Marker Of Congestive Heart Failure Research Articles

The Relationship of Inflammatory Chemokine, CXCL12, with NT-proBNP: A Marker of Congestive Heart Failure in Rheumatoid Arthritis Patients

Background: Cardiovascular disease (CVD) is the most considerable long-term outcome of rheumatoid arthritis (RA) and the leading cause of premature death in RA patients. The pathogenesis of CVD in RA is largely determined by persistent systemic inflammation and its underlying factors, including chemokines. In this regard, C-X-C motif chemokine ligand 12 (CXCL12) has a crucial role in the CVD and RA pathogenesis. For the first time, plasma CXCL12 was related to conventional CV risk and well-established cardiac biomarkers in RA patients. Methods: This study was conducted on 30 RA patients who have been newly diagnosed, 30 under-treatment RA patients, and 30 healthy subjects. The plasma levels of CXCL12 and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) were measured using the enzyme-linked immunosorbent assay (ELISA) technique. The high sensitivity C-reactive protein (HS-CRP) concentration was evaluated in plasma samples using the ADVIA 1800 Clinical Chemistry System based on the latex-enhanced immunoturbidimetric assay. The CVD risk was measured by calculating the Framingham risk score (FRS) and systematic coronary risk evaluation (SCORE). Results: The mean FRS and plasma concentration of high-density lipid (HDL), NT-proBNP, and HS-CRP were significantly different between the three groups (P = 0.029, P < 0.001, P = 0.016, P < 0.001, respectively). A significant positive correlation was found between CXCL12 with disease activity score-28 (DAS-28) (P = 0.024, r = 0.293) and NT-proBNP (P < 0.0001, r = 0.570) in the patients’ group. Conclusions: Based on the results, there was a significant relationship between the inflammatory mediator CXCL12 and a well-known cardiac biomarker, NT-proBNP.

Evaluating Goldberger's triad as a marker of congestive heart failure: A systematic review and retrospective study

BackgroundIn 1982, Drs. Barold and Goldberger described an ECG triad associated with left ventricular dysfunction (LVD) consisting of high precordial QRS voltage, low limb lead voltage, and poor precordial R wave progression. Studies have since attempted to replicate the originally reported sensitivity (70%), specificity (>99%), and positive predictive value (PPV, 100%) of Goldberger's triad (GT) with variable results. PurposeTo assess sensitivity, specificity and PPV of GT as a screening tool for LVD in the current era. MethodsWe performed: (1) A systematic review of the published studies; (2) Searched our hospital ECG database (GE MUSE) for diagnoses of “low limb-voltage” and “left ventricular hypertrophy” from 2017 to 2022; identified ECGs were analyzed for GT criteria and their medical records were screened for LVD. (3) ECG analysis of patients with known idiopathic LVD for the GT. ResultsA total of 11,115 patients from 8 studies were included in the systematic review of published studies and showed widely varying sensitivity, specificity and PPV. A total of 4576 ECGs (in GE MUSE) from 372 patients met initial screening criteria of low limb lead voltage and LVH; only 12 patients had ECGs that satisfied GT. Of these 12, only 1 patient had evidence of LVD, yielding a PPV of 8%. Finally, of the 40 patients with known LVD, only 1 met the ECG criteria for GT, resulting in a sensitivity of 2.5%. ConclusionOur literature review does not support the original results of GT. ECGs from our database that met GT (searched by low limb-voltage and left ventricular hypertrophy) over a span of 5 years were rare. When present, the PPV of GT was 8%. In patients with established LVD, the sensitivity was 2.5%. These data do not validate GT as tool to identify LVD in the current era.

