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European Journal of Heart Failure 2005 7(5):820-828; doi:10.1016/j.ejheart.2005.02.003
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© 2005 European Society of Cardiology

"Pure" diastolic dysfunction is associated with long-axis systolic dysfunction. Implications for the diagnosis and classification of heart failure

Dragos Vinereanu, Eleftherios Nicolaides, Ann C. Tweddel and Alan G. Fraser*

Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom

* Corresponding author. Tel.: +44 2920 743489; fax: +44 2920 743500. E-mail address:fraserag{at}cf.ac.uk


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Aims: To investigate regional systolic function of the left ventricle, to test the hypothesis that "pure" diastolic dysfunction (impaired global diastolic filling, with a preserved ejection fraction ≥50%) is associated with longitudinal systolic dysfunction.

Methods and results: One hundred thirty subjects (31 patients with asymptomatic diastolic dysfunction, 30 with diastolic heart failure, 30 with systolic heart failure; and 39 age-matched normal volunteers) were studied by conventional and tissue Doppler echocardiography. Global diastolic function was assessed using the flow propagation velocity, and by estimating left ventricular filling pressure from the ratio of transmitral E and mitral annular ETDE velocities (E/ETDE); and global systolic function by measurement of ejection fraction. Radial and longitudinal functions were assessed separately from posterior wall and mitral annular velocities. Global and radial systolic function were similar in patients with "pure" diastolic dysfunction and normal subjects, but patients with either asymptomatic diastolic dysfunction or diastolic heart failure had impaired longitudinal systolic function (mean velocities: 8.0±1.2 and 7.7±1.5 cm/s, respectively, versus 10.1±1.5 cm/s in controls; p<0.001). In subjects with normal ejection fraction, global diastolic function correlated with longitudinal systolic function (r=0.56 for flow propagation velocity, and r=–0.53 for E/ETDE ratio, both p<0.001), but not with global systolic function.

Conclusion: Worsening global diastolic dysfunction of the left ventricle is associated with a progressive decline in longitudinal systolic function. Diastolic heart failure as conventionally diagnosed is associated with regional, subendocardial systolic dysfunction that can be revealed by tissue Doppler of long-axis shortening. Diagnostic algorithms and definitions of heart failure need to be revised.

Key Words: Diastolic heart failure • Tissue Doppler echocardiography • Cardiac function

Received July 20, 2004; Revised January 2, 2005; Accepted February 3, 2005


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Patients with symptoms and clinical signs of heart failure but with apparently normal global systolic function of the left ventricle on echocardiography are described as having diastolic heart failure caused by pure diastolic dysfunction. They constitute an important clinical group, which accounts for 40–50% of cases of heart failure, especially in the elderly [1–4]. In addition, asymptomatic diastolic dysfunction is reported to be present in 40–60% of those patients with coronary artery disease, hypertension, valvular heart disease, hypertrophic cardiomyopathy, diabetes, or cardiac amyloidosis, who develop heart failure [5,6].

Diagnosis of diastolic heart failure can be difficult because published guidelines are complex, and thus mechanisms of disease and optimal methods of treatment remain controversial [5,6]. Better understanding of the early stages of diastolic dysfunction and simple clear diagnostic tests are needed.

Using standard echocardiograpic methods, diastolic dysfunction is usually diagnosed as the cause of dyspnoea when Doppler assessment of transmitral flow is abnormal and left ventricular ejection fraction is normal. Transmitral flow reflects global filling and it becomes abnormal (E/A<1) only when more than 50% of ventricular segments have impaired relaxation, so it is insensitive to less extensive diastolic dysfunction [7]. Ejection fraction may be measured accurately by planimetry of left ventricular end-diastolic and end-systolic areas, but it reflects only global function; furthermore, ejection fraction derived by the Teichholz method, which is calculated by making simplistic geometric assumptions, measures only radial left ventricular systolic function [8]. Current guidelines include no assessment of regional longitudinal left ventricular function, yet this is the most sensitive marker of early changes in systolic function with age or disease [9–11]. Longitudinal descent of the mitral annulus towards the apex in systole is governed by the subendocardial fibres [12], which are most vulnerable to ischemia [13] and most affected by interstitial fibrosis [14].

