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1.
Novel effects of the gastrointestinal hormone secretin on cardiac metabolism and renal function.
Laurila, S, Rebelos, E, Lahesmaa, M, Sun, L, Schnabl, K, Peltomaa, TM, Klén, R, U-Din, M, Honka, MJ, Eskola, O, et al
American journal of physiology. Endocrinology and metabolism. 2022;(1):E54-E62
Abstract
The cardiac benefits of gastrointestinal hormones have been of interest in recent years. The aim of this study was to explore the myocardial and renal effects of the gastrointestinal hormone secretin in the GUTBAT trial (NCT03290846). A placebo-controlled crossover study was conducted on 15 healthy males in fasting conditions, where subjects were blinded to the intervention. Myocardial glucose uptake was measured with [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography. Kidney function was measured with [18F]FDG renal clearance and estimated glomerular filtration rate (eGFR). Secretin increased myocardial glucose uptake compared with placebo (secretin vs. placebo, means ± SD, 15.5 ± 7.4 vs. 9.7 ± 4.9 μmol/100 g/min, 95% confidence interval (CI) [2.2, 9.4], P = 0.004). Secretin also increased [18F]FDG renal clearance (44.5 ± 5.4 vs. 39.5 ± 8.5 mL/min, 95%CI [1.9, 8.1], P = 0.004), and eGFR was significantly increased from baseline after secretin, compared with placebo (17.8 ± 9.8 vs. 6.0 ± 5.2 ΔmL/min/1.73 m2, 95%CI [6.0, 17.6], P = 0.001). Our results implicate that secretin increases heart work and renal filtration, making it an interesting drug candidate for future studies in heart and kidney failure.NEW & NOTEWORTHY Secretin increases myocardial glucose uptake compared with placebo, supporting a previously proposed inotropic effect. Secretin also increased renal filtration rate.
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2.
Factor V Leiden Does Not Modify the Phenotype of Acute Coronary Syndrome or the Extent of Myocardial Necrosis.
Mahmoodi, BK, Eriksson, N, Vos, GJA, Meijer, K, Siegbahn, A, James, S, Wallentin, L, Ten Berg, JM
Journal of the American Heart Association. 2021;(11):e020025
Abstract
Background The prothrombotic defect factor V Leiden (FVL) may confer higher risk of ST-segment-elevation myocardial infarction (STEMI), compared with non-ST-segment-elevation acute coronary syndrome, and may be associated with more myocardial necrosis caused by higher thrombotic burden. Methods and Results Patients without history of cardiovascular disease were selected from 2 clinical trials conducted in patients with acute coronary syndrome. FVL was defined as G-to-A substitution at nucleotide 1691 in the factor V (factor V R506Q) gene. Odds ratios were calculated for the association of FVL with STEMI adjusted for age and sex in the overall population and in the subgroups including sex, age (≥70 versus <70 years), and traditional cardiovascular risk factors. The peak biomarker levels (ie, creatine kinase-myocardial band and high-sensitivity troponin I or T) after STEMI were contrasted between FVL carriers and noncarriers. Because of differences in troponin assays, peak high-sensitivity troponin levels were converted to a ratio scale. The prevalence of FVL mutation was comparable in patients with STEMI (6.0%) and non-ST-segment-elevation acute coronary syndrome (5.8%). The corresponding sex- and age-adjusted odds ratio was 1.06 (95% CI, 0.86-1.30; P=0.59) for the association of FVL with STEMI. Subgroup analysis did not show any differences. In patients with STEMI, neither the median peak creatine kinase-myocardial band nor the peak high-sensitivity troponin ratio showed any differences between wild-type and FVL carriers (P for difference: creatine kinase-myocardial band=0.33; high sensitivity troponin ratio=0.54). Conclusions In a general population with acute coronary syndrome, FVL did not discriminate between a STEMI or non-ST-segment-elevation acute coronary syndrome presentation and was unrelated to peak cardiac necrosis markers in patients with STEMI. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00391872 and NCT01761786.
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3.
