Periaortic fat and cardiovascular risk: a comparison of high-risk older adults and age-matched healthy controls.

OBJECTIVE: Fat accumulation around the heart and aorta may impact cardiovascular (CV) health. The purpose of this study was to conduct a systematic investigation to examine potential associations of these fat depots with risk factors for CV events, which has not been done before. METHODS: Pericardial fat, periaortic fat around the ascending aorta (AA), descending aorta (DA) and aortic arch, and abdominal subcutaneous and visceral fat were measured by MRI in older adults with (n = 385, 69 ± 8 years, 52% female) and without (n = 50, 69 ± 8 years, 58% female) risk factors for a CV event. RESULTS: Individuals with CV risk factors exhibited greater fat volumes across all fat depots compared with those without risk factors. In analysis of covariance accounting for age, gender, race/ethnicity, diabetes, hypertension, coronary artery disease, smoking and body mass index (BMI), individuals with risk factors possessed higher epicardial, pericardial, AA, DA and abdominal visceral fat (P < 0.05). When matched one-to-one on age, gender, race/ethnicity and BMI, AA and DA fat were higher in those with versus without CV risk factors (P < 0.01). CONCLUSIONS: Older adults with a high risk for CV events have greater periaortic fat than low-risk adults, even after accounting for BMI. More studies are needed to determine whether greater periaortic fat predicts future CV events.

Aerobic exercise training can reverse age-related peripheral circulatory changes in healthy older men.

BACKGROUND: The age-related decline in maximal oxygen consumption is attenuated by habitual aerobic exercise. However, the relative effects of training on central and peripheral responses to exercise in older subjects are not known. The present study assessed the contribution of central and peripheral responses to the age-associated decline in peak oxygen consumption and compared the effect of exercise training in healthy older and younger subjects. METHODS AND RESULTS: Ten older and 13 younger men underwent invasive measurement of central and peripheral cardiovascular responses during an upright, staged cycle exercise test before and after a 3-month period of exercise training with cycle ergometry. At baseline, cardiac output and AV oxygen difference during exercise were significantly lower in older subjects. With training, the older and younger groups increased maximal oxygen consumption by 17.8% and 20.2%, respectively. Peak cardiac output was unchanged in both groups. Systemic AV oxygen difference increased 14.4% in the older group and 14.3% in the younger group and accounted for changes in peak oxygen consumption. Peak leg blood flow increased by 50% in older subjects, whereas the younger group showed no significant change. There was no change in peak leg oxygen extraction in the older group, but in the younger group, leg AV oxygen difference increased by 15.4%. CONCLUSIONS: These findings suggest that the age-related decline in maximal oxygen consumption results from a reversible deconditioning effect on the distribution of cardiac output to exercising muscle and an age-related reduction in cardiac output reserve.

Utility of fast cine magnetic resonance imaging and display for the detection of myocardial ischemia in patients not well suited for second harmonic stress echocardiography.

BACKGROUND: Some patients referred for pharmacological stress testing with transthoracic echocardiography (TTE) are unable to undergo testing owing to poor acoustic windows. Fast cine MRI can be used to assess left ventricular contraction, but its utility for detection of myocardial ischemia in patients poorly suited for echocardiography is unknown. METHODS AND RESULTS: One hundred fifty-three patients (86 men and 67 women aged 30 to 88 years) with poor acoustic windows that prevented adequate second harmonic TTE imaging were consecutively referred for MRI to diagnose inducible myocardial ischemia during intravenous dobutamine and atropine. Diagnostic studies were completed in an average of 53 minutes. No patients experienced myocardial infarction, ventricular fibrillation, exacerbation of congestive heart failure, or death. In patients who underwent computer-assisted quantitative coronary angiography, the sensitivity and specificity for detecting a >50% luminal diameter narrowing were 83% and 83%, respectively. In the 103 patients with a negative MRI examination, the cardiovascular occurrence-free survival rate was 97%. CONCLUSIONS: Fast cine cardiac MRI provides a mechanism to assess left ventricular contraction and diagnose inducible myocardial ischemia in patients not well suited for stress echocardiography.

Effect of type 2 diabetes mellitus on left ventricular geometry and systolic function in hypertensive subjects: Hypertension Genetic Epidemiology Network (HyperGEN) study.

BACKGROUND: Type 2 diabetes is a cardiovascular risk factor. It remains to be elucidated in a large, population-based sample whether diabetes is associated with changes in left ventricular (LV) structure and systolic function independent of obesity and systolic blood pressure (BP). METHODS AND RESULTS: Among 1950 hypertensive participants in the HyperGEN Study without overt coronary heart disease or significant valve disease, 20% (n=386) had diabetes. Diabetics were more likely to be women, black, older, and have higher BMI and waist/hip ratio than were nondiabetics. After adjustment for age and sex, diabetics had higher systolic BP, pulse pressure, and heart rate; lower diastolic BP; and longer duration of hypertension than nondiabetics. LV mass and relative wall thickness were higher in diabetic than nondiabetic subjects independent of covariates. Compared with nondiabetic hypertensives, diabetics had lower stress-corrected midwall shortening, independent of covariates, without difference in LV EF. Insulin levels and insulin resistance were higher in non-insulin-treated diabetics (n=195) than nondiabetic (n=1439) subjects (both P:<0.01). Insulin resistance positively but weakly related to LV mass and relative wall thickness. CONCLUSIONS: In a relatively healthy, population-based sample of hypertensive adults, type 2 diabetes was associated with higher LV mass, more concentric LV geometry, and lower myocardial function, independent of age, sex, body size, and arterial BP. structural and functional abnormalities in addition to, and independent of, atherosclerosis.(13) (14) In the Framingham cohort, diabetes was associated with higher LV mass in women but not men.(15) High blood pressure (BP), obesity, and abnormal lipid profile, which often coexist with diabetes, tend to be associated with preclinical cardiovascular abnormalities(16) and may contribute to the association of diabetes with cardiovascular events. Cardiac features of diabetic and nondiabetic hypertensive subjects remain incompletely described in population-based samples. Therefore, we compared clinical and metabolic characteristics, LV geometry, and systolic function between diabetic and nondiabetic hypertensive participants in the Hypertension Genetic Epidemiology Network (HyperGEN) Study.

Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism.

Invasive cardiopulmonary exercise testing was performed in 7 patients who presented with congestive heart failure, normal left ventricular ejection fraction and no significant coronary or valvular heart disease and in 10 age-matched normal subjects. Compared with the normal subjects, patients demonstrates severe exercise intolerance with a 48% reduction in peak oxygen consumption (11.6 +/- 4.0 versus 22.7 +/- 6.1 ml/kg per min; p less than 0.001), primarily due to a 41% reduction in peak cardiac index (4.2 +/- 1.4 versus 7.1 +/- 1.1 liters/min per m2; p less than 0.001). In patients compared with normal subjects, peak left ventricular stroke volume index (34 +/- 9 versus 46 +/- 7 ml/min per m2; p less than 0.01) and end-diastolic volume index (56 +/- 14 versus 68 +/- 12 ml/min per m2; p less than 0.08) were reduced, whereas peak ejection fraction and end-systolic volume index were not different. In patients, the change in end-diastolic volume index during exercise correlated strongly with the change in stroke volume index (r = 0.97; p less than 0.0001) and cardiac index (r = 0.80; p less than 0.03). Pulmonary wedge pressure was markedly increased at peak exercise in patients compared with normal subjects (25.7 +/- 9.1 versus 7.1 +/- 4.4 mm Hg; p less than 0.0001). Patients demonstrated a shift of the left ventricular end-diastolic pressure-volume relation upward and to the left at rest. Increases in left ventricular filling pressure during exercise were not accompanied by increases in end-diastolic volume, indicating a limitation to left ventricular filling.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-related alterations of Doppler left ventricular filling indexes in normal subjects are independent of left ventricular mass, heart rate, contractility and loading conditions.

