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or nitrates on left ventricular function in angina pectoris
LEllERS EFFECT OF NIFEDIPINE ALONE VERSUS IN COMBINATION WITH BETA BLOCKERS AND/OR NITRATES ON LEFT VENTRICULAR FUNCTION IN ANGINA PECTORIS Although this letter is in reference to an article, published in October, 1982, by Zacca et al,’ the point which I wish to draw attention to may well apply to future articles published in the Journal. The title of the paper in question is “The Effect of Nifedipine on Exercise-Induced Left Ventricular Dysfunction and Myocardial Hypoperfusion in Stable Angina.” Neither the title nor the abstract mention the fact that all patients were taking nitrates or beta blocking agents or both. Hence, the title is therefore inaccurate and misleading in my opinion. Furthermore, Figure 1, on page 691, is similarly misleading in attributing to nifedipine the effects depicted in that figure. In their discussion, the authors again attribute their findings to nifedipine, failing to mention concomitant therapy. The conclusions drawn in the abstract and in the text fail to mention the possibility of the combined effect of the test drug with the preexisting antianginal regimen. AnthonyMiller, MD, FRCP(C) Winnipeg,Manitoba,Canada 1. Zacca NM, Verani MS, Chahlna RA, Miller RR. Effect of nifedlpine on exercise-induced left ventricular dysfuwtlon and myocatdiil hypoperfusion in stable angina. Am J Cardiol 1982;50:889-895.
REPLY: Dr. Miller believes we should not attribute our results to the effects of nifedipine alone, since he feels some of these results could have been influenced by nitrates and/or beta blockers. Unfortunately, he overlooked our statement on lines 4 and 5 of the section on Material and Methods, where we stated that both of these drugs “. were withheld for at least 72 hours before the investigation.” Of course, one should not have any significant persistent effect of either beta blockers or nitrates’ after discontinuing them for 72 hours. Thus, we believe that our findings represent true effects of nifedipine. Nadlm 1. Zacca, MD Marlo S. Verani, MD
Houston, Texas 1. Romspnolll A, Keats AS. Plasma and atrial propranolol after preoperative withdrawal. Circulation 1975;52: 1123-1127.
MYOCARDIAL METABOLIC ALTERATIONS AFTER CONTRAST ANGIOGRAPHY Wisneski et al1 recently presented convincing evidence of the deleterious effects of contrast medium on myocardial metabolism. There is little doubt that these findings have important implications in the interpretation of some studies reporting changes in myocardial metabolism. However, the authors seriously misquoted our study.2 Angiography was not performed during this study, reported by Wisneski et al. A deleterious effect of contrast medium on myocardial metabolism has always been considered to be a potential
FIGURE 1. Pericardium (P) is outlined by subepicardial adipose tissue (SEAT) and mediastinal fat (MF).
problem, and we have accordingly performed all metabolic studies on a separate occasion from diagnostic angiography. Furthermore, if small amounts of contrast medium are used in positioning of the coronary sinus catheter our protocol allows >30 minutes to elapse before making any hemodynamic or metabolic measurements. These details were stressed in the paper3 that followed our misquoted abstract and thus emphasizes the need to reference more formal publications. G. Bergman, BSc, MRCP D. E. Jewltt, FRCP London,England 1. Wlsnmkl JA, Gerlz EW, Nease R, SW WJ, S&tow DJ, Adams JR, Beaudry JP. Myocardial metabolic alterations after contrast angiography. Am J Car&o1 1982; 50:239-245. 2. esFpman 0, Atfdnsom L, MelcaMe JM, Jackson N, JewlIt DE. Enhanced myocardial carbohydrate utilisation after UK25842: potential protective effect in ischaemic heart disease (abstr). Circulation 1979;59,6O:suppl ll:ll82. 3. Suqnan 0, AtkInson L, Mefcalfe JM, Jackson N, Jewfff DE. Beneficial effects of enhanced myocardial carbohydrate utillsation after oxfanicine (lhydroxyphenylglycine) in angina pectoris. Eur Heart J 1980:1:247253.
