Thiazide therapy and ventricular arrhythmias

FORUM-LETTERS

TO THE EDITOR

ECHOGRAPHIC LV WALL MOTION IN MITRAL PROLAPSE To the Editor: Doi et al.’ observed on M-mode echocardiography an abnormal late systolic “dip” in posterior wall motion, either slightly below or at the mitral valve in all patients with mitral valve prolapse (30 cases). In nine of these patients a dip was also present at the chordal level. A similar investigation has been performed by us?,3 on 150 cases of idiopathic mitral valve prolapse (IMVP) free from other heart disease and without left ventricular volume overload; 200 normal subjects were considered as controls. On the endocardium of the left ventricular posterior wall many types of alterations were found in 65”O of patients with IMVP, namely: late systolic dip (type 1) in 85O’b of these patients; early diastolic dip pattern (type 3) in 7 O(. Irregulari(type 2) in 8”1~ ; and a plateau ties of the posterior wall, almost exclusively of type 1. were present in 15Crj of controls. In our opinion, the dips that Doi et al. found slightly below or at the mitral valve (Fig. 2 of their study) do not belong to the left, ventricular posterior wall, but correspond to the auriculo-ventricular junction. According to our experience: (1) The late systolic dip of the left ventricular posterior wall is frequently but not exclusively observed in patients with IMVP, being present also in healthy individuals. (2) The late systolic dip at the chordal level is the most common but not the single echocardiographic alteration to be found on the endocardium of the left ventricular posterior wall. (3) At variance with observations by Doi et al., in our series we did not find any correlation between the presence of a dip at the chordal level and the occurrence of transient cerebral ischemic attacks or embolic episodes. Franc-o Casarza, M.D. Department of Cardiology S. Carlo Rorromeo Hospital via Pi0 II no. 3 20100 Milan, Italy Erminia Giagnoni, M.D. Consorzio Provinciale Antitubercolare Vialc Zara n’. 81 20100 Milan, Italy REFERENCES 1. Doi YL, Spodick DH, Hamashige N, Yonezawa Y, Sugiura T, Bishop RL: Echocardiographic study of left ventricular wall motion in mitral valve prolapse. AM HEART J 108:105, 1984. 2. Casazza F, Disco T, Giagnoni E, Morabito A, Sachero A, Saviotti M: Caratteristiche morfofunzionali de1 ventricolo sinistro nel prolasso idiopatico della mitrale. Atti Congress0 Nazionale di Cardiologia, Bologna, 1983, p 141. 3. Casazza F, Disco T, Giagnoni E, Morabito A, Sachero A, Saviotti M: Ipercinesia isolata de1 setto interventricolare nel prolasso idiopatico della mitrale. Atti Congress0 Nazionale di Cardiologia, Firenze, 1984, p 263.

REPLY To the Editor: I am interested to read the comments and observations of Dr. Casazza et al., since it is encouraging to have one’s data confirmed by other investigators. The only difference in the results of the 1214

two investigations may lie in how one defines a “dip” in ventricular wall motion. We did not find any abnormal wall motion at chordal level during systole in normal controls, since we defined and included the “dip” only when there was definite downward motion of the posterior wall during systole, thus excluding slight changes which may be observed in the normals of Dr. Casazza et al. (irregularities of the posterior wall) and in patients with mitral valve prolapse (plateau pattern, their type 3). In addition, it is difficult for me to imagine how Casazza et al. correlate the dip during diastole (their type 2) to mitral valve prolapse, which is mainly an event during systole. We agree that the dip in posterior wall motion slightly below or at mitral valve level could correspond to the atrioventricular junction as we stated in our paper; “it is difficult to exclude the possibility of seeing a composite of ventricular and atria1 wall at end systole within the sound beam at this level.” This dip at mitral valve level should, therefore, be assessed with caution and overreading of this finding should be avoided. Prevalence of embolic episodes seems very low, as Casazza et al. have observed in their series, although we have seen two more patients with mitral valve prolapse who developed transient cerebral ischemic attack and hemiparesis since the completion of our prevoius study. Further study may be needed to answer this specific question: whether the prevalence of a dip at chordal level correlates to the episodes of transient ischemic attack. Yoshinori L. Doi, M.D. Section of Cardiolog> Kochi Medical School Hospital Kochi 781-51, Japan

