ORIGINAL RESEARCH

Coronary

Validation of the MIRACLE2 Score for Prognostication

After Out-of-hospital Cardiac Arrest

Nicholas Sunderland ,1 Francine Cheese ,1 Zoe Leadbetter,1 Nikhil V Joshi ,1 Mark Mariathas ,1 Ioannis Felekos ,1
Sinjini Biswas ,1 Geoff Dalton,1 Amardeep Dastidar ,2 Shahid Aziz,2 Dan McKenzie ,3 Raveen Kandan,3 Ali Khavandi ,3
Hazim Rahbi,4 Christopher Bourdeaux ,5 Kieron Rooney ,5 Matt Govier5, Matthew Thomas ,5 Stephen Dorman ,1
Julian Strange 1 and Thomas W Johnson 1

1. Bristol Heart Institute, University Hospitals Bristol & Weston NHS Foundation Trust, Bristol, UK; 2. Cardiology Department,
North Bristol NHS Trust, Bristol, UK; 3. Cardiology Department, Royal United Hospital Bath NHS Foundation Trust, Combe Park, Bath, UK;
4. Cardiology Department, Great Western Hospital NHS Foundation Trust, Swindon, UK; 5. Department of Anaesthesia, University Hospitals
Bristol & Weston NHS Foundation Trust, Bristol, UK

Abstract
Background: Out-of-hospital cardiac arrest (OHCA) is associated with very poor clinical outcomes. An optimal pathway of care is yet to be defined,
but prognostication is likely to assist in the challenging decision-making required for treatment of this high-risk patient cohort. The MIRACLE2
score provides a simple method of neuro-prognostication but as yet it has not been externally validated. The aim of this study was therefore
to retrospectively apply the score to a cohort of OHCA patients to assess the predictive ability and accuracy in the identification of neurological
outcome. Methods: Retrospective data of patients identified by hospital coding, over a period of 18 months, were collected from a large tertiary-
level cardiac centre with a mature, multidisciplinary OHCA service. MIRACLE2 score performance was assessed against three existing OHCA
prognostication scores. Results: Patients with all-comer OHCA, of presumed cardiac origin, with and without evidence of ST-elevation MI (43.4%
versus 56.6%, respectively) were included. Regardless of presentation, the MIRACLE2 score performed well in neuro-prognostication, with a low
MIRACLE2 score (≤2) providing a negative predictive value of 94% for poor neurological outcome at discharge, while a high score (≥5) had a positive
predictive value of 95%. A high MIRACLE2 score performed well regardless of presenting ECG, with 91% of patients receiving early coronary
angiography having a poor outcome. Conclusion: The MIRACLE2 score has good prognostic performance and is easily applicable to cardiac-origin
OHCA presentation at the hospital front door. Prognostic scoring may assist decision-making regarding early angiographic assessment.

Keywords
Out-of-hospital cardiac arrest, neuro-prognostication, coronary angiography

Disclosure: The authors have no conflicts of interest to declare.

Consent: This study involves the secondary use of data collected by the clinical team as part of the patients’ normal care; specific patient consent was not sought. Only
members of the patients’ direct clinical care team were involved in processing the raw data.
Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request and subject to ethics approval.
Ethics: This study falls outside the scope of the UK policy framework for health and social care research and was registered with University Hospitals Bristol and Weston
NHS Foundation Trust as a service evaluation. It is a retrospective analysis of routinely collected anonymised data. The study was carried out in accordance with the Code
of Ethics of the World Medical Association (Declaration of Helsinki).
Authors’ contributions: Conceptualisation: TWJ, NS, FC, ZL; data curation: NS, FC, ZL; formal analysis: NS; investigation: TWJ, NVJ, MM, IF, SB, GD, AD, SA, DM, RK, AK,
HR, CB, KR, MG, MT, SD, JS; supervision: TWJ; writing – original draft preparation: NS, FC, ZL; writing – review & editing: NS, FC, ZL, TWJ, NVJ, MM, IF, SB, GD, AD, SA, DM,
RK, AK, HR, CB, KR, MG, MT, SD, JS.
Received: 16 February 2023 Accepted: 22 August 2023 Citation: Interventional Cardiology 2023;18:e29. DOI: https://doi.org/10.15420/icr.2023.08
Correspondence: Thomas Johnson, Bristol Heart Institute, University Hospitals Bristol & Weston NHS Foundation Trust, Terrell St, Bristol BS2 8ED, UK.
E: [email protected]

Open Access: This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial
purposes, provided the original work is cited correctly.

