Seward, James B.

Background —Atherosclerosis of the thoracic aorta is associated with stroke. The association between hypertension, a major risk factor for stroke, and aortic atherosclerosis has not been determined in the general population. Methods and Results —Transesophageal echocardiography was performed in 581 subjects, a random sample of the Olmsted County (Minnesota) population aged ≥45 years participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. Blood pressure was assessed by multiple office measurements and 24-hour ambulatory blood pressure monitoring. The association between blood pressure variables and aortic atherosclerosis was evaluated by multiple logistic regression, adjusting for other associated variables. Among subjects with atherosclerosis, blood pressure variables associated with complex aortic atherosclerosis (protruding plaques ≥4 mm thick, mobile debris, or ulceration) were determined. Age and smoking history were independently associated with aortic atherosclerosis of any degree ( P ≤0.001) and with complex atherosclerosis ( P =0.002), whereas sex, diabetes mellitus, and body mass index were not. Multiple systolic and pulse pressure variables (office and ambulatory), but none of the diastolic blood pressure variables, were associated with atherosclerosis and complex atherosclerosis, adjusting for age and smoking. Among subjects with atherosclerosis, the odds of complex atherosclerosis increased as ambulatory out-of-bed systolic blood pressure increased (odds ratio 1.43 per 10 mm Hg increase, 95% CI 1.10 to 1.87) and with hypertension treatment, adjusting for age and smoking history. Conclusions —High blood pressure is independently associated with aortic atherosclerosis. Among subjects with atherosclerosis, high blood pressure is associated with complex atherosclerosis.

Background —Functional mitral regurgitation (FMR) occurs with a structurally normal valve as a complication of systolic left ventricular dysfunction (LVD). Determinants of degree of FMR are poorly defined; thus, mechanistic therapeutic approaches to FMR are hindered. Methods and Results —In a prospective study of 21 control subjects and 128 patients with LVD (defined as ejection fraction <50%, mean 31±9%) in sinus rhythm, we quantified simultaneously by echocardiography the effective regurgitant orifice (ERO) of FMR by using 2 methods: mitral deformation (valve and annulus) and left ventricular (LV) global (volumes, stress, function, and sphericity) and local (papillary muscle displacements and regional wall motion index) remodeling. A wide range of ERO (15±14 mm 2 , 0 to 87 mm 2 ) was observed, unrelated to ejection fraction ( P =0.32). The major determinant of ERO was mitral deformation, ie, systolic valvular tenting and annular contraction in univariate ( r =0.74 and r =−0.61, respectively; both P <0.0001) and multivariate (both P <0.0001) analyses, independent of global LV remodeling. Systolic valvular tenting was strongly determined by local LV alterations, particularly apical ( r =0.75) and posterior ( r =0.70) displacement of papillary muscle, with confirmation in multivariate analysis (both P <0.0001), independent of LV volumes, function, and sphericity. Conclusions —The presence and degree of FMR complicating LVD are unrelated to the severity of LVD. Local LV remodeling (apical and posterior displacement of papillary muscles) leads to excess valvular tenting independent of global LV remodeling. In turn, excess tenting and loss of systolic annular contraction are associated with larger EROs. These determinants of FMR warrant consideration for specific approaches to the treatment of FMR complicating LVD.

Background —Increasingly, dobutamine stress echocardiography has been used for detection of coronary artery disease. Less information exists regarding the incremental prognostic value of the test, including semiquantitative wall scoring, compared with clinical and rest echocardiographic variables. Methods and Results —Follow-up information was obtained from 860 patients who underwent dobutamine stress echocardiography over a 2-year period. To determine the value of dobutamine stress echocardiography in predicting cardiac events, including cardiac death and myocardial infarction, clinical and rest and stress echocardiographic data were considered in a stepwise Cox multivariate regression model. During follow-up of up to 52 months, 72 patients underwent coronary revascularization before any cardiac event and were censored. Eighty-six patients had cardiac events, including nonfatal myocardial infarction in 36 and cardiac death in 50. In a multivariate model, a history of congestive heart failure, the percentage of abnormal segments at peak stress, and an abnormal left ventricular end-systolic volume response to stress were independent predictors of cardiac events. The model that best predicted subsequent cardiac events included clinical and stress echocardiographic data. Conclusions —Dobutamine stress echocardiography with semiquantitative segmental wall scoring provides important incremental information in predicting subsequent cardiac events.

Background Transesophageal echocardiography (TEE) is the diagnostic modality of choice for visualizing the left atrial appendage (LAA). This study defined the morphology of the LAA in normal autopsy specimen hearts and considered the implications of these findings for TEE studies. Methods and Results Five hundred normal autopsy hearts were reviewed (25 male and 25 female subjects from each decade for 10 decades). LAA length, width, orifice size, and number of lobes were recorded. Number of lobes was compared between sexes with the rank sum test and regressed against age. Mean length, width, and orifice size increased with age, up to age 20 years, in both sexes. Rates were significantly different between sexes for LAA size ( P =.011) and width ( P =.006). After age 20, statistically significant but clinically insignificant age-related changes were observed. Fifty-four percent of LAAs had two lobes (range, 1 to 4), with no age or sex differences. Lobes exist in different planes of the heart. Most pectinate muscles were ≥1 mm in width. Pectinate muscles <1 mm (2.6% of cases) were seen in only the first and last decades. Conclusions Age- and sex-related differences in LAA dimensions exist. These differences and the existence of multilobed appendages are important in the accurate TEE evaluation of LAA. Because lobes exist in different planes, imaging must be done in multiple planes to visualize the entire LAA.

Background The optimal timing for surgery in patients with mitral regurgitation is disputed. Because of the frequency of left ventricular dysfunction, which is difficult to predict, early surgery has been recommended, but its potential benefits have not been demonstrated. Methods and Results The outcomes of 221 patients (mean age, 65±13 years; 71% males) with flail leaflets diagnosed with two-dimensional echocardiography between 1980 and 1989 who were eligible for operation were analyzed. Group I comprised 63 patients who had early mitral valve surgery (within 1 month after diagnosis). Group II comprised 158 patients initially treated conservatively (80 of whom were operated on later). Group I patients were younger ( P =.009), had more symptoms ( P <.0001), and were more frequently in atrial fibrillation ( P =.023) than group II patients. There was no difference in ejection fraction between the groups. The early surgery strategy was followed by an improved overall survival rate ( P= .028) and a lower incidence of cardiovascular deaths ( P =.025), congestive heart failure ( P =.046), and new chronic atrial fibrillation ( P =.032), as confirmed by multivariate analysis (adjusted risk ratios of 0.31, 0.18, 0.38, and 0.05, respectively; all P< .02). Conclusions In patients with mitral regurgitation due to flail leaflets, the strategy of early surgery versus conservative management is associated with an improved long-term survival rate, decreased cardiac mortality, and decreased morbidity after diagnosis. This outcome advantage suggests that early surgery is a reasonable treatment option to be considered in low-risk candidates with repairable valves and severe mitral regurgitation.

BackgroundQuantitative Doppler echocardiography and proximal flow convergence methods are validated techniques for quantifying mitral regurgitation. However, the clinical interpretation of the values calculated is hindered by the absence of calibration of ranges of severity in large numbers of patients.Methods and ResultsIn 180 consecutive patients (men, 62%; mean age±SD, 66±11 years), the results of Doppler quantification of isolated mitral regurgitation were calibrated by use of left ventricular angiographic grading performed within 3 months in routine practice and without intervening events. The thresholds of the quantitative variables corresponding to the angiographic grades were identified by maximizing the sum of sensitivity and specificity and minimizing their difference. The mitral regurgitation grade by angiography was 2.7±1.3. The mean value and correlation with angiographic grades for effective regurgitant orifice were 43±37 mm andr=.79 (P<.0001); for regurgitant volume, 62±45 mL andr=.80 (P<.0001); and for regurgitant fraction, 45±17% andr=.78 (P<.0001). Despite some overlap, differences between mitral regurgitation grades were all significant (allP<.05). The thresholds for severe mitral regurgitation (grade 4) were 60 mL, 50%, and 40 mm2for regurgitant volume, regurgitant fraction, and orifice, respectively.ConclusionsIn routine practice in large numbers of patients in a clinical laboratory, Doppler echocardiographic quantification of mitral regurgitation shows highly significant correlation with qualitative angiographic grades. Despite an expected overlap between classes, the calibration by angiography of grading ranges for the quantitative variables provides a framework for their interpretation and allows the definition in clinical practice of thresholds for severe mitral regurgitation.

Background The use of exercise echocardiography for the diagnosis of coronary artery disease (CAD) has been validated in pilot studies but is not documented in clinical practice and in women comparatively with men. The objectives of this study were to determine the effects of sex and of test verification bias on the diagnostic performance of exercise echocardiography. Methods and Results Three thousand six hundred seventy-nine consecutive patients (1714 women, 1965 men) who underwent an exercise echocardiographic study were studied; the observed sensitivity, specificity, and correct classification rate were calculated among 340 patients (244 men, 96 women) who underwent angiography; to study the effect of test verification bias, sensitivity and specificity were estimated for all patients who underwent exercise echocardiography including those not referred to angiography. In the angiographic group, the prevalence of CAD was 60% in women and 80% in men. The observed sensitivity and specificity of exercise echocardiography was 78% and 44% in men and 79% and 37% in women. After adjustment for test verification bias, the estimated sensitivity was lower in women (32% versus 42% in men), whereas specificity was similar in both sexes. The positive predictive value was lower in women (66%) compared with men (84%). Conclusions In clinical practice, test verification bias results in a lower observed specificity and a higher sensitivity of exercise echocardiography. In women, positive predictive value and adjusted sensitivity are lower compared with that in men.

