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(Circulation. 2002;105:1195.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
From the Division of Cardiology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.
Correspondence to Dr Cheuk-Man Yu, Director of Non-Invasive Cardiac Services, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam Road, Hong Kong. E-mail cmyua{at}hkucc.hku.hk
| Abstract |
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Methods and Results Echocardiography with tissue Doppler imaging was performed in 339 subjects, of whom 92 had systolic heart failure (SHF) (EF<50%), 73 had DHF (EF
50% with diastolic abnormalities on Doppler echocardiography), and 68 had isolated diastolic dysfunction (DD); 106 were normal control subjects. Regional myocardial velocity curves were constructed off-line with the use of a 6-basal, 6-midsegmental model. The peak regional myocardial sustained systolic (SM) and early diastolic (EM) velocities were significantly lower in patients with SHF, DHF, and DD than in control subjects in almost all the myocardial segments. Likewise, the mean SM (SHF<DHF<DD<control subjects; 3.3±1.0<4.6±1.3<5.4±1.0<6.3±1.0 cm/s; all P
0.001) and mean EM (SHF=DHF<DD<control subjects; 3.6±1.2 =3.9±1.3<5.3±1.6<7.2±1.7 cm/s; all P<0.001) from the six basal segments were decreased in all the disease groups. A mean SM of 4.4cm/s (-2 SD of control subjects) predicted the presence of systolic dysfunction in 92% of patients with SHF, 52% with DHF, and 14% with DD.
Conclusions Through the use of tissue Doppler imaging, systolic abnormalities were evident in patients previously labeled as DHF and to a much lesser extent, isolated DD. This indicates the common coexistence of systolic and diastolic dysfunction in a spectrum of different severity in the pathophysiological process of heart failure.
Key Words: echocardiography heart failure ventricles systole diastole
| Introduction |
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| Methods |
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50%), and evidence of DD by Doppler echocardiography; and 68 had isolated DD who never presented with heart failure (Table 1). For underlying disease, 158 had ischemic heart disease, 23 had dilated cardiomyopathy, 50 had hypertensive heart disease, and 2 had alcoholic cardiomyopathy. For patients with ischemic heart disease, 51 had history of myocardial infarction (all in the SHF group), 84 had coexisting hypertension, and 65 had percutaneous coronary intervention performed. Coronary angiography was performed in 111 patients with ischemic heart disease, 9 patients with hypertensive heart disease, and all the patients with cardiomyopathy. Patients with atrial fibrillation, coexisting major organ dysfunction (such as kidney failure, respiratory disease, and hepatic dysfunction), or systemic illness or infection were excluded from the study. Informed consent was obtained from all subjects.
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Echocardiography
Standard echocardiography with Doppler studies was performed (System 5, Vingmed-General Electric). The left ventricular dimension and ejection fraction were measured by a 2-dimensionally guided, M-mode method according to the guidelines of the American Society of Echocardiography.16 Left ventricular diastolic dysfunction was classified as restrictive filling pattern (RFP) (defined as E/A ratio
2 or E/A ratio=1 to 2 and DT<140 ms), abnormal relaxation pattern (defined as E/A ratio<1 or E/A ratio=1 to 2 and deceleration time [DT]>240 ms), or pseudonormal (normal E/A ratio and DT but abnormal pulmonary venous inflow pattern of reversed systolic/diastolic forward flow ratio), as previously described.2,17,18 At least 3 consecutive beats in sinus rhythm were measured, and the average values were taken. Left ventricular midwall systolic stress was calculated according to the method of Shimizu19:
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where SBP is the systolic blood pressure, LVIDs is left ventricular end-systolic internal dimension, and PWTs is end-systolic posterior wall thickness. The modified midwall fractional shortening was calculated by the formula19
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where a is the distance from the posterior wall endocardium of the midwall fiber at end-systole, which is calculated from the preset formula as previously described.19
