Journal of Cardiovascular Nursing
Vol. 31, No. 1, pp E1YE10 x Copyright B 2016 Wolters Kluwer Health, Inc. All rights reserved.
Impact of Prodromal Symptoms on Future Adverse Cardiac-Related Events A Systematic Review Sheila O’Keefe-McCarthy, PhD, RN; Linda Ready, RN, BNSc, CNCC(C) Background: Recognition of specific and nonspecific cardiac-related prodromal symptoms, indicative of myocardial ischemia, is critical for preemptive coronary heart disease (CHD) screening and effective diagnosis and treatment. In this systematic review, we examined whether prodromal symptoms were predictive of acute symptom presentations, cardiac events, or treatment interventions. Methods: Studies that measured the association of prodromal symptoms with acute coronary syndrome (ACS) symptom presentation, acute cardiac event, and/or intervention in men and/or women with confirmed CHD were included. Data sources: Electronic searches in the Cochrane Library, MEDLINE, PubMed, PsyhINFO, Embase, CINAHL, and Scopus databases from 1990 to 2013 were conducted using medical subject heading terms including prodromal symptoms, ACS, acute myocardial infarction, unstable angina, and CHD. Key words such as shortness of breath, anxiety, atypical pain, sleep disturbance, fatigue, and nausea/vomiting were also used. Abstracts, relevant journals, key authors, and reference lists were reviewed. Results: Seven studies that included 6716 individuals with prodromal symptoms (65.7% women). Mean age was 68 T 13 and 58.5 T 9 years for women and men, respectively. Cardiac-related prodromal symptoms were predictive of patients’ ACS-related symptoms and associated events from 3 to 24 months. Across studies, the prodromal symptoms consistently reported before cardiac event were chest discomfort/pain (n = 4, 57%), arm pain/discomfort (n = 6, 86%), jaw pain (n = 3, 43%), back/shoulder blade pain (n = 3, 43%), unusual fatigue (n = 7, 100%), shortness of breath (n = 6, 86%), sleep disturbance (n = 2, 29%), dizziness (n = 3, 43%), headache (n = 3, 43%), anxiety (n = 7, 100%), and gastrointestinal complaints (nausea, vomiting, indigestion; n = 5, 71%). Patients with prodromal arm, jaw, and back pain; fatigue; and shortness of breath had increased risk of experiencing similar symptoms during an ACS episode. Prodromal symptoms were predictive of adverse cardiac events and cardiac interventions. There is some preliminary evidence to suggest that prodromal symptoms of headache, sleep disturbance, and anxiety may predict ACS symptom presentation during an acute cardiac event. Conclusion: Future research is warranted that would examine prospectively the predictive value of prodromal headache, sleep disturbance, and anxiety within this cardiovascular population on major adverse cardiac events. Preemptive screening for cardiac-related prodromal symptoms in men and women should be considered as a standard in clinical practice. This may potentiate early diagnosis, effective risk modification, timely pain management, and treatment intervention and decrease CHD-related morbidity and mortality. KEY WORDS:
acute coronary syndrome, adverse cardiac event, pain, prodromal symptoms
Background Prodromal symptoms, indicative of myocardial ischemia, associated with acute cardiac-related events remain elusive to recognize, understand, and respond to for some patients and healthcare professionals.1,2 Prodromal symptoms are those specific and nonspecific sensations inSheila O’Keefe-McCarthy, PhD, RN Adjunct Scientist, Ross Memorial Hospital, Lindsay, Ontario, Canada.
Linda Ready, RN, BNSc, CNCC(C) Clinical Practice Coordinator, City of Kawartha Lakes Family Health Care Team, Lindsay, Ontario, Canada. The authors have no conflicts of interest to disclose.
Correspondence Sheila O’Keefe-McCarthy, PhD, RN, Ross Memorial Hospital, 10 Angeline St North, Lindsay, Ontario, K9V 4M8 Canada ([email protected]). DOI: 10.1097/JCN.0000000000000207
dividuals may experience that serve as a warning sign of an impending acute coronary syndrome (ACS).3 Convincing evidence identifies that prodromal symptoms, experienced days, weeks, or months before a cardiac event, may relate to acute symptoms experienced during an ACS-related hospital admission.1,3Y5 Men and women have reported varied descriptions of prodromal symptoms that have included unusual chest and arm pain, shortness of breath (SOB), fatigue, sleep disturbances, dizziness, and anxiety, as some examples.6Y11 Within the prodromal literature, most studies have focused on women’s experience of cardiac-related symptoms and identify that women tend to report greater number of symptoms compared with men.9,10,12Y14 However, it has been recently reported that both men and women experience some form of prodromal symptoms before E1
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E2 Journal of Cardiovascular Nursing x January/February 2016 their cardiac event.1,13,18 Men report unique individual prodromal symptoms but may use different descriptors compared with their counterparts.1 Prodromata in individuals with coronary heart disease (CHD) have also been related to delay in acquiring immediate medical attention, and therefore, less aggressive treatment interventions have occurred.15,16 Perhaps, 1 of the reasons for this is that, typically, prodromal symptoms are vague in nature and as a result, are hard to recognize and relate to heart disease. Lack of recognition of these overt and covert warning signs related to CHD may increase cardiovascular-related morbidity and mortality.6,7 To date, little is known about whether prodromal symptoms are associated with the kind of acute symptom presentation that individuals may experience during an ACS event. Moreover, there is minimal literature available that demonstrates the relationship between prodromal symptoms and subsequent cardiac events or future treatment interventions.
Methods Aim The aim was to examine whether prodromal symptoms were predictive of acute ACS-related pain presentations, cardiac events (ACS-related unstable angina or acute myocardial infarction), and/or treatment interventions (percutaneous coronary intervention, angioplasty, stent, and/or coronary artery bypass grafting). Data Sources Electronic searches were conducted of PubMed, CINAHL, Embase, MEDLINE, PsychINFO, Cochrane Data Base of Systematic Reviews, and Scopus, using combinations of key medical subject heading terms, including prodromal symptoms, atypical cardiac presentation, ACS, unstable angina, acute myocardial infarction, heart attack, chest pain, anginal equivalence, major adverse cardiac event, coronary heart disease, angiogram, angioplasty, stents, coronary artery bypass grafting, and percutaneous coronary intervention. Other keywords were used, such as shortness of breath, fatigue, anxiety, syncope, unusual pain, sleep disturbance, headaches, nausea, and vomiting, to capture the subjectivity and complexity of cardiac-related prodromal symptoms. All search titles and abstracts were independently rated for relevance by 2 reviewers, based on the inclusion criteria. Hand searches of relevant journals, secondary references, and the abstracts and proceedings from national and international conferences were conducted. Where necessary, authors were contacted for access to study data from abstracts that met inclusion criteria. Inclusion Criteria To be eligible for inclusion, studies were subjected to the following inclusion criteria:
1. The articles were peer reviewed and published between 1990 and 2013. 2. Studies that included adult men and women or men and/or women (all ages) with confirmed CHD who reported prodromal symptoms. Coronary heart disease was defined as follows: individuals admitted to hospital with ACS, including unstable angina or myocardial infarction (non-ST-elevation or ST-elevation myocardial infarction. 3. Articles that examined the prognostic value of cardiacrelated prodromal symptoms on major adverse cardiac events and/or future cardiac treatment interventions; and 4. Articles that were published in English. Review Process Both authors conducted an independent literature search and together examined each computer search to identify potential articles using the aforementioned inclusion criteria. All titles and abstracts concerning prodromal symptoms were initially included, and subsequently, articles meeting the inclusion criteria were examined and reviewed. Eligibility was determined by mutual consensus from both authors. Data Extraction The authors conducted a systematic data extraction to provide a thorough description of participants, prodromes, and future related cardiac events and treatment interventions (Table 1). Each reviewer conducted her own data extraction of each article included in terms of the year of publication, journal type, study design, study participants, sample, setting, study objectives, and main results of each study. Authors compared the extractions and together summarized the main results based on the text provided in the original articles to achieve consensus. Study Quality Included studies in this review were either descriptivecorrelational and/or predictive studies (nonrandomized/ nonexperimental studies). Therefore, the methodological quality of included studies was appraised via the NewcastleOttawa Scale (NOS) for nonrandomized studies.17 This quality assessment instrument awards stars based on 3 levels of quality for an overall score of 9. The first category assesses the quality of the sample cohort. The second examines the comparability of design and data analysis (ie, Are the research design and analysis appropriate to answer the research question(s)?), and the third, the assessment of the outcome measure(s) of each study (ie, Are outcome measures captured with psychometrically valid and reliable instruments?). The NOS was adapted for the purposes of this review as follows: Representativeness of the study cohort was given a full star if it was explicit that participants had confirmed CHD and had ACS-related events. Half stars were awarded if the sample was mostly representative of an ACS sample (ie, 50%
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N = 515 Women MAPMISS Age mean, 66.4 T 12 y Section 1: Acute symptoms Age range, 29Y97 y Section 2: PSs, 30 questions Multisite- 5 Section 3 Y demographic, Retrospective survey over 3 y risk factors, comorbidity, medications Nominal /ordinal data = Content development percentage calculated; outlined, content validity continuous variables = median, was established by 7 content means, and SDs; t tests for univariate experts: survey expert, comparisons; multiple regression cardiologists, patients, and cardiac nurses. Retest reliability ranged from r = 0.72 to r = 0.91. N = 14 230 population DBs Based on 5 groups of PSs Women = 45.6%; on MAPMISS age = 65.3 T 13.5 y Pain (chest/arm/shoulder/ ACS sample, N = 2266 neck/jaw/leg) Anxiety/fatigue (anxiety/ Retrospective: DB: ACCS, HDD, sleep disturbance/ Statistics Canada, PCD, AHCIPR weakness/fatigue) Mean (SD), t tests, Mann-Whitney GI disturbances (N/V, loss tests, categorical = with %, # 2 for comparisons, Kaplan-Meier survival of appetite, indigestion) analysis, multivariable Cox proportional Head related (dizziness, hazards regression headache, visual disturbance) Other (sweating, SOB, heart racing, cough, numbness) No pilot work or psychometrics reported
1. The most frequent PSs of AMI 2. How prodromal and acute symptoms relate to comorbidities and CAD risk 3. Whether PSs were predictive of AMI symptoms
Examine the association between PS and 1-y mortality and cardiac catheterization and revascularization procedures (not specified)
2. McSweeney et al, 20033 United States
3. Graham et al, 200813 Canada
Prodromal Questionnaire 7 questions relating to prehospital admission prodromal signs, occurrence, frequency, and duration. Prodromal questionnaire was pilot tested on several patients for clarity and comprehension. No psychometric evaluation was provided.
