Abstract 283: Western Diet Induces Diastolic Dysfunction Linked to Impaired Cardiac Lipid Storage Dynamics That Predate Systolic Dysfunction

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
E Douglas K Lewandowski ◽  
Andrew N Carley ◽  
E Douglas D Lewandowski
Keyword(s):  
Diastolic Dysfunction ◽  
Cardiac Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Western Diet ◽  
Lipid Storage ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Cardiac Lipid ◽  
Lipid Dynamics

Western diet (WD), containing high fat and high refined sugar, is associated with increased risk of cardiovascular disease. However, mechanisms linking WD to cardiomyopathy are far from understood. We hypothesize that WD induces cardiac dysfunction by dysregulation of cardiac lipid dynamics. Adult C57BL/6J mice were fed with either standard chow (CON, fat 4.5 %, sucrose 0%) or western diet (WD, fat 45%, sucrose 21%). At 20 weeks, WD mice exhibited higher body mass, reduced glucose tolerance, and increased isovolumetric relaxation time (IVRT), with no systolic dysfunction vs. CON. However, at 24 weeks, WD caused both systolic and diastolic dysfunction with decreases in left ventricular ejection fraction (66±2% CON vs. 54±2 WD, P <0.05) and fractional shortening (35±2% CON vs. 27±1 WD), with elevated IVRT and E/E’ ratio vs CON. Real time, dynamic-mode 13 C NMR and endpoint LC/MS of isolated perfused hearts supplied 13 C palmitate and 13 C oleate, with unlabeled glucose and lactate, revealed elevated TG content (28% increase vs. CON) with reduced TG turnover in WD hearts (35% decrease vs. CON), concurrent with early diastolic dysfunction at 20 weeks and preceding systolic dysfunction at 24 weeks. WD induced lower content of the TG lipase, ATGL (48% vs. CON), with no change in the TG synthase, DGAT1, suggesting elevated cardiac TG and lower TG turnover are due to reduced TG hydrolysis and not TAG synthesis. Impaired lipid storage dynamics can cause increased generation of potentially lipotoxic acyl intermediates, leading to cardiac dysfunction. The mitochondrial long chain fatty acid transporter, CPT1b was reduced (50%), with no change in the lesser, co-expressed CPT1a isoform in WD hearts. Despite reduced CPT1b in WD hearts, contributions from LCFAs to acetyl CoA production in the citric acid cycle were unchanged, suggesting that the WD provided sufficient LCFAs for mitochondrial oxidation and that the reduced CPT1b was not limiting. In conclusion, western diet expands the TG pool but impairs fat storage dynamics via low ATGL, leading to early diastolic dysfunction and eventual systolic dysfunction. Nutrient overload from WD leads to impaired cardiac lipid dynamics with early diastolic dysfunction that is distinguished from HFpEF due to later systolic dysfunction.

Pathophysiology and causes of cardiac failure

2016 ◽  
Author(s):  
Alexandre Mebazaa ◽  
Mervyn Singer
Keyword(s):  
Stroke Volume ◽  
Diastolic Dysfunction ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Stroke Work ◽  
Compensatory Mechanisms ◽  
Ventricular Ejection Fraction

Organ congestion upstream of the dysfunctional left and/or right ventricle, with preserved stroke volume, is the most frequkeywordent feature of myocardial failure.Clinical manifestations do not necessarily correlate with the degree of left ventricular systolic dysfunction (i.e. left ventricular ejection fraction).Systolic and/or diastolic dysfunction may be present, with systolic dysfunction usually predominating.Pulmonary oedema is related to left ventricular diastolic dysfunction. Compensatory mechanisms (within the heart and/or periphery) may prove paradoxically disadvantageous on ventricular stroke work and stroke volume.

scholarly journals P966 Impact of systolic dysfunction and elevated left ventricular end diastolic pressure on three years clinical outcome in patients with atrial fibrillation

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
J Ahn ◽  
H Y Yu
Keyword(s):  
Atrial Fibrillation ◽  
Diastolic Dysfunction ◽  
Clinical Outcomes ◽  
Systolic Dysfunction ◽  
Prognostic Significance ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Diastolic Filling ◽  
Ventricular Ejection Fraction

