Tissue Doppler imaging to predict clinical course of patients with hypertrophic cardiomyopathy
1 Department of Cardiology, Yeditepe University Hospital, Devlet yolu Ankara Cad No 102-104, 34752 Kozyatagi, Istanbul, Turkey
2 Department of Cardiology, Rize State Hospital, Rize, Turkey
3 Department of Cardiology, Kosuyolu Heart and Research Hospital, Istanbul, Turkey
Received 1 October 2007; accepted after revision 9 January 2008.
* Corresponding author. Tel: +90 216 5784240; fax: +90 216 5784963. E-mail address: dfatihbayrak{at}yahoo.com
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Abstract |
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Aims: Diastolic tissue Doppler (TD) parameters allow prediction of patients with hypertrophic cardiomyopathy (HC) at risk of sudden death, ventricular tachycardia, or cardiac arrest. The aim of this study was to assess the value of TD imaging in predicting the clinical course of patients with HC.
Methods and results: Eighty-six HC patients were prospectively included in the study and followed-up for clinical endpoints (cardiovascular death or hospitalization due to worsening of heart failure symptoms). Patients with clinical endpoints (n = 25) had larger left atrium diameters, thicker left ventricle (LV) walls, more often LV outflow obstruction and lower TD velocities of LV. LV outflow tract obstruction (r=0.54, R²=0.29, P<0.03) and LV lateral mitral annular systolic tissue Doppler velocity (LMSa) (r=0.50, R²=0.25, P<0.0001) were found to be independent predictors for clinical endpoints in forward stepwise regression. The best value of LMSa with the highest sensitivity (75%) and specificity (88%) was 4 cm/s for predicting clinical endpoints. Patients with LMSa velocities > 4 cm/s were significantly free of clinical endpoints.
Conclusion: In conclusion, LMSa seems to be a reliable parameter that can be used in predicting the HC patients at risk for clinical deterioration or death at long-term follow-up.
Keywords: Hypertrophic cardiomyopathy; Tissue Doppler imaging; Clinical outcome
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Introduction |
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Hypertrophic cardiomyopathy (HC) is a complex genetic cardiac disorder with heterogeneous clinical course and expression.1–3 Although several factors have been associated with an unfavourable outcome, the identification of patients at risk for clinical deterioration remains a difficult clinical challenge, because there is no agreement on which factors or their combination are best to predict the high-risk patients. Besides, clinical deterioration can be observed in HC patients without any of these risk factors.1,2 So, new parameters for clinical follow-up of patients with HC are highly desirable.
Prognostic value of tissue Doppler (TD) is well known in systolic heart failure,4 ischaemic heart disease,5,6 and non-valvular atrial fibrillation.7 Diastolic TD parameters allow prediction of HC patients at risk of sudden death, ventricular tachycardia, or cardiac arrest.8,9 Besides risk of sudden death, heart failure related disability is also a major concern for HC patients.1 Thus, the aim of this study was to assess the value of TD imaging in predicting the clinical course of patients with HC.
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Methods |
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Study population
One hundred and eleven consecutive patients who were admitted to our echocardiography laboratory between January 2003 and December 2005 and diagnosed as HC were prospectively included in the study. The diagnosis of HC was based on the demonstration of a hypertrophied, non-dilated left ventricle (LV) (wall thickness of at least 15 mm) by two-dimensional echocardiography in the absence of another cardiac or systemic disease capable of producing a similar degree of hypertrophy.3 A detailed clinical evaluation and blood sampling for Nt-proBNP were obtained for each patient after the echocardiographic examination. Functional capacity was assessed according to the New York Heart Association (NYHA) classification by one investigator without the knowledge of the laboratory results. Age- and gender-matched 40 healthy subjects were also studied as control group. Twenty patients with co-morbid cardiovascular, pulmonary, or renal conditions and five patients with apical hypertrophy were excluded from the study and the remaining 86 patients were followed-up. The study complies with the Declaration of Helsinki, was approved by the local ethical committee and each patient gave written informed consent.
