Plasma renin activity in patients with heart failure and reduced ejection fraction on optimal medical therapy.
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ABSTRACT: Background
Renin-angiotensin-aldosterone system (RAAS) activation in heart failure with reduced ejection fraction (HFREF) is detrimental through promotion of ventricular remodeling and salt and water retention.Aims
The aims of this article are to describe RAAS activity in distinct HFREF populations and to assess its prognostic impact.Methods
Venous blood samples were prospectively obtained in 76 healthy volunteers, 72 patients hospitalized for acute decompensated HFREF, and 78 ambulatory chronic HFREF patients without clinical signs of congestion. Sequential measurements were performed in patients with acute decompensated HFREF.Results
Plasma renin activity (PRA) was significantly higher in ambulatory chronic HFREF (7.6 ng/ml/h (2.2; 18.1)) compared to patients with acute decompensated HFREF (1.5 ng/ml/h (0.8; 5.7)) or healthy volunteers (1.4 ng/ml/h (0.6; 2.3)) (all p < 0.05). PRA was significantly associated with arterial blood pressure and renin-angiotensin system blocker dose. A progressive rise in PRA (+4 ng/ml/h (0.4; 10.9); p < 0.001) was observed in acute decompensated HFREF patients after three consecutive days of decongestive treatment. Only in acute HFREF were PRA levels associated with increased cardiovascular mortality or HF readmissions ( p = 0.035).Conclusion
PRA is significantly elevated in ambulatory chronic HFREF patients but is not associated with worse outcome. In contrast, in acute HFREF patients, PRA is associated with cardiovascular mortality or HF readmissions.
SUBMITTER: Nijst P
PROVIDER: S-EPMC5843922 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC7197490 | 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
Project description:OBJECTIVES AND DESIGN:Guideline-directed medical therapy (GDMT) with renin-angiotensin system (RAS) inhibitors and beta-blockers has improved survival in patients with heart failure with reduced ejection fraction (HFrEF). As clinical trials usually do not include very old patients, it is unknown whether the results from clinical trials are applicable to elderly patients with HF. This study was performed to investigate the clinical characteristics and treatment strategies for elderly patients with HFrEF in a large prospective cohort. SETTING:The Korean Acute Heart Failure (KorAHF) registry consecutively enrolled 5625 patients hospitalised for acute HF from 10 tertiary university hospitals in Korea. PARTICIPANTS:In this study, 2045 patients with HFrEF who were aged 65 years or older were included from the KorAHF registry. PRIMARY OUTCOME MEASUREMENT:All-cause mortality data were obtained from medical records, national insurance data or national death records. RESULTS:Both beta-blockers and RAS inhibitors were used in 892 (43.8%) patients (GDMT group), beta-blockers only in 228 (11.1%) patients, RAS inhibitors only in 642 (31.5%) patients and neither beta-blockers nor RAS inhibitors in 283 (13.6%) patients (no GDMT group). With increasing age, the GDMT rate decreased, which was mainly attributed to the decreased prescription of beta-blockers. In multivariate analysis, GDMT was associated with a 53% reduced risk of all-cause mortality (HR 0.47, 95% CI 0.39 to 0.57) compared with no GDMT. Use of beta-blockers only (HR 0.57, 95%?CI 0.45 to 0.73) and RAS inhibitors only (HR 0.58, 95%?CI 0.48 to 0.71) was also associated with reduced risk. In a subgroup of very elderly patients (aged ?80 years), the GDMT group had the lowest mortality. CONCLUSIONS:GDMT was associated with reduced 3-year all-cause mortality in elderly and very elderly HFrEF patients. TRIAL REGISTRATION NUMBER:NCT01389843.
| S-EPMC7044987 | biostudies-literature
Project description:There are gaps in the use of therapies that save lives and improve quality of life for patients with heart failure with reduced ejection fraction, both in the US and abroad. The evidence is clear that initiation and titration of guideline-directed medical therapy (GDMT) and comprehensive disease-modifying medical therapy (CDMMT) to maximally tolerated doses improves patient-focused outcomes, yet observational data suggest this does not happen. The purpose of this review is to describe the gap in the use of optimal treatment worldwide and discuss the benefits of newer heart failure therapies including angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors. It will also cover the efficacy and safety of such treatments and provide potential pathways for the initiation and rapid titration of GDMT/CDMMT.