Abstract Background Systolic and diastolic dysfunction is related with adverse clinical outcomes in the patients with sinus rhythm. Purpose: The aim of this study is to clarify the prognostic significance of both systolic and diastolic dysfunction in the patients with chronic persistent atrial fibrillation (AF). Methods: A total of 114 consecutive patients who have chronic persistent AF. Whole patients were divided into 2 groups according to left ventricular ejection fraction (LVEF): those with an LVEF &lt; 50 (n = 24) (REF) and those with an LVEF ≥ 50 (n = 90) (PEF). And PEF group was also divided into two groups according to left ventricular end diastolic filling pressure (LVEDP): patients with LVEDP ≥ 15 mmHg (n = 38) and those with &lt; 15 mmHg (n = 52). Results: 3-year clinical outcomes were compared between each groups (PEF groups vs. REF groups and LVEDP ≥ 15 mmHg vs LVEDP &lt; 15 mmHg). The incidence of death, hospitalization, stroke, bleeding, AF with rapid ventricular rhythm (RVR) and heart failure (HF) hospitalization were similar PEF and REF group. However, during 3-year follow up period, the incidence of HF hospitalization (29.2% vs 8.9%, p &lt; 0.02) and AF with RVR (20.8% vs 3.3%, p &lt; 0.01) were frequent in REF group compared with PEF group. In multivariate analysis, REF is an only predictor of HF hospitalization (Table 1). Conclusion: During 3-year follow up period, systolic dysfunction is an important predictor of HF hospitalization in AF patients. However, elevated LVEDP is not related with 3-year adverse clinical outcomes in AF patients without systolic dysfunction. Table 1 variable Odd Ratio (HR) 95% Confidence Interval (CI) P Age .973 .925-1.023 .286 Diabetes mellitus .487 .138-1.721 .264 BNP 1.000 1.000-1.000 .908 Hypertension 1.061 .330-3.413 .921 LVEDP &gt; 15 mmHg 1.302 .396-4.285 .664 EF &lt; 50 4.712 1.478-15.016 .009 Predictors of 3-year follow-up clinical outcomes of all participants

Abstract 15618: Cardiac Magnetic Resonance Evaluation of Diastolic Indices in Boys With Duchenne Muscular Dystrophy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jeffrey Weiner ◽  
Kristen GeorgeDurrett ◽  
Kimberly Crum ◽  
Joshua Chew ◽  
Christopher Spurney ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Diastolic Dysfunction ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
End Diastolic Volume ◽  
Mean Time

Introduction: Cardiomyopathy (CM) is the leading cause of death in boys with Duchenne Muscular Dystrophy (DMD). Diastolic dysfunction precedes systolic dysfunction in DMD, but while CMR is used routinely to assess fibrosis and left ventricular ejection fraction (LVEF), CMR measures of DMD diastolic dysfunction have not been reported. Hypothesis: Boys with DMD have diastolic dysfunction based on CMR indices when compared with healthy controls. Methods: Prospectively enrolled DMD patients (n = 54) and healthy male controls (n = 40) underwent CMR. Standard volumes and function were calculated. LV filling curves were generated by contouring every phase in the short axis. Indices were compared between groups using a Wilcoxon rank sum and within DMD using a Spearman’s rho test. Results: There was no difference in LVEF between DMD and controls, though DMD patients had significantly smaller indexed left ventricular end diastolic volume (LVEDVi) (see data in Table 1). Peak ventricular filling rates (PFR) were significantly slower in DMD vs controls as were peak ventricular emptying rates (PER). Mean time to PFR (tPFR) and mean time to PER (tPER) were significantly shorter in DMD patients vs controls. In a subset analysis excluding patients with LVEF < 55%, observed differences in PFR, PER, tPFR and TPER remain statistically significant. In DMD patients, tPER correlates negatively with LVEF (rho = -0.57, p <0.001). PER corrected to LVEDVi correlated strongly with LVEF (rho = 0.74, p <0.001). PFR corrected to LVEDVi also correlated strongly with LVEF (rho = 0.75, p <0.001). Conclusions: Despite having normal baseline systolic function, boys with DMD have significantly different CMR diastolic indices compared with controls. CMR diastolic indices may help detect subclinical dysfunction in DMD. Future analyses should evaluate for correlation between diastolic dysfunction and clinical outcomes.

Trastuzumab-Associated Cardiac Adverse Effects in the Herceptin Adjuvant Trial

2007 ◽  
Vol 25 (25) ◽  
pp. 3859-3865 ◽  
Author(s):  
Thomas M. Suter ◽  
Marion Procter ◽  
Dirk J. van Veldhuisen ◽  
Michael Muscholl ◽  
Jonas Bergh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Adverse Effects ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Neo Adjuvant Chemotherapy

Purpose The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

scholarly journals Are high NT-proBNP levels more related to inflammation than to left ventricular systolic dysfunction in acute myocarditis?

