Device Autonomic Regulation Therapy in Patients with Heart Failure with Reduced Ejection Fraction.
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ABSTRACT:
SUBMITTER: N Williford N
PROVIDER: S-EPMC7533145 | biostudies-literature | 2020 Jun-Jul
REPOSITORIES: biostudies-literature
Publications
Device Autonomic Regulation Therapy in Patients with Heart Failure with Reduced Ejection Fraction.
N Williford Noah N Statz Giselle G L Mann Douglas D Olshansky Brian B
Journal of atrial fibrillation 20200630 1
Heart failure with reduced ejection fraction (HFrEF) is a common, incompletely treatable, complex, progressive, and severe medical problem despite guideline-directed medical therapy. HFrEF is associated with sympathetic activation and parasympathetic inhibition; these reflexive processes may ultimately be maladaptive and exacerbate or even perpetuate the problem. Attempts to regulate autonomic tone during HFrEF in animal models and in humans has shown promise with beneficial effects that include ...[more]
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Project description:BackgroundRecent heart failure studies have associated lower baseline natriuretic peptide levels with improved morbidity/mortality outcomes during pharmaceutical treatment, and better clinical outcomes during neuromodulation (NM) with carotid nerve plexus stimulation for HFrEF when NT-proBNP < 1600 pg/ml. Whether baseline NT-proBNP is associated with HFrEF responsiveness to NM using vagus nerve stimulation (VNS) has not been examined. Hence, we evaluated the interaction of baseline NT-proBNP with changes in symptoms and function that occurred during chronic VNS in the ANTHEM-HF study.MethodsA repeated measures, generalized-estimating, equations model evaluated the relationship of baseline NT-proBNP values above and below 1600 pg/ml to symptomatic and functional responses in ANTHEM-HF.ResultsMedian (interquartile range; maximum) NT-proBNP was 868 (322, 1875; 14,656) pg/ml (N = 58). Heart rate (HR), HR variability (SDNN), 6-minute walk distance, MLWHF mean score, and NYHA improved significantly, independent of baseline NT-proBNP. While there was a statistical interaction between baseline NT-proBNP and better LVEF improvement during VNS, LVEF improved overall in the study cohort (N = 60; 32 ± 7 to 37 ± 10%; p = 0.0042), and in those patients whose baseline NT-proBNP was below the median baseline NT-proBNP value (n = 29; 36 ± 6 to 42 ± 10%; p < 0.0025)] or above this value (n = 29; 29 ± 7 to 32 ± 9%; p < 0.05).ConclusionsIn ANTHEM-HF, overall symptomatic and functional improvement during chronic VNS was independent of baseline NTproBNP. These are preliminary and hypothesis-generating findings, and the reason for a differing interaction between baseline NT-proBNP and response to CNPS and VNS remains unclear. It is anticipated that the ongoing ANTHEM-HFrEF Pivotal Study of VNS will provide additional insight.
| S-EPMC7264752 | biostudies-literature
Project description:AimsThis study aimed to investigate the prognostic value of dynamic changes in left ventricular ejection fraction (EF) for cardiovascular (CV) outcomes in an all-comer heart failure (HF) population with reduced EF (HFrEF, EF < 40%). We sought to identify independent factors related to improvement in EF and to identify risk factors for increased risk of CV events in the subgroups of improved EF (iEF) and non-improved EF (niEF), respecively.Methods and resultsThis is a retrospective sub-analysis from the REDEAL HF trial, which included consecutive patients with chronic HF who were hospitalized from July 2009 to December 2017. Baseline and follow-up echocardiography data (interval ≥12 months) of 573 consecutive patients with HFrEF were analysed. iEF was defined as absolute improvement in EF ≥ 10% and follow-up EF over 40%. The primary endpoint was defined as a composite endpoint of cardiovascular (CV) death, CV hospitalization, or appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular arrhythmia. EF improved in 37.2% of patients with HFrEF during follow-up (median period of 17 months). iEF was independently associated with shorter HF duration (>4 vs. ≤4 years, odd ratio [OR] = 0.477, 95% CI 0.305-0.745), no coronary artery disease (CAD vs. no CAD, OR = 0.583, 95% CI 0.396-0.858), and no ICD implantation (ICD vs. no ICD, OR = 0.341, 95% CI 0.228-0.511). Compared with niEF, iEF was significantly and independently associated with lower all-cause mortality (22.1% vs. 31.1%, P = 0.019; hazard ratio [HR] = 0.674, 95% CI 0.469-0.968), lower CV mortality (8.9% vs. 16.1%, P = 0.015; HR = 0.539, 95% CI 0.317-0.916), and lower CV events risk (27.2% vs. 49.2%, P < 0.001; HR 0.519, 95% CI 0.381-0.708), after adjustment for age, sex, duration of HF, and other clinical risk factors. Hypertension (HR = 2.452, P = 0.032) and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP >1153 pg/mL, HR = 4.372, P < 0.001) were identified as independent risk factors for CV events in the iEF subgroup. ICD implantation (HR = 1.533, P = 0.011), elevated NT-proBNP (HR = 1.626, P = 0.018), increased left atrial volume index (HR = 1.461, P = 0.021), reduced lateral mitral annular plane systolic excursion (HR = 1.478, P = 0.025), and reduced tricuspid plane systolic excursion (HR = 1.491, P = 0.039) were identified as risk factors for CV events in the niEF subgroup.ConclusionsImprovement in EF is independently related to the longer survival and lower CV related mortality and hospitalization rate of HFrEF. Elevated baseline NT-proBNP is identified as the strongest prognostic factor associated with increased CV events risk in HFrEF patients both with and without improved EF, regardless of age, sex, duration of HF, and other clinical risk factors.
