In-treatment HDL cholesterol levels and development of new diabetes mellitus in hypertensive patients: the LIFE Study.

AIMS: Although hypertensive patients with low baseline HDL cholesterol levels have a higher incidence of diabetes mellitus, whether changing levels of HDL over time are more strongly related to the risk of new diabetes in hypertensive patients has not been examined. METHODS: Incident diabetes mellitus was examined in relation to baseline and in-treatment HDL levels in 7485 hypertensive patients with no history of diabetes randomly assigned to losartan- or atenolol-based treatment. RESULTS: During 4.7 ± 1.2 years follow-up, 520 patients (6.9%) developed new diabetes. In univariate Cox analyses, compared with the highest quartile of HDL levels (> 1.78 mmol/l), baseline and in-treatment HDL in the lowest quartile (< 1.21 mmol/l) identified patients with > 5-fold and > 9 fold higher risks of new diabetes, respectively; patients with baseline or in-treatment HDL in the 2nd and 3rd quartiles had intermediate risk of diabetes. In multivariable Cox analyses, adjusting for randomized treatment, age, sex, race, prior anti-hypertensive therapy, baseline uric acid, serum creatinine and glucose entered as standard covariates, and in-treatment non-HDL cholesterol, Cornell product left ventricular hypertrophy, diastolic and systolic pressure, BMI, hydrochlorothiazide and statin use as time-varying covariates, the lowest quartile of in-treatment HDL remained associated with a nearly 9-fold increased risk of new diabetes (hazard ratio 8.7, 95% CI 5.0-15.2), whereas the risk of new diabetes was significantly attenuated for baseline HDL < 1.21 mmol/l (hazard ratio 3.9, 95% CI 2.8-5.4). CONCLUSIONS: Lower in-treatment HDL is more strongly associated with increased risk of new diabetes than baseline HDL level.

Impact of overweight and obesity on cardiac benefit of antihypertensive treatment.

BACKGROUND AND AIMS: Increased body mass index (BMI) has been associated with increased cardiovascular morbidity and mortality in hypertension. Less is known about the impact of BMI on improvement in left ventricular (LV) structure and function during antihypertensive treatment. METHODS AND RESULTS: Annual BMI, echocardiograms and cardiovascular events were recorded in 875 hypertensive patients with LV hypertrophy during 4.8 years randomized treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy. Patients were grouped by baseline BMI into normal (n = 282), overweight (n = 405), obese (n = 150) and severely obese groups (n = 38) (BMI ≤24.9, 25.0-29.9, 30.0-34.9, and ≥35.0 kg/m(2), respectively). At study end, residual LV hypertrophy was present in 54% of obese and 79% of severely obese patients compared to 31% of normal weight patients (both p < 0.01). In regression analyses, adjusting for initial LV mass/height(2.7), higher BMI predicted less LV hypertrophy reduction and more reduction in LV ejection fraction (both p < 0.05), independent of blood pressure reduction, diabetes and in-study weight change. During follow-up, 91 patients suffered cardiovascular death, myocardial infarction or stroke. In Cox regression analysis 1 kg/m(2) higher baseline BMI predicted a 5% higher rate of cardiovascular events and 10% higher cardiovascular mortality over 4.8 years (both p < 0.05). CONCLUSIONS: In hypertensive patients in the LIFE study, increased BMI was associated with less reduction of LV hypertrophy and less improvement in LV systolic function which may contribute to the observed higher cardiovascular event rate of treated hypertensive patients.

Changes in electrocardiographic left ventricular hypertrophy and risk of major cardiovascular events in isolated systolic hypertension: the LIFE study.

