Cardiac Biomarkers For Risk Stratification Research Articles

RISK STRATIFICATION OF STAGE B HEART FAILURE USING HOME BLOOD PRESSURE MONITORING AND EFFECT ON THE INCIDENCE OF HEART FAILURE

Objective: Recently, the international guideline recommends use of the universal definition of Stage B heart failure (HF) based on cardiac biomarkers for risk stratification of asymptomatic HF. There is a few study reporting the association between home blood pressure (BP) and the stage B of HF. We thus assessed this issue by using the dataset of the nationwide prospective study regarding home BP monitoring, the Japan Morning Surge Home BP (J-HOP) study. Design and method: In the J-HOP study, 4,310 outpatients with cardiovascular risk were enrolled and underwent a consecutive 14-days home BP monitoring in morning and evening. In the present study, we assessed 3,218 participants after excluding participants with pre-history of HF and other cardiovascular diseases and lack of data in biomarkers. NT-proBNP 125pg/ml or Hs-cTnT >0.014ng/ml in women, >0.022ng/ml in men were defined as the Stage B of HF based on the guideline (n = 604). Results: In the multivariable logistic model, increase of morning home systolic BP was significantly associated with the risk of the stage B of HF (adjusted OR per 10mmHg, 1.25; 95%CI, 1.16–1.33). After followed-up of median 6 years, 19 patients were hospitalized for HF. The stage B of HF was at greater risk of developing heart failure than the stage A patients (adjusted HR, 3.76; 95% CI, 1.40–10.06) in the multivariable Cox model. Conclusions: From our findings, morning home BP might be useful for risk stratification of early stage of HF.

Debate - The use of cardiac biomarkers in risk stratification.

Debate - The use of cardiac biomarkers in risk stratification.

From Classic to Modern Prognostic Biomarkers in Patients with Acute Myocardial Infarction.

Despite all the important advances in its diagnosis and treatment, acute myocardial infarction (AMI) is still one of the most prominent causes of morbidity and mortality worldwide. Early identification of patients at high risk of poor outcomes through the measurement of various biomarker concentrations might contribute to more accurate risk stratification and help to guide more individualized therapeutic strategies, thus improving prognoses. The aim of this article is to provide an overview of the role and applications of cardiac biomarkers in risk stratification and prognostic assessment for patients with myocardial infarction. Although there is no ideal biomarker that can provide prognostic information for risk assessment in patients with AMI, the results obtained in recent years are promising. Several novel biomarkers related to the pathophysiological processes found in patients with myocardial infarction, such as inflammation, neurohormonal activation, myocardial stress, myocardial necrosis, cardiac remodeling and vasoactive processes, have been identified; they may bring additional value for AMI prognosis when included in multi-biomarker strategies. Furthermore, the use of artificial intelligence algorithms for risk stratification and prognostic assessment in these patients may have an extremely important role in improving outcomes.

Serial cardiac biomarkers for risk stratification of patients with COVID-19

ObjectivesSeveral studies have demonstrated an association between elevated cardiac biomarkers and adverse outcomes in patients with COVID-19. However, the prognostic and predictive capability of a multimarker panel in a prospectively collected, diverse “all-comers” COVID-19 population has not been fully elucidated. Design & methodsWe prospectively assessed high sensitivity cardiac troponin I (hsTnI), NT-pro B-type Natriuretic Peptide (NT-proBNP), Galectin-3 (Gal-3), and procalcitonin (PCT) in 4,282 serial samples from 358 patients admitted with symptomatic, RT-PCR confirmed SARS-CoV-2 infection. Outcomes examined were 30-day in-hospital mortality and requirement for intubation within 10 days. ResultsBaseline hsTnI had the highest AUC for predicting 30-day mortality (0.81; 95% CI, 0.73–0.88), followed by NT-proBNP (0.80; 0.74–0.86), PCT (0.77; 0.70–0.84), and Gal-3 (0.68; 0.60–0.76). HsTnI < 3.5 ng/L at baseline identified patients at low risk for in-hospital mortality (NPV 95.9%, sensitivity 97.3%) and 10-day intubation (NPV 90.4%, sensitivity 88.5%). Continuous, log-2 increases in troponin concentration were associated with reduced survival (p < 0.001) on Kaplan-Meier curves and increased risk of 30-day mortality: HR 1.26 (1.16–1.37) in univariate and 1.19 (1.03–1.4) in multivariate models. Time-varying doubling of concentrations of hsTnI and Gal-3 were associated with increased risk of 30-day mortality (adjusted HR 1.21, 1.06–1.4, and 1.92, 1.40–2.6). ConclusionHsTnI, NT-proBNP, Gal-3, and PCT are elevated at baseline in patients that have worse outcomes from COVID-19. HsTnI was the only independent predictor of 30-day mortality and intubation. Time-varying, doubling in hsTnI and Gal-3 further aided in prognostication of adverse outcomes. These results support the use of hsTnI for triaging patients with COVID-19.

