Cardiovascular disease (CVD) is the third leading cause of death in Korea, and the acute myocardial infarction (AMI) mortality rate is rapidly increasing, from 16.9 per 100 000 in 2001 to 21.6 per 100 000 in 2007.1 However, public awareness of AMI symptoms and the benefits of rapid reperfusion therapy are very low in Korea.2 The median prehospital delay time reported in the Korean Acute Myocardial Infarction Registry was 12 hours in all populations,3 notably longer than the 1.5 to 6.0 hours reported in other international countries.4,5
Prodromal symptoms can be defined as preinfarction angina and cardiac-related ischemic symptoms of a threatening ischemic process before the acute cardiac event. Previous studies on women reported that 78% to 90% of women with AMI experienced at least 1 prodromal symptom for more than 1 month either daily or several times a week before the acute cardiac event.6,7 Medical studies focusing on angina have reported that more than 50% of patients with AMI had a history of preinfarction angina and experienced intermittent chest symptoms.8,9 Previous clinical studies have reported that patients with preinfarction angina pain were associated with smaller infarcts and a lower incidence of in-hospital complications compared with outcomes of AMI patients who did not experience antecedent angina.10-13 A study also demonstrated that prodromal symptoms were associated with increased treatment-seeking before acute coronary syndromes (ACSs) and were associated with improved 1-year survival in women.13 However, inconsistent study results also exist, showing no protective effects of preinfarction angina in patients with AMI on cardiac markers estimating infarct size or in-hospital morbidity and mortality.14,15
Experiencing symptoms is a key factor in patients' decisions to seek medical care during an acute coronary event; it also critically influences the health care providers' decisions regarding further evaluation and treatment initiation.16 Thus, patients' earlier recognition of prodromal symptoms could facilitate seeking medical attention, and it may prevent serious AMI-related complications in some of these patients. However, few studies have examined the relationship between prodromal ischemic symptoms and treatment-seeking behaviors. Previous studies reported that 59% of 914 Swedish patients with suspected AMI17 and 15.9% of 14230 Canadian patients with ACSs18 sought medical attention for prodromal symptoms preceding cardiac events. A recent study of 498 patients in China reported that AMI patients with preischemic symptoms within 48 hours of the event were more likely to have longer prehospital delay and less likely to use an ambulance.19
Therefore, examining whether the presence of prodromal symptoms is associated with prehospital delay will be useful in planning educational strategies to increase public awareness of acting in a timely manner to seek medical care. Furthermore, identifying how the affected individuals interpret and respond to the early warning symptoms before their acute coronary event will add to the understanding of prodromal symptoms.
This study aimed at providing answers to the following questions:
- What are the characteristics of the most troubling prodromal symptoms experienced by patients who had undergone percutaneous coronary intervention (PCI) with a first-time AMI?
- Does the presence of prodromal symptoms predict prehospital delay of more than 3 hours and prolonged delay of more than 12 hours in patients with a first-time AMI?
This study was of a descriptive design using semistructured interviews in first-time AMI patients to identify the relationship between patients' prodromal symptoms and prehospital delay.
A total of 271 patients diagnosed with AMI were recruited from November 2007 to December 2008 from Chonnam National University Hospital, the principal site of the Korean Acute Myocardial Infarction Registry20 located in the southern part of Korea. This hospital is the primary facility offering treatment for ACSs in Gwangju and Chonnam province, the population of which is approximately 3.4 million.21
Eligible patients during the study period included about 900 patients who were hospitalized with the diagnosis of first-time ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) at the cardiovascular care unit. Most of the STEMI patients had emergent PCIs, and some of the NSTEMI patients had them at a later time during their stay in the coronary care unit. Inclusion criteria were first-known occurrence of AMI, ability to communicate verbally, and informed consent for participation. The primary investigator (PI) visited the hospital once a week and visited patients who were hospitalized at that time to solicit their participation. A total of 279 patients were interviewed during that time, but 8 patients were excluded because of incomplete answers.
