Cardiac Electrical Biomarker Research Articles

Changes in Cardiac Electrical Biomarker in Response to Coronary Arterial Occlusion: An Experimental Observation.

Cardiac electrical biomarker (CEB), an indicator of ischaemia-induced change in myocyte polarity, has been proposed for diagnosis of acute coronary syndrome. However, effect of coronary occlusion on CEB has not been demonstrated. CEB was acquired before (CEB0), during maximal adenosine hyperaemia (CEBhyp), balloon inflations (CEBmax) and 1 (CEB1h), 2 (CEB2h) and 3 (CEB3h) h after percutaneous coronary intervention along with pre- and post-procedural troponin-I. CEB of subjects with non-cardiac chest pain without risk factors was used as controls (CEBc). "Late recovery" (LR) of CEB was defined as CEB3h > median-CEB0. CEB was recorded in 75 patients undergoing stenting (group 1) including 8 with FFR < 0.8 (group 1a), 25 with FFR ≥ 0.8 (group 2) and 49 controls. In group 1, CEB0 (median, IQR) was higher than CEBc (48.0; 29.5-88.3 vs 30.0; 17.0-44.0; p < 0.001). CEBmax (185; 105.0-331.0) was higher than CEB0 (p < 0.0001). CEB1h (78.0; 31.5-143.8; p < 0.0001) and CEB2h (63.0; 31.5-114.3; p = 0.039) were higher than CEB0 while CEB3h (54.0; 24.3-94.8, p = 0.152) was similar. LR occurred in 50.7% patients. CEBmax predicted LR (OR 1.01, 95% CI 1.00-1.01, p < 0.001) (AUC 0.759, p < 0.001). CEB0 in group 1a and group 2 were similar (p = 0.524). CEBhyp was higher than CEB0 in group 1a (126.0, 109.5-266.0 vs 47.5, 20.5-73.5; p = 0.016) and group 2 (44.0, 27.8-104.8 vs 39.0, 24.0-90.3; p = 0.014). CEBhyp was higher in group 1a than 2 (p = 0.039). CEBhyp (AUC 0.75, p = 0.017) accurately predicted FFR < 0.8. Coronary arterial occlusion increases CEB that retains a "memory" of the ischaemic event. CEBhyp was higher only when FFR was ischaemic and accurately identified FFR < 0.8.

Changes in cardiac electrical biomarker with hyperaemic stress: an experimental perspective

Abstract Background "Cardiac electrical biomarker" (CEB) is a numerical index measured by the Vectraplex ECG (vECG) System with Vectraplex AMI software that measures changes in the cardiac electrical field vectors from dipolar to multipolar during myocardial ischemia. CEB performs well in detecting NSTEMI and STEMI against physician adjudicated diagnosis. Purpose To assess changes in CEB during adenosine stress induced ischaemia. Method Thirty-three patients, in the VECTRA-PCI trial, with normal surface ECG (sECG) had CEB measured before (CEB0), at maximal hyperaemia (CEBh)) and 1-(CEB1), 2-(CEB2) and 3-(CEB3) hours after standard fractional flow reserve (FFR) assessment using intravenous adenosine. vECGs were adjudicated for quality by 2 blinded observers. vECGs with artefacts and arrhythmias were discarded and CEBs from best traces were analysed. Forty-nine individuals with non-cardiac chest pain, without past medical history or risk factors for CAD, on no medications, normal ECGs, normal blood profile acted as controls. CEBs (median, IQR) were compared using appropriate tests. Results FFR was normal (&amp;gt;/=0.80) (nFFR) in 25 and ischaemic (&amp;lt;0.80) (iFFR) in 8 patients. CEB0 in nFFR and iFFR groups were similar to each other (p=0.785) (Fig 1) and to controls (30.0; IQR 17.0-44.0, vs nFFR: p=0.057, vs iFFR: p=0.241). Compared to CEB0, CEBh was higher in nFFR (p=0.014) (Fig 1A) and iFFR (p=0.016) groups (Fig 1B). CEBh in iFFR (126.0; 109.5-216.0) higher than nFFR (44.0; 27.8-104.8), (p=0.039). In nFFR group, CEB1, 2 and 3, though numerically lower, were statistically similar to CEBh and CEB0 (Fig 1A) suggesting quick recovery. In iFFR group CEB1 was similar to and CEB2 and 3 were lower than CEBh (Fig 1B) suggesting a slower recovery of CEB. Both CEBh and change from CEB0 to CEBh (δCEB0-h), but not CEB0, predicted ischaemic FFR with similar accuracy (p=0.570) (Fig 2). CEBh &amp;gt;96 and δCEB0-h &amp;gt;28 had similar sensitivity of 87.5% with specificity of 68% and 80% respectively. Conclusion Obstructive coronary atheroma is associated with higher CEB than non-obstructive atheroma under hyperaemic stress. Both CEBh and δCEB0-h accurately predict ischaemic FFR with higher specificity of δCEB0-h. This is the first study to measure CEB changes with hyperaemic stress in patients with coronary artery disease and could have potential for wider clinical application. Figure 1. Changes in the CEB during and after hyperaemic stress in patients with normal (A) and ischaemic (B) FFR. Figure 2. Area under the ROC curve to determine the diagnostic accuracy of pre-procedural CEB, hyperaemic CEB and change in CEB from baseline to hyperaemia in determining ischaemic FFR.Fig 1. Changes in CEB with stress.Fig 2. CEB for ischaemic FFR

