SYSTEMIC HYPERTENSION Risk of Ventricular Arrhythmias in Hypertensive Men with Left Ventricular Hypertrophy David Siegel, MD, MPH, Melvin D. Cheitlin, MD, Dennis M. Black, PhD, Dana Seeley, MS, Norman Hearst, MD, MPH, and Stephen B. l-lulley, MD, MPH The echocardiographic predictors of ventricular arrhythmias are reported for the Hypertension Arrhythmia Reduction Trial. Men with mild hyper- tension were withdrawn from their diuretic therapy and repleted with 40 mEq/day of oral potassium and 20 mEq/day of oral magnesium for 1 month. M-mode echocardiography and 24-hour continuous ambulatory eledrocardiography were performed on 123 men, mean age 62 years. Forty-eight men (39%) had echocardiiaphic evidence of left ven- tricular (LV) hypertrophy defined as an LV mass index >134 g/m* and this ffnding was not related to the presence of LV hypertrophy on dectrocar- diogram or to age. Men who had echocardiiaphic LV hypertrophy were more likely than men without echocardiographic LV hypertrophy to have 130 ventricular premature complexes (VPCs)/hr (odds ratio = 2.7; 95% confidence interval = 0.9,&O), multiform extrasystoles (odds ratio = 1.7; confi- dence interval = 0.8,3.7), episodes of ventricular tachycardia (odds ratio = 2.3; confidence interval = 0.7,7.1) and the combination of frequent (130 VPCs/hr) or complex (ventricular couplets, multi- form extrasystoles or episodes of ventricular tachy- cardia) ventricular arrhythmia (odds ratio = 1.7; confidence interval = 0.8,3.5). Similar associations between echocardiographic LV hypertrophy and ventricular arrhythmias were observed on 24-hour tracings obtained on entry to the study (before ele&olyte repletion) in the 96 men who were tak- ing diuretics at this time. The combination of a fre- quent or complex arrhythmia was also more com- mon in men aged 60 to 70 compared to men aged 35 to 59 (odds ratio = 3.4; confidence interval = 1.4,8.2). These findings suggest that ventricular arrhythmias occur more commonly in older hyper- tensive men and in hypertensive men with echocar- diographic LV hypertrophy. (Am J Cardid l-,65:742-747) From the Departments of Epidemiology and Biostatistics, Medicine, and Family and Community Medicine, University of California, San Francisco, California. This study was supported in part by grant HL 36821 from the National Institutes of Health, Bethesda, Maryland. Manuscript received September 25, 1989; revised manuscript received November 10,1989, and accepted November 15. Address for reprints: David Siegel, MD, MPH, Prevention Sciences Group, 74 New Montgomery, San Francisco, California 94105. L eft ventricular (LV) hypertrophy, whether de- fined by electrocardiographic criteria, chest x-rays or echocardiography, is associated with an in- creased risk of heart attack and sudden death.’ Hyper- tensive patients with LV hypertrophy by electrocardio- graphic criteria who are not receiving treatment have been shown to have significantly more ventricular ec- topy than either hypertensive patients without electro- cardiographic evidence of LV hypertrophy or normoten- sive patients.* It is not known whether this effect is also found in hypertensive patients with LV hypertrophy di- agnosed by echocardiography. One recent study found that patients with LV hyper- trophy by electrocardiographic criteria had significantly more premature ventricular contractions and more com- plex (higher Lown’s class) ventricular ectopy than hy- pertensive subjects without LV hypertrophy or with LV hypertrophy diagnosed only by echocardiographic crite- ria.3,4 However, tlie investigators used measurements of posterior wall thickness, septal wall thickness and rela- tive wall thickness to define echocardiographic LV hy- pertrophy. This definition has not been found to corre- late as well with clinical and necropsy LV hypertrophy as that calculated by LV mass index.5 Thus, many of the individuals included in the LV hypertrophy group in this study did not meet LV mass criteria of LV hyper- trophy. A recent Framingham study found that the presence of echocardiographic LV hypertrophy was associated with an increased risk for ventricular arrhythmias on l- hour ambulatory electrocardiographic readings.6 