| S-EPMC8674626 | biostudies-literature
Project description:IntroductionHeart failure is associated with recurrent hospitalizations and high mortality. Guideline directed medical treatment (GDMT), including beta blockers (BBs), angiotensin converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs) and aldosterone antagonists (AAs) has shown to improve outcomes. Current guidelines recommend the use of these medication classes at maximally tolerated dosages. Despite the evidence, <?25% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) are on the appropriate medical regimen titrated to the target doses. As such, we sought to assess the utility of a focused GDMT clinic to reduce this gap.MethodsWe conducted a retrospective chart review through existing patient data in a single center teaching hospital of patients referred to a focused GDMT clinic primarily staffed with heart failure trained nurse specialists, physician assistants and cardiologists. Management guidelines were developed with protocols for the initiation and uptitration of all therapeutic agents considered as GDMT.Our primary objective was to determine whether enrollment into a dedicated nursing led guideline directed medical therapy clinic would increase the proportion of patients with heart failure with reduced ejection fraction on appropriate medications as well as medication dosages in patients, the percentage of patients on the following medications and percentage at target doses: Renin-Angiotensin-Aldosterone System Blockers, Evidence Based Beta Blockers, and Aldosterone Antagonists. Our secondary objective was to determine if there was any clinical benefit on objective measures including renal function, hospital admissions, mortality and implantable defibrillator shocks.ResultsBetween October 2015 and March 2017, 63 patients were identified by requisition forms, in which 61 were able to be identified based on legibility of identifying information. Mean duration of follow up was 264.44?±?162.68 days over 7?±?3.94 days. Mean ejection fraction was 21.8?±?7.3%. New onset cardiomyopathies (diagnosed within 30?days) compiled 21% of the patient population while those with demonstrated cardiomyopathies (>?90?days) compiled 48% of the patient population. Patients with NYHA class III heart failure compiled 65% of the patient population.There was a statistically significant increase in the mean number of GDMT at any dose (2.31?±?0.76 to 2.74?±?0.66; p?<?0.001) and mean number of GDMT at target doses (0.54?±?0.79 to 1.52?±?1.1; p?<?0.001). Percentage of the population that were on no target doses at initial visit was 62% which was reduced to 18% after intervention.Clinical improvement was reflected in significant improvement in ejection fraction from 21.8?±?7.8% to 36.2?±?14.3% (p?<?0.001). Increases in sodium and chloride were statistically small but significant. There a significant reduction in heart failure hospitalizations in comparison to a year prior to after the initial encounter in the clinic (p?<?0.001).ConclusionThis pilot study showed that a nurse directed GDMT titration program successfully increased the number of GDMT that patients were able to tolerate in a timely fashion, all the while enhancing ejection fraction, sodium and chloride levels, with a reduction in rehospitalization rates.
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Project description: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 improvement in symptoms, mitigation of arrhythmic events, reduction in mortality, and correction in hemodynamics. Several modalities to regulate autonomic tone such as unilateral parasympathetic nerve activation, baroreceptor activation, renal nerve ablation and spinal cord stimulation have been investigated. Although they demonstrated some benefit, the long-term efficacy in HFrEF has not been proven. Considering specific limitations of each modality, to draw definitive conclusions is impossible at this time. Here, we review the present state-of-the-art hiterature? of device of autonomic regulation therapy to affect outcomes in HFrEF.