Abstract 11100: Modified EDACS-ADP Score Using Derived 12-Lead Electrocardiogram and Cardiac Electrical Biomarker

Introduction: The EDACS-ADP risk score includes 12-lead electrocardiogram (ECG) and troponin (cTn) to stratify patients presenting with chest pain. The ECG can be derived (dECG) from 3 measured leads with high correlation. A new cardiac electrical biomarker (CEB®) that correlates with cTn can be constructed in real-time from the dECG with reportedly high diagnostic accuracy for detection of acute myocardial infarction (AMI). Objective: Compare the EDACS-ADP to a modified risk score that includes substitution of dECG for ECG, and CEB® for cTn. Methods: This study included 138 consecutive patients presenting to an emergency facility with complaints of chest pain. The prevalence of AMI was 14.5% including 7 STEMI and 13 Non-STEMI. The dECG and CEB® were constructed from leads {I, II, V2} directly from an ECG device (VectraplexECG System, VectraCor Inc, Totowa, NJ). Each EDACS-ADP was calculated and compared to a modified score that utilized the dECG instead of the actual ECG, and CEB® instead of cTn. Sensitivities and specificities were calculated for the EDACS-ADP scores and respective modified scores. ROC curves were constructed to identify risk score cut-offs. Results: The CEB® showed high diagnostic accuracy for AMI with sensitivity 85%, specificity 95.8%, negative predictive value 97.4%, and positive predictive value 77.3%. The cTn showed sensitivity 100%, specificity 89.8%, negative predictive value 100%, and positive predictive value 62.5%. EDACS-ADP with ECG and cTn showed sensitivity 100%, specificity 88.1%, negative predictive value 100%, and positive predictive value 58.8% compared to the modified score with dECG and CEB that showed sensitivity 85%, specificity 94.9%, negative predictive value 97.4%, and positive predictive value 73.9%. The reported EDACS cut-off of 16 was validated by ROC curve analysis. Conclusions: The modified EDACS-ADP risk score based on substitution of the dECG for ECG and CEB® for cTn is comparable to the customary risk score. The modified risk score is easy to calculate and is available immediately allowing a shorter time to decision for possible admission. Also, the modified risk scores may be applicable in facilities where cTn is not immediately available such as in outpatient urgent care and post-acute care centers.

