Abstract 16928: Discordant Mechanisms in Heart Failure and Hypertrophy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Aleksandra Binek ◽  
Justyna P Fert-bober ◽  
Simion Kreimer ◽  
Alejandro Rivas ◽  
Pyzel Anna ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Death ◽  
Heart Function ◽  
Artery Bypass ◽  
Left Ventricular ◽  
Upstream Regulator ◽  
Proteome Changes ◽  
Cabg Patients ◽  
Cell Growth And Proliferation ◽  
Myocardial Biopsies

Introduction: Patients with heart failure and a preserved ejection fraction (HFpEF) present heart function abnormalities that remain poorly understood. Defining proteomic signature of HF that is independent of left ventricular hypertrophy (LVH) should allow for stratification of its subtypes and potential mechanism that contributes to the disease. Hypothesis: We hypothesized that HFpEF proteomic signature would be comprised of the hypertrophy and contractile protein phenotype. Methods: Intraoperative left ventricular (LV) myocardial biopsies were obtained from patients (n=21) recruited to undergo coronary artery bypass grafting (CABG). Patients were categorized to: control non-hypertensive (n=9), LVH (n=5), and HFpEF (n=7). Myocardial tissue was subfractionated: cytoplasmic- (neutral pH), myofilament- (acidic pH), and membrane-enriched extract (SDS-soluble). All fractions were assessed for protein quantity and Lys/Arg modifications using liquid chromatography mass spectrometry (LC-MS). Results: In HFpEF, 13% of the cardiac LV proteome changed compared to control heart, with a substantial proportion (77%) decreasing in quantity across all three cardiac fractions, while with LVH, 61% of the proteomic LV changes were increased. Although glycolysis and gluconeogenesis increased in both cardiopathies with respect to control, in HFpEF more subtly than in LVH. Modified proteome of the HFpEF was dominated by decreases in protein succinylation (e.g. ATP5L, THIM, IDHP, APOB, GSH1, KNTC1) and to a lesser degree in methylation (ROA3, HSP7C) or acetylation compared to control. This general trend of down-regulation of succinylation can be attributed to depletion in the levels of succinyl-CoA, the cofactor of enzymatic Lys succinylation. Importantly, there was a striking discordant activation/inhibition of cell death and proliferation pathways between the HFpEF and LVH. Two major upstream regulator clusters linked the proteome changes in cell growth and proliferation to RICTOR and Myc that showed completely opposite trends in LVH and HFpEF groups. Conclusions: HFpEF has a unique proteome signature compared to LV hypertrophy profile which does not arise from sub-proteome involved in contraction but rather is involved in overall cell death.

scholarly journals Right ventricular function and its coupling with the pulmonary circulation in acute heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Barki ◽  
M Losito ◽  
M.M Caracciolo ◽  
F Bandera ◽  
M Rovida ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Heart Failure ◽  
Acute Phase ◽  
Pulmonary Circulation ◽  
Heart Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Response To Treatment ◽  
The Right ◽  
B Lines

Abstract Background The right ventricle (RV) is extremely sensitive to hemodynamic changes and increased impedance. In acute heart failure (AHF), the development of pulmonary venous congestion and the increase of left ventricular (LV) filling pressures favors pulmonary vascular adverse remodeling and ultimately RV dysfunction, leading to the onset of symptoms and to a further decay of cardiac dynamics. Purpose The aim of the study was to evaluate RV morphology and functional dynamics at admission and discharge in patients hospitalized for AHF, analyzing the role and the response to treatment of the RV and its coupling with pulmonary circulation (PC). Methods Eighty-one AHF patients (mean age 75.75±10.6 years, 59% males) were prospectively enrolled within 24–48 hours from admission to the emergency department (ED). In either the acute phase and at pre-discharge all patients underwent M-Mode, 2-Dimensional and Doppler transthoracic echocardiography (TTE), as well as lung ultrasonography (LUS), to detect an increase of extravascular lung water (EVLW) and development of pleural effusion. Laboratory tests were performed in the acute phase and at pre-discharge including the evaluation of NT-proBNP. Results At baseline we observed a high prevalence of RV dysfunction as documented by a reduced RV systolic longitudinal function [mean tricuspid annular plane systolic excursion (TAPSE) at admission of 16.47±3.86 mm with 50% of the patients exhibiting a TAPSE<16mm], a decreased DTI-derived tricuspid lateral annular systolic velocity (50% of the subjects showed a tricuspid s' wave<10 cm/s) and a reduced RV fractional area change (mean FAC at admission of 36.4±14.6%). Furthermore, an increased pulmonary arterial systolic pressure (PASP) and a severe impairment in terms of RV coupling to PC was detected at initial evaluation (mean PASP at admission: 38.8±10.8 mmHg; average TAPSE/PASP at admission: 0.45±0.17 mm/mmHg). At pre-discharge a significant increment of TAPSE (16.47±3.86 mm vs. 17.45±3.88; p=0.05) and a reduction of PASP (38.8±10.8 mmHg vs. 30.5±9.6mmHg, p<0.001) was observed. Furthermore, in the whole population we assisted to a significant improvement in terms of RV function and its coupling with PC as demonstrated by the significant increase of TAPSE/PASP ratio (TAPSE/PASP: 0.45±0.17 mm/mmHg vs 0.62±0.20 mm/mmHg; p<0.001). Patients significantly reduced from admission to discharge the number of B-lines and NT-proBNP (B-lines: 22.2±17.1 vs. 6.5±5 p<0.001; NT-proBNP: 8738±948 ng/l vs 4227±659 ng/l p<0.001) (Figure 1). Nonetheless, no significant changes of left atrial and left ventricular dimensions and function were noted. Conclusions In AHF, development of congestion and EVLW significantly impact on the right heart function. Decongestion therapy is effective for restoring acute reversal of RV dysfunction, but the question remains on how to impact on the biological properties of the RV. Funding Acknowledgement Type of funding source: None