The study design and protocol were approved by the institutional review board of Chonnam National University Hospital. This data was obtained from a funded study that assessed the prehospital delay time and treatment-seeking behaviours among patients with ACSs.2 When the patients agreed to participate in the study, they were asked to sign an informed consent document. After obtaining informed consent, the PI interviewed all patients, along with their spouse or family member who knew about the acute event, if available. A research assistant (RA) assisted the PI during the interview. Each patient was queried in a semistructured interview format for 20 to 40 minutes in the education room of the cardiovascular care unit on the second to fifth day of their stay in the hospital following PCI. Each patient was queried to describe the most troubling symptom prior to his/her acute symptom that he/she experienced in the preceding week(s) that he/she retrospectively believed was related to the AMI. The patients were also asked to describe early interpretations and actions they used to alleviate their discomfort. All interviews included the following questions: "Did you experience any new or a most troubling symptom before your acute cardiac event that you believe may be associated with your heart attack?," "Could you explain to me about the troubling symptoms you experienced before the acute cardiac event?," "What did you think when those symptoms started?," and "How did you act during the symptom presentation?"
A questionnaire was used to collect demographic and clinical information from patients, including prehospital delay time, presenting symptoms, and prior medical history. The prehospital delay time from acute symptom onset to admission to the emergency department was calculated from all patients or accompanying bystanders and was compared with the time documented in the electronic medical records. In cases of discrepancy, the delay time was calculated based on the patient's or bystander's statements.
Having prodromal symptoms was defined as the presence of cardiac or associated symptoms that had occurred within 60 days prior to presentation to the emergency department for AMI. However, those symptoms experienced within 24 hours of the AMI attack were not considered prodromal symptoms. Prodromal symptoms were identified on the basis of the questionnaire symptom profile and then categorized based on the agreement of the RA according to the classification of McSweeney et al,22 which was developed for women and included the following 5 groups: pain related, gastrointestinal related, fatigue/weakness, head related, and other.
Questionnaire data were compared with electronic medical record data, which were reviewed to collect data such as length of total stay in hospital, length of stay in the coronary care unit, and laboratory data.
All interviews were audio-recorded and transcribed. The PI and RA then read repeatedly the transcripts of the patients' interpretations and responses to the symptoms. When the 2 raters agreed with each other, the interpretations and responses were coded as numbers for quantitative analysis.
From the interview data, some variables such as early interpretation and decisional actions were coded using SPSS version 13.0 (SPSS, Chicago, Illinois) for quantitative determination of frequency and mean values. Statistical differences were determined between presence and absence of prodromal symptoms, sample characteristics, and delay time. Student t test was used to evaluate continuous variables, and χ2 or Fisher exact probability test was used to compare categorical variables. A histogram revealed that the delay time showed a skewed distribution, pointing to variables of 3 and 12 hours.
Multiple logistic regression analyses were conducted to determine whether the presence of prodromal symptoms was predictive of prehospital delays longer than 3 hours and longer than 12 hours. All significant variables that were confirmed by bivariate analyses were entered in the logistic regression analysis for adjustment of the confounding variables, in which odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were presented. Statistical significance (P) was set at .05.
