Changing Features of Anginal Pain After PTCA Suggest a Stenosis on a Different Artery Rather Than Restenosis
Background We recently found that patients who had had two myocardial infarctions in different myocardial regions frequently reported different locations of infarct pain, whereas patients who had had two infarcts at the same site had a similar distribution of pain. The aim of this study was to assess whether a different location of anginal pain may help identify patients with a new stenosis on an artery perfusing another myocardial region as opposed to those with restenosis after coronary angioplasty (PTCA).
Methods and Results We studied 38 patients (59±11 years old) who underwent PTCA for single-vessel disease, with recurrence of symptoms requiring repeat coronary angiography during a 3-year follow-up. According to our inclusion criteria, angiography showed either a significant restenosis of the dilated lesion, with no evidence of lesions in the other vessels (n=26), or a new stenosis in either of the other coronary arteries, with no restenosis in the dilated vessel (n=12). Before each procedure, patients reported the location and radiation of anginal pain. There was no relation between location of pain and site of the coronary stenosis. However, none of the patients with restenosis reported a different location of pain after angioplasty, compared with 5 patients with new stenosis (0% versus 42%, P=.002). Radiation of pain involved different areas of the body in 1 patient with restenosis and in 6 with new stenosis (4% versus 50%, P=.002). Overall, location or radiation of pain in a different body area had a specificity of 96% and a sensitivity of 58% in detecting a stenosis on a new artery.
Conclusions A different location of anginal pain may distinguish patients with a new coronary stenosis from those with restenosis after PTCA for single-vessel disease. These findings suggest that in individual patients, differences in the location of cardiac pain may be indicative of the occurrence of ischemia in different myocardial regions.
Although angina pectoris is the most characteristic symptom of ischemic heart disease, it can provide rather limited information about the specific features of myocardial ischemia.1 In particular, several clinical studies have shown no clear relation between the somatic location of anginal pain and the site of myocardial ischemia.2,3 In a recent study, however, we found that patients who had had two myocardial infarctions in different myocardial regions (anterior versus inferior) often reported different locations of infarct pain.3 Moreover, intracoronary infusion of adenosine into the right or left coronary arteries caused pain in different locations in 28% of patients.4 These findings indicate that, at least in some patients, painful stimuli arising from different myocardial regions may induce somatic pain referred to different areas of the body, yet the possible clinical application of these observations is still unclear. We reasoned that a change in the location of pain may help distinguish patients with a new stenosis in a different artery from those with restenosis after percutaneous coronary angioplasty (PTCA).
We included in the study only patients who had undergone successful coronary angioplasty (residual diameter stenosis <30%) for single-vessel disease with no lesions in other coronary vessels (diameter stenosis <30%) and who experienced a recurrence of symptoms requiring repeat angiography between 1 and 48 months after revascularization. Furthermore, repeat angiography was required to show either a significant restenosis of the dilated lesion (diameter stenosis >70%), with no evidence of lesions in the other vessels (maximal diameter stenosis <30%), or a significant stenosis (diameter stenosis >70%) in either of the other main coronary arteries, with no evidence of restenosis in the dilated vessel (diameter stenosis <30%).
The study group comprised 38 consecutive patients who had undergone PTCA between January 1994 and January 1995 (31 men and 7 women 41 to 75 years old; mean, 59±11 years).
All patients undergoing PTCA for single-vessel disease were asked to report the location and the radiation of chest pain experienced during episodes of angina pectoris. Patients readmitted to hospital for a recurrence of symptoms after PTCA had to report the location and the radiation of chest pain occurring during new episodes of angina pectoris. The location and the radiation of pain were classified according to the following areas of the body: (1) left hemithorax and/or left shoulder; (2) left arm, forearm, and/or hand; (3) right hemithorax and/or right shoulder; (4) right arm, forearm, and/or hand; (5) retrosternal region; (6) epigastric region; and (7) neck (above the clavicles). Pain location was defined as the site of maximal pain intensity and, by definition, may involve only one body area, whereas pain radiation may involve one or more area(s).
Arteriography was performed by the Judkins technique. Coronary stenoses were assessed by two expert observers blinded to the clinical data using the Computerized Cardiovascular Angiography Analysis System.
Continuous variables between groups were compared by unpaired t test. Differences in discrete variables were analyzed by Fisher’s exact test. All data are expressed as mean±SD. A value of P<.05 was considered significant.
A total of 27 patients underwent PTCA on the left anterior descending coronary artery (LAD), 7 on the left circumflex artery, and the remaining 4 on the right coronary artery. A total of 26 patients (21 men, 60±11 years old) developed restenosis of the dilated lesion (restenosis group), and the remaining 12 (10 men, 57±10 years old) developed new stenoses on different vessels (new stenosis group). The main clinical features of these two groups of patients are summarized in Table 1⇓. In the new stenosis group, 10 patients had undergone PTCA on the LAD (repeat angiography revealed new significant stenosis in the right coronary artery in 5 patients, new stenosis in the circumflex in 2, and new stenoses in both right and circumflex arteries in the remaining 3 patients), 1 on the circumflex, and 1 on the right coronary artery (both these patients had a new stenosis in the LAD at repeat angiography).
Location of Pain
Pain locations before PTCA are summarized in Table 2⇓. The location of pain was similar in patients with stenosis of the LAD compared with those with stenosis of the circumflex or right coronary artery (see Table 2⇓). During follow-up, none of the 26 patients with restenosis reported a different location of pain when symptoms recurred, whereas 5 of 12 patients with a new stenosis did report a different location of pain (0% versus 42%, P=.002). Detailed clinical and angiographic features of these patients are reported in Table 3⇓.
