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Ventricular diastolic mechanical properties are important determinants of cardiac function and are optimized by changes in cardiac structure and physical properties. Oncorhynchus masou masou is an anadromous migratory fish of the Salmonidae family, and several ecological studies on it have been conducted; however, the cardiac functions of the fish are not well known. Therefore, we investigated ventricular diastolic function in landlocked (masu salmon) and sea-run (cherry salmon) types at 29–30 months post fertilization. Pulsed-wave Doppler echocardiography showed that the atrioventricular inflow waveforms of cherry salmon were biphasic with early diastolic filling and atrial contraction, whereas those of masu salmon were monophasic with atrial contraction. In addition, end-diastolic pressure–volume relationship analysis revealed that the dilatability per unit myocardial mass of the ventricle in cherry salmon was significantly suppressed compared to that in masu salmon, suggesting that the ventricle of the cherry salmon was relatively stiffer (relative ventricular stiffness index; p = 0.0263). Contrastingly, the extensibility of cardiomyocytes, characterized by the expression pattern of Connectin isoforms in their ventricles, was similar in both types. Histological analysis showed that the percentage of the collagen accumulation area in the compact layer of cherry salmon increased compared with that of the masu salmon, which may contribute to ventricle stiffness. Although the heart mass of cherry salmon was about 11-fold greater than that of masu salmon, there was no difference in the morphology of the isolated cardiomyocytes, suggesting that the heart of the cherry salmon grows by cardiomyocyte proliferation, but not cell hypertrophy. The cardiac physiological function of the teleosts varies with differences in their developmental processes and life history. Our multidimensional analysis of the O. masou heart may provide a clue to the process by which the heart acquires a biphasic blood-filling pattern, i.e., a ventricular diastolic suction. [ABSTRACT FROM AUTHOR]

Background/aim: Vitamin D insufficiency is a common public health problem that is often unrecognized in children with congenital heart disease, and is not generally evaluated at congenital heart disease (CHD) follow-up. Recent studies have suggested that inadequate vitamin D status may have an adverse effect on cardiovascular health. This study investigates the relationship between vitamin D levels and hemodynamic parameters in children with CHD. Methods: Included in the study 40 patients (25 females, 15 males) with CHD, who were evaluated for Ross heart failure score, vitamin D, parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase (ALP), whole blood count (WBC) and echocardiographic measurements, and all measurements were repeated in the third month of the therapy. Results: The mean vitamin D level was 16.4 ± 6.6 ug/L before and 27.5 ± 9.9 μg/L in the third month of therapy, while the mean PTH level was 53.3 ± 34.9 pg/mL before and 43.8 ± 21.4 pg/mL in the third month of therapy. The mean WBC was 8084 ± 2324/µL before and 7378±1893/µL in the third month of the therapy, and the mean platelet (PLT) count was 280,897 ± 80,119/µL before and 307,179 ± 60,202/µL in the third month of the therapy. The mean ejection fraction (EF) was 64% ± 7.2% before and 66.7% ± 6.2% in the third month of therapy, while the right ventricle (RV) myocardial performance index (MPI) was 32.1% ± 6.7% before and 28.9% ± 6.5% in the third month of the therapy. IL10 level was increased in four patients in the third month of therapy. A statistically significant decrease in PTH level and WBC, and an increase in PLT number and IL-10 level were detected by the therapy. Furthermore, echocardiographic findings revealed a statistically significant increase in EF and a decrease in RVMPI attributable to the therapy. Conclusion: The decreased levels of PTH, which is a proinflammatory marker, the increases in IL-10, which is an antiinflammatory cytokine, and the decreases in the number of WBC resulting from vitamin D treatment demonstrate the antiinflammatory effects of vitamin D. An improvement in EF means improvement in left ventricular contractility, while a decrease in RV MPI has been shown to improve the systolic and diastolic function of the right ventricle. These results suggest that vitamin D therapy has a positive effect on the heart, and so vitamin D levels should be evaluated during the routine follow-up of congenital heart disease. [ABSTRACT FROM AUTHOR]

Shear wave elastography (SWE) is a promising technique used to assess cardiac function through the evaluation of cardiac stiffness non-invasively. However, in the literature, SWE varies in terms of tissue motion data (displacement, velocity or acceleration); method used to characterize mechanical wave propagation (time domain [TD] vs. frequency domain [FD]); and the metric reported (wave speed [WS], shear or Young's modulus). This variety of reported methodologies complicates comparison of reported findings and sheds doubt on which methodology better approximates the true myocardial properties. We therefore conducted a simulation study to investigate the accuracy of various SWE data analysis approaches while varying cardiac geometry and stiffness. Lower WS values were obtained by the TD method compared with the FD method. Acceleration-based WS estimates in the TD were systematically larger than those based on velocity (∼10% difference). These observations were confirmed by TD analysis of 32 in vivo SWE mechanical wave measurements. In vivo data quality is typically too low for accurate FD analysis. Therefore, our study suggests using acceleration-based TD analysis for in vivo SWE to minimize underestimation of the true WS and, thus, to maximize the sensitivity of SWE to detect stiffness changes resulting from pathology. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the main cause of death worldwide. Recent studies have revealed the influence of histone-modifying enzymes in cardiac remodeling and heart dysfunction. The Set7 methyltransferase regulates the expression of several genes through the methylation of histones and modulates the activity of non-histone proteins. However, the role of Set7 in cardiac remodeling and heart dysfunction remains unknown. To address this question, wild-type (WT) and Set7 knockout (KO) male mice were injected with isoproterenol or saline. WT mice injected with isoproterenol displayed a decrease in Set7 activity in the heart. In addition, WT and Set7 KO mice injected with isoproterenol exhibited cardiac hypertrophy. Interestingly, Set7 deletion exacerbated cardiac hypertrophy in response to isoproterenol but attenuated myocardial fibrosis. Echocardiograms revealed that WT mice injected with isoproterenol had lowered ejection fractions and fractional shortening, and increased E′-wave deceleration time and E/A ratio compared with their controls. Conversely, Set7 KO mice did not show alteration in these parameters in response to isoproterenol. However, prolonged exposure to isoproterenol induced cardiac dysfunction both in WT and Set7 KO mice. Both isoproterenol and Set7 deletion changed the transcriptional profile of the heart. Moreover, Set7 deletion increased the expression of Pgc1α and mitochondrial DNA content in the heart, and reduced the expression of cellular senescence and inflammation markers in response to isoproterenol. Taken together, our data suggest that Set7 deletion attenuates isoproterenol-induced myocardial fibrosis and delays heart dysfunction, suggesting that Set7 plays an important role in cardiac remodeling and dysfunction in response to stress. [ABSTRACT FROM AUTHOR]

Cardiac shock wave therapy (CSWT) is a novel therapeutic procedure for patients with angina that is refractory to conventional therapy. We investigated the potential mechanism and therapeutic efficacy of non-R-wave-triggered CSWT to attenuate myocardial dysfunction in a large animal model of hypertensive cardiomyopathy. Sustained elevated blood pressure (BP) was induced in adult pigs using a combination of angiotensin-II and deoxycorticosterone acetate (DOCA). Two sessions of non-R-wave-triggered CSWT were performed at 11 and 16 weeks. At 10 weeks, systolic and diastolic blood pressure, LV posterior wall thickness and intraventricular septum thickness significantly increased in both the hypertension and CSWT groups. At 20 weeks, +dP/dt and end-systolic pressure-volume relationship (ESPVR) decreased significantly in the hypertension group but not the CSWT group, as compared with week 10. A significant improvement in end-diastolic pressure-volume relationship (EDPVR) was observed in the CSWT group. The CSWT group exhibited significantly increased microvascular density and vascular endothelial growth factor (VEGF) expression in the myocardium. Cytokine array demonstrated that the CSWT group had significantly reduced inflammation compared with the hypertension group. Our results demonstrate that non-R-wave-triggered CSWT is safe and can attenuate LV systolic and diastolic dysfunction via enhancement of myocardial neovascularization and anti-inflammatory effect in a large animal model of hypertensive cardiomyopathy. [ABSTRACT FROM AUTHOR]

