Critical role of farnesyltransferase inhibitor in protective myocardial function after endotoxemia in rat model

2015 ◽  
Vol 3 (4) ◽  
pp. 322-334
Author(s):  
Richard Durum ◽  
John F. Memon
Keyword(s):  
Ejection Fraction ◽  
Proinflammatory Cytokines ◽  
Myocardial Function ◽  
Troponin I ◽  
Critical Role ◽  
Left Ventricular ◽  
Cellular Damage ◽  
Tail Vein ◽  
Ftase Inhibitor ◽  
Rat Tail

Farnesyltransferase (FTase) is one of the three enzymes in the prenyltransferase group that catalyzes most prenylation reactions and has been proposed as one component of acute inflammation. Endotoxemia was induced in male Wistar rats weighing 300-340 g by lipopolysaccharide (LPS) injection (10 mg/kg BW IV rout via the rat tail vein). Hemodynamic evaluation was performed 4-6 h post-LPS injection by measuring left ventricular end-diastolic pressure, dP/dtmax and myocardial tissue was histologically assessed to analyze macrophage infiltration and cellular damage. Left ventricular function was significantly impaired in the LPS-treated rats, as demonstrated by dP/dtmax (5579±213 vs. 2929±246 mmHg, ctrl vs. LPS; P=0.002) and ejection fraction (61% vs. 23%, ctrl vs. LPS; P=0.0035). LPS was significantly correlated with prominent myocardial cell injury characterized by the increased plasma cardiac troponin-I (cTn-I) and upregulation of proinflammatory cytokines. Furthermore, rats pretreated with FTase inhibitor (Tipifarnib 15 mg/kg BW, IV rout via the rat tail vein) shortly before LPS administration improved myocardial function, dP/dtmax (2929±246 vs. 4125±126 mmHg, LPS vs. Tipifarnib; P<0.05) and ejection fraction (23% vs. 41%, LPS vs. Tipifarnib; P<0.05). The proinflammatory cytokines level, cTn-I level and macrophage accumulation are reduced after neutralized the LPS by FTase inhibitor P<0.05. These data suggest that FTase is a new potential molecular target to improved myocardial function in sepsis.

scholarly journals Predictive values of multiple non-invasive markers for myocardial fibrosis in hypertrophic cardiomyopathy patients with preserved ejection fraction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yumin Li ◽  
Jia Liu ◽  
Yukun Cao ◽  
Xiaoyu Han ◽  
Guozhu Shao ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ejection Fraction ◽  
Myocardial Fibrosis ◽  
Troponin I ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Predictive Values ◽  
Non Invasive ◽  
Potential Biomarker

AbstractMyocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiac-specific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. The LGE-positive patients had significant higher serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels and lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group. The LGE% was independently associated with the Nt-proBNP levels, GCS, LV end-diastolic maximum wall thickness (MWT) and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP ≥ 108.00 pg/mL and MWT ≥ 17.30 mm had good diagnostic performance for LGE, with a specificity of 81.25% and sensitivity of 70.00%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.

COVID-19-associated myocarditis: single center experience of pathogenetic treatment

2021 ◽  
Vol 28 (3) ◽  
pp. 9-19
Author(s):  
V. M. Kovalenko ◽  
E. G. Nesukay ◽  
N. S. Titova ◽  
S. V. Cherniuk ◽  
R. M. Kirichenko ◽  
...  
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Left Ventricle ◽  
Ejection Fraction ◽  
Proinflammatory Cytokines ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Glucocorticoid Therapy ◽  
Volume Index ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