The purpose of this study was to determine whether age-related alterations in Doppler diastolic filling indexes occur independent of cardiovascular disease and confounding physiologic variables. Ten old (62 to 73 years) and 10 young (21 to 32 years) healthy male volunteers were rigorously screened for cardiovascular disease and underwent comprehensive Doppler echocardiography, radionuclide ventriculography and invasive measurements of right heart and left atrial pressures. There were no differences between the two groups in the physiologic variables of left ventricular mass, volumes, ejection fraction, end-systolic wall stress, left atrial size, heart rate and right atrial, pulmonary artery, pulmonary capillary wedge and systemic arterial pressures. However, there were marked differences in Doppler left ventricular filling indexes. Compared with the young group, the old group had reduced peak early diastolic flow velocity (56 +/- 13 vs. 82 +/- 12 cm/s, p = 0.0002) and increased atrial diastolic flow velocity (59 +/- 14 vs. 43 +/- 10 cm/s, p = 0.009) and had a peak atrial/early flow velocity (A/E) ratio twice that of the young group (1.09 +/- 0.29 vs. 0.54 +/- 0.15, p less than 0.0001). Similar results were obtained for the time-velocity integrals of the peaks. Subjects in the old group also had a markedly reduced peak filling rate (274 +/- 62 vs. 448 +/- 152 ml/s, p = 0.004). In univariate and multivariate regression analyses, peak early and atrial flow velocities were not related to any of the physiologic variables measured once age was accounted for, although peak filling rate, a volumetric measure flow, was related to body surface area as well as age.(ABSTRACT TRUNCATED AT 250 WORDS)

Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise.

OBJECTIVES: The aim of the study was to test the hypothesis that angiotensin II (Ang II) blockade would improve exercise tolerance in patients with diastolic dysfunction and a marked increase in systolic blood pressure (SBP) during exercise. BACKGROUND: Diastolic dysfunction may be exacerbated during exercise, especially if there is a marked increase in SBP. Angiotensin II may contribute to the hypertensive response to exercise and impair diastolic performance. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover study of two weeks of losartan (50 mg q.d.) on exercise tolerance and quality of life. The subjects were 20 patients, mean age 64 +/- 10 years with normal left ventricular systolic function (EF >50%), no ischemia on stress echocardiogram, mitral flow velocity E/A <1, normal resting SBP (<150 mm Hg), and a hypertensive response to exercise (SBP >200 mm Hg). Exercise echocardiograms (Modified Bruce Protocol) and the Minnesota Living With Heart Failure questionnaire were administered at baseline, and after each two-week treatment period, separated by a two-week washout period. RESULTS: Resting blood pressure (BP) was unaltered by placebo or losartan. During control, patients were able to exercise for 11.3 +/- 2.5 (mean +/- SD) min, with a peak exercise SBP of 226 +/- 24 mm Hg. After two weeks of losartan, baseline BP was unaltered, but peak SBP during exercise decreased to 193 +/- 27 mm Hg (p < 0.05 vs. baseline and placebo), and exercise time increased to 12.3 +/- 2.6 min (p < 0.05 vs. baseline and placebo). With placebo, there was no improvement in exercise duration (11.0 +/- 2.0 min) or peak exercise SBP (217 +/- 26 mm Hg). Quality of life improved with losartan (18 +/- 22, p < 0.05) compared to placebo (22 +/- 26). CONCLUSIONS: In patients with Doppler evidence of diastolic dysfunction at rest and a hypertensive response to exercise, Ang II receptor blockade blunts the hypertensive response to exercise, increases exercise tolerance and improves quality of life.

Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study.

