- Email: [email protected]
Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity
RESUS 8232 No. of Pages 7
RESUSCITATION XXX (2019) XXX
XXX
Available online at www.sciencedirect.com
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Clinical paper
Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity R. Lagedal a, * , L. Elfwe´n b , M. Jonsson c , E. Lindgren a , D. Smekal a,e , L. Svensson c , S. James d , P. Nordberg c , S. Rubertsson a a
Department of Surgical Sciences/Anesthesiology and Intensive Care Medicine, Uppsala University, Sweden Department of Clinical Science and Education, So¨dersjukhuset, Karolinska Institute, Sweden c Department of Medicine, Center for Resuscitation Science, Karolinska Institute, Solna, Sweden d Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center Uppsala University, Sweden e UCPR, Uppsala Center for Prehospital Research, Uppsala University, Sweden b
Abstract Introduction: The relations between specific ECG patterns and coronary angiographic findings in cardiac arrest patients with different comorbidities are not properly assessed. More evidence is needed to identify patients with the highest risk for acute coronary artery disease as a cause of the cardiac arrest. This study aims to describe the coronary artery findings after cardiac arrest in relation to ECG and comorbidity. Method: A retrospective study of out-of-hospital cardiac arrest patients, with coronary angiography performed within 28 days. ECG on admission, comorbidity, PCI attempts and angiographic findings are described. Data were retrieved from national registries in Sweden. Results: Among 1133 patients with available ECG and angiography information the mean age was 64 years. The rate of shockable rhythm was 79%. The total incidence of any significant stenosis in cardiac arrest patients without ST-elevation who underwent coronary angiography within 28 days was 71%. The incidence of any stenosis in patients with normal ECG was 62.1% and in patients with LBBB, 59.3%. In patients with ST-depression or RBBB, PCI attempts were made in 47.1% and 42.4% respectively, compared with 33.3% in patients with normal ECG. Among patients without ST-elevation, those with diabetes mellitus and those with initial shockable rhythm respectively, 84.8% and 71.5 had at least one significant stenosis. Conclusion: Our study suggests, that evaluation of ECG patterns and comorbidities in out-of-hospital cardiac arrest patients without ST-segment elevation may be important to identify those with a high risk of coronary artery lesions that could benefit from early revascularization. Keywords: Cardiac arrest, Coronary angiography, Percutaneous coronary intervention
Introduction Out-of-hospital cardiac arrest (OHCA) is, despite improvement in resuscitation and post arrest care, a condition with high mortality. Even in patients with return of spontaneous circulation (ROSC) admitted to intensive care, mortality rates are approximately 50%.1 The majority of OHCAs are of cardiac cause most often due to acute coronary syndromes2,3 and today, there is consensus that patients
presenting with ST-segment elevation on the electrocardiogram (ECG) after ROSC should undergo immediate coronary angiography.1 Retrospective studies show a high incidence of acute coronary occlusions and significant stenosis suitable for revascularization among these patients.2 5 On one hand, ST-elevations on the ECG seem to have good positive predictive value in diagnosing acute coronary lesions even after cardiac arrest. It would therefore be reasonable to believe that these patients would benefit from immediate coronary angiography. On the other hand, it seems that
* Corresponding author at: Akademiska sjukhuset, 751 85, Uppsala, Sweden. E-mail addresses: [email protected] (R. Lagedal), [email protected] (L. Elfwén), [email protected] (M. Jonsson), [email protected] (E. Lindgren), [email protected] (D. Smekal), [email protected] (L. Svensson), [email protected] (S. James), [email protected] (P. Nordberg), [email protected] (S. Rubertsson). https://doi.org/10.1016/j.resuscitation.2019.09.021 Received 17 March 2019; Received in revised form 15 August 2019; Accepted 16 September 2019 Available online xxx 0300-9572/© 2019 Elsevier B.V. All rights reserved.
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
2
RESUSCITATION XXX (2019) XXX
the negative predictive value of ECG after ROSC is lower. Several studies have shown rates of acute coronary occlusion at approximately 30% and a high incidence of significant coronary artery stenosis in patients without ST-elevation thereby challenging the use of ECG as an accurate instrument for detecting coronary artery occlusion.2,3,5 7 If cardiac arrest patients without ST-segment elevation actually benefit from immediate coronary angiography and potential percutaneous coronary intervention (PCI) is today unknown. Until recently, only retrospective studies, with varying results, have been presented. A newly published trial did not show any differences in survival or neurologic outcome in patients resuscitated from cardiac arrest without ST-segment elevation randomized to either immediate or delayed coronary angiography.8 The rate of PCI in this trial was 33% in patients randomized to immediate coronary angiography which is lower than in many of the retrospective studies comparing early vs late coronary angiography. Guidelines suggest that coronary angiography should be considered in high risk patients, but the evidence to support this is weak.1,9 In the majority of the retrospective studies and guidelines, the non-ST-elevation patients are presented as one group, and little is known about how specific ECG changes and previous comorbidities affects the risk of coronary vessel pathology after cardiac arrest. Previous studies addressing more specific ECG changes have been rather small with a large proportion of ST-elevation patients.2,5,7,10 The aim of this study is to describe coronary angiographic findings and rate of PCI after cardiac arrest in relation to specified ECG changes and comorbidities to be able to define the high-risk population that may benefit from an immediate coronary angiography.
Registers Swedish Register for Cardio-pulmonary Resuscitation (SRCR): A national registry covering all emergency medical services in Sweden with an almost 100% coverage for OHCA in which resuscitation attempts are made. Contains mainly pre-hospital data. Swedeheart (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies). Swedeheart is a national quality register consisting of several separate registers in the
XXX
cardiovascular field, e.g. SCAAR (Swedish Coronary Angiography and Angioplasty Registry) and RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive Care Admission). The coverage for SCAAR has been excellent during the years presented in this study with coverage rates over 97% every year. National Patient Register (NPR) is run by the Swedish National Board of Health and Welfare. Diagnoses set on Swedish patients are registered in NPR and the coverage is almost 100%. Due to the Swedish system with unique personal identification numbers, data from other registers can be merged with NPR. Information on date of the discharge diagnoses is available, thus enabling us to use only diagnoses made prior to the cardiac arrest.
Method This is a national retrospective descriptive study. Data from four different Swedish registers were retrieved and analyzed. Data from the Swedish Register for Cardio-pulmonary Resuscitation (SRCR) were ordered from the registry holder. We requested data on all patients admitted alive to Swedish hospitals after OHCA and registered in the SRCR regardless of initial ECG rhythm. The data withdrawal was made for the time period 2008 2013 and 5177 patients were identified and data sent to us for further analyses (Fig. 1). Patients registered as awake on admission (n = 1315) were excluded. Data were then merged with the Swedeheart registry to identify patients with coronary angiography performed during the first 28 days after the cardiac arrest. Using date of the coronary angiography, patients were separated into one “early group” with angiography performed the same date as the cardiac arrest and one “late group” with angiography performed between day 2 28 after the cardiac arrest. Patients with no coronary angiography or angiography performed later than 28 days post cardiac arrest were excluded (n = 2586). From Swedeheart, coronary angiographic findings and procedures were retrieved as well as data on ECG findings after ROSC. In Swedeheart, a significant coronary artery stenosis is defined as 50% stenosis or significant fractional flow reserve (FFR < 0.8). If ECG data were missing in Swedeheart, this was completed from patients’ electronic health records. ECG’s from electronic health records were interpreted by a cardiologist blinded
Fig. 1 – Participant flow (Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity). Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
RESUSCITATION XXX (2019) XXX
to angiography data. Those without ECG data, despite this completion, were excluded (n = 143). The definition of the various ECG patterns follows international guidelines as stated by the international cardiology organizations.11,12 ECG classified as “other” includes abnormal findings that do not fulfil the criteria for the other groups, e.g. pacemaker rhythm and other broad QRS patterns not meeting the criteria for bundle branch blocks. Before 2017 guidelines, a more active approach with immediate coronary angiography, in line with that recommended for ST-segment elevation, were recommended for patients with left bundle branch block (LBBB). Thus, in our analysis, patients with LBBB are separated from other patients with non-ST-elevation. Finally, comorbidity data, based on diagnoses set prior to the cardiac arrest, were collected from the National Patient Register (NPR). All Swedish citizens have a unique personal identification number including date of birth. Data retrieved from SRCR included personal numbers and these were used to merge data with the other registers as well as obtaining individual patient records. After completion with data from NPR, the registry holders removed the personal numbers, thus anonymizing data for the research group to protect the patients’ integrity. The linking of the various data bases was made by the registry holders and the use of unique personal numbers ensures that patients were not linked to wrong data. During the years included in this study, Swedeheart contains no data on which lesion was considered as the culprit lesions. The study was approved by the regional ethical committee in Stockholm (Identifier: 2014/1139-31/2). The approval included that data could be retrieved without patient consent.