SGLT2 Inhibition Does Not Affect Myocardial Fatty Acid Oxidation or Uptake, but Reduces Myocardial Glucose Uptake and Blood Flow in Individuals With Type 2 Diabetes: A Randomized Double-Blind, Placebo-Controlled Crossover Trial.
Lauritsen, KM, Nielsen, BRR, Tolbod, LP, Johannsen, M, Hansen, J, Hansen, TK, Wiggers, H, Møller, N, Gormsen, LC, Søndergaard, E
Diabetes. 2021;(3):800-808
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular morbidity and mortality in individuals with type 2 diabetes. Beneficial effects have been attributed to increased ketogenesis, reduced cardiac fatty acid oxidation, and diminished cardiac oxygen consumption. We therefore studied whether SGLT2 inhibition altered cardiac oxidative substrate consumption, efficiency, and perfusion. Thirteen individuals with type 2 diabetes were studied after 4 weeks' treatment with empagliflozin and placebo in a randomized, double-blind, placebo-controlled crossover study. Myocardial palmitate and glucose uptake were measured with 11C-palmitate and 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT). Oxygen consumption and myocardial external efficiency (MEE) were measured with 11C-acetate PET/CT. Resting and adenosine stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) were measured using 15O-H2O PET/CT. Empagliflozin did not affect myocardial free fatty acids (FFAs) uptake but reduced myocardial glucose uptake by 57% (P < 0.001). Empagliflozin did not change myocardial oxygen consumption or MEE. Empagliflozin reduced resting MBF by 13% (P < 0.01), but did not significantly affect stress MBF or MFR. In conclusion, SGLT2 inhibition did not affect myocardial FFA uptake, but channeled myocardial substrate utilization from glucose toward other sources and reduced resting MBF. However, the observed metabolic and hemodynamic changes were modest and most likely contribute only partially to the cardioprotective effect of SGLT2 inhibition.
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4.
A prospective randomized study comparing effects of empagliflozin to sitagliptin on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes: the ASSET study.
Hiruma, S, Shigiyama, F, Hisatake, S, Mizumura, S, Shiraga, N, Hori, M, Ikeda, T, Hirose, T, Kumashiro, N
Cardiovascular diabetology. 2021;(1):32
Abstract
BACKGROUND While the cardioprotective benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been established in patients with cardiovascular disease (CVD), their advantages over other anti-diabetic drugs at earlier stages remain unclear. We compared the cardioprotective effects of empagliflozin, an SGLT2 inhibitor, with those of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, focusing on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes mellitus (T2DM) without CVD complications. METHODS This was a prospective, randomized, open-label, blinded-endpoint, parallel-group trial that enrolled 44 Japanese patients with T2DM. The patients were randomized for 12-week administration of empagliflozin or sitagliptin. Pericardial fat accumulation and myocardial triglyceride content were evaluated by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Echocardiography, 123I-β-methyl-iodophenyl pentadecanoic acid myocardial scintigraphy, and laboratory tests were performed at baseline and after the 12-week treatment period. RESULTS The patients were middle-aged (50.3 ± 10.7 years, mean ± standard deviation) and overweight (body mass index 29.3 ± 4.9 kg/m2). They had a short diabetes duration (3.5 ± 3.2 years), HbA1c levels of 7.1 ± 0.8%, and preserved cardiac function (ejection fraction 73.8 ± 5.0%) with no vascular complications, except for one baseline case each of diabetic nephropathy and peripheral arterial disease. After the 12-week treatment, no differences from baseline were observed between the two groups regarding changes in pericardial, epicardial, and paracardial fat content; myocardial triglyceride content; cardiac function and mass; and cardiac fatty acid metabolism. However, considering cardiometabolic biomarkers, high-density lipoprotein cholesterol and ketone bodies, including β-hydroxybutyric acid, were significantly increased, whereas uric acid, plasma glucose, plasma insulin, and homeostasis model assessment of insulin resistance were significantly lower in the empagliflozin group than in the sitagliptin group (p < 0.05). CONCLUSIONS Although the effects on cardiac fat and function were not statistically different between the two groups, empagliflozin exhibited superior effects on cardiometabolic biomarkers, such as uric acid, high-density lipoprotein cholesterol, ketone bodies, and insulin sensitivity. Therefore, when considering the primary preventive strategies for CVD, early supplementation with SGLT2 inhibitors may be more beneficial than DPP-4 inhibitors, even in patients with early-stage T2DM without current CVD complications. CLINICAL TRIAL REGISTRATION UMIN000026340; registered on February 28, 2017. https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000030257.