OBJECTIVES: We sought to characterize the predictors of incident congestive heart failure (CHF), as determined by central adjudication, in a community-based elderly population. BACKGROUND: The elderly constitute a growing proportion of patients admitted to the hospital with CHF, and CHF is a leading source of morbidity and mortality in this group. Elderly patients differ from younger individuals diagnosed with CHF in terms of biologic characteristics. METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of 5,888 elderly people >65 years old (average 73 +/- 5, range 65 to 100) at four locations. Multiple laboratory measures of cardiovascular structure and function, blood chemistries and functional assessments were obtained. RESULTS: During an average follow-up of 5.5 years (median 6.3), 597 participants developed incident CHF (rate 19.3/1,000 person-years). The incidence of CHF increased progressively across age groups and was greater in men than in women. On multivariate analysis, other independent predictors included prevalent coronary heart disease, stroke or transient ischemic attack at baseline, diabetes, systolic blood pressure (BP), forced expiratory volume 1 s, creatinine >1.4 mg/dl, C-reactive protein, ankle-arm index <0.9, atrial fibrillation, electrocardiographic (ECG) left ventricular (LV) mass, ECG ST-T segment abnormality, internal carotid artery wall thickness and decreased LV systolic function. Population-attributable risk, determined from predictors of risk and prevalence, was relatively high for prevalent coronary heart disease (13.1%), systolic BP > or =140 mm Hg (12.8%) and a high level of C-reactive protein (9.7%), but was low for subnormal LV function (4.1%) and atrial fibrillation (2.2%). CONCLUSIONS: The incidence of CHF is high in the elderly and is related mainly to age, gender, clinical and subclinical coronary heart disease, systolic BP and inflammation. Despite the high relative risk of subnormal systolic LV function and atrial fibrillation, the actual population risk of these for CHF is small because of their relatively low prevalence in community-dwelling elderly people.

Cardiac cycle-dependent changes in aortic area and distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance.

OBJECTIVES: The goal of this study was to determine if cardiac cycle-dependent changes in proximal thoracic aortic area and distensibility are associated with exercise intolerance in elderly patients with diastolic heart failure (DHF). BACKGROUND: Aortic compliance declines substantially with age. We hypothesized that a reduction in cardiac cycle-dependent changes in thoracic aortic area and distensibility (above that which occurs with aging) could be associated with the exercise intolerance that is prominent in elderly diastolic heart failure patients. METHODS: Thirty subjects (20 healthy individuals [10 < 30 years of age and 10 > 60 years of age] and 10 individuals > the age of 60 years with DHF) underwent a magnetic resonance imaging (MRI) study of the heart and proximal thoracic aorta followed within 48 h by maximal exercise ergometry with expired gas analysis. RESULTS: The patients with DHF had higher resting brachial pulse and systolic blood pressure, left ventricular mass, aortic wall thickness and mean aortic flow velocity, and, compared with healthy older subjects, they had a significant reduction in MRI-assessed cardiac cycle-dependent change in aortic area and distensibility (p < 0.0001) that correlated with diminished peak exercise oxygen consumption (r = 0.79). After controlling for age and gender in a multivariate analysis, thoracic aortic distensibility was a significant predictor of peak exercise oxygen consumption (p < 0.04). CONCLUSIONS: Older patients with isolated DHF have reduced cardiac cycle-dependent changes in proximal thoracic aortic area and distensibility (beyond that which occurs with normal aging), and this correlates with and may contribute to their severe exercise intolerance.

Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study.

OBJECTIVES: The aim of this study was to determine the prevalence of aortic sclerosis and stenosis in the elderly and to identify clinical factors associated with degenerative aortic valve disease. BACKGROUND: Several lines of evidence suggest that degenerative aortic valve disease is not an inevitable consequence of aging and may be associated with specific clinical factors. METHODS: In 5,201 subjects > or = 65 years of age enrolled in the Cardiovascular Health Study, the relation between aortic sclerosis or stenosis identified on echocardiography and clinical risk factors for atherosclerosis was evaluated by using stepwise logistic regression analysis. RESULTS: Aortic valve sclerosis was present in 26% and aortic valve stenosis in 2% of the entire study cohort; in subjects > or = 75 years of age, sclerosis was present in 37% and stenosis in 2.6%. Independent clinical factors associated with degenerative aortic valve disease included age (twofold increased risk for each 10-year increase in age), male gender (twofold excess risk), present smoking (35% increase in risk) and a history of hypertension (20% increase in risk). Other significant factors included height and high lipoprotein(a) and low density lipoprotein cholesterol levels. CONCLUSIONS: Clinical factors associated with aortic sclerosis and stenosis can be identified and are similar to risk factors for atherosclerosis.