Demographic and Clinical Characteristics
Baseline and clinical characteristics of the subjects are shown in Table 1. Of the 271 patients, 145 (53.5%) indicated the presence of prodromal symptoms before the acute cardiac event. The mean age (range, 29-89 years) was significantly higher in patients with prodromal symptoms (65.1 [SD, 12.4] years) than in those with no prodromal symptoms (60.9 [SD, 12.6] years; P = .001). There were no significant differences between the 2 groups according to sex, education level, monthly income, or marital status. Comorbid diseases such as stroke, angina, congestive heart failure or cardiomyopathy, and chronic renal failure were more prevalent in patients with prodromal symptoms (P = .020). Patients with prodromal symptoms were less likely to have chest pain (P = .001) and more likely to have symptoms other than chest pain as their chief complaints at admission (P < .001). Because of a skewed distribution, the delay time was compared in the time points of longer than 3 hours and longer than 12 hours and revealed that patients with prodromal symptoms presented to the hospital after a significantly longer time than those with no prodromal symptoms in both time points (P < .001). Left ventricular ejection fraction (LVEF) was significantly lower in those with prodromal symptoms compared with those with no prodromal symptoms (P = .040). Patients with prodromal symptoms were likely to remain hospitalized longer compared with those with no prodromal symptoms (P = .034).
Prodromal Symptoms and Subjects' Interpretations and Actions
The most unusual prodromal symptoms experienced by patients are shown in Table 2. Among 145 patients experiencing prodromal symptoms, chest pain and epigastric pain were most prevalent (34.5%) followed by indigestion (19.3%), shortness of breath (9.7%), and fatigue (8.3%). The interview data revealed diverse interpretations of prodromal symptoms and differing responses. Approximately 38% of those who experienced intermittent chest or epigastric pain thought that something was wrong but either did not view the situation as being serious or attributed their symptoms to their advanced age or comorbidities. Nearly 64% of those who experienced fatigue or general weakness recognized that something was wrong, but their interpretation was the same as just described (Table 3).
When prodromal symptoms occurred, 40% of the patients (n = 58/145) visited their local clinic or hospital. The other 60% decided to wait to see if the symptoms disappeared or tried to alleviate the symptoms by self-medication or other actions (Table 4).
Impact of the Presence of Prodromal Symptoms on Prehospital Delay
The adjusted impact of the presence of prodromal symptoms is shown in Table 5. In bivariate analyses, prehospital delays of more than 3 hours and more than 12 hours were significantly associated with age, sex, education level, monthly income, presence of chest pain, final medical diagnosis, Killip class, C-reactive protein, LVEF, and length of hospital stay (P < .05). Multiple logistic regression analyses were then performed to examine the adjusted impact of the presence of prodromal symptoms on prehospital delay. The logistic regression models that tested the prediction of prehospital delay and prolonged delay were significant in cases of more than 3 hours and more than 12 h, respectively (χ210 = 64.916, P < .001; χ210 = 68.482, P < .001). All variables confirmed by bivariate analysis were entered into the regression models except for the clinical data (Killip class, C-reactive protein, LVEF, and length of hospital stay) that were not considered prehospital delay factors. Patients with prodromal symptoms had about a 40% greater chance of having delayed presentation of more than 3 hours compared with patients who had no prodromal symptoms (OR, 3.962; 95% CI, 2.22-7.05) (P < .001). Patients with prodromal symptoms had about a 32% greater chance of having delayed presentation of more than 12 hours compared with the patients who had no prodromal symptom (OR, 3.153; 95% CI, 1.80-5.51) (P < .001). In addition, low education level and no chest pain were found as predictors of prolonged delay in presentation of more than 12 hours (P < .05).
