Comparative role of hematological indices for the assessment of in-hospital outcome of heart failure patients.

Background. The mutual relation between heart failure (HF) and inflammation is reflected in blood cell homeostasis. Neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR) and platelet-lymphocyte ratio (PLR) were linked to HF severity and prognosis. Aims. Our objective was to compare the three ratios for predicting in-hospital outcome of HF patients, in order to establish which is best suited for clinical practice. Methods. Consecutive HF patients admitted to a Cardiology Department from a tertiary hospital were retrospectively evaluated for inclusion. Readmissions and pathologies modifying the hematological indices were excluded. Extended length of hospital stay (LOS) was considered over 7 d. In-hospital all-cause mortality was evaluated. Results: The hematological indices in heart failure (HI-HF) cohort included 1299 patients with a mean age of 72.35 ± 10.45 years, 51.96% women. 2.85% died during hospitalization. 22.17% had extended LOS. In Cox regression for in-hospital mortality alongside parameters from the OPTIMIZE-HF proposed model, all three ratios were independent predictors of mortality. In Cox regression including NT-proBNP, dyspnea at rest, chronic obstructive pulmonary disease (COPD), age and systolic blood pressure, only MLR was an independent predictor of in-hospital mortality (HR 1.68, 95% CI 1.22 - 2.32, p = .002). In multivariable logistic regression, all three ratios independently predicted extended LOS. MLR > 0.48 associated the highest probability (OR 1.76, 95% CI 1.25 - 2.46, p = .001). Conclusions. Hematological indices could be cost-effective and easily available auxiliary biomarkers for in-hospital prognosis of HF patients. We propose MLR > 0.48 as the strongest predictor of in-hospital mortality and prolonged hospitalization.

Prognostic value of the modified model for end-stage liver disease (MELD) score including albumin in acute heart failure.

BACKGROUND: Liver and renal function evaluated by the model for end-stage liver disease (MELD) score, the MELD excluding the international normalized ratio (MELD_XI) score and the MELD including sodium (MELD_sodium) score have been considered predictors of adverse events for patients with acute heart failure (AHF). However, the prognostic value of the MELD including albumin (MELD_albumin) score in patients with AHF has not been assessed. METHODS: A total of 466 patients with AHF were prospectively evaluated. We compared the accuracy of the 4 MELD score formulas using the time-dependent receiver operating characteristic (ROC) curve and corresponding areas under the curve (AUC). RESULTS: During a median follow-up period of 34 months, 196 deaths occurred. In the fully adjusted Cox regression model, standardized hazard ratios with 95% confidence interval expressing the risk of all-cause mortality were 1.22 (1.06-1.40), 1.20 (1.04-1.39), 1.23 (1.06-1.42) and 1.21 (1.05-1.41) for MELD, MELD_XI, MELD_sodium and MELD_albumin scores, respectively. The MELD_albumin score showed the best prognostic accuracy (AUC = 0.658) for the prediction of long-term all-cause mortality, followed by the MELD_sodium score (AUC = 0.590), the MELD score (AUC = 0.580), and the MELD_XI score (AUC = 0.544); the MELD_albumin score performs significantly more accurate than MELD and MELD_XI score for predicting the risk of all-cause mortality. Considering reclassification, MELD_albumin score increased the net reclassification improvement over and beyond MELD (13.1%, P = 0.003), MELD_XI (14.8%, P = 0.002), and MELD_sodium (11.9%, P = 0.006) scores for all-cause mortality. CONCLUSIONS: The MELD_albumin score increases risk stratification of all-cause mortality over and beyond the MELD score and the other modified MELD scores in patients with acute heart failure.

Economic Evaluation of an N-terminal Pro B-type Natriuretic Peptide-Supported Diagnostic Strategy Among Dyspneic Patients Suspected of Acute Heart Failure in the Emergency Department.

