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(Circulation. 1996;93:259-265.)
© 1996 American Heart Association, Inc.

Articles

Midwall Left Ventricular Mechanics

An Independent Predictor of Cardiovascular Risk in Arterial Hypertension

Giovanni de Simone, MD; Richard B. Devereux, MD; Michael J. Koren, MD; George A. Mensah, MD; Paul N. Casale, MD; John H. Laragh, MD

From the Department of Medicine and Hypertension Center, The New York Hospital–Cornell Medical Center, New York, NY.

Correspondence to Dr Giovanni de Simone, Division of Cardiology, Box 222, The New York Hospital–Cornell Medical Center, 525 E 68th St, New York, NY 10021.

	Abstract

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Background An appreciable proportion of asymptomatic hypertensive patients have depressed left ventricular (LV) performance that is identified by midwall shortening/end-systolic stress relations but not by indexes that use endocardial shortening. It has not been established, however, whether depressed midwall ventricular performance has prognostic implications.

Methods and Results Echocardiographic endocardial and midwall LV fractional shortening/circumferential end-systolic stress relations in 294 hypertensive patients were analyzed as predictors of the occurrence of cardiovascular morbid events that occurred in 50 patients (including 14 deaths) during a 10-year mean follow-up. Patients with initially lower midwall but not endocardial shortening, either in absolute terms or as a percentage of predicted from observed end-systolic stress, were more likely to suffer morbid events than those with initially normal values (P<.004). Cardiovascular events occurred in 29 of 100 patients (29%) and death in 10 of 100 patients (10%) among those who were in both the two highest quartiles of LV mass index and the two lowest quartiles of midwall shortening, as opposed to 21 of 194 (11%) and 4 of 194 (2.1%) of the remaining patients (odds ratio, 3.4; 95% CI, 1.8 to 6.3; P<.0001; and odds ratio, 5.3; 95% CI, 1.6 to 17.3; P<.006, respectively). In logistic analysis, increasing age, high LV mass, high systolic blood pressure, and low values for an interaction term between LV mass index and midwall shortening independently predicted cardiovascular events (.04<P<.001); increasing age, low midwall LV shortening as a percentage of predicted, and high value of the interaction term predicted the occurrence of cardiac death (.004<P<.0002). Survival analysis controlling for age confirmed that low midwall shortening independently predicted cardiac morbidity or death, especially in the subgroup of patients with LV hypertrophy.

Conclusions Depressed midwall shortening is a predictor of adverse outcome in arterial hypertension; the combination of higher LV mass and lower midwall shortening identifies individuals at markedly increased risk.

Key Words: echocardiography • hypertension • hypertrophy • mechanics • prognosis

	Introduction

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Arterial hypertension is associated with increased cardiovascular risk, and reduction of blood pressure by antihypertensive therapy decreases stroke mortality substantially. However, the reduction of risk of myocardial infarction and cardiac death associated with antihypertensive therapy is smaller than expected for the degree of blood pressure reduction.^{1 2 3} In recent years, two findings have begun to change the traditional view of the relation between high blood pressure and cardiovascular risk: first, evidence suggesting that too great a reduction of blood pressure might increase rather than decrease cardiovascular risk^{4 5 6} and second, the demonstration that increased left ventricular (LV) mass is a stronger predictor than blood pressure of cardiovascular morbidity and mortality.^{7 8 9 10 11} The ability to predict cardiovascular complications has been improved by the addition of increased LV mass to previously recognized markers of risk, but further improvement of risk stratification would be valuable.

