Cardioprotective effect of intradialytic exercise on left atrial mechanics.

Left atrial (LA) function plays a pivotal role in cardiac performance by modulating left ventricular (LV) function. Impairments in LV function are commonly reported during hemodialysis (HD), but available data describing changes in LA function are limited. There is growing evidence of the cardioprotective effect of intradialytic exercise (IDE) on LV function, but studies analyzing its effect on LA function are scarce. Our aim was to evaluate whether IDE can limit the severity of HD-induced impairment in LA myocardial function. In this prospective, open-label, two-center randomized crossover trial, 56 stable individuals receiving HD participated in 2 HD sessions in random order: standard HD and a session incorporating 30 min of aerobic exercise. LA and LV global longitudinal strains (GLSs) were obtained before and at peak stress of HD (i.e., 30 min before the HD ending). IDE totally eradicated the decline in LA reservoir strain observed during HD (estimated difference: 3.1%, 95% confidence interval: 0.4/5.8, P = 0.02), whereas it did not affect the other components of LA mechanics. A similar result favoring IDE intervention was also demonstrated on GLS changes over the HD procedure (P < 0.001). Between-session differences of changes in GLS and LA reservoir strain were correlated (r = -0.32, P = 0.03). The cardioprotective effect of IDE disappeared in patients with LA enlargement (i.e., LA volume index >34 mL/m2). In conclusion, even a short duration of IDE at moderate intensity is effective in preventing HD-associated decline in LA reservoir function. Further research is needed to explore the long-term benefits of IDE on LA function.NEW & NOTEWORTHY A single bout of intradialytic exercise (IDE) at moderate intensity can prevent the hemodialysis-associated decline in left atrial (LA) function. This was partially explained by the relative preservation of left ventricular systolic function with IDE. Benefits of IDE on LA function were lost in patients with LA dilation. Further studies are needed to explore the mechanisms behind IDE-induced cardioprotection and evaluate the clinical impacts of the repetitive cardioprotective effects of IDE on LA function.

Cardioprotective Effect of Acute Intradialytic Exercise: A Comprehensive Speckle-Tracking Echocardiography Analysis.

SIGNIFICANCE STATEMENT: Hemodialysis (HD) can lead to acute left ventricular (LV) myocardial wall motion abnormalities (myocardial stunning) due to segmental hypoperfusion. Exercise during dialysis is associated with favorable effects on central hemodynamics and BP stability, factors considered in the etiology of HD-induced myocardial stunning. In a speckle-tracking echocardiography analysis, the authors explored effects of acute intradialytic exercise (IDE) on LV regional myocardial function in 60 patients undergoing HD. They found beneficial effects of IDE on LV longitudinal and circumferential function and on torsional mechanics, not accounted for by cardiac loading conditions or central hemodynamics. These findings support the implementation of IDE in people with ESKD, given that LV transient dysfunction imposed by repetitive HD may contribute to heart failure and increased risk of cardiac events in such patients. BACKGROUND: Hemodialysis (HD) induces left ventricular (LV) transient myocardial dysfunction. A complex interplay between linear deformations and torsional mechanics underlies LV myocardial performance. Although intradialytic exercise (IDE) induces favorable effects on central hemodynamics, its effect on myocardial mechanics has never been comprehensively documented. METHODS: To evaluate the effects of IDE on LV myocardial mechanics, assessed by speckle-tracking echocardiography, we conducted a prospective, open-label, two-center randomized crossover trial. We enrolled 60 individuals with ESKD receiving HD, who were assigned to participate in two sessions performed in a randomized order: standard HD and HD incorporating 30 minutes of aerobic exercise (HDEX). We measured global longitudinal strain (GLS) at baseline (T0), 90 minutes after HD onset (T1), and 30 minutes before ending HD (T2). At T0 and T2, we also measured circumferential strain and twist, calculated as the net difference between apical and basal rotations. Central hemodynamic data (BP, cardiac output) also were collected. RESULTS: The decline in GLS observed during the HD procedure was attenuated in the HDEX sessions (estimated difference, -1.16%; 95% confidence interval [95% CI], -0.31 to -2.02; P = 0.008). Compared with HD, HDEX also demonstrated greater improvements from T0 to T2 in twist, an important component of LV myocardial function (estimated difference, 2.48°; 95% CI, 0.30 to 4.65; P = 0.02). Differences in changes from T0 to T2 for cardiac loading and intradialytic hemodynamics did not account for the beneficial effects of IDE on LV myocardial mechanics kinetics. CONCLUSIONS: IDE applied acutely during HD improves regional myocardial mechanics and might warrant consideration in the therapeutic approach for patients on HD.

Major impact of vitamin D3 deficiency and supplementation on left ventricular torsional mechanics during dobutamine stress in uncomplicated type 2 diabetes.