BackgroundAortic valve replacement for aortic stenosis (AS) carries an increased risk in the presence of left ventricular (LV) systolic dysfunction. Few data are available on the outcome of such patients.Methods and ResultsBetween 1985 and 1992, 154 consecutive patients (107 men and 47 women) with LV systolic dysfunction (ejection fraction [EF] ≤35%) underwent aortic valve replacement for AS. The mean preoperative characteristics included EF, 27±6%; aortic valve mean gradient, 44±18 mm Hg; aortic valve area, 0.6±0.2 cm2; and cardiac output, 4.1±1.5 L/min. Simultaneous coronary artery bypass graft surgery was performed in 78 patients (51%). Perioperative (30-day) mortality was 9% (14 of 154 patients). Fifty patients died during follow-up. Coronary artery disease (P=.002) and a reduced preoperative cardiac output (P=.03) were significantly related to reduced overall survival rate by multivariate analysis. Postoperative improvement occurred in most patients; 88% were New York Heart Association class III or IV before surgery versus 7% after surgery. Postoperative EF was assessed in 76% of survivors; 76% of these demonstrated improvement. By multivariate analysis, change in EF was inversely related to coronary disease (P=.002) and preoperative aortic valve area (P=.03).ConclusionsDespite LV dysfunction, the risk of aortic valve replacement for AS was acceptable and related to coronary artery disease and mean aortic gradient, and long-term survival was related to coronary disease and cardiac output. Improvement in symptoms and EF occurred in most patients.

BackgroundSinus venosus atrial septal defect (SVD) is underdiagnosed with transthoracic echocardiography because of its posterior (far field) location. Transesophageal echocardiography (TEE) should be ideally suited to diagnose SVD, given the proximity of the transducer to the defect.Methods and ResultsA retrospective study was undertaken that used the medical history, echocardiographic findings, and surgical data of patients identified from computer records as having the diagnosis of SVD during the period in which TEE has been in use (1987 to 1995). Twenty-five patients (14 females and 11 males; median age, 45 years; range, 10 to 75 years) with SVD had TEE between 1987 and 1995. Prior transthoracic echocardiography clearly defined the SVD in 3 of these patients, and it was suspected in another 11 on the basis of color-flow imaging. Ten patients had unexplained dilatation of the right side of the heart, which prompted TEE examination. SVD was visualized with TEE in all 25 patients and ranged in size from 1 to 3 cm. Thirty-seven right-sided anomalous pulmonary venous connections were identified in 23 patients. No left-sided anomalous pulmonary venous connections were detected. Anatomic confirmation was obtained in all 23 surgical patients. No patient required preoperative cardiac catheterization for diagnosis.ConclusionsTEE is accurate for the diagnosis of SVD and should be undertaken in any patient with unexplained dilatation of the right side of the heart. The associated pulmonary venous abnormalities can be identified with TEE. Cardiac catheterization for diagnostic purposes should not be required before surgical correction.

BackgroundIndications for surgical correction of aortic regurgitation have been established mostly in men and have not been validated in women. The outcome of this surgical correction in women is unknown.Methods and ResultsBaseline characteristics and postoperative outcomes were compared between 51 women and 198 men undergoing surgery for isolated aortic regurgitation between 1980 and 1989. Compared with men, women had surgery rarely for severe left ventricular enlargement (systolic diameter ≥55 mm in 11% versus 27%,P=.031; diastolic diameter ≥80 mm in 0% versus 16%,P<.0001) and more often for class III to IV symptoms (59% versus 32%,P<.0001). Operative mortalities were similar in women and men (3.9% and 4.5%, respectively). Among operative survivors, 10-year survival was worse for women than for men (39±9% versus 72±4%,P=.0002) and, in contrast with men, was worse than expected for women (P<.0001). Independent predictors of late survival were different for men (age and ejection fraction) and women (age and concomitant coronary bypass grafting). By multivariate analysis, female sex was an independent predictor of worse late survival (adjusted relative risk, 1.80; 95% CI, 1.04 to 3.11).ConclusionsThe generalization to women of the unadjusted left ventricular diameter surgical criteria established in men results in irrelevant criteria almost never reached in women, who often undergo surgery after developing severe symptoms. After surgery, women exhibit an excess late mortality, suggesting that surgical correction of aortic regurgitation should be considered at an earlier stage in women.