Among Unstable Angina and Non-ST Elevation MI Patients, Transient Myocardial Ischemia and Early Invasive Treatment are Predictors of Major In-Hospital Complications

Abstract

Background

Treatment for unstable angina (UA) or non-STEMI (NSTEMI) is aimed at plaque stabilization to prevent infarction. Two treatment strategies are: (1) invasive (i.e., cardiac catheterization laboratory < 24 hours after admission), or (2) selectively invasive (i.e., medications with cardiac catheterization laboratory > 24 hours for recurrent symptoms). However, it is not known if the frequency of transient myocardial ischemia (TMI), or complications during hospitalization varies by treatment.

Purpose

We examine; (1) occurrence of TMI in UA/NSTEMI, (2) compare frequency of TMI by treatment pathway and (3) determine predictors of in-hospital complications (i.e., death, MI, pulmonary edema, shock, arrhythmia w/intervention).

Method

Hospitalized patients with CAD (i.e., history of MI, PCI/stent, CABG, > 50% lesion via angiogram, or positive troponin) were recruited and 12-lead ECG Holter initiated. Clinicians, blinded to Holter data, decided treatment strategy; off-line analysis was done post discharge. TMI was defined as > 1 mm ST-segment ↑ or ↓, in > 1 ECG lead, > 1 minute.

Results

Of 291 patients, 91% were white, 66% male, 44% prior MI, and 59% prior PCI/stent or CABG. Treatment pathway was early in 123 (42%), and selective in 168 (58%). Forty-nine (17%) had TMI; 19 (15%) early invasive, 30 (18%) selective (p = 0.637). Acute MI after admission was higher in patients with TMI regardless of treatment strategy (early no TMI 4% vs yes TMI 21%; p = 0.020; selective no TMI 1% vs yes TMI 13%; p = .0004). Predictors of major in-hospital complication were TMI (OR 9.9; 95% CI, 3.84 to 25.78), and early invasive (OR 3.5; 95% CI, 1.23 to 10.20).

Conclusions

In UA/NSTEMI patients treated with contemporary therapies, TMI in not uncommon. The presence of TMI and early invasive treatment are predictors of major in-hospital complications.

Introduction

Acute coronary syndrome (ACS) is an umbrella term used to describe three specific diagnoses: unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Of these, UA and NSTEMI represent the largest proportion of ACS patients (two-thirds), and both are clinically challenging to diagnose since these patients often have atypical symptoms, and non-specific or no electrocardiographic (ECG) changes.^{1, 2} While biomarkers (i.e., troponin, CK-MB) are the gold standard for identifying myocardial infarction, these biomarkers are not sensitive to transient myocardial ischemia seen among ACS patients with UA, and may not become positive in patients with NSTEMI for several hours after symptom onset.³ Therefore, the treatment goal in UA/NSTEMI is timely identification of myocardial ischemia, or pre-infarction so that treatment(s) to optimize blood flow to the myocardium can be administered immediately. Because nurses provide ongoing assessment of patients for symptoms and electrocardiographic (ECG) changes associated with ACS, their role is pivotal in the detection of myocardial ischemia.

Currently, two treatment pathways are used, early invasive, which includes anti-ischemic, antithrombotic, and antiplatelet medications with coronary angiography in fewer than 24 hours after admission, or selectively invasive which include pharmacological management as above and angiography (typically >24 hours after admission) only if a patient fails to respond to intensive medical management (e.g., refractory angina, angina at rest, etc.) or has objective evidence of ongoing ischemia (e.g., dynamic ST-segment changes, positive biomarkers, etc.).³ Data from a number of randomized clinical trials and meta-analyses show that long term outcomes, two to five years, are better in UA\NSTEMI patients when an early invasive strategy is used versus a selectively invasive approach.^4–13 While long term outcomes are more favorable when an early invasive approach is used, some of these studies showed that death and MI are higher during the index hospitalization when an early invasive strategy is used, indicating increased hazard for early invasive.^{9, 14–16} Another important consideration is that cross-over from selectively invasive to invasive (i.e., PCI/stent, or coronary artery bypass graft surgery) is not uncommon.^{3, 8, 13, 17, 18} These studies show that both strategies have inherent risks/benefits; thus, current recommendations from the ACC/AHA guidelines for management of NSTEMI/UA emphasize the need to carefully risk stratify each patient when choosing the optimal treatment pathway.^{1, 2} There is a need for additional diagnostic information during hospitalization that might help clinicians decide which patients are responding well to anti-ischemia therapies and which need more aggressive management.

The 12-lead ECG is an important part of risk stratification in UA/NSTEMI because it has advantages over symptoms, which are often unreliable or non-existent,^19–25 or biomarkers, since ECG changes may precede the elevation of these blood tests.^{1, 3} Most commonly, clinicians obtain serial resting 12-lead ECGs, at 15 to 30 minute intervals, which are within guideline recommendations,³ and then apply dual lead continuous bedside ECG monitoring, ideally with ST-segment monitoring software activated,^{3, 26, 27} in order to expedite prompt detection of dynamic ST-segment changes indicative of ischemia. Several problems exist with these ECG approaches: (1) plaque rupture in ACS is dynamic, with cycles of occlusion and reperfusion, therefore, intermittent (“snap-shot”) ECG’s will miss acute ST-segment changes; (2) typical bedside monitors utilize only two to six ECG leads, rather than the recommended 12-leads, and (3) ST-segment monitoring software is vastly underutilized because it is plagued by a high number of false positive alarms.^26–32 Given the challenges clinicians face when risk stratifying UA/NSTEMI patients for early versus selectively invasive treatment, there is a need to reexamine the potential value of continuous 12-lead ECG ST-segment monitoring for detection of ischemia during the initial hospital phase. Continuous ECG information could add to our understanding of how these two treatment strategies evolve during the acute phase of treatment, which could ultimately be used to guide treatment for UA/NSTEMI.

The purpose of this study was three-fold: (1) examine the occurrence of transient myocardial ischemia (TMI), in a group of hospitalized UA/NSTEMI patients treated with contemporary therapy; (2) compare the frequency of TMI by treatment pathway, early versus selectively invasive, and (3) determine if demographic, clinical history, treatment strategy, or TMI predict serious in-hospital complications.

Methods & Materials

The COMPARE study (R21 NR-011202, PI: MMP), described previously,³³ was a prospective observational study designed to examine the frequency and consequences of TMI in hospitalized patients with UA/NSTEMI. In the COMPARE study, early invasive was defined as cardiac catheterization ≤ 24 hours after admission, with PCI/stent, or CABG if indicated. Selectively invasive was defined as pharmacological therapies, with cardiac catheterization >24 hours after hospital admission for failed aggressive medical treatment, as indicated by recurrent symptoms, ECG changes or positive stress test. Prior to recruitment and enrollment, approval from local institutional review boards was obtained, and all patients provided written informed consent prior to participation.

Sample/Settings

Inclusion criteria were: (1) admitted for treatment of UA, NSTEMI, or suspected ACS and (2) English speaking. Patients were excluded if, admitted for STEMI, were comatose, had a major psychiatric disorder, isolation precautions, or left bundle branch block or ventricular pacing because these conditions distort the ST-segment, making it difficult to reliably interpret the ECG for ischemia.²⁷

During the hours of 7 am to 5 pm, Monday through Friday, any patient presenting to the hospital for symptoms suggestive of ACS were invited to participate. Reported in this paper are only those with confirmed coronary artery disease (CAD) defined by: > 50% coronary lesion assessed by angiography, prior MI (i.e., medical record, or Q-waves on 12-lead ECG), positive biomarkers (i.e., troponin, CK-MB), or prior diagnosis of CAD (i.e., medical record, stent, CABG).

Data were collected at three private hospitals, two in Northern Nevada, one 380 beds the other 720 beds, and one in Northern California, with 366 beds; each hospital had well-developed cardiac service lines, board certified cardiologists, and a full range of invasive and non-invasive treatments (e.g., cardiac catheterization, operating rooms, cardiac rehabilitation, etc.).

