a b s t r a c t

Background: Detecting acute ST-segment elevation myocardial infarction in the setting of Left bundle branch block (LBBB) remains a challenge to clinicians. Several diagnostic and triage algorithms have been pro- posed to accurately identify LBBB patients with an acute culprit vessel. We aimed to validate the algorithm pro- posed by Cai et al., which uses patients’ hemodynamic status and the modified Sgarbossa electrocardiography criteria to guide reperfusion therapy.

Methods: This retrospective study was performed with a chart review in emergency departments (EDs) of 2 med- ical centers, 2 Regional hospitals, and 1 local hospital. From January 2010 to December 2014, 2432 consecutive patients were diagnosed as having STEMI in the ED, including 65 patients with LBBB (2.6%).

Results: The patients with LBBB were older and more frequently presented with acute pulmonary edema (58.5% vs 22.1%, p b 0.001), cardiogenic shock (16.9% vs 6.3% p = 0.006), and VT/VF episodes (7.7% vs 2.2%, p = 0.034) and had a higher 30-day mortality rate (20.0% vs 10.4% p = 0.032) than those without LBBB. We then tested the algorithm proposed by Cai et al. and noted a sensitivity of 93.8% in identifying a culprit lesion.

Conclusions: The inconsistency of the Guideline recommendations reflects the uncertainty of diagnostic and ther- apeutic strategies and the pressing need for tools to accurately identify the true acute myocardial infarction in patients presenting with chest pain and LBBB. The algorithm proposed by Cai et al. had good sensitivity and would allow emergency physicians to implement the timely treatment protocol for this high-risk population.

(C) 2020

Introduction

For patients presenting with myocardial Ischemic symptoms, elec- trocardiograms (ECG) are a crucial test for accurate diagnosis and directing timely reperfusion therapy. However, the recognition of acute myocardial infarction (AMI) remains a challenge for clinicians due to baseline ST-segment deviations in the setting of left bundle branch block (LBBB) [1].

The 2004 American College of Cardiology (ACC)/American Heart As- sociation (AHA) ST-elevation myocardial infarction and the 2012 European Society of Cardiology (ESC) STEMI guidelines

Abbreviations: ECG, electrocardiogram; AMI, acute myocardial infarction; LBBB, left bundle branch block; ACC, American College of Cardiology; AHA, American Heart Association; ESC, European Society of Cardiology; STEMI, ST-elevation myocardial infarc- tion; VT, ventricular tachycardia; VF, ventricular fibrillation; ACS, acute coronary syndrome.

* Corresponding author at: Department of Emergency Medicine, Chang Gung Memorial Hospital, No.6, W. Sec., Jiapu Rd., Puzih City, Chiayi County 613, Taiwan.

E-mail address: [email protected] (Y.-C. Chen).

recommend reperfusion therapy for patients with the clinical presenta- tion of STEMI within 12 h of symptom onset and with new or presum- ably new LBBB [2,3]. This recommendation was made based on trials in the fibrinolytic era [4,5], and was rescinded in the 2013 ACC/AHA STEMI guidelines as several studies have demonstrated that a significant proportion of these patients did not have occluded culprit arteries at catheterization [6-9]. The current 2017 ESC STEMI guidelines recom- mend the use of Sgarbossa criteria to improve the diagnostic accuracy of STEMI in LBBB [10], and emphasized that the presence of a (pre- sumed) new LBBB does not predict MI per se [11].

Inconsistencies in the guideline recommendations reflect the uncer- tainty of diagnostic and therapeutic strategies and highlight the press- ing need for tools to accurately identify true AMIs among patients presenting with chest pain and LBBB. In contrast to calculating the abso- lute 5 mm discordant ST-segment elevation in the Sgarbossa’s rule [10], Smith et al. proposed a revised rule developed using a proportional criteria (any ST/S ratio b 0.25) [12]. H. Pendell Meyers et al. conducted a validation trial and reported improved sensitivity of the modified criteria compared with the original criteria (80% vs 49%, p b 0.001)

https://doi.org/10.1016/j.ajem.2020.03.024

0735-6757/(C) 2020

Fig. 1. Original diagnosis and triage algorithm as proposed by Cai [15] for patients with suspected acute myocardial infarction and left bundle branch block.

