scholarly journals Targeting cardiac myocyte Na+-K+ pump function with β3 adrenergic agonist in rabbits and patients with severe congestive heart failure

2019 ◽  
Author(s):  
Natasha AS Fry ◽  
Chia-Chi Liu ◽  
Alvaro Garcia ◽  
Elisha J Hamilton ◽  
Keyvan Karimi Galougahi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Myocyte ◽  
Oral Treatment ◽  
Nyha Class ◽  
Signs And Symptoms ◽  
Pump Current ◽  
Severe Congestive Heart Failure ◽  
Post Discharge ◽  
Treatment Target ◽  
Coronary Ligation

AbstractBackgroundReported one- and two-year mortality for patients with advanced heart failure (HF) treated medically are ~75% and nearly 100%. In such patients, reversible cellular abnormalities are potential treatment targets and a raised cytosolic Na+ concentration that impairs their myocardial contractility is one potential target. β3 adrenoceptor (β3 AR) agonists stimulate the myocyte Na+-K+ pump.MethodsWe induced severe HF in rabbits by coronary ligation and measured indices of organ congestion after treatment with β3 AR agonists. Na+-K+ pump current was measured in voltage-clamped myocytes isolated from non-infarct myocardium. To assess if β3 ARs might add benefit to optimised guideline-directed medical treatment we report outcomes of giving the β3 AR agonist mirabegron to patients hospitalized with advanced, treatment-refractory stage D HF.ResultsTreatment of rabbits after coronary ligation with β3 AR agonist reversed a decreased myocyte Na+-K+ pump current and significantly reduced organ congestion and prevalence of ascites. Oral treatment with mirabegron rapidly improved signs and symptoms of 9 patients with advanced HF and improvement of ≥1 NYHA Class was maintained early post-discharge with continued treatment. One patient died from HF at 16 months, 4 died from other causes at 2 – 30 months and 4 remain alive at 38 ± 4 months with NYHA Class II symptoms.ConclusionsParallel β3 AR agonist-induced reversal of Na+-K+ pump inhibition and severe HF in rabbits identify pump inhibition as a treatment target, and changed in-hospital clinical trajectory and post-discharge course more favorable than expected suggest efficacy of mirabegron in advanced human HF.

scholarly journals Targeting Cardiac Myocyte Na + -K + Pump Function With β3 Adrenergic Agonist in Rabbit Model of Severe Congestive Heart Failure

2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Natasha A.S. Fry ◽  
Chia-Chi Liu ◽  
Alvaro Garcia ◽  
Elisha J. Hamilton ◽  
Keyvan Karimi Galougahi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Cardiac Myocyte ◽  
Rabbit Model ◽  
Severe Heart Failure ◽  
Pump Current ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Coronary Ligation

Background: Abnormally high cytosolic Na + concentrations in advanced heart failure impair myocardial contractility. Stimulation of the membrane Na + -K + pump should lower Na + concentrations, and the β3 adrenoceptor (β3 AR) mediates pump stimulation in myocytes. We examined if β3 AR-selective agonists given in vivo increase myocyte Na + -K + pump activity and reverse organ congestion in severe heart failure (HF). Methods: Indices for HF were lung-, heart-, and liver: body weight ratios and ascites after circumflex coronary artery ligation in rabbits. Na + -K + pump current, I p , was measured in voltage-clamped myocytes from noninfarct myocardium. Rabbits were treated with the β3 AR agonists CL316,243 or ASP9531, starting 2 weeks after coronary ligation. Results: Coronary ligation caused ascites in most rabbits, significantly increased lung-, heart-, and liver: body weight ratios, and decreased I p relative to that for 10 sham-operated rabbits. Treatment with CL316,243 for 3 days significantly reduced lung-, heart-, and liver: body weight ratios and prevalence of ascites in 8 rabbits with HF relative to indices for 13 untreated rabbits with HF. It also increased I p significantly to levels of myocytes from sham-operated rabbits. Treatment with ASP9531 for 14 days significantly reduced indices of organ congestion in 6 rabbits with HF relative to indices of 6 untreated rabbits, and it eliminated ascites. β3 AR agonists did not significantly change heart rates or blood pressures. Conclusions: Parallel β3 AR agonists-induced reversal of Na + -K + pump inhibition and indices of congestion suggest pump inhibition is a useful target for treatment with β3 AR agonists in congestive HF.

