Article Text
PDF
Abstract
Background Patients with low HEART (History, Electrocardiogram, Age, Risk factors, and Troponin level) risk scores who are discharged from the emergency department (ED) may present clinical challenges and diagnostic dilemmas. The use of downstream non-invasive stress imaging (NISI) tests in this population remains uncertain. Therefore, this study aims to investigate the value of NISI in risk stratification and predicting cardiac events in patients with low-risk HEART scores (LRHSs).
Methods We prospectively included 1384 patients with LRHSs between March 2019 and March 2021. All the patients underwent NISI (involving myocardial perfusion imaging/stress echocardiography). The primary endpoints included cardiac death, non-fatal myocardial infarction and unplanned coronary revascularisation. Secondary endpoints encompassed cardiovascular-related admissions or ED visits.
Results The mean patient age was 64±14 years, with 670 (48.4%) being women. During the 634±104 days of follow-up, 58 (4.2%) patients experienced 62 types of primary endpoints, while 60 (4.3%) developed secondary endpoints. Multivariable Cox models, adjusted for clinical and imaging variables, showed that diabetes (HR: 2.38; p=0.008), HEART score of 3 (HR: 1.32; p=0.01), history of coronary artery disease (HR: 2.75; p=0.003), ECG changes (HR: 5.11; p<0.0001) and abnormal NISI (HR: 16.4; p<0.0001) were primary endpoint predictors, while abnormal NISI was a predictor of secondary endpoints (HR: 3.05; p<0.0001).
Conclusions NISI significantly predicted primary cardiac events and cardiovascular-related readmissions/ED visits in patients with LRHSs.
- Chest Pain
- Tomography, Emission-Computed, Single-Photon
- Echocardiography
Data availability statement
Data are available upon reasonable request. Data generated or analysed during the study are available from the corresponding author by request.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
WHAT IS ALREADY KNOWN ON THIS TOPIC
Patients with low HEART risk scores discharged from the emergency department (ED) pose clinical challenges and diagnostic dilemmas.
The utility of downstream non-invasive stress imaging (NISI) in these patients remains uncertain, necessitating this study.
WHAT THIS STUDY ADDS
This study demonstrates that NISI is a significant predictor of primary cardiac events and cardiovascular-related readmissions/ED visits in patients with low-risk heart scores (LRHSs).
Factors such as diabetes, a HEART score of 3, a history of coronary artery disease, ECG changes and abnormal NISI results are identified as primary endpoint predictors.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE, OR POLICY
The findings support the use of NISI for better risk stratification and management of patients with LRHSs and high clinical risk features including LRHSs score of 3, diabetes and history of coronary artery disease.
These results could influence clinical guidelines and policies regarding the follow-up and treatment of patients discharged with LHRSs from the ED.
Introduction
Chest pain is the second most common reason for emergency department (ED) visits in Canada.1 However, a small proportion (<10%) of these patients are diagnosed with acute coronary syndrome (ACS) or other life-threatening conditions.2
Since its introduction in 2008, the HEART score has emerged as the most used scoring system in the ED for risk assessment of patients with chest pain or symptoms suggestive of ACS. Several studies have validated the safety, efficacy and cost-effectiveness of the HEART score regarding acute chest pain.3–5 Following discharge from the ED, patients with low-risk heart scores (LRHSs) had considerably lower risks of major adverse cardiovascular events (MACE).6
Nevertheless, a recent large-scale multiethnic cohort study presented conflicting findings, indicating a 4.6% MACE rate within 6 weeks of ED discharge among patients with LRHSs7; in this study, MACE was defined as coronary revascularisation, myocardial infarction (MI), or all-cause death. Consequently, these statistics cannot be disregarded.8 9
In clinical practice, patients with LRHS (scores 0–3) represent a challenging subgroup, imposing a burden on healthcare facilities with their recurrent visits for chest pain, and presenting a clinical dilemma regarding the optimal diagnostic approach to be employed.8
Prominent cardiovascular organisations continue to recommend non-invasive stress imaging (NISI) assessments for inpatients with acute chest pain or after hospital discharge given its high value in ruling-out obstructive coronary artery disease (CAD) and ability to predict short-term and long-term MACE.9 The most commonly employed NISI examinations encompass stress echocardiography (SE), single-photon emission CT (SPECT), positron emission tomography and cardiovascular magnetic resonance imaging.2 NISI provides crucial insights into both the burden of CAD and myocardial ischaemia, facilitating the refinement of risk assessment and guiding subsequent management decisions.10
Despite the growing interest in using downstream NISI for risk stratification in patients with low HEART risk scores, there remains a paucity of evidence regarding their clinical effectiveness and impact on patient outcomes. This highlights the need for further research to evaluate the role of NISI in this specific patient population and to assess its potential to enhance risk stratification and clinical decision-making. Therefore, this study aims to investigate the effectiveness of downstream NISI in stratifying risk and predicting cardiac events in patients presenting with chest pain who were discharged early from the ED due to LRHSs.
