The CORONARY ARlERY DISEASE American JUNE 15, 1990, VOL. 65, NO. 22

Journal of

Cardiology

The Prehospital Phase of Acute Myocardial Infarction in the Era of Thrombolysis

Stanley B. Schmidt, MD, and Mark A. Borsch, MD

To evaluate the factors affecting the time between symptom onset and hospital arrival in patlents with acute myocardlal lnfarctlon (AM), we gave a de- tailed questkumalre to all who were admRted or transfenwf with AMI from January 1969 to Febru- ary 1969. In these 126 patients (94 men, 32 wom- Ctll)thellWlMl prchorpitslthnewas5.9* 11.0 hours (median 2.0, range 0.4 to 69.0). Yhe time between symptom onset and reaching a decMon that medkal care shoukl be sought was 62% of the mean preho@tal time. In 100 (79%) pattents, the pmhospltal time was 16 hours; of these, 61(61%) were Mroqectlvely judged to have been optimal candidabs for lytlc therapy. Stepwise multiple re- gresslon seiected the folk~wlng 4 variables as hute- pendent predktors of Ml tlme: slow symp- tom progredm; low IncMe, female gender; and advanced age. All of these variabRs are predictive (p <0.03) of hrcreased Btal time; absence of prior AMI was of borderline additional significance (p = 0.093). Similarly, logistic regression analysis selected skbw symptom progression, female gender and low income as slgnifkant (p 10.02) huiepen- dent predictors of prehospltal time >6 hours. The logistic regression model lncorporatlng these 3 variables had a sensltlvRy of 6456, a speciticity of 95% and a posltlve predictive value of 72% In identifylng pa6ents wlth prehospltal time S hours. Thus, these data indicate it is possible to character- ize patients likely to experience undue prehospltal delay during AMI, which may be of importance to future public education efforts.

(Am J Cardiol1990;65:1411-1415)

From the Section of Cardiology, West Virginia University School of Medicine, Morgantown, West Virginia. Manuscript received Novem- ber 14, 1989; revised manuscript received and accepted February 6, 1990.

Address for reprints: Stanley B. Schmidt, MD, Section of Cardiolo- gy, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506.

P rompt treatment of patients with acute myocardial infarction (AMI) decreases death from early ar- rhythmia and maximizes the potential benefit of

thrombolytic therapy. Both the Italian Group for the Study of Streptokinase in Myocardial Infarction and the Second International Study of Infarct Survival showed strong associations between the promptness of treatment and the amount of decrease in AM1 mortali- ty using intravenous streptokinase.1,2 In the Italian study, no advantage was shown to lytic therapy when delayed beyond 6 hours after symptom onset. While some patients who present late may be found to benefit from thrombolysis,3 the time to treatment will remain a critical determinant of therapeutic outcome. Unfortu- nately, clinical experience shows that many patients with AM1 continue to arrive relatively late after devel- opment of symptoms. This study evaluates the factors affecting the time between symptom onset and hospital arrival in patients with AM1 to determine if a profile can be developed of those most likely to exhibit undue delay in seeking medical care.

METHOD9 Study patian& The study sample consisted of 161

patients admitted or transferred to our medical center between January 1988 and February 1989 with out-of- hospital AMI. Those who agreed to participate were given a detailed questionnaire supplemented by chart review to determine factors affecting prehospital time and subsequent hospital course. The study was purely observational and was not designed to affect patient evaluation or treatment. Reasons for exclusion in 35 (22%) patients were death before completion of the sur- vey (23 patients), painless AM1 (2), patient refusal (1) and miscellaneous (9), leaving 126 patients (78%) in the final study sample. Admitted (42, 33%) and transferred (84, 67%) patients were similar in regard to most vari- ables and were grouped together for subsequent data analysis. Confirmation of AM1 required a peak serum creatine kinase of 2 150% of the laboratory’s upper nor- mal value, in addition to conventional clinical and/or electrocardiographic criteria.