Radiation of Pain
Before PTCA, 15 patients reported pain radiation in the retrosternal region, 10 in the left arm, 5 in the right arm, 17 in the left hemithorax, 3 in the right hemithorax, 8 in the supraclavicular region, and 3 in the epigastrium. Pain radiation was similar in patients with stenosis of the LAD and in those with stenosis of the circumflex or of the right coronary artery (data not shown). During follow-up, only 1 of 26 patients with restenosis reported a different radiation of anginal pain, compared with 6 of 12 patients with a new stenosis (4% versus 50%, P=.002). Overall, a different location or radiation of pain was reported by 1 of 26 patients with restenosis and 7 of 12 patients with new stenosis (4% versus 58%, P=.0004). A different location or radiation of pain could predict a new stenosis in a different vessel with a sensitivity of 58% and a specificity of 96%, with a positive predictive value of 87%.
The present study demonstrated that after PTCA for single-vessel disease, patients with restenosis usually had the same location and radiation of anginal pain, whereas the location and the radiation of pain often changed in patients with a new stenosis in a different vessel.
Several clinical studies have shown that angina pectoris is mediated by release of algogenic substances (in particular adenosine) from ischemic myocardium.1,5,6 Although specific pain receptors have not been identified in the myocardium,7 stimulation of polymodal receptors on cardiac afferent nervous fibers causes painful stimuli that reach the dorsal horn neurons of the spinal cord. Transmission and processing of pain inputs imply a large convergence of both visceral and somatic inputs on the same neurons, and this is the anatomic reason for the somatic localizations of cardiac pain. However, the peripheral pathways of cardiac pain stimuli are not completely understood. Although sympathetic afferents have a central role in the transmission of cardiac pain,7 vagal afferents may also be involved.8 Indeed, the pattern of distribution of sympathetic nervous fibers, which parallels the main coronary branches, and the greater number of vagal afferents in the inferoposterior cardiac wall9 suggest that painful stimuli arising from different myocardial regions may stimulate different nervous fibers, thus causing different locations of somatic pain. Conversely, the convergence on the same neurons of nociceptive inputs from different myocardial regions blurs the relation between the site of ischemia and the location of cardiac pain. A previous study including a large number of patients has reported, on average, an association between the site of coronary occlusion and the location of pain during PTCA2 so weak that it could not be useful in the clinical setting. In a recent study including 104 patients with acute myocardial infarction, we found that patients with either anterior or inferior infarction had a remarkably similar distribution of cardiac pain.3 Yet, the lack of a clear relation between the site of myocardial ischemia and pain location in a group of patients does not imply that such a relation cannot be valuable in individual patients. In old studies of surgical sympathetic ganglionectomy for relief of angina, some patients reported a migration of pain after transection of sympathetic afferents, suggesting that stimulation of different nervous afferents may induce pain in different somatic regions.10 More recently, we found that infusion of adenosine, a mediator of anginal pain, into the right and left coronary arteries can elicit pain in different somatic regions in 28% of patients.4 These results were confirmed in a group of 32 patients with a history of having suffered two myocardial infarctions: ≈67% of patients with two infarctions in different myocardial regions (anterior versus inferior) reported pain in different areas of the body, compared with none of the patients with two infarcts in the same region.3 These findings led us to hypothesize that, in individual patients, the different location of anginal pain is due to ischemia involving different myocardial regions caused by multivessel disease.
The present study showed that a different location of anginal pain was a highly specific sign of a new stenosis in a different vessel after PTCA. To the best of our knowledge, this is the first study to have found that simple clinical features may help distinguish patients with a new stenosis from those with restenosis after PTCA, an issue often requiring imaging stress tests or even coronary angiography. It is not clear why the stimulation of cardiac nerves in different myocardial regions causes pain in different areas of the body only in some patients, and it probably depends on a variable rate of convergence of afferent cardiac stimuli. However, the percentage of patients reporting different locations of pain during stimulation of different myocardial regions seems to be related to the intensity of the algogenic stimulus, because only 28% of patients reported a different location of pain during infusion of adenosine,4 42% did so in the present study when pain was caused by transient myocardial ischemia occurring during daily life, and 67% did so when pain was caused by Q-wave myocardial infarction.3
In conclusion, our study demonstrates that a change of the features of anginal pain has important clinical implications and helps identify patients with new stenoses on different vessels from those with restenosis after coronary angioplasty. These results further confirm that, at least in a subgroup of patients, nociceptive stimuli arising from different myocardial regions are associated with somatic pain in different areas of the body, suggesting that transmission of pain inputs involves different pathways.
- Received June 17, 1997.
- Revision received September 17, 1997.
- Accepted September 23, 1997.
- Copyright © 1997 by American Heart Association
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Sylven C, Beerman B, Jonzon B, Brandt R. Angina pectoris-like pain provoked by intravenous adenosine. BMJ. 1986;293:227–230.
Crea F, Pupita G, Galas AR, El-Tamini H, Kaski JC, Davies G, Maseri A. Role of adenosine in pathogenesis of anginal pain. Circulation. 1990;81:164–172.
Malliani A. Cardiovascular sympathetic afferent fibers. Rev Physiol Biochem Pharmacol. 1982;94:11–74.