I would like to acknowledge the interesting work published by Coulden et al [1] in the February 2000 edition of the journal. The concept of noninvasive arterial wall imaging with MR is an exciting new field with numerous potential implications, including atherosclerotic plaque characterisation. However, I would like to raise a few questions about the selection of MR imaging parameters.

Firstly, I was interested to note that the resolution is different in all 3 axes. Although a characteristic of 2-D imaging is a loss of z-axis resolution (slice thickness), previous work in animal models [2] [3] [4] and humans [5] [6] has generally been with the same resolution in the x- and y- axes allowing homogeneity of the resolution within the artery wall and thus the atherosclerotic plaque.

Secondly, using a slice thickness of 3-mm with an image interval of 1.5-mm means that one third of the arterial wall and associated atherosclerosis is missed. Although consecutive imaging without gaps leads to cross excitation, one may interleave slices or if more than one acquisition is performed, acquire alternating slices, to obtain MR images of the entire arterial segment of interest without this interference.

Finally, the authors note the previously reported utility of T2- weighted imaging for the characterisation of atherosclerotic plaque [6] and yet use T1-weighted imaging in their study. Although for the purpose of documenting arterial plaque burden and vessel wall remodelling T1- weighted imaging is adequate, data on the relative contribution of fibrotic and lipidic components to the atherosclerotic process and how this influences the angioplasty process would be of great interest. I do appreciate, however, that given the number of patients studied (n=4), and the need for probably at least two imaging sequences (i.e. T1 and T2 weighted) to discern all components of complex human atherosclerotic lesions, [6] conclusions regarding these concepts would be limited in this study.

References

1. Coulden RA, Moss H, Graves MJ, et al. High resolution magnetic resonance imaging of atherosclerosis and the response to balloon angioplasty. Heart 2000;83:188-91.

2. Worthley SG, Helft G, Fuster V, et al. Serial in vivo MRI documents arterial remodeling in experimental atherosclerosis. Circulation 2000;101:586-9.

3. Skinner MP, Yuan C, Mitsumori L, et al. Serial magnetic resonance imaging of experimental atherosclerosis detects lesion fine structure, progression and complications in vivo. Nat Med 1995;1:69-73.

4. McConnell MV, Aikawa M, Maier SE, et al. MRI of rabbit atherosclerosis in response to dietary cholesterol lowering. Arterioscler Thromb Vasc Biol 1999;19:1956-9.

5. Yuan C, Beach KW, Smith LH, Jr., et al. Measurement of atherosclerotic carotid plaque size in vivo using high resolution magnetic resonance imaging. Circulation 1998;98:2666-71.

6. Toussaint JF, LaMuraglia GM, Southern JF, et al. Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo. Circulation 1996;94:932-8.

Dear Editor:

The excellent review by Ward on the clinical significance of the bicuspid aortic valve (Heart 2000;83:81-85) is of great interest and value. The extensive reference list as well put a good bit of the pertinent bicuspid valve literature in one place. The paper adds greatly to our knowledge.

However, without critiquing every issue in the paper, there are two areas in particular I would like to discuss. As a pediatric cardiologist who has been in one division for 40 years, there is considerable natural history which has been learned, although, perhaps in order to make my statements I would really have to work in one place for 70 years.

I have seen a huge number of patients with a true bicuspid aortic valve and I have never seen a patient with a dissecting aneurysm. As Dr. Ward states, the reason for the reported high incidence of aortic dissection in the presence of an aortic bicuspid aortic valve is unclear, particularly since the author states that the bicuspid valve is usually normally functioning. Although the post bicuspid valve dilatation of the ascending aorta in the presence of systemic hypertension certainly makes the environment possible, Dr. Ward’s paper makes no mention as to whether he has personally seen a patient with dissection. The estimated incidence of 5% of patients with bicuspid valve having dissection of the aorta seems very much too high.

The second issue refers to whether or not the patient born with bicuspid aortic valve and no stenosis is expected to progress to reach real aortic stenosis as the patient ages in the absence of infective endocarditis. The accepted knowledge over the years has been that the elderly with calcific aortic stenosis began with a bicuspid aortic valve, including the valve with no stenosis to begin with. Evidence for such has never been documented and perhaps cannot, unless a 100 year prospective study is planned and funded. The implication of Dr. Ward’s article is not quite that, for he doesn’t really discuss the patient with bicuspid aortic valve and no stenosis. He only states, appropriately, that patients with mild aortic stenosis are expected to progress in adulthood, even patients with echocardiographic mean gradient of less than 25 mmHg. However, this does not answer the question as to whether the patients with true bicuspid aortic valve and no stenosis are expected to progress. In order to discuss this issue, one needs the physical examination. Is there a difference in natural history between the patient with true bicuspid aortic valve with no stenosis and a true bicuspid aortic valve with mild stenosis? In the early two decades of my 40 years, the diagnosis of bicuspid aortic valve without stenosis was made by recognizing an aortic ejection click with no heart murmur. I accept that occasionally an error can be made in that the presumed aortic ejection click is in actual fact an unusually loud tricuspid valve component of a normally split first sound. But in the recent two decades, with echocardiography, confirmation has been readily available. The patient with a bicuspid aortic valve and mild aortic stenosis is diagnosed by having the aortic ejection click plus a normally split second sound and an aortic stenosis murmur at the second right interspace that is significant but usually stops clearly before aortic valve closure. The latter will usually have a mean gradient of less than 25 mmHg in the echo, just as will obviously the patient with no stenosis. Dr. Ward because of the nature of his review does not separate these groups. In my 40 years, I have seen many patients with mild stenosis progress, but I have seen none with no stenosis progress. In addition, the subgroup of patients with coarctation of the aorta has a very high incidence of bicuspid valve without stenosis. I have never seen one of these develop aortic stenosis either.