Our objective was to perform an economic evaluation of an N-terminal pro B-type natriuretic peptide (NT-proBNP)-supported diagnostic strategy in dyspneic patients suspected of acute heart failure in the emergency department (ED). A decision-tree model was developed to evaluate clinical outcomes and costs for NT-proBNP-supported assessment compared with clinical assessment alone over 6 months from the United States (US) Medicare perspective. The model considered rule-in/rule-out cutoffs identified in the ICON and ICON-RELOADED studies. Acute heart failure prevalence, diagnostic accuracies, and medical resource use conditional on disease status and test results were derived from ICON-RELOADED. Several assumptions based on previous studies of NT-proBNP acute dyspnea and verified with clinicians were applied to medical resource use and assessed in sensitivity analyses. Compared with clinical assessment alone, NT-proBNP-supported assessment improved overall probability of correct diagnosis by a relative 7% (18% for true-positive and 5% for true-negative). This led to relative reductions in medical resource use in ED and hospital, including fewer initial hospitalizations (-14%), required echocardiograms (-31%), cardiology admissions (-16%), intensive care unit admissions (-12%), ED readmissions (-3%), and hospital readmissions (-22%). NT-proBNP use decreased average inpatient management costs by a relative 10%, yielding cost savings of US$2,337 per patient ED visit. These findings were robust in sensitivity analyses. In conclusion, based on a contemporary trial of patients with acute dyspnea, this analysis reaffirmed that using NT-proBNP as a diagnostic tool may improve the management of patients with dyspnea presenting to EDs and is likely to be cost-saving from the US Medicare perspective.

Cardiac Graft Assessment in the Era of Machine Perfusion: Current and Future Biomarkers.

Heart transplantation remains the treatment of reference for patients experiencing end-stage heart failure; unfortunately, graft availability through conventional donation after brain death is insufficient to meet the demand. Use of extended-criteria donors or donation after circulatory death has emerged to increase organ availability; however, clinical protocols require optimization to limit or prevent damage in hearts possessing greater susceptibility to injury than conventional grafts. The emergence of cardiac ex situ machine perfusion not only facilitates the use of extended-criteria donor and donation after circulatory death hearts through the avoidance of potentially damaging ischemia during graft storage and transport, it also opens the door to multiple opportunities for more sensitive monitoring of graft quality. With this review, we aim to bring together the current knowledge of biomarkers that hold particular promise for cardiac graft evaluation to improve precision and reliability in the identification of hearts for transplantation, thereby facilitating the safe increase in graft availability. Information about the utility of potential biomarkers was categorized into 5 themes: (1) functional, (2) metabolic, (3) hormone/prohormone, (4) cellular damage/death, and (5) inflammatory markers. Several promising biomarkers are identified, and recommendations for potential improvements to current clinical protocols are provided.

[Impact of the COVID-19 pandemic on the management of heart failure outpatient clinics. Lessons during the lockdown restrictions]. / Le ricadute della pandemia COVID-19 sulla gestione dell'Ambulatorio Scompenso. Esperienze e considerazioni operative dopo il lockdown.

BACKGROUND: During the COVID-19 pandemic, non-urgent outpatient activities were temporarily suspended. The aim of this study was to assess the impact of this measure on the management of the heart failure outpatient clinic at our institution. METHODS: We analyzed the clinical outcome of 110 chronic heart failure patients (mean age 73 ± 9 years) whose follow-up visit had been delayed. RESULTS: At their last visit before the lockdown, 80.9% was in NYHA class II, had an ejection fraction of 37 ± 7%, and B-type natriuretic peptide level was moderately elevated (266 ± 138 pg/ml). All patients received loop diuretics, 97.2% beta-blockers, 64.9% an aldosterone antagonist, 60.9% sacubitril/valsartan (S/V), and 72.2% of the remaining patients were on angiotensin-converting enzyme inhibitor or valsartan therapy. Patients were contacted by phone during and at the end of the lockdown period to fix a new appointment and underwent a structured interview to assess their clinical conditions and ongoing therapy and to verify whether they had contracted SARS-CoV-2 infection. Twelve patients (13.2%) contracted COVID-19. None was hospitalized for worsening heart failure or reported defibrillator shocks and none changed autonomously the prescribed therapy. Overall, 75% of patients reported stable or improved general well-being from the last in-person visit, while 25% described subjective worsening due to the social effect of the pandemic. Unchanged body weight and blood pressure values were reported by 86% and 78.4% of patients, respectively. Lower blood pressure values compared to baseline were recorded in 15.2% of patients on conventional renin-angiotensin system inhibition vs 21% of those on S/V, one of whom had to down-titrate S/V for persistent but asymptomatic hypotension; 4 patients up-titrated S/V to 200 mg/day following phone indications. CONCLUSIONS: Cancellation of scheduled follow-up visits during 3 months did not have significant negative effects in a cohort of stable patients with chronic heart failure on optimized medical therapy. Telephone support was effective in keeping connections with the patients during the lockdown, allowing appropriate management and implementation of drug therapy. In particular, patients who received S/V were not affected by delays in scheduled visits, confirming the tolerability and safety of this novel therapy in terms of both clinical and biohumoral parameters.