The predictive value of changes in the severity of electrocardiographic left ventricular hypertrophy (ECG-LVH) during antihypertensive therapy remains unclear in isolated systolic hypertension (ISH). In a Losartan Intervention For Endpoint reduction in hypertension substudy, we included 1320 patients aged 54-83 years with systolic blood pressure (BP) of 160-200 mm Hg, diastolic BP <90 mm Hg and ECG-LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria, randomized to losartan- or atenolol-based treatment with a mean follow-up of 4.8 years. The composite end point of cardiovascular death, non-fatal myocardial infarction (MI) or stroke occurred in 179 (13.6%) patients. In Cox regression models controlling for treatment, Framingham risk score, as well as baseline and in-treatment BP, less severe in-treatment ECG-LVH by Cornell product and Sokolow-Lyon voltage was associated with 17 and 25% risk reduction for the composite end point (adjusted hazard ratio (HR) 0.83, 95% confidence interval (95% CI:) 0.75-0.92, P=0.001 per 1050 mm × ms (1 s.d.) lower Cornell product; and HR 0.75, 95% CI: 0.65-0.87, P<0.001 per 10.5 mm (1 s.d.) lower Sokolow-Lyon voltage). In parallel analyses, lower Cornell product and Sokolow-Lyon voltage were associated with lower risks of cardiovascular mortality and MI, and lower Sokolow-Lyon voltage with lower risk of stroke. Lower Cornell product and Sokolow-Lyon voltage during antihypertensive therapy are associated with lower likelihoods of cardiovascular events in patients with ISH.

Clustered metabolic abnormalities blunt regression of hypertensive left ventricular hypertrophy: the LIFE study.

BACKGROUND AND AIMS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two or more metabolic abnormalities (MetAb, including obesity, high plasma glucose without diabetes, low HDL-cholesterol) in addition to hypertension were associated to levels of ECG LVH reduction comparable to that obtained in hypertensive subjects without or with only one additional metabolic abnormality (no-MetAb). METHODS AND RESULTS: We studied 5558 non-diabetic participants without MetAb (2920 women) and 1235 with MetAb (751 women) from the LIFE-study cohort. MetAb was defined by reported LIFE criteria, using partition values from the ATPIII recommendations. Time-trends of Cornell voltage-duration product (CP) over 5 years was assessed using a quadratic polynomial contrast, adjusting for age, sex, prevalent cardiovascular disease and treatment arm (losartan or atenolol). At baseline, despite similar blood pressures, CP was greater in the presence than in the absence of MetAb (p<0.0001). During follow-up, despite similar reduction of blood pressure, CP decreased less in patients with than in those without MetAb, even after adjustment for the respective baseline values (both p<0.002). Losartan was more effective than atenolol in reducing CP independently of MetAb. CONCLUSIONS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome are related to greater initial ECG LVH in hypertensive patients with value of blood pressure similar to individuals without metabolic abnormalities, and are associated with less reduction of ECG LVH during antihypertensive therapy, potentially contributing to the reported adverse prognosis of metabolic syndrome.

Impact of diabetes on treatment-induced changes in left ventricular structure and function in hypertensive patients with left ventricular hypertrophy. The LIFE study.

BACKGROUND AND AIM: Diabetes is associated with left ventricular hypertrophy (LVH) and impaired systolic function in hypertensive patients, but less is known about its impact on LVH regression and functional improvement during antihypertensive treatment. METHODS AND RESULTS: We performed annual echocardiography in 730 non-diabetic and 93 diabetic patients (aged 55-80 years) with hypertension and electrocardiographic LVH during 4.8-year losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Baseline mean blood pressure (BP) and LV mass did not differ between groups. Diabetic patients had higher body mass index and pulse pressure, and lower LV ejection fraction, midwall shortening, stress-corrected midwall shortening, and estimated glomerular filtration rate (all p<0.05), and were more likely to have albuminuria. Despite comparable BP reduction in diabetic and non-diabetic groups during treatment (33/18 vs. 28/16mmHg (ns)), diabetes was associated with higher prevalence of persistent LVH (47 vs. 39%, p<0.05). In multivariate analyses, diabetes independently predicted less LV mass reduction and less improvement in stress-corrected LV midwall shortening (both p<0.01). CONCLUSION: Among hypertensive patients with LVH, diabetes is associated with more residual LVH and less improvement in systolic LV function by echocardiography over 4.8 years of antihypertensive treatment.

Regression of electrocardiographic left ventricular hypertrophy predicts regression of echocardiographic left ventricular mass: the LIFE study.