In this study we investigated the relationships between early changes in systolic function and abnormalities of ventricular filling, in order to test the hypothesis that patients with "pure" diastolic dysfunction also have impaired longitudinal systolic function. If this is true, then it might be possible to diagnose subclinical changes and early disease in patients at risk of heart failure, and to monitor changes more effectively during treatment designed to influence the natural history of heart failure.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Subjects
In a cross-sectional study, 91 patients from a total of 129 undergoing echocardiographic studies performed in a specialist outpatient clinic, fulfilled the criteria for diastolic or systolic dysfunction. Diagnosis of diastolic dysfunction was based on the echocardiographic criteria published by the European Study Group on Diastolic Heart Failure [5]. Diagnosis of systolic dysfunction was based on an impaired ejection fraction (<50%), as recommended by Vasan et al. [6].

Underlying diagnoses in the patients are presented in Table 2. Patients were excluded if they were not in sinus rhythm, or if they had ventricular aneurysm or severe regional wall motion abnormalities, mitral or aortic stenosis, obstructive (intraventricular gradient>30 mm Hg) hypertrophic cardiomyopathy, more than mild aortic regurgitation, severe mitral regurgitation, pericardial disease, cor pulmonale, or severe renal or hepatic failure.

We defined 31 patients to have "asymptomatic diastolic dysfunction" because they had no signs or symptoms of congestive heart failure, but they did have echocardiographic criteria of diastolic dysfunction and a normal ejection fraction (Table 1). Another 30 patients were defined to have "diastolic heart failure" because they had signs or symptoms of congestive heart failure (dyspnoea, gallop sounds, and/or lung crepitations) [5], with echocardiographic criteria of diastolic dysfunction and a normal ejection fraction (Table 1). Finally, 30 patients had "systolic heart failure" based on symptoms and an impaired ejection fraction. The 91 patients were compared with 39 healthy volunteers matched for age.


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  		Table 1 Echocardiographic criteria for diastolic dysfunction in patients with normal systolic function

 
Normal subjects had no cardiovascular symptoms and no history of heart disease, diabetes mellitus or hypercholesterolemia. They all had a normal resting electrocardiogram and a normal transthoracic echocardiographic study.

The protocol was approved by the Local Research Ethics Committee, and each subject gave informed consent.

2.2. Echocardiography
Subjects were studied by one echocardiographer (D.V.), by conventional and tissue Doppler echocardiography (Vingmed System 5, GE Vingmed, Horten, Norway), using a 1.5–2.5 MHz transducer. Heart rate and blood pressure were measured after 15 min of rest, just before the echocardiographic study. The electrocardiogram was recorded simultaneously. Digital echocardiographic data containing a minimum of 3 consecutive beats were acquired during passively held end-expiration and transferred to a Macintosh computer for measurement. All measurements were taken as the mean of 3 consecutive beats.

Standard echocardiographic studies consisted of M-mode, cross-sectional, and Doppler blood flow measurements. M-mode tracings from the parasternal long-axis view were used to measure diameter of the aortic root, diameter of the left atrium, and end-diastolic diameter of the right ventricle; and septal thickness, left ventricular diameter, and posterior wall thickness in systole and diastole. Cross-sectional images were recorded from the apex for measurement of end-diastolic and end-systolic areas.

