Trimethylamine N-oxide and outcomes in patients hospitalized with acute heart failure and preserved ejection fraction.
Ontology highlight
ABSTRACT: Aims
Trimethylamine N-oxide (TMAO) is a metabolite derived from the gut microbiota. Elevated TMAO levels are associated with a poor prognosis in patients with heart failure with reduced ejection fraction. However, the prognostic effect of elevated TMAO levels on heart failure with preserved ejection fraction (HFpEF) remains unclear.Methods and results
We consecutively enrolled 146 patients who were hospitalized and discharged from Tottori University Hospital with the primary diagnosis of HFpEF (ejection fraction ≥ 50%). High TMAO levels were defined as those greater than the median value in the patients (20.37 μmol/L). Patients with high TMAO levels had a significantly higher prevalence of prior hospitalization for heart failure and severe renal dysfunction than those with low TMAO levels. They also had a significantly higher acylcarnitine to free carnitine ratio than those with low TMAO levels, which indicated abnormal fatty acid metabolism and relative carnitine deficiency. After adjustment for differences in the patients' background in multivariate analysis, high TMAO levels remained independently associated with a high incidence of the composite endpoints of death due to cardiac causes and hospitalization for heart failure (adjusted hazard ratio, 1.91; 95% confidence interval, 1.01 to 3.62; P < 0.05). There was a significant interaction between TMAO and nutritional status on the primary outcome, and the prognostic effect of TMAO was enhanced in patients with malnutrition.Conclusions
Elevated TMAO levels at discharge are associated with an increased risk of post-discharge cardiac events in patients with HFpEF, especially those with the complication of malnutrition.
SUBMITTER: Kinugasa Y
PROVIDER: S-EPMC8120352 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The aim of this study was to determine whether left atrial ejection fraction (LAEF) quantified with cardiovascular magnetic resonance (CMR) was different between heart failure with preserved ejection fraction (HFpEF) and controls, and its relation to prognosis. As part of our single-centre, prospective, observational study, 188 subjects (HFpEF n?=?140, controls n?=?48) underwent phenotyping with contrast-enhanced CMR, transthoracic echocardiography, blood sampling and six-minute walk testing. LAEF was calculated using the biplane method. Atrial fibrillation (AF) was present in 43 (31%) of HFpEF subjects. Overall, LAEF (%) was lower in HFpEF patients inclusive of AF (32?±?16) or those in sinus rhythm alone (41?±?12) compared to controls (51?±?11), p?<?0.0001. LAEF correlated inversely with maximal and minimal left atrial volumes indexed (r?=??-?0.602, r?=??-?0.762), and plasma N-terminal pro-atrial natriuretic peptide (r?=??-?0.367); p?<?0.0001. During median follow-up (1429 days), there were 67 composite events of all-cause death or hospitalization for heart failure (22 deaths, 45 HF hospitalizations) in HFpEF. Lower LAEF (below median) was associated with an increased risk of composite endpoints (Log-Rank: all p?=?0.028; sinus p?=?0.036). In multivariable Cox regression analysis, LAEF (adjusted hazard ratio [HR] 0.767, 95% confidence interval [CI] 0.591-0.996; p?=?0.047) and indexed extracellular volume (HR 1.422, CI 1.015-1.992; p?=?0.041) were the only parameters that remained significant when added to a base prognostic model comprising age, prior HF hospitalization, diastolic blood pressure, lung disease, NYHA, six-minute-walk-test-distance, haemoglobin, creatinine and B-type natriuretic peptide. CMR-derived LAEF is lower in HFpEF compared to healthy controls and is a strong prognostic biomarker.
| S-EPMC6942575 | biostudies-literature
Project description:Heart failure with preserved ejection fraction (HFpEF) represents a heterogeneous collection of conditions that are unified by the presence of a left ventricular ejection fraction ≥50%, evidence of impaired diastolic function and elevated natriuretic peptide levels, all within the context of typical heart failure signs and symptoms. However, while HFpEF is steadily becoming the predominant form of heart failure, disease-modifying treatment options for this population remain sparse. This review provides an overview of the diagnosis, management and prevention of HFpEF for general physicians.
