Clinical evaluation of heart failure patients: what good are biomarkers bringing us?
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ABSTRACT:
SUBMITTER: de Boer RA
PROVIDER: S-EPMC3931850 | biostudies-literature | 2014 Mar
REPOSITORIES: biostudies-literature
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Clinical evaluation of heart failure patients: what good are biomarkers bringing us?
Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 20140301 3
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Project description:Cardiovascular inflammation and vascular endothelial dysfunction are involved in chronic heart failure (CHF), and cellular adhesion molecules are considered to play a key role in these mechanisms. We evaluated temporal patterns of 12 blood biomarkers of cell adhesion in patients with CHF. In 263 ambulant patients, serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (1.4-2.5) years. The primary endpoint (PE) was a composite of cardiovascular mortality, HF hospitalization, heart transplantation and implantation of a left ventricular assist device and was reached in 70 patients. We selected the baseline blood samples in all patients, the two samples closest to a PE, or, for event-free patients, the last sample available. In these 567 samples, associations between biomarkers and PE were investigated by joint modelling. The median age was 68 (59-76) years, with 72% men and 74% New York Heart Association class I-II. Repeatedly measured levels of Complement component C1q receptor (C1qR), Cadherin 5 (CDH5), Chitinase-3-like protein 1 (CHI3L1), Ephrin type-B receptor 4 (EPHB4), Intercellular adhesion molecule-2 (ICAM-2) and Junctional adhesion molecule A (JAM-A) were independently associated with the PE. Their rates of change also predicted clinical outcome. Level of CHI3L1 was numerically the strongest predictor with a hazard ratio (HR) (95% confidence interval) of 2.27 (1.66-3.16) per SD difference in level, followed by JAM-A (2.10, 1.42-3.23) and C1qR (1.90, 1.36-2.72), adjusted for clinical characteristics. In conclusion, temporal patterns of C1qR, CDH5, CHI3L1, EPHB4, ICAM2 and JAM-A are strongly and independently associated with clinical outcome in CHF patients.
| S-EPMC7020068 | biostudies-literature
Project description:Methods commonly used clinically to assess cardiac function in patients with heart failure include ejection fraction (EF), exercise treadmill testing (ETT), and symptom evaluation. Although these approaches are useful in evaluating patients with heart failure, there are at times substantial mismatches between individual assessments. For example, ETT results are often discordant with EF, and patients with minimal symptoms sometimes have surprisingly low EFs. To better define the relationship of these methods of assessment, we studied 56 patients with heart failure with reduced EF (HFrEF) who underwent measurement of ETT duration, EF by echocardiography, quantitative symptom evaluation, and LV peak dP/dt (rate of left ventricular pressure development and decline, measured invasively). Correlations were determined among these four tests in order to assess the relationship of EF, ETT, and symptoms against LV peak dP/dt. In addition, we sought to determine whether EF, ETT, and symptoms correlated with each other. Overall, correlations were poor. Only 15 of 63 total correlations (24%) were significant (p < 0.05). EF correlated most closely with LV peak -dP/dt. Linear regression analysis indicated that EF, ETT, and symptoms taken together predicted LV peak dP/dt better than any one measure alone. We conclude that clinical tests used to assess LV function in patients with HFrEF may not be as accurate or correlate as well as expected. All three clinical measures considered together may be the best representation of cardiac function in HFrEF patients currently available.