Statistics Background data and coronary angiographic data are presented in tables. Flowchart on the inclusion process are presented in Fig. 1. All angiographic data presented has been mandatory to register in the
3
XXX
Swedeheart registry minimizing the problem with missing data. Comparison between various ECG groups and the rate of PCI attempts were analyzed with logistic regression and presented as odds ratios with 95% confidence intervals. Significance testing for categorical data were made with the use of the chi-square test and for continuous data with the Mann-Whitney test.
Results We included 1133 patients with cardiac arrest between 2008 2013 in the final analysis. The incidence of the various ECG patterns and baseline characteristics are presented in Table 1. Correlations between ECG pattern/comorbidity with coronary angiography findings are presented in Table 2 and Table 3. In Table 4, coronary angiographic findings in relation to ECG in patients with shockable and non-shockable rhythm are presented. Table 5 presents a comparison between the patients included in the analyses and patients admitted to Swedish hospitals during the study period and not included in the analyses (see Fig. 1). In patients without ST-elevation or LBBB, 71% had at least one significant stenosis, and PCI attempts were made in 41.6%. In the ECG subgroups 79% of patients with ST-depression had significant stenoses and PCI attempts were made in 47.1%. If ECG were interpreted as normal the rate of any significant stenosis was 62.1% and PCI attempts were made in 33.3%. When comparing rate of PCI attempts for the ECG subgroups to patients with normal ECG, patients with ST-depression and those classified as “other findings” had significantly higher rates, OR 1.78 (CI 1.13 2.82) and 1.65 (CI 1.04 2.61) respectively. Patients with previous ischaemic heart disease or diabetes mellitus had a high rate of significant stenoses but the proportion of patients where PCI attempts were made, were similar between the analyzed comorbidity groups and in the same numerical range as for the whole group of non-ST-elevation group (where all
Table 1 – Background characteristics for included patients in relation to ECG. ECG
All
n Female (%) Shockable rythm (%) Age (std) IHDe (%) Kidneyf (%) COPDg (%) DMh (%) Early angioi (%) Late angioj (%)
1133 249 (22) 897 (79) 64.3 (12) 181 (16) 22 (2) 43 (4) 119 (11) 829 (73) 304 (27)
STelevation 463 92 (20) 372 (80) 63.9 (12) 64 (14) 7 (2) 9 (2) 39 (8) 418 (90) 45 (10)
LBBBa 108 23 (21) 86 (80) 65.1 (10) 20 (19) 3 (3) 3 (3) 14 (13) 83 (77) 25 (23)
Non-ST elevationb
Normal ECG
562 134 (24) 439 (78) 64.5 (12) 97 (17) 12 (2) 31 (6) 66 (12) 329 (59) 233 (41)
153 40 (26) 115 (75) 61.3 (14) 34 (22) 2 (1) 12 (8) 18 (12) 73 (48) 80 (52)
STdepression 157 37 (24) 129 (82) 65.3 (11) 23 (15) 4 (3) 6 (4) 14 (9) 93 (59) 64 (41)
Pathologic T-wave
RBBBc
Otherd
38 11 (29) 24 (63) 64.6 (13) 8 (21) 1 (3) 3 (8) 6 (16) 16 (42) 22 (58)
59 11 (19) 59 (100) 68.2 (11) 10 (17) 1 (2) 3 (5) 9 (15) 37 (63) 22 (37)
155 35 (23) 112 (72) 65.3 (12) 22 (14) 4 (3) 7 (5) 19 (12) 109 (70) 46 (30)
Background characteristics and rate of early vs late coronary angiography described for the whole population and the various ECG findings. a Left bundle branch block. b All patients except ST-elevation and LBBB. c Right bundle branch block. d Other ECG findings, e.g. pacemaker rhythm. e Ischaemic heart disease. f Kidney disease (acute or chronic). g Chronic obstructive pulmonary disease. h Diabetes mellitus (Type 1 or 2). i Coronary angiography performed the same date as cardiac arrest. j Coronary angiography performed between 1 and 28 days after cardiac arrest. ECG = Electro cardiogram.
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
4
RESUSCITATION XXX (2019) XXX
XXX
Table 2 – Coronary angiographic findings in relation to ECG. ECG All patients Left maine (%) 1 vesself (%) 2 vesself (%) 3 vesself (%) Normalg (%) PCI attemptedh (%)
ST elevation
32 (6.8) 198 (42.8) 105 (22.7) 79 (17.1) 36 (7.8) 374 (80.8) OR 8.40 (5.59 12.64) PCI successi (%) 345 (92.2) Early coronary angiographyj Left maine (%) 27 (6.4) 1 vesself (%) 182 (43.5) 97 (23.2) 2 vesself (%) 71 (17.0) 3 vesself (%) 30 (7.2) Normalg (%) PCI attempted (%) 346 (82.8) 318 (91.9) PCI successi (%) Late coronary angiographyk Left maine (%) 5 (11.1) 16 (35.6) 1 vesself (%) 8 (17.8) 2 vesself (%) 8 (17.8) 3 vesself (%) 6 (13.3) Normalg (%) 28 (62.2) PCI attempted (%) 27 (96.4) PCI successi (%)
LBBBa
Non-ST elevationb
Normal
ST depression
Pathologic T-wave
RBBBc
Otherd
6 (5.5) 12 (11.1) 19 (17.6) 23 (21.3) 44 (40.7) 36 (33.5) OR 1.00 (0.59 1.69) 31 (86.1)
44 (7.8) 138 (24.6) 91 (16.2) 104 (18.5) 163 (29.0) 234 (41.6)
207 (88.5)
13 (8.5) 35 (22.9) 20 (13.1) 22 (14.4) 58 (37.9) 51 (33.3) OR 1.00 (ref) 49 (96.1)
16 (10.2) 38 (24.2) 32 (20.4) 33 (21.0) 33 (21.0) 74 (47.1) OR 1.78 (1.13 2.82) 66 (89.2)
4 (10.5) 8 (21.1) 3 (7.9) 11 (28.9) 9 (23.7) 14 (36.8) OR 1.17 (0.56 2.45) 11 (78.6)
5 (8.5) 17 (28.8) 9 (15.3) 10 (16.9) 17 (28.8) 25 (42.4) OR 1.47 (0.79 2.72) 23 (92.0)
6 (3.8) 40 (25.8) 27 (17.4) 28 (18.1) 46 (29.7) 70 (45.1) OR 1.65 (1.04 2.61) 58 (82.9)
6 (7.2) 10 (12.0) 15 (18.1) 19 (22.9) 32 (38.6) 29 (34.9) 25 (86.2)
23 (5.0) 90 (27.4) 56 (17.0) 59 (17.9) 92 (28.0) 164 (49.9) 147 (89.6)
2 (2.8) 19 (25.7) 10 (13.5) 12 (16.2) 28 (37.8) 30 (40.6) 29 (96.7)
12 23 19 16 22 48 45
(12.9) (24.7) (20.4) (17.2) (23.7) (51.6) (93.8)
2 4 2 3 5 7 5
(12.5) (25.0) (12.5) (18.8) (31.3) (43.8) (71.4)
3 (8.1) 12 (32.4) 6 (16.2) 5 (13.5) 10 (27.0) 18 (48.6) 17 (94.4)
4 (3.7) 32 (29.4) 19 (17.4) 23 (21.1) 27 (24.8) 61 (56.0) 51 (83.6)
0 (0.0) 2 (8.0) 4 (16.0) 4 (16.0) 12 (48.0) 7 (28.0) 6 (85.7)
21 48 35 45 71 70 60
11 (13.9) 16 (20.3) 10 (12.7) 10 (12.7) 30 (38.0) 21 (26.6) 20 (95.2)
4 (6.3) 15 (23.4) 13 (20.3) 17 (26.6) 11 (17.2) 26 (40.6) 21 (80.8)
2 4 1 8 4 7 6
(9.0) (18.2) (4.5) (36.4) (18.2) (31.8) (85.7)
2 (9.1) 5 (22.7) 3 (13.6) 5 (22.7) 7 (31.8) 7 (31.8) 6 (85.7)
2 (4.4) 8 (17.4) 8 (17.4) 5 (10.9) 19 (41.3) 9 (19.5) 7 (77.8)
(9.0) (20.6) (15.0) (19.3) (30.5) (30.1) (85.7)
Coronary angiographic findings in relation to ECG presented for total group and for patients with early vs late coronary angiography. a Left bundle branch block. b All patients except ST elevation or LBBB. c Right bundle branch block. d Other ECG findings, e.g. pacemaker rhythm. e Patients with significant stenoses in left main stem (0 3 other vessel territories affected). f Number of affected coronary artery regions with at least 1 significant stenoses. Patients with main stem disease not included. g Normal finding/atheromatosis. h Odds ratios with confidence intervals presented for PCI attempts for the various ECG findings with normal ECG as reference. i Numbers of successful PCI’s. Percentages presented as number of successful PCI’s compared to number of PCI attempts. j Coronary angiography performed the same date as cardiac arrest. k Coronary angiography performed between 1 and 28 days after cardiac arrest. ECG = Electro cardiogram. In total, 35 of 1133 patients (3.1%) had missing coronary angiographic values.
patients, with and without comorbidities were included). In the LBBB group, at least one significant stenosis was found in 59.3%, PCI attempts were made in 33.5%. In patients with initial shockable rhythm and non-ST-elevation, at least one significant stenosis was present in 71.5% and PCI were attempted in 42.3%. In patients with nonshockable rhytm, the rates of significant stenosis and PCI attempts were 68.5% and 40.7% respectively. Patients included in the analyses differed from cardiac arrest patients not included. The included group had lower mean age, higher rate of male sex, shockable rhythm, presumed cardiac cause and witnessed arrests but lower rates of comorbidity than the group not included.
Discussion The main finding of this observational study is that, in OHCA patients with ROSC undergoing coronary angiography, there is an association between specific ECG patterns and the rate of significant stenosis and PCI attempts. In these patients, selected for coronary angiography,
ST-depression and “other” ECG patterns, e.g. pacemaker rhythm, increased the likelihood that a PCI attempt were made, suggesting a higher rate of culprit lesions in these groups. There is also a higher rate of coronary artery stenosis in patients with certain comorbidities such as diabetes and previous ischemic heart disease. Our results are in accordance with previous studies, i.e. that ST-elevation is associated with the highest risk of coronary artery lesions2,10 but also that high incidence of significant coronary artery disease is seen in patients without ST-elevation3 that undergoes coronary angiography. Current guidelines recommend considering early coronary angiography after OHCA in high risk patients even without STelevation.9 However, the evidence how to define the high-risk group is limited in the cardiac arrest population and is mainly based on an extrapolation from non-cardiac arrest patients. The results from this study presents the incidence of both significant stenosis and the rate of PCI attempts in patients with specified ECG changes and comorbidities undergoing coronary angiography after OHCA. Whether immediate angiography in patients without ST-elevation after OHCA improves outcome is not clear. Previous retrospective
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
RESUSCITATION XXX (2019) XXX
5
XXX
Table 3 – Coronary angiographic findings in relation to comorbidities existing prior to cardiac arrest. IHDa
Comorbidity (no ST-elevation, no LBBB) c
Left main (%) 1 vesseld (%) 2 vesseld (%) 3 vesseld (%) Normale (%) PCI attempted (%) PCI successf (%) Early coronary angiographyg (%)
6 (6.2) 17 (17.5) 19 (19.6) 35 (36.1) 7 (7.2) 42 (43.3) 33 (78.6) 48 (49.5)
Diabetes mellitus
COPDb
3 (4.5) 11 (16.7) 14 (21.2) 23 (34.8) 10 (15.2) 28 (42.4) 26 (92.9) 43 (65.2)
2 (6.4) 4 (12.9) 5 (16.1) 8 (25.8) 8 (25.8) 14 (45.1) 9 (64.3) 18 (58.1)
Kidney disease 0 3 2 3 4 5 4 8
(0.0) (25.0) (16.7) (25.0) (33.3) (45.1) (80.0) (66.7)
Patients with ST-elevation and LBBB (Left bundle branch block) excluded. a Ischaemic heart disease. b Chronic obstructive pulmonary disease. c Patients with significant stenoses in left main stem (0 3 other vessel territories affected). d Number of affected coronary artery regions with at least 1 significant stenoses. Patients with main stem disease not included. e Normal finding/atheromatosis. f Numbers of successful PCI’s. Percentages presented as number of successful PCI’s compared to number of PCI attempts. g Patients with coronary angiography performed the same date as cardiac arrest.
studies present somewhat conflicting results3,6,13 15 thereby limiting the strength of current guidelines. Several ongoing randomized studies addressing this important question are currently including patients, and the results from these will certainly provide more knowledge about optimal strategy and timing concerning angiography.16,17 No difference in survival or neurologic outcome could be found in the newly published, first randomized trial investigating this important issue8 The finding in this trial of a lower rate of PCI (33% in patients randomized to immediate coronary angiography) compared to many of the previously published
retrospective studies is interesting. One interpretation is that clinicians can identify patients with high risk of culprit lesions, e.g. by combining ECG, comorbidities and factors associated to the arrest. This would create a selected high-risk group in the retrospective studies. This highlights the need for strategies to identify high risk patients. It is reasonable to believe that patients with acute coronary artery occlusions would benefit the most from a strategy with immediate angiography and thus, current guidelines support this strategy in patients with ST-elevation. As previously described, the incidence of significant coronary artery disease is high even in patients without ST-
Table 4 – Coronary angiographic findings in relation to ECG in patients with shockable and non-shockable rhythm. ECG Shockable rhythm n = 897 Left maine n (%) 1 vesself n (%) 2 vesself n (%) 3 vesself n (%) Normalg n (%) PCI attempted n (%) PCI successh n (%) Non-shockable rhythm n = 196 Left maine n (%) 1 vesself n (%) 2 vesself n (%) 3 vesself n (%) Normalg n (%) PCI attempted n (%) PCI successh n (%)
ST elevation
LBBBa
Non-ST elevationb
Normal
Pathologic T-wave
RBBBc
Otherd
24 (6.6) 163 (43.8) 85 (22.8) 63 (16.9) 27 (7.3) 304 (81.7) 284 (93.4)
4 (4.7) 8 (9.3) 14 (16.3) 18 (20.9) 39 (45.3) 22 (25.6) 18 (81.8)
38 (8.7) 114 (26.0) 73 (16.6) 72 (16.4) 125 (28.5) 186 (42.3) 163 (87.6)
9 (7.8) 27 (23.5) 14 (12.2) 16 (13.9) 47 (40.9) 37 (32.1) 35 (94.6)
15 33 26 24 27 61 54
(11.7) (25.6) (20.2) (18.6) (20.9) (47.3) (88.5)
3 (12.5) 4 (16.7) 2 (8.3) 7 (29.2) 5 (20.8) 9 (37.5) 8 (88.9)
5 (8.5) 17 (28.8) 9 (15.3) 10 (16.9) 17 (28.8) 25 (42.4) 23 (92.0)
6 (5.4) 33 (29.5) 22 (19.6) 15 (13.4) 29 (25.9) 54 (48.2) 43 (79.6)
3 (4.6) 25 (38.5) 15 (23.1) 12 (18.5) 8 (12.3) 51 (78.5) 47 (92.2)
2 (12.5) 2 (12.5) 3 (18.8) 3 (18.8) 5 (31.3) 8 (50.1) 7 (87.5)
5 (4.7) 19 (17.6) 16 (14.8) 29 (26.9) 34 (31.5) 44 (40.7) 40 (90.9)
3 (10.0) 5 (16.7) 5 (16.7) 5 (16.7) 9 (30.0) 12 (40.0) 12 (100)
1 (4.0) 3 (12.0) 6 (24) 8 (32) 6 (24) 12 (48.0) 11 (91.7)
1 (7.1) 4 (28.6) 1 (7.1) 4 (28.6) 4 (28.6) 5 (35.7) 3 (60.0)
0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
0 (0) 7 (17.9) 4 (10.3) 12 (30.8) 15 (38.5) 15 (38.5) 14 (93.3)
ST depression
Coronary angiographic findings in relation to ECG presented for patients with shockable and non-shockable rhythm. a Left bundle branch block. b All patients except ST elevation or LBBB. c Right bundle branch block. d Other ECG findings, e.g. pacemaker rhythm. e Patients with significant stenoses in left main stem (0 3 other vessel territories affected). f Number of affected coronary artery regions with at least 1 significant stenoses. Patients with main stem disease not included. g Normal finding/atheromatosis. h Numbers of successful PCI’s. Percentages presented as number of successful PCI’s compared to number of PCI attempts.
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
6
RESUSCITATION XXX (2019) XXX
XXX
Table 5 – Comparison of background data between included and excluded patients.
n Female Shockable rhythm Witnessed IHDa Kidneyb COPDc DMd Age (SD) Presumed cardiac causee
Patients included in analysis n (%)
Patients not included n (%)
p-Value
1133 249 (22) 897 (79) 1008 (91) 181 (16) 22 (2) 43 (4) 119 (11) 64. 3 (12.0) 948 (84)
4044 1351 (33) 1523 (38) 3225 (83) 689 (17) 178 (4) 360 (9) 544 (14) 65.3 (19.3) 2288 (57)
<0.001 <0.001 <0.001 0.40 <0.001 <0.001 0.009 <0.001 <0.001
Patients included and excluded from analysis as described in Fig. 1. Age presented as means. a Ischaemic heart disease. b Acute or chronic kidney disease. c Chronic obstructive pulmonary disease. d Diabetes mellitus type 1 or 2. e Presumed cardiac cause reported by prehospital nurse.
elevation, but few studies have tried to identify patients with the highest risk of lesions available for immediate PCI. In a prospective study from 2015, only 210 OHCA patients with both ST-elevation and other ECG patterns were included and divided into three ECG “risk groups”. The authors’ interpretation was that initial ECG findings were unreliable when selecting patients for immediate angiography.7 One of the strengths of our study is that we have included considerably more patients. We have been able to show the angiographic findings in relation to ECG and comorbidities in a large cohort of OHCA patients, thereby suggesting that ECG pattern and previous comorbidities may be used to predict the probability of coronary artery lesions, even in the absence of ST-elevation. An interesting finding is the high rate of coronary artery disease and PCI attempts even in the group with non-shockable rhythm. This finding highlights the importance of including even these patients in randomized trials investigating potential benefit of early invasive strategies. There are several limitations of our study. The selected population including only patients who had undergone coronary angiography limits its generalizability. The risk of e.g. missing data when performing registry studies is a concern even if the Swedish registries are of high quality and missing data were filled in from patients’ files. In the Swedeheart registry, significant stenoses, number of vessels affected, and PCI attempts are mandatory variables. Suspected culprit lesions are not registered in this material. We do however present the rate of PCI attempts that could be used as a surrogate marker for culprit lesion. Obviously, this parameter is not optimal since PCI attempts might be performed towards significant stenosis not considered as culprit and some lesions might be considered not available for PCI. However, we think that PCI attempts are a reasonable surrogate marker to compare the groups but care should be taken not to focus on the absolute numbers. This view is strengthened by the fact that the ST-elevation group and patients with normal ECG has the highest and lowest rates of PCI attempts respectively. The total incidence of significant stenoses in the group without ST-elevation is 71% which is higher than some of the previous studies3 Some of these studies present data from centers where all patients with a likely cardiac cause to the cardiac arrest underwent early coronary angiography. The higher incidence in our material is likely to represent the clinicians’ selection of high-risk patients for
coronary angiography in Sweden. Unfortunately, the registry data do not contain more specific data on the LBBB group, e.g. distinction between new and previously known LBBB or subgrouping patients according to the Sgarbossa criteria. This lack of information limits the value of the angiographic findings in the LBBB group. Despite these limitations, the finding that the rate of PCI attempts in the LBBB was similar to the group with normal ECG, highlights the importance of including these patients in future randomized trials and not routinely treat them as ST-elevation. This is however, to our knowledge, the largest patient population published, where specific ECG findings are correlated to coronary angiographic findings after OHCA. The possibility to combine angiographic data with the Swedish hospital discharge diagnosis registry where all diagnoses recorded on patients in the Swedish healthcare system are collected, provides high quality comorbidity data compared to relying on disease specific registries were comorbidity data in general have a high degree of missing data, e.g. Swedeheart. Due to the limitations described above we have chosen to limit our statistical comparisons. We present incidence of PCI attempts, multi vessel disease and left main stem vessel disease in relation to ECG changes and previous comorbidities in a large group of OHCA patients undergoing coronary angiography. We consider this a valuable contribution in the ongoing discussion regarding which patients that represent the high-risk population of coronary artery disease whom may benefit from coronary angiography after cardiac arrest.
Conclusion Coronary angiographic findings, including coronary artery occlusions, significant stenosis and the rate of PCI attempts after cardiac arrest varies between patients with different ECG patterns as well as between patients with different known comorbidities. The different rates of PCI attempts indicates that ECG pattern might be used for identifying patients at high-risk for acute coronary lesions even in OHCA patients without ST-elevation on the ECG after return of spontaneous circulation. The rate of PCI attempts between the analyzed comorbidity groups were similar, suggesting that the differences in burden of vascular disease between the groups do not necessarily implies higher incidences of culprit lesions.
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
RESUSCITATION XXX (2019) XXX
Conflict of interest statement None of the authors have reported any conflict of interest. REFERENCES
1. Nolan JP, Soar J, Cariou A, et al. European resuscitation council and European society of intensive care medicine guidelines for postresuscitation care 2015: section 5 of the European resuscitation council guidelines for resuscitation 2015. Resuscitation 2015;95:202 22. 2. Anyfantakis ZA, Baron G, Aubry P, et al. Acute coronary angiographic findings in survivors of out-of-hospital cardiac arrest. Am Heart J 2009;157:312 8. 3. Dumas F, Cariou A, Manzo-Silberman S, et al. Immediate percutaneous coronary intervention is associated with better survival after out-of-hospital cardiac arrest: insights from the PROCAT (Parisian Region Out of hospital Cardiac ArresT) registry. Circulation Cardiovasc Interv 2010;3:200 7. 4. Spaulding CM, Joly L-M, Rosenberg A, et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. New Engl J Med 1997;336:1629 33. 5. Zanuttini D, Armellini I, Nucifora G, et al. Predictive value of electrocardiogram in diagnosing acute coronary artery lesions among patients with out-of-hospital-cardiac-arrest. Resuscitation 2013;84:1250 4. 6. Hollenbeck RD, McPherson JA, Mooney MR, et al. Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI. Resuscitation 2014;85: 88 95. 7. Staer-Jensen H, Nakstad ER, Fossum E, et al. Post-resuscitation ECG for selection of patients for immediate coronary angiography in out-ofhospital cardiac arrest. Circulation Cardiovasc Interv 20158:. 8. Lemkes JS, Janssens GN, van der Hoeven NW, et al. Coronary angiography after cardiac arrest without ST-segment elevation. New Engl J Med 2019.
XXX
7
9. Ibanez B, James S, Agewall S, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119 77. 10. Radsel P, Knafelj R, Kocjancic S, Noc M. Angiographic characteristics of coronary disease and postresuscitation electrocardiograms in patients with aborted cardiac arrest outside a hospital. Am J Cardiol. 2011;108:634 8. 11. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019;40:237 69. 12. Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Col Cardiol 2009;53:976 81. 13. Millin MG, Comer AC, Nable JV, et al. Patients without ST elevation after return of spontaneous circulation may benefit from emergent percutaneous intervention: a systematic review and meta-analysis. Resuscitation 2016;108:54 60. 14. Dankiewicz J, Nielsen N, Annborn M, et al. Survival in patients without acute ST elevation after cardiac arrest and association with early coronary angiography: a post hoc analysis from the TTM trial. Intensive Care Med 2015;41:856 64. 15. Elfwen L, Lagedal R, James S, et al. Coronary angiography in out-ofhospital cardiac arrest without ST elevation on ECG-Short- and longterm survival. Am Heart J 2018;200:90 5. 16. Lagedal R, Elfwen L, James S, et al. Design of DISCO-direct or subacute coronary angiography in out-of-hospital cardiac arrest study. Am Heart J 2018;197:53 61. 17. Lemkes JS, Janssens GN, Straaten HM, et al. Coronary angiography after cardiac arrest: rationale and design of the COACT trial. Am Heart J 2016;180:39 45.
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUSCITATION XXX (2019) XXX
XXX
Available online at www.sciencedirect.com
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Clinical paper
Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity R. Lagedal a, * , L. Elfwe´n b , M. Jonsson c , E. Lindgren a , D. Smekal a,e , L. Svensson c , S. James d , P. Nordberg c , S. Rubertsson a a
Department of Surgical Sciences/Anesthesiology and Intensive Care Medicine, Uppsala University, Sweden Department of Clinical Science and Education, So¨dersjukhuset, Karolinska Institute, Sweden c Department of Medicine, Center for Resuscitation Science, Karolinska Institute, Solna, Sweden d Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center Uppsala University, Sweden e UCPR, Uppsala Center for Prehospital Research, Uppsala University, Sweden b
Abstract Introduction: The relations between specific ECG patterns and coronary angiographic findings in cardiac arrest patients with different comorbidities are not properly assessed. More evidence is needed to identify patients with the highest risk for acute coronary artery disease as a cause of the cardiac arrest. This study aims to describe the coronary artery findings after cardiac arrest in relation to ECG and comorbidity. Method: A retrospective study of out-of-hospital cardiac arrest patients, with coronary angiography performed within 28 days. ECG on admission, comorbidity, PCI attempts and angiographic findings are described. Data were retrieved from national registries in Sweden. Results: Among 1133 patients with available ECG and angiography information the mean age was 64 years. The rate of shockable rhythm was 79%. The total incidence of any significant stenosis in cardiac arrest patients without ST-elevation who underwent coronary angiography within 28 days was 71%. The incidence of any stenosis in patients with normal ECG was 62.1% and in patients with LBBB, 59.3%. In patients with ST-depression or RBBB, PCI attempts were made in 47.1% and 42.4% respectively, compared with 33.3% in patients with normal ECG. Among patients without ST-elevation, those with diabetes mellitus and those with initial shockable rhythm respectively, 84.8% and 71.5 had at least one significant stenosis. Conclusion: Our study suggests, that evaluation of ECG patterns and comorbidities in out-of-hospital cardiac arrest patients without ST-segment elevation may be important to identify those with a high risk of coronary artery lesions that could benefit from early revascularization. Keywords: Cardiac arrest, Coronary angiography, Percutaneous coronary intervention
Introduction Out-of-hospital cardiac arrest (OHCA) is, despite improvement in resuscitation and post arrest care, a condition with high mortality. Even in patients with return of spontaneous circulation (ROSC) admitted to intensive care, mortality rates are approximately 50%.1 The majority of OHCAs are of cardiac cause most often due to acute coronary syndromes2,3 and today, there is consensus that patients
presenting with ST-segment elevation on the electrocardiogram (ECG) after ROSC should undergo immediate coronary angiography.1 Retrospective studies show a high incidence of acute coronary occlusions and significant stenosis suitable for revascularization among these patients.2 5 On one hand, ST-elevations on the ECG seem to have good positive predictive value in diagnosing acute coronary lesions even after cardiac arrest. It would therefore be reasonable to believe that these patients would benefit from immediate coronary angiography. On the other hand, it seems that
* Corresponding author at: Akademiska sjukhuset, 751 85, Uppsala, Sweden. E-mail addresses: [email protected] (R. Lagedal), [email protected] (L. Elfwén), [email protected] (M. Jonsson), [email protected] (E. Lindgren), [email protected] (D. Smekal), [email protected] (L. Svensson), [email protected] (S. James), [email protected] (P. Nordberg), [email protected] (S. Rubertsson). https://doi.org/10.1016/j.resuscitation.2019.09.021 Received 17 March 2019; Received in revised form 15 August 2019; Accepted 16 September 2019 Available online xxx 0300-9572/© 2019 Elsevier B.V. All rights reserved.
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
2
RESUSCITATION XXX (2019) XXX
the negative predictive value of ECG after ROSC is lower. Several studies have shown rates of acute coronary occlusion at approximately 30% and a high incidence of significant coronary artery stenosis in patients without ST-elevation thereby challenging the use of ECG as an accurate instrument for detecting coronary artery occlusion.2,3,5 7 If cardiac arrest patients without ST-segment elevation actually benefit from immediate coronary angiography and potential percutaneous coronary intervention (PCI) is today unknown. Until recently, only retrospective studies, with varying results, have been presented. A newly published trial did not show any differences in survival or neurologic outcome in patients resuscitated from cardiac arrest without ST-segment elevation randomized to either immediate or delayed coronary angiography.8 The rate of PCI in this trial was 33% in patients randomized to immediate coronary angiography which is lower than in many of the retrospective studies comparing early vs late coronary angiography. Guidelines suggest that coronary angiography should be considered in high risk patients, but the evidence to support this is weak.1,9 In the majority of the retrospective studies and guidelines, the non-ST-elevation patients are presented as one group, and little is known about how specific ECG changes and previous comorbidities affects the risk of coronary vessel pathology after cardiac arrest. Previous studies addressing more specific ECG changes have been rather small with a large proportion of ST-elevation patients.2,5,7,10 The aim of this study is to describe coronary angiographic findings and rate of PCI after cardiac arrest in relation to specified ECG changes and comorbidities to be able to define the high-risk population that may benefit from an immediate coronary angiography.
Registers Swedish Register for Cardio-pulmonary Resuscitation (SRCR): A national registry covering all emergency medical services in Sweden with an almost 100% coverage for OHCA in which resuscitation attempts are made. Contains mainly pre-hospital data. Swedeheart (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies). Swedeheart is a national quality register consisting of several separate registers in the
XXX
cardiovascular field, e.g. SCAAR (Swedish Coronary Angiography and Angioplasty Registry) and RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive Care Admission). The coverage for SCAAR has been excellent during the years presented in this study with coverage rates over 97% every year. National Patient Register (NPR) is run by the Swedish National Board of Health and Welfare. Diagnoses set on Swedish patients are registered in NPR and the coverage is almost 100%. Due to the Swedish system with unique personal identification numbers, data from other registers can be merged with NPR. Information on date of the discharge diagnoses is available, thus enabling us to use only diagnoses made prior to the cardiac arrest.
Method This is a national retrospective descriptive study. Data from four different Swedish registers were retrieved and analyzed. Data from the Swedish Register for Cardio-pulmonary Resuscitation (SRCR) were ordered from the registry holder. We requested data on all patients admitted alive to Swedish hospitals after OHCA and registered in the SRCR regardless of initial ECG rhythm. The data withdrawal was made for the time period 2008 2013 and 5177 patients were identified and data sent to us for further analyses (Fig. 1). Patients registered as awake on admission (n = 1315) were excluded. Data were then merged with the Swedeheart registry to identify patients with coronary angiography performed during the first 28 days after the cardiac arrest. Using date of the coronary angiography, patients were separated into one “early group” with angiography performed the same date as the cardiac arrest and one “late group” with angiography performed between day 2 28 after the cardiac arrest. Patients with no coronary angiography or angiography performed later than 28 days post cardiac arrest were excluded (n = 2586). From Swedeheart, coronary angiographic findings and procedures were retrieved as well as data on ECG findings after ROSC. In Swedeheart, a significant coronary artery stenosis is defined as 50% stenosis or significant fractional flow reserve (FFR < 0.8). If ECG data were missing in Swedeheart, this was completed from patients’ electronic health records. ECG’s from electronic health records were interpreted by a cardiologist blinded
Fig. 1 – Participant flow (Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity). Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
RESUSCITATION XXX (2019) XXX
to angiography data. Those without ECG data, despite this completion, were excluded (n = 143). The definition of the various ECG patterns follows international guidelines as stated by the international cardiology organizations.11,12 ECG classified as “other” includes abnormal findings that do not fulfil the criteria for the other groups, e.g. pacemaker rhythm and other broad QRS patterns not meeting the criteria for bundle branch blocks. Before 2017 guidelines, a more active approach with immediate coronary angiography, in line with that recommended for ST-segment elevation, were recommended for patients with left bundle branch block (LBBB). Thus, in our analysis, patients with LBBB are separated from other patients with non-ST-elevation. Finally, comorbidity data, based on diagnoses set prior to the cardiac arrest, were collected from the National Patient Register (NPR). All Swedish citizens have a unique personal identification number including date of birth. Data retrieved from SRCR included personal numbers and these were used to merge data with the other registers as well as obtaining individual patient records. After completion with data from NPR, the registry holders removed the personal numbers, thus anonymizing data for the research group to protect the patients’ integrity. The linking of the various data bases was made by the registry holders and the use of unique personal numbers ensures that patients were not linked to wrong data. During the years included in this study, Swedeheart contains no data on which lesion was considered as the culprit lesions. The study was approved by the regional ethical committee in Stockholm (Identifier: 2014/1139-31/2). The approval included that data could be retrieved without patient consent.
Statistics Background data and coronary angiographic data are presented in tables. Flowchart on the inclusion process are presented in Fig. 1. All angiographic data presented has been mandatory to register in the
3
XXX
Swedeheart registry minimizing the problem with missing data. Comparison between various ECG groups and the rate of PCI attempts were analyzed with logistic regression and presented as odds ratios with 95% confidence intervals. Significance testing for categorical data were made with the use of the chi-square test and for continuous data with the Mann-Whitney test.
Results We included 1133 patients with cardiac arrest between 2008 2013 in the final analysis. The incidence of the various ECG patterns and baseline characteristics are presented in Table 1. Correlations between ECG pattern/comorbidity with coronary angiography findings are presented in Table 2 and Table 3. In Table 4, coronary angiographic findings in relation to ECG in patients with shockable and non-shockable rhythm are presented. Table 5 presents a comparison between the patients included in the analyses and patients admitted to Swedish hospitals during the study period and not included in the analyses (see Fig. 1). In patients without ST-elevation or LBBB, 71% had at least one significant stenosis, and PCI attempts were made in 41.6%. In the ECG subgroups 79% of patients with ST-depression had significant stenoses and PCI attempts were made in 47.1%. If ECG were interpreted as normal the rate of any significant stenosis was 62.1% and PCI attempts were made in 33.3%. When comparing rate of PCI attempts for the ECG subgroups to patients with normal ECG, patients with ST-depression and those classified as “other findings” had significantly higher rates, OR 1.78 (CI 1.13 2.82) and 1.65 (CI 1.04 2.61) respectively. Patients with previous ischaemic heart disease or diabetes mellitus had a high rate of significant stenoses but the proportion of patients where PCI attempts were made, were similar between the analyzed comorbidity groups and in the same numerical range as for the whole group of non-ST-elevation group (where all
Table 1 – Background characteristics for included patients in relation to ECG. ECG
All
n Female (%) Shockable rythm (%) Age (std) IHDe (%) Kidneyf (%) COPDg (%) DMh (%) Early angioi (%) Late angioj (%)
1133 249 (22) 897 (79) 64.3 (12) 181 (16) 22 (2) 43 (4) 119 (11) 829 (73) 304 (27)
STelevation 463 92 (20) 372 (80) 63.9 (12) 64 (14) 7 (2) 9 (2) 39 (8) 418 (90) 45 (10)
LBBBa 108 23 (21) 86 (80) 65.1 (10) 20 (19) 3 (3) 3 (3) 14 (13) 83 (77) 25 (23)
Non-ST elevationb
Normal ECG
562 134 (24) 439 (78) 64.5 (12) 97 (17) 12 (2) 31 (6) 66 (12) 329 (59) 233 (41)
153 40 (26) 115 (75) 61.3 (14) 34 (22) 2 (1) 12 (8) 18 (12) 73 (48) 80 (52)
STdepression 157 37 (24) 129 (82) 65.3 (11) 23 (15) 4 (3) 6 (4) 14 (9) 93 (59) 64 (41)
Pathologic T-wave
RBBBc
Otherd
38 11 (29) 24 (63) 64.6 (13) 8 (21) 1 (3) 3 (8) 6 (16) 16 (42) 22 (58)
59 11 (19) 59 (100) 68.2 (11) 10 (17) 1 (2) 3 (5) 9 (15) 37 (63) 22 (37)
155 35 (23) 112 (72) 65.3 (12) 22 (14) 4 (3) 7 (5) 19 (12) 109 (70) 46 (30)
Background characteristics and rate of early vs late coronary angiography described for the whole population and the various ECG findings. a Left bundle branch block. b All patients except ST-elevation and LBBB. c Right bundle branch block. d Other ECG findings, e.g. pacemaker rhythm. e Ischaemic heart disease. f Kidney disease (acute or chronic). g Chronic obstructive pulmonary disease. h Diabetes mellitus (Type 1 or 2). i Coronary angiography performed the same date as cardiac arrest. j Coronary angiography performed between 1 and 28 days after cardiac arrest. ECG = Electro cardiogram.
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
4
RESUSCITATION XXX (2019) XXX
XXX
Table 2 – Coronary angiographic findings in relation to ECG. ECG All patients Left maine (%) 1 vesself (%) 2 vesself (%) 3 vesself (%) Normalg (%) PCI attemptedh (%)
ST elevation
32 (6.8) 198 (42.8) 105 (22.7) 79 (17.1) 36 (7.8) 374 (80.8) OR 8.40 (5.59 12.64) PCI successi (%) 345 (92.2) Early coronary angiographyj Left maine (%) 27 (6.4) 1 vesself (%) 182 (43.5) 97 (23.2) 2 vesself (%) 71 (17.0) 3 vesself (%) 30 (7.2) Normalg (%) PCI attempted (%) 346 (82.8) 318 (91.9) PCI successi (%) Late coronary angiographyk Left maine (%) 5 (11.1) 16 (35.6) 1 vesself (%) 8 (17.8) 2 vesself (%) 8 (17.8) 3 vesself (%) 6 (13.3) Normalg (%) 28 (62.2) PCI attempted (%) 27 (96.4) PCI successi (%)
LBBBa
Non-ST elevationb
Normal
ST depression
Pathologic T-wave
RBBBc
Otherd
6 (5.5) 12 (11.1) 19 (17.6) 23 (21.3) 44 (40.7) 36 (33.5) OR 1.00 (0.59 1.69) 31 (86.1)
44 (7.8) 138 (24.6) 91 (16.2) 104 (18.5) 163 (29.0) 234 (41.6)
207 (88.5)
13 (8.5) 35 (22.9) 20 (13.1) 22 (14.4) 58 (37.9) 51 (33.3) OR 1.00 (ref) 49 (96.1)
16 (10.2) 38 (24.2) 32 (20.4) 33 (21.0) 33 (21.0) 74 (47.1) OR 1.78 (1.13 2.82) 66 (89.2)
4 (10.5) 8 (21.1) 3 (7.9) 11 (28.9) 9 (23.7) 14 (36.8) OR 1.17 (0.56 2.45) 11 (78.6)
5 (8.5) 17 (28.8) 9 (15.3) 10 (16.9) 17 (28.8) 25 (42.4) OR 1.47 (0.79 2.72) 23 (92.0)
6 (3.8) 40 (25.8) 27 (17.4) 28 (18.1) 46 (29.7) 70 (45.1) OR 1.65 (1.04 2.61) 58 (82.9)
6 (7.2) 10 (12.0) 15 (18.1) 19 (22.9) 32 (38.6) 29 (34.9) 25 (86.2)
23 (5.0) 90 (27.4) 56 (17.0) 59 (17.9) 92 (28.0) 164 (49.9) 147 (89.6)
2 (2.8) 19 (25.7) 10 (13.5) 12 (16.2) 28 (37.8) 30 (40.6) 29 (96.7)
12 23 19 16 22 48 45
(12.9) (24.7) (20.4) (17.2) (23.7) (51.6) (93.8)
2 4 2 3 5 7 5
(12.5) (25.0) (12.5) (18.8) (31.3) (43.8) (71.4)
3 (8.1) 12 (32.4) 6 (16.2) 5 (13.5) 10 (27.0) 18 (48.6) 17 (94.4)
4 (3.7) 32 (29.4) 19 (17.4) 23 (21.1) 27 (24.8) 61 (56.0) 51 (83.6)
0 (0.0) 2 (8.0) 4 (16.0) 4 (16.0) 12 (48.0) 7 (28.0) 6 (85.7)
21 48 35 45 71 70 60
11 (13.9) 16 (20.3) 10 (12.7) 10 (12.7) 30 (38.0) 21 (26.6) 20 (95.2)
4 (6.3) 15 (23.4) 13 (20.3) 17 (26.6) 11 (17.2) 26 (40.6) 21 (80.8)
2 4 1 8 4 7 6
(9.0) (18.2) (4.5) (36.4) (18.2) (31.8) (85.7)
2 (9.1) 5 (22.7) 3 (13.6) 5 (22.7) 7 (31.8) 7 (31.8) 6 (85.7)
2 (4.4) 8 (17.4) 8 (17.4) 5 (10.9) 19 (41.3) 9 (19.5) 7 (77.8)
(9.0) (20.6) (15.0) (19.3) (30.5) (30.1) (85.7)
Coronary angiographic findings in relation to ECG presented for total group and for patients with early vs late coronary angiography. a Left bundle branch block. b All patients except ST elevation or LBBB. c Right bundle branch block. d Other ECG findings, e.g. pacemaker rhythm. e Patients with significant stenoses in left main stem (0 3 other vessel territories affected). f Number of affected coronary artery regions with at least 1 significant stenoses. Patients with main stem disease not included. g Normal finding/atheromatosis. h Odds ratios with confidence intervals presented for PCI attempts for the various ECG findings with normal ECG as reference. i Numbers of successful PCI’s. Percentages presented as number of successful PCI’s compared to number of PCI attempts. j Coronary angiography performed the same date as cardiac arrest. k Coronary angiography performed between 1 and 28 days after cardiac arrest. ECG = Electro cardiogram. In total, 35 of 1133 patients (3.1%) had missing coronary angiographic values.