Pulsed-wave Doppler of transmitral flow was used to assess global diastolic function, with the sample volume placed at the tips of the mitral leaflets in the apical 4-chamber view. The following Doppler indices were measured: peak early velocity (E), peak atrial velocity (A), E-wave deceleration time, and atrial wave duration. Mitral E/A ratio was calculated. Isovolumic relaxation time was measured on the pulsed-wave Doppler trace recorded with the sample volume placed between mitral inflow and aortic outflow. Left ventricular inflow was also recorded by colour M-mode echocardiography in the apical 4-chamber view, and flow propagation velocity (FPV) was measured as the slope of the first aliasing velocity from the mitral tips to a position 4 cm distally into the left ventricle [15,16]. E/FPV ratio was calculated [16]. Pulmonary venous flow recordings were obtained from the apical 4-chamber view, with the sample volume placed 1 cm into the right upper pulmonary vein, and the following parameters were measured: peak systolic velocity (S), peak diastolic velocity (D), peak atrial velocity (A), and atrial wave duration.

Data analysis. Analysis was performed off-line for the calculation of left ventricular volumes, ejection fraction, end-systolic wall stress, and left ventricular mass. Left ventricular volumes and mass were indexed by body surface area.

Left ventricular volumes and ejection fraction were calculated by the modified biplane Simpson's method [17]. Fractional shortening and radial "ejection fraction" (using the Teichholz formula) were also calculated [8].

End-systolic wall stress (ESWS) in 103 dynes/cm2 was calculated according to the following validated formula:


Formula

where SBP is the systolic blood pressure (mm Hg) measured by a cuff sphygmomanometer, LVESD is the left ventricular end-systolic diameter, and LVSPW is the left ventricular end-systolic posterior wall thickness (cm) [18].

Left ventricular mass was estimated by the method of Devereux with the application of the Penn convention:


Formula

where IVSD is the septal thickness, LVDPW is the posterior wall thickness, and LVEDD is the left ventricular diameter, all measured at the end of diastole [19].

Long-axis function by tissue Doppler. To obtain recordings of mitral annular motion in the longitudinal axis, we used colour-guided pulsed wave tissue Doppler from the apical 4-chamber view for the lateral and medial sites, and from the apical 2-chamber view for the anterior and inferior sites. The pulsed sample volume was placed over the mitral annulus in systole. From the waveforms (Fig. 1) we measured the peak systolic velocity (S) during ejection, and the peak diastolic velocities during early filling (ETDE) and atrial contraction (ATDE). Four-site averaged velocities, and the ETDE/ATDE and E/ETDE ratios [20], were calculated.


Figure 1
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  		Fig. 1 Example of a tissue Doppler trace recorded from the lateral site of the mitral annulus. S—peak systolic velocity; E—early diastolic velocity; A—atrial velocity. Each division on the scale represents 1 cm/s.

 
Short-axis function by tissue Doppler. Pulsed-wave tissue Doppler of the basal posterior wall was recorded from the parasternal long-axis view. The sample volume was placed over the myocardium in systole, above the insertion of the papillary muscle.

2.3. Reproducibility
We have reported detailed studies of reproducibility in our laboratory elsewhere [11,21]. Ninety-five percent confidence limits of a single estimate of the measurements were calculated as 2SD/{surd}2, and reported as percent from the mean value [22]. Reproducibility of flow propagation velocity, E/FPV ratio, and E/ETDE ratio in our laboratory is <10%, similar with the values reported by other studies [15,16,20].

2.4. Statistical analysis
Statistical analysis was performed with SPSS software (version 10.0) (SPSS Chicago, Illinois). Results are presented as mean value±standard deviation. Differences between groups were tested for significance using analysis of variance (ANOVA), with subgroup analysis by the Scheffè F test. Comparisons of non-parametric data were performed by chi-square test. Linear regression was used to investigate the relation between two parametric variables. Multiple linear regression analysis was used to assess the influence of selected variables on parameters of global diastolic function. A p<0.05 for a two-tailed test was considered significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Subjects
General and standard echocardiographic characteristics of the study groups are given in Tables 2 and 3.


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  		Table 2 Clinical details of the patient groups

 


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  		Table 3 General and echocardiographic characteristics of the study groups

 
3.2. Radial and global systolic function
Radial or short-axis systolic function (fractional shortening, end-systolic wall stress, and ejection fraction by Teichholz method), and global systolic function (ejection fraction by Simpson's method), were not different between patients with either asymptomatic diastolic dysfunction or diastolic heart failure, and normal subjects (Table 3).

3.3. Long-axis systolic function by tissue Doppler
Patients with "pure" diastolic dysfunction had impaired longitudinal systolic function of the left ventricle. Their longitudinal systolic velocities were intermediate between those of normal subjects and those of patients with systolic heart failure (Table 4). With reference to normal ranges (defined as the mean±2SD of the value in age-matched controls), 16% of the patients with asymptomatic diastolic dysfunction, 34% of the patients with diastolic heart failure, and 90% of the patients with systolic heart failure had impaired longitudinal systolic function (defined as a 4-site mean velocity<7.05 cm/s). However, if we define the normal ranges as the mean±95% confidence intervals of the value in age-matched controls, 90% of the patients with asymptomatic diastolic dysfunction, 87% of the patients with diastolic heart failure, and all patients with systolic heart failure had impaired longitudinal systolic function (defined as a 4-site mean velocity<9.57 cm/s).


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  		Table 4 Myocardial velocities (cm/s) in the 4 groups

 
3.4. Short-axis systolic function by tissue Doppler
Radial left ventricular function was similar between patients with "pure" diastolic dysfunction and normal subjects, but significantly impaired in patients with systolic heart failure (Table 4).

3.5. Correlations between diastolic and systolic function
In the 100 subjects with normal ejection fraction, global diastolic function correlated with longitudinal systolic function (Fig. 2), but not with radial systolic function or ejection fraction (Fig. 3 and Table 5). By multiple stepwise regression (parameters entered: age, systolic and diastolic blood pressure, heart rate, body mass index, long-axis systolic velocity, radial systolic velocity, and global ejection fraction), the best correlation of E/ETDE ratio was with an association between long-axis systolic velocity and diastolic blood pressure (r=0.56, r2=0.32, p<0.001). For the whole group (i.e. including the patients with systolic heart failure), the correlations of longitudinal systolic function with global diastolic function were 0.66 for flow propagation velocity, –0.61 for E/FPV ratio, and –0.66 for E/ETDE ratio (both p<0.001). There was also a strong correlation (r=0.81, p<0.001) between longitudinal diastolic and systolic function, measured as 4-site mean velocities (Fig. 4).


Figure 2
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  		Fig. 2 Correlations between longitudinal systolic and global diastolic function for subjects with normal ejection fraction. FPV—flow propagation velocity; E/ETDE—ratio of mitral E velocity to lateral mitral annular ETDE velocity; S—4-site mean systolic velocity of the mitral annulus.

 


Figure 3
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  		Fig. 3 Correlations between global systolic and global diastolic function for subjects with normal ejection fraction. FPV—flow propagation velocity; E/ETDE—ratio of mitral E velocity to lateral mitral annular ETDE velocity; EF—ejection fraction.

 


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  		Table 5 Correlations (r) between diastolic and systolic function in 100 subjects with normal ejection fraction

 


Figure 4
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  		Fig. 4 Relation between 4-site mean systolic (S) and diastolic (ETDE) mitral annular velocities in the 4 study groups. bullet Normal subjects; {square} patients with asymptomatic diastolic dysfunction; {blacktriangleup} patients with diastolic heart failure; {bigtriangledown} patients with systolic heart failure.

 
3.6. Reproducibility
Interobserver variability was ±6.8% for the posterior wall velocities, and between ±2.0% and ±6.1% for the mitral annular velocities. Intraobserver variability was similar: ±2.7% for the posterior wall velocities, and between ±1.8% and ±2.5% for the mitral annular velocities [11,21].


