Correlation between symptomatology and site of acute myocardial infarction

International Journal of Cardiology 77 (2001) 163–168 www.elsevier.com / locate / ijcard

Correlation between symptomatology and site of acute myocardial infarction ˇ ´ a , *, Dinko Miric´ b , Davor Eterovic´ c Viktor Culic b

a Emergency Medical Services Center, Split, Croatia Medical School in Split; Department of Medicine, Clinical Hospital Split, Split, Croatia c Department of Biophysics, Medical School in Split, Split, Croatia

Received 21 February 2000; received in revised form 25 September 2000; accepted 29 September 2000

Abstract Objective: We determined the occurrence of presenting symptoms in patients with different sites of acute myocardial infarction after controlling for age and conventional risk factors. Methods: Hospital-based study of patients hospitalized because of first anterior (n5731), inferior (n5719) and lateral (n596) infarction in Clinical Hospital Split between 1990 and 1994. Data form about presenting symptoms and clinical profile was completed for each patient. Results: Anterior infarctions were more often presented by headache (adjusted odds ratio (OR)51.67, 95%CI51.06–2.62), weakness (OR51.60, 95%CI51.31–1.96), dyspnea (OR51.40, 95%CI51.14–1.72), cough (OR52.24, 95%CI51.59–3.16), vertigo (OR52.04, 95%CI51.40–2.99) and tinnitus (OR52.09, 95%CI51.06–4.14). Inferior infarctions were more often associated with epigastric (OR51.71, 95%CI51.30–2.24), neck (OR51.47, 95%CI51.10–1.98) and jaw pain (OR52.16, 95%CI51.42–3.27), sweating (OR51.56, 95%CI51.27–1.92), nausea (OR52.01, 95%CI5l.64–2.46), vomiting (OR51.55, 95%CI51.22–1.97), belching (OR51.57, 95%CI51.21–2.03) and hiccups (OR52.88, 95%CI51.53–5.42). Patients with lateral infarctions were more likely to complain of left arm (OR51.80, 95%CI51.07–3.05), left shoulder (OR51.82, 95%CI51.19–2.79) and back pain (OR52.40, 95%CI51.28–4.46). Pain was less frequently reported by hypercholesterolemic (P5l.4310 27 ), patients over 70 years (P50.002), women (P50.0007) and those with non-triggered infarction (P50.0009), whereas those over 70 (P51.7310 26 ) and men (P50.0003) were less likely to report other relevant symptoms. Conclusions: Our study suggests a linkage between different infarction sites and specific groups of symptoms. Furthermore, coronary patients should give their full attention to non-specific symptoms and any kind of discomfort.  2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Myocardial infarction; Site; Referred pain; Symptoms

1. Introduction A large number of patients with acute myocardial infarction die before reaching hospital. First and the most important point in giving the adequate care is early recognition of symptoms and diagnostic evalua-

*Corresponding author. Tel.: 1385-21-525-220; fax: 1385-21-382601.

tion of this disorder. Furthermore, it may be useful to, upon the presence of individual or multiple symptoms, presume which myocardial region is damaged. Previous studies have observed particular clinical features of different sites of myocardial infarction [1–11]. Only few studies have investigated symptoms of anterior and inferior infarctions providing limited and conflicting data [12–14], and none to date has investigated symptoms of lateral infarctions. In this study we analyzed the relationship between present-

0167-5273 / 01 / $ – see front matter  2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 00 )00414-9

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ˇ ´ et al. / International Journal of Cardiology 77 (2001) 163 – 168 V. Culic

ing symptoms and electrocardiographic site of myocardial infarction.

2. Materials and methods Our investigation of circumstances preceding the onset of myocardial infarction enrolled patients admitted to the coronary care unit of Clinical Hospital Split between January 1990 and December 1994. It was designed to examine the incidence of possible triggers, circadian rhythm [15] and symptom presentation according to electrocardiographic site of infarction. The protocol was approved by the Hospital Ethical Committee, and informed consent was obtained from each patient. For inclusion, patients were required to meet the following criteria: electrocardiographic changes suggestive of an evolving infarction according to the Minnesota coding system [16], pain typical of myocardial ishemia and increase in level of at least one of the cardiac enzymes (creatine kinase–MB fraction, aspartate aminotransferase, lactate dehydrogenase) to more than twice the upper limit of normal. The infarctions were categorized as anterior (pathologic Q waves present in V1 – V4 ), inferior (inferior: Q in D 2 , D 3 , aVF; inferoposterior: Q in D 2 , D 3 , aVF and R in V1 and V2 ) and lateral (Q in V5 , V6 , D 1 and aVL) [17]. Three-hundred and seventy-seven patients were excluded from the study because of second, anterior extended, non-Q or electrocardiographic uncategorised infarction, bundle branch block and unobtainable or unreliable anamnestic data. An extensive data form about presenting symptoms and clinical profile (age, gender, smoking, hypertension and hypercholesterolemia) was completed for each patient during hospitalization. Symptoms were classified into the two main groups: (1) pain at the different body areas (chest, left and right arm, left and right shoulder, epigastrium, neck, back, jaw and other), (2) other symptoms (sweating, weakness, nausea, dyspnea, vomiting, belching, cough, vertigo, faintness and other). The patients were also asked to report the location of first pain sensation. Univariate x 2 analyses were run to evaluate the presence of pain and other symptoms in relation to age, gender, smoking, hypertension, hypercholesterolemia and existence of possible external trigger of