patients, with and without comorbidities were included). In the LBBB group, at least one significant stenosis was found in 59.3%, PCI attempts were made in 33.5%. In patients with initial shockable rhythm and non-ST-elevation, at least one significant stenosis was present in 71.5% and PCI were attempted in 42.3%. In patients with nonshockable rhytm, the rates of significant stenosis and PCI attempts were 68.5% and 40.7% respectively. Patients included in the analyses differed from cardiac arrest patients not included. The included group had lower mean age, higher rate of male sex, shockable rhythm, presumed cardiac cause and witnessed arrests but lower rates of comorbidity than the group not included.
Discussion The main finding of this observational study is that, in OHCA patients with ROSC undergoing coronary angiography, there is an association between specific ECG patterns and the rate of significant stenosis and PCI attempts. In these patients, selected for coronary angiography,
ST-depression and “other” ECG patterns, e.g. pacemaker rhythm, increased the likelihood that a PCI attempt were made, suggesting a higher rate of culprit lesions in these groups. There is also a higher rate of coronary artery stenosis in patients with certain comorbidities such as diabetes and previous ischemic heart disease. Our results are in accordance with previous studies, i.e. that ST-elevation is associated with the highest risk of coronary artery lesions2,10 but also that high incidence of significant coronary artery disease is seen in patients without ST-elevation3 that undergoes coronary angiography. Current guidelines recommend considering early coronary angiography after OHCA in high risk patients even without STelevation.9 However, the evidence how to define the high-risk group is limited in the cardiac arrest population and is mainly based on an extrapolation from non-cardiac arrest patients. The results from this study presents the incidence of both significant stenosis and the rate of PCI attempts in patients with specified ECG changes and comorbidities undergoing coronary angiography after OHCA. Whether immediate angiography in patients without ST-elevation after OHCA improves outcome is not clear. Previous retrospective
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
RESUSCITATION XXX (2019) XXX
5
XXX
Table 3 – Coronary angiographic findings in relation to comorbidities existing prior to cardiac arrest. IHDa
Comorbidity (no ST-elevation, no LBBB) c
Left main (%) 1 vesseld (%) 2 vesseld (%) 3 vesseld (%) Normale (%) PCI attempted (%) PCI successf (%) Early coronary angiographyg (%)
6 (6.2) 17 (17.5) 19 (19.6) 35 (36.1) 7 (7.2) 42 (43.3) 33 (78.6) 48 (49.5)
Diabetes mellitus
COPDb
3 (4.5) 11 (16.7) 14 (21.2) 23 (34.8) 10 (15.2) 28 (42.4) 26 (92.9) 43 (65.2)
2 (6.4) 4 (12.9) 5 (16.1) 8 (25.8) 8 (25.8) 14 (45.1) 9 (64.3) 18 (58.1)
Kidney disease 0 3 2 3 4 5 4 8
(0.0) (25.0) (16.7) (25.0) (33.3) (45.1) (80.0) (66.7)
Patients with ST-elevation and LBBB (Left bundle branch block) excluded. a Ischaemic heart disease. b Chronic obstructive pulmonary disease. c Patients with significant stenoses in left main stem (0 3 other vessel territories affected). d Number of affected coronary artery regions with at least 1 significant stenoses. Patients with main stem disease not included. e Normal finding/atheromatosis. f Numbers of successful PCI’s. Percentages presented as number of successful PCI’s compared to number of PCI attempts. g Patients with coronary angiography performed the same date as cardiac arrest.
studies present somewhat conflicting results3,6,13 15 thereby limiting the strength of current guidelines. Several ongoing randomized studies addressing this important question are currently including patients, and the results from these will certainly provide more knowledge about optimal strategy and timing concerning angiography.16,17 No difference in survival or neurologic outcome could be found in the newly published, first randomized trial investigating this important issue8 The finding in this trial of a lower rate of PCI (33% in patients randomized to immediate coronary angiography) compared to many of the previously published
retrospective studies is interesting. One interpretation is that clinicians can identify patients with high risk of culprit lesions, e.g. by combining ECG, comorbidities and factors associated to the arrest. This would create a selected high-risk group in the retrospective studies. This highlights the need for strategies to identify high risk patients. It is reasonable to believe that patients with acute coronary artery occlusions would benefit the most from a strategy with immediate angiography and thus, current guidelines support this strategy in patients with ST-elevation. As previously described, the incidence of significant coronary artery disease is high even in patients without ST-
Table 4 – Coronary angiographic findings in relation to ECG in patients with shockable and non-shockable rhythm. ECG Shockable rhythm n = 897 Left maine n (%) 1 vesself n (%) 2 vesself n (%) 3 vesself n (%) Normalg n (%) PCI attempted n (%) PCI successh n (%) Non-shockable rhythm n = 196 Left maine n (%) 1 vesself n (%) 2 vesself n (%) 3 vesself n (%) Normalg n (%) PCI attempted n (%) PCI successh n (%)
ST elevation
LBBBa
Non-ST elevationb
Normal
Pathologic T-wave
RBBBc
Otherd
24 (6.6) 163 (43.8) 85 (22.8) 63 (16.9) 27 (7.3) 304 (81.7) 284 (93.4)
4 (4.7) 8 (9.3) 14 (16.3) 18 (20.9) 39 (45.3) 22 (25.6) 18 (81.8)
38 (8.7) 114 (26.0) 73 (16.6) 72 (16.4) 125 (28.5) 186 (42.3) 163 (87.6)
9 (7.8) 27 (23.5) 14 (12.2) 16 (13.9) 47 (40.9) 37 (32.1) 35 (94.6)
15 33 26 24 27 61 54
(11.7) (25.6) (20.2) (18.6) (20.9) (47.3) (88.5)
3 (12.5) 4 (16.7) 2 (8.3) 7 (29.2) 5 (20.8) 9 (37.5) 8 (88.9)
5 (8.5) 17 (28.8) 9 (15.3) 10 (16.9) 17 (28.8) 25 (42.4) 23 (92.0)
6 (5.4) 33 (29.5) 22 (19.6) 15 (13.4) 29 (25.9) 54 (48.2) 43 (79.6)
3 (4.6) 25 (38.5) 15 (23.1) 12 (18.5) 8 (12.3) 51 (78.5) 47 (92.2)
2 (12.5) 2 (12.5) 3 (18.8) 3 (18.8) 5 (31.3) 8 (50.1) 7 (87.5)
5 (4.7) 19 (17.6) 16 (14.8) 29 (26.9) 34 (31.5) 44 (40.7) 40 (90.9)
3 (10.0) 5 (16.7) 5 (16.7) 5 (16.7) 9 (30.0) 12 (40.0) 12 (100)
1 (4.0) 3 (12.0) 6 (24) 8 (32) 6 (24) 12 (48.0) 11 (91.7)
1 (7.1) 4 (28.6) 1 (7.1) 4 (28.6) 4 (28.6) 5 (35.7) 3 (60.0)
0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
0 (0) 7 (17.9) 4 (10.3) 12 (30.8) 15 (38.5) 15 (38.5) 14 (93.3)
ST depression
Coronary angiographic findings in relation to ECG presented for patients with shockable and non-shockable rhythm. a Left bundle branch block. b All patients except ST elevation or LBBB. c Right bundle branch block. d Other ECG findings, e.g. pacemaker rhythm. e Patients with significant stenoses in left main stem (0 3 other vessel territories affected). f Number of affected coronary artery regions with at least 1 significant stenoses. Patients with main stem disease not included. g Normal finding/atheromatosis. h Numbers of successful PCI’s. Percentages presented as number of successful PCI’s compared to number of PCI attempts.
