353
have disappeared or look less suspicious’-or by use of ultrasound plus aspiration.2 The remainder, amounting to about 10%, will appear sufficiently abnormal either initially or on review to warrant removal for histological examination. This figure can be reduced further by regular use of fine-needle aspiration of non-palpable lesions by means of ultrasound or stereotactic mammography.3,4 Many methods have been used for localisation before excision. The simplest approach is "geographic" estimation of the site of abnormality, with measurements taken from the mammogram and transposed to the breast. This technique can be refined with skin marking.5,6 More accuracy can be obtained with injection of a mixture of radiographic contrast media and a coloured dye near the suspicious area, under mammographic control. This method is popular with many surgeons, who locate the coloured dye easily at operation, but the small amount of contrast media makes it less satisfactory for radiologists. Another disadvantage is that dye injection must be followed by surgery within hours because the dye diffuses through the breast, making accurate localisation difficult. This timing of localisation and surgery may not always be easy. The relation of localisation and surgery is not as critical when needles and wires are inserted under radiographic control; this approach enhances the accuracy of localisation. Numerous types of wires and needles are now available, all with their own advocates. Difficulties are encountered with needle misplacement, displacement, and migration,8 although the last mentioned is uncommon. Many ways of preventing displacement have been devised, from hooks and curves to crosses.9-11 Misplacement can be managed by use of a perforated compression plate12 or illuminated cross-wires on the mammographic machine, but the most accurate method of wire placing is probably by use of stereotactic mammography, for which an accuracy to 1-2 mm has been claimed. (Many users have found such claims rather optimistic.) To diminish the possibility of wire migration, surgery should be carried out within a few hours of localisation. Simple methods of securing the wire that protrudes out of the breast-eg, by bending, suturing, or taping-will usually be sufficient. Ultrasoundguided insertion of wires on the operating table has also been advocated.13 The procedure can be unsettling for anxious patients, and even the most experienced operators can take several minutes to do it. Nevertheless, it is important not to use premedication because cooperation is essential and drowsy patients can cause considerable technical difficulties, giving rise to even more distress. Some surgeons, especially those who do only a few biopsies of non-palpable lesions a year, may have trouble in palpating or finding the end of the wire. Moreover, thinner wires and hooks are used with increasing frequency. To overcome this
drawback, methods such
as
leaving
a
stiffening
cannula over the wire have been devised. 14 Whatever method of localisation is used, a radiograph of the excised specimen should be taken with a mammography machine while the patient is still anaesthetised so that the suspicious area is known to have been removed. is However, with cooperation between patients and radiographers, aided by increasing experience of radiologists and surgeons with this technique, almost all impalpable lesions are removed successfully. 1. Brenner RJ, Sickles EA. Acceptability of periodic follow up as an alternative to biopsy for mammographically detected lesions
interpreted as probably benign. Radiology 1989; 171: 645-46. EA, Filly RA, Cullen PW. Benign breast lesions, ultrasound detection and diagnosis. Radiology 1984; 151: 467-70. 3. Kopans DB, Mayer JE, Lindfoss KK, Bucchianeri SS. Breast sonography to guide cyst aspiration and wire localisation of occult solid lesions. AJR 1984; 143: 489-92. 4. Azavedo E, Svane G, Auer G. Stereotactic fine-needle biopsy in 2594 mammographically detected non-palpable lesions. Lancet 1989; i:
2. Sickles
1033-36.
Snyder RE. Specimen radiography and preoperative localisation of non palpable breast cancer. Cancer 1980; 46: 950-60. 6. Stevens MG, Jampus RW. Mammographically directed biopsy of non palpable breast lesions. Arch Surg 1971; 102: 292-95. 7. Wayne RW, Darby RE. Injection mammography. JAMA 1977; 237:
5.
2219-20. 8. Owen AWMC, Kumar EN. Migration of localising wires used in guided biopsy of the breast. Clin Radiol 1991; 43: 251. 9. Frank HA, Hall FM, Steer ML. Pre operative localisation of non palpable breast lesion demonstrated by mammography. N Engl J Med 1976; 295: 259-60. 10. Homer MJ. Non palpable breast lesion localisation using a curved end retractable wire. Radiology 1985; 157: 259-60. 11. Chaudary MA, Reidy JF, Chaudhuri R, Millis RR, Hayward JL, Fentiman IS. Localisation of impalpable breast lesions. A new device.
