Introduction and Objective: Type 2 diabetes (T2D) and obesity are associated with left ventricular (LV) dysfunction, but the impact of exercise interventions on LV function remains unclear. This study aims to assess LV function in individuals with obesity, with and without T2D via supervised aerobic exercise training, using cardiac MRI and time-resolved three-dimensional phase-contrast MRI (4D flow MRI). Methods: 16 overweight controls (OWC; HbA1c = 5.3 ± 0.2%; age = 42.8 ± 6.0 years; 56% female) and 7 individuals with obesity and T2D (HbA1c = 6.8 ± 0.8%; age = 48.3 ± 6.0 years; 57%) completed 15 weeks of exercise training. Maximal oxygen consumption was measured as a marker of cardiorespiratory fitness. Global LV function and strain were analyzed using cardiac MRI. E/A velocity, a standard echocardiographic marker, was assessed using 4D flow MRI. Participants were categorized into low SVi (20.5 ± 3.0 mL/m2) and high SVi groups (30.1 ± 3.6 mL/m2) based on an SVi threshold of 25 mL/m2. Pre- and post-exercise data were compared using paired t-tests. Results: Reclassifying the cohort by SVi showed a significant increase in E/A velocity only in the high SVi group after exercise, with no other biomarkers showing significant changes in either group. Conclusion: Early LV function changes via exercise intervention may be detectable in E/A velocity in individuals with high SVi. S. Park: None. E.K. Englund: None. T. Fujiwara: None. D. Enge: Employee; Epic. M. Schäfer: None. B.M. Fonseca: Consultant; Siemens Healthcare Diagnostics. K.S. Hunter: None. J.G. Regensteiner: None. J.E.B. Reusch: Advisory Panel; Medtronic. A.J. Barker: None. American Diabetes Association (4-24-PDF-51)

Pulse wave velocity (PWV) is an important measure of cardiovascular health, related to vascular stiffness. Aortic PWV can be evaluated with a variety of MRI methods, however a direct comparison of PWV results quantified from 4D flow, 2D phase contrast (PC), and 1D projection PC MRI has not been performed. Here, PWV derived from 4D, 2D, and 1D-PC MRI acquisitions and associated analysis strategies were compared in the aortic arch. Relative agreement was observed among methods. 2D-PC PWV derived from the flow-area approach had substantial variability, likely due to the limited spatial/temporal resolution, and user-dependence of analysis.

OBJECTIVE:Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D.METHODS:Physically inactive age and BMI-similar premenopausal women and men with ( n  = 22) and without [ n  = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n  = 20). Left ventricular (LV) structure, function, and aortic stiffness were assessed by MRI. Global arterial pulse wave velocity (PWV) was assessed using carotid-to-femoral applanation tonometry. Regional PWV was measured via 2D phase-contrast MRI and 4D flow MRI.RESULTS:Global arterial PWV did not differ between CWO and T2D. 2D PC-MRI PWV in the ascending aorta was higher in people with T2D compared with CWOs ( P  < 0.01). 4D flow PWV in the thoracic aorta was higher in CWO ( P  < 0.01), and T2D ( P  < 0.001) compared with RC. End-diastolic volume, end-systolic volume, stroke volume, and cardiac output were lower in CWO and T2D groups compared with reference control.CONCLUSION:Subclinical changes in arterial stiffening and cardiac remodeling in inactive CWO and T2D compared with reference control support obesity and/or physical inactivity as determinants of incipient CVD complications in uncomplicated T2D. Future studies should determine the mechanistic causes of the CVD complications in greater detail in order to create therapeutic targets.CLINICAL TRIAL REGISTRATION:Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex (NCT03419195).

