Dataset Information

Effects of neurohormonal antagonists on blood pressure in patients with heart failure with reduced ejection fraction (HFrEF): a systematic review protocol.

ABSTRACT: BACKGROUND:Several cardiovascular pathologies cause heart failure. Heart failure with reduced ejection fraction (HFrEF) is deteriorated by neurohormonal activation, so neurohormonal antagonists are recommended in HFrEF patients. They improve morbidity, mortality, and quality of life and reduce hospital admissions. Heart failure treatment guidelines recommend achieving target doses of those drugs. However, many clinicians prescribe suboptimal doses for the fear of inducing hypotension. The aim of this systematic review and meta-analysis is to understand whether it is still beneficial to uptitrate the doses of those drugs even if the patient is at the risk of developing hypotension. METHODS:The primary outcome is symptomatic or asymptomatic hypotension in patients on neurohormonal antagonist drugs for HFrEF. Secondary outcomes are blood pressure reduction, New Yok Heart Association functional class deterioration, non-fatal cardiovascular events, cardiovascular mortality, all-cause mortality, heart failure hospitalizations, and adverse events. Randomized controlled trials involving adults with HFrEF will be included. Comprehensive literature search will be done in MEDLINE, Scopus, Web of Science, WHO Global Index Medicus, and the Cochrane Central Register of Controlled Trials. MEDLINE will be searched first using controlled vocabulary and free text terms and then adapted to other databases. Linear and nonlinear dose-response meta-analyses will be conducted. Publication bias and statistical heterogeneity will be tested by Egger's regression and Cochran's Q tests, respectively. Sensitivity, subgroup, and meta-regression analyses will be performed. Grading of Recommendations Assessment, Development and Evaluation approach will be used to judge the quality of evidence. DISCUSSION:This systematic review and meta-analysis will provide information about the risk of hypotension in patients on neurohormonal antagonist drugs for HFrEF. The results will be published in a peer-reviewed journal. The implications for further research will be discussed. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42019140307.

SUBMITTER: Guggilla RK

PROVIDER: S-EPMC7445895 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of neurohormonal antagonists on blood pressure in patients with heart failure with reduced ejection fraction (HFrEF): a systematic review protocol.

Guggilla Rama Krishna RK Sowa Pawel Mateusz PM Jamiolkowski Jacek J Sinnadurai Siamala S Amin Adnan A Kaminski Karol Adam KA

Systematic reviews 20200824 1

<h4>Background</h4>Several cardiovascular pathologies cause heart failure. Heart failure with reduced ejection fraction (HFrEF) is deteriorated by neurohormonal activation, so neurohormonal antagonists are recommended in HFrEF patients. They improve morbidity, mortality, and quality of life and reduce hospital admissions. Heart failure treatment guidelines recommend achieving target doses of those drugs. However, many clinicians prescribe suboptimal doses for the fear of inducing hypotension. Th ...[more]

PMID: 32838804

Similar Datasets

Project description:OBJECTIVES:The purpose of this study was to investigate the effects of mineralocorticoid receptor antagonists (MRAs) on systolic blood pressure (SBP) and outcomes according to baseline SBP in patients with heart failure with reduced ejection fraction (HFrEF). BACKGROUND:MRAs are greatly underused in patients with HFrEF, often because of fear of adverse events. Concern about hypotension has been raised by the demonstration that MRAs are particularly effective treatment for resistant hypertension. METHODS:The effect of MRA therapy was studied in 4,396 patients with HFrEF randomized in the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials. RESULTS:Mean SBP change from baseline to 6 months was +1.4 ± 18.1 mm Hg in the placebo group and -1.2 ± 17.9 mm Hg in the MRA group. The between-treatment difference was 2.6 mm Hg (95% confidence interval [CI]: 1.5 to 3.6; p < 0.001). All outcomes were reduced by MRA therapy overall, with consistent effects across SBP categories (e.g., all-cause mortality, overall hazard ratio [HR] of 0.72; 95% CI: 0.64 to 0.82; p < 0.001; SBP ?105 mm Hg; HR: 0.72; 95% CI: 0.56 to 0.94; SBP >105 to ?115 mm Hg; HR: 0.78; 95% CI: 0.60 to 1.02; SBP >115 to ?125 mm Hg; HR: 0.71; 95% CI: 0.53 to 0.94; SBP >125 to ?135 mm Hg; HR: 0.79; 95% CI: 0.57 to 1.10; and SBP > 135 mm Hg; HR: 0.67; 95% CI: 0.50 to 0.90; p for interaction = 0.95). Hypotension was infrequent and not more common with MRA therapy than with placebo, overall (4.6% vs. 3.9%; p = 0.25) or in any SBP category. CONCLUSIONS:MRA treatment had little effect on SBP in patients with HFrEF, and the clinical benefits were not modified by baseline SBP. MRA treatment infrequently caused hypotension, even when the baseline SBP was low. The treatment discontinuation rates between MRA and placebo therapy were similar. Low SBP is not a reason to withhold MRA therapy in patients with HFrEF.