Cardiac biomarkers for risk stratification of arrhythmic death in patients with heart failure and reduced ejection fraction

ABSTRACT Objectives. Patients with heart failure and reduced left ventricular ejection fraction (HFrEF) are prone to ventricular tachyarrhythmias. We tested whether biomarkers C-terminal Endothelin 1 (CT-ET1), midregional pro atrial natriuretic peptide (MR-proANP) and midregional pro adrenomedullin (MR-proADM) might improve risk stratification for arrhythmic death. Methods: This prospective observational study included 160 heart failure patients with ischaemic cardiomyopathy (ICM) or non-ischaemic, dilated cardiomyopathy (DCM) and 30 control patients without heart disease. Primary endpoint was arrhythmic death (ArD) or resuscitated cardiac arrest (resCA). Results: A total of 61 patients died during the median follow-up of 7.0 [5.2–8.4] years. An ArD or resCA was observed in 48 patients. Plasma levels of CT-ET1 (p = 0.002), MR-proANP (p < 0.001) and MR-proADM (p = 0.013) were significantly higher in ICM or DCM patients compared to controls. MR-proANP levels in ICM patients were associated with a significantly increased risk for ArD or resCA (hazard ratio (HR) = 1.42, [95%CI: 1.08–1.85], p = 0.011) in a multivariable Cox regression model. Plasma levels of CT-ET1 (HR = 1.07 [0.98–1.17], p = 0.113) and MR-proADM (HR = 1.80 [0.92–3.55], p = 0.087) were not associated with ArD or resCA in ICM patients. No significant association with ArD or resCA was found in DCM patients. Multivariable Cox regression showed that CT-ET1 (HR = 1.14 [1.07–1.22], p < 0.001), MR-proANP (HR = 1.64 [1.29–2.08], p < 0.001) and MR-pro ADM (HR = 2.06 [1.12–3.77], p = 0.020) were associated with a higher risk for overall mortality. Conclusion: Patients with HFrEF had elevated levels of CT-ET1, MR-proANP and MR-proADM. Plasma levels of MR-proANP are useful as predictor for arrhythmic death in patients with ICM.

Cardiac biomarkers in noncardiac surgery patients : Review of cardiac biomarkers for risk stratification and detection of postoperative adverse cardiac events

Yearly, more than 200million people worldwide undergo noncardiac surgery of whom about 5% will suffer adverse cardiac events. Therefore, risk stratification and early detection of these events is crucial. The goal of this review is to summarize the currently available evidence on the role of biomarkers in perioperative cardiac risk assessment. It presents current data of the established biomarkers troponin and brain natriuretic peptide (BNP), and it also reports on new biomarkers that are still under evaluation, e.g. copeptin (amarker of neurohumoral activation) and presepsin (an inflammation marker). Narrative review. According to currently available data, there is astrong association between preoperative troponin or BNP values and postoperative adverse cardiac events and mortality. However, to date, there is only aweak recommendation for routine measurement of these biomarkers even in high-risk patients because the evidence on outcome improvement is still very limited. The evidence on treatment options in case of increased postoperative troponin values is also scarce so that international guidelines come to different conclusions regarding postoperative measurement of toponin. Meanwhile, several new biomarkers are under evaluation.

