- Original research
- Open Access
Dyspnea, a high-risk symptom in patients suspected of myocardial infarction in the ambulance? A population-based follow-up study
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicinevolume 24, Article number: 15 (2016)
Systematic management of patients suffering high-risk symptoms is essential in emergency medical services. Patients with chest pain receive algorithm-based work-up and treatment. Though dyspnea is recognized as an independent predictor of mortality, no generally accepted prehospital treatment algorithm exists and this may affect outcome. The objective of this study was to compare mortality in patients suspected of myocardial infarction (MI) presenting with dyspnea versus chest pain in the ambulance.
Follow-up study in patients undergoing electrocardiogram-based telemedical triage because of suspected MI in an ambulance in the Central Denmark Region from 1 June 2008 to 1 January 2013. Primary outcome was 30-day mortality. Secondary outcomes were 4-year mortality and mortality rates in subgroups of patients with and without a confirmed MI. Absolute risk differences adjusted for comorbidity, age, systolic blood pressure and heart rate were calculated by a generalized linear regression model.
Of 17,398 patients, 12,230 (70 %) suffered from chest pain, 1464 (8 %) from dyspnea, 3540 (20 %) from other symptoms and 164 (1 %) from cardiac arrest. Among patients with dyspnea, 30-day mortality was 13 % (CI 12–15) and 4-year mortality was 50 % (CI 47–54) compared to 2.9 % (CI 2.6-3.2) and 20 % (CI 19–21) in patients with chest pain. MI was confirmed in 121 (8.3 %) patients with dyspnea and in 2319 (19 %) with chest pain. Patients with dyspnea and confirmed MI had a 30-day and 4-year mortality of 21 % (CI 15–30) and 60 % (CI 50–70) compared to 5.0 % (CI 4.2-5.8) and 23 % (CI 21–25) in patients with chest pain and confirmed MI. Adjusting for age, comorbidity, systolic blood pressure and heart rate did not change these patterns.
Patients suspected of MI presenting with dyspnea have significantly higher short- and long-term mortality than patients with chest pain irrespective of a confirmed MI diagnosis. Future studies should examine if supplementary prehospital diagnostics can improve triage, facilitate early therapy and improve outcome in patients presenting with dyspnea.
In emergency medical services (EMS), a systematic approach to patients suffering high-risk symptoms is essential. Systematic guidelines for prehospital management of chest pain were developed more than a decade ago and prehospital management plays an increasingly important role in cardiac arrest guidelines [1, 2]. Timely prehospital diagnostics and early primary percutaneous coronary intervention or fibrinolysis in ST-elevation myocardial infarction (STEMI) have contributed significantly to a reduced mortality in myocardial infarction (MI) [3, 4]. In out-of-hospital cardiac arrest (OHCA), a combination of layperson cardiopulmonary resuscitation, early defibrillation, improved skills among EMS personnel and advanced life support has improved outcome . For patients with dyspnea, however, we have no commonly accepted guidelines for prehospital management. This is a paradox, since dyspnea is recognized as an independent predictor of mortality [6, 7]. In Denmark, a prehospital electrocardiogram (ECG) based telemedical diagnosis of STEMI is sought not only in patients with chest pain but also among other symptoms suggestive of MI, including dyspnea [4, 8]. However, STEMI is less frequent in patients with dyspnea than in chest pain . In dyspnea, multiple other tentative diagnoses are possible – often as interacting comorbid conditions [10–12]. At the same time, treatment is often necessary before a final diagnosis is made and giving the right treatment to the right patient is a difficult task. We therefore hypothesize that a primary complaint of dyspnea predicts a higher mortality than chest pain in patients suspected of MI in the ambulance.
The primary aim of the present study was to compare mortality in telemedically triaged patients suspected of MI presenting with dyspnea or chest pain. The secondary aim was to compare mortality in these patients according to whether a diagnosis of MI was established or not.
