Biomarkers in acute myocardial infarction

Myocardial infarction causes significant mortality and morbidity. Timely diagnosis allows clinicians to risk stratify their patients and select appropriate treatment. Biomarkers have been used to assist with timely diagnosis, while an increasing number of novel markers have been identified to predict outcome following an acute myocardial infarction or acute coronary syndrome. This may facilitate tailoring of appropriate therapy to high-risk patients. This review focuses on a variety of promising biomarkers which provide diagnostic and prognostic information

B-type natriuretic peptide molecular forms for risk stratification and prediction of outcome after acute myocardial infarction

Background: B-type natriuretic peptide (BNP) is known to be a risk marker following acute myocardial infarction (MI). More recently, truncated molecular forms of the BNP molecule have been identified, with the association of these forms and outcome in acute MI not known. The present study investigated their use as risk stratifying biomarkers of this condition. Methods: BNP molecular forms (BNP 5-32, BNP 4-32 and BNP 3-32) were measured in plasma from 1,078 acute MI patients using immunocapture followed by MALDI-ToF-mass spectrometry. Associations of molecular forms with short-term and long-term adverse outcomes were assessed. Results: BNP molecular forms were independent predictors of mortality/reinfarction, mortality/rehospitalization due to heart failure, and a composite of all events at 6 months, 1 year and 2 years and showed prognostic ability comparable with conventional BNP measurements (P <0.001-0.026 vs. N-terminal [NT]-proBNP P <0.001-0.020, respectively). Reclassification analyses showed BNP molecular forms successfully reclassified patient risk when used in addition to the GRACE clinical risk score (P ≤0.005). BNP 5-32 showed utility as a secondary risk stratification biomarker when used in combination with the GRACE score and NT-proBNP by successful down-classification of high-risk patients. Conclusions: BNP molecular forms were associated with poor prognosis at 6 months, 1 year and at 2 years in patients with acute MI. BNP 5-32 showed successful utility as a secondary marker in combination with NT-proBNP after GRACE scoring. This study suggests a potential role for BNP molecular forms in prognosis and risk stratification after acute MI

In reply: Response to letter to the editor ‘Predictive Value of NT-proBNP in Patients with Acute Myocardial Infarction’; Regarding Article ‘Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction"

In reply: Response to letter to the editor ‘Predictive Value of NT-proBNP in Patients with Acute Myocardial Infarction’; Regarding Article ‘Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction

Plasma Desmosine for Prediction of Outcomes after Actue Myocardial Infarction

BACKGROUND: Elastin degradation is implicated in the pathology of vulnerable plaque. Recent studies show promising results for plasma desmosine (pDES), an elastin-specific degradation product, as a marker of cardiovascular disease (CVD) outcomes. The aim of this study was to investigate the potential role of pDES as a marker of clinical outcome in patients with acute myocardial infarction (AMI). MATERIALS AND METHODS: In this case-control study, we studied 236 AMI patients: 79 patients who had death and/or myocardial infarction (MI) at 2 years, and 157 patients who did not have an event at 2 years. pDES was measured using a validated liquid chromatography-tandem mass spectrometry method. Association of pDES with adverse outcomes, and the incremental value of pDES to global registry of acute coronary events (GRACE) score for risk stratification was assessed. RESULTS: pDES levels were elevated in patients with the composite outcome of death/MI at 2 years (p = 0.002). Logistic regression analyses showed pDES to be associated with death/MI at 2 years [Odds ratio (OR) 5.99 (95% CI 1.81–19.86) p = 0.003]. pDES remained a significant predictor of death/MI at 2 years even after adjustment for age, sex, history of CVD, revascularisation, blood pressure, medications on discharge, Troponin I, and NT-proBNP levels.[OR 5.60 (95% CI 1.04–30.04) p = 0.044]. In another multivariable model including adjustment for eGFR, pDES was significantly associated with the composite outcome at 6 months, but not at 2 years follow up. DES was also able to reclassify risk stratification for death/MI at 6 months, when added to the GRACE risk model [Net Reclassification Index (NRI) 41.2 (95% CI 12.0–70.4) p = 0.006]. CONCLUSION: pDES concentrations predict clinical outcomes in patients with AMI, demonstrating its potential role as a prognostic marker in AMI

Relation of microvascular dysfunction to exercise capacity and symptoms in patients with severe aortic stenosis