THIAZIDE THERAPY AND VENTRICULAR ARRHYTHMIAS To the Editor: In a recent issue of the AMERICANHEART JOURNAL,a study by Dr. Papademetriou et al. concludes “that thiazide therapy does not increase ventricular arrhythmias either in patients with or without LVH.“’ We would agree with the authors that recently published studies associate the use of diuretics with ventricular arrhythmias2 or sudden death.’ As diuretics are a commonly prescribed drug for the treatment of hypertension, it is crucial that this association be further investigated. However, statistical analysis of the results of Papademetriou et al. indicates that their study is of insufficient size to reach their conclusions. In order to calculate power for the paired t test in their study, one needs to estimate the standard error of the mean difference of PVC&our for patients before and after treatment with hydrochlorothiazide. This estimate is not given in the article. However, by the use of the before and after standard deviations given in Table II of 9.9 PVC&our (premature ventricular contractions per hour) before treatment and 16.6 PVC&our after treatment with hydrochlorothiazide, and the conservative assumption that the before and after values have a correlation coefficient of 0.5, yields an estimate of the standard deviation of the difference of 13.7. By means of the standard power calculation method for the paired t test, we calculate that at alpha = 0.05 (one-sided) with a sample size of 18, the true difference that could be detected with power = 0.80 is 8.3 PVC&our. Furthermore, in their study, there is only approximately a 50% chance of detecting a doubling of the

Volume 111 Number 6

Letters

observed pretreatment mean of 5.7 PVC&our after treatment with hydrochlorothiazide. Smaller, but potentially significant differences in numbers of PVCs would be even less likely to be detected. Thus, we must conclude that while Dr. Papademetriou et al. raise a very important issue, their study was too small to detect a substantial difference in PVC&our before and after treatment with hydrochlorothiazide. In addition, it is of interest that they treated their patients for 4 weeks. The small sample size and short duration of treatment may partially explain why their results are at variance with that reported by the Medical Research Council,’ which did find increased PVCs after longterm (average, 24 months) thiazide treatment when compared to placebo in a group of 164 nonrandomized subjects. Clearly, more studies are needed on this very important issue. David

Siegel, M.D., M.P.H. Dennis M. Black, M.A. Department of Epidemiology University of California San Francisco, CA 94110

REPLY To the Editor:

Drs. Siegel and Black express concern about the sample size in our recently published study in THE JOURNAL.’Their concern is based on statistical analysis of only the simplest type of arrhythmias (premature ventricular contractions, PVCs) in only one of the groups of patients studied (left ventricular hypertrophy, LVH). To further clarify the subject, the following data are provided: The mean and standard deviation of the difference was 1.4 + 16.1 in the LVH group, 0.9 + 4.5 in the non-LVH group, and 1.2 * 12.5 for all patients. These values give us an 80% statistical power to detect a change of 9.8 PVCs/hr in the LVH group, 3.2 PVCslhr in the non-LVH group, and 5.7 PVC&r in the group as a whole. Even though small changes in the number of PVCs would not have been detected, the significance of such changes as an independent risk factor for sudden death is questionable. More complex arrhythmias weigh much more heavily as predictors of sudden death. These arrhythmias were decreased following hydrochlorothiazide therapy in our study. In the LVH group, we observed 29 couplets and four runs of ventricular tachycardia at baseline, and 10 couplets but no runs of ventricular tachycardia after hydrochlorothiazide. These results remain essentially unchanged in the expanded group of 44 patients that we have so far completed. The authors of the above letter also make a point about the duration of diuretic therapy. The hypothesis proposed by some investigators is that thiazide diuretics may cause arrhythmias by inducing hypokalemia. Potassium changes, however, occur and stabilize within the first few days of diuretic therapy.Z For this reason, diuretic therapy for 4 weeks has in general been considered sufficient enough time for changes in arrhythmias to manifest.