OT > QS2 SYNDROME AS A MORTALITY RISK FACTOR IN CORONARY HEART DISEASE The recent article by Boudoulas et al’ described QT > QS, as a mortality risk indicator for patients with coronary artery disease. QT > QS, was described by Heggli$ (perhaps not noted by the authors, since the text is in German), in a different context, namely hypokalemia. Both QT prolongation and QS, shortening was present, as also observed in Boudoulas’s patients. Diuretics were a (moderate) risk factor in the coronary nonsurvivors with QT > QS,. It would be interesting if the authors have data concerning serum electrolytes, in particular, hypokalemia which might account for this finding and predispose to (fatal) dysrhythmias. David L. Lubell, MD Chicago,Illinois 1152
1. Sourbulas H, Yang, HS, O’NaHl W, Sowen R, Welssfw A. OT > OS2 syndrome: a new nwtality risk Indicator in coronary artery disease. Am J Cardiol 1982:50: 1229-1235. 2. He##ln R. Differential diagnose innerer KrankheiWn. Stuttgart: Georg Thieme Verlag. 1956:218.
REPLY: We appreciate Dr. Lubell’s interest. The QT-QS2 relation has been of special interest to our laboratory for several years.lA The work by Hegglins, therefore, which is also published in English, is well known to us.5 We are also aware of other conditions that may influence the QT-QS2 relation, but the clinical significance of those conditions has not been defined. Our study was directly related to patients with coronary artery disease and, more specifically, to patients who have recovered from a myocardial infarction. The clinical significance of QT > QSz in patients with coronary artery disease without previous infarction and in patients with recent myocardial infarction remains to be established. Thus, the QT > QS2 syndrome as a risk prognostic indicator is applicable at present to patients who have recovered from remote myocardial infarction. In comparing patients with or without QT > QSz, the frequency of therapy with diuretics was not different. Fifty-five percent of patients with and 50% of patients without QT > QS, were treated with diuretics (Table II). Therapy with diuretics was more common in nonsurvivors than in survivors (75 vs 45%, p = 0.03, Table III), regardless of the QT-Q& relation. Multivariate analysis by the proportional hazards general linear model demonstrated that therapy with diuretics was not an independent risk prognostic indicator. Thus, while diuretic therapy may be a risk indicator, it does not appear to act independently. Further, the frequency of QT > QS, was not related to diuretic therapy. Periodic potassium determinations were not available, and thus it is unknown whether any of the deaths are related to hypokalemia. Among the 20 patients with QT >Qs, the QT corrected for heart rate (QTc) tended to cluster within the upper range of normal, whereas the QS, corrected for heart rate (Q&l) fell within the lower range of normal (Fig. 5). Abnormal lengthening of the QTc
REPLY: Dr. Miller believes we should not attribute our results to the effects of nifedipine alone, since he feels some of these results could have been influenced by nitrates and/or beta blockers. Unfortunately, he overlooked our statement on lines 4 and 5 of the section on Material and Methods, where we stated that both of these drugs “. were withheld for at least 72 hours before the investigation.” Of course, one should not have any significant persistent effect of either beta blockers or nitrates’ after discontinuing them for 72 hours. Thus, we believe that our findings represent true effects of nifedipine. Nadlm 1. Zacca, MD Marlo S. Verani, MD
Houston, Texas 1. Romspnolll A, Keats AS. Plasma and atrial propranolol after preoperative withdrawal. Circulation 1975;52: 1123-1127.
