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The number of patients with cardiovascular implantable electronic devices (CIED), including ventricular pacemakers, continues to increase. However, there are no accurate electrocardiographic (ECG) criteria to diagnose acute myocardial infarction (AMI), even if due to acute coronary occlusion (ACO), with a ventricular pacemaker in situ. In this retrospective, multicenter, case-control study the investigators will examine ECG criteria to diagnose ACO in patients with ventricular paced rhythms. During this process, the investigators will also create a database from which investigators will be able to answer multiple additional questions on this population of patients.
BACKGROUND Diagnosis and management of ACO (the anatomic substrate for ST-elevation myocardial infarction) is time sensitive. Diagnosis necessitates emergent reperfusion therapy. An important predictor of death from ACO includes time to reperfusion.1 Delays in reperfusion therapy, including primary percutaneous coronary intervention (PCI) or fibrinolysis, are associated with worse 30-day and 1-year mortality. American Heart Association (AHA) guidelines for treatment of ACO recommend that the first medical contact to device time be less than 120 minutes in patients who have no contraindications to treatment.2 Though cardiac biomarkers are helpful in making the diagnosis in uncertain cases, the time sensitive nature of intervention for ACO precludes their use to direct emergent reperfusion therapy. Furthermore, biomarkers do not diagnose ACO but rather any AMI, including those without occlusion that do not need emergent intervention.
The "traditional" ECG diagnosis of ACO, which includes ST-elevation cutoffs based upon age and sex, excludes patients with ventricular paced rhythm (VPR).3 The small field of research on the topic of ACO in VPR has extrapolated and analyzed data from patients with left bundle branch block (LBBB). That is because VPR with right ventricular pacing and LBBB both result in depolarization from right to left through myocardium (not through conducting fibers) and thus result in similar ECG findings (e.g. wide QRS, delayed onset of depolarization, and abnormal repolarization with "discordant" [in the opposite direction of the QRS] T-waves and ST-segment deviation). In the presence of known LBBB, AHA guidelines recommend using the Sgarbossa criteria to make the diagnosis of ACO.4 Sgarbossa et al. proposed requiring at least 3 points from the following criteria for the diagnosis of acute myocardial infarction in the presence of LBBB: (1) concordant ST-segment elevation of 1 mm (0.1 mV) in at least 1 lead (5 points), (2) concordant ST-segment depression of at least 1 mm in leads V1 to V3 (3 points), or (3) excessively discordant ST-segment elevation, defined as greater than or equal to 5 mm of ST-segment elevation when the QRS complex is negative (2 points). There have been only a handful of evaluations of Sgarbossa's criteria in VPR, with variable methodologies and patient populations; sensitivities in the studies ranged from 10-53% and specificities ranged from 84-99%.5,6 Neither study used angiographic endpoints, but only used biomarker definitions of AMI; one study used a very flawed biomarker definition with no adjudication. Thus, the number of occlusions is entirely unknown and probably very small.
For LBBB, Smith et al. derived and validated a "modified Sgarbossa rule" in which they replaced Sgarbossa's third criterion (excessively discordant ST elevation as defined by 5 mm) with a proportion-based criterion (defined by > 25% of the previous S-wave) (see Table 1). This rule resulted in much higher sensitivity and accuracy for diagnosis of ACO than the original Sgarbossa.7,8
Table 1: MODIFIED SGARBOSSA CRITERIA
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Angiogram Cohort w Acute Coronary Occlusion | Inclusion Criteria: Angiogram Cohort. Patients who present 1) directly through the study site Emergency Department (ED) OR 2) as a transfer or referral patient from the ED of another institution OR 3) as a direct admission to the study site's Catheterization Laboratory by an ambulance service, who also met the following criteria: 1.Underwent urgent or emergent coronary angiography during the index presentation for suspected ischemic symptoms (including but not limited to chest pain [CP] and/or shortness of breath [SOB]) AND 2. Had a VPR ECG recorded during the index presentation prior to the angiogram AND 3. Had sufficient troponins to rule in or rule out acute myocardial injury, per the study site's institutional protocol. From this Angiogram Cohort, a group of patients will be identified who had angiographic evidence of ACO, defined as an acute lesion with TIMI flow 0 or 1 when evaluated by an experienced study-site adjudicator. | ||