Assessment of the Clinical Utility of Interleukin-6 in Congestive Heart Failure

Objective: To determine the clinical utility of Interleukin-6 in Congestive heart failure by comparing its association with N terminal-pro brain natriuretic peptide (NT-pro BNP). Study Design: Diagnostic Accuracy Study. Place and Duration: Department of Chemical Pathology, Combined Military Hospital (CMH), Lahore, from 1st September 2022 to 30th November 2022. Methodology: Patients reporting to the CMH Lahore Emergency Department with symptoms suggestive of Congestive Heart Failure (CHF) and Left Ventricular Ejection Fraction (LVEF) < 40% were included in the study after a detailed physical examination. Sample collection was done for analysis of N terminal-pro brain natriuretic peptide and interleukin-6. Standard echocardiography results were obtained from the patients. Their past medical history, the results of the clinical examination, and any additional findings were considered together when evaluating the data for diagnostic reasons. Results: The levels of N terminal-pro brain natriuretic peptide displayed a very weak positive correlation with interleukin-6 (r value=0.016; p value=0.859). Therefore, N terminal-pro brain natriuretic peptide and interleukin-6 were found to have a statistically insignificant association. Interleukin-6 was found to have sensitivity, specificity, and Area under Curve (AUC) (11.11%, 91.18%, and 0.482) respectively at a cut-off level of 65.6pg/ml, for the diagnosis of congestive heart failure. Conclusion: Interleukin-6 has a causative role in the progression and monitoring of congestive heart failure, however; we were unable to show its usefulness as a diagnostic marker of congestive heart failure. The positive correlation of interleukin-6 with N terminal-pro brain natriuretic peptide suggests that interleukin-6 can still be a target for therapeutics. Keywords: Interleukin-6, Diagnostic Accuracy, NT Pro-BNP (Gold Standard), Congestive Heart Failure, Biochemical Markers, Left Ventricular Ejection Fraction. How to Cite This: Saeed M, Rana MZ, Khan N, Anwar H, Awais H, Ahmed S. Assessment of the Clinical Utility of Interleukin-6 in Congestive Heart Failure. Isra Med J. 2023; 15(1): 7-10. DOI: https://doi.org/10.55282/imj.oa1380 This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Non-invasive Assessment Of Elevated Left Ventricular End Diastolic Pressure Using A Small Portable Device: Design For Tele-Monitoring