Br J Surg 1990; 77: 1191-92. 12. Lee MJR, Lee JR, Thompson H, Oates GD. Mammographic identification and biopsy of occult breast cancer. Ann R Coll Surg Engl 1986; 68: 188-90. 13. Schwartz GF, Goldberg BB, Rifkin MD, D’Orazio SE. Ultrasonography: an alternative to X-ray guided needle localisation of non palpable breast masses. Surgery 1988; 104: 870-73. 14. Kwasnik EM, Sadowsky NL, Vollman RW. An improved system for surgical excision of needle localised non palpable breast lesions. Ann J
Surg 1987; 154: 476-77. 15. Boulter PS. The mammographic cancer.
Explaining
Br J Surg 1988; 75:
401.
syncope
for 1-3% of attendances at accident and emergency departments and 3-6% of hospital admissions.1,2 In 30-50% of patients no underlying cause is found despite extensive tests. Subsequent case-fatality in such patients is low but morbidity remains high:l,2 about half will have one or more recurrences, often associated with minor lacerations or bruising, and occasionally syncope results in a serious fracture or even a road traffic accident. Repeated investigations are seldom helpfu1.1 The head-up tilt test reproduces symptoms and also identifies a specific abnormality of the heart rate/blood pressure response to postural stress in patients with syncope,2-13 In susceptible individuals venous pooling and increased sympathetic drive seem to activate ventricular mechanoreceptors (and afferent vagal
Syncope
accounts
354
C-fibre activity). Stimulation of these receptors leads increased efferent vagal outflow and withdrawal of sympathetic noradrenergic outflow. Clinically, sinus tachycardia and vigorous ventricular contraction to
(believed to cause mechanoreceptor stimulation), often accompanied by feelings of nausea and warmth, are followed by an abrupt and precipitous fall in blood pressure and heart rate (there may be sinus bradycardia, sinus arrest, or atrioventricular block).2-13 Patients recover rapidly when they are returned from the upright to the horizontal position. Certain features of the test protocol are important: (a) the angle of tilt needs to be at least 60° to the horizontal for adequate test sensitivity;10 (b) foot rather than saddle support should be used to prevent a high rate of "false-positive" syncope;10 and (c) tilt duration of 45 min has been suggested as ideal, though some workers use an abbreviated protocol of 10-30 min tilt followed by an incremental infusion of isoprenaline 1-5 µg/min if there is no response. 3-5,13 How does the tilt test perform in practice? Researchers in the UK, North America, Israel, and Italy have reported their experience with this investigation.2-12 Most have studied selected patients, usually those who have had two or more syncopal episodes and have undergone extensive investigations, including invasive electrophysiological testing, without reaching a diagnosis. About 70% of these patients (range 50-90%) will have a positive response to tilt.3,4,6,9,10 In less selected populations the limited evidence available suggests a sensitivity in the range
30-60%.5,7,11 What about
specificity? A positive test is occasionally observed in age and sex matched healthy controls, in young people with vasovagal faints, and in patients with syncope due to disease of cardiac conducting tissue (sinoatrial/atrioventricular or His bundle). The only group showing substantial overlap are those with syncope and carotid sinus syndrome. 8-10 Overall, tilt testing (with or without isoprenaline) has a high specificity-about 80-85 %.2-12 Reproducibility is also an important aspect if the test is to be useful for evaluating therapy6,10,13 Repeat tilting within hours or days of a positive test gives a reproducible response in 70-90% of patients. Nevertheless, test results may not be totally concordant-ie, a predominantly cardioinhibitory response may occur on the first occasion and a mainly vasodepressor response on the second. Long-term reproducibility and the response to repeat tilting after an initial negative test are not known. Control subjects seem to have reproducibly negative tests .6,10,14 Does the tilt test have a role in routine clinical practice? Tilt testing is useful in allowing identification of a largely benign disorder and, indirectly, in excluding other possibly life-threatening conditions. Wasteful investigation and reinvestigation can be avoided once a firm diagnosis has been made. Elucidation of the pathophysiology of this type of syncope by tilt testing allows the logical selection of
treatments.4-6,8,15 Valuable responses have been reported with uncontrolled studies of several agents:
(a) anticholinergics (eg, scopolamine), &bgr;-blockers, and disopyramide (to reduce myocardial contractility and activation); mechanoreceptor (b) mineralocorticoids (to expand plasma volume and limit the fall in venous return); and (c) adrenergic vasoconstrictors (to prevent the sudden loss of vascular tone).4-6 Dual chamber pacing has benefited patients with a predominantly cardioinhibitory response.8 Several double-blind placebo-controlled cross-over
studies
are
underway.