The electrocardiogram (ECG) is widely used for detection of left ventricular hypertrophy (LVH). However, whether changes in ECG LVH during antihypertensive therapy predict changes in LV mass remains unclear. Baseline and year-1 ECGs and echocardiograms were assessed in 584 hypertensive patients with ECG LVH by Sokolow-Lyon or Cornell voltage-duration product criteria at entry into the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. A >/=25% decrease in Cornell product defined regression of ECG LVH; a <25% decrease defined no significant regression; and an increase defined progression of ECG LVH. Regression of echocardiographic LVH was defined by a >/=20% reduction in LV mass. After 1 year of therapy, 155 patients (27%) had regression of ECG LVH, 286 (49%) had no significant change, and 143 (25%) had progression of ECG LVH. Compared with patients with progression of ECG LVH, patients with no significant decrease and patients with regression of ECG LVH had stepwise greater absolute decreases in LV mass (-16+/-33 vs -29+/-37 vs -32+/-41 g, P<0.001), greater percent reductions in LV mass (-5.7+/-14.6 vs -11.3+/-13.6 vs -12.3+/-15.6%, P<0.001), and were more likely to decrease LV mass by >/=20% (11.2 vs 24.8 vs 36.1%, P<0.001), even after adjusting for possible effects of baseline and change in systolic and diastolic pressures. Compared with progression of ECG LVH, regression of the Cornell product ECG LVH is associated with greater reduction in LV mass and a greater likelihood of regression of anatomic LVH.

Association of left bundle branch block with left ventricular structure and function in hypertensive patients with left ventricular hypertrophy: the LIFE study.

Electrocardiographic (ECG) left bundle branch block (LBBB) is associated with left ventricular hypertrophy (LVH), but its relation to left ventricular (LV) geometry and function in hypertensive patients with ECG LVH is unknown. Echocardiograms were performed in 933 patients (548 women, mean age 66+/-7 years) with essential hypertension and LVH by baseline ECG in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. LBBB, defined by Minnesota code 7.1, was present in 47 patients and absent in 886 patients. Patients with and without LBBB were similar in age, gender, body mass index, blood pressure, prevalence of diabetes, and history of myocardial infarction. Despite similarly elevated mean LV mass (126+/-25 vs 124+/-26 g/m(2)) and relative wall thickness (0.41+/-0.07 vs 0.41+/-0.07, P=NS), patients with LBBB had lower LV fractional shortening (30+/-6 vs 34+/-6%), ejection fraction (56+/-10 vs 61+/-8%), midwall shortening (14+/-2 vs 16+/-2%), stress-corrected midwall shortening (90+/-13 vs 97+/-13%) (all P<0.001), and lower LV stroke index (38+/-7 vs 42+/-9 ml/m(2)) (P<0.05). Patients with LBBB also had reduced LV inferior wall and lower mitral E/A ratio (0.75+/-0.18 vs 0.87+/-0.38) (all P<0.05). The above univariate results were confirmed by multivariate analyses adjusted for gender, age, blood pressures, height, weight, body mass index, heart rate, and LV mass index. Among hypertensive patients at high risk because of ECG LVH, the presence of LBBB identifies individuals with worse global and regional LV systolic function and impaired LV relaxation without more severe LVH by echocardiography.

A blood pressure independent association between glomerular albumin leakage and electrocardiographic left ventricular hypertrophy. The LIFE Study. Losartan Intervention For Endpoint reduction.

In the Losartan Intervention For Endpoint reduction (LIFE) study left ventricular (LV) hypertrophy was associated with increased urine albumin/creatinine ratio (UACR) at baseline. To evaluate whether this association was due only to parallel blood pressure (BP)-induced changes we re-examined the patients after 1 year of antihypertensive treatment to investigate whether changes in LV hypertrophy and UACR were related independently of changes in BP. In 7,142 hypertensive patients included in the LIFE study, we measured UACR, LV hypertrophy by electrocardiography, plasma glucose and BP after 2 weeks of placebo treatment and again after 1 year of antihypertensive treatment with either an atenolol or a losartan based regime. At baseline and still after 1 year of treatment logUACR (R = 0.28, P < 0.001) was still correlated to LV hypertrophy (beta = 0.05) assessed by ECG independently of systolic BP (beta = 0.16), plasma glucose (beta = 0.19) and age (beta = 0.08). Change in logUACR (R = 0.19, P < 0.001) during treatment was correlated to change in LV hypertrophy (beta = 0.10) independently of reduction in systolic BP (beta = 0.13) and change in plasma glucose (beta = 0.06). After 1 year of antihypertensive treatment UACR was still related to LV hypertrophy independently of systolic BP, and the reduction in UACR during that first year of treatment was related to regression of LV hypertrophy independently of reduction in systolic BP. This suggests that the relationship between LV hypertrophy and glomerular albumin leakage is not just due to parallel BP-induced changes. As glomerular albumin leakage may represent generalised vascular damage we hypothesise a vascular relationship between cardiac and glomerular damage.

Relation of QT interval and QT dispersion to echocardiographic left ventricular hypertrophy and geometric pattern in hypertensive patients. The LIFE study. The Losartan Intervention For Endpoint Reduction.

OBJECTIVE: In hypertensive patients, left ventricular hypertrophy (LVH) predicts increased mortality, in part due to an increased incidence of sudden death. Repolarization-related arrhythmogenesis may be an important mechanism of sudden death in hypertensive patients with LVH. Increased QT interval and QT dispersion are electrocardiographic (ECG) measures of ventricular repolarization, and also risk markers for ventricular tachyarrhythmias. We assessed the relation of QT intervals and QT dispersion to echocardiographically determined left ventricular (LV) mass and geometry in a large population of hypertensive patients with ECG evidence of LVH. METHODS: QT intervals and QT dispersion were determined from baseline 12-lead ECGs in 577 (57% male; mean age 65 +/- 7 years) participants in the LIFE study. LV mass index (LVMI) and geometric pattern were determined by echocardiography and QT interval duration and QT dispersion were assessed in relation to gender-specific LVMI quartiles. RESULTS: In both genders, increasing LVMI was associated with longer rate-adjusted QT intervals. QT dispersion measures showed a weaker association with LVMI quartiles. Both concentric and eccentric LVH were associated with increased QT interval duration and QT dispersion. These relations remained significant after controlling for relevant clinical variables. CONCLUSIONS: In hypertensive patients with ECG evidence of LVH, increased LVMI and LVH are associated with a prolonged QT interval and increased QT dispersion. These findings suggest that an increased vulnerability to repolarization-related ventricular arrhythmias might in part explain the increased risk of sudden death in hypertensive patients with increased LV mass.

Relation of echocardiographic left ventricular mass and hypertrophy to persistent electrocardiographic left ventricular hypertrophy in hypertensive patients: the LIFE Study.

BACKGROUND: The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) trial used left ventricular hypertrophy (LVH) on a screening ECG to identify patients at high risk for morbid events. Because of regression to the mean, not all patients who met screening criteria had persistent ECG LVH on the ECG performed at study baseline. METHODS: The relationship of echocardiographic LV mass and LVH to persistence or loss of ECG LVH between screening and baseline evaluation was examined in 906 hypertensive patients in the LIFE study, who had echocardiograms and additional ECG performed at study baseline. Patients were categorized according to the presence or absence of ECG LVH by Cornell voltage-duration product criteria or Sokolow-Lyon voltage criteria; echocardiographic LVH was defined by LV mass index (LVMI) > 104 g/m2 in women and > 116 g/m2 in men. RESULTS: A total of 678 patients (75%) had persistent ECG LVH at baseline evaluation. Compared with the 228 patients without ECG LVH on the second ECG by either criterion, the 106 patients with LVH by both Cornell product and Sokolow-Lyon criteria had significantly higher LVMI (140+/-31 v 114+/-21 g/m2, P < .001) and a higher prevalence of echocardiographic LVH (86% v 55%, P < .001). Patients with ECG LVH on the baseline ECG by either Cornell product criteria (n = 410) or Sokolow-Lyon voltage criteria (n = 162) had intermediate values of LVMI (125+/-25 and 121+/-21 g/m2) and prevalences of echocardiographic LVH (78% and 62%). After controlling for possible effects of age, sex, ethnicity, systolic blood pressure, and body mass index, persistence of ECG LVH on the baseline ECG was associated with an increased risk of echocardiographic LVH: compared with patients with neither ECG criteria for LVH, patients with only Sokolow-Lyon voltage criteria had a 1.2-fold increased risk of echocardiographic LVH, those with only Cornell product criteria had a 2.7-fold increased risk, and patients with both ECG criteria had a 4.1-fold increased risk of echocardiographic LVH (P < .001). CONCLUSIONS: Persistent ECG LVH between screening and LIFE study baseline identified patients with greater LV mass and a higher prevalence of echocardiographic LVH, suggesting that these patients may be at higher risk for subsequent morbid and mortal events.