BACKGROUND AND AIMS: Hypovitaminosis D is associated with the risk of diabetic complications. Its role in diabetic-related cardiac abnormalities remain poorly understood. We aimed therefore to evaluate the effect of vitamin D deficiency and supplementation on early left ventricular (LV) dysfunction in vitamin D deficient patients with uncomplicated T2D. METHODS AND RESULTS: Sixty-three consecutive T2D patients who had a diagnosis of vitamin D3 were prospectively recruited and allocated into 2 groups (25(OH)D < 20 ng/mL: VDD, >20 ng/mL VDND). Twenty-eight of them with 25(OH)D < 20 ng/mL benefited from a 3-month supplementation. At baseline and follow-up, after conventional echocardiography including evaluation of epicardial adipose tissue (EAT), both LV longitudinal (LS) and circumferential (CS) strains and rotation/twist mechanics were evaluated at rest and during dobutamine (DOB) stress. After treatment, T2D patients successfully normalized their 25(OH)D levels. The strongest associations between vitamin D deficiency and supplementation with LV myocardial function were noticed for torsional mechanics indexes under DOB. EAT correlated significantly (p < 0.01) with baseline 25(OH)D and was reduced after supplementation. Significant correlations were obtained between these 2 parameters with twist or apical rotation at baseline (p < 0.01) and between their delta changes at follow-up (p < 0.01) under DOB. Significant improvements in LS and CS (p < 0.05) under DOB were also underlined at follow-up, with major enhancements noticed in the apical region (p < 0.01) of the LV. CONCLUSIONS: This study provides the first evidences of the potential of vitamin D supplementation as an efficient prophylactic strategy to alleviate the progression of myocardial dysfunction in asymptomatic patients with uncomplicated T2D. CLINICALTRIALS: NCT03437421.

Cardiorespiratory Fitness and Bone Turnover Markers in Adults With Metabolic Syndrome: The Mediator Role of Inflammation.

The relationship between inflammatory markers and bone turnover in adults is well known, and a negative association between cardiorespiratory fitness (CRF) and inflammatory markers has also been described. Hence, we tested whether the association between CRF and bone turnover markers is mediated by inflammatory markers in adults with metabolic syndrome. A total of 81 adults (58.5 ± 5.0 years, 62.7% women) were included in the analysis. CRF was measured by the 6-min walking test. Serum interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor alpha, high-sensitivity c-reactive protein (hsCRP) and vascular endothelial growth factor, collagen type I cross-linked C-telopeptide, procollagen type I N-terminal propeptide (P1NP), and total osteocalcin were assessed using a sensitive ELISA kit. Body composition was assessed by dual-energy X-ray absorptiometry. Partial correlation was used to test the relationship between CRF, inflammatory markers, and bone turnover markers, controlling for sex, lean mass, and fat mass. Boot-strapped mediation procedures were performed, and indirect effects with confidence intervals not including zero were interpreted as statistically significant. CRF was positively correlated with P1NP levels (r = .228, p = .044) and osteocalcin levels (r = .296, p = .009). Furthermore, CRF was positively correlated with IL-1ß levels (r = .340, p = .002) and negatively correlated with hsCRP levels (r = -.335, p = .003), whereas IL-1ß levels were positively correlated with P1NP levels (r = .245, p = .030), and hsCRP levels were negatively correlated with P1NP levels (r = -.319, p = .004). Finally, the association between CRF and P1NP levels was totally mediated by hsCRP (percentage of mediation = 39.9). Therefore, CRF benefits on bone formation could be dependent on hsCRP concentrations in this population.

Vitamin D3 Supplementation Alleviates Left Ventricular Dysfunction in a Mouse Model of Diet-Induced Type 2 Diabetes: Potential Involvement of Cardiac Lipotoxicity Modulation.

PURPOSE: To evaluate the effectiveness of vitamin D3 supplementation, in secondary prevention, on cardiac remodeling and function, as well as lipid profile, in a mouse model of diet-induced type 2 diabetes. METHODS: Mice were fed a high fat and sucrose diet for 10 weeks. Afterward, diet was maintained for 15 more weeks and two groups were formed, with and without cholecalciferol supplementation. A control group was fed with normal chow. Glucose homeostasis and cardiac function were assessed at baseline and at the 10th and 24th weeks. Animals were killed at the 10th and 25th weeks for plasma and cardiac sample analysis. Cardiac lipid profile was characterized by LC-MS/MS. RESULTS: After 10 weeks of diet, mice exhibited pre-diabetes, mild left ventricle hypertrophy, and impaired longitudinal strain, but preserved myocardial circumferential as well as global diastolic and systolic cardiac function. After 15 more weeks of diet, animals presented with well-established type 2 diabetes, pathological cardiac hypertrophy, and impaired regional myocardial function. Cholecalciferol supplementation had no effect on glucose homeostasis but improved cardiac remodeling and regional myocardial function. After 25 weeks, non-supplemented mice exhibited increased myocardial levels of ceramides and diacylglycerol, both of which were normalized by vitamin D3 supplementation. CONCLUSION: This work brought to light the beneficial effects of cholecalciferol supplementation, in secondary prevention, on cardiac remodeling and function in a mouse model of diet-induced type 2 diabetes. Those cardioprotective effects may be, at least in part, attributed to the modulation of myocardial levels of lipotoxic species by vitamin D.