N = 914 Women, 262; men, 652 Age 966 y = 417, e66 y= 497 1 urban hospital CCU Fisher exact test for comparison between proportions, with 2-tailed test computed; P e .05 considered significant Retrospective survey post-CCU admission
Prodromal Instrument/ Psychometric Properties
1. Examine PSs in suspected AMI patients and relate them to the final diagnosis. 2. Examine whether PSs differ with respect to infarct location. 3. Did the patient seek medical help in the prodromal phase?
Sample (n) /Sex/Mean (SD) Age/Site/Design/Statistics
1. Hofgren et al, 199519 Sweden
Aim
Studies Examining the Predictive Value of Prodromal Symptoms
Author/Year/ Country
TABLE 1
Unusual fatigue Sleep disturbance SOB Indigestion Anxiety Chest discomfort
Pain (neck, jaw teeth, arms, shoulder, throat) Anxiety/fatigue GI disturbances Head related (dizziness, headache, visual disturbance) Other (diaphoresis, SOB, cough, numbness, racing heart)
1. 2. 3. 4. 5. 6.
CP symptoms Extreme tiredness Loss of appetite 948 h prehospital admission Emotional stress Did the patient seek medical help with these PSs? Described the frequency and duration of PS
PSs
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(continues)
28% tiredness Chest discomfort, 27% No difference between large or small infarcts 35% experienced emotional distress PS experienced included tiredness, chest discomfort, gastrointestinal, arm pain, dyspnea and other symptoms 61% with AMI had PSs other than CP 948 h prehospital admission. Same frequency of PSs in nonYAMI-diagnosed patients 1. 70%: fatigue 2. 47.8%: sleep disturbance 3. 42.1%: SOB 4. 39.4: indigestion 5. 35.5%: anxiety 6. 43.5% reported no CP/discomfort 78% of women experienced PSs greater than 1 mo before AMI. PSs were significant in predicting the severity of the acute symptoms. Controlling for risk factors. PS score accounted for 33.25% of the variance in acute symptoms scores. PSs were associated with improved 1-y mortality in women (HR, 0.74; 95% CI, 0.58Y9.95; P = .016), but not in men (HR, 0.92; 95% CI, 0.76Y1.12; P = .422). Both men and women with reported PSs were more commonly provided with cardiac catheterization. PS in men predicted more revascularization procedures compared with women.
Results
Impact of Prodromal Symptoms on Cardiac-Related Events E3
1. To assess PSs of AMI within 1 y of AMI 2. Do PSs have any influence on acute AMI symptoms? 3. To examine gender differences
5. Cole et al, 201216 1. Describe the relationships United States among sleep disturbance, cardiac PSs, and cognitive impairment
4. Løvlien et al, 200918 Norway
Aim Prodromal questionnaire 48 questions, asked about AMI, describe PS and acute symptoms Content Validity established by clinical researchers (nurses physicians) Reliability testing: Cronbach’s ! = 0.79 Questionnaire was pilot tested on 20 patients for user friendliness and clarity of content
Prodromal Instrument/ Psychometric Properties
N = 1270 women diagnosed MAPMISS with first time ACS Prodromal section used; Retrospective telephone survey 30 questions/symptoms Descriptive statistics = sample and Content development prevalence of sleep disturbance, outlined; content validity # 2Yprevalence of risk factors, was established by 7 content linear regression, logistic experts: survey expert, regression for associations cardiologists, patients, and between sleep cardiac nurses. disturbance and PS Retest reliability ranged from r = 0.72 to r = 0.91
N = 533 Women, n = 149; men, n = 384 Age e75 y Mean age: women, 61.2 y; men, 58.5 y Multicenter Retrospective survey (self-administered) Means (SD) for continuous variables, percentage for proportions, 2-tailed # 2 tests comparing men and women, logistic regression
Sample (n) /Sex/Mean (SD) Age/Site/Design/Statistics
Studies Examining the Predictive Value of Prodromal Symptoms, Continued
Author/Year/ Country
TABLE 1
Sleep disturbance Cognition change Anxiety Leg pain Headaches Fatigue
1. Chest discomfort 2. Fatigue 3. Dyspnea (SOB) 4. Anxiety 5. Nervousness
PSs
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(continues)
Patients with PS of chest, shoulder, back pain, numbness in the arms, SOB, and fatigue had increased risk of experiencing similar symptoms during AMI phase. Women who experienced PS-CP were 95 times more likely to have CP symptoms in the acute AMI phase (OR, 5.11; 95% CI, 1.38Y18.88) and nearly 3 times greater than in men (OR, 2.80; 95% CI, 1.17Y6.70). Risk of experiencing shoulder pain was almost 5 times greater in men (OR, 4.96; 95% CI, 3.01Y8.19) but not women. Risk of numbness and arm pain in the acute phase was 2 times greater for women with PS of arm pain (OR, 2.66; 95% CI, 1.19Y6.20) and 3 times greater for men (OR, 3.11; 95% CI, 1.90Y5.07). Those with previous SOB and fatigue were 2Y3 times at risk for similar symptoms in the index ACS event (dyspnea: women, OR, 2.67; 95% CI, 1.25Y5.71; men, OR, 5.73; 95% CI, 3.42Y9.62; fatigue: women, OR, 2.97; 95% CI, 1.28Y6.85; men, OR, 2.51; 95% CI, 1.54Y4.11). Women (84%) and men (76%) reported PSs 1 y before AMI. PS is predictive of symptoms in the acute event. 632 women reported new-onset sleep disturbance, anxiety, and fatigue before an ACS event. Prodromal sleep disturbance was common across ethnic groups (50.2% overall; 52.1% blacks; 50.5% Hispanics; and 48.2% whites). Prodromal sleep disturbance was predictive of an ACS event.
Results
E4 Journal of Cardiovascular Nursing x January/February 2016
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Unusual pain Fatigue SOB Headache Anxiety Sleep disturbance CP Dizziness Other (gastric complaints, palpitations, diaphoresis, numbness, and visual disturbances)
N = 121; men, n = 63; women, PS-SS n = 58 Indentifies 8 PSs: unusual Age, 67.6 (13) y located aches and/or pain, One rural community hospital; unusual fatigue, sleep prospective, individual interviews disturbances, CP, anxiety, Association between ACS pain headaches, dizziness, and SOB intensity and presence/absence The category of other of PS: Wilcoxon rank-sum symptom was offered to nonparametric test patients in case the 8-item scale State/trait anxiety, examined by did not adequately capture all PS: Student t tests the patients’ subjective PS. Unadjusted comparison of PSs Content validity index = 0.85; between men and women and ICR = 0.613 across comorbidities: # 2 tests Pilot tested on 10 ACS patients for clarity, ease of use, Multivariable logistic regression for comprehension, and scoring association between comorbidities and PS controlling for confounders
Examined the prevalence and predictive value of cardiac PSs on acute coronary syndrome pain intensity, state, and trait anxiety
7. O’Keefe-McCarthy et al, 20131 Canada
77 women (7%) experienced cardiac events during the 2 y follow-up. Angioplasty, 5.2%; stent alone, 38.9%; stent/angioplasty, 18.2%; CABG, 19.5%; AMI, 17.2% 3 PSs were associated with cardiac events controlling for all covariates: (1) general chest discomfort, (2) SOB, and (3) unusual fatigue. Adjusting for age and race, 4 PSs revealed in risk of cardiac event: (1) discomfort in jaws/teeth, (2) unusual fatigue, (3) discomfort in arms, and (4) SOB. Women reporting more than 1 of the 4 PSs were 4 times more likely to have a cardiac event (HR, 4.19; 95% CI, 2.63Y7.44). Women who were older, had comorbidities, and had poor economic status had greater cardiac events. The MAPMISS is useful for screening at-risk women for CAD-related cardiac events. Increased ACS pain intensity was significantly associated with prodromal headaches (P = .006); sleep disturbances (P = .012), and anxiety (P = .017). PSs were not associated with patients’ state or trait anxiety. Patients with comorbidity of hypertension were 7.5 times more likely to experience unusual fatigue before an ACS-related event. Overall PS prevalence = 49%; no difference in prevalence of PS between men and women Patients reported at least 1 PS. The 4 most reported PSs included CP (n = 66, 70.8%), SOB (n = 74, 62%), anxiety (n = 70, 59%), and unusual fatigue (n = 54, 53.3%). Intensities ranged from moderate to severe. PS frequency ranged from daily to several times per week.
Results
Abbreviations: ACCS, Ambulatory Care Classification System; ACS, acute coronary syndrome; AHCIPR, Alberta Health Care Insurance Plan Registry; AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; CAD, coronary artery disease; CCU, cardiac care unit; CI, confidence interval; CP, chest pain; DB, databases; GI, gastrointestinal; HDD, hospital discharge data base; HR, hazard ratio; ICR, internal consistency reliability; MACE, major adverse cardiac event; MAPMISS, McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey; N/V, nausea and vomiting; OR, odds ratio; PCD, physician claims data; PS, prodromal symptoms; PS-SS, Prodromal Symptom Screening Scale; SOB, shortness of breath.