Cardiac autonomic neuropathy (CAN), a common complication of type 2 diabetes (T2D), is often not detected until late in disease progression. Autonomic nervous system (ANS) dysfunction impairs control of heart rate (HR) and vascular dynamics, manifesting as decreased HR variability (HRV) and impaired blood pressure (BP) regulation. We hypothesized that ANS function is impaired in participants with uncomplicated T2D and correlates with cardiac measures. We measured HRV during cycled breathing and Valsalva and postural HR and BP on overweight physically inactive adults aged 22-70 years with (N=53) and without (N=56) T2D. HRV with cycled breathing and Valsalva was lower in participants with T2D (p=0.007 and 0.005, respectively). HRV with respiration was lower with age >50 years (p=0.0001). HRV with respiration correlated with increased age in T2D but not in overweight control participants. There were no significant changes in postural BP or HR with age >50 years or T2D. Significant correlations between ANS measures and cardiac function were only seen in those with T2D. Valsalva ratio was positively correlated with end-diastolic volume (Pearson’s r 0.58, p=0.02) and stroke volume (Pearson’s r 0.55, p=0.03). HRV with respiration was positively correlated with longitudinal, diastolic peak strain rate (SR) (Pearson’s r 0.68, p=0.007). Postural BP was positively correlated with circumferential and longitudinal, systolic peak SR (Pearson’s r =0.45 and 0.48 and p-value=0.05 and 0.04, respectively) and negatively correlated with radial and circumferential peak strain (Pearson’s r =-0.49 and -0.48 and p-value=0.03 and 0.03, respectively). These data suggest subclinical CAN associated with cardiac dysfunction is present in people with otherwise uncomplicated T2D and is exacerbated with age. Detecting CAN changes early may identify people at risk for cardiac disease and inform targeted intervention to restore cardiometabolic health in people with T2D. Disclosure A.Johnston: None. L.A.Abushamat: None. D.Enge: None. A.J.Barker: None. E.W.Clark: None. D.Rafferty: None. J.G.Regensteiner: None. J.E.B.Reusch: Advisory Panel; Medtronic. Funding American Diabetes Association (1-21-CMF-003 to L.A.A.); National Institutes of Health (T32DK120520-01A1); U.S. Department of Veterans Affairs (CX001532)

T2D is a global epidemic leading to excess cardiovascular (CV) mortality including heart failure (HF) . Strategies are emerging to prevent HF progression, so early detection is needed. We have identified preclinical cardiac dysfunction associated with central arterial stiffness and decreased cardiorespiratory fitness. We hypothesized that cardiac magnetic resonance (CMR) would identify changes in diabetes. Methods: Age and BMI-similar premenopausal women and men with (n=24) and without (n=30) uncomplicated T2D were studied. CMR for cardiac function, regionally resolved pulse wave velocity (PWV) via 2D phase-contrast MRI assessed proximal arterial stiffness, and carotid to femoral applanation tonometry PWV (C-F PWV) using SphygmoCor assessed global arterial stiffness. The vascular territories covered by SphygmoCor does not include the ascending aorta. Results: CMR showed significant changes consistent with cardiac dysfunction in T2D (Table 1) . PWV was significantly greater with T2D in the ascending and proximal descending aorta (p<0.05) . Subclinical diastolic cardiac dysfunction (EDVi) correlated with proximal PWV in T2D (p=0.046, r2=0.24) . C-F PWV did not differ between groups. Conclusions: CMR detects early arterial stiffening in people with uncomplicated T2D and mild cardiac dysfunction. These findings support the use of CMR for detecting central arterial stiffness and incipient CV complications. Disclosure D.Enge: None. M.O.Whipple: None. K.S.Hunter: None. K.J.Nadeau: None. J.G.Regensteiner: None. A.J.Barker: None. J.Reusch: Advisory Panel; Medtronic. M.Schäfer: None. T.Fujiwara: None. E.Clark: None. E.Englund: None. R.L.Scalzo: None. D.Rafferty: None. I.E.Schauer: None. L.Abushamat: None. Funding National Institutes of Health (CX001532) University of Colorado Denver (NCT03419195) National Institutes of Health (R01-DK-124344) National Institutes of Health (K25HL119608)

Type 2 diabetes (T2D) is a global epidemic leading to excess cardiovascular (CV) mortality. CV risk factor modification does not prevent progression to non-ischemic heart failure (HF), so early detection and intervention are needed. Our group has identified preclinical cardiac dysfunction associated with central arterial stiffness and decreased cardiorespiratory fitness which is responsive to exercise training (ET) intervention.Cardiac parameters were measured in BMI-similar participants with and without T2D, before and after a 90-day progressive aerobic ET program and compared to lean nondiabetic historical controls. Left ventricular end systolic volume (LV ESV), end diastolic volume (EDV), stroke volume, and cardiac output for both groups pre- and post-exercise training were significantly lower than those of lean controls (Table 1). ESV and EDV increased post-exercise in T2D but not in the control group. While ejection fraction did not differ between groups, decreased heart rate in people with T2D following ET suggests compensation. Pulse wave velocity (PWV) by carotid to femoral tonometry (SphygmoCor) did not change with ET, but thoracic aortic PWV from 4D flow MRI significantly improved with ET across both groups. Cardiac and central arterial function are deleteriously and differently impacted by obesity and T2D. Advanced imaging may be a useful tool to longitudinally assess function and response to intervention.View largeDownload slideView largeDownload slide DisclosureD. Enge: None. K. Jarvis: None. T. Fujiwara: None. M. Markl: None. K. S. Hunter: None. A. J. Barker: None. K. J. Nadeau: None. J. G. Regensteiner: None. J. E. Reusch: Advisory Panel; Self; Medtronic. M. Schafer: None. R. L. Scalzo: None. D. Rafferty: None. I. E. Schauer: None. L. Abushamat: None. M. O. Whipple: None. E. Johnson: None. M. B. Scott: None.FundingNational Institutes of Health (R01DK124344, R01HL133504)