Echocardiographic analysis
A complete echocardiographic examination was performed with a Vivid Five System (GE, Vingmed Ultrasound, Horten, Norway) in each patient at rest by a single-blinded observer. LV hypertrophy was assessed with two-dimensional echocardiography according to published criteria.3 The greatest thickness measured at any site in the LV wall was considered to represent LV maximal wall thickness.10 Peak instantaneous LV outflow gradient was estimated under basal conditions with continuous wave Doppler.11
Two-dimensional measurements included LV end-diastolic and end-systolic diameters, posterior wall thickness, interventricular septal thickness, and LV ejection fraction.12 Mitral inflow Doppler was measured in standard fashion to determine peak E- and A-wave velocities, deceleration time of the transmitral E wave, and isovolumic relaxation time.13 Apical four-chamber views of colour two-dimensional TD images were acquired during end-expiration at a frame rate of 100–140 frames per second to minimize background noise. TD digital data were stored and analysed offline (EchoPac, GE Vingmed). Sample volumes were placed in the inner half of the myocardium on the basal segments of the left ventricle at the septal, lateral walls and of the right ventricle at the lateral wall adjacent to the atrio-ventricular valve hinge points in the apical four-chamber view. Systolic (Sa), early diastolic (Ea), and late diastolic (Aa) TD velocities were measured and subsequently averaged over three cardiac cycles in accordance with previous reports.13,14 Transmitral E/Ea ratios of LV (lateral and septal) were calculated for each patient.
Statistical analysis
Statistical analysis was performed with SPSS 11.5 (SPSS, Chicago, IL, USA) software. Data are expressed as mean ± SD. Relevant relationships were tested by 
2 analysis for proportions and unpaired Student’s t-test for continuous variables. The statistical relationship between TD parameters and other relevant demographic and echocardiographic variables were examined by Spearman’s correlation and t-tests. Statistical significance was taken as P < 0.05. Forward stepwise regression was performed to determine predictors of the clinical endpoints. A probability value < 0.05 was required for retention within the final stepwise regression model. Inter-observer and intra-observer reproducibility were evaluated by means of the interclass correlation coefficient.
Follow-up and study endpoints
After inclusion, patients were prospectively followed with respect to clinical endpoints. Information at follow-up was obtained by personal or telephone contact with patients or relatives by an investigator blinded to laboratory results and clinical findings. The clinical endpoints were defined as a composite of cardiovascular death (sudden death, death due to worsening heart failure, and cerebrovascular accident), or hospitalization due to worsening of heart failure symptoms (progression to NYHA Class III or IV).
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Results |
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Patient characteristics
Eighty-six patients with HC were compared with 40 age- and gender-matched controls. The pattern of LV hypertrophy was asymmetric septal in 80 patients, concentric in 5 patients, and isolated posterior wall hypertrophy in 1 patient. Forty-three patients (50%) had basal resting left ventricular outflow tract obstruction with a peak gradient >30 mmHg. Thirty patients had a positive family history of HC (36%) and 18 patients had a history of sudden death in first degree relatives (22%). Seventy patients (85%) were treated with β-blockers and 10 (12%) with calcium channel blockers. At admission, 32 (37%) of the total patients were asymptomatic (NYHA class I), 37 (43%) patients had NYHA class II symptoms, and the remaining 17 (19%) patients had severe symptoms. Mean plasma Nt-proBNP level of the patients was 2006 ± 4256 pg/mL (range: 17–32 827 pg/mL).
The comparison of demographic, echocardiographic, and TD variables of HC patients and the control subjects are presented in Table 1. As expected, HC patients had smaller LV cavities, thicker interventricular septal and LV posterior walls, increased LV ejection fractions and longer E wave deceleration and isovolumetric relaxation times than controls. There were significant reductions in all TD velocities except lateral tricuspid late diastolic velocity in HCM patients when compared with controls. The comparison of TD profiles of HC patients with and without LV outflow obstruction and a control subject are demonstrated in Figure 1.
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Effect of LV outflow obstruction on echocardiographic and TD variables
HC patients with LV outflow obstruction had significantly smaller left ventricle cavities, thicker posterior walls, larger left atrium diameters, and longer deceleration times than patients without obstruction. TD velocities of left and right ventricle (except lateral mitral Ea) tended to be lower in HC patients with LV outflow obstruction when compared with patients without obstruction, but that did not reach statistical significance.
Predictors of clinical endpoints
Mean follow-up period was 589 ± 365 days (range 31–1142 days). Of the 25 patients (29%) with a clinical endpoint, 3 died of sudden death, 22 were hospitalized due to worsening of heart failure symptoms (10 patients with baseline NYHA Class II and 12 with baseline NYHA Class III were hospitalized due to worsening heart failure).
Table 2 presents the comparison of echocardiographic parameters including TD velocities of patients with and without clinical endpoints. Patients with clinical endpoints had larger left atrium diameters, thicker LV walls, more often LV outflow obstruction, and lower TD velocities of LV when compared with patients without clinical endpoints. Medical therapies of the patients with and without clinical endpoints were similar.
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Table 3 shows the results of univariate and multivariable analyses for clinical endpoints. LV outflow obstruction (r = 0.54, R2 = 0.29, P < 0.03) and LV lateral mitral annular systolic tissue Doppler velocity (LMSa) (r = 0.50, R2 = 0.25, P < 0.0001) were found to be the independent predictors for clinical endpoints in forward stepwise regression.
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Intra-observer reproducibility with interclass coefficient was 0.93, and inter-observer reproducibility was 0.94 for LMSa.
LMSa correlated with various echocardiograpic and clinical parameters such as left atrium diameter (P = 0.004, R: –0.30), maximal wall thickness (P = 0.001, R: –0.36), posterior wall diastolic thickness (P = 0.0001, R: –0.41), ejection fraction (P = 0.01, R: 0.27), NYHA functional class (P = 0.001, R: –0.36), and plasma Nt-proBNP level (P = 0.0001, R: –0.46).
We also compared TD variables of patients with and without LV lateral wall hypertrophy. Patients with lateral wall hypertrophy had significantly lower systolic and diastolic lateral mitral annular TD velocities (for LMSa; 4.5 ± 1.9 vs. 2.8 ± 1.5 cm/s, P = 0.009, for lateral mitral Ea; 4.5 ± 2.3 vs. 2.0 ± 1.5 cm/s, P = 0.001, for lateral mitral Aa; 5.3 ± 2.8 vs. 3.0 ± 2.8 cm/s, P = 0.04).
We examined the sensitivity and specificity of various cut-off values of LMSa for predicting clinical endpoints and created receiver operating characteristic curves. The best value of LMSa with the highest sensitivity (75%) and specificity (88%) was 4 cm/s. Patients with LMSa velocities >4 cm/s were significantly free of clinical endpoints (Figure 2).
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Discussion |
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In the present study, we found that HC is associated with a prominent decrease in both systolic and diastolic annular tissue Doppler velocities of left ventricle and right ventricle when compared with healthy controls. Our findings were in agreement with the results of Cardim et al.15 and Tabata et al.16 who reported reduced systolic velocities, and Severino et al.17 who reported reduced long-axis diastolic velocities in patients with HC.
In addition, we have shown that LV lateral annular systolic tissue Doppler velocity (LMSa) and LV outflow obstruction independently predict clinical course of HC patients. Patients with baseline LMSa <4 cm/s had an increased risk of clinical deterioration in the following 3 years (Figure 2). That was an interesting finding because lateral LV walls of the included patients were not hypertrophied except five patients with concentric hypertrophy. It has been shown in previous studies that the regional systolic and diastolic functions are abnormal in hypertrophied and also in non-hypertrophied segments,18,19 and even in patients who have a mutation for HC but have not yet developed clear phenotypic changes.13 It is also known that cellular disarray is observed in segments without hypertrophy such as LV and right ventricular free walls.20 Myocardial disarray might result in a reduction of myocardial function and the degree of involvement of non-hypertrophied segments might reflect the severity of the disease course, but there are not enough data to support this hypothesis.
Although tissue Doppler velocities of lateral LV myocardium were significantly lower in HC patients with lateral wall hypertrophy in our study, LMSa remained as an independent predictor of clinical outcome irrespective of the presence of lateral wall hypertrophy. As a result, the decrease in LMSa may be explained with progressive remodelling and/or fibrosis of non-hypertrophied segments over time and may be of value as a predictor of impending heart failure symptoms.
In the present study, LMSa correlated with a number of echocardiographic and clinical parameters of prognostic significance including left atrium diameter,21,22 maximal wall thickness,11 NYHA functional class, and plasma Nt-proBNP level.23 These findings also support the value of LMSa in predicting the clinical course of HC patients.
TD data on HC population concerning clinical outcome (cardiovascular death and heart failure related hospitalization) is insufficient to date. Prognostic value of TD imaging is demonstrated in systolic heart failure,4 ischaemic heart disease,5,6 and non-valvular atrial fibrillation.7 TD has been shown to predict gene mutations underlying HCM, estimate left atrial filling pressure, correlate response to specific therapies in HC patients,13,24,25 and has been shown to be of value in discrimination of HC from hypertensive LV hypertrophy14,26 and athlete heart.27,28 Diastolic TD parameters predict risk of sudden death, ventricular tachycardia, or cardiac arrest in patients with HC.8,9 McMahon et al.8 have reported that transmitral E/septal Ea ratio predicts children with HC who are at risk of death, cardiac arrest, and ventricular tachycardia. Efthimiadis et al.9 have reported that septal E/Ea>15 is a predictor of adverse outcome including sustained ventricular tachycardia, cardiac arrest, ICD discharge, and sudden death in adult patients with HC. In our study, lateral mitral and septal E/Ea ratios were significantly higher in patients with clinical endpoints (Table 2), but they were not found to be independent predictors of clinical course. Differences between endpoints of these studies and ours may be the explanation for these findings. Our clinical endpoints were softer, mainly including heart failure related disability and hospitalization. Decrease in systolic TD parameters (LMSa in our study) might be a marker of occult systolic dysfunction and may be more important in respect of heart failure related disability and hospitalization when compared with diastolic TD parameters, but these data are to be validated with larger scale trials.
The study was conducted at a tertiary referral cardiac hospital; as a result most of the included HC patients were symptomatic. The high values of E/Ea ratio (both septal and lateral) even in patients who were clinically stable during follow-up might be explained with the high prevalence of heart failure symptoms (57%) and LV outflow tract obstruction (50%) in our study population.
We did not observe statistically significant differences in systolic and diastolic TD velocities of left and right ventricle (except lateral mitral Ea) between HC patients with and without LV outflow obstruction. These findings were in accordance with previously published studies.29,30
Because of the low rate of sudden death in HC, the contribution of tissue Doppler parameters to risk stratification of sudden death remains limited. As the vast majority of the clinical endpoints were heart failure related hospitalization, it should be emphasized that the present study is not a survival study. It might also be of value to examine how tissue Doppler parameters would be affected by the subsequent treatment, including medical and interventional therapies. Colour-coded tissue Doppler and post process analysis was a limitation of our study, as tracking of sample volume errors might be less in spectral tissue Doppler analysis, but we tried to minimize tracking errors by using a relatively large sample volume.
In conclusion, LMSa seems to be a reliable parameter that can be used in predicting the HC patients at risk for clinical deterioration or death at long-term follow-up. Measurement of LMSa might find a place in the routine clinical follow-up of patients with HC.
Conflict of interest: none declared.
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- Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, et al. ACC/ESC Clinical expert document on hypertophic cardiomyopathy: a report of American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol (2003) 42:1687–713.
[Free Full Text] - Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA (2002) 287:1308–20.
[Abstract/Free Full Text] - Klues HG, Schiffers A, Maron BJ. Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two dimensional echocardiography in 600 patients. J Am Coll Cardiol (1995) 26:1699–708.[Abstract]
- Willenheimer R, Cline C, Erhardt L, Israelsson B. Left ventricular atrioventricular plane displacement: an echocardiographic technique for rapid assessment of prognosis in heart failure. Heart (1997) 78:230–6.
[Abstract/Free Full Text] - Hillis GS, Moller JE, Pellikka PA, Gersh BJ, Wright RS, Ommen SR, et al. Noninvasive estimation of left ventricular filling pressure by E/e' is a powerful predictor of survival after acute myocardial infarction. J Am Coll Cardiol (2004) 43:360–7.
[Abstract/Free Full Text] - Dokainish H, Abbey H, Gin K, Ramanathan K, Lee PK, Jue J. Usefulness of tissue Doppler imaging in the diagnosis and prognosis of acute right ventricular infarction with inferior wall acute left ventricular infarction. Am J Cardiol (2005) 95:1039–42.[CrossRef][Web of Science][Medline]
- Okura H, Takada Y, Kubo T, Iwata K, Mizoguchi S, Taguchi H, et al. Tissue Doppler-derived index of left ventricular filling pressure, E/E', predicts survival of patients with non-valvular atrial fibrillation. Heart (2006) 92:1248–52.
[Abstract/Free Full Text] - McMahon CJ, Nagueh SF, Pignatelli RH, Denfield SW, Dreyer WJ, Price JF, et al. Characterization of left ventricular diastolic function by tissue Doppler imaging and clinical status in children with hypertrophic cardiomyopathy. Circulation (2004) 109:1756–62.
[Abstract/Free Full Text] - Efthimiadis GK, Giannakoulas G, Parcharidou DG, Karvounis HI, Mochlas ST, Styliadis IH, et al. Clinical significance of tissue Doppler imaging in patients with hypertrophic cardiomyopathy. Circ J (2007) 71:897–903.[CrossRef][Medline]
- Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy predicts the risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med (2000) 342:1778–85.
[Abstract/Free Full Text] - Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med (2003) 348:295–303.
[Abstract/Free Full Text] - Ikeda H, Maki S, Yoshida N, Murohara T, Adachi H, Koga Y, et al. Predictors of death from congestive cardiac failure in hypertrophic cardiomyopathy. Am J Cardiol (1999) 83:1280–3.[CrossRef][Web of Science][Medline]
- Nagueh SF, Bachinski LL, Meyer D, Hill R, Zoghbi WA, Tam JW, et al. Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy. Circulation (2001) 104:128–30.
[Abstract/Free Full Text] - Kato TS, Noda A, Izawa H, Yamada A, Obata K, Nagata K, et al. Discrimination of nonobstructive hypertrophic cardiomyopathy from hypertensive left ventricular hypertrophy on the basis of strain rate imaging by tissue Doppler ultrasonography. Circulation (2004) 110:3808–14.
[Abstract/Free Full Text] - Cardim N, Castela S, Cordeiro R, Longo S, Ferreira T, Pereira A, et al. Tissue Doppler imaging assessment of long axis left ventricular function in hypertrophic cardiomyopathy. Rev Port Cardiol (2002) 21:953–85.[Medline]
- Tabata T, Oki T, Yamada H, Abe M, Onose Y, Thomas JD. Subendocardial motion in hypertrophic cardiomyopathy: assessment from long and short-axis views by pulsed tissue Doppler imaging. J Am Soc Echocardiogr (2000) 13:108–15.[Web of Science][Medline]
- Severino S, Caso P, Galderisi M, De Simone L, Petrocelli A, de Divitiis O, et al. Use of pulsed Doppler tissue imaging to assess regional left ventricular diastolic dysfunction in hypertrophic cardiomyopathy. Am J Cardiol (1998) 82:1394–8.[CrossRef][Web of Science][Medline]
- Cardim N, Oliveira AG, Longo S, Ferreira T, Pereira A, Reis RP, et al. Doppler tissue imaging: regional myocardial function in hypertrophic cardiomyopathy and in athlete’s heart. J Am Soc Echocardiogr (2003) 16:223–32.[CrossRef][Web of Science][Medline]
- Cardim N, Cordeiro R, Correia MJ, Gomes E, Longo S, Ferreira T, et al. Tissue Doppler imaging and long axis left ventricular function: hypertrophic cardiomyopathy versus athlete’s heart. Rev Port Cardiol (2002) 21:679–707.[Medline]
- Kuribayashi T, Roberts WC. Myocardial disarray at junction of ventricular septum and left and right ventricular free walls in hypertrophic cardiomyopathy. Am J Cardiol (1992) 70:1333–40.[CrossRef][Web of Science][Medline]
- Nistri S, Olivotto I, Betocchi S, Losi MA, Valsecchi G, Pinamonti B, et al, on behalf Participating Centers. Prognostic significance of left atrial size in patients with hypertrophic cardiomyopathy (from the Italian Registry for Hypertrophic Cardiomyopathy). Am J Cardiol (2006) 98:960–5.[CrossRef][Web of Science][Medline]
- Yang H, Woo A, Monakier D, Jamorski M, Fedwick K, Wigle ED, et al. Enlarged left atrial volume in hypertrophic cardiomyopathy: a marker for disease severity. J Am Soc Echocardiogr (2005) 18:1074–82.[CrossRef][Web of Science][Medline]
- Mutlu B, Bayrak F, Kahveci G, Degertekin M, Eroglu E, Basaran Y. Usefulness of N-terminal pro-B-type natriuretic peptide to predict clinical course in patients with hypertrophic cardiomyopathy. Am J Cardiol (2006) 98:1504–6.[CrossRef][Web of Science][Medline]
- Nagueh SF, Lakkis NM, Middleton KJ, Spencer WH 3rd, Zoghbi WA, Quinones MA. Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy. Circulation (1999) 99:254–61.
[Abstract/Free Full Text] - Nagueh SF, Kopelen HA, Lim DS, Zoghbi WA, Quinones MA, Roberts R, et al. Tissue Doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation (2000) 102:1346–50.
[Abstract/Free Full Text] - Cardim N, Longo S, Ferreira T, Pereira A, Gouveia A, Reis RP, et al. Tissue Doppler imaging assessment of long axis left ventricular function in hypertensive patients with concentric left ventricular hypertrophy: differential diagnosis with hypertrophic cardiomyopathy. Rev Port Cardiol (2002) 21:709–40.[Medline]
- Palka P, Lange A, Fleming AD, Donnelly JE, Dutka DP, Starkey IR, et al. Differences in myocardial velocity gradient measured throughout the cardiac cycle in patients with hypertrophic cardiomyopathy, athletes and patients with left ventricular hypertrophy due to hypertension. J Am Coll Cardiol (1997) 30:760–8.[Abstract]
- 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 function in patients with hypertrophic cardiomyopathy or systemic hypertension and in athletes. Am J Cardiol (2001) 88:53–8.[CrossRef][Web of Science][Medline]
- Cardim N, Torres D, Morais H, Candido A, Duarte R, Longo S, et al. Tissue Doppler imaging in hypertrophic cardiomyopathy: impact of intraventricular obstruction on longitudinal left ventricular function. Rev Port Cardiol (2002) 21:271–97.[Medline]
- Barac I, Upadya S, Pilchik R, Winson G, Passick M, Chaudhry FA, et al. Effect of obstruction on longitudinal left ventricular shortening in hypertrophic cardiomyopathy. J Am Coll Cardiol (2007) 49:1203–11.
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