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
We have demonstrated that patients who would be diagnosed to have "pure" diastolic dysfunction using current guidelines, in fact have reduced longitudinal systolic function. In these patients, normal global ejection fraction is maintained by preservation of radial systolic function. Our data suggest that "pure" diastolic dysfunction is therefore diagnosed erroneously, when systolic function is assessed by established echocardiographic techniques; these measure global function and short-axis (radial) function, but not long-axis function which is most sensitive for quantifying subendocardial disease. Tissue Doppler reveals the subtle and progressive changes that affect longitudinal systolic function.

4.1. Tissue Doppler for the diagnosis of subendocardial dysfunction
Functionally, there are two major myocardial layers of the left ventricle. Mid-wall fibres are orientated in a circumferential direction, and subendocardial fibres are aligned longitudinally from apex to base. The first group of fibres is responsible mainly for short-axis or radial contraction of the left ventricle (analogous to the motion of bellows), while the second group of fibres causes long-axis contraction (which can be compared with the motion of a piston) [12]. Longitudinal fibres are anatomically connected with the mitral annulus, and so long-axis contraction results in apical displacement of the mitral annulus in systole [23,24], which can be measured accurately in terms of velocities by pulsed-wave tissue Doppler echocardiography [25]. Since longitudinal, subendocardial function is more sensitive to ischemia and fibrosis, mitral annular velocities are decreased in the subclinical stages of heart failure, as has been shown in volume or pressure overload [10,11], as well as in ischaemic heart disease [26]. Subendocardial function and long-axis contraction also decrease with ageing [27–29].

In a large number of subjects with normal ejection fractions, we have shown that a decrease of subendocardial systolic function parallels the impairment of global diastolic function. The maintenance of ejection fraction in these patients must be achieved by a compensatory mechanism, which may be the preservation or augmentation of radial contraction in the early stages of left ventricular dysfunction [30].

To assess global diastolic function, we used new criteria that are not affected by pseudonormalization [31]. We found that 32% of variability in the E/ETDE ratio, a non-invasive indicator of left ventricular filling pressure [20], was related to longitudinal systolic velocity and diastolic blood pressure.

4.2. Does "pure" diastolic dysfunction exist?
Initial studies reported that the prognosis of patients with pure diastolic dysfunction is intermediate between normal subjects and patients with reduced systolic function, with an annual mortality <17.5% [3]. However, more recent studies showed no differences in mortality between patients with diastolic and systolic heart failure [1,4]. Such studies suggest that diastolic and systolic heart failure are the same disease, with the difference that so called pure diastolic heart failure represents an earlier stage in the natural history [32]. Our data also imply that diastolic dysfunction with absolutely normal regional and global systolic function, if it ever occurs, is extremely rare; one example might be pericardial constriction.

Petrie et al. measured displacement of the mitral annulus by M-mode echocardiography, and showed that between 21% and 33% of patients with diastolic heart failure had abnormal systolic mitral annular motion [33]. Similar results were reported by others, using either M-mode echocardiography or tissue Doppler analysis of mitral annular motion [34–37]. Mitral annular displacement was independently correlated with diastolic filling in patients with coronary heart disease; thus, given the same level of ejection fraction, it was found that the greater the impairment in diastolic filling, the lower the mitral annular displacement [34]. Similarly, mitral annular systolic velocities were lower in patients with diastolic heart failure than in normal subjects, and 38% of patients had velocities below the normal range [35]. However, ejection fraction and fractional shortening were also significantly lower in patients with diastolic heart failure, and these investigators did not include an intermediate group of asymptomatic patients with diastolic dysfunction alone. Other investigators have also reported that longitudinal velocities are decreased in patients with "pure" diastolic heart failure but in those studies also, ejection fraction was lower in patients than in controls [38,39]. Yu et al. showed that 14% of patients with asymptomatic diastolic dysfunction and 52% of patients with diastolic heart failure had reduced longitudinal systolic velocities [39]. They did not find that radial function was maintained in their patients with diastolic dysfunction, but they had worse global systolic function, and it is possible that radial compensatory changes may only be observed in the initial stages of heart failure.

