Dataset Information

The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure.

ABSTRACT:

Aims

Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into heart failure pathophysiology. We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters as well as with elevated left atrial pressure (LAP), in patients with HFrEF, to provide insights into underlying mechanisms.

Methods and results

In 173 patients with HFrEF, we performed 6-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7 (inter-quartile range: 2.5-2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular [left ventricular ejection fraction (LVEF), global longitudinal strain (GLS)] and left atrial function [left atrial reservoir strain (LASr)] and elevated LAP (E/e' ratio >15) and used gene enrichment analyses to identify underlying pathophysiological processes. We found 723, 249, 792, and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr, and E/e' ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix. Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: cystatin-D, fibulin-5, and HSP40.

Conclusion

Circulating proteins show varying associations with different echocardiographic parameters in patients with HFrEF. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.

SUBMITTER: Abou Kamar S

PROVIDER: S-EPMC11346355 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure.

Abou Kamar S S Andrzejczyk K K Petersen T B TB Chin J F JF Aga Y S YS de Bakker M M Akkerhuis K M KM Geleijnse M M Brugts J J JJ Sorop O O de Boer R A RA Rizopoulos D D Asselbergs F W FW Boersma E E den Ruijter H H van Dalen B M BM Kardys I I

European heart journal. Cardiovascular Imaging 20240801 9

<h4>Aims</h4>Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into heart failure pathophysiology. We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters as well as with elevated left atrial pressure (LAP), in patients with HFrEF, to pro ...[more]

PMID: 38597740

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Project description:BackgroundLeft atrial (LA) and ventricular (LV) functional impairment often co-exist in patients with heart failure (HF). However, some patients with HF have a disproportionate LA or LV dysfunction. We aimed to characterize patients with predominant LA and LV myopathy in a cohort of patients with chronic HF across the spectrum of LV ejection fraction (LVEF).MethodsFrom a nationwide, prospective, multi-center, observational HF cohort, transthoracic echocardiographic examination was performed on each patient. LA reservoir strain and LV global longitudinal strain (LVGLS) were measured using dedicated software of the two-dimensional speckle tracking analysis to evaluate LA and LV function and to define the myopathy.ResultsA total of 374 patients with chronic HF (mean age 58.9±11.5 years, 20% female, mean LVEF 39±17%) were included. By calculating the residuals from the linear regression between LA reservoir and LVGLS, we identified 47 patients with predominant LA myopathy, 271 patients with balanced LA/LV and 56 patients with predominant LV myopathy. Patients with predominant LA myopathy were older, had a higher prevalence of atrial fibrillation (AF), diabetes, higher plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), Growth differential factor 15(GDF15), high sensitivity Troponin T (hs-TNT) as well as more dilated left and right atria, and worse right atrial function compared to other groups (all p-values < 0.05). Using multivariable logistic regression adjusted for LVEF and LA size, independent predictors of predominant LA myopathy were the presence of AF, diabetes, and higher GDF15, whereas absence of diabetes independently predicted predominant LV myopathy. Patients with predominant LA myopathy group had a lower probability of survival than the other groups (Log rank p-value = 0.01).ConclusionWhile most patients with HF have balanced LA/LV myopathy, those with predominant LA myopathy are characterized by older age, more AF, more diabetes, higher circulating biomarkers of cardiac stress and injury, and worse outcomes.

