- Email: [email protected]
Exercise test in coronary spasm
1844
Letters
to the Editor
American
of the molecule, and it has been suggested2 that this side chain my be responsible for hypoprothrombinemia and bleeding. Therefore it should be emphasize that patients receiving cephalosporin therapy should have their prothrombin time monitored, especially if they are elderly and chronically ill. Professor Saeed Ahmad, MD, FRCP, FACC Cardio-Diagnostic Clinique 1000 Brookside Dr. Fairmont. W. V. 26554
very with
REFERENCES
REFERENCES
1. Riggs T. Cardiomyopathy and pulmonary emboli in terminal Duchenne’s muscular dystrophy. AM HEART J 1990;119:690-3. 2. Neu HC. The in vitro activity, human pharmacology and clinical effectiveness of new antibiotics. Annu Rev Pharmacol Toxic01 1982;22:599-642.
REPLY To the Editor: The patient in question (case 1) did receive intravenous cefotaxime as treatment for a presumed lower respiratory infection; the patient was treated for several days before the prothrombin time was found to be prolonged.’ Since there had been no previous measurements of this patient’s prothrombin time, one cannot ascertain whether or not cefotaxime was associated with the observed prolongation of this hemostatic parameter. The cephalosporins are semisynthetic derivatives of a 7-aminocephalosporanic acid nucleus. The N-methylthiotetrazole side chain at position 3 of this nucleus, referred to by Dr. Ahmad, is present in only some of the cephalosporins currently in use, including cefamandole, cefoperazone, cefotetan, cefonicid, cefpiramide, cefmenoxime, cefmetazole, and moxalactam (an oxa-beta-lactam antibiotic, and is not a true cephalosporin). This side chain is not present in cefotaxime.2 Approximately 60% of a dose of cefotaxime is excreted in the urine in unchanged form within 24 hours. Urinary excretion of desacetylcefotaxime (the major product. of the hepatic metabolism of cefotaxime) and the M2 and Ma metabolites (products of desacetylcefotaxime transformation in the liver) accounts for an additional 29% and 6%) of an administered dose of cefotaxime, respectively. Biliary excretion usually accounts for only 0.01% to O.l?; of a cefotaxime dose.3 The tenet that antibiotic-associated hypoprothrombinemia is a consequence of inhibiting intestinal bacteria that are capable of vitamin K production, such as Escherichia cob and Bacteroides, remains unproved. Hypoprothrombinemia is primarily encountered in patients treated with N-methylthiotetrazole-containing cephalosporins, and it is generally believed that this moiety may inhibit the vitamin K-dependent gamma-carboxylation of glutamic acid residues in clotting factors II (prothrombin), VII, IX, and X, thereby leading to the appearance of inactive forms of these factors in plasma.4 It is also worth noting that administration of N-methylthiotetrazole-containing cephalosporins to healthy volunteers does not lead to hypoprothrombinemia. Risk factors for this complication include poor nutritional status, renal failure, cancer, and ileus. For cefotaxime, a non-N-methylthiotetrazole-containing antibiotic, the average prolongation of prothrombin time from pretherapy values was shown to be 0.5 second (range, 0.0 to 2.5 seconds) in adults hospitalized for treatment of severe pneumonia.5 Taking all these points into consideration, we believe that it is possible but
unlikely that the prolonged prothrombin the use of cefotaxime in our patient.
time
June 1991 Heart Journal
was associated
Thomas Riggs, MD of Pediatric Cardiology Bishara J. Freij, MD of Pediatric Infectious Diseases Department of Pediatrics William Beaumont Hospital Royal Oak, Mich. 48073-6769
Division Division
1. Riggs T. Cardiomyopathy and pulmonary emboli in terminal Duchenne’s muscular dystrophy. AM HEART J 1990;119:690-3. 2. Elks J. Appendix I: structural formulae and nomenclature of the cephalosporin antibiotics. Drugs 1987;34(suppl 2):240-6. 3. Kucers A, Bennett NM. The use of antibiotics: a comprehensive review with clinical emphasis. 4th ed. Philadelphia: JB Lippincott Co, 1987:459-60. 4. Lipsky JJ. Antibiotic-associated hypoprothrombinaemia. J Antimicrob Chemother 1988;21:281-300. 5. Nichols RL, Wikler MA, McDevitt JT, Lentnek AL, Hosutt JA. Coagulopathy associated with extended-spectrum cephalosporins in patients with serious infections. Antimicrob Agents Chemother 1987;31:281-5.