Background Left ventricular end-diastolic pressure (LVEDP) provides crucial information on the LV operating compliance and is a key marker for congestive heart failure and pulmonary hypertension. The diagnosis and monitoring of the left-sided filling pressure often requiring invasive procedures. HEMOTAG, is a small portable device that uses micro-sensors to capture cardiac vibrations and electrocardiogram (ECG), transduced via thoracic electrodes. It is a viable option to measure cardiac time intervals (CTIs), surrogate markers of hemodynamics and intracardiac pressure. In this study, diastolic-to-systolic time ratio (DSR) and systolic time ratio (STR) along with the patient's age, height, and weight were assessed as valid markers for elevated LVEDP, compared against left heart catheterization LVEDP measurement. Methods In 44 female and 49 male patients, mean LVEDP was measured during cardiac catheterization. Simultaneously, Hemotag generated CTIs: systolic time (ST): mitral valve closure (MVC) to aortic valve closure (AVC), diastolic time (DT): AVC to MVC, STR: Aortic valve opening/(Aortic valve opening to Aortic valve closing), and DSR: DT/ST. The predictability value of non-invasively HEMOTAG-derived CTI ratios - diastolic time normalize by heart rate (DT/HR), DSR, and STR - plus biological information of age, height, and weight were assessed to determine elevated LVEDP (> 15 mmHg). Logistic regression analysis between the markers and LVEDP was performed. Sensitivity, specificity, correlation, and p-values were calculated. Results Mean age for the female (male) patients was 69.41 ± 11.84 (63.12 ± 10.80) and mean LVEDP was 17.20 ± 6.17 (16.57 ± 5.42). Using logistic regression with DSR, STR, age, height, and weight as features, sensitivity of 88.00%, specificity of 94.74%, AUC of 0.94, r = 0.74, p-value = 4.31e-06, were obtained for female patients; using DT/HR, STR, age, height, and weight, a sensitivity of 89.29%, specificity of 71.43%, AUC of 0.79, r = 0.40, and p-value = 0.0419 were obtained in the male patients. Conclusions HEMOTAG detected elevated LVEDP with high sensitivity and high specificity for both female and male patients. This preliminary study has demonstrated the feasibility of estimating LVEDP using a portable, non-invasive device that empowers patients to transmit such data from home instantaneously to providers. Further studies are required to validate HEMOTAG as a point-of-care non-invasive assessment for heart failure and pulmonary hypertension patients. HEMOTAG® development and the clinical study is supported by NIMHD SBIR grant # R44MD009556. Left ventricular end-diastolic pressure (LVEDP) provides crucial information on the LV operating compliance and is a key marker for congestive heart failure and pulmonary hypertension. The diagnosis and monitoring of the left-sided filling pressure often requiring invasive procedures. HEMOTAG, is a small portable device that uses micro-sensors to capture cardiac vibrations and electrocardiogram (ECG), transduced via thoracic electrodes. It is a viable option to measure cardiac time intervals (CTIs), surrogate markers of hemodynamics and intracardiac pressure. In this study, diastolic-to-systolic time ratio (DSR) and systolic time ratio (STR) along with the patient's age, height, and weight were assessed as valid markers for elevated LVEDP, compared against left heart catheterization LVEDP measurement. In 44 female and 49 male patients, mean LVEDP was measured during cardiac catheterization. Simultaneously, Hemotag generated CTIs: systolic time (ST): mitral valve closure (MVC) to aortic valve closure (AVC), diastolic time (DT): AVC to MVC, STR: Aortic valve opening/(Aortic valve opening to Aortic valve closing), and DSR: DT/ST. The predictability value of non-invasively HEMOTAG-derived CTI ratios - diastolic time normalize by heart rate (DT/HR), DSR, and STR - plus biological information of age, height, and weight were assessed to determine elevated LVEDP (> 15 mmHg). Logistic regression analysis between the markers and LVEDP was performed. Sensitivity, specificity, correlation, and p-values were calculated. Mean age for the female (male) patients was 69.41 ± 11.84 (63.12 ± 10.80) and mean LVEDP was 17.20 ± 6.17 (16.57 ± 5.42). Using logistic regression with DSR, STR, age, height, and weight as features, sensitivity of 88.00%, specificity of 94.74%, AUC of 0.94, r = 0.74, p-value = 4.31e-06, were obtained for female patients; using DT/HR, STR, age, height, and weight, a sensitivity of 89.29%, specificity of 71.43%, AUC of 0.79, r = 0.40, and p-value = 0.0419 were obtained in the male patients. HEMOTAG detected elevated LVEDP with high sensitivity and high specificity for both female and male patients. This preliminary study has demonstrated the feasibility of estimating LVEDP using a portable, non-invasive device that empowers patients to transmit such data from home instantaneously to providers. Further studies are required to validate HEMOTAG as a point-of-care non-invasive assessment for heart failure and pulmonary hypertension patients. HEMOTAG® development and the clinical study is supported by NIMHD SBIR grant # R44MD009556.

Is there an association between the nutritional and functional parameters and congestive heart failure severity?

The association between markers of nutritional status (handgrip strength [HGS] and adductor pollicis muscle thickness [APMT]) and clinical markers of congestive heart failure (CHF) severity is currently unclear. The objective of this study was to evaluate the association between HGS, APMT, as markers of nutritional status and CHF severity. APMT and muscle strength was measured in 500 CHF patients bilaterally. Nutritional status was assessed by Subjective Global Assessment (SGA). Functional classification was performed according to guidelines provided by the New York Heart Association (NYHA) and ejection fraction (EF) was measured to classify CHF severity. Poisson regression, adjusted for sex and age, was performed to verify the association between nutritional factors and CHF severity markers. The majority of patients (75.8%) were ≥60 years old and 53.6% were either overweight or obese. SGA identified 42.2% of the patients as malnourished, 12.6% with low APMT, and 29.0% with low HGS. Most of the patients were classified as NYHA III/IV (56.8%) and almost one third of patients (31.1%) had EF≤40%. HGS and APMT were significantly lower in malnourished male patients and in male patients with a lower EF or worse NYHA classification. Even after controlling for the EF, malnourished patients showed a 2.5-fold increased risk of CHF severity by NYHA classification and for each kilogram of increase in the HGS, there was a significant decrease of 2% in the risk (RR: 0.98 p<0.001). Malnourished patients presented a 52% higher risk (RR: 1.52 p=0.016) of having a low EF, whereas for each APMT increase, there was a 5% decrease in the risk (RR: 0.95 p<0.001), even after controlling for NYHA classification. Malnutrition is highly prevalent among patients with CHF and it is associated with the functional class and the severity of the disease. Objective markers of strength (HGS) and muscle (APMT) are independently associated with the CHF severity, assessed by NYHA classification and EF, respectively, even after adjustment for other confounding variables. Thus, the implementation of these nutritional assessment methods in hospital routines, either by SGA or by objective methods, such as HGS and APMT, can configure effective measurements for early detection of malnutrition in patients at higher risk, and possibly a way to avoid their further functional decline.