Despite complications were significantly reduced due to the popularity of percutaneous coronary intervention (PCI) in clinical trials, reperfusion injury and chronic cardiac remodeling significantly contribute to poor prognosis and rehabilitation in AMI patients. We revealed the effects of HSP47 on myocardial ischemia–reperfusion injury (IRI) and shed light on the underlying molecular mechanism. We generated adult mice with lentivirus-mediated or miRNA (mi1/133TS)-aided cardiac fibroblast-selective HSP47 overexpression. Myocardial IRI was induced by 45-min occlusion of the left anterior descending (LAD) artery followed by 24 h reperfusion in mice, while ischemia-mediated cardiac remodeling was induced by four weeks of reperfusion. Also, the role of HSP47 in fibrogenesis was evaluated in cardiac fibroblasts following hypoxia–reoxygenation (HR). Extensive HSP47 was observed in murine infarcted hearts, human ischemic hearts, and cardiac fibroblasts and accelerated oxidative stress and apoptosis after myocardial IRI. Cardiac fibroblast-selective HSP47 overexpression exacerbated cardiac dysfunction caused by chronic myocardial IRI and presented deteriorative fibrosis and cell proliferation. HSP47 upregulation in cardiac fibroblasts promoted TGF β 1–Smad4 pathway activation and Smad4 deubiquitination by recruiting ubiquitin-specific peptidase 10 (USP10) in fibroblasts. However, cardiac fibroblast specific USP10 deficiency abolished HSP47-mediated fibrogenesis in hearts. Moreover, blockage of HSP47 with Col003 disturbed fibrogenesis in fibroblasts following HR. Altogether, cardiac fibroblast HSP47 aggravates fibrosis post-myocardial IRI by enhancing USP10-dependent Smad4 deubiquitination, which provided a potential strategy for myocardial IRI and cardiac remodeling. Cardiac fibroblast HSP47 inspired TGF β 1–Smad4 pathway by USP10 dependent deubiquitination in fibrogenesis under hypoxia. HSP47 suppression by chemicals with Col003 may have therapeutic potential for alleviating ischemic cardiac fibrosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: To explore whether hepatic vein systolic filling fraction (SFF) is associated with central venous pressure (CVP) and right ventricular (RV) systolic function in critically ill patients. Methods: Adult patients admitted to ICU with echocardiographic examination were retrospectively enrolled. Echocardiographic parameters including hepatic vein systolic velocity (S) and diastolic phase velocity (D) and haemodynamic information at the time of echo examination were collected. RV systolic dysfunction was defined as tricuspid annular plane systolic excursion (TAPSE) < 16 mm. SFF was calculated as S/(S + D). Results: Two hundred four patients were enrolled in this study among whom 40 patients had a CVP ≤5 mmHg, 110 patients had a CVP 6–9 mmHg and 54 patients had a CVP ≥10 mmHg. The three groups had similar S velocity, D velocity and SFF. No correlation between SFF and CVP was found (r = − 0.046, p = 0.500), but correlation between SFF and TAPSE was noticed (r = 0.468, p < 0.001). The ROC analysis showed that the area under curve (AUC) of SFF for determining CVP ≥10 mmHg was 0.513 (95% CI: 0.420–0.606, p = 0.775), but the AUC of SFF for determining RV systolic dysfunction was 0.759 (95% CI: 0.686–0.833, p < 0.001). Conclusion: Hepatic vein systolic filling fraction is associated with RV systolic function in critically ill patients and is not associated with CVP. [ABSTRACT FROM AUTHOR]

Background. Heart failure with preserved ejection fraction (HFpEF) has a complex pathophysiology that encompasses systemic proinflammatory state and dysregulated levels of cardiometabolic and oxidative stress biomarkers. The prevalence of both HFpEF and atrial fibrillation (AF) is continuously rising, especially in the elderly. The aim of our study was to explore if there were any differences in biomarker levels and vascular function in the elderly patients with HFpEF with and without AF and to assess interconnections between clinically relevant biomarkers and cardiac and vascular function. Methods. This was a cross-sectional study of patients ≥ 65 years with HFpEF who were divided into 2 groups based on the presence or absence of AF. We have sonographically assessed echocardiographic parameters of left ventricular systolic and diastolic function and the peripheral vascular function parameters, namely, pulse wave velocity (PWV) and flow-mediated dilation (FMD). NT-proBNP, irisin, leptin, adiponectin, insulin-like growth factor 1 (IGF-1), and malondialdehyde (MDA) blood levels were determined. Results. Fifty-two patients (mean age 80 ± 7 years, 67% females) were included. Patients with HFpEF and AF had significantly lower levels of irisin (median 4.75 vs. 13.5 ng/mL, p = 0.007), leptin (median 9.5 vs. 15.0 ng/L, p = 0.023), and MDA (median 293 vs. 450 ng/mL, p = 0.017) and significantly higher values of NT-proBNP (median 2365 vs. 529 ng/L, p < 0.001) but not vascular function parameters, as compared to HFpEF patients without AF. MDA was significantly correlated with diastolic function (r = 0.395 , p = 0.007) and FMD (r = 0.394 , p = 0.011), while adiponectin was inversely associated with FMD (r = − 0.325 , p = 0.038) and left ventricular ejection fraction (r = − 0.319 , p = 0.029). Conclusions. Our results have demonstrated that patients with HFpEF and AF have significantly lower leptin, irisin, and MDA levels compared to patients with HFpEF but without AF. These results offer new insights into the complexity of vascular function and cardiometabolic and oxidative stress biomarkers in the context of HFpEF, AF, and aging. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF), the final stage of cardiovascular diseases, is a clinical syndrome of cardiac structural or functional abnormalities. QiShenYiQi Dripping Pills (T101), short for QSYQ (T101), showed effectiveness and safety in the treatment of HF according to modern pharmacological research and clinical studies, but the mechanism remains unclear. This study aims to clarify the mechanism of QSYQ (T101) in treating heart failure through the analysis to critical biomarkers, targets and pathways. Materials and Methods: In this study, the efficacies of QSYQ (T101) in nonhuman primates and rodents were evaluated, and the mechanism was demonstrated by integrating network pharmacology and metabolomics analysis. Furthermore, the targets from network pharmacology and the metabolites from targeted metabolomics were jointly analyzed to screen the critical pathways. Results: In rhesus monkeys with spontaneous chronic heart failure, nasogastric administration of QSYQ (T101) for 12 weeks caused profound improvement of systolic and diastolic function as evidenced by echocardiography detection. Consistently, QSYQ (T101) administration especially with higher dose lowered the blood pressure and improved the ventricular remodeling, collagen deposition and fibrosis markedly in Spontaneous Hypertension Rats (SHR) model. Computational prediction showed that QSYQ (T101) exhibited anti-HF effects possibly through HIF-1 signaling pathway, FoxO signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway and other enriched paths. Metabolomics analysis obtained 23 significantly altered metabolites, revealing that QSYQ (T101) significantly regulated the abnormal levels of fatty acids, carnitines, organic acids pyridines, nucleosides, which were mostly involved in myocardial energy metabolism related pathways. Conclusion: Based on serum and myocardium metabolomics and network pharmacology, the present study revealed that the actions of QSYQ (T101) in treating HF depend on multi-components, multi-targets and multi-pathways. [ABSTRACT FROM AUTHOR]

Intrauterine growth restriction (IUGR) is associated with a higher incidence of perinatal complications as well as cardiovascular and renal diseases later on. A better insight into the disease mechanisms underlying these sequalae is important in order to identify which IUGR infants are at a higher risk and find strategies to improve their outcome. In this prospective case–control study we examined whether IUGR had any effect on renal and cerebral perfusion and oxygen saturation in term neonates. We integrated near-infrared spectroscopy (NIRS), echocardiographic, Doppler and renal function data of 105 IUGR infants and 105 age/gender-matched controls. Cerebral and renal regional oxygen saturation values were measured by NIRS during the first 12 h after birth. Echocardiography alongside Doppler assessment of renal and anterior cerebral arteries were performed at 6, 24, 48 and 72 h of age. Glomerular and tubular functions were also assessed. We found a left ventricular dysfunction together with a higher cerebral oxygen saturation and perfusion values in the IUGR group. IUGR term infants showed a higher renal oxygen saturation and a reduced oxygen extraction together with a subclinical renal damage, as indicated by higher values of urinary neutrophil gelatinase-associated lipocalin and microalbumin. These data suggest that some of the haemodynamic changes present in growth-restricted foetuses may persist postnatally. The increased cerebral oxygenation may suggest an impaired transition to normal autoregulation as a consequence of intra-uterine chronic hypoxia. The higher renal oxygenation may reflect a reduced renal oxygen consumption due to a subclinical kidney damage. [ABSTRACT FROM AUTHOR]

Background. Left ventricular (LV) diastolic dysfunction (LVDD) is the defining feature of heart failure with preserved ejection fraction (HFpEF) and predicts subsequent incident heart failure (HF) and all-cause mortality. Mounting evidence reveals that cardiometabolic risk factors play critical roles in the development of LVDD. In this study, we sought to investigate the relation between serum uric acid (SUA) level and the progression of LVDD in apparently healthy patients. Methods. A total of 1082 apparently healthy subjects without diagnosed cardiovascular disease and LVDD were consecutively enrolled. SUA levels were measured, and repeat echocardiography and tissue Doppler imaging (TDI) were performed at baseline and during 1-year follow-up. Results. By dividing the study population based on quartiles of SUA, we found subjects in higher quartiles had greater increases in TDI-derived early diastolic velocity (e ′) and E (peak LV filling velocity)/e ′ ratios during 1-year follow-up. After multivariate adjustment, high SUA persisted to be an independent predictor for the subsequent worsening of LVDD (odds ratio: 1.351 [95% CI 1.125~1.625], per 100 μmol/L SUA). Subgroup analysis suggested that the association between SUA and LVDD development was more pronounced in subjects without other cardiometabolic risk factors involved. Factor analysis demonstrated that high SUA was the major cardiometabolic attribute in patients with LVDD progression. Conclusion. Our findings suggest that high SUA is an independent cardiometabolic risk factor for the progression of LVDD in apparently healthy subjects. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of a structured yogic training program on the blood pressure of Manipur University students using a quasi-experimental design. Design and method: A total of fifty female subjects were purposively selected from the students of Manipur University, whose ages ranged from 21-25 years. It was hypothesized that structured yogic training may have a significant effect on the blood pressure of the subjects. The training was regularly practiced for one hour, five days a week for nine weeks. The data were collected by using a sphygmomanometer. For statistical analysis, descriptive analysis and paired sample t-test were employed to see the characteristic of data and mean differences between the pre-test and post-test respectively. Results: The Mean and Standard Deviation of Systolic Blood Pressure for the pre-test and post-test were 119.34 ± 14.41 and 122.14 ± 13.94 respectively. The Mean and Standard Deviation of Diastolic Blood Pressure for the pre-test and post-test were 79.90 ± 18.79 and 79.42 ± 8.86 respectively. The value of the range, standard error, and variance of systolic blood pressure for the pre-test and post-test were 67, 2.03 & 207.78, and 55, 1.97 & 194.49 respectively. The value of the range, standard error, and variance of Diastolic Blood Pressure for the pretest and post-test were 130, 2.65 & 353.23, and 37, 1.25 & 78.61 respectively. The insignificance was found in the p-value while comparing the mean for Systolic Blood Pressure between the pre-test and post-test. The calculated 't' value was 1.41 which is lesser than the tabulated 't' which was 1.699, with 29 degrees of freedom at a 0.05 level of confidence. An insignificant difference was also found between the pretest and post-test mean comparison of the systolic blood pressure, and the p-value is 0.16, (p>0.05). There was an insignificant difference in systolic blood pressure after nine weeks of yogic training compared to baseline data. The insignificance was found in the p-value while comparing the mean for the diastolic blood pressure between the pre-test and post-test. The calculated 't' value was 0.20 which is lesser than the tabulated 't' which was 1.69, with 29 degrees of freedom at a 0.05 level of confidence. An insignificant difference was also found between the pre-test and post-test mean comparison of the diastolic blood pressure, and the p-value is 0.84, (p>0.05). There was an insignificant difference in diastolic blood pressure after nine weeks of yogic training compared to baseline data. Thus, regular practice of yogic training results in insignificance although it helps to maintain the blood pressure at the normal range. Conclusion: The study concluded that an insignificant difference between the pre-test and post-test was found. So, an insignificant increase was detected in systolic blood pressure, and a reduction was detected in diastolic blood pressure but within the normal range of blood pressure among students of Manipur University. Thus, the alternative hypothesis of the study is rejected and the null hypothesis is accepted. Regular yogic training help to maintain the blood pressure of the body, which can help to reduce the risk of hypotension, heart attack or stroke, or other complications. This study would help our brain and heart, receive nutrients and oxygen through our blood flow and also help to improve the overall health of the subject. [ABSTRACT FROM AUTHOR]