Cardiac Biomarkers for Risk Stratification of Acute Kidney Injury After Pediatric Cardiac Surgery

Children undergoing a cardiac surgical procedure are at increased risk for acute kidney injury (AKI). Novel biomarkers are needed to improve risk stratification of AKI after cardiac surgery. We enrolled children aged 1 month to 18 years old from July 2007 to December 2010 undergoing cardiopulmonary bypass. Three United States Food andDrug Administration-approved plasma biomarkers of cardiac stretch, N-terminal pro B-type natriuretic peptide (NTproBNP), inflammation (ST2), or fibrosis (galectin-3), were measured preoperatively and postoperatively within 6 hours of cardiac surgery. All analyseswere stratified by age (<2 or ≥2 years old) toaccount for changing biomarker distributions duringchildhood and due to a significant interaction between biomarker and age for galectin-3 and NTproBNP (P <.05). Postoperatively, AKI, defined by a doubling of baseline serum creatinine, was diagnosed in 51 of 194 children <2 years and in 28 of 201 children ≥2 years. After multivariable adjustment, for children <2 years, none of the biomarkers were independently associated with AKI, whereas for children ≥2 years, the highest tertile of preoperative galectin-3 and NTproBNP as well as the postoperative galectin-3 and ST2 were associated with AKI. Preoperative plasma galectin-3 and NTproBNP and the first postoperative galectin-3 and ST2 levels were independently associated with AKI in children ≥2 years old. The performance of cardiac biomarkers after cardiac surgical procedure is affected by age, and research is required to develop biomarkers for children <2 years old.

Prognostic and Added Value of Two-Dimensional Global Longitudinal Strain for Prediction of Survival in Patients with Light Chain Amyloidosis Undergoing Autologous Hematopoietic Cell Transplantation

Autologous hematopoietic cell transplantation (HCT) is a first-line therapy for prolonging survival in patients with light-chain (AL) amyloidosis. Cardiac involvement is the most important determinant of survival. However, patients with advanced cardiac involvement have often been excluded from HCT because of high risk for transplantation-related mortality and poor overall survival. Whether baseline left ventricular global longitudinal strain (GLS) can provide additional risk stratification and predict survival after HCT in this high-risk population remains unclear. The aim of this study was to evaluate the prognostic implication of baseline GLS and the added value of GLS beyond circulating cardiac biomarkers for risk stratification in patients with AL amyloidosis undergoing HCT. Eighty-two patients with newly diagnosed AL amyloidosis who underwent upfront HCT betweenJanuary 2007 and April 2014 were included in the study. Clinical, echocardiographic, and serum cardiac biomarker data were collected at baseline and 12months following HCT. GLS measurements were performed using a vendor-independent offline system. The median follow-up time for survivors was 58months. Sixty-four percent of patients were in biomarker-based Mayo stage II or III. GLS, brain natriuretic peptide, troponin, and mitral E/A ratio were identified as the strongest predictors of survival (P<.0001). Other predictors included sex, creatinine, free AL, wall thickness, and ejection fraction. Mayo stage was significantly associated with outcome, with 5-year survival of 93%, 72% and 31% in stage I, II, and III patients, respectively. GLS of 17% was identified as the value that best discriminated survivors from nonsurvivors, and the application of this cutoff value provided further mortality risk stratification within each Mayo stage. GLS is a strong predictor of survival in patients with AL amyloidosis undergoing HCT, potentially providing incremental value over serum cardiac biomarkers for risk stratification. GLS should be considered as a standard parameter along with serum cardiac biomarkers when evaluating eligibility for HCT or other investigational therapies.

Sleep Apnea in Total Joint Arthroplasty Patients and the Role for Cardiac Biomarkers for Risk Stratification: an Exploration of Feasibility

Obstructive sleep apnea (OSA) is highly prevalent in patients undergoing total joint arthroplasty (TJA) and is a major risk factor for postoperative cardiovascular complications and death. Recognizing this, the American Society of Anesthesiologists urges clinicians to implement special considerations in the perioperative care of OSA patients. However, as the volume of patients presenting for TJA increases, resources to implement these recommendations are limited. This necessitates mechanisms to efficiently risk stratify patients having OSA who may be susceptible to post-TJA cardiovascular complications. We explore the role of perioperative measurement of cardiac troponins (cTns) and brain natriuretic peptides (BNPs) in helping determine which OSA patients are at increased risk for post-TJA cardiovascular-related morbidity.