The aim – to evaluate the effectiveness of glucocorticoid therapy in patients with myocarditis with reduced left ventricular ejection fraction that developed after COVID-19 infection.Materials and methods. The results of glucocorticoid therapy in 32 patients aged (35.2±2.3) years with acute myocarditis after COVID-19 infection and left ventricular ejection fraction < 40 % are presented. All patients were prescribed a 3-month course of methylprednisolone at a daily dose of 0.25 mg/kg, followed by a gradual dose reduction of 1 mg per week until complete withdrawal 6 months after the start of treatment.Results and discussion. The analysis of the results of the examinations was performed in the 1st month from the onset of myocarditis to the appointment of glucocorticoids and after 6 months of observation. Six months later, the end-diastolic volume index decreased by 18.5 %, the left ventricular ejection fraction increased by 23.8 %, and the longitudinal global systolic straine increased by 39.8 %. On cardiac MRI, the number of left ventricular segments affected by inflammatory changes decreased from 6.22±0.77 to 2.89±0.45 segments, and the number of segments with fibrotic changes did not change significantly. After 6 months of treatment, there was a significant decrease in the concentrations of proinflammatory cytokines and cardiospecific antibodies.Conclusions. The use of a 6-month course of glucocorticoid therapy in patients with myocarditis that developed after COVID-19 infection improved the contractility of the left ventricle against the background of a significant reduction in inflammatory lesions of the left ventricle and reduced concentrations of proinflammatory cytokines and cardiospecific antibodies.

scholarly journals Looking beyond ejection fraction: what we have in echocardiography

2019 ◽  
Vol 3 (Issue 4) ◽  
pp. 143
Author(s):  
Oben Baysan ◽  
İlke Akyıldız
Keyword(s):  
Ejection Fraction ◽  
Myocardial Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Decision Making Process ◽  
Ventricular Ejection Fraction ◽  
Failure Classification ◽  
Echocardiographic Examination ◽  
Measurement And Evaluation ◽  
Made In

Left ventricular ejection fraction (LVEF) is the most frequently used echocardiographic parameter. LVEF based heart failure classification, timely intervention in a patient with valvular disease (e.g. aortic stenosis, mitral regurgitation), deterioration of myocardial function in a patient treated with chemotherapy; all need a simple LVEF value for decision-making process. An echocardiographic examination  also contains several parameters with invaluable importance. Measurement and evaluation of these parameters should be made in every patient suspected of having myocardial disease.

scholarly journals Effects of continuous physical training on exercise tolerance and left ventricular myocardial function in patients with heart failure

2007 ◽  
Vol 135 (9-10) ◽  
pp. 516-520 ◽  
Author(s):  
Marina Deljanin-Ilic ◽  
Stevan Ilic ◽  
Viktor Stoickov
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Physical Training ◽  
Exercise Tolerance ◽  
Myocardial Function ◽  
Left Ventricular ◽  
Rehabilitation Programme ◽  
Patients With Heart Failure ◽  
Lv Ejection Fraction ◽  
Residential Rehabilitation

Introduction Physical training is an important method in the rehabilitation programme for cardiovascular patients. Nevertheless, some controversies about physical training in patients with heart failure still exist. Objective The aim of the study was to assess the effects of continuous physical training on exercise tolerance, ejection fraction and regional systolic and diastolic left ventricular (LV) myocardial function in patients with stable heart failure. Method The study involved 48 male patients with stable heart failure and LV ejection fraction ?35% determined by echocardiography. At the end of a two-week residential rehabilitation programme, the patients were divided in two groups. The group of 27 patients (T group) continued with regular physical training (4 to 5 times weekly) during 6 months, while 21 patients (K group) did not have regular physical training. In all patients, the exercise test and echocardiography studies were performed after residential rehabilitation and 6 months later. Regional myocardial function of LV was evaluated by the pulsed wave tissue Doppler imaging. Results After 6 months, an increase in exercise tolerance was more significant in T group. LV ejection fraction increased significantly (p<0.05) only in T group. After six months, in T group, regional systolic (p<0.01) and diastolic (p<0.005) myocardial function improved significantly, while in K group a significant improvement was seen only for regional diastolic function (p<0.05), and it was less than in T group. Conclusion The results of our study suggest that continuous physical training during the period of 6 months in patients with stable heart failure induced significant improvement of exercise tolerance, ejection fraction and regional systolic and diastolic LV myocardial function.