Background: In human medicine, arrhythmogenic left ventricular cardiomyopathy was described as a primary disease of the heart characterized by fibroadipose replacement of the myocardium. Case Description: We report the case of a dog, with history of syncope and irregular cardiac rhythm. Electrocardiogram, echocardiography, and a 24-hour Holter monitoring showed, respectively, the presence of premature ventricular complexes with right bundle branch block morphology, an increase of the left ventricle end-diastolic diameter with preserved fractional shortening and ejection fraction, and a sinus arrhythmia as baseline rhythm with supraventricular tachycardia episodes and ventricular complexes with left bundle branch block morphology. After the death of the canine, a postmortem examination showed cardiomegaly. Fibroadipose replacement of the septum and both ventricles, with left ventricle myocardial fibrosis, suggestive of previous necrosis, was observed. Conclusion: These findings are suggestive of left-dominant arrhythmogenic cardiomyopathy which, to the best of our knowledge, has not been described in veterinary medicine. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effect of C-type natriuretic peptide and amiodarone in Chinese patients with arrhythmia. Method: Chinese men and women aged 18 to 65 years with premature ventricular complexes (PVCs), were administered C-type natriuretic peptide (CNP) - test group or amiodarone (study group) in ratio of 1:1 for 96 h. Patients in CNP group received infusion of synthetic human CNP (10 pmol/kg/min) for an initial 2 h, and then for 30 min every day until discharge. Patients in amiodarone group received initial dose of 1000 mg over the first 24 h. Change in PVCs from baseline was the primary efficacy endpoint. Secondary efficacy endpoint includes: change in PVCs-related symptom scores from baseline, change in ejection fraction of left ventricle (LV), end-diastolic diameter of LV, and cardiac events as composite outcome (CCE). The effect of both treatments on hemodynamic and electrocardiography parameters, and safety were evaluated. Data from 200 patients were analyzed. Results: The CNP showed significantly greater decrease in the number of PVCs when compared to amiodarone (p < 0.005). Moreover, CNP was superior in alleviating PVCs-related symptoms when compared to amiodarone (p < 0.005). A similar trend of favorable effect of CNP was observed for other endpoints. Conclusion: The C-type natriuretic peptide offers significantly greater benefits of suppressing PVCs and related symptoms, and demonstrates significantly greater improvement of cardiac function and clinical outcome. Thus, CNP can be considered for further investigation as a suitable alternative in the management of ventricular arrhythmia with PVC among Chinese patients. [ABSTRACT FROM AUTHOR]

We used transverse aortic constriction (TAC) in mice to test the hypothesis that urocortin 2 (Ucn2) gene transfer would increase left ventricular (LV) systolic and diastolic function in the pressure-stressed LV. Three groups were studied: (1) control mice (no TAC); (2) mice that received saline 6 weeks after TAC; and (3) mice that received Ucn2 gene transfer 6 weeks after TAC, using adeno-associated virus 8 encoding murine Ucn2 (AAV8.mUcn2; 2 × 1013 genome copies (gc)/kg, i.v. per mouse). Echocardiography was performed 6 and 12 weeks after TAC. In terminal studies 12 weeks after TAC, rates of LV pressure development and decay and Tau were measured, and LV cardiac myocytes (CMs) were isolated and cytosolic Ca2+ transients and sarcomere shortening rates recorded. Reverse transcription polymerase chain reaction and immunoblotting were used to measure key proteins in LV samples. A CM cell line (HL-1) was used to explore mechanisms. Concentric LV hypertrophy was evident on echocardiography 6 weeks after TAC. Twelve weeks after TAC, LV ejection fraction (EF) was higher in mice that received Ucn2 gene transfer (TAC-saline: 65% ± 3%; TAC-Ucn2: 75% ± 2%; p = 0.01), as was LV peak +dP/dt (1.9-fold increase; p = 0.001) and LV peak −dP/dt (1.7-fold increase; p = 0.017). Tau was more rapid (23% reduction, p = 0.02), indicating improved diastolic function. The peak rates of sarcomere shortening (p = 0.002) and lengthening (p = 0.002) were higher in CMs from TAC-Ucn2 mice, and Tau was reduced (p = 0.001). LV (Ser-16) phosphorylation of phospholamban (PLB) was increased in TAC-Ucn2 mice (p = 0.025), and also was increased in HL-1 cells treated with angiotensin II to induce hypertrophy and incubated with Ucn2 peptide (p = 0.001). Ucn2 gene transfer in TAC-induced heart failure with preserved ejection fraction increased cardiac function in the intact LV and provided corresponding benefits in CMs isolated from study animals, including increased myofilament Ca2+ sensitivity during contraction. The mechanism includes enhanced CM Ca2+ handling associated with increased (Ser-16)-PLB. [ABSTRACT FROM AUTHOR]

Background: Pulsed-wave Doppler measures blood flow at specific point and provides information on velocity, direction and uniformity of blood flow throughout cardiac cycle. Till date, there is no published data on study of cardiac parameters using pulsed-wave Doppler echocardiography in Indian Spitz dogs. Methods: Twenty-four clinically normal Indian Spitz dogs were subjected to pulsed-wave Doppler echocardiography to determine the reference intervals for Doppler parameters of blood flow through mitral, tricuspid and aortic valves. Mitral peak E and A-wave velocities, E/A ratio, deceleration time, isovolumic relaxation time, E and A-wave velocity time integral, E duration and A duration were 0.69±0.09 m/s, 0.43±0.12 m/s, 1.69±0.45, 111.25±35.94 ms, 48.50±24.77 ms, 0.07±0.01 m and 0.04±0.02 m, 196.88±44.38 ms and 181.25±64.89 ms, respectively. Tricuspid peak E and A-wave velocities, E/A ratio and E and A-wave velocity time integral were 0.57±0.11 m/s, 0.38±0.08 m/s, 1.56±0.32 and 0.07±0.02 m and 0.05±0.01 m, respectively. Aortic peak velocity, velocity time integral and ejection time were 0.87±0.07 m/s, 0.11±0.02 m and 0.25±0.04 s, respectively. Conclusion: The reference values of flow parameters across mitral, tricuspid and aortic valves using pulsed-wave Doppler echocardiography were determined. Mitral, tricuspid and aortic valve flow variables were unaffected by gender whereas isovolumic relaxation correlated positively with body weight. [ABSTRACT FROM AUTHOR]

This phase Ib study compared the effects of AZD9977, a selective mineralocorticoid receptor modulator with predicted low hyperkalemia risk, with spironolactone on serum potassium (sK+) in patients with heart failure (HF) with preserved or mildly reduced ejection fraction (EF; ≥40%), and renal impairment. Patients with HF with EF greater than or equal to 40% and estimated glomerular filtration rate of 40–70 ml/min/1.73 m2 were randomized to once‐daily AZD9977 100 mg or spironolactone 25 mg for 14 days, up‐titrated to AZD9977 200 mg or spironolactone 50 mg for another 14 days. The primary end point was relative change (%) in sK+ for AZD9977 versus spironolactone (baseline to day 28). Serum/urinary electrolytes, fractional excretion (FE) of Na+/K+, plasma aldosterone, cortisol, and renin, and safety were also assessed. Sixty‐eight patients were randomized (AZD9977, n = 33; spironolactone, n = 35). Mean (SD) age was 73.0 (8.5) years, 51.5% men. Mean sK+ change from baseline to day 28 was 5.7% (AZD9977) and 4.2% (spironolactone), and 1.5% and 4.2% at day 14. Relative change (95% confidence interval) in sK+ with AZD9977 versus spironolactone was −0.3% (−5.3% to 4.4%; day 28), and 3.4% (−0.8% to 7.5%; day 14). Median increase from baseline in plasma aldosterone at day 28 was 89.8 pmol/L for AZD9977 and 67.4 pmol/L for spironolactone. Median FE of K+ was 12.9% (AZD9977) and 10.1% (spironolactone). AZD9977 was well‐tolerated. No discontinuations due to hyperkalemia occurred with either treatment. Evidence of target engagement for AZD9977 with a favorable safety profile, supports further evaluation of AZD9977 in patients with HF and renal impairment. [ABSTRACT FROM AUTHOR]