Project description:This study aimed to investigate the functional correlate, clinical relevance, and prognostic implications of novel left ventricular (LV) deformations in patients with atrial fibrillation (AF). LV deformational indices, including peak global longitudinal strain (GLS), systolic strain rates (SRs), and early diastolic strain rates (SRe) were measured in a large-scale AF population. We related such measures to key clinical heart failure (HF) markers, conventional echocardiographic ventricular parameters, and clinical outcomes. Among 1483 subjects with newly diagnosed AF (mean age, 71.6 ± 12.4 years; 55.5% male), worsened GLS (mean, - 12.6 ± 3.9%) and strain rates (SRs and SRe: mean, - 0.86 ± 0.27 and 1.25 ± 0.41 1/s, respectively) by our three-beat measures were independently correlated with higher C-reactive protein, N-terminal pro-B-type natriuretic peptide, higher E/e', more impaired LV ejection fraction (LVEF < 50%), lower estimated glomerular filtration rate, permanent AF, and prevalent HF (all P < 0.05). LV deformations by three-beat analysis well correlated with the respective results of traditional methods. Abnormal GLS (>- 14.7%) was common in our cohort (67.8%) despite an averaged preserved LVEF (58.4 ± 14.2%), with worse GLS and SRe being associated with higher composite HF re-admissions/death during the 2.9 year follow-up (inter-quartile range, 1.6-4.1 years) in multivariate models incorporating key LV indices (LVEF, LV mass index, and E/e') (all P < 0.001). Sensitivity analysis by excluding those with regional wall motion abnormality showed broadly similar findings. An improved risk reclassification was observed when GLS and SRe were separately added to the LVEF. Comparison of the AF cohort with a fully matched independent non-AF cohort at the same baseline LVEF level showed a substantially lower GLS [- 13.2 ± 3.8% (AF) vs. 18.1 ± 3.2% (non-AF)] and higher clinical events rate (hazard ratio, 1.41 [95% confidence interval, 1.14-1.75]; log-rank P = 0.002) in the AF cohort. Impaired LV function defined by myocardial deformation was common in patients with AF and provides independent prognostic values over conventional measures with improved risk prediction. Our data highlight the need for implementing cardiac deformations in daily practice for patients with AF.

Project description:AimsTwo key echocardiographic parameters that are currently used to diagnose heart failure (HF) with preserved ejection fraction (HFpEF) are left atrial volume index (LAVi) and left ventricular mass index (LVMi). We investigated whether patients' characteristics, biomarkers, and co-morbidities are associated with these parameters and whether the relationships differ between patients with HFpEF or HF with reduced ejection fraction (HFrEF).MethodsWe consecutively enrolled 831 outpatients with typical signs and symptoms of HF and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels and categorized patients based upon left ventricular ejection fraction (LVEF): LVEF < 40% (HFrEF), LVEF between 40% and 50% (HF with mid-range ejection fraction), and LVEF ≥ 50% (HFpEF). The study includes consecutively enrolled HF patients from an HF outpatient clinic at a tertiary medical centre in the Netherlands. All patients underwent baseline characterization, laboratory measurements, and echocardiography.ResultsFour hundred sixty-nine patients had HFrEF, 189 HF with mid-range ejection fraction, and 173 HFpEF. The patients with HFrEF were rather male [HFrEF: 323 (69%); HFpEF: 80 (46%); P < 0.001], and the age was comparable (HFrEF 67 ± 13; HFpEF 70 ± 14; P = 0.069). In HFpEF, more patients had hypertension [190 (40.5%); 114 (65.9%); P < 0.001], higher body mass indices (27 ± 8; 30 ± 7; P < 0.001), and atrial fibrillation [194 (41.4); 86 (49.7); P = 0.029]. The correlation analyses showed that in HFrEF patients, LAVi was significantly associated with age (β 0.293; P < 0.001), male gender (β 0.104; P = 0.042), body mass index (β -0160; P = 0.002), diastolic blood pressure (β -0.136; P < 0.001), New York Heart Association (β 0.174; P = 0.001), atrial fibrillation (β 0.381; P < 0.001), galectin 3 (β 0.230; P < 0.001), NT-proBNP (β 0.183; P < 0.001), estimated glomerular filtration rate (β -0.205; P < 0.001), LVEF (β -0.173; P = 0.001), and LVMi (β 0.337; P < 0.001). In HFpEF patients, only age (β 0.326; P < 0.001), atrial fibrillation (β 0.386; P < 0.001), NT-proBNP (β 0.176; P = 0.036), and LVMi (β 0.213; P = 0.013) were associated with LAVi.ConclusionsAlthough LVMi and LAVi are hallmark parameters to diagnose HFpEF, they only correlate with a few characteristics of HF and mainly with atrial fibrillation. In contrast, in HFrEF patients, LAVi relates strongly to several other HF parameters. These findings underscore the complexity in visualizing the pathophysiology of HFpEF and question the relation between cardiac structural remodeling and the impact of co-morbidities.

