Navaid Iqbal

Prognostic utility of plasma neutrophil gelatinase-associated lipocalin in patients with acute heart failure: The NGAL EvaLuation Along with B-type NaTriuretic Peptide in acutely decompensated heart failure (GALLANT) trial

Neutrophil gelatinase‐associated lipocalin (NGAL) is a measure of acute kidney injury. Renal dysfunction portends significant risk after discharge from acute heart failure (AHF). Thus, a sensitive marker of renal injury might also help to risk stratify HF patients.

Primary Results of the HABIT Trial (Heart Failure Assessment With BNP in the Home)

OBJECTIVES This study was a multicenter, single-arm, double-blinded observational prospective clinical trial designed to monitor daily concentrations of B-type natriuretic peptide (BNP) and to determine how these concentrations correlate with acute clinical heart failure decompensation (ADHF) and related adverse clinical outcomes in at-risk HF patients. BACKGROUND Although BNP at discharge is predictive of 30-day outcomes, outpatient serial testing may improve the risk of detecting early decompensation. METHODS A total of 163 patients with HF signs and symptoms of ADHF discharged from the hospital or in an outpatient setting measured their weight and BNP levels daily for 60 days with a finger-stick test. Patients and physicians were blinded to BNP levels. The composite outcome was ADHF events: cardiovascular death, admission for decompensated HF, or clinical HF decompensation requiring either parenteral HF therapy or changes in oral HF medications. RESULTS A total of 6,934 daily BNP values were recorded, with a median of 46 measures per patient over a monitoring period of 65 days. Forty patients had 56 events. Correlations between BNP measures weakened over time, and the dispersion between BNP measures grew. During 10,035 patient-days, there were 494 (4.9%) days of weight gain (≥5 lbs). The hazard ratio per unit increase of ln BNP was 1.84, and the hazard ratio on a day of weight gain was 3.63. These effects retained significance when controlling for symptoms. When the monitoring period for each subject was broken into intervals based on ADHF events, there were 39 (18.4%) intervals of upward trending BNP corresponding to a risk increase of 59.8% and 64 (30.2%) downward trending intervals corresponding to a risk decrease of 39.0%. There were 94 (44.3%) intervals with 1 or more days of weight gain corresponding to a risk increase of 26.1%. CONCLUSIONS This pilot study demonstrates that home BNP testing is feasible and that trials using home monitoring for guiding therapy are justifiable in high-risk patients. Daily weight monitoring is complementary to BNP, but BNP changes correspond to larger changes in risk, both upward and downward. (Heart Failure [HF] Assessment with B-type Natriuretic Peptide [BNP] In the Home [HABIT]; NCT00946231).

Biomarkers in acute myocardial injury

Acute coronary syndrome (ACS) is a significant cause of morbidity and mortality worldwide. The proper diagnosis of ACS requires reliable and accurate biomarker assays to detect evidence of myocardial necrosis. Currently, troponin is the gold standard biomarker for myocardial injury and is used commonly in conjunction with creatine kinase-MB (CK-MB) and myoglobin to enable a more rapid diagnosis of ACS. A new generation of highly sensitive troponin assays with improved accuracy in the early detection of ACS is now available, but the correct interpretation of assay results will require a careful consideration of assay characteristics and the clinical setting prior to incorporation into routine practice. B-type natriuretic peptides, copeptin, ischemia-modified albumin, heart-type fatty-acid-binding protein, myeloperoxidase, C-reactive protein, choline, placental growth factor, and growth-differentiation factor-15 make up a promising group of other biomarkers that have shown the ability to improve prognosis and diagnosis of ACS compared with traditional markers.

Association of ST2 levels with cardiac structure and function and mortality in outpatients

BACKGROUND ST2, an interleukin-1 receptor family member up-regulated in the setting of cardiomyocyte strain, has prognostic value in patients with acute myocardial infarction, chronic severe heart failure, and acute heart failure. The predictive value of ST2 levels in outpatients is unknown. We studied the clinical and echocardiographic correlates of ST2 levels and evaluated their prognostic use in outpatients referred for echocardiograms. METHODS ST2 levels were measured in 588 outpatients referred for echocardiogram. Subjects were analyzed by quartile as well as by optimal ST2 cut-point (28.25 ng/mL) derived from receiver operating characteristic curve analysis. All-cause death at 1 year was the primary outcome. RESULTS In this cohort with mean age of 68 ± 12 years and median ST2 level of 19.8 ng/mL (interquartile range 15.8-23.7), 25 deaths occurred. Heart rate, creatinine clearance, use of diuretics, and the presence of right ventricular hypokinesis were independently associated with ST2 levels. At 6 months, no patients with ST2 below the median had died. Patients with high ST2 levels had an increased risk of death (adjusted hazard ratio [HR] 2.5, P = .02); those with elevated levels of both ST2 and B-type natriuretic peptide were at even higher risk (adjusted HR 4.3, P = .01 vs none elevated). CONCLUSIONS ST2 levels reflect right-side heart size and function and are independent predictors of 1-year mortality in outpatients referred for echocardiograms. The optimal cut-point derived in this cohort is comparable with the previously identified prognostic cut-point for sicker patients. ST2 may be an especially strong prognostic marker for short-term mortality risk.

MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma

Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis. Oxidized low density lipoprotein (OxLDL) induces profound inflammatory responses in vascular cells, such as production of monocyte chemoattractant protein-1 (MCP-1) [chemokine (C-C motif) ligand 2], a key chemokine in the initiation and progression of vascular inflammation. Here we demonstrate that OxLDL also binds MCP-1 and that the OxLDL-bound MCP-1 retains its ability to recruit monocytes. A human MCP-1 mutant in which basic amino acids Arg-18 and Lys-19 were replaced with Ala did not bind to OxLDL. The MCP-1 binding to OxLDL was inhibited by the monoclonal antibody E06, which binds oxidized phospholipids (OxPLs) in OxLDL. Because OxPLs are carried by lipoprotein(a) [Lp(a)] in human plasma, we tested to determine whether Lp(a) binds MCP-1. Recombinant wild-type but not mutant MCP-1 added to human plasma bound to Lp(a), and its binding was inhibited by E06. Lp(a) captured from human plasma contained MCP-1 and the Lp(a)-associated endogenous MCP-1 induced monocyte migration. These results demonstrate that OxLDL and Lp(a) bind MCP-1 in vitro and in vivo and that OxPLs are major determinants of the MCP-1 binding. The association of MCP-1 with OxLDL and Lp(a) may play a role in modulating monocyte trafficking during atherogenesis.

Cardiac biomarkers: new tools for heart failure management

The last decade has seen exciting advances in the field of biomarkers used in managing patients with heart failure (HF). Biomarker research has broadened our knowledge base, shedding more light on the underlying pathophysiological mechanisms occurring in patients with both acute and chronic HF. The criterion required by an ideal cardiovascular biomarker has been progressively changing to an era of sensitive assays that can be used to guide treatment. Recent technological advances have made it possible to rapidly measure even minute amounts of these proteins by means of higher sensitivity assays. With a high prevalence of comorbidities associated with HF, an integrated approach utilizing multiple biomarkers have shown promise in predicting mortality, better risk stratification and reducing re-hospitalizations, thus lowering health-care costs. This review provides a brief insight into recent advances in the field of biomarkers currently used in the diagnosis and prognosis of patients with acute and chronic HF.

Cardiac biomarkers, mortality, and post-traumatic stress disorder in military veterans.

Post-traumatic stress disorder (PTSD) is gaining increasing recognition as a risk factor for morbidity and mortality. The aim of this study was to examine the impact of PTSD and abnormal cardiovascular biomarkers on mortality in military veterans. Eight hundred ninety-one patients presenting for routine echocardiography were enrolled. Baseline clinical data and serum samples for biomarker measurement were obtained and echocardiography was performed at the time of enrollment. Patients were followed for up to 7.5 years for the end point of all-cause mortality. Ninety-one patients had PTSD at the time of enrollment. There were 33 deaths in patients with PTSD and 221 deaths in those without PTSD. Patients with PTSD had a trend toward worse survival on Kaplan-Meier analysis (p = 0.057). Among patients with elevated B-type natriuretic peptide (>60 pg/ml), those with PTSD had significantly increased mortality (p = 0.024). Among patients with PTSD, midregional proadrenomedullin (MR-proADM), creatinine, and C-terminal proendothelin-1 were significant univariate predictors of mortality (p = 0.006, p = 0.024, and p = 0.003, respectively). In a multivariate model, PTSD, B-type natriuretic peptide, and MR-proADM were independent predictors of mortality. In patients with PTSD, MR-proADM was a significant independent predictor of mortality after adjusting for B-type natriuretic peptide, cardiovascular risk factors, cancer, and sleep apnea. Adding MR-proADM to clinical predictors of mortality increased the C-statistic from 0.572 to 0.697 (p = 0.007). In conclusion, this study demonstrates an association among PTSD, abnormal cardiac biomarker levels, and increased mortality.

Mid‐region pro‐adrenomedullin adds predictive value to clinical predictors and Framingham risk score for long‐term mortality in stable outpatients with heart failure

The aim of this study was to evaluate the long‐term prognostic utility of mid‐region prohormone adrenomedullin (MR‐proADM) in stable outpatients with heart failure (HF).

Novel biomarkers for heart failure.

Heart failure (HF) has proven to be a major burden on the health system. The continuing prevalence of the condition and its rising associated costs and care, has amplified the need for earlier diagnosis, better risk stratification and cost-effective treatment to cut rates of hospitalization. Biomarkers seem poised to undertake such tasks, with biomarker management of patients with HF quickly evolving over the past several years. Biomarker guided diagnosis and treatment has become vital, especially during the acute setting in which the majority of patients with HF, were initially present. An adequate assessment of risk requires a multi-marker approach to a given HF patient. Established markers including brain natriuretic peptide and NT-proBNP are a significant clinical aid to physicians, though their utility is limited. In the past few years, momentous effort has been put into the discovery of new biomarkers. These endeavors have led to the emergence of several capable and promising biomarkers for HF management including troponins, mid-regional pro-adrenomedullin, GDF-15, C-reactive protein, Galectin-3, IL-6, ST-2, neutrophil gelatinase-associated lipocalin, copeptin and procalcitonin. This review will offer an insight into the novel biomarkers considered as the cutting-edge in the diagnosis and management of HF.

Heart Failure Biomarkers

Biomarker testing in patients with heart failure (HF) is rapidly expanding. With high-quality research indicating its diagnostic and prognostic capabilities, biomarkers are excellent adjuncts to manage patients with HF. Their superiority lies mainly in their reflection of ongoing pathophysiological events at a cellular level. Monitoring biomarker levels has been shown to provide incremental information on the progression of disease, thus allowing to better tailor treatment and management. Several biomarkers have gained attention in the past decade and continuing research demonstrates the specificity of each biomarker to be used on its own or in combination to improve diagnostic accuracy. This review will provide an insight into the role of such biomarkers, which are widely studied in the setting of HF so as to delineate their role in diagnosing, prognosticating, and titrating HF therapy.