This study evaluated all surviving members of the Framing- ham cohort and did not control for the diagnosis of hy- pertension, the use of antihypertensive medicines or se- rum electrolyte values. Thus, the results may have been confounded by the use of antihypertensive medicines, especially hydrochlorothiazide, in the echocardiographic LV hypertrophy group who had higher systolic and dia- stolic blood pressures than those without echocardio- graphic LV hypertrophy. We compared the presence of ventricular arrhyth- mias on 24-hour ambulatory electrocardiographic read- ings in hypertensive men with and without echocardio- graphic LV hypertrophy who had been withdrawn from diuretic therapy and repleted with oral potassium and magnesium for 1 month. MFTHOD5 BackgrouM The Hypertension Arrhythmia Reduc- tion Trial is a clinical trial designed to assess the frequency and severity of ventricular arrhythmias asso- 742 THE AMERICAN JOURNAL OF CARDIOLOGY VOCUME 65
Transcript
SYSTEMIC HYPERTENSION
Risk of Ventricular Arrhythmias in Hypertensive Men with Left Ventricular Hypertrophy
David Siegel, MD, MPH, Melvin D. Cheitlin, MD, Dennis M. Black, PhD, Dana Seeley, MS, Norman Hearst, MD, MPH, and Stephen B. l-lulley, MD, MPH
The echocardiographic predictors of ventricular arrhythmias are reported for the Hypertension Arrhythmia Reduction Trial. Men with mild hyper- tension were withdrawn from their diuretic therapy and repleted with 40 mEq/day of oral potassium and 20 mEq/day of oral magnesium for 1 month. M-mode echocardiography and 24-hour continuous ambulatory eledrocardiography were performed on 123 men, mean age 62 years. Forty-eight men (39%) had echocardiiaphic evidence of left ven- tricular (LV) hypertrophy defined as an LV mass index >134 g/m* and this ffnding was not related to the presence of LV hypertrophy on dectrocar- diogram or to age. Men who had echocardiiaphic LV hypertrophy were more likely than men without echocardiographic LV hypertrophy to have 130 ventricular premature complexes (VPCs)/hr (odds ratio = 2.7; 95% confidence interval = 0.9,&O), multiform extrasystoles (odds ratio = 1.7; confi- dence interval = 0.8,3.7), episodes of ventricular tachycardia (odds ratio = 2.3; confidence interval = 0.7,7.1) and the combination of frequent (130 VPCs/hr) or complex (ventricular couplets, multi- form extrasystoles or episodes of ventricular tachy- cardia) ventricular arrhythmia (odds ratio = 1.7; confidence interval = 0.8,3.5). Similar associations between echocardiographic LV hypertrophy and ventricular arrhythmias were observed on 24-hour tracings obtained on entry to the study (before ele&olyte repletion) in the 96 men who were tak- ing diuretics at this time. The combination of a fre- quent or complex arrhythmia was also more com- mon in men aged 60 to 70 compared to men aged 35 to 59 (odds ratio = 3.4; confidence interval = 1.4,8.2). These findings suggest that ventricular arrhythmias occur more commonly in older hyper- tensive men and in hypertensive men with echocar- diographic LV hypertrophy.
(Am J Cardid l-,65:742-747)
From the Departments of Epidemiology and Biostatistics, Medicine, and Family and Community Medicine, University of California, San Francisco, California. This study was supported in part by grant HL 36821 from the National Institutes of Health, Bethesda, Maryland. Manuscript received September 25, 1989; revised manuscript received November 10,1989, and accepted November 15.
Address for reprints: David Siegel, MD, MPH, Prevention Sciences Group, 74 New Montgomery, San Francisco, California 94105.
L eft ventricular (LV) hypertrophy, whether de- fined by electrocardiographic criteria, chest x-rays or echocardiography, is associated with an in-
creased risk of heart attack and sudden death.’ Hyper- tensive patients with LV hypertrophy by electrocardio- graphic criteria who are not receiving treatment have been shown to have significantly more ventricular ec- topy than either hypertensive patients without electro- cardiographic evidence of LV hypertrophy or normoten- sive patients.* It is not known whether this effect is also found in hypertensive patients with LV hypertrophy di- agnosed by echocardiography.
