Efficacy of trimetazidine – an inhibitor of free fatty acids oxidation in the treatment of patients with stable angina pectoris and heart failure

Kardiologiia ◽  
2021 ◽  
Vol 61 (11) ◽  
pp. 65-76
Author(s):  
M. G. Bubnova ◽  
D. M. Aronov

Aim      To evaluate efficacy of modified-release trimetazidine (TMZ) included into the standard therapy for patients with stable angina and chronic heart failure (CHF) as a part of a subgroup analysis in the PERSPECTIVE study.Material and methods  The study included 806 patients: group 1 (n=691), patients receiving a standard therapy and modified-release TMZ (TMZ group); and group 2 (n=115), patients receiving a standard therapy (control group). Total duration of the study was 12 months.Results In the TMZ group, the weekly number of angina attacks decreased by 41.9% (p<0.0001) in 2 months and by 69.6 % (from baseline, р<0.0001) in 12 months, and the frequency of nitroglycerine dosing decreased by 40.8 % (р<0.0001) and 67.7 % (р<0.0001), respectively. In the control group, the respective values did not change. In the TMZ group compared to the control group, the QT interval was shorter (7.9 %; р<0.05), the left ventricular (LV) end-systolic dimension was reduced (13.4 %; р<0.01), interventricular septal thickness and LV posterior wall thickness were decreased (9.5 %; р<0.01 and 12.2 %; р<0.01, respectively), and the ejection fraction was increased (11.4; р<0.05). Following the TMZ treatment, the leukocyte count in peripheral blood was decreased (5.3 %; р<0.01) and the serum concentration of high-sensitivity C-reactive protein was decreased (30.7 %; р<0.01) vs. increases of these indexes in the control group (17.9 %; р<0.05 and 17.8 %; р<0.05, respectively). The proportion of patients hospitalized for exacerbation of CHF or angina for 12 months was 8.6 % in the TMZ group and 15.7 % in the control group (p=0,001).Conclusion      In patients with stable angina and CHF, inclusion of modified-release TMZ into the standard therapy decreases the number of angina attacks, reduces the activity of inflammatory factors, and improves the course of disease.

2020 ◽  
Vol 19 (2) ◽  
pp. 181-187
Author(s):  
Jing Li ◽  
Yun Zhang ◽  
Weizhong Huangfu ◽  
Yuhong Ma

Using rat models of heart failure, we evaluated the effects of rosuvastatin and Huangqi granule alone and in combination on left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole, and left ventricular posterior wall thickness at end-systole. Results showed that left ventricular end-diastolic dimension, left ventricular end-systolic dimension in the rosuvastatin + Huangqi granule group were significantly decreased (P ‹ 0.01), while left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole were significantly increased (P ‹ 0.05). The serum IL-2, IFN-β, and TNF-α in rosuvastatin + Huangqi granule group were significantly lower than those in model group (P ‹ 0.05). However, the levels of S-methylglutathione and superoxide dismutase in rosuvastatin + Huangqi granule group were significantly higher, while nitric oxide was significantly lower than that in the model group (P ‹ 0.05). Also, compared to the model group, the apoptosis rate, and the autophagy protein LC3-II in the cardiomyocytes of rosuvastatin + Huangqi granule group was significantly decreased (P ‹ 0.01), while the level of p62 protein was significantly increased (P ‹ 0.01). The levels of AMPK and p-AMPK in cardiomyocytes were significantly lower in rosuvastatin + Huangqi granule group; however, the levels of mTOR and p-mTOR showed an opposite trend (P ‹ 0.05). To sum up, rosuvastatin + Huangqi granule could improve the cardiac function, decrease the level of oxidative stress, and inflammatory cytokines in rats with HF. The possible underlying mechanism might be inhibition of autophagy and reduced apoptosis in cardiomyocytes by regulating AMPK-mTOR signaling pathway.