Project description:AimsPulmonary hypertension (PH) represents an important phenotype among the broader spectrum of patients with heart failure with preserved ejection fraction (HFpEF), but its mechanistic basis remains unclear. We hypothesized that activation of endothelin and adrenomedullin, two counterregulatory pathways important in the pathophysiology of PH, would be greater in HFpEF patients with worsening PH, and would correlate with the severity of haemodynamic derangements and limitations in aerobic capacity and cardiopulmonary reserve.Methods and resultsPlasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM), central haemodynamics, echocardiography, and oxygen consumption (VO2) were measured at rest and during exercise in subjects with invasively-verified HFpEF (n = 38) and controls free of HF (n = 20) as part of a prospective study. Plasma levels of CT-proET-1 and MR-proADM were highly correlated with one another (r = 0.89, P < 0.0001), and compared to controls, subjects with HFpEF displayed higher levels of each neurohormone at rest and during exercise. C-terminal pro-endothelin-1 and MR-proADM levels were strongly correlated with mean pulmonary artery (PA) pressure (r = 0.73 and 0.65, both P < 0.0001) and pulmonary capillary wedge pressure (r = 0.67 and r = 0.62, both P < 0.0001) and inversely correlated with PA compliance (r = -0.52 and -0.43, both P < 0.001). As compared to controls, subjects with HFpEF displayed right ventricular (RV) reserve limitation, evidenced by less increases in RV s' and e' tissue velocities, during exercise. Baseline CT-proET-1 and MR-proADM levels were correlated with worse RV diastolic reserve (ΔRV e', r = -0.59 and -0.67, both P < 0.001), reduced cardiac output responses to exercise (r = -0.59 and -0.61, both P < 0.0001), and more severely impaired peak VO2 (r = -0.60 and -0.67, both P < 0.0001).ConclusionSubjects with HFpEF display activation of the endothelin and adrenomedullin neurohormonal pathways, the magnitude of which is associated with pulmonary haemodynamic derangements, limitations in RV functional reserve, reduced cardiac output, and more profoundly impaired exercise capacity in HFpEF. Further study is required to evaluate for causal relationships and determine if therapies targeting these counterregulatory pathways can improve outcomes in patients with the HFpEF-PH phenotype.Clinical trial registrationNCT01418248; https://clinicaltrials.gov/ct2/results? term=NCT01418248&Search=Search.

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.

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.

Project description:AimsEchocardiographic assessment of left ventricular filling pressures is performed using a multi-parametric algorithm. Unselected sample of patients with heart failure with reduced ejection fraction (HFrEF) patients may demonstrate an indeterminate status of diastolic indices making interpretation challenging. We sought to test improvement in the diagnostic accuracy of standard and strain echocardiography of the left ventricle and left atrium (LA) to estimate a pulmonary capillary wedge pressure (PCWP) > 15 mmHg in patients with HFrEF.Methods and resultsOut of 82 consecutive patients, 78 patients were included in the final analysis and right heat catheterization, and echocardiogram was performed simultaneously. According to the univariable analysis, E wave velocity, the ratio between E-wave/A-wave (E/A, area under the curve [AUC] = 0.81, respectively), isovolumic relaxation time (AUC = 0.83), pulmonary vein D wave (AUC = 0.84), pulmonary vein S/D Ratio (AUC = 0.85), early pulmonary regurgitation velocity (AUC = 0.80), and accelerationa time at right ventricular out-flow tract (RVOT AT, AUC = 0.84) identified with the highest accuracy PCWP > 15 mmHg. They were all tested in multivariate analysis, and they were not independently correlated with PCWP. Tricuspid regurgitation (TR) velocity was measurement with the highest predictive value in identifying PCWP > 15 mmHg (AUC = 0.89), compared with other established parameters such as the ratio between e-wave velocity divided by mitral annular e' velocity (E/e'), deceleration time, or LA indexed volume (LAVi), which all reached a lower accuracy level (AUC = 0.75; 0.78; 0.76). Among strain measures, global longitudinal strain in four chamber view (GLS 4ch), the ratio between e-wave velocity divided by mitral annular e' strain rate (E/e'sr), and LA longitudinal strain at the reservoir phase were helpful in estimating elevated PCWP (AUC = 0.77; 0.76; 0.75). According to multivariable analysis, the following two models had the greatest accuracy in detecting PCWP > 15 mmHg: (i) TR velocity, LAVi, and E wave velocity (receiver operating characteristic [ROC]-AUC = 0.98), (ii) AT RVOT, LAVi and GLS 4ch (ROC-AUC = 0.96). Neither E/A (ROC-AUC = 0.81) nor E/e' (ROC-AUC = 0.75) was an independent predictor when included in the model. The two MODELS were applicable to the entire population and demonstrated better agreement with the invasive reference (91% and 88%) than the guidelines algorithm (77%) regardless of the type of rhythm.ConclusionsOur suggested echocardiographic approach could be used to potentially reduce the frequency of "doubtful" classification and increase the accuracy in predicting elevated left ventricular filling pressure leading to a decrease in the number of invasive assessment made by right heart catheterization.

Dataset Information

Effects of neurohormonal antagonists on blood pressure in patients with heart failure with reduced ejection fraction (HFrEF): a systematic review protocol.

Publications

Effects of neurohormonal antagonists on blood pressure in patients with heart failure with reduced ejection fraction (HFrEF): a systematic review protocol.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets