Does cardiovascular phenotype explain the association between diabetes and incident heart failure? The Strong Heart Study.

BACKGROUND AND AIMS: Diabetes remains a predictor of incident heart failure (HF), independent of intercurrent myocardial infarction (MI) and concomitant risk factors. Initial cardiovascular (CV) characteristics, associated with incident heart failure (HF) might explain the association of diabetes with incident HF. METHODS AND RESULTS: Participants to the 2nd Strong Heart Study exam, without prevalent HF or coronary heart disease, or glomerular filtration rate <30 mL/min/1.73 m(2), were analyzed (n = 2757, 1777 women, 1278 diabetic). Cox regression of incident HF (follow-up 8.91 ± 2.76 years) included incident MI censored as a competing risk event. Acute MI occurred in 96 diabetic (7%) and 84 non-diabetic participants (6%, p = ns). HF occurred in 156 diabetic (12%) and in 68 non-diabetic participants (5%; OR = 2.89, p < 0.001). After accounting for competing MI and controlling for age, gender, BMI, systolic blood pressure, smoking habit, plasma cholesterol, antihypertensive treatment, heart rate, fibrinogen and C-reactive protein, incident HF was predicted by greater LV mass index, larger left atrium, lower systolic function, greater left atrial systolic force and urinary albumin/creatinine excretion. Risk of HF was reduced with more rapid LV relaxation and anti-hypertensive therapy. Diabetes increases hazard of HF by 66% (0.02 < p < 0.001). The effect of diabetes could be explained by the level of HbA1c. CONCLUSIONS: Incident HF occurs more frequently in diabetes, independent of intercurrent MI, abnormal LV geometry, subclinical systolic dysfunction and indicators of less rapid LV relaxation, and is influenced by poor metabolic control. Identification of CV phenotype at high-risk for HF in diabetes should be advised.

Metabolic syndrome and left ventricular hypertrophy in the prediction of cardiovascular events: the Strong Heart Study.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is associated with increased prevalence of echocardiographic LV hypertrophy (LVH), a potent predictor of cardiovascular (CV) outcome. Whether MetS increases risk of CV events independently of presence of LVH has never been investigated. It is also unclear whether LVH predicts CV risk both in the presence and absence of MetS. METHODS AND RESULTS: Participants in the 2nd Strong Heart Study examination without prevalent coronary heart disease, congestive heart failure or renal insufficiency (plasma creatinine >2.5mg/dL) were studied (n=2758; 1746 women). MetS was defined by WHO criteria. Echocardiographic LV hypertrophy was defined using population-specific cut-point value for LV mass index (>47.3g/m(2.7)). After controlling for age, sex, LDL-cholesterol, smoking, plasma creatinine, diabetes, hypertension and obesity, participants with MetS had greater probability of LVH than those without MetS (OR=1.55 [1.18-2.04], p<0.002). Adjusted hazard of composite fatal and non-fatal CV events was greater when LVH was present, in participants without (HR=2.03 [1.33-3.08]) or with MetS (HR=1.64 [1.31-2.04], both p<0.0001), with similar adjusted population attributable risk (12% and 14%). After adjustment for LVH, risk of incident CV events remained 1.47-fold greater in MetS (p<0.003), an effect, however, that was not confirmed when diabetic participants were excluded. CONCLUSION: LVH is a strong predictor of composite 8-year fatal and non-fatal CV events either in the presence or in the absence of MetS and accounts for a substantial portion of the high CV risk associated with MetS.

Relations of stroke volume and cardiac output to body composition: the strong heart study.

BACKGROUND: Although cardiac output (CO) plays the vital role of delivering nutrients to body tissues, few data are available concerning the relations of stroke volume (SV) and CO to body composition in large population samples. METHODS AND RESULTS: Doppler and 2D echocardiography and bioelectric impedance in 2744 Strong Heart Study participants were used to calculate SV and CO and to relate them to fat-free body mass (FFM), adipose mass, and demographic variables. Both SV and CO were higher in men than women and in overweight than normal-weight individuals, but these differences were diminished or even reversed by normalization for FFM or body surface area. In both sexes, SV and CO were more strongly related to FFM than adipose mass, other body habitus measures, arterial pressure, diabetes, or age. In multivariate analyses using the average of Doppler and left ventricular SV to minimize measurement variability, FFM was the strongest correlate of SV and CO; other independent correlates were adipose mass, systolic pressure, diabetes, age, and use of digoxin and calcium channel and beta-blockers. CONCLUSIONS: In a population-based sample, SV and CO are more strongly related to FFM than other variables; increased FFM may be the primary determinant of increased SV and CO in obesity.