Relationship of the electrocardiographic strain pattern to left ventricular structure and function in hypertensive patients: the LIFE study. Losartan Intervention For End point.

OBJECTIVES: This study was designed to assess the relation of electrocardiographic (ECG) strain to increased left ventricular (LV) mass, independent of its relation to coronary heart disease (CHD). BACKGROUND: The classic ECG strain pattern, ST depression and T-wave inversion, is a marker for left ventricular hypertrophy (LVH) and adverse prognosis. However, the independence of the relation of strain to increased LV mass from its relation to CHD has not been extensively examined. METHODS: Electrocardiograms and echocardiograms were examined at study baseline in 886 hypertensive patients with ECG LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage enrolled in the Losartan Intervention For End point (LIFE) echocardiographic substudy. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite to the QRS axis in leads V5 and/or V6. RESULTS: Strain occurred in 15% of patients, more commonly in patients with than without evident CHD (29%, 51/175 vs. 11%, 81/711, p < 0.001). When differences in gender, race, diabetes, systolic pressure, serum creatinine and high density lipoprotein cholesterol were controlled, strain on baseline ECG was associated with greater indexed LV mass in patients with (152 +/- 33 vs. 131 +/- 32 g/m2, p < 0.001) or without CHD (131 +/- 24 vs. 119 +/- 22 g/m2, p < 0.001). In logistic regression analyses, strain was associated with an increased risk of anatomic LVH in patients with CHD (relative risk 5.14, 95% confidence interval [CI] 1.16 to 22.85, p = 0.0315), without evident CHD (relative risk 2.91, 95% CI 1.50 to 5.65, p = 0.0016), and in the overall population when CHD was taken into account (relative risk 2.98, 95% CI 1.65 to 5.38, p = 0.0003). CONCLUSIONS: When clinical evidence of CHD is accounted for, ECG strain is likely to indicate the presence of anatomic LVH. Greater LV mass and higher prevalence of LVH in patients with strain offer insights into the known association of the strain pattern with adverse outcomes.

Echocardiographic left ventricular geometry in hypertensive patients with electrocardiographic left ventricular hypertrophy: The LIFE Study.

AIM: To assess the prevalence of echocardiographic left ventricular hypertrophy (LVH) and concentric remodeling in hypertensive patients with electrocardiographic (ECG)-LVH and to estimate the cost-effectiveness of echocardiography and ECG for detection of LVH. DESIGN: Echocardiographic LV measurements and the prevalence of abnormal LV geometric patterns were compared between 964 hypertensive patients with ECG-LVH (Cornell voltage-duration product > 2440 and/or SV1 +/- RV5-6 > 38 mm) participating in the LIFE trial and groups of 282 employed hypertensives and 366 apparently normal adults. RESULTS: Among both women and men, stepwise increases from reference subjects to employed hypertensives to LIFE patients were observed for LV wall thicknesses, chamber size and mass. Mean LV mass/body surface area (BSA) and LV mass/height(2.7) were substantially larger in LIFE patients than normal adults among women (113 vs 69 g/m2 and 55 vs 32 g/m(2.7), p <0.001) and men (127 vs 83 g/m2 and 55 vs 36 g/m(2.7), p < 0.001), with intermediate values in employed hypertensives. Compared to the latter group, LIFE patients had higher prevalences of concentric LVH (25-29% vs 3-4%) and eccentric LVH (45-51% vs 13-17%) but not concentric LV remodeling (8-11% vs 12-14%). LVH was present in 70% of LIFE patients by LV mass/BSA criteria and 76% by LV mass/height(2.7) criteria (odds ratios = 11.4 and 13.5 vs employed hypertensives). CONCLUSIONS: The ECG criteria used in LIFE identify hypertensive patients with a >70% prevalence of anatomic LVH, allowing accurate identification of high-risk status by this commonly used technique.

Spontaneous interpolated atrial premature complex detected by 12-lead ambulatory monitoring.

Spontaneous occurrence of an interpolated atrial premature complex, an unusual finding outside of the experimental electrophysiology laboratory, was detected and confirmed by evaluation of P-wave morphology in a patient who underwent 12-lead ambulatory electrocardiography.