Phase III multicenter trial comparing the efficacy of 2% dodecafluoropentane emulsion (EchoGen) and sonicated 5% human albumin (Albunex) as ultrasound contrast agents in patients with suboptimal echocardiograms.

OBJECTIVES: This study was performed to compare the safety and efficacy of intravenous 2% dodecafluoropentane (DDFP) emulsion (EchoGen) with that of active control (sonicated human albumin [Albunex]) for left ventricular (LV) cavity opacification in adult patients with a suboptimal echocardiogram. BACKGROUND: The development of new fluorocarbon-based echocardiographic contrast agents such as DDFP has allowed opacification of the left ventricle after peripheral venous injection. We hypothesized that DDFP was clinically superior to the Food and Drug Administration-approved active control. METHODS: This was a Phase III, multicenter, single-blind, active controlled trial. Sequential intravenous injections of active control and DDFP were given 30 min apart to 254 patients with a suboptimal echocardiogram, defined as one in which the endocardial borders were not visible in at least two segments in either the apical two- or four-chamber views. Studies were interpreted in blinded manner by two readers and the investigators. RESULTS: Full or intermediate LV cavity opacification was more frequently observed after DDFP than after active control (78% vs. 31% for reader A; 69% vs. 34% for reader B; 83% vs. 55% for the investigators, p < 0.0001). LV cavity opacification scores were higher with DDFP (2.0 to 2.5 vs. 1.1 to 1.5, p < 0.0001). Endocardial border delineation was improved by DDFP in 88% of patients versus 45% with active control (p < 0.001). Similar improvement was seen for duration of contrast effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to affect patient management. There was no difference between agents in the number of patients with adverse events attributed to the test agent (9% for DDFP vs. 6% for active control, p = 0.92). CONCLUSIONS: This Phase III multicenter trial demonstrates that DDFP is superior to sonicated human albumin for LV cavity opacification, endocardial border definition, duration of effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to influence patient management. The two agents had similar safety profiles.

Reproducibility of cardiopulmonary exercise testing in elderly patients with congestive heart failure.

Elderly patients with congestive heart failure, including those with preserved systolic function, underwent maximal cardiopulmonary exercise testing. Maximal exercise oxygen consumption, exercise time, heart rate, respiratory exchange ratio, and ventilatory anaerobic threshold showed good reproducibility.

Efficacy and safety of the novel ultrasound contrast agent perflutren (definity) in patients with suboptimal baseline left ventricular echocardiographic images.

Suboptimal left ventricular (LV) cavity visualization and endocardial border delineation often compromise the clinical utility of echocardiography. This study examines the safety and efficacy of perflutren, a novel ultrasound contrast agent, for LV cavity opacification and endocardial border delineation in patients with suboptimal baseline echocardiograms. In a multicenter, randomized, placebo-controlled, double-blind trial, 211 patients with suspected cardiac disease and suboptimal baseline echocardiograms were enrolled at 17 sites. Two intravenous injections of either placebo (saline) or perflutren (5 or 10 microl/kg) were given approximately 30 minutes apart. Images of the apical 4- and 2-chamber views were acquired and scored. Perflutren opacified the LV cavity after both dosages (5 and 10 microl/kg dosages). Clinically useful contrast was observed in 89% of patients who received perflutren and in 0% of patients who received placebo (p < 0.01). Quantitative assessment of LV opacification with videodensitometry showed similar results. The mean duration of clinically useful contrast was 90 seconds. Improvement in endocardial border delineation was demonstrated in 91% of patients who received perflutren and in 12% of those who received placebo (p < 0.001). Following perflutren, an average of 4 more segments per patient were evaluable compared with baseline. Salvage of nondiagnostic baseline examinations by perflutren was demonstrated in 48% of eligible subjects. The safety profile of perflutren was similar to placebo. These data indicate that administration of perflutren to patients with suboptimal baseline images is well tolerated and provides substantial LV cavity opacification and improvement in endocardial border delineation.