Pain (neck, jaw teeth, arms, shoulder, throat and leg) Anxiety/fatigue GI Head related (dizziness, headache and visual disturbance) Other (diaphoresis, SOB, cough, numbness, and racing heart)
PSs
N = 1097 women MAPMISS Age 921 y Section 1: Acute symptom Multisite: 4 cardiac clinics Section 2: PSs; 30 questions Longitudinal- observational, Section 3: demographic, retrospective surveyY every risk factors, comorbidity, 3 mo for 2 y medications Estimated HRs and corresponding Content development 95% CI for experiencing outlined; content validity was MACE using multivariate established by 7 content Cox proportional hazards experts: survey expert, regression modeling cardiologists, patients, and cardiac nurses. Retest reliability ranged from r = 0.72 to r = 0.91
Prodromal Instrument/ Psychometric Properties
Evaluated the usefulness of the MAPMISS in 1. To identify women who would have a cardiac event (AMI, ACS, stent, angioplasty, CABG, death) 2. To identify the most parsimonious subset of PSs predictive of cardiac events
Sample (n) /Sex/Mean (SD) Age/Site/Design/Statistics
6. McSweeney et al, 20134 United States
Aim
Studies Examining the Predictive Value of Prodromal Symptoms, Continued
Author/Year/ Country
TABLE 1
Impact of Prodromal Symptoms on Cardiac-Related Events E5
E6 Journal of Cardiovascular Nursing x January/February 2016 of the sample were diagnosed with unstable angina or acute myocardial infarction). For the assessment of outcome, records from established databases, medical records, and telephone and face-to-face interviews were allotted full stars. Studies that provided full descriptions of the instruments used to collect prodromal symptoms and the associated psychometric properties were awarded full stars. Two items were not applicable to the review and were excluded: (a) the selection of nonexposed cohort was representative of sample and (b) outcome of interest was not present at the start of the study. Studies were excluded if they did not achieve, at minimum, 5 allotted stars of the possible 7 for overall methodological quality.
Results A total of 800 article titles were found from the electronic searches. Thirty-six were duplicates, leaving 764 for consideration. Of these, 745 articles were removed because they were general or review articles, case reports, editorials, opinion pieces, or annotated bibliographies and/or did not fit the a priori inclusion criteria. Remaining were 19 studies that examined prodromata in CHD. At closer examination, 12 were further excluded as they examined children and youth, were qualitative studies, or were psychometric property evaluation studies (see the Figure for study selection).
2 were from Canada (29%), and 1 each was from Norway (14%) and Sweden (14%). Most of the study designs were a retrospective cohort (5, 71%). One study was a longitudinal, observational study with a retrospective 3-month survey over a 2-year period.4 One was a prospective, descriptive-correlational study and the other was a prospective, cross-sectional study.1,18 Data were collected by population database extraction (n = 2),13,16 combination of retrospective telephone interview/questionnaire survey (n = 2),3,4 face-to-face questionnaire interview survey/medical record (n = 1),1 and patient self-administered questionnaire survey (n = 2).18,19 Prodromal symptoms were captured in 3 studies (43%) by the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (MAPMISS), 3,4,16 and 1 used only a part of the prodromal section of the MAPMISS.13 Three others (43%) developed a prodromal questionnaire and provided descriptions of instrument development, psychometric properties, and associated pilot work.1,18,19 Across studies, age varied from 21 to 97 years. The mean age ranged from 68 T13 years for women to 58.5 T 9 for men, respectively. Sample sizes varied from 121 to more than 2300 participants. The results of the NOS assessment revealed that the quality across studies was moderate to strong and ranged from 5 to 7 stars. See Table 2 for methodological quality.
Characteristics of the Included Studies Table 1 summarizes the descriptive data from the 7 studies included. Studies were published between 1995 and 2013. Three studies were conducted in the United States (43%),
Cardiac-Related Prodromal Symptoms For most of the studies, prodromal symptoms were identified as either occurring (yes) or not (no). Across
Figure. Summary of data extraction.
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Impact of Prodromal Symptoms on Cardiac-Related Events E7 TABLE 2
Methodological Quality Assessment Scale of Prodromal Studies
Study 1. 2. 3. 4. 5. 6. 7.
Hofgren et al, 1995 McSweeney et al, 2003 Graham et al, 2008 Lovlien et al, 2009 Cole et al, 2012 McSweeney et al, 2013 O’Keefe-McCarthy et al, 2013
Selection (Max = 2a)
Comparability (2a)
Outcome (3a)
Total Score (Max = 7a)
b
a
b
b
a
c
b
b
b
b
b
a
b
b
c
b
b
c
b
b
b
5 6 6 5 7 7 6
Based on the Newcastle-Ottawa Quality Assessment Scale for Nonrandomized Studies (Wells et al, 2001). a 1 star. b 2 stars. c 3 stars.
all studies, the percentages of reported prodromal symptoms were as follows: chest discomfort/pain, n = 4, 57%; arm pain/discomfort, n = 6, 86%; jaw pain, n = 3, 43%; back/shoulder blade pain, n = 3, 43%; unusual fatigue, n = 7, 100%; SOB, n = 6, 86%; sleep disturbance, n = 2, 29%; dizziness, n = 3, 43%; headache, n = 3, 43%; anxiety, n = 7, 100%; and gastrointestinal complaints (nausea, vomiting, indigestion), n = 5, 71%.1,3,4,13,16,18,19 Prodromal symptoms occurred from 48 hours1 to several days,1 weeks,3,16 and/or months13,18,19 before patients’ acute cardiac event. Prodromal symptoms were prevalent in 49% to 95% of the samples.1,3,4,13,16,18,19 Five studies (71%) also reported other nonspecific prodromal symptoms: gastrointestinal complaints of indigestion, dizziness, visual disturbances, changes in cognition, palpitations, diaphoresis, numbness and tingling in the hands and arms, and loss of appetite.1,3,4,13,19 Of the 4 studies that examined prodromal symptoms in men and women, 2 found that women tended to report more symptoms compared with men.18,19 Women presented with less prodromal chest pain but reported greater fatigue, anxiety, and head-related symptoms (headache, dizziness) compared with men.13,18,19 Associated Prodromal Symptoms With Acute Symptoms of Acute Coronary Syndrome Table 1 provides the prodromal symptoms reported by men and women that were predictive of the acute symptoms experienced during an index cardiac event. Of the 7 studies, 6 (85%) reported that patients with prodromal chest pain/discomfort or shoulder/back/neck/headache pain, pain or numbness in the arms/hands, SOB, fatigue, sleep disturbance, and/or anxiety were more likely to experience similar symptoms during the acute phase of an ACS.1,3,4,16,18,19 For example, risks of experiencing chest-related symptoms (pain, discomfort, pressure, palpitations) in the acute stage of an acute myocardial infarction were more than 5 times greater in women who had experienced prodromal chest pain symptoms (adjusted odds ratio [OR], 5.11; 95% confidence interval [CI], 1.38Y18.88) and almost 3 times more likely in men (OR,
2.80; 95% CI, 1.17Y6.70).18 Similarly, individuals with jaw/teeth pain (hazard ratio [HR], 1.14; 95% CI, 1.07Y1.21) and fatigue (HR, 1.08; 95% CI, 1.05Y1.11) were more likely to go on to have an acute ACS event reporting similar symptoms compared with those with no reported prodromal symptoms.4 According to McSweeney et al,3 prodromal symptoms are predictive of the severity of acute symptoms experienced. In their recent study, McSweeney and colleagues4 identified that unusual fatigue, SOB, pain in the jaw and teeth, and discomfort in the arms were predictive of increased risk of admission with acute symptoms of AMI. In another study, O’Keefe-McCarthy et al1 found that ACS patients’ pain intensity, experienced by men and women (n = 121) during the first 8 hours of an emergency department visit, was related to preexisting prodromal symptoms. Specifically, median pain scores (numerical rating scale, 0Y10) were higher by 2 points for those with prodromal headache (P = .006) and anxiety (P = .017) and 1 point higher for those with sleep disturbances (P = .012).1
Associated Prodromal Symptoms with Treatment Intervention Two studies examined the influence of prodromal symptoms on related treatment interventions.4,13 Graham and colleagues13 investigated the association of prodromal symptoms, 1- year mortality, and revascularization procedures in 2266 women (45.6%) and men with ACS. For both men and women, prodromal symptoms in individuals were associated with increased cardiac investigations (electrocardiogram, echocardiogram, stress test, cardiac catheterization, and revascularization procedures [percutaneous coronary intervention/coronary artery bypass grafting]). However, prodromal symptoms in men predicted more revascularization procedures performed (n = 1243, 1.8%; P = .01) compared with women (n = 1034, 1.2%; P = .25).13 McSweeney and colleagues4 assessed the predictive value of the prodromal symptoms section of the MAPMISS in 1097 women with cardiac-related events (acute myocardial infarction and ACS) and interventions (angioplasty, stent placement,
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E8 Journal of Cardiovascular Nursing x January/February 2016 coronary artery bypass grafting, and death) over a 2-year period. Results indicated that 77 women (7%) had a cardiac-related event and/or intervention. The most common events were stents alone (n = 30, 38.9%), in combination with angioplasty (n = 14, 18.2%), acute myocardial infarction (n = 10, 15.2%), and death (n = 4, 5.2 %). Overall, 3 prodromal symptoms that were associated with risk of cardiac event after adjusting for age, race, and all covariates were general chest discomfort (HR, 1.09; 95% CI, 1.03Y1.16), SOB (HR, 1.07; 95% CI, 1.03Y1.11), and unusual fatigue (HR, 1.05; 95% CI, 1.01Y1.08).4 Women reporting 1 or more prodromal symptoms were more than 4 times more likely to have a major adverse cardiac event within 3 months to 2 years (HR, 4.19; 95% CI, 2.63Y7.44) compared with women who reported none.4
Discussion This review appraised and summarized the results of 7 studies of prodromal symptoms reported by individuals with CHD, and their association to clinical presentation, adverse cardiac events, and treatment interventions, conducted across 4 countries in various clinical settings. The methodological quality of studies ranged from medium to high.17 These results corroborate with others, that both men and women tend to report subjective prodromal symptoms before their acute cardiac event.6Y9 It would appear that there are more similarities than differences in prodromal symptoms experienced by men and women, which may not be totally explained by sex alone. Perhaps, a more detailed examination of prodromata in men and women is required. Future investigations should include adjustment for differences in age, sex, race, socioeconomic status, level of function, and comorbidities, while stratifying for ACS designation (unstable angina, non-ST-elevation and ST-elevation myocardial infarction), which may yield a more thorough and subjective description of individuals’ prodromal symptoms that affect both men and women with CHD. Prodromal symptoms reported in this review were arm pain/discomfort (86%), jaw pain (43%), back/shoulder blade pain (43%), chest discomfort/pain (57%), increasing anxiety (100%), SOB (86%), headaches (29%), dizziness (43%), sleep disturbance (29%), gastrointestinal complaints (71%), and unusual fatigue (100%). Of note, across studies, along with anxiety, fatigue was 1 of the most reported symptoms experienced by men and women before a cardiac event. This resonates with existing prodromal literature, where prodromal fatigue seems to be the symptom most often reported within the CHD population.3Y5,10,13,18,19 Fatigue as a symptom is difficult to assess because it is often confounded by other associated symptoms and other concurrent illnesses and comorbidities. Prodromal fatigue has been specifically described as an ‘‘unusual fatigue’’ and is significantly