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5.
Seven-day overfeeding enhances adipose tissue dietary fatty acid storage and decreases myocardial and skeletal muscle dietary fatty acid partitioning in healthy subjects.
Noll, C, Montastier, É, Amrani, M, Kunach, M, Frisch, F, Fortin, M, Bouffard, L, Dubreuil, S, Phoenix, S, Cunnane, SC, et al
American journal of physiology. Endocrinology and metabolism. 2020;(2):E286-E296
Abstract
Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV) function is associated with insulin resistance in prediabetes. We hypothesized that enhanced myocardial DFA partitioning and reduced LV function might be induced concomitantly with reduced insulin sensitivity upon a 7-day hypercaloric (+50% in caloric intake), high-saturated fat (~11%energy), and simple carbohydrates (~54%energy) diet (HIGHCAL) versus an isocaloric diet (ISOCAL) with a moderate amount of saturated fat (~8%energy) and carbohydrates (~50%energy). Thirteen healthy subjects (7 men/6 women) underwent HIGHCAL versus ISOCAL in a randomized crossover design, with organ-specific DFA partitioning and LV function measured using the oral 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid and [11C]acetate positron emission tomography methods at the end of both interventions. HIGHCAL induced a decrease in insulin sensitivity indexes with no significant change in body composition. HIGHCAL led to increased subcutaneous abdominal (+4.2 ± 1.6%, P < 0.04) and thigh (+2.4 ± 1.2%, P < 0.08) adipose tissue storage and reduced cardiac (-0.31 ± 0.11 mean standard uptake value [(SUV), P < 0.03] and skeletal muscle (-0.17 ± 0.08 SUV, P < 0.05) DFA partitioning without change in LV function. We conclude that early increase in adipose tissue DFA storage protects the heart and skeletal muscles from potential deleterious effects of DFA.
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6.
Noninvasive Imaging Estimation of Myocardial Iron Repletion Following Administration of Intravenous Iron: The Myocardial-IRON Trial.
Núñez, J, Miñana, G, Cardells, I, Palau, P, Llàcer, P, Fácila, L, Almenar, L, López-Lereu, MP, Monmeneu, JV, Amiguet, M, et al
Journal of the American Heart Association. 2020;(4):e014254
Abstract
Background Intravenous ferric carboxymaltose (FCM) improves symptoms, functional capacity, and quality of life in heart failure and iron deficiency. The mechanisms underlying these effects are not fully understood. The aim of this study was to examine changes in myocardial iron content after FCM administration in patients with heart failure and iron deficiency using cardiac magnetic resonance. Methods and Results Fifty-three stable heart failure and iron deficiency patients were randomly assigned 1:1 to receive intravenous FCM or placebo in a multicenter, double-blind study. T2* and T1 mapping cardiac magnetic resonance sequences, noninvasive surrogates of intramyocardial iron, were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. Results are presented as least-square means with 95% CI. The primary end point was the change in T2* and T1 mapping at 7 and 30 days. Median age was 73 (65-78) years, with N-terminal pro-B-type natriuretic peptide, ferritin, and transferrin saturation medians of 1690 pg/mL (1010-2828), 63 ng/mL (22-114), and 15.7% (11.0-19.2), respectively. Baseline T2* and T1 mapping values did not significantly differ across treatment arms. On day 7, both T2* and T1 mapping (ms) were significantly lower in the FCM arm (36.6 [34.6-38.7] versus 40 [38-42.1], P=0.025; 1061 [1051-1072] versus 1085 [1074-1095], P=0.001, respectively). A similar reduction was found at 30 days for T2* (36.3 [34.1-38.5] versus 41.1 [38.9-43.4], P=0.003), but not for T1 mapping (1075 [1065-1085] versus 1079 [1069-1089], P=0.577). Conclusions In patients with heart failure and iron deficiency, FCM administration was associated with changes in the T2* and T1 mapping cardiac magnetic resonance sequences, indicative of myocardial iron repletion. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03398681.