TDI was performed at apical views (apical 4-chamber, 2-chamber, and long-axis) for the long-axis/major-axis motion of the left ventricle as previously described.12,20 In brief, 2D echocardiography with TDI color imaging was set by bypassing the high-pass filter while allowing the low-frequency Doppler signals input directly into an autocorrelator. The imaging angle was adjusted to ensure a parallel alignment of the sampling window with the myocardial segment of interest. Color noise reduction was adjusted, and a color Doppler scanning frame rate of 100 to 140 Hz was used. Images in at least 3 consecutive beats were stored. Myocardial pulseDoppler velocity profile signals were reconstituted from the digitized images and analyzed off-line with a computer. In each apical view, both the basal and mid segments were assessed at the following wall: septal, lateral, anteroseptal, posterior, anterior, and inferior segments.20 The peak myocardial sustained systolic (SM) and early diastolic (EM) velocities were measured in each segment. In addition, the short-axis/circumferential fiber systolic and diastolic velocities were measured by the parasternal views over the mid anteroseptal and posterior segments.21
Validation of TDI has been performed extensively in physical models,22 animal models,23,24 and human subjects.2527 In physical models, the TDI-derived velocity was exactly representing the velocity of the moving phantom (r=0.99).22 In animal studies, the TDI measured velocities correlated with regional segmental shortening by piezoelectric crystals (r=0.89 to 0.90).24 In human studies, the systolic long-axis velocities by TDI had been shown to correlate with dp/dt by catheterization (r=0.82 to 0.88, P<0.0001),25,26 whereas the long-axis early diastolic velocity closely correlated with tau, the time constant of relaxation (r=-0.80, P<0.0001).27 The usefulness of TDI to detect abnormal cardiac function in various disease groups was also validated in human studies, such as hypertrophic cardiomyopathy,28 hypertension,29 and diastolic dysfunction.11,30 In patients with known regional abnormalities with hypokinetic and akinetic segments, reduction in regional systolic and diastolic wall velocities were observed.24,31 The mean velocity from the 6basal segmental model was also reported to be a sensitive index of global cardiac function,10 whereas the EM was found to be a good discriminator of normal from DD in clinical studies.13 In our own laboratory, validation was performed in 40 patients by invasive hemodynamic measurement and found that there was a good correlation between mean basal SM and +dp/dt (r=0.84, P<0.001) and mean basal EM and -dp/dt (r=0.69, P=0.001). The interobserver variability and intraobserver variability have been compared in 60 consecutive measurements, which were 4.7% and 3.2%, respectively.
Statistics
Data were analyzed with the use of a statistical software program (SPSS for Windows, version 10.0, SPSS Inc). For comparison of peak myocardial velocities and other echocardiographic data among various groups, the general linear model was used in which age, heart rate, and medications were input as independent covariates to examine their effect on the dependent variables and followed by 1-way ANOVA with Scheffés correction for significance. Linear regression was used to investigate the correlation between two parametric variables. Comparison of nonparametric data was performed by
2 test. The results are expressed as mean±SD. A value of P<0.05 was considered statistically significant.
| Results |
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By the general linear model, it was found that age, heart rate, and individual medications including ß-blockers and calcium channel blockers were not significant covariates that affected echocardiographic parameters; statistical adjustment was therefore not performed.
Systolic Parameters
Patients with SHF had significantly larger left ventricular end-systolic (SHF, 5.3±1.0; DHF, 3.5±0.8; DD, 3.1±0.6 cm) and end-diastolic (SHF, 6.2±1.0; DHF, 5.1±0.8; DD, 4.8±0.7 cm) diameters than those with DHF or DD (all P<0.001). As expected, the fractional shortening (SHF, 15±4%; DHF, 31±8%; DD, 36±8%) and ejection fraction (SHF, 38±9%; DHF, 66±11%; DD, 72±10%) were significantly lower in patients with SHF than in those with DHF or DD (all P<0.001). All these parameters were not different when comparing patients with DD with those with DHF.
On TDI measurement, the peak myocardial sustained systolic velocities (SM) in patients with SHF, DHF, and DD were significantly lower than in control subjects (Table 2). This abnormality was consistently seen in all 12 myocardial segments in SHF and DHF and in 8 of 12 myocardial segments in DD. In addition, the SM was lower in patients with SHF than in those with DHF or DD in most of the myocardial segments and to a lesser extent when comparing patients with DHF and DD (Table 2 and Figure 1A). For the short-axis fiber function, it was significantly reduced in the anteroseptal and posterior segments in SHF and DHF groups and in the DD group to a lesser extent (Table 2).
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The mean value of the 6 basal segments (mean SM) was calculated to represent global left ventricular systolic function. The 6 basal segments were taken because they represent the cumulative speed of wall contraction in that particular wall from the base to the apex. It was found that the order of magnitude of mean