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Project description:Device therapy is a nonpharmacological approach that presents a crucial advancement for managing patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). This review investigated the impact of device-based interventions and emphasized their potential for optimizing treatment for this complex patient demographic. Cardiac resynchronization therapy, augmented by atrioventricular node ablation with His-bundle pacing or left bundle-branch pacing, is effective for enhancing cardiac function and establishing atrioventricular synchrony. Cardiac contractility modulation and vagus nerve stimulation represent novel strategies for increasing myocardial contractility and adjusting the autonomic balance. Left ventricular expanders have demonstrated short-term benefits in HFpEF patients but require more investigation for long-term effectiveness and safety, especially in patients with AF. Research gaps regarding complications arising from left ventricular expander implantation need to be addressed. Device-based therapies for heart valve diseases, such as transcatheter aortic valve replacement and transcatheter edge-to-edge repair, show promise for patients with AF and HFpEF, particularly those with mitral or tricuspid regurgitation. Clinical evaluations show that these device therapies lessen AF occurrence, improve exercise tolerance, and boost left ventricular diastolic function. However, additional studies are required to perfect patient selection criteria and ascertain the long-term effectiveness and safety of these interventions. Our review underscores the significant potential of device therapy for improving the outcomes and quality of life for patients with AF and HFpEF.
| S-EPMC10943171 | biostudies-literature
Project description:Heart failure (HF) can occur in patients with preserved (HFpEF, EF?50%) or reduced (HFrEF, EF<50%) ejection fraction (EF), but changes in EF after HF diagnosis are not well described.Among a community cohort of incident HF patients diagnosed from 1984 to 2009 in Olmsted County, Minnesota, we obtained all EFs assessed by echocardiography from initial HF diagnosis until death or last follow-up through March 2010. Mixed effects models fit a unique linear regression line for each person using serial EF data. Compiled results allowed estimates of the change in EF over time in HFpEF and HFrEF. Among 1233 HF patients (48.3% male, mean age 75.0 years, mean follow-up 5.1 years), 559 (45.3%) had HFpEF at diagnosis. In HFpEF, on average, EF decreased by 5.8% over 5 years (P<0.001) with greater declines in older individuals and those with coronary disease. Conversely, EF increased in HFrEF (average increase 6.9% over 5 years, P<0.001). Greater increases were noted in women, younger patients, individuals without coronary disease, and those treated with evidence-based medications. Overall, 39% of HFpEF patients had an EF<50% and 39% of HFrEF patients had an EF?50% at some point after diagnosis. Decreases in EF over time were associated with reduced survival whereas increases in EF were associated with improved survival.These data suggest that progressive contractile dysfunction may contribute to the pathophysiology of HFpEF. Prospective longitudinal studies are needed to confirm these observations and establish the mechanism and clinical relevance of decline in EF over time in HFpEF.