different from how individuals have typically described being tired or fatigued. Descriptors frequently used to qualify prodromal fatigue have included ‘‘an all-encompassing and/or overwhelming fatigue.’’3 Noticeably, fatigue had changed in severity and intensity so much so that patients were unable to complete simple activities of daily living.3,9,15 Clinicians should continue to assess for prodromal symptoms, which may alert them of an impending ACS event. More importantly, prodromal symptom screening for those at high risk for CHD would be prudent to preemptively identify those at increased risk and provide appropriate cardiac investigation. Results indicated that individuals who experienced prodromal symptoms were more likely to report the same or similar symptoms during their ACS presentation. For example, Løvlien et al18 reported that the risk of experiencing radiating arm pain or numbness in the acute event more than doubled for women (OR, 2.68; 95% CI, 1.19Y6.20) and more than tripled for men (OR, 3.11; 95% CI, 1.90Y5.07) who reported prodromal symptoms of arm pain. Similarly, this was also evident for those who reported prodromal SOB. Men were more than 5 times more likely to experience (OR, 5.73; 95% CI, 3.42Y9.62) and women were more than 2 times more at risk of experiencing (OR, 2.67; 95% CI, 3.42Y9.62) SOB during the acute phase.18 In this review, there is some evidence to suggest that prodromal symptoms were predictive of cardiac events and treatment interventions. McSweeney and colleagues4 identified that 5 specific prodromal symptoms (discomfort in the jaw/teeth, unusual fatigue, discomfort in the arms, generalized chest discomfort, or SOB) were predictive of future cardiac events. Specifically, women who reported 1 or more of the 5 symptoms were 4 times more likely at risk of an adverse cardiac event as compared with women who reported no prodromal symptoms (HR, 3.97; 95% CI, 2.32Y6.78).4 In this study, only 77 women (7%) went on to experience an ACS event. Although statistically significant, one may argue that clinically, this is of little value as the predictive ability is quite low. Authors did acknowledge that further testing within primary care samples was needed to identify those with early prodromal symptoms, most indicative of CHD, and would require further evaluation.4 Graham et al13 reported that all patients with prodromes undergo greater cardiac testing before their index event than do patients without prodromal symptoms. For men, prodromal symptoms predicted more revascularization procedures performed (n = 1243, 1.8%; P = .01) as compared with women (n = 1034, 1.2%; P = .25)13 Again, although statistically significant, the predictive value is very low and warrants further investigation This does, however, support the potential benefit of early screening for prodromal warning signs as an effective strategy to seek medical advice before an ACS event occurs. To begin with, it would seem prudent to conduct in the
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Impact of Prodromal Symptoms on Cardiac-Related Events E9
What’s New or Important h Individuals who experienced cardiac-related prodromal symptoms were more likely to report the same or similar symptoms during their ACS presentation. h Early recognition of prodromal symptoms is imperative for effective targeting, screening, and diagnosis and timely treatment to identify those at risk for future CHD-related events. h Preemptive recognition of prodromal symptoms has the potential to reduce unnecessary healthcare burden, influence clinical practice, and improve cardiovascular-related outcomes for people living with CHD.
future a meta-analysis to determine the influence of prodromal symptoms across studies on major adverse cardiac events, accounting for differences in sex, age, risk factors, level of function, ACS designation, and the intensity, frequency, and number of prodromal symptoms. In addition, future prospective randomized controlled trials sufficiently powered to detect the predictive value of prodromal symptoms on major adverse cardiac events should be considered. One study in the review provided preliminary evidence to suggest that prodromal symptoms of headache, sleep disturbance, and anxiety may influence the presentation of ACS-related pain symptoms during an acute cardiac event.1 However, the sample was small (n = 121) and therefore generalizable only to the study setting. Future studies that would examine the predictive value of prodromal headaches, sleep disturbance, and anxiety on major adverse cardiac events require a longitudinal examination with larger sample sizes. The potential implications of these results are considerable. This systematic review expands what is known about cardiac prodromal symptoms in men and women with CHD. In particular, it provides increased awareness of the subjective and often ambiguous nature of prodromal symptoms that may occur before an acute cardiac event. These findings may provide clinicians with some further clarity, particularly the recognition and interpretation of patients’ prodromal symptoms. For patients with CHD, these results will provide additional knowledge of possible prodromal symptoms that may be experienced before their cardiac event. Also, this information may create heightened awareness of those patients in clinical practice that are at higher risk of prodromal symptoms and permit early healthcare education of when to seek prompt medical attention for cardiac-related prodromal warning signs. Proactive recognition of prodromal symptoms is imperative for effective targeting, screening, diagnosis and timely cardiac investigation. Study Limitations, Summary and Implications The present study has a few limitations. The results of the impact of prodromal symptoms on major adverse cardiac events are based on only 7 studies conducted
over the last 18 years. Of the 7 studies, 5 implemented a retrospective study design and may be subject to recall bias. In addition, generalizability may be limited as the included studies were published only in English. Also, across studies, because of differences in data collection methods, pertaining to prodromal symptoms, it was not possible to provide more than a qualitative synthesis of the literature. In summary, prodromal symptoms seem to be associated with the symptoms individuals may experience during an acute cardiac event and may predict future cardiac events and treatment interventions. However, future research is warranted that would examine the predictive value of prodromal symptoms on acute cardiac symptom presentation, cardiac-related events, and treatment interventions that would use a more thorough statistical inquiry with use of meta-analytic strategies, to adequately provide the prognostic importance of prehospital prodromal symptoms on major adverse cardiac events. In addition, prospective future examination of the predictive value of prodromal headache, sleep disturbance, and anxiety on major adverse cardiac events within this cardiovascular population warrants a closer look with a larger sample size. Moreover, research is necessary that focuses on further development and evaluation of pre-emptive screening instruments for cardiacrelated prodromal symptoms in men and women that may potentiate early diagnosis, effective risk modification, and timely cardiac treatment intervention. REFERENCES 1. O’Keefe-McCarthy S, McGillion M, Victor JC, McFetridgeDurdle J. The influence of prodromal symptoms on acute coronary syndrome pain severity. Pain Res Manage. 2013; 18:eY28. 2. Ready L, O’Keefe-McCarthy S. Early cardiac prodromal symptoms: an elusive clinical challenge. Can J Cardiol. 2013;29: S393. 3. McSweeney JC, Cody M, O’Sullivan P, Elberson K, Moser DK, Garvin B. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003;108:2619Y2623. 4. McSweeney JC, Cleves MA, Fisher EP, et al. Predicting coronary heart disease events in women: a longitudinal cohort study. J Cardiovasc Nurs. 2013;1Y11. doi:10.1097/JCN.ob013 e3182a409cc. 5. O’Keefe-McCarthy S. Women’s experiences of cardiac pain: a review of the literature. Can J Cardiovasc Nurs. 2008;18:18Y25. 6. Gallagher R, Marshall A, Fisher M. Symptoms and treatmentseeking responses in women experiencing acute coronary syndrome for the first time. Heart Lung. 2010;39:477Y484. 7. Hwang SY, Zerwic J, Jeong MH. Impact of prodromal symptoms on prehospital delay in patients with first time acute myocardial infarction. J Cardiovasc Nurs. 2011;26:194Y201. 8. O’Donnell S, McKee G, O’Brien F, Mooney M, Moser DK. Gendered symptom presentation in acute coronary syndrome: a cross sectional analysis. Int J Nurs Stud. 2012;49:1325Y1332. 9. McSweeney JC, Cody M, Crane PB. Do you know them when you see them? Women’s prodromal and acute symptoms of myocardial infarction. J Cardiovasc Nurs. 2001;15: 26Y38.
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E10 Journal of Cardiovascular Nursing x January/February 2016 10. McSweeney JC, Crane PB. Challenging the rules: women’s prodromal and acute symptoms of myocardial infarction. Res Nurs Health. 2000;23:135Y146. 11. Ottolini F, Modena MG, Rigatelli M. Prodromal symptoms in myocardial infarction. Psychother Psychosom. 2005;74: 323Y327. 12. Canto JC, Goldberg RJ, Hand MM, et al. Symptom presentation of women with acute coronary syndromes: myth vs reality: a literature review. Arch Intern Med. 2007;167: 2405Y2413. 13. Graham MM, Westerhout CM, Kaul P, Norris CM, Armstrong P. Sex differences in patients seeking medical attention for prodromal symptoms before an acute coronary event. Am Heart J. 2008;158:1210Y1216. 14. McSweeney JC, O’Sullivan O, Cleves MA, et al. Racial differences in women’s prodromal and acute symptoms of myocardial infarction. Am J Crit Care. 2010;19:63Y73. 15. Albarran JW, Clarke BA, Crawford J. It was not chest pain
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really, I can’t explain it! An exploratory study on the nature of symptoms experienced by women during their myocardial infarctions. J Clin Nurs. 2007;16:1292Y1301. Cole CS, McSweeney JC, Cleves MA, Armbya N, Bliwise DL, Petty CM. Sleep disturbance in women before myocardial infarction. Heart Lung. 2012;45:438Y445. Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis. 2001. Updated 2001; sited 2010. Available at http://ohri.ca/programs/clinical_epidemiology/oxford_web.ppt. Accessed August 2013. Løvlien M, Johansson I, Hole T, Schei B. Early warning signs of an acute myocardial infarction and their influence on symptoms during the acute phase, with comparisons by gender. Gender Med. 2009;6:444Y453. Hofgren C, Karlson W, Herlitz J. Prodromal symptoms in subsets of patients hospitalized for suspected acute myocardial infarction. Heart Lung. 1995;24:3Y10.