DetinRionsr Precall time was the interval between symptom onset and calling to be taken to a hospital. It was subdivided into the following: a notification time, extending from symptom onset to notification of anoth- er person of the presence of symptoms; a decision time, extending from the time of symptom notification to the time a decision was made that medical care should be

THE AMERICAN JOURNAL OF CARDIOLOGY JUNE 15, 1990 1411

TABLE I Time Periods in Early and Late Arrival Groups

Early Group Late Group n=100 n=26

Time Period G-0 (W p Value

Notification 0.7f 1.2 5.1 f7.1 O.CO80 Decision 0.5 f 0.9 13.9 f 21.9 0.0006 Delay 0.1 f0.2 1.4f3.4 NS Wait 0.3 f 0.4 0.2 f 2.5 NS Travel 0.6 f 0.5 0.5 f 0.4 NS Precall 1.3f 1.4 20.4f 19.4 <0.0001 Prehospital 2.2f 1.5 21.1 f 19.3 <o.ooo1

NS = not significant.

sought; and a delay time, which comprised the interval between reaching a decision care should be sought and calling for hospital transportation,

Wait time extended from summoning transportation to leaving for a hospital and transportation time was the time between leaving for and arriving at a hospital.

Prehospital time comprised the total period between symptom onset and hospital arrival. Patients were divid- ed into early and late arrival subgroups based on pre- hospital time I or >6 hours, respectively. Some time periods did not apply or could not be determined in some patients. Prehospital time, however, was recorded for every patient.

Denial was scored as present if patients agreed with the statement, “I have not been afraid during this heart attack.” 4

Suppression was scored as present if patients agreed with the statement, “I tried not to think about my symptoms.” 4

Locus of control5 was measured as the sum of scores on 7 items, 4 of which dealt specifically with control of personal health (e.g., “most people cannot do much to influence their health”). Scores were determined using the following point scale: agree strongly = 1; agree somewhat = 2; disagree somewhat = 3; disagree strong- ly = 4. Possible scores ranged from 7 (maximum exter- nal locus of control) to 28 (maximum internal locus of control).

Depression was measured as the sum of scores on 4 items taken from the Zung self-rating depression scale.6

Possible scores ranged from 4 (least depressed) to 16 (most depressed). In a separate validation sample of nonhospitalized volunteers, the responses to these 4 items correlated well with the total 20-item Zung de- pression scale score (r, = 0.85, p = 0.0002).

Patency of the infarct artery was defined as when coronary angiography done within 12 hours of symptom onset showed grade 2 or 3 perfusion of the presumed infarct artery.7 Participation in the study did not affect the performance or timing of coronary angiography or other procedures. Patients were retrospectively consid- ered to be optimal lytic therapy candidates if they met the following criteria: pain 16 hours; age <80 years; Thrombolysis in Myocardial Infarction Trial electrocar- diographic criteria7; and absence of strong contraindica- tions3 to treatment. As this was not a study of thrombo- lytic therapy per se, no uniform prospective indications for lytic therapy existed.

AM1 complications were scored as present if the pa- tient developed congestive heart failure, post-AM1 angi- na, cardiogenic shock, or if he or she required a pace- maker, Swan-Ganz catheter or readmission to the coro- nary care unit.

Data analysis: Group frequencies were compared by chi-square test and group means were compared by Mann-Whitney tests. Spearman correlation coefficients were calculated for selected pairs of continuous vari- ables. Time of symptom onset was analyzed after angu- lar transformation of data.* The multivariable proce- dures that were performed were forward stepwise re- gression analysis of total prehospital time and logistic regression analysis of total prehospital time <6 or >6 hours. Mean values are expressed as f standard devi- ation. A p value <0.05 was considered statistically sig- nificant.