Out-of-hospital cardiac arrest (OHCA) poses a significant challenge, being rate of neurological injury.5 The EuReCa2 study found that of those with an
a major cause of mortality and ongoing morbidity. In the UK, >30,000 OHCA on whom cardiopulmonary resuscitation (CPR) was started, 36%
resuscitation attempts occur annually, with the majority recognised as survive to hospital and 8% survive to discharge.6 Of those admitted to an
primarily cardiac in origin.1,2 There is international consensus that optimal intensive care unit (ICU) around half will die before discharge, with hypoxic
management involves transport to the nearest heart attack centre (HAC) neurological injury as the primary cause of death.5–9 Clinical decision-
for prompt investigation and treatment.3,4 making in this context is extremely difficult and early accurate prognostication
is desirable, given that management of OHCA patients carries a high clinical
Despite advances in treatment, survival following OHCA is low, with a high cost and is a significant emotional burden to family and caregivers.

© The Author(s) 2023. Published by Radcliffe Group Ltd.

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 Validation of the MIRACLE2 Score

In OHCA of primary cardiac origin, an urgent invasive management blood pH <7.20 (1 point) and age category (≤60 years, 0 points; 61–
strategy should be considered. Early coronary angiography (CAG) in 80 years, 1 point; >80 years, 2 points).
patients presenting with ST-elevation MI (STEMI) has proven benefit,
however there is uncertainty regarding the best management strategy in As part of the external validation process, we elected to assess the
OHCA patients with non-ST-elevation MI (NSTEMI).10 Despite a high performance of the MIRACLE2 score against previously reported scores,
incidence of significant coronary artery disease in these patients, recent that is, CAHP, OHCA and TTM.
randomised controlled trials have demonstrated no benefit to routine
early CAG.7,8,11 However, patients without ST-elevation but with significant The CAHP score uses a complex nomogram to generate an overall score
haemodynamic or electrical instability were excluded from these trials from the following factors: age, arrest setting, initial rhythm, zero-flow
and therefore it remains unclear whether routine early intervention in this time, low-flow time, initial blood pH and total adrenaline dose.
group may be beneficial.
The OHCA score uses an equation to compute an overall score, with
Several clinical scoring systems have been developed to assist early different weights on the factors: initial rhythm, zero-flow time, low-flow
prognostication after OHCA: the Out-of-Hospital Cardiac Arrest score, time, initial serum creatinine and initial arterial lactate level.
Cardiac Arrest Hospital Prognosis (CAHP) score, Target Temperature
Management (TTM) risk score and the MIRACLE2 score.12–15 These can all The TTM score is similar to the MIRACLE2 score but uses a more granular
aid decision-making regarding the appropriateness of medical system with differing points for 37 subcategories across 10 main factors:
interventions, as well as supporting family discussions. While the OHCA, age, arrest setting, initial rhythm, zero-flow time, low-flow time, use of
CAHP and TTM scores rely on relatively complex nomograms/equations, adrenaline, pupillary or corneal reflex at ROSC, Glasgow Coma Score
the MIRACLE2 score is a simple point-based system easily deployed on (GCS) motor score, initial blood pH and initial arterial partial pressure of
patient arrival in hospital. CO2.

The aim of this study was to externally validate the MIRACLE2 risk score in Endpoints
an independent cohort of OHCA patients. The primary study endpoint was poor neurological recovery, defined as
CPC 3–5 (severe disability to death) at hospital discharge. The secondary
Methods endpoint was poor neurological recovery at 6 months.
Population
This single-centre retrospective cohort study was conducted at the Bristol Ethics Statement
Royal Infirmary (BRI) between January 2019 and July 2020. The BRI is a This study falls outside the scope of the UK policy framework for health
tertiary cardiac centre with access to 24-hour emergency CAG, cardiac and social care research and was a service evaluation at University
surgery and specialist intensive care services. All admission records were Hospitals Bristol and Weston NHS Foundation Trust. It is a retrospective
screened for cardiac arrest ICD-10 codes (I46.0, I46.1, or I46.9). Records analysis of routinely collected anonymised data. The study was carried
were then manually reviewed, with inclusion of all patients aged ≥18 years out in accordance with the Code of Ethics of the World Medical Association
who presented with an OHCA of presumed cardiac origin and had return (Declaration of Helsinki).
of spontaneous circulation (ROSC). Patients who died before hospital
arrival, had evidence of a non-cardiac cause of arrest (respiratory arrest, Statistical Analysis
suicide, trauma, drowning, substance overdose), confirmed intra-cerebral Categorical variables are expressed as absolute numbers (percentage)
haemorrhage, previous significant neurological disability (Cerebral and were compared using the Fisher’s exact test for 2 × 2 contingency
Performance Category [CPC] 3 or 4) or comorbidity leading to life tables or Pearson’s χ2 test for categorical variables of greater dimensions.
expectancy <6 months were excluded. Normality was assessed using the Shapiro–Wilk test. Variables not
normally distributed are expressed as median (lower quartile–upper
Data Collection quartile) and were compared using the Mann–Whitney U-test.
Pre-hospital data were obtained from the South Western Ambulance
Service Foundation Trust electronic patient care records and initial The relationship between predictor variables and the binary primary
Emergency Department written records. Zero-flow time was defined as outcome variable ‘poor neurological recovery’ was evaluated in
the time from cardiac arrest to commencement of CPR. Low-flow time was univariable and multivariable logistic regression models. Standard SPSS
defined as the total CPR time, including periods of CPR after re-arrest in multiple imputation methods, using 50 imputations and pooling of data,
the case of multiple ROSC. Baseline blood results were obtained from the were used to handle missing predictor variables.
hospital’s laboratory database. Twelve-lead ECG, echocardiography and
CAG reports were manually extracted from their respective hospital All tests were two-tailed, and p<0.05 was considered significant. The
systems and reviewed. An early CAG strategy was defined as within SPSS27.0.1.0 software package was used to conduct the statistical
24 hours of hospital admission. analysis.