Objective: The aim of this study was to assess the impact of left ventricular hypertrophy, myocardial fibrosis, myocardial perfusion reserve (MPR) and diastolic dysfunction on objectively measured aerobic exercise capacity (peak VO$_{2}$) in severe aortic stenosis (AS). Background: The management of asymptomatic patients with severe AS remains controversial and clinical practice varies. Echocardiographic measures of severity do not discriminate between symptomatic status or predict exercise capacity. The purpose of this study was to investigate the mechanisms contributing to symptom generation and exercise intolerance. This needs to be fully understood to optimise the management of asymptomatic AS. Methods: Patients were prospectively enrolled from a single cardiac surgical centre. Inclusion criteria: age 18-85, isolated severe AS referred for valve replacement. Exclusion criteria: syncope; other moderate/severe valve disease, previous valve surgery, obstructive coronary artery disease (>50% luminal stenosis on invasive angiography), chronic obstructive pulmonary disease, atrial fibrillation, estimated glomerular filtration rate <30mL/min. Investigations and primary outcome measures; cardiac magnetic resonance (CMR) - left ventricular mass index (LVMI), MPR (calculated from absolute myocardial blood flow during adenosine hyperaemia and rest determined by model-independent deconvolution of signal intensity curves with an arterial input function), late gadolinium enhancement (LGE); echocardiography - AS severity, tissue Doppler-derived diastolic function; symptom-limited bicycle ergometer cardiopulmonary exercise testing (CPEX) - peak VO$_{2}$. Linear regression investigated possible predictors of continuous outcome measures. Stepwise selection methods were used to determine the most important predictors of outcome. Results: Four patients with variable LVMI, LGE and MPR are shown, Figure 1. Univariate analyses and results from the stepwise model selection for peak VO$_{2}$ are summarised in Table 1. Only MPR was of independent significance in predicting age and sex corrected peak VO$_{2}$. The relationship between peak VO$_{2}$ and MPR is shown, Figure 2. Patients with higher NYHA Class had lower MPR (p=0.001). Examining predictors of MPR the best stepwise model contained LVMI and LGE category as independent predictors, Table 2. Conclusions: MPR is a novel independent predictor of peak VO$_{2}$ and is inversely related to NYHA functional class in severe AS. Microvascular dysfunction is determined by a combination of factors including AS severity, LVMI, diastolic perfusion time, myocardial fibrosis and LV filling pressure. Further work is required to determine the clinical significance of microvascular dysfunction in AS

Clinical Determinants and Prognostic Implications of Renin and Aldosterone in Patients with Symptomatic Heart Failure

Aims Activation of the renin-angiotensin-aldosterone system plays an important role in the pathophysiology of heart failure (HF) and has been associated with poor prognosis. There are limited data on the associations of renin and aldosterone levels with clinical profiles, treatment response, and study outcomes in patients with HF. Methods and results We analysed 2,039 patients with available baseline renin and aldosterone levels in BIOSTAT-CHF (a systems BIOlogy study to Tailored Treatment in Chronic Heart Failure). The primary outcome was the composite of all-cause mortality or HF hospitalization. We also investigated changes in renin and aldosterone levels after administration of mineralocorticoid receptor antagonists (MRAs) in a subset of the EPHESUS trial and in an acute HF cohort (PORTO). In BIOSTAT-CHF study, median renin and aldosterone levels were 85.3 (percentile(25-75) = 28-247) mu IU/mL and 9.4 (percentile(25-75) = 4.4-19.8) ng/dL, respectively. Prior HF admission, lower blood pressure, sodium, poorer renal function, and MRA treatment were associated with higher renin and aldosterone. Higher renin was associated with an increased rate of the primary outcome [highest vs. lowest renin tertile: adjusted-HR (95% CI) = 1.47 (1.16-1.86), P = 0.002], whereas higher aldosterone was not [highest vs. lowest aldosterone tertile: adjusted-HR (95% CI) = 1.16 (0.93-1.44), P = 0.19]. Renin and/or aldosterone did not improve the BIOSTAT-CHF prognostic models. The rise in aldosterone with the use of MRAs was observed in EPHESUS and PORTO studies. Conclusions Circulating levels of renin and aldosterone were associated with both the disease severity and use of MRAs. By reflecting both the disease and its treatments, the prognostic discrimination of these biomarkers was poor. Our data suggest that the "point" measurement of renin and aldosterone in HF is of limited clinical utility