4.3. Implications for diagnosis of heart failure
We report a parallel impairment of global diastolic dysfunction and longitudinal systolic function. We showed that despite normal global systolic function, there is a progressive decrease of both systolic and diastolic longitudinal function of the left ventricle with increasing severity of disease. The differences between patients with asymptomatic diastolic dysfunction and those with diastolic heart failure were not significant, but longitudinal systolic and early diastolic velocities were all lower in the symptomatic patients. Our study strongly supports the hypothesis that diastolic dysfunction and diastolic heart failure do not constitute a separate disease that is different from systolic heart failure. Instead, there is continuous spectrum of left ventricular function from normal, through global diastolic dysfunction with subendocardial systolic dysfunction, to severe combined systolic and diastolic heart failure. It is therefore inappropriate to seek to define discrete dichotomous diagnostic variables for "pure diastolic dysfunction". These observations should now be tested in large, prospective studies to investigate if measurements of long-axis function can predict clinical events in patients with heart failure, and if they can be used to monitor the effects of treatment on left ventricular function.

4.4. Study limitations
The prevalences of hypertension and diabetes were different between the three groups of patients (Table 2), but this was expected because these conditions cause diastolic dysfunction and reduced long-axis systolic function. The differences in the prevalence of ischaemic heart disease may have contributed to the degree of impairment of subendocardial function. However, since we excluded patients with ventricular aneurysm and severe regional wall motion abnormalities, this factor is unlikely to affect our results. Indeed, longitudinal velocities were decreased homogeneously for all 4 investigated sites of the mitral annulus (Table 4).

A small number of patients with hypertrophic cardiomyopathy were studied, but none had significant outflow tract obstruction or mitral regurgitation. We included these patients because hypertrophic cardiomyopathy is associated with diastolic dysfunction, as diagnosed by traditional echocardiographic criteria, and some patients progress to congestive heart failure.

Medication was also different between the study groups (Table 2). More patients with diastolic heart failure received beta-blockers, but this was not statistically significant, and the patients with diastolic heart failure still had higher systolic velocities than the patients with systolic heart failure. Verapamil was used in only 2 patients with asymptomatic diastolic dysfunction. It would not be possible to conduct a study of systolic and diastolic function across the spectrum from normality to severe disease, without including patients on drug treatment.

4.5. Conclusion
Worsening global diastolic dysfunction is associated with a progressive decline in longitudinal systolic function. This suggests that "pure" diastolic dysfunction is diagnosed erroneously when systolic function is assessed only by imprecise echocardiographic techniques, such as those derived from M-mode measurements. Since tissue Doppler longitudinal velocities reveal more subtle changes of systolic function, they should be studied and monitored when diagnosing left ventricular dysfunction and while monitoring treatment for heart failure. Diagnostic criteria for diastolic heart failure need to be re-examined.