Scoring Systems Results

The MIRACLE2 score is composed of seven variables with a potential total Cohort
of 10 points. Higher scores predict an increasing risk of poor neurological There were 682 hospital admissions with an associated cardiac arrest
outcome (CPC 3–5). The score components are: unwitnessed cardiac ICD-10 code between January 2019 and July 2020. Exclusions totalled
arrest (1 point), non-shockable initial rhythm (1 point), changing rhythms 463 patients: 321 records did not relate to a new presentation of OHCA,
(any two of VF, pulseless electrical activity (PEA) or asystole; 1 point), any 40 patients had an obvious non-cardiac cause for arrest, two were dead
adrenaline dose (2 points), no pupil reactivity at ROSC (1 point), initial on arrival, 33 were aged <18 years old, six had a life expectancy of

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 Validation of the MIRACLE2 Score

Table 1: Patient Baseline Characteristics

Variable Total (n=219) CPC 0–2 (n=122, 56%) CPC 3–5 (n=97, 44%) p-value*
Age (years) 63 (52–74) 60 (49–68) 71 (58–80) <0.001
Man 169/219 (77) 101/122 (83) 68/97 (70) 0.035
Blood results:
• Haemoglobin (g/l) 140 (125–150) 142 (130–153) 133 (120–148) 0.021
• Platelets (10 /l)
9
229 (188–284) 238 (191–290) 221 (183–257) 0.052
• Sodium (mmol/l) 139 (136–141) 140 (137–141) 139 (135–141) 0.143
• Potassium (mmol/l) 4.0 (3.6–4.6) 3.8 (3.5–4.6) 4.1 (3.7–4.7) 0.075
• Creatinine (µmol/l) 94 (77–113) 89 (74–105) 103 (83–127) <0.001
• hs-cT (ng/l) 188 (59–596) 173 (44–500) 264 (114–812) 0.049
ECG: 0.020
• ST elevation 69/219 (32) 47/122 (39) 22/97 (23)
• LBBB 26/219 (12) 11/122 (9) 15/97 (16)
• ST depression 31/219 (14) 13/122 (11) 18/97 (19)
• RBBB 25/219 (11) 10/122 (8) 15/97 (16)
• Normal 68/219 (31) 41/122 (34) 27/97 (28)
Echocardiogram:
• LVEF (%) 50 (40–55) 50 (41–55) 45 (35–55) 0.078
LV wall motion abnormalities: 0.002
• No hypokinesis 54/200 (27) 30/122 (25) 24/78 (31)
• Global hypokinesis 34/200 (17) 13/122 (11) 21/78 (27)
• Regional hypokinesis 112/200 (56) 79/122 (65) 33/78 (42)
Data are presented as n (%) or median (interquartile ratio). *Mann–Whitney U-test for median (interquartile ratio) comparisons (non-parametric), Fisher’s exact test for categorical 2 × 2 contingency
tables and Pearson’s χ2 test for categorical variables of greater dimensions. CPC = Cerebral Performance Category; hs-cT = high-sensitivity cardiac troponin; LBBB = left bundle branch block; LV = left
ventricle; LVEF = left ventricular ejection fraction; RBBB = right bundle branch block.

<6 months and five had significant prior neurological disability. An Overall, good neurological outcome (CPC score 1–2) was observed in 122
additional 28 patients did not initially present to our centre (transferred in) patients (56%) at hospital discharge, whereas 97 (44%) had a poor
and 35 had no medical information available. After exclusions, 219 neurological outcome (CPC score 3–5). Outcomes at 6 months were
patients were included in the validation cohort (Supplementary Figure 1). similar and are detailed in Supplementary Figure 1.