| S-EPMC4990285 | biostudies-literature
Project description:We hypothesized that patients with heart failure (HF) who recover left ventricular function (HF-Recovered) have a distinct clinical phenotype, biology, and prognosis compared with patients with HF with reduced ejection fraction (HF-REF) and those with HF with preserved ejection fraction (HF-PEF).The Penn Heart Failure Study (PHFS) is a prospective cohort of 1821 chronic HF patients recruited from tertiary HF clinics. Participants were divided into 3 categories based on echocardiograms: HF-REF if EF was <50%, HF-PEF if EF was consistently ?50%, and HF-Recovered if EF on enrollment in PHFS was ?50% but prior EF was <50%. A significant portion of HF-Recovered patients had an abnormal biomarker profile at baseline, including 44% with detectable troponin I, although in comparison, median levels of brain natriuretic factor, soluble fms-like tyrosine kinase receptor-1, troponin I, and creatinine were greater in HF-REF and HF-PEF patients. In unadjusted Cox models over a maximum follow-up of 8.9 years, the hazard ratio for death, transplantation, or ventricular assist device placement in HF-REF patients was 4.1 (95% confidence interval, 2.4-6.8; P<0.001) and in HF-PEF patients was 2.3 (95% confidence interval, 1.2-4.5; P=0.013) compared with HF-Recovered patients. The unadjusted hazard ratio for cardiac hospitalization in HF-REF patients was 2.0 (95% confidence interval, 1.5-2.7; P<0.001) and in HF-PEF patients was 1.3 (95% confidence interval, 0.90-2.0; P=0.15) compared with HF-Recovered patients. Results were similar in adjusted models.HF-Recovered is associated with a better biomarker profile and event-free survival than HF-REF and HF-PEF. However, these patients still have abnormalities in biomarkers and experience a significant number of HF hospitalizations, suggesting persistent HF risk.
| S-EPMC4053508 | biostudies-literature
Project description:IntroductionHeart failure (HF) is a complex clinical syndrome with diverse risk factors and etiologies, differing underlying pathophysiology, and large phenotypic heterogeneity.Recent findingsAdvances in imaging techniques coupled with clinical trials that targeted only in those with impaired left ventricular ejection fraction (LVEF) have largely shaped the current management strategy for HF that focuses predominantly in patients with systolic HF. In contrast, there are no effective treatments for HF with preserved ejection fraction (HFpEF). Instead of this "one-size-fits-all" approach to treatment, better precision to define HF phenotypic classifications may lead to more efficient and effective HF disease management.ConclusionIntegrating variables-including clinical variables, HF biomarkers, imaging, genotypes, metabolomics, and proteomics-can identify different pathophysiologies, lead to more precise phenotypic classification, and warrant investigation in future clinical trials.
| S-EPMC5357587 | biostudies-literature
Project description:BACKGROUND:The wearable cardioverter defibrillator (WCD) records electrocardiograms and cardiohemic vibrations that can be algorithmically combined to provide cardiac acoustic biomarkers (CABs). We characterized CAB variability, diurnal variations, and changes over time among heart failure patients. METHODS:Wearable cardioverter defibrillator heart failure patients who had CAB recordings from March 2015 to July 2017 were included. CAB parameters included: electromechanical activation time (EMAT), EMATc (EMAT/RR interval), left ventricular systolic time (LVST), LVSTc (LVST/RR interval), S3 and S4 strengths, and systolic dysfunction index (SDI). Descriptive statistics, correlation analysis, and analysis of variance were used to report temporal and clinical associations. RESULTS:One thousand and sixty-six WCD patients met the study criteria. Diastolic CAB parameters showed significantly greater intra-subject variability than systolic CAB parameters (>29% vs. <15%, p < .01). CAB parameters varied very little with age, gender, and ejection fraction (R2 = 0.004 to 0.06) in this heart failure population. Similarly, all CABs except SDI (R2 = 0.58) were independent of QRS duration, (R2 = -0.01 to 0.58). Heart rate had a more of significant influence on the systolic CABs than the diastolic CABs (p < .05). CABs were significantly different when measured at daytime versus nighttime (p < .01) and were significantly lower at the end of WCD wear compared with the beginning of wear (p < .05). CONCLUSIONS:Noninvasive CABs offer the possibility to assess parameters associated with LV function, clinical status, and other aspects of cardiovascular physiology that differ between normal and heart failure states. The present study provides critical information about typical values in heart failure patients, intra-subject variability, circadian rhythms, and changes over time of these parameters.