EXERCISE TEST IN CORONARY SPASM To the Editor: We would like to comment on the article by Caste110 et al.’ in the February 1990 issue of the JOURNAL, in which it was stated that exercise tests in patients with coronary spasm resulted in the ST segment changes in only 507; of these patients and that this constitutes a relevant finding in patients with fixed coronary obstructions. It is well known that frequency of positive exercise test results in patients with Prinzmetal’s angina is between 10% and 30%. Exercise test findings in patients with coronary spasm have been studied by several investigators.2-4 It was found that in patients with a previous diagnosis of coronary spasm, exercise test results were more likely to be positive when there was significant atherosclerotic obstruction. Therefore since negative exercise test results are common in patients with variant angina, it is necessary to use other means to provoke ischemia. For this reason we have used ingestion of cold water with exercise to detect patients who are likely to have coronary spasm.5 This test, in view of the results obtained and following other publications,sr 7 shows the usefulness of this method of provoking ECG changes with minimal risk in patients prone to coronary spasm. Miguel Perez de Juan Romero, MD Luis Fernandez Dominguez, MD General France, Hospital Prou. 147-Entresuelo, 32003 Orense, Spain REFERENCES
Caste110 R, Alegria E, Merino A, et al. The value of exercise testing in patients with coronary artery spasm. AM HEART J 1990;119:259. Caste110 R, Alegria E, Merino A, et al. Syndrome of coronary artery spasm of normal coronary arteries. Clinical and angiographic features. Angiology 1988;39:8. Caitman BR, Waters DD, Theroux P, et al. ST segment elevation and coronary spasm in response to exercise. Am J Cardiol 1981;47:1350.
Volume
121
Number
6.
Part
Letters
1
4. Waters DD, Szlachic J, Bourasa MG, et al. Exercise testing in patients with variant angina: results, correlation with clinical and angiographic features and prognostic significance. Circulation 1982;65:265. 5. Perez de Juan M, Marcuschamer J, Espinosa JS, et al. Prueba de esfuerzo con ingestion de agua fria. Resultados preliminares. Arch Inst Cardiol Mex 1989;59:55. 6. Marcuschamer J, Pbrez de Juan M, Castellano C, et al. Infarto de1 miocardio relacionado a la asociaci6n de esfuerzo y la ingesta de bebida fria. Arch Inst Cardiol Mex 1987; 57:223. 7. Maroto JM, Aguilera M, Mufioz ML, et al. Fibrilacibn ventricular por espasmo de1 tronco de la coronaria izquierda en mujer joven. Rev Esp Cardiol 1987;40:147.
REPLY To the Editor: We appreciate the comments of Drs. Miguel Perez De Juan and Dominguez. However, our study was not designed to analyze the diagnostic ability of exercise testing in patients with coronary artery spasm but to evaluate its usefulness in predicting the presence of fixed coronary artery obstruction in patients with active coronary artery spasm. Our results indicated that ST segment elevation was not useful for predicting coronary anatomy, whereas ST segment depression strongly suggested the presence of underlying fixed coronary artery lesions with a specificity of 87% and a positive predictive value of 89s.’ For diagnosis of coronary artery spasm, a number of noninvasive techniques have been proved to be more sensitive than exercise testing.2y3 The addition of cold water might be of interest in eliciting myocardial ischemia in these patients.