| Non-ACO Angiogram Cohort | Inclusion Criteria: Angiogram Cohort. Each study site will first identify adult patients (age 18 years or older) who presented to the study site 1) directly through the study site ED OR 2) as a transfer or referral patient from the ED of another institution OR 3) as a direct admission to the study site's Catheterization Laboratory by an ambulance service, who also met the following criteria: 1. Underwent coronary angiography during the index presentation for suspected ischemic symptoms (including but not limited to CP and/or SOB AND 2. Had a VPR ECG recorded during the index presentation prior to the angiogram AND 3. Had sufficient troponins to rule in or rule out acute myocardial injury, per the study site's institutional protocol. From this Angiogram Cohort, those who had TIMI-2 or greater flow will be identified for several research questions. | ||
| Random ED Sample w Paced Rhythm but No AMI | Each site will select a random sample of all adult patients who present to the ED (or by ambulance directly to the Catheterization Lab) with suspected ischemic symptoms and a VPR ECG. Each study site will randomly select 5 unique encounters for every one 1 ACO subject identified by the site. If a study site identifies no ACO subjects, they will randomly select 30 unique encounters. Study subjects who are included as subjects in the Angiogram Cohort (data set #1, above) and who are also selected as part of the random sample (data set #2) will be identified in REDCap as subjects for analysis in both groups, but their data will be submitted only once. The primary control group selected from this search will be all patients in this group who do not meet criteria for acute myocardial injury, as defined by 1) all troponins below the 99th percentile or 2) Peak troponin < 3x the upper limit of normal AND no rise and/or fall of > 30%. |
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| Measure | Description | Time Frame |
|---|---|---|
| Sensitivity and Specificity of Modified Sgarbossa Criteria for Diagnosis of Acute Coronary Occlusion in the Setting of Ventricular Paced Rhythm in Patients with Potential Ischemic Symptoms | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Sensitivity and Specificity of the modified Sgarbossa criteria with criterion #2 extended from electrocardiogram leads V1-V3 to leads V1-V6 | 7 days | |
| Performance characteristics of the modified Sgarbossa criteria using a maximum ST/S ratio of -0.20, and of -0.30, instead of -0.25 |
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Inclusion Criteria:
Exclusion Criteria:
Exclusion from Primary Analysis:
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I. Adults who presented either 1) directly through the Emergency Department (ED), 2) as a transfer or referral patient, or 3) as a direct ambulance admission to the Catheterization Laboratory, who also:
II. Next, each study site will identify all adult ED patients with a VPR ECG recorded during the index presentation who presented with suspected ischemic symptoms. Simple random selection will be used to identify subjects from this population. There may be overlap between this group and the angiogram group above and this will be considered at the data analysis stage (see Procedures Manual for more detail).
The first group will not be a probability sample, but the second group will be.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Stephen W Smith, M.D. | Contact | 612-875-4226 | smith253@umn.edu | |
| Deborah L Zvosec, Ph.D. | Contact | 612-432-1677 | Deborah.Zvosec@hcmed.org |
| Name | Affiliation | Role |
|---|---|---|
| Kenneth W Dodd, M.D. | Hennepin County Medical Center, Minneapolis, MN | Study Chair |
| Stephen W Smith, M.D. | Hennepin County Medical Center, Minneapolis, MN | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hennepin County Medical Center | Recruiting | Minneapolis | Minnesota | 55415 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23256914 | Background | O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Jan 29;61(4):e78-e140. doi: 10.1016/j.jacc.2012.11.019. Epub 2012 Dec 17. No abstract available. | |
| 22922414 |
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| ID | Term |
|---|---|
| D000072657 | ST Elevation Myocardial Infarction |