Material and methods
Study design and population
We conducted a prospective single-centre interventional study in Ontario province, Canada. Between March 2019 and March 2021, an assessment was conducted to determine the eligibility for study enrolment of all patients who presented to the ED with suspected cardiac chest pain. ED physicians used the HEART score for risk stratification and ACS probability assessment. The initial evaluation included five key components: the presenting history of the patient, ECG, age, cardiovascular risk factors and troponin levels. Patients with LRHSs (defined as scores of ≤3) were discharged from the ED in <6 hours without further intervention and were included in our analysis. All included patients provided a written informed consent to participate in the study and agreed to undergo the NISI test. They were followed up after <30 days by a cardiologist in a dedicated chest pain clinic designed for the study. The exclusion criteria were as follows: patients with obvious non-cardiac chest pain, such as musculoskeletal or traumatic cases; see figure 1.
Patients inclusion. ED, emergency department; LRHSs, low-risk heart scores; NISI, non-invasive stress imaging.
Non-invasive stress imaging
All the included patients underwent SE or SPECT, as these are the most commonly available NISI in real-world clinical practice. The treadmill was the recommended exercise method for physically active patients, while pharmacological stress agents (dobutamine for SE and dipyridamole for SPECT) were used for physically inactive individuals. The choice of imaging modalities (SE vs SPECT) was primarily determined through patient–physician conversations (radiation risk and anthropometric implications on test diagnostic accuracy), test booking capacity and patient preferences.
SE results were assessed according to the American Society of Echocardiography guidelines.11 The studies were defined as normal (normally augmented myocardial segments), abnormal (new regional wall motion abnormalities suggestive of stress-inducible myocardial ischemia) or inconclusive (uninterpretable images). SPECT scan was performed using Technetium-99m with a 2-day stress/rest protocol. The reporting of the SPECT studies adhered to the guidelines of the American Society of Nuclear Cardiology.12 Results were categorised as normal (no reversible perfusion defects), abnormal (presence of >5% reversible perfusion defects or transient left ventricular dilatation without perfusion defects) or inconclusive (uninterpretable images).
Chest pain clinic follow-up
Following NISI testing, a cardiologist examined all patients at a dedicated chest pain clinic. Patients with stress-induced ischaemia involving >1 segment in SE or the presence of reversible perfusion defects in>10% of the myocardium in MPI were classified as high-risk scans. The ultimate decision for further evaluation using invasive coronary angiography (ICAG) was based on the results of the NISI tests, symptom recurrence and the presence of multiple risk factors. Patients with normal and low-risk NISI scans, or those with insignificant coronary artery stenosis detected through ICAG, received ongoing medical treatment. Conversely, patients with haemodynamically significant coronary artery lesions underwent coronary revascularisation, guided by angiographic findings and a consensus reached by a multidisciplinary ‘Heart Team’.
Outcomes
The study cohorts were prospectively followed up for 2 years to assess primary and secondary endpoints. The primary outcome included cardiac death, non-fatal MI, or unplanned revascularisation (3 months after NISI) for significant coronary stenosis (defined as stenosis >70% or fractional flow reserve <0.8).6 The secondary outcome was defined as repeated ED visits or hospital admissions related to cardiovascular events, including chest pain and arrhythmia.7
Statistics analysis
Continuous data are expressed as means and SD, while categorical variables are presented as numbers and percentages. To compare categorical variables, the χ2 test was employed, and for continuous variables, the Student’s t-test was used.
HR with 95% CIs were calculated using univariate Cox regression models to assess the association between clinical and stress variables and the time-to-event of the primary and secondary endpoints, considering the ED as the initial time index for our Cox model. Subsequently, three multivariate Cox regression analyses were conducted, with adjustments made for clinical variables (age, gender, traditional CAD risk factors, history of CAD and HEART scores), stress test variables (ischaemic ECG changes, hypertensive response to stress test and positive imaging test for ischaemia), and both clinical and stress test variables. Finally, survival curves were generated using Kaplan-Meier analysis. Statistical significance was set at p<0.05. All data analyses were performed using the Statistical Package for Social Sciences (SPSS V.22).
Results
Study population
Overall, 1384 patients were included in the final analysis. Among them, 670 (48.4%) were women, with a mean age of 64±14 years (range: 20–98 years). The median time between the ER visit and the stress test was 20 days, with an IQR of 6 days. The mean follow-up period was 634±104 days. Table 1 summarises other baseline characteristics of the study population.