Importance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study.

Although congestive heart failure (CHF) is a common syndrome among the elderly, there is a relative paucity of population-based data, particularly regarding CHF with normal systolic left ventricular function. A total of 4,842 independent living, community-dwelling subjects aged 66 to 103 years received questionnaires on medical history, family history, personal habits, physical activity, and socioeconomic status, confirmation of pre-existing cardiovascular and cerebrovascular disease, anthropometric measurements, casual seated random-zero blood pressure, forced vital capacity and expiratory volume in 1 second, 12-lead supine electrocardiogram, fasting glucose, creatinine, plasma lipids, carotid artery wall thickness by ultrasonography, and echocardiography-Doppler examinations. Participants with at least 1 confirmed episode of CHF by Cardiovascular Health Study criteria were considered prevalent for CHF. The prevalence of CHF was 8.8% and was associated with increased age, particularly for women, in whom it increased more than twofold from age 65 to 69 years (6.6%) to age > or = 85 years (14%). In multivariate analysis, subjects with CHF were more likely to be older (odds ratio [OR] 1.2 for 5-year difference, men OR 1.1), and more often had a history of myocardial infarction (OR 7.3), atrial fibrillation (OR 3.0), diabetes mellitus (OR 2.1), renal dysfunction (OR 2.0 for creatinine < or = 1.5 mg/ dl), and chronic pulmonary disease (OR 1.8; women only). The echocardiographic correlates of CHF were increased left atrial and ventricular dimensions. Importantly, 55% of subjects with CHF had normal left ventricular systolic function and 80% had either normal or only mildly reduced systolic function. Among subjects with CHF, women had normal systolic function more frequently than men (67% vs 42%; p < 0.001). Thus, CHF is common among community-dwelling elderly. It increases with age and is usually associated with normal systolic LV function, particularly among women. The finding that a large proportion of elderly with CHF have preserved LV systolic function is important because there is a paucity of data to guide management in this dominant subset.

Physician management of patients with heart failure and normal versus decreased left ventricular systolic function. Council on Geriatric Cardiology.

A questionnaire was administered to a random sample of family practitioners, internists, cardiologists, and geriatricians to examine the current management of heart failure patients with preserved versus reduced left ventricular systolic function. In patients with preserved systolic function, electrocardiogram at rest, chest x-ray, echocardiography, digitalis, angiotensin-converting enzyme inhibitors, and restriction of dietary sodium and physical activity are used less often, whereas calcium channel blockers and beta blockers are given more often than to patients with reduced systolic function.

Left ventricular diastolic filling in the elderly: the cardiovascular health study.