One recent study found that patients with LV hyper- trophy by electrocardiographic criteria had significantly more premature ventricular contractions and more com- plex (higher Lown’s class) ventricular ectopy than hy- pertensive subjects without LV hypertrophy or with LV hypertrophy diagnosed only by echocardiographic crite- ria.3,4 However, tlie investigators used measurements of posterior wall thickness, septal wall thickness and rela- tive wall thickness to define echocardiographic LV hy- pertrophy. This definition has not been found to corre- late as well with clinical and necropsy LV hypertrophy as that calculated by LV mass index.5 Thus, many of the individuals included in the LV hypertrophy group in this study did not meet LV mass criteria of LV hyper- trophy.
A recent Framingham study found that the presence of echocardiographic LV hypertrophy was associated with an increased risk for ventricular arrhythmias on l- hour ambulatory electrocardiographic readings.6 This study evaluated all surviving members of the Framing- ham cohort and did not control for the diagnosis of hy- pertension, the use of antihypertensive medicines or se- rum electrolyte values. Thus, the results may have been confounded by the use of antihypertensive medicines, especially hydrochlorothiazide, in the echocardiographic LV hypertrophy group who had higher systolic and dia- stolic blood pressures than those without echocardio- graphic LV hypertrophy.
We compared the presence of ventricular arrhyth- mias on 24-hour ambulatory electrocardiographic read- ings in hypertensive men with and without echocardio- graphic LV hypertrophy who had been withdrawn from diuretic therapy and repleted with oral potassium and magnesium for 1 month.
MFTHOD5 BackgrouM The Hypertension Arrhythmia Reduc-
tion Trial is a clinical trial designed to assess the frequency and severity of ventricular arrhythmias asso-
742 THE AMERICAN JOURNAL OF CARDIOLOGY VOCUME 65
TABLE I Characteristics of Study Sample According to Echocardiographic Left Ventricular Hypertrophy Status
Present Absent Total (n=48) (n = 75) (n = 123)
Black
Hispanic Indian White Other
Systolic BP (mm Hg) Diastolic BP (mm Hg) Pulse
BSA (m2) Potassium Magnesium Cigarette smoker (%)
Current Past Never
Antihypertensive other than diuretic (%)
62 f 8 62 f 6 62 f 7
6 7 13 24
8 5 2 0
69 64 2 0
144 f 17.2 147 f 18.4 86 f 9.7 88 f 10.9
68 f 9.6 76 f 11.6 1.91 f 0.20 1.91 f 0.17 4.29 f 0.32 4.34 f 0.43 1.99 f0.18 2.01 f 0.16
19 19 19 67 59 62 15 23 20 33 35 34
7 20
7
62, 1
146 f 17.9 87 f 10.4
73 f 11.5 1.91 f 0.18 4.32 f 0.40 2.00 f 0.17
All * data are mean i standard deviation. BP = blood pressure: BSA = body surface area
TABLE II Echocardiographic Characteristics of the Study Population
Echocardiographic LV Hypertrophy
Present Absent (n=48) (n = 75)
Total
(n = 123)
Septal wall thickness (cm) Posterior wall thickness (cm) Left ventricle in diastole (cm) LV mass (9)
LV mass index (g/m?)