Left ventricular dyssynchrony and post-systolic shortening in young bodybuilders using anabolic-androgenic steroids.

Left ventricular (LV) remodeling, characterized by increased LV hypertrophy and depressed systolic and diastolic function, is observed in strength-trained athletes who use anabolic-androgenic steroids (AAS). Previous studies suggested a pathological remodeling with an increase in cardiac fibrosis in these athletes, which could promote intraventricular dyssynchrony. In this context, this study evaluated LV dyssynchrony in strength-trained athletes using AAS, hypothesizing that the use of AAS would lead to an increase in post-systolic shortening. Forty-four male subjects (aged 20-40 yr) were divided into three age-matched groups: strength-trained athletes using (users, n = 14) or not (nonusers, n = 15) AAS and healthy sedentary men (controls, n = 15). After completing a survey, each participant was assessed with two-dimensional (2D)-strain echocardiography. LV dyssynchrony was quantified using the standard deviation (SD) of the time to peak for longitudinal strain of the 18 LV-segments (from the apical 4, 3, and 2 chambers views), the longitudinal strain delay index (LSDI), and the segmental post-systolic index (PSI). Users showed mean AAS dosages of 564 ± 288 mg[Formula: see text]wk-1 with a mean protocol duration of 12 ± 6 wk and a history of use of 4.7 ± 1.8 yr. They exhibited a greater LV mass index and depressed systolic and diastolic function when compared with both nonusers and controls. The decrease in LV strain in users was predominantly observed at the interventricular septum level (-16.9% ± 2.5% vs. -19.2% ± 1.8% and -19.0% ± 1.6% in users, nonusers, and controls, respectively, P < 0.01). Users showed higher SD than controls (43 ± 8 ms vs. 32 ± 5 ms, respectively, P < 0.01). The LSDI was significantly higher in users compared with both nonusers and controls (-23.4 ± 9.5 vs. -15.9 ± 9.3 and -9.8 ± 3.9, respectively, P < 0.01). PSI, calculated on the basal inferoseptal, basal anteroseptal, and basal inferolateral segments, were also greater in users compared with the two other groups. Our results reported an increase in LV dyssynchrony in young AAS users that brought new evidences of a pathologic cardiac remodeling in this specific population.NEW & NOTEWORTHY Illicit androgenic anabolic steroids (AAS) use is widespread, but data on LV dyssynchrony are lacking, although it could be increased by a higher prevalence of myocardial fibrosis reported in this population. In AAS users, the decrease in LV strain was predominantly observed in interventricular segments. All dyssynchrony indices were higher in AAS users and several segments exhibited post-systolic shortening. These results showed an association between AAS consumption, LV remodeling, and dyssynchrony.

Regional myocardial function abnormalities are associated with macro- and microcirculation dysfunction in the metabolic syndrome: the RESOLVE study.

Abnormalities in myocardial and vascular function have been reported in the metabolic syndrome (MetS), but whether these alterations are related remains poorly documented. Our aim was accordingly to investigate interrelationships between macro- and microcirculatory vasoreactivity and left ventricular (LV) myocardial function in MetS patients. Eighty-eight MetS individuals and 44 age- and gender-matched healthy controls were enrolled. LV global longitudinal strain (GLS) was measured using Vector Velocity Imaging. Endothelial-dependent and independent reactivity in macro- and microcirculatory territories was established using flow-mediated dilation and nitrate-mediated dilation of the brachial artery and cutaneous blood flow measured with laser Doppler flowmetry in response to iontophoresis of acetylcholine and sodium nitroprusside, respectively. Carotid intima-media thickness (cIMT) was measured according to the Mannheim consensus. Compared to controls, MetS patients presented with reduced GLS (p < 0.001) increased cIMT and impaired (p < 0.001) endothelial and smooth muscle function of the brachial artery and the forearm skin microcirculation. Highly significant relationships (p < 0.01) were noticed between GLS and vascular outcomes. In addition, cIMT (ß = 0.21, p = 0.024) and microcirculatory endothelium-dependent reactivity (ß = - 0.20, p = 0.035) were identified as independent predictors of GLS. In MetS, abnormalities in myocardial function and endothelial as well as smooth muscle function of small and large arteries co-exist and are closely associated. This study supports a role for microvascular dysfunction in the pathogenesis of LV myocardial dysfunction.