Correlation between Serum Level of Matrix Metalloproteinase-2 with Left Ventricular End-diastolic Volume in Children with Heart Failure

BACKGROUND: Left ventricular end-diastolic volume (LVEDV) on echocardiography is one of the tests performed on heart failure. This refers to the volume of the left ventricle at the end of the diastolic phase, which would be increased when there is a disturbance in preload, afterload, and contractility factors. Matrix metalloproteinase-2 (MMP2) is a marker of congestive heart failure that can be examined through laboratory examinations.&#x0D; AIM: The objective of the study was to provide evidence of the association between MMP and inflammatory process as well as its correlation with LVEDV in children with heart failure.&#x0D; METHODS: This was a cross-sectional study conducted on children aged 3 months–12 years old with heart failure, who visited Sanglah Hospital, Denpasar, Indonesia from May 2017 to March 2018. Echocardiographic examination (LVEDV) and blood samples were taken to measure the serum level of MMP2 on day 1 after the subjects were diagnosed with heart failure.&#x0D; RESULTS: A total of 32 subjects with heart failure were analyzed in this study. Acyanotic congenital heart defect (CHD) was the most common cause of heart failure, as observed in 23 subjects (71.9%). Characteristics data revealed that 24 subjects (75%) were underweight, 23 (71.9%) had cardiomegaly, and 22 (68.8%) had mild heart failure. Data analysis showed a moderate positive correlation between MMP2 levels with LVEDV after controlling for the influence of age (p = 0.02; r = 0.425).&#x0D; CONCLUSION: There was a moderate positive correlation between MMP2 level and LVEDV after controlling for the age factor.

Multiparametric Differentiation of Idiopathic Dilated Cardiomyopathy With and Without Congestive Heart Failure by Means of Cardiac and Hepatic T1-Weighted MRI Mapping.

OBJECTIVE. The purpose of this study was to test the hypothesis that patients with idiopathic dilated cardiomyopathy (IDCM) and heart failure have increased liver T1 relaxation times at MRI owing to congestion compared with the T1 relaxation times in patients with IDCM without heart failure and healthy control subjects. MATERIALS AND METHODS. For this retrospective cross-sectional study, 55 subjects (33 men, 22 women; mean age, 47 ± 15 years) who had undergone cardiac MRI were included: 20 healthy control subjects and 35 consecutively registered patients with IDCM. Twenty-one patients were hospitalized for acute heart failure, and 14 patients were in stable condition without heart failure. The performances of cardiac volume, left ventricular (LV) longitudinal strain, and ejection fraction (LVEF) in differentiating IDCM with and without heart failure were compared with myocardial and liver T1 relaxation times by means of Mann-Whitney U test and ROC analysis. RESULTS. The native T1 relaxation time of myocardium was significantly greater in patients with IDCM than in healthy control subjects (p < 0.001) but could not be used to differentiate between IDCM with and IDCM without heart failure (p = 0.653). Conversely, the native T1 relaxation time of liver was significantly greater in patients with IDCM and heart failure than in those without heart failure (p < 0.001). Native T1 relaxation time of liver was the overall best parameter for identifying the presence of heart failure in patients with IDCM (AUC, 0.96). It performed better than LVEF (AUC, 0.88) and global longitudinal LV strain (AUC, 0.85). CONCLUSION. Native T1 relaxation time of liver is an easily accessible and accurate noninvasive imaging marker of congestive heart failure in patients with IDCM. It can be measured on standard short-axis cardiac MRI T1-weighted maps and facilitates differentiating patients with IDCM with from those without heart failure more accurately than established functional parameters, such as LV volume, LVEF, and LV strain.

The dynamics of the blood content of N-terminal fragment of brain natriuretic peptide (NT-proBNP) in hypertrophic cardiomyopathy in children

N-terminal pro-brain natriuretic peptide (NT-proBNP) is the unbiased marker of congestive heart failure. Levels of this marker have not been studied in children with hypertrophic cardiomyopathy (HCM). There are presented data of the comparison of blood concentrations of NT-proBNP in hereditary HCM and other diseases associated with myocardial hypertrophy in children. There was examined 41 patient (age: from 3 to 90 months) with myocardial hypertrophy The patients were divided into 3 groups. There was evaluated the interrelationship between NT-proBNP concentrations and the severity of heart failure and echocardiographic parameters. Results. It was established that in the first group of patients with hereditary HCM (41,4%) there was revealed the significant positive relationship between NT-proBNP concentrations and values of the bloodflow velocity and pressure gradient in the LV outflow track, interventricular septum thickness and LVposterior wall thickness (LVPWT), in cases from the second group (34.1%) with syndromes of malformations and metabolic diseases - with RV anterior wall thickness and LVposterior wall thickness, bloodflow velocity and pressure gradient in the RV outflow track, in the third group with myocardial remodeling against background of arterial hypertension the positive correlation was revealed with LVPWT, whereas negative one - with the fraction of left ventricular output. Maximal blood level of NT-proBNP in blood was detected in pronounced hemodynamic disturbances in patients from the second and third group Conclusion. NT-proBNP level assessment is necessary for differentiated diagnostics of HCM and associated diseases.

Contemporary Outcomes of Pediatric Restrictive Cardiomyopathy: A Single-Center Experience.

Pediatric restrictive cardiomyopathy (RCM) has high mortality in historical cohorts, and traditional management often involves early referral for heart transplantation (HTx). This study sought to determine outcomes of pediatric RCM at a center that has favored medical management over early listing for HTx. All patients (N = 43) with pure RCM phenotype (RCM, N = 26) and hypertrophic cardiomyopathy with restrictive physiology (RCM/HCM, N = 17) managed at our center over a 15-year period were investigated. Outcomes of those listed for HTx (N = 18) were compared to a benchmark of contemporaneous pediatric RCM patients in the UNOS database (N = 377). Proportional hazards models were used to determine predictors of adverse outcomes. The mean age was 11 ± 9years and 49% were male. 14 of 18 patients listed received HTx. Overall mortality (12%) was identical between the phenotypes; however, RCM patients were more likely to be listed (P = 0.001) and receive HTx (P = 0.02) compared to RCM/HCM. Prior to HTx, 60% had documented arrhythmia, 16% had cardiac arrest, and 7% required mechanical circulatory support. 4 of 17 patients with an ICD/PM received device therapies (four of five shocks appropriate for VT/VF, and two effective anti-tachycardia pacing interventions). Outcomes of those listed for HTx at our center were similar to the UNOS benchmark. In multivariate analysis, markers of congestive heart failure were associated with adverse outcomes. Heart failure and arrhythmia treatments can delay or possibly prevent the need for HTx in some cases of pediatric RCM. Survival post-HTx is not compromised using this approach.

Chest Radiographs in Congestive Heart Failure: Visualizing Neural Network Learning.