Galectins for Diagnosis and Prognostic Assessment of Human Diseases: An Overview of Meta-Analyses.

An increasing number of studies have explored the activities and functions of galectins. However, translation of these researches into clinical practice seems to be lacking. As compared to scattered individual studies, meta-analyses can provide a more comprehensive review of current evidence and reach a more unbiased and powered conclusion by synthesizing data from diverse studies. In this paper, findings from meta-analyses were reviewed to establish the role of galectins in diagnosis and prognostic assessment of various human diseases. First, in patients with cancer, galectin-1 expression is often associated with poorer survival, but galectin-9 expression is associated with better survival. Galectin-3 is a diagnostic biomarker for thyroid cancer and a predictor of worse survival in patients with colorectal cancer and improved survival in patients with gastric cancer. Second, galectin-3 is useful for diagnosis and prognostic assessment of heart failure and prediction of atrial fibrillation and its recurrence. Third, in chronic kidney disease, galectin-3 is valuable for predicting poor survival. Fourth, during pregnancy, galectin-13 is potentially helpful for identifying patients who do not have preeclampsia.

Noninvasive Assessment of Cardiac Output: Accuracy and Precision of the Closed-Circuit Acetylene Rebreathing Technique for Cardiac Output Measurement.

Background Accurate assessment of cardiac output is critical to the diagnosis and management of various cardiac disease states; however, clinical standards of direct Fick and thermodilution are invasive. Noninvasive alternatives, such as closed-circuit acetylene (C2H2) rebreathing, warrant validation. Methods and Results We analyzed 10 clinical studies and all available cardiopulmonary stress tests performed in our laboratory that included a rebreathing method and direct Fick or thermodilution. Studies included healthy individuals and patients with clinical disease. Simultaneous cardiac output measurements were obtained under normovolemic, hypovolemic, and hypervolemic conditions, along with submaximal and maximal exercise. A total of 3198 measurements in 519 patients were analyzed (mean age, 59 years; 48% women). The C2H2 method was more precise than thermodilution in healthy individuals with half the typical error (TE; 0.34 L/min [r=0.92] and coefficient of variation, 7.2%) versus thermodilution (TE=0.67 [r=0.70] and coefficient of variation, 13.2%). In healthy individuals during supine rest and upright exercise, C2H2 correlated well with thermodilution (supine: r=0.84, TE=1.02; exercise: r=0.82, TE=2.36). In patients with clinical disease during supine rest, C2H2 correlated with thermodilution (r=0.85, TE=1.43). C2H2 was similar to thermodilution and nitrous oxide (N2O) rebreathing technique compared with Fick in healthy adults (C2H2 rest: r=0.85, TE=0.84; C2H2 exercise: r=0.87, TE=2.39; thermodilution rest: r=0.72, TE=1.11; thermodilution exercise: r=0.73, TE=2.87; N2O rest: r=0.82, TE=0.94; N2O exercise: r=0.84, TE=2.18). The accuracy of the C2H2 and N2O methods was excellent (r=0.99, TE=0.58). Conclusions The C2H2 rebreathing method is more precise than, and as accurate as, the thermodilution method in a variety of patients, with accuracy similar to an N2O rebreathing method approved by the US Food and Drug Administration.

Association of Cardiac Biomarkers With the Kansas City Cardiomyopathy Questionnaire in Patients With Chronic Kidney Disease Without Heart Failure.