Abstract 337: Activation of Myocardial AMP-activated Protein Kinase by Metformin Prevents Progression of Heart Failure in Dogs; Involvement of eNOS Activation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hideyuki Sasaki ◽  
Hiroshi Asanuma ◽  
Masashi Fujita ◽  
Hiroyuki Takahama ◽  
Masanori Asakura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Heart Failure ◽  
Cell Death ◽  
Protein Kinase ◽  
Left Ventricular ◽  
Vehicle Group ◽  
Mrna Levels ◽  
Compound C ◽  
Amp Activated Protein Kinase

Background; Several studies have shown that metformin activates AMP-activated protein kinase (AMPK), which mediates potent cardioprotection against ischemia-reperfusion injury. AMPK is also activated in experimental failing myocardium, suggesting that activation of AMPK is beneficial for the pathophysiology of heart failure. We investigated whether metformin prevents oxidative stress-induced cell death in rat cardiomyocytes and attenuates the progression of heart failure in dogs. Methods and Results; The treatment with metformin (10 μmol/L) protected the rat cultured cardiomyocytes against cell death due to H 2 O 2 exposure (50 μmol/L) as indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), TUNEL staining, and flow cytometry. These effects were blunted by an AMPK inhibitor, compound-C (20 μmol/L), suggesting that the activation of AMPK decreased the extent of apoptosis-induced cell death due to H 2 O 2 exposure. Continuous rapid ventricular pacing (230/min for 4 weeks) in dogs caused heart failure and the treatment with metformin (100 mg/kg/day PO, n=8) decreased left ventricular (LV) end-diastolic dimension (32.8±0.4 vs. 36.5±1.0 mm, p< 0.01) and pressure (11.8±1.1 vs. 22±0.9 mmHg, p< 0.01), and increased LV fractional shortening (18.6±1.8 vs. 9.6±0.7 %, p< 0.01) along with enhanced phosphorylation of AMPK and the decreased the number of TUNEL-positive cells of the LV myocardium compared with the vehicle group (n=8). Interestingly, metformin increased the protein and mRNA levels of endothelial nitric oxide synthase of the LV myocardium and plasma nitric oxide levels. Metformin improved the plasma insulin resistance without increased myocardial GLUT-4 translocation. Furthermore, the subcutaneous administration of AICAR (50 mg/kg/every other day), another AMPK activator mediated the equivalent effects to metformin, strengthening the pivotal role of AMPK in reduction of apoptosis and prevention of heart failure. Conclusions; Activation of myocardial AMPK attenuated the oxidative stress-induced cardiomyocyte apoptosis and prevented the progression of heart failure in dogs, along with eNOS activation. Thus, metformin or AICAR may be applicable as a novel therapy for heart failure.

scholarly journals Echocardiographic parameters of left ventricular non-systolic function predict length of stay following coronary artery bypass graft -- a prospective observational study

