Richard B. Devereux

Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms.

We have presented recommendations for the optimum acquisition of quantitative two-dimensional data in the current echocardiographic environment. It is likely that advances in imaging may enhance or supplement these approaches. For example, three-dimensional reconstruction methods may greatly augment the accuracy of volume determination if they become more efficient. The development of three-dimensional methods will depend in turn on vastly improved transthoracic resolution similar to that now obtainable by transesophageal echocardiography. Better resolution will also make the use of more direct methods of measuring myocardial mass practical. For example, if the epicardium were well resolved in the long-axis apical views, the myocardial shell volume could be measured directly by the biplane method of discs rather than extrapolating myocardial thickness from a single short-axis view. At present, it is our opinion that current technology justifies the clinical use of the quantitative two-dimensional methods described in this article. When technically feasible, and if resources permit, we recommend the routine reporting of left ventricular ejection fraction, diastolic volume, mass, and wall motion score.

Echocardiographic assessment of left ventricular hypertrophy: Comparison to necropsy findings

To determine the accuracy of echocardiographic left ventricular (LV) dimension and mass measurements for detection and quantification of LV hypertrophy, results of blindly read antemortem echocardiograms were compared with LV mass measurements made at necropsy in 55 patients. LV mass was calculated using M-mode LV measurements by Penn and American Society of Echocardiography (ASE) conventions and cube function and volume correction formulas in 52 patients. Penn-cube LV mass correlated closely with necropsy LV mass (r = 0.92, p less than 0.001) and overestimated it by only 6%; sensitivity in 18 patients with LV hypertrophy (necropsy LV mass more than 215 g) was 100% (18 of 18 patients) and specificity was 86% (29 of 34 patients). ASE-cube LV mass correlated similarly to necropsy LV mass (r = 0.90, p less than 0.001), but systematically overestimated it (by a mean of 25%); the overestimation could be corrected by the equation: LV mass = 0.80 (ASE-cube LV mass) + 0.6 g. Use of ASE measurements in the volume correction formula systematically underestimated necropsy LV mass (by a mean of 30%). In a subset of 9 patients, 3 of whom had technically inadequate M-mode echocardiograms, 2-dimensional echocardiographic (echo) LV mass by 2 methods was also significantly related to necropsy LV mass (r = 0.68, p less than 0.05 and r = 0.82, p less than 0.01). Among other indexes of LV anatomy, only measurement of myocardial cross-sectional area was acceptably accurate for quantitation of LV mass (r = 0.80, p less than 0.001) or diagnosis of LV hypertrophy (sensitivity = 72%, specificity = 94%).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of Left Ventricular Mass and Geometry to Morbidity and Mortality in Uncomplicated Essential Hypertension

OBJECTIVE To assess the prognostic significance of left ventricular mass and geometry in initially healthy persons with essential hypertension. DESIGN An observational study of a prospectively identified cohort. SETTING University medical center. PATIENTS Two hundred and eighty patients with essential hypertension and no pre-existing cardiac disease were evaluated using echocardiography between 1976 and 1981. Two hundred and fifty-three subjects or their family members (90%) were contacted for a follow-up interview an average of 10.2 years after the initial echocardiogram was obtained; the survival status of 27 patients lost to follow-up was ascertained using National Death Index data. MEASUREMENTS AND MAIN RESULTS Left ventricular mass exceeded 125 g/m2 in 69 of 253 patients (27%). Cardiovascular events occurred in a higher proportion of patients with than without left ventricular hypertrophy (26% compared with 12%; P = 0.006). Patients with increased ventricular mass were also at higher risk for cardiovascular death (14% compared with 0.5%; P less than 0.001) and all-cause mortality (16% compared with 2%; P = 0.001). Electrocardiographic left ventricular hypertrophy did not predict risk. Patients with normal left ventricular geometry had the fewest adverse outcomes (no cardiac deaths; morbid events in 11%), and those with concentric hypertrophy had the most (death in 21%; morbid events in 31%). In a multivariate analysis, only age and left ventricular mass--but not gender, blood pressure, or serum cholesterol level--independently predicted all three outcome measures. CONCLUSIONS Echocardiographically determined left ventricular mass and geometry stratify risk in patients with essential hypertension independently of and more strongly than blood pressure or other potentially reversible risk factors and may help to stratify the need for intensive treatment.

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.

Revised diagnostic criteria for the Marfan syndrome

In 1986, the diagnosis of the Marfan syndrome was codified on the basis of clinical criteria in the Berlin nosology [Beighton et al., 1988]. Over time, weaknesses have emerged in these criteria, a problem accentuated by the advent of molecular testing. In this paper, we propose a revision of diagnostic criteria for Marfan syndrome and related conditions. Most notable are: more stringent requirements for diagnosis of the Marfan syndrome in relatives of an unequivocally affected individual; skeletal involvement as a major criterion if at least 4 of 8 typical skeletal manifestations are present; potential contribution of molecular analysis to the diagnosis of Marfan syndrome; and delineation of initial criteria for diagnosis of other heritable conditions with partially overlapping phenotypes.

Two-Dimensional Echocardiographic Aortic Root Dimensions in Normal Children and Adults

Two-dimensional echocardiography is increasingly used to measure aortic root dimensions, which provide prognostic information in aortic regurgitation and the Marfan syndrome. Aortic root dilatation is currently detected by nomograms based on M-mode echocardiographic data. Aortic root diameters measured by 2-dimensional echocardiography at the anulus, sinuses of Valsalva, supra-aortic ridge and proximal ascending aorta in 135 normal adults and 52 normal children were compared with age, gender, body habitus, blood pressure and stroke volume, and with M-mode findings and normal limits. Two-dimensional measurements at the sinuses of Valsalva were larger than M-mode aortic root values (p less than 0.001), and use of 2-dimensional values with M-mode nomograms falsely diagnosed aortic dilatation in 40% of normal children and 19% of normal adults. Two-dimensional measurements at the sinuses closely correlated with body surface area in children (r = 0.93, p less than 0.0005), moderately in adults younger than 40 years of age (r = 0.71, p less than 0.0005) and weakly in older adults (r = 0.40, p less than 0.0005). In adults, gender influenced aortic root size at all levels (p less than 0.001), but dimensions were similar when indexed for body surface area. Age strongly influenced supraaortic ridge and ascending aortic diameters; blood pressure and stroke volume had no independent effect on aortic size. In conclusion, (1) 2-dimensional echocardiographic aortic root dimensions are influenced by age and body size but not by blood pressure; (2) aortic root dilatation is overdiagnosed when aortic diameter at the sinuses of Valsalva is compared with M-mode nomograms; (3) nomograms comparing aortic diameter with body surface area should be used in children; and (4) although use of nomograms based on body size in adults should maximize sensitivity for aortic dilatation, 98% specificity is attained by use of an upper normal limit of 2.1 cm/m2 for aortic diameter at the sinuses of Valsalva in both men and women.

Effect of Growth on Variability of Left Ventricular Mass: Assessment of Allometric Signals in Adults and Children and Their Capacity to Predict Cardiovascular Risk

OBJECTIVES We sought to determine whether growth influences the relation between left ventricular mass and body size and whether use of different body size indexes affects the ability of ventricular mass to predict complications of hypertension. BACKGROUND Allometric (or growth) signals between left ventricular mass and height have recently been reported to improve previous approaches for normalization of ventricular mass for body size. METHODS Residuals of left ventricular mass-height2.7 relations were analyzed in a learning series of 611 normotensive, normal-weight subjects 4 months to 70 years old and, separately, in 383 children (< 17 years old) and 228 adults. Ten-year cardiovascular morbidity in a test series of 253 hypertensive adults was compared with groups with normal or high baseline left ventricular mass normalized for body weight, height, body surface area and allometric powers of height. RESULTS The dispersion of residuals of ventricular mass versus height2.7 increased with increasing height or age in children but not in adults, suggesting that the effect of other variables on ventricular growth increases during body growth and stabilizes in adulthood. Therefore, we derived separate allometric signals for adults (predicted ventricular mass = 45.4 x height2.13, r = 0.48) and children (32.3 x height2.3, r = 0.85) (both p < 0.0001). Patients with left ventricular hypertrophy had 3.3 times higher cardiac risk with elevated left ventricular mass/height2.7 (p < 0.001), 2.6 to 2.7 times higher risk with left ventricular mass indexed for height, height2.13 and body surface area (all p < 0.01) and 1.7 times the risk with ventricular mass/weight (p > 0.1). CONCLUSIONS These results show the following: 1) Variability of left ventricular mass in relation to height increases during human growth; 2) allometric signals of left ventricular mass versus height are lower in adults and children than those obtained across the entire age spectrum; 3) height-based indexes of left ventricular mass at least maintain and may enhance prediction of cardiac risk by hypertensive left ventricular hypertrophy; and 4) the allometric signal derived across the entire spectrum of age appears to be more useful for prediction of cardiovascular risk than that computed in adults.

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.

Standardization of M-mode echocardiographic left ventricular anatomic measurements

To improve standardization of echocardiographic left ventricular anatomic measurements, echographic left ventricular dimensions and mass were related to body size indexes, sex, age and blood pressure. Independent normal populations comprised 92 hospital-based subjects (64 women, 28 men) and 133 subjects from a population sample (55 women, 78 men). All measurements of chamber size, wall thickness and mass differed between men and women in both series (p less than 0.01 to p less than 0.001). Left ventricular mass was related most closely to body surface area among measurements of body size (r = 0.37, p less than 0.01 to r = 0.57, p less than 0.001) in all four groups. Indexation by body surface area eliminated sex differences in wall thicknesses and internal dimension, but a significant sex difference in left ventricular mass index persisted (89 +/- 21 g/m2 in men versus 69 + 19 g/m2 in women in the entire series, p less than 0.0001). The 97th percentile of left ventricular mass index was identical in both groups of men (136 and 132 g/m2) and women (112 and 109 g/m2). A highly significant difference in lean body mass, estimated from 24 hour urine creatine excretion, was observed between men and women (58 +/- 15 versus 40 +/- 13 kg, p less than 0.001) and no sex difference existed in left ventricular mass indexed by lean body mass (3.4 +/- 1.3 versus 3.5 +/- 1.5 g/kg). Weak correlations were observed between left ventricular mass/lean body mass and systolic or diastolic blood pressure (r = 0.25, p less than 0.05 and r = 0.28, p less than 0.01, respectively) but not age (18 to 72 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiogenesis Gene Therapy Phase I Assessment of Direct Intramyocardial Administration of an Adenovirus Vector Expressing VEGF121 cDNA to Individuals With Clinically Significant Severe Coronary Artery Disease

BACKGROUND Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.