First, there are no formal studies of the cost-effectiveness of risk stratification after infarction, and in their absence it is not warranted to extrapolate from the effectiveness and cost of individual tests to a statement on cost-effectiveness. To do so ignores induced costs (for instance when an abnormal exercise ECG leads to angiography without subsequent intervention), it ignores the relatively high failure rate of the exercise ECG after infarction (submaximal exercise, abnormal resting ECG, etc), and it ignores the need for further investigation in the chronic phase (such as myocardial perfusion imaging if this has not already been performed). For the diagnosis of coronary artery disease, there is now powerful evidence to indicate that strategies that include myocardial perfusion imaging are more cost effective than those that do not.[3][4] Because diagnosis involves the detection of ischaemia and because persistent ischaemia after infarction is a key factor in prognosis, it is likely that formal studies of cost effectiveness of risk stratification would provide similar results.

Second, although the positive predictive value of any form of pre-discharge non-invasive testing is low,[2] Dr Timmis ignores the superior positive predictive value of perfusion imaging compared with the exercise ECG in patients who have not received thrombolysis (13% versus 9% for death and 24% versus 18% for death or reinfarction). Since the distinction between patients who have and who have not received thrombolysis is mainly the size of their infarcts, it seems to us that a test that is capable of assessing infarct size and prognosis in those with large infarcts should not be cast aside so easily. Shaw and colleagues[2] also emphasised the relatively poor quality of the studies available. For instance, three quarters of the studies were retrospective and one third reported fewer than 5 deaths, and they recognised the need for further studies to provide more reliable information. Further high quality studies are now available and we believe that the weight of evidence is that perfusion imaging is more effective than the exercise ECG for risk stratification after myocardial infarction.

Numerous studies have shown that inducible perfusion abnormalities are more common than ST segment changes on the exercise ECG.[5][6][7] This extends observations from the era before thrombolysis when an inducible thallium defect was shown to be better than the exercise ECG for detecting and localising ischaemia and for identifying multi-vessel disease. However, because thrombolysis has reduced the event rate after infarction, there are those who argue that the event rate is now so low that myocardial perfusion imaging is less valuable after infarction than it was.[5] [8] However these studies included a relatively low risk group with younger patients, preserved left ventricular function, and a low prevalence of multi-vessel disease. The higher risk patients were excluded because they mainly went straight to angiography and revascularisation and it is precisely these who would have been best identified by myocardial perfusion imaging if doubt remained after clinical assessment. In addition, selection bias was operating against perfusion imaging because when it was performed the results were used to guide intervention and hence to exclude the patient from follow-up. It is not surprising that non-invasive testing was not found to be valuable in the few remaining low risk patients.

In better designed studies there is now ample evidence that perfusion imaging is a valuable tool for risk stratification after infarction. Dakik and colleagues[7] reported that a predischarge exercise myocardial perfusion scan in patients who had received thombolysis provided incremental prognostic information over and above clinical and ejection fraction data. In contrast, none of the variables from the exercise ECG contributed to the assessment of prognosis. Similarly, Travin and colleagues[9] found that myocardial perfusion imaging within 14 days of infarction frequently revealed residual ischaemia and was better than clinical and exercise ECG variables in identifying patients at high risk. More recently, Brown and colleagues[10] reported a multi-centre trial in patients with first acute infarction. Three hundred and thirty nine patients were randomised to early (2 to 4 days) dipyridamole myocardial perfusion imaging followed by predischarge (6 to 12 days) sub-maximal exercise imaging, and 112 patients were randomised to submaximal predischarge imaging alone. The findings of the early perfusion study were not available to the responsible physicians and hence patient management was not affected. Early dipyridamole imaging was safe and was predictive of both in-hospital and late cardiac events, and it was a stronger predictor than predischarge submaximal exercise ECG or submaximal exercise perfusion imaging. This prognostic value was independent of thrombolytic status.

Third, with regard to the influence of left ventricular function on prognostic power, Mahmarian and colleagues[11] compared adenosine perfusion imaging and ejection fraction after infarction and found them to have complementary roles. They found that even patients with an ejection fraction greater than 40% were further stratified into low and high risk groups by the extent of the inducible perfusion defect. This study and the guidelines of the American College of Physicians[12] contradict Dr Timmis's recommendation that further risk stratification is not required in asymptomatic patients with an ejection fraction greater than 40%. Indeed, the ACP guidelines suggest that these are the patients in whom non-invasive risk stratification is most successful.

With the growing pressure to reduce costs but maintain quality of care, accurate risk stratification at an early stage using myocardial perfusion imaging with vasodilator stress in all but the highest risk patients could have important benefits. Low risk patients could be discharged earlier than those at a higher risk and in-hospital cardiac events might be prevented. Because of the complementary role of perfusion and functional information, it is conceivable that combined assessment of both using gated SPECT could be highly effective in routine use, particularly since left ventricular end systolic volume appears to be more powerful in prognostic terms than ejection fraction alone.

In summary, we believe that there is sufficient evidence to modify Dr Timmis's algorithm to require early myocardial perfusion imaging rather than exercise ECG in all but the highest risk patients assessed by clinical criteria, and to include patients with relatively preserved LVEF in this strategy. We predict that such an approach will be cost-effective.

S Richard Underwood, MD, FRCP, FRCR, FESC
Imperial College School of Medicine
Royal Brompton Hospital
Sydney St, London SW3 6NP

Constantinos Anagnostopoulos MD, PhD
Royal Brompton Hospital
Sydney St, London SW3 6NP

Leslee J Shaw PhD
Emory University School of Medicine
1518 Clifton Road NE, Rm638
Atlanta, Georgia 30322, USA
References

1 Timmis A. Acute coronary syndromes: risk stratification. Heart 2000;83:241-6.

2 Shaw LJ, Peterson ED, Kesler K, et al. A metaanalysis of predischarge risk stratification after acute myocardial infarction with stress electrocardiographic, myocardial perfusion and ventricular function imaging. Am J Cardiol 1996;78:1327-37.

3 Underwood SR, Godman B, Salyani S, et al. Economics of myocardial perfusion imaging in Europe: the EMPIRE study. Eur Heart J 1999;20:157-66.

4 Shaw LJ, Hachamovitch R, Berman DS, et al. The economic consequences of available diagnostic and prognostic strategies for the evaluation of stable angina patients: an observational assessment of the value of precatheterisation ischaemia. J Am Coll Cardiol 1999;33:661-9.

5 Tilkemeier PL, Guiney TE, LaRaia PJ, et al. Prognostic value of predischarge low-level exercise thallium testing after thrombolytic treatment of acute myocardial infarction. Am J Cardiol 1990;66:1203-7.

6 Haber HL, Beller GA, Watson DD, et al. Exercise thallium-201 scintigraphy after thrombolytic therapy with or without angioplasty for acute myocardial infarction. Am J Cardiol 1993;71:1257-61.

7 Dakik HA, Mahmarian JJ, Kimball KT, et al. Prognostic value of exercise 201Tl tomography in patients treated with thrombolytic therapy during acute myocardial infarction. Circulation 1996;94:2735-42.

8 Miller TD, Gersh BJ, Christian TF, et al. Limited prognostic value of thallium-201 exercise treadmill testing early after myocardial infarction in patients treated with thrombolysis. Am Heart J 1995;130:259-66.

9 Travin MI, Dessouki A, Cameron T, et al. Use of exercise technetium-99m sestamibi SPECT imaging to detect residual ischemia and for risk stratification after acute myocardial infarction. Am J Cardiol 1995;75:665-9.

10 Brown KA, Heller GV, Landin RS, et al. Early dipyridamole (99m)Tc-sestamibi single photon emission computed tomographic imaging 2 to 4 days after acute myocardial infarction predicts in-hospital and postdischarge cardiac events: comparison with submaximal exercise imaging. Circulation 1999;100:2060-6.

11 Mahmarian JJ, Mahmarian AC, Marks GF, et al. Role of adenosine thallium-201 tomography for defining long-term risk in patients after acute myocardial infarction. J Am Coll Cardiol 1995;25:1333-40.

12 Peterson ED, Shaw LJ, Kesler K, et al. Clinical guideline: part II. Risk stratification after myocardial infarction. Ann Intern Med 1997;126:561-82.

While December's editorial on non-cardiac chest pain is thoughtful and thorough,(1) there is a strange lack of emphasis on skeletal chest pain. I am not sure if this is due to selection of patients, but I wonder if it is the lack of a diagnostic test for skeletal pain. Since this may involve up to 73% of patients referred with chest pain to cardiac clinics,(2) it would seem to be of paramount importance. The authors comment on the possibility that "abnormalities" (namely oesophageal and respiratory) may be "coincidental rather than causative" and that 60% of patients with normal coronary angiograms and non-cardiac chest pain have a psychiatric disorder. We all occasionally recommend angiography in patients who cannot adapt to the pidgeonhole we offer to give more strength to our arm, which suggests that a higher percentage of patients with non-cardiac chest pain and psychiatric disorders will get angiography than those who are mentally more balanced; in addition Mayou and his colleagues have themselves demonstrated that patients who are told that their hearts are normal but are not given a clear diagnosis remain in trouble,(3) so it is perhaps not surprising that psychiatrists find a high level of psychiatric disorder in these people.

In a letter to Heart,(4) I reported the reproduction of chest pain by testing the passive range of movements and found that of 27 patients with clinically non-cardiac chest pain one had oesophageal reflux (and responded to treatment for this), one had costochondral joint pain and 22 had their symptoms reproduced by spinal movements. Incidentally at one year some still had symptoms but none had been off work because of their presenting symptoms or admitted to hospital with chest pain. This pain can sometimes be both reproduced and relieved by intercostal nerve block (C Davidson, personal communication). We are doing a larger study at present but it does seem that manipulating the spine as described by Chambers et al is a sound way of demonstrating to patient and doctor that the the pain is mechanical. Only 7 out of 27 responded to non-steroidal anti-inflammatory drugs; I think it is likely that postural training or (pace the unbelievers) manipulation will do better. The hardest patients to manage seem to be those with cardiac and skeletal pain.

The authors suggest a psychological cause if there is a situational or phobic component to the somatic symptoms; but anxiety appears to increase mechanical symptoms such as sciatica due to a lumbar disc, perhaps by increased muscle tone; it is not the cause of the symptoms.

Exercise testing is a two edged sword (did they ever make single edged swords?). The authors mention the value of a negative test, but of equal importance is the danger of a positive in someone with coronary disease but non-cardiac chest pain, and the risk of intervention with no relief of symptoms, further angiography etc.

Finally the authors suggest that for patients with "continuing symptoms---with coexisting psychological problems" a specialist nurse who has received additional training should be employed in the cardiac clinic to help them. Surely if the patient has been told that they have no cardiac disease the last place they should be followed is the cardiac clinic whatever the actual cause of their symptoms.

I know the north-south divide involves more than house prices, but I find it hard to believe that chest pain in Oxford or London is too different from that in Lancashire, assuming that referral is not biased. To demonstrate a physical cause is of tremendous importance as we are looking at thousands of referrals per year who, if managed by their general practitioner, would contribute to a significant drop in our waiting lists. I suggest that some of those thousands have demonstrable skeletal pain, and that we are missing them.

References

1 Chambers J, Bass C, Mayou R. Non-cardiac chest pain: assessment and management. Heart 1999;82:656-7.
2 Jain D, Fluck D, Sayer JW, et al. Ability of a one-stop chest pain clinic to identify high risk patients... J R Coll Phys Lond 1997;31:401-4.
3 Mayou R, Bryant B, Sanders D, et al. A controlled trial of cognitive behavioural therapy for non-cardiac chest pain. Psychol Med 1997;27:1021-31.
4 Best RA. Non-cardiac chest pain: a useful physical sign? [letter] Heart 1999;81:450.

Dear Editor:

We read with great interest the review "Cardiocutaneous fistula" published by Dr. Danias and co-workers. At our Institution, we encountered a similar case, concerning a 72-year-old female, who developed this complication eleven months after coronary bypass sugery and linear resection of an anteroapical left ventricular aneurysm; the postoperative course had been complicated by mediastinitis necessitating surgical debridement and irrigation with 0.5% povidone-iodine until removal of chest tubes. Initially, the patient presented mimicking subacute endocarditis and subsequently developed the fistulous tract from the cardiac apex through the chest wall. As stated by others [1] [2] [3] there was no tendency to spontaneous healing, and bleeding was only mild and transient, resembling chronic fistula secondary to chronic sternal osteomyelitis; cultures were negative. Elective operation was not planned because of poor general state and relative paucity of symptoms. Conditions gradually declined until, during hospitalization, massive hemorrhage ensued; no hemodynamic instability was observed during compressive maneuvers. Emergency operation was accomplished through re-sternotomy after institution of moderately hypothermic (28 °C) cardiopulmonary bypass through the femoral vessels. Cooling was continued during dissection of extremely dense adhesions and fragile tissues to obtain complete exposure the left ventricle, avoiding free dissection of the great vessels; the defect was repaired during circulatory arrest (20 °C) removing all foreign material and infected tissue along with two chronically eroded costal segments. The patient died on the fourth postoperative day in multi-organ failure.

It is difficult to give guidelines, but some points should be stressed:

High-risk surgery is probably the only therapeutic option and should be planned electively avoiding life-saving emergency operations.

In our case, infection was not secondary to chest wall erosion due to prosthetic material (a theoretical possibility previously stated by others [3]). Mediastinitis may represent the inital cause, but also a consequence of implantation of contaminated prosthetic material during aneurysmectomy.

The role of extensive use of prosthetic material (in particular, Teflon felt) outside the heart is unclear, but may be important. This specifically applies to patients undergoing left ventricular aneurysm repair, who often present additional risk factors for infection (advanced age, associated heart failure, longer cardiopulmonary bypass times, etc).