RESULTS Time pe&dar The frequency distributions of precall

and prehospital times are shown in Figure 1. The mean precall time was 5.1 f 11.1 hours (median 1.1, range 0 to 68.5) and the mean prehospital time was 5.9 f 11.0 hours (median 2.0, range 0.4 to 69.0). Precall time cor- related closely with total prehospital time (rs = 0.91, p

n preoall ths totalpreho@dtime

P” a

; ‘5

e n lo t s 5

<.25 .25-.5 S-1 1-1.5 1.5-Z 2-4 4-6 6-9 9-12 12-24 Z-24

hour6

FIGURE 1. Red and totd pmhospbl

1412 THE AMERICAN JOURNAL OF CARDfOLOGY VOLUME 65

<O.OOOl). In 100 (79%) patients, the prehospital time was 16 hours (early arrival group); in the remaining 26 (21%) patients, the prehospital time was >6 hours (late arrival group). Time periods for the early and late arriv- al groups are listed in Table I. The longer prehospital time in the late group was largely accounted for by much longer notification and decision periods, which together accounted for 90% of prehospital time in the late group compared to 54% in the early group (p = 0.0001). The delay, wait and transportation periods did not differ significantly between the 2 groups.

UnivariaW analysis of ear@ and late adval sub- groups: Further characteristics of the early and late ar- rival groups are listed in Table II. Female gender, low income, advanced age, slow symptom progression and history of hypertension were all significant univariate predictors of greater prehospital delay. Low intensity of initial symptoms was of borderline significance (p = 0.05). Women were almost twice as likely as men to report a history of hypertension (69 vs 35%, p = 0.001) and this probably accounts for the observed univariate association between hypertension and prehospital delay. Only 2 (6%) of the 31 patients with prior AM1 had previously received thrombolytic therapy; both were in the early arrival group (difference not significant).

Several time variables were analyzed, including the month, day and hour of symptom onset. These time variables, as well as weekend versus weekday onset of symptoms, did not differ significantly between the early and late groups.

In response to questions about the nature of patients’ initial symptoms, 22 (17%) denied chest “pain” or chest “discomfort” and 19 (15%) denied the presence of ini- tial pain in any body area. The frequency of the absence of these symptoms was similar in the early and late ar- rival groups. There were 34 (27%) patients who report- ed deciding “almost from the start” that their symp toms were “probably due to a heart attack,” but the proportion of patients reaching such a decision did not differ significantly between the early and late groups.

An attempt was made to contact a physician by 43 (34%) patients before hospital transport and late group patients were significantly more likely to make such an attempt (p = 0.002). Of these, 8 went to their doctor’s office before going to a hospital and 7 did so on their physician’s advice. The time spent in the physician’s of- fice averaged 45 f 22 minutes and ranged from 20 to 90 minutes.

Outcome data: Outcome data are listed in Table III. Aside from the expected greater use of thrombolytic therapy in patients who arrived within 6 hours of symp tom onset, no important differences in outcome vari- ables were demonstrated between early and late arrival groups. The location of infarction was inferior in 58 pa- tients (46%), anterior in 43 (34%), lateral in 6 (5%) and indeterminate in 19 (15%). Infarct location did not dif- fer significantly between the early and late groups.

All lytic therapy was given intravenously and con- sisted of either tissue-type plasminogen activator (39 of 47 patients, 83%) or streptokinase (8 of 47, 17%). In patients given lytic therapy, the mean time to drug ad- ministration was 3.7 f 2.3 hours after symptom onset

TABLE II Characteristics of Early and Late Arrival Groups

Early Group Late Group n=lfX n = 26 (%) p Value

Demographic M/F Age b-s) Married Income <$lO.OOO/yr Health insurance Rural area

History Angina AMI Coronary angiography Bypass surgery Diabetes mellitus Systemic hypertension Cigarette smoking Family history

Medical care Physician Cardiologist

Setting Alone At home At work Hour of onset

Symptoms Chest pain Intensity (1 to 3)* Progression (1 to 6)*

Response Self-treatment Called physician

Transport Ambulance Distance (1 to 3)*

Knowledge Lytic therapy (0 to 3)” Early treatment (0 to 2)* Risk factors (0 to 6).