| S-EPMC6334030 | biostudies-literature
Project description:BackgroundLow flow (LF) in heart failure with preserved ejection fraction (HFpEF) is a paradox but is associated with worse prognosis. Determinants of LF in HFpEF have not been clarified but their assessment could corroborate recognition and definition of such a paradoxical condition.MethodsA cohort of 193 patients hospitalized with HFpEF was retrospectively studied and divided in a group with LF (N = 45), defined by a left ventricular (LV) stroke volume index (SVI) < 30 ml/m2, and a group with normal flow (N = 148). A small LV cavity was pre-defined as LV end diastolic diameter index (EDDI) below median values (<25 mm/m2 for males and <26 mm/m2 for females). Right ventricular dysfunction (RVD) was defined as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure < 0.36 mm/mmHg. An endpoint of all-cause mortality was evaluated after a median follow-up of 2.4 years.ResultsRVD (OR = 7.4; P < 0.001), atrial fibrillation (AF) during echocardiography (OR = 3.26; P = 0.008), and small LV cavity (OR = 3.81; P = 0.003) were independently associated with LF. After adjusting for age, body mass index, systolic blood pressure, renal function, chronic obstructed pulmonary disease, use of ACE inhibitors/angiotensin receptor blockers, moderate tricuspid regurgitation, RVD), LF was associated with mortality (HR = 3.69; P < 0.001) whereas the combination of the determinants of LF was not.ConclusionParadoxical LF in HFpEF is associated with small LV cavity, AF and RVD. None of the combination of different factors associated with LF could substitute direct assessment of LF status in predicting prognosis in this cohort.
| S-EPMC7262439 | biostudies-literature
Project description:AimsThis study aimed to assess short-term outcomes among emergency department (ED) patients with acute heart failure (AHF) by preserved (≥50%) vs. reduced (<50%) ejection fraction (EF).Methods and resultsWe conducted a retrospective, multicentre study of adult ED patients with AHF from 2017 to 2018 in an integrated healthcare system with 21 hospitals. Among patients with known EF, our primary outcome was 30 day all-cause mortality, comparing patients with heart failure with preserved EF (HFpEF) and heart failure with reduced EF (HFrEF), adjusted for known risk factors. We ran separate multivariate regression models to compare 30 day mortality between HFpEF and HFrEF patients stratified by ED disposition (admit, observe, and discharge). Our secondary outcomes were adjusted 30 day all-cause return hospital admission and rates of non-fatal serious adverse events, including new intra-aorta balloon pump, endotracheal intubation, renal failure requiring dialysis, myocardial infarction, or coronary revascularization. We conducted a sensitivity analysis among patients with EF ≤ 40% and compared our primary and secondary outcomes among patients with EF ≤ 40% with those with EF ≥ 50%. Among the 26 050 total ED encounters for AHF, 15 275 (58.6%) had known EF and 62.4% had HFpEF. The mean age was 76, 49.6% were women, and 60.5% were white. We found that 62.4% of patients were admitted, 18.3% were observed, and 19.3% were discharged from the ED. The 30 day all-cause mortality rate was lowest among discharged patients (3.9%), intermediate among observed patients (5.9%), and highest among admitted patients (13.9%). Overall, the adjusted 30 day mortality rate was significantly higher among HFpEF patients compared with HFrEF patients (10.2% vs. 8.4%, P = 0.0004). HFpEF patients had higher mortality regardless of ED disposition, although the difference was only significant among admitted patients. The adjusted 30 day return hospital admission rates were not significantly different between HFpEF and HFrEF patients (17.9% vs. 17.8%, P = 0.89). The adjusted 30 day non-fatal serious adverse event rates were significantly higher among HFrEF patients compared with HFpEF patients (13.7% vs. 11.1%, P < 0.0001), driven by myocardial infarction and coronary revascularization. We found that 3692 patients had EF ≤ 40%. Patients with EF ≥ 50% had significantly higher adjusted 30 day mortality rates compared with those with EF ≤ 40% (10.2% vs. 8.4%, P < 0.05).ConclusionIn a contemporary population, almost three quarters of ED patients with AHF and known EF have HFpEF. These patients have higher 30 day adjusted mortality compared with those with HFrEF. Further studies might evaluate the underlying factors associated with this difference and target interventions to improve outcomes.
| S-EPMC8318513 | biostudies-literature
Project description:Endothelial function may be deranged in heart failure with preserved ejection fraction (HFpEF). Serum NO-derived metabolites (NOm) might provide a biochemical surrogate of endothelial function in patients with heart failure (HF). We measured serum NOm in 415 participants in the Penn HF Study. Participants with HFpEF (n = 82) and those whose EF had recovered (Recovered-HF, n = 125) were matched 1:1 to heart failure with reduced ejection fraction (HFrEF) participants based on age, gender, race, tobacco use, and eGFR. Serum NOm levels were quantified after chemical reduction coupled with gas-phase chemiluminescence detection. After adjustment for matching covariates and BMI, HFpEF (34.5 ?M; interquartile range [IQR] 25.0, 51.5) participants had lower NOm levels than HFrEF (41.0 ?M; IQR 28.3, 58.0; ratio of HFpEF:HFrEF 0.82, 95% confidence interval [CI] 0.67 to 0.99; p = 0.04), which further decreased when adjusted for covariates that affect endothelial function (ratio 0.79, 95% CI 0.65 to 0.98; p = 0.03). There were no differences between HFrEF (34.0; IQR 25.3, 49.0) and matched Recovered-HF (36.0 ?M; IQR 25.0, 55.0) or HFpEF and Recovered-HF. Age (+21%/10-year increase, p <0.001) and black race (-28%, p = 0.03) associated with NOm in HFpEF, whereas age (+11%/10-year increase, p = 0.03), current tobacco use (+67%, p = 0.01), and eGFR (p = 0.01) associated with NOm in Recovered-HF. In conclusion, HFpEF participants have reduced NOm compared with HFrEF in this matched cohort. This might suggest either compromised endothelial function or poor dietary intake. Black race was associated with lower NOm in HFpEF.
| S-EPMC5127733 | biostudies-literature
Project description:Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence as the general population ages. Poorly managed heart failure symptoms of decompensated HFpEF is one of the most common reasons for prolonged hospital admission. The high rate of morbidity and mortality associated with HFpEF is compounded by a poor understanding of the underpinning pathophysiology. Randomized controlled trials have so far been unable to identify an evidence base for reducing morbidity and mortality in patients with HFpEF, although there is some evidence to support quality of life (QOL) improvement. In this review, we described the recent advances on the pathophysiological understanding of HFpEF, the current and emerging treatment strategies, and what this may mean for individual patients. Potential treatments for HFpEF were divided into their relative management strategies and the current evidence assessed for effect on HFpEF mortality, hospital admission frequency, and QOL improvement. Overall, the understanding of HFpEF pathophysiology is improving and has been made a priority in identifying potential therapeutic targets. There is growing evidence that patients with ejection fractions (EF) of less than 60% may obtain a mortality benefit from ACE-inhibitors, angiotensin-neprilysin inhibitors, Angiotensin Receptor Blockers, and Mineralocorticoid Receptor Antagonists. However, this covers only a small proportion of the HFpEF spectrum. Therefore, currently there are no universal treatment strategies recommended for HFpEF, and management should focus on an individualised approach and this should take into account the comorbidities of each patient.
| S-EPMC7186731 | biostudies-literature
Project description:BackgroundIn the SPRINT (Systolic Blood Pressure Intervention Trial), intensive BP treatment reduced acute decompensated heart failure (ADHF) events. Here, we report the effect on HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF) and their subsequent outcomes.MethodsIncident ADHF was defined as hospitalization or emergency department visit, confirmed, and formally adjudicated by a blinded events committee using standardized protocols. HFpEF was defined as EF ≥45%, and HFrEF was EF <45%.ResultsAmong the 133 participants with incident ADHF who had EF assessment, 69 (52%) had HFpEF and 64 (48%) had HFrEF (P value: 0.73). During average 3.3 years follow-up in those who developed incident ADHF, rates of subsequent all-cause and HF hospital readmission and mortality were high, but there were no significant differences between those who developed HFpEF versus HFrEF. Randomization to the intensive arm had no effect on subsequent mortality or readmissions after the initial ADHF event, irrespective of EF subtype. During follow-up among participants who developed HFpEF, although relatively modest number of events limited statistical power, age was an independent predictor of all-cause mortality, and Black race independently predicted all-cause and HF hospital readmission.ConclusionsIn SPRINT, intensive BP reduction decreased both acute decompensated HFpEF and HFrEF events. After initial incident ADHF, rates of subsequent hospital admission and mortality were high and were similar for those who developed HFpEF or HFrEF. Randomization to the intensive arm did not alter the risks for subsequent all-cause, or HF events in either HFpEF or HFrEF. Among those who developed HFpEF, age and Black race were independent predictors of clinical outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.