[13]. Andrea Di Marco et al. assessed the Smith rule (Sgarbossa score ? 3 and/or discordant ST-segment deviation with a ST/S or ST/R ratio ?-0.25) and reported that it had good specificity (90%) and sub- optimal sensitivity (67%) [14]. These validating studies demonstrated that although the modified Sgarbossa criteria was significantly more sensitive than the original criteria and remained highly specific, to fur- ther improve the Diagnostic efficacy and sensitivity, several diagnosis and triage algorithms were proposed.

Cai et al. proposed a diagnosis and triage algorithm (Fig. 1) that applied the patients’ hemodynamic status and modified Sgarbossa criteria for the guidance of reperfusion therapy, and evaluated serial ECGs, biomarkers, and bedside ECGs in patients who did not met the hemodynamic and ECG criteria [15]. This algorithm was used in a case series of 5 cases, and was reported to be useful for the identification of patients with suspected MI in the setting of LBBB and to determine the right time for catheterization [16].

The main goal of the present study was to provide an external vali- dation and clarify the performance of the algorithm proposed by Cai et al. in the accuracy of predicting AMI in chest pain and LBBB patients.

Method

Study design and population

We performed a retrospective cohort investigation of data of all adult STEMI patients (N18 years old) admitted to the Emergency De- partment (ED) of 5 hospitals between January 2010 and December 2014, using a prospective registry system. We recorded all patients with Typical symptoms of AMI with ST-elevation or LBBB at the study sites in our system. Therefore, the cohort used in this study included all patients with typical symptoms and signs of AMI and LBBB. This study was conducted in 5 branches of Chang Gung Memorial Hospital, with 2 medical centers, 2 regional hospitals, and 1 local hospital. A med- ical center was defined as a hospital equipped with at least 1 well- trained cardiac catheterization team and 24/7 accessibility and avail- ability of cardiologists, cardiovascular surgeons, and radiologists. A non-medical center, such as a regional hospital or a local hospital, was defined as a hospital without a cardiac catheterization team or without 24/7 availability of cardiologists, cardiovascular surgeons, and radiolo- gists. The study was approved by the Chang Gung Medical Foundation Institutional Review Board (IRB No. 201801520B0C501), and the

requirement for written informed consent was waived by the IRB owing to the retrospective and observational nature of this study.

Data obtained from all patients with an ED diagnosis of STEMI were reviewed and documented including clinical, ECG, echocardiographic, laboratory, angiographic, and follow-up data. Comparisons were made between all patients in the LBBB group and the STEMI without LBBB group.

Electrocardiographic analysis

All ECGs were interpreted in accordance with Standardized reporting Criteria. LBBB was defined as the presence of a QRS duration

>=120 ms, QS or rS in V1, broad notched or slurred R wave in leads I,

aVL, V5, and V6, and the absence of Q wave in leads V5, V6 and I [17]. The chronicity of LBBB was determined by reviewing previous ECGs available in the presenting hospital.

All ECGs were reviewed with blinded patient information and angio- graphic results to determine whether LBBB criteria and modified Sgarbossa criteria were present. When LBBB criteria were present, the modified Sgarbossa criteria were evaluated in patients with LBBB:

(A) ST-segment elevation of at least 1 mm (0.1 mV) concordant with the QRS complex in at least 1 lead; (B) ST-segment depression of 1 mm concordant with the QRS complex in leads V1 to V3, or (C) exces- sively discordant ST-segment elevation (any ST-segment elevation to S-wave ratio less than -0.25) [12].

Definition of study variables

A coronary culprit lesion was defined as the presence of an acute cor- onary occlusion with a Thrombolysis in Myocardial Infarction score of 0, total or near total occlusion, or an acute coronary lesion re- sponsible for the AMI, in accordance with new focal hypokinesia com- patible to the acute coronary occlusion territory shown in the echocardiography and the clinical presentation. The peak serum tropo- nin I or T levels were recorded and defined as abnormal if N0.04 ng/mL (I assay) or N14 ng/L (T assay). Hemodynamic instability features were not clearly defined in the original article proposed by Cai et al., and were defined in this study as patients presenting with cardiac arrest, cardio- genic shock (systolic blood pressure (SBP) of b90 mmHg or ED inotropies use), acute pulmonary edema, ventricular arrhythmia episodes (ventricular tachycardia with pulsation), with a ventricular rate of N50 beats per minute (bpm) related to high-grade atrioventricu- lar conduction block (AV block) or sinus node dysfunction.

