Mandy L. Simon

Incident Type 2 Myocardial Infarction in a Cohort of Patients Undergoing Coronary or Peripheral Arterial Angiography

Background: Despite growing recognition of type 2 myocardial infarction (T2MI; related to supply/demand mismatch), little is known about its risk factors or its association with outcome. Methods: A single-center cohort of patients undergoing coronary or peripheral angiography with or without intervention was prospectively enrolled and followed for incident type 1 and T2MI, and major adverse cardiovascular events (MACE, a composite of all-cause death, nonfatal myocardial infarction [MI], heart failure, stroke, transient ischemic attack, peripheral arterial complication, and cardiac arrhythmia), as well. T2MI was adjudicated using criteria from the Third Universal Definition of MI. Baseline characteristics, blood samples, and angiography information were obtained. Major end points subsequent to first MI were assessed using landmark analyses to compare the rates of first events only where everyone with a prior history of any MACE before MI were censored and adjusted for follow-up times. Cox proportional hazard models were used for time-to-event analyses with age and sex forced into all models and additional covariates evaluated by using the stepwise option for the selection. Results: One thousand two hundred fifty-one patients were enrolled and followed for a median of 3.4 years. Of these patients, 152 (12.2%) had T2MI during follow-up; T2MI was frequently recurrent. Multivariable predictors of T2MI were older age, lower systolic blood pressure, history of coronary artery disease, heart failure, chronic obstructive pulmonary disease, diabetes mellitus, nitrate use, and elevated concentrations of glucose, N-terminal pro-B type natriuretic peptide, and cystatin C. Patients with T2MI had higher rates of subsequent adverse events than those without T2MI (per 100 person-years: MACE, 53.7 versus 21.1, P<0.001; all-cause death, 23.3 versus 3.3, P<0.001; cardiovascular death, 17.5 versus 2.6, P<0.001; heart failure events, 22.4 versus 7.4, P<0.001); these rates are similar to those seen in patients with type 1 MI. Incident diagnosis of T2MI strongly predicted risk for subsequent MACE (adjusted hazard ratio, 1.90; 95% confidence interval, 1.46–2.48; P<0.001), all-cause death (adjusted hazard ratio, 2.96; 95% confidence interval, 2.01–4.36; P<0.001), and cardiovascular death (adjusted hazard ratio, 2.16; 95% confidence interval, 1.36–3.43; P=0.001). Conclusions: T2MI is common and associated with poor prognosis. Studies evaluating treatment strategies for management of T2MI are needed. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842868.

Comparison between admission natriuretic peptides, NGAL and sST2 testing for the prediction of worsening renal function in patients with acutely decompensated heart failure

Abstract Background: In order to predict the occurrence of worsening renal function (WRF) and of WRF plus in-hospital death, 101 emergency department (ED) patients with acute decompensated heart failure (ADHF) were evaluated with testing for amino-terminal pro-B-type natriuretic peptide (NT-proBNP), BNP, sST2, and neutrophil gelatinase associated lipocalin (NGAL). Methods: In a prospective international study, biomarkers were collected at the time of admission; the occurrence of subsequent in hospital WRF was evaluated. Results: In total 26% of patients developed WRF. Compared to patients without WRF, those with WRF had a longer in-hospital length of stay (LOS) (mean LOS 13.1±13.4 days vs. 4.8±3.7 days, p<0.001) and higher in-hospital mortality [6/26 (23%) vs. 2/75 (2.6%), p<0.001]. Among the biomarkers assessed, baseline NT-proBNP (4846 vs. 3024 pg/mL; p=0.04), BNP (609 vs. 435 pg/mL; p=0.05) and NGAL (234 vs. 174 pg/mL; p=0.05) were each higher in those who developed WRF. In logistic regression, the combination of elevated natriuretic peptide and NGAL were additively predictive for WRF (ORNT-proBNP+NGAL=2.79; ORBNP+NGAL=3.11; both p<0.04). Rates of WRF were considerably higher in patients with elevation of both classes of biomarker. Comparable results were observed in a separate cohort of 162 patients with ADHF from a different center. Conclusions: In ED patients with ADHF, the combination of NT-proBNP or BNP plus NGAL at presentation may be useful to predict impending WRF (Clinicaltrials.gov NCT#0150153).

Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

Objective The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). Methods In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. Results 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. Conclusions In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153).

Single‐Molecule Counting of High‐Sensitivity Troponin I in Patients Referred for Diagnostic Angiography: Results From the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) Study

Background The meaning of high‐sensitivity troponin I (hsTnI) concentrations in patients without acute myocardial infarction (MI) requires clarity. We hypothesized that among patients referred for diagnostic coronary angiography without acute MI, hsTnI concentrations would correlate with prevalent coronary artery disease (CAD) and predict incident cardiovascular events and mortality. Methods and Results We measured hsTnI using a single‐molecule counting assay (99th percentile, 6 ng/L) in samples from 991 patients obtained at the time of angiography. Concentrations of hsTnI were assessed relative to the severity of CAD and prognosis during mean follow‐up of 3.7 years. Median hsTnI concentration was 4.19 ng/L; 38% of patients had hsTnI concentrations ≥99th percentile. Across increasing hsTnI quartiles, patients had higher prevalence of angiographic CAD; in multivariate models, hsTnI ≥99th percentile independently predicted obstructive CAD (odds ratio: 2.57; P<0.001) and incident MI (hazard ratio [HR]: 2.68; P<0.001), cardiovascular death (HR: 2.29; P=0.001), and all‐cause death (HR: 1.84; P=0.004). In those with >70% coronary stenosis, hsTnI ≥99th percentile independently predicted incident MI (HR: 1.87; P=0.01), cardiovascular mortality (HR: 2.74; P=0.001), and the composite end point of MI and all‐cause death (HR: 2.06; P<0.001). In participants with coronary stenosis <70%, hsTnI ≥99th percentile even more strongly predicted incident MI (HR: 8.41; P<0.001), cardiovascular mortality (HR: 3.60; P=0.03), and the composite end point of MI and all‐cause death (HR: 3.62; P<0.001). Conclusions In a large prospective cohort of patients who were free of prevalent MI and undergoing diagnostic coronary angiography, hsTnI concentrations were associated with higher prevalence of CAD and predicted incident MI, cardiovascular death, and all‐cause death. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842868.

A clinical and proteomics approach to predict the presence of obstructive peripheral arterial disease: From the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) Study

Peripheral arterial disease (PAD) is a global health problem that is frequently underdiagnosed and undertreated. Noninvasive tools to predict the presence and severity of PAD have limitations including inaccuracy, cost, or need for intravenous contrast and ionizing radiation.

MULTIPLE BIOMARKERS FOR PREDICTING MAJOR ADVERSE CARDIAC EVENTS IN AT-RISK PATIENTS UNDERGOING DIAGNOSTIC CORONARY ANGIOGRAPHY: RESULTS FROM THE CATHETER SAMPLED BLOOD ARCHIVE IN CARDIOVASCULAR DISEASES (CASABLANCA) STUDY

Background: Clinical prediction of major adverse cardiac events (MACE) in patients undergoing cardiac evaluation or entering clinical trials remains challenging due to low sensitivity and specificity. We assessed whether a multiple biomarker approach improves prediction of incident MACE (composite

A PROSPECTIVE, BLINDED STUDY OF BIOIMPEDANCE VECTOR ANALYSIS AND BIOMARKER TESTING FOR THE PREDICTION OF WORSENING RENAL FUNCTION IN CONSECUTIVE PATIENTS WITH ACUTELY DECOMPENSATED HEART FAILURE: PRIMARY RESULTS OF THE BIOMONITORING AND CARDIORENAL SYNDROME IN HEART FAILURE (BIONICS-HF) TRIAL

Worsening renal function (WRF) commonly affects patients with acutely decompensated heart failure (ADHF), and is associated with significant morbidity and mortality. The ability to predict WRF is limited. In a prospective, blinded international study, 101 consecutive emergency department patients