Identification of a chromosome 11q23.2-q24 locus for familial aortic aneurysm disease, a genetically heterogeneous disorder.

BACKGROUND: Aortic aneurysms cause significant mortality, and >20% relate to hereditary disorders. Familial aortic aneurysm (FAA) has been described in such conditions as the Marfan and Ehlers-Danlos type IV syndromes, due to defects in the fibrillin-1 and type III procollagen genes, respectively. Other gene defects that cause isolated aneurysms, however, have not thus far been described. METHODS AND RESULTS: We studied 3 families affected by FAA. No family met the diagnostic criteria for either Marfan or Ehlers-Danlos syndrome. Echocardiography defined involvement of both the thoracic and abdominal aorta. In family ANA, candidate gene analysis excluded linkage to loci associated with aneurysm formation, including fibrillin-1, fibrillin-2, and type III procollagen, and chromosome 3p24.2-p25. Genome-wide linkage analysis identified a 2.3-cM FAA locus (FAA1) on chromosome 11q23.3-q24 with a maximum multipoint logarithm of the odds score of 4.4. In family ANB, FAA was linked to fibrillin-1. In family ANF, however, FAA was not linked to any locus previously associated with aneurysm formation, including fibrillin-1 and FAA1. CONCLUSIONS: FAA disease is genetically heterogeneous. We have identified a novel FAA locus at chromosome 11q23.3-q24, a critical step toward elucidating 1 gene defect responsible for aortic dilatation. Future characterization of the FAA1 gene will enhance our ability to achieve presymptomatic diagnosis of aortic aneurysms and will define molecular mechanisms to target therapeutics.

Impact of diabetes on cardiac structure and function: the strong heart study.

BACKGROUND: Whether diabetes mellitus (DM) adversely affects left ventricular (LV) structure and function independently of increases in body mass index (BMI) and blood pressure is controversial. METHODS AND RESULTS: Echocardiography was used in the Strong Heart Study, a study of cardiovascular disease in American Indians, to compare LV measurements between 1810 participants with DM and 944 with normal glucose tolerance. Participants with DM were older (mean age, 60 versus 59 years), had higher BMI (32.4 versus 28.9 kg/m(2)) and systolic blood pressure (133 versus 124 mm Hg), and were more likely to be female, to be on antihypertensive treatment, and to live in Arizona (all P<0.001). In analyses adjusted for covariates, women and men with DM had higher LV mass and wall thicknesses and lower LV fractional shortening, midwall shortening, and stress-corrected midwall shortening (all P<0.002). Pulse pressure/stroke volume, a measure of arterial stiffness, was higher in participants with DM (P<0.001 independent of confounders). CONCLUSIONS: Non-insulin-dependent DM has independent adverse cardiac effects, including increased LV mass and wall thicknesses, reduced LV systolic chamber and myocardial function, and increased arterial stiffness. These findings identify adverse cardiovascular effects of DM, independent of associated increases in BMI and arterial pressure, that may contribute to cardiovascular events in diabetic individuals.

Electrocardiographic identification of increased left ventricular mass by simple voltage-duration products.

OBJECTIVES: This study was conducted to validate the hypothesis that the product of QRS voltage and duration, as an approximation of the time-voltage area of the QRS complex, can improve the electrocardiographic (ECG) detection of echocardiographically determined left ventricular hypertrophy and to further assess the relative contribution of QRS duration to the ECG detection of hypertrophy. BACKGROUND: The ECG identification of left ventricular hypertrophy has been limited by the poor sensitivity of standard voltage criteria alone. However, increases in left ventricular mass can be more accurately related to increases in the time-voltage area of the QRS complex than to changes in QRS voltage or duration alone. METHODS: Standard 12-lead ECGs and echocardiograms were obtained for 389 patients, including 116 patients with left ventricular hypertrophy. Simple voltage-duration products were calculated by multiplying Cornell voltage by QRS duration (Cornell product) and the 12-lead sum of voltage by QRS duration (12-lead product). RESULTS: In a stepwise logistic regression model that also included Cornell voltage, Sokolow-Lyon voltage, age and gender, QRS duration remained a highly significant predictor of the presence of left ventricular hypertrophy (chi-square 26.9, p < 0.0001). At a matched specificity of 96%, each voltage-duration product significantly improved sensitivity for the detection of left ventricular hypertrophy compared with simple voltage criteria alone (Cornell product 37% vs. Cornell voltage 28%, p < 0.02, and 12-lead product 50% vs. 12-lead voltage 43%, p < 0.005). Sensitivities of both the Cornell product and the 12-lead product were significantly greater than the 27% sensitivity of QRS duration alone (p < 0.01 vs. p < 0.001), the 20% sensitivity of a Romhilt-Estes point score > 4 (p < 0.001) and the 33% sensitivity of the best-fit logistic regression model in this cohort (p < 0.05 vs. p < 0.001). CONCLUSIONS: QRS duration is an independent ECG predictor of the presence of left ventricular hypertrophy, and the simple product of either Cornell voltage or 12-lead voltage and QRS duration significantly improves identification of left ventricular hypertrophy relative to other ECG criteria that use QRS duration and voltages in linear combinations.