We then used the diagnosis and triage algorithm proposed by Cai et al. to evaluate the patients presenting with LBBB, which included evaluation of hemodynamic status and initial ECG. We excluded the pa- tients without angiography for the definite final diagnosis to improve the accuracy of the prediction ability of the algorithm.

Statistical analysis

Statistical analysis was performed using MedCalc Statistical Soft- ware version 17.0.4 (MedCalc Software bvba, Ostend, Belgium; https://www.medcalc.org; 2017). Categorical variables are presented as percentages. Continuous variables are presented as medians with in- terquartile ranges. Mann-Whitney U test and Fisher’s exact test were used to compare the statistically significant differences between the LBBB and non-LBBB groups. Mortality at 3 days and 30 days were assessed using Kaplan-Meier analysis. A p value b0.05 was considered to be statistically significant.

Result

A total of 2432 patients were admitted with an Initial diagnosis of STEMI for whom the STEMI treatment was initiated. Of these, 65 pa- tients (2.6%) had LBBB on their presenting ECGs. Baseline characteristics

Table 1

Characteristics of ST-segment elevation myocardial infarction in patients with or without left bundle branch block (LBBB).

Characteristics	Non-LBBB group			LBBB group		p value did not undergo Angiography. The cardiac catheterization was not per-
	N = 2367 %			N = 65	%	formed in these patients for several reasons. Of the 13 patients without
Age (IQR)	63 (53-74)			76 (65-85)		b0.001 angiography reports, 7 were declined by the cardiologist due to the fact
Male	1809 76.4			39	60.0	0.002 that other differential diagnoses were more likely to be responsible for
Initial SBP	133			134		0.59 the ECG changes and clinical presentations; 6 were declined by the fam-
	(109-156)			(101.75-159.25)		ilies due to the extremely old age or multiple underlying diseases and
Initial DBP	80 (66-95)			77 (63-95.25)		0.51 the conservative medical treatment were preferred. Of the 7 excluded
Initial heart rate	84 (69-100)			90 (73.5-112.5)		0.09 patients who were declined by cardiologists, 5 patients would have re-
GCS	15 (15-15)			15 (14-15)		0.0001
Acute pulmonary	524 22.1			38	58.5	b0.001 ceived emergent catheterization and 1 would have received urgent
edema						catheterization using the Cai algorithm. Of the 52 patients enrolled
Cardiogenic shock	148	6.3	11		16.9	0.0006 with LBBB, 34 patients presented with hemodynamic instability, includ-
VT/VF episode	52	2.2	5		7.7	0.0167 ing 9 with cardiac arrest, 10 with cardiogenic shock, 25 with acute pul-
Cardiac arrest	129	5.4	11		16.9	0.0001 monary edema, 2 with pulsatile VT, and 3 with bradycardia (HR b 50).
Diabetes mellitus	161	6.8	6		9.2	0.90
Hypertension	31	1.3	1		1.5	1.00 Among the remaining 18 patients, there were 7 patients who met the
Hyperlipidemia	123	5.2	2		3.1	1.00 modified Sgarbossa criteria. The total 41 patients (79%) were referred
Coronary artery	41	1.7	1		1.5	1.00 for emergent Primary percutaneous coronary intervention .
disease
Congestive heart	3	0.1	0		0	1.00
failure						criteria, and 27 did not meet. A total of 22 of the 25 patients who met

Retrospective application of the diagnostic and triage algorithm pro- posed by Cai et al. for patients with LBBB and ACS-like symptoms is shown in Fig. 3. Of the initial 65 patients, 13 were excluded since they

Of the total 52 patients, 25 patients met the modified Sgarbossa

Creatinine (mg/dL) 1.12

Troponin I (highest	(0.90-1.64) 2.95	1.81 (0.16-7.83)		0.13
in 1st 24 h) Treated with PPCI	(0.41-16.04) 1375	58.1	34	52.3	0.35

1.45 (1.08-2.27) 0.0002

the modified Sgarbossa criteria had culprit coronary lesions (Table 2). Furthermore, 13 (52%) of the 25 patients and 3 (42.9%) of the 7 patients in the hemodynamic stable subgroup of patients met the modified Sgarbossa C criteria (Table 3).