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7.
Myocardial Injury After Balloon Predilatation Versus Direct Transcatheter Aortic Valve Replacement: Insights From the DIRECTAVI Trial.
Akodad, M, Roubille, F, Marin, G, Lattuca, B, Macia, JC, Delseny, D, Gandet, T, Robert, P, Schmutz, L, Piot, C, et al
Journal of the American Heart Association. 2020;(24):e018405
Abstract
Background Myocardial injury is associated with higher mortality after transcatheter aortic valve replacement (TAVR) and might be increased by prior balloon aortic valvuloplasty (BAV). We aimed to evaluate the impact of prior BAV versus direct prosthesis implantation on myocardial injury occurring after (TAVR) with balloon-expandable prostheses. Methods and Results The DIRECTAVI (Direct Transcatheter Aortic Valve Implantation) trial, an open-label randomized study, demonstrated noninferiority of TAVR without BAV (direct TAVR group) compared with systematic BAV (BAV group) with the Edwards SAPIEN 3 valve. High-sensitivity troponin was assessed before and the day after the procedure. Incidence of myocardial injury after the procedure (high-sensitivity troponin elevation >15× the upper reference limit [14 ng/L]) was the main end point. Impact of myocardial injury on 1-month adverse events (all-cause mortality, stroke, major bleeding, major vascular complications, transfusion, acute kidney injury, heart failure, pacemaker implantation, and aortic regurgitation) was evaluated. Preprocedure and postprocedure high-sensitivity troponin levels were available in 211 patients. The mean age of patients was 83 years (78-87 years), with 129 men (61.1%). Mean postprocedure high-sensitivity troponin was 124.9±81.4 ng/L in the direct TAVR group versus 170.4±127.7 ng/L in the BAV group (P=0.007). Myocardial injury occurred in 42 patients (19.9%), including 13 patients (12.2%) in the direct TAVR group and 29 (27.9%) in the BAV group (P=0.004). BAV increased by 2.8-fold (95% CI, 1.4-5.8) myocardial injury probability. Myocardial injury was associated with 1-month adverse events (P=0.03). Conclusions BAV increased the incidence and magnitude of myocardial injury after TAVR with new-generation balloon-expandable valves. Myocardial injury was associated with 1-month adverse events. These results argue in favor of direct SAPIEN 3 valve implantation. Registration URL: https://www.Clinicaltrials.gov; Unique identifier: NCT02729519.
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8.
Association Between Adherence To The French Dietary Guidelines And Lower Resting Heart Rate, Longer Diastole Duration, And Lower Myocardial Oxygen Consumption. The NUTRIVASC Study.
Fysekidis, M, Kesse-Guyot, E, Valensi, P, Arnault, N, Galan, P, Hercberg, S, Cosson, E
Vascular health and risk management. 2019;:463-475
Abstract
BACKGROUND To investigate whether chronic adherence to the French Nutrition and Health Program (PNNS) guidelines was associated with better cardiovascular health. METHODS A study nested within the SU.VI.MAX2 cohort was conducted on participants without cardiovascular risk factors. Long-term adherence to the PNNS guidelines was estimated using validated dietary scores from 2007 and 2012. Individuals who did (PNNS+) and did not (PNNS-) continuously adhere to the PNNS guidelines were included. Applanation tonometry, impedance cardiography, laser doppler flowmetry, heart rate, heart rate variability, endothelial function was used for the assessment of cardiovascular health. RESULTS A total of 49 subjects (mean age 65.4 ± 5.6 years, 75.5% women) had been included. Those in the PNNS+ group (n=26) were older, had a higher BMI and fat mass than those in the PNNS- group, both groups had similar metabolic parameters. After adjusting for sex, age, and BMI, PNNS+ subjects were found to have a lower heart rate (60.2 ± 8.0 vs 64.3 ± 8.4 beats/min, p=0.042), a lower heart rate × systolic blood pressure product (7166 ± 1323 vs 7788 ± 1680 beats× mmHg/min, p = 0.009), a longer diastole duration (66.7 ± 3.1% vs 64.6 ± 4.1% of the cardiac cycle duration, p=0.049), and a shorter tension-time index (2145 ± 489 vs 2307 ± 428 ms * mmHg, p=0.018) compared to the PNNS- group. CONCLUSION Long-term adherence to the PNNS guidelines had a favorable impact on heart rate, diastole duration, and myocardial oxygen consumption. CLINICAL TRIAL REGISTRATION NUMBER NCT01579409.