1.20+0.16 1.07 fO.ll 1.12 f 0.14 1.11*0.14 1.03 f 0.07 1.06f0.11 5.44 f 0.53 4.90 f 0.35 5.11 f0.50 302 f 52 221 f 32 253 f 57
159f24 116f 14 133 f 28
Data are mea” f standard dewatmn. LV = left ventricular
ciated with different diuretic combinations in hyperten- sive men. The study group represents a target popula- tion of hypertensive men between the ages of 35 and 70 with abnormal electrocardiograms. Subjects were in- cluded in the study if they had been taking diuretics for at least 6 months and their diastolic blood pressure was <95 mm Hg, or had not been on diuretic therapy but had a history of hypertension and were either taking nondiuretic antihypertensive drugs or had a diastolic blood pressure 190 mm Hg. Informed consent was ob- tained from all subjects and the study design was ex- plained to the subjects’ physicians. Twelve-lead electro- cardiograms were performed on all patients at entry into the study. Only patients with abnormal resting electrocardiograms were entered. For purposes of the study, abnormality on electrocardiogram was defined as any deviation from normal, including nonspecific ST-T- wave changes, arrhythmias, conduction abnormalities and LV hypertrophy. We report here on the association between LV hypertrophy and ventricular arrhythmias during the baseline period in a subset of study subjects: men who were examined by echocardiography.
Patients who were taking medications that might in- fluence the development of ventricular arrhythmias
such as antiarrhythmic drugs, including /3 blockers, the- ophylline and digitalis, were excluded. Other antihyper- tensive medication not commonly associated with ar- rhythmias, such as a! methyldopa, clonidine, enalapril or prazosin, were not a basis for exclusion and were contin- ued throughout the study. We also excluded patients with a history of recent myocardial infarction (within 6 months), congestive heart failure, angina pectoris, renal insufficiency (creatinine >2.0 mg/dl) or other serious illness including psychiatric disabilities, or inability or unwillingness to give informed consent.
Design oveniew: All patients were withdrawn from diuretic treatment for 1 month with a determination of their blood pressure 2 weeks after stopping the diuretic. After 1 month of oral therapy with both 40 mEq of potassium chloride and 20 mEq of magnesium oxide daily, serum potassium and magnesium were deter- mined. Continuous 24-hour electrocardiographic moni- toring was performed at the beginning and end of the electrolyte repletion month.
Echocardiographii measurements: M-mode echo- cardiograms were performed on all patients at entry into the study using either an ATL 851-B or General Electric class C model. Measurements were made ac-
THE AMERICAN JOURNAL OF CARDIOLOGY MARCH 15. 1990 743
TABLE III Echocardiographic Left Ventricular Hypertrophy Status by Electrocardiographic Left Ventricular Hypertrophy Status
Echocardiographic LV Hypertrophy
Electrocardiographic LV Hypertrophy
Present Absent Total
Present Absent Total
4 12 16 44 63 107 43 75 123
3
cording to the recommendations of the American Soci- ety of Echocardiography using a leading edge to leading edge convention.7 Two-dimensional echocardiography was used in the parasternal long-axis view to select the place where the M-mode echocardiographic measure- ments would be taken. Measurements were made at the tips of the mitral valve leaflets posterior to the tips of the papillary muscles. Measurements of the LV internal dimension, posterior wall thickness and ventricular sep- tal thickness were used to calculate LV mass according to the formula: 1.04 [(LV internal dimension + posteri- or wall thickness + ventricular septal thickness)3 - (LV internal dimension)3] - 14 g.5 LV mass index was cal- culated by dividing the LV mass by the bcdy surface area. LV hypertrophy was defined as a calculated echo- cardiographic LV mass index of >134 g/m2.
Ekctrocardiiraphic measurementr: Standard 12- lead electrocardiograms were performed on all subjects and interpretation was performed by one of the investi- gators (MC) who was blinded to the echocardiographic and continuous 24-hour electrocardiographic monitor- ing results. Participants were judged as meeting criteria for electrocardiographic LV hypertrophy if they met ei- ther E&es, Sokolow-Lyons or frontal plane criteria.8-10
Continueus electrocardiiraphii monitoring: Con- tinuous 24-hour electrocardiographic monitoring was performed using the Cardiotechorder III dual lead sys- tem. The electrocardiogram was recorded continuously on tape using a cassette system. Whole tapes were print- ed at high speed on recording paper using the Cardio Data Corp. Mark IV. Specific areas of interest, identi- fied by irregularity on the QRS pattern, were printed at real time and analyzed by a cardiologist who was blind- ed to the blood pressure and echocardiographic status of the participant. Ventricular arrhythmias were classified in a manner similar to that of Lown et a1,3 according to the presence of the following arrhythmia types: ventric- ular premature complexes (VPCs), multiform extrasys- tales, ventricular couplets, ventricular tachycardia and R-on-T ventricular premature complexes. A summary category of the presence of a frequent (230 VPCs/hr) or a complex (presence in 24 hours of any of the follow- ing: multiform extrasystoles, ventricular couplets, ven- tricular tachycardia or R-on-T VPC) ventricular ar- rhythmia was also created.