| S-EPMC3661289 | biostudies-literature
Project description:BACKGROUND:Guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) have medical therapy titrated to target doses derived from clinical trials, as tolerated. The degree to which titration occurs in contemporary U.S. practice is unknown. OBJECTIVES:This study sought to characterize longitudinal titration of HFrEF medical therapy in clinical practice and to identify associated factors and reasons for medication changes. METHODS:Among 2,588 U.S. outpatients with chronic HFrEF in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry with complete medication data and no contraindications to medical therapy, use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) were examined at baseline and at 12-month follow-up. RESULTS:At baseline, 658 (25%), 525 (20%), 287 (11%), and 45 (2%) patients were receiving target doses of MRA, beta-blocker, ACEI/ARB, and ARNI therapy, respectively. At 12 months, proportions of patients with medication initiation or dose increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding proportions with discontinuation or dose decrease were 4%, 7%, 11%, and 3%, respectively. Over 12 months, <1% of patients were simultaneously treated with target doses of ACEI/ARB/ARNI, beta-blocker, and MRA. In multivariate analysis, across the classes of medications, multiple patient characteristics were associated with a higher likelihood of initiation or dose increase (e.g., previous HF hospitalization, higher blood pressure, lower ejection fraction) and discontinuation or dose decrease (e.g., previous HF hospitalization, impaired quality of life, more severe functional class). Medical reasons were the most common reasons for discontinuations and dose decreases of each therapy, but the relative contributions from patient preference, health team, and systems-based reasons varied by medication. CONCLUSIONS:In this contemporary U.S. registry, most eligible HFrEF patients did not receive target doses of medical therapy at any point during follow-up, and few patients had doses increased over time. Although most patients had no alterations in medical therapy, multiple clinical factors were independently associated with medication changes. Further quality improvement efforts are urgently needed to improve guideline-directed medication titration for HFrEF.
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Project description:In chronic heart failure (CHF), functional and metabolic alterations are detected not only in cardiac muscle but also in skeletal muscle tissue. The molecular mechanisms responsible for muscle dysfunction in patients with CHF remain unknown as well as the biological processes responsible for the positive effect of physical exercise training. In this work, using the results of transcriptome sequencing (3' mRNA-Seq), authors identify the molecular mechanisms responsible for reducing muscle dysfunctions in patients with CHF undergoing a personalized program of physical rehabilitation. 3 patients with CHF were enrolled in the study, biopsies of gastrocnemius muscle were taken before and after 12 weeks of individual training program (intensity was determined at 90% of lactate inflection point). Analysis of RNA-Seq data shows the strong upregulation of pathways that control skeletal muscle cell differentiation, muscle contraction, recovery of membrane potential.
2019-12-04 | GSE134698 | GEO
Project description:Heart failure with preserved ejection fraction is responsible for half of all heart failure and confers substantial morbidity and mortality, and yet to date, there have been no effective pharmacologic interventions. Although the pathophysiology is complex, the primary aetiology of exercise intolerance is due to an elevated left atrial pressure, particularly with exercise. In this context, device-based therapy has become a focus. Several companies have developed techniques to percutaneously create an iatrogenic left to right shunt at the atrial level, thereby reducing left atrial pressure and reducing transmitted pressures to the pulmonary circulation and reducing pulmonary congestion. In this review, we explore the pathophysiology, evidence base, benefits, and considerations of these devices and their place in the therapeutic landscape of heart failure with preserved ejection fraction.
| S-EPMC9941219 | biostudies-literature
Project description:The optimal heart rate (HR) in patients with heart failure with reduced ejection fraction (HFrEF) has been ill-defined. Recently, a formula was proposed for estimating the target heart rate (THR), which eliminates the overlap between the E and A wave (E-A overlap). We aim to validate its prognostic significance in the multicenter WET-HF registry. This study used data from 647 patients with HFrEF hospitalized for acute decompensated HF (ADHF). The patients were divided into the 2 groups by THR. The primary endpoint was defined as the composite of all-cause death and ADHF readmission. The THR successfully discriminated the incidence of the primary endpoint, whereas no significant difference was observed in the primary endpoint when dividing the patients by uniform cutoff 70 bpm. HR at discharge ≤ THR was inversely associated with the primary endpoint. Restricted cubic spline analysis demonstrated the difference between HR at discharge, and THR (ΔHR) from -10 to ±0 was associated with a lower risk of primary endpoint and ΔHR from ±0 to +15 was associated with a higher risk. THR discriminated long-term outcomes in patients with HFrEF more efficiently than the uniform cutoff, suggesting that it may aid in tailored HR reduction strategies.
