SYSTEMIC HYPERTENSION

Hemodynamic, Humoral and Volume Findings in Systemic Hypertension with Isolated

Ventricular Septal Hypertrophy Roland E. Schmieder, MD, Franz H. Messerli, MD, Boris D. Nunez, MD,

Guillermo E. Garavaglia, MD, and Edward D. Frohlich, MD

To analyze the hemodynamic, endocrine and volume characteristics of isolated septal hypertro- phy (ISH) in established systemic hypertension, 22 patients with ISH were compared to 23 patients with symmetric hypertrophy and to 28 without left ventricular (LV) hypertrophy. Mean arterial pres- sure and 24-hour ambulatory pressure readings did not differ between the 2 groups. At the same level of arterial pressure, patients with ISH had a high cardiac index (p <0.02) and a faster heart rate (p <O.OS); consequently, total peripheral resistance was decreased (p <0.05). Although there was no change in intravascular volume, central blood vol- ume was expanded (p <0.02), and the ratio of cen- tral to peripheral blood volume was increased (p <0.02), thereby indicating peripheral venoconstric- tion. Patients with isolated ISH had greater re- sponses of diastolic pressure and heart rate (p <0.05) to isometric stress than the other 2 groups. A hyperdynamic circulatory state is a hemodynam- ic hallmark of ISH in early essential hypertension that might be produced by increased sympathetic activity.

A chronic pressure overload such as that occurring in systemic arterial hypertension induces cardi- ac structural adaptation resulting in left ventric-

(Am J Cardiol 1988;62:1053-1057)

From the Department of Internal Medicine, Section on Hypertensive Diseases, Ochsner Clinic and Alton Ochsner Medical Foundation, New Orleans, Louisiana. This study was supported in part by a grant from the Deutsche Forschungsgemeinschaft, Federal Republic of Germany. Manuscript received February 11, 1988; revised manuscript received July 1, 1988, and accepted July 3.

Address for reprints: Franz H. Messerli, MD, Ochsner Clinic, 1514 Jefferson Highway, New Orleans, Louisiana 70121.

ular (LV) hypertrophy. &hocardiography allows us to identify different morphologic types of LV hypertrophy in patients with arterial hypertension. A symmetrical progressive thickening of all parts of the LV wall repre- sents the classic hypertrophic adaptation to increased afterload (concentric type). lm3 When increased preload and afterload simultaneously burden the ventricle-a finding typical in obese hypertensive patients-the in- creased LV wall thickness is accompanied by dilation of the chamber.4

In some hypertensive patients, LV changes are solely or predominantly localized in the septum (isolated sep- tal hypertrophy [ISH]). The prevalence of these find- ings was reported in 5 to 50% of patients with essential hypertension, depending on the population and echocar- diographic criteria selected.5,6 Whether the ISH in cs- sential hypertension has the same implications as idio- pathic hypertrophic cardiomyopathy confined to tlhe septum is unknown. Conceivably, ISH is at one end of a continuous spectrum of various types of hypertrophic patterns in systemic arterial hypertension and symmet- rical or concentric hypertrophy is at the other end.6m8 Alternatively, hypertrophic cardiomyopathy with or without LV outflow obstruction seems to represent a separate entity of hypertrophic cardiomyopathies coinci- dentally being present in 5 to 10% of patients having essential hypertension.5,9J0

The present study evaluates cardiovascular and en- docrine findings in patients with systemic hypertension and ISH and compares them with those in patients with “classic” concentric LV hypertrophy and patients with- out LV hypertrophy.

METHODS Study population: Seventy-three patients with mild

to moderate essential hypertension are included. Secon- dary causes of arterial hypertension were excluded by our clinical evaluation.’ I No patient had clinical signs of obstructive hypertrophic cardiomyopathy, inferior wall myocardial infarction, right ventricular pressure over- load or coronary artery disease. Patients were consid- ered to have established hypertension if their diastolic pressure was consistently >90 mm Hg (Korotkoff phase V) measured (with an appropriate cuff in obese pa- tients) after 5 minutes of rest in the outpatient clinic.

