Increased expression of endothelin-converting enzyme-1 in failing human myocardium

2002 ◽  
Vol 103 (s2002) ◽  
pp. 237S-240S ◽  
Author(s):  
Henning MORAWIETZ ◽  
Winfried GOETTSCH ◽  
Marten SZIBOR ◽  
Matthias BARTON ◽  
Sidney SHAW ◽  
...  
Keyword(s):  
Heart Failure ◽  
New York ◽  
Coronary Bypass ◽  
Heart Association ◽  
Right Atrial ◽  
Converting Enzyme ◽  
Atrial Myocardium ◽  
Endothelin Converting Enzyme ◽  
The Right

Endothelin-1 (ET-1) is considered to be involved in the development and progression of heart failure. Therefore, we analysed the expression of endothelin-converting enzyme-1 (ECE-1), endothelin receptors A (ETA) and B (ETB) mRNAs by standard-calibrated, competitive reverse transcriptase-PCR using an internal-deleted in vitro-transcribed cRNA standard. ET-1 peptide levels were measured using isoform-specific rabbit antibodies against synthetic ET-1. mRNA and protein expression was determined in the right atrial myocardium of New York Heart Association class I patients and class IV patients undergoing aorto-coronary bypass surgery. ECE-1 mRNA was upregulated in failing atrial myocardium. Furthermore, ET-1 peptide levels were increased in failing atrial myocardium. Atrial ETA mRNA expression was not changed, while ETB mRNA was downregulated in the failing atrial myocardium. Our results support an upregulation of ET-1 synthesis by induction of ECE-1 in failing atrial myocardium. Pharmacological inhibition of augmented ECE-1 expression might provide a new therapeutic perspective in the treatment of heart failure.

Abstract 418: Caveolar Disruption of L-type Calcium Channel and Ryanodine Receptor Facilitates Atrial Ectopy and Arrhythmogenesis in Heart Failure Mice

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Di Lang ◽  
Lucas ratajczyk ◽  
Leonid Tyan ◽  
Daniel Turner ◽  
Francisco Alvarado ◽  
...  
Keyword(s):  
Heart Failure ◽  
Optical Mapping ◽  
Ryanodine Receptors ◽  
Tissue Level ◽  
Confocal Imaging ◽  
Right Atrial ◽  
Isolated Atria ◽  
The Right

Atrial fibrillation (AF) often occurs during heart failure (HF). Ectopic foci that trigger AF, are linked to discrete atrial regions that experience the highest remodeling and clinically used for AF ablation; however, mechanisms of their arrhythmogenic propensity remain elusive. We employed in vivo ECG telemetry, in vitro optical mapping and confocal imaging of Ca 2+ transients (CaT) from myocytes isolated from the right atrial appendage (RAA) and inter-caval region (ICR) of wild type (WT, n=10), caveolin-3 knockout (KO, n=6) and 8-weeks post-myocardial infarction HF (n=8) mice. HF and KO mice showed an increased susceptibility to pacing-induced AF and enhanced ectopy originated exclusively from ICR. Optical mapping in isolated atria showed prolongation of CaT rise up time (CaT-RT) in HF ICR, which suggested a remodeled coupling between L-type Ca 2+ channels (LTCCs) and ryanodine receptors (RyRs) in this specific region. In WT mice, RAA consists of structured myocytes with a prominent transverse-axial tubular system (TATS) while ICR myocytes don’t have TATS. In RAA, CaT-RT depends on LTCCs in TATS triggering RyR, while in ICR, all the LTCCs are localized in surface caveolae where they can activate subsarcolemmal RyRs and lead to a slow diffusion of Ca 2+ inside the cell interior. Downregulation of caveolae was observed specifically in HF ICR. To mimic this, we used cav3-KO mice. Triggered activities were observed in myocytes isolated from HF and KO ICR, which presumably underlie the ectopic activities in tissue level. These myocytes presented significantly unsynchronized sarcoplasmic reticulum (SR) Ca 2+ releases (synchronization index: 10.8±0.9 in WT vs 38.3±4.1 in HF vs 21.5±2.1 in KO, p <0.01 for HF and KO vs WT respectively) especially at the subsarcolemmal space that prolongs CaT-RT (62.2±4.1 ms in WT vs 122.5±12.8 ms in KO, p <0.01). In addition, failing ICR myocytes showed a higher occurrence and size of spontaneous Ca 2+ sparks which were linked to CaMKII activity and associated phosphorylation of RyR. Our findings demonstrate that in HF, caveolar disruption creates “hot spots” for arrhythmogenic ectopic activity emanated from discrete vulnerable regions of the right atrium which are associated with desynchronized SR Ca 2+ release and elevated fibrosis.