The median patient age was 63 years and 77% were men. Admission ECG MIRACLE2 Scoring and Predictors of Outcome
demonstrated ST-elevation in 32% and left bundle branch block (LBBB) in MIRACLE2 scores were calculated for each patient. Complete data were
12% of patients. The median left ventricular ejection fraction on available in 168 cases (77%) to compute the MIRACLE2 score. Missing data
echocardiogram was 50% (IQR 40–55%; Table 1). were observed for pupillary response in 40 cases (18%), and initial blood
pH for 13 patients (6%). In one patient the initial rhythm was unknown.
OHCA occurred at home in 53% (116/219 cases) of the cohort, 85% were
witnessed and 88% received bystander CPR. The median no-flow time The number of patients split across the MIRACLE2 score risk categories:
was 0 minutes (range 0–20 minutes) and the median low-flow time was low (≤2), intermediate, and high (≥5), was 89 (41%), 66 (30%) and 64 (29%),
21 minutes (range 1–139 minutes). An initial shockable rhythm was respectively.3,4 There was a stepwise increase in the risk of poor
observed in 79% and a median of 2 defibrillations delivered. Rhythm neurological outcome with increasing MIRACLE2 score (Figure 1A).
change during resuscitation was observed in 30%, and the median dose
of adrenaline administered was 1 mg. On initial assessment after ROSC, The rates of poor neurological outcome at hospital discharge in patients
80% of patients had reactive pupils, the median GCS was 3, and median with a low or high admission MIRACLE2 score were 6 and 95%, respectively.
initial blood pH was 7.20 with a median lactate of 4.8 mmol/l (Table 2). In those with an intermediate score, good or poor neurological outcome
was relatively balanced (53 versus 47%, respectively).
The majority (80%) of patients were admitted to intensive care, with an
equal split crosss MIRACLE2 score risk categories: low (0–2), 33%; The results of the univariable and multivariable logistic regression analysis
intermediate; 34%; and high (≥5), 33%.3,4 Across the same MIRACLE2 risk are listed in Table 3. The multivariable analysis was conducted
categories, the 45 patients (20%) not admitted to intensive care were incorporating the individual MIRACLE2 score components.
more likely to have a low MIRACLE2 score (71% versus 16% versus 13%,
respectively). Significant cardiogenic shock requiring intervention (Society MIRACLE2 Score Performance
for Cardiovascular Angiography and Interventions [SCAI] shock grade Receiver operating characteristic (ROC) curves were derived for the
C–E) was observed in 34%. MIRACLE2 score and three other OHCA prognostication scoring systems.

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 Validation of the MIRACLE2 Score

Table 2: Out-of-hospital Cardiac Arrest Circumstances and Initial Emergency Department Assessment

Variable Total (n=219) CPC 0–2 CPC 3–5 p-value*

(n=122, 56%) (n=97, 44%)
Resuscitation events:
• Residence, n (%) 116/219 (53) 53/122 (43) 63/97 (65) 0.002
• Witnessed, n (%) 186/219 (85) 107/122 (88) 79/97 (81) 0.198
• Bystander CPR, n (%) 193/219 (88) 113/122 (93) 80/97 (82) 0.021
• Zero-flow time (min), median (range) 0 (0–20) 0 (0–7.5) 0 (0–20) 0.013
• Low-flow time (min), median (IQR) 21 (12–34) 17 (9–26) 32 (20–45) <0.001
• Shockable rhythm, n (%) 172/219 (79) 117/122 (96) 55/97 (57) <0.001
• No. defibrillations, median (IQR) 2 (1–4) 2 (1–4) 2 (0–5) 0.081
• Changing rhythms, n (%) 66/219 (30) 13/122 (11) 53/97 (55) <0.001
• Adrenaline dose (total mg), median (IQR) 1 (0–3) 0 (0–1) 2 (1–4) <0.001
• Any adrenaline dose, n (%) 128/219 (58) 39/122 (32) 89/97 (92) <0.001
Initial physiology:
• Assisted ventilation, n (%) 163/219 (74) 76/122 (62) 87/97 (90) <0.001
• SCAI shock grade, n (%): <0.001
A–B 143/219 (65) 101/122 (83) 42/97 (43)
C–E 76/219 (35) 21/122 (17) 55/97 (57)
pH, median (IQR) 7.20 (7.10–7.30) 7.26 (7.18–7.35) 7.11 (6.96–7.21) <0.001
Lactate (mmol/l), median (IQR) 4.8 (2.1–7.0) 3.9 (1.9–5.8) 6.1 (3.6–8.8) <0.001
Reactive pupils, n (%) 145/179 (80) 93/99 (94) 51/80 (64) <0.001
GCS, median (IQR) 3 (3–5) 3 (3–15) 3 (3–3) <0.001
GCS motor score = 1, n (%) 157/214 (73) 67/117 (57) 90/97 (93) <0.001
MIRACLE2 risk categories: <0.001
• Low MIRACLE2 score (≤2) 89/219 (41) 84/122 (69) 5/97 (5)
• Intermediate MIRACLE2 score (3,4) 66/219 (30) 35/122 (29) 31/97 (32)
• High MIRACLE2 score (≥5) 64/219 (29) 3/122 (2) 61/97 (63)
*Mann–Whitney U-test for median (IQR) comparisons (non-parametric), Fisher’s exact test for categorical 2 × 2 contingency tables and Pearson’s χ2 test for categorical variables of greater dimensions.
CPC = Cerebral Performance Category; CPR = cardiopulmonary resuscitation; ED = emergency department; GCS = Glasgow Coma Score; SCAI = Society for Cardiovascular Angiography and
Interventions.