12-Lead Holter Electrocardiographic Data

A 12-lead ECG Holter recorder (Mortara Instruments, Milwaukee, WI) was applied to patients meeting inclusion criteria. The Holter recorder was a “black box,” hence, data were not available to clinicians for decision making and there were no alarms generated: off-line analysis (described below) was conducted after hospital discharge. To ensure high quality ECG data, the skin on the torso was carefully prepped to remove any dirt, oils or creams that might interfere with signal quality, chest hair was cautiously clipped if necessary, radiolucent ECG electrodes were applied in the Mason-Likar limb lead configuration so as to not interfere with X-rays, and template ECGs were obtained with patients assuming supine, right- and left-side lying positions for use during off-line analysis to identify false positive ECGs due to positional changes.^34–36 The ECG Holter recorder remained in place until the patient was discharged. All patients were maintained on the hospital’s bedside ECG monitor (five or six lead system) as per the hospital protocol. The research assistant made frequent rounds during the day to maintain accurate placement of the ECG electrodes/lead wires and reapply any that had fallen off or been taken off for procedures (e.g., cardiac catheterization, echocardiogram, X-ray, etc.). The research assistant also retrieved demographic, clinical and outcome data from the electronic health record.

ECG Ischemia Analysis

The 12-lead ECG Holter data were downloaded to a research computer and analyzed after hospital discharge using H-Scribe Analysis System (Mortara Instruments, Milwaukee, WI). TMI was defined as ST deviation (elevation or depression) ≥ 100 microvolts in ≥ 2 ECG leads ≥ 60 seconds.²⁷ The H-Scribe software displays 24 hours of ECG tracings into trended data for easy inspection, and semi-automatically analyzes and codes ischemic events. While the H-Scribe provides semi-automated analysis, all of the ECG data were manually over read by the principal investigator (MMP) who was blinded to treatment group and clinical outcomes. In cases where there were questions about whether TMI was present/absent, two co-investigators (MGC, TMK) reviewed the ECG data and consensus was reached.

Outcome Measures

The six in-hospital complications, identified from EHR review, are listed in Table 1.

Table 1.

List of Six in-hospital complications identified from review of the electronic health record following hospital discharge.

1. Arrhythmia requiring intervention with antiarrhythmic drugs, defibrillation, pacemaker

2. Hemodynamic compromise requiring intervention with drugs, intra-aortic balloon pump counterpulsation, pacemaker

3. New onset pulmonary edema during hospitalization requiring treatment with diuretics

4. Unplanned transfer from the telemetry unit to coronary care unit (CCU) due to acute complications, including unrelieved chest pain, ECG changes, acute heart failure, arrhythmias, hemodynamic compromise, or cardiac arrest

5. Cardiovascular related death

6. MI after hospital admission:51, 52 Non-procedural MI: CK-MB > upper limit of normal or > 50% over previous level; Procedural MI: CK-MB > 3 times upper limit of normal or > 50% over previous post PCI/stent.

ECG = electrocardiogram

MI = myocardial infarction

CK-MB = creatine kinase – myocardium

PCI = percutaneous coronary intervention

Statistical Analysis

Data were analyzed using SPSS 22.0 (IBM Corporation 1994, 2014). Descriptive statistics were used to report demographic (i.e., age, gender, and ethnicity) and clinical information including medical history (i.e., prior angina, prior MI, hypertension, hyperlipidemia, diabetes, prior cardiac procedures, and CAD). In addition, descriptive statistics were used to examine procedures performed (i.e., PCI/stent, CABG, treadmill test, and echocardiography), and medications administered. These values are expressed as means ± standard deviation and percentages for the entire sample, and by treatment group. Categorical variables were analyzed with χ² analyses, with two sided Fisher’s Exact Test p-values reported. Two-tailed unpaired Student t-tests were used to compare continuous variables. A p value of < 0.05 was adopted as the critical value to determine whether differences between the two groups were statistically significant.

The occurrence of each complication was examined initially by χ² analyses. To determine if patients with TMI compared to patients without TMI had more major in-hospital complications, a multiple logistic regression analysis was conducted. The independent predictors entered into the model were covariates known to increase adverse events in ACS patients including: age, gender, ethnicity, history of angina, MI, PCI, CABG, diabetes, hypertension, hypercholesterolemia, as well as treatment group (early or selective), and presence of TMI detected with 12-lead ECG Holter. The multiple logistic regression analysis examined the odds afforded by each covariate for the occurrence of the dependent variable, any adverse in-hospital complication. Odds ratios, and adjusted odds ratios, with 95% confidence intervals were calculated.