It is well known that LV systolic dysfunction is the strongest predictor of cardiac morbid events in coronary artery disease.^{12 13} Among patients with arterial hypertension, LV ejection fraction and fractional shortening measured at the endocardium are normal or supranormal,^{14 15} with little evidence of depressed myocardial performance. However, there is a conceptual mismatch involved in relating fractional shortening at the endocardium to the mean level of LV end-systolic stress, which is, on average, applied approximately at the level of the LV midwall^{16 17} ; this mismatch may be exaggerated in the presence of abnormalities of LV geometry. Recently, we showed that assessment of midwall fiber shortening in relation to end-systolic LV wall stress but not of endocardial shortening–stress relations identified a subgroup of asymptomatic hypertensive patients with depressed LV performance and clinical and hemodynamic characteristics associated with high cardiovascular risk.¹⁸ In the present study, we analyzed endocardial and midwall LV function in a clinical population sample of hypertensive patients followed for a mean period of 10 years to evaluate whether or not decreased LV myocardial midwall performance is an independent predictor of cardiovascular complications in arterial hypertension.

	Methods

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Study Population
Patients were selected from among 612 consecutive hypertensive subjects initially evaluated by echocardiography at New York Hospital–Cornell Medical Center between 1976 and 1986.^{10 19} Criteria for inclusion in the follow-up study were exclusion of secondary hypertension by an extensive laboratory examination, absence of cardiac or other chronic diseases, and good-quality echocardiograms at baseline evaluation. Among 322 patients meeting the criteria of eligibility, direct follow-up or contact with relatives and physicians of those who died was possible in 294 patients (91%), who were included in the present analysis. Complications included sudden death, stroke, myocardial infarction, new-onset angina, congestive heart failure, coronary artery bypass graft or angioplasty, and carotid endarterectomy. More detailed information about diagnostic criteria has been reported previously.^{10 19}

Body mass index in kg/m² was used as a measure of obesity. Obesity was defined by a body mass index >27.8 in men and >27.3 in women. Arterial blood pressure was measured at the first and fifth Korotkoff phases by arm cuff and mercury manometer at the end of the echocardiograms. Standard analytic techniques were used to measure serum cholesterol.

Echocardiography
M-mode echocardiograms were recorded with commercially available echocardiographs and 2.25-MHz transducers, in a dimly lit room, with the patients in partial left decubitus, after discontinuation of antihypertensive therapy for a period of 2 to 3 weeks. Previously described procedures for visualization and interpretation of LV structures were followed.^{20 21} Measurements were made according to the Penn Convention recommendations to calculate LV mass.²²

An LV mass index was derived by dividing LV mass by height to the 2.7th power. This exponent represents the "allometric signal,"²³ or power of the growth relation between LV mass and body height, and was calculated by use of a model of nonlinear regression analysis in which LV mass=axheight^b, developed in a population sample of 611 normal-weight normotensive subjects over a wide range of age (4 months to 70 years).²⁴ Normal LV mass index values by this method of indexation were 34.4±9.2 g/m^2.7 in 73 adult men and 32.3±10.4 g/m^2.7 in 69 adult women.¹⁸ The 97.5th percentile of the normal distribution (51 g/m^2.7) was used as a partition value to define LV hypertrophy, on the basis of our previous observations that hypertensive or normotensive adults in the upper end of the apparently normal distribution are at increased risk of suffering morbid events^{7 10} or developing arterial hypertension.²⁵ For consistency with previous reports, normalizations of LV mass for both body surface area and height to the first power are shown in descriptive statistics. Relative wall thickness (ie, the ratio of posterior wall thickness to short-axis radius) was also calculated as index of LV geometric pattern. Values >0.44 were considered to be indicative of concentric LV geometry.²⁶