2017 ◽  
Vol 68 (7) ◽  
pp. 1506-1511
Author(s):  
Cerasela Mihaela Goidescu ◽  
Anca Daniela Farcas ◽  
Florin Petru Anton ◽  
Luminita Animarie Vida Simiti

Oxidative stress (OS) is increased in chronic diseases, including cardiovascular (CV), but there are few data on its effects on the heart and vessels. The isoprostanes (IsoP) are bioactive compounds, with 8-iso-PGF25a being the most representative in vivo marker of OS. They correlate with the severity of heart failure (HF), but because data regarding OS levels in different types of HF are scarce, our study was aimed to evaluate it by assessing the urinary levels of 8-iso-PGF2aand its correlations with various biomarkers and parameters. Our prospective study included 53 consecutive patients with HF secondary to ischemic heart disease or dilative cardiomyopathy, divided according to the type of HF (acute, chronic decompensated or chronic compensated HF). The control group included 13 hypertensive patients, effectively treated. They underwent clinical, laboratory - serum NT-proBNP, creatinine, uric acid, lipids, C reactive protein (CRP) and urinary 8-iso-PGF2a and echocardiographic assessment. HF patients, regardless the type of HF, had higher 8-iso-PGF2a than controls (267.32pg/�mol vs. 19.82pg/�mol, p[0.001). The IsoP level was directly correlated with ejection fraction (EF) (r=-0.31, p=0.01) and NT-proBNP level (r=0.29, p=0.019). The relative wall thickness (RWT) was negatively correlated with IsoP (r=-0.55, p[0.001). Also 8-iso-PGF25a was higher by 213.59pg/�mol in the eccentric left ventricular (LV) hypertrophy subgroup comparing with the concentric subgroup (p=0.014), and the subgroups with severe mitral regurgitation (MR) and moderate/severe pulmonary hypertension (PAH) had the highest 8-iso-PGF2a levels. Male sex, severe MR, moderate/severe PAH, high LV mass and low RWT values were predictive for high OS level in HF patients.Eccentric cardiac remodeling, MR severity and PAH severity are independent predictors of OS in HF patients.


Author(s):  
Anna Chuda ◽  
Maciej Banach ◽  
Marek Maciejewski ◽  
Agata Bielecka-Dabrowa

AbstractHeart failure (HF) is the only cardiovascular disease with an ever increasing incidence. HF, through reduced functional capacity, frequent exacerbations of disease, and repeated hospitalizations, results in poorer quality of life, decreased work productivity, and significantly increased costs of the public health system. The main challenge in the treatment of HF is the availability of reliable prognostic models that would allow patients and doctors to develop realistic expectations about the prognosis and to choose the appropriate therapy and monitoring method. At this moment, there is a lack of universal parameters or scales on the basis of which we could easily capture the moment of deterioration of HF patients’ condition. Hence, it is crucial to identify such factors which at the same time will be widely available, cheap, and easy to use. We can find many studies showing different predictors of unfavorable outcome in HF patients: thorough assessment with echocardiography imaging, exercise testing (e.g., 6-min walk test, cardiopulmonary exercise testing), and biomarkers (e.g., N-terminal pro-brain type natriuretic peptide, high-sensitivity troponin T, galectin-3, high-sensitivity C-reactive protein). Some of them are very promising, but more research is needed to create a specific panel on the basis of which we will be able to assess HF patients. At this moment despite identification of many markers of adverse outcomes, clinical decision-making in HF is still predominantly based on a few basic parameters, such as the presence of HF symptoms (NYHA class), left ventricular ejection fraction, and QRS complex duration and morphology.


2014 ◽  
Vol 9 ◽  
pp. IMI.S13939 ◽  
Author(s):  
Bandi Hari Krishna ◽  
Pravati Pal ◽  
G. K. Pal ◽  
J. Balachander ◽  
E. Jayasettiaseelon ◽  
...  