Early-onset cardiomyopathy is a major concern for people with type 1 diabetes mellitus (DM). Studies examining myocardial deformation indices early in the disease process in people with have provided conflicting results. Accordingly, the objective was to examine left ventricular (LV) function in adolescents with type 1 DM using novel measures of cardiomyopathy, termed ventricular discoordination indices, including systolic stretch fraction (SSF), and our newly developed diastolic relaxation fraction (DRF). Adolescents with DM (n = 16) and healthy controls (n = 20) underwent cardiac MRI (CMR) tissue tracking analysis for standard volumetric and functional analysis. Segment-specific circumferential strain and strain rate indices were evaluated to calculate standard mechanical dyssynchrony and discoordination. SSF and DRF were calculated from strain rate data. There were no global or regional group differences between participants with DM and controls in standard LV strain mechanics. However, youth with DM had lower diastolic strain rate around the inferior septal and free wall region (all p <0.05) as well as higher SSF (p = 0.03) and DRF (p <0.001) compared with controls. None of the CMR indices correlated with HbA1c or diabetes duration. In conclusion, our results suggest that adolescents with DM have LV systolic and diastolic discoordination, providing early evidence of cardiomyopathy despite their young age. The presence of discoordination in the setting of normal LV size and function suggests that the proposed novel discoordination indices could serve as a more sensitive marker of cardiomyopathy than previously employed mechanical deformation indices.

Type 2 diabetes (T2D) confers a greater likelihood of heart failure (HF) and hospitalization due to HF. Our group has reported sub-clinical cardiac dysfunction and aortic stiffness in youth and adults with uncomplicated T2D. As aortic stiffening is reported to precede HF and is common in people with uncomplicated T2D, we tested the hypothesis that aerobic exercise training will improve cardiac function and central arterial stiffness in people with T2D compared to participants of similar BMI without T2D. Sedentary adults with (n = 18, age 48±7, 45% female) and without (n = 20, age 45±7, 46% female) T2D, underwent MRI for cardiac function and aortic compliance (aortic relative area change [RAC] and pulse wave velocity [PWV]) before and after 15 weeks of aerobic exercise training. At baseline, both cohorts exhibit subclinical diastolic dysfunction, however, those with T2D had lower end-diastolic volume (EDVN,47.2±9.9 vs. 52.3±9.1 mL/m2) and end-systolic volume (ESVN,21.1±5.4 vs. 23.6±5.2 mL/m2), than controls. The T2D group had higher max thickness of the left ventricular (LV) septal wall (LVMTs, 10.5±1.8 vs. 9.3±1.6 mm) and LV lateral wall (LVMTl, 8.4±1.6 vs. 7.6±1.3 mm) than controls. Those with T2D also had lower RAC (12.7±1.6 vs. 20.2±1.6%) and higher PWV (7.4±1.3 vs. 3.9±0.6 m/s) than controls. Preliminary data in a subset post exercise intervention (n=7 with and n=8 without T2D), revealed increased EDVN(42.8±7.9 to 51.5±11.3 mL/m2) and ESVN(19.7±4.0 to 24.3±6.5 mL/m2) and decreased LVMTs(11.35±1.5 to 9.96±1.3 mm) and LVMTl(8.42±0.81 to 7.74±0.89 mm) in the T2D group, but cardiac endpoints were unchanged in controls. Post-intervention in both groups, ascending aorta RAC increased (control: 16.2±4 % to 18.5±1.7 and T2D: 10.6±1.7 % to 19.6±2.2 %) and PWV decreased (control: 6.3±2.0 to 3.4±0.3 and T2D: 8.0±1.4 to 2.9±0.7). Data from this study in progress suggest that adults with T2D have a greater degree of cardiac dysfunction and arterial stiffness than controls of similar BMI, which improve to a greater degree with exercise than in controls. Disclosure D. Enge: None. J.E. Reusch: None. J.G. Regensteiner: None. M. Schäfer: None. K.S. Hunter: None. A.J. Barker: None. K.J. Nadeau: None. R.L. Scalzo: None. I.E. Schauer: None. L. Abushamat: None. M.O. Whipple: None. D. Rafferty: None. Funding U.S. Department of Veterans Affairs (CX001532)