Changes in left ventricular (LV) diastolic function (e.g., as measured by transmitral flow velocity) are known to occur with aging. In addition, impaired LV diastolic function plays an important role in such cardiovascular disorders common in the elderly as hypertension, ischemic heart disease, and congestive heart failure (CHF). Participants in the Cardiovascular Health Study, a multicenter study of community-dwelling men (n=2,239) and women (n=2,962) > or = 65 years of age, underwent an extensive baseline evaluation, including echocardiography. Early diastolic LV Doppler (transmitral) peak filling velocity decreased, and peak late diastolic (atrial) velocity increased with age in multivariate analyses (all p <0.001). Early and late diastolic peak filling velocities were both significantly higher in women than in men, even after adjustment for body surface area (or height and weight). In multivariate models in the entire cohort and a healthy subgroup (n=703), gender, age, heart rate, and blood pressure (BP) were most strongly related to early and late diastolic transmitral peak velocities. Early and late diastolic peak velocities both increased with increases in systolic BP and decreased with increases in diastolic BP (p <0.001). Doppler transmitral velocities were compared among health status subgroups. In multiple regression models adjusted for other covariates, and in analysis of variance models examining differences across subgroups adjusted only for age, the subgroup with CHF had the highest early diastolic peak velocities. All clinical disease subgroups had higher late diastolic peak velocities than the healthy subgroup, with the subgroups with either CHF or hypertension having the highest age-adjusted means. The subgroup with hypertension had the lowest ratio of early-to-late diastolic peak velocity, and men with CHF had the highest ratio. These findings are consistent with previous reports that hypertensive subjects exhibit an abnormal relaxation pattern, whereas patients with CHF develop a pattern suggestive of an increased early diastolic left atrial-LV pressure gradient.

Relation of various degrees of body mass index in patients with systemic hypertension to left ventricular mass, cardiac output, and peripheral resistance (The Hypertension Genetic Epidemiology Network Study).

The impact of different methods of indexation of left ventricular (LV) mass and systemic hemodynamic variables on prevalences and correlates of cardiovascular abnormalities in relation to level of obesity in populations remains unclear. We evaluated 1,672 participants in the Hypertension Genetic Epidemiology Network Study to investigate the relations of overweight and level of obesity to LV mass and prevalences of LV hypertrophy, abnormal cardiac output, and peripheral resistance detected using different indexations for body size. In our study population, 1,577 subjects were clinically healthy nondiabetic hypertensive and 95 were normotensive normal-weight nondiabetic reference subjects. Fat-free mass (FFM) did not differ between the reference group and the normal-weight hypertensive subjects, and increased with overweight. In hypertensive subjects, LV mass and cardiac output increased and total peripheral resistance decreased with overweight. Indexation of LV mass for FFM or body surface area (BSA) resulted in no difference or even lower prevalence of LV hypertrophy in severely obese compared with normal-weight hypertensive subjects. In contrast, indexation of LV mass for height(2.7) identified an increased prevalence of LV hypertrophy with overweight and obesity. Absolute cardiac output increased and total peripheral resistance decreased with overweight. Prevalence of elevated cardiac output indexed for height(1.83) increased and for elevated total peripheral resistance-height(1.83) index decreased with greater overweight, whereas opposite trends were seen when cardiac output and total peripheral resistance were indexed for BSA or FFM. Thus, in hypertensive subjects, FFM increases with overweight and is directly related to LV mass, stroke volume, and cardiac output, and inversely related to total peripheral resistance. Indexations of LV mass and systemic hemodynamics for FFM or BSA obscured associations of LV hypertrophy and abnormal cardiac and total peripheral resistance indexes with overweight, whereas LV mass/height(2,7), cardiac output/height(1.83), and total peripheral resistance-height(1.83) detected significant preclinical cardiovascular abnormalities with obesity.

Doppler left ventricular diastolic filling abnormalities in aortic stenosis and their relation to hemodynamic parameters.

Doppler mitral flow indexes and their relation to invasively measured hemodynamic diastolic indexes were assessed in 13 patients with isolated aortic stenosis (AS), and compared to Doppler indexes in 10 normal subjects matched for age, heart rate, left ventricular (LV) ejection fraction and LV load. Patients with AS showed no difference in Doppler early filling (E) indexes, but demonstrated greater Doppler atrial filling (A) indexes in comparison to normal subjects: atrial velocity (89 +/- 31 vs 56 +/- 7 cm/s), atrial integral (11.4 +/- 4.8 vs 5.7 +/- 1.6 cm), A/E velocity (1.69 +/- 0.89 vs 1.06 +/- 0.26) and A/E integral (3.53 +/- 6.64 vs 0.81 +/- 0.27) (all p less than 0.05). Doppler indexes in patients with AS did not correlate with hemodynamic indexes of LV relaxation or chamber stiffness. Significant correlations were observed between Doppler and angiographic peak filling rates (r = 0.70) and between Doppler atrial filling velocity and LV end-diastolic volume (r = -0.66), LV end-diastolic pressure (r = -0.48) and LV ejection fraction (r = 0.53) (all p less than 0.05). These data indicate that, compared to matched normal subjects, most patients with AS have an increased atrial contribution to LV filling. However, in patients with decreased LV function, atrial function may also be depressed, as indicated by a decreased atrial contribution to LV filling, resulting in "normalization" of the Doppler mitral flow pattern.