Serum electrolytes: Peripheral venous blood was drawn from the antecubital fossa in lo-ml Vacutainers (Be&on-Dickinson) using the standard tourniquet
744 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 65
method. The subjects were seated and the arm firmly supported on a flat surface at about waist level. Care was taken to apply the tourniquet for no longer than 2 minutes. The vacutainer tube was centrifuged at 200 rpm at room temperature for 10 minutes to separate serum from clotted erythrocytes. Serum was then re- moved from the tube and centrifuged a second time to remove any remaining cells. For serum magnesium de- terminations, the serum was diluted 1:lOO in 0.5% lan- thanum chloride and magnesium content of samples was measured in flame mode with a Perk&Elmer (model 2380) atomic absorption spectrophotometer us- ing a 3-slot head. For serum potassium determinations, the serum was diluted 1:lOO in 0.5% lanthanum chlo- ride and potassium content of samples was measured directly on a flame photometer.
Statistical analysis: Statistical analysis was per- formed using Statistical Analysis System software on an IBM 4341 mainframe computer.” Odds ratios and 95% confidence intervals were calculated to evaluate the re- lation between age (35 to 59 vs 60 to 70) and arrhyth- mia outcomes (230 VPCs/hr, presence in 24 hours of any of the following: multiform extrasystoles, ventricu- lar couplets, ventricular tachycardia or R on T VPC or complex or frequent arrhythmia). Odds ratios and 95% confidence intervals were also computed for the associa- tion between the presence of echocardiographic LV hy- pertrophy and the various arrhythmia outcomes. A sim- ilar analysis was performed to evaluate the association between LV hypertrophy by electrocardiographic and arrhythmia outcomes.
RESULTS Study population: Clinical characteristics of the
echocardiographic LV hypertrophy positive compared to the echocardiographic LV hypertrophy negative men are listed in Table I. There was little difference between the 48 echocardiographic LV hypertrophy positive and 75 echocardiographic LV hypertrophy negative men in terms of age, race, systolic and diastolic blood pressures, body surface area, serum electrolyes and smoking histo- ry. Electrocardiographic LV hypertrophy positive men tended to differ from electrocardiographic LV hypertro- phy negative men: they were younger (mean age 56 vs 63 years), more commonly black (44 vs 16%), had high- er systolic (152 vs 145 mm Hg) and diastolic (93 vs 87 mm Hg) blood pressures and body surface areas (1.99 vs 1.90 m2), and were less frequently a current smoker (0 vs 22%). However, there were only 16 men in the electrocardiographic LV hypertrophy positive group and the differences were not statistically significant.
Echocardiiraphic characteristiis: Echocardio- graphic LV hypertrophy positive men had greater septal wall thickness, posterior wall thickness and greater LV internal dimension in diastole than echocardiographic LV hypertrophy negative men (p <O.Ol in each) (Table II). The mean LV mass index was 159 in the echocar- diographic LV hypertrophy positive men and 116 in the echocardiographic LV hypertrophy negative men. There was no association between echocardiographic LV hy- pertrophy and electrocardiographic LV hypertrophy in our study. The majority (92%) of echocardiographic LV
TABLE IV Prevalence of Ventricular Arrhythmias in Hypertensive Men One Month After Stopping Diuretics and Repleting
Abbreviabons as !n Table IV. * Odds ratio for 230 vs <3O VPCs/hr.
hypertrophy positive men were electrocardiographic LV hypertrophy negative and the majority (75%) of electro- cardiographic LV hypertrophy positive men were echo- cardiographic LV hypertrophy negative (Table III).