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
6
RESUSCITATION XXX (2019) XXX
XXX
Table 5 – Comparison of background data between included and excluded patients.
n Female Shockable rhythm Witnessed IHDa Kidneyb COPDc DMd Age (SD) Presumed cardiac causee
Patients included in analysis n (%)
Patients not included n (%)
p-Value
1133 249 (22) 897 (79) 1008 (91) 181 (16) 22 (2) 43 (4) 119 (11) 64. 3 (12.0) 948 (84)
4044 1351 (33) 1523 (38) 3225 (83) 689 (17) 178 (4) 360 (9) 544 (14) 65.3 (19.3) 2288 (57)
<0.001 <0.001 <0.001 0.40 <0.001 <0.001 0.009 <0.001 <0.001
Patients included and excluded from analysis as described in Fig. 1. Age presented as means. a Ischaemic heart disease. b Acute or chronic kidney disease. c Chronic obstructive pulmonary disease. d Diabetes mellitus type 1 or 2. e Presumed cardiac cause reported by prehospital nurse.
elevation, but few studies have tried to identify patients with the highest risk of lesions available for immediate PCI. In a prospective study from 2015, only 210 OHCA patients with both ST-elevation and other ECG patterns were included and divided into three ECG “risk groups”. The authors’ interpretation was that initial ECG findings were unreliable when selecting patients for immediate angiography.7 One of the strengths of our study is that we have included considerably more patients. We have been able to show the angiographic findings in relation to ECG and comorbidities in a large cohort of OHCA patients, thereby suggesting that ECG pattern and previous comorbidities may be used to predict the probability of coronary artery lesions, even in the absence of ST-elevation. An interesting finding is the high rate of coronary artery disease and PCI attempts even in the group with non-shockable rhythm. This finding highlights the importance of including even these patients in randomized trials investigating potential benefit of early invasive strategies. There are several limitations of our study. The selected population including only patients who had undergone coronary angiography limits its generalizability. The risk of e.g. missing data when performing registry studies is a concern even if the Swedish registries are of high quality and missing data were filled in from patients’ files. In the Swedeheart registry, significant stenoses, number of vessels affected, and PCI attempts are mandatory variables. Suspected culprit lesions are not registered in this material. We do however present the rate of PCI attempts that could be used as a surrogate marker for culprit lesion. Obviously, this parameter is not optimal since PCI attempts might be performed towards significant stenosis not considered as culprit and some lesions might be considered not available for PCI. However, we think that PCI attempts are a reasonable surrogate marker to compare the groups but care should be taken not to focus on the absolute numbers. This view is strengthened by the fact that the ST-elevation group and patients with normal ECG has the highest and lowest rates of PCI attempts respectively. The total incidence of significant stenoses in the group without ST-elevation is 71% which is higher than some of the previous studies3 Some of these studies present data from centers where all patients with a likely cardiac cause to the cardiac arrest underwent early coronary angiography. The higher incidence in our material is likely to represent the clinicians’ selection of high-risk patients for
coronary angiography in Sweden. Unfortunately, the registry data do not contain more specific data on the LBBB group, e.g. distinction between new and previously known LBBB or subgrouping patients according to the Sgarbossa criteria. This lack of information limits the value of the angiographic findings in the LBBB group. Despite these limitations, the finding that the rate of PCI attempts in the LBBB was similar to the group with normal ECG, highlights the importance of including these patients in future randomized trials and not routinely treat them as ST-elevation. This is however, to our knowledge, the largest patient population published, where specific ECG findings are correlated to coronary angiographic findings after OHCA. The possibility to combine angiographic data with the Swedish hospital discharge diagnosis registry where all diagnoses recorded on patients in the Swedish healthcare system are collected, provides high quality comorbidity data compared to relying on disease specific registries were comorbidity data in general have a high degree of missing data, e.g. Swedeheart. Due to the limitations described above we have chosen to limit our statistical comparisons. We present incidence of PCI attempts, multi vessel disease and left main stem vessel disease in relation to ECG changes and previous comorbidities in a large group of OHCA patients undergoing coronary angiography. We consider this a valuable contribution in the ongoing discussion regarding which patients that represent the high-risk population of coronary artery disease whom may benefit from coronary angiography after cardiac arrest.
Conclusion Coronary angiographic findings, including coronary artery occlusions, significant stenosis and the rate of PCI attempts after cardiac arrest varies between patients with different ECG patterns as well as between patients with different known comorbidities. The different rates of PCI attempts indicates that ECG pattern might be used for identifying patients at high-risk for acute coronary lesions even in OHCA patients without ST-elevation on the ECG after return of spontaneous circulation. The rate of PCI attempts between the analyzed comorbidity groups were similar, suggesting that the differences in burden of vascular disease between the groups do not necessarily implies higher incidences of culprit lesions.
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021
RESUS 8232 No. of Pages 7
RESUSCITATION XXX (2019) XXX
Conflict of interest statement None of the authors have reported any conflict of interest. REFERENCES
1. Nolan JP, Soar J, Cariou A, et al. European resuscitation council and European society of intensive care medicine guidelines for postresuscitation care 2015: section 5 of the European resuscitation council guidelines for resuscitation 2015. Resuscitation 2015;95:202 22. 2. Anyfantakis ZA, Baron G, Aubry P, et al. Acute coronary angiographic findings in survivors of out-of-hospital cardiac arrest. Am Heart J 2009;157:312 8. 3. Dumas F, Cariou A, Manzo-Silberman S, et al. Immediate percutaneous coronary intervention is associated with better survival after out-of-hospital cardiac arrest: insights from the PROCAT (Parisian Region Out of hospital Cardiac ArresT) registry. Circulation Cardiovasc Interv 2010;3:200 7. 4. Spaulding CM, Joly L-M, Rosenberg A, et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. New Engl J Med 1997;336:1629 33. 5. Zanuttini D, Armellini I, Nucifora G, et al. Predictive value of electrocardiogram in diagnosing acute coronary artery lesions among patients with out-of-hospital-cardiac-arrest. Resuscitation 2013;84:1250 4. 6. Hollenbeck RD, McPherson JA, Mooney MR, et al. Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI. Resuscitation 2014;85: 88 95. 7. Staer-Jensen H, Nakstad ER, Fossum E, et al. Post-resuscitation ECG for selection of patients for immediate coronary angiography in out-ofhospital cardiac arrest. Circulation Cardiovasc Interv 20158:. 8. Lemkes JS, Janssens GN, van der Hoeven NW, et al. Coronary angiography after cardiac arrest without ST-segment elevation. New Engl J Med 2019.
XXX
7
9. Ibanez B, James S, Agewall S, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119 77. 10. Radsel P, Knafelj R, Kocjancic S, Noc M. Angiographic characteristics of coronary disease and postresuscitation electrocardiograms in patients with aborted cardiac arrest outside a hospital. Am J Cardiol. 2011;108:634 8. 11. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019;40:237 69. 12. Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Col Cardiol 2009;53:976 81. 13. Millin MG, Comer AC, Nable JV, et al. Patients without ST elevation after return of spontaneous circulation may benefit from emergent percutaneous intervention: a systematic review and meta-analysis. Resuscitation 2016;108:54 60. 14. Dankiewicz J, Nielsen N, Annborn M, et al. Survival in patients without acute ST elevation after cardiac arrest and association with early coronary angiography: a post hoc analysis from the TTM trial. Intensive Care Med 2015;41:856 64. 15. Elfwen L, Lagedal R, James S, et al. Coronary angiography in out-ofhospital cardiac arrest without ST elevation on ECG-Short- and longterm survival. Am Heart J 2018;200:90 5. 16. Lagedal R, Elfwen L, James S, et al. Design of DISCO-direct or subacute coronary angiography in out-of-hospital cardiac arrest study. Am Heart J 2018;197:53 61. 17. Lemkes JS, Janssens GN, Straaten HM, et al. Coronary angiography after cardiac arrest: rationale and design of the COACT trial. Am Heart J 2016;180:39 45.
Please cite this article in press as: R. Lagedal, et al., Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity, Resuscitation (2019), https://doi.org/10.1016/j.resuscitation.2019.09.021