Metabolic syndrome individuals with and without type 2 diabetes mellitus present generalized vascular dysfunction: cross-sectional study.

OBJECTIVES: The first objective of this study was to demonstrate differences within endothelial-dependent and endothelial-independent vasoreactivity in macro- and microcirculation beds among patients with metabolic syndrome (MetS) with and without type 2 diabetes mellitus (T2D) compared with healthy counterparts. The second objective was to determine relationships among the function of macro- and microvascular systems and abdominal adiposity, as well as inflammatory markers in the 3 groups. APPROACH AND RESULTS: Cross-sectional analyses of 53 patients with MetS without T2D and 25 with T2D, as well as aged 40 years and sex-matched healthy controls included microvascular (cutaneous blood flow measured with laser Doppler flowmetry in response to iontophoresis of acetylcholine and sodium nitroprusside), and macrovascular reactivity (flow-mediated dilation and nitrate-mediated dilation) along with anthropometric measures, plasma glucose, and insulin and inflammatory markers. Compared with controls, MetS participants showed depressed endothelial function of both micro- and macrocirculation beds. T2D in patients with MetS revealed an exacerbated vascular smooth muscle dysfunction in micro- and macrocirculation compared with MetS without T2D. Indices of micro- and macrocirculation were predominantly inversely related to abdominal fat and inflammatory markers. CONCLUSIONS: MetS was associated with endothelial-dependent and endothelial-independent dysfunction, affecting both the macro- and the microvascular systems. Participants with diabetes mellitus demonstrated the most severe smooth muscle dysfunction. The presence of central abdominal fat and systemic inflammation seems implicated in the pathogenesis of vascular dysfunctions in MetS.

Carbon monoxide increases inducible NOS expression that mediates CO-induced myocardial damage during ischemia-reperfusion.

We investigated the role of inducible nitric oxide (NO) synthase (iNOS) on ischemic myocardial damage in rats exposed to daily low nontoxic levels of carbon monoxide (CO). CO is a ubiquitous environmental pollutant that impacts on mortality and morbidity from cardiovascular diseases. We have previously shown that CO exposure aggravates myocardial ischemia-reperfusion (I/R) injury partly because of increased oxidative stress. Nevertheless, cellular mechanisms underlying cardiac CO toxicity remain hypothetical. Wistar rats were exposed to simulated urban CO pollution for 4 wk. First, the effects of CO exposure on NO production and NO synthase (NOS) expression were evaluated. Myocardial I/R was performed on isolated perfused hearts in the presence or absence of S-methyl-isothiourea (1 µM), a NOS inhibitor highly specific for iNOS. Finally, Ca(2+) handling was evaluated in isolated myocytes before and after an anoxia-reoxygenation performed with or without S-methyl-isothiourea or N-acetylcystein (20 µM), a nonspecific antioxidant. Our main results revealed that 1) CO exposure altered the pattern of NOS expression, which is characterized by increased neuronal NOS and iNOS expression; 2) cardiac NO production increased in CO rats because of its overexpression of iNOS; and 3) the use of a specific inhibitor of iNOS reduced myocardial hypersensitivity to I/R (infarct size, 29 vs. 51% of risk zone) in CO rat hearts. These last results are explained by the deleterious effects of NO and reactive oxygen species overproduction by iNOS on diastolic Ca(2+) overload and myofilaments Ca(2+) sensitivity. In conclusion, this study highlights the involvement of iNOS overexpression in the pathogenesis of simulated urban CO air pollution exposure.

Right ventricle free wall mechanics in metabolic syndrome without type-2 diabetes: effects of a 3-month lifestyle intervention program.