Prognostic significance of the pattern of aortic root dilation in the Marfan syndrome.

OBJECTIVES: The present study examines the incidence of aortic complications (dissection, marked dilation requiring surgery or progressive moderate to severe aortic regurgitation) and their relation to clinical features and aortic root morphology in patients with the Marfan syndrome. BACKGROUND: Considerable phenotypic variability exists in the Marfan syndrome, and the prospective prediction of the risk for aortic complications in individual patients remains elusive. METHODS: One hundred thirteen patients with the Marfan syndrome underwent anthropometric and echocardiographic evaluation and were followed-up for 49 +/- 24 (mean +/- SD) months. Aortic root dilation was defined as localized when confined to the sinuses of Valsalva (based on two-dimensional echocardiographic confidence limits utilizing age and body size) and generalized if dilation additionally involved the supraaortic ridge and proximal ascending aorta. RESULTS: Aortic root dilation was present in 80% of patients and was localized in 28% and generalized in 51%. Aortic complications occurred during follow-up in none of 23 patients with normal initial aortic size, in 2 (6%) of 32 patients with initially localized dilation and in 19 (33%) of 58 patients with generalized dilation (p < 0.0005). Complications were associated with larger initial aortic size (p < 0.00005), higher systolic blood pressure (p < 0.005), height (p < 0.05), aortic growth rate (p < 0.05) and older age (p < 0.01). The only independent predictor of aortic complications was initial aortic root size (p < 0.005). However, when aortic size, one of the indications for surgical referral, was excluded from analyses, the only independent predictor of aortic complications was generalized aortic dilation (p < 0.005). CONCLUSIONS: The present study indicates that generalized aortic root dilation is a potent marker of an increased risk for subsequent aortic complications in Marfan syndrome.

Association of aortic dilation with regurgitant, stenotic and functionally normal bicuspid aortic valves.

To determine whether aortic root dilation associated with a bicuspid aortic valve occurs independently of valvular hemodynamic abnormality, aortic root dimensions were measured by two-dimensional echocardiography in 83 adults with a functionally normal (n = 19), mildly regurgitant (n = 26), severely regurgitant (n = 27) or stenotic (n = 11) bicuspid aortic valve and compared with findings in normal subjects matched for age and gender. Aortic root measurements were made at four levels: anulus, sinuses of Valsalva, supraaortic ridge and proximal ascending aorta. Seventy-one percent of patients with a bicuspid aortic valve were men. When compared with control subjects, all hemodynamic subgroups showed a significantly larger aortic root size at three levels: sinuses of Valsalva, supraaortic ridge and proximal ascending aorta (p less than 0.05 to p less than 0.001). The prevalence of aortic root enlargement among all hemodynamic subgroups ranged from 9% to 59% at the level of the anulus, 36% to 78% at the sinuses, 47% to 79% at the supraaortic ridge and 50% to 64% in the ascending aorta. Thus, there is a high prevalence of aortic root enlargement in patients with a bicuspid aortic valve that occurs irrespective of altered hemodynamics or age. These findings support the hypothesis that bicuspid aortic valve and aortic root dilation may reflect a common developmental defect.

Electrocardiographic identification of left ventricular hypertrophy: test performance in relation to definition of hypertrophy and presence of obesity.