P6600Cardiac electrical biomarker retains memory of myocardial ischaemia not severe enough to cause myonecrosis

Abstract Background “Cardiac electrical biomarker” (CEB) is a numerical index measured by the Vectraplex ECG (vECG) System with Vectraplex AMI software that detects changes in the cardiac electrical fields from dipolar to multipolar vectors during myocardial ischemia. CEB has been validated with ECG traces derived from patients with acute myocardial infarction. However the threshold of CEB for diagnosis of NSTEMI is varied between studies. Purpose To examine the effect of myocardial ischemia during transient coronary occlusion on CEB and the time-course of its recovery. Method Seventy-five consecutive patients with normal (without Q waves, ST-T changes, arrhythmias, bundle branch blocks, left ventricular hypertrophy etc) surface ECG (sECG) had CEBs measured from vECGs recorded before, during and 1, 2 and 3 hours after balloon occlusion during elective percutaneous coronary intervention (PCI). HsTnI was measured before and 1, 2 and 3 after the procedure. The balloon was inflated to the clinically indicated pressures till the appearance of symptoms and/or ST changes or to a maximum of 90 seconds. Ischemia induction during balloon occlusion was confirmed by the presence of ST-T changes on sECG and/or TIMI-0 flow on angiogram. Multiple vECGs were recorded at each balloon occlusion. Every vECG used to derive CEBs was adjudicated for quality by 2 observers blinded to the results. vECGs with wandering baseline, transient arrhythmias, bundle branch blocks etc. were discarded. The highest CEBs derived from best traces were analysed. The pre- and post-PCI CEBs, were compared with the maximum CEB during balloon occlusion using Wilcoxon rank and Friedman test. Results Fifteen subjects with negative FFR and 2 subjects with totally occluded arteries that could not be revascularised were excluded. Mean duration of balloon occlusion resulting in the highest CEB was 54.1 secs. The maximum CEB was reached in 20, 27 and 11 patients during pre-dilatation, stent deployment and post-dilatation respectively. The CEB increased with balloon inflation (pre-PCI median (interquartile range, IQR) 53.5 (31–105) vs balloon occlusion 202 (108–332), p&lt;0.0001). The CEB during balloon occlusion gradually recovered over 1, 2 and 3 hrs post-PCI (vs 74.5 (35–135), p&lt;0.0001; vs 66 (37–118), p&lt;0.0001; vs 58.5 (29–97), p&lt;0.0001 respectively). The 1hr (p=0.0011) and 2hr (p=0.0352) post-PCI CEB remained higher than pre-PCI CEB and returned to the pre-PCI level at 3h post-PCI (p=0.4433). All except 2 patients had normal 3hr TnI; both being below the threshold for diagnosis of peri-procedural MI. Figure 1 Conclusion CEB increases with short transient coronary artery occlusion not severe enough to cause myocardial necrosis and took 3 hours to return to the pre-procedural level suggesting its feature of “ischemic memory”. Thus CEB may have a value in detecting an ischemic episode in patients with chest pain but without a raised hs-Tn. Acknowledgement/Funding None

Sensitivity and specificity of the Vectraplex electrocardiogram system with a cardiac electric biomarker in the diagnosis of ST-elevation myocardial infarction

ST-elevation myocardial infarction (STEMI) is a clinical diagnosis based on a compatible history and characteristic electrocardiographic changes. In the current era, STEMI is treated emergently with angiography, leading to percutaneous coronary intervention. However, false-positive electrocardiograms (ECGs) occur, resulting in unnecessary emergent catheterizations. We hypothesized that the Vectraplex cardiac electrical biomarker (CEB) would increase the specificity for the diagnosis of STEMI. We studied 50 patients who were identified by standard of care (clinical history, physical exam, and 12-lead ECG) as suspected to have STEMI and tested the sensitivity and specificity of the Vectraplex ECG system. Using the final clinical diagnosis (based on history, ECGs, troponin values, and angiographic findings) as the gold standard, we found the CEB value to be quite dynamic, with a reasonable sensitivity and a good positive predictive value but generally poor specificity and negative predictive value. It offered only a 20% improvement compared to 50-50 performance on receiver operator curves.

Diagnostic value of the cardiac electrical biomarker, a novel ECG marker indicating myocardial injury, in patients with symptoms suggestive of non-ST-elevation myocardial infarction.