Results

Of the 488 total subjects enrolled, 174 (36%) did not have confirmed CAD, and 23 (5%) had left BBB, or a ventricular pacemaker and therefore were excluded; hence, the final sample was 291 patients. The mean time from hospital presentation to enrollment was 6 ± 5 hours, and mean monitoring time was 28 ± 20 hours. Of the 291 patients, 123 (42%) were treated with an early invasive strategy and 168 (58%) with a selectively invasive strategy. Sample characteristics were typical of those with CAD with regards to age (65 ± 12 years), and gender (male, 66%), and did not differ by treatment strategy (Table 2). Of the mostly white sample (91%), a higher proportion of ethnic minorities were in the selectively invasive group, 12% vs 5%; p = 0.04. Patients with a history of prior angina were more likely to be treated with an early invasive approach (49% versus 24%; p = 0.001), whereas those with prior CAD (56% versus 81%; p = 0.001), MI (32% versus 53%; p = 0.001), or CABG (15% versus 31%; p = 0.001) were more often treated with a selectively invasive strategy. Prior PCI was equivalent by group. The only risk factor that differed by treatment group was diabetes (23% early versus 38% selective; p = 0.007). While the majority of patients were admitted to the telemetry unit (85%), a higher proportion of early invasive patients were admitted to the coronary care unit (18% versus 7%; p = 0.006). There were no differences with regards to prescribed medication by treatment group, except for beta blocker (87% early versus 71% selective; p = 0.002). Hospital length of stay was longer in the early invasive group 88 ± 92 hours versus 63 ± 62 hours; p = 0.018.

Table 2.

Demographic, Clinical History and Hospital Treatment for All Subjects and By Group

Characteristics	Study Sample n = 291	Early Invasive n = 123 (42%)	Selectively Invasive n = 168 (58%)	p-Value Early vs Selectively Invasive
	n (%)	n (%)	n (%)
Demographics
Age (mean ± SD, in years)	65 ± 12	63 ± 11	66 ± 12	0.062
Gender
Male	192 (66)	87 (71)	105 (63)	0.169
Race
Asian	6 (2)	0	6 (4)
American Indian/Alaskan Native	5 (2)	3 (2)	2 (1)	0.046
Black	10 (3)	3 (2)	7 (4)
Pacific Islander	5 (2)	0	5 (3)
White	265 (91)	117 (95)	148 (88)
Race Comparing Non-White to White	265 (91)	117 (95)	148 (88)	0.040*
Cardiac history
Prior angina	101 (35)	60 (49)	41 (24)	0.001**
Prior coronary artery disease	205 (70)	69 (56)	136 (81)	0.001**
Prior acute myocardial infarction	127 (44)	39 (32)	88 (53)	0.001**
Prior percutaneous coronary intervention	126 (43)	51 (42)	75 (45)	0.633
Prior coronary artery bypass graft	70 (24)	18 (15)	52 (31)	0.001**
Risk factors
Current Smoker	65 (22)	34 (28)	31 (19)	0.066
High cholesterol	209 (72)	87 (71)	122 (73)	0.792
High blood pressure	212 (73)	83 (68)	129 (77)	0.084
Diabetes	91 (31)	28 (23)	63 (38)	0.007*
Admission unit
Cardiac Telemetry	244 (85)	100 (81)	144 (86)	0.336
Cardiac Intensive Care	34 (12)	22 (18)	12 (7)	0.006*
Cardiac medications
Nitrate	171 (59)	79 (64)	92 (55)	0.118
Beta blocker	227 (78)	107 (87)	120 (71)	0.002*
Angiotensin-converting enzyme inhibitor	135 (46)	63 (51)	72 (43)	0.191
Antiplatelet	275 (95)	118 (96)	157 (94)	0.441
Aspirin	272 (94)	118 (96)	154 (92)	0.159
Antithrombin	209 (72)	94 (76)	115 (69)	0.148
Lipid lowering	224 (77)	101 (82)	123 (73)	0.091
Hospital Length of Stay
Hours	75 ± 82	88 ± 92	63 ± 62	0.018*

Early Invasive = pharmacological therapies, and cardiac catheterization ≤ 24 hours of hospital admission). Selectively Invasive = pharmacological therapies, with cardiac catheterization > 24 hours after hospital admission for failed aggressive medical treatment, as indicated by recurrent symptoms, ECG changes (hospital monitor or ordered 12-lead) or positive stress test.