Aims We aimed to determine the effect of increasing body weight upon right ventricular (RV) volumes, energetics, systolic function, and stress responses using cardiovascular magnetic resonance (CMR). Methods and results We first determined the effects of World Health Organization class III obesity [body mass index (BMI) > 40 kg/m2, n = 54] vs. healthy weight (BMI < 25 kg/m2, n = 49) upon RV volumes, energetics and systolic function using CMR. In less severe obesity (BMI 35 ± 5 kg/m2, n = 18) and healthy weight controls (BMI 21 ± 1 kg/m2, n = 9), we next performed CMR before and during dobutamine to evaluate RV stress response. A subgroup undergoing bariatric surgery (n = 37) were rescanned at median 1 year to determine the effects of weight loss. When compared with healthy weight, class III obesity was associated with adverse RV remodelling (17% RV end-diastolic volume increase, P < 0.0001), impaired cardiac energetics (19% phosphocreatine to adenosine triphosphate ratio reduction, P < 0.001), and reduction in RV ejection fraction (by 3%, P = 0.01), which was related to impaired energetics (R = 0.3, P = 0.04). Participants with less severe obesity had impaired RV diastolic filling at rest and blunted RV systolic and diastolic responses to dobutamine compared with healthy weight. Surgical weight loss (34 ± 15 kg weight loss) was associated with improvement in RV end-diastolic volume (by 8%, P = 0.006) and systolic function (by 2%, P = 0.03). Conclusion Increasing body weight is associated with significant alterations in RV volumes, energetic, systolic function, and stress responses. Adverse RV modelling is mitigated with weight loss. Randomized trials are needed to determine whether intentional weight loss improves symptoms and outcomes in patients with obesity and heart failure. [ABSTRACT FROM AUTHOR]

Aims The left atrium (LA) has a pivotal role in cardiac performance and LA deformation is a well-known prognostic predictor in several clinical conditions including heart failure with reduced ejection fraction. The aim of this study is to investigate the effect of cardiac resynchronization therapy (CRT) on both LA morphology and function and to assess the impact of LA reservoir strain (LARS) on left ventricular (LV) systolic and diastolic remodelling after CRT. Methods and results Two hundred and twenty-one CRT-candidates were prospectively included in the study in four tertiary centres and underwent echocardiography before CRT-implantation and at 6-month follow-up (FU). CRT-response was defined by a 15% reduction in LV end-systolic volume. LV systolic and diastolic remodelling were defined as the percent reduction in LV end-systolic and end-diastolic volume at FU. Indexed LA volume (LAVI) and LV-global longitudinal (GLS) strain were the main parameters correlated with LARS, with LV-GLS being the strongest determinant of LARS (r = −0.59, P < 0.0001). CRT induced a significant improvement in LAVI and LARS in responders (both P < 0.0001). LARS was an independent predictor of both LV systolic and diastolic remodelling at follow-up (r = −0.14, P = 0.049 and r = −0.17, P = 0.002, respectively). Conclusion CRT induces a significant improvement in LAVI and LARS in responders. In CRT candidates, the evaluation of LARS before CRT delivery is an independent predictor of LV systolic and diastolic remodelling at FU. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported that six transmembrane protein of prostate 2 (STAMP2) attenuates metabolic inflammation and insulin resistance in diabetes mellitus. However, the role of STAMP2 in the diabetic heart is still unclear. Methods: A diabetic rat cardiomyopathy model was established via intraperitoneal STZ injection. STAMP2 was overexpressed in the treatment group using adeno-associated virus. Rat heart diastolic function was measured using echocardiography and a left ventricular catheter, and cardiac interstitial fibrosis was detected by immunohistochemistry and histological staining. Insulin sensitivity and NF-κB expression were shown by Western blotting. NMRAL1 distribution was illustrated by immunofluorescence. Results: STAMP2 expression in the diabetic rat heart was reduced, and exogenous overexpression of STAMP2 improved glucose tolerance and insulin sensitivity and alleviated diastolic dysfunction and myocardial fibrosis. Furthermore, we found that NF-κB signaling is activated in the diabetic heart and that exogenous overexpression of STAMP2 promotes NMRAL1 translocation from the cytoplasm to the nucleus and inhibits p65 phosphorylation. Conclusion: STAMP2 attenuates cardiac dysfunction and insulin resistance in diabetic cardiomyopathy, likely by promoting NMRAL1 retranslocation and NF-κB signaling inhibition. [ABSTRACT FROM AUTHOR]

Simple Summary: Standard echocardiography is an essential diagnostic tool for the assessment of cardiac performance in healthy and diseased animals. Two-dimensional speckle-tracking echocardiography is an advanced echocardiographic technique that is useful for the assessment of myocardial function. Factors such as dog breed, age, and body weight (BW) are known to influence the echocardiographic parameters. This study aimed to evaluate the effect of breed, age, and BW on the echocardiographic parameters in healthy Retrievers, including Flat-coated, Golden, and Labrador Retrievers. The results showed that there were no significant associations between breed and echocardiographic parameters. On the other hand, they revealed that left ventricular dimensions increased with BW. Furthermore, parameters including peak aortic blood flow velocity, trans-mitral rapid ventricular filling flow, the ratio of trans-mitral rapid ventricular filling flow to atrial contraction, and global radial strain were influenced by age. Standard echocardiography is vital for the assessment of cardiac performance in healthy and diseased animals. Similarly, two-dimensional speckle-tracking echocardiography (2D-STE) is an advanced echocardiographic technique that is becoming increasingly important for the assessment of myocardial function. Breeds, age, and body weight (BW) are known to be important factors affecting the echocardiographic parameters; therefore, the aim of this study was to evaluate the effect of breed, age, and BW on the echocardiographic parameters in three breeds of clinically healthy Retrievers. A total of 46 Retrievers, including 16 Flat-coated Retrievers (FR), 16 Golden Retrievers (GR), and 14 Labrador Retrievers (LR) were included in the study. The comparison of the breeds revealed significant differences in the LV wall thickness of FR and GR, although further analysis using MLR showed that the differences were most likely associated with BW, similarly to the other LV dimensions. Functional parameters, including ejection fraction, fractional shortening, and left-atrial-to-aortic ratio, were independent of breed, age, and BW. On the other hand, peak aortic blood flow velocity, trans-mitral rapid ventricular filling flow, and the ratio of trans-mitral rapid ventricular filling flow to atrial contraction were influenced by age. The 2D-STE-derived radial and circumferential strain parameters were independent of breed, age, and BW, except for global strain in the radial direction. [ABSTRACT FROM AUTHOR]

Aims: The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) programme consisted of three parallel, randomized, double‐blind clinical trials comparing candesartan with placebo in patients with heart failure (HF) categorized according to left ventricular ejection fraction and tolerability to an angiotensin‐converting enzyme inhibitor. We conducted a pharmacogenomic study of the CHARM trials with the objective of identifying genetic predictors of HF progression and of the efficacy and safety of treatment with candesartan. Methods: We performed genome‐wide association studies in 2727 patients of European ancestry from CHARM‐Overall and stratified by CHARM study according to preserved and reduced ejection fraction and according to assignment to the interventional treatment with candesartan. We tested genetic association with the composite endpoint of cardiovascular death or hospitalization for heart failure for drug efficacy in candesartan‐treated patients and for HF progression using patients from both candesartan and placebo arms. The safety endpoints for response to candesartan were hyperkalaemia, renal dysfunction, hypotension, and change in systolic blood pressure between baseline and 6 weeks of treatment. To support our observations, we conducted a genome‐wide gene‐level collapsing analysis from whole‐exome sequencing data with the composite cardiovascular endpoint. Results: We found that the A allele (14% allele frequency) of the genetic variant rs66886237 at 8p21.3 near the gene GFRA2 was associated with the composite cardiovascular endpoint in 1029 HF patients with preserved ejection fraction from the CHARM‐Preserved study (hazard ratio: 1.91, 95% confidence interval: 1.55–2.35; P = 1.7 × 10−9). The association was independent of candesartan treatment, and the genetic variant was not associated with the cardiovascular endpoint in patients with reduced ejection fraction. None of the genome‐wide association studies for candesartan safety or efficacy conducted in patients treated with candesartan passed the significance threshold. We found no significant association from the gene‐level collapsing analysis. Conclusions: We have identified a candidate genetic variant potentially predictive of the progression of heart failure in patients with preserved ejection fraction. The findings require further replication, and we cannot exclude the possibility that the results may be chance findings. [ABSTRACT FROM AUTHOR]

Restrictive cardiomyopathy (RCM) is a rare disease characterized by increased ventricular stiffness and preserved ventricular contraction. Various sarcomere gene variants are known to cause RCM; however, more than a half of patients do not harbor such pathogenic variants. We recently demonstrated that cardiac fibroblasts (CFs) play important roles in inhibiting the diastolic function of cardiomyocytes via humoral factors and direct cell–cell contact regardless of sarcomere gene mutations. However, the mechanical properties of CFs that are crucial for intercellular communication and the cardiomyocyte microenvironment remain less understood. In this study, we evaluated the rheological properties of CFs derived from pediatric patients with RCM and healthy control CFs via atomic force microscopy. Then, we estimated the cellular modulus scale factor related to the cell stiffness, fluidity, and Newtonian viscosity of single cells based on the single power-law rheology model and analyzed the comprehensive gene expression profiles via RNA-sequencing. RCM-derived CFs showed significantly higher stiffness and viscosity and lower fluidity compared to healthy control CFs. Furthermore, RNA-sequencing revealed that the signaling pathways associated with cytoskeleton elements were affected in RCM CFs; specifically, cytoskeletal actin-associated genes (ACTN1, ACTA2, and PALLD) were highly expressed in RCM CFs, whereas several tubulin genes (TUBB3, TUBB, TUBA1C, and TUBA1B) were down-regulated. These results implies that the signaling pathways associated with cytoskeletal elements alter the rheological properties of RCM CFs, particularly those related to CF–cardiomyocyte interactions, thereby leading to diastolic cardiac dysfunction in RCM. [ABSTRACT FROM AUTHOR]