scholarly journals Age-Dependent Protein Expression of Serine/Threonine Phosphatases and Their Inhibitors in the Human Cardiac Atrium

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Ulrich Gergs ◽  
Theresa Trapp ◽  
Hasan Bushnaq ◽  
Andreas Simm ◽  
Rolf-Edgar Silber ◽  
...  
Keyword(s):  
Heart Failure ◽  
New York ◽  
Protein Expression ◽  
Protein Phosphatase ◽  
Heart Association ◽  
Catalytic Subunit ◽  
Right Atrial ◽  
Chronic Coronary Artery Disease ◽  
Age Dependent ◽  
Dependent Protein

Heart failure and aging of the heart show many similarities regarding hemodynamic and biochemical parameters. There is evidence that heart failure in experimental animals and humans is accompanied and possibly exacerbated by increased activity of protein phosphatase (PP) 1 and/or 2A. Here, we wanted to study the age-dependent protein expression of major members of the protein phosphatase family in human hearts. Right atrial samples were obtained during bypass surgery. Patients (n=60) were suffering from chronic coronary artery disease (CCS 2-3; New York Heart Association (NYHA) stage 1–3). Age ranged from 48 to 84 years (median 69). All patients included in the study were given β-adrenoceptor blockers. Other medications included angiotensin-converting enzyme (ACE) or angiotensin-receptor-1 (AT1) inhibitors, statins, nitrates, and acetylsalicylic acid (ASS). 100 µg of right atrial homogenates was used for western blotting. Antibodies against catalytic subunits (and their major regulatory proteins) of all presently known cardiac serine/threonine phosphatases were used for antigen detection. In detail, we studied the expression of the catalytic subunit of PP1 (PP1c); I1PP1 and I2PP1, proteins that can inhibit the activity of PP1c; the catalytic subunit of PP2A (PP2Ac); regulatory A-subunit of PP2A (PP2AA); regulatory B56α-subunit of PP2A (PP2AB); I1PP2A and I2PP2A, inhibitory subunits of PP2A; catalytic and regulatory subunits of calcineurin: PP2BA and PP2BB; PP2C; PP5; and PP6. All data were obtained within the linear range of the assay. There was a significant decline in PP2Ac and I2PP2A expression in older patients, whereas all other parameters remained unchanged with age. It remains to be elucidated whether the decrease in the protein expression of I2PP2A might elevate cardiac PP2A activity in a detrimental way or is overcome by a reduced protein expression and thus a reduced activity of PP2Ac.

scholarly journals Association between ventilatory efficiency, oxygen uptake, and Glittre-ADL test results in patients with chronic heart failure: a preliminary study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hebert Olímpio Júnior ◽  
Agnaldo José Lopes ◽  
Fernando Silva Guimarães ◽  
Sergio Luiz Soares Marcos da Cunha Chermont ◽  
Sara Lúcia Silveira de Menezes
Keyword(s):  
Heart Failure ◽  
New York ◽  
Chronic Heart Failure ◽  
Functional Capacity ◽  
Treatment Plan ◽  
Minute Ventilation ◽  
Heart Association ◽  
Gas Analysis ◽  
Ventilatory Efficiency ◽  
Scale Scores

Abstract Objective The Glittre-ADL test (GA-T) is a functional capacity test that stands out for encompassing multiple tasks similar to activities of daily living. As ventilatory efficiency is one of the variables valued in the prognosis of chronic heart failure (CHF), this study aimed to evaluate associations between functional capacity and ventilatory variables in patients with CHF during the GA-T. Results Eight patients with CHF and New York Heart Association (NYHA) functional classification II–III underwent the GA-T coupled with metabolic gas analysis to obtain data by means of telemetry. The median total GA-T time was 00:04:39 (00:03:29–00:05:53). Borg dyspnoea scale scores before and after the GA-T were 2 (0–9) and 3 (1–10), respectively (P = 0.011). The relationship between the regression slope relating minute ventilation to carbon dioxide output (VE/VCO2 slope) was correlated with the total GA-T time (rs = 0.714, P = 0.047) and Borg dyspnoea score (rs = 0.761, P = 0.028). The other ventilatory variables showed no significant correlations. Our results suggest that the total GA-T time can be applied to estimate the ventilatory efficiency of patients with CHF. Future studies may use the GA-T in conjunction with other functional capacity tests to guide the treatment plan and evaluate the prognosis.