Background The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF-15 (growth differentiation factor-15), galectin-3, sST2 (soluble suppression of tumorigenesis-2), hsTnT (high-sensitivity troponin T), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known. Methods and Results We studied participants with CKD without HF in the multicenter prospective CRIC (Chronic Renal Insufficiency Cohort) Study. Outcomes included (1) low KCCQ score <75 at year 1 and (2) incident decline in KCCQ score to <75. We used multivariable logistic regression and Cox regression models to evaluate the associations between baseline cardiac biomarkers and cross-sectional and longitudinal KCCQ scores. Among 2873 participants, GDF-15 (adjusted odds ratio 1.42 per SD; 99% CI, 1.19-1.68) and galectin-3 (1.28; 1.12-1.48) were significantly associated with KCCQ scores <75, whereas sST2, hsTnT, and NT-proBNP were not significantly associated with KCCQ scores <75 after multivariable adjustment. Of the 2132 participants with KCCQ ≥75 at year 1, GDF-15 (adjusted hazard ratio, 1.36 per SD; 99% CI, 1.12-1.65), hsTnT (1.20; 1.01-1.44), and NT-proBNP (1.30; 1.08-1.56) were associated with incident decline in KCCQ to <75 after multivariable adjustment, whereas galectin-3 and sST2 did not have significant associations with KCCQ decline. Conclusions Among participants with CKD without clinical HF, GDF-15, galectin-3, NT-proBNP, and hsTnT were associated with low KCCQ either at baseline or during follow-up. Our findings show that elevations in cardiac biomarkers reflect early symptomatic changes in HF health status in CKD patients.

Detection of B-type natriuretic peptide by establishing a low-cost and replicable fluorescence resonance energy transfer platform.

Aiming at the establishment of a sensitive and specific diagnostic method for early heart failure (HF), we developed a cost-effective fluorescence resonance energy transfer (FRET) platform for the detection of B-type natriuretic peptide (BNP), a characteristic biomarker of HF. Graphene oxide (GO) was selected as the FRET receptor in view of its advantages including commercial availability, low-cost and chemical stability, and dye-modified aptamer was used as the energy donor of FRET as well as in charge of the specific recognition of BNP. Based on the ON (strong emission) and OFF (quenching) states of FRET in the presence and absence of BNP, respectively, specific detection of BNP was achieved in the range 0.074-0.56 pg/mL with a limit of detection as low as 45 fg/mL (3σ). This FRET platform was applied to detect BNP in 45 blood samples to demonstrate its practicability in clinical diagnosis. Compared to the commonly used Siemens method (chemiluminescence immunoassay, CLIA) in hospital, our approach is more accurate and specific for HF diagnosis with areas under the receiver operating characteristic curves of 0.869 (95% CI 0.733-1.00, P < 0.05) vs 0.850 (95% CI 0.703-0.997, P < 0.05) and specificity of 68.8% vs 65.6%. This platform is promising in early diagnosis of HF through ultrasensitive and specific detection of BNP. Graphical abstract To solve the clinical diagnostic problem for early heart failure (HF) which lacks sensitivity and specificity, we established a cost-effective and rapid fluorescence analysis method based on fluorescence resonance energy transfer (FRET) platform for the detection of B-type natriuretic peptide (BNP), a characteristic biomarker of HF.

Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading.

Patients with heart failure (HF) and left ventricular assist devices (LVAD) have dysregulated thrombo-inflammatory responses, mediated in part by platelets. While studies of platelet activation have been undertaken in HF, changes in the platelet transcriptome in HF patients following mechanical unloading with an LVAD have not been investigated. We prospectively enrolled and longitudinally followed advanced HF patients (n = 32) for a mean of 57 months post-LVAD implantation. For comparison, healthy donors were also enrolled (n = 20). Platelets were hyperactive in HF, as evidenced by significantly increased formation of circulating platelet-monocyte aggregate formation. Platelet transcriptome interrogation by next-generation RNA-sequencing identified that the expression of numerous genes (n = 588) was significantly (FDR < 0.05) altered in HF patients prior to LVAD implantation. Differentially expressed genes were predicted to have roles in angiogenesis, immune and inflammatory responses, apoptosis, and cardiac muscle contraction. 90 days following LVAD implantation, the majority (80%) of differentially expressed genes in HF patients normalized, as compared to the platelet transcriptomes of healthy donors. In conclusion, advanced HF is associated with marked alterations in the platelet transcriptome. While LVAD implantation to off load the failing heart results in resolution in the majority of differentially expressed genes, a subset of the platelet transcriptome remains persistently altered.

Change in admission blood glucose from chronic glycemic status in acute heart failure hospitalization and 30-day outcomes: A retrospective analysis.