myocardial infarction. Since it has been observed that age and conventional risk factors influenced on symptom presentation [18,19], we estimated the occurence of individual symptoms as well as symptom clusters in patients with different infarction site after controlling for age, smoking, hypertension and hypercholesterolemia. On the basis of previous analysis, symptom clusters were defined as a combination of the original symptoms that are likely to be associated. When testing the occurence of both individual symptoms and symptom clusters for x site, other two sites comprised non-x group (inferior1 lateral5non-anterior, and so forth). The adjusted odds ratios were obtained from regression coefficients of the unconditional logistic regression. All statistical analysis was performed using version 8.0 of the SPSS package (SPSS Inc., Chicago, IL, USA).

3. Results The present study enrolled 1546 patients; 731 with anterior, 719 with inferior and 96 with lateral infarction. The detailed anthropometric and clinical data of the study population have been published previously [15]. Briefly, the patients with anterior infarctions had greater mean body weight, required more morphine, were more frequently decompensated and hypercholesterolemic and had higher hospital mortality. The patients with inferior infarctions were younger and more frequently smokers, and those with lateral infarctions were more often hypertensive. Pain was less frequently present in hypercholesterolemic, those over 70 years, women and those with possible trigger as a precipitator of infarction onset. Patients over 70 and men were less likely to report other relevant symptoms (Table 1). Table 2 shows occurence of individual symptoms in all patients and in subgroups according to site of myocardial infarction. Anterior infarctions were more often associated with headache, weakness, dyspnea, cough, vertigo and tinnitus, whereas inferior infarctions were more often presented by epigastric, neck and jaw pain, sweating, nausea, vomiting, belching and hiccups. As a curiosity, two patients with inferior infarction reported occurence of scrotal pain during the onset. Left arm, left shoulder and back pain were more likely to be signs of lateral infarctions.

ˇ ´ et al. / International Journal of Cardiology 77 (2001) 163 – 168 V. Culic Table 1 Clinical profile and presence of symptoms of acute myocardial infarction Pain

Other symptoms

Age #50 years 50–70 years $70 years x 2 P value

96.4% 92.8% 89% 0.002

87% 91.7% 82.2% 1.7310 26

Gender Male Female x 2 P value

92.9% 87.5% 0.0007

85.1% 90.8% 0.003

Smoking Yes No x 2 P value

92.7% 90.2% NS

88.3% 85.2% NS

Hypertension Yes No x 2 P value

92.1% 91.1% NS

86.1% 86.9% NS

Hypercholesterolemia Yes No x 2 P value

85.6% 93.8% 1.4310 27

85.4% 87.2% NS

Triggered infarction Yes No x 2 P value

94.2% 89.2% 0.0009

87.1% 86.3% NS

NS: not significant.

Body areas of the first pain sensation in patients with inferior infarctions more frequently were epigastrium, neck and jaw, and less frequently chest and left arm. In patients with lateral infarctions, pain was more likely to start at arms, left shoulder and back (Table 3). Cluster analysis revealed large number of aggregated symptoms constellations, and those specific for particular infarction site are shown in Table 4.

4. Discussion Differences in clinical course and prognosis between patients with different infarction sites have been documented [1–11,15]. Anterior infarctions are more often associated with significant left ventricular dysfunction: greater decrease in left ventricular ejection fraction, aneurysm formation, cardiac thrombosis