THE AMERICAN JOURNAL OF CARDIOLOGY NOVEMBER 15, 1988 1053

lSOLATEDSEPTALHYPERTROPHYINHYPERTENSlON

TABLE I Echocardiographic Findings in Hypertensive Patients Without Left Ventricular Hypertrophy (LVH) or With Concentric (CH) or Isolated Septal Hypertrophy (ISH)

No LVH With CH With ISH

No. 28 23 22 Age M-s)* 44flO 46f 11 44;t 11 Race (white:black) 23:5 14:9 17:5 Sex (male:female) 16:12 16:7 17:5 Height (cm)* 174f9 172&;8 174 f 10 Weight (kg)* 82f 19 82Jc21 85f 16 Body mass index(kg/m2)* 27&5 29 f 7 28h4 Body surface area (mz)* 1.90 zk 0.23 2.02 + 0.19 1.99 f 0.24

* Values are mean f 1 standard devlation.

t

TABLE II Echocardiographic Findings in Hypertensive Patients Without Left Ventricular Hypertrophy (LVH) or With Concentric (CH) or Isolated Septal Hypertrophy (ISH)

No LVH With CH With ISH

Septal wall thickness 0.89f0.11 1.26f0.18” 1.30i0.11”

(cm) Posterior wall thickness 0.90 f 0.10 1.21 f 0.08” 0.92 f 0.08

(cm) Ratio of septal-to-pos- 1.03f0.13 1.07f0.15 1.42f0.16’

terior wall thickness Diastolic diameter (cm) 4.72 f 0.47 4.79 f 0.46 4.84 f 0.30 Systolic diameter (cm) 3.2 f 0.5 3.1 f 0.7 3.1 * 0.5 Left ventricular mass (g) 169 f 40 271 k 59* 230 z’c 42* Left ventricular mass 89k18 137 f 31’ 117 f 22+

index (g/m2) Fractional fiber shorten- 33zk9 34f8 34flO

ing (“IO) Ejection fraction (%) 61 f 12 64% 13 63f 12 Velocity of circumferen- 1.18f0.3 1.21fO.l 1.18 f 0.3

tial fiber shortening (circumference/s)

* p <O.oOl; + p <O.Ol (compared with No LVH).

r

L

All patients either had never been treated with antihy- pertensive medication or had discontinued its use at least 4 weeks before the examination. In some patients, the mean arterial pressure measured after at least 30 minutes of rest in the supine position dropped below 90 mm Hg. The study protocol was approved by our Insti- tutional Clinical Investigation Committee, and in- formed consent was obtained from each patient.

Echocardiography: To categorize the patients ac- cording to their hypertrophic pattern, echocardiograph- ic studies were conducted by using an ultrasonoscope (Smith-Kline Echoline 28) interfaced with a strip chart recorder (Honeywell) and a probe measuring 1.27 cm in diameter.12 Ultrasonic emission characteristics were as follows: frequency, 1,000/s; wave length, 2.25 MHz; and focal length, 10 cm. All echocardiograms were re- corded in the third or fourth interspace lateral to the left sternal border.

Septal and posterior LV wall thicknesses, and dia- stolic and systolic LV diameters were evaluated from M-mode echocardiograms recorded slightly before the tips of the mitral valve leaflets. Appropriate adjust- ments of the damp, reject and gain modalities were made to obtain a good definition of the walls and LV cavity. All echocardiograms were independently read by 2 physicians according to the standards of the American

1054 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 62

Society of Echocardiography.12Js A ratio of septal to posterior wall thickness Il.3 cm was considered to re- flect disproportionate septal thickening. It should be stressed that septal wall thickness ranged between 1 .l and 1.6 cm, and no patient had severe septal thickening (>1.6 cm), displayed systolic anterior motion of the an- terior mitral leaflet or had electrocardiographic evi- dence of asymmetric septal hypertrophy. The LV mass was calculated according to the formulae of Troy et al (taking septal and posterior wall thicknesses into ac- count).14

Classification of patients: All patients were catego- rized into 3 groups. Only those without chamber dila- tion were included for further analysis (diastolic diame- ter <3.2 cm/m2 for men and <3.1 cm/m* for wom- en),i4 thereby excluding patients with dilated left ventricle. Twenty-eight patients had no sign of LV hy- pertrophy (group I); their septal and posterior walls were <l .l cm thick. Group II comprised 23 patients with symmetric or concentric LV hypertrophy as de- lined by septal and posterior wall thickness Il.1 cm and a ratio of septal to posterior wall thickness <1.3. Group III included 22 patients with isometric septal LV hypertrophy characterized by a ratio of septal to poste- rior wall thickness that was 11.3 with a septal wall thickness >l.l cm and posterior wall thickness <l .l cm.