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Vol. 31, No. 1, pp E1YE10 x Copyright B 2016 Wolters Kluwer Health, Inc. All rights reserved.
Impact of Prodromal Symptoms on Future Adverse Cardiac-Related Events A Systematic Review Sheila O’Keefe-McCarthy, PhD, RN; Linda Ready, RN, BNSc, CNCC(C) Background: Recognition of specific and nonspecific cardiac-related prodromal symptoms, indicative of myocardial ischemia, is critical for preemptive coronary heart disease (CHD) screening and effective diagnosis and treatment. In this systematic review, we examined whether prodromal symptoms were predictive of acute symptom presentations, cardiac events, or treatment interventions. Methods: Studies that measured the association of prodromal symptoms with acute coronary syndrome (ACS) symptom presentation, acute cardiac event, and/or intervention in men and/or women with confirmed CHD were included. Data sources: Electronic searches in the Cochrane Library, MEDLINE, PubMed, PsyhINFO, Embase, CINAHL, and Scopus databases from 1990 to 2013 were conducted using medical subject heading terms including prodromal symptoms, ACS, acute myocardial infarction, unstable angina, and CHD. Key words such as shortness of breath, anxiety, atypical pain, sleep disturbance, fatigue, and nausea/vomiting were also used. Abstracts, relevant journals, key authors, and reference lists were reviewed. Results: Seven studies that included 6716 individuals with prodromal symptoms (65.7% women). Mean age was 68 T 13 and 58.5 T 9 years for women and men, respectively. Cardiac-related prodromal symptoms were predictive of patients’ ACS-related symptoms and associated events from 3 to 24 months. Across studies, the prodromal symptoms consistently reported before cardiac event were chest discomfort/pain (n = 4, 57%), arm pain/discomfort (n = 6, 86%), jaw pain (n = 3, 43%), back/shoulder blade pain (n = 3, 43%), unusual fatigue (n = 7, 100%), shortness of breath (n = 6, 86%), sleep disturbance (n = 2, 29%), dizziness (n = 3, 43%), headache (n = 3, 43%), anxiety (n = 7, 100%), and gastrointestinal complaints (nausea, vomiting, indigestion; n = 5, 71%). Patients with prodromal arm, jaw, and back pain; fatigue; and shortness of breath had increased risk of experiencing similar symptoms during an ACS episode. Prodromal symptoms were predictive of adverse cardiac events and cardiac interventions. There is some preliminary evidence to suggest that prodromal symptoms of headache, sleep disturbance, and anxiety may predict ACS symptom presentation during an acute cardiac event. Conclusion: Future research is warranted that would examine prospectively the predictive value of prodromal headache, sleep disturbance, and anxiety within this cardiovascular population on major adverse cardiac events. Preemptive screening for cardiac-related prodromal symptoms in men and women should be considered as a standard in clinical practice. This may potentiate early diagnosis, effective risk modification, timely pain management, and treatment intervention and decrease CHD-related morbidity and mortality. KEY WORDS:
acute coronary syndrome, adverse cardiac event, pain, prodromal symptoms
Background Prodromal symptoms, indicative of myocardial ischemia, associated with acute cardiac-related events remain elusive to recognize, understand, and respond to for some patients and healthcare professionals.1,2 Prodromal symptoms are those specific and nonspecific sensations inSheila O’Keefe-McCarthy, PhD, RN Adjunct Scientist, Ross Memorial Hospital, Lindsay, Ontario, Canada.
Linda Ready, RN, BNSc, CNCC(C) Clinical Practice Coordinator, City of Kawartha Lakes Family Health Care Team, Lindsay, Ontario, Canada. The authors have no conflicts of interest to disclose.
Correspondence Sheila O’Keefe-McCarthy, PhD, RN, Ross Memorial Hospital, 10 Angeline St North, Lindsay, Ontario, K9V 4M8 Canada ([email protected]). DOI: 10.1097/JCN.0000000000000207
dividuals may experience that serve as a warning sign of an impending acute coronary syndrome (ACS).3 Convincing evidence identifies that prodromal symptoms, experienced days, weeks, or months before a cardiac event, may relate to acute symptoms experienced during an ACS-related hospital admission.1,3Y5 Men and women have reported varied descriptions of prodromal symptoms that have included unusual chest and arm pain, shortness of breath (SOB), fatigue, sleep disturbances, dizziness, and anxiety, as some examples.6Y11 Within the prodromal literature, most studies have focused on women’s experience of cardiac-related symptoms and identify that women tend to report greater number of symptoms compared with men.9,10,12Y14 However, it has been recently reported that both men and women experience some form of prodromal symptoms before E1
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E2 Journal of Cardiovascular Nursing x January/February 2016 their cardiac event.1,13,18 Men report unique individual prodromal symptoms but may use different descriptors compared with their counterparts.1 Prodromata in individuals with coronary heart disease (CHD) have also been related to delay in acquiring immediate medical attention, and therefore, less aggressive treatment interventions have occurred.15,16 Perhaps, 1 of the reasons for this is that, typically, prodromal symptoms are vague in nature and as a result, are hard to recognize and relate to heart disease. Lack of recognition of these overt and covert warning signs related to CHD may increase cardiovascular-related morbidity and mortality.6,7 To date, little is known about whether prodromal symptoms are associated with the kind of acute symptom presentation that individuals may experience during an ACS event. Moreover, there is minimal literature available that demonstrates the relationship between prodromal symptoms and subsequent cardiac events or future treatment interventions.
Methods Aim The aim was to examine whether prodromal symptoms were predictive of acute ACS-related pain presentations, cardiac events (ACS-related unstable angina or acute myocardial infarction), and/or treatment interventions (percutaneous coronary intervention, angioplasty, stent, and/or coronary artery bypass grafting). Data Sources Electronic searches were conducted of PubMed, CINAHL, Embase, MEDLINE, PsychINFO, Cochrane Data Base of Systematic Reviews, and Scopus, using combinations of key medical subject heading terms, including prodromal symptoms, atypical cardiac presentation, ACS, unstable angina, acute myocardial infarction, heart attack, chest pain, anginal equivalence, major adverse cardiac event, coronary heart disease, angiogram, angioplasty, stents, coronary artery bypass grafting, and percutaneous coronary intervention. Other keywords were used, such as shortness of breath, fatigue, anxiety, syncope, unusual pain, sleep disturbance, headaches, nausea, and vomiting, to capture the subjectivity and complexity of cardiac-related prodromal symptoms. All search titles and abstracts were independently rated for relevance by 2 reviewers, based on the inclusion criteria. Hand searches of relevant journals, secondary references, and the abstracts and proceedings from national and international conferences were conducted. Where necessary, authors were contacted for access to study data from abstracts that met inclusion criteria. Inclusion Criteria To be eligible for inclusion, studies were subjected to the following inclusion criteria:
1. The articles were peer reviewed and published between 1990 and 2013. 2. Studies that included adult men and women or men and/or women (all ages) with confirmed CHD who reported prodromal symptoms. Coronary heart disease was defined as follows: individuals admitted to hospital with ACS, including unstable angina or myocardial infarction (non-ST-elevation or ST-elevation myocardial infarction. 3. Articles that examined the prognostic value of cardiacrelated prodromal symptoms on major adverse cardiac events and/or future cardiac treatment interventions; and 4. Articles that were published in English. Review Process Both authors conducted an independent literature search and together examined each computer search to identify potential articles using the aforementioned inclusion criteria. All titles and abstracts concerning prodromal symptoms were initially included, and subsequently, articles meeting the inclusion criteria were examined and reviewed. Eligibility was determined by mutual consensus from both authors. Data Extraction The authors conducted a systematic data extraction to provide a thorough description of participants, prodromes, and future related cardiac events and treatment interventions (Table 1). Each reviewer conducted her own data extraction of each article included in terms of the year of publication, journal type, study design, study participants, sample, setting, study objectives, and main results of each study. Authors compared the extractions and together summarized the main results based on the text provided in the original articles to achieve consensus. Study Quality Included studies in this review were either descriptivecorrelational and/or predictive studies (nonrandomized/ nonexperimental studies). Therefore, the methodological quality of included studies was appraised via the NewcastleOttawa Scale (NOS) for nonrandomized studies.17 This quality assessment instrument awards stars based on 3 levels of quality for an overall score of 9. The first category assesses the quality of the sample cohort. The second examines the comparability of design and data analysis (ie, Are the research design and analysis appropriate to answer the research question(s)?), and the third, the assessment of the outcome measure(s) of each study (ie, Are outcome measures captured with psychometrically valid and reliable instruments?). The NOS was adapted for the purposes of this review as follows: Representativeness of the study cohort was given a full star if it was explicit that participants had confirmed CHD and had ACS-related events. Half stars were awarded if the sample was mostly representative of an ACS sample (ie, 50%
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N = 515 Women MAPMISS Age mean, 66.4 T 12 y Section 1: Acute symptoms Age range, 29Y97 y Section 2: PSs, 30 questions Multisite- 5 Section 3 Y demographic, Retrospective survey over 3 y risk factors, comorbidity, medications Nominal /ordinal data = Content development percentage calculated; outlined, content validity continuous variables = median, was established by 7 content means, and SDs; t tests for univariate experts: survey expert, comparisons; multiple regression cardiologists, patients, and cardiac nurses. Retest reliability ranged from r = 0.72 to r = 0.91. N = 14 230 population DBs Based on 5 groups of PSs Women = 45.6%; on MAPMISS age = 65.3 T 13.5 y Pain (chest/arm/shoulder/ ACS sample, N = 2266 neck/jaw/leg) Anxiety/fatigue (anxiety/ Retrospective: DB: ACCS, HDD, sleep disturbance/ Statistics Canada, PCD, AHCIPR weakness/fatigue) Mean (SD), t tests, Mann-Whitney GI disturbances (N/V, loss tests, categorical = with %, # 2 for comparisons, Kaplan-Meier survival of appetite, indigestion) analysis, multivariable Cox proportional Head related (dizziness, hazards regression headache, visual disturbance) Other (sweating, SOB, heart racing, cough, numbness) No pilot work or psychometrics reported
1. The most frequent PSs of AMI 2. How prodromal and acute symptoms relate to comorbidities and CAD risk 3. Whether PSs were predictive of AMI symptoms
Examine the association between PS and 1-y mortality and cardiac catheterization and revascularization procedures (not specified)
2. McSweeney et al, 20033 United States
3. Graham et al, 200813 Canada
Prodromal Questionnaire 7 questions relating to prehospital admission prodromal signs, occurrence, frequency, and duration. Prodromal questionnaire was pilot tested on several patients for clarity and comprehension. No psychometric evaluation was provided.