2021 ◽  
Author(s):  
samhati Mondal ◽  
Nauder Faraday ◽  
Weidong Gao ◽  
Sarabdeep Singh ◽  
Sachidanand Hebbar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Hospital Stay ◽  
Coronary Artery Bypass ◽  
Prospective Observational Study ◽  
Systolic Function ◽  
Artery Bypass ◽  
Left Ventricular ◽  
Echocardiographic Parameters ◽  
Systolic Phase

Background: Abnormal left ventricular (LV) echocardiographic parameters during non-systolic phase, with or without a diagnosis of heart failure, is a common finding that can be easily diagnosed by intra-operative transesophageal echocardiography (TEE). However, its association with duration of hospital stay after coronary artery bypass (CAB) is unknown. Objective: To determine if Abnormal left ventricular (LV) echocardiographic parameters during non-systolic phase is associated with length of hospital stay after coronary artery bypass surgery (CAB). Method: Prospective observational study at a single tertiary academic medical center Result: Median time to hospital discharge was significantly longer for subjects with abnormal left ventricular (LV) echocardiographic parameters during non-systolic phase (9.1/IQR 6.6-13.5 days) than those with normal LV non-systolic function (6.5/IAR 5.3-9.7days) (P< 0.001). The probability of hospital discharge was 34% lower (HR 0.66/95% CI 0.47-0.93) for subjects with abnormal LV function even during non-systole despite a normal LV systolic function, independent of potential confounders, including a baseline diagnosis of heart failure Conclusions and Relevance: In patients with normal systolic function undergoing CAB, non-systolic LV dysfunction is associated with prolonged duration of postoperative hospital stay. This association cannot be explained by baseline comorbidities or common post-operative complications.

Abstract 4177: Quantitative Evaluation of Regional Myocardial Blood Flow Using Multi-detector Row Computed Tomography in Pre- and Post- Coronary Artery Bypass Grafting Patients; Assessment with Regional Left Ventricular Function

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hiroshi Imagawa ◽  
Fumiaki Shikata ◽  
Teruhito Kido ◽  
Akira Kurata ◽  
Hiroshi Higashino ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Blood Flow ◽  
Coronary Artery ◽  
Myocardial Blood Flow ◽  
Artery Bypass ◽  
Left Ventricular ◽  
Adenosine Stress ◽  
Bypass Grafting ◽  
Regional Left Ventricular Function ◽  
Cabg Patients

Introduction: The advent of high resolution multidetector computed tomography (MDCT) created the potential to quantify myocardial blood flow (MBF) reduction. The effect in regional MBF produced by coronary artery bypass grafting has not been quantitatively evaluated. The purpose of this study was to test the hypothesis that adenosine stress/rest MDCT can detect ischemia by measuring MBF differences in pre- versus post-CABG patients. Methods: Ninety regional areas in 10 patients (median age 71; 65–79, 7 males), scheduled for CABG at our institution, were studied. Each patient underwent adenosine stress 64-slice MDCT perfusion imaging in both pre- and postoperative period. Myocardial blood flow was calculated with Patlak plots analysis. Regional left ventricular function (LVF) was assessed by Echocardiography. Results: Preoperative mean MBF in ischemic and non-ischemic areas was 0.76±0.49 (ml/g/min) and 2.15±0.66, respectively (p<0.05). Postoperative MBF increased to 1.40±0.77 (ml/g/min) in ischemic areas (p<0.05), though the non-ischemic area showed no differences. The degree of ischemia on MDCT was correlated to change in regional LVF. Postoperative assessment revealed the improved regional LVF that was correlated with the increase in regional MBF. Conclusions: The regional MBF can be quantitatively assessed by adenosine stress 64-slice MDCT perfusion imaging. This technique provides quantitative information about regional MBF in pre- and post- CABG patients, which may predict the regional LVF recovery after CABG.

Abstract 122: Characteristics of Patients with Multivessel Coronary Disease Treated with Percutaneous Intervention Versus Bypass Surgery and Preliminary Mortality Outcomes: A Province-wide Field Evaluation

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Laurie J Lambert ◽  
Nataliya Dragieva ◽  
François Reeves ◽  
Yves Langlois ◽  
Michel Nguyen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Cardiogenic Shock ◽  
Coronary Disease ◽  
Bypass Surgery ◽  
Artery Bypass ◽  
Valve Surgery ◽  
Study Cohort ◽  
Wide Field ◽  
Cabg Patients