Predictive Values of Multiple Non-Invasive Markers for Myocardial Fibrosis in Hypertrophic Cardiomyopathy Patients With Preserved Ejection Fraction

2020 ◽  
Author(s):  
Yumin Li ◽  
Jia Liu ◽  
Yukun Cao ◽  
Xiaoyu Han ◽  
Guozhu Shao ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ejection Fraction ◽  
Myocardial Fibrosis ◽  
Troponin I ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Predictive Values ◽  
Non Invasive ◽  
Potential Biomarker

Abstract Myocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiacspecific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. Serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels were elevated in LGE-positive patients compared with LGE-negative patients. The LGE-positive patients had lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group and the healthy controls. The LGE% was independently associated with the Nt-proBNP levels, GCS, MWT and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP≥108 pg/mL and MWT≥17.3 mm had good diagnostic performance for LGE, with a specificity of 81.3% and sensitivity of 70.0%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.

scholarly journals Prognostic impacts of changes in left ventricular ejection fraction in heart failure patients with preserved left ventricular ejection fraction

Open Heart ◽  
2020 ◽  
Vol 7 (1) ◽  
pp. e001112 ◽  
Author(s):  
Akiomi Yoshihisa ◽  
Yu Sato ◽  
Yuki Kanno ◽  
Mai Takiguchi ◽  
Tetsuro Yokokawa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Cardiac Event ◽  
Troponin I ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
All Cause Mortality

BackgroundIt has been reported that recovery of left ventricular ejection fraction (LVEF) is associated with better prognosis in heart failure (HF) patients with reduced EF (rEF). However, change of LVEF has not yet been investigated in cases of HF with preserved EF (HFpEF).Methods and resultsConsecutive 1082 HFpEF patients, who had been admitted to hospital due to decompensated HF (EF >50% at the first LVEF assessment at discharge), were enrolled, and LVEF was reassessed within 6 months in the outpatient setting (second LVEF assessment). Among the HFpEF patients, LVEF of 758 patients remained above 50% (pEF group), 138 patients had LVEF of 40%–49% (midrange EF, mrEF group) and 186 patients had LVEF of less than 40% (rEF group). In the multivariable logistic regression analysis, younger age and presence of higher levels of troponin I were predictors of rEF (worsened HFpEF). In the Kaplan-Meier analysis, the cardiac event rate of the groups progressively increased from pEF, mrEF to rEF (log-rank, p<0.001), whereas all-cause mortality did not significantly differ among the groups. In the multivariable Cox proportional hazard analysis, rEF (vs pEF) was not a predictor of all-cause mortality, but an independent predictor of increased cardiac event rates (HR 1.424, 95% CI 1.020 to 1.861, p=0.039).ConclusionAn initial assessment of LVEF and LVEF changes are important for deciding treatment and predicting prognosis in HFpEF patients. In addition, several confounding factors are associated with LVEF changes in worsened HFpEF patients.

P5266Renal denervation improves diastolic dysfunction in patients with HFpEF - initial results of a multicenter CMR study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Zamani ◽  
F Mahfoud ◽  
L Stoiber ◽  
M Boehm ◽  
B Pieske ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Ejection Fraction ◽  
Resistant Hypertension ◽  
Renal Denervation ◽  
Myocardial Function ◽  
Left Ventricular ◽  
Cine Mri ◽  
Preserved Ejection Fraction