| S-EPMC7358835 | biostudies-literature
Project description:Background The significant morbidity associated with systolic heart failure makes it imperative to identify patients with a reversible cause. We thus sought to evaluate the proportion of patients who received an ischemic evaluation after a hospitalization for new-onset systolic heart failure. Methods and Results Patients admitted with a new diagnosis of heart failure and a reduction in left ventricular ejection fraction (≤40%) were identified in the VA Healthcare System from January 2006 to August 2017. Among those who survived 90 days without a readmission, we evaluated the proportion of patients who underwent an ischemic evaluation. We identified 9625 patients who were admitted with a new diagnosis of systolic heart failure with a concomitant reduction in ejection fraction. A minority of patients (3859, 40%) underwent an ischemic evaluation, with significant variation across high-performing (90th percentile) and low-performing (10th percentile) sites (odds ratio, 3.79; 95% CI, 2.90-4.31). Patients who underwent an evaluation were more likely to be treated with angiotensin-converting enzyme inhibitors (75% versus 64%, P<0.001) or beta blockers (92% versus 82%, P<0.001) and subsequently undergo percutaneous (8% versus 0%, P<0.001) or surgical (2% versus 0%, P<0.001) revascularization. Patients with an ischemic evaluation also had a significantly lower adjusted hazard of all-cause mortality (hazard ratio, 0.54; 95% CI, 0.47-0.61) compared with those without an evaluation. Conclusions Ischemic evaluations are underutilized in patients admitted with heart failure and a new reduction in left ventricular systolic function. A focused intervention to increase guideline-concordant care could lead to an improvement in clinical outcomes.
| S-EPMC8174286 | biostudies-literature
Project description:AimsThe importance of true worsening renal failure (WRF), which is associated with a poor prognosis, had been suggested in patients with acute heart failure (AHF). The aim of the present study was to establish the biomarker strategy for the prediction of true WRF in AHF.Methods and resultsTwo hundred eighty-one patients with AHF were analysed. Their biomarkers were measured within 30 min of admission. Patients were assigned to the non-WRF (n = 168), pseudo-WRF (n = 56), or true-WRF (n = 57) groups using the criteria of both acute kidney injury on admission and increasing serum creatinine value during the first 7 days. A Kaplan-Meier curve showed that the survival and heart failure event rate of the true-WRF group within 1000 days was significantly lower than that of the non-WRF and pseudo-WRF groups (P ≤ 0.001). The multivariate Cox regression model also indicated that true WRF was an independent predictor of 1000 day mortality and heart failure events [hazard ratio: 4.315, 95% confidence interval (CI): 2.466-7.550, P ≤ 0.001, and hazard ratio: 2.834, 95% CI: 1.893-4.243, P ≤ 0.001, respectively]. The serum heart-type fatty acid-binding protein (s-HFABP) levels were significantly higher in the true-WRF group than in the non-WRF and pseudo-WRF groups (P ≤ 0.001). The multivariate logistic regression model indicated that the predictive biomarker for the true-WRF group was the s-HFABP level (odds ratio: 5.472, 95% CI: 2.729-10.972, P ≤ 0.001). The sensitivity and specificity for indicating the presence of true WRF were 73.7% and 76.8% (area under the curve = 0.831) for s-HFABP in whole patients, respectively, and 94.7% and 72.7% (area under the curve = 0.904) in non-chronic kidney disease (CKD) patients, respectively.ConclusionsCardiac biomarkers, especially the s-HFABP, might predict the development of true WRF in AHF patients. Furthermore, the predictive value was higher in AHF patients without CKD than in those with CKD.