Computerized ST depression analysis improves prediction of all-cause and cardiovascular mortality: the strong heart study.

BACKGROUND: Nonspecific ST depression assessed by standard visual Minnesota coding (MC) has been demonstrated to predict risk. Although computer analysis has been applied to digital ECGs for MC, the prognostic value of computerized MC and computerized ST depression analyses have not been examined in relation to standard visual MC. METHODS: The predictive value of nonspecific ST depression as determined by visual and computerized MC codes 4.2 or 4.3 was compared with computer-measured ST depression >or= 50 microV in 2,127 American Indian participants in the first Strong Heart Study examination. Computerized MC and ST depression were determined using separate computerized-ECG analysis programs and visual MC was performed by an experienced ECG core laboratory. RESULTS: The prevalence of MC 4.2 or 4.3 by computer was higher than by visual analysis (6.4 vs 4.4%, P < 0.001). After mean follow-up of 3.7 +/- 0.9 years, there were 73 cardiovascular deaths and 227 deaths from all causes. In univariate Cox analyses, visual MC (relative risk [RR] 4.8, 95% confidence interval [CI] 2.6-9.1), computerized MC (RR 6.0, 95% CI 3.5-10.3), and computer-measured ST depression (RR 7.6, 95% CI 4.5-12.9) were all significant predictors of cardiovascular death. In separate multivariate Cox regression analyses that included age, sex, diabetes, HDL and LDL cholesterol, body mass index, systolic and diastolic blood pressure, microalbuminuria, smoking, and the presence of coronary heart disease, computerized MC (RR 3.0, 95% CI 1.6-5.6) and computer-measured ST depression (RR 3.1, 95% CI 1.7-5.7), but not visual MC, remained significant predictors of cardiovascular mortality. When both computerized MC and computer-measured ST depression were entered into the multivariate Cox regression, each variable provided independent risk stratification (RR 2.1, 95% CI 1.0-4.4, and RR 2.1, 95% CI 1.0-4.4, respectively). Similarly, computerized MC and computer-measured ST depression, but not visual MC, were independent predictors of all-cause mortality after controlling for standard risk factors. CONCLUSIONS: Computer analysis of the ECG, using computerized MC and computer-measured ST depression, provides independent and additive risk stratification for cardiovascular and all-cause mortality, and improves risk stratification compared with visual MC. These findings support the use of routine computer analysis of ST depression on the rest ECG for assessment of risk and suggest that computerized MC can replace visual MC for this purpose.

Prognostic implications of left ventricular hypertrophy.

BACKGROUND: To date there has been no comprehensive review of the association between left ventricular hypertrophy (LVH) at baseline and subsequent adverse clinical events. METHODS: A total of 20 studies (with 48,545 participants) published between January 1960 and January 2000, identified through MEDLINE and other sources, related baseline electrocardiographic (ECG) or echocardiographic data on LVH to subsequent cardiovascular morbidity and all-cause mortality. RESULTS: The prevalence of baseline LVH was higher in echocardiographic studies than in ECG studies (16%-74% vs 1%-44%, respectively). The adjusted risk of future cardiovascular morbidity associated with baseline LVH ranged from 1.5 to 3.5, with a weighted mean risk ratio of 2.3 for all studies combined. The adjusted risk of all-cause mortality associated with baseline LVH ranged from 1.5 to 8.0, with a weighted mean risk ratio of 2.5 for all studies combined. There was a trend toward a worse prognosis among women with baseline LVH compared with men. These findings persisted in the various population and ethnic groups studied. CONCLUSION: With the exception of one study in dialysis patients, LVH consistently predicted high risk, independently of examined covariates, with no clear difference in relation to race, presence or absence of hypertension or coronary disease, or between clinical and epidemiologic samples. These results clarify the strong relation between LVH and adverse outcome and emphasize the clinical importance of its detection.

QT dispersion, T-wave projection, and heterogeneity of repolarization in patients with coronary artery disease.