Purpose To examine Generative Visual Rationales (GVRs) as a tool for visualizing neural network learning of chest radiograph features in congestive heart failure (CHF). Materials and Methods A total of 103 489 frontal chest radiographs in 46 712 patients acquired from January 1, 2007, to December 31, 2016, were divided into a labeled data set (with B-type natriuretic peptide [BNP] result as a marker of CHF) and unlabeled data set (without BNP result). A generative model was trained on the unlabeled data set, and a neural network was trained on the encoded representations of the labeled data set to estimate BNP. The model was used to visualize how a radiograph with high estimated BNP would look without disease (a "healthy" radiograph). An overfitted model was developed for comparison, and 100 GVRs were blindly assessed by two experts for features of CHF. Area under the receiver operating characteristic curve (AUC), κ coefficient, and mixed-effects logistic regression were used for statistical analyses. Results At a cutoff BNP of 100 ng/L as a marker of CHF, the correctly trained model achieved an AUC of 0.82. Assessment of GVRs revealed that the correctly trained model highlighted conventional radiographic features of CHF as reasons for an elevated BNP prediction more frequently than the overfitted model, including cardiomegaly (153 [76.5%] of 200 vs 64 [32%] of 200, respectively; P < .001) and pleural effusions (47 [23.5%] of 200 vs 16 [8%] of 200, respectively; P = .003). Conclusion Features of congestive heart failure on chest radiographs learned by neural networks can be identified using Generative Visual Rationales, enabling detection of bias and overfitted models. © RSNA, 2018 See also the editorial by Ngo in this issue.

Decrease in exhaled hydrogen as marker of congestive heart failure

Objective Hydrogen excretion is thought to be related to systemic antioxidation activity. H2 selectively reduces the hydroxyl radical of free hydrogen (·OH), a highly cytotoxic form of reactive oxygen species,...

Mortality Prediction in Severe Congestive Heart Failure Patients with Multifractal Point-Process Modeling of Heartbeat Dynamics.

Multifractal analysis of human heartbeat dynamics has been demonstrated to provide promising markers of Congestive Heart Failure (CHF). Yet, it crucially builds on the interpolation of RR intervals series, which has been generically performed with limited links to CHF pathophysiology. We devise a novel methodology estimating multifractal autonomic dynamics from heartbeat-derived series defined in the continuous time. We hypothesize that markers estimated from our novel framework are also effective for mortality prediction in severe CHF. We merge multifractal analysis within a methodological framework based on inhomogeneous point process models of heartbeat dynamics. Specifically, wavelet coefficients and wavelet leaders are computed over measures extracted from instantaneous statistics of probability density functions characterizing and predicting the time until the next heartbeat event occurs. The proposed approach is tested on data from 94 CHF patients, aiming at predicting survivor and non-survivor individuals as determined after a 4 years follow up. Instantaneous markers of vagal and sympatho-vagal dynamics display power-law scaling for a large range of scales, from s to s. Using standard SVM algorithms, the proposed inhomogeneous point-process representation based multifractal analysis achieved the best CHF mortality prediction accuracy of 79.11 % (sensitivity 90.48%, specificity 67.74%). Our results suggest that heartbeat scaling and multifractal properties in CHF patients are not generated at the sinus-node level, but rather by the intrinsic action of vagal short-term control and of sympatho-vagal fluctuations associated with circadian cardiovascular control, especially within the VLF band. These markers might provide critical information in devising a clinical tool for individualized prediction of survivor and non-survivor CHF patients.

Abstract 423: Potential Role of Natriuretic Peptides in Atherosclerosis and Inflammation

Background: Brain natriuretic peptide (BNP) is currently recognized as one of the important markers of Congestive heart failure (CHF). BNP levels are simple and objective measures of cardiac function in patients with ischemic injury. These measurements can be used to diagnose HF, including diastolic dysfunction and inflammation. Plasma levels of BNP and ANP are elevated in CHF, especially after myocardial infarction (MI). Furthermore, within the heart tissue, gene expression of BNP and ANP is reportedly up-regulated in animal models with MI and CHF, and in human heart disease. In this study, we tested the natriuretic peptides ability in reduction of peroxides as well as inflammation Methods: BNP and ANP were commercially synthesized and their ability to reduce lipid peroxides (LOOH) was measured using 13-hydroperoxyoctadecadienoic acid (13-HPODE). Low density lipoprotein (LDL) was isolated from human plasma and its oxidation was performed using copper in the presence or absence of the peptides. The ability of these peptides to neutralize charges of modified lipoproteins, as well as attenuate inflammation, were analyzed. Oxidized LDL (Ox-LDL)/Ac-LDL was pretreated with increasing concentrations of peptides to evaluate charge neutralizing properties of the peptides. RAW cells were incubated with LPS pretreated with peptides. RNA was isolated from treated cells and real time PCR was performed using mouse IL-1α and IL-6 primers. Results: Natriuretic peptides reduced 13-HPODE and inhibited the oxidation of LDL. Reduced IL-1α and IL-6 gene expression was observed in the presence of LPS. Conclusion: The results of our studies suggest that these peptides a) inhibit the oxidation of LDL and b) have an inhibitory effect on inflammatory cytokine/gene production in the presence of LPS. Based on these results, we predict that natriuretic peptides could have therapeutic potential in reducing CVD/atherosclerosis-associated inflammation.

Novel prognostic tissue markers in congestive heart failure.

Heart failure is a relatively common disorder associated with high morbidity, mortality, and economic burden. Better tools to predict outcomes for patients with heart failure could allow for better decision making concerning patient treatment and management and better utilization of health care resources. Endomyocardial biopsy offers a mechanism to pathologically diagnose specific diseases in patients with heart failure, but such biopsies can often be negative, with no specific diagnostic information. Novel tissue markers in endomyocardial biopsies have been identified that may be useful in assessing prognosis in heart failure patients. Such tissue markers include ubiquitin, Gremlin-1, cyclophilin A, and heterogeneous nuclear ribonucleoprotein C. In some cases, tissue markers have been found to be independent of and even superior to clinical indices and serum markers in predicting prognosis for heart failure patients. In some cases, these novel tissue markers appear to offer prognostic information even in the setting of an otherwise negative endomyocardial biopsy.

B Type Natriuretic Peptide as a Prognostic Marker in Acute Exacerbation of Chronic Obstructive Pulmonary Disease, Asthma and Pneumonia

Acute exacerbation of chronic obstructive pulmonary disease (COPD)/asthma and pneumonia are the major reason for the hospitalization and emergency room visit in the US. In 2011, chronic lower respiratory diseases and pneumonia were among top ten causes of mortality in 2011. Hospitalization and emergency room visit due to these morbidities account for high health care cost. B type natriuretic peptide level (BNP) of more than 400 is a prognostic and diagnostic marker for congestive heart failure (CHF). However, BNP can be raised in other conditions and significance of it is unknown. Aims: To identify role of BNP in prognosticating asthma/copd exacerbation and pneumonia. Study Design: Retrospective study. Place and Duration of Study: Emergency room and Hospital at Interfaith Medical Center between January 2008 to July 2012. Methodology: We retrospectively reviewed the charts of the patients admitted to our hospital with diagnosis of asthma, pneumonia and COPD in whom CHF had been ruled Original Research Article British Journal of Medicine & Medical Research, 4(5): 1106-1114, 2014 1107 out. We collected data about BNP, length of stay, mortality and other demographic data. Results: 461 patients met inclusion criteria 28% had asthma, 31% had COPD exacerbation and 41% had pneumonia. 21% patients had BNP > 100 pg/ml. Patient with BNP > 100 pg/ml had higher mortality as compared to patients with BNP 100 group and BNP 100 pg/ml were more likely to required ICU care as compared to patients with BNP < 100 pg/ml – 30% vs 9% (P value .0001). Conclusion: Our study suggests that BNP can be used as prognostic marker for mortality and severity of the disease in Asthma, COPD and Pneumonia. Higher BNP levels can also predict the prolong length of stay in the hospital.

Plasma proANP Decreases after Meal Intake

To the Editor: Cardiac natriuretic peptides and their molecular precursor fragments are sensitive plasma markers of congestive heart failure and left ventricular dysfunction. Most studies on their value as markers in cardiac diseases have also addressed the effects of aging and sex, in which increasing age and female sex are associated with higher concentrations per se and thus are recommended to be included in establishing reference intervals. Biological variation has also been associated with the circadian pattern of cardiac natriuretic peptide mRNA contents in mice and the concomitant plasma concentrations in humans. New findings have demonstrated that natriuretic peptides and their receptors are involved in fat and muscle metabolism (1). These data, combined with the observation that obese people display lower plasma concentrations than individuals of normal weight, suggest that cardiac natriuretic peptides are also involved, for instance, in the metabolic syndrome and perhaps even in diabetes. No study thus far has tested whether plasma concentrations of pro–atrial-type natriuretic peptide (proANP)1 and pro–brain-type natriuretic peptide (BNP) may be affected by meal intake, a standard stimulus for the gastrointestinal output of hormones involved in glucose metabolism. Therefore, …

Association of N-terminal pro-brain natriuretic peptide with cognitive function and depression in elderly people with type 2 diabetes.