BACKGROUND: Admission blood glucose (BG) has demonstrated contradictory association with 30-day mortality in acute heart failure (AHF) hospitalization. To explore these contradictory findings, we aimed to determine if admission BG reflects an acute change from chronic glucose control and investigate the association between the admission and chronic BG change (ΔBG) with 30-day mortality in AHF. METHODS: We analyzed patients (n = 1045) age ≥ 65 with Centers of Medicare Services benefits and known 30-day all-cause mortality hospitalized with AHF at an academic medical center from 2009 to 2016. We included diabetic (n = 736) and non-diabetic (n = 309) patients with recent Hemoglobin A1c (HbA1c). We defined ΔBG as the difference in the admission and chronic BG, calculated from HbA1c. RESULTS: Admission BG was 126 (101, 167) mg/dl and was moderately elevated (≥170 mg/dl) in 25% of admissions. The median (IQR) ΔBG was -7 (-29, 26) mg/dl, with 74% of all admissions (66% diabetic, 92% non-diabetic) presenting within ±50 mg/dl of the chronic BG. Admission BG was not associated with mortality. ΔBG > +100 mg/dl displayed increased 30-day mortality (18.6% vs 6.9%, p < 0.001) compared to -26 to +25 mg/dl. When admission BG was >200 mg/dl (n = 166), a ΔBG > +100 mg/dl was present in 77% of those deceased vs 31% of those alive at 30 days (p = 0.003; positive likelihood ratio = 5.7). ΔBG > +100 mg/dl was strongly associated with 30-day mortality risk (OR 6.4, 95% CI 2.3-18.9; p = 0.0005) after multivariate adjustment. CONCLUSIONS: Admission BG predominantly reflects chronic glycemic status. Increased change in admission from chronic BG was associated with increased 30-day mortality.

Long-term statin persistence is poor among high-risk patients with dyslipidemia: a real-world administrative claims analysis.

BACKGROUND: A decade ago, statin persistence was < 50% after 1 year, and recent short-term analyses have revealed very little progress in improving statin persistence, even in patients with a prior cardiovascular (CV) event. Data on longer-term statin persistence are lacking. We measured long-term statin persistence in patients with high CV risk. METHODS: This retrospective administrative claims analysis of the Optum Research Database included patients aged ≥ 45 years with diabetes and/or atherosclerotic CV disease (ASCVD) who had a statin prescription filled in 2010. It included an elevated triglycerides (TG) cohort of patients with index date in 2010 and TG ≥ 150 mg/dL (n = 23,181) and a propensity-matched comparator cohort with TG < 150 mg/dL and high-density lipoprotein cholesterol > 40 mg/dL (n = 23,181). Both cohorts were followed for ≥ 6 months up to March 2016. RESULTS: The probability of remaining on a prescription fill for index statin therapy was 47% after 1 year and 19% after 5 years in both cohorts. Statin persistence was worse among women than men, and among younger versus older patients (P < 0.001 for all comparisons). After 5 years, the probability of remaining on a prescription fill for index statin was < 25% across all subgroups assessed including patients with and without baseline revascularization, heart failure, peripheral artery disease and renal disease. Similar results were observed in a subcohort analysis of patients with TG 200-499 mg/dL. CONCLUSIONS: Long-term statin persistence after 5 years is alarmingly low (< 25%) and is a public health concern.

Amino Acid-Based Metabolic Profile Provides Functional Assessment and Prognostic Value for Heart Failure Outpatients.

Functional capacity is a crucial parameter correlated with outcomes. The currently used New York Heart Association functional classification (NYHA Fc) system has substantial limitations, leading to inaccurate classification. This study investigated whether amino acid-based assessment on metabolic status provides an objective way to assess functional capacity and prognosis in heart failure (HF) outpatients. Plasma concentrations of histidine, ornithine, and phenylalanine (HOP) were measured on 890 HF outpatients to assess metabolic status by calculating the HOP score. Cardiopulmonary exercise testing (CPET) was performed in 387 patients to measure metabolic equivalents (MET) in order to define the functional class based on MET (MET Fc). Patients were followed for composite events (death/HF-related rehospitalization) up to one year. We found only 47% concordance between the MET Fc and NYHA Fc. HOP scores worked better than NYHA Fc for discriminating patients with MET Fc II and III from those with MET Fc I, with the optimal cutoff value set at 8.8. HOP scores ≥ 8.8 were associated with risk factors for composite events in different kinds of HF populations and were a powerful predictor of composite events in univariate analysis. In multivariable analysis, HOP scores ≥ 8.8 remained a powerful event predictor, independent of other risk factors. Kaplan-Meier curves revealed that HOP scores of ≥8.8 stratified patients at higher risk of composite events in a variety of HF populations. In conclusion, amino acid-based assessment of metabolic status correlates with functional capacity in HF outpatients and provides prognostic value for a variety of HF populations.