The clinically useful prognostic value of precordial QT dispersion in patients with heart disease is generally attributed to its measurement of regional heterogeneity of ventricular repolarization. However, when repolarization is abnormal, differences in measured QT intervals might result simply from variation in projection of the T-wave loop. To provide insight into the mechanism of QT dispersion, we used an analog device to transform conventional 12-lead electrocardiograms (ECGs) of 78 patients to derived 12-lead ECGs based on the heart vector. Because the electrical activity of the heart is represented by a single dipole, all QT dispersion in the transformed ECGs results from variation in projection of the T-wave loop and cannot be due to local heterogeneity of repolarization. Measured as the difference between the longest and shortest precordial QT intervals, QT dispersion in the derived ECGs, with no local heterogeneity of repolarization, was 53 +/- 49 ms (mean +/- SD). QT dispersion in these derived ECGs was similar in magnitude to that measured from the original standard 12-lead ECGs in these patients (49 +/- 23 ms, p = NS). Therefore, the precordial QT dispersion measured from standard ECGs of patients with coronary artery disease can be explained by interlead variation in precordial projection of the T-wave loop. Although regional heterogeneity might still contribute to precordial repolarization findings and to prognosis, this is not required to explain the QT dispersion observed in patients with coronary artery disease. Therefore, QT interval dispersion is not equivalent to heterogeneity of repolarization.

Baseline characteristics in relation to electrocardiographic left ventricular hypertrophy in hypertensive patients: the Losartan intervention for endpoint reduction (LIFE) in hypertension study. The Life Study Investigators.

The Losartan Intervention For Endpoint (LIFE) reduction in hypertension study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of atenolol on the reduction of cardiovascular morbidity and mortality. A total of 9194 patients with hypertension and ECG left ventricular hypertrophy (LVH) by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria were enrolled in the study, with baseline clinical and ECG data available in 8785 patients (54% women; mean age, 67+/-7 years). ECG LVH by Cornell voltage-duration product criteria was present in 5791 patients (65.9%) and by Sokolow-Lyon voltage in 2025 patients (23.1%). Compared with patients without ECG LVH by Cornell voltage-duration product criteria, patients with ECG LVH by this method were older; more obese; more likely to be female, white, and to have never smoked; more likely to be diabetic and have angina; and had slightly higher systolic, diastolic, and pulse blood pressures. In contrast, patients with ECG LVH by Sokolow-Lyon criteria were slightly younger; less obese; more likely to be male, black, and current smokers; less likely to have diabetes; more likely to have angina and a history of cerebrovascular disease; and had higher systolic and pulse blood pressure but slightly lower diastolic blood pressure than patients without ECG LVH by this method. By use of multivariate logistic regression analyses, presence of ECG LVH by Cornell voltage-duration product criteria was predominantly associated with higher body mass index, increased age, and female gender, whereas presence of ECG LVH by Sokolow-Lyon voltage criteria was predominantly related to lower body mass index, male gender, and black race. Thus, hypertensive patients who meet Cornell product and Sokolow-Lyon voltage criteria are associated with different, but potentially equally adverse, risk factor profiles.

Transmyocardial laser revascularization with excimer laser: clinical results at 1 year.

BACKGROUND: Transmyocardial laser revascularization, a new strategy for the treatment of diffuse ischemic heart disease, uses laser technology for the theoretical purpose of forming transmyocardial channels in the heart to increase perfusion to ischemic zones. This report summarizes our initial clinical experience with the procedure. METHODS: Excimer transmyocardial laser revascularization was performed in a reversibly ischemic region of the heart in 15 patients. Ischemia and myocardial viability were evaluated by assessment of symptoms and of results of radionuclide single photon emission computed tomography imaging, exercise tolerance testing, and 24-hour Holter monitoring. RESULTS: No adverse events occurred as a result of the laser revascularization, although 1 patient with preoperative ventricular arrhythmias died 48 hours postoperatively as a result of refractory ventricular tachycardia. Angina class decreased significantly from base line values in patients who had undergone the procedure (mean Canadian Cardiovascular Association angina class, 3.5+/-0.5 at base line, 1.6+/-0.6 at 1 month, 1.5+/-0.8 at 3 months, 1.9+/-0.9 at 6 months, 1.8+/-0.8 at 12 months; p<0.002), and nitroglycerin requirements were similarly decreased in patients who had undergone laser revascularization (mean g/wk of sublingual nitroglycerin, 19+/-4 at baseline, 5+/-3 at 1 month, 4+/-2 at 3 months, 4+/-2 at 6 months, 2+/-1 at 12 months; p<0.02). Exercise tolerance testing demonstrated increase in exercise duration compared with base line values (mean minutes, 7.4+/-3.1 at base line, 8.0+/-3.9 at 1 month, 8.5+/-4.4 at 3 months, and 9.0+/-3.9 at 12 months; p>0.05); those increases were not large enough to be statistically significant, however. CONCLUSIONS: Our data are consistent with the concept that excimer transmyocardial laser revascularization in individuals with significant ischemic heart disease appears to be well tolerated, can be performed safely, and may lead to a reduction in ischemic symptomatology.