To measure LV systolic function, measurements of septal and posterior wall thicknesses and LV chamber dimensions were obtained according to American Society of Echocardiography recommendations.²⁷ Standard methods were used to calculate endocardial fractional shortening.^{28 29} Circumferential end-systolic stress (cESS) was calculated at the midwall at the level of the LV minor axis by the method of Gaasch et al^{17 30} as the primary measure of myocardial afterload:

where SBP is systolic blood pressure measured by arm cuff and mercury manometer at the end of echocardiogram, LVID is LV internal dimension, PWT is posterior wall thickness, and s is systolic. Meridional end-systolic stress, calculated by the standard method of Reichek et al,³¹ is also shown in descriptive statistics. Calculation of midwall fractional shortening took into account the epicardial migration of the midwall during systole by using a modified ellipsoidal model similar to that used to calculate LV mass. As in the method that Shimuzu et al¹⁷ used, based on a cylindrical model (ie, including the long-axis dimension) to assess the physiological position of midwall fibers during systole, a constant LV wall volume during the cardiac cycle has been assumed, so that (LVIDd+Hd)³-LVIDd³=(LVIDn+Hn)³-LVIDn³, where d is diastolic, H is wall thickness (ie, septum+posterior wall), and n is any moment during the cardiac cycle. Analogously, the inner LV wall shell volume at end systole can be calculated as (LVIDd+Hd)³-LVIDd³=(LVIDs+Hs)³-LVIDs³. From this formula, the thickness of the inner shell can be calculated, taking into account the migration toward the epicardium of LV midwall fibers from end diastole to end systole: [(LVIDd+Hd)-(LVIDs+Hs)]/(LVIDd+Hd).

An equation relating midwall shortening to circumferential end-systolic stress in 142 normal subjects¹⁸ was used to predict expected midwall shortening for observed end-systolic stress in this hypertensive population. The ratio of observed to predicted midwall shortening was therefore used as an index of LV performance independent of afterload conditions. Examination of the distribution of the ratio of observed to predicted midwall shortening obtained in 142 normotensive adults showed that a value of 0.78 (78% of predicted) corresponded to the 5th percentile; accordingly, values <0.78 were considered indicative of depressed LV performance. Similarly, 0.80 represented the 5th percentile of the ratio of observed to predicted endocardial shortening.

Statistical Analysis
Data were analyzed by a personal computer using SYSTAT Statistical Package (Systat, Inc).^{32 2} statistics and two-tailed Fisher's exact tests (for 2x2 tables) were used to examine the incidence of cardiovascular morbid events in prospectively defined subgroups and to assess descriptive statistics of patients with or without cardiovascular events or death. One-factor ANOVA was used to detect crude differences between patients with or without cardiovascular events. Least-squares linear regression analysis was used to assess univariate associations between variables. One-factor ANOVA and a post hoc stepdown multiple stage F test (REGWF—Ryan, Einot, Gabriel, Welsch F test) has been used to compare LV geometric patterns.

To identify variables that independently predicted cardiovascular morbid events or death, stepwise multiple logistic regression was performed using conventional risk factors. Because of a significant inverse relation between LV mass and midwall fractional shortening, an interaction term was obtained by multiplying the two variables.³³ Alternative analyses were also performed in which LV mass was indexed by body surface area or height, as has been conventional in previous studies.^{7 8 9 10 11 14 15 19 20 25 28}

Product-limit Kaplan-Meier estimation of survival functions was computed for patients with normal or depressed midwall fractional shortening as a percentage of predicted for observed circumferential end-systolic stress. Because of the potential confounding effect of age, adjusted log cumulative hazard functions were also computed by Cox proportional hazards analysis. Identical analyses compared event-free or cardiovascular death–free survival between patients with normal and depressed LV midwall function in the subgroup of patients exhibiting LV hypertrophy by LV mass/height^2.7 criteria. The Breslow-Gehan log-rank test was used to compare the survival curves.

The null hypothesis was rejected at a two-tailed P<.05.

	Results

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Patients were followed through a mean period of 10 years (3.4 to 15 years for subjects without cardiovascular events and 3.7 to 13.4 years for those experiencing cardiovascular complications; P=NS). At the time of follow-up, 50 subjects, or 17%, had suffered cardiovascular morbid events. During follow-up, 83% of patients took antihypertensive medication all or most of the time, while the remainder used medication less consistently or opted for nonpharmacological therapy. Diuretics and ß-blockers were each used by a majority of patients, and angiotensin-converting enzyme inhibitors, calcium channel blockers, other sympatholytic agents, and vasodilators were used by smaller proportions. No relation existed between medications used and outcome, possibly because of a high frequency of combination therapy or serial monotherapy with different drugs.