In the present study, 53% of male patients and 54.2% of female patients answered that they experienced prodromal symptoms that they retrospectively believed to be related to their AMI attack. The prevalence of prodromal symptoms in male patients is comparable with the study that reported that 58% of men who experienced an AMI had experienced nonspecific symptoms in the week before admission.17 Whereas previous international studies linked a more prevalent occurrence of prodromal symptoms with women,17,18,23 we found no significant sex-based difference in the presentstudy. Moreover, other interview-based surveys or qualitative studies reported that 78% to 90% of surveyed women experienced at least 1 prodromal symptom for more than 1 month either daily or several times a week before the AMI attack.6,7,24 The lack of sex-based difference might be related to the study participants' characteristics and the difference in cultural background. In the present study, female patients with prodromal symptoms were significantly older (72 [SD, 9.3] years) compared with male patients with prodromal symptoms (62 [SD, 12.3] years). Cultural background, personal and families'/friends' illness experiences, and tacit knowledge all influence an individual's symptom interpretation.25 In a similar vein, older Korean women tend to be more passive and demonstrate internal coping responses compared with women of Western countries. They also show a higher incidence of more patience with their symptoms of fatigue or tiredness, tending to believe that neither symptom was indicative of a big health problem. Hence, they might have lesser recall of the presence of prodromal symptoms than women in Western countries. In addition, this study contained a small sample of female patients (n = 45) with prodromal symptoms and first-time AMI, which might differ from the study by Graham et al18 of 1034 women with ACSs and unstable angina (60%) and the study by McSweeney et al6 that included 72% female patients with first-time AMI. Further investigation is warranted on the relationship between sex and the presence of prodromal symptoms to elucidate it more clearly. However, there are few studies in Korea on the relationship between prodromal symptoms and sex difference, which limits our discussion.
The most frequently reported prodromal symptoms in this study were pain-related symptoms such as chest, epigastric, or back pain (n = 56/145, 38.6%). This result was consistent with a previous study that reported that the most frequent prodromal symptoms were pain related and that 58.4% of 2268 ACS patients with prodromal symptoms experienced that kind of symptoms.5 However, a retrospective survey of 515 women with AMI reported that the most frequent symptoms were fatigue and tiredness and that patients experienced an average of 5 different symptoms more than once per month.10 This discrepancy might be related to the question asked of the study subjects about the most troubling symptom rather than specifics of all prodromal symptoms. This might have reduced the number of prodromal symptoms in the present study, which limits the study findings.
Multivariate analysis showed that the presence of prodromal symptoms was an independent predictor affecting prehospital delay, and this is consistent with a recent study showing that the presence of prodromal symptoms predicted prehospital delay of more than 2 hours.19 In our study, the median prehospital delay time in patients with prodromal symptoms was significantly longer than the one of patients without prodromal symptoms. This is also similar to a previous study finding that preinfarction symptoms occurring within the last 4 weeks before the infarction were more likely to be related to longer prehospital delay.15 The major reason might be the significantly higher prevalence of atypical acute symptoms in patients with prodromal symptoms compared with those with no prodromal symptoms. Atypical symptom indicates that chief complaints are not principally chest pain or absence of chest pain but rather involve other gastrointestinal or respiratory distress that could be accompanied by less intense chest pain. In this study, patients with prodromal symptoms were significantly older than those with no prodromal symptoms. It is conceivable that older AMI patients were less likely to report classic pain and used fewer words to describe their discomfort compared with younger patients.26 The higher prevalence of atypical acute symptoms in older people reported in previous studies27-29 supports this finding. The symptoms differed from classic chest symptoms, and the vagueness of these symptoms could well not be recognized as an indication of a cardiac problem, resulting in a delay in seeking medical care. This might be related to patients' having attributed their discomfort to a digestive problem or to their weak physical strength due to natural aging. Actually, this was supported by this study result that no chest pain was found as a predicting factor on prolonged delay of more than 12 hours.
Another possible explanation for the delay in seeking medical attention by patients with prodromal symptoms concerns the intermittent development of ischemic symptoms that can occur and the presence of comorbid conditions. Patients felt a lack of seriousness about their symptoms, had intermittent symptom presentations, and attributed the symptoms to their chronic disease or to weakened physical strength. Then, not surprisingly, they typically waited for the symptoms to lessen. This was supported by a previous study that intermittent symptoms were related to increased patient delay.30 Even though about 39% of patients with prodromal symptoms had chest pain, only 46.5% of them recognized something was wrong with their health. The others decided that they had no health problem, which might be related to their lack of knowledge about AMI. In this study, about 60% of the patients had a middle school or lower education; this low education level resulted in a prolonged delay (>12 hours) in hospitalization. Lower education and failure to recognize their symptoms as cardiac in origin were supported as confirmed predictors for delay by previous studies.2,31
The 26.2% of patients with prodromal symptoms in this study had comorbid conditions such as a previous stroke, congestive heart failure/cardiomyopathy, or chronic renal failure; comorbidities were significantly more prevalent in those with prodromal symptoms than in those without. A previous study involving Korean ACS patients reported that the presence of comorbid conditions significantly predicted atypical symptoms in older patients.32 In the case of fatigue or weakness, half of the patients thought that the symptoms might be caused by the natural course of aging or were exacerbated symptoms of their comorbid chronic diseases, and only 23% visited a local clinic or hospital to see a physician.