Assessment of N-terminal pro-B-type natriuretic peptide level in screening for atrial fibrillation in primary health care.

BACKGROUND: Atrial fibrillation (AF), an important cause of thromboembolic events, is often silent and intermittent, thus presenting a diagnostic challenge. The aim of this study was to assess whether the plasma level of N-terminal pro-brain natriuretic peptide (NT-proBNP) is related to the presence of AF and thereby might be used to facilitate screening programs for AF in primary care. METHODS: This was a cross sectional screening study. A population of 70-74-year-old individuals registered at a single primary care center in Stockholm were invited to AF screening. Intermittent ECG recording, 30 seconds twice a day using a hand-held device over 2 weeks, was offered to participants without previously known AF. Of the 324 participating persons, 34 patients had already known AF and 16 new cases of AF were detected by screening. Plasma NT-proBNP was measured in patients with previously known AF, newly detected AF, and 53 control participants without AF. FINDINGS: The median NT-proBNP was 697 ng/L in patients with previously known AF, 335 ng/L in new cases of AF, and 146 ng/L in patients without AF. After adjustment for several clinical variables and morbidities, the differences of median NT-proBNP levels were statistically significant between cases of previously known AF and new cases of AF as well as between new cases of AF and those without AF. The area under receiver operating characteristic curve of detection of new AF was 0.68 (95% CI 0.56 to 0.79) yielding a cut-off point of 124 ng/L with 75% sensitivity, 45% specificity, and 86% negative predictive value. CONCLUSIONS: The NT-proBNP plasma levels among patients with known AF are higher than those with newly detected AF, and the latter have higher levels than those without AF. Therefore NT-proBNP might be a useful screening marker for the detection of AF and its persistence.

A Global Assessment of Circulating Prolysyl Oxidase in Nonischemic Patients With Garden-variety Heart Failure With Preserved Ejection Fraction.

INTRODUCTION AND OBJECTIVES: Lysyl oxidase is overexpressed in the myocardium of patients with hypertensive cardiomyopathy. We aimed to explore whether patients with hypertensive-metabolic heart failure with preserved ejection fraction (HM-HFpEF) also have increased concentrations of circulating prolysyl oxidase (cpLOX) and its possible consequences. METHODS: We quantified cpLOX concentrations in 85 nonischemic patients with stage C, HM-HFpEF, and compared them with those of 51 healthy controls. We also assessed the correlations of cpLOX with myocardial stiffness parameters, collagen turnover products and fibrogenic cytokines, as well as the predictive value of plasma proenzyme levels at 1-year of follow-up. RESULTS: We detected raised cpLOX values and found that they correlated with calculated E/E' ratios and stiffness constants. The subgroup of patients with type I diastolic dysfunction showed a single negative correlation between cpLOX and B-type natriuretic peptide whereas patients with a restrictive diastolic pattern showed a strong correlation between cpLOX and galectin-3. Kaplan-Meier analysis revealed that cpLOX > 52.20 ng/mL slightly increased the risk of a fatal outcome (log-rank = 4.45; P = .034). When Cox regression was used, cpLOX was found to be a significant independent predictor of cardiovascular death or hospitalization due to the decompensation of HM-HFpEF (HR, 1.360; 95%CI, 1.126-1.638; P = .046). CONCLUSIONS: Patients with symptomatic HM-HFpEF show high cpLOX serum levels associated with restrictive diastolic filling indices. These levels represent a moderate risk factor for poor clinical outcome. Throughout the natural history of HM-HFpEF, we observed that cpLOX concentrations were initially negatively correlated with B-type natriuretic peptide but positively correlated with galectin-3 as advanced diastolic dysfunction developed.

Complex assessment of patients with decompensated heart failure: The clinical value of impedance cardiography and N-terminal pro-brain natriuretic peptide.