OBJECTIVES: This study sought to assess a test performance of the electrocardiogram (ECG) in relation to 1) varying definitions of left ventricular hypertrophy based on different methods of adjusting left ventricular mass for body size, and 2) the presence or absence of obesity. BACKGROUND: Although left ventricular mass is most commonly indexed for body surface area or height when defining left ventricular hypertrophy, recent work suggests that normalization for height to the power of 2.7 (height2.7) may decrease variability among normal subjects and correctly identify the impact of obesity on hypertrophy. METHODS: The product of Cornell voltage and QRS duration (Cornell product) and Framingham-adjusted Cornell voltage were determined from 12-lead ECGs in 212 patients. Left ventricular hypertrophy was defined on the basis of left ventricular mass indexed to body surface area, height and height2.7. RESULTS: Using partitions with matched specificity of 95%, the sensitivity of ECG criteria varied with the definition of hypertrophy, ranging from 39% to 52% for the Cornell product and from 24% to 33% for adjusted Cornell voltage. When left ventricular mass was indexed to body surface area or to height2.7, the 52% and 39% sensitivities of the Cornell product were significantly greater than the 24% (p < 0.001) and 29% (p < 0.05) sensitivities of adjusted Cornell voltage, with a similar trend when left ventricular mass was indexed to height (43% vs. 33%, p = 0.10). Comparison of receiver operating characteristic curves confirmed the superior overall performance of the Cornell product relative to adjusted Cornell voltage for hypertrophy defined by body surface area and height2.7 and demonstrated greater reproducibility of overall performance, as measured by the coefficient of variability, for the Cornell product (1.7%) than for adjusted Cornell voltage (5.8%). Sensitivity of adjusted Cornell voltage was significantly greater in obese than in nonobese subjects (50% to 59% vs. 18% to 24%, p < 0.01), but the Cornell product had only minimally higher sensitivity in nonobese than in obese subjects (40% to 54% vs. 32% to 44%, p = NS). CONCLUSIONS: The ability of ECG criteria to detect left ventricular hypertrophy differs depending on the method of indexing left ventricular mass for body size and with the presence or absence of obesity. Further, the Cornell product provides the best combination of overall accuracy and low variability of performance between definitions of hypertrophy. These findings have important implications for the clinical and epidemiologic use of 12-lead ECG criteria for the detection of left ventricular hypertrophy.

Association of carotid atherosclerosis and left ventricular hypertrophy.

OBJECTIVES: This study was undertaken to determine the prevalence of carotid atherosclerosis in a large group of asymptomatic hypertensive and normotensive adults and to examine its relation to the presence of left ventricular hypertrophy. BACKGROUND: Both electrocardiographic and echocardiographic left ventricular hypertrophy predict an increased risk of cardiovascular events and mortality, including cerebrovascular disease, but the mechanism of association is unknown. METHODS: Four hundred eighty-six (277 normotensive and 209 untreated hypertensive) adults, free of clinical evidence of cardiovascular disease, were studied prospectively with echocardiography to determine left ventricular mass and carotid ultrasound to detect atherosclerosis and to measure common carotid artery dimensions. RESULTS: Carotid atherosclerosis was present in 16% of normotensive and 23% of hypertensive participants (p < 0.05) and was associated with older age, higher systolic and pulse pressures and larger left ventricular mass index ([mean +/- SD] 91 +/- 19 vs. 82 +/- 18 g/m2, p < 0.0001). The difference in mass persisted after adjustment for baseline differences in age and blood pressure. Subjects with left ventricular hypertrophy were twice as likely to have carotid atheromas (35% vs. 18%, p < 0.01). Logistic regression analyses, including standard risk factors, indicated that only age and left ventricular mass index independently predicted the presence of carotid plaque, both in the entire study group and when normotensive and hypertensive subjects were considered separately. CONCLUSIONS: We believe that the present study provides the first evidence that higher left ventricular mass as detected by echocardiography is associated with the presence of carotid plaque. The association between cardiac hypertrophy and systemic atherosclerosis may contribute to the pathogenesis of the high incidence of vascular events that is well documented in patients with left ventricular hypertrophy.

Relation of arterial pressure waveform to left ventricular and carotid anatomy in normotensive subjects.