| S-EPMC8692397 | biostudies-literature
Project description:Background and objectivesThe relationship among anemia, renal dysfunction, left ventricular ejection fraction, and outcomes of patients hospitalized for acute decompensated heart failure is unclear. The aim of this study was to evaluate the association between cardiorenal anemia syndrome and postdischarge outcomes in patients hospitalized for heart failure with a preserved or reduced ejection fraction.Design, setting, participants, & measurementsOf 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes Registry between April 1, 2007 and December 31, 2011, 4393 patients were evaluated to investigate the association among anemia, renal dysfunction, preserved or reduced ejection fraction, and the primary end point (mortality and readmission for heart failure since discharge). The patients were divided into four groups on the basis of eGFR and hemoglobin at discharge. The median follow-up period after discharge was 432 (range=253-659) days.ResultsThe primary end point was reached in 37.6% and 34.8% of the preserved and reduced ejection fraction groups, respectively. After adjustment for multiple comorbidities, there was no significant association of either renal dysfunction or anemia alone with the primary end point in patients with preserved ejection fraction, but the combination of renal dysfunction and anemia was associated with a significantly higher risk than that without either condition (hazard ratio, 1.54; 95% confidence interval, 1.12 to 2.12; P<0.01). In patients with reduced ejection fraction, adjusted analysis showed that a significantly higher risk of the primary end point was associated with renal dysfunction alone (hazard ratio, 1.65; 95% confidence interval, 1.21 to 2.25; P=0.002) and also, renal dysfunction plus anemia relative to the risk without either condition (hazard ratio, 2.19; 95% confidence interval, 1.62 to 2.96; P<0.001).ConclusionsThe findings show that renal dysfunction combined with anemia is associated with an increased risk of adverse postdischarge outcomes in patients with preserved ejection fraction, whereas renal dysfunction is an independent predictor of the risk of adverse outcomes in patients with reduced ejection fraction, regardless of anemia.
| S-EPMC4220765 | biostudies-literature
Project description:BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Some patients develop elevated filling pressures exclusively during exercise and never require hospitalization, whereas others periodically develop congestion that requires inpatient treatment. The features differentiating these cohorts are unclear.MethodsWe performed a secondary analysis of 7 National Institutes of Health-sponsored multicenter trials of HFpEF (EF ≥ 50%, N = 727). Patients were stratified by history of hospitalization because of HF, comparing patients never hospitalized (HFpEFNH) to those with a prior hospitalization (HFpEFPH). Currently hospitalized (HFpEFCH) patients were included to fill the spectrum. Clinical characteristics, cardiac structure, biomarkers, quality of life, functional capacity, activity levels, and outcomes were compared.ResultsAs expected, HFpEFCH (n = 338) displayed the greatest severity of congestion, as assessed by N-terminal pro B-type natriuretic peptide levels, edema and orthopnea. As compared to HFpEFNH (n = 109), HFpEFPH (n = 280) displayed greater comorbidity burden, with more lung disease, renal dysfunction and anemia, along with lower activity levels (accelerometry), poorer exercise capacity (6-minute walk distance and peak exercise capacity), and more orthopnea. Patients with current or prior hospitalization displayed higher rates of future HF hospitalization, but quality of life was similarly impaired in all patients with HFpEF, regardless of hospitalization history.ConclusionsA greater burden of noncardiac organ dysfunction, sedentariness, functional impairment, and higher event rates distinguish patients with HFpEF and prior HF hospitalization from those never hospitalized. Despite lower event rates, quality of life is severely and similarly limited in patients with no history of hospitalization. These data suggest that the 2 clinical profiles of HFpEF may require different treatment strategies.
| S-EPMC7704788 | biostudies-literature
Project description:BackgroundThere is little evidence addressing the use and differential impact of respiratory support in acute heart failure (AHF) patients with preserved (HFPEF) vs reduced (HFREF) ejection fraction. Therefore, our objective was to determine the usage and clinical outcomes of critical care respiratory support in AHF across the two populations.HypothesisRespiratory support would be associated with adverse outcome in both HFPEF and HFREF.MethodsWe identified HFPEF, HFREF, invasive mechanical ventilation (IMV), and noninvasive ventilation (NIV) using International Classification of Disease-Ninth Edition codes in the National Inpatient Sample between January 1, 2008 and December 31, 2014. We determined rates of IMV and NIV use. We identified predictors of need for IMV and NIV and the association between ventilation strategies and in-hospital mortality in HFPEF vs HFREF.Results1.3 million AHF-HFPEF and 1.7 million AHF-HFREF hospitalizations were included; 5.98% of AHF HFPEF hospitalizations included NIV and 0.57% included IMV. Among HFREF hospitalizations, fewer (4.1%) included NIV and more (0.93%) included IMV. In HFPEF hospitalization, NIV use was associated with 2.24-fold increased risk for death compared to no respiratory support in an adjusted model (HR 2.24 95% CI 2.05-2.44) and IMV use was associated with 2.85-fold increased risk for death (HR 2.85 95% CI 2.30-3.53). This increased risk of in-hospital mortality was similar among HFREF patients.ConclusionsUse of respiratory support is increasing among patients with both HFPEF and HFREF and associated with substantially increased mortality in both heart failure subtypes.
| S-EPMC7144479 | biostudies-literature