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Background: Pulmonary transit time (PTT) from first-pass perfusion imaging is a novel parameter to evaluate hemodynamic congestion by cardiac magnetic resonance (cMR). We sought to evaluate the additional prognostic value of PTT in heart failure with reduced ejection fraction over other well-validated predictors of risk including the Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause., Methods: We prospectively followed 410 patients with chronic heart failure with reduced ejection fraction (61±13 years, left ventricular (LV) ejection fraction 24±7%) who underwent a clinical cMR to assess the prognostic value of PTT for a primary endpoint of overall mortality and secondary composite endpoint of cardiovascular death and heart failure hospitalization. Normal reference values of PTT were evaluated in a population of 40 asymptomatic volunteers free of cardiovascular disease. Results PTT was significantly increased in patients with heart failure with reduced ejection fraction as compared to controls (9±6 beats and 7±2 beats, respectively, P <0.001), and correlated not only with New York Heart Association class, cMR-LV and cMR-right ventricular (RV) volumes, cMR-RV and cMR-LV ejection fraction, and feature tracking global longitudinal strain, but also with cardiac output. Over 6-year median follow-up, 182 patients died and 200 reached the secondary endpoint. By multivariate Cox analysis, PTT was an independent and significant predictor of both endpoints after adjustment for Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Importantly in multivariable analysis, PTT in beats had significantly higher additional prognostic value to predict not only overall mortality (χ 2 to improve, 12.3; hazard ratio, 1.35 [95% CI, 1.16-1.58]; P <0.001) but also the secondary composite endpoints (χ 2 to improve=20.1; hazard ratio, 1.23 [95% CI, 1.21-1.60]; P <0.001) than cMR-LV ejection fraction, cMR-RV ejection fraction, LV-feature tracking global longitudinal strain, or RV-feature tracking global longitudinal strain. Importantly, PTT was independent and complementary to both pulmonary artery pressure and reduced RV ejection fraction<42% to predict overall mortality and secondary combined endpoints., Conclusions: Despite limitations in temporal resolution, PTT derived from first-pass perfusion imaging provides higher and independent prognostic information in heart failure with reduced ejection fraction than clinical and other cMR parameters, including LV and RV ejection fraction or feature tracking global longitudinal strain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03969394.

Background and Aims: In type 2 diabetes mellitus (T2DM), sexual dimorphisms modulate the natural histories of hyperglycemia, anthropophysical/cardiometabolic phenotype, and susceptibility to chronic micro and macrovascular complications. The purpose of this work was to revisit known or new dimorphisms within a multiethnic cohort., Methods: Among 1238 T2DM patients, men (63%) were compared to women (37%), including leading ethnicities: Whites (67.4%; 542 men; 293 women); Maghrebians (9.4%; 62 men; 54 women); and Blacks (12.5%; 92 men; 63 women)., Results: Age, BMI, diabetes duration, insulin sensitivity, B-cell function loss, HbA1c, and hyperglycemia index were similar in both genders. All-cause microangiopathy and cerebrovascular disease did not differ between sexes. Women had significantly more retinopathy (27% vs. 21%) and men more microalbuminuria (25% vs. 19%), all-cause macroangiopathy (40% vs. 26%), CAD (29% vs. 17%) and PAD (11% vs. 6%). Among Blacks, sexual dimorphism in terms of retinopathy was more pronounced (24% in women vs. 11%), while there was no sexual dimorphism in all-cause macroangiopathy, CAD or PAD. B-cell function loss was faster among North African men (+15%), who also had more hepatic steatosis (+27%) than women., Conclusions: T2DM abolishes the CV protection provided by the female gender in Blacks. In White women, the loss of CV protection in diabetes is limited to cerebrovascular disease. In Black women, a markedly increased risk of retinopathy is present, despite glycemic exposure similat to men. Sexual dimorphisms do not affect glucose homeostasis and metabolic control in all ethnicities, except for lesser B-cell function loss in Maghrebian women., Competing Interests: Disclosure of