]. Zva was derived Czestkowska et al. Cardiovasc Diabetol (2019) 18:92 Page 3 of 9 from systolic blood pressure, mean aortic pressure gra- mwFS < 14% in women and < 16% in men, we performed dient and stroke volume index, whereas systemic arterial stepwise logistic regression with low mwFS as a dichot- compliance from stroke volume index and pulse pressure omous dependent variable, and the following potential [24], as in our earlier reports [25, 26]. predictors: cESS, systolic blood pressure, hypertension Also, in agreement with a simplifed cylindrical LV and metabolic syndrome, separately for diabetic and non- model [27–29], from 2D-guided M-mode LV measure- diabetic AS patients. A p-value below 0.05 was assumed ments and blood pressure, mwFS and circumferential signifcant. end-systolic LV midwall stress (cESS) at the LV minor axis, an estimate of afterload at the ventricular level, were com-
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