| S-EPMC7533145 | biostudies-literature
Project description:BackgroundChronic congestive heart failure is a common condition that, if untreated, markedly impairs the quality of life and is associated with a high risk of recurrent hospitalization and death.MethodsThis review is based on articles retrieved by a selective search in PubMed, as well as on relevant guidelines.ResultsEvidence-based treatment options are available only for congestive heart failure with a low ejection fraction. Pharma - cotherapy is based on neurohumoral inhibition of the renin-angiotensin-aldosterone system and the adrenergic system. The prognosis of patients with this condition has been further improved recently through the introduction of combined angiotensin receptor antagonists and neprilysin inhibitors. Modern implantable devices are a further component of treatment. Implantable defibrillators and special pacemakers for cardiac resynchronization are well established; the utility of alternative devices (baroreflex modulation or cardiac contractility modulation) needs to be investigated in further studies. It was recently shown that the catheter-based treatment of secondary mitral regurgitation with a MitraClip improves the outcome of selected patients.ConclusionThe treatment of chronic systolic heart failure as recommended in the relevant guidelines, with drugs and implanted devices if indicated, can significantly improve the clinical outcome.
| S-EPMC7643567 | biostudies-literature
Project description:Large randomized clinical trials (RCT) supporting guidelines for the management of heart failure with reduced ejection fraction (HFrEF) have typically excluded patients with advanced chronic kidney disease (CKD). Patients with concomitant advanced CKD and HFrEF experience poor cardiovascular outcomes and mortality relative to either disease in isolation and have been shown to consistently receive lower rates of HFrEF guideline-directed medical therapy (GDMT). This review evaluated recent evidence for the use of GDMT in patients with HFrEF and advanced CKD approaching dialysis from RCTs and observational cohorts. The authors also discuss the limitations and challenges inherent in the evidence for GDMT in this population, and offer guidance to clinicians for proper clinical use and future research directions.
| S-EPMC6501813 | 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:INTRODUCTION:The pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. We aimed to characterize HFpEF compared to heart failure with reduced ejection fraction (HFrEF) and asymptomatic hypertensive or non-hypertensive controls. MATERIALS AND METHODS:Prospective, observational study of 234 subjects (HFpEF n = 140; HFrEF n = 46, controls n = 48, age 73±8, males 49%) who underwent echocardiography, cardiovascular magnetic resonance imaging (CMR), plasma biomarker analysis (panel of 22) and 6-minute walk testing (6MWT). The primary end-point was the composite of all-cause mortality and/or HF hospitalization. RESULTS:Compared to controls both HF groups had lower exercise capacity, lower left ventricular (LV) EF, higher LV filling pressures (E/E', B-type natriuretic peptide [BNP], left atrial [LA] volumes), more right ventricular (RV) systolic dysfunction, more focal and diffuse fibrosis and higher levels of all plasma markers. LV remodeling (mass/volume) was different between HFpEF (concentric, 0.68±0.16) and HFrEF (eccentric, 0.47±0.15); p<0.0001. Compared to controls, HFpEF was characterized by (mild) reductions in LVEF, more myocardial fibrosis, LA remodeling/dysfunction and RV dysfunction. HFrEF patients had lower LVEF, increased LV volumes, greater burden of focal and diffuse fibrosis, more RV remodeling, lower LAEF and higher LA volumes compared to HFpEF. Inflammatory/fibrotic/renal dysfunction plasma markers were similarly elevated in both HF groups but markers of cardiomyocyte stretch/damage (BNP, pro-BNP, N-terminal pro-atrial natriuretic peptide and troponin-I) were higher in HFrEF compared to HFpEF; p<0.0001. Focal fibrosis was associated with galectin3, GDF-15, MMP-3, MMP-7, MMP-8, BNP, pro-BNP and NTproANP; p<0.05. Diffuse fibrosis was associated with GDF-15, Tenascin-C, MMP-2, MMP-3, MMP-7, BNP, proBNP and NTproANP; p<0.05. Composite event rates (median 1446 days follow-up) did not differ between HFpEF and HFrEF (Log-Rank p = 0.784). CONCLUSIONS:HFpEF is a distinct pathophysiological entity compared to age- and sex-matched HFrEF and controls. HFpEF and HFrEF are associated with similar adverse outcomes. Inflammation is common in both HF phenotypes but cardiomyocyte stretch/stress is greater in HFrEF.
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