Background: Seasonal variations in the ambient temperature may affect the exacerbation of cardiovascular diseases. Our primary objective was to evaluate the seasonality of the monthly proportion of cardiac surgeries associated with diabetes, smoking and/or elderly age at a tertiary-care university hospital in East-Central Europe with a temperate climate zone. As a secondary objective, we also assessed whether additional factors affecting small blood vessels (smoking, aging, obesity) modulate the seasonal variability of diabetes. Methods: Medical records were analyzed for 9838 consecutive adult patients who underwent cardiac surgery in 2007–2018. Individual seasonal variations of diabetes, smoking, and elderly patients were analyzed monthly, along with the potential risk factors for cardiovascular complication. We also characterized whether pairwise coexistence of diabetes, smoking, and elderly age augments or blunts the seasonal variations. Results: Seasonal variations in the monthly proportion of cardiac surgeries associated with diabetes, smoking and/or elderly age were observed. The proportion of cardiac surgeries of non-elderly and smoking patients with diabetes peaked in winter (amplitude of change as [peak-nadir]/nadir: 19.2%, p<0.02), which was associated with increases in systolic (6.1%, p<0.001) and diastolic blood pressures (4.4%, p<0.05) and serum triglyceride levels (27.1%, p<0.005). However, heart surgery in elderly patients without diabetes and smoking was most frequently required in summer (52.1%, p<0.001). Concomitant occurrence of diabetes and smoking had an additive effect on the requirement for cardiac surgery (107%, p<0.001), while the simultaneous presence of older age and diabetes or smoking eliminated seasonal variations. Conclusions: Scheduling regular cardiovascular control in accordance with periodicities in diabetes, elderly, and smoking patients more than once a year may improve patient health and social consequences. Trial registration: NCT03967639. [ABSTRACT FROM AUTHOR]

Diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) is characterised by increased left ventricular stiffness and impaired active relaxation. Underpinning pathomechanisms are incompletely understood. Cardiac hypertrophy and end stage heart disease are associated with alterations in the cardiac microtubule (MT) network. Increased amounts and modifications of α-tubulin associate with myocardial stiffness. MT alterations in HFpEF have not been analysed yet. Using ZSF1 obese rats (O-ZSF1), a validated HFpEF model, we characterised MT-modifying enzymes, quantity and tyrosination/detyrosination pattern of α-tubulin at 20 and 32 weeks of age. In the left ventricle of O-ZSF1, α-tubulin concentration (20 weeks: 1.5-fold, p = 0.019; 32 weeks: 1.7-fold, p = 0.042) and detyrosination levels (20 weeks: 1.4-fold, p = 0.013; 32 weeks: 1.3-fold, p = 0.074) were increased compared to lean ZSF1 rats. Tyrosination/α-tubulin ratio was lower in O-ZSF1 (20 weeks: 0.8-fold, p = 0.020; 32 weeks: 0.7-fold, p = 0.052). Expression of α-tubulin modifying enzymes was comparable. These results reveal new alterations in the left ventricle in HFpEF that are detectable during early (20 weeks) and late (32 weeks) progression. We suppose that these alterations contribute to diastolic dysfunction in HFpEF and that reestablishment of MT homeostasis might represent a new target for pharmacological interventions. [ABSTRACT FROM AUTHOR]

Background: In people, the cardiovascular effects of obesity include systemic hypertension, cardiac remodelling and both systolic and diastolic dysfunction, whilst weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. To date, variable results are reported in studies of the effect of obesity and controlled weight reduction on cardiovascular morphology and function in dogs. This prospective study aimed to assess cardiac function, heart rate variability, cardiac biomarkers and body composition before and after weight reduction in pet dogs with obesity. Twenty-four client-owned dogs referred for weight management due to obesity were recruited. To assess the cardiac effects of obesity, body composition analysis (by dual energy X-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, Doppler blood pressure, electrocardiography, cardiac biomarkers) were performed prior to weight management. Twelve dogs completed the study and reached target weight, receiving a further cardiovascular assessment and DEXA. A Wilcoxon-signed rank test was used to compare each variable pre- and post- weight reduction. Results: Median (interquartile range) duration of weight loss was 224 days (124–245 days), percentage weight loss was 23% (18–31%) of starting weight. Median change in body fat mass was -50% (-44% to -55%; P = 0.004), whilst median change in lean mass was -7% (+ 1% to -18%, P = 0.083). Before weight reduction, diastolic dysfunction (evidence of impaired relaxation in all dogs), increased left ventricular wall thickness and mildly elevated systolic blood pressure (14/24 ≥ 160 mmHg, median 165 mmHg (140–183)) were common features in dogs with obesity. However, systolic left ventricular wall dimensions were the only variables that changed after weight reduction, with a decrease in both the systolic interventricular septum (P = 0.029) and systolic left ventricular free wall (P = 0.017). There was no evidence of decreased heart rate variability in dogs with obesity (P = 0.367), and no change in cardiac biomarker concentrations with weight reduction (N-terminal proBNP, P = 0.262; cardiac troponin I P = 0.657). Conclusions: Canine obesity results in diastolic dysfunction and left ventricular hypertrophy, the latter of which improves with significant weight and fat mass reduction. Further studies are required to clarify the clinical consequences of these findings. [ABSTRACT FROM AUTHOR]

Age-related cardiac fibrosis contributes to the development of heart failure with preserved ejection fraction which lacks ideal treatment. Transient receptor potential ankyrin 1 (TRPA1) is an oxidative stress sensor and could attenuate age-related pathologies in invertebrates. The present study aimed to test whether TRPA1 plays a role in age-related cardiac remodeling and dysfunction. The cardiac function and pathology of 12-week-old (young) and 52-week-old (older) Trpa1-/- mice and wild-type (WT) littermates were evaluated by echocardiography and histologic analyses. The expression levels of 84 fibrosis-related genes in the heart were measured by quantitative polymerase chain reaction array. Young Trpa1-/- and WT mice had similar left ventricular wall thickness, volume, and systolic and diastolic function. Older Trpa1-/- mice had significantly increased left ventricular internal diameter and volume and impaired systolic (lower left ventricular ejection fraction) and diastolic (higher E/A ratio and isovolumetric relaxation time) functions compared with older WT mice (P<0.05 or P<0.01). Importantly, older Trpa1-/- mice had enhanced cardiac fibrosis than older WT mice (P<0.05) while the two strains had similar degree of cardiac hypertrophy. Among the 84 fibrosis-related genes, Acta2, Inhbe, Ifng, and Ccl11 were significantly upregulated, while Timp3, Stat6, and Ilk were significantly downregulated in the heart of older Trpa1-/- mice compared with older WT mice. Taken together, we found that knocking out Trpa1 accelerated age-related myocardial fibrosis, ventricular dilation, and cardiac dysfunction. These findings suggest that TRPA1 may become a therapeutic target for preventing and/or treating cardiac fibrosis and heart failure with preserved ejection fraction in the elderly. [ABSTRACT FROM AUTHOR]

Whole-Body Periodic Acceleration (WBPA) has been reported to induce endothelial nitric oxide and cause vasodilation. However, the effects of WBPA on blood pressure and cardiovascular hemodynamics are still unclear and controversial. The objective of this study was to determine whether a single session of 160-degree V-shape Whole-Body Periodic Acceleration (WBPA-V-160), i.e., periodic motion of the supine body headward to footward, improved blood pressure and cardiovascular parameters. A pre-evaluation and post-evaluation of blood pressure and cardiovascular hemodynamics via DynaPulse Noninvasive and Quantitative Hemodynamic Profile Analysis were performed after a single 30 min trial of WBPA-V-160 with a moving distance, headward to footward, of 2 mm, at a constant frequency of 4 Hz. Systolic BP, diastolic BP, heart rate, end systolic pressure, end diastolic pressure, mean arterial BP, and pulse pressure at post-evaluation were significantly lower than at pre-evaluation after WBPA-V-160, whereas systemic vascular compliance and brachial artery distensibility at post-evaluation were significantly higher than at pre-evaluation. The WBPA-V-160, performed for 30 min, did improve blood pressure and cardiovascular hemodynamics by lowing the BP parameters and enhancing systemic vascular compliance. [ABSTRACT FROM AUTHOR]