a useful addition to the tilt-testing investigation of syncope. In patients with an inconclusive history and examination and negative
is
Thus
non-invasive
tests
of cardiac
structure
and function
ambulatory (including electrocardiographic should the next step.2-12,16 tilt be monitoring), testing with heart In those disease, an organic electrophysiological test (or possibly signal-averaged electrocardiography) is more useful; patients with structural heart disease seldom have a positive tilt test but up to 70% have an abnormal electrophysiological test. 17 1.
Kapoor WN. Evaluation and outcome of patients with syncope. Medicine
2.
Fitzpatrick A, Theodorakis G, et al. The incidence of malignant vasovagal syndrome in patients with recurrent syncope. Eur Heart J 1991; 12:
3.
Almquist A, Goldenberg IF, Milstein S, et al. Provocation of bradycardia and hypotension by isoproterenol and upright posture in patients with unexplained syncope. N Engl J Med 1989; 320: 346-51. Sra JS, Anderson AJ, Sheikh SH, et al. Unexplained syncope evaluated by electrophysiologic studies and head-up tilt testing. Ann Intern Med
1990; 69: 160-75.
389-94.
4.
1991; 114: 1013-19. BP, Temesy-Armos P, Hahn H, Elliott L. Utility of upright
5. Grubb
tilt-table testing in the evaluation and management of syncope of unknown origin. Am J Med 1991; 90: 6-10. 6. Raviele A, Gasparini G, Di Pede F, Delise P, Bonso A, Piccolo E. Usefulness of head-up tilt test in evaluating patients with syncope of unknown origin and negative electrophysiologic study. Am J Cardiol 1990; 65: 1322-27. 7. Strasberg B, Rechavia E, Sagie A, et al. The head-up tilt table test in patients with syncope of unknown origin. Am Heart J 1989; 118: 923. 8. Fitzpatrick A, Sutton R. Tilting towards a diagnosis in recurrent unexplained syncope. Lancet 1989; i 658-60. 9. Kenny RA, Ingram A, Bayliss J, Sutton R. Head-up tilt: a useful test for investigating unexplained syncope. Lancet 1986; i: 1352-54. 10. Fitzpatrick AP, Theodorakis G, Varda P, Sutton R. Methodology of head-up tilt testing in patients with unexplained syncope. JACC 1991; 17: 125-30. 11. Grossi D, Nozzoli C, Roca ME, Santostasi R, Simone F. Head-up tilt for triggering and diagnosing syncope. Func Neurol 1987; II: 457-64. 12. Abi-Samra F, Maloney JD, Fouad-Tarazi FM, Castel LW. The usefulness of head-up tilt testing and haemodynamic investigations in the work up of syncope of unknown origin. PACE 1988; 11: 1202-14. 13. Waxman MB, Yao L, Cameron DA, Wald RW, Roseman J. Isoproterenol induction of vasodepressor type reaction in vasodepressor prone persons. Am J Cardiol 1989; 63: 58-65. 14. Cheny MY, Milstein S, Dunnigan A, Goldberg I, Gornick C, Benditt HD. Reproducibility of upright tilt testing for eliciting neurallymediated syncope. Circulation 1988; 78 (suppl II): II239 (abstr). 15. Milstein S, Buetikofar J, Dunnigan A, Benditt DG, Gornick C, Reyes WJ. Usefulness of disopyramide for prevention of upright tilt induced hypotension-bradycardia. Am J Cardiol 1990; 65: 1339-44. 16. Kapoor WN. Diagnostic evaluation of syncope. Am J Med 1991; 90: 91-106. 17. Kapoor WN, Hammill SC, Gersh BJ. Diagnosis and natural history of syncope and the role of invasive electrophysiologic testing. Am J Cardiol 1989; 63: 730-34.