Introduction: Wide variation in choice of revascularization treatment for patients with multivessel coronary disease has been observed and outcomes of percutaneous coronary intervention (PCI) versus coronary artery bypass surgery (CABG) are increasingly examined. Our publicly funded cardiology evaluation unit was mandated by the Quebec Ministry of Health to evaluate the practice of multivessel revascularization and its outcomes across Quebec’s 8 tertiary cardiac centers offering both PCI and CABG. Methods: Hospital records were used to identify all multivessel (≥2 myocardial territories) interventions by PCI and isolated CABG in each center in 2010-12. Primary PCI patients were excluded. A maximum of 300 patients treated with CABG and 300 patients treated with PCI in each center were randomly selected for chart review by our evaluation unit. Results: The study cohort included 2018 PCI patients and 2274 isolated CABG patients. Median age was 66 years for both PCI (interquartile range, IQR: 59-76) and CABG (IQR: 59-72) and prevalence of most risk factors and comorbidities was very similar. However, compared to CABG patients, there were more females in the PCI group (27% vs 17%), more cardiogenic shock (2.2% vs 0.6%), more patients with previous PCI (27% vs 16%) and previous valve surgery (1.2% vs 0.1%), and more patients with interventions in only 2 myocardial territories (89% vs 31%). The PCI group was more likely than the CABG group to have acute myocardial infarction (AMI) (32% vs 18%) but less likely to have heart failure on admission (9% vs 18%). Almost 1 in 5 (19%) PCI patients were treated for left main disease. Diabetes was present in 29% of PCI patients vs 37% of CABG patients. Compared to CABG, PCI patients had a shorter median delay between admission and intervention (0 vs 2 days) as well as between intervention and discharge (1 vs 6 days) and were more likely to be transferred out to another hospital (37% vs 14%). However, mortality before discharge or transfer from tertiary cardiac centers was higher for PCI than CABG patients both with AMI (3.1% vs 0.7%) and without AMI (1.0% vs 0.5%). The differences of all reported comparisons were statistically significant (p< 0.001) except for in-hospital mortality without AMI (p=0.25). Conclusions: Patients with multivessel disease who were treated with PCI were more likely to present with acute symptoms, have more cardiogenic shock and more previous valve surgery but have less extensive coronary disease, less diabetes and less heart failure. Age and other risk factors and comorbidities were very similar in the 2 groups. Crude mortality during the index surgical hospital admission was higher for PCI despite a shorter length of stay. To gain more insight into these results, it will be important to link to medico-administrative data to examine 30-day and 1-year mortality and to adjust appropriately for potential confounders.

Surgical Alternatives for Patients with Heart Failure

1993 ◽  
Vol 4 (2) ◽  
pp. 244-259
Author(s):  
Rita Vargo ◽  
Josephine M. Dimengo
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Ventricular Remodeling ◽  
Artery Bypass ◽  
Treatment Options ◽  
Myocardial Revascularization ◽  
Left Ventricular ◽  
Surgical Interventions ◽  
Cardioverter Defibrillator ◽  
Artery Disease

Chronic heart failure is a progressive syndrome characterized by diffuse coronary artery disease (CAD) or left ventricular failure not amenable to acute interventions of myocardial revascularization. A spectrum of treatment options is available to such patients. Medical therapies consist largely of pharmacologic alternatives and are used in the early stages of heart failure to slow the processes of ventricular remodeling. Surgical interventions are used as adjunctive therapies in the later stages of heart failure. These procedures include coronary endarterectomy, high-risk surgical revascularization, automatic internal cardioverter-defibrillator insertion (Coronary Artery Bypass Grafting in Conjunction with Implantable Cardioverter Defibrillator Trial), cardiac transplantation, and dynamic cardiomyoplasty. This article provides an overview of each of these surgical therapies. Indications for each procedure and patient selection criteria are outlined. A description of each surgical procedure is included. Guidelines for postoperative nursing care are provided, and postoperative complications are discussed

Safety of Electroconvulsive Therapy in Patients With a History of Heart Failure and Decreased Left Ventricular Systolic Heart Function

2011 ◽  
Vol 27 (3) ◽  
pp. 207-213 ◽  
Author(s):  
Fernando A. Rivera ◽  
Maria I. Lapid ◽  
Shirlene Sampson ◽  
Paul S. Mueller
Keyword(s):  
Heart Failure ◽  
Electroconvulsive Therapy ◽  
Heart Function ◽  
Left Ventricular ◽  
History Of

scholarly journals High N-Terminal proB-Type Natriuretic Peptide Indicates Elevated Risk of Death after Percutaneous Coronary Intervention Compared to Coronary Artery Bypass Surgery in Patients with Left Ventricular Dysfunction