There is need for a reliable in vitro system that can accurately replicate the cardiac physiological environment for drug testing. The limited availability of human heart tissue culture systems has led to inaccurate interpretations of cardiac-related drug effects. Here, we developed a cardiac tissue culture model (CTCM) that can electro-mechanically stimulate heart slices with physiological stretches in systole and diastole during the cardiac cycle. After 12 days in culture, this approach partially improved the viability of heart slices but did not completely maintain their structural integrity. Therefore, following small molecule screening, we found that the incorporation of 100 nM tri-iodothyronine (T3) and 1 μM dexamethasone (Dex) into our culture media preserved the microscopic structure of the slices for 12 days. When combined with T3/Dex treatment, the CTCM system maintained the transcriptional profile, viability, metabolic activity, and structural integrity for 12 days at the same levels as the fresh heart tissue. Furthermore, overstretching the cardiac tissue induced cardiac hypertrophic signaling in culture, which provides a proof of concept for the ability of the CTCM to emulate cardiac stretch-induced hypertrophic conditions. In conclusion, CTCM can emulate cardiac physiology and pathophysiology in culture for an extended time, thereby enabling reliable drug screening. A physiological culture system to electro-mechanically stimulate pig heart slices to assess the drug effects on the functionality, metabolic activity, and structural integrity of the heart tissue under physiological and hypertrophic condition. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy (HCM) is an inherited autosomal dominant heart disease, characterized by increased left ventricular wall thickness and abnormal loading conditions. Imaging modalities are the first choice for diagnosis and risk stratification. Although heart dimensions have been characterized widely in HCM adults from cardiac imaging, there is limited information about children affected by HCM. The aim of this study is to evaluate left ventricular function and left heart dimensions in a small population of children diagnosed with HCM. Methods: A total of 16 (seven male, nine female) pediatric patients with an average age of 14.0 ± 2.5 years diagnosed with HCM at Great Ormond Street Hospital for Children were included in this study. Cardiac magnetic resonance (CMR) images were used to measure left and right ventricular dimensions, and septal and left ventricular free wall thicknesses in Simpleware ScanIP. The gender groups were compared using student t‐test or non‐parametric Mann‐Whitney U‐test depending on the sample distribution. Results: Differences in heart rate, left ventricular end‐diastolic volume and end‐diastolic volume index, left ventricular stroke volume and stroke volume index, left ventricular end‐systolic long axis length, left ventricular end‐systolic long axis length index, left ventricular end‐diastolic mid‐cavity diameter, left ventricular end‐diastolic free wall thickness, left ventricular end‐diastolic free wall thickness index, right ventricular end‐diastolic long axis length were statistically significant in males and females. Conclusion: Left ventricular wall and intraventricular septal thickness increase affecting left ventricle cavity dimensions and there may be differences in anatomical and physiological parameters in males and females affected by HCM. [ABSTRACT FROM AUTHOR]

Objective: High blood pressure is a serious health condition. Patients and clinicians need tools to early detect deviations from normal blood pressure. Adapting modern methods of monitoring to blood pressure monitoring (BPM) has been a favorable solution. This study focuses on adaptation of machine learning to BPM. The daily chrono-biological changes effect blood pressure and may lead to false alarms in an early detection system. We provide an approach that detects changes in blood pressure with limited baseline data. Material and Methods: Our approach uses random forest as an alternative to traditional process monitoring algorithms which test each data point compared to a baseline dataset. In addition, our method converts testing problem into a supervised learning problem using a sliding baseline. We used real data and synthetic data to show the potential of the proposed method for different types of hypertension: sisto-diastolic hypertension, isolated diastolic hypertension and white coat effect. Results: Our observations support that the method can detect various patterns such as sisto-diastolic hypertension, isolated diastolic hypertension and white coat effect successfully. Conclusion: We described the development of a machine learning based monitoring approach to early detect changes in blood pressure. The proposed method (1) requires relatively small baseline data, (2) can be adapted to realtime patient data, and (3) can detect various types of hypertension. [ABSTRACT FROM AUTHOR]

Cardiogenic shock remains a deadly complication of acute on chronic decompensated heart failure (ADHF-CS). Despite its increasing prevalence, it is incompletely understood and therefore often misdiagnosed in the early phase. Precise diagnosis of the underlying cause of CS is fundamental for undertaking the correct therapeutic strategy. Temporary mechanical circulatory support (tMCS) is the mainstay of management: identifying and selecting optimal patients through understanding of the hemodynamics and a prompt profiling and timing, is key for success. A recent statement from the American Heart Association provided pragmatic suggestions on tMCS device selection, escalation, and weaning strategies. However, several areas of uncertainty still remain in clinical practice. Accordingly, we present an overview of the main pitfalls that can occur during patients' management with tMCS through a clinical case. This case illustrates the strict interdependency between left ventricular unloading and right ventricular dysfunction in the case of low filling pressures. Moreover, it further illustrates the pivotal role of stepwise escalation of therapy in a patient with an ADHF-CS and its peculiarities as compared to other forms of acute heart failure. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) leads to ischemia and afterward to left ventricular (LV) remodeling. Matrix metalloproteinase−1 (MMP1) and −3 (MMP3) belong to the family of endopeptidases and together they can dissolve most of the components of the extracellular matrix. MMP1 and MMP3 variants have been investigated solely in association with ischemic heart disease and LV dysfunction, but not in haplotype. The aims of this study were to investigate the association of haplotypes inferred from MMP1 rs1799750 (−1607 1G/2G; NC_000011.9:g.102670497del) and MMP3 rs35068180 (−1612 5A/6A; NC_000011.9:g.102715952dup) with MI and their effect on the change in echocardiographic parameters of LV structure and function in patients within 6 months after MI. Methods: The study included 325 patients with the first MI and 283 healthy controls. Gene variants were detected by PCR‐RFLP method. Parameters of LV structure and function were assessed by conventional 2D echocardiography, 3–5 days and 6 months after the first MI, on a subgroup of 160 patients. Haplotype analysis was performed with Thesias software. Results: Haplotypes 2G‐5A and 1G‐6A were significantly and independently associated with MI compared with the reference haplotype 2G‐6A (adjusted, p = 0.009 and p = 0.026, respectively). After Bonferroni correction for multiple testing, MMP1 and MMP3 haplotypes lost their association with the change in LV long diameter and stroke volume within 6 months after MI. Conclusion: MMP1 and MMP3 haplotypes are strongly associated with MI. Further studies are needed to validate this result and to examine their association with echocardiographic parameters of LV structure and function after MI. [ABSTRACT FROM AUTHOR]

Nowadays, the problem of preventing acute heart failure (AHF) in patients with ST-elevation myocardial infarction (STEMI) and preserved left-ventricular ejection fraction (pLVEF) is still not completely resolved, especially in late-presented patients. The purpose of study was: (1) assessment of free plasma amino acid (PAA) alterations in STEMI patients [not receiving reperfusion therapy (RT)], depending on sex and LVEF; (2) analysis of development of late/persistent AHF more than 48 h after admission (pAHF) in STEMI patients with pLVEF depending on PAA levels. This prospective cohort study included 92 STEMI patients (33 women and 59 men), not receiving RT. The free PAA were investigated by ion-exchange liquid-column chromatography. The women had significantly higher PAA levels than men in general cohort and cohort with pLVEF (n = 69). There were associations between female sex and pAHF in general cohort (OR 3.7, p = 0.004) and cohort with pLVEF (OR 11.4, p = 0.0001) by logistic regression. The association between pAHF and glycine level [OR 2.5, p < 0.0001; AUC 0.84, p < 0.0001; 86.7% sensitivity and 77.8% specificity for > 2.6 mg/dL] was revealed in cohort with pLVEF (including female and male). Glycine remained a predictor of pAHF with pLVEF by multivariable logistic regression adjusting for comorbidities, demographic and clinical variables. Higher rate of pAHF in female than in male STEMI patients with pLVEF is associated with higher plasma glycine in women. The glycine level may be genetically determinated by female sex. The plasma glycine > 2.6 mg/dL is a predictor of pAHF in STEMI with pLVEF (including female and male). [ABSTRACT FROM AUTHOR]

To research the effects of melatonin on cardiac function, myocardial cell metabolic stress and apoptosis in heart failure after myocardial infarction rats. Thirty specific-pathogen-free male Sprague Dawley rats were randomly divided into sham operation group (n=10), model group (n=10) and melatonin group (n=10). The model group and the melatonin group were constructed by ligating the left anterior descending coronary artery, while not in the sham operation group. Melatonin group (10 mg/kg) was intraperitoneally injected with melatonin (Sigma, United States of America) 30 min before operation. The sham operation group and the model group were injected intraperitoneally with the same amount of normal saline. The cardiac function of rats was measured by left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end diastolic diameter and left ventricular end-systolic diameter. The myocardial cell apoptosis in ischemic areas of each group was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of related proteins, measure myocardial fibrosis and determine the oxidative stress parameters (nicotinamide adenine dinucleotide phosphate oxidases activity, superoxide anion, malondialdehyde and superoxide dismutase) were detached via Western blot. Left ventricular fractional shortening % and left ventricular ejection fraction % in the melatonin group were significantly increased than those in the model group (p<0.05), while left ventricular end diastolic diameter and left ventricular end-systolic diameter in the melatonin group were significantly decreased (p<0.05). The apoptotic cardiomyocytes number in melatonin group was significantly less in model group (p<0.05). The levels of B-cell lymphoma 2 associated X-protein and caspase-3 protein in rat cardiomyocytes in melatonin group were significantly lower than those in model group (p<0.05). The proportion of sirius red staining in the melatonin group was significantly less than that in model group (p<0.05). Collagen I/III and transforming growth factor of rat cardiomyocytes in melatonin group-beta was significantly down-regulated than that in the model group (p<0.05). Nicotinamide adenine dinucleotide phosphate oxidase activity, superoxide anion and malondialdehyde level of rats in melatonin group were significantly decreased than those in model group, while superoxide dismutase activity was significantly increased than that in model group (p<0.05). Melatonin can improve heart failure and cardiac fibrosis by restraining oxidative stress in heart failure rats. Nicotinamide adenine dinucleotide phosphate oxidases 1 play an important role in regulating the role of melatonin in reducing cardiac fibroblasts fibrosis. [ABSTRACT FROM AUTHOR]