Hemodynamic, humoral and volume measurements: Hemodynamic evaluation was performed during the same echocardiographic study previously described. * l Cardiac output was measured invasively in triplicate with indocyanine green dye technique, and renal blood flow was estimated by measuring the clearance of io- dine- 13 1 paraaminohippuric acid.

Plasma volume was measured during the hemody- namic study with the patient supine using iodine-125- labeled plasma serum albumin and was related to height as previously suggested.15 Central blood volume was assessed from the dye dilution curve by calculating the product of mean transit time and blood flow per se~o,d.l1~16,17

About I hour after the catheters were inserted but before hemodynamics measurements were harvested, blood was withdrawn in ice-cooled tubes and stored at -21°C for later determinations of circulating plasma norepinephrine and epinephrine levels18 (radioenzyma- tic assay) and plasma renin activity.lg

Isometric stress: After all baseline data were mea- sured, an isometric exercise stress test (handgrip test at 30% of voluntary maximal contraction over 3 minutes) was performed in 18 hypertensive patients with concen- tric LV hypertrophy and in 14 patients with ISH. Dur- ing the third minute, the evaluation of systemic hemo- dynamics was repeated.

Ambulatory blood pressure monitoring: In addition to the hemodynamic evaluation, in 12 patients with con- centric LV hypertrophy and in 10 patients with ISH we recorded 24-hour ambulatory blood pressure during dai- ly life and during sleep. The ambulatory blood pressure was recorded every 15 minutes for 24 hours by an auto- matic device (Del Mar Avionics Pressurometer II). An

I

TABLE III Hemodynamic, Endocrine and Volume Findings in Hypertensive Patients Without Left Ventricular liypertrophy (LVH) or With Concentric (CH) or Isolated Septal Hypertrophy (ISH)

No LVH With CH With ISH p Value

Mean arterial pressure (mm Hg) 107fll 109 f 10 107 f 13 NS Heart rate (beats/min) 70flO 66zk9 73 f lo+ 0.05 Cardiac index (liters/min/m”) 2.87 f 0.36 2.79 * 0.53 3.19 f 0.5s 0.02 Stroke volume index (ml/m’) 42f7 43zk8 45fll NS Total peripheral resistance (units) 37 f 6 4Of8 35f85 0.05 Renal blood flow (ml/min) 548 f 149 436 f 126+,11 512 f 116 0.02 Renal blood flow/cardiac output (%) 19.1 f 4 15.6 f 3 16.1 f 3+ 0.01 Plasma norepinephrine (pg/ml) 302 f 107 352 f 154 254 f 99 NS Plasma epinephrine (pg/ml) 139 f 116 ii3 f loo 72zk75 NS Plasma renin activity (nl/ml/hr) 0.89 f 0.98 1.6 f 1.9 1.16zkO.89 NS Plasma volume/height (ml/cm) 16 f 2.8 17 f 2.1 17 f 3.7 NS Total blood volume (liter) 4.61 f 1.0 4.81 ZIG 1.7 4.91 f 1.1 NS Central blood volume (liter) 2.49 f 0.5 2.82 f 0.5” 3.12f0.8* 0.01 Central/total blood volume (%) 55f8 56f14 64 f 13+,* 0.02

* p value = l-way analysis of variance for all 3 groups. + p <0.05 = ISH versus CH; f p <0.02 = ISH versus No LVH; 5 p <0.02 = ISH versus CH: ‘1 p <O.Ol = Ch versus No LVH; and f p <0.05 = CH versus No LVH. NS = not significant.

average systolic and diastolic pressure was calculated for each 2-hour period.

Statistics: One-way analysis of variance and Bonfer- roni’s conservative correction were used to evaluate any significant difference between the 3 groups. Linear re- gression coefficient (Pearson) and chi-square analysis were calculated where indicated. All data are expressed as mean f 1 standard deviation.

RESULTS Age, body mass index and body surface area were

similar in all 3 patient groups, and no significant differ- ence in race and sex was noted (Table I). Hence, demo- graphic characteristics did not appear to explain the 3 types of LV hypertrophy.