In case of postoperative mediastinitis should extracardiac Teflon be replaced with autologous pericardium? This is a very difficult issue, due to the different extensiveness of surgical options, but may be important in the development of fistulae/pseudaneurysms of the heart/great vessels. In case of extensive use of prosthetic material, removal should probably be considered.

Re-sternotomy [1] may not be the optimal approach for repair. If operation involves the left ventricle alone, an anterior thoracotomy through the 5th or 6th intercostal space [4] is more appealing and less cumbersome, despite the necessity of extrathoracic cannulation, deep hypothermia and low-flow bypass/circulatory arrest. Sternotomy may prolong surgery rather than represent a more expeditious technique. We reccomend to avoid re-sternotomy whenever possible, especially in case of previous mediastinitis.

Marco Pocar, MD - Francesco Donatelli, MD - Adalberto Grossi, MD
Istituto di Malattie dell'apparato cardiovascolare e respiratorio - Università degli Studi di Milano
Divisione di Cardiochirurgia - IRCCS, Ospedale Maggiore Policlinico - Via Francesco Sforza, 35 - 20122 Milano, Italy

References

1 McHenry MC, Longworth DL, Rehm SJ, et al. Infection of the cardiac suture line after left ventricular surgery. Am J Med 1988;85:292-300.

2 Stanford W, Reuben CF, Flemma RJ, et al. Management of long-standing cardiocutaneous fistulas after resection of left ventricular aneurysms. J Thorac Cardiovasc Surg 1980;79:789-792.

3 Deuvaert FE, Wellens F, De Paepe J, at al. Cardiocutaneous fistula after left ventricular anuerysm repair. Case report and review of the literature. J Cardiovasc Surg (Torino) 1984;25:560-562.

4 Wellens F, Vanermen H. Treatment of the infected cardiac suture line. J Cardiac Surg 1988;3:109-118.

Dear Editor

We have read with great interest the short case in cardiology reported by E Zakynthinos et al (1) in the March 2000 edition of Heart. The ECG recordings after acute ingestion of amitriptyline are remarkable, especially the ST segment elevation in the precordial leads V1 - V3, 6 to 100 hours after admission in the intensive care unit.

The ECG pattern resembles markedly the ones described in the Brugada syndrome (2). Thus this case could represent a specific effect of the ionic action of tricyclic agents with selective blockade of the sodium channels (3,4), mimicking temporarily a Brugada pattern, as an acquired phenomenon in an otherwise electrically normal myocardium.

Another mechanism could be an unmasking effect of amitriptyline similar to that of other sodium channel blockers which revealed a silent dysfunction of the sodium channels in a "concealed" Brugada Syndrome (5). This has, in our opinion, to be discussed and verified by means of a pharmacological test with ajmaline (5), at distance of the acute event. The apparent absence of threatening arrhythmias in the presence of such a high concentration of amitriptyline is however an argument pleading against this hypothesis.

In the same issue of Heart, R P Steeds et al (6) report a case of abnormal ventricular conduction following dothiepin overdose with images resembling an acute myocardial infarction. The ST segment elevation in leads V1-V3 is however somewhat different and less suggestive of a Brugada Syndrome. Nevertheless, the ionic mechanism of intoxication could be the same, though occurring in an electrically otherwise normal myocardium. Similarly in this case, an ajmaline pharmacological test could be appropriate to ensure the integrity of sodium ionic channels. A genetic study would be also advocated in these two cases.

L DE ROY, MD
C SCAVEE, MD
J MUCUMBITSI, MD
D BLOMMAERT, MD
Department of Cardiology, Arrhythmia Unit
University of Louvain
B 5530 YVOIR Belgium

References

1. E. Zakynthinos, T. Vassilakopoulos, C. Roussos, S Zakynthinos. Abnormal atrial and ventricular repolarisation resembling myocardial injury after tricyclic antidepressant drug intoxication. Heart 2000;83:353-354.

2. P Brugada, J Brugada. Right bundle-branch block persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report J Am Coll Cardiol 1992;20:1391-1396.

3. MJ Barber, CF Starmer, AO Grant. Blockade of cardiac sodium channels by amitriptyline and diphenylhydantoïne.Evidence for two use-dependent binding sites. Circ Res 1991;69:677-96.

4. C Nau, M Seaver, SY Wang, GK Wang. Block of human heart hH1 sodium channels by amitriptyline.J Pharmacol Exp Ther 2000;292:1015-23.

5. R Brugada, J Brugada, C Antzelevitch, G E Kirsch, D Potenza, J A Towbin, P Brugada: Sodium channel blockers identify risk for sudden death in patients with ST segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000;101:510-515.

6. R P Steeds, R Muthusamy: Abnormal ventricular conduction following dothiepin overdose simulating acute myocardial infarction. Heart 2000;83:289.