BACKGROUND: Acute decompensated heart failure (ADHF) is a serious clinical problem and a condition requiring immediate diagnostics, supporting the therapeutic decision adequate to the specific ADHF mechanism. N-terminal pro-brain natriuretic peptide (NT-proBNP) is an established biochemical marker of heart failure, strongly related to hemodynamic status. Impedance cardiography (ICG) provides non-invasive hemodynamic assessment that can be performed immediately at the bedside and revealed to be useful diagnostic tool in some clinical settings in cardiology. OBJECTIVES: The aim of this study was to evaluate the usefulness of ICG in the admission diagnostics and monitoring the effects of treatment in patients hospitalized due to ADHF, with special emphasis on its relation to NT-proBNP. METHODS: This study enrolled 102 patients, aged over 18 years, hospitalized due to ADHF. The subjects underwent detailed clinical assessment, including ICG and NT-proBNP at admission and at discharge day. RESULTS: Among all analyzed ICG parameters thoracic fluid content (TFC), a marker of chest overload, was the most significantly correlated with NT-proBNP level (R = 0.46; p = 0.000001). In comparison with patients with low thoracic fluid content (TFC ≤ 35/kΩ), those with higher TFC values (>35/kΩ) exhibited a greater severity of symptoms (NYHA functional class); higher NT-proBNP levels; lower left ventricular ejection fraction (LVEF), stroke index (SI), and cardiac index (CI); as well as significantly higher systemic vascular resistance index (SVRI). These TFC-based subgroups showed no significant differences in terms of heart rate (HR), systolic blood pressure (SBP), or diastolic blood pressure (DBP). CONCLUSIONS: The evaluation of hemodynamic parameters, especially TFC, seems to be a worthwhile addition to standard diagnostics, both at the stage of hospital admission and while monitoring the effects of treatment. Impedance cardiography is a useful method in evaluating individual hemodynamic profiles in patients with ADHF.

Association with outcomes and response to treatment of trimethylamine N-oxide in heart failure: results from BIOSTAT-CHF.

AIMS: Association of elevated circulating levels of trimethylamine N-oxide (TMAO) with adverse outcomes in patients with heart failure (HF) has been described. However, response of TMAO levels to treatment and medications has not been investigated. Therefore, we investigated whether TMAO levels are responsive to guideline-recommended treatment and medications, and further reflect changes in outcomes. METHODS AND RESULTS: TMAO levels were investigated in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), which addressed response to guideline-recommended pharmacological treatment. TMAO levels in 2234 patients with new-onset or progressively worsening HF showed strong associations with adverse events (mortality and/or rehospitalisation) at 1, 2 and 3 years [hazard ratio (HR) 1.37-1.51, P ≤ 0.019). Analysis of 972 patients with plasma available at both enrolment and follow-up visit showed reductions of B-type natriuretic peptide (BNP) levels with guideline-based treatment (P < 0.001), but not for TMAO levels. Moreover, patients with higher TMAO levels than median before and after treatment showed increased association with adverse outcomes [HR 2.21, 95% confidence interval (CI) 1.43-3.43, P < 0.001] compared to patients with lower than median levels either before or after treatment (HR 1.13, 95% CI 0.63-2.04, P = 0.684 and HR 1.14, 95% CI 0.64-2.03, P = 0.662, respectively). CONCLUSION: TMAO levels were associated with adverse outcomes (mortality and/or rehospitalisation) in BIOSTAT-CHF, and did not respond to guideline-based pharmacological treatment in contrast to BNP levels which did as expected. Lower TMAO levels were associated with favourable outcome regardless of treatment.

The clinical application value of the plasma copeptin level in the assessment of heart failure with reduced left ventricular ejection fraction: A cross-sectional study.

This study aimed to evaluate the clinical applicability of the plasma copeptin level to assess heart failure with reduced left ventricular ejection fraction (HFrEF).One hundred thirty-one patients with HFrEF, 127 patients with heart failure with preserved left ventricular ejection fraction (HFpEF), and 119 healthy candidates were involved. The basic data and examination results of patients were collected. The heart function of the patients with HFrEF and HFpEF were graded on the basis of the criteria of New York Heart Association (NYHA) classification. The plasma copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were tested using enzyme-linked immunosorbent assays (ELISAs).The copeptin and NT-proBNP levels were higher in the HFrEF group than in the HFpEF group. The copeptin and NT-proBNP values increased as the NYHA grade increased in the patients with HFrEF. However, for the patients with HFpEF, the copeptin levels did not change markedly as the NYHA grade increased. The copeptin levels were positively correlated with the NT-proBNP levels in the patients with HFrEF; however, there was no correlation between the copeptin and NT-proBNP values in the patients with HFpEF.Copeptin is involved in the process of progression in patients with HFrEF and the copeptin values might be useful for HFrEF prediction and assessment in the clinic.

Risk stratification with longitudinal neutrophil to lymphocyte ratio assessment after left ventricular assist device implantation.

INTRODUCTION: Inflammatory processes are well-characterized risk factors in cardiovascular disease including advanced heart failure. Previous studies have utilized individual white cell subtypes in risk analysis, and a recent study has focused on the efficacy of the neutrophil-to-lymphocyte ratio in evaluating negative outcomes following left ventricular assist device implantation. To investigate the interaction between the left ventricular assist device and white cell counts, we assessed longitudinal changes in neutrophil-to-lymphocyte ratio following left ventricular assist device implantation. METHODS: This retrospective study included 100 patients who underwent left ventricular assist device implantation between 2012 and 2013. The neutrophil-to-lymphocyte ratio was calculated prior to left ventricular assist device implantation, daily for the first 30 postoperative days, and at the first two postoperative outpatient visits. Preoperative demographic and clinical data were collected for all patients. RESULTS: The mean neutrophil-to-lymphocyte ratio immediately before left ventricular assist device implantation was 5.2 ± 4.9. After surgery, the neutrophil-to-lymphocyte ratio decreased asymptotically, from a peak of 29.2 on postoperative day 1 to 4.1 at the second outpatient visit ( p < 0.001). Lack of improvement in the neutrophil-to-lymphocyte ratio at postoperative day 10 was associated with increased length of stay, right heart failure, and a trend toward worsened survival. CONCLUSION: Our results indicate a significant inflammatory response to implantation of the left ventricular assist device, a known effect. The magnitude of this response may be effectively and easily monitored over time using the neutrophil-to-lymphocyte ratio. In general, approximately 30 days is required for the neutrophil-to-lymphocyte ratio to return to preoperative levels. After several months, the neutrophil-to-lymphocyte ratio improves to below preoperative levels. It is possible that this reduction reflects the reversal of various heart failure-mediated inflammatory processes following left ventricular assist device implantation.

Diagnostic accuracy of point-of-care natriuretic peptide testing for chronic heart failure in ambulatory care: systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic accuracy of point-of-care natriuretic peptide tests in patients with chronic heart failure, with a focus on the ambulatory care setting. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Embase, Health Technology Assessment Database, Science Citation Index, and Conference Proceedings Citation Index until 31 March 2017. STUDY SELECTION: Eligible studies evaluated point-of-care natriuretic peptide testing (B-type natriuretic peptide (BNP) or N terminal fragment pro B-type natriuretic peptide (NTproBNP)) against any relevant reference standard, including echocardiography, clinical examination, or combinations of these, in humans. Studies were excluded if reported data were insufficient to construct 2×2 tables. No language restrictions were applied. RESULTS: 42 publications of 39 individual studies met the inclusion criteria and 40 publications of 37 studies were included in the analysis. Of the 37 studies, 30 evaluated BNP point-of-care testing and seven evaluated NTproBNP testing. 15 studies were done in ambulatory care settings in populations with a low prevalence of chronic heart failure. Five studies were done in primary care. At thresholds >100 pg/mL, the sensitivity of BNP, measured with the point-of-care index device Triage, was generally high and was 0.95 (95% confidence interval 0.90 to 0.98) at 100 pg/mL. At thresholds <100 pg/mL, sensitivity ranged from 0.46 to 0.97 and specificity from 0.31 to 0.98. Primary care studies that used NTproBNP testing reported a sensitivity of 0.99 (0.57 to 1.00) and specificity of 0.60 (0.44 to 0.74) at 135 pg/mL. No statistically significant difference in diagnostic accuracy was found between point-of-care BNP and NTproBNP tests. CONCLUSIONS: Given the lack of studies in primary care, the paucity of NTproBNP data, and potential methodological limitations in these studies, large scale trials in primary care are needed to assess the role of point-of-care natriuretic peptide testing and clarify appropriate thresholds to improve care of patients with suspected or chronic heart failure.