N = 914 Women, 262; men, 652 Age 966 y = 417, e66 y= 497 1 urban hospital CCU Fisher exact test for comparison between proportions, with 2-tailed test computed; P e .05 considered significant Retrospective survey post-CCU admission
Prodromal Instrument/ Psychometric Properties
1. Examine PSs in suspected AMI patients and relate them to the final diagnosis. 2. Examine whether PSs differ with respect to infarct location. 3. Did the patient seek medical help in the prodromal phase?
Sample (n) /Sex/Mean (SD) Age/Site/Design/Statistics
1. Hofgren et al, 199519 Sweden
Aim
Studies Examining the Predictive Value of Prodromal Symptoms
Author/Year/ Country
TABLE 1
Unusual fatigue Sleep disturbance SOB Indigestion Anxiety Chest discomfort
Pain (neck, jaw teeth, arms, shoulder, throat) Anxiety/fatigue GI disturbances Head related (dizziness, headache, visual disturbance) Other (diaphoresis, SOB, cough, numbness, racing heart)
1. 2. 3. 4. 5. 6.
CP symptoms Extreme tiredness Loss of appetite 948 h prehospital admission Emotional stress Did the patient seek medical help with these PSs? Described the frequency and duration of PS
PSs
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(continues)
28% tiredness Chest discomfort, 27% No difference between large or small infarcts 35% experienced emotional distress PS experienced included tiredness, chest discomfort, gastrointestinal, arm pain, dyspnea and other symptoms 61% with AMI had PSs other than CP 948 h prehospital admission. Same frequency of PSs in nonYAMI-diagnosed patients 1. 70%: fatigue 2. 47.8%: sleep disturbance 3. 42.1%: SOB 4. 39.4: indigestion 5. 35.5%: anxiety 6. 43.5% reported no CP/discomfort 78% of women experienced PSs greater than 1 mo before AMI. PSs were significant in predicting the severity of the acute symptoms. Controlling for risk factors. PS score accounted for 33.25% of the variance in acute symptoms scores. PSs were associated with improved 1-y mortality in women (HR, 0.74; 95% CI, 0.58Y9.95; P = .016), but not in men (HR, 0.92; 95% CI, 0.76Y1.12; P = .422). Both men and women with reported PSs were more commonly provided with cardiac catheterization. PS in men predicted more revascularization procedures compared with women.
Results
Impact of Prodromal Symptoms on Cardiac-Related Events E3
1. To assess PSs of AMI within 1 y of AMI 2. Do PSs have any influence on acute AMI symptoms? 3. To examine gender differences
5. Cole et al, 201216 1. Describe the relationships United States among sleep disturbance, cardiac PSs, and cognitive impairment
4. Løvlien et al, 200918 Norway
Aim Prodromal questionnaire 48 questions, asked about AMI, describe PS and acute symptoms Content Validity established by clinical researchers (nurses physicians) Reliability testing: Cronbach’s ! = 0.79 Questionnaire was pilot tested on 20 patients for user friendliness and clarity of content
Prodromal Instrument/ Psychometric Properties
N = 1270 women diagnosed MAPMISS with first time ACS Prodromal section used; Retrospective telephone survey 30 questions/symptoms Descriptive statistics = sample and Content development prevalence of sleep disturbance, outlined; content validity # 2Yprevalence of risk factors, was established by 7 content linear regression, logistic experts: survey expert, regression for associations cardiologists, patients, and between sleep cardiac nurses. disturbance and PS Retest reliability ranged from r = 0.72 to r = 0.91
N = 533 Women, n = 149; men, n = 384 Age e75 y Mean age: women, 61.2 y; men, 58.5 y Multicenter Retrospective survey (self-administered) Means (SD) for continuous variables, percentage for proportions, 2-tailed # 2 tests comparing men and women, logistic regression
Sample (n) /Sex/Mean (SD) Age/Site/Design/Statistics
Studies Examining the Predictive Value of Prodromal Symptoms, Continued
Author/Year/ Country
TABLE 1
Sleep disturbance Cognition change Anxiety Leg pain Headaches Fatigue
1. Chest discomfort 2. Fatigue 3. Dyspnea (SOB) 4. Anxiety 5. Nervousness
PSs
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(continues)
Patients with PS of chest, shoulder, back pain, numbness in the arms, SOB, and fatigue had increased risk of experiencing similar symptoms during AMI phase. Women who experienced PS-CP were 95 times more likely to have CP symptoms in the acute AMI phase (OR, 5.11; 95% CI, 1.38Y18.88) and nearly 3 times greater than in men (OR, 2.80; 95% CI, 1.17Y6.70). Risk of experiencing shoulder pain was almost 5 times greater in men (OR, 4.96; 95% CI, 3.01Y8.19) but not women. Risk of numbness and arm pain in the acute phase was 2 times greater for women with PS of arm pain (OR, 2.66; 95% CI, 1.19Y6.20) and 3 times greater for men (OR, 3.11; 95% CI, 1.90Y5.07). Those with previous SOB and fatigue were 2Y3 times at risk for similar symptoms in the index ACS event (dyspnea: women, OR, 2.67; 95% CI, 1.25Y5.71; men, OR, 5.73; 95% CI, 3.42Y9.62; fatigue: women, OR, 2.97; 95% CI, 1.28Y6.85; men, OR, 2.51; 95% CI, 1.54Y4.11). Women (84%) and men (76%) reported PSs 1 y before AMI. PS is predictive of symptoms in the acute event. 632 women reported new-onset sleep disturbance, anxiety, and fatigue before an ACS event. Prodromal sleep disturbance was common across ethnic groups (50.2% overall; 52.1% blacks; 50.5% Hispanics; and 48.2% whites). Prodromal sleep disturbance was predictive of an ACS event.
Results
E4 Journal of Cardiovascular Nursing x January/February 2016
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Unusual pain Fatigue SOB Headache Anxiety Sleep disturbance CP Dizziness Other (gastric complaints, palpitations, diaphoresis, numbness, and visual disturbances)
N = 121; men, n = 63; women, PS-SS n = 58 Indentifies 8 PSs: unusual Age, 67.6 (13) y located aches and/or pain, One rural community hospital; unusual fatigue, sleep prospective, individual interviews disturbances, CP, anxiety, Association between ACS pain headaches, dizziness, and SOB intensity and presence/absence The category of other of PS: Wilcoxon rank-sum symptom was offered to nonparametric test patients in case the 8-item scale State/trait anxiety, examined by did not adequately capture all PS: Student t tests the patients’ subjective PS. Unadjusted comparison of PSs Content validity index = 0.85; between men and women and ICR = 0.613 across comorbidities: # 2 tests Pilot tested on 10 ACS patients for clarity, ease of use, Multivariable logistic regression for comprehension, and scoring association between comorbidities and PS controlling for confounders
Examined the prevalence and predictive value of cardiac PSs on acute coronary syndrome pain intensity, state, and trait anxiety
7. O’Keefe-McCarthy et al, 20131 Canada
77 women (7%) experienced cardiac events during the 2 y follow-up. Angioplasty, 5.2%; stent alone, 38.9%; stent/angioplasty, 18.2%; CABG, 19.5%; AMI, 17.2% 3 PSs were associated with cardiac events controlling for all covariates: (1) general chest discomfort, (2) SOB, and (3) unusual fatigue. Adjusting for age and race, 4 PSs revealed in risk of cardiac event: (1) discomfort in jaws/teeth, (2) unusual fatigue, (3) discomfort in arms, and (4) SOB. Women reporting more than 1 of the 4 PSs were 4 times more likely to have a cardiac event (HR, 4.19; 95% CI, 2.63Y7.44). Women who were older, had comorbidities, and had poor economic status had greater cardiac events. The MAPMISS is useful for screening at-risk women for CAD-related cardiac events. Increased ACS pain intensity was significantly associated with prodromal headaches (P = .006); sleep disturbances (P = .012), and anxiety (P = .017). PSs were not associated with patients’ state or trait anxiety. Patients with comorbidity of hypertension were 7.5 times more likely to experience unusual fatigue before an ACS-related event. Overall PS prevalence = 49%; no difference in prevalence of PS between men and women Patients reported at least 1 PS. The 4 most reported PSs included CP (n = 66, 70.8%), SOB (n = 74, 62%), anxiety (n = 70, 59%), and unusual fatigue (n = 54, 53.3%). Intensities ranged from moderate to severe. PS frequency ranged from daily to several times per week.
Results
Abbreviations: ACCS, Ambulatory Care Classification System; ACS, acute coronary syndrome; AHCIPR, Alberta Health Care Insurance Plan Registry; AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; CAD, coronary artery disease; CCU, cardiac care unit; CI, confidence interval; CP, chest pain; DB, databases; GI, gastrointestinal; HDD, hospital discharge data base; HR, hazard ratio; ICR, internal consistency reliability; MACE, major adverse cardiac event; MAPMISS, McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey; N/V, nausea and vomiting; OR, odds ratio; PCD, physician claims data; PS, prodromal symptoms; PS-SS, Prodromal Symptom Screening Scale; SOB, shortness of breath.