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
B Sara ◽  
JJ Monteiro ◽  
P Carvalho ◽  
C Ribeiro Carvalho ◽  
J Chemba ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Plasma Levels ◽  
Left Ventricular Systolic Dysfunction ◽  
Small Sample Size ◽  
Acute Myocarditis ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Small Sample ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract Funding Acknowledgements Type of funding sources: None. Background Plasma levels and N-terminal pro B-type natriuretic peptide (NT- proBNP), a cardiac neurohormone released in response to increased ventricular stress, represent an important predictor of clinical outcomes and left ventricular (LV) dysfunction; Although, its diagnostic and prognostic role in patients with acute myocarditis is not completely established; Our aim was to evaluate the relationship of BNP levels and LV ejection fraction (LVEF) in patients with myocarditis; Methods Data from patients (pts) discharged with the diagnosis of myocarditis, from 2008 and 2018 were retrospectively analysed. Results 62 pts were included. Mean age was 39.7 17 years and 89% (58 patients) were men. Plasma levels of NT-proBNP measured at admission ranged from 24 to 3110 pg/mL (median 514, IQR 947), and exceeded upper normal levels in 51 pts (82%). This values positively correlated with C- reactive protein (CRP) (p= 0.005, r = 0.36), leucocytes (p = 0.03, r= 0.37) and neutrophil-to-lymphocyte ratio (p= 0.05, r= 0.35), but not with left ventricular ejection fraction (LVEF) (p= 0.829). Higher levels of BNP were associated with higher troponin peak levels but not with increased mortality (p = 0.811), need of inotropic support (p= 0.059) or arrhythmic events (p= 0.130). Inflammatory parameters were significantly increased when BNP&gt; 514 pg/mL vs BNP &lt;514 pg/mL (CRP 7.2 vs 4 mg/dL, p= 0.008). This relationship was maintained at BNP &gt; 900. LVEF was comparable in both groups (p = 0.938); In this population, the magnitude of recovery of the NT- proBNP values (variation between NT-proBNP at admission and discharge) strongly correlated with the magnitude of the inflammatory markers at admission (all p &lt; 0,005) Conclusion In patients with acute myocarditis, there is a significant relationship between NT-proBNP levels and inflammation (as measured by leucocytes, NLR or CRP), but not with LVEF; Despite the limitation of a small sample size, we could hypothesize that NTproBNP in this subset of patients appears to be regulated not only by hemodynamic changes but also by the underlying systemic inflammatory process and, therefore, it interpretation should take that into account;

Abstract 1213: Cardiac Overexpression of Epac1 in Transgenic Mice Protects Heart from Lipopolysaccharide-induced Cardiac Dysfunction and Inhibits JAK-STAT Pathway

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoshi Okumura ◽  
Yunzhe Bai ◽  
Meihua Jin ◽  
Sayaka Suzuki ◽  
Akiko Kuwae ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cyclic Amp ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
Proinflammatory Cytokines ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Stat Pathway

The sympathetic nervous system and proinflammatory cytokines are believed to play independent roles in the pathophysiology of heart failure. However, the recent identification of Epac (exchange protein activated by cyclic AMP), a new cyclic AMP-binding protein that directly activates Rap1, have implicated that there may be a potential cross talk between the sympathetic and cytokine signals. In order to examine the role of Epac in cytokine signal to regulate cardiac function, we have generated transgenic mice expressing the human Epac1 gene under the control of alpha-cardiac myosin heavy chain promoter (Epac1-TG), and examined their response in lipopolysaccharide (LPS)-induced cardiac dysfunction, a well established model for sepsis-induced cardiac dysfunction. Sepsis-induced cardiac dysfunction results from the production of proinflammatory cytokines. At baseline, left ventricular ejection fraction (LVEF) was similar (TG vs. NTG, 67±1.7 vs. 69±2.1%, n =7–9). The degree of cardiac hypertrophy (LV(mg)/tibia(mm)) was also similar at 3 months old (TG vs. NTG 4.0±0.1 vs. 4.2±0.1, n =5–6), but it became slightly but significantly greater in Epac1-TG at 5 month old (TG vs. NTG 4.9±0.1 vs. 4.4±0.1, p< 0.05, n =5–7). LPS (5mg/kg) elicited a significant and robust reduction of LVEF in both Epac1-TG and NTG, but the magnitude of this decrease was much less in Epac1-TG at 6 hr after injection (TG vs. NTG 48±2.4 vs. 57±1.8%, p< 0.01, n =6–9). At 24 hr after injection, cardiac function was restored to the baseline in both Epac1-TG and NTG. We also examined the activation of JAK-STAT pathway at 24 hr after injection. The tyrosine phosphorylation of STAT1 (Tyr701) and STAT3 (Tyr705) in LV, which is an indicator of STAT activation, was reduced to a greater degree in Epac1-TG by 31±8.8% ( p< 0.05, n =4) and 29±5.9% ( p< 0.05, n =7), respectively, relative to that in NTG. Taken together, Epac1 protects the heart from the cytokine-induced cardiac dysfunction, at least in part, through the inhibition of the JAK-STAT pathway, suggesting the beneficial role played by sympathetic signal to antagonize proinflammatory cytokine signal in heart failure.