^*p < 0.05;

^**p < 0.001

Frequency of Transient Myocardial Ischemia by Treatment Strategy

During 8,140 hours of 12-lead ECG Holter monitoring in 291 patients, 49 (17%) had 109 total TMI events. Of the 49 patients with TMI events, 19 (15%) were treated with early invasive, and 30 (18%) with selectively invasive (p = 0.637). The mean number of TMI events was 2 ± 1 (range one to six), and was equivalent by treatment group (p = 0.269). Of the 49 patients, only 16 (33%) experienced symptoms during TMI. A higher number of patients in the early invasive group complained of symptoms (early 10/19 [53%] versus selective 6/30 [20%]; p 0.028). Figure 1 illustrates transient ischemia in a patient treated with a selectively invasive treatment strategy.

Figure 1.

Illustrates a patient treated with a selectively invasive strategy. Top figure A shows an ST-segment trend (Y-axis electrocardiographic (ECG) leads; X-axis time). This trend was recorded in a 67 year old male presenting to the emergency department at 0345 with pain between his shoulder blades and in his right arm. His cardiac history included paroxysmal atrial fibrillation treated with metoprolol and Coumadin, the latter was discontinued for unknown reasons one month prior. His initial troponin I was normal and his 12-lead ECG was unremarkable for acute ischemia. A CT scan ruled out aortic aneurysm, and he was admitted to the telemetry unit for further workup.

At 0300 (23 hours post admission) abrupt ST elevation is seen in leads V1–V4, and concomitant ST depression in leads V6, I, II, aVF and III. At 0345 the patient complained of back and right arm pain. The nurse gave the patient a sublingual nitroglycerin, IV morphine and obtained a 12-lead ECG. The hospital 12-lead ECG was obtained after the ST changes resolved; hence ischemia was not diagnosed. The patient went back to sleep. At 0555 the patient contacted the nurse complaining of 10/10 chest pain in his back and both arms. A hospital 12-lead ECG obtained by the nurse showed ST elevation in leads V2 and V3. The cardiologist was phoned and the patient was taken urgently to the cardiac catheterization laboratory where a stent was placed in the left anterior descending coronary artery. Of note, are the small ST segment changes during the day at 1320, 1800, and 2345, likely indicating acute but brief coronary occlusion followed by reperfusion.

Figure A. ST-segment Trend with time on X-axis and ECG Leads on Y axis.

Figure B. Left figure shows leads V1 to V3 (#1 in above figure), was obtained before transient myocardial ischemia. Right figure shows leads V1 to V3 (#2 in above figure), was obtained during transient myocardial ischemia and illustrates ST elevation indicative of complete coronary occlusion.

Major In-Hospital Complications

Of the 291 patients, 26 (9%) experienced a major in-hospital complication. Regardless of treatment strategy, major in-hospital complications were higher in those with TMI (5% no TMI versus 31% with TMI; p < .001). Of the 26 patients who experienced a major in-hospital complication, a higher proportion were in the early invasive group (14% early versus 5% selective; p = 0.021). Table 3 shows comparisons of major in-hospital complications by treatment strategy, and absence/presence of TMI. No patient died. Acute MI after hospital admission was higher in patients who experienced TMI regardless of treatment strategy (early no TMI 4% versus yes TMI 21%; p = 0.020; selective no TMI 1% versus yes TMI 13%; p = 0.004). Acute pulmonary edema occurred more often in early invasive patients with TMI (no TMI 0 patients versus 16% yes TMI; p = 0.003), however this was not different in the selective group. Among the early invasive group, a higher proportion with TMI were transferred from telemetry to the CCU due to acute complications (no TMI 2% versus yes TMI 32%; p = 0.001). While more patients with TMI in the selectively invasive group were transferred from telemetry to CCU this was not statistically different (no TMI 1% versus yes TMI 7%; p = 0.083). When any major in-hospital complications was combined into one variable, patients with TMI, regardless of treatment strategy, had more complications (early no TMI 8% versus yes TMI 47%; p = 0.001; selective no TMI 2% versus yes TMI 20%; p = 0.001).

Table 3.