   Acknowledgements
 
This study was supported by a grant from the Heart Research Fund for Wales.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Senni M., Tribouilloy C.M., Rodeheffer R.J., et al. Congestive heart failure in the community: a study of all incident cases in Olmsted County Minnesota, in 1991. Circulation (1998) 98:2282–2289.[Abstract/Free Full Text]
  2. Grossman W. Defining diastolic dysfunction. Circulation (2000) 101:2020–2021.[Free Full Text]
  3. Vasan R.S., Benjamin E.J., Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol (1995) 26:1565–1574.[Abstract]
  4. Senni M., Redfield M.M. Heart failure with preserved systolic function. A different natural history? J Am Coll Cardiol (2001) 38:1277–1282.[Abstract/Free Full Text]
  5. European Study Group on Diastolic Heart Failure. How to diagnose diastolic heart failure. Eur Heart J (1998) 19:990–1003.[Free Full Text]
  6. Vasan R.S., Levy D. Defining diastolic heart failure. A call for standardized diagnostic criteria. Circulation (2000) 101:2118–2121.[Free Full Text]
  7. Wilkenshoff U.M., Hatle L., Sovany A., Wranne B., Sutherland G.R. Age-dependent changes in regional diastolic function evaluated by color Doppler myocardial imaging: a comparison with pulsed Doppler indexes of global function. J Am Soc Echocardiogr (2001) 14:959–969.[CrossRef][Web of Science][Medline]
  8. Teichholz L.E., Kreulen T., Herman M.V., Gorlin R. Problems in echocardiographic volume determinations: echocardiographic–angiographic correlations in the presence or absence of asynergy. Am J Cardiol (1976) 37:7–11.[CrossRef][Web of Science][Medline]
  9. Takeda S., Rimington H., Smeeton N., Chambers J. Long axis excursion in aortic stenosis. Heart (2001) 86:52–56.[Abstract/Free Full Text]
  10. Vinereanu D., Ionescu A.A., Fraser A.G. Assessment of left ventricular long axis contraction can detect early myocardial dysfunction in asymptomatic patients with severe aortic regurgitation. Heart (2001) 85:30–36.[Abstract/Free Full Text]
  11. Vinereanu D., Florescu N., Sculthorpe N., Tweddel A.C., Stephens M.R., Fraser A.G. 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) 88:53–58.[CrossRef][Web of Science][Medline]
  12. Greenbaum R.A., Ho S.Y., Gibson D.G., Becker A.E., Anderson R.H. Left ventricular fibre architecture in man. Br Heart J (1981) 45:248–263.[Abstract/Free Full Text]
  13. Mundhenke M., Schwartzkopff B., Strauer B.E. Structural analysis of arteriolar and myocardial remodelling in the subendocardial region of patients with hypertensive heart disease and hypertrophic cardiomyopathy. Virchows Arch (1997) 431:265–273.[CrossRef][Web of Science][Medline]
  14. Shan K., Bick R.J., Poindexter B.J., et al. Relation of tissue Doppler derived myocardial velocities to myocardial structure and beta-adrenergic receptor density in humans. J Am Coll Cardiol (2000) 36:891–896.[Abstract/Free Full Text]
  15. Brun P., Tribouilloy C., Duval A.M., et al. Left ventricular flow propagation during early filling is related to wall relaxation: a color M-mode Doppler analysis. J Am Coll Cardiol (1992) 20:420–432.[Abstract]
  16. Garcia M.J., Ares M.A., Asher C., Rodriguez L., Vandervoort P., Thomas J.D. An index of early left ventricular filling that combined with pulsed Doppler peak E velocity may estimate capillary wedge pressure. J Am Coll Cardiol (1997) 29:448–454.[Abstract]
  17. Schiller N.B., Shah P.M., Crawford M., et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr (1989) 2:358–367.[Medline]
  18. Grossman W., Jones D., McLaurin L.P. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest (1975) 56:56–64.[Web of Science][Medline]
  19. Devereux R.B. Detection of left ventricular hypertrophy by M-mode echocardiography. Anatomic validation, standardization, and comparison to other methods. Hypertension (1987) 9:II9–II26.
  20. Nagueh S.F., Middleton K.J., Kopelen H.A., Zoghbi W.A., Quinones M.A. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol (1997) 30:1527–1533.[Abstract]
  21. Vinereanu D., Khokhar A., Fraser A.G. Reproducibility of pulsed-wave tissue Doppler echocardiography. J Am Soc Echocardiogr (1999) 12:492–499.[CrossRef][Web of Science][Medline]