OBJECTIVES: The purpose of this study was to examine the relation of the central arterial pressure waveform to left ventricular and carotid structure. BACKGROUND: The pressure waveform in the central arteries is affected by reflection of the pressure wave from the periphery. When reflected waves merge with the incident wave during systole, a late systolic peak and increment in systolic blood pressure are observed. The consequent increase in hemodynamic load may stimulate left ventricular and vascular adaptive changes. METHODS: Sixty-seven normotensive adults were studied by noninvasive techniques. Anatomy and function of the left ventricle and carotid artery were investigated by ultrasonography. Pressure waveforms were recorded by an external tonometer applied to the carotid artery, and waveform shape was expressed by the augmentation index, calculated from the difference between the maximal systolic pressure and that at the inflection between early and late systolic pressure peaks divided by the pulse pressure. Subjects were assigned to groups with a dominant early (group 1, augmentation index < or = 0) or dominant late systolic peak (group 2, augmentation index > 0). RESULTS: Left ventricular mass index was significantly higher in group 2 than in group 1, a difference that persisted after controlling for the confounding effects of gender, age and blood pressure. Carotid wall thickness and regional arterial stiffness were significantly increased in group 2, but differences disappeared in the analysis of covariance for age. CONCLUSIONS: Left ventricular and carotid artery structure are related to the shape of the central pressure waveform. Although the increase in left ventricular mass seen in subjects with a dominant late systolic peak pressure appears to be directly related to the shape of the pressure waveform, changes in the structural and physical properties of the carotid artery appear to be more closely related to the aging process.

Mitral valve dimensions and motion and familial transmission of mitral valve prolapse with and without mitral leaflet billowing.

To test the hypothesis that mitral valve prolapse may be due either to billowing of mitral leaflets into the left atrium or to dynamic expansion of the mitral anulus, mitral leaflet and annular dimensions and motion were measured by computer-assisted two-dimensional echocardiography in 35 normal adults and 48 subjects with auscultatory and M-mode echocardiographic evidence of mitral prolapse. Among normal subjects, mitral leaflet and annular dimensions tended to be larger compared with body size or left ventricular size in women than in men. Mitral leaflet billowing was observed in 24 (50%) of 48 patients with mitral prolapse and 0 of 35 normal subjects (100% specificity). The 24 patients without leaflet billowing had greater systolic expansion of the mitral anulus (p less than 0.0001) than did normal adults or patients with leaflet billowing (41 +/- 14% versus 27 +/- 12% and 22 +/- 11%, respectively) and a significantly lower body mass index (p less than 0.005 versus normal group). The ratio of anterior plus posterior mitral leaflet length to end-systolic annular diameter was lower in patients with prolapse without leaflet billowing than in normal subjects (1.09 +/- 0.12 versus 1.19 +/- 0.15, respectively, p less than 0.01) or patients with leaflet billowing (1.21 +/- 0.17, p less than 0.05). Among 35 relatives with mitral prolapse in the families of 23 patients with prolapse, the pattern was the same as in the proband in 31 (89%) (p less than 0.000002).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of arterial structure and function to left ventricular geometric patterns in hypertensive adults.

OBJECTIVES: The present study sought to determine whether conduit artery structure and function vary according to the pattern of left ventricular adaptation to hypertension. BACKGROUND: Although left ventricular geometric pattern has been shown to predict cardiovascular events in hypertension, the arterial status in patients with the different patterns is unknown. METHODS: We evaluated arterial structure and function by carotid ultrasound and applanation tonometry in 271 unmedicated hypertensive patients classified by echocardiography as having normal ventricular geometry (n = 176), concentric remodeling (n = 54), concentric hypertrophy (n = 16) or eccentric hypertrophy (n = 25). RESULTS: All groups were similar in age, gender distribution and body size. Patients with concentric and eccentric hypertrophy had similar blood pressures (mean 173/100 and 171/99 mm Hg, respectively) and left ventricular mass, but compared with patients with normal left ventricular geometry and concentric remodeling, only those with concentric hypertrophy had increased arterial wall thickness (0.96 +/- 0.20 vs. 0.80 +/- 0.18 mm, p < 0.05), end-diastolic diameter (6.38 +/- 0.97 vs. 5.76 +/- 0.87 mm, p < 0.05), cross-sectional area (22.1 +/- 5.71 vs. 16.6 +/- 5.4 mm(1)2 p < 0.05) and elastic modulus (713 +/- 265 vs. 471 +/- 241 dynes/cm2 x 10(-5), p < 0.05). Patients with concentric remodeling and eccentric hypertrophy had similar values for these measures (0.85 +/- 0.22 and 0.89 +/- 0.21 mm, 5.67 +/- 0.77 and 6.04 +/- 0.44 mm, 17.2 +/- 5.4 and 19.7 +/- 5.9 mm2, 558 +/- 263 and 614 +/- 257 dynes/cm2 x 10(-6), respectively), despite lower systolic blood pressures in the former group (156/94 mm Hg, p < 0.001). The prevalence of plaque was comparable in patients with concentric (56%) and eccentric (42%) hypertrophy and significantly greater than that in patients [corrected] with normal geometry (21%). CONCLUSIONS: Among patients with generally mild, uncomplicated systemic hypertension, arterial structure and function are most abnormal when concentric left ventricular hypertrophy is present and may contribute to the more adverse outcome associated with this geometric pattern.