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ED Patients w Paced Rhythm Without AMI excluded | Each site will select a random sample of all adult patients who present to the ED (or by ambulance directly to the Catheterization Lab) with suspected ischemic symptoms and a VPR ECG. Each study site will randomly 5 unique encounters for every 1 ACO subject identified by the site. If a study site identifies no ACO subjects, they will randomly select 30 unique encounters. Study subjects who are included as subjects in the Angiogram Cohort (data set #1, above) and who are also selected as part of the random sample (data set #2) will be identified in REDCap as subjects for analysis in both groups, but their data will be submitted only once. The secondary control group will include patients in this group in whom Acute MI cannot be excluded because they either have at least 1 troponin > 3x the upper limit of normal or they have at least 1 troponin between 1x and 3x the ULN AND have a rise and/or fall of at least 30%. |
| 7 days |
| Performance characteristics of absolute ECG millimeter measurements of ST discordance (including both discordant ST elevation and ST depression), using various ratio cutoffs (e.g. -0.2, -0.25, -0.3). | 7 days |
| Performance characteristics of 0.5 mm (vs. 1 mm) concordant ST-deviation. | 7 days |
| Performance characteristics of non-concave ST-morphology | 7 days |
| Mean QRS amplitude of occlusion vs. no occlusion groups. Plot receiver-operator curve for QRS amplitude | 7 days |
| Find mean T-wave amplitude in occlusion vs. no occlusion groups. Plot ROC curves for T/QRS ratio between groups. | 7 days |
| Mean QTc, JTc, and TpTe in occlusion vs no occlusion groups, and plot ROC curves for QTc, JTc, and TpTe | 7 days |
| Multivariate regression model including measurements of concordant and discordant ST elevation or depression, and of QRS amplitude, all in millimeters, and of repolarization time, in milliseconds. | 7 days |
| Deborah L Zvosec, Ph.D. |
| Hennepin Healthcare Research Institute |
| Study Director |
| Rehan Karim, MBBS | Hennepin County Medical Center, Minneapolis, MN | Study Chair |
| Louise Cullen, MD | Royal Brisbane and Women's Hospital | Study Chair |
| Richard Body, MD, PhD | The University of Manchester | Study Chair |
| Background |
| Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction; Thygesen K, Alpert JS, White HD, Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA, Chaitman BA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S; ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct;33(20):2551-67. doi: 10.1093/eurheartj/ehs184. Epub 2012 Aug 24. No abstract available. |
| 8880802 | Background | Sgarbossa EB. Recent advances in the electrocardiographic diagnosis of myocardial infarction: left bundle branch block and pacing. Pacing Clin Electrophysiol. 1996 Sep;19(9):1370-9. doi: 10.1111/j.1540-8159.1996.tb04217.x. No abstract available. |
| 23127386 | Background | Jaffe AS. Third universal definition of myocardial infarction. Clin Biochem. 2013 Jan;46(1-2):1-4. doi: 10.1016/j.clinbiochem.2012.10.036. Epub 2012 Nov 2. No abstract available. |
| 21757183 | Result | Nielsen PH, Terkelsen CJ, Nielsen TT, Thuesen L, Krusell LR, Thayssen P, Kelbaek H, Abildgaard U, Villadsen AB, Andersen HR, Maeng M; Danami-2 Investigators. System delay and timing of intervention in acute myocardial infarction (from the Danish Acute Myocardial Infarction-2 [DANAMI-2] trial). Am J Cardiol. 2011 Sep 15;108(6):776-81. doi: 10.1016/j.amjcard.2011.05.007. Epub 2011 Jul 15. |
| 8559200 | Result | Sgarbossa EB, Pinski SL, Barbagelata A, Underwood DA, Gates KB, Topol EJ, Califf RM, Wagner GS. Electrocardiographic diagnosis of evolving acute myocardial infarction in the presence of left bundle-branch block. GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) Investigators. N Engl J Med. 1996 Feb 22;334(8):481-7. doi: 10.1056/NEJM199602223340801. |
| 21079708 | Result | Maloy KR, Bhat R, Davis J, Reed K, Morrissey R. Sgarbossa Criteria are Highly Specific for Acute Myocardial Infarction with Pacemakers. West J Emerg Med. 2010 Sep;11(4):354-7. |
| 26678648 | Result | Meyers HP, Limkakeng AT Jr, Jaffa EJ, Patel A, Theiling BJ, Rezaie SR, Stewart T, Zhuang C, Pera VK, Smith SW. Validation of the modified Sgarbossa criteria for acute coronary occlusion in the setting of left bundle branch block: A retrospective case-control study. Am Heart J. 2015 Dec;170(6):1255-64. doi: 10.1016/j.ahj.2015.09.005. Epub 2015 Sep 24. |
| 22939607 | Result | Smith SW, Dodd KW, Henry TD, Dvorak DM, Pearce LA. Diagnosis of ST-elevation myocardial infarction in the presence of left bundle branch block with the ST-elevation to S-wave ratio in a modified Sgarbossa rule. Ann Emerg Med. 2012 Dec;60(6):766-76. doi: 10.1016/j.annemergmed.2012.07.119. Epub 2012 Aug 31. |
| D014652 |
| Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |