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Use of Tissue Doppler to Distinguish Discrete Upper Ventricular Septal Hypertrophy from Obstructive Hypertrophic Cardiomyopathy
Use of Tissue Doppler to Distinguish Discrete Upper Ventricular Septal Hypertrophy from Obstructive Hypertrophic Cardiomyopathy Annabel Chen-Tournoux, MDa, Michael A. Fifer, MDa, Michael H. Picard, MDa, and Judy Hung, MDa,* Discrete upper septal hypertrophy (DUSH) is a well-recognized but poorly understood echocardiographic finding that may indicate localized remodeling modulated by pressure loading or a forme fruste variant of obstructive hypertrophic cardiomyopathy (HC). It was hypothesized that (1) a comparison of tissue Doppler indexes of myocardial function in normal patients and those with DUSH or aortic stenosis (AS) could provide insight into the clinical significance of DUSH and (2) these indexes could distinguish between DUSH and obstructive HC. A retrospective analysis was performed on patients aged 50 to 80 years who underwent routine echocardiography and who could be classified into normal, DUSH, AS, and HC groups (n ⴝ 25, 33, 23, and 34, respectively) on the basis of clinical and echocardiographic criteria. Early diastolic mitral annular velocities (Ea) in the DUSH (7.1 ⴞ 1.8 cm/s) and AS (7.1 ⴞ 1.7 cm/s) groups were lower compared with those in the normal group (9.3 ⴞ 1.9 cm/s) and higher compared with those in the HC group (5.4 ⴞ 1.3 cm/s), whereas the E/Ea ratio was higher in the DUSH and AS groups (10.0 ⴞ 3.1 and 11.3 ⴞ 2.8, respectively) compared with the normal group (7.1 ⴞ 1.6) and lower compared with the HC group (18.8 ⴞ 7.5). These differences remained significant after adjusting for age and the use of  blockers and calcium channel blockers. E/Ea >13 distinguished between patients with HC and those with DUSH (sensitivity 78%, specificity 90%, positive predictive value 90%, negative predictive value 81%). In conclusion, abnormal Ea and E/Ea in patients with DUSH, with values similar to those in patients with AS, suggest that DUSH may represent a variant hypertrophic response to chronic pressure loading. Simple echocardiographic indexes may be helpful in distinguishing between patients with DUSH and those with obstructive HC. © 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;101:1498 –1503)
Although thickening of the upper ventricular septum is a classic feature of obstructive hypertrophic cardiomyopathy (HC), discrete upper septal hypertrophy (DUSH) has also been observed in subjects with no evidence of cardiac disease. Variously termed sigmoid septum,1 localized subaortic or septal hypertrophy,2,3 or subaortic septal bulge,4 DUSH is a common finding of uncertain origin and significance. Although some postulate that it represents a forme fruste variant of obstructive HC, DUSH has not been associated with myocyte disarray3 and is generally considered to be an incidental finding associated with older age and hypertension, in conjunction with increased angulation between the ascending aorta and left ventricular (LV) outflow tract.4,5 Because the outflow tract gradient is dynamic in HC and because an outflow tract gradient may be present in an underfilled, hypercontractile left ventricle with DUSH, it may be difficult to determine on the basis of conventional 2-dimensional echocardiography whether upper septal hypertrophy indicates HC or the more benign DUSH (Figure a Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts USA. Manuscript received September 17, 2007; revised manuscript received and accepted January 3, 2008. *Corresponding author: Tel: 617-726-0995; fax: 617-726-8383. (J. Hung). E-mail address: [email protected]
0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2008.01.027
1). To test our hypothesis that DUSH could represent a variant hypertrophic response to chronic pressure load, we compared mitral annular velocities in patients with DUSH with those in normal controls and patients with aortic stenosis (AS), a pressure overload condition associated with decreased mitral annular velocities.6,7 We also compared these values with those in patients with obstructive HC to see if mitral annular velocities could distinguish between DUSH and obstructive HC. Methods Routine transthoracic echocardiography performed at Massachusetts General Hospital from 2005 and 2007 were screened for patients aged 50 to 80 years with normal results, DUSH, AS, or HC. Patients were excluded if complete clinical data regarding medical histories and medications were not available or if echocardiograms did not have adequate image quality. Patients were excluded if they had a history of coronary artery disease or myocardial infarction, atrial fibrillation, conduction disturbances, congenital heart disease, cardiac or thoracic surgery, diabetes mellitus, renal insufficiency (creatinine ⬎1.5 mg/dl), malignancy, radiation therapy, or hepatic failure. In addition, patients were excluded if echocardiography revealed regional wall motion abnormalities, LV ejection fraction ⬍50%, LV diwww.AJConline.org
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Figure 1. Transthoracic echocardiography in the parasternal long-axis view showing similar appearance between DUSH (A) and obstructive HC (B).
lation, right ventricular dilation or hypokinesia, or pericardial abnormalities. Patients were included in the analysis if they fell into 1 of 4 groups: normal, DUSH, HC, and AS. The normal group had no history of hypertension and had structurally normal hearts. The DUSH group had structurally normal hearts except for DUSH, defined as a focal area (⬍33% of total septal length) of ventricular septal thickness ⱖ13 mm and maximal septal–to–posterior wall thickness ⱖ1.3 as measured in the parasternal long-axis view, without an outflow tract gradient or systolic anterior motion of the mitral valve leaflets. The HC group had ⱖ1 symptom (dyspnea, angina, syncope, or documented tachyarrhythmia) referable to HC, maximal ventricular septal thickness ⱖ15 mm, systolic anterior motion of the mitral valve and mild or greater mitral regurgitation, and a rest or provoked outflow tract gradient ⱖ30 mm Hg. The AS group had typical AS with a peak aortic gradient ⱖ25 mm Hg. Patients who met the inclusion criteria for ⬎1 group were excluded. A history of hypertension and the use of  blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretics were recorded. Transthoracic echocardiography was performed with commercially available systems using 2.5- to 3.5-MHz transducers (Sonos 5500 or 7500; Philips Medical Systems, Andover, Massachusetts). Patients’ height and weight were recorded at the time of echocardiography. Two-dimensional, spectral, and color Doppler imaging was performed according to a standard protocol. Pulsed-wave Doppler of transmitral and pulmonary venous flow was recorded. The peak LV outflow tract gradient was determined at rest and during the Valsalva maneuver using pulsed-wave Doppler and continuous-wave Doppler when the velocity aliased in the LV outflow tract (apical 5-chamber view). Peak and mean transaortic gradients were determined using continuous-wave Doppler of the aortic valve (apical 5-chamber view). Pulsed-wave tissue Doppler imaging was performed of the lateral and septal mitral annulus from the apical 4-chamber view, aligning the cursor to the motion of the annulus. A single observer (AC-T) analyzed the echocardiographic data off-line using commercially available software (Xcelera version 1.2; Philips Medical Systems). The heart rate at the time of echocardiography was recorded. Wall thickness and chamber dimensions were measured according to established criteria.8 LV volumes were indexed to
body surface area. The LV ejection fraction was calculated using the biplane method of discs. The Doppler indexes measured were early and late diastolic mitral inflow velocities, early diastolic deceleration time, and systolic and diastolic pulmonary vein velocities. The tissue Doppler indexes measured were the early (Ea) and late (Aa) diastolic and systolic (Sa) velocities at the lateral and septal annulus. A sample size of ⱖ22 patients in each group was determined to be necessary for 90% power to detect a 25% difference in annular velocity. Results are presented as mean ⫾ SD. Normality was evaluated for each variable using the Kolmogorov-Smirnov test. Differences between groups were tested for significance using analysis of variance, followed by subgroup analysis using the StudentNewman-Keuls test. Proportions were compared using the chi-square test. Univariate and multivariate regression analyses were used to assess the relative contributions and independence of clinical and echocardiographic parameters on mitral annular velocities and the diagnosis of DUSH or HC. Receiver-operating characteristic curve analysis was used to determine optimal cut points for discriminating between DUSH and HC. The intraclass correlation coefficient was calculated to assess the interobserver laboratory measurement variability of tissue Doppler measurements using a random 10-patient sample. Statistical analysis was performed using MedCalc version 9.3.2.0 (http://www.medcalc.com) and SPSS version 15.0 (SPSS, Inc., Chicago, Illinois). Results The clinical characteristics of the 4 patient groups are listed in Table 1. There was no difference in body surface area or body mass index among the 4 groups (not shown). One patient in the normal group took a low-dose diuretic for mild leg edema. Compared with patients with HC, those with DUSH and AS were more likely to take angiotensinconverting enzyme inhibitors or angiotensin receptor blockers and less likely to take  blockers and calcium channel blockers (Table 1). The echocardiographic findings of the patient groups are listed in Tables 2 and 3. In 24 patients with HC, outflow tract gradients at rest were ⬎30 mm Hg (86 ⫾ 36). In the 10 patients with outflow tract gradients ⬍30 mm Hg, the gradient increased to 57 ⫾ 24 mm Hg during the Valsalva maneuver. The AS group had peak and mean aortic gradi-
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Table 1 Clinical characteristics of the patient groups Variable Age (yrs) Women Hypertension  blocker Calcium channel blocker Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker Diuretic
Normal (n ⫽ 25)
DUSH (n ⫽ 33)
AS (n ⫽ 23)
Obstructive HC (n ⫽ 34)
p Value (ANOVA)
62 ⫾ 8 17 (68%) 0 0 0 0
65 ⫾ 8 18 (55%) 28 (85%)* 17 (52%)* 5 (15%) 19 (58%)*
71 ⫾ 7* 10 (43%) 17 (74%)* 9 (39%)* 4 (17%) 10 (43%)*
65 ⫾ 9 16 (47%) 13 (38%)*,†,‡ 25 (74%)*,†,‡ 16 (47%)*,†,‡ 6 (18%)†,‡
0.002 0.34 ⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001
1 (4%)
12 (36%)*
10 (43%)*
10 (29%)*
Data are expressed as mean ⫾ SD or as number (percentage). ANOVA ⫽ analysis of variance. * p ⬍0.05 compared with normal group; † p ⬍0.05 compared with DUSH group;
‡
0.03
p ⬍0.05 compared with AS group.
Table 2 Echocardiographic characteristics of patient groups Variable Heart rate (beats/min) Maximal ventricular septal thickness (mm) Posterior wall thickness (mm) Maximal/midventricular septal thickness ratio Left atrial dimension (mm) LV ejection fraction (%) Early diastolic mitral inflow velocity (cm/s) Late diastolic mitral inflow velocity (cm/s) Early to late diastolic mitral inflow velocity ratio ⬍1 Early diastolic mitral inflow deceleration time (ms)
Normal (n ⫽ 25)
DUSH (n ⫽ 33)
70 ⫾ 12 8.9 ⫾ 1.1
66 ⫾ 13 15.6 ⫾ 2.7*
8.8 ⫾ 0.9 —
AS (n ⫽ 23)
HC (n ⫽ 34)
p value (ANOVA)
68 ⫾ 14 12 ⫾ 1.9*,†
66 ⫾ 11 19.7 ⫾ 3.1*,†,‡
0.59 ⬍0.001
9.2 ⫾ 1.5 1.8 ⫾ 0.3
10.8 ⫾ 1.7*,† —
13.3 ⫾ 2.3*,†,‡ 1.3 ⫾ 0.3†
⬍0.001 ⬍0.001
32 ⫾ 4 65 ⫾ 7 62 ⫾ 12
37 ⫾ 7* 65 ⫾ 7 68 ⫾ 16
37 ⫾ 4* 65 ⫾ 9 76 ⫾ 13*
42 ⫾ 6*,†,‡ 72 ⫾ 7*,†,‡ 91 ⫾ 25*,†,‡
⬍0.001 ⬍0.001 ⬍0.001
64 ⫾ 17
74 ⫾ 18*
91 ⫾ 21*,†
88 ⫾ 25*,†
⬍0.001
11 (41%)
20 (60%)
15 (65%)
15 (44%)
0.21
206 ⫾ 35
212 ⫾ 61
233 ⫾ 62
Data are expressed as mean ⫾ SD or as number (percentage). * p ⬍0.05 compared with normal group; † p ⬍0.05 compared with DUSH group;
ents of 53 ⫾ 30 and 29 ⫾ 17 mm Hg, respectively. There was no difference in pulmonary vein velocities among the 4 groups (not shown). As listed in Table 3 and shown in Figures 2 and 3, compared with the normal group, the DUSH, AS, and HC groups had significantly lower Ea and higher E/Ea. Furthermore, patients in the DUSH and AS groups had significantly higher Ea, Aa, and Sa and lower E/Ea compared with patients in the HC group. These relations were evident whether the annular velocities were measured at the lateral or septal wall or averaged from the 2 walls. There was no significant difference among the groups in the ratio of lateral to septal Ea, Aa, or Sa or in the ratio of septal, lateral, or averaged Ea to Aa (not shown). Univariate predictors of Ea, E/Ea, Aa, and Sa among all patients were clinical group, age, the use of  blockers and/or calcium channel blockers, maximal ventricular septal thickness, and left atrial dimension. In addition, a history of hypertension was a predictor of Ea. As listed in Table 4, in multiple regression analysis using these covariates, clinical group remained an independent predic-
‡
230 ⫾ 47
0.15
p ⬍0.05 compared with AS group.
tor of the mitral annular indexes. Beta-blocker or calcium channel blocker use was an independent predictor of E/Ea, Aa, and Sa but not of Ea. Several echocardiographic indexes were identified by univariate analysis to distinguish HC from DUSH: the ratio of maximal to midventricular septal thickness, the LV ejection fraction, left atrial dimension, averaged E/Ea, and averaged Sa. In multivariate logistic regression analysis, averaged E/Ea (odds ratio 1.3, coefficient 0.24, p ⬍0.01), left atrial dimension (odds ratio 1.2, coefficient 0.21, p ⫽ 0.02), and the ratio of maximal to midventricular septal thickness (odds ratio 0.01, coefficient ⫺4.72, p ⬍0.01) remained independent predictors of HC. Receiver-operating characteristic curve analysis identified an optimal cut point of averaged E/Ea ⱖ13 to differentiate HC from DUSH (78% sensitivity, 90% specificity, 90% positive predictive value, 81% negative predictive value, area under the curve 0.89). The mean laboratory reproducibility for tissue Doppler indexes was 0.99, as assessed using the intraclass correlation coefficient.
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Table 3 Tissue Doppler mitral annular velocities of patient groups Variable Ea (cm/s) Lateral Septal Averaged E/Ea Lateral Septal Averaged Aa (cm/s) Lateral Septal Averaged Sa (cm/s) Lateral Septal Averaged
normal (n ⫽ 25)
DUSH (n ⫽ 33)
AS (n ⫽ 23)
HC (n ⫽ 34)
p value (ANOVA)
10.3 ⫾ 2.1 8.2 ⫾ 2.0 9.3 ⫾ 1.9
8.1 ⫾ 2.4* 6.4 ⫾ 1.9* 7.1 ⫾ 1.8*
7.7 ⫾ 1.8* 6.5 ⫾ 2.0* 7.1 ⫾ 1.7*
6.2 ⫾ 2.0*,†,‡ 4.6 ⫾ 11*,†,‡ 5.4 ⫾ 1.3*,†,‡
⬍0.001 ⬍0.001 ⬍0.001
6.3 ⫾ 1.1 8.0 ⫾ 1.9 7.1 ⫾ 1.6
9.0 ⫾ 3.2* 11.1 ⫾ 3.4* 10.0 ⫾ 3.1*
10.1 ⫾ 2.9* 12.6 ⫾ 4.4* 11.3 ⫾ 2.8*
16.3 ⫾ 6.9*,†,‡ 21.5 ⫾ 9.3*,†,‡ 18.8 ⫾ 7.5*,†,‡
⬍0.001 ⬍0.001 ⬍0.001
10.6 ⫾ 2.6 10.4 ⫾ 2.4 10.7 ⫾ 2.3
11.0 ⫾ 2.9 10.2 ⫾ 2.2 10.9 ⫾ 2.9
10.4 ⫾ 1.8 9.3 ⫾ 2.1 9.8 ⫾ 1.5
8.6 ⫾ 3.6*,†,‡ 7.6 ⫾ 2.9*,†,‡ 8.1 ⫾ 3.1*,†,‡
0.006 ⬍0.001 ⬍0.001
9.0 ⫾ 2.0 7.7 ⫾ 1.7 8.6 ⫾ 1.7
8.2 ⫾ 2.5 7.1 ⫾ 1.7 7.9 ⫾ 2.2
8.1 ⫾ 2.0 7.0 ⫾ 1.1 7.6 ⫾ 1.4
6.7 ⫾ 2.3*,†,‡ 6.1 ⫾ 1.6*,†,‡ 6.4 ⫾ 1.7*,†,‡
⬍0.001 0.003 ⬍0.001
Data are expressed as mean ⫾ SD. * p ⬍0.05 compared with normal group; † p ⬍0.05 compared with DUSH group;
Figure 2. Averaged Ea velocity in the normal, DUSH, AS, and HC groups. Mean values and SDs are indicated. *p ⬍0.05 compared with normal group; †p ⬍0.05 compared with DUSH group; ‡p ⬍0.05 compared with AS group.
Discussion To our knowledge, our study was the first to apply tissue Doppler imaging to characterize myocardial function in DUSH and delineate the physiologic implications of this well-recognized but poorly understood echocardiographic finding. We found that Ea was lower and E/Ea higher in patients with DUSH compared with normal patients and similar to values in older patients with AS. We also found that mitral annular velocities were helpful in differentiating between DUSH and HC. Although the degree of overlap in the values of Ea and E/Ea between the 2 groups may be too great to set a strict cut point, our study indicates that lower Ea and higher E/Ea, as well as higher left atrial dimension and lower maximal to midventricular septal thickness ratio, support a diagnosis of HC. In contrast to the study by Krasnow,4 we found that
‡
p ⬍0.05 compared with AS group.
Figure 3. Averaged E/Ea in the normal, DUSH, AS, and HC groups. Mean values and standard deviations are indicated. *p ⬍0.05 compared with normal group; †p ⬍0.05 compared with DUSH group; ‡p ⬍0.05 compared with AS group.
diastolic function is abnormal in patients with DUSH. This discrepancy is not surprising, given that the earlier study evaluated diastolic function using mitral inflow velocities, which may poorly detect diastolic abnormalities because of their greater load dependence and inability to differentiate between pseudonormal and normal patterns. Indeed, in another study, mitral inflow velocities were able to discriminate only 25% of patients with hypertensive LV hypertrophy from normal patients, compared with 91% using mitral annular velocities.9 Similarly, we did not detect any evidence of diastolic abnormalities by mitral inflow or pulmonary venous patterns. Chronic pressure overload from hypertension may largely explain the decreased Ea and increased E/Ea observed in the patients with DUSH. Eighty-five percent of the patients with DUSH had a diagnosis of hypertension, and
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Table 4 Independent predictors of mitral annular velocities averaged between the septal and lateral walls Variable Ea Clinical group Maximal ventricular septal thickness Age E/Ea  blocker or calcium channel blocker Clinical group Aa  blocker or calcium channel blocker Clinical group Sa  blocker or calcium channel blocker Clinical group Age
 Regression Coefficient
p Value
⫺0.67 ⫺0.13 ⫺0.06
⬍0.001 0.002 0.004
2.9 2.7
⬍0.001 ⬍0.001
⫺0.87 ⫺0.65
0.04 0.01
⫺0.66 ⫺0.44 ⫺0.04
0.02 0.01 0.03
79% were taking at least 1 antihypertensive medication. A recent study demonstrated that mitral annular velocities are decreased in hypertensive patients even if they do not have LV hypertrophy.10 It is unknown whether any of the patients in this study had a typical DUSH pattern. The decrease in velocities in the lateral and septal walls suggests a global rather than regional abnormality in patients with DUSH, despite the focal morphologic finding. In patients with hypertension, LV hypertrophy usually develops concentrically as a compensatory response to normalize wall stress, although asymmetric hypertrophy has also been reported.11 Some patients may develop a DUSH pattern of hypertrophy in response to pressure overload for genetic, hemodynamic, or geometric reasons. This is supported by the observation that the values of Ea and E/Ea were similar between the patients with DUSH and those with AS, who are exposed to chronic pressure overload. Because tissue Doppler mitral annular velocities have prognostic value in patients with systemic hypertension and LV hypertrophy,12 our results suggest that further investigation is warranted to elucidate the clinical significance of abnormal Ea velocities in DUSH. Although Sa predicted clinical group in univariate analysis, it did not remain an independent predictor in multivariate analysis including age and the use of  blockers and calcium channel blockers as covariates. This is in contrast to the findings of Vinereanu et al13 that Sa could discriminate between pathologic and physiologic hypertrophy and of Kato et al14 that systolic strain could discriminate between HC and hypertensive LV hypertrophy. Our patients were much older than those in the earlier studies. Longitudinal myocardial function decreases with age,15,16 and perhaps Sa is more affected than Ea by age. In addition, in the earlier studies,  blockers and calcium channel blockers were discontinued before echocardiography, reducing their inhibitory effects on annular velocities.17 In our study, patients remained on their usual medications, and these may have masked the influence of DUSH, AS, or HC on Sa. Our findings may imply that Ea and E/Ea are less influenced by these medications and nevertheless remain clinically rele-
vant, because most patients do not discontinue medications before they undergo routine echocardiography. The main limitation of our study was our reliance on clinical and echocardiographic, rather than histologic or genetic, criteria to confirm the diagnosis of HC. We cannot exclude the possibility that some patients with DUSH in fact had milder or earlier forms of obstructive HC. To be confident in our clinical assignment of patients to the HC and DUSH groups, our inclusion criteria were stringent. By focusing our analysis on patients with or without “classic” features of obstructive HC, we identified echocardiographic parameters for differentiation between DUSH and obstructive HC in an idealized setting. In addition, it was impossible to maintain complete blinding to the patients’ clinical diagnoses during echocardiographic analysis given the characteristic findings. We excluded patients who fell into ⬎1 clinical category, a situation that would certainly complicate the interpretation of the echocardiographic indexes. Finally, we did not specifically investigate the relation between LV mass and the tissue Doppler indexes. It is well established that LV mass is inversely related to longitudinal myocardial function. However, we would expect the absolute increase in LV mass due to DUSH to be quite modest: the area of hypertrophy in DUSH is generally ⬍3 cm of the basal anterior septum,4 and the posterior wall and distal septal thicknesses were in the normal range in our DUSH group. Furthermore, commonly used formulas to estimate LV mass are based on geometric assumptions of LV shape and would have limited accuracy in the context of a focal septal irregularity. The accurate measurement of LV mass would best be performed with 3-dimensional echocardiography or magnetic resonance imaging and would be of future interest. 1. Goor D, Lillehei CW, Edwards JE. The “sigmoid septum.” Variation in the contour of the left ventricular outflow tract. Am J Roentgenol Radium Ther Nucl Med 1969;107:366 –376. 2. Shapiro LM, Howat AP, Crean PA, Westgate CJ. An echocardiographic study of localized subaortic hypertrophy. Eur Heart J 1986; 7:127–32. 3. Belenkie I, MacDonald RP, Smith ER. Localized septal hypertrophy: part of the spectrum of hypertrophic cardiomyopathy or an incidental echocardiographic finding? Am Heart J 1988;115:385–90. 4. Krasnow N. Subaortic septal bulge simulates hypertrophic cardiomyopathy by angulation of the septum with age, independent of focal hypertrophy. An echocardiographic study. J Am Soc Echocardiogr 1997;10:545–555. 5. Feigenbaum H, Armstrong WF, Ryan T. Feigenbaum’s Echocardiography. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins, 2005. 6. Bruch C, Stypmann J, Grude M, Gradaus R, Breithardt G, Wichter T. Tissue Doppler imaging in patients with moderate to severe aortic valve stenosis: clinical usefulness and diagnostic accuracy. Am Heart J 2004;148:696 –702. 7. Giorgi D, Di Bello V, Talini E, Palagi C, Delle Donne MG, Nardi C, Verunelli F, Mariani MA, Di Cori A, Caravelli P, Mariani M. Myocardial function in severe aortic stenosis before and after aortic valve replacement: a Doppler tissue imaging study. J Am Soc Echocardiogr 2005;18:8 –14. 8. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440 –1463.
Miscellaneous/Tissue Doppler in DUSH 9. Di Bello V, Giorgi D, Pedrinelli R, Talini E, Palagi C, Delle Donne MG, Zucchelli G, Dell’omo G, Di Cori A, Dell’Anna R, et al. Left ventricular hypertrophy and its regression in essential arterial hypertension. A tissue Doppler imaging study. Am J Hypertens 2004;17: 882– 890. 10. Borges MC, Colombo RC, Goncalves JG, Ferreira Jde O, Franchini KG. Longitudinal mitral annulus velocities are reduced in hypertensive subjects with or without left ventricle hypertrophy. Hypertension 2006;47:854 – 860. 11. Shapiro LM, Kleinebenne A, McKenna WJ. The distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: comparison to athletes and hypertensives. Eur Heart J 1985;6:967–974. 12. Wang M, Yip GW, Wang AY, Zhang Y, Ho PY, Tse MK, Yu CM, Sanderson JE. Tissue Doppler imaging provides incremental prognostic value in patients with systemic hypertension and left ventricular hypertrophy. J Hypertens 2005;23:183–191. 13. Vinereanu D, Florescu N, Sculthorpe N, Tweddel AC, Stephens MR, Fraser AG. Differentiation between pathologic and physiologic left ventricular hypertrophy by tissue Doppler assessment of long-axis
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function in patients with hypertrophic cardiomyopathy or systemic hypertension and in athletes. Am J Cardiol 2001;88:53–58. Kato TS, Noda A, Izawa H, Yamada A, Obata K, Nagata K, Iwase M, Murohara T, Yokota M. Discrimination of nonobstructive hypertrophic cardiomyopathy from hypertensive left ventricular hypertrophy on the basis of strain rate imaging by tissue Doppler ultrasonography. Circulation 2004;110:3808 –3814. Nikitin NP, Witte KK, Thackray SD, de Silva R, Clark AL, Cleland JG. Longitudinal ventricular function: normal values of atrioventricular annular and myocardial velocities measured with quantitative twodimensional color Doppler tissue imaging. J Am Soc Echocardiogr 2003;16:906 –921. Tighe DA, Vinch CS, Hill JC, Meyer TE, Goldberg RJ, Aurigemma GP. Influence of age on assessment of diastolic function by Doppler tissue imaging. Am J Cardiol 2003;91:254 –257. Gorcsan J III, Strum DP, Mandarino WA, Gulati VK, Pinsky MR. Quantitative assessment of alterations in regional left ventricular contractility with color-coded tissue Doppler echocardiography. Comparison with sonomicrometry and pressure-volume relations. Circulation 1997;95:2423–2433.
Although thickening of the upper ventricular septum is a classic feature of obstructive hypertrophic cardiomyopathy (HC), discrete upper septal hypertrophy (DUSH) has also been observed in subjects with no evidence of cardiac disease. Variously termed sigmoid septum,1 localized subaortic or septal hypertrophy,2,3 or subaortic septal bulge,4 DUSH is a common finding of uncertain origin and significance. Although some postulate that it represents a forme fruste variant of obstructive HC, DUSH has not been associated with myocyte disarray3 and is generally considered to be an incidental finding associated with older age and hypertension, in conjunction with increased angulation between the ascending aorta and left ventricular (LV) outflow tract.4,5 Because the outflow tract gradient is dynamic in HC and because an outflow tract gradient may be present in an underfilled, hypercontractile left ventricle with DUSH, it may be difficult to determine on the basis of conventional 2-dimensional echocardiography whether upper septal hypertrophy indicates HC or the more benign DUSH (Figure a Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts USA. Manuscript received September 17, 2007; revised manuscript received and accepted January 3, 2008. *Corresponding author: Tel: 617-726-0995; fax: 617-726-8383. (J. Hung). E-mail address: [email protected]
0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2008.01.027
1). To test our hypothesis that DUSH could represent a variant hypertrophic response to chronic pressure load, we compared mitral annular velocities in patients with DUSH with those in normal controls and patients with aortic stenosis (AS), a pressure overload condition associated with decreased mitral annular velocities.6,7 We also compared these values with those in patients with obstructive HC to see if mitral annular velocities could distinguish between DUSH and obstructive HC. Methods Routine transthoracic echocardiography performed at Massachusetts General Hospital from 2005 and 2007 were screened for patients aged 50 to 80 years with normal results, DUSH, AS, or HC. Patients were excluded if complete clinical data regarding medical histories and medications were not available or if echocardiograms did not have adequate image quality. Patients were excluded if they had a history of coronary artery disease or myocardial infarction, atrial fibrillation, conduction disturbances, congenital heart disease, cardiac or thoracic surgery, diabetes mellitus, renal insufficiency (creatinine ⬎1.5 mg/dl), malignancy, radiation therapy, or hepatic failure. In addition, patients were excluded if echocardiography revealed regional wall motion abnormalities, LV ejection fraction ⬍50%, LV diwww.AJConline.org
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Figure 1. Transthoracic echocardiography in the parasternal long-axis view showing similar appearance between DUSH (A) and obstructive HC (B).
lation, right ventricular dilation or hypokinesia, or pericardial abnormalities. Patients were included in the analysis if they fell into 1 of 4 groups: normal, DUSH, HC, and AS. The normal group had no history of hypertension and had structurally normal hearts. The DUSH group had structurally normal hearts except for DUSH, defined as a focal area (⬍33% of total septal length) of ventricular septal thickness ⱖ13 mm and maximal septal–to–posterior wall thickness ⱖ1.3 as measured in the parasternal long-axis view, without an outflow tract gradient or systolic anterior motion of the mitral valve leaflets. The HC group had ⱖ1 symptom (dyspnea, angina, syncope, or documented tachyarrhythmia) referable to HC, maximal ventricular septal thickness ⱖ15 mm, systolic anterior motion of the mitral valve and mild or greater mitral regurgitation, and a rest or provoked outflow tract gradient ⱖ30 mm Hg. The AS group had typical AS with a peak aortic gradient ⱖ25 mm Hg. Patients who met the inclusion criteria for ⬎1 group were excluded. A history of hypertension and the use of  blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretics were recorded. Transthoracic echocardiography was performed with commercially available systems using 2.5- to 3.5-MHz transducers (Sonos 5500 or 7500; Philips Medical Systems, Andover, Massachusetts). Patients’ height and weight were recorded at the time of echocardiography. Two-dimensional, spectral, and color Doppler imaging was performed according to a standard protocol. Pulsed-wave Doppler of transmitral and pulmonary venous flow was recorded. The peak LV outflow tract gradient was determined at rest and during the Valsalva maneuver using pulsed-wave Doppler and continuous-wave Doppler when the velocity aliased in the LV outflow tract (apical 5-chamber view). Peak and mean transaortic gradients were determined using continuous-wave Doppler of the aortic valve (apical 5-chamber view). Pulsed-wave tissue Doppler imaging was performed of the lateral and septal mitral annulus from the apical 4-chamber view, aligning the cursor to the motion of the annulus. A single observer (AC-T) analyzed the echocardiographic data off-line using commercially available software (Xcelera version 1.2; Philips Medical Systems). The heart rate at the time of echocardiography was recorded. Wall thickness and chamber dimensions were measured according to established criteria.8 LV volumes were indexed to
body surface area. The LV ejection fraction was calculated using the biplane method of discs. The Doppler indexes measured were early and late diastolic mitral inflow velocities, early diastolic deceleration time, and systolic and diastolic pulmonary vein velocities. The tissue Doppler indexes measured were the early (Ea) and late (Aa) diastolic and systolic (Sa) velocities at the lateral and septal annulus. A sample size of ⱖ22 patients in each group was determined to be necessary for 90% power to detect a 25% difference in annular velocity. Results are presented as mean ⫾ SD. Normality was evaluated for each variable using the Kolmogorov-Smirnov test. Differences between groups were tested for significance using analysis of variance, followed by subgroup analysis using the StudentNewman-Keuls test. Proportions were compared using the chi-square test. Univariate and multivariate regression analyses were used to assess the relative contributions and independence of clinical and echocardiographic parameters on mitral annular velocities and the diagnosis of DUSH or HC. Receiver-operating characteristic curve analysis was used to determine optimal cut points for discriminating between DUSH and HC. The intraclass correlation coefficient was calculated to assess the interobserver laboratory measurement variability of tissue Doppler measurements using a random 10-patient sample. Statistical analysis was performed using MedCalc version 9.3.2.0 (http://www.medcalc.com) and SPSS version 15.0 (SPSS, Inc., Chicago, Illinois). Results The clinical characteristics of the 4 patient groups are listed in Table 1. There was no difference in body surface area or body mass index among the 4 groups (not shown). One patient in the normal group took a low-dose diuretic for mild leg edema. Compared with patients with HC, those with DUSH and AS were more likely to take angiotensinconverting enzyme inhibitors or angiotensin receptor blockers and less likely to take  blockers and calcium channel blockers (Table 1). The echocardiographic findings of the patient groups are listed in Tables 2 and 3. In 24 patients with HC, outflow tract gradients at rest were ⬎30 mm Hg (86 ⫾ 36). In the 10 patients with outflow tract gradients ⬍30 mm Hg, the gradient increased to 57 ⫾ 24 mm Hg during the Valsalva maneuver. The AS group had peak and mean aortic gradi-
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Table 1 Clinical characteristics of the patient groups Variable Age (yrs) Women Hypertension  blocker Calcium channel blocker Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker Diuretic
Normal (n ⫽ 25)
DUSH (n ⫽ 33)
AS (n ⫽ 23)
Obstructive HC (n ⫽ 34)
p Value (ANOVA)
62 ⫾ 8 17 (68%) 0 0 0 0
65 ⫾ 8 18 (55%) 28 (85%)* 17 (52%)* 5 (15%) 19 (58%)*
71 ⫾ 7* 10 (43%) 17 (74%)* 9 (39%)* 4 (17%) 10 (43%)*
65 ⫾ 9 16 (47%) 13 (38%)*,†,‡ 25 (74%)*,†,‡ 16 (47%)*,†,‡ 6 (18%)†,‡
0.002 0.34 ⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001
1 (4%)
12 (36%)*
10 (43%)*
10 (29%)*
Data are expressed as mean ⫾ SD or as number (percentage). ANOVA ⫽ analysis of variance. * p ⬍0.05 compared with normal group; † p ⬍0.05 compared with DUSH group;
‡
0.03
p ⬍0.05 compared with AS group.
Table 2 Echocardiographic characteristics of patient groups Variable Heart rate (beats/min) Maximal ventricular septal thickness (mm) Posterior wall thickness (mm) Maximal/midventricular septal thickness ratio Left atrial dimension (mm) LV ejection fraction (%) Early diastolic mitral inflow velocity (cm/s) Late diastolic mitral inflow velocity (cm/s) Early to late diastolic mitral inflow velocity ratio ⬍1 Early diastolic mitral inflow deceleration time (ms)
Normal (n ⫽ 25)
DUSH (n ⫽ 33)
70 ⫾ 12 8.9 ⫾ 1.1
66 ⫾ 13 15.6 ⫾ 2.7*
8.8 ⫾ 0.9 —
AS (n ⫽ 23)
HC (n ⫽ 34)
p value (ANOVA)
68 ⫾ 14 12 ⫾ 1.9*,†
66 ⫾ 11 19.7 ⫾ 3.1*,†,‡
0.59 ⬍0.001
9.2 ⫾ 1.5 1.8 ⫾ 0.3
10.8 ⫾ 1.7*,† —
13.3 ⫾ 2.3*,†,‡ 1.3 ⫾ 0.3†
⬍0.001 ⬍0.001
32 ⫾ 4 65 ⫾ 7 62 ⫾ 12
37 ⫾ 7* 65 ⫾ 7 68 ⫾ 16
37 ⫾ 4* 65 ⫾ 9 76 ⫾ 13*
42 ⫾ 6*,†,‡ 72 ⫾ 7*,†,‡ 91 ⫾ 25*,†,‡
⬍0.001 ⬍0.001 ⬍0.001
64 ⫾ 17
74 ⫾ 18*
91 ⫾ 21*,†
88 ⫾ 25*,†
⬍0.001
11 (41%)
20 (60%)
15 (65%)
15 (44%)
0.21
206 ⫾ 35
212 ⫾ 61
233 ⫾ 62
Data are expressed as mean ⫾ SD or as number (percentage). * p ⬍0.05 compared with normal group; † p ⬍0.05 compared with DUSH group;
ents of 53 ⫾ 30 and 29 ⫾ 17 mm Hg, respectively. There was no difference in pulmonary vein velocities among the 4 groups (not shown). As listed in Table 3 and shown in Figures 2 and 3, compared with the normal group, the DUSH, AS, and HC groups had significantly lower Ea and higher E/Ea. Furthermore, patients in the DUSH and AS groups had significantly higher Ea, Aa, and Sa and lower E/Ea compared with patients in the HC group. These relations were evident whether the annular velocities were measured at the lateral or septal wall or averaged from the 2 walls. There was no significant difference among the groups in the ratio of lateral to septal Ea, Aa, or Sa or in the ratio of septal, lateral, or averaged Ea to Aa (not shown). Univariate predictors of Ea, E/Ea, Aa, and Sa among all patients were clinical group, age, the use of  blockers and/or calcium channel blockers, maximal ventricular septal thickness, and left atrial dimension. In addition, a history of hypertension was a predictor of Ea. As listed in Table 4, in multiple regression analysis using these covariates, clinical group remained an independent predic-
‡
230 ⫾ 47
0.15
p ⬍0.05 compared with AS group.
tor of the mitral annular indexes. Beta-blocker or calcium channel blocker use was an independent predictor of E/Ea, Aa, and Sa but not of Ea. Several echocardiographic indexes were identified by univariate analysis to distinguish HC from DUSH: the ratio of maximal to midventricular septal thickness, the LV ejection fraction, left atrial dimension, averaged E/Ea, and averaged Sa. In multivariate logistic regression analysis, averaged E/Ea (odds ratio 1.3, coefficient 0.24, p ⬍0.01), left atrial dimension (odds ratio 1.2, coefficient 0.21, p ⫽ 0.02), and the ratio of maximal to midventricular septal thickness (odds ratio 0.01, coefficient ⫺4.72, p ⬍0.01) remained independent predictors of HC. Receiver-operating characteristic curve analysis identified an optimal cut point of averaged E/Ea ⱖ13 to differentiate HC from DUSH (78% sensitivity, 90% specificity, 90% positive predictive value, 81% negative predictive value, area under the curve 0.89). The mean laboratory reproducibility for tissue Doppler indexes was 0.99, as assessed using the intraclass correlation coefficient.
Miscellaneous/Tissue Doppler in DUSH
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Table 3 Tissue Doppler mitral annular velocities of patient groups Variable Ea (cm/s) Lateral Septal Averaged E/Ea Lateral Septal Averaged Aa (cm/s) Lateral Septal Averaged Sa (cm/s) Lateral Septal Averaged
normal (n ⫽ 25)
DUSH (n ⫽ 33)
AS (n ⫽ 23)
HC (n ⫽ 34)
p value (ANOVA)
10.3 ⫾ 2.1 8.2 ⫾ 2.0 9.3 ⫾ 1.9
8.1 ⫾ 2.4* 6.4 ⫾ 1.9* 7.1 ⫾ 1.8*
7.7 ⫾ 1.8* 6.5 ⫾ 2.0* 7.1 ⫾ 1.7*
6.2 ⫾ 2.0*,†,‡ 4.6 ⫾ 11*,†,‡ 5.4 ⫾ 1.3*,†,‡
⬍0.001 ⬍0.001 ⬍0.001
6.3 ⫾ 1.1 8.0 ⫾ 1.9 7.1 ⫾ 1.6
9.0 ⫾ 3.2* 11.1 ⫾ 3.4* 10.0 ⫾ 3.1*
10.1 ⫾ 2.9* 12.6 ⫾ 4.4* 11.3 ⫾ 2.8*
16.3 ⫾ 6.9*,†,‡ 21.5 ⫾ 9.3*,†,‡ 18.8 ⫾ 7.5*,†,‡
⬍0.001 ⬍0.001 ⬍0.001
10.6 ⫾ 2.6 10.4 ⫾ 2.4 10.7 ⫾ 2.3
11.0 ⫾ 2.9 10.2 ⫾ 2.2 10.9 ⫾ 2.9
10.4 ⫾ 1.8 9.3 ⫾ 2.1 9.8 ⫾ 1.5
8.6 ⫾ 3.6*,†,‡ 7.6 ⫾ 2.9*,†,‡ 8.1 ⫾ 3.1*,†,‡
0.006 ⬍0.001 ⬍0.001
9.0 ⫾ 2.0 7.7 ⫾ 1.7 8.6 ⫾ 1.7
8.2 ⫾ 2.5 7.1 ⫾ 1.7 7.9 ⫾ 2.2
8.1 ⫾ 2.0 7.0 ⫾ 1.1 7.6 ⫾ 1.4
6.7 ⫾ 2.3*,†,‡ 6.1 ⫾ 1.6*,†,‡ 6.4 ⫾ 1.7*,†,‡
⬍0.001 0.003 ⬍0.001
Data are expressed as mean ⫾ SD. * p ⬍0.05 compared with normal group; † p ⬍0.05 compared with DUSH group;
Figure 2. Averaged Ea velocity in the normal, DUSH, AS, and HC groups. Mean values and SDs are indicated. *p ⬍0.05 compared with normal group; †p ⬍0.05 compared with DUSH group; ‡p ⬍0.05 compared with AS group.
Discussion To our knowledge, our study was the first to apply tissue Doppler imaging to characterize myocardial function in DUSH and delineate the physiologic implications of this well-recognized but poorly understood echocardiographic finding. We found that Ea was lower and E/Ea higher in patients with DUSH compared with normal patients and similar to values in older patients with AS. We also found that mitral annular velocities were helpful in differentiating between DUSH and HC. Although the degree of overlap in the values of Ea and E/Ea between the 2 groups may be too great to set a strict cut point, our study indicates that lower Ea and higher E/Ea, as well as higher left atrial dimension and lower maximal to midventricular septal thickness ratio, support a diagnosis of HC. In contrast to the study by Krasnow,4 we found that
‡
p ⬍0.05 compared with AS group.
Figure 3. Averaged E/Ea in the normal, DUSH, AS, and HC groups. Mean values and standard deviations are indicated. *p ⬍0.05 compared with normal group; †p ⬍0.05 compared with DUSH group; ‡p ⬍0.05 compared with AS group.
diastolic function is abnormal in patients with DUSH. This discrepancy is not surprising, given that the earlier study evaluated diastolic function using mitral inflow velocities, which may poorly detect diastolic abnormalities because of their greater load dependence and inability to differentiate between pseudonormal and normal patterns. Indeed, in another study, mitral inflow velocities were able to discriminate only 25% of patients with hypertensive LV hypertrophy from normal patients, compared with 91% using mitral annular velocities.9 Similarly, we did not detect any evidence of diastolic abnormalities by mitral inflow or pulmonary venous patterns. Chronic pressure overload from hypertension may largely explain the decreased Ea and increased E/Ea observed in the patients with DUSH. Eighty-five percent of the patients with DUSH had a diagnosis of hypertension, and
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Table 4 Independent predictors of mitral annular velocities averaged between the septal and lateral walls Variable Ea Clinical group Maximal ventricular septal thickness Age E/Ea  blocker or calcium channel blocker Clinical group Aa  blocker or calcium channel blocker Clinical group Sa  blocker or calcium channel blocker Clinical group Age
 Regression Coefficient
p Value
⫺0.67 ⫺0.13 ⫺0.06
⬍0.001 0.002 0.004
2.9 2.7
⬍0.001 ⬍0.001
⫺0.87 ⫺0.65
0.04 0.01
⫺0.66 ⫺0.44 ⫺0.04
0.02 0.01 0.03
79% were taking at least 1 antihypertensive medication. A recent study demonstrated that mitral annular velocities are decreased in hypertensive patients even if they do not have LV hypertrophy.10 It is unknown whether any of the patients in this study had a typical DUSH pattern. The decrease in velocities in the lateral and septal walls suggests a global rather than regional abnormality in patients with DUSH, despite the focal morphologic finding. In patients with hypertension, LV hypertrophy usually develops concentrically as a compensatory response to normalize wall stress, although asymmetric hypertrophy has also been reported.11 Some patients may develop a DUSH pattern of hypertrophy in response to pressure overload for genetic, hemodynamic, or geometric reasons. This is supported by the observation that the values of Ea and E/Ea were similar between the patients with DUSH and those with AS, who are exposed to chronic pressure overload. Because tissue Doppler mitral annular velocities have prognostic value in patients with systemic hypertension and LV hypertrophy,12 our results suggest that further investigation is warranted to elucidate the clinical significance of abnormal Ea velocities in DUSH. Although Sa predicted clinical group in univariate analysis, it did not remain an independent predictor in multivariate analysis including age and the use of  blockers and calcium channel blockers as covariates. This is in contrast to the findings of Vinereanu et al13 that Sa could discriminate between pathologic and physiologic hypertrophy and of Kato et al14 that systolic strain could discriminate between HC and hypertensive LV hypertrophy. Our patients were much older than those in the earlier studies. Longitudinal myocardial function decreases with age,15,16 and perhaps Sa is more affected than Ea by age. In addition, in the earlier studies,  blockers and calcium channel blockers were discontinued before echocardiography, reducing their inhibitory effects on annular velocities.17 In our study, patients remained on their usual medications, and these may have masked the influence of DUSH, AS, or HC on Sa. Our findings may imply that Ea and E/Ea are less influenced by these medications and nevertheless remain clinically rele-
vant, because most patients do not discontinue medications before they undergo routine echocardiography. The main limitation of our study was our reliance on clinical and echocardiographic, rather than histologic or genetic, criteria to confirm the diagnosis of HC. We cannot exclude the possibility that some patients with DUSH in fact had milder or earlier forms of obstructive HC. To be confident in our clinical assignment of patients to the HC and DUSH groups, our inclusion criteria were stringent. By focusing our analysis on patients with or without “classic” features of obstructive HC, we identified echocardiographic parameters for differentiation between DUSH and obstructive HC in an idealized setting. In addition, it was impossible to maintain complete blinding to the patients’ clinical diagnoses during echocardiographic analysis given the characteristic findings. We excluded patients who fell into ⬎1 clinical category, a situation that would certainly complicate the interpretation of the echocardiographic indexes. Finally, we did not specifically investigate the relation between LV mass and the tissue Doppler indexes. It is well established that LV mass is inversely related to longitudinal myocardial function. However, we would expect the absolute increase in LV mass due to DUSH to be quite modest: the area of hypertrophy in DUSH is generally ⬍3 cm of the basal anterior septum,4 and the posterior wall and distal septal thicknesses were in the normal range in our DUSH group. Furthermore, commonly used formulas to estimate LV mass are based on geometric assumptions of LV shape and would have limited accuracy in the context of a focal septal irregularity. The accurate measurement of LV mass would best be performed with 3-dimensional echocardiography or magnetic resonance imaging and would be of future interest. 1. Goor D, Lillehei CW, Edwards JE. The “sigmoid septum.” Variation in the contour of the left ventricular outflow tract. Am J Roentgenol Radium Ther Nucl Med 1969;107:366 –376. 2. Shapiro LM, Howat AP, Crean PA, Westgate CJ. An echocardiographic study of localized subaortic hypertrophy. Eur Heart J 1986; 7:127–32. 3. Belenkie I, MacDonald RP, Smith ER. Localized septal hypertrophy: part of the spectrum of hypertrophic cardiomyopathy or an incidental echocardiographic finding? Am Heart J 1988;115:385–90. 4. Krasnow N. Subaortic septal bulge simulates hypertrophic cardiomyopathy by angulation of the septum with age, independent of focal hypertrophy. An echocardiographic study. J Am Soc Echocardiogr 1997;10:545–555. 5. Feigenbaum H, Armstrong WF, Ryan T. Feigenbaum’s Echocardiography. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins, 2005. 6. Bruch C, Stypmann J, Grude M, Gradaus R, Breithardt G, Wichter T. Tissue Doppler imaging in patients with moderate to severe aortic valve stenosis: clinical usefulness and diagnostic accuracy. Am Heart J 2004;148:696 –702. 7. Giorgi D, Di Bello V, Talini E, Palagi C, Delle Donne MG, Nardi C, Verunelli F, Mariani MA, Di Cori A, Caravelli P, Mariani M. Myocardial function in severe aortic stenosis before and after aortic valve replacement: a Doppler tissue imaging study. J Am Soc Echocardiogr 2005;18:8 –14. 8. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440 –1463.
Miscellaneous/Tissue Doppler in DUSH 9. Di Bello V, Giorgi D, Pedrinelli R, Talini E, Palagi C, Delle Donne MG, Zucchelli G, Dell’omo G, Di Cori A, Dell’Anna R, et al. Left ventricular hypertrophy and its regression in essential arterial hypertension. A tissue Doppler imaging study. Am J Hypertens 2004;17: 882– 890. 10. Borges MC, Colombo RC, Goncalves JG, Ferreira Jde O, Franchini KG. Longitudinal mitral annulus velocities are reduced in hypertensive subjects with or without left ventricle hypertrophy. Hypertension 2006;47:854 – 860. 11. Shapiro LM, Kleinebenne A, McKenna WJ. The distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: comparison to athletes and hypertensives. Eur Heart J 1985;6:967–974. 12. Wang M, Yip GW, Wang AY, Zhang Y, Ho PY, Tse MK, Yu CM, Sanderson JE. Tissue Doppler imaging provides incremental prognostic value in patients with systemic hypertension and left ventricular hypertrophy. J Hypertens 2005;23:183–191. 13. Vinereanu D, Florescu N, Sculthorpe N, Tweddel AC, Stephens MR, Fraser AG. Differentiation between pathologic and physiologic left ventricular hypertrophy by tissue Doppler assessment of long-axis
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function in patients with hypertrophic cardiomyopathy or systemic hypertension and in athletes. Am J Cardiol 2001;88:53–58. Kato TS, Noda A, Izawa H, Yamada A, Obata K, Nagata K, Iwase M, Murohara T, Yokota M. Discrimination of nonobstructive hypertrophic cardiomyopathy from hypertensive left ventricular hypertrophy on the basis of strain rate imaging by tissue Doppler ultrasonography. Circulation 2004;110:3808 –3814. Nikitin NP, Witte KK, Thackray SD, de Silva R, Clark AL, Cleland JG. Longitudinal ventricular function: normal values of atrioventricular annular and myocardial velocities measured with quantitative twodimensional color Doppler tissue imaging. J Am Soc Echocardiogr 2003;16:906 –921. Tighe DA, Vinch CS, Hill JC, Meyer TE, Goldberg RJ, Aurigemma GP. Influence of age on assessment of diastolic function by Doppler tissue imaging. Am J Cardiol 2003;91:254 –257. Gorcsan J III, Strum DP, Mandarino WA, Gulati VK, Pinsky MR. Quantitative assessment of alterations in regional left ventricular contractility with color-coded tissue Doppler echocardiography. Comparison with sonomicrometry and pressure-volume relations. Circulation 1997;95:2423–2433.