have disappeared or look less suspicious’-or by use of ultrasound plus aspiration.2 The remainder, amounting to about 10%, will appear sufficiently abnormal either initially or on review to warrant removal for histological examination. This figure can be reduced further by regular use of fine-needle aspiration of non-palpable lesions by means of ultrasound or stereotactic mammography.3,4 Many methods have been used for localisation before excision. The simplest approach is "geographic" estimation of the site of abnormality, with measurements taken from the mammogram and transposed to the breast. This technique can be refined with skin marking.5,6 More accuracy can be obtained with injection of a mixture of radiographic contrast media and a coloured dye near the suspicious area, under mammographic control. This method is popular with many surgeons, who locate the coloured dye easily at operation, but the small amount of contrast media makes it less satisfactory for radiologists. Another disadvantage is that dye injection must be followed by surgery within hours because the dye diffuses through the breast, making accurate localisation difficult. This timing of localisation and surgery may not always be easy. The relation of localisation and surgery is not as critical when needles and wires are inserted under radiographic control; this approach enhances the accuracy of localisation. Numerous types of wires and needles are now available, all with their own advocates. Difficulties are encountered with needle misplacement, displacement, and migration,8 although the last mentioned is uncommon. Many ways of preventing displacement have been devised, from hooks and curves to crosses.9-11 Misplacement can be managed by use of a perforated compression plate12 or illuminated cross-wires on the mammographic machine, but the most accurate method of wire placing is probably by use of stereotactic mammography, for which an accuracy to 1-2 mm has been claimed. (Many users have found such claims rather optimistic.) To diminish the possibility of wire migration, surgery should be carried out within a few hours of localisation. Simple methods of securing the wire that protrudes out of the breast-eg, by bending, suturing, or taping-will usually be sufficient. Ultrasoundguided insertion of wires on the operating table has also been advocated.13 The procedure can be unsettling for anxious patients, and even the most experienced operators can take several minutes to do it. Nevertheless, it is important not to use premedication because cooperation is essential and drowsy patients can cause considerable technical difficulties, giving rise to even more distress. Some surgeons, especially those who do only a few biopsies of non-palpable lesions a year, may have trouble in palpating or finding the end of the wire. Moreover, thinner wires and hooks are used with increasing frequency. To overcome this
drawback, methods such
as
leaving
a
stiffening
cannula over the wire have been devised. 14 Whatever method of localisation is used, a radiograph of the excised specimen should be taken with a mammography machine while the patient is still anaesthetised so that the suspicious area is known to have been removed. is However, with cooperation between patients and radiographers, aided by increasing experience of radiologists and surgeons with this technique, almost all impalpable lesions are removed successfully. 1. Brenner RJ, Sickles EA. Acceptability of periodic follow up as an alternative to biopsy for mammographically detected lesions
interpreted as probably benign. Radiology 1989; 171: 645-46. EA, Filly RA, Cullen PW. Benign breast lesions, ultrasound detection and diagnosis. Radiology 1984; 151: 467-70. 3. Kopans DB, Mayer JE, Lindfoss KK, Bucchianeri SS. Breast sonography to guide cyst aspiration and wire localisation of occult solid lesions. AJR 1984; 143: 489-92. 4. Azavedo E, Svane G, Auer G. Stereotactic fine-needle biopsy in 2594 mammographically detected non-palpable lesions. Lancet 1989; i:
2. Sickles
1033-36.
Snyder RE. Specimen radiography and preoperative localisation of non palpable breast cancer. Cancer 1980; 46: 950-60. 6. Stevens MG, Jampus RW. Mammographically directed biopsy of non palpable breast lesions. Arch Surg 1971; 102: 292-95. 7. Wayne RW, Darby RE. Injection mammography. JAMA 1977; 237:
5.
2219-20. 8. Owen AWMC, Kumar EN. Migration of localising wires used in guided biopsy of the breast. Clin Radiol 1991; 43: 251. 9. Frank HA, Hall FM, Steer ML. Pre operative localisation of non palpable breast lesion demonstrated by mammography. N Engl J Med 1976; 295: 259-60. 10. Homer MJ. Non palpable breast lesion localisation using a curved end retractable wire. Radiology 1985; 157: 259-60. 11. Chaudary MA, Reidy JF, Chaudhuri R, Millis RR, Hayward JL, Fentiman IS. Localisation of impalpable breast lesions. A new device.