Aims The purpose of this study was to evaluate whether yoga training in addition to standard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF). Methods 130 patients were recruited and randomized into two groups: Control Group (CG) ( n = 65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the study. Cardiac function using left ventricular ejection fraction (LVEF), myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was assessed at baseline and after 12 weeks. Result Improvement in LVEF, Tei index, and NT pro BNP were statistically significant in both the groups. Furthermore, when the changes in before and after 12 weeks were in percentage, LVEF increased 36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and 2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG. The between group comparisons from pre to post 12 weeks were significant for YG improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01). Conclusion These results indicate that the addition of yoga therapy to standard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
N Kraenkel ◽  
A Koc ◽  
S Kaczmarek ◽  
K Lehnert ◽  
I Urbaneck ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BMBF Background Patients with heart failure with reduced ejection fraction (HFrEF) have an increased inflammatory load and impaired cardiac oxidative lipid phosphorylation. Early dysregulations of pathophysiological alterations may not be detectable if patients are assessed under resting conditions. Purpose We exposed HFrEF patients to a physical exertion challenge by cardiopulmonary exercise testing (CPET) and determined inflammatory and metabolic parameters before, during and 2 hours after the test. Methods A symptom-limited CPET was performed in participants with HFrEF (n = 16) and age and sex matched controls (CON, n = 13). In addition to clinical and physiological parameters, we assessed blood counts of leukocyte subtypes, their morphology, aggregation with platelets and microvesicle release, as well as plasma cytokines and metabolites at baseline (T1), immediately after CPET (T2), and after 2 hours of rest (T3). Inflammatory and metabolic parameters were measured using the ThermoFischer ProcartaPlex Human Inflammation-Panel and Biocrates MxP® Quant 500 kit, respectively. Non-parametric tests were chosen and all multiple tests were adjusted by the Benjamini-Hochberg method. Results Cardiovascular risk profile of HFrEF and CON was similar. In agreement with the definition for HFrEF, these patients had a lower EF and a greater left ventricular enddiastolic diameter compared to CON. There were no differences between groups for leukocyte, cytokine or metabolic parameters at T1. Immediately after CPET, 20 parameters were significantly increased in both groups, including an increase of lactate, natural killer (NK) and NK T cell blood counts. In addition, 131 inflammatory and metabolic parameters were upregulated only in HFrEF, as compared to only 17 in CON. In HFrEF-platelet aggregates with NK cells, CD8+ cytotoxic T cells and "classical" CD14++CD16-monocytes, 58 different phosphatidylcholines and 21 triglycerides were upregulated immediately after exercise. At T3 almost all altered parameters returned to baseline in CON while in HFrEF blood counts and morphological markers of inflammatory effector cell types, including NK cells, CD8+ T cells and neutrophils, as well as genomic nuclear DNA, an indicator of cell death, remained elevated. Moreover, several triglycerides did not return to baseline in HFrEF after a 2-hour resting period. In these patients, but not in CON, the different lipids (i.e. phosphatidylcholine, triglycerides) strongly correlated with pro-inflammatory cytokines and NK cells. Conclusion Our data support the concept of impaired fatty acid utilization and inflammation-mediated metabolic dysregulation in HFrEF. However, the correlations between metabolic and inflammatory parameters were not detected at baseline in comparison to a control group with similar cardiovascular risk profile. Therefore, investigating patients in response to a physical or metabolic challenge might reveal early pathological changes.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Marcus Sandri ◽  
Stephan Gielen ◽  
Norman Mangner ◽  
Volker Adams ◽  
Sandra Erbs ◽  
...  