Electrocardiographic diagnosis of left ventricular hypertrophy by the time-voltage integral of the QRS complex.

OBJECTIVES: This study was conducted to test the hypothesis that the time-voltage integral of the QRS complex can improve the electrocardiographic (ECG) identification of left ventricular hypertrophy. BACKGROUND: Standard ECG criteria have exhibited poor sensitivity for left ventricular hypertrophy at acceptable levels of specificity. However, left ventricular mass may be more closely related to the time-voltage integral of the summed left ventricular dipole than to QRS duration or voltages used in standard ECG criteria. METHODS: Standard 12-lead ECGs, orthogonal lead signal-averaged ECGs and echocardiograms were obtained in 62 male control subjects without left ventricular hypertrophy and 51 men with left ventricular hypertrophy defined by echocardiographic criteria (indexed left ventricular mass > 125 g/m2). Voltage of the QRS complex was integrated over the total QRS duration in leads X, Y and Z to calculate the time-voltage integral of each orthogonal lead, of the maximal spatial vector complex and of the horizontal, frontal and sagittal plane vector complexes. RESULTS: At matched specificity of 99%, the 73% (37 of 51) sensitivity of the time-voltage integral of the vector QRS complex in the horizontal plane was significantly greater than the 10% sensitivity of the Romhilt-Estes point score, the 16% sensitivity of QRS duration alone, the 22% sensitivity of Cornell voltage, the 33% sensitivity of the 12-lead sum of QRS voltage and the 37% sensitivity of Sokolow-Lyon voltage (each p < 0.001). Sensitivity of the horizontal plane time-voltage integral was also greater than the 10% to 51% sensitivity of the time-voltage integral calculated in the individual X, Y or Z leads (p < 0.01 to < 0.001), the 18% and 35% sensitivity of the time-voltage integrals of the frontal and sagittal plane vectors (p < 0.001) and the 49% sensitivity of the time-voltage integral of the maximal spatial vector complex calculated from all three orthogonal leads (p < 0.001). Comparison of receiver operating characteristic curves confirmed that the superior performance of the horizontal plane time-voltage integral relative to standard and other signal-averaged criteria was independent of partition value selection. CONCLUSIONS: These findings suggest that use of the time-voltage integral of the QRS complex, a method that can be readily implemented on commercially available computerized ECG systems, can improve the accuracy of ECG methods for the identification of left ventricular hypertrophy.

Geometric and functional correlates of electrocardiographic repolarization and voltage abnormalities in aortic regurgitation.

Although electrocardiographic left ventricular hypertrophy is a recognized marker of disease severity in patients with chronic aortic regurgitation, the quantitative relations of repolarization abnormalities and QRS voltage to measurements of cardiac structure and function have not been established. The presence or absence of the "strain" pattern of repolarization and QRS voltage was compared with echocardiographic and radionuclide cineangiographic findings in 95 adults with sever, pure, chronic aortic regurgitation and no evidence of coronary artery disease. In contrast to 54 patients with normal repolarization, 41 patients with an abnormal repolarization pattern had greater left ventricular end-diastolic and end-systolic dimensions (7.2 +/- 1.1 versus 6.6 +/- 0.8 cm, p less than 0.002 and 5.2 +/- 1.2 versus 4.4 +/- 0.7, p less than 0.001, respectively), greater left ventricular mass (431 +/- 138 versus 303 +/- 89 g, p less than 0.001), higher end-systolic stress (128 +/- 46 versus 95 +/- 27 dynes-cm2 X 10(3), p less than 0.001), lower fractional shortening (28 +/- 8 versus 34 +/- 5%, p less than 0.001) and lower exercise ejection fraction (39 +/- 11 versus 51 +/- 8%, p less than 0.001). Multiple logistic regression analysis revealed that left ventricular mass and end-systolic stress were independently related to the presence of repolarization abnormalities (p less than 0.005). Among the 73 asymptomatic patients, those with normal repolarization had significantly lower prevalences of fractional shortening less than 25% (1 of 45 versus 5 of 27, p less than 0.05), left ventricular systolic dimension greater than 5.5 cm (1 of 45 versus 8 of 27, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma atrial natriuretic factor in essential hypertension: relation to cardiac size, function and systemic hemodynamics.