Ramon Castello, MD Diuision of Cardiology St. Louis University Medical Center 3635 Vista Ave. at Grand Blvd. PO Box 15250 St. Louis, MO. 63110-0250
gitation jet is seen. This also appears the aortic valve is closed.
VALVE MORPHOLOGY
frame,
since
Joram Glaser, MD Cardiology I/nit PO Box 3235 Shaare Zedek Medical Center Jerusalem, Israel
REPLY To the Editor: Dr. Glaser questions the timing of the echocardiographic frames shown in Figs. 1, A and 2 B of our recent article. Specifically he states that Fig. 1, A appears to be a diastolic frame because the aortic valve is closed. This ignores the fact that during isovolumic ventricular systole, both the aortic and mitral valves are closed. The ECG in Fig. 1, A shows that the frame was taken after the QRS complex, and furthermore pulsed Doppler spectral recordings showed holosystolic mitral regurgitation occurring at the same point in the cardiac cycle (as judged by the ECG). Thus this frame was indeed systolic. Fig. 2, B shows a posteriorly directed mitral regurgitation jet in a patient with anterior mitral leaflet prolapse. Again Dr. Glaser’s concern is prompted by the observation that the aortic valve is closed. However, it is well known that the low frame rate associated with Doppler color flow imaging results in some degree of temporal uncertainty regarding the timing of color flow jets in the cardiac cycle.2s 3 Several milliseconds are required for the instrument to interrogate, process, and display the information derived from multiple scan lines, such that temporally disparate events may overlap onto a single frame. Thus the patient shown in Fig. 2, B had systolic not diastolic mitral regurgitation, a fact that was confirmed by pulsed Doppler spectral recordings. We recognize that the echocardiographic findings of this study are better appreciated when viewed in real-time and that single-frame images may not fully demonstrate the abnormalities we encountered.
University
IN MITRAL PROLAPSE
to be a diastoiic
1845
Pediatric
REFERENCES
Caste110 R, Alegria E, Merino A, Fidalgo ML, Martinez-Car0 D. The value of exercise testing in patients with coronary artery spasm. AM HEART J 1990;119:259-63. Waters DD, Szlachic J, Bonan R, Miller DD, Dauwe F, Theroux P. Comparative sensitivity of exercise, cold pressor and ergonovine testing in provoking attacks of variant angina in patients with active disease. Circulation 1983;67: 310-5. Aoki M, Koyanagi S, Sakai K, Irie T, Takeshita A, Nakamura M, Nakagaki 0. Exercise-induced silent myocardial ischemia in patients with vasospastic angina. AM HEART J 1990; 119:551-66.
to the Editor
Paul A. Grayburn, MD Division of Cardiology of Texas Southwestern Medical School and VA Medical Center (1llA) 4500 S. Lancaster Rd. Dallas, Texas 75216
REFERENCES
1. Grayburn PA, Berk MR, Spain MG, Harrison MR, Smith MD, DeMaria AN. Relation of echocardiographic morphology of the mitral apparatus to mitral regurgitation in mitral valve prolapse: assessment by Doppler color flow imaging. AM HEART J 1990;119:1095. 2. Grayburn PA, Pryor SL. Pitfalls in the interpretation of color Doppler images due to limited temporal resolution. Echocardiography 1988;5:239. 3. Goldberg SJ. Relation between color Doppler-detected directional flow in a ventricular septal defect and frame rate. J Am Co11 Cardiol 1990;16:1445.