Design and setting
This is a population-based follow-up study of 23,184 telemedical contacts registered in the Danish Tele-database from 1 June 2008 to 1 January 2013. The setting is the Central Denmark Region which covers an area of 13,053 km2 of mixed urban, suburban and rural land with 1.3 million inhabitants corresponding to 23 % of the Danish population . The EMS response in this region is two-tiered with basic-level care delivered by ambulances sent to all urgent cases. Anesthesiologist or nurse anesthetist staffed prehospital critical care teams deliver supplementary advanced prehospital care in suspected life-threatening cases. Acutely ill patients are brought to one of five public hospitals within the region. Revascularization therapy (percutaneous coronary intervention or surgery) is centralized at Aarhus University Hospital. Health care is public and provided free of charge by the Danish National Health Service.
Ambulance personnel establish an ECG-based telemedical contact to an on-call cardiologist at a local department of cardiology in patients suspected of an MI according to predefined criteria: 1) patients with on-going or recent chest pain within the past 12 h and/or clinical suspicion of MI (e.g. pallor and diaphoresis) 2) patients with new onset of dyspnea within the past 12 h and no known lung disease 3) patients with other symptoms raising suspicion of heart disease (e.g. syncope/somnolence, palpitations, abdominal/back pain, intoxication etc.) and 4) patients resuscitated from OHCA. In case of STEMI, OHCA with no obvious non-cardiac cause, or cardiogenic shock, the ambulance is re-routed directly to the pre-alerted catheterization laboratory at Aarhus University Hospital for coronary angiography and primary percutaneous coronary intervention. Patients not re-routed directly to the catheterization laboratory are generally admitted to the nearest hospital receiving acute patients. On-call cardiologists receiving the telemedical calls perform all registrations in the Danish Tele-database, including which of the above-mentioned symptoms/conditions is the predominant cause of MI suspicion in the individual patient.
The criterion for inclusion in the study was a registration of an ECG-based telemedical contact in the Tele-database at a department of cardiology in the Central Denmark Region with a valid personal identification number. Only the first contact during the study period in each patient was included. Participants were followed until 9 October 2013. Contacts with invalid personal identification number or foreigners were considered lost to follow up and were excluded from the study.
Vital status was retrieved from the Danish Civil Registration System; and data on previous diseases and present diagnoses according to the 10th version of the International Classification of Disease (ICD-10) were retrieved from the Danish National Registry of Patients. Full medical files were retrieved from a total of 200 patients with dyspnea for development of an algorithm for determining the cause of dyspnea in the ambulance and for validation of this algorithm.
The present study was exempt from ethical approval according to Danish law. The Danish Data Protection agency (Journal nr. 1-16-02-158-12) and the Danish Health and Medicines Authority (Journal nr. 3-3013-247/1/) approved the study.
Exposures and outcomes
The predominant symptoms/conditions leading to suspicion of MI as registered by the on-call cardiologists were regarded as exposures. The primary outcome was 30-day mortality. Secondary outcomes were long-term mortality (4 years), the number of patients in each group diagnosed with an MI and the associated mortality rates, and causes of dyspnea in patients triaged because of dyspnea. The following potential confounders were considered to be relevant: comorbidities, age, gender, smoking status, alcohol consumption, heart rate and systolic blood pressure. Because of an expected mixture of different underlying diseases causing the different symptoms, we opted on using a comorbidity index rather than adjusting for specific diseases. We chose the Charlson Comorbidity Index based on the ICD-10 diagnoses as described by Sundararajan et al. as this is extensively validated - also in a Danish population [14, 15]. Information on age, gender, heart rate and systolic blood pressure was obtained from the Tele-database. Vital signs were measured at first encounter – in patients resuscitated from cardiac arrest immediately following ROSC. We had no information on smoking status or alcohol consumption.