Left ventricular wall stresses and wall stress-mass-heart rate products in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint reduction in hypertension.

OBJECTIVE: Left ventricular (LV) hypertrophy on echocardiogram (ECG) strongly predicts coronary heart disease events, but the mechanisms linking increased LV mass to ischemic vascular events is uncertain. DESIGN: Variables related to myocardial oxygen demand were compared among normotensive adults and patients with mild and more severe hypertension, and among groups of moderately hypertensive patients with target organ damage in relation to gender, LV geometry and LV systolic function. SETTING: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial, in which hypertensive patients with ECG LV hypertrophy (Cornell voltage-duration product, > 2440 mm x ms and/or SV1 + RV(5-6) > 38 mm) were randomized to > or = 4 years double-blinded treatment with losartan or atenolol. PATIENTS/PARTICIPANTS: A total of 964 LIFE participants enrolled in an echocardiographic substudy, and groups of 282 employed hypertensive and 366 apparently normal adults. INTERVENTIONS: None. MAIN OUTCOME MEASURES: ECG LV parameters contributing to myocardial oxygen demand (wall stresses, LV mass, heart rate and wall stress-mass-heart rate products). RESULTS: In both women and men, stepwise increases from reference subjects to employed hypertensives to LIFE patients were observed for LV wall stresses, mass and stress-mass-heart rate products. LIFE men patients had slightly higher wall stresses and significantly higher triple products than women. Wall stresses were increased in patients with normal LV geometry, eccentric or concentric hypertrophy; triple products were about three and two times normal with eccentric and concentric hypertrophy, with smaller increases in other geometric groups. Patients with decreased LV fractional shortening had two times normal end-systolic stresses and three or four times normal triple products; smaller increases in stresses and triple products occurred with decreased LV midwall function. CONCLUSIONS: Hypertensive patients with ECG LV hypertrophy have increased LV wall stresses and stress-mass-heart rate products, suggesting a contribution of high myocardial oxygen demand to increased risk in such patients. Particularly high stresses and triple products were associated with echocardiographic LV hypertrophy, and subnormal LV chamber and midwall function.

Left ventricular geometry and function preceding neurally mediated syncope.

BACKGROUND: Neurally mediated syncope has been associated with increased left ventricular (LV) fractional shortening (FS) during tilt testing, which is consistent with the hypothesis that the stimulation of LV mechanoreceptors leads to reflex hypotension and/or bradycardia. However, FS does not represent true LV contractility because of its dependence on afterload and preload. METHODS AND RESULTS: To elucidate the role of increased contractility in the mediation of neurally mediated syncope, we compared echocardiographic measures of LV performance corrected for end-systolic stress (ESS) in 21 patients (13 women and 8 men) with unexplained syncope who had either positive (n=10) or negative (n=11) responses to a tilt-table test. Two-dimensional echocardiographic LV imaging was performed at baseline and during the initial 5 minutes of upright tilt. In the supine position, both groups had similar LV end-diastolic volume indexes, stroke volumes, FS, circumferential ESS, and afterload-independent measures of LV performance (stress-corrected midwall and FS). However, after 5 minutes of upright tilt, patients who subsequently had a positive test had a lower stroke volume, lower stress-corrected midwall shortening, and endocardial FS. The tilt-positive group also had a greater fall in ESS and FS early during upright tilt. CONCLUSIONS: Reduced ESS, LV volume, and chamber function during initial upright tilt are associated with a subsequent positive tilt response in patients with unexplained syncope. These data suggest that if paradoxic activation of LV mechanoreceptors has a role in mediating neurally mediated syncope, it is not triggered by LV hypercontractility or increased systolic wall stress during the initial period of upright tilt.