| S-EPMC6437438 | biostudies-literature
Project description:AimsBiomarkers can be used for diagnosis, risk stratification, or management of patients with heart failure (HF). Knowledge about the biological variation is needed for proper interpretation of serial measurements. Therefore, we aimed to determine and compare the biological variation of a large panel of biomarkers in healthy subjects and in patients with chronic HF.Methods and resultsThe biological variability of established biomarkers [NT-proBNP and high-sensitivity troponin T (hsTnT)], novel biomarkers [galectin-3, suppression of tumorigenicity 2 (ST2), and growth differentiation factor 15 (GDF-15)], and renal/neurohormonal biomarkers (aldosterone, phosphate, parathyroid hormone, plasma renin concentration, and creatinine) was determined in 28 healthy subjects and 83 HF patients, over a period of 4 months and 6 weeks, respectively. The analytical (CVa ), intraindividual (CVi ), and interindividual (CVg ) variations were calculated, as well as the reference change value (RCV), which reflects the percentage of change that may indicate a 'relevant' change. All crude biomarker levels were significantly increased or decreased in HF patients compared with controls (all P < 0.01). Variation indices were comparable in healthy individuals and HF patients. CVi was not influenced by the individual levels of the biomarker itself. NT-proBNP and GDF-15 had relatively high CVi (21.8% and 16.6%) and RCV (61.7% and 64.3%), whereas ST2 (CVi , 15.0; RCV, 42.9%), hsTnT (CVi , 11.1; RCV, 31.4%), and galectin-3 (CVi , 8.1; RCV, 25.0%) had lower indices of variation.ConclusionBiological variation indices are comparable between healthy subjects and HF patients for a broad spectrum of biomarkers. NT-proBNP and GDF-15 have substantial variation, with lower variation for ST2, hsTnT, and galectin-3. These data are instrumental in proper interpretation of biomarker levels in HF patients.
| S-EPMC5347881 | biostudies-literature
Project description:The aim of our observational study was to derive a small set out of 92 repeatedly measured biomarkers with optimal predictive capacity for adverse clinical events in heart failure, which could be used for dynamic, individual risk assessment in clinical practice. In 250 chronic HFrEF (CHF) patients, we collected trimonthly blood samples during a median of 2.2 years. We selected 537 samples for repeated measurement of 92 biomarkers with the Cardiovascular Panel III (Olink Proteomics AB). We applied Least Absolute Shrinkage and Selection Operator (LASSO) penalization to select the optimal set of predictors of the primary endpoint (PE). The association between repeatedly measured levels of selected biomarkers and the PE was evaluated by multivariable joint models (mvJM) with stratified fivefold cross validation of the area under the curve (cvAUC). The PE occurred in 66(27%) patients. The optimal set of biomarkers selected by LASSO included 9 proteins: NT-proBNP, ST2, vWF, FABP4, IGFBP-1, PAI-1, PON-3, transferrin receptor protein-1, and chitotriosidase-1, that yielded a cvAUC of 0.88, outperforming the discriminative ability of models consisting of standard biomarkers (NT-proBNP, hs-TnT, eGFR clinically adjusted) - 0.82 and performing equally well as an extended literature-based set of acknowledged biomarkers (NT-proBNP, hs-TnT, hs-CRP, GDF-15, ST2, PAI-1, Galectin 3) - 0.88. Nine out of 92 serially measured circulating proteins provided a multivariable model for adverse clinical events in CHF patients with high discriminative ability. These proteins reflect wall stress, remodelling, endothelial dysfunction, iron deficiency, haemostasis/fibrinolysis and innate immunity activation. A panel containing these proteins could contribute to dynamic, personalized risk assessment.Clinical Trial Registration: 10/05/2013 https://clinicaltrials.gov/ct2/show/NCT01851538?term=nCT01851538&draw=2&rank=1 .
| S-EPMC8857321 | biostudies-literature
Project description:Natriuretic peptides (NP) are well-validated aids in the diagnosis of acute decompensated heart failure (ADHF). In acute presentations, both brain natriuretic peptide (BNP) and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) offer high sensitivity (>90 %) and negative predictive values (>95 %) for ruling out ADHF at thresholds of 100 and 300 pg/ml, respectively. Plasma NP rise with age. For added rule-in performance age-adjusted thresholds (450 pg/ml for under 50 years, 900 pg/ml for 50-75 years and 1,800 pg/ml for those >75 years) can be applied to NT-proBNP results. Test performance (specificity and accuracy but not sensitivity) is clearly reduced by renal dysfunction and atrial fibrillation. Obesity offsets the threshold downwards (to ~50 pg/ml for BNP), but overall discrimination is preserved. Reliable markers for impending acute kidney injury in ADHF constitute an unmet need, with candidates, such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, failing to perform sufficiently well, and new possibilities, including the cell cycle markers insulin growth factor binding protein 7 and tissue inhibitor of metalloproteinases type 2, remain the subject of research.
| S-EPMC5490877 | biostudies-other