  22. Bland J.M., Altman D.G. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet (1986) 1:307–310.[CrossRef][Web of Science][Medline]
  23. Jones C.J.H., Raposo L., Gibson D.G. Functional importance of the long-axis dynamics of the human left ventricle. Br Heart J (1990) 63:215–220.[Abstract/Free Full Text]
  24. Alam M., Hoglund C., Thorstrand C. Longitudinal systolic shortening of the left ventricle: an echocardiographic study in subjects with and without preserved global function. Clin Physiol (1992) 12:443–452.[Web of Science][Medline]
  25. Isaaz K., Munoz-del-Romeral L., Lee E., Schiller N.B. Quawntitation of the motion of the cardiac base in normal subjects by Doppler echocardiography. J Am Soc Echocardiogr (1993) 6:166–176.[Medline]
  26. Derumeaux G., Ovize M., Loufoua J., et al. Doppler tissue imaging quantitates regional wall motion during myocardial ischemia and reperfusion. Circulation (1998) 97:1970–1977.[Abstract/Free Full Text]
  27. Madler C.F., Vinereanu D., Payne N., Brodin L.A., Fraser A.G. Does preservation of radial function of the left ventricle compensate for loss of longitudinal function with age? Eur Heart J (2002) 23(abstr suppl):91.[Free Full Text]
  28. Hoglund C., Alam M., Thorstrand C. Atrioventricular valve plane displacement in healthy persons. An echocardiographic study. Acta Med Scand (1988) 224:557–562.[Web of Science][Medline]
  29. Nikitin N.P., Witte K.K., Thackray S.D., de Silva R., Clark A.L., Cleland J.G. Longitudinal ventricular function: normal values of atrioventricular annular and myocardial velocities measured with quantitative two-dimensional color Doppler tissue imaging. J Am Soc Echocardiogr (2003) 16:906–921.[CrossRef][Web of Science][Medline]
  30. Vinereanu D., Nicolaides E., Tweddel A.C., et al. Subclinical left ventricular dysfunction in asymptomatic patients with type II diabetes mellitus, related to serum lipids and glycated haemoglobin. Clin Sci (2003) 105:591–599.[CrossRef][Web of Science][Medline]
  31. Garcia M.J., Thomas J.D., Klein A.L. New Doppler echocardiographic applications for the study of diastolic function. J Am Coll Cardiol (1998) 32:865–875.[Abstract/Free Full Text]
  32. Kitzman D.W., Little W.C., Brubaker P.H., et al. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA (2002) 288:2144–2150.[Abstract/Free Full Text]
  33. Petrie M.C., Caruana L., Berry C., McMurray J.J. "Diastolic heart failure" or heart failure caused by subtle left ventricular systolic dysfunction. Heart (2002) 87:29–31.[Abstract/Free Full Text]
  34. Rydberg E., Willenheimer R., Brand B., Erhardt L.R. Left ventricular diastolic filling is related to the atrioventricular plane displacement in patients with coronary artery disease. Scand Cardiovasc J (2001) 35:30–34.[CrossRef][Web of Science][Medline]
  35. Yip G., Wang M., Zhang Y., Fung J.W., Ho P.Y., Sanderson J.E. Left ventricular long axis function in heart failure is reduced in both diastole and systole: time for a redefinition? Heart (2002) 87:121–125.[Abstract/Free Full Text]
  36. Willenheimer R., Israelsson B., Cline C., Rydberg E., Broms K., Erhardt L. Left atrioventricular plane displacement is related to both systolic and diastolic left ventricular performance in patients with chronic heart failure. Eur Heart J (1999) 20:612–618.[Abstract/Free Full Text]
  37. Bruch C., Gradaus R., Gunia S., Breithardt G., Wichter T. Doppler tissue analysis of mitral annular velocities: evidence for systolic abnormalities in patients with diastolic heart failure. J Am Soc Echocardiogr (2003) 16:1031–1036.[CrossRef][Web of Science][Medline]
  38. Nikitin N.P., Witte K.K., Clark A.L., Cleland J.G. Color tissue Doppler-derived long-axis left ventricular function in heart failure with preserved global systolic function. Am J Cardiol (2002) 90:1174–1177.[CrossRef][Web of Science][Medline]
  39. Yu C.M., Lin H., Yang H., Kong S.L., Zhang Q., Lee S.W. Progression of systolic abnormalities in patients with "isolated" diastolic heart failure and diastolic dysfunction. Circulation (2002) 105:1195–1201.[Abstract/Free Full Text]

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