By study design, the septal wall was thicker in both groups with LV hypertrophy, whereas the posterior wall was thicker only in patients with concentric LV hyper- trophy (Table II). Left ventricular mass and its index were increased in both groups with LV hypertrophy, as would be expected. Most importantly, all 3 indexes of LV function (i.e., fractional fiber shortening, velocity of circumferential fiber shortening and ejection fraction) were similar in all 3 groups.

Mean arterial pressure was not different among the 3 groups (Table III). Similarly, ambulatory blood pres- sure monitoring revealed that the average systolic and diastolic pressures were similar in a subsample of pa- tients with concentric and ISH during daytime activities (141 f 11/93 f 5 vs 142 f lo/93 f 3 mm Hg), at home (137 f 12/86 f vs 138 f 14/87 f 8 mm Hg), andduringsleep(133fl 84&6vs131f13/87f7

6‘2/.p mm Hg). These subsamples a peared to.be representa- tive of their respective LV hypertrophy groups because mean arterial pressures in the subgroups with concen- tric LV hypertrophy (108 f 7 mm Hg) and ISH (107 f 12 mm Hg) were nearly identical to those of their larger groups (Table III).

Patients with ISH had a higher cardiac index than those with concentric LV hypertrophy or those without LV hypertrophy (p <0.02) iFigure l), and, as would be expected, their total peripheral resistance was reduced

(p <0.0’5). The higher cardiac output in the patients with ISH was produced mainly by a faster heart rate (p <0.05), although their stroke volume was slightly high- er as well (Table III). Renal blood flow was normal in patients with ISH and was not different from that in the hypertensive patients without LV hypertrophy. In contrast, renal blood flow was clearly diminished in pa- tients with concentric hypertrophy (p <O.Ol). However, the fraction of the systemic circulation distributed to the kidneys was equally reduced in both LV hypertrophy groups. Total blood volume and plasma volume were similar in all 3 groups (Table III). In contrast, central blood volume and the ratio of central to total blood vol- ume were markedly increased in patients with ISH (p <0.02), indicating a shift of total blood volume towards cardiopulmonary circulation. Plasma renin activity, plasma epinephrine and norepinephrine were not signifi- cantly different among the 3 groups; this may be due to the high standard deviation (Table III).

The hypertensive patients with ISH showed a hemo- dynamic hyperresponsiveness to isometric exercise: t’he increase in diastolic pressure was greater in patients with ISH than in those with concentric LV hypertrophy

Cardiac Index (I lmin/m2)

3.5 1 p 1 0.02

, 8 T

3.0

NO LVH CH ISH

FIGURE 1. Cardiac index in patients without lefl ventricular hypertrophy (LVH) or with isolated septal (ISH) or concentric GH) hypertropb

THE AMERICAN JOURNAL OF CARDIOLOGY NOVEMBER 15, 1988 iosi5

ISOLATED SEPTAL HYPERTROPHY IN HYPERTENSION

(23 f 13 vs 14 f 11 mm Hg, p <0.05); their increase in heart rate was more pronounced (11 f 9 vs 5 f 5 beats/min, p <0.05); and the cardiac index tended to increase more as well (1.09 f 1.03 vs 0.45 f 0.95 liter/ min, p <O. 10). When the percentage changes from baseline were calculated, diastolic pressure, heart rate and cardiac index consistently revealed an increased re- sponse in patients with ISH, suggesting that these changes were not caused by different baselines (Figure 2).

DISCUSSION Arterial pressure, whether measured invasively or by

24-hour monitoring, was nearly identical in the 3 groups of hypertensive patients (i.e., those without LV hyper- trophy, those with ISH and those with concentric LV hypertrophy) .

In the present study, in patients with established hy- pertension, disproportionate septal thickening was relat- ed to a higher cardiac index predominantly resulting from a faster heart rate. Conversely, as one would ex- pect since mean arterial pressures were similar, total pe- ripheral resistance was lower in the ISH group. Patients with ISH also exhibited an overreactive response in dia- stolic pressure, heart rate and cardiac index to isometric exercise. In addition, ISH was linked to peripheral ven- oconstriction with a shift of the intravascular volume to the cardiopulmonary system. Renal hemodynamics (re- nal blood flow and renal vascular resistance) were un- changed in patients with ISH whereas in patients with concentric LV hypertrophy, both the heart and the kid- neys were equally affected as shown by symmetric myo- cardial hypertrophy and increased renal vascular re- sistance. These findings are consistent with a previous report from our laboratory demonstrating that echocar- diographically demonstrable LV hypertrophy precedes

hemodynamic involvement of the renal circulation in patients with essential hypertension.20