To the Editor: Grayburn et al., in the May 1990 issue of the JOURNAL, the relationship between morphology of the mitral valve tus and mitral regurgitation in mitral valve prolapse. In they describe abnormal leaflet coaptation. However, this to be a diastolic frame, since the aortic valve is closed and tral valve is open. In Fig. 2, B a posteriorly directed mitral
discuss apparaFig. 1, A appears the miregur-
ADENOSINE FOR SVT To the Editor: Articles on better treatment for termination praventricular tachycardia (SVT) published
of paroxysmal suin American litera-
Letters
to the Editor
American
of the molecule, and it has been suggested2 that this side chain my be responsible for hypoprothrombinemia and bleeding. Therefore it should be emphasize that patients receiving cephalosporin therapy should have their prothrombin time monitored, especially if they are elderly and chronically ill. Professor Saeed Ahmad, MD, FRCP, FACC Cardio-Diagnostic Clinique 1000 Brookside Dr. Fairmont. W. V. 26554
very with
REFERENCES
REFERENCES
1. Riggs T. Cardiomyopathy and pulmonary emboli in terminal Duchenne’s muscular dystrophy. AM HEART J 1990;119:690-3. 2. Neu HC. The in vitro activity, human pharmacology and clinical effectiveness of new antibiotics. Annu Rev Pharmacol Toxic01 1982;22:599-642.
REPLY To the Editor: The patient in question (case 1) did receive intravenous cefotaxime as treatment for a presumed lower respiratory infection; the patient was treated for several days before the prothrombin time was found to be prolonged.’ Since there had been no previous measurements of this patient’s prothrombin time, one cannot ascertain whether or not cefotaxime was associated with the observed prolongation of this hemostatic parameter. The cephalosporins are semisynthetic derivatives of a 7-aminocephalosporanic acid nucleus. The N-methylthiotetrazole side chain at position 3 of this nucleus, referred to by Dr. Ahmad, is present in only some of the cephalosporins currently in use, including cefamandole, cefoperazone, cefotetan, cefonicid, cefpiramide, cefmenoxime, cefmetazole, and moxalactam (an oxa-beta-lactam antibiotic, and is not a true cephalosporin). This side chain is not present in cefotaxime.2 Approximately 60% of a dose of cefotaxime is excreted in the urine in unchanged form within 24 hours. Urinary excretion of desacetylcefotaxime (the major product. of the hepatic metabolism of cefotaxime) and the M2 and Ma metabolites (products of desacetylcefotaxime transformation in the liver) accounts for an additional 29% and 6%) of an administered dose of cefotaxime, respectively. Biliary excretion usually accounts for only 0.01% to O.l?; of a cefotaxime dose.3 The tenet that antibiotic-associated hypoprothrombinemia is a consequence of inhibiting intestinal bacteria that are capable of vitamin K production, such as Escherichia cob and Bacteroides, remains unproved. Hypoprothrombinemia is primarily encountered in patients treated with N-methylthiotetrazole-containing cephalosporins, and it is generally believed that this moiety may inhibit the vitamin K-dependent gamma-carboxylation of glutamic acid residues in clotting factors II (prothrombin), VII, IX, and X, thereby leading to the appearance of inactive forms of these factors in plasma.4 It is also worth noting that administration of N-methylthiotetrazole-containing cephalosporins to healthy volunteers does not lead to hypoprothrombinemia. Risk factors for this complication include poor nutritional status, renal failure, cancer, and ileus. For cefotaxime, a non-N-methylthiotetrazole-containing antibiotic, the average prolongation of prothrombin time from pretherapy values was shown to be 0.5 second (range, 0.0 to 2.5 seconds) in adults hospitalized for treatment of severe pneumonia.5 Taking all these points into consideration, we believe that it is possible but
unlikely that the prolonged prothrombin the use of cefotaxime in our patient.
time
June 1991 Heart Journal
was associated
Thomas Riggs, MD of Pediatric Cardiology Bishara J. Freij, MD of Pediatric Infectious Diseases Department of Pediatrics William Beaumont Hospital Royal Oak, Mich. 48073-6769
Division Division
1. Riggs T. Cardiomyopathy and pulmonary emboli in terminal Duchenne’s muscular dystrophy. AM HEART J 1990;119:690-3. 2. Elks J. Appendix I: structural formulae and nomenclature of the cephalosporin antibiotics. Drugs 1987;34(suppl 2):240-6. 3. Kucers A, Bennett NM. The use of antibiotics: a comprehensive review with clinical emphasis. 4th ed. Philadelphia: JB Lippincott Co, 1987:459-60. 4. Lipsky JJ. Antibiotic-associated hypoprothrombinaemia. J Antimicrob Chemother 1988;21:281-300. 5. Nichols RL, Wikler MA, McDevitt JT, Lentnek AL, Hosutt JA. Coagulopathy associated with extended-spectrum cephalosporins in patients with serious infections. Antimicrob Agents Chemother 1987;31:281-5.
