Association of Insulin Resistance and Glycemic Metabolic Abnormalities With LV Structure and Function in Middle Age: The CARDIA Study.

This study sought to investigate how cumulative exposure to glycemic abnormalities and trajectories of insulin resistance (IR) relate to left ventricular (LV) remodeling and function during young to middle adulthood. Cumulative exposure to glycemic abnormalities and trajectories of IR may adversely influence LV remodeling and function over a 25-year period in subjects who were young adults, predisposing individuals to heart failure later in life. In the CARDIA (Coronary Artery Risk Development in Young Adults) Year 25 examination, 3,179 participants were identified with information on glucose metabolism; these participants were stratified into 4 subgroups: group 1 normal glucose tolerance (NGT), group 2 impaired glucose tolerance (IGT) or impaired fasting glucose, group 3 late diabetes mellitus (DM) (DM diagnosed at year 15 or later), and group 4 early DM (DM diagnosed at year 0 to year 15). Among the subgroup without DM, 3 trajectory groups of change in the homeostasis model assessment of IR were identified: low IR, moderate IR, and high IR. LV mass, relative wall thickness, LV ejection fraction (LVEF), longitudinal systolic strain (Ell), and early diastolic strain rate (Ell_SRe) at year 25 were assessed by echocardiography. Clinically relevant systolic and diastolic dysfunction were defined as LVEF <50% for systolic dysfunction, and E/e' ≥13 for diastolic dysfunction. The early DM group had less favorable LV mass (coefficient = 11.04; p < 0.001), LVEF (coefficient = -2.72; p < 0.05), Ell (coefficient = 1.53; p < 0.001), and Ell_SRe (coefficient = -0.09; p < 0.05) than did the NGT group. Being in the early DM group and having high hemoglobin A1c were independently associated with greater odds of having systolic dysfunction (odds ratio = 5.44; p < 0.005) compared with the NGT group. High IR was associated with worse relative wall thickness (coefficient = 0.019; p < 0.0001) and worse Ell, E', and Ell_SRe, depending on obesity level. Cumulative exposure to DM or higher IR beginning in early adulthood adversely impacts LV remodeling and function at middle age.

Kishi S ，Gidding SS ，Reis JP ，Colangelo LA ，Venkatesh BA ，Armstrong AC ，Isogawa A ，Lewis CE ，Wu C ，Jacobs DR Jr ，Liu K ，Lima JA ... -  《-》

The impact of diabetes mellitus on cardiac function assessed by magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (β = - 6.05, P < 0.001) and impaired global longitudinal strain (β = 1.40, P = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (β = - 45.81, P = 0.008), LV global circumferential strain (β = 18.25, P = 0.003), LA reservoir strain (β = - 59.20, P < 0.001) and strain rate (β = - 2.90, P = 0.002). Diabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients.

Yu SQ ，Shi K ，Li Y ，Wang J ，Gao Y ，Shi R ，Yan WF ，Xu HY ，Guo YK ，Yang ZG ... -  《Cardiovascular Diabetology》

The role of body composition in left ventricular remodeling, reverse remodeling, and clinical outcomes for heart failure with mildly reduced ejection fraction: more knowledge to the "obesity paradox".

Although the "obesity paradox" is comprehensively elucidated in heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), the role of body composition in left ventricular (LV) remodeling, LV reverse remodeling (LVRR), and clinical outcomes is still unclear for HF with mildly reduced ejection fraction (HFmrEF). Our study is a single-centre, prospective, and echocardiography-based study. Consecutive HFmrEF patients, defined as HF patients with a left ventricular ejection fraction (LVEF) between 40 and 49%, between January 2016 to December 2021 were included. Echocardiography was re-examined at 3-, 6-, and 12-month follow-up to assess the LVRR dynamically. Body mass index (BMI), fat mass, fat-free mass, percent body fat (PBF), CUN-BAE index, and lean mass index (LMI) were adopted as anthropometric parameters in our study to assess body composition. The primary outcome was LVRR, defined as: (1) a reduction higher than 10% in LV end-diastolic diameter index (LVEDDI), or a LVEDDI < 33 mm/m2, (2) an absolute increase of LVEF higher than 10 points compared with baseline echocardiogram, or a follow-up LVEF ≥50%. The secondary outcome was a composite of re-hospitalization for HF or cardiovascular death. A total of 240 HFmrEF patients were enrolled in our formal analysis. After 1-year follow-up based on echocardiography, 113 (47.1%) patients developed LVRR. Patients with LVRR had higher fat mass (21.7 kg vs. 19.3 kg, P = 0.034) and PBF (28.7% vs. 26.6%, P = 0.047) compared with those without. The negative correlation between anthropometric parameters and baseline LVEDDI was significant (all P < 0.05). HFmrEF patients with higher BMI, fat mass, PBF, CUN-BAE index, and LMI had more pronounced and persistent increase of LVEF and decline in LV mass index (LVMI). Univariable Cox regression analysis revealed that higher BMI (HR 1.042, 95% CI 1.002-1.083, P = 0.037) and fat mass (HR 1.019, 95% CI 1.002-1.036, P = 0.026) were each significantly associated with higher cumulative incidence of LVRR for HFmrEF patients, while this relationship vanished in the adjusted model. Mediation analysis indicated that the association between BMI and fat mass with LVRR was fully mediated by baseline LV dilation. Furthermore, higher fat mass (aHR 0.957, 95% CI 0.917-0.999, P = 0.049) and PBF (aHR 0.963, 95% CI 0.924-0.976, P = 0.043) was independently associated with lower risk of adverse clinical events. Body composition played an important role in the LVRR and clinical outcomes for HFmrEF. For HFmrEF patients, BMI and fat mass was positively associated with the cumulative incidence of LVRR, while higher fat mass and PBF predicted lower risk of adverse clinical events but not LMI.