BACKGROUND: Growing evidence demonstrates subtle left ventricular myocardial dysfunction in patients with metabolic syndrome (MetS), with central obesity, glucose intolerance and inflammation emerging as important contributors. Whether these results can be translated to the right ventricle (RV) is not yet fully elucidated. Furthermore, although lifestyle intervention favorably impacts MetS components and inflammatory biomarkers, its effect on RV myocardial function remains unknown today. METHODS: Thirty-nine MetS adults free of diabetes were enrolled in a three month lifestyle intervention program including diet and physical exercise, and compared with forty healthy controls. Blood biochemistry, echocardiography including tissue Doppler imaging (TDI), and vector velocity imaging of the RV free wall to assess global longitudinal strain (GLS) and strain rates (SR) were obtained at baseline and after the intervention. RESULTS: Compared with controls, MetS patients presented similar right atrial and RV morphology but reduced systolic (P = 0.04) and early diastolic (P = 0.02) velocities of the tricuspid annulus. They showed attenuated RV GLS (-21.4 ± 4.5 vs -25.7 ± 4.9%, P < 0.001) as well as early diastolic (P = 0.003) and systolic (P < 0.001) SR. Multiple regression analyses revealed log PAI-1 active, (P < 0.001), log adiponectin, (P = 0.01), LV mass indexed (P = 0.004) and central fat (P = 0.03) as independent predictors of RV GLS (R2 = 0.46, P < 0.001). Biological markers of MetS and inflammation as well as RV GLS (-21.8 ± 3.8 vs -24.3 ± 3.0%, P = 0.009) and systolic (P = 0.003) and early diastolic (P = 0.01) SR, but not TDI indexes, significantly improved after diet and exercise training, and vector velocity imaging data in MetS following the lifestyle intervention no longer differed from controls. CONCLUSIONS: MetS is associated with subtle impairments in both RV free wall diastolic and systolic myocardial function which could be partly related to central-obesity induced changes in pro- and anti-inflammatory cytokines and left ventricular remodeling. The favorable impact of healthy dieting and physical activity on RV free wall mechanics indicates that cellular and sub-cellular alterations responsible for the RV myocardial abnormalities are probably not permanent and modifiable throughout adequate interventional strategies. TRIAL REGISTRATION: American National Institutes of Health database NCT00917917.

Increased myocardial dysfunction, dyssynchrony, and epicardial fat across the lifespan in healthy males.

BACKGROUND: Evaluation of sensitive myocardial mechanics with speckle tracking echocardiography (STE) across the lifespan may reveal early indicators of cardiovascular disease (CVD) risk. Epicardial adipose tissue (EAT) and left ventricular (LV) myocardial dyssynchrony; subclinical risk-factors of CVD, are of particular clinical interest. However, the evolution of EAT and LV-dyssynchrony across the lifespan, and their influence on myocardial dysfunction remains unclear. We aimed to establish a profile of the healthy aging-heart using conventional, tissue-Doppler imaging (TDI) and speckle-tracking echocardiography (STE), while also exploring underlying contributions from EAT and LV-dyssynchrony towards LV myocardial mechanics, independent of blood biology. METHODS: Healthy males aged 19-94 years were recruited through University-wide advertisements in Victoria and New-South Wales, Australia. Following strict exclusion criteria, basic clinical and comprehensive echocardiographic profiles (conventional, TDI and STE) were established. LV-dyssynchrony was calculated from the maximum-delay of time-to-peak velocity/strain in the four LV-annulus sites (TDI), and six LV-segments (STE longitudinal and circumferential axes). Epicardial fat diameter was obtained from two-dimensional grey-scale images in the parasternal long-axis. Blood biological measures included glycemia, hsCRP, triglycerides, total cholesterol, high-density and low-density lipoprotein levels. RESULTS: Three groups of 15 were assigned to young (<40 years), middle (40-65 years), and older (>65) aged categories. Five participants were excluded from STE analyses due to inadequate image quality. Decreased longitudinal strain, increased circumferential apical strain and LV twist were age-related. Moreover, independent of blood biology, significant increases were observed across age categories for EAT (young: 2.5 ± 0.9 mm, middle: 3.9 ± 1.0 mm, older 5.7 ± 2.4 mm; p < 0.01), longitudinal STE-dyssynchrony (young: 42 ± 7.7 ms, middle: 58.8 ± 18.9 ms, older 88.6 ± 18.2 ms; p < 0.05), and circumferential-basal STE-dyssynchrony (young: 50.2 ± 20.5 ms, middle: 75.9 ± 20.6 ms, older 97.9 ± 20.2 ms; p < 0.05). These variables collectively explained 37% and 31% (p < 0.01) of longitudinal strain and LV twist, respectively. CONCLUSIONS: This study enabled comprehensive profiling of LV mechanics at different stages of aging using sensitive echocardiographic technology. Novel findings included increased epicardial fat, and both longitudinal and circumferential LV-dyssynchrony across the healthy age groups. These factors may be key underlying contributors to myocardial dysfunction during aging, and their recognition may promote an advanced understanding of early signs of cardiovascular disease.

Atherogenic subfractions of lipoproteins in the treatment of metabolic syndrome by physical activity and diet - the RESOLVE trial.