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or rupture, ventricular tachycardia and fibrillation, left ventricular failure, cardiogenic shock, asystole and higher hospital mortality. Inferior infarctions more often occur in smokers under 45 years and lateral infarctions are usually smaller. We have shown [15] that infarctions of the different sites might also differ in typical external triggers. Appearance of pain in particular body areas is a result of the convergence of visceral and somatic afferents on the same neurons in the central nervous system [20]. Both afferent sympathetic and vagal fibers can transmit cardiac pain after stimulation by myocardial ishemia [21–24]. Sympathetic fibers follow coronary tree and terminate in the anterolateral cardiac wall, whereas vagal afferent fibers are mainly located in the inferoposterior wall region and may be involved in the mechanism for referred pain to the neck or jaw [25–27]. Stimulation of vagal fibers by ishemia can also cause gastric dilatation, which could account for higher frequency of epigastric pain in patients with inferior infarction [28]. Lichstein and coworkers [29] have reported location of pain in relation to the site of coronary occlusion during balloon angioplasty. Left chest pain was less likely to be a sign of right coronary artery occlusion, and epigastric pain radiating to the neck or jaw less likely to be present in left anterior descending coronary artery occlusion. They have not found any pattern of pain location in left circumflex artery occlusion, probably because of its various anatomic distribution. Two smaller studies have found [13,14] non-significant differences in distribution of cardiac pain between patients with anterior and inferior infarctions. Our patients with anterior infarctions tended to report more multiple symptoms involving chest, shoulder and arm pain. While no previous data were available about symptoms of lateral infarctions, our patients with lateral infarctions were more likely to complain of left arm, left shoulder and back pain, and clusters of these symptoms and chest pain. On the other side, probably vagally referred epigastric, neck and jaw pain were more often symptoms of inferior infarction. All these results agree with observed distribution of sympathetic and vagal fibers in the cardiac wall, as discussed above. We first observed headache, vertigo and tinnitus to be more frequent symptoms of anterior infarctions.

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Table 2 Presenting symptoms of acute myocardial infarction a A n5731 (%)

I n5719 (%)

L n596 (%)

Pain location Chest Left arm Right arm Left shoulder Right shoulder Epigastric Neck Back Jaw Headache

89.1 72.4 53.4 49.7 37.8 13.3 9.2 7.5 2.7 7.3

84.1 68.7 51.3 45.1 36.4 21.7 17.9 4 8.3 3.5

Other symptoms Sweating Weakness Nausea Dyspnea Vomiting Belching Cough Vertigo Faintness Hiccups Tinnitus

54.6 58.3 42.2 41.9 19.3 15.2 14.9 11.1 6.2 1.1 4.2

66.6 46.7 59.2 34.4 27.8 22.8 6.3 4.7 4.9 5.3 0.7

Odds ratio (95%CI)*

All n51546 (%)

A / non-A

I / non-I

L / non-L

95.8 82.3 49 68.8 32.3 4.2 8.3 18.8 3.1 3.1

1.14 (0.84–1.54) 1.06 (0.85–1.33) 1.07 (0.88–1.31) 1.04 (0.85–1.27) 1.11 (0.90–1.36) 0.70 (0.54–0.92) 0.77 (0.57–1.04) 0.99 (0.66–1.48) 0.53 (0.35–0.81) 1.67 (1.06–2.62)

0.76 (0.56–1.02) 0.83 (0.67–1.04) 0.95 (0.78–1.16) 0.84 (0.68–1.02) 0.93 (0.75–1.14) 1.71 (1.30–2.24) 1.47 (1.10–1.98) 0.76 (0.51–1.14) 2.16 (1.42–3.27) 0.66 (0.42–1.05)

2.29 (0.99–5.30) 1.80 (1.07–3.05) 0.91 (0.60–1.38) 1.82 (1.19–2.79) 0.89 (0.58–1.38) 0.32 (0.14–0.74) 0.50 (0.23–1.10) 2.40 (1.28–4.46) 0.44 (0.14–1.40) 0.57 (0.18–1.83)

87.2 71.3 52.1 48.7 36.8 16.6 13.2 6.6 5.4 5.2

51 38.5 27.1 29.2 16.7 9.4 3.1 8.3 4.2 2.1 1

0.69 (0.56–0.85) 1.60 (1.31–1.96) 0.60 (0.49–0.74) 1.40 (1.14–1.72) 0.69 (0.55–0.88) 0.73 (0.56–0.94) 2.24 (1.59–3.16) 2.04 (1.40–2.99) 1.12 (0.69–1.83) 0.36 (0.19–0.70) 2.09 (1.06–4.14)

1.56 (1.27–1.92) 0.70 (0.58–0.86) 2.01 (1.64–2.46) 0.79 (0.64–0.97) 1.55 (1.22–1.97) 1.57 (1.21–2.03) 0.54 (0.38–0.76) 0.51 (0.34–0.75) 0.90 (0.58–1.40) 2.88 (1.53–5.42) 0.48 (0.23–0.98)

0.62 (0.41–0.94) 0.59 (0.39–0.90) 0.43 (0.27–0.67) 0.63 (0.40–0.99) 0.70 (0.41–1.20) 0.50 (0.26–0.97) 0.27 (0.08–0.87) 0.76 (0.33–1.77) 0.95 (0.38–2.41) 0.65 (0.16–2.72) 0.86 (0.20–3.63)

60 51.7 49.2 37.6 23.1 18.4 10.2 8 5.3 3.1 2.4

a A5anterior; I5inferior; L5lateral. * Adjusted for age, smoking, hypertension and hypercholesterolemia.