To evaluate determinants of elevated plasma atrial natriuretic factor levels in patients with hypertension, immunoreactive plasma atrial natriuretic factor in 54 normal subjects and 40 untreated hypertensive patients was compared with echocardiographic measurements of cardiac size, function and systemic hemodynamics. In normal subjects, plasma atrial natriuretic factor was related to age, systolic blood pressure and left atrial and ventricular chamber sizes, but only age and ventricular size were independent predictors. In untreated hypertensive patients, atrial natriuretic factor was directly related to age, atrial size, systolic pressure, peripheral resistance and ventricular systolic performance; age, atrial size and peripheral resistance were independent predictors. Eight patients with elevated atrial natriuretic factor values (greater than 25 fmol/ml) were significantly (p less than 0.01) older and had greater atrial and ventricular size and higher systolic pressure and function than normal subjects or patients with normal natriuretic factor levels. Plasma atrial natriuretic factor was inversely related to peak diastolic filling rate in normal subjects (r = -0.59; p less than 0.001), whereas it was positively related to the proportional contribution of atrial systole to left ventricular filling in hypertensive patients (r = 0.77; p less than 0.001). These findings suggest that in normal subjects, impairment of ventricular relaxation with age may contribute to atrial natriuretic factor secretion by increasing left atrial afterload; the correlation with left ventricular size may reflect physiologic fluctuations in plasma volume. In patients with uncomplicated hypertension, left atrial enlargement and consequent stronger atrial contraction contributed to increased atrial natriuretic factor release, whereas no independent relation existed with left ventricular hypertrophy or systolic function. Because ventricular relaxation was normal and ventricular size and systolic performance were increased in hypertensive patients with high atrial natriuretic factor levels, the observed increase in left atrial size and atrial contribution to ventricular filling might reflect a primary increase in venous return in this subset of hypertensive patients.

Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension.

The spectrum of left ventricular geometric adaptation to hypertension was investigated in 165 patients with untreated essential hypertension and 125 age- and gender-matched normal adults studied by two-dimensional and M-mode echocardiography. Among hypertensive patients, left ventricular mass index and relative wall thickness were normal in 52%, whereas 13% had increased relative wall thickness with normal ventricular mass ("concentric remodeling"), 27% had increased mass with normal relative wall thickness (eccentric hypertrophy) and only 8% had "typical" hypertensive concentric hypertrophy (increase in both variables). Systemic hemodynamics paralleled ventricular geometry, with the highest peripheral resistance in the groups with concentric remodeling and hypertrophy, whereas cardiac index was super-normal in those with eccentric hypertrophy and low normal in patients with concentric remodeling. The left ventricular short-axis/long-axis ratio was positively related to stroke volume (r = 0.45, p less than 0.001), with cavity shape most elliptic in patients with concentric remodeling and most spheric in those with eccentric hypertrophy. Normality of left ventricular mass in concentric remodeling appeared to reflect offsetting by volume "underload" of the effects of pressure overload, whereas eccentric hypertrophy was associated with concomitant pressure and volume overload. Thus, arterial hypertension is associated with a spectrum of cardiac geometric adaptation matched to systemic hemodynamics and ventricular load. Concentric left ventricular remodeling and eccentric hypertrophy are more common than the typical pattern of concentric hypertrophy in untreated hypertensive patients.

Family history of severe cardiovascular disease in Marfan syndrome is associated with increased aortic diameter and decreased survival.

OBJECTIVES: We attempted to determine whether a family history of severe cardiovascular disease in patients with the Marfan syndrome is associated with increased aortic dilation or decreased survival, or both. BACKGROUND: The prognostic importance of a family history of severe cardiovascular disease in patients with the Marfan syndrome has been incompletely examined. We hypothesized that such a family history would correlate with increased aortic dilation and would be associated with decreased survival. METHODS: One hundred eight affected patients and 48 unaffected family members from 33 multigenerational families with the Marfan syndrome underwent echocardiographic measurement of the aortic root, arch and mid-abdominal aorta. Date of birth and age at death ascertained from family pedigrees were used to perform life table analysis and estimate survival. RESULTS: Aortic root and arch diameters were significantly greater in patients with a family history of severe cardiovascular disease than in patients without such a family history. Of subjects in the highest quartile for aortic size, > 80% had such a family history in contrast to < 10% of those in the lowest quartile (chi-square 57.37, p < 0.00001). Mean age at death and cumulative probability of survival were significantly lower in patients with such a family history. CONCLUSIONS: Among patients with the Marfan syndrome, aortic dilation is greater and life expectancy shorter in those with a family history of severe cardiovascular manifestations. These data suggest that such a family history is an important risk factor for cardiovascular events in patients with the Marfan syndrome.

Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight.

OBJECTIVES: This study was designed to determine the most appropriate method to normalize left ventricular mass for body size. BACKGROUND: Left ventricular mass has been normalized for body weight, surface area or height in experimental and clinical studies, but it is uncertain which of these approaches is most appropriate. METHODS: Three normotensive population samples--in New York City (127 adults), Naples, Italy (114 adults) and Cincinnati, Ohio (444 infants to young adults)--were studied by echocardiography. Relations of left ventricular mass to body size were similar in all normal weight groups, as assessed by linear and nonlinear regression analysis, and results were pooled (n = 611). RESULTS: Left ventricular mass was related to body weight to the first power (r = 0.88), to body surface area to the 1.5 power (r = 0.88) and to height to the 2.7 power (r = 0.84), consistent with expected allometric (growth) relations between variables with linear (height), second-power (body surface area) and volumetric (left ventricular mass and body weight) dimensions. Strong residual relations of left ventricular mass/body surface area to body surface area (r = 0.54) and of ventricular mass/height to height (r = 0.72) were markedly reduced by normalization of ventricular mass for height2.7 and body surface area1.5. The variability among subjects of ventricular mass was also reduced (p < 0.01 to p < 0.002) by normalization for body weight, body surface area, body surface area1.5 or height2.7 but not for height. In 20% of adults who were overweight, ventricular mass was 14% higher (p < 0.001) than ideal mass predicted from observed height and ideal weight; this increase was identified as 14% by left ventricular mass/height2.7 and 9% by ventricular mass/height, whereas indexation for body surface area, body surface area1.5 and body weight erroneously identified left ventricular mass as reduced in overweight adults. CONCLUSIONS: Normalizations of left ventricular mass for height or body surface area introduce artifactual relations of indexed ventricular mass to body size and errors in estimating the impact of overweight. These problems are avoided and variability among normal subjects is reduced by using left ventricular mass/height2.7. Simple nomograms of the normal relation between height and left ventricular mass allow detection of ventricular hypertrophy in children and adults.

Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in human hypertension.

OBJECTIVES: This study examined left ventricular performance in relatively unselected hypertensive patients by use of physiologically appropriate midwall shortening/end-systolic stress relations. BACKGROUND: Supranormal left ventricular function has been reported in hypertensive patients, possibly due to an artifact of mismatching endocardial rather than midwall fractional shortening to mean left ventricular end-systolic stress. METHODS: Samples of 474 hypertensive patients (150 women, 324 men) and 140 normal subjects (68 women, 72 men) were drawn from a large urban employed population. The inverse relations (p < 0.0001) of both echocardiographic endocardial and midwall fractional shortening to end-systolic stress in normal subjects were used to calculate the ratios of observed to predicted endocardial and midwall fractional shortening in hypertensive patients. Midwall shortening was calculated from an elliptic model, taking into account the epicardial migration of the midwall during systole. RESULTS: Use of midwall fractional shortening in hypertensive patients reduced the proportion of patients with function above the 95th percentile of normal from 22% to 4% (p < 0.0001) and fractional shortening as a percent of predicted from 107% (p < 0.001 vs. 100% in normotensive control subjects) to 95% (p < 0.0001; p < 0.001 vs. 101% in normotensive control subjects). Midwall shortening was below the 5th percentile of normal in 16% of hypertensive patients instead of 2% with endocardial shortening (p < 0.0001): They tended to be older than other hypertensive patients and had concentric left ventricular hypertrophy. Among hypertensive patients, those with concentric left ventricular hypertrophy or remodeling had reduced midwall shortening as a percent of predicted from end-systolic stress (p < 0.0001). CONCLUSIONS: Use of the physiologically more appropriate midwall shortening/end-systolic stress relation 1) markedly reduces the proportion of hypertensive subjects identified as having high endocardial left ventricular function; and 2) identifies a substantial subgroup of patients with reduced left ventricular function who have concentric geometry of the left ventricle, a pattern associated with high cardiovascular risk.