By the new classification for LV geometry based on normalization of LV mass for height^2.7, follow-up cardiovascular fatal or nonfatal events occurred in 16 of 163 patients (9.8%) with normal left ventricle, in 4 of 32 patients (12.5%) with concentric remodeling, in 15 of 53 patients (28.3%) with eccentric LV hypertrophy, and in 15 of 46 patients (32.6%) with concentric LV hypertrophy. At baseline, patients with concentric LV hypertrophy had higher blood pressure than those with normal LV geometry (164±26/100±15 versus 151±19/94±10 mm Hg, both P<.006). Body mass index was higher in patients with eccentric or concentric LV hypertrophy (27.1±3.6 and 28.0±5.6 kg/m²) than in the groups with normal left ventricle (25.4±3.7 kg/m²) or concentric remodeling (24.9±3.2 kg/m², all P<.02).

At baseline, 56 of 294 hypertensive patients (19%) exhibited depressed midwall LV performance. Table 1 shows that these patients exhibited higher body mass index (P<.04) but were statistically indistinguishable from the remaining patients in sex and race distribution, prevalence of smoking (23% versus 18%), age, cholesterol levels, and blood pressure values. In ² analysis, the prevalence of obesity was higher in patients with depressed LV function (46%) than in those with normal LV function (23%, P<.003). Concentric LV hypertrophy, characterized by increases in both LV mass/height^2.7 and relative wall thickness, was more prevalent in the group of patients with depressed LV midwall function (53% versus 7%, P<.0001).

View this table: [in this window] [in a new window]   Table 1. Characteristics of Hypertensive Patients With Normal or Depressed Midwall Left Ventricular (LV) Fractional Shortening

Midwall LV Performance
Table 2 shows that patients who suffered morbid events during follow-up had lower baseline midwall shortening than patients without events, both as an absolute value and as a percentage of that predicted for end-systolic stress (both P<.005), while differences in endocardial shortening did not achieve statistical significance. Analogously, Table 3 shows that occurrence of cardiovascular death was more strongly associated with depressed baseline midwall shortening both as an absolute value and as a percentage of predicted (both P<.01). Endocardial shortening was not significantly reduced in patients who suffered cardiovascular death.

View this table: [in this window] [in a new window]   Table 2. Endocardial and Midwall Left Ventricular Performance in Hypertensive Patients With or Without Follow-up Cardiovascular Morbid Events

View this table: [in this window] [in a new window]   Table 3. Endocardial and Midwall Left Ventricular Performance in Hypertensive Patients With or Without Follow-up Fatal Cardiovascular Events

Midwall shortening was inversely related to LV mass index (r=-.53, SEE=3%, P<.0001), whereas endocardial shortening was not (r=-.10, P<.09).

Predictors of Cardiovascular Morbid Events or Death
Use of LV mass/height^2.7 criteria identified more patients as having LV hypertrophy than did the LV mass/body surface area–based criteria we have previously used^{10 19} : 99 patients (34%) were classified as having LV hypertrophy, as opposed to 76 (26%) whose LV mass/body surface area exceeded 125 g/m². Thirty of 99 patients (31%) with baseline LV mass/height^2.7 >51 g/m^2.7 suffered follow-up cardiovascular morbid events, as did 22 of 76 (29%) of those with LV mass/body surface area >125 m². Correspondingly, the proportion of patients without LV hypertrophy who suffered cardiovascular morbid events was 20 of 195 (10%) for LV mass/height^2.7 criteria and 28 of 218 (13%) for LV mass/body surface area criteria.

Cardiac death occurred in 13 of 99 patients (13%) with baseline LV hypertrophy as opposed to 1 of 195 (0.5%) with normal LV mass/height^2.7 (P<.0001). One patient who died of myocardial infarction had not been considered to have LV hypertrophy by LV mass/body surface area criteria but was reclassified by LV mass/height^2.7 criteria (56 g/m^2.7); this patient was a 56-year-old obese (40 kg/m²) white man with high serum cholesterol (284 mg/dL) and high relative wall thickness (0.46) but normal LV mass/body surface area (112 g/m²).

Cardiac death occurred during follow-up in 7 of 56 patients (13%) whose midwall LV performance was initially depressed as opposed to 7 of 238 (3%) of those with initially normal midwall shortening (P<.002). Fig 1 shows that midwall shortening and LV mass index had an effect that was at least additive in terms of prediction of cardiovascular morbid events. Cardiovascular events occurred in 29 of 100 patients (29%) who were in both the two highest quartiles of LV mass index and the two lowest quartiles of midwall shortening, as opposed to 21 of 194 (11%) of the remaining patients (odds ratio, 3.4; 95% CI, 1.8 to 6.3; P<.0001). Analogously, cardiovascular death occurred in 10 of 100 patients (10%) who were in both the two highest quartiles of LV mass index and the two lowest quartiles of midwall shortening, as opposed to 4 of 194 of the other patients (2%) (odds ratio, 5.3; 95% CI, 1.6 to 17.3; P<.006).

View larger version (32K): [in this window] [in a new window]   Figure 1. Three-dimensional bar graph showing occurrence of cardiovascular morbid events (vertical axis) in relation to increasing quartiles of left ventricular (LV) mass index (horizontal axis) and decreasing quartiles of midwall fractional shortening (diagonal axis). Of all patients with cardiovascular morbid events, 58% fell into both the two highest quartiles of LV mass index and the two lowest quartiles of midwall shortening. Analogously, 10 of 14 patients (71%) who died of cardiovascular complications were in the highest quartile of LV mass index and in the lowest quartile of midwall shortening.

Consistent with the previous analysis, among the 99 patients with LV hypertrophy (high LV mass/height^2.7), midwall LV shortening as a percentage of that predicted from wall stress was statistically lower in the 30 patients with follow-up fatal or nonfatal cardiovascular events (78±22%) than in the event-free survivors (88±18%, P<.02). A less statistically significant difference was observed with endocardial shortening as a percentage of predicted (100±20% versus 107±14%, P<.05). Of note, in the subgroup of patients with LV hypertrophy, LV mass index, indexed for either height^2.7 or body surface area criteria, was statistically indistinguishable between subjects with and those without follow-up cardiovascular events (70±21 versus 65±15 g/m^2.7, P>.2, and 156±46 versus 143±32 g/m², P>.1, respectively). Among patients with concentric LV hypertrophy (n=46), midwall shortening as a percentage of predicted was significantly lower in the 15 patients with follow-up cardiovascular morbid events (64±21%) than in the event-free patients (76±10%, P<.01). The same trend, although not statistically significant, was found among the 53 patients with eccentric LV hypertrophy (92±11% versus 98±17%, P<.2).

Age, cholesterol levels, systolic and diastolic blood pressures, sex, LV mass index, midwall shortening as a percentage of predicted, and the interaction term of LV mass index times midwall shortening were tested as potential independent predictors of both cardiovascular morbidity and mortality. Table 4 shows that age, systolic blood pressure, LV mass index, and the interaction between LV mass index and midwall LV shortening were independent predictors of cardiovascular morbid events and that age, the ratio of observed to predicted midwall shortening, and the midwall shorteningxLV mass index interaction term were independent predictors of cardiovascular death. The interaction term had opposite influences as a predictor of cardiovascular events or death, suggesting that it was influenced primarily by decreased midwall LV performance in the model predicting cardiovascular events and by increased LV mass index in that predicting cardiac death. Good degrees of agreement were found between observed and predicted frequencies in the logistic models, using both the Hosmer-Lemeshow goodness-of-fit ² and the group membership concordance index.

View this table: [in this window] [in a new window]   Table 4. Independent Predictors of Occurrence of Cardiovascular Morbid Events or Cardiovascular Death in Hypertensive Patients

Time-Dependent Analyses
In analyses that used time-dependent procedures to avoid confounding effects of different follow-up times, depressed midwall LV performance significantly influenced the likelihood of both event-free survival (P<.003; Fig 2, top; Breslow-Gehan log-rank test) and crude survival from cardiovascular death (P<.001; Fig 2, bottom). In the subgroup of 99 patients with increased LV mass, the 36 with depressed LV midwall function had a greater incidence of either cardiovascular fatal and nonfatal events or death (P<.02 and P<.05, Fig 3). The predictive value of depressed midwall shortening for event-free survival and for cardiovascular death persisted after the effect of age in the entire population sample (P<.04 and P<.001) or in the subgroup with LV hypertrophy was controlled for (both P<.05).

View larger version (16K): [in this window] [in a new window]   Figure 2. Graphs. Top, Probability of event-free survival (vertical axis) in patients with (dashed line) and those without (solid line) midwall left ventricular (LV) dysfunction. The difference remained significant after age was controlled for by Cox proportional hazards analysis (P<.04). Bottom, Probability of crude survival in patients with (dashed line) and those without (solid line) midwall LV dysfunction. The difference remained significant after age was controlled for by Cox proportional hazards analysis (P<.001).

View larger version (17K): [in this window] [in a new window]   Figure 3. Graphs. Top, Probability of event-free survival (vertical axis) in hypertensive patients with left ventricular (LV) hypertrophy further subdivided into those with (dashed line) and those without (solid line) midwall LV dysfunction. The difference remained significant after age was controlled for by Cox proportional hazards analysis (P<.05). Bottom, Probability of crude survival in hypertensive patients with LV hypertrophy further subdivided into those with (dashed line) and those without (solid line) midwall LV dysfunction. The difference remained significant after age was controlled for by Cox proportional hazards analysis (P<.05).

	Discussion

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LV dysfunction is a major predictor of adverse outcome in coronary heart disease.^{12 13} The possibility that it might also influence outcome in arterial hypertension has not been considered previously because of the lack of an appreciable proportion of patients with depressed LV function in available clinical studies. Many clinical studies, on the contrary, showed supranormal resting LV function to be common in hypertensive patients.^{14 15 34 35} However, recent analyses^{17 18} indicate that the absence of patients with depressed and the presence of patients with supernormal LV function in those studies was, in large part, the consequence of overestimation of LV myocardial performance due to the usual practice of relating measurement of changes of LV muscle length (fractional shortening or velocity of circumferential fiber shortening) at the level of endocardium to the mean level of end-systolic stress across the LV wall. This practice differs from the experimental model by which stress-shortening relations were validated primarily as a measure of myocardial inotropic state, because both the degree of shortening and the level of opposing forces in a papillary muscle preparation are oriented along the central axis of the muscle strip. In the intact ventricle, in which both circumferentially and meridionally oriented muscle fibers follow curvilinear paths, both the degree of myocardial fiber shortening and the level of wall stress in systole vary systematically from endocardium to epicardium. The conceptual mismatch between endocardial shortening and mean wall stress has little effect on results when inotropic status is assessed during different interventions in the same subjects or is compared among subjects with similar ratios of LV wall thickness to chamber radius (relative wall thickness) but will lead to overestimation of myocardial performance when patients with higher relative wall thickness are compared with patients with lower relative wall thickness by use of endocardial measurements of fiber shortening. Measuring midwall shortening directly avoided this overestimation and revealed that a substantial proportion of hypertensive patients had reduced LV performance in previous studies.^{16 18}