The centripetal redistribution of intravascular vol- ume, the hyperkinetic circulation and the augmented re- action to isometric exercise observed in hypertensive pa- tients with ISH are typical features of increased sym- pathetic adrenergic activity. The autonomic nervous system also has a trophic role in cardiac muscle cells.21,22 Corea et a123 reported that plasma norepineph- rine levels in supine and upright borderline hypertensive patients correlated positively with septal wall thickness as well as with the ratio of septal-to-posterior wall thick- ness. Hence, sympathetic renal or humoral drive direct- ed to the intraventricular septum might be enhanced in hypertensive patients with asymmetric septal thicken- ing, whereas overall myocardial performance as mea- sured by ejection fraction, fractional fiber shortening and velocity of circumferential fiber shortening was not found to be altered in patients with septal LV hypertro- phy.6,8 A net increase in sympathetic adrenergic activity has been suggested to elicit the cardiovascular danger in borderline hypertension.1*J6,24-27 Furthermore, in pa- tients with borderline hypertension and a hyperkinetic circulation, ISH was a frequent echocardiographic tind- ing,8,28-30 whereas thickening of both the septum and the free wall was observed in those patients with border- line hypertension whose cardiac output was not elevat- ed 3o Another analysis confirmed that ISH was more prevalent in borderline hypertensive subjects with a high cardiac output than in those with a low cardiac output.8 Thus, a higher cardiac index is linked to ISH in border- line and subsequent established hypertension-as dem- onstrated in the current study. Our data do not indicate whether the hyperkinetic state and the shift of the intra- vascular volume to the cardiopulmonary system pro- vokes ISH or whether this hypertrophic pattern per se

Mean Arterial Pressure Ph)

301 p 4 0.05

Cardiac index Pw

301 p I 0.10

20 20

10 10

CH ISH CH ISH VW Heart Rate P/o) Total Peripheral

20 1 20 Resistance p 4 0.05 T 1

CH ISH CH ISH

FIGURE 2. Hemodynamic changes during isometric exer- cise in patients with isolated septal (ISH) or concentric (CH) lett ventricular hypertrophy.

1056 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 62

induces the hyperdynamic circulatory state. Alterna- tively, increased activity or sensitivity of the sympathet- ic adrenergic system might be the common denominator of both the volume and cardiovascular findings and of ISH.

REFERENCES 1. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man: anatomic validation of the method. Circularion 1977;55:613-618. 2. Messerli FH. Clinical determinants and consequences of left ventricular hyper- trophy. Am J Med 1983:75:51-56. 3. Grossman” W, Jones D, McLaurin LP. Wall stress and patterns of hypertro- phy in the human left ventricle. J Clin Irwest 1975;56:56-64. 4. Messerli FH, Sundgaard-Riise K, Reisin ED, Dreslinski GH, Dunn FG, Frohlich ED. Disparate cardiovascular effects of obesity and arterial hyperten- sion. Am J Med 1983;74:808-812. 5. Maron GJ, Clark CE, Henry WL, Fukuda T, Edwards JE, Mathews EC, Redwood DR, Epstein SE. Prevalence and characteristics of disproportionate ventricular septal thickening in patients with acquired or congenital heart disease: echocardiographic and morphologic findings. Circulation 1977;55:489-496. 6. Toshima H, Koga Y, Yoshioka H, Akiyoshi T, Kimura N. Echocardiographic classification of hypertensive heart disease. A correlative study with clinical fea- tures. Jpn Heart J 1975;16:377-393. 7. Savage DD, Garrison RJ, Kannel WB, Levy D, Anderson SJ, Stokes J III, Feinleib M, Castelli WP. The spectrum of left ventricular hypertrophy in a general population sample: the Framingham Study. Circulation 1987:7X1 part 2):126-133. 8. Niederle P, Widimsky J, Jandova R, Ressl J, Grospic A. Echwardiographic assessment of the left ventricle in juvenile hypertension. Znt J Cardioll982;2:91- 101. 9. Maron BJ, Epstein SE. Hypertrophic cardiomyopathy: Recent observations regarding the specificity of three hallmarks of the disease: asymmetric septal hypertrophy, septal disorganization and systolic anterior motion of the anterior mitral leaflet. Am J Cardiol 1980;45:14/~154. 10. Goodwin JF. Hypertrophic cardiomyopathy: a disease in search of its own identity. Am J Cardiol 1980;45:177-180. 11. Messerli FH, deCarvalho JGR, Christie B, Frohlich ED. Systemic and regional hemodynamics in low, normal and high cardiac output borderline hyper- tension. Circulation 1978;58:441&448. 12. Culpepper WS, Sodt PC, Messerli FH, Ruschhaupt DG, Arcilla RA. Cardiac status in juvenile borderline hypertension. Ann Intern Med 1983;98:lL7. 13. Sahn DJ, Demaria A, Kisslo J, Weymann A. Recommendations regarding