EXERCISE TEST IN CORONARY SPASM To the Editor: We would like to comment on the article by Caste110 et al.’ in the February 1990 issue of the JOURNAL, in which it was stated that exercise tests in patients with coronary spasm resulted in the ST segment changes in only 507; of these patients and that this constitutes a relevant finding in patients with fixed coronary obstructions. It is well known that frequency of positive exercise test results in patients with Prinzmetal’s angina is between 10% and 30%. Exercise test findings in patients with coronary spasm have been studied by several investigators.2-4 It was found that in patients with a previous diagnosis of coronary spasm, exercise test results were more likely to be positive when there was significant atherosclerotic obstruction. Therefore since negative exercise test results are common in patients with variant angina, it is necessary to use other means to provoke ischemia. For this reason we have used ingestion of cold water with exercise to detect patients who are likely to have coronary spasm.5 This test, in view of the results obtained and following other publications,sr 7 shows the usefulness of this method of provoking ECG changes with minimal risk in patients prone to coronary spasm. Miguel Perez de Juan Romero, MD Luis Fernandez Dominguez, MD General France, Hospital Prou. 147-Entresuelo, 32003 Orense, Spain REFERENCES
Caste110 R, Alegria E, Merino A, et al. The value of exercise testing in patients with coronary artery spasm. AM HEART J 1990;119:259. Caste110 R, Alegria E, Merino A, et al. Syndrome of coronary artery spasm of normal coronary arteries. Clinical and angiographic features. Angiology 1988;39:8. Caitman BR, Waters DD, Theroux P, et al. ST segment elevation and coronary spasm in response to exercise. Am J Cardiol 1981;47:1350.
Volume
121
Number
6.
Part
Letters
1
4. Waters DD, Szlachic J, Bourasa MG, et al. Exercise testing in patients with variant angina: results, correlation with clinical and angiographic features and prognostic significance. Circulation 1982;65:265. 5. Perez de Juan M, Marcuschamer J, Espinosa JS, et al. Prueba de esfuerzo con ingestion de agua fria. Resultados preliminares. Arch Inst Cardiol Mex 1989;59:55. 6. Marcuschamer J, Pbrez de Juan M, Castellano C, et al. Infarto de1 miocardio relacionado a la asociaci6n de esfuerzo y la ingesta de bebida fria. Arch Inst Cardiol Mex 1987; 57:223. 7. Maroto JM, Aguilera M, Mufioz ML, et al. Fibrilacibn ventricular por espasmo de1 tronco de la coronaria izquierda en mujer joven. Rev Esp Cardiol 1987;40:147.
REPLY To the Editor: We appreciate the comments of Drs. Miguel Perez De Juan and Dominguez. However, our study was not designed to analyze the diagnostic ability of exercise testing in patients with coronary artery spasm but to evaluate its usefulness in predicting the presence of fixed coronary artery obstruction in patients with active coronary artery spasm. Our results indicated that ST segment elevation was not useful for predicting coronary anatomy, whereas ST segment depression strongly suggested the presence of underlying fixed coronary artery lesions with a specificity of 87% and a positive predictive value of 89s.’ For diagnosis of coronary artery spasm, a number of noninvasive techniques have been proved to be more sensitive than exercise testing.2y3 The addition of cold water might be of interest in eliciting myocardial ischemia in these patients.