Other baseline characteristics of the study population
Non-invasive stress test results
All patients underwent at least one NISI test. Among the 1384 patients, 988 (72%) underwent SPECT, 411 (29.7%) underwent SE and 15 underwent SPECT and SE owing to inconclusive results. The stress methods employed were as follows: dipyridamole, used in 731 (52.8%); treadmill, used in 617 (44.6%); and dobutamine, administered in 36 (2.6%). Inducible ischaemia was positive in 28/411 (6.8%) patients based on SE results with 19 patients had regional wall motion abnormalities in more than one segment within a single coronary artery territory, while 9 patients had abnormalities in more than one region, indicating multivessel territory affection. Regarding SPECT scans, 63/998 (6.4%) patients exhibited reversible ischaemia, with 30 showing mild defects (5%–10% of myocardial mass), 22 exhibiting moderate defects (10%–20% of myocardial mass), 11 having large defects (>20% of the myocardial mass) and 21 experiencing fixed defects.
Invasive coronary angiography
In total, 92/1384 (6.6%) patients underwent ICAG. Among them, 53/92 (54.3%) patients exhibited significant coronary artery stenosis, 18 had non-obstructive CAD and 21 had healthy coronary arteries. Among patients with significant stenosis, the distribution across the number of coronary arteries affected was as follows: 27 had single-vessel CAD, 10 with two-vessel CAD and 16 with three-vessel CAD. Regarding the management, 39 patients were treated with percutaneous coronary intervention, 11 underwent coronary artery bypass graft surgery and 3 were managed with medical therapy The indications for undergoing ICAG were abnormal NISI results in 40/92 (43.5%) patients and clinical indications in 52/92 (56.5%) patients.
Primary and secondary outcomes
Throughout the follow-up duration, 58/1384 (4.2%) patients developed 62 severe cardiac events, comprising 4 cardiac deaths (3 occurred in patients with a HEART score of 3, and 1 death was recorded in the HEART score of 2 group), 5 non-fatal MIs (two instances were observed in patients with a HEART score of 3, 1 in the HEART score of 2 group and 1 in the HEART score of 1 group), and 53 significant CAD. Most events (89.5%) occurred within the first year following the initial ED visit. After excluding patients with primary outcomes, 60 (4.3%) patients experienced secondary endpoints, including 49 readmissions/ED recurrent visits due to chest pain, 5 cases of cerebrovascular accidents and 6 hospitalisations for arrhythmia.
Cox models for endpoints
Univariate Cox regression demonstrated that significant predictors of primary endpoint events included diabetes, a history of CAD, having HEART score of 3 and ECG changes during the stress test, as well as abnormal NISI test results (table 2). Similar findings were observed in the three multivariable Cox models, which were adjusted for clinical variables, imaging variables (abnormal ECG, hypertensive response and abnormal NISI), and both clinical and imaging variables. The latter demonstrated that diabetes (HR: 2.38; 95% CI 1.25 to 4.49, p=0.008), a HEART score of 3 (HR: 1.32; 95% CI 0.98 to 1.57; p=0.01), CAD history (HR: 2.75; 95% CI 1.40 to 5.41; p=0.003), ECG changes (HR: 5.11; 95% CI 2.61 to 10.01; p<0.0001) and abnormal NISI (HR: 16.4; 95% CI 9.56 to 28.03; p<0.0001) were all significant predictors of primary endpoint events (online supplemental table 1). In contrast, the univariable and multivariable Cox regression model, adjusted for clinical and imaging variables, revealed that abnormal NISI is the sole predictor of secondary endpoint events (HR: 3.07; 95% CI 1.32 to 7.15; p=0.009 and HR: 3.05; 95% CI 1.31 to 7.14; p=0.01, respectively) (table 3). Kaplan-Meier survival analysis revealed that abnormal NISI could significantly predict primary events at 1-year and 2-year follow-up (p<0.0001, figure 2) and also predicted 2-year secondary endpoint events (p=0.001, figure 3).
Supplemental material
Kaplan-Meier survival analysis showed that abnormal non-invasive stress imaging can significantly predict primary events at (A)1-year and (B) 2-year follow-up with p value <0.0001.
Kaplan-Meier survival analysis showed that abnormal non-invasive stress imaging can significantly predict secondary events with p value <0.001. MACE, major adverse cardiovascular events.
Univariable Cox regression analysis for prediction primary endpoints (MACE; death, non-fatal MI and significant coronary stenosis)
Univariable and multivariable Cox regression analysis for prediction of secondary endpoints (cardiovascular-related readmission or emergency department visit)
Discussion
In this prospective study, all patients with a low LRHS who presented to the ED with chest pain, were discharged early and underwent NISI were included. The study revealed that diabetes, CAD history, ECG changes during the stress test and abnormal NISI were significant predictors of primary endpoints (including cardiac death, non-fatal MI and severe coronary artery stenosis) and cardiovascular-related readmissions/ED recurrent visits.