Abstract Introduction Renal denervation (RDN) significantly reduces blood pressure (BP) and improves myocardial function in patients with resistant hypertension. Purpose This multicenter study aimed to investigate the intermediate term effect of RDN on left ventricular global longitudinal strain (GLS), a surrogate for diastolic myocardial function in RDN patients with proven heart failure with preserved ejection fraction (HFpEF), assessed by cardiac magnetic resonance imaging (CMR). Methods We analyzed data from 22 patients with resistant hypertension (mean age 68±6 years). 16 patients underwent renal denervation (RDN) and 6 matched control patients received optimal medical therapy (OMT). Both groups had diastolic dysfunction defined by preserved ejection fraction (EF ≥50%) and pathologically elevated GLS at baseline (GLS >−18%) quantified by cardiac magnetic resonance (CMR). A standardized CMR protocol was performed at baseline (BL) and 6 months follow-up (FU). Left ventricular mass index (LVMI) was quantified in end-diastolic and end-systolic endo- and epicardial contouring in short axis cine-MRI images. GLS was measured by end-diastolic and end-systolic endocardial contouring in 2-, 3- and 4-chamber view cine-MRI images. MRI-Images have been analyzed with Medis, Netherlands. Results GLS following RDN patients significantly improved after 6 months by 21% (−14.21% ±3.19 vs. −17.17%± 3.1; p=0.007). In control patients with OMT, no significant change in GLS was detected (−14.77% ±3.05 vs. −17.39% ± 4.49; p=0.327). LVMI was numerically reduced in the RDN group at follow-up but did not reach statistical significance (58.55 g/m2±11.37 vs. 55.46 g/m2±12.76; p=0.085). There was no such effect in control patients with OMT (49.25 g/m2±8.2 vs. 50.18 g/m2±7.27; p=0.665). (See also: Figure A and B). Conclusions We found significantly improved diastolic function (GLS) in patients with HFpEF and resistant hypertension undergoing RDN. Future studies are needed to determine whether RDN represents a treatment option in patients with HFpEF.

NT-ProBNP and hsTnI: A Multistate Survival Analysis in Outpatients with Reduced Left-Ventricular Ejection Fraction

Cardiology ◽  
2019 ◽  
Vol 142 (1) ◽  
pp. 7-13
Author(s):  
Gabriele Di Gesaro ◽  
Giuseppa Caccamo ◽  
Diego Bellavia ◽  
Calogero Falletta ◽  
Chiara Minà ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Troponin I ◽  
Serum Levels ◽  
Left Ventricular ◽  
Clinical Event ◽  
Left Ventricular Ejection ◽  
Baseline Serum ◽  
Ventricular Ejection Fraction ◽  
Increased Risk

Heart failure (HF) with reduced ejection fraction (HFrEF) has a well-known epidemic relevance in western countries. It affects up to 1–2% of patients > 60 years and reaches a prevalence of 12% in octogenarian patients. The role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin I (hsTnI) in risk stratifying HFrEF patients has been established; at present, evidence is exclusively based on one-time assessments, and the prognostic usefulness of serial biochemical assessments in this population still remains to be determined. We prospectively recruited 226 patients with chronic HFrEF, who were all referred to the Outpatient Clinic of our institution from November 2011 through September 2014. Recruited patients underwent full clinical evaluation with complete history taking and physical examination as well as ECG, biochemical assessment, and standard 2D and Doppler flow echocardiography at the first visit, and then again at each visit during the follow-up, repeated every 6 months. During the follow-up period, cardiovascular (CV) death, which occurred in 16 patients, was not statistically correlated with gender (p = 0.088) or age (p = 0.1636); however, baseline serum levels of NT-proBNP, which were 3 times higher in deceased patients, were significantly related to this clinical event (p = 0.001). We found that NT-proBNP represents a strong and independent predictor of CV outcome; serum levels of hsTnI, which are significantly related to an increased risk of hospitalization, cannot properly predict the relative risk of CV mortality. Our study validates, eventually, the multimarker strategy, which reflects the complexity of the HF pathophysiology.

scholarly journals Bacillus anthracis edema but not lethal toxin challenge in rats is associated with depressed myocardial function in hearts isolated and tested in a Langendorff system

2015 ◽  
Vol 308 (12) ◽  
pp. H1592-H1602 ◽  
Author(s):  
Yan Li ◽  
Mones Abu-Asab ◽  
Junwu Su ◽  
Ping Qiu ◽  
Jing Feng ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Bacillus Anthracis ◽  
Myocardial Function ◽  
Constant Pressure ◽  
Left Ventricular ◽  
Lethal Toxin ◽  
Myocardial Depression ◽  
Arterial Blood ◽  
Lv Ejection Fraction