Prognostic value of cardiac biomarkers in the risk stratification of syncope: a systematic review

The role of cardiac biomarkers in risk stratification of syncope is unclear. We undertook a systematic review to assess their predictive value for short-term major adverse cardiovascular events (MACE). We conducted a systematic review using MEDLINE, EMBASE, DARE and Cochrane databases from inception to July 2014. We included studies involving adult syncope patients that evaluated cardiac biomarker levels for risk stratification during acute management and excluded case reports, reviews and studies involving children. Primary outcome (MACE) included death, cardiopulmonary resuscitation, myocardial infarction (MI), structural heart disease, pulmonary embolism, significant hemorrhage or cardiac procedural interventions. Secondary outcome analysis assessed for prediction of MI, cardiac syncope and death. Two reviewers extracted patient-level data based on the cut-off reported. Pooled sensitivities and specificities were calculated using patient-level data. A total of 1862 articles were identified, and 11 studies with 4246 patients were included. Studies evaluated 3 biomarkers: contemporary troponin (2693 patients), natriuretic peptides (1353 patients) and high-sensitive troponin (819 patients). The pooled sensitivities and specificities for MACE were: contemporary troponin 0.29 (95 % CI 0.24, 0.34) and 0.88 (95 % CI 0.86, 0.89); natriuretic peptides 0.77 (95 % CI 0.69, 0.85) and 0.73 (95 % CI 0.70, 0.76); high-sensitive troponin 0.74 (95 % CI 0.65, 0.83) and 0.65 (95 % CI 0.62, 0.69), respectively. Natriuretic peptides and high-sensitive troponin showed good diagnostic characteristics for both primary and secondary outcomes. Natriuretic peptides and high-sensitive troponin might be useful in risk stratification.

A Correction to the Research Article Titled: “Computationally Generated Cardiac Biomarkers for Risk Stratification After Acute Coronary Syndrome” by Z. Syed, C. M. Stultz, B. M. Scirica, J. V. Guttag

A Correction to the Research Article Titled: “Computationally Generated Cardiac Biomarkers for Risk Stratification After Acute Coronary Syndrome” by Z. Syed, C. M. Stultz, B. M. Scirica, J. V. Guttag

Computationally Generated Cardiac Biomarkers for Risk Stratification After Acute Coronary Syndrome

The existing tools for estimating the risk of death in patients after they experience acute coronary syndrome are commonly based on echocardiography and clinical risk scores (for example, the TIMI risk score). These identify a small group of high-risk patients who account for only a minority of the deaths that occur in patients after acute coronary syndrome. Here, we investigated the use of three computationally generated cardiac biomarkers for risk stratification in this population: morphologic variability (MV), symbolic mismatch (SM), and heart rate motifs (HRM). We derived these biomarkers from time-series analyses of continuous electrocardiographic data collected from patients in the TIMI-DISPERSE2 clinical trial through machine learning and data mining methods designed to extract information that is difficult to visualize directly in these data. We evaluated these biomarkers in a blinded, prespecified, and fully automated study on more than 4500 patients in the MERLIN-TIMI36 (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36) clinical trial. Our results showed a strong association between all three computationally generated cardiac biomarkers and cardiovascular death in the MERLIN-TIMI36 trial over a 2-year period after acute coronary syndrome. Moreover, the information in each of these biomarkers was independent of the information in the others and independent of the information provided by existing clinical risk scores, electrocardiographic metrics, and echocardiography. The addition of MV, SM, and HRM to existing metrics significantly improved model discrimination, as well as the precision and recall of prediction rules based on left ventricular ejection fraction. These biomarkers can be extracted from data that are routinely captured from patients with acute coronary syndrome and will allow for more accurate risk stratification and potentially for better patient treatment.

Cardiac biomarkers for risk stratification in non-massive pulmonary embolism: a multicenter prospective study.