BACKGROUND: We aimed to comprehensively evaluate lipoprotein profile including lipid particle size following a lifestyle intervention in metabolic syndrome (MetS) volunteers and to assess the associations between lipoprotein subfractions and carotid-intima-media-thickness (CIMT) - a surrogate indicator of atherogenesis. METHODS: 100 participants (50-70 years) from the RESOLVE trial, underwent a one-year follow-up beginning with a three-week residential program combining high exercise volume (15-20 h/week), restrictive diet (-500 kcal/day), and education. For baseline references, 40 aged-matched healthy controls were recruited. Independent associations between subfractions of lipoproteins and CIMT were evaluated using a generalized estimating equations model accounting for variation in correlations between repeated measures. The lipoprotein subfractions profile was assessed using Lipoprint® electrophoresis allowing to separate: the very low-density lipoprotein (VLDL) fraction, then the intermediate-density lipoprotein (IDL) C, B and A, the low-density lipoprotein (LDL) with subfractions 1 and 2 as large LDL and subfractions 3 to 7 as small dense LDL (sdLDL), and the high density lipoprotein (HDL) subfractions categorized into large, intermediate, and small HDL. Apolipoproteins A1 and B were also measured. RESULTS: 78 participants completed the program. At baseline, apolipoproteins B/A1, VLDL, sdLDL and small HDL were higher in MetS than in healthy controls; IDL, LDL size, large and intermediate HDL were lower. Despite time-related regains during the follow-up, lipoprotein subfractions traditionally involved in cardiovascular risk, such as sdLDL, improved immediately after the residential program with values closest to those of healthy controls. CIMT improved throughout the lifestyle intervention. Using a generalized estimating equations model, none of the subfractions of lipoproteins nor apolipoproteins were linked to CIMT. CONCLUSIONS: Lipoprotein subfractions traditionally involved in CVR, decreased after the 3-week residential program. During a 12 month follow-up, the time-related regains remained closer to the values of healthy controls than they were at baseline. CIMT improved throughout the lifestyle intervention. However, we failed to demonstrate a link between some lipoprotein subfractions and the atherogenicity directly measured from the wall thickness of arteries (CIMT). Further investigations are required to explore the atherogenicity of lipoprotein subfractions. TRIAL REGISTRATION: NCT00917917.

Additive effects of type 2 diabetes and metabolic syndrome on left ventricular torsion and linear deformation abnormalities during dobutamine stress echocardiography.

Objective: The interplay between metabolic syndrome (MS) and type 2 diabetes (T2D) on regional myocardial mechanics and the potential additional effects of their combination remain poorly understood. In this context, we evaluated left ventricular (LV) torsion and linear deformation at rest and under dobutamine (DB) stress in patients with T2D, MS or both. Methods: Thirty-nine T2D patients without MS (T2D), 37 MS patients free from T2D (MS), 44 patients with both T2D and MS (T2D-MS group) and 38 healthy patients (control group) were prospectively recruited. Speckle-tracking echocardiography (STE) was conducted at rest and low dose DB to evaluate LV myocardial longitudinal (LS) as well as circumferential (CS) strain and early diastolic strain rate (LSrd, CSrd) and twist-untwist mechanics. Results: At rest, MS, T2D and controls presented with similar resting LS and LSrd while significant lower values were obtained in T2D-MS compared to controls. DB revealed reduced LS, LSrd, CS and CSrd in MS and T2D groups compared to controls. In T2-MS, the decline in LS and LSrd established at rest was exacerbated under DB. Stress echocardiography revealed also lower basal rotation and subsequently lower twist in MS and T2D patients compared to controls. T2D-MS showed major impairments of apical rotation and twist under DB stress, with values significantly lower compared to the 3 other groups. From stepwise multiple linear regression analysis, epicardial adipose tissue for Δ (rest to DB) LS, numbers of MS factors for Δ CS and Δ Twist emerged as major independent predictors. Conclusion: These results demonstrate synergic and additive effects of T2D and MS on LV torsion and linear deformation abnormalities in asymptomatic patients with metabolic diseases. They also highlight the usefulness of speckle tracking echocardiography under DB stress in detecting multidirectional myocardial mechanics impairments that can remain barely detectable at rest, such as in isolated T2D or MS patients.

Corrigendum: Left Ventricular Strains and Myocardial Work in Adolescents With Anorexia Nervosa.

[This corrects the article DOI: 10.3389/fcvm.2022.798774.].

Cardiac Remodeling and Its Determinants in Anorexia Nervosa Adolescents: Impact of Weight Recovery.