When predicting poor neurological outcome at discharge, the area Low MIRACLE2 score patients, compared with intermediate and high
under the ROC curve (AUC) for the MIRACLE2 score was 0.93. The AUC score patients, comprised the greatest proportion of those taken for CAG,
for the CAHP, OHCA and TTM scores was 0.92, 0.83 and 0.94, as either an early-CAG strategy (low 45%; intermediate 32%; high 23%) or
respectively (Figure 1D). The AUC was almost identical when predicting delayed-CAG strategy (low 67%; intermediate 28%; high 6%). Conversely,
poor neurological outcome at 6 months: 0.92, 0.92, 0.86 and 0.94, patients with a high MIRACLE2 score were more likely not to undergo any
respectively. CAG (55%), compared with patients with either intermediate (25%) or low
(21%) scores.
The model performance and discrimination characteristics are listed in
Supplementary Table 1. A low-risk MIRACLE2 score (≤2) had a negative In the 148 patients taken for early-CAG, a low MIRACLE2 score was
predictive value of 94% for poor neurological outcome at discharge, associated with higher rates of good neurological outcome at discharge,
whereas a high MIRACLE2 score (≥5) had a positive predictive value of compared with intermediate or high scores (97% versus 56% versus 9%,
95%. respectively).

Coronary Angiography In the 18 patients who had a delayed-CAG strategy, all of the low-risk
The referral characteristics for patients undergoing CAG and invasive (n=12) and intermediate-risk (n=5) patients had a good neurological
procedures are listed in Table 4. A total of 166 patients (76%) underwent outcome at discharge. The one patient with a high MIRACLE2 score had a
CAG, of whom 148 (89%) underwent CAG ≤24 hours after admission (early- poor neurological outcome.
CAG) and 18 (11%), >24 hours (delayed-CAG). The median time to early-CAG
was 1.0 hour and to delayed-CAG, 142.1 hours. A culprit lesion was In the 53 patients who did not undergo CAG or PCI, a low MIRACLE2 score
demonstrated in 101 (61%) of the patients taken for CAG, with 92 (55% of was associated with a 91% chance of good neurological outcome at
laboratory cases, 42% of cohort) proceeding to percutaneous coronary discharge. The 77% of patients with an intermediate MIRACLE2 score, and
intervention (PCI). Surgical revascularisation was performed in nine cases 100% of those with a high MIRACLE2 score, however, had a poor
during admission. neurological outcome.

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 Validation of the MIRACLE2 Score

Figure 1: Probability of Poor Neurological Outcome at Discharge by

MIRACLE2 Score and Coronary Angiography Timing.

A 100 B 100
Poor neurological outcome at discharge (%)

Poor neurological outcome at discharge (%)

80 80

60 60

40 40

20 20

0 0
0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10

MIRACLE2 score MIRACLE2 score

C 100 D 100
Poor neurological outcome at discharge (%)

80 80

60 60
Sensitivity

40 40

20 20

0 0
0 1 2 3 4 5 6 7 8 9 10 0 20 40 60 80 100

MIRACLE2 score 100 – Specificity

Outcome – CAG timing

Good: early CAG Good: late CAG Good: no CAG TTM score (AUC 0.94) OHCA score (AUC 0.83)

Bad: early CAG Bad: late CAG Bad: no CAG CAHP score (AUC 0.92) MIRACLE2 score (AUC 0.93)

All patients (A), NSTEMI–LBBB patients (B) and STEMI–LBBB patients (C). D: Receiver operating characteristic (ROC) curves for prediction of poor neurological outcome at discharge by MIRACLE2 score,
for all patients. AUC = area under the ROC curve; CAG = coronary angiography; CAHP = Cardiac Arrest Hospital Prognosis; LBBB = left bundle branch block; NSTEMI = non-ST-elevation MI; OHCA = out-of-
hospital cardiac arrest; STEMI = ST-elevation MI; TTM = Target Temperature Management.