This could be due to pain transmission via cardiac sympathetic fibers, which are mainly located in anterior cardiac wall and supplied by cervical and thoracic ganglia, since fibers from these ganglia also

supply cerebrovasculature, eye and face structures [30]. Whatsoever, it is to be noted that these symptoms occurred only in 2–8% of all patients. The greater percent of dyspnea and cough in our

Table 3 Primary pain locations in acute myocardial infarction a A (%) Pain location Chest Left arm Right arm Left shoulder Right shoulder Epigastric Neck Back Jaw Headache a

78.8 47.7 30.1 26.3 11.6 8.3 5.6 6.6 1.1 4.5

I (%)

60.2 41.2 28.8 21.1 9.6 19.9 11.8 3.6 6.3 2.4

L (%)

83.3 64.6 41.7 43.8 14.6 2.1 4.2 9.4 2.1 2.1

Odds ratio (95%CI)*

All (%)

A / non-A

I / non-I

L / non-L

1.79 (1.43–2.24) 1.15 (0.94–1.41) 0.97 (0.78–1.20) 1.11 (0.88–1.40) 1.10 (0.80–1.52) 0.47 (0.34–0.64) 0.63 (0.43–0.91) 1.15 (0.74–1.79) 0.49 (0.27–0.87) 1.21 (0.70–2.11)

0.43 (034–0.53) 0.75 (0.61–0.91) 0.92 (0.74–1.14) 0.79 (0.63–1.02) 0.87 (0.63–1.20) 2.46 (1.81–3.35) 2.02 (1.39–2.92) 0.67 (0.43–1.06) 2.66 (1.49–4.75) 0.71 (0.40–1.25)

1.75 (1.05–2.93) 2.07 (1.35–3.17) 1.63 (1.07–2.49) 2.39 (1.57–3.64) 1.31 (0.71–2.40) 0.20 (0.06–0.63) 0.58 (0.23–1.46) 2.19 (1.09–4.40) 0.87 (0.27–2.83) 0.92 (0.28–3.02)

A5anterior; I5inferior; L5lateral. * Adjusted for age, smoking, hypertension and hypercholestrolemia.

70.4 45.7 30.2 25 10.9 13.3 8.4 5.4 3.6 3.4

ˇ ´ et al. / International Journal of Cardiology 77 (2001) 163 – 168 V. Culic Table 4 Symptom clusters associated with different sites of acute myocardial infarction

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should give their attention to any kind of discomfort, even in the absence of typical and dramatic pain.

Odds ratio (95%CI)* Anterior Chest pain and headache Chest pain and dyspnea Chest pain and cough Chest pain and vertigo Shoulder and arm pain

1.99 2.48 3.75 2.51 1.52

(1.07–3.71) (2.01–3.05) (2.27–6.20) (1.62–3.89) (1.21–1.90)

Inferior Epigastric and arm pain Epigastric pain and sweating Jaw and neck pain Sweating and nausea

1.54 1.89 5.55 1.84

(1.16–2.05) (1.42–2.54) (3.20–9.65) (1.49–2.28)

Lateral Chest and left shoulder pain Chest and back pain Left shoulder and left arm pain

1.62 (1.0 1–2.60) 3.38 (1.89–6.05) 2.32 (1.37–3.90)

* Adjusted for age, smoking, hypertension and hypercholesteroemia.

patients with anterior infarctions may be related to more significant dysfunction of left ventricle [1–4,6]. Previous smaller studies have not produced consistent relations between gastrointestinal symptoms and inferior infarctions [12,13,31]. Our patients with inferior infarctions were more likely to experience belching, nausea and vomiting. Since we have previously reported association of overeating and triggering of inferior infarctions [15], it is tempting to hypothesize that vagus nerve is a two-way street for excitation between stomach and inferoposterior cardiac wall. This study corroborates one previous observation [13] that hiccups are more often associated with inferior infarctions. It could be a consequence of phrenic nerve stimulation, which run near the inferior wall region. We found sweating to be more often present in patients with inferior infarction, especially clustered with nausea, a sign of vagus nerve stimulation, which was not observed previously [13]. In conclusion, the present study suggests a linkage between different sites of infarction and particular individual or multiple symptoms. Although these symptoms are relatively specific, they are not very sensitive. Whatsoever, this study indicates that coronary patients, particularly elderly, hypercholesterolemic, more sedentary persons and women,

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