Background: The concept of ventricular-arterial coupling implies that LV-function is determined by the three factors left ventricular diastolic, left ventricular systolic and arterial elastance. We have previously documented an improvement in endothelial function and systolic LV-function in patients with chronic heart failure (CHF) after 6 months of exercise training (ET). It remains, however, unclear, how shorter ET periods may affect endothelial, systolic and diastolic ventricular function as echocardiographic parameters related to ventricular arterial coupling in patients with CHF. METHODS: In this ongoing study we randomised 43 patients with stable CHF (age 60.3 ± 2.9 years, EF 27.4 ± 1.7%, VO 2 max 14.7 ± 4.3ml/kg*min) to a training or a control group (C). Patients in the training group exercised 4 times daily at 70% of the individual heart rate reserve for 4 weeks under supervision. At baseline and after 4 weeks the E/A ratio and septal/lateral E’/A’ velocities were determined by echocardiography with tissue Doppler. Exercise capacity was measured by ergospirometry and flow-mediated dilatation (FMD) was assessed by high-resolution radial ultrasound. RESULTS: After only 4 weeks of ET oxygen uptake at peak exercise increased from 14.9 ± 3.3 to 18.1 ± 4.7 ml/min/kg, (p<0.01 vs. C) in training subjects. Left ventricular ejection fraction improved from 26.8 ± 4.6 to 33.1 ± 5.5% (p<0.05 vs. C) in patients of the training group while it remained unchanged in the control group. E/A-ratio mended from 0.63 ± 0.12 to 0.81 ± 0.22 (p<0.01 vs. C) in training patients. Septal E’ velocities increased from 5.5 ± 0.5 to 7.8 ± 1.4 cm/s in training patients (p<0.05 vs. C). FMD of the radial artery improved from 8.2 ± 2.1 to 15.2 ± 3.8% (p<0.01 vs. C) as a result of ET. CONCLUSIONS: Only 4 weeks of endurance training are highly effective with significantly improved FMD accompanied by an emended systolic and diastolic LV-function. We hypothesise that the improvement in LV-EF in training patients may be caused by a corrected ventricular-arterial coupling: ventricular diastolic relaxation and effective endothelial function are ameliorated resulting in an augmentation of stroke volume.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomomi Meguro

Introduction: The exacerbation of heart failure (HF) induces brain damage and the cognitive impairment that attenuates the effects of treatment. The medial lateral lobe of brain, including parahippocampal gyrus, is known to reduce its volume in patients with cognitive disorder especially in Alzheimer’s disease. The magnetic resonance imaging (MRI) scans identify morphological changes in the brains of patients with HF. Therefore, the Voxel-based morphometry (VBM) of three-dimensional brain MRI may contribute to predict the potential risk of mild cognitive impairment (MCI) of patients with HF. Hypothesis: The severity of local atrophy of parahippocampal gyrus, a potential risk of MCI, is prominent in heart failure patients without dementia. Methods: Ten HF patients (age 72+/-15 years, NYHA class II, EF43+/-15 %) and 9 control (age 76+/- 8 years) were enrolled. Patients with dementia were excluded from this study. Three dimensional T1 weighted sagittal images of whole brain were taken using 1.5T MRI. Image analysis was performed to evaluate the severity of local brain atrophy of gray matter using 2mm VBM by the software based on statistical parametric mapping. The Z-score value of volume of interest (VOI) was calculated to evaluate the severity of atrophy in parahippocampal gyrus. Results: The severity of total brain atrophy was similar between HF (8.3+/-3.4%) and control (8.0+/-4.1%). However, as shown in the figure of representative cases, the Z-score value of VOI (pink circle), reflecting the severity of atrophy in parahippocampal gyrus (white arrows), was larger in HF patients group (1.4+/-0.7) in comparison with control group (0.8+/-0.4, P=0.034). The Z-score value was not correlated with age, ejection fraction, left atrial dimension, left ventricular dimensions, or BNP in HF group. Conclusions: In patients with HF, atrophy in parahippocampal gyrus was prominent in comparison with control. Patients with heart failure have potential risk of MCI and dementia.


Author(s):  
Fang-Fei Wei ◽  
Yuzhong Wu ◽  
Ruicong Xue ◽  
Xiao Liu ◽  
Xin He ◽  
...  

It remains debated whether pulse pressure is associated with left ventricular traits and adverse outcomes over and beyond mean arterial pressure (MAP) in patients with heart failure (HF) with preserved ejection fraction. We investigated these associations in 3428 patients with HF with preserved ejection fraction (51.5% women; mean age, 68.6 years) enrolled in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). We computed association sizes and hazards ratios with 1-SD increase in MAP and pulse pressure. In multivariable-adjusted analyses, association sizes ( P ≤0.039) for MAP were 0.016 cm and 0.014 cm for septal and posterior wall thickness, −0.15 for E/A ratio, −0.66 for E/e′, and −0.64% for ejection fraction, independent of pulse pressure. With adjustment additionally applied for MAP, E/A ratio and longitudinal strain increased with higher pulse pressure with association sizes amounting to 0.067 ( P =0.026) and 0.40% ( P =0.023). In multivariable-adjusted analyses of both placebo and spironolactone groups, lower MAP and higher pulse pressure predicted the primary composite end point ( P ≤0.028) and hospitalized HF ( P ≤0.002), whereas MAP was also significantly associated with total mortality ( P ≤0.007). Sensitivity analyses stratified by sex, median age, and region generated confirmatory results with exception for the association of adverse outcomes with pulse pressure in patients with age ≥69 years. In conclusion, the clinical application of MAP and pulse pressure may refine risk estimates in patients with HF with preserved ejection fraction. This finding may help further investigation for the development of HF with preserved ejection fraction preventive strategies targeting pulsatility and blood pressure control.