Patients diagnosed with MI were identified by ICD-10 codes ranging from DI21.0 to DI23.8A. By studying information from the full medical files from the first 100 of the 1,464 patients with dyspnea, we developed an algorithm to predict the cause of dyspnea (heart disease/lung disease/other cause) based on the ICD-10 codes assigned at discharge (Additional file 1 and 2). A new random sample of 100 patients from the 1464 patients with dyspnea was then drawn to test the algorithm. For these patients, full medical files including imaging and blood tests were retrieved and reviewed by an end-point adjudication committee consisting of two investigators blinded to the result of the ICD-10 algorithm. The members of the committee adjudicated the cause of dyspnea, dividing it into one of three main categories: 1) heart disease 2) lung disease and 3) other cause. In case of incongruence, a third investigator reviewed the material and chose one of the two previously adjudicated causes. Thus, the majority vote was accepted as consensus. It was decided a priori that the performance of the ICD-10 algorithm was satisfactory if in agreement with the adjudication committee in at least 75 % of cases. This decision was based on previously reported variations in sensitivity and specificity in which ICD-10 codes were used to evaluate whether a diagnosis of heart failure and chronic obstructive pulmonary disease was established [16, 17].
Mortality was displayed as Kaplan Meier curves which were truncated when less than 10 % of the original cohort was left. To adjust for potential confounders, we planned to perform a Cox proportional hazards regression analysis. The survival curves did not fulfill the proportional hazards assumption, so this plan was waived. Instead we calculated adjusted risk differences by a generalized linear regression using pseudo-observations. The pseudo-observations approach is a transformation of data like log-transformation and others – although it is mathematically more complex. In contrast to Cox regression it allows for non-proportional survival curves and analysis of risk differences at specific time points. It has been well described by Klein et al. . Analyses were conducted in STATA12 (StataCorp LP, Texas, USA) according to the method described by Parner and Andersen . P-values <0.05 was considered to be significant and 95 % confidence intervals (CIs) were used. Participants were categorized into Charlson Comorbidity Index Groups according to the original classification by Charlson et al. . Participants were categorized according to systolic blood pressure and heart rate into four groups approximated to quartiles. Missing data were expected to be missing completely at random and no imputation was made.
Of 23,184 telemedical contacts, 17,398 correct registrations of first telemedical contacts in individual patients were included (Fig. 1). The patients’ baseline characteristics are presented in Table 1. Median follow-up time was 2.4 years (IQR: 1.3 – 3.7). An MI was diagnosed in 2319 of 12,230 (19 %) patients with chest pain and in 121 of 1464 (8.3 %) patients with dyspnea. Patients suffering dyspnea had higher mortality rates than patients with chest pain at both day 30 (primary endpoint) and 4 years, irrespective of whether a diagnosis of MI was confirmed or not (Table 2). Kaplan-Meier estimates for mortality in all four groups of patients are displayed in Fig. 2. Kaplan-Meier estimates for mortality in patients with chest pain and dyspnea with and without confirmed MI are displayed in Fig. 3. Age, comorbidity, systolic blood pressure and heart rate remained significant predictors of mortality in the generalized linear regression model. Adjusted for these potential confounders, patients suffering dyspnea still had higher mortality rates than patients suffering chest pain (Table 3).
Cause of dyspnea
Two endpoint committee adjudicators agreed on the primary cause of dyspnea in all but four of 100 patients sampled for validation. In these patients, the third adjudicator was involved and the majority vote was accepted. The ICD-10 diagnosis algorithm was in agreement with the endpoint adjudication committee in 78 % of the 100 patients sampled for validation. The predominant underlying cause of dyspnea in this cohort of patients suspected of MI was heart disease, but only 8,3 % actually had an MI (Table 4). Among patients in whom heart disease was the primary cause of dyspnea, 20 % were also diagnosed with a lung disease. When lung disease was the primary cause for dyspnea, 41 % of patients were also diagnosed with a heart disease.
We performed three sensitivity analyses, all related to different ways of adjusting for age and comorbidity (included in Additional file 3). We accounted for a possible higher risk with increasing age in older age categories than in younger by including both age and age squared and for a possible polynomial development by including age as qubic splines with seven knots. This reduced the effect of dyspnea slightly but did not change the overall patterns. Including specific diseases related to chest pain and dyspnea rather than the Charlson Comorbidity Index in addition to using qubic splines to adjust for age did not change the results.
This study demonstrates that among patients suspected of MI in the ambulance, patients presenting dyspnea have a three-fold higher mortality than patients with chest pain irrespective of a confirmation of the MI diagnosis. Adjustment for potential confounders does not change these patterns.