Pd Treatment for Severe Congestive Heart Failure

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 231-235 ◽  
Author(s):  
Bernd G. Stegmayr ◽  
Ravi Banga ◽  
Lennart Lundberg ◽  
Ann Marie Wikdahl ◽  
Marianne Plum-Wirell
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Nyha Class ◽  
Fatal Outcome ◽  
Severe Congestive Heart Failure ◽  
Class Iii ◽  
Refractory Heart Failure ◽  
Nyha Classification ◽  
Heart Size ◽  
Angiotension Converting Enzyme

Our objective was to evaluate if peritoneal dialysis (PD) could improve survival of patients with progressive severe congestive heart failure resistant to drug therapy. The patients were selected by the cardiologist in cooperation with a nephrologist, including patients not responding to conventional medication with an expected fatal outcome within the next months. The study included 16 consecutive patients with a chronic progressive severe refractory heart failure (sHF) of NYHA class III (n = 6) or IV (n = 10) who did not respond to diuretics and angiotension converting enzyme (ACE) inhibitors. They had a mean age of 60 years (±14, range 30 -75, median 62 years). Nine of the patients had sHF as the only reason for initiating PD (all NYHA IV), while 7 also needed dialysis due to uremia. Five of 7 had been on hemodialysis but switched to PD due to a progressive congestive sHF. ln 2 patients, PD was decided already at start of dialysis therapy due to the severity of their heart failure. The reason for sHF was: valvular dysfunction (n = 5) with defect prosthesis (n = 3); in the course of a myocardial infarction (n = 4); and cardiomyopathy (n = 4). Tenckhoff catheters were inserted under local anesthesia and ultrafiltration was started and maintained until discharge. The survival time and change in heart size by x ray was used for analyses. All patients improved their stage of congestive heart failure by NYHA classification already during the first month. Six patients died during the follow-up period due to cardiac reasons (sudden death, relapse of sHF) after a mean of 10.7 months (±3.7, range 1 24 months). Ten were alive after a median observation period of 10 months (±12.5, range 1–36 months). Heart size was reduced in 15 of the patients. Three of the patients with sHF but without uremia could stop the PD. The results showed that ultrafiltration by PD was easy to perform despite low initial blood pressure. The sHF was reduced and life span was prolonged with improved quality of life.

scholarly journals ‘Subcutaneous furosemide in advanced heart failure: service improvement project’

2021 ◽  
pp. bmjspcare-2020-002803
Author(s):  
Francesca Birch ◽  
Emily Boam ◽  
Sharon Parsons ◽  
Justin Ghosh ◽  
Miriam J Johnson
Keyword(s):  
Heart Failure ◽  
Controlled Trial ◽  
Nyha Class ◽  
Care Home ◽  
Severe Heart Failure ◽  
Heart Association ◽  
Signs And Symptoms ◽  
Service Improvement ◽  
Nurse Specialist ◽  
Improvement Project

ObjectivesIn severe heart disease, parenteral administration of loop diuretic is often needed. We present clinical outcomes from episodes of care using subcutaneous continuous subcutaneous infusion of furosemide (CSCI-furosemide).MethodsRetrospective review of service improvement data. The heart failure nurse specialist, supported by the heart failure-palliative care multidisciplinary team, works with the community or hospice staff who administer the CSCI-furosemide. Data collected for consecutive patients receiving CSCI-furosemide included: age, sex, New York Heart Association (NYHA) class, preferred place of care, goal of treatment, infusion-site reactions, and signs and symptoms of fluid retention (including weight and self-reported breathlessness).Results116 people (men 86 (66%); mean age 79 years, 49–97; NYHA class 3 (36/116, 31%) or 4 heart failure (80/116, 69%)) received 130 episodes of CSCI-furosemide (average duration 10 days, 1–49), over half in the patient’s own home/care home (80/129,; 61%) aiming to prevent hospital admission. 40/129 (31%) were managed in the hospice, and 9 (7.0%) in a community hospital. Average daily furosemide dose was 125 mg (40–300 mg). The goal of treatment was achieved in (119/130, 91.5%) episodes.The median reduction in weight was 4 kg (IQR −7 to −2 kgs, −22 to 9 kgs). Self-reported breathlessness reduced from 8.2 (±1.9) to 5.2 (±1.8). Adverse events occurred in 31/130 (24%) episodes; all but 4/130 (3%, localised skin infection) were mild.ConclusionsThese preliminary data indicate that CSCI-furosemide is safe and effective for people with severe heart failure. An adequately powered randomised controlled trial is indicated.

Abstract 305: Characteristics of Heart Failure Patients Referred to the Bridge Transitional Care Clinic By Time to Readmission

2020 ◽  
Vol 13 (Suppl_1) ◽  
Author(s):  
George Cholack ◽  
Joshua Garfein ◽  
Rachel H Krallman ◽  
Delaney Feldeisen ◽  
Kim Eagle ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Characteristics ◽  
Transitional Care ◽  
Discharge Planning ◽  
Nyha Class ◽  
Index Admission ◽  
Post Discharge ◽  
Care Clinic ◽  
Early Readmission