Continuous twenty-four-hour ekctrocardiograms: The prevalence of the various forms of ventricular ar- rhythmias at the end of the l-month electrolyte reple- tion phase is listed in Table IV. Men aged 60 to 70 compared to men aged 35 to 59 were more likely to have 130 VPCs/hr (odds ratio = 6.4; 95% confidence interval = 0.8, 50.9), ventricular couplets (odds ratio = 2.0; confidence interval = 0.7, 5.8), multiform extrasys- toles (odds ratio = 4.4; confidence interval = 1.5, 12.3), episodes of ventricular tachycardia (odds ratio = 5.9; confidence interval = 0.7, 46.9) and the combination of a frequent (130 VPCs/hr) or complex arrhythmia (odds ratio = 3.4; confidence interval = 1.4, 8.2). The 95% confidence interval excluded one for both multi- form extrasystoles and for the combination of a fre- quent or complex arrhythmia and thus these differences are statistically significant (p <0.05).
Men who met echocardiographic criteria of LV hy- pertrophy were more likely to have 130 VPCs/hr (odds ratio = 2.7; confidence interval = 0.9, 8.0), multiform
extrasystoles (odds ratio = 1.7; confidence interval = 0.8, 3.7), episodes of ventricular tachycardia (odds ratio = 2.3; confidence interval = 0.7, 7.1), and the combina- tion of a frequent or complex arrhythmia (odds ratio = 1.7; confidence interval = 0.8, 3.5) compared to LV hy- pertrophy negative men (Table V). The difference be- tween echocardiographic LV hypertrophy positive and negative men did not quite reach statistical significance for any of the arrhythmia classifications studied with the 95% confidence intervals including one in each case.
Ninety-six of the participants (38 echocardiographic LV hypertrophy positive and 58 echocardiographic LV hypertrophy negative men) also had continuous 24-hour electrocardiographic monitoring performed while taking diuretics before repletion with oral potassium and mag- nesium. Analysis of the prevalence of the above ar- rhythmia categories was similar to the results after withdrawal from diuretics: 230 VPCs/hr (odds ratio = 2.0; confidence interval = 0.5, 8.2), multiform extrasys- toles (odds radio = 1.6; confidence interval = 0.7, 3.7), episodes of ventricular tachycardia (odds ratio = 4.2; confidence interval = 0.8, 23.1) and the combination of a frequent or complex arrhythmia (odds ratio = 1.7; confidence interval = 0.7, 3.9) comparing echocardio-
THE AMERICAN JOURNAL OF CARDIOLOGY MARCH 15. 1990 745
graphic LV hypertrophy positive to echocardiographic LV hypertrophy negative men.
The prevalence of the various forms of ventricular arrhythmias according to electrocardiographic LV hy- pertrophy was also analyzed. There was no substantial difference between the electrocardiographic LV hyper- trophy positive and negative subjects, but our analysis is hampered by the small number of electrocardiographic LV hypertrophy positive men.
DISCUSSION Although our study results cannot be viewed as con-
clusive because they did not quite reach statistical sig- nificance, the odds ratios of 1.7 to 2.7 and the corre- sponding 95% confidence intervals for 4 of 5 of the arrhythmia outcomes studied strongly suggest that echocardiographic LV hypertrophy positive men have more frequent and complex arrhythmias than echocar- diographic LV hypertrophy negative men. These find- ings extend and clarify those of the Framingham study.6 In the Framingham cohort, all individuals who had sur- vived until 1979 were studied and the echocardiographic LV hypertrophy positive group may have contained a higher proportion of hypertensive patients taking medi- cation with electrolyte abnormalities than the echocar- diographic LV hypertrophy negative group. Thus, their finding that echocardiographic LV hypertrophy positive individuals had more frequent and complex ventricular arrhythmias than echocardiographic LV hypertrophy negative individuals may have reflected more electrolyte abnormalities in the LV hypertrophy positive group or some unmeasured effect of their hypertensive medica- tion, particularly diuretics.