Aims This study aimed to investigate the incremental value offered by left atrial reservoir strain (LASr) to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) diastolic algorithm to identify elevated left ventricular (LV) filling pressure in patients with preserved ejection fraction (EF). Methods and results Near-simultaneous echocardiography and right heart catheterization were performed in 210 patients with EF ≥50% in a large, dual-centre study. Elevated filling pressure was defined as invasive pulmonary capillary wedge pressure (PCWP) ≥15 mmHg. LASr was evaluated using speckle-tracking echocardiography. Diagnostic performance of the ASE/EACVI diastolic algorithm was validated against invasive reference and compared with modified algorithms incorporating LASr. Modest correlation was observed between E / e ′, E / A ratio, and LA volume index with PCWP (r = 0.46, 0.46, and 0.36, respectively; P < 0.001 for all). Mitral e ′ and TR peak velocity showed no association. The ASE/EACVI algorithm (89% feasibility, 71% sensitivity, 68% specificity) demonstrated reasonable ability (AUC = 0.69) and 68% accuracy to identify elevated LV filling pressure. LASr displayed strong ability to identify elevated PCWP (AUC = 0.76). Substituting TR peak velocity for LASr in the algorithm (69% sensitivity, 84% specificity) resulted in 91% feasibility, 81% accuracy, and stronger agreement with invasive measurements. Employing LASr as per expert consensus (71% sensitivity, 70% specificity) and adding LASr to conventional parameters (67% sensitivity, 84% specificity) also demonstrated greater feasibility (98% and 90%, respectively) and overall accuracy (70% and 80%, respectively) to estimate elevated PCWP. Conclusions LASr improves feasibility and overall accuracy of the ASE/EACVI algorithm to discern elevated filling pressures in patients with preserved EF. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis is a common pathological consequence of most myocardial diseases. It is associated with the excessive accumulation of extracellular matrix proteins as well as fibroblast differentiation into myofibroblasts in the cardiac interstitium. This structural remodeling often results in myocardial dysfunctions such as arrhythmias and impaired systolic function in patients with heart conditions, ultimately leading to heart failure and death. An understanding of the precise mechanisms of cardiac fibrosis is still limited due to the numerous signaling pathways, cells, and mediators involved in the process. This review article will focus on the pathophysiological processes associated with the development of cardiac fibrosis. In addition, it will summarize the novel strategies for anti-fibrotic therapies such as epigenetic modifications, miRNAs, and CRISPR technologies as well as various medications in cellular and animal models. [ABSTRACT FROM AUTHOR]

Level of Evidence: 5 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Background: A familial predisposition to sudden and/or arrhythmic death (SAD) in the setting of coronary artery disease (CAD) exists; however, the genetic basis is poorly understood.Objectives: The purpose of this study was to determine whether a genome-wide polygenic score for coronary artery disease (GPSCAD) might have utility in SAD risk stratification in CAD patients without severe systolic dysfunction.Methods: A previously validated GPSCAD was generated utilizing genome-wide genotyping in 4,698 PRE-DETERMINE participants of European ancestry with CAD and left ventricular ejection fraction >30%-35%. The population was dichotomized according to top GPSCAD decile as defined by the general population, and absolute, proportional, and relative risks for SAD and non-SAD were estimated using competing risk analyses.Results: Over a median follow-up of 8.0 years, participants in the top GPSCAD decile were at elevated absolute SAD risk (8.0%; 95% CI: 5.1%-12.4% vs 4.8%; 95% CI: 3.3%-7.0%; P = 0.005) and proportional SAD risk (29% vs 16%; P = 0.0003) compared with the remainder. After controlling for left ventricular ejection fraction, clinical factors, and electrocardiogram parameters, the top GPSCAD decile was associated with SAD (subdistribution HR: 1.77; 95% CI: 1.23-2.54; P = 0.002) but not non-SAD (subdistribution HR: 1.00; 95% CI: 0.80-1.25; P = 0.98) (P for Δ = 0.003). The addition of the top GPSCAD decile to the multivariable model significantly improved net reclassification indexes (NRIs) (continuous NRI: 14.0%; P = 0.024; and categorical NRI: 6.6%; P = 0.005) but not the C-index (difference in C-index: 0.007; P = 0.143).Conclusions: Among CAD patients without severe systolic dysfunction, high GPSCAD specifically predicted SAD and enriched for both absolute and proportional SAD risk, identifying a population who might benefit from defibrillator therapy. [ABSTRACT FROM AUTHOR]

Objective. To offer a baseline for clinical diagnosis, echocardiography was performed to evaluate the disparities in heart function comparing pregnant women with diabetes mellitus (GDM) and ordinary pregnant women. Methods. A prospective case-control study is being conducted on pregnant women with or without gestational diabetes. The sample size for both the intervention and control groups is the same: no diabetes diagnosis or previous forms, a single pregnancy, and no issues (such as preeclampsia or fetal growth restriction). The females were all subjected to routine echocardiograms to examine the morphology and function of their left and right hearts. Results. In the research, 51 women with GDM and 50 healthy controls volunteered. Women with GDM had a significantly higher heartrate (82 ± 9 vs. 74 ± 8), left ventricular (LV) relative wall thickness (0.39 ± 0.06 vs. 0.31 ± 0.07 ; P < 0.001), LV early diastolic transmitral valve velocity (E) (0.79 ± 0.14 vs. 0.72 ± 0.13 m/s; P = 0.031), and LV late diastolic implementing regulations valve velocity (0.6). Speckle-tracking analysis showed significant decrease in LV right ventricular (RV). A study indicated a reduced pulmonary acceleration time (59 ± 9 vs. 68 ± 12 ms; P = 0.001), RV E/A ratio (1.21 ± 0.19 vs. 1.31 ± 0.31 ; P = 0.022), and a greater RV myocardial systolic annular velocity (0.17 ± 0.03 vs. 0.12 ± 0.03 ; P = 0.023). Conclusions. Our results revealed that the heart function of diabetic pregnant women differed considerably from that of the control group, such as LV-RWT, LV diastolic transmitral valve speed, and LV late diastolic transmitral valve speed. Given these results, further research into the postpartum cardiovascular healing of pregnant women with gestational diabetes mellitus is required. [ABSTRACT FROM AUTHOR]

Background: Despite current resuscitation strategies, circulatory shock and organ injury after cardiac surgery occur in 25–40% of patients. Goal-directed resuscitation after cardiac surgery has generated significant interest, but clinical practice to normalize hemodynamic variables including mean arterial pressure, cardiac filling pressures, and cardiac output may not reverse microcirculation abnormalities and do not address cellular dysoxia. Recent advances in technology have made it possible to measure critical components of oxygen delivery and oxygen utilization systems in live human tissues and blood cells. The MicroRESUS study will be the first study to measure microcirculatory and mitochondrial function in patients with circulatory shock and link these findings with clinical outcomes. Methods and analysis: This will be a prospective, observational study that includes patients undergoing elective cardiovascular surgery with cardiopulmonary bypass (CPB). Microcirculation will be quantified with sublingual incident dark field videomicroscopy. Mitochondrial respiration will be measured by performing a substrate–uncoupler–inhibitor titration protocol with high resolution respirometry on peripheral blood mononuclear cells at baseline and serial timepoints during resuscitation and at recovery as a possible liquid biomarker. Plasma samples will be preserved for future analysis to examine endothelial injury and other mechanisms of microcirculatory dysfunction. Thirty-day ventilator and vasopressor-free days (VVFDs) will be measured as a primary outcome, along with sequential organ failure assessment scores, and other clinical parameters to determine if changes in microcirculation and mitochondrial respiration are more strongly associated with clinical outcomes compared to traditional resuscitation targets. Discussion: This will be the first prospective study to examine both microcirculatory and mitochondrial function in human patients with circulatory shock undergoing cardiac bypass and address a key mechanistic knowledge gap in the cardiovascular literature. The results of this study will direct future research efforts and therapeutic development for patients with shock. [ABSTRACT FROM AUTHOR]

Background. Bisoprolol is commonly used to treat moderate or severe chronic stable heart failure, coronary heart disease, and hypertension. This study is aimed at analyzing the efficacy of bisoprolol in the treatment of myocardial infarction with cardiac insufficiency and its effect on cardiac function, Hcy, and CRP through meta-analysis. Methods. A total of 120 patients with myocardial infarction and cardiac insufficiency from February 2020 to February 2021 were selected and randomly divided into two groups (control and the observation, n = 60) according to the random number table method. The control group was given conventional treatment. The observation group was given bisoprolol on the basis of control group. The clinical efficacy, systolic blood pressure, diastolic blood pressure, heart rate, cardiac function indexes, homocysteine (Hcy), and C-reactive protein (CRP) levels were compared between the two groups before and after treatment through data analysis. Adverse reactions were observed during treatment. Results. Compared with the control group, the total effective rate of the observation group was significantly increased (p < 0.05). After treatment, the levels of heart rate, left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) and serum Hcy and CRP levels in the observation group were significantly lower than those in the control group (p < 0.05). Meanwhile, left ventricular ejection fraction (LVEF) level in the observation group after treatment was higher than that of the control group (p < 0.05). Conclusion. Bisoprolol combined with conventional treatment can reduce serum Hcy and CRP levels in patients with myocardial infarction and cardiac insufficiency and improve cardiac function. Moreover, there are no obvious adverse reactions during the treatment. [ABSTRACT FROM AUTHOR]