| S-EPMC8777886 | biostudies-literature
Project description:AimsHeart failure with mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared with heart failure (HF) with reduced ejection fraction (EF). We assessed whether left ventricular ejection fraction (LVEF) trajectory can be used to identify groups of patients with HFmrEF who have different clinical outcomes in a large retrospective study of patients with serial imaging.Methods and resultsPatients with HF and ≥2 echocardiograms performed ≥6 months apart were included if the LVEF measured 40-49% on the second study. Patients were classified as HFmrEF-Increasing if LVEF had increased ≥10% (n = 450), HFmrEF-Decreasing if LVEF had decreased ≥10% (n = 512), or HFmrEF-Stable if they did not meet other criteria (n = 389). The primary outcome was all-cause mortality or cardiovascular hospitalization after the second echocardiogram. Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, co-morbidities, and medications. In total, 1351 patients with HFmrEF (median age 74, 64.2% male) were included with 28.8% exhibiting stable LVEF. During median follow-up of 15.3 months, the composite outcome occurred in 811 patients. During follow-up, patients with HFmrEF-Increasing were less likely to experience the primary outcome [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.60-0.88, P < 0.001] compared with HFmrEF-Stable. Patients with HFmrEF-Decreasing were more likely to experience the composite outcome in unadjusted analyses (unadjusted HR 1.19, 95% CI 1.01-1.40, P = 0.040) but not adjusted analyses (adjusted HR 1.16, 95% CI 0.98-1.37, P = 0.092). Associations with death or HF hospitalizations were similar (HFmrEF-Increasing: adjusted HR 0.72, 95% CI 0.59-0.88, P = 0.005; HFmrEF-Decreasing: adjusted HR 1.20, 95% CI 1.01-1.44, P = 0.044). Patients with HFmrEF-Decreasing had a similar risk of the composite outcome as patients with HF with reduced EF (adjusted HR 1.03, 95% CI 0.89-1.20, P = 0.670). Patients with HFmrEF-Increasing were less likely to experience the composite outcome compared with patients with HF with preserved EF (adjusted HR 0.73, 95% CI 0.62-0.87, P < 0.001).ConclusionsAmongst patients with HFmrEF, those exhibiting positive LVEF trajectory were less likely to experience adverse outcomes after correcting for important confounders including medical therapy. Categorizing HFmrEF patients based on LVEF trajectory provides meaningful clinical information and may assist clinicians with management decisions.
| S-EPMC9065872 | biostudies-literature
Project description:ImportanceOptimal treatment of heart failure with reduced ejection fraction (HFrEF) is scripted by treatment guidelines, but many eligible patients do not receive guideline-directed medical therapy (GDMT) in clinical practice.ObjectiveTo determine whether a remote, algorithm-driven, navigator-administered medication optimization program could enhance implementation of GDMT in HFrEF.Design, setting, and participantsIn this case-control study, a population-based sample of patients with HFrEF was offered participation in a quality improvement program directed at GDMT optimization. Treating clinicians in a tertiary academic medical center who were caring for patients with heart failure and an ejection fraction of 40% or less (identified through an electronic health record-based search) were approached for permission to adjust medical therapy according to a sequential titration algorithm modeled on the current American College of Cardiology/American Heart Association heart failure guidelines. Navigators contacted participants by telephone to direct medication adjustment and conduct longitudinal surveillance of laboratory tests, blood pressure, and symptoms under supervision of a pharmacist, nurse practitioner, and heart failure cardiologist. Patients and clinicians declining to participate served as a control group.ExposuresNavigator-led remote optimization of GDMT compared with usual care.Main outcomes and measuresProportion of patients receiving GDMT in the intervention and control groups at 3 months.ResultsOf 1028 eligible patients (mean [SD] values: age, 68 [14] years; ejection fraction, 32% [8%]; and systolic blood pressure, 122 [18] mm Hg; 305 women (30.0%); 892 individuals [86.8%] in New York Heart Association class I and II), 197 (19.2%) participated in the medication optimization program, and 831 (80.8%) continued with usual care as directed by their treating clinicians (585 [56.9%] general cardiologists; 443 [43.1%] heart failure specialists). At 3 months, patients participating in the remote intervention experienced significant increases from baseline in use of renin-angiotensin system antagonists (138 [70.1%] to 170 [86.3%]; P < .001) and β-blockers (152 [77.2%] to 181 [91.9%]; P < .001) but not mineralocorticoid receptor antagonists (51 [25.9%] to 60 [30.5%]; P = .14). Doses for each category of GDMT also increased from baseline in the intervention group. Among the usual-care group, there were no changes from baseline in the proportion of patients receiving GDMT or the dose of GDMT in any category.Conclusions and relevanceRemote titration of GDMT by navigators using encoded algorithms may represent an efficient, population-level strategy for rapidly closing the gap between guidelines and clinical practice in patients with HFrEF.
| S-EPMC7495335 | biostudies-literature