The median length of hospital stay was 9.0 days. Good neurological independent predictors of poor outcome with the highest statistical
outcome was associated with a significantly longer length of stay association, clinical relevance, and practical applicability. The ability of
compared with those with poor neurological outcome (16.0 days versus the MIRACLE2 score components to predict neurological outcome in our
4.0 days, p<0.001). cohort was assessed using a multivariable logistic regression model and
demonstrated good agreement with the original published data.15 The
Discussion variables associated with the greatest increase in odds of poor
This study provides external validation of the MIRACLE2 score as a simple neurological outcome were: age category, initial non-shockable rhythm,
risk stratification tool, predicting poor neurological outcome following and any use of adrenaline.
OHCA of presumed cardiac origin. A high-risk MIRACLE2 score ≥5
predicted poor neurological outcome with a specificity of 97.5%. Older age is associated with poorer neurological outcomes after OHCA,
Conversely, a low-risk MIRACLE2 score ≤2 predicted good neurological reflecting higher comorbidity and lower physiological reserve.16 In our
outcome with a specificity of 94.9%. Intermediate-risk MIRACLE2 scores cohort there was a 92-fold increase in the likelihood of poor neurological
are associated with less prognostic certainty, with approximately half outcome in patients aged >80 years, and a sevenfold increase in patients
(32/68, 47%) of patients going on to have a poor outcome. aged 60–80 years, compared with those <60 years old. This compares to
a 21-fold and threefold greater likelihood in the original MIRACLE2 cohort.15
MIRACLE2 Score
The MIRACLE2 score was developed from a range of demographic and OHCA patients presenting with ventricular tachycardia or VF have a higher
clinical factors.15 Its authors identified a simplified model of seven survival rate than those in PEA or asystole.17 Shockable rhythms are more

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 Validation of the MIRACLE2 Score

Table 3: Univariable and Multivariable Logistic Regression Analysis of Poor Neurological Outcome at Discharge

Predictor Univariable, OR [95% CI] p-value Multivariable, OR [95% CI] p-value Log (OR)
Unwitnessed 1.63 [0.77–3.42] 0.201 1.19 [0.35–4.01] 0.782 0.17
Initial non-shockable rhythm 22.34 [7.63–65.41] <0.001 15.95 [4.16–61.13] <0.001 2.77
Changing rhythms 10.10 [5.01–20.35] <0.001 5.00 [1.83–13.70] 0.002 1.61
Age category (ref: ≤60 years):
• 60–80 years 1.71 [0.96–3.05] 0.068 6.93 [2.39–20.12] <0.001 1.94
• >80 years 18.29 [3.99–83.87] <0.001 92.31 [9.39–907.81] <0.001 4.53
pH < 7.20 5.46 [3.00–9.94] <0.001 4.23 [1.55–11.57] 0.005 1.44
Unreactive pupils 8.81 [3.43–22.63] <0.001 5.05 [1.17–21.84] 0.030 1.62
Any adrenaline 23.68 [10.46–55.62] <0.001 6.50 [2.17–19.44] <0.001 1.87
Bystander CPR 0.38 [0.16–0.88] 0.025
• LVEF (%): 0.98 [0.95–1.01] 0.179
• Zero-flow time (min) 1.23 [1.07–1.41] 0.004
• Low-flow time (min) 1.06 [1.04–1.09] <0.001
• Serum creatinine (µmol/l) 1.01 [1.00–1.02] 0.002
• Lactate (mmol/l) 1.20 [1.10–1.31] <0.001
SCAI shock grade (ref: A):
• B 3.73 [1.21–11.52] 0.022
• C 6.85 [3.57–13.13] <0.001
• D 11.18 [1.21–103.53] 0.034
• E – –
CPR = cardiopulmonary resuscitation; LVEF = left ventricular ejection fraction; SCAI = Society for Cardiovascular Angiography and Interventions.