Although it is true that the presence of prodromal symptoms was significantly associated with atypical presentation in this study, we cannot exclude the possibility that the question wording influenced the results. Patients were queried regarding the occurrence of their most unusual symptom rather than specifics of all prodromal symptoms. Further study is needed to examine all prodromal symptoms and to explore in more detail the relationship between prodromal symptoms and atypical acute symptoms.
In terms of clinical impact of prodromal symptoms, this study demonstrated that only patients with prodromal symptoms were more likely to have lower LVEF and a longer hospital stay compared with those with no prodromal symptoms. Recent multicenter clinical trials regarding preinfarction angina drew contradictory conclusions that patients with AMI preceded by angina pain had a lower incidence of in-hospital complications11,12 and no protective effects.14,15 Prospective longitudinal studies are therefore needed to clarify the clinical significance of prodromal symptoms, such as prevalence of a major adverse cardiac event or mortality rate for Korean AMI patients.
The result of this current study suggests that even though the protective effect of preinfarction angina exists, the early reperfusion rate of the patients with prodromal symptoms can be lower because of patients' hesitation and resulting prehospital delay. When other risk factors were controlled for, AMI prodromal symptom score was the most important predictor of acute symptoms in a previous study.6 Accordingly, health care providers should pay attention to not only acute symptoms of AMI but also prodromal symptoms. Education of individuals at risk for CVD should include the patterns of early warning symptoms and encourage quick treatment-seeking behaviors when such symptoms are experienced, to prevent some AMI events. This education is more critical for patients suspected of having STEMI.
The present study had limitations that a recall bias could exist in the calculation of delay time and symptom specifics because patients were asked to recall the episode of early symptoms that occurred several days prior to the interview. In addition, the prodromal symptom categorization was based on the survey that was developed for women only,22 and the participating patients were recruited from only 1 hospital. Moreover, although Chonnam National University Hospital treats the largest number of AMI patients in Korea, it is located in a predominantly rural area, where residents tend to have lower education levels and socioeconomic status than what would be typical of patients in a large urban hospital. Therefore, the study population cannot be considered representative of all AMI patients in Korea. Finally, the retrospective nature of the study and the fact that patient information involved personal recollections are limitations.
In the present study, AMI patients who experienced prodromal symptoms were likely to be older and have no chest pain during the acute phase of than those with no prodromal symptoms. Most patients did not recognize the importance of their early symptoms; in fact, only 40% of patients visited a clinic or a hospital for prodromal symptoms. After adjustment for baseline characteristics, the presence of prodromal symptoms was found as a significant predictor affecting delayed presentation to the hospital. Recognizing prodromal symptoms will be an essential step in improving recognition of impending AMI by both the public and health care providers. Health care providers need to ask patients presenting with suspected ACSs about prodromal symptoms, especially NSTEMI, when the diagnosis is not obvious as in STEMI. When educational strategy is planned for the public who are in a high-risk group for CVD, improving awareness of the early warning symptoms of AMI and quickly getting to a hospital should be emphasized.
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Keywords:© 2011 Lippincott Williams & Wilkins, Inc.
acute myocardial infarction; symptoms; treatment-seeking behavior