1.09-5.01

CABG	81	3.4	0	0	0.54	The remaining 11 patients were examined with serial ECGs, serial
Mortality 3 days	Hazard ratio	-	2.33	95% CI:	0.0296	cardiac enzyme (troponin I or troponin T) levels, and bedside echocar-

Mortality 30 days Hazard ratio - 1.96 95% CI:

1.12-3.42

0.0181

diography. There would have been 7 patients (13%) referred for urgent cardiac catheterization, 6 of whom had elevated Troponin levels and 1 with positive echocardiographic evidence of regional hypokinesia. The

IQR: interquartile range; SBP: systolic blood pressure; DBP: diastolic blood pressure; GCS: Glasgow Coma Scale; VT: ventricular tachycardia; VF: ventricular fibrillation; PPCI: pri- mary percutaneous coronary intervention; CABG: coronary artery bypass graft.

of these patients are summarized in Table 1. Patients with LBBB were older; more frequently presented with cardiac arrest, cardiogenic shock, VT/VF episodes, acute pulmonary edema; had a higher 3-day and 30-day mortality rate; and showed a trend of lower peak Troponin I levels than patients without LBBB. Fig. 2 illustrates the process of pa- tient selection.

Fig. 2. The process of patient selection.

remaining 4 patients (8%) would have been managed as non-ACS chest pain, and ongoing evaluation to identify the underlying causes of chest pain.

Using this algorithm, all the 32 patients with acute culprit lesions would have been referred for emergent or urgent cardiac catheteriza- tion, and 30 of the 32 (93.8%) would have been identified initially with clinical presentation and ECG, and would have underwent reperfu- sion therapy without waiting for laboratory or echocardiography re- sults. Eleven of the 20 (55%) patients without a culprit lesion would have been referred for catheterization. This algorithm, which combines hemodynamic instability and the modified Sgarbossa criteria, yields a sensitivity of 93.8% and a negative predictive value of 81.8% to identify Culprit coronary artery lesions in patients with LBBB and ischemic symptoms, and has a specificity of 45% and a positive predictive value of 73.2% (Table 4). However, the Cai algorithm was applied retrospec- tively in our cohort. Further prospective validation should be investigated.

In regards to the relationship between the chronicity of LBBB and the prediction of AMI, there was no difference in the culprit coronary lesion rate between the 2 groups: patients with a new or Presumed new LBBB (nLBBB) had a 60.9% rate and patients with Old LBBB (oLBBB) had 66.7% rate. Among the 4 patients with oLBBB and culprit coronary lesions, 3 had new morphologic change of their initial ECG, and there were no ECG morphologic changes in the 2 patients with oLBBB and no culprit coronary lesions.

Discussion

The diagnosis of AMI in the presence of LBBB is extremely challeng- ing for emergency physicians and would lead many to undergo unnec- essary invasive procedures, radiation, and aggressive anticoagulation if all patients were treated with coronary angiography [8]. However, it is also very dangerous to delay reperfusion therapy in AMI patients with new LBBB due to the high severity and association with extensive myo- cardial damage [14,18,19].

Fig. 3. Application of the original algorithm in our patient groups with a retrospective analysis.

The 2017 EHJ STEMI guidelines recommend using the Sgarbossa criteria to improve the diagnostic accuracy, which was shown to have a high specificity (98%) but low sensitivity (20%) in the validation stud- ies [20]. The modified Sgarbossa criteria proposed by Smith et al. had been validated and shown to be more accurate, but was still limited by suboptimal sensitivity [13,14]. We believe that an algorithm that combines the evaluation of the clinical condition and ECG findings could further improve the diagnostic accuracy and sensitivity.