Background: Chronic Chagas Cardiomyopathy (CCM) is characterized by a unique pathophysiology in which inflammatory, microvascular and neuroendocrine processes coalesce in the development of one of the most severe cardiomyopathies affecting humans. Despite significant advances in understanding the molecular mechanisms involved in this disease, scarce information is available regarding microRNAs and clinical parameters of disease severity. We aimed to evaluate the association between circulating levels of six microRNAs with markers of myocardial injury and prognosis in this population. Methods: Patients with CCM and reduced ejection fraction were included in a prospective exploratory cohort study. We assessed the association of natural log-transformed values of six circulating microRNAs (miR-34a-5p, miR-208a-5p, miR-185-5p, miR-223-5p, let-7d-5p, and miR-454-5p) with NT-proBNP levels and echocardiographic variables using linear regression models adjusted for potential confounders. By using Cox Proportional Hazard models, we examined whether levels of microRNAs could predict a composite outcome (CO), including all-cause mortality, cardiac transplantation, and implantation of a left ventricular assist device (LVAD). Finally, for mRNAs showing significant associations, we predicted the target genes and performed pathway analyses using Targetscan and Reactome Pathway Browser. Results: Seventy-four patients were included (59% males, median age: 64 years). After adjustment for age, sex, body mass index, and heart failure medications, only increasing miR-223-5p relative expression levels were significantly associated with better myocardial function markers, including left atrium area (Coef. -10.2; 95% CI -16.35; -4.09), end-systolic (Coef. -45.3; 95% CI -74.06; -16.61) and end-diastolic volumes (Coef. -46.1; 95% CI -81.99; -10.26) of the left ventricle. Moreover, we observed that higher miR-223-5p levels were associated with better left-ventricle ejection fraction and lower NT-proBNP levels. No associations were observed between the six microRNAs and the composite outcome. A total of 123 target genes for miR-223-5p were obtained. From these, several target pathways mainly related to signaling by receptor tyrosine kinases were identified. Conclusions: The present study found an association between miR-223-5p and clinical parameters of CCM, with signaling pathways related to receptor tyrosine kinases as a potential mechanism linking low levels of miR-223-5p with CCM worsening. [ABSTRACT FROM AUTHOR]

Background: Trans‐catheter device closure of secundum type atrial septal defects (ASDs) has now become the treatment of choice. Device closure affects the hemodynamics and function of the heart. In the current study, we investigated the remodeling of the heart as assessed by advanced echocardiographic parameters following successful device closure. Methods: A prospective cohort study was conducted and 45 patients who were eligible for ASD device closure were evaluated for volumetric, functional, Doppler, strain, and strain rate data of left and right atrium and ventricle pre‐procedural and 48 h post‐procedure Results: In a prospective cohort study 45 patients who were eligible for ASD device closure; atrial and ventricular volumetric, functional, Doppler, strain, and strain rate data were recorded and compared pre‐procedurally and 48 h post‐procedure.We found significant changes in the left ventricular (LV) end diastolic volume index (p‐value =.03), right ventricular (RV) diameter (p‐value = <.001), left atrial (LA) volume index (p‐value =.05), right atrial (RA) volume index (p‐value =.001), and right and left sided E/e' ratio with a p‐value of.001 and.004, respectively. Our findings showed a significant reduction in the strains of the right and left atria and the right ventricular free wall after ASD device closure. LV global longitudinal strain decreased after the procedure but did not reach statistical significance. Conclusion: ASD patients have impaired global strains compared to normal defined ranges. LA, RA, and RV strains show significant reduction after device closure. Decline in LA function following closure was greater in those with larger ASDs. In adult patients undergoing the procedure, abnormal LA function is a clinically relevant issue demanding pre and post‐ procedural precautions and treatment. [ABSTRACT FROM AUTHOR]

Stress echocardiography helps to diagnose cardiac diseases that cannot easily be detected or do not even manifest at rest. In clinical practice, assessment of the stress test is usually performed visually and, therefore, in a qualitative and subjective way. Although speckle tracking echocardiography (STE) has been proposed for the quantification of function during stress, its time resolution is inadequate at high heart rates. Recently, high-frame-rate (HFR) imaging approaches have been proposed together with dedicated STE algorithms capable of handling small interframe displacements. The aim of this study was to determine if HFR STE is effective in assessing strain and strain rate parameters during echocardiographic stress testing. Specifically, stress echocardiography, at four different workload intensities, was performed in 25 healthy volunteers. At each stress level, HFR images from the apical four-chamber view were recorded using the ULA-OP 256 experimental scanner. Then, the myocardium was tracked with HFR STE, and strain and strain rate biomarkers were extracted to further analyze systolic and diastolic (early and late) peaks, as well as a short-lived isovolumic relaxation peak during stress testing. The global systolic strain response was monophasic, revealing a significant (p < 0.001) increase at low stress but then reaching a plateau. In contrast, all strain rate indices linearly increased (p < 0.001) with increasing stress level. These findings are in line with those reported using tissue Doppler imaging and, thus, indicate that HFR STE can be a useful tool in assessing cardiac function during stress echocardiography. [ABSTRACT FROM AUTHOR]

Mortality rates associated with myocardial dysfunction due to sepsis and septic shock are generally high across the world. The present study focused on the antioxidant and anti‐inflammatory effects of perindopril (PER) for the purpose of preventing the adverse effects of sepsis on the myocardium and developing new alternatives in treatment. The control group received only saline solution via the oral route for 4 days. The second group underwent cecal ligation puncture (CLP), and the third underwent CLP and received PER (2 mg/kg). Rats in the third group received 2 mg/kg PER per oral (p.o.) from 4 days before induction of sepsis. Thiobarbituric acid reactive species (TBARS), total thiol (‐SH), interleukin‐1 beta (IL‐1β), IL‐6, 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), and nuclear factor kappa B (NF‐κB/p65) levels increased in the CLP groups. In contrast, PER (2 mg/kg) decreased the levels of biochemical parameters other than total‐SH and decreased 8‐OHdG, NF‐κB/p65 immunopositivity in rat heart tissues. The data from this study show that impairment of the oxidant/antioxidant balance and inflammatory cytokine levels in favor of inflammation in heart tissue under septic conditions results in severe tissue damage. PER administration before sepsis was shown to exhibit antioxidant and anti‐inflammatory properties by reducing these effects. This in turn increased the importance of PER as new evidence of its protective effects in heart tissue. [ABSTRACT FROM AUTHOR]

Furthermore, after HFpEF patients were stratified according to the New York Heart Association (NYHA) [[89]] functional classes, d-ROM levels were found to be significantly higher in patients with NYHA III/IV than in those with NYHA II (median d-ROMs = 405 UCARR; IQR = 346-478 UCARR vs. median d-ROMs = 338 UCARR; IQR = 308-383 UCARR; I p i < 0.001). After matching the HFpEF and non-HF groups ( I n i = 212 each) for age, gender, and equal incidence of risk factors, d-ROM levels were found to be significantly higher in the HFpEF group than in the non-HF group (median d-ROMs = 343 UCARR; IQR = 312-394 UCARR vs. median d-ROMs = 336 UCARR; IQR = 288-381 UCARR; I p i < 0.001). Keywords: oxidative stress; blood biomarkers; d-ROMs; prognostic value; cardiovascular diseases; mortality EN oxidative stress blood biomarkers d-ROMs prognostic value cardiovascular diseases mortality N.PAG N.PAG 26 08/29/22 20220801 NES 220801 1. The d-ROM median value of 303 UCARR was used as the threshold to divide patients into a low-d-ROM group (group L; mean d-ROMs = 235 ± 45 UCARR) and a high-d-ROM group (group H; mean d-ROMs = 421 ± 85 UCARR). Below, we summarise the main results obtained in clinical studies that evaluated the correlations between d-ROM plasma levels and the risk of future CVD events and death in individuals affected by CVD (Table 1). 7.1. d-ROMs in Coronary Artery Disease (CAD) Masaki et al. [[77]] analysed the correlation between d-ROM values and the risk of future CVD events in a prospective cohort of 265 subjects with stable CVD, of whom 130 had known coronary artery disease CAD (defined as having at least one coronary stenosis proven by coronary angiography (CAG) or history of coronary revascularisation). [Extracted from the article]

After multivariable adjustment (energy intake, demographics, lifestyle factors, prevalent cardiovascular disease, diabetes, hypertension), HF risk was higher with a greater intake of eggs (1.23) and high-fat dairy (1.08) and HF risk was lower with greater whole-grain intake (0.93) [[32]]. Keywords: Western diet; cardiomyocyte; oxidative stress; bioactive agents; dietary fat; heart hypertrophy; cardiac failure EN Western diet cardiomyocyte oxidative stress bioactive agents dietary fat heart hypertrophy cardiac failure N.PAG N.PAG 18 08/29/22 20220801 NES 220801 In the ancient scripture Bhagavad Gita (3000 BCE) in India, Sattvic diets were advised for health, happiness, peace and longevity (https://www.holy-bhagavad-gita.org/chapter/17/verse/8, accessed on 15 June 2022). It seems that an increase in free fatty acids and oxidative dysfunction with reference to variability in biomarkers such as glucose levels, and levels of oxidative stress, predispose individuals to multifold greater inflammation and immune deficiency, leading to cardiac cell apoptosis and heart failure (HF) [[23], [25]]. Protective Dietary Patterns in the Prevention of Heart Failure In the USA, as well as in other Western countries, dietary patterns of patients with HF reveal a generally poor Western-type diet that may have a negative impact and a Mediterranean-style diet that may have a beneficial effect on pathophysiology and progression of CVDs and HF [[46], [52]]. Such diets may begin their adverse effects by causing twist dysfunction (Stage 1 HF) and later on sub-endocardial dysfunction (Stage 2 of HF) due to oxidative damage of proteins, enzymes, fatty acids and DNA. [Extracted from the article]