commonly associated with primary cardiac aetiology and more effective in the likelihood of poor neurological outcome, comparable with a 2.49-
treatment strategies. An initial non-shockable rhythm had a 16-fold higher fold increase in the original MIRACLE2 cohort.15
likelihood of poor neurological outcome compared with an initial
shockable rhythm. Our results are broadly in agreement with those for the Unwitnessed arrest was not significant in our model. Patients coded as
original MIRACLE2 cohort, who had a fivefold increased likelihood of poor unwitnessed totalled 33 (15%), of whom 25 (76%) had bystander CPR once
neurological outcome. found. The median estimated total downtime compared favourably with
witnessed arrest (28 minutes versus 23 minutes, p=0.139), suggesting that
The role of adrenaline in OHCA remains uncertain, with survival benefit the unwitnessed no-flow period was short in this group. This will have had
but no neurological benefit observed in randomised trials, although it the effect of reducing the predictive contribution of the unwitnessed
remains a part of the European resuscitation guidelines.18,19 The use of arrest component of the MIRACLE2 score.
adrenaline may reflect the complexity of resuscitation, with greater use in
those with multiple cycles and prolonged downtime. Regional variation in MIRACLE2 Score and Coronary
adrenaline use has been reported, and use of adrenaline in our cohort Angiography Decision-making
was lower (58%) than in the original MIRACLE2 cohort (72%).15,20 However, The majority of our data come from the post-COACT era, but before
the increased likelihood of poor neurological outcome with any adrenaline publication of the TOMAHAWK trial.7,8 These landmark clinical trials have
use remained comparable (6.50-fold versus 7.67-fold). been interpreted by many as a strong mandate not to take patients
without ST-elevation to the catheterisation laboratory. Although routine
Low pH on initial blood gas after OHCA commonly reflects both CAG may not be an appropriate strategy in the absence of ST-elevation
respiratory and metabolic (lactic) acidosis. We found that pH <7.2 was on ECG, the decision is more nuanced than existing trial data allow for
associated with a fourfold increase in the likelihood of poor neurological and many factors need to be considered, including haemodynamic and
outcome, consistent with the original MIRACLE2 cohort (2.26-fold electrical instability and overall chances of a good neurological
increase).15 outcome. It is particularly important to emphasise that patients with
haemodynamic or electrical instability were excluded from COACT and
Pupillary reflex is a more controversial proxy of neurological insult due to TOMAHAWK.
its subjective nature, with a risk of over-reporting reflex absence.21,22 A
study of >10,000 post-OHCA patients described lack of pupil reactivity in It is important to note that our OHCA service, as indicated by the
64% of cases, but on follow-up 10% of these patients had a favourable percentage of ventilated patients undergoing PCI, has been an outlier in
recovery.23 However, hypoxic brain injury occurs within minutes of a low- the UK national dataset for many years.26 This reflects early adoption of a
cardiac output, and in the absence of one universal clinical finding collaborative multidisciplinary pathway, involving emergency physicians,
signifying futility, pupil reactivity remains a valued predictive parameter.24,25 cardiologists and intensivists, with a low threshold for early CAG.
In our cohort, non-reactive pupils were associated with a fivefold increase Retrospective application of the MIRACLE2 score to our contemporary

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 Validation of the MIRACLE2 Score

Table 4: Referral Patient Characteristics for Coronary Angiography and Invasive Therapy

Variable Total (n=219), n (%) CPC 0–2 (n=122, 56%), n (%) CPC 3–5 (n=97, 44%), n (%) p-value*
Coronary angiogram 166/219 (76) 109/122 (89) 57/97 (59) <0.001
Early CAG (<24 h): 148/219 (68) 92/122 (75) 56/97 (58) <0.001
• MIRACLE2 score ≤2 points 66/148 (45) 62/66 (94) 4/66 (6)
• MIRACLE2 score 3–4 points 48/148 (32) 27/48 (56) 21/48 (44)
• MIRACLE2 score ≥5 points 34/148 (23) 3/34 (9) 31/34 (91)
• Time to angiogram (h), median (IQR) 1.0 (0.6–1.5) 0.9 (0.6–1.4) 1.2 (0.8–1.9)
Delayed CAG (≥24 h): 18/219 (8) 17/122 (14) 1/97 (1) <0.001
• MIRACLE2 score ≤2 points 12/18 (67) 12/12 (100) 0/12 (0)
• MIRACLE2 score 3–4 points 5/18 (28) 5/5 (100) 0/5 (0)
• MIRACLE2 score ≥5 points 1/18 (6) 0/1 (0) 1/1 (100)
• Time to angiogram (h), median (IQR) 142.1 (77.8–256.8) 142.9 (91.7–262.9) 37.9 (NA)
No CAG: 53/219 (24) 13/122 (11) 40/97 (41) <0.001
• MIRACLE2 score ≤2 points 11/53 (21) 10/11 (91) 1/11 (9)
• MIRACLE2 score 3–4 points 13/53 (25) 3/13 (23) 10/13 (77)
• MIRACLE2 score ≥5 points 29/53 (55) 0/29 (0) 29/29 (100)
Culprit lesion found 101/166 (61) 65/109 (60) 36/57 (63) 0.659
No. vessels with severe CAD: 0.994
• 0 40/166 (24) 26/109 (24) 14/57 (25)
• 1 72/166 (43) 47/109 (43) 25/57 (44)
• 2 37/166 (22) 25/109 (23) 12/57 (21)
• 3 17/166 (10) 11/109 (10) 6/57 (11)
Invasive therapy during admission:
• PCI 92/219 (42) 61/122 (50) 31/97 (32)
• MIRACLE2 score ≤2 points 43/89 (48) 41/43 (95) 2/43 (5)
• MIRACLE2 score 3–4 points 33/66 (50) 17/33 (52) 16/33 (48)
• MIRACLE2 score ≥5 points 16/64 (25) 3/16 (19) 13/16 (81)
• CABG 9/219 (4) 9/122 (7) 0/97 (0) 0.006
*Mann–Whitney U-test for median (IQR) comparisons (non-parametric), Fisher’s exact test for categorical 2 × 2 contingency tables and Pearson’s χ2 test for categorical variables of greater dimensions.
CABG = coronary artery bypass graft; CAD = coronary artery disease; CAG = coronary angiography; CPC = Cerebral Performance Category; PCI = percutaneous coronary intervention.