1996 ◽  
Vol 42 (2) ◽  
pp. 15-17
Author(s):  
Ye. I. Sokolov ◽  
A. P. Zayev ◽  
R. P. Olkha ◽  
T. P. Morozova ◽  
S. A. Zhizhina ◽  
...  

Echocardiographic parameters of the central and intracardiac hemodynamics were analyzed in 67 patients with compensated diabetes mellitus of types I and II of 2 to 6 years standing. The control group consisted of 30 subjects. The increase of the minute volume, stroke volume, specific power of the left ventricle, and reduction of total peripheral resistance were revealed in both groups of patients. These shifts are characteristic of a hyperkinetic type of central hemodynamics. The hyperdynamic syndrome was due to left-ventricular hypertrophy in patients with noninsulin-dependent diabetes and due to increased heart rate and the rate of circulatory shortening of myocardial fibers in patients with the insulin-dependent condition. Impaired diastolic function presenting as an increase of the end diastolic volume and a reduced rate of relaxation of the left-ventricular posterior wall myocardium were observed in all the patients, no matter what the type of the condition. The above shifts are predictors of a reduction of myocardial contractility, responsible for the grave and atypical course of coronary disease in diabetics.


2021 ◽  
Author(s):  
Chao Liu ◽  
Chengyu Ni ◽  
Weichu Liu ◽  
Xiaolian Yang ◽  
Renyi Zhang ◽  
...  

Abstract Background: Myocardial fibrosis is a critical pathological basis for the poor prognosis of cardiovascular diseases. Studies have found that myocardial fibrosis is closely associated with exposure to environmental estrogens such as nonylphenol (NP), as a representative of environmental estrogens. The aim of this study was to examine the effects of NP chronic exposure on myocardial fibrosis as well as cardiac structure and function. Forty Sprague Dawley rats were randomly divided into four groups (n = 10): control group (C), low NP dose (0.4 mg/kg, L), medium NP dose (4 mg/kg, M), and high NP dose (40 mg/kg, H) groups. The NP dose groups were gavaged with NP for 180 days. Results: The NP level in the heart of the NP groups was significantly higher than those in the control group (F = 43.658, P < 0.001). Serum aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isozyme (CK-MB), lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) significantly increased in the NP groups compared with the control group (). Histopathological examination of the heart biopsy illustrates that in the medium and high NP groups, the fibrous connective tissue had a disordered and loose gridding shape, muscle fibers had fractured, and muscle fibers were loose with a widened gap. Extensive inflammatory cell infiltration and fibroblast proliferation in the myocardial interstitium were also found. With increasing NP dose, the degree of muscle fiber loosing and disorder became more significant in the NP treatment groups, and the collagen volume fraction (CVF) was higher than that in the control group (P < 0.01). Compared with the control group, the expression of collagen I and collagen III increased significantly in the medium and high NP groups (P < 0.05). The values of the systolic thickness of the left ventricular anterior wall (LVAWs), the diastolic thickness of the left ventricular posterior wall (LVPWd), the systolic thickness of the left ventricular posterior wall (LVPWs), and the left ventricular anterior wall (LVAWd) in the NP groups are were slightly lower than those in of the control group. The values of left ventricular end systolic dimensions (LVIDs) in the NP groups increased compared with the control group. Conclusions: Long-term NP exposure could lead to fibrosis in the rat myocardium, which is characterized by increased expressions of myocardial collagen I and collagen III, as well as elevated cardiac enzymes. In addition, the cardiac structure was affected and changes were observed in the thinner ventricular wall and as an enlarged ventricular cavity.


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