Comparison of major in-hospital complications by treatment strategy, with groups divided further by transient myocardial ischemia (TMI) absent/present (n = 291).

Complication	Early Invasive (n = 123) n (%)			Selectively Invasive (n = 168) n (%)
	No TMI 104 (85)	Yes TMI 19 (15)	p-value	No TMI 138 (82)	Yes TMI 30 (18)	p-value
Arrhythmia with intervention	5 (5)	1 (5)	1.000	0	0	0
Hemodynamic Compromise	1 (1)	1 (5)	0.268	0	0	0
Pulmonary Edema	0	3 (16)	0.003	1 (1)	0	1.000
Transfer from Tele to CCU	2 (2)	6 (32)	0.001	1 (1)	2 (7)	0.083
Death	0	0	0	0	0	0
MI After Admit	4 (4)	4 (21)	0.020	1 (1)	4 (13)	0.004
Any Major Complication	8 (8)	9 (47)	0.001	3 (2)	6 (20)	0.001

Two sided Fisher’s Exact Test is reported.

TMI = transient myocardial ischemia; MI = myocardial infarction; CCU = cardiac intensive care unit

Results of the logistic regression analysis examining whether demographic, clinical history, treatment strategy or TMI were predictors of major in-hospital complications are shown in Table 4. Compared to patients without TMI, patients with TMI were 9.9 times more likely to experience a major in-hospital complication (95% CI, 3.84 to 25.78, p=0.001), and patients treated with an early invasive strategy were 3.5 times more likely to have a major in-hospital complication (95% CI, 1.23 to 10.20, p=0.019).

Table 4.

Multiple logistic regression analysis with any major in-hospital complication used as the dependent variable.

Variable	B	P-value	Odds Ratio	95% Confidence Interval
Age	0.000	0.983	1.000	[0.959, 1.042]
Gender (male = 0 female = 1)	−0.612	0.278	0.542	[0.179, 1.638]
History Angina	0.097	0.845	1.102	[0.418, 2.902]
History MI	−0.287	0.632	0.750	[0.232, 2.427]
History PCI	−0.435	0.436	0.648	[0.217, 1.935]
History CABG	0.207	0.733	1.231	[0.374, 4.052]
Hypertension	0.392	.483	1.480	[0.495, 4.425]
Hypercholesterolemia	−0.575	0.267	0.563	[0.204, 1.553]
Transient myocardial Ischemia	2.297	0.001*	9.949	[3.839, 25.784]
Early Invasive Treatment Group	1.266	0.019*	3.547	[1.233, 10.204]

^*p < 0.05

Discussion

Among hospitalized UA/NSTEMI patients, TMI is not uncommon; occurring in 17%, and its presence is highly predictive of untoward in-hospital complications, particularly MI after admission. This study is unique in that we explore the frequency and consequences of TMI, measured with continuous 12-lead ECG, comparing groups by contemporary treatment pathway (early versus selectively invasive). At the outset of this study, we hypothesized TMI would be higher in the selectively invasive group, thinking reperfusion would not be as complete with medications alone, but found there was no difference in the rate of TMI between the groups. Our data indicate that when combined, major in-hospital complications are more common in patients with TMI, regardless of treatment pathway, but are more frequent among patients treated with an early invasive strategy as compared to those treated with a selectively invasive strategy.

Occurrence of Transient Myocardial Ischemia & Comparison by Treatment Pathway

As mentioned, we found that 17% of our sample had TMI (early 15%; selective 18%), which is similar to prior studies.^{23–25, 28, 30, 37–42} Importantly, most of these prior studies are dated, thus one could argue, may not represent patients treated with present-day therapies. However, we show that this pathology is still occurring in a relatively high number of UA/NSTEMI patients despite advances in ACS treatment modalities.

Similar to previous reports we found that only a third of the patients with TMI complained of chest pain or an angina equivalent.^{22, 24, 25, 28, 36, 37, 40, 41, 43} While this is not a new finding, our study underscores the problem of symptoms as a reliable indicator of myocardial ischemia. It is worth noting that a criterion for failing intensive medical management in patients treated with a selectively invasive strategy is refractory angina, or angina at rest. Given that the vast majority of patients with TMI do not experience symptoms during ECG detected ischemia, identification of failed medical therapy is very likely to be missed using symptoms alone.