data demonstrates a selective decision-making process (24% of patients MIRACLE2 scores who underwent early-CAG, only 3 (9%) had a good
not undergoing CAG) but suggests that prospective application of the neurological outcome at hospital, whereas the majority (31, 91%) had a
score may avoid unnecessary intervention in some of the highest risk poor outcome. A similar pattern was seen in the presence or absence of
individuals. ST-elevation with LBBB on initial ECG, suggesting that a high MIRACLE2
score is a useful prognostic tool regardless of presenting ECG,
For patients who underwent CAG within 24 hours of hospital admission, representing damage already done in this unfortunate cohort.
the median admission-to-laboratory time was comparable to that reported
in both COACT and TOMAHAWK (1.0 hour versus 2.3 hours and 2.9 hours, A MIRACLE2 score ≥5 was 97.5% specific for poor neurological outcome in
respectively).7,8 Our cohort included STEMI and LBBB presentations, which our cohort. Although a single scoring system will never cover all cases,
these trials did not. However, the median time to laboratory was still this suggests that the MIRACLE2 score is a useful tool that can aid in
1.0 hour in the early-CAG group even after the removal of STEMI and LBBB discussions between specialist hospital teams and the patient’s family, to
patients. As expected, the primary outcome was observed less in the minimise futile treatments and enable better palliative care.
STEMI–LBBB cohort (39%) but importantly the outcomes in the TOMAHAWK
cohort mirrored the study (48% CPC 3–5).8 Intermediate-risk MIRACLE2 Score
Our data suggest that much of the prognostication in the low and high
In our cohort, a low-risk MIRACLE2 score (≤2) was associated with good MIRACLE2 risk categories can be achieved at the hospital front door using
neurological outcomes regardless of early-CAG (62/66, 94%), late-CAG basic clinical information. However, intermediate-risk MIRACLE2 patients
(12/12, 100%) or no-CAG (10/11, 91%) strategies. This most likely reflects have the greatest prognostic uncertainty and represent 31% of our cohort.
appropriate individualised clinical decision-making. Good neurological recovery was observed in 35 of the 66 (53%)
intermediate-risk patients at hospital discharge. This was similar
A high-risk MIRACLE2 score (≥5) was associated with poor neurological regardless of presenting ECG (STEMI–LBBB, 16/32, 50%; NSTEMI–LBBB,
outcomes regardless of CAG strategy. Of the 34 patients with high-risk 19/34, 56%).

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 Validation of the MIRACLE2 Score

Limitations While this retrospective study provided a large and detailed dataset,
This study has several limitations. The MIRACLE2 score has been created there were missing variables, particularly those of pupil reactivity and
from a retrospective registry of OHCA patients, and as yet it has not blood pH measurements.
undergone prospective validation. The present cohort attended a tertiary
centre with immediate access to specialised care and a dedicated cardiac Conclusion
service, similar to the original cohort; therefore, it is unclear how the score The MIRACLE2 score demonstrates good prognostic performance and is
would perform in a centre with a less mature service. easily applicable to cardiac-origin OHCA presentation at the hospital front
door. Prognostic scoring may assist decision-making regarding early
The MIRACLE2 score is based upon an immediate static assessment of a angiographic assessment.
critically ill patient. The pupillary response is one factor that may evolve as
a patient progresses through their post-resuscitation care. The response
captured in the MIRACLE2 score represents an initial assessment at the
point of presentation, typically in the first hour. Ongoing pupillary Clinical Perspective
assessment is required as part of a patient’s neuro-prognostication. • Out-of-hospital cardiac arrest (OHCA) is associated with poor
clinical outcome, and consensus on the pathway of care is yet to
Generation of a dynamic model tracking continuously monitored data may be agreed. Neuro-prognostication scoring may assist in
provide greater accuracy of outcome and further guide the complex treatment decision-making but external validation of scores is
management of this high-risk population. essential before considering prospective utility.
• This study has validated the MIRACLE2 score as a predictor of
Intermediate-risk MIRACLE2 patients represent a difficult population in neurological outcome after OHCA.
terms of identifying those most likely to achieve a good neurological • The MIRACLE2 score demonstrates excellent performance and
outcome. The utility of an intermediate score, in isolation, is low. This suggests possible utility in guiding treatment decisions in OHCA
group requires careful consideration of the most appropriate approach, patients, particularly for those at highest risk of poor outcomes.
on a case-by-case basis, within a multidisciplinary framework.

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