scholarly journals Remote monitoring of chronic heart failure patients: invasive versus non-invasive tools for optimising patient management

2019 ◽  
Vol 28 (1) ◽  
pp. 3-13 ◽  
Author(s):  
J. F. Veenis ◽  
J. J. Brugts
Keyword(s):  
Heart Failure ◽  
New York ◽  
Chronic Heart Failure ◽  
Remote Monitoring ◽  
Heart Association ◽  
The United States ◽  
Pharmacological Therapy ◽  
Functional Class ◽  
Class Iii ◽  
Additional Tool

AbstractExacerbations of chronic heart failure (HF) with the necessity for hospitalisation impact hospital resources significantly. Despite all of the achievements in medical management and non-pharmacological therapy that improve the outcome in HF, new strategies are needed to prevent HF-related hospitalisations by keeping stable HF patients out of the hospital and focusing resources on unstable HF patients. Remote monitoring of these patients could provide the physicians with an additional tool to intervene adequately and promptly. Results of telemonitoring to date are inconsistent, especially those of telemonitoring with traditional non-haemodynamic parameters. Recently, the CardioMEMS device (Abbott Inc., Atlanta, GA, USA), an implantable haemodynamic remote monitoring sensor, has shown promising results in preventing HF-related hospitalisations in chronic HF patients hospitalised in the previous year and in New York Heart Association functional class III in the United States. This review provides an overview of the available evidence on remote monitoring in chronic HF patients and future perspectives for the efficacy and cost-effectiveness of these strategies.

scholarly journals Knowledge about self-care and associated factors among heart-failure patients in Ayder Referral Hospital, Ethiopia, 2018: A cross-sectional study

2020 ◽  
pp. 201010582096214
Author(s):  
Tsegu Hailu Gebru ◽  
Haftea Hagos Mekonen ◽  
Kbrom Gemechu Kiros
Keyword(s):  
Heart Failure ◽  
New York ◽  
Logistic Regression ◽  
Self Care ◽  
Heart Association ◽  
Cross Sectional Study ◽  
Referral Hospital ◽  
Sectional Study ◽  
Cross Sectional ◽  
Knowledge Age

Background: Good knowledge of self-care related to heart failure (HF) is key to improve patient outcomes. However, information regarding how much patients know about self-care is lacking in developing countries, particularly in the study setting. Objective: The objectives of this study were to assess HF patients’ knowledge about self-care and to explore predictors among HF patients in Ayder comprehensive specialised referral hospital, Tigray, Ethiopia. Methods: This hospital-based cross-sectional study design was undertaken in Ayder comprehensive specialised referral hospital, Tigray, Ethiopia. A total of 408 HF patients participated, and the study was done between February and April 2018. An interviewer-assisted structured questionnaire was used to collect data. Bivariate logistic regression and multivariable logistic regression were conducted to identify the predictors associated with knowledge about self-care. Results: The mean age of the participants was 45.4 years (standard deviation=19 years). Around 255 (62.5%) of the participants had poor self-care knowledge. Age, New York Heart Association classes, duration of the disease and previous hospitalisation were the factors associated with knowledge about self-care. Conclusion: More than half of all participants had poor knowledge about self-care. Improving existing prevention strategies and strengthening patients’ knowledge are recommended to address this knowledge deficit.

“I Can’t Go Far”: Perceptions and Experiences of Heart Failure Patients Regarding Physical Activity: A Qualitative Study Using Semistructured Face-to-Face Interviews

2021 ◽  
pp. 109019812110532
Author(s):  
Elodie Charuel ◽  
Martial Bernard ◽  
Hélène Vaillant Roussel ◽  
Benoit Cambon ◽  
Thibault Ménini ◽  
...  
Keyword(s):  
Physical Activity ◽  
Heart Failure ◽  
New York ◽  
General Practitioner ◽  
Qualitative Study ◽  
Heart Association ◽  
Enabling Factors ◽  
Face To Face ◽  
New York Heart Association

Background Participation in regular physical activity (RPA) is beneficial to the quality of life and life expectancy of patients with chronic heart failure (CHF). However, it is inadequate in many patients. Aims To determine the factors that influence the practice of RPA in patients with CHF managed in general practice. Method This was a qualitative study using semistructured, individual face-to-face interviews. Patients with CHF (New York Heart Association Stages 1–3) capable of participating in RPA were enrolled by their general practitioner. A longitudinal and transversal inductive thematic analysis was performed by two researchers. Results Five themes emerged from the 19 interviews that were conducted. Poor knowledge of the disease and the benefits of participating in RPA, as well as the lack of motivation or enjoyment, in particular due to the absence of previous participation, were considered significant obstacles. Fear associated with CHF or other comorbidities was also an obstacle. Attendance at a rehabilitation center, family and social circles, and having a pet all appeared to be beneficial. Family and friends were important for motivating the patient to participate in an activity but could also be an obstacle when they were overprotective. Conclusion This study helps highlight the difficulties for patients with CHF associated with participation in RPA. Despite the obstacles, there are enabling factors on which the general practitioner may rely to motivate their patients.

Abstract 2848: Medication Knowledge And Assistance In Older Chronic Heart Failure Patients.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Robyn Gallagher ◽  
Judith Donoghue ◽  
Lynn Chenoweth ◽  
Jane Stein-Parbury
Keyword(s):  
Heart Failure ◽  
New York ◽  
Chronic Heart Failure ◽  
Self Efficacy ◽  
Heart Association ◽  
Post Discharge ◽  
Medication Knowledge ◽  
Moderate Heart Failure ◽  
Association Class ◽  
New York Heart Association

Medication knowledge and assistance in older chronic heart failure (CHF) patients. Medication adherence is central to the optimal management of CHF. Little is known about older patients’ knowledge of their medications or the factors that contribute to this knowledge. Aim: To describe and identify the predictors of medication knowledge in older CHF patients. Method: Subjects ( n = 62) aged over 55 years with moderate heart failure (New York Heart Association Class II and III) who identified as self-managing were recruited from hospital or rehabilitation. Interviews occurred at home four weeks post-discharge using a medication checklist and the Self-Efficacy in Chronic Illness Scale (Lorig et al, 2001). Multiple regression analysis determined the predictors of medication knowledge. Results: Patients were aged mean 78.4 years (sd 8.54 years), mostly male (57%) and had an average 8 (median, range 3–22) medications to take daily, of which 6 (median, range 3–14) were for CHF. Most managed their own medications (54%) but more than a quarter (28%) were assisted by reminding, dispensing and supervision. Compliance with medications was high (84%), although only half (53%) knew the name, main purpose and side effect of their medications. Patients with better self-efficacy (β = 2.88) and no help with medication (β = -21.05) had better medication knowledge (model F = 13.6, p = .000, R = .61, r 2 = .37). Conclusion: Older CHF patients have poor knowledge of their medications, which may be improved by promoting overall self-efficacy for disease management. Less knowledgeable patients received appropriate assistance with medications, but the consequence may be less knowledge and thus warrants further investigation.

Abstract 216: Left Ventricular Enlargement and Heart Failure Events: Is Bigger Better?

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Farbod Raiszadeh ◽  
Neeraja Yedlapati ◽  
Ileana L Piña ◽  
Daniel M Spevack
Keyword(s):  
Heart Failure ◽  
New York ◽  
Cox Regression ◽  
Systolic Heart Failure ◽  
Heart Association ◽  
Left Ventricular ◽  
Left Ventricular Volumes ◽  
End Diastolic Volume ◽  
New York Heart Association ◽  
The Individual

Background: Since stroke volume (SV) is a function of ejection fraction (EF) and end-diastolic volume (EDV) (SV = EF x EDV), we hypothesized that increased EDV may be advantageous in systolic heart failure (HF), allowing the left ventricle to supply increased cardiac output. Methods: Echocardiograms from 968 consecutive patients seen in our hospital’s HF clinic were reviewed. Left ventricular volumes were measured both at end systole and end diastole using the bi-plane Simpson’s method and were indexed to body surface area. EF was calculated using (EDV-ESV)/EDV. Dates of subsequent HF events (death or admission for HF exacerbation) were obtained from our database. Results: Systolic HF (EF < 50%) was found in 649 of the study subjects. Increased SV index was associated with increased EDV index. The strength of this association varied with EF, Figure. In a bivariate Cox regression model, lower SV index and higher EDV index were each independent predictors of HF events. Increase in EDV by 50 cc was associated with a 20% increase in HF events, p<0.001. Decrease in SVI by 5 cc was associated with 5% increase in HF events, p<0.001. These associations were limited to those with systolic HF. The associations between both EDVI and SVI and HF events were not confounded by patient age, sex and New York Heart Association Class. Conclusion: Increased EDV index was independently associated with increased HF events, indicating that LV enlargement in HF is not favorable. These findings underscore the individual contributions of the components of EF (SV and EDV) in predicting HF outcomes.

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