Feasibility, accuracy, and incremental value of intraoperative three-dimensional transesophageal echocardiography in valve surgery.

In this prospective trial, intraoperative 2-dimensional (2-D) and 3-dimensional (3-D) transesophageal echocardiography (TEE) examinations were performed on 60 consecutive patients undergoing cardiac valve surgery. Both 2-D (including color flow and Doppler data) and 3-D images were reviewed by blinded observers, and major valvular morphologic findings recorded. In vivo morphologic findings were noted by the surgeon and all explanted valves underwent detailed pathologic examination. To test reproducibility, 6 patients also underwent 3-D TEE 1 day before surgery. A total of 132 of 145 attempted acquisitions (91%) were completed with a mean acquisition time of 2.8 +/- 0.2 minutes. Acquisition time was significantly shorter in patients with regular rhythms. Reconstructions were completed in 121 of 132 scans (92%) and there was at least 1 good reconstruction in 56 of 60 patients (93%). Mean reconstruction time was 8.6 +/- 0.7 minutes. Mean effective 3-D time, which was the time taken to complete an acquisition and a clinically interpretable reconstruction, was 12.2 +/- 0.8 minutes. Intraoperative 3-D echocardiography was clinically feasible in 52 patients (87%). Three-D echocardiography detected most of the major valvular morphologic abnormalities, particularly leaflet perforations, fenestrations, and masses, confirmed on pathologic examination. Three-D echocardiography predicted all salient pathologic findings in 47 patients (84%) with good quality images. In addition, in 15 patients (25%), 3-D echocardiography provided new additional information not provided by 2-D echocardiography, and in 1 case, 3-D echocardiographic findings resulted in a surgeon's decision to perform valve repair rather than replacement. In several instances, 3-D echocardiography provided complementary morphologic information that explained the mechanism of abnormalities seen on 2-D and color flow imaging. In the reproducibility subset, preoperative and intraoperative 3-D imaging detected a similar number of findings when compared with pathology. Thus, in routine clinical intraoperative settings, 3-dimensional TEE is feasible, accurately predicts valve morphology, and provides additional and complementary valvular morphologic information compared with conventional 2-D TEE, and is probably reproducible.

Age-related changes in normal human hearts during the first 10 decades of life. Part I (Growth): A quantitative anatomic study of 200 specimens from subjects from birth to 19 years old.

Heart weight, ventricular wall thicknesses, and valve circumferences were measured in 200 autopsy specimens of normal hearts from persons who ranged from birth to 19 years old. During this period of body growth, all cardiac measurements increased progressively and correlated with both age and body size (height, weight, and surface area). For most measurements, the mean predicted values were greater in male than in female subjects. Heart weight correlated better with body weight and body surface area than with body height or age of patients. In contrast, ventricular wall thicknesses and valve circumferences correlated better with age of the patients than with measurements of body size. In both sexes at all ages, the thickness of the left ventricle was greater than that of the right ventricle and was generally less than that of the ventricular septum. The circumference of the tricuspid valve usually exceeded that of the mitral valve, but aortic and pulmonary valve circumferences were similar. On the basis of these data, equations were derived and reference tables were constructed to predict normal values for heart weight, ventricular wall thicknesses, and valve circumferences.