Our study subjects were hypertensive men with- drawn from their diuretics and given oral potassium and magnesium for 1 month before their ambulatory elec- trocardiograms. After electrolyte repletion, serum po- tassium and magnesium determinations, as well as age, systolic and diastolic blood pressures and smoking, were similar between the echocardiographic LV hypertrophy positive and negative men. Thus, we believe that our findings of increased frequency and complexity of ven- tricular arrhythmias do not represent the effects of elec- trolyte or other cardiac risk factor differences between groups. Rather we think they represent an increased risk for ventricular arrhythmias in hypertensive men with echocardiographic LV hypertrophy based on in- trinsic cardiac mechanisms. Additionally, 96 of the par- ticipants also had continuous 24-hour electrocardio- graphic monitoring performed while taking diuretics be- fore repletion with oral potassium and magnesium. Analysis of the prevalence of the arrhythmia categories was similar to the results after withdrawal from diu- retics suggesting that diuretic therapy did not confer ad- ditional arrhythmia risk in echocardiographic LV hy- pertrophy positive patients and that repletion with po- tassium and magnesium did not diminish arrhythmia risk. This finding also supports results from the Fra- mingham study, indicating that their findings were due to LV hypertrophy rather than the unmeasured effects of diuretics.
746 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 65
Considerable controversy remains around the influ- ence of diuretic therapy on ventricular arrhythmias. Some studies indicate an association between diuretic therapy and ventricular arrhythmias in patients with or- ganic heart disease12m14 while others do not.’ 5.16 One study evaluated the association of hypertension, LV hy- pertrophy and diuretic treatment using continuous 24- hour electrocardiographic monitoring to detect the fre- quency and severity of ventricular arrhythmias.” In 18 patients with LV hypertrophy studied, there were 5.7 f 9.9 VPCs/hr before treatment and 7.1 f 16.6 VPCs/hr after treatment with 100 mg of hydrochlorothiazide dai- ly for 1 month. The investigators claim that the differ- ences were not statistically significant, but no actual p value was given, and the study was far too small to reli- ably detect even a 2-fold increase in the number of VPCs.18 Although our results appear to support a lack of association between diuretic therapy and ventricular arrhythmias in hypertensive patients with LV hypertro- phy, the patients reported here were not randomized to diuretics and thus our results should be interpreted with caution.
We found that most (92%) men with echocardio- graphic LV hypertrophy did not have electrocardio- graphic LV hypertrophy and most (75%) men with elec- trocardiographic LV hypertrophy did not have echocar- diographic LV hypertrophy. This is consistent with prior studies6J9 and indicates that echocardiography identifies a larger and to some degree different group of individuals with LV hypertrophy than does LV hyper- trophy based on electrocardiographic criteria. Unlike other studies,2,20 the individuals with electrocardio- graphic LV hypertrophy in our study did not appear to be at increased risk of ventricular arrhythmias. How- ever, we had relatively few (16) subjects in our study with electrocardiographic LV hypertrophy. As in prior studies,6 we found a higher prevalence of all the ventric- ular arrhythmia outcomes studied with older age; differ- ences between subjects 60 and 70 years of age and 35 and 59 years of age reached statistical significance for multiform extrasystoles and the combination of a fre- quent or complex arrhythmia.
The clinical relevance of the ventricular arrhythmias that we studied is not yet known. The importance of determining LV hypertrophy in hypertensive individuals is based on the recognition that these individuals are at increased risk of cardiovascular mortality.] Determining the mechanism of increased risk could lead to testing therapeutic interventions aimed at either reversing LV mass with specific antihypertensive medication21,22 or by controlling specific manifestations such as ventricu- lar arrhythmias. Studies are needed to determine if a decrease in cardiovascular risk will result from a de- crease in cardiac mass.