Cardiovascular alterations in anorexia nervosa (AN) adolescents include bradycardia and decreased systolic blood pressure and left ventricular mass. However, their determinants remain poorly understood. We assessed the associations between morphological and functional left ventricular (LV) remodeling, autonomic control by heart rate variability (HRV) analysis, thyroid hormones and brain natriuretic peptide (BNP) levels in AN female adolescents without or with weight recovery (WR). Fifty-nine female adolescents including 16 AN patients without WR (mean age 13.9 years (10−16)), 10 AN patients with WR (15.7 years (12−18)) and 33 controls (14.1 years (10−18)) underwent night heart rate (HR) recording to measure HRV (and especially SD1/SD2, the ratio between instantaneous (SD1) and long-term (SD2) standard deviation of R-R intervals, reflecting sympatho-vagal balance), speckle tracking echocardiography to assess LV global longitudinal strain (GLS) and blood test for dosage of tri-iodothyronine (T3) hormone and NT-proBNP. Compared to controls, AN patients without WR presented with lower HR (55 ± 7 vs. 68 ± 6 bpm; p < 0.001), parasympathetic hyperactivity, and higher GLS (−19.2 ± 1.8 vs. −16.9 ± 2.8%; p = 0.009). These alterations were partly abolished in AN patients with WR. In a multivariate regression analysis, T3 was the main factor explaining the variance of SD1/SD2, a sympatho-vagal balance marker. NT-proBNP levels were not correlated with cardiac alterations. AN patients had parasympathetic hyperactivity linked with their rate of T3, and a higher GLS. These alterations were partly restored in AN patients with WR.

Anabolic Steroids Use Is Associated with Impairments in Atrial and Ventricular Cardiac Structure and Performance in Athletes.

PURPOSE: Despite potential severe cardiac side effects, anabolic androgenic steroids (AAS) are increasingly used by strength athletes. However, previous echocardiographic studies focused on the left ventricular (LV) strains but did not assess LV twist and untwist mechanics. Moreover, left atrial (LA) function has been often neglected, and its stiffness, an important determinant of LA reservoir function, has never been challenged. The aim of this study was to investigate the effects of AAS on LA and LV morphologies and functions in strength athletes. METHODS: Fifty subjects including 20 strength-trained young athletes age 32.0 ± 8.5 yr with a mean duration of AAS use of 4.7 ± 1.8 yr (users), 15 athletes with no history of AAS use (nonusers) and 15 sedentary controls underwent speckle tracking echocardiography to assess LA and LV morphology and function. RESULTS: Users showed higher LA reservoir dysfunction than nonusers (33.7% ± 10.9% vs 44.9% ± 9.9% respectively, P = 0.004) and higher LA stiffness (0.13 ± 0.05 vs 0.19 ± 0.08 A.U., respectively; P = 0.02), higher LV mass index and lower global and regional LV diastolic and systolic dysfunction (global longitudinal strain: -15.5% ± 3.2% vs -18.9% ± 1.8% respectively; P = 0.003), with a drop of LV twist-untwist mechanics (untwisting velocity: 61.5°·s-1 ± 20.2°·s-1 vs 73.7°·s-1 ± 16.1°·s-1 respectively, P = 0.04). There were significant correlations between LV mass and LV apical rotation (P = 0.003, r = 0.44) and diastolic longitudinal strain rate (P = 0.015, r = 0.33). CONCLUSIONS: Our results showing significant LA and LV remodeling and dysfunctions in young AAS using athletes are alarming. Screening echocardiography based on speckle tracking echocardiography parameters for early diagnosis, as well as a stronger awareness in athletes and in physicians are warranted in this context.

Non-invasive biomarkers of non-alcoholic fatty liver disease in patients with Metabolic Syndrome: insights from the RESOLVE study.

BACKGROUND: The aim of the present study was to evaluate i) the presence of liver steatosis using Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI) and Liver Fat Score (LFS) in patients suffering from MS and ii) the association of FLI, HSI and LFS with the cardiometabolic risks. METHODS: A total of 91 patients with MS (MS; 39 men, 52 women) and 44 age matched healthy subjects (Control; 23 men and 21 women) were enrolled in the study. A continuous cardiometabolic score (MetsScore) and the noninvasive tests of hepatic steatosis were calculated for comparison and association analysis. RESULTS: Liver steatosis was detected in 86%, 84% and 80% of people diagnosed with MS using FLI, HSI and LFS respectively and MetsScore increases with FLI severity (p<0,05). Also, FLI and LFS were positively associated with MetsScore (p<0.01 and p<0.05 respectively) but not HSI. Multivariate linear regression models revealed that FLI has a stronger association with MetsScore compared with HSI and LFS (p<0,001). CONCLUSIONS: FLI is associated with the severity of MS and represent a good indicator to assess the relation between liver steatosis and a cardiometabolic disorders in clinical routine.

Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress.