Project description:AimsIn a large proportion of heart failure with reduced ejection fraction (HFrEF) patients, echocardiographic estimation of left atrial pressure (LAP) is not possible when the ratio of the peak early left ventricular filling velocity over the late filling velocity (E/A ratio) is not available, which may occur due to several potential causes. Left atrial reservoir strain (LASr) is correlated with LV filling pressures and may serve as an alternative parameter in these patients. The aim of this study was to determine whether LASr can be used to estimate LAP in HFrEF patients in whom E/A ratio is not available.Methods and resultsEchocardiograms of chronic HFrEF patients were analysed and LASr was assessed with speckle tracking echocardiography. LAP was estimated using the current ASE/EACVI algorithm. Patients were divided into those in whom LAP could be estimated using this algorithm (LAPe) and into those in whom this was not possible because E/A ratio was not available (LAPne). We assessed the prognostic value of LASr on the primary endpoint (PEP), which comprised the composite of hospitalization for the management of acute or worsened HF, left ventricular assist device implantation, cardiac transplantation, and cardiovascular death, whichever occurred first in time. We studied 153 patients with a mean age of 58 years of whom 76% men and 82% who were in NYHA class I-II. A total of 86 were in the LAPe group and 67 in the LAPne group. LASr was significantly lower in the LAPne group as compared with the LAPe group (15.8% vs. 23.8%, P < 0.001). PEP-free survival at a median follow-up of 2.5 years was 78% in LAPe versus 51% in LAPne patients. An increase in LASr was significantly associated with a reduced risk of the PEP in LAPne patients (adjusted hazard ratio: 0.91 per %, 95% confidence interval 0.84-0.98). An abnormal LASr (<18%) was associated with a five-fold increase in reaching the PEP.ConclusionsIn HFrEF patients in whom echocardiographic estimation of LAP is not possible due to due to unavailability of E/A ratio, assessing LASr potentially carries added clinical and prognostic value.

Project description:AimsAtrial fibrillation (AF) increases the risk of heart failure (HF); however, little focus has been placed on the prevention of HF in patients with AF. Left ventricular ejection fraction (LVEF) is an established echocardiographic parameter in HF patients. We sought to investigate the association of LVEF with HF events in AF patients without pre-existing HF.Methods and resultsThe Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Japan. In this analysis, we excluded patients with pre-existing HF (defined as having one of the following: prior HF hospitalization, New York Heart Association class ≥ 2 in association with heart disease, or LVEF < 40%). Among 3233 AF patients without pre-existing HF, we investigated 2459 patients with the data of LVEF at enrolment. We divided the patients into three groups stratified by LVEF [mildly reduced LVEF (40-49%), below normal LVEF (50-59%), and normal LVEF (≥60%)] and compared the backgrounds and incidence of HF hospitalization between the groups. Of 2459 patients [mean age: 72.4 ± 10.5 years, female: 917 (37%), paroxysmal AF: 1405 (57%), and mean CHA2 DS2 -VASc score: 3.0 ± 1.6], the mean LVEF was 66 ± 8% [mildly reduced LVEF: 114 patients (5%), below normal LVEF: 300 patients (12%), and normal LVEF: 2045 patients (83%)]. Patients with lower LVEF demonstrated lower prevalence of female and paroxysmal AF (both P < 0.01), but age and CHA2 DS2 -VASc score were comparable between the three groups (both P > 0.05). During the median follow-up period of 6.0 years, 255 patients (10%) were hospitalized for HF (annual incidence: 1.9% per person-year). Multivariable Cox regression analysis demonstrated that lower LVEF strata were independently associated with the risk of HF [mildly reduced LVEF (40-49%): hazard ratio = 2.98, 95% confidence interval = 1.99-4.45 and below normal LVEF (50-59%): hazard ratio = 2.01, 95% confidence interval = 1.44-2.82, compared with normal LVEF (≥60%)] after adjustment by age, sex, type of AF, and CHA2 DS2 -VASc score. LVEF < 60% was significantly associated with the higher risk of HF hospitalization across all major subgroups without significant interaction (P for interaction; all P > 0.05). LVEF had an independent and incremental prognostic value for HF hospitalization in addition to natriuretic peptide levels in AF patients without pre-existing HF.ConclusionsLower LVEF was significantly associated with the higher incidence of HF hospitalization in AF patients without pre-existing HF, leading to the future risk stratification for and prevention of incident HF in AF patients.

Dataset Information

The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure.

Aims

Methods and results

Conclusion

Publications

The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure.

Similar Datasets

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