To our knowledge, this study is the first to validate the algorithm proposed by Cai et al. which evaluates the modified Sgarbossa criteria and hemodynamic conditions for the diagnosis of AMI in the patients with ischemic symptoms and LBBB [15].

Neeland et al. proposed a diagnosis and treatment algorithm in 2012 for patients with LBBB (new or old) with suspected MI and suggested that Fibrinolytic therapy should be considered if the patient is hemody- namically unstable or the ECG met the Sgarbossa concordance [21]. Re- cently, Pera et al. developed a new hierarchical algorithm in 2017 for patients with symptoms of ischemia and nLBBB and yielded a high sen- sitivity (97%) and negative predictive value (94%) [22]. In the group of patients with culprit coronary lesion, 37/71 (52%) were referred for pri- mary PCI, and 34/71 (48%) were referred for urgent coronary angiogram after cardiac biomarkers or the ECG suggested the likelihood of ACS. In the Pera et al. study, Sgarbossa concordance criteria was used, and spared the ST/S ratio criteria in the modified Sgarbossa C, due to con- cerns regarding its complexity in the emergent situation.

In the current study, application of the algorithm proposed by Cai et al. yielded high sensitivity (93.8%) and 30/32 of the patients with

Table 2

Proportion of LBBB patients who met the modified Sgarbossa criteria and had culprit cor- onary lesions.

culprit coronary lesions were referred for emergent cardiac angiogram and Primary PCI, similar to the Standard care of other STEMI patients without LBBB. Among the 32 patients with culprit coronary lesions, 22 of them met the modified Sgarbossa criteria, 10 met the concordant criteria, and the other 12 met the modified Sgarbossa C criteria alone. This reflects that an important factor that improved the sensitivity of this algorithm was the application of the modified Sgarbossa C criteria. The ratio of patients with culprit coronary lesions was the same in the group of patients with oLBBB and the group of patients with nLBBB. This finding was compatible with the study proposed by Chang et al. which concluded that chronicity of LBBB does not influence the risk of AMI [1]. In the current study, new changes in ECG morphology appeared to be more important for predicting the presence of culprit le-

sions than chronicity of LBBB.

Limitations

There are several limitations of this study, such as the observational and retrospective nature of the study. The retrospective application of the algorithm and the exclusion of the 13 patients who did not undergo angiography may raise concerns regarding selection bias and confound- ing factors. The timing of the ECG related to the angiogram may be var- iable due to the retrospective chart review nature of the study and the

Table 3

Distribution of Sgarbossa criteria met in the unstable and stable patient groups.

	Hemodynamically unstable	Hemodynamically stable
	patients (n = 18), n (%)	patients (n = 7), n (%)
A + B + modified C	3 (16.6%)	2 (28.6%)
A + B	0	0
A + modified C	4 (22.2%)	1 (14.3%)
A	1 (5.6%)	1 (14.3%)
B + modified C	0	0
B	0	0
Modified C	10 (55.6%)	3 (42.8%)

Patients meeting modified Sgarbossa criteria (n = 25), n (%)

Patients not meeting modified

Sgarbossa criteria (n = 27),

n (%)

Sgarbossa criteria A: ST-segment elevation of at least 1 mm (0.1 mV) concordant with

Culprit lesion present

22 (88%) 10 (37%)

the QRS complex in at least 1 lead; Sgarbossa criteria B: ST-segment depression of 1 mm concordant with the QRS complex in leads V1 to V3; modified Sgarbossa

No culprit lesion 3 (12%) 17 (63%)

criteria C: excessively discordant ST-segment elevation (any ST-segment elevation

to S-wave ratio less than -0.25).

Table 4

Application of the Cai algorithm to identify patients with ST-elevation myocardial infarc- tion requiring primary percutaneous coronary intervention for existing culprit vessels.