BackgroundType 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).Methodology and Principal FindingsCross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores).ConclusionRaised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.

2 Evaluation of Mid-Regional Pro-Adrenomedullin, Mid-Regional Pro-atrial Natriuretic Peptide, and Procalcitonin for the Diagnosis and Risk Stratification of Emergency Department Patients With Dyspnea

2 Evaluation of Mid-Regional Pro-Adrenomedullin, Mid-Regional Pro-atrial Natriuretic Peptide, and Procalcitonin for the Diagnosis and Risk Stratification of Emergency Department Patients With Dyspnea

N-terminal pro-b-type natriuretic peptide and left atrial function in patients with congestive heart failure and severely reduced ejection fraction

Amino-terminal portion of pro-B-type natriuretic peptide (NT-pro-BNP) is a valuable diagnostic and prognostic marker in congestive heart failure (CHF). In CHF patients, elevation of natriuretic peptide levels correlate with decreased left ventricular (LV) ejection fraction (EF) and increased left atrial (LA) volumes, but a correlation with LA function that is a determinant of haemodynamic and clinical status in CHF with independent prognostic value has never been investigated. Aim of this study was to evaluate the relationship between cardiac neurohormonal activation and LA function in patients with CHF due to dilated cardiomyopathy. One hundred and one patients (86% males; mean age, 64 ± 11 years) with dilated ischaemic or non-ischaemic cardiomyopathy, LV EF ≤45% (mean LV EF, 33 ± 8%), and New York Heart Association class II-IV underwent transthoracic echocardiography to evaluate LA fractional active and total emptying from M- and B-Mode images, and, on the same day, venous blood sample collection to dose NT-pro-BNP. By univariate analyses, NT-pro-BNP significantly correlated to age, LA dimensions, LA function indexes, EF, and functional class. At multivariate analysis, LV EF and M- or B-Mode indexes of LA function were the only independent predictors of NT-pro-BNP values. A NT-pro-BNP cut-off of 1480 pg/mL identified LA dysfunction with 89% specificity and 54% sensitivity. In CHF patients with severely impaired systolic function, NT-pro-BNP levels reflect LA and LV dysfunction. These data should prompt studies to investigate the relationship between changes of LA function and NT-pro-BNP levels and their clinical value as prognostic and therapeutic targets in CHF.

Reply: Letter to the Editor by Zorli et al.

The letter by Zorli et al. highlights that right heart failure may be an independent cause of CA125 elevation. The topic of CA125 as a marker of congestive heart failure is very interesting and I am glad the authors found my article enjoyable. As elevations of CA125 are not solely limited to specific causes of heart failure I had only included references (originally numbered 52 and 53) that indirectly related to right heart failure in tricuspid stenosis [ [1] Gupta S. Maheshwari A. Wuntkal R. Mazid T. Tongaonkar H.B. Diagnostic dilemma in an elderly woman with intractable ascites and elevated CA-125 level. J Assoc Phys India. 2006; 54: 655-656 PubMed Google Scholar ] and atrial septal defect [ [2] Mathew B. Bhatia V. Mahy I.R. Ahmed I. Francis L. Elevation of the tumor marker CA125 in right heart failure. South Med J. 2004; 97: 1013-1014 Crossref PubMed Scopus (12) Google Scholar ]. The authors’ recent work adds to the specific link of CA125 to right heart failure, and is a useful addendum to readers, however this was not available to me at the time of writing my review. Of particular interest is the question of whether heart failure and inflammation act synergistically to elevate serum CA125 levels and this could be quite important in COPD where inflammation is often present.