Dyspnea vs. other symptoms
Studies comparing mortality rates in patients with dyspnea and patients with other symptoms in a prehospital setting are scarce. However, a large study in emergency medical technician witnessed OHCA showed that patients suffering chest pain prior to cardiac arrest were five times more likely to survive than patients suffering dyspnea prior to cardiac arrest . In a retrospective analysis of hospitalized patients with first-time MI, dyspnea was associated with higher long-term mortality than other presenting symptoms, including chest pain . In patients undergoing coronary angiography for suspected acute coronary syndrome, a four-fold higher mortality in dyspneic compared to non-dyspneic patients was demonstrated . Thus, the observation of higher mortality among dyspneic patients is consistent across the prehospital setting, the acute hospital setting, and the catheterization laboratory. Nevertheless, we still do not have broadly accepted guidelines for management of the dyspneic patient in the prehospital setting.
Diagnoses, comorbidities and age
Approximately 8 % of the patients suffering dyspnea had an MI. ECG acquisition is thus important also in prehospital diagnostics in dyspnea patients, but it seems inadequate to establish a prehospital diagnosis and identify high-risk patients in this patient group in general. These patients suffer from a variety of diseases not only including MI but also heart failure, pulmonary infections, and obstructive pulmonary disorders. Furthermore, our study also demonstrates that heart and lung disease frequently coexist. This is supported by other studies [11, 12], and this co-existence deteriorates the prognosis . As it is seen from Table 1, age and comorbidities do play a major role in the high mortality in patients with dyspnea. At long term, the independent effect on mortality of being in CCI group ≥ 3 or being 10 years older is more pronounced than the effect of suffering dyspnea. At short term, the same applies to age, but not comorbidities. In addition, no matter how we tried to adjust for age and comorbidities, we were not able to eliminate an independent effect of dyspnea compared to chest pain. This indicates, that there is a potential for improving care of patients with dyspnea. Based on the very high mortality observed in the first short period of time after ambulance contact, there seems to be a window of opportunity in the acute phase (refer to the Kaplan-Meier curves in Fig. 2).
Towards a systematic approach
As of now, a stethoscope and an ECG is the most advanced diagnostics routinely used in dyspneic patients in the prehospital setting. Treatment is often broad rather than specific and the evidence behind different new interventions is scarce. We are currently witnessing several, promising technological developments that may aid prehospital decision-making and treatment in dyspneic patients. Point-of-care testing with biomarkers, like brain natriuretic peptides and focused ultrasonography, has been suggested [24–26]. Establishing an accurate diagnosis already in the ambulance to facilitate earlier correct therapy and triage high-risk patients to specialized departments or intensive care unit may improve outcome, but this has not been examined. New treatment regimes facilitating oxygenation and ventilation by continuous positive airway pressure or non-invasive ventilation has also been suggested, but has not been sufficiently examined in relation to patient outcome . Validating the findings of this study in unselected patients with dyspnea in the prehospital setting and the systematic use of prehospital point-of-care diagnostics and novel treatments for this patient group are potential subjects for future research.
Strengths and limitations
A high number of consecutively registered patients and adjustment for major confounding factors including age and comorbidity are strengths of this study. Unlike most epidemiological studies, we were also able to adjust for prehospital values of systolic blood pressure and heart rate. An endpoint-adjudication committee validated the use of ICD-10 diagnoses to establish the cause of dyspnea. Owing to the predefined criteria for telemedical contact, only a fraction of all patients with dyspnea in the ambulance were telemedically triaged and registered. A selection bias that favors a higher proportion of patients with heart disease is evident. Dyspneic patients suspected of MI might be more severely affected than those not suspected of MI because some of them may have large anterior infarctions and non-cardiac acute conditions like pulmonary embolism and pneumothorax. This might have led to an overestimation of the mortality in patients with dyspnea compared with a general prehospital dyspnea population. As we did not have data on smoking status, alcohol consumption, left ventricular systolic function or pulmonary function, residual confounding might be present. However, adjusting for smoking status did not change the association between dyspnea and mortality in several other studies [7, 28]. Pulmonary disease and heart failure are included in the Charlson Comorbidity Index and adjustment was inherent for pulmonary function and left ventricular systolic function.