	Culprit lesion present (n = 32)	No culprit lesion (n = 20)
Emergent angiography (PPCI)	30	11
Urgent angiography	2	5
Treat as non-ACS	0	4

PPCI: primary percutaneous coronary intervention; ACS: acute coronary syndrome.

lack of a standard protocol. The relatively small sample size of LBBB pa- tients decreased the statistical significance in the differences between subgroups. A further limitation is the lack of high-sensitivity cardiac tro- ponin (hs-cTn) assays in the enrolled hospitals which may further in- crease the accuracy of AMI diagnosis if evaluated in combination with ECG [23]. Furthermore, the definition of hemodynamic instability in our study was different from that by Cai et al., resulting in a possible low specificity. This algorithm may need prospective validation with a larger sample size to prove its accuracy. Additionally, only patients un- dergoing angiography were enrolled in the study. This approach en- sures that all the diagnoses of culprit coronary lesions were definite; however, at the same time, this may cause ascertainment bias and de- crease the sample size of this study.

Conclusion

Patients with ischemic symptoms with LBBB remain a challenge to physicians due to their high risk and the difficulty in diagnosing AMI. Furthermore, guideline suggestions have been constantly changing. Several algorithms were proposed to increase the accuracy of diagnosis in these patients. In this study, the algorithm proposed by Cai et al. using the hemodynamic instability and modified Sgarbossa criteria was shown to be highly sensitive and allowed physicians to arrange emer- gent catheterization and reperfusion therapy without waiting for labo- ratory data as the standard care in patients with acute STEMI. Further validation of the algorithm with a larger cohort in a prospective study is warranted, as it may improve the accuracy of diagnosis and facilitate appropriate emergent angiogram and primary PCI activation.

Author contributions

YCL, YCC, YHC and KHW conceived the study, designed the method. YCC supervised the conduct of the data collection. YCC undertook re- cruitment of participating centers and patients and managed the data, including quality control. YCC provided statistical advice on study de- sign and analyzed the data; YCC chaired the data oversight committee. YCL, YCC, YHC and KHW drafted the manuscript, and all authors contrib- uted substantially to its revision. YCC takes responsibility for the paper as a whole.

CRediT authorship contribution statement

Yi-Chen Lai: Conceptualization, Methodology, Data curation, Writing - original draft. Yu-Han Chen: Investigation, Validation, Formal analysis. Kai-Hsiang Wu: Visualization, Resources. Yi-Chuan Chen: Su- pervision, Software, Writing - review & editing.

Declaration of competing interest

There is no conflict of interest in this study.

Acknowledgments

The authors are grateful to Po-Chang Wang, MD of the Department of Cardiology, Chiayi Chang Gung Memorial Hospital, for his assistance in ECG reading.

References

1. Chang AM, Shofer FS, Tabas JA, Magid DJ, McCusker CM, Hollander JE. Lack of asso- ciation between Left bundle-branch block and acute myocardial infarction in symp- tomatic ED patients. Am J Emerg Med 2009;27:916-21. https://doi.org/10.1016/j. ajem.2008.07.007.
2. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Man- agement of patients with acute myocardial infarction). J Am Coll Cardiol 2004;44: E1-211.
3. Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569-619. https://doi.org/10.1093/ eurheartj/ehs215.
4. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994;343:311-22. https://doi.org/10.1016/S0140-6736(94)

   91161-4.

   Antman EM. General hospital management. In: Julian DG, Braunwald E, editors. Management of acute myocardial infarction. London, England: WB Saunders Co Ltd; 1994. p. 42-4.