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The MRC trial’ indeed showed some increase in PVCs in a subgroup of diuretic-treated patients as compared to placebotreated patients. However, this group is not comparable to the patients in our study because they had no baseline recordings. Another group of patients in the same study that had monitoring before and after diuretic therapy showed no change in the incidence of arrhythmias. More importantly, the final report of the MRC trial’ did not reveal any adverse effect of diuretic therapy on cardiovascular mortality. Several other recently published, large-scale trials5-’ failed to show any adverse cardiovascular effects of long-term diuretic therapy. In particular, data from the Glasgow Blood Pressure Clinic’ showed a significantly decreased mortality in patients with LVH, treated with regimens which included thiazide diuretics for an average of 6.5 years. In conclusion, we stand firm in our belief that diuretic therapy is a safe and effective way of treatment for patients with essential hypertension.

Veterans

REFERENCES

Papademetriou V, Price M, Notargiacomo A, Gottdiener J, Fletcher RD, Freis ED: Effect of diuretic therapy on ventricular arrhythmias in hypertensive patients with or without left ventricular hypertrophy. AM HEART J 110:595, 1985. Whelton PK: Diuretics and arrhythmias in the Medical Research Council trial. Drugs 28(suppl 1):54, 1984. Multiple Risk Factor Intervention Trial: Risk factor changes and mortality results. JAMA 248:1465, 1982.

to the Editor

Vasilios Papademetriou, M.D. Department of Cardiology Administration Medical Center 50 Irving Street, NW Washington, DC 20422

REFERENCES 1.

Papademetriou V, Price M, et al: Effect of diuretic therapy on ventricular arrhythmias in hypertensive patients with or without left ventricular hynertronhy. AM HEART J llOz595, __ __ 1985.

2. Morgan DB, Davidson C: Hypokalemia and diuretics: An analvsis of nublications. Br Med J 1:905. 1980. 3. Medical Research Council Working Party on Mild to Moderate Hypertension: Mild hypertension trial. Br Med J 287:1249, 1983. 4. Medical Research Council Working Party on Mild to Moderate Hypertension: Principal results. Br Med J 291:97, 1985. 5. Miettinen TA, Huttunen JK, et al: Multifactorial primary prevention of cardiovascular disease in middle-aged men. JAMA 254:2097, 1985. 6. Amery A, Brixko P, et al: Mortality and morbidity results from the Euronean Working Partv on High Blood Pressure in the Elderly trial. Lancet 13349, -1985. 7. Dunn FG, Isles CG, et al: The influence of left ventricular hypertrophy on mortality in the Glasgow blood pressure clinic (abstr). Circulation 72:111, 1985.

TYPE A BEHAVIOR AND MYOCARDIAL INFARCTION To the Editor:

In the recent study by Friedman et al.,’ a 3-year cumulative cardiac recurrence rate of 7.2% was found in participants who initially were enrolled in type A behavioral counseling. This was significantly less than the 13% observed in patients who received only cardiologic counseling. These results are based on data from their Table IV (p. 244). A closer look at the data reported in this table, however, reveals contradictory results. In this table the data are presented for all patients including treatment failures (“intention-to-treat principle”) and for those patients who remained active in treatment. Therefore it is also possible to determine rehabilitation outcome for treatment failures. In the enclosed Table I the data from Friedman et al. are presented again, here for subjects who received treatment and for those who did not, for both type A and cardiologic counseling. Combining both groups and comparing treatment vs treatment failure groups results in x 2 = 15.1, df = 1, p < 0.0003. The 3-year