REFERENCES 1. Kannel WB. Prevalence and natural history of electrocardiographic left ven- tricular hypertrophy. Am J Med 1983;75(supp/ 3.4):4-l/. 2. Messerli FH, Ventura HO, Elizardi DJ, Dunn FG, Frohlich ED. Hypertension and sudden death: increased ventricular ectopic activity in left ventricular hyper- trophy. Am J Med 1984;77:18-22. 3. Lawn B, Calvert AF, Armington R. Ryan M. Monitoring for serious arrhyth-
mias and high risk of sudden death. Circulation /975;5/(suppl IIl):I//-/%I//- 198. 4. Lavie CJ, Nunez BD, Garavaglia GE, Messerli FH. Hypertensive concentric left ventricular hypertrophy: when is ventricular ectopic activity increased? S Med J 1988;81:696-700. 5. Devereux RB, Casale PN, Kligfield, P, Eisenb-erg RR, Miller D, Campa E. Alonso DR. Performance of primary and derived M-mode echocardiographic measurements for detection of left ventricular hypertrophy in necropsied subjects and in patients with systemic hypertension, mitral regurgitation and dilated car- diomyopathy. Am J Cardiol 1986;57:1388-1393. 6. Levy D, Anderson KM, Savage DD, Balkus SA, Kannel WB, Castelli WP. Risk of ventricular arrhythmias in left ventricular hypertrophy: the Framingham study. Am J Cardiol 1987,60:560~565. 7. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardio- graphic measurements. Circulation 1978;58:1072-1083: 8. Romhilt KDW, Estes EH Jr. A point-score system for the ECG diagnosis of left ventricular hypertrophy. Am Heart J /968:175:752-758. 9. Sokolow M, Lyon TP. The ventricular complex in left ventricular hypertrophy as obtained by precordial and limb leads. Am Heart J /949;37:16/-186. 10. Goldschlager N, Goldman MJ. Principles of Electrocardiography. Seconded. San Mateo, California: Appleton and Lange; 1989:58-72. 11. Statistical Analysis System Institute, Inc. User’s Guide: Statistics, 1982. Gary, North Carolina: SAS Institute, Inc., 1982. 12. Caralis PV. Materson BJ, Perez-Stable E. Potassium and diuretic-induced ventricular arrhythmias in ambulatory hypertensive patients. Miner Electrolyte Metab 1984;10:148-154. 13. Perez-Stable E. Thiazide-induced disturbances in carbohydrate, lipid, and
potassium. Am Hearr J i983;106.245-251. 14. Lichstein E. Morganroth J, Harrist R. Hubble E. Effect of propranolol on ventricular arrhythmia: the Beta-Blocker Heart Attack Trial Experience. Circrr- lotion 1983:67(suppl l):I-5. 15. Papademetriou V, Fletcher RD. Khatri IM. Freis ED. Diuretic-induced hypokalemia in uncomplicated systemic hypertension: effect of plasma potassium correction on cardiac arrhythmias. Am J Cardiol /983,52:/O/ 7-1022. 16. Papademetriou V, Burris JF, Notargiacomo A. Fletcher RD, Frels ED Thiazide therapy is not a cause of arrhythmia in patients with systemic hyperten- sion. Arch lnfern Med 1988:l48:1272-1276. 17. 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 Hearr J /985:/ /0:595- 599. 18. Siegel D. Black DM. Thiazide therapy and ventricular arrhythmias (letter). Am Hearr J 1986;11/:/2/4-1215, 19. Dreslinski CR. Identification of left ventricular hypertrophy: chest roentgen- ography, echocardiography. and electrocardiography. Am J Mrd 1983;75(supp/ 3A):47-50. 20. McLenachan JM, Henderson E, Morris KI, Dargie HJ. Ventricular arrhyth- mias in patients with hypertensive left ventricular hypertrophy. N Engl J Med 1987;317:787-792. 21. Rowlands DB, Glover DR, Ireland MA, McLeay RA, Stallard TJ. Watson RD, Littler WA. Assessment of left ventricular mass and its response to antihy- pertensive treatment. Lancet 1982:2:467-471. 22. Dunn FG. Ventura HO, Messerli FH. Korbin I, Frohlich ED. Time course of regression of left ventricular hypertrophy in hypertensive patients treated with atenolol. Circulation /987:76:254-258.
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