In this study, the 19% of hypertensive patients who had reduced midwall shortening at baseline were three to five times more likely than the remaining patients to experience fatal or nonfatal cardiovascular events during follow-up. The adverse effect of decreased midwall LV shortening on mortality was independent of the presence of traditional cardiovascular risk factors and, at least partially, of increased LV mass. Prediction of cardiovascular adverse events by midwall LV shortening (but not by LV mass index) was indeed still present when only patients with LV hypertrophy were considered in the analysis. In particular, in patients with concentric LV hypertrophy, the individuals suffering follow-up cardiovascular morbid events exhibited significantly lower levels of midwall shortening at baseline than those who remained event free. A parallel trend was also observed in patients with eccentric LV hypertrophy.

The presence of LV hypertrophy and depressed midwall shortening appear to be two closely associated biological phenomena. An interesting interaction between midwall LV dysfunction and increased LV mass was evident in our analysis. LV performance, as measured by midwall shortening, was inversely related to LV mass index, an association that has been reported previously.^{36 37} The biological interaction between the two variables was confirmed mathematically by the logistic regression analysis, indicating that LV hypertrophy remained a potent independent predictor of cardiovascular morbid events, whereas midwall LV dysfunction was the strongest predictor of cardiac death. LV dysfunction identified by the relation of midwall shortening to end-systolic stress predicts an increased likelihood of cardiovascular events. The level of cardiovascular risk became highest when low-normal to depressed LV midwall performance was associated with high-normal to elevated LV mass index (see Fig 1). In time-dependent analyses, midwall LV dysfunction was confirmed to be as important as LV hypertrophy in the prediction of both overall cardiovascular morbid events and cardiovascular death. Of particular note, the predictive value of low midwall fiber shortening was still present in the subgroup of patients with LV hypertrophy. However, LV mass and midwall shortening are not independent of each other, for physiological reasons. In experimental renovascular hypertension in rats, Buttrick et al³⁸ showed that increasing LV mass is strongly associated with an increased ratio of ß- to -myosin heavy chain RNA expression, a molecular shift that is associated with reduced velocity of LV contraction. Also in human atria, which normally express -myosin heavy chain, a switch to the ß-myosin heavy chain has been reported in response to pressure overload, suggesting that molecular phenotype associated with decreased myocardial contractility can also parallel and may contribute to stimulating human myocardial hypertrophy.³⁹ The clinical evidence of both LV hypertrophy and midwall dysfunction, therefore, identifies a subset of patients with a particularly high risk of future fatal or nonfatal cardiovascular events.

The absolute difference in midwall shortening between groups of patients with or without cardiovascular fatal and nonfatal events is small, being 2% or 3% in Tables 2 and 3. However, this fact needs to be put into context by considering that these values represent 1 to 1.5 SEE of midwall shortening in relation to end-systolic stress. For proportionate differences between groups to represent an equivalent proportion of the variability of measurements, groups would need to differ by 21 to 32 mm Hg for systolic blood pressure or 34 to 51 g/m² for LV mass. Thus, the differences in baseline midwall shortening between groups with or without subsequent morbid events are proportionate, for a variable with relatively small intragroup variability, to clinically striking intergroup differences in more traditional variables.

In conclusion, midwall LV dysfunction assessed by M-mode echocardiography is an independent predictor of cardiac death and also contributes independently to the prediction of cardiovascular morbid events in patients with arterial hypertension. Assessment of midwall LV mechanics appears to be substantially more useful than endocardial shortening for prognostic stratification of hypertensive patients. These effects are independent of the presence of LV hypertrophy and, in fact, are most striking in the presence of myocardial hypertrophy.

	Acknowledgments

 
This study was supported in part by grant HL-18323 from the National Heart, Lung, and Blood Institute, Bethesda, MD. We would like to thank Virginia Burns for her assistance in the preparation of this manuscript.

Received October 31, 1994; revision received August 31, 1995; accepted September 12, 1995.

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