Although direct myocardial depression has been implicated in the lethal effects of Bacillus anthracis lethal toxin (LT), in hearts isolated from healthy rats and perfused under constant pressure, neither LT or edema toxin (ET) in typically lethal concentrations depressed myocardial function. In the present study, we challenged rats with LT and ET and performed in vivo and ex vivo heart measures. Sprague-Dawley rats infused over 24 h with LT ( n = 94), ET ( n = 99), or diluent (controls; n = 50) were studied at 8, 24, or 48 h. Compared with control rats (all survived), survival rates with LT (56.1%) and ET (37.3%) were reduced ( P < 0.0001) similarly ( P = 0.66 for LT vs. ET). LT decreased mean arterial blood pressure from 12 to 20 h ( P ≤ 0.05), whereas ET decreased it progressively throughout ( P < 0.05). On echocardiography, LT decreased left ventricular (LV) ejection fraction at 8 and 48 h but increased it at 24 h and decreased cardiac output ( P ≤ 0.05 for the time interaction or averaged over time). ET decreased systolic and diastolic volumes and increased LV ejection fraction at 24 h ( P ≤ 0.05). In isolated hearts perfused for 120 min under constant pressure, LT did not significantly alter LV systolic or developed pressures at any time point, whereas ET decreased both of these at 24 h ( P < 0.0001 initially). ET but not LT progressively increased plasma creatine phosphokinase and cardiac troponin levels ( P < 0.05). In conclusion, despite echocardiographic changes, in vivo lethal LT challenge did not produce evidence of myocardial depression in isolated rat hearts. While lethal ET challenge did depress isolated heart function, this may have resulted from prior hypotension and ischemia.

scholarly journals Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Tanaka ◽  
F Soga ◽  
K Tatsumi ◽  
Y Mochizuki ◽  
H Sano ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Function ◽  
Myocardial Function ◽  
Sglt2 Inhibitor ◽  
Left Ventricular ◽  
Sglt2 Inhibitors ◽  
Prospective Multicenter Study ◽  
Lv Diastolic Function

Abstract Background Type 2 diabetes mellitus (T2DM) has come to be considered an independent predictor of mortality, and also a contributor to the development of heart failure (HF) with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Left ventricular (LV) longitudinal myocardial dysfunction as assessed in terms of lower global longitudinal strain (GLS), has been identified even in T2DM patients with preserved LV ejection fraction (LVEF), and should be considered the first marker of a preclinical form of DM-related cardiac dysfunction, leading to HFpEF. Sodium glucose cotransporter type 2 (SGLT2) inhibitors represent a new class of anti-hyperglycemic agents for T2DM, but the effect of SGLT2 inhibitors on LV longitudinal myocardial function in T2DM patients with HF remains uncertain. To examine this effect, as well as the association of LV longitudinal myocardial function with LV diastolic function after administration of SGLT2 inhibitor in T2DM patients with stable HF, we analyzed data from our previous prospective multicenter study, in which we investigated the effect of SGLT2 inhibitor on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Methods Our previous trial was a prospective multicenter study of 58 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitors started the administration of 5 mg/day of dapagliflozin. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e' annular velocities (E/e'). LV longitudinal myocardial function was assessed as GLS based on the current guidelines. Results E/e' significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p=0.020) as previously described, while GLS showed significant improvement from 15.5±3.5% to 16.9±4.1% (p&lt;0.01) 6 months after administration of dapagliflozin. Furthermore, improvement of GLS in HFpEF patients was more significant from 17.0±1.9% to 18.7±2.0% (p&lt;0.001), compared to that in HFrEF patients from 11.3±3.8% to 11.8±4.6% (p=0.13). It was noteworthy that multiple regression analysis showed that the change in GLS after administration of dapagliflozin was the only independent determinant parameter for the change in E/e' after administration of dapagliflozin. Conclusion Dapagliflozin was found to be associated with improvement of LV longitudinal myocardial function, which led to further improvement of LV diastolic function of T2DM patients with stable HF. GLS-guided management may thus lead to improved management of T2DM patients with stable HF. Representative case Funding Acknowledgement Type of funding source: None

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