Pain (neck, jaw teeth, arms, shoulder, throat and leg) Anxiety/fatigue GI Head related (dizziness, headache and visual disturbance) Other (diaphoresis, SOB, cough, numbness, and racing heart)
PSs
N = 1097 women MAPMISS Age 921 y Section 1: Acute symptom Multisite: 4 cardiac clinics Section 2: PSs; 30 questions Longitudinal- observational, Section 3: demographic, retrospective surveyY every risk factors, comorbidity, 3 mo for 2 y medications Estimated HRs and corresponding Content development 95% CI for experiencing outlined; content validity was MACE using multivariate established by 7 content Cox proportional hazards experts: survey expert, regression modeling cardiologists, patients, and cardiac nurses. Retest reliability ranged from r = 0.72 to r = 0.91
Prodromal Instrument/ Psychometric Properties
Evaluated the usefulness of the MAPMISS in 1. To identify women who would have a cardiac event (AMI, ACS, stent, angioplasty, CABG, death) 2. To identify the most parsimonious subset of PSs predictive of cardiac events
Sample (n) /Sex/Mean (SD) Age/Site/Design/Statistics
6. McSweeney et al, 20134 United States
Aim
Studies Examining the Predictive Value of Prodromal Symptoms, Continued
Author/Year/ Country
TABLE 1
Impact of Prodromal Symptoms on Cardiac-Related Events E5
E6 Journal of Cardiovascular Nursing x January/February 2016 of the sample were diagnosed with unstable angina or acute myocardial infarction). For the assessment of outcome, records from established databases, medical records, and telephone and face-to-face interviews were allotted full stars. Studies that provided full descriptions of the instruments used to collect prodromal symptoms and the associated psychometric properties were awarded full stars. Two items were not applicable to the review and were excluded: (a) the selection of nonexposed cohort was representative of sample and (b) outcome of interest was not present at the start of the study. Studies were excluded if they did not achieve, at minimum, 5 allotted stars of the possible 7 for overall methodological quality.
Results A total of 800 article titles were found from the electronic searches. Thirty-six were duplicates, leaving 764 for consideration. Of these, 745 articles were removed because they were general or review articles, case reports, editorials, opinion pieces, or annotated bibliographies and/or did not fit the a priori inclusion criteria. Remaining were 19 studies that examined prodromata in CHD. At closer examination, 12 were further excluded as they examined children and youth, were qualitative studies, or were psychometric property evaluation studies (see the Figure for study selection).
2 were from Canada (29%), and 1 each was from Norway (14%) and Sweden (14%). Most of the study designs were a retrospective cohort (5, 71%). One study was a longitudinal, observational study with a retrospective 3-month survey over a 2-year period.4 One was a prospective, descriptive-correlational study and the other was a prospective, cross-sectional study.1,18 Data were collected by population database extraction (n = 2),13,16 combination of retrospective telephone interview/questionnaire survey (n = 2),3,4 face-to-face questionnaire interview survey/medical record (n = 1),1 and patient self-administered questionnaire survey (n = 2).18,19 Prodromal symptoms were captured in 3 studies (43%) by the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (MAPMISS), 3,4,16 and 1 used only a part of the prodromal section of the MAPMISS.13 Three others (43%) developed a prodromal questionnaire and provided descriptions of instrument development, psychometric properties, and associated pilot work.1,18,19 Across studies, age varied from 21 to 97 years. The mean age ranged from 68 T13 years for women to 58.5 T 9 for men, respectively. Sample sizes varied from 121 to more than 2300 participants. The results of the NOS assessment revealed that the quality across studies was moderate to strong and ranged from 5 to 7 stars. See Table 2 for methodological quality.
Characteristics of the Included Studies Table 1 summarizes the descriptive data from the 7 studies included. Studies were published between 1995 and 2013. Three studies were conducted in the United States (43%),
Cardiac-Related Prodromal Symptoms For most of the studies, prodromal symptoms were identified as either occurring (yes) or not (no). Across
Figure. Summary of data extraction.
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Impact of Prodromal Symptoms on Cardiac-Related Events E7 TABLE 2
Methodological Quality Assessment Scale of Prodromal Studies
Study 1. 2. 3. 4. 5. 6. 7.
Hofgren et al, 1995 McSweeney et al, 2003 Graham et al, 2008 Lovlien et al, 2009 Cole et al, 2012 McSweeney et al, 2013 O’Keefe-McCarthy et al, 2013
Selection (Max = 2a)
Comparability (2a)
Outcome (3a)
Total Score (Max = 7a)
b
a
b
b
a
c
b
b
b
b
b
a
b
b
c
b
b
c
b
b
b
5 6 6 5 7 7 6
Based on the Newcastle-Ottawa Quality Assessment Scale for Nonrandomized Studies (Wells et al, 2001). a 1 star. b 2 stars. c 3 stars.
all studies, the percentages of reported prodromal symptoms were as follows: chest discomfort/pain, n = 4, 57%; arm pain/discomfort, n = 6, 86%; jaw pain, n = 3, 43%; back/shoulder blade pain, n = 3, 43%; unusual fatigue, n = 7, 100%; SOB, n = 6, 86%; sleep disturbance, n = 2, 29%; dizziness, n = 3, 43%; headache, n = 3, 43%; anxiety, n = 7, 100%; and gastrointestinal complaints (nausea, vomiting, indigestion), n = 5, 71%.1,3,4,13,16,18,19 Prodromal symptoms occurred from 48 hours1 to several days,1 weeks,3,16 and/or months13,18,19 before patients’ acute cardiac event. Prodromal symptoms were prevalent in 49% to 95% of the samples.1,3,4,13,16,18,19 Five studies (71%) also reported other nonspecific prodromal symptoms: gastrointestinal complaints of indigestion, dizziness, visual disturbances, changes in cognition, palpitations, diaphoresis, numbness and tingling in the hands and arms, and loss of appetite.1,3,4,13,19 Of the 4 studies that examined prodromal symptoms in men and women, 2 found that women tended to report more symptoms compared with men.18,19 Women presented with less prodromal chest pain but reported greater fatigue, anxiety, and head-related symptoms (headache, dizziness) compared with men.13,18,19 Associated Prodromal Symptoms With Acute Symptoms of Acute Coronary Syndrome Table 1 provides the prodromal symptoms reported by men and women that were predictive of the acute symptoms experienced during an index cardiac event. Of the 7 studies, 6 (85%) reported that patients with prodromal chest pain/discomfort or shoulder/back/neck/headache pain, pain or numbness in the arms/hands, SOB, fatigue, sleep disturbance, and/or anxiety were more likely to experience similar symptoms during the acute phase of an ACS.1,3,4,16,18,19 For example, risks of experiencing chest-related symptoms (pain, discomfort, pressure, palpitations) in the acute stage of an acute myocardial infarction were more than 5 times greater in women who had experienced prodromal chest pain symptoms (adjusted odds ratio [OR], 5.11; 95% confidence interval [CI], 1.38Y18.88) and almost 3 times more likely in men (OR,
2.80; 95% CI, 1.17Y6.70).18 Similarly, individuals with jaw/teeth pain (hazard ratio [HR], 1.14; 95% CI, 1.07Y1.21) and fatigue (HR, 1.08; 95% CI, 1.05Y1.11) were more likely to go on to have an acute ACS event reporting similar symptoms compared with those with no reported prodromal symptoms.4 According to McSweeney et al,3 prodromal symptoms are predictive of the severity of acute symptoms experienced. In their recent study, McSweeney and colleagues4 identified that unusual fatigue, SOB, pain in the jaw and teeth, and discomfort in the arms were predictive of increased risk of admission with acute symptoms of AMI. In another study, O’Keefe-McCarthy et al1 found that ACS patients’ pain intensity, experienced by men and women (n = 121) during the first 8 hours of an emergency department visit, was related to preexisting prodromal symptoms. Specifically, median pain scores (numerical rating scale, 0Y10) were higher by 2 points for those with prodromal headache (P = .006) and anxiety (P = .017) and 1 point higher for those with sleep disturbances (P = .012).1
Associated Prodromal Symptoms with Treatment Intervention Two studies examined the influence of prodromal symptoms on related treatment interventions.4,13 Graham and colleagues13 investigated the association of prodromal symptoms, 1- year mortality, and revascularization procedures in 2266 women (45.6%) and men with ACS. For both men and women, prodromal symptoms in individuals were associated with increased cardiac investigations (electrocardiogram, echocardiogram, stress test, cardiac catheterization, and revascularization procedures [percutaneous coronary intervention/coronary artery bypass grafting]). However, prodromal symptoms in men predicted more revascularization procedures performed (n = 1243, 1.8%; P = .01) compared with women (n = 1034, 1.2%; P = .25).13 McSweeney and colleagues4 assessed the predictive value of the prodromal symptoms section of the MAPMISS in 1097 women with cardiac-related events (acute myocardial infarction and ACS) and interventions (angioplasty, stent placement,
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E8 Journal of Cardiovascular Nursing x January/February 2016 coronary artery bypass grafting, and death) over a 2-year period. Results indicated that 77 women (7%) had a cardiac-related event and/or intervention. The most common events were stents alone (n = 30, 38.9%), in combination with angioplasty (n = 14, 18.2%), acute myocardial infarction (n = 10, 15.2%), and death (n = 4, 5.2 %). Overall, 3 prodromal symptoms that were associated with risk of cardiac event after adjusting for age, race, and all covariates were general chest discomfort (HR, 1.09; 95% CI, 1.03Y1.16), SOB (HR, 1.07; 95% CI, 1.03Y1.11), and unusual fatigue (HR, 1.05; 95% CI, 1.01Y1.08).4 Women reporting 1 or more prodromal symptoms were more than 4 times more likely to have a major adverse cardiac event within 3 months to 2 years (HR, 4.19; 95% CI, 2.63Y7.44) compared with women who reported none.4