Patients suspected of MI presenting with dyspnea have a markedly higher short- and long-term mortality than patients with chest pain irrespective of the presence of MI. ECG acquisition and interpretation are insufficient to diagnose such high-risk patients in this group. Further studies are needed to clarify whether supplementary prehospital diagnostics can improve triage, facilitate earlier correct therapy and improve outcome in patients presenting with dyspnea.
Erhardt L, Herlitz J, Bossaert L, Halinen M, Keltai M, Koster R, et al. Task force on the management of chest pain. Eur Heart J. 2002;23(15):1153–76.
Monsieurs KG, Nolan JP, Bossaert LL, Greif R, Maconochie IK, Nikolaou NI, et al. European Resuscitation Council Guidelines for Resuscitation 2015: Section 1. Exec Summ Resusc. 2015;95:1–80.
Schmidt M, Jacobsen JB, Lash TL, Botker HE, Sorensen HT. 25 year trends in first time hospitalisation for acute myocardial infarction, subsequent short and long term mortality, and the prognostic impact of sex and comorbidity: a Danish nationwide cohort study. BMJ. 2012;doi:10.1136/bmj.e356.
Terkelsen CJ, Jensen LO, Tilsted HH, Thaysen P, Ravkilde J, Johnsen SP, et al. Primary percutaneous coronary intervention as a national reperfusion strategy in patients with ST-segment elevation myocardial infarction. Circ Cardiovasc Interv. 2011;4(6):570–6.
Wissenberg M, Lippert FK, Folke F, Weeke P, Hansen CM, Christensen EF, et al. Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest. JAMA. 2013;310(13):1377–84.
Ebi-Kryston KL, Hawthorne VM, Rose G, Shipley MJ, Gillis CR, Hole DJ, et al. Breathlessness, chronic bronchitis and reduced pulmonary function as predictors of cardiovascular disease mortality among men in England, Scotland and the United States. Int J Epidemiol. 1989;18(1):84–8.
Sorlie PD, Kannel WB, O’Connor G. Mortality associated with respiratory function and symptoms in advanced age. The Framingham Study. Am Rev Respir Dis. 1989;140(2):379–84.
Terkelsen CJ, Norgaard BL, Lassen JF, Gerdes JC, Ankersen JP, Romer F, et al. Telemedicine used for remote prehospital diagnosing in patients suspected of acute myocardial infarction. J Intern Med. 2002;252(5):412–20.
Campo Dell’ Orto M, Hamm C, Liebetrau C, Hempel D, Merbs R, Cuca C et al. Telemetry-assisted early detection of STEMI in patients with atypical symptoms by paramedic-performed 12-lead ECG with subsequent cardiological analysis. Eur J Emerg Med. 2015; doi:10.1097/MEJ.0000000000000353.
Fisher K, Stefan M, Darling C, Lessard D, Goldberg RJ. Impact of COPD on the Mortality and Treatment of Patients Hospitalized with Acute Decompensated Heart Failure (The Worcester Heart Failure Study). Chest. 2014;147(3):637–45.
Iversen KK, Kjaergaard J, Akkan D, Kober L, Torp-Pedersen C, Hassager C, et al. Chronic obstructive pulmonary disease in patients admitted with heart failure. J Intern Med. 2008;264(4):361–9.
Rutten FH, Cramer MJ, Lammers JW, Grobbee DE, Hoes AW. Heart failure and chronic obstructive pulmonary disease: An ignored combination? Eur J Heart Fail. 2006;8(7):706–11.
Area and population - Central Denmark Region. Danmarks Statistik, Copenhagen. 2015. http://www.statistikbanken.dk. Accessed 17 April 2015.
Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol. 2004;57(12):1288–94.
Thygesen SK, Christiansen CF, Christensen S, Lash TL, Sorensen HT. The predictive value of ICD-10 diagnostic coding used to assess Charlson comorbidity index conditions in the population-based Danish National Registry of Patients. BMC Med Res Methodol. 2011;doi: 10.1186/1471-2288-11-83.
Lacasse Y, Daigle JM, Martin S, Maltais F. Validity of chronic obstructive pulmonary disease diagnoses in a large administrative database. Can Respir J. 2012;19(2):e5–9.