Br J Surg 1990; 77: 1191-92. 12. Lee MJR, Lee JR, Thompson H, Oates GD. Mammographic identification and biopsy of occult breast cancer. Ann R Coll Surg Engl 1986; 68: 188-90. 13. Schwartz GF, Goldberg BB, Rifkin MD, D’Orazio SE. Ultrasonography: an alternative to X-ray guided needle localisation of non palpable breast masses. Surgery 1988; 104: 870-73. 14. Kwasnik EM, Sadowsky NL, Vollman RW. An improved system for surgical excision of needle localised non palpable breast lesions. Ann J
Surg 1987; 154: 476-77. 15. Boulter PS. The mammographic cancer.
Explaining
Br J Surg 1988; 75:
401.
syncope
for 1-3% of attendances at accident and emergency departments and 3-6% of hospital admissions.1,2 In 30-50% of patients no underlying cause is found despite extensive tests. Subsequent case-fatality in such patients is low but morbidity remains high:l,2 about half will have one or more recurrences, often associated with minor lacerations or bruising, and occasionally syncope results in a serious fracture or even a road traffic accident. Repeated investigations are seldom helpfu1.1 The head-up tilt test reproduces symptoms and also identifies a specific abnormality of the heart rate/blood pressure response to postural stress in patients with syncope,2-13 In susceptible individuals venous pooling and increased sympathetic drive seem to activate ventricular mechanoreceptors (and afferent vagal
Syncope
accounts
354
C-fibre activity). Stimulation of these receptors leads increased efferent vagal outflow and withdrawal of sympathetic noradrenergic outflow. Clinically, sinus tachycardia and vigorous ventricular contraction to
(believed to cause mechanoreceptor stimulation), often accompanied by feelings of nausea and warmth, are followed by an abrupt and precipitous fall in blood pressure and heart rate (there may be sinus bradycardia, sinus arrest, or atrioventricular block).2-13 Patients recover rapidly when they are returned from the upright to the horizontal position. Certain features of the test protocol are important: (a) the angle of tilt needs to be at least 60° to the horizontal for adequate test sensitivity;10 (b) foot rather than saddle support should be used to prevent a high rate of "false-positive" syncope;10 and (c) tilt duration of 45 min has been suggested as ideal, though some workers use an abbreviated protocol of 10-30 min tilt followed by an incremental infusion of isoprenaline 1-5 µg/min if there is no response. 3-5,13 How does the tilt test perform in practice? Researchers in the UK, North America, Israel, and Italy have reported their experience with this investigation.2-12 Most have studied selected patients, usually those who have had two or more syncopal episodes and have undergone extensive investigations, including invasive electrophysiological testing, without reaching a diagnosis. About 70% of these patients (range 50-90%) will have a positive response to tilt.3,4,6,9,10 In less selected populations the limited evidence available suggests a sensitivity in the range
30-60%.5,7,11 What about
specificity? A positive test is occasionally observed in age and sex matched healthy controls, in young people with vasovagal faints, and in patients with syncope due to disease of cardiac conducting tissue (sinoatrial/atrioventricular or His bundle). The only group showing substantial overlap are those with syncope and carotid sinus syndrome. 8-10 Overall, tilt testing (with or without isoprenaline) has a high specificity-about 80-85 %.2-12 Reproducibility is also an important aspect if the test is to be useful for evaluating therapy6,10,13 Repeat tilting within hours or days of a positive test gives a reproducible response in 70-90% of patients. Nevertheless, test results may not be totally concordant-ie, a predominantly cardioinhibitory response may occur on the first occasion and a mainly vasodepressor response on the second. Long-term reproducibility and the response to repeat tilting after an initial negative test are not known. Control subjects seem to have reproducibly negative tests .6,10,14 Does the tilt test have a role in routine clinical practice? Tilt testing is useful in allowing identification of a largely benign disorder and, indirectly, in excluding other possibly life-threatening conditions. Wasteful investigation and reinvestigation can be avoided once a firm diagnosis has been made. Elucidation of the pathophysiology of this type of syncope by tilt testing allows the logical selection of
treatments.4-6,8,15 Valuable responses have been reported with uncontrolled studies of several agents:
(a) anticholinergics (eg, scopolamine), &bgr;-blockers, and disopyramide (to reduce myocardial contractility and activation); mechanoreceptor (b) mineralocorticoids (to expand plasma volume and limit the fall in venous return); and (c) adrenergic vasoconstrictors (to prevent the sudden loss of vascular tone).4-6 Dual chamber pacing has benefited patients with a predominantly cardioinhibitory response.8 Several double-blind placebo-controlled cross-over
studies
are
underway.