Psychologic Denial Suppression Locus of control (7 to 28)” Depression score (4 to 16)*

82/18 12/14 0.001 56.4f 13 63.7 f 13 0.01 72 17(65) NS 42 17 (65) 0.03 87 23(88) NS 38 8(31) NS

18 5(19) NS 24 7(27) NS 20 6(23) NS

5 2 (8) NS 17 9(35) NS 38 17 (65) 0.01 83 16(62) NS 52 19 (73) 0.05

77 22(85) NS 26 lO(38) NS

21 7(27) NS 69 22(85) NS 12 2 (8) NS 605 f 3.6 hr 6:25 f 4 hr NS

67 14(54) NS 2.1 f0.8 1.7 f 0.9 0.05 2.4~ 1.1 3.8 f 1.9 0.002

53 27

42 2.4 f 0.6

0.9 f 0.9 1.8f0.5

4.2f 1.9

25 15 21.2 f 4.5

6.9 f 2.4

14(54) NS 16 (61) 0.002

9(35) NS 2.5 &0.7 NS

0.8f 1.1 NS 1.8f0.5 NS 4.2f1.8 NS

8(31) NS 5(19) NS

19.4f6.1 NS 7.3f3.0 NS

* Potential range of scores. AMI = acute myocardial infarction: Intensity = Initial intensity of symptoms (1 =

mild. 3 = severe); Medical care = current care by physician or cardiologist; NS = not signkant; Progression = speed of symptom progression (1 = rapid, 6 = slow); Setting = circumstances of symptom onset.

and 1.6 f 0.8 hours after hospital arrival. A nondiag- nostic electrocardiogram was cited as the reason for withholding lytic therapy in 27 of 54 (50%) early group patients who did not receive thrombolysis. “Prolonged’ prehospital time (4.2 f 0.8 hours) and advanced age (82.1 f 4.0 years) were cited as reasons for withholding treatment in 3 (6%) cases each and miscellaneous con- traindications were present in 11 (20%); several patients were felt to have >l contraindication to treatment. No apparent reason for withholding lytic therapy was pres- ent in 13 (24%) early group patients who did not receive lytic treatment. Of these, 12 (92%) were initially treat- ed at outside referring hospitals, 9 (69%) had anterior AM1 and only 1 lacked health insurance. The 1 patient in the late arrival group who received lytic therapy was a 39-year-old man who experienced a stuttering course of symptoms over a 15-hour-period before hospital ar- rival.

THE AMERICAN JOURNAL OF CARDIOLOGY JUNE 15. 1990 1413

TABLE III Outcome Data I

Early Group Late Group n=lOO n=26(%) p Value

ER pain ER systolic BP (mm Hg) ER CK (NJ/liter) Peak CK (If-f/liter) Q-wave infarct AMI complication Optimal lytic candidate Lytic therapy Lytic success CCU days Coronary angiography Acute PTCA Bypass surgery

91 20 (77) 145f30 139f24 119f353 540 f 641

2058 f 1994 119Of820 76 17 (65) 55 12w3) 61 0 46 l(4) 30/44 (68%) O/l

3.7 f 1.6 4.0 f 2.6 82 18 (69) 11 l(4) 18 l(4)

NS NS

0.01 0.03

NS NS <O.OOOl

NS NS NS NS NS

AMI = acute myocardial infarction; BP = blood pressure; CCU = coronary care unit; CK = creatine kinase; ER = emergency room; PTCA = coronary balloon angloplasty.

TABLE IV SteDwise Linear Regression Analysis

Dependent variable: total prehospital time I

Step Variable F B SEofB p Value

1 Progression 68.00 3.29 0.54 <o.Oca 2 Income 10.03 -1.88 0.77 0.016 3 Gender 2.72 -4.13 1.87 0.029 4 Age 3.57 0.08 0.03 0.027 5 Prior AMI 3.81 -2.58 1.32 0.053 Multiple R = 0.688 Multiple R-square = 0.474 F=19.83 DF=5,110 p<0.00001

AMI - acute myocardial infarction; B = sample partial regression coefficient; DF = degrees of freedom; F = variance ratio; R = regression coefficient: R-square = coefficient of determination; SE = standard error.

In this study, patients were interviewed 5.9 f 3.5 days after their AMI, generally after transfer from the coronary care unit, and those who died before being sur- veyed were excluded from analysis. Mortality was therefore low, with only 1 in-hospital death observed.