The cardiac electrical biomarker (CEB) is a novel electrocardiographic (ECG) marker quantifying the dipolar activity of the heart with higher levels indicating myocardial injury. We prospectively enrolled 1097 patients presenting with suspected non-ST-elevation myocardial infarction (NSTEMI) to the emergency department (ED). Digital 12-lead ECGs were recorded at presentation and the CEB values were calculated in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. The prognostic endpoint was all-cause mortality during 2years of follow-up. NSTEMI was the final diagnosis in 14% of patients. CEB levels were higher in patients with NSTEMI compared to other causes of chest pain (median 44 (IQR 21-98) vs. 30 (IQR 16-61), p<.001). A weak but significant correlation between levels of high-sensitivity cardiac troponin T (hs-cTnT) at admission to the ED and the CEB was found (r=.23, p<.001). The use of the CEB in addition to conventional ECG criteria improved the diagnostic accuracy for the diagnosis of NSTEMI as quantified by the area under the receiver operating characteristics curve from 0.66 to 0.71 (p<.001) and the sensitivity improved from 43% to 79% (p<.001). In conclusion, the CEB, an ECG marker of myocardial injury, significantly improves the accuracy and sensitivity of the ECG for the diagnosis of NSTEMI.

Bayesian analysis of a new cardiac electrical biomarker

Bayesian analysis of a new cardiac electrical biomarker

44 Modified HEART Score Using the Derived 12-Lead Electrocardiogram and Cardiac Electrical Biomarker

44 Modified HEART Score Using the Derived 12-Lead Electrocardiogram and Cardiac Electrical Biomarker

CARDIAC ELECTRICAL BIOMARKER RESPONSE DURING PERCUTANEOUS CORONARY INTERVENTION

Background: A new cardiac electrical biomarker (CEB) has been identified that is a measure of dipolar energy in a 12-lead ECG derived from 3 leads (I, aVF, V2). The CEB can potentially detect myocardial ischemia in real time. During PCI an obstruction to blood flow is induced causing localized

47 Correlation of Troponin With a Novel Cardiac Electrical Biomarker in Detection of Acute Myocardial Infarction

47 Correlation of Troponin With a Novel Cardiac Electrical Biomarker in Detection of Acute Myocardial Infarction

NOVEL CARDIAC ELECTRICAL BIOMARKER FOR DETECTION OF ACUTE MYOCARDIAL ISCHEMIC INJURY

The measured 12-lead electrocardiogram (mECG) describes a dipolar electric field such that only 3 leads are needed to construct a derived 12-lead ECG (dECG). A new cardiac electrical biomarker (CEB) that is a measure of dipolar energy has been identified from the dECG, directly from a cardiac

Detection of acute myocardial ischemic injury by gender using a novel cardiac electrical biomarker

ObjectiveThe objective of this study us to stratify by gender a new cardiac electrical biomarker (CEB) diagnostic accuracy for detection of acute myocardial ischemic injury (AMII). MethodsThis is a noninferiority retrospective, case-control, blinded study of 310 archived measured electrocardiograms (ECGs) acquired from 218 men and 92 women. The CEB is constructed from the derived ECG (dECG) synthesized from 3 leads. Electrocardiograms were included if acquired less than or equal to 1 day from patient presentation. Electrocardiograms were interpreted by 2 blinded physicians and adjudicated by consensus. Standard ST analyses and computerized ECG interpretations were active controls. Electrocardiograms were excluded for noise and baseline wander, age younger than 18 years, and ectopic beats in the 10-second ECG acquisition. Diagnostic accuracy measures of sensitivity, specificity, positive and negative predictive values, and likelihood ratios were stratified by gender. Measured vs derived ECG correlations were quantitatively compared using Pearson correlation and qualitatively by percent agreement methodology. ResultsThe CEB sensitivities for AMII detection in men and women were 93.9% and 90.5%, respectively, and CEB specificities were 90.7% and 95.2%, respectively, and were superior to active controls. Derived and measured ECGs showed high correlation for both men and women with r = 0.857 and r = 0.893, respectively. Reference standard intra-agreement analysis for measured ECGs and dECGs with AMII was 99.4%. ConclusionsThe CEB demonstrates high diagnostic accuracy for detection of AMII in men and women. The ECG can be derived with accuracy from 3 leads. This technology is an efficient real-time method of identifying patients with AMII who are being monitored in acute care settings.

311 Detection of Acute Myocardial Ischemic Injury by Sex Using a Novel Cardiac Electrical Biomarker

311 Detection of Acute Myocardial Ischemic Injury by Sex Using a Novel Cardiac Electrical Biomarker

Automated Analysis of the 12-lead ECG in the Emergency Department

Timely detection of myocardial injury is essential for appropriate management of patients in emergency department (ED) evaluated for acute myocardial infarction. A novel electrocardiogram (ECG) metric, the Cardiac Electrical Biomarker (CEB), uses eigenvalue modeling of the 12-lead ECG and quantifies dipolar vs. multipolar forces. The goal of this project was to study association between the CEB and high-sensitivity troponin I (HsTnI). We conducted a retrospective study of patients, evaluated in the ED for acute myocardial infarction [n = 411; 57.6 ± 13.2 years; 186 (45%) men; 266 (64%) African-Americans]. Resting 12-lead ECG and HsTnI were measured at presentation and at 3, 6, and 9 hours after the initial measurement. The CEB was measured by the VectraplexECG System (VectraCor, Totowa, NJ). Patient-specific longitudinal analysis was performed to study association between the CEB with HsTnI changes over time. The CEB indicated myocardial injury in 116 (28.2%) study participants. HsTnI was significantly elevated during ED observation period in patients with myocardial injury, diagnosed by the CEB [median (interquartile range), 10.3 (5.2-31.4) vs. 6.3 (3.5-16.5) ng/L; P = 0.002]. In a mixed-effects linear regression adjusted for age, race, and sex, increasing HsTnI was associated with the CEB elevation [β-coefficient, 0.071 (95% confidence interval, 0.008-0.134); P = 0.027]. In conclusion, in patients in ED evaluated for acute myocardial injury, increasing values of HsTnI were associated with increasing values of the CEB, suggesting that myocardial injury is the mechanism that underlines acute changes in the CEB.

Diagnostic Accuracy of a New Cardiac Electrical Biomarker for Detection of Electrocardiogram Changes Suggestive of Acute Myocardial Ischemic Injury

ObjectiveA new cardiac “electrical” biomarker (CEB) for detection of 12‐lead electrocardiogram (ECG) changes indicative of acute myocardial ischemic injury has been identified. Objective was to test CEB diagnostic accuracy.MethodsThis is a blinded, observational retrospective case‐control, noninferiority study. A total of 508 ECGs obtained from archived digital databases were interpreted by cardiologist and emergency physician (EP) blinded reference standards for presence of acute myocardial ischemic injury. CEB was constructed from three ECG cardiac monitoring leads using nonlinear modeling. Comparative active controls included ST voltage changes (J‐point, ST area under curve) and a computerized ECG interpretive algorithm (ECGI). Training set of 141 ECGs identified CEB cutoffs by receiver‐operating‐characteristic (ROC) analysis. Test set of 367 ECGs was analyzed for validation. Poor‐quality ECGs were excluded. Sensitivity, specificity, and negative and positive predictive values were calculated with 95% confidence intervals. Adjudication was performed by consensus.ResultsCEB demonstrated noninferiority to all active controls by hypothesis testing. CEB adjudication demonstrated 85.3–94.4% sensitivity, 92.5–93.0% specificity, 93.8–98.6% negative predictive value, and 74.6–83.5% positive predictive value. CEB was superior against all active controls in EP analysis, and against ST area under curve and ECGI by cardiologist.ConclusionCEB detects acute myocardial ischemic injury with high diagnostic accuracy. CEB is instantly constructed from three ECG leads on the cardiac monitor and displayed instantly allowing immediate cost‐effective identification of patients with acute ischemic injury during cardiac rhythm monitoring.