quantitation in M-mode echocardiography: results of a survey of echocardio- graphic measurements. Circulation 1978:58:1072-1083. 14. Troy BL, Pombo J, Rackley CE. Measurement of left ventricular wall thickness and mass by echocardiography. Circulation 1972;45:602-611. 15. Tarazi RC, Frohlich ED, Dustan HP. Plasma volume in men with essential hypertension. N Engl J Med 1978:278:762-765. 16. Ulrych M, Frohlich ED, Tarazi RC, Dustan HP. Cardiac output and distri- bution of blood volume in central and peripheral circulation in hypertensive and normotensive man. Br Heart J 1969;31:570-574. 17. Meier P, Bresler KL. On the theory of the indicator dilution method of measurement of blood flow and volume. J Appl Physiol 1954;6:731L736. 18. Peuler JD, Johnson GA. Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine. Life Sci 1977;21:625-636. 19. Sealey JE, Laragh JH. Radioimmunoassay of plasma renin activity. Semin Nucl Med 197S;5:189-202. 20. Kobrin I, Frohlich ED, Ventura HO, Messerli FH. Renal involvement follows cardiac enlargement in essential hypertension. Arch Intern Med 1986;146:272- 276. 21. Tarazi RC, Sen S. Catecholamines and cardiac hypertrophy. In: Hezzy KC, Caldwell ADS, eds. Catecholamines and the Heart. L.ondorr Academic Press and Royal Society of Medicine, 1979:47-55. 22. Ostman-Smith I. Cardiac sympathetic nerves as the final common pathway in the induction of adaptive cardiac hypertrophy. Clin Sci 1981,61:265-272. 23. Corea L, Bentivoglio M, Verdecchia P, Mot&se M. Left ventricular wall thickness and plasma catecholamines in borderline and stable essential hyperten- sion. Eur Heart J 1982;3:164-170. 24. Julius S, Esler M. Autonomic newus cardiovascular regulation in borderline hypertension. Am J Cardiol 1975;36:685-696. 25. Frohlich ED, Dustan HP, Tarazi RC. Hyperdynamic beta-adrenergic circu- latory state. Arch Intern Med 1970;126:1068-1069. 26. Widimsky J, Fejfarova MD, Ferfar Z. Changes in cardiacoutput in hyperten- sive disease. Cardiologica 1957;31:381. 27. Messerli FH, Ventura HO, Reisin ER, Dreslinski GR, Dunn FG, MacPhee AA, Frohlich ED. Borderline hypertension and obesity: two prehypertensive states with elevated cardiac output. Circulation 1982;66:55-60. 28. Safar ME, Lehner JP, Vincent MI, Plainfosse MT, Simon AC. Echocardio- graphic dimensions in borderline and sustained hypertension. Am J Cardiol 1979:44:930-935. 29. Wicker P, Roudaut R, Haissaguere M, Villega-Arino P, Clementy J, Dalloc- chio M. Prevalence and significance of asymmetric septal hypertrophy in hyper- tension: an echocardiographic and clinical study. Eur Heart J 1983;4(suppl G):l- 5. 30. Dreslinski GR, Messerli FH, Dunn FG, Suarez DH, Frohlich ED. Patterns of left ventricular adaptation in borderline and mild essential hypertension. Chest 1981;80:592-595,

THE AMERICAN JOURNAL OF CARDIOLOGY NOVEMBER 15. 1988 1057