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9.
Effect of ticagrelor on brain natriuretic peptide, heart rate and myocardial enzymes in patients with coronary atherosclerotic heart disease after stenting.
Jia, D, Qin, B, Wei, X
Pakistan journal of pharmaceutical sciences. 2019;(3 Special):1371-1373
Abstract
The main aim of the current work was to investigate the application of ticagrelor in patients with coronary atherosclerotic heart disease (CAHD) and its effects on brain natriuretic peptide (BNP), heart rate (HR) and myocardial enzymes. Seventy-four postoperative patients who underwent stenting for CAHD were selected as subjects, randomly divided into control group (n=37) and observation group (n=37). The control group was treated with clopidogrel after operation, while the observation group was given ticagrelor treatment. The plasma BNP, HR, myocardial zymogram and adverse cardiac events were compared between the two groups. SPSS18.0 software was used for statistical analysis and the count data was analyzed by χ2 test and the measurement data was detected by t-test The levels of BNP, HR, creatine kinase isoenzyme (CK-MB) and troponin (cTnI) in the observation group were all lower than those in the control group at 3 months after treatment (P<0.05). There was no significant difference in the incidence of myocardial infarction, angina pectoris and arrhythmia between the two groups at 3 months after treatment (P>0.05). The utilization of ticagrelor in patients with postoperative stenting for CAHD improved the BNP, HR and myocardial enzyme level in patients, and also reduced the incidence of adverse cardiac events.
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10.
Changes in myocardial iron content following administration of intravenous iron (Myocardial-IRON): Study design.
Miñana, G, Cardells, I, Palau, P, Llàcer, P, Fácila, L, Almenar, L, López-Lereu, MP, Monmeneu, JV, Amiguet, M, González, J, et al
Clinical cardiology. 2018;(6):729-735
Abstract
Treatment with intravenous ferric carboxymaltose (FCM) has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure and iron deficiency. However, the underlying mechanisms for these beneficial effects remain undetermined. The aim of this study is to quantify cardiac magnetic resonance changes in myocardial iron content after administration of intravenous FCM in patients with heart failure and iron deficiency and contrast them with parameters of heart failure severity. This is a multicenter, double-blind, randomized study. Fifty patients with stable symptomatic heart failure, left ventricular ejection fraction <50%, and iron deficiency will be randomly assigned 1:1 to receive intravenous FCM or placebo. Intramyocardial iron will be evaluated by T2* and T1 mapping cardiac magnetic resonance sequences before and at 7 and 30 days after FCM. After 30 days, patients assigned to placebo will receive intravenous FCM in case of persistent iron deficiency. The main endpoint will be changes from baseline in myocardial iron content at 7 and 30 days. Secondary endpoints will include the correlation of these changes with left ventricular ejection fraction, functional capacity, quality of life, and cardiac biomarkers. The results of this study will add important knowledge about the effects of intravenous FCM on myocardial tissue and cardiac function. We hypothesize that short-term (7 and 30 days) myocardial iron content changes after intravenous FCM, evaluated by cardiac magnetic resonance, will correlate with simultaneous changes in parameters of heart failure severity. The study is registered at http://www.clinicaltrials.gov (NCT03398681).