a useful addition to the tilt-testing investigation of syncope. In patients with an inconclusive history and examination and negative
is
Thus
non-invasive
tests
of cardiac
structure
and function
ambulatory (including electrocardiographic should the next step.2-12,16 tilt be monitoring), testing with heart In those disease, an organic electrophysiological test (or possibly signal-averaged electrocardiography) is more useful; patients with structural heart disease seldom have a positive tilt test but up to 70% have an abnormal electrophysiological test. 17 1.
Kapoor WN. Evaluation and outcome of patients with syncope. Medicine
2.
Fitzpatrick A, Theodorakis G, et al. The incidence of malignant vasovagal syndrome in patients with recurrent syncope. Eur Heart J 1991; 12:
3.
Almquist A, Goldenberg IF, Milstein S, et al. Provocation of bradycardia and hypotension by isoproterenol and upright posture in patients with unexplained syncope. N Engl J Med 1989; 320: 346-51. Sra JS, Anderson AJ, Sheikh SH, et al. Unexplained syncope evaluated by electrophysiologic studies and head-up tilt testing. Ann Intern Med
1990; 69: 160-75.
389-94.
4.
1991; 114: 1013-19. BP, Temesy-Armos P, Hahn H, Elliott L. Utility of upright
5. Grubb
tilt-table testing in the evaluation and management of syncope of unknown origin. Am J Med 1991; 90: 6-10. 6. Raviele A, Gasparini G, Di Pede F, Delise P, Bonso A, Piccolo E. Usefulness of head-up tilt test in evaluating patients with syncope of unknown origin and negative electrophysiologic study. Am J Cardiol 1990; 65: 1322-27. 7. Strasberg B, Rechavia E, Sagie A, et al. The head-up tilt table test in patients with syncope of unknown origin. Am Heart J 1989; 118: 923. 8. Fitzpatrick A, Sutton R. Tilting towards a diagnosis in recurrent unexplained syncope. Lancet 1989; i 658-60. 9. Kenny RA, Ingram A, Bayliss J, Sutton R. Head-up tilt: a useful test for investigating unexplained syncope. Lancet 1986; i: 1352-54. 10. Fitzpatrick AP, Theodorakis G, Varda P, Sutton R. Methodology of head-up tilt testing in patients with unexplained syncope. JACC 1991; 17: 125-30. 11. Grossi D, Nozzoli C, Roca ME, Santostasi R, Simone F. Head-up tilt for triggering and diagnosing syncope. Func Neurol 1987; II: 457-64. 12. Abi-Samra F, Maloney JD, Fouad-Tarazi FM, Castel LW. The usefulness of head-up tilt testing and haemodynamic investigations in the work up of syncope of unknown origin. PACE 1988; 11: 1202-14. 13. Waxman MB, Yao L, Cameron DA, Wald RW, Roseman J. Isoproterenol induction of vasodepressor type reaction in vasodepressor prone persons. Am J Cardiol 1989; 63: 58-65. 14. Cheny MY, Milstein S, Dunnigan A, Goldberg I, Gornick C, Benditt HD. Reproducibility of upright tilt testing for eliciting neurallymediated syncope. Circulation 1988; 78 (suppl II): II239 (abstr). 15. Milstein S, Buetikofar J, Dunnigan A, Benditt DG, Gornick C, Reyes WJ. Usefulness of disopyramide for prevention of upright tilt induced hypotension-bradycardia. Am J Cardiol 1990; 65: 1339-44. 16. Kapoor WN. Diagnostic evaluation of syncope. Am J Med 1991; 90: 91-106. 17. Kapoor WN, Hammill SC, Gersh BJ. Diagnosis and natural history of syncope and the role of invasive electrophysiologic testing. Am J Cardiol 1989; 63: 730-34.