Ramon Castello, MD Diuision of Cardiology St. Louis University Medical Center 3635 Vista Ave. at Grand Blvd. PO Box 15250 St. Louis, MO. 63110-0250
gitation jet is seen. This also appears the aortic valve is closed.
VALVE MORPHOLOGY
frame,
since
Joram Glaser, MD Cardiology I/nit PO Box 3235 Shaare Zedek Medical Center Jerusalem, Israel
REPLY To the Editor: Dr. Glaser questions the timing of the echocardiographic frames shown in Figs. 1, A and 2 B of our recent article. Specifically he states that Fig. 1, A appears to be a diastolic frame because the aortic valve is closed. This ignores the fact that during isovolumic ventricular systole, both the aortic and mitral valves are closed. The ECG in Fig. 1, A shows that the frame was taken after the QRS complex, and furthermore pulsed Doppler spectral recordings showed holosystolic mitral regurgitation occurring at the same point in the cardiac cycle (as judged by the ECG). Thus this frame was indeed systolic. Fig. 2, B shows a posteriorly directed mitral regurgitation jet in a patient with anterior mitral leaflet prolapse. Again Dr. Glaser’s concern is prompted by the observation that the aortic valve is closed. However, it is well known that the low frame rate associated with Doppler color flow imaging results in some degree of temporal uncertainty regarding the timing of color flow jets in the cardiac cycle.2s 3 Several milliseconds are required for the instrument to interrogate, process, and display the information derived from multiple scan lines, such that temporally disparate events may overlap onto a single frame. Thus the patient shown in Fig. 2, B had systolic not diastolic mitral regurgitation, a fact that was confirmed by pulsed Doppler spectral recordings. We recognize that the echocardiographic findings of this study are better appreciated when viewed in real-time and that single-frame images may not fully demonstrate the abnormalities we encountered.
University
IN MITRAL PROLAPSE
to be a diastoiic
1845
Pediatric
REFERENCES
Caste110 R, Alegria E, Merino A, Fidalgo ML, Martinez-Car0 D. The value of exercise testing in patients with coronary artery spasm. AM HEART J 1990;119:259-63. Waters DD, Szlachic J, Bonan R, Miller DD, Dauwe F, Theroux P. Comparative sensitivity of exercise, cold pressor and ergonovine testing in provoking attacks of variant angina in patients with active disease. Circulation 1983;67: 310-5. Aoki M, Koyanagi S, Sakai K, Irie T, Takeshita A, Nakamura M, Nakagaki 0. Exercise-induced silent myocardial ischemia in patients with vasospastic angina. AM HEART J 1990; 119:551-66.
to the Editor
Paul A. Grayburn, MD Division of Cardiology of Texas Southwestern Medical School and VA Medical Center (1llA) 4500 S. Lancaster Rd. Dallas, Texas 75216
REFERENCES
1. Grayburn PA, Berk MR, Spain MG, Harrison MR, Smith MD, DeMaria AN. Relation of echocardiographic morphology of the mitral apparatus to mitral regurgitation in mitral valve prolapse: assessment by Doppler color flow imaging. AM HEART J 1990;119:1095. 2. Grayburn PA, Pryor SL. Pitfalls in the interpretation of color Doppler images due to limited temporal resolution. Echocardiography 1988;5:239. 3. Goldberg SJ. Relation between color Doppler-detected directional flow in a ventricular septal defect and frame rate. J Am Co11 Cardiol 1990;16:1445.
To the Editor: Grayburn et al., in the May 1990 issue of the JOURNAL, the relationship between morphology of the mitral valve tus and mitral regurgitation in mitral valve prolapse. In they describe abnormal leaflet coaptation. However, this to be a diastolic frame, since the aortic valve is closed and tral valve is open. In Fig. 2, B a posteriorly directed mitral
discuss apparaFig. 1, A appears the miregur-
ADENOSINE FOR SVT To the Editor: Articles on better treatment for termination praventricular tachycardia (SVT) published
of paroxysmal suin American litera-