5. O’Gara PT, Kushner FG, Ascheim DD, Casey Jr DE, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Associa- tion Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:e78-140.
6. Larson DM, Menssen KM, Sharkey SW, Duval S, Schwartz RS, Harris J, et al. “False- positive” cardiac Catheterization laboratory activation among patients with suspected ST-segment elevation myocardial infarction. JAMA 2007;298:2754-60. https://doi.org/10.1001/jama.298.23.2754.
7. Lopes RD, Siha H, Fu Y, Mehta RH, Patel MR, Armstrong PW, et al. Diagnosing acute myocardial infarction in patients with left bundle branch block. Am J Cardiol 2011; 108:782-8. https://doi.org/10.1016/j.amjcard.2011.05.006.
8. Jain S, Ting HT, Bell M, Bjerke CM, Lennon RJ, Gersh BJ, et al. Utility of left bundle branch block as a diagnostic criterion for acute myocardial infarction. Am J Cardiol 2011;107:1111-6. https://doi.org/10.1016/j.amjcard.2010.12.007.
9. Sgarbossa EB, Pinski SL, Barbagelata A, Underwood DA, Gates KB, Topol EJ, et al. Elec- trocardiographic 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;334:481-7. https://doi.org/10.1056/NEJM199602223340801.
10. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. ESC Guidelines for the management of acute myocardial infarction in patients present- ing with STsegment elevation: The Task Force for the management of acute myocar- dial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119-77.
11. 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;60: 766-76. https://doi.org/10.1016/j.annemergmed.2012.07.119.
12. Meyers HP, Limkakeng Jr AT, Jaffa EJ, Patel A, Theiling BJ, Rezaie SR, et al. 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;170: 1255-64. https://doi.org/10.1016/j.ahj.2015.09.005.
13. Di Marco A, Anguera I, Rodriguez M, Sionis A, Bayes-Genis A, Rodriguez J, et al. As- sessment of Smith algorithms for the diagnosis of acute myocardial infarction in the presence of left bundle branch block. Rev Esp Cardiol (Engl Ed) 2017;70: 559-66. https://doi.org/10.1016/j.recesp.2016.11.010.
14. Cai Q, Mehta N, Sgarbossa EB, Pinski SL, Wagner GS, Califf RM, et al. The left bundle- branch block puzzle in the 2013 ST-elevation myocardial infarction guideline: from falsely declaring emergency to denying reperfusion in a high-risk population. Are the sgarbossa criteria ready for prime time? Am Heart J 2013;166:409-13. https://doi.org/10.1016/j.ahj.2013.03.032.
15. Ciliberti G, Del Pinto M, Notaristefano F, Zingarini G, Ambrosio G, Cavallini C. Left bundle branch block, chest pain and catheterization laboratory activation: an un- avoidable cascade reaction? J Electrocardiol 2016;49:504-8. https://doi.org/10. 1016/j.jelectrocard.2016.02.020.
16. Surawicz B, Childers R, Deal BJ, Gettes LS, Bailey JJ, Gorgels A, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardio- gram part III: intraventricular conduction disturbances. Circulation 2009;119(10): e235-40. https://doi.org/10.1161/CIRCULATIONAHA.108.191095 (17).
17. Stenestrand U, Tabrizi F, Lindback J, Englund A, Rosenqvist M, Wallentin L. Co- morbidity and myocardial dysfunction are the main explanations for the higher 1-year mortality in acutemyocardial infarction with left bundle-branch block. Circulation 2004;110:1896-902. https://doi.org/10.1161/01.CIR.0000143136.

    51424.38.

    Moreno R, Garcia E, Lopez de Sa E, Abeytua M, Soriano J, Ortega A, et al. Implications of left bundle branch block in acute myocardial infarction treated with primary an- gioplasty. Am J Cardiol 2002;90:401-3. https://doi.org/10.1016/S0002-9149(02) 02497-9.

18. Tabas JA, Rodriguez RM, Seligman HK, Goldschlager NF. electrocardiographic criteria for detecting acute myocardial infarction in patients with left bundle branch block: a metaanalysis. Ann Emerg Med 2008;52:329-36. https://doi. org/10.1016/j.annemergmed.2007.12.006.
19. Neeland IJ, Kontos MC, de Lemos JA. Evolving considerations in the management of patients with left bundle branch block and suspected myocardial infarction. J Am Coll Cardiol 2012;60:96-105. https://doi.org/10.1016/j.jacc.2012.02.054.
20. Pera VK, Larson DM, Sharkey SW, Garberich RF, Solie CJ, Wang YL, et al. New or pre- sumed new left bundle block in patients with suspected ST-elevation myocardial

    infarction. Eur Heart J Acute Cardiovasc Care 2018;7(3):208-17. https://doi.org/10. 1177/2048872617691508.

    Nestelberger T, Cullen L, Lindahl B, Reichlin T, Greenslade JH, Giannitsis E, et al. Di- agnosis of acute myocardial infarction in the presence of left bundle branch block. Heart 2019;105(20):1559-67. https://doi.org/10.1136/heartjnl-2018-314673.