Background: Readmission reduction initiatives emphasize prompt follow-up post-discharge. Identifying factors that influence early readmission may inform discharge planning. We compared characteristics of heart failure (HF) patients (pts) based on time to readmission to determine which pt characteristics were associated with early readmission. Methods: Pts referred to the BRIDGE clinic following index admission for HF from 2008-2017 were eligible. Demographics and inpatient clinical characteristics were compared between 1) pts who were and were not readmitted within 30 days post-index discharge, and 2) pts who were readmitted early (0-7 days post-discharge) versus late (8-30 days post-discharge). Results: Of 978 HF pts, 226 (23.1%) were readmitted within 30 days. Compared to those not readmitted, 30-day readmits were more likely to be male, white, and have higher NYHA class, longer index stay, ICU admission during index admission, and lower Hgb, higher Cr, and higher BUN during index admission. Among those with a 30 day readmit, 56 (24.8%) were readmitted within 7 days of discharge. Early readmits were more often female (p=0.07) and had index stays in the ICU (p=0.07). Conclusion: Pts readmitted within 30 days had more complicated hospital courses than those not readmitted, and those readmitted early had higher incidences of females and index stays in the ICU. Efforts to define a high risk subset of HF pts likely to be readmitted early and targeting them for enhanced discharge planning is warranted.

scholarly journals Effects of Sacubitril-Valsartan in Heart Failure With Preserved Ejection Fraction in Patients Undergoing Peritoneal Dialysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Sha Fu ◽  
Zhenjian Xu ◽  
Baojuan Lin ◽  
Junzhe Chen ◽  
Qiuyan Huang ◽  
...  
Keyword(s):  
Heart Failure ◽  
New York ◽  
Peritoneal Dialysis ◽  
Ejection Fraction ◽  
Nyha Class ◽  
Heart Association ◽  
Signs And Symptoms ◽  
Preserved Ejection Fraction ◽  
Nyha Classification ◽  
Neprilysin Inhibitor

Aims: The effect of the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear, and data on ARNI treatment in peritoneal dialysis (PD) patients are lacking. The present study was designed to assess the efficacy and safety of sacubitril-valsartan in patients with HFpEF undergoing peritoneal dialysis.Methods and Results: End-stage kidney disease (ESKD) patients undergoing PD for 3 months with New York Heart Association (NYHA) class II–IV heart failure, ejection fraction of 50% or higher, and elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP) were assigned to receive sacubitril-valsartan. Patients were followed up regularly after medication treatment. The alterations in clinical and biochemical parameters before and after taking sacubitril-valsartan (generally 50–100 mg b.i.d) were investigated, and safety was also assessed. Twenty-one patients were recruited in this study. Compared with baseline levels, NT-proBNP levels [9769.0 (3093.5–21941.0) vs. 3034.0 (1493.2–6503.0), P = 0.002], and heart rate [80.0 (74.5–90.5) vs. 75.0 (70.3–87.0), P = 0.031] were markedly decreased after treatment with sacubitril-valsartan. Signs and symptoms of heart failure (21/21 vs. 15/21, P = 0.021) were obviously alleviated, NYHA classification and E/e' ratio showed a notable trend of improvement after 3–12 months of follow-up. None of the patients showed adverse drug reactions.Conclusions: The present data suggested that sacubitril-valsartan treatment in patients with HFpEF undergoing PD was effective and safe.

scholarly journals Cardiac contractility modulation therapy in elderly patients with chronic heart failure: results of the 12-month follow-up

2021 ◽  
Vol 28 (2) ◽  
pp. 5-10
Author(s):  
I. A. Chugunov ◽  
K. V. Davtyan ◽  
A. H. Topchyan ◽  
N. A. Mironova ◽  
E. M. Gupalo
Keyword(s):  
Heart Failure ◽  
Elderly Patients ◽  
Nyha Class ◽  
Cardiac Contractility ◽  
Signs And Symptoms ◽  
Left Ventricular ◽  
Additional Treatment ◽  
Cardiac Contractility Modulation ◽  
Reduced Ejection Fraction

Aim. This study aimed to evaluate the efficacy and safety of cardiac contractility modulation (CCM) therapy in elderly patients with heart failure with reduced ejection fraction (HFrEF).Methods. Sixteen patients older than 65 years old (median age 70 years) undergoing CCM Optimizer (Impulse Dynamics) device implantation due to HFrEF (NYHA class II - 9 (56%), III - 4 (25%), IV - 3 (19%)) were enrolled in this two-center observational study. Before implantation 6-minute walk test (6MWT), transthoracic echocardiography (TTE) was performed on all patients, and NTproBNP levels were assessed. The follow-up duration was 12 months with 2, 6, 12-month follow-up visits. Control 6MWT, TTE and NTproBNP tests were performed at 6-month and 12-month follow-up visits.Results. Two patients died during follow-up due to HF decompensation. The remaining patients showed a significant improvement in 6MWT (350 m vs 402.5 m, p=0,01). We also noted a tendency towards the left ventricular EF improvement (33% vs 40%, p=0,2) and lower values of NTproBNP levels (1112 pg/ml vs 527 pg/ml, p=0,19).Conclusion. CCM therapy is a safe and efficient additional treatment option to manage elderly patients with HFrEF for reducing signs and symptoms of HF.

Abstract 2412: Chronic Vagus Nerve Stimulation in Patients with Chronic Heart Failure is Feasible and Appears Beneficial

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Gaetano M De Ferrari ◽  
Antonio Sanzo ◽  
Martin Borggrefe ◽  
Christian Wolpert ◽  
Jürgen Kuschyk ◽  
...  
Keyword(s):  
Heart Failure ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Large Scale ◽  
Nyha Class ◽  
Severe Congestive Heart Failure ◽  
Heart Beat ◽  
Controlled Study ◽  
6 Minute Walk Test

Introduction Enhancement of vagal nerve activity has a strong experimental rationale as a potential therapeutic approach to patients with severe Congestive Heart Failure (CHF). The CardioFit (BioControl Medical, Ltd.) is an implantable system capable of delivering chronic vagus nerve stimulation (CVNS) synchronized with the heart beat via a multipolar stimulation lead. Methods Twenty-nine patients with stable CHF, NYHA class II–IV, LVEF ≤ 35% on optimal medical therapy were enrolled and successfully implanted in a 7-site international 6-month safety and efficacy pilot study. Optimization of CVNS parameters occurred during a four week run-in period, two to four weeks post-implantation. Results Twenty subjects (mean age 57 years, range 30 –75; ischemic etiology in 70%; prior ICD in 50%) completed six-month follow-up; one NYHA class IV subject died due to worsening HF two months after implantation. At 6-months, 14 subjects had improved their NYHA class, and 6 remained stable. A significant improvement (p < 0.05) was found in the subjects’ quality of life (MLwHF® questionnaire); exercise capacity (6-minute walk test; see graph); and blindly evaluated LV ejection fraction (from 24 ± 2% to 29 ± 2%). The most commonly reported transient adverse events were expected side-effects of CVNS such as pain at cuff site (n = 6), cough (n = 7), and voice alteration (n = 5), which were resolved by optimizing stimulation parameters. Conclusions Chronic Vagus Nerve Stimulation in patients with advanced heart failure is feasible and appears to be well tolerated and safe. Initial data suggest a favorable trend of clinical outcomes. At this point a large scale randomized controlled study is warranted.

scholarly journals Correlates and prognostic impact of new-onset heart failure after ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: insights from the INFUSE-AMI trial

2017 ◽  
Vol 7 (4) ◽  
pp. 339-347 ◽  
Author(s):  
Gennaro Giustino ◽  
Björn Redfors ◽  
Sorin J Brener ◽  
Ajay J Kirtane ◽  
Philippe Généreux ◽  
...  
Keyword(s):  
Heart Failure ◽  
Percutaneous Coronary Intervention ◽  
Infarct Size ◽  
Primary Percutaneous Coronary Intervention ◽  
Nyha Class ◽  
Coronary Intervention ◽  
Post Discharge ◽  
St Segment Elevation ◽  
Risk Of Death ◽  
Percutaneous Coronary

Background: The determinants and significance of early (30-day) heart failure symptoms after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) remain unclear. We investigated the clinical and imaging correlates of early post-discharge heart failure in patients with STEMI, and evaluated its impact on clinical outcomes. Methods: Patients from the INFUSE-AMI trial were categorized according to New York Heart Association (NYHA) functional classification at their 30-day visit (NYHA class ≥2 versus 1). Independent correlates of NYHA class ≥2 were determined by multivariable logistic regression. A landmark analysis beyond 30 days was performed to assess the impact of 30-day NYHA class ≥2 on 1-year risk of death or hospitalization for heart failure. Results: Among 402 patients enrolled in the INFUSE-AMI trial with data on NYHA class at 30 days, 76 (18.9%) had NYHA class ≥2. Independent correlates of 30-day NYHA class ≥2 were age, Killip class ≥2 at presentation, heart rate at presentation, intraprocedural no-reflow, and 30-day infarct size (% total ventricular mass). After adjustment for infarct size, patients with NYHA class ≥2 remained at higher risk of death or hospitalization for heart failure at 1-year follow-up compared to those in NYHA class 1 (11.8% vs. 2.8%, adjusted hazard ratio 3.78, 95% confidence interval 1.16–12.22, P=0.03). Conclusions: Clinical, procedural, and imaging variables predict the development of clinical heart failure after primary percutaneous coronary intervention in patients with STEMI. Early post-discharge heart failure symptoms identify a high-risk patient cohort for subsequent heart failure hospitalization and death, independent of infarct size. Trial Registration: ClinicalTrials.gov ; NCT00976521

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