Troponins (cTnI and cTnT), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP), myoglobin, heart-type fatty acid-binding protein (H-FABP) and fibrin D-Dimer are emergent candidates for risk stratification in pulmonary embolism (PE). To compare the respective prognostic values of biomarker with non-massive PE to predict an adverse outcome at 3 months. One hundred and forty-six consecutive patients with non-massive PE were included in this multicenter prospective study. The combined outcome consisted of intensive care monitoring on admission, death or hospitalization attributable to either a PE-related complication [defined by PE/deep vein thrombosis (DVT) relapse or major bleeding under anticoagulation] or to dyspnoea with or without chest pain during follow-up. The outcome was met in 12% of patients. In univariate analysis, a NT-proBNP level above 300 pg/ml was the strongest predictor of unfavorable outcome with an odds ratio (OR) of 15.8 [95% confidence interval (CI): 2.05-122). ORs for the other variables were: 8.0 for D-dimer >2000 ng/ml (95% CI: 1.1-64), 4.7 for H-FABP >6 ng/ml (95% CI:1.5-14.8), 3.5 for cTnI >0.09 ng/ml (95% CI:1.2-9.7), 3.4 for myoglobin >70 ng/ml (95% CI:0.9-12.2). Receiver operating curve (ROC) analysis indicated that NT-proBNP was the best predictor [area under the curve (AUC) 0.84; 95%CI: 0.76-0.92; P < 0.0001] with a negative predictive value of 100% (95% CI: 91-100) at 300 pg/ml. At that cut-off, the true negative rate for NT-proBNP was 40%. In multivariate analysis, NT-proBNP was the only significant independent predictors. NT-proBNP appears to be a good risk stratification marker in identifying low-risk patients with non-massive PE who could be treated in an outpatient setting.

The association between the proximal extension of the clot and the severity of pulmonary embolism (PE): a proposal for a new radiological score for PE

The aim of the study was to investigate the association between the proximal level of the clot and the severity of pulmonary embolism (PE). The cohort consisted of 99 consecutive patients with PE diagnosed by multi-detector computed tomography. A new score was constructed by calculating the mean value of the largest affected vessel [sub-segmental = 1, segmental = 2, lobar = 3, main pulmonary artery (MPA) = 4] in each lung. A significant association was found between the most proximal level of PE and pulmonary artery obstruction index (PAOI) (P < 0.0001), right ventricular (RV)/left ventricular (LV) ratio (P < 0.0001), and PaO(2) (P = 0.004). No significant association was found between systolic blood pressure and the level of PE. Troponin-T was elevated in none of the sub-segmental, 5% of segmental, 20% of lobar, and in 56% of PEs in the MPA (P = 0.001). Significant association was found between the proposed score and PAOI (P < 0.0001), RV/LV ratio (P < 0.0001), PaO(2) (P < 0.008). Troponin-T was elevated in 10% of level 1, 0% of level 2, 43% level of 3, 66% of level 4 PE (P < 0.0001). Cut-off level score 4 yielded a sensitivity of 84% and a specificity of 74% for the detection of elevated troponin-T. In conclusion, the study indicates that both the most proximal level of PE and the proposed score are related to the severity of PE as determined by blood oxygenation, biochemical and radiological parameters and could therefore be of value for rapid risk stratification of PE. However, the prognostic value of these classifications and their clinical significance needs to be evaluated in properly designed studies.

Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism.

Patients with pulmonary embolism (PE) present with a wide spectrum of clinical acuity that necessitates different therapeutic strategies. Most patients maintain normal systolic arterial pressure and normal right ventricular function. With therapeutic levels of anticoagulation, they will likely have a benign clinical course. Unfortunately, some PE patients suffer rapid clinical deterioration with adverse clinical events, including death from right ventricular failure or the need for cardiopulmonary resuscitation, mechanical ventilation, or administration of pressors for systolic arterial hypotension. Selected patients will benefit from thrombolysis or surgical embolectomy in addition to anticoagulation.1,2 Severe dyspnea, cyanosis, and syncope indicate life-threatening PE. The clinical examination may reveal signs of acute right ventricular dysfunction, including tachycardia, a low arterial blood pressure, distended neck veins, an accentuated P 2, or a tricuspid regurgitation murmur. On the ECG, T-wave inversion or a pseudoinfarction pattern (Qr) in the anterior precordial leads indicates right ventricular dilation and dysfunction.3 Chest computed tomography or magnetic resonance imaging may not only confirm PE but also demonstrate right ventricular dilation. Echocardiography has emerged as the principal tool for risk stratification in acute PE. From a prognostic point of view, echocardiography helps to classify patients with PE into 3 groups: Low-risk PE (no right ventricular dysfunction), with a hospital mortality of <4%, submassive PE (right ventricular dysfunction and a preserved arterial pressure), with a hospital mortality of 5% to 10%, and massive PE (right ventricular dysfunction and cardiogenic shock), with a hospital mortality of approximately 30%.4 Right ventricular dysfunction on the echocardiogram is an independent and powerful predictor of early death in patients with acute PE.5 Indirect signs are systolic pulmonary …