I realize that 40 years is not 70 years, but since it is unlikely to be able to find all these patients with no stenosis for an associate to follow for 30 or 40 more years answering the question for certain at this time appears unlikely. However, it would be in cumbent upon all of us to modify what we teach our students and what we advise our families. As far as we know, the bicuspid aortic valve without stenosis remains without stenosis.

Sincerely,

Jerome Liebman MD
Division of Pediatric Cardiology
Professor of Pediatrics
Rainbow Babies & Children’s Hospital
Case Western Reserve University

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.

In my review on risk stratification in acute coronary syndromes, "diagnostic value" was used conventionally to refer to the ability of predischarge tests to predict future coronary events, particularly death and myocardial infarction.

In response to the 3 additional points:

1. Cost-effectiveness Underwood et al are correct to caution me on statements of cost-effectiveness. My contention was (and remains) that predischarge stress testing is usually as effective as perfusion imaging for risk stratification and costs less. The superior quality of SPECT compared with conventional perfusion imaging may confer some advantage (see below) but the considerable capital costs involved will inevitably limit its application.

2. Exercise ECG versus Perfusion Imaging Underwood et al are incorrect to infer superiority of predischarge perfusion imaging from the data presented in the metaanalysis of Shaw et al (1). Cardiac event rates were higher in the studies of myocardial perfusion imaging, readily accounting for the apparent difference between positive predictive values for these diagnostic tests. It is for the same reason, incidentally, that both tests appear to perform better in patients who have not received thrombolytic therapy. Shaw emphasises in her metaanalysis that both the exercise ECG and the radionuclide perfusion scan are blunt tools for risk stratification and my algorithm recommends use of either test, without expressing a preference. Underwood et al draw attention to 3 papers comparing the exercise ECG with SPECT imaging that post-dated ShawÆs metaanalysis (2-4). Two showed some advantage for SPECT imaging although positive predictive values for events after hospital discharge appeared low (specific data not provided), confirming previous reports (2-3). The other was a small (n=71) retrospective series, in which the only multivariate predictor of death and recurrent infarction was LV ejection fraction (4). Only when the endpoint was extended to incorporate unstable angina and heart failure did perfusion imaging provide independent prognostic information. Set against the 36 studies (16,960 patients) included in ShawÆs metaanalysis, the additional 3 selected by Underwood et al are not overly persuasive but suggest that SPECT technology may have an edge over the exercise ECG for risk stratification.

3. Incremental value of perfusion imaging Although one of the studies quoted by Underwood et al found that SPECT perfusion imaging was not independently predictive of death and recurrent infarction if LV ejection fraction was included in the multivariate model (4), they quote another in which incremental value was demonstrated (5). Data for stress testing are similarly contradictory. For this reason I recommended application of these tests (exercise ECG or perfusion scan) only in patients with advanced LV dysfunction (LVEF <_40 in="in" whom="whom" risk="risk" is="is" greatest.="greatest." unpublished="unpublished" data="data" for="for" our="our" own="own" low="low" patients="patients" discharged="discharged" with="with" lvef="lvef"/>40% by GUSTO criteria (6)) show the estimated risk of death in the first year is only 3.8% (2.1-5.4%) and of death and recurrent infarction 9.8% (7.1-12.4%). The idea that these relatively low risk survivors of acute myocardial infarction would benefit from further risk stratification using perfusion imaging (or stress tesing) seems barely credible. This does not of course mean that the tests should not be done but it does mean that incautious predictions of "cost-effectiveness" may be incorrect.

In summary, SPECT imaging may offer a small advantage over the exercise ECG for detection of residual ischaemia in patients with acute coronary syndromes, although it remains a blunt tool for risk stratification. Speaking from the perspective of the coronary care unit, there is no doubt that the availability and low cost of exercise testing (as opposed to the relative nonavailabiltiy and high cost of SPECT imaging) will make it a more practical solution for predischarge risk stratification in most centres. However, perfusion imaging is a reasonable, perhaps better, alternative in those units able to provide a predischarge service for upward of 700 coronary patients per year, and my algorithm allows for this.

Adam D Timmis MD, FRCP

References

1. Shaw LJ, Peterson ED, Kesler K, Hasselblad V, Califf RM. 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.

2. Travin MI, Dessouki A, Cameron T, Heller GV. 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.

3. Brown KA, Heller GV, Landin RS, Shaw LJ, Beller GA, Pasquale MJ, Haber SB. 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.

4. Dakik HA, Mahmarian JJ, Kimball KT, Koutelou MG, Medrano R, Verani MS. Prognostic value of exercise 201Tl tomography in patients treated with thrombolytic therapy during acute myocardial infarction. Circulation. 1996;94:2735-42.

5. Mahmarian JJ, Mahmarian AC, Marks GF, Pratt CM, Verani MS. 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.