Fu K ，Dong Y ，Wang Z ，Teng J ，Cheng C ，Su C ，Ji X ，Lu H ... -  《Cardiovascular Diabetology》

Cumulative effect of metabolic risk factors on left ventricular geometry in those with versus without early-onset type 2 diabetes or prediabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

To investigate metabolic risk factors (RFs) that accumulated over 20 years related to left ventricular mass index (LVMI), relative wall thickness (RWT) and LV remodelling patterns in participants with versus without early-onset type 2 diabetes (T2D) or prediabetes (pre-D). A total of 287 early-onset T2D/pre-D individuals versus 565 sociodemographic-matched euglycaemic individuals were selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study, years 0-25. We used the area under the growth curve (AUC) derived from quadratic random-effects models of four or more repeated measures of RFs (fasting glucose [FG], insulin, triglycerides [TG], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), total cholesterol (total-c), blood pressure and body mass index) to estimate the cumulative burden, and their associations with LV outcomes. One standard deviation greater AUC of log (TG) (per 0.48) and HDL-c (per 13.5 mg/dL) were associated with RWT (β 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (β 0.01 and 0.05, P interactions .02 and .03). In both the early-onset T2D/pre-D and euglycaemia groups, greater AUCs of log (FG) (per 0.17) and log (insulin) (per 0.43) were associated with higher RWT (β ranges 0.12-0.24). Greater AUCs of systolic blood pressure (per 10 mmHg) and diastolic blood pressure (per 7.3 mmHg) were associated with higher RWT and LVMI, irrespective of glycaemic status (β ranges 0.17-0.28). Cumulative TG (odds ratio 3.4, 95% confidence interval: 1.8-6.3), HDL-c (0.23, 0.09-0.59), total-c (1.9, 1.1-3.1) and FG (2.2, 1.25-3.9) were statistically associated with concentric hypertrophy in the T2D/pre-D group only. Sustained hyperglycaemia and hyperinsulinaemia are associated with RWT, and those individuals with early T2D/pre-D are potentially at greater risk because of their higher levels of glucose and insulin. Dyslipidaemia was associated with LV structural abnormalities in those individuals with early-onset T2D/pre-D.

Yoshida Y ，Zu Y ，Fan B ，Li S ，Yoshida T ，Harville E ，Zhang T ，Bae S ，Shikany J ，Fonseca VA ... -  《-》

The adverse effect of metabolic syndrome on left ventricular global strains and myocardial energetic efficiency in non-ischemic dilated cardiomyopathy patients: a cardiac magnetic resonance study.

Metabolic syndrome (MetS) is a known risk factor for cardiovascular dysfunction; however, its impact on left ventricular (LV) global strains and myocardial energetic efficiency in non-ischemic dilated cardiomyopathy (NIDCM) remains inadequately understood. This study aimed to investigate the effect of MetS on LV dysfunction in NIDCM patients using cardiovascular magnetic resonance (CMR) imaging. A total of 557 NIDCM patients (378 without MetS and 179 with MetS) who underwent CMR examination were included. CMR-derived LV strains, remodeling index (LVRI), global function index (LVGFI), and indexed myocardial energetic efficiency (MEEI) were assessed and compared between the groups. The independent determinants of LV global longitudinal peak strain (GLPS), LVRI, LVGFI, and MEEI were evaluated using multivariable linear regression analyses. Compared to NIDCM patients without MetS, those with MetS had significantly lower LVSVI, LVEF, and LVGFI, along with higher LVMI and LVRI (all p < 0.05). However, no significant differences were found in LVEDVI and LVESVI (both p > 0.05). In terms of LV strain, the NIDCM(MetS+) group exhibited worse global peak strain and peak diastolic strain rate in all three directions, as well as decreased radial and longitudinal peak systolic strain rate (PSSR) compared to the NIDCM (MetS-) group (all p < 0.05), while circumferential PSSR did not differ significantly (p > 0.05). The MEEI was significantly lower in the NIDCM(MetS+) group compared to the NIDCM(MetS-) group (0.30 [0.20, 0.45] ml/s/g vs. 0.39 [0.25, 0.58] ml/s/g, p < 0.001). Multivariable analysis identified the presence of MetS as an independent determinant of LV GLPS (β = 0.211, p < 0.001), LVRI (β = 0.147, p = 0.003), and MEEI (β = - 0.160, p < 0.001). The presence of MetS worsens LV function, remodeling, and myocardial energetic efficiency in patients with NIDCM, as evidenced by declines in LV strain, global function parameters, and indexed myocardial energetic efficiency. These findings suggest that addressing metabolic abnormalities may be crucial for improving LV function and outcomes for patients with NIDCM.

Shen MT ，Li Y ，Shi K ，Wang J ，Jiang L ，Jiang Y ，Gao Y ，Yu SQ ，Li XM ，Yan WF ，Yang ZG ... -  《Cardiovascular Diabetology》