Although multiple reports have validated the safety of early discharge for patients with chest pain and LRHS, with a substantially low MACE incidence of 1.7%,4 we found a significantly higher MACE rate of 4.2%, consistent with that reported by de Hoog et al (4.6%).7 This incidence is approximately four times higher than the acceptable MACE miss rate as defined by ED physicians and the published guidelines.7 Additionally, it was almost three times greater than the rate of cardiac death within 18 months following non-ST-segment MI.13
Few retrospective studies14 15 have examined the utility of downstream NISI in patients with LRHSs. These studies concluded that while there was an increase in ICAG and revascularisation procedures, no substantial reduction in MI occurrence during follow-up was observed. However, recent studies challenged the practice of excluding coronary revascularisation as an outcome in patients following ED visits.16 17
Regarding cardiovascular-related readmission, a small retrospective analysis18 revealed that 20% of patients with LRHSs experienced repeat ED visits within the first year. Furthermore, in a prospective study conducted by Wang et al,19 NISI was performed in 60% of patients with LRHS, and they reported a 30% readmission rate over 6 months. Similarly, a randomised trial revealed that within a 3-month timeframe, the rate of ED visits and readmissions was 22%, and an additional 12% visited general practitioners for cardiac-related symptoms.20
In this study, the 2-year cardiovascular-related admission or ED visit rate was 60/1384 (4.3%), significantly lower than that reported previously.18–20 This notable reduction in readmission rates may be attributed to patient reassurance following receipt of a negative NISI test result and evaluation by cardiologists in a dedicated chest pain clinic.
Following the HEART pathway, fewer NISI tests were performed in the short term; however, these changes were transient, as 40%–60% of the tested population subsequently had a form of NISI during their follow-up.14 19 21 A retrospective analysis by Innocenti et al22 represents the sole report of the HEART score in the literature. In their analysis, all 348 patients with LRHSs underwent NISI testing in the ED and their follow-up was limited to only 30 days. Our study in turn is the largest prospective investigation to date, systematically evaluating the value of NISI in all patients with LRHSs, and it includes a substantial follow-up period.
In this study, we identified patients with LRHSs at higher risk of MACE who may potentially benefit from undergoing the downstream NISI test. We identified three clinical predictors (diabetes, HEART score of 3 and history of CAD) and two test-related predictors (ECG changes and abnormal NISI) of MACE. Given the large percentage of LRHSs among ED patients with chest pain, implementing NISI for every LRHS case in clinical practice may pose a significant logistical challenge; thus, the NISI should be reserved for patients with LRHSs at a higher risk for MACE. The findings of this study were incorporated into the design of a systematic approach to guide the management of patients with LRHSs after discharge (figure 4).
Systematic approach to guide the management of patients with low-risk heart scores (LRHSs) after discharge. CAD, coronary artery disease; ED, emergency department; ICAG, invasive coronary angiography.
Our study has some limitations. First, there are insufficient data regarding the cost of procedures performed on patients. Second, although coronary CT angiography is a useful imaging tool to risk stratify low-risk patients which is commonly used in many centres across Canada, it was not readily available in our institution. Third, owing to the constraints imposed by the COVID-19 pandemic and strict healthcare facility rules, most physically active patients underwent dipyridamole stress tests (52.8%). Further studies should consider this aspect.
Conclusions
Our findings emphasise the importance of risk stratification in the patients with LRHSs and highlight the potential of NISI as a valuable tool for identifying those at higher risk of adverse cardiac events. These insights have the potential to inform more precise clinical decision-making, improve patient outcomes and contribute to the ongoing refinement of guidelines and practices in the management of chest pain in the ED.
Data availability statement
Data are available upon reasonable request. Data generated or analysed during the study are available from the corresponding author by request.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by Lawson Research Institute, London ON, CA. Participants gave informed consent to participate in the study before taking part.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors NT is guarantor. Conception and design of study: NT and RMA. Literature review: RMA, NP, ME, SA, AA and MMA. Acquisition of data: RMA, NP, ME, RB, CA and NT. Data collection: RMA, NP, ME, SA, AA and MMI. Analysis and interpretation of data: YB, RMA and RB. Drafting of manuscript: RMA, NP, ME, SA, AA, MMI and YB. Revising and editing the manuscript critically for important intellectual contents: RMA, NP, ME, SA, AA, MMI, YB, CA and NT. Supervision of the research: NT. All authors have reviewed and agreed the contents of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.