MYOCARDIAL METABOLIC ALTERATIONS AFTER CONTRAST ANGIOGRAPHY Wisneski et al1 recently presented convincing evidence of the deleterious effects of contrast medium on myocardial metabolism. There is little doubt that these findings have important implications in the interpretation of some studies reporting changes in myocardial metabolism. However, the authors seriously misquoted our study.2 Angiography was not performed during this study, reported by Wisneski et al. A deleterious effect of contrast medium on myocardial metabolism has always been considered to be a potential
FIGURE 1. Pericardium (P) is outlined by subepicardial adipose tissue (SEAT) and mediastinal fat (MF).
problem, and we have accordingly performed all metabolic studies on a separate occasion from diagnostic angiography. Furthermore, if small amounts of contrast medium are used in positioning of the coronary sinus catheter our protocol allows >30 minutes to elapse before making any hemodynamic or metabolic measurements. These details were stressed in the paper3 that followed our misquoted abstract and thus emphasizes the need to reference more formal publications. G. Bergman, BSc, MRCP D. E. Jewltt, FRCP London,England 1. Wlsnmkl JA, Gerlz EW, Nease R, SW WJ, S&tow DJ, Adams JR, Beaudry JP. Myocardial metabolic alterations after contrast angiography. Am J Car&o1 1982; 50:239-245. 2. esFpman 0, Atfdnsom L, MelcaMe JM, Jackson N, JewlIt DE. Enhanced myocardial carbohydrate utilisation after UK25842: potential protective effect in ischaemic heart disease (abstr). Circulation 1979;59,6O:suppl ll:ll82. 3. Suqnan 0, AtkInson L, Mefcalfe JM, Jackson N, Jewfff DE. Beneficial effects of enhanced myocardial carbohydrate utillsation after oxfanicine (lhydroxyphenylglycine) in angina pectoris. Eur Heart J 1980:1:247253.
OT > QS2 SYNDROME AS A MORTALITY RISK FACTOR IN CORONARY HEART DISEASE The recent article by Boudoulas et al’ described QT > QS, as a mortality risk indicator for patients with coronary artery disease. QT > QS, was described by Heggli$ (perhaps not noted by the authors, since the text is in German), in a different context, namely hypokalemia. Both QT prolongation and QS, shortening was present, as also observed in Boudoulas’s patients. Diuretics were a (moderate) risk factor in the coronary nonsurvivors with QT > QS,. It would be interesting if the authors have data concerning serum electrolytes, in particular, hypokalemia which might account for this finding and predispose to (fatal) dysrhythmias. David L. Lubell, MD Chicago,Illinois 1152
1. Sourbulas H, Yang, HS, O’NaHl W, Sowen R, Welssfw A. OT > OS2 syndrome: a new nwtality risk Indicator in coronary artery disease. Am J Cardiol 1982:50: 1229-1235. 2. He##ln R. Differential diagnose innerer KrankheiWn. Stuttgart: Georg Thieme Verlag. 1956:218.
REPLY: We appreciate Dr. Lubell’s interest. The QT-QS2 relation has been of special interest to our laboratory for several years.lA The work by Hegglins, therefore, which is also published in English, is well known to us.5 We are also aware of other conditions that may influence the QT-QS2 relation, but the clinical significance of those conditions has not been defined. Our study was directly related to patients with coronary artery disease and, more specifically, to patients who have recovered from a myocardial infarction. The clinical significance of QT > QSz in patients with coronary artery disease without previous infarction and in patients with recent myocardial infarction remains to be established. Thus, the QT > QS2 syndrome as a risk prognostic indicator is applicable at present to patients who have recovered from remote myocardial infarction. In comparing patients with or without QT > QSz, the frequency of therapy with diuretics was not different. Fifty-five percent of patients with and 50% of patients without QT > QS, were treated with diuretics (Table II). Therapy with diuretics was more common in nonsurvivors than in survivors (75 vs 45%, p = 0.03, Table III), regardless of the QT-Q& relation. Multivariate analysis by the proportional hazards general linear model demonstrated that therapy with diuretics was not an independent risk prognostic indicator. Thus, while diuretic therapy may be a risk indicator, it does not appear to act independently. Further, the frequency of QT > QS, was not related to diuretic therapy. Periodic potassium determinations were not available, and thus it is unknown whether any of the deaths are related to hypokalemia. Among the 20 patients with QT >Qs, the QT corrected for heart rate (QTc) tended to cluster within the upper range of normal, whereas the QS, corrected for heart rate (Q&l) fell within the lower range of normal (Fig. 5). Abnormal lengthening of the QTc