conflicts interest The authors declare that they have no conflict of interest., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Fibroblast growth factor 23 (FGF-23), a key hormone for the regulation of the phosphorus homeostasis, has also several direct effects on cardiac function. In heart failure (HF), the increase of FGF-23 participates to cardiac hypertrophy and remodeling. Measurement of the intact, biologically active hormone is now available. We determined intact FGF-23 in HF patients with reduced ejection fraction and assess its prognosis value for cardiovascular death over a long-term follow-up. We observed that intact FGF-23 is an independent predictor of cardiovascular death in HF patients and provides added value to the standard of care, natriuretic peptide, for risk estimation., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: The metabolic syndrome (MetS) predicts cardiovascular risk and incident type 2 diabetes mellitus. The presence of a MetS is defined by the clustering of ≥3 out of 5 cardiometabolic criteria (hyperglycemia; hypertension; enlarged waist; low high-density lipoprotein-cholesterol; and hypertriglyceridemia), each of which is connected with insulin resistance. It is not known whether the severity of MetS, ranked from the sextet of scores range [0/5 to 5/5], is linearly related to reduced insulin sensitivity (IS) and/or lesser hyperbolic product across the glycemic spectrum., Patients and Methods: A total of 839 adults (54 normoglycemic; 785 with abnormal glucose homeostasis, among whom 711 type 2 diabetes mellitus) had insulin sensitivity assessed together with their cardiometabolic phenotype., Results: There was a significant gradient according to interval-scale MetS score in insulinemia; body mass index; (visceral) fat; hepatic steatosis; and macroangiopathy. There was an inverse linear relationship between increasing MetS scores and decreased insulin sensitivity, allowing to define an insulin resistance-predicting linear equation: IS (%) = [-15.1 × MetS score] + 109.4 (R(2)  = 0.221). For each MetS category, mean IS values did not significantly differ between groups of patients across the glycemic spectrum. The hyperbolic product (β-cell function × IS) and/or its loss rate were inversely related to MetS severity., Conclusion: Insulin sensitivity is linearly and inversely related to MetS severity across the 6 scores. This novel way to exploit information intrinsic to the MetS criteria provides an easy and low cost means to quantify insulin sensitivity across the glycemic spectrum. Moreover, a higher MetS score is associated with lesser residual insulin secretion, and faster B-cell function loss. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: OSAS, a frequently neglected, yet frequent comorbidity in T2DM, is associated with obesity, metabolic syndrome and central fat. OSAS is better documented in males, and this study explored novel gender dimorphisms in T2DM., Methods: Cross-sectional study: 815 T2DM (541 males; 274 females) classified into OSAS[-] and OSAS[+] were assessed for cardiometabolic risk factors, glucose homeostasis, micro/macroangiopathies, CV risk, autoimmune thyroid disease (AITD); and GAD65 antibodies., Results: There was a gender dimorphism in glucose control (worse in females), apolipoprotein B100 (higher in females), with apoB100/apoA1 and log(TG)/HDL-C sexually dimorphic. There was also a marked gender dimorphism in GAD65 positivity, higher (+793%) in OSAS[+] females vs. males. There were clear sexual dimorphisms in macro-/microangioathies, regarding stroke, retinopathy and polyneuropathy. OSAS was not sexually dimorphic regarding age; education; and diabetes duration. There was a significant dimorphism in ethnicity. There were no gender-specific dimorphisms related to OSAS in anthropometrics, nor in hypertension, insulin sensitivity, or hyperbolic product loss rate., Conclusion: We report a series of novel OSAS-related sexual dimorphisms, concerning GAD65 auto-antibodies; polyneuropathy; atherogenic dyslipidemia [all increased in females]; diabetic retinopathy; North-Caucasian ethnicity; metabolic control; and TIA/stroke prevalence [all lower in females]. These findings raise challenging questions regarding the reciprocal pathophysiology between obstructive sleep disorders and cardiometabolic risk in T2DM., (Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.)