Discussion This review appraised and summarized the results of 7 studies of prodromal symptoms reported by individuals with CHD, and their association to clinical presentation, adverse cardiac events, and treatment interventions, conducted across 4 countries in various clinical settings. The methodological quality of studies ranged from medium to high.17 These results corroborate with others, that both men and women tend to report subjective prodromal symptoms before their acute cardiac event.6Y9 It would appear that there are more similarities than differences in prodromal symptoms experienced by men and women, which may not be totally explained by sex alone. Perhaps, a more detailed examination of prodromata in men and women is required. Future investigations should include adjustment for differences in age, sex, race, socioeconomic status, level of function, and comorbidities, while stratifying for ACS designation (unstable angina, non-ST-elevation and ST-elevation myocardial infarction), which may yield a more thorough and subjective description of individuals’ prodromal symptoms that affect both men and women with CHD. Prodromal symptoms reported in this review were arm pain/discomfort (86%), jaw pain (43%), back/shoulder blade pain (43%), chest discomfort/pain (57%), increasing anxiety (100%), SOB (86%), headaches (29%), dizziness (43%), sleep disturbance (29%), gastrointestinal complaints (71%), and unusual fatigue (100%). Of note, across studies, along with anxiety, fatigue was 1 of the most reported symptoms experienced by men and women before a cardiac event. This resonates with existing prodromal literature, where prodromal fatigue seems to be the symptom most often reported within the CHD population.3Y5,10,13,18,19 Fatigue as a symptom is difficult to assess because it is often confounded by other associated symptoms and other concurrent illnesses and comorbidities. Prodromal fatigue has been specifically described as an ‘‘unusual fatigue’’ and is significantly
different from how individuals have typically described being tired or fatigued. Descriptors frequently used to qualify prodromal fatigue have included ‘‘an all-encompassing and/or overwhelming fatigue.’’3 Noticeably, fatigue had changed in severity and intensity so much so that patients were unable to complete simple activities of daily living.3,9,15 Clinicians should continue to assess for prodromal symptoms, which may alert them of an impending ACS event. More importantly, prodromal symptom screening for those at high risk for CHD would be prudent to preemptively identify those at increased risk and provide appropriate cardiac investigation. Results indicated that individuals who experienced prodromal symptoms were more likely to report the same or similar symptoms during their ACS presentation. For example, Løvlien et al18 reported that the risk of experiencing radiating arm pain or numbness in the acute event more than doubled for women (OR, 2.68; 95% CI, 1.19Y6.20) and more than tripled for men (OR, 3.11; 95% CI, 1.90Y5.07) who reported prodromal symptoms of arm pain. Similarly, this was also evident for those who reported prodromal SOB. Men were more than 5 times more likely to experience (OR, 5.73; 95% CI, 3.42Y9.62) and women were more than 2 times more at risk of experiencing (OR, 2.67; 95% CI, 3.42Y9.62) SOB during the acute phase.18 In this review, there is some evidence to suggest that prodromal symptoms were predictive of cardiac events and treatment interventions. McSweeney and colleagues4 identified that 5 specific prodromal symptoms (discomfort in the jaw/teeth, unusual fatigue, discomfort in the arms, generalized chest discomfort, or SOB) were predictive of future cardiac events. Specifically, women who reported 1 or more of the 5 symptoms were 4 times more likely at risk of an adverse cardiac event as compared with women who reported no prodromal symptoms (HR, 3.97; 95% CI, 2.32Y6.78).4 In this study, only 77 women (7%) went on to experience an ACS event. Although statistically significant, one may argue that clinically, this is of little value as the predictive ability is quite low. Authors did acknowledge that further testing within primary care samples was needed to identify those with early prodromal symptoms, most indicative of CHD, and would require further evaluation.4 Graham et al13 reported that all patients with prodromes undergo greater cardiac testing before their index event than do patients without prodromal symptoms. For men, prodromal symptoms predicted more revascularization procedures performed (n = 1243, 1.8%; P = .01) as compared with women (n = 1034, 1.2%; P = .25)13 Again, although statistically significant, the predictive value is very low and warrants further investigation This does, however, support the potential benefit of early screening for prodromal warning signs as an effective strategy to seek medical advice before an ACS event occurs. To begin with, it would seem prudent to conduct in the
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Impact of Prodromal Symptoms on Cardiac-Related Events E9
What’s New or Important h Individuals who experienced cardiac-related prodromal symptoms were more likely to report the same or similar symptoms during their ACS presentation. h Early recognition of prodromal symptoms is imperative for effective targeting, screening, and diagnosis and timely treatment to identify those at risk for future CHD-related events. h Preemptive recognition of prodromal symptoms has the potential to reduce unnecessary healthcare burden, influence clinical practice, and improve cardiovascular-related outcomes for people living with CHD.
future a meta-analysis to determine the influence of prodromal symptoms across studies on major adverse cardiac events, accounting for differences in sex, age, risk factors, level of function, ACS designation, and the intensity, frequency, and number of prodromal symptoms. In addition, future prospective randomized controlled trials sufficiently powered to detect the predictive value of prodromal symptoms on major adverse cardiac events should be considered. One study in the review provided preliminary evidence to suggest that prodromal symptoms of headache, sleep disturbance, and anxiety may influence the presentation of ACS-related pain symptoms during an acute cardiac event.1 However, the sample was small (n = 121) and therefore generalizable only to the study setting. Future studies that would examine the predictive value of prodromal headaches, sleep disturbance, and anxiety on major adverse cardiac events require a longitudinal examination with larger sample sizes. The potential implications of these results are considerable. This systematic review expands what is known about cardiac prodromal symptoms in men and women with CHD. In particular, it provides increased awareness of the subjective and often ambiguous nature of prodromal symptoms that may occur before an acute cardiac event. These findings may provide clinicians with some further clarity, particularly the recognition and interpretation of patients’ prodromal symptoms. For patients with CHD, these results will provide additional knowledge of possible prodromal symptoms that may be experienced before their cardiac event. Also, this information may create heightened awareness of those patients in clinical practice that are at higher risk of prodromal symptoms and permit early healthcare education of when to seek prompt medical attention for cardiac-related prodromal warning signs. Proactive recognition of prodromal symptoms is imperative for effective targeting, screening, diagnosis and timely cardiac investigation. Study Limitations, Summary and Implications The present study has a few limitations. The results of the impact of prodromal symptoms on major adverse cardiac events are based on only 7 studies conducted
over the last 18 years. Of the 7 studies, 5 implemented a retrospective study design and may be subject to recall bias. In addition, generalizability may be limited as the included studies were published only in English. Also, across studies, because of differences in data collection methods, pertaining to prodromal symptoms, it was not possible to provide more than a qualitative synthesis of the literature. In summary, prodromal symptoms seem to be associated with the symptoms individuals may experience during an acute cardiac event and may predict future cardiac events and treatment interventions. However, future research is warranted that would examine the predictive value of prodromal symptoms on acute cardiac symptom presentation, cardiac-related events, and treatment interventions that would use a more thorough statistical inquiry with use of meta-analytic strategies, to adequately provide the prognostic importance of prehospital prodromal symptoms on major adverse cardiac events. In addition, prospective future examination of the predictive value of prodromal headache, sleep disturbance, and anxiety on major adverse cardiac events within this cardiovascular population warrants a closer look with a larger sample size. Moreover, research is necessary that focuses on further development and evaluation of pre-emptive screening instruments for cardiacrelated prodromal symptoms in men and women that may potentiate early diagnosis, effective risk modification, and timely cardiac treatment intervention. REFERENCES 1. O’Keefe-McCarthy S, McGillion M, Victor JC, McFetridgeDurdle J. The influence of prodromal symptoms on acute coronary syndrome pain severity. Pain Res Manage. 2013; 18:eY28. 2. Ready L, O’Keefe-McCarthy S. Early cardiac prodromal symptoms: an elusive clinical challenge. Can J Cardiol. 2013;29: S393. 3. McSweeney JC, Cody M, O’Sullivan P, Elberson K, Moser DK, Garvin B. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003;108:2619Y2623. 4. McSweeney JC, Cleves MA, Fisher EP, et al. Predicting coronary heart disease events in women: a longitudinal cohort study. J Cardiovasc Nurs. 2013;1Y11. doi:10.1097/JCN.ob013 e3182a409cc. 5. O’Keefe-McCarthy S. Women’s experiences of cardiac pain: a review of the literature. Can J Cardiovasc Nurs. 2008;18:18Y25. 6. Gallagher R, Marshall A, Fisher M. Symptoms and treatmentseeking responses in women experiencing acute coronary syndrome for the first time. Heart Lung. 2010;39:477Y484. 7. Hwang SY, Zerwic J, Jeong MH. Impact of prodromal symptoms on prehospital delay in patients with first time acute myocardial infarction. J Cardiovasc Nurs. 2011;26:194Y201. 8. O’Donnell S, McKee G, O’Brien F, Mooney M, Moser DK. Gendered symptom presentation in acute coronary syndrome: a cross sectional analysis. Int J Nurs Stud. 2012;49:1325Y1332. 9. McSweeney JC, Cody M, Crane PB. Do you know them when you see them? Women’s prodromal and acute symptoms of myocardial infarction. J Cardiovasc Nurs. 2001;15: 26Y38.
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E10 Journal of Cardiovascular Nursing x January/February 2016 10. McSweeney JC, Crane PB. Challenging the rules: women’s prodromal and acute symptoms of myocardial infarction. Res Nurs Health. 2000;23:135Y146. 11. Ottolini F, Modena MG, Rigatelli M. Prodromal symptoms in myocardial infarction. Psychother Psychosom. 2005;74: 323Y327. 12. Canto JC, Goldberg RJ, Hand MM, et al. Symptom presentation of women with acute coronary syndromes: myth vs reality: a literature review. Arch Intern Med. 2007;167: 2405Y2413. 13. Graham MM, Westerhout CM, Kaul P, Norris CM, Armstrong P. Sex differences in patients seeking medical attention for prodromal symptoms before an acute coronary event. Am Heart J. 2008;158:1210Y1216. 14. McSweeney JC, O’Sullivan O, Cleves MA, et al. Racial differences in women’s prodromal and acute symptoms of myocardial infarction. Am J Crit Care. 2010;19:63Y73. 15. Albarran JW, Clarke BA, Crawford J. It was not chest pain
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