Interestingly, we found that patients treated with an early invasive approach and who had TMI were more likely to experience symptoms as compared to the selectively invasive TMI group. This might suggest ischemic burden was higher in the early invasive group. In a prior study, we reported that patients were more likely to experience symptoms during TMI as the magnitude (microvolts) of ST-segment changes increased.³⁷ Our data highlight the value of continuously recorded 12-lead ECG’s as a way to identify transient, mostly silent, ischemia in NSTEMI/UA patients who represent the largest portion of patients presenting for ACS.

Major In-Hospital Complication Rates and Predictor of Major In-Hospital Complication

Major in-hospital complications were significantly higher in patients with TMI as compared to those without TMI regardless of treatment strategy group. When complications were assessed by group, patients treated with an early invasive strategy, and who had TMI, were more likely to have MI after admission, acute pulmonary edema, and require transfer from the telemetry unit to the CCU due to acute clinical changes. Among the selectively invasive group, those with TMI were more likely to experience MI after admission, and there was only a trend for those with TMI to be transferred from the telemetry unit to the CCU due to acute clinical changes. Our findings are in agreement with others showing the relationship of ECG detected TMI and untoward in-hospital complications. ^{19, 24, 25, 40, 43} Our findings are unique in that we examine not only the influence of TMI on in-hospital outcomes, but further assess this pathology by treatment group. Our finding of higher complication rates among early invasive patients is in contrast to a meta-analysis of a large number of randomized clinical trials with large sample sizes comparing early versus selectively invasive treatment, which showed a non-significant trend for higher rates for non-fatal MI among patient treated with an early invasive strategy.¹¹ A possible explanation for this may be how MI after admission was defined in our study compared to the aforementioned clinical trials, dated from 1994 to 2005, which are prior to high sensitivity troponin tests.

When controlling for known risk factors, logistic regression analysis showed two predictors of major in-hospital complication were; early invasive treatment (OR 3.5) and TMI (OR 9.9). The latter reiterates the sensitivity of TMI to identify high risk patients that might benefit from more aggressive anti-ischemia therapies.

Limitations

Convenience sampling did not yield all consecutive patients; thus patients were missed. This could be important because we examined the group by treatment pathway (early versus selective). It is possible patients presenting on the weekend or at night are more likely to have selective treatment due to cardiac catheterization laboratory availability and staffing. While the mean time from hospital presentation to initiation of 12-lead ECG Holter was six hours, it is possible we missed TMI during the early course of hospitalization, which would underestimate the rate of TMI. This was a hospital based study, therefore, long term outcomes cannot be examined.

Conclusions

The data from this study supports three conclusions: that nearly 20% of hospitalized UA/NSTEMI patients had TMI, that the frequency of TMI between treatment pathway (early vs selectively invasive) was not different and that major in-hospital complications were significantly higher in patients with TMI and early invasive treatment. An important strength of this study was that it included UA/NSTEMI patients treated with contemporary therapies. Transient myocardial ischemia detected with continuous 12-lead ECG is a significant contributor to major in-hospital complications and should be carefully assessed for in this patient population. This finding is not necessarily novel. However, there has been marked paucity of studies on this topic in the past decade – why? Underutilization of ST-segment monitoring software for detection of TMI is multifaceted including; physician factors (lack of interest or unaware of current recommendations for ST-segment monitoring),^{31, 32} nurse factors (lack of knowledge, skill and ability),^{29, 44, 45} and the high number of false positive alarms.⁴⁶ The value of assessing for dynamic, often clinically silent myocardial ischemia should not be ignored because of these issues, rather each of these challenges should be further explored and strategies and interventions developed to address each. For example, guidance from the American Association of Critical Care Nurses’ Alarm Management recommendations including: providing proper skin preparation for ECG electrodes, change ECG electrodes daily and customize alarm parameters and levels on ECG monitors.⁴⁷ Additionally, several quality assurance projects have shown that educational programs improve nurses knowledge and use of ST-segment monitoring.^48–50 This technology has the potential to identify high risk patients requiring treatment adjustments. Finally, while we highlight the usefulness of ECG monitoring for detection of TMI, this software might also be useful for ruling out cardiac pathology in patients with symptoms suggestive of ACS, in which there is not a cardiac cause.