2019 ◽  
Vol 8 (6) ◽  
pp. 898 ◽  
Author(s):  
Christian Roth ◽  
Matthias Schneider ◽  
Daniel Dalos ◽  
Clemens Gangl ◽  
Christian Toth ◽  
...  
Keyword(s):  
Heart Failure ◽  
Percutaneous Coronary Intervention ◽  
Survival Benefit ◽  
Cox Regression ◽  
Artery Bypass ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Revascularization Procedure ◽  
Risk Of Death ◽  
Percutaneous Coronary

Background: Reduced left ventricular function (LVF) is a predictor for stent-thrombosis. In advanced heart failure (characterized by high NT-proBNP) with an activated coagulation system, coronary events clinically perceived as sudden death or death from heart failure may be more common in patients treated by percutaneous coronary intervention (PCI) than in patients treated by coronary artery bypass grafting (CABG). Our study analyses (1) if patients with reduced LVF who require coronary revascularization will have a better survival benefit with CABG or PCI, and (2) if the survival benefit is predicted by NT-proBNP. Methods: This observational retrospective study included patients from the coronary catheter laboratory database of the Medical University of Vienna (CCLD-MUW). Multivariate Cox regression analyses were performed to test the hypothesis that there is an interaction in the risk of death between those with lower or elevated NT-proBNP levels and the revascularization procedure (PCI or CABG). The relative risk of PCI compared to CABG as reference was calculated for patients with low and elevated NT-proBNP levels. Results: In the entire study population with 398 patients (340 PCI and 58 CABG) the revascularization procedure had no predictive value. When the revascularization procedure*NTproBNP interaction was forced into the Cox regression model, this term was an independent predictor of death. The relative risk of PCI compared to CABG was similar in patients with lower NT-proBNP—1.01 (95% confidence interval (CI), 0.45–2.24), but was significantly increased in patients with elevated NT-proBNP—1.58 (95% CI, 1.07–2.33). Conclusion: Death is associated to the revascularization procedure, but only in those patients with elevated NT-proBNP levels. NT-proBNP is a predicting factor for the revascularization procedure: elevated levels showed an increased risk of death after PCI compared to CABG, whereas lower levels were associated with a similar risk after both revascularization procedures.

scholarly journals Influence of polypharmacy on patients with heart failure with preserved ejection fraction: a retrospective analysis on adverse outcomes in the TOPCAT trial

2020 ◽  
Vol 71 (702) ◽  
pp. e62-e70
Author(s):  
Yuzhong Wu ◽  
Wengen Zhu ◽  
Xin He ◽  
Ruicong Xue ◽  
Weihao Liang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Retrospective Analysis ◽  
Heart Function ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Left Ventricular Ejection ◽  
Controlled Study ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

BackgroundPolypharmacy is common in heart failure (HF), whereas its effect on adverse outcomes in patients with HF with preserved ejection fraction (HFpEF) is unclear.AimTo evaluate the prevalence, prognostic impacts, and predictors of polypharmacy in HFpEF patients.Design and settingA retrospective analysis performed on patients in the Americas region (including the US, Canada, Argentina, and Brazil) with symptomatic HF and a left ventricular ejection fraction ≥45% in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial, an international, randomised, double-blind, placebo-controlled study conducted during 2006–2013 in six countries.MethodPatients were categorised into four groups: controls (<5 medications), polypharmacy (5–9 medications), hyperpolypharmacy, (10–14 medications), and super hyperpolypharmacy (≥15 medications). The outcomes and predictors in all groups were assessed.ResultsOf 1761 participants, the median age was 72 years; 37.5% were polypharmacy, 35.9% were hyperpolypharmacy, and 19.6% were super hyperpolypharmacy, leaving 7.0% having a low medication burden. In multivariable regression models, three experimental groups with a high medication burden were all associated with a reduction in all-cause death, but increased risks of HF hospitalisation and all-cause hospitalisation. Furthermore, several comorbidities (dyslipidemia, thyroid diseases, diabetes mellitus, and chronic obstructive pulmonary disease), a history of angina pectoris, diastolic blood pressure <80 mmHg, and worse heart function (the New York Heart Association functional classification level III and IV) at baseline were independently associated with a high medication burden among patients with HFpEF.ConclusionA high prevalence of high medication burden at baseline was reported in patients with HFpEF. The high medication burden might increase the risk of hospital readmission, but not the mortality.

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