MultIvarIable analyeee: Results of forward stepwise regression analysis of total prehospital time are listed in Table IV. Slow symptom progression, low income, fe- male gender and advanced age were all independently predictive (p 10.02) of increased prehospital time. Ab sence of prior AM1 was of borderline additional signifi- cance (p = 0,053). Similarly, logistic regression analysis selected slow symptom progression, female gender and low income as significant (p 10.02) independent predic- tors of prehospital time >6 hours. The logistic regres- sion model containing these 3 variables had a sensitivity of 541, a specificity of 95% and a positive predictive value of 72% in identifying those who arrived >6 hours after symptom onset.

Pati8ntpercepaonoffactors contrhdng to pm- hospital de4ay: At the end of the survey, patients were asked to report the factors which they felt added to their delay in reaching a hospital; 92 (73%) cited Ll contributing factor. Among these, the most frequently listed were the perception that “symptoms did not seem serious” (33 of 126 patients, 26%) and similarity of the AM1 symptoms to past non-AM1 symptoms (32, 25%). The advice of friends or family was cited as a factor

contributing to delay by 23 (18%) and 7 (6%) reported that concern about the cost of treatment contributed to their delay.

DISCUSSION In this study, the strongest predictor of prehospital

time was the pattern of symptom progression. Patients whose symptoms rapidly worsened exhibited little delay seeking medical care and had the shortest prehospital times. Demographic factors were also important with low income, female gender and advanced age all corre- lating with increased prehospital time. Prior AM1 was a significant univariate predictor of (short) prehospital time and was of borderline significance in the linear re- gression analysis. The majority of total prehospital time was accounted for by the period between symptom on- set and reaching a decision to seek medical care. Even in this largely rural population, the time spent being transported to a hospital was a relatively small fraction of total prehospital time.

Most previous studies of the prehospital phase of AM1 antedate the widespread use of thrombolytic ther- apy.9-r6 Many of these have included a mixture of pa- tients with and without confirmed infarctions and have generally evaluated a limited number of potentially im- portant variables. The pattern of symptom progression was examined only in the study by Alonzo,17 in which rapid symptom progression was identified as the vari- able most strongly associated with a short phase of self- evaluation of symptoms. Demographic variables have not been found to predict prehospital delay in most pri- or studies. Cooper et alI8 evaluated prehospital delay in 111 black patients treated for AM1 at Cook County Hospital in Chicago and observed a mean prehospital time of approximately 23 hours, which is considerably longer than in any other published study. While most of these late-arriving patients were poor enough to qualify for Medicaid (J. Ferlinz, MD, personal communication, October 1989), the association between income and pre- hospital delay was not directly examined.

Previous studies of prehospital delay have generally concluded with calls for further public education re garding the symptoms of AM1 and the urgency of prompt medical evaluation. The results of this study may help direct future education to patient groups iden- tified as currently being at particularly high risk for ex- cessive prehospital delay. Two studies of broad educa- tional campaigns have in fact shown that intense public education efforts can produce at least a short-term decrease in prehospital time among patients with AMI.19v20 The possible utility of a campaign directed specifcally at groups identified as being at high risk for delay has not been examined.

The need for further physician education is support- ed by the observation that many early arrival patients who were retrospectively judged to have been good lytic therapy candidates were either not treated or were treated relatively late after hospital arrival. Other inves- tigators have reported a similar degree of undertreat- ment21 and it is likely that this is a general problem not confined to unique geographic circumstances.

1414 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 65

This study represents findings from 1 rurally based medical center and the results may not be applicable to other regions with markedly different patient popula- tions. Further work is needed to better define the im- pact of local conditions on prehospital delay. We did not observe any significant differences in patient character- istics or prehospital times between those who were brought directly to the university hospital and those ini- tially treated at outlying community hospitals. It is also possible that our results have been affected by the ex- clusion of patients who died before being interviewed. Available chart data indicate that AM1 patients who were admitted but died before being interviewed were generally similar to those who were surveyed, except for a higher proportion of women in the former group.

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