Arrhythmias following cardiac stress are a key predictor of death in healthy population. Carbon monoxide (CO) is a ubiquitous pollutant promoting oxidative stress and associated with hospitalization for cardiovascular disease and cardiac mortality. We investigated the effect of chronic CO exposure on the occurrence of arrhythmic events after a cardiac stress test and the possible involvement of related oxidative stress. Wistar rats exposed chronically (4 weeks) to sustained urban CO pollution presented more arrhythmic events than controls during recovery after cardiac challenge with isoprenaline in vivo. Sudden death occurred in 22% of CO-exposed rats versus 0% for controls. Malondialdehyde (MDA), an end-product of lipid peroxidation, was increased in left ventricular tissue of CO-exposed rats. Cardiomyocytes isolated from CO-exposed rats showed higher reactive oxygen species (ROS) production (measured with MitoSox Red dye), higher diastolic Ca(2+) resulting from SR calcium leak and an higher occurrence of irregular Ca(2+) transients (measured with Indo-1) in comparison to control cells after a high pacing sequence. Acute treatment with a ROS scavenger (N-acetylcysteine, 20 mmol/L, 1 h) prevented this sequence of alterations and decreased the number of arrhythmic cells following high pacing. Chronic CO exposure promotes oxidative stress that alters Ca(2+) homeostasis (through RYR2 and SERCA defects) and thereby mediates the triggering of ventricular arrhythmia after cardiac stress that can lead to sudden death.

Carbon monoxide pollution promotes cardiac remodeling and ventricular arrhythmia in healthy rats.

RATIONALE: Epidemiologic studies associate atmospheric carbon monoxide (CO) pollution with adverse cardiovascular outcomes and increased cardiac mortality risk. However, there is a lack of data regarding cellular mechanisms in healthy individuals. OBJECTIVES: To investigate the chronic effects of environmentally relevant CO levels on cardiac function in a well-standardized healthy animal model. METHODS: Wistar rats were exposed for 4 weeks to filtered air (CO < 1 ppm) or air enriched with CO (30 ppm with five peaks of 100 ppm per 24-h period), consistent with urban pollution. Myocardial function was assessed by echocardiography and analysis of surface ECG and in vitro by measuring the excitation-contraction coupling of single left ventricular cardiomyocytes. MEASUREMENTS AND MAIN RESULTS: Chronic CO pollution promoted left ventricular interstitial and perivascular fibrosis, with no change in cardiomyocyte size, and had weak, yet significant, effects on in vivo cardiac function. However, both contraction and relaxation of single cardiomyocytes were markedly altered. Several changes occurred, including decreased Ca(2+) transient amplitude and Ca(2+) sensitivity of myofilaments and increased diastolic intracellular Ca(2+) subsequent to decreased SERCA-2a expression and impaired Ca(2+) reuptake. CO pollution increased the number of arrhythmic events. Hyperphosphorylation of Ca(2+)-handling and sarcomeric proteins, and reduced responses to beta-adrenergic challenge were obtained, suggestive of moderate CO-induced hyperadrenergic state. CONCLUSIONS: Chronic CO exposure promotes a pathological phenotype of cardiomyocytes in the absence of underlying cardiomyopathy. The less severe phenotype in vivo suggests a role for compensatory mechanisms. Arrhythmia propensity may derive from intracellular Ca(2+) overload.

Key role of left ventricular untwisting in endurance cyclists at onset of exercise.

The rise in oxygen consumption during the transition from rest to exercise is faster in those who are endurance-trained than those who have sedentary lifestyles, partly due to a more efficient cardiac response. However, data regarding this acute cardiac response in trained individuals are limited to heart rate (HR), stroke volume, and cardiac output. Considering this, we compared cardiac kinetics, including left ventricular (LV) strains and twist/untwist mechanics, between endurance-trained cyclists and their sedentary counterparts. Twenty young, male, trained cyclists and 23 untrained participants aged 18-25 yr performed five similar constant workload exercises on a cyclo-ergometer (target HR: 130 beats/min). During each session, LV myocardial diastolic and systolic linear strains, as well as torsional mechanics, were assessed using speckle-tracking echocardiography. Cardiac function was evaluated every 15 s during the first minute and every 30 s thereafter, until 240 s. Stroke volume increased during the first 30-45 s in both groups but to a significantly greater extent in trained cyclists (31% vs. 24%). Systolic parameters were similar in both groups. Transmitral peak filling velocity and peak filling rate responded faster to exercise and with greater amplitude in trained cyclists. Left ventricular filling pressure was lower in the former, whereas LV relaxation was greater but only at the base of the left ventricle. Basal rotation and peak untwisting rate responded faster and to a greater extent in the cyclists. This study provides new mechanical insights into the key role of LV untwisting in the more efficient acute cardiac response of endurance-trained athletes at onset of exercise.NEW & NOTEWORTHY Our study assessed for the first time, to our knowledge, the kinetics of left ventricular function during the transition from rest to constant-load exercise in endurance-trained subjects. We observed a faster cardiac response in cyclists characterized by a faster response of cardiac output, left ventricular transmitral filling, basal rotation, and untwisting. This study highlighted the key role of left ventricular twisting mechanics in the more efficient acute cardiac response of endurance-trained athletes at onset of exercise.