Abstract 137: Deficiency of Senescence Marker Protein 30 Exacerbates Doxorubicin-Induced Cardiac Dysfunction in Mice

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Makiko Miyata ◽  
Satoshi Suzuki ◽  
Tomofumi Misaka ◽  
Shu-ichi Saitoh ◽  
Yasuchika Takeishi
Keyword(s):  
Cardiac Dysfunction ◽  
Protective Role ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Marker Protein ◽  
Morphological Examination ◽  
Protective Function ◽  
Ventricular Ejection Fraction ◽  
Wide Range ◽  
Oxidative Effects

Background: Senescence marker protein 30 (SMP30) was originally identified as an aging marker protein in the rat liver. The expression of SMP30 decreases with aging androgen-independently. Doxorubicin (DOX) has been used as a potent anticancer agent, but serious cardiotoxicity precludes its use in a wide range of patients. SMP30 may have anti-oxidative and anti-apoptosis functions in several organs, but functional role of SMP30 has not been rigorously examined in the heart. We hypothesized that SMP30 has cardio-protective function by anti-aging and anti-oxidant effects on DOX-induced cardiac dysfunction. Method and Results: Male SMP30 knockout (SMP30KO) and age-matched littermate male wild-type (WT) mice at 12-14 weeks of age were given intraperitoneal injections of DOX (20 mg/kg) or saline. Seven days after DOX injection, echocardiography revealed that left ventricular ejection fraction in DOX-treated SMP30KO mice was more severely reduced than in DOX-treated WT mice (40.9 ± 3.1% vs. 46.9 ± 4.9%, P<0.01). Morphological examination of myocardial sections showed fibrotic change in DOX-treated SMP30KO mice significantly increased compared to DOX-treated WT mice (3.2 ± 0.5% vs. 1.3 ± 0.2%, P<0.01). Generation of reactive oxygen species assessed by dihydroethidium staining was greater in DOX-treated SMP30KO mice than DOX-treated WT mice (166.9 ± 8.6% vs. 131.6 ± 5.8%, P<0.01). Moreover, apoptotic signaling pathways such as caspase-3 activity (1.8 ± 0.1% vs. 1.1 ± 0.2%, P<0.01), bax/bcl-2 ratio (2.4 ± 0.3% vs.1.6 ± 0.2%, P<0.05) and phosphorylation activity of c-Jun N-terminal kinase (1.6 ± 0.3 vs. 1.0 ± 0.1, P<0.05) were significantly elevated in the SMP30KO mice compared with WT mice after DOX injection. The numbers of TUNEL-positive nuclei in the myocardium were higher in DOX-treated SMPKO mice than in DOX-treated WT mice (0.15 ± 0.02% vs. 0.08 ± 0.01%, P<0.01). Conclusions: The results of this study demonstrated that DOX-induced cardiotoxicity is aggravated in SMP30KO mice by exacerbating of superoxide generation, leading to enhanced apoptosis of cardiomyocytes. SMP30 has a cardio-protective role by anti-apoptotic and anti-oxidative effects in DOX-induced cardiotoxicity.

Trastuzumab-Induced Cardiotoxicity: Clinical and Prognostic Implications of Troponin I Evaluation

2010 ◽  
Vol 28 (25) ◽  
pp. 3910-3916 ◽  
Author(s):  
Daniela Cardinale ◽  
Alessandro Colombo ◽  
Rosalba Torrisi ◽  
Maria T. Sandri ◽  
Maurizio Civelli ◽  
...  
Keyword(s):  
At Risk ◽  
Cardiac Dysfunction ◽  
Troponin I ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Trastuzumab Therapy ◽  
Before And After ◽  
Patients At Risk ◽  
Prognostic Implications

Purpose Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%. Results TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P < .001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P < .001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P < .001). Conclusion TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.

Sign in / Sign up

Export Citation Format

Share Document