Quach S, Blais C, Quan H. Administrative data have high variation in validity for recording heart failure. Can J Cardiol. 2010;26(8):306–12.
Klein JP, Logan B, Harhoff M, Andersen PK. Analyzing survival curves at a fixed point in time. Stat Med. 2007;26(24):4505–19.
Parner ET, Andersen PK. Regression analysis of censored data using pseudo-observations. Stata Journal. 2010;10(3):408–22.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.
De Maio VJ, Stiell IG, Wells GA, Spaite DW. Cardiac arrest witnessed by emergency medical services personnel: descriptive epidemiology, prodromal symptoms, and predictors of survival. OPALS study group. Ann Emerg Med. 2000;35(2):138–46.
Kirchberger I, Heier M, Kuch B, von Scheidt W, Meisinger C. Presenting symptoms of myocardial infarction predict short- and long-term mortality: the MONICA/KORA Myocardial Infarction Registry. Am Heart J. 2012;164(6):856–61.
Hellenkamp K, Darius H, Giannitsis E, Erbel R, Haude M, Hamm C, et al. The German CPU Registry: Dyspnea independently predicts negative short-term outcome in patients admitted to German Chest Pain Units. Int J Cardiol. 2015;181:88–95.
Neesse A, Jerrentrup A, Hoffmann S, Sattler A, Gorg C, Kill C, et al. Prehospital chest emergency sonography trial in Germany: a prospective study. Eur J Emerg Med. 2012;19(3):161–6.
Prosen G, Klemen P, Strnad M, Grmec S. Combination of lung ultrasound (a comet-tail sign) and N-terminal pro-brain natriuretic peptide in differentiating acute heart failure from chronic obstructive pulmonary disease and asthma as cause of acute dyspnea in prehospital emergency setting. Crit Care. 2011;doi:10.1186/cc10140.
Teboul A, Gaffinel A, Meune C, Greffet A, Sauval P, Carli P. Management of acute dyspnoea: use and feasibility of brain natriuretic peptide (BNP) assay in the prehospital setting. Resuscitation. 2004;61(1):91–6.
Bakke SA, Botker MT, Riddervold IS, Kirkegaard H, Christensen EF. Continuous positive airway pressure and noninvasive ventilation in prehospital treatment of patients with acute respiratory failure: a systematic review of controlled studies. Scand J Trauma Resusc Emerg Med. 2014; doi:10.1186/s13049-014-0069-8.
Tessier JF, Nejjari C, Letenneur L, Filleul L, Marty ML, Barberger Gateau P, et al. Dyspnea and 8-year mortality among elderly men and women: the PAQUID cohort study. Eur J Epidemiol. 2001;17(3):223–9.
We thank Professor Erik Parner, Department of Biostatistics at Aarhus University for statistical assistance. This study was funded by the Prehospital Emergency Medical Services, Central Denmark Region, the Health Research fund of the Central Denmark Region, the Research Centre for Emergency Medicine, Aarhus University hospital and the Department of Cardiology B, Aarhus University Hospital. No external funding was received. The Danish Teledatabase was supported by a grant from The Tryg Foundation.
The authors declare that they have no competing interests.
MTB, CJT, EFC and HK designed the study. CJT, HMS, KKD and TN were responsible for data collection. MSA and CS conducted an endpoint committee review of patient files. MTB and CJT conducted the analyses and interpretation of data. MTB drafted the manuscript and CJT, EFC, HK, HMS, KKD, TN, CS and MSA revised it critically for important intellectual contents. All authors approved the final version before publication.
The ICD-10 diagnosis algorithm. (PDF 38 kb)
ICD-10 codes (text in Danish). (XLSX 610 kb)
Sensitivity analyses of the generalized linear regressions analyses of covariates associated with mortality. Results of regression analysis using 1) age/age2 2) restricted cubic splines 3) restricted cubic splines and specific diagnosis. Analyzed at 30 days and 4 years in patients suspected of myocardial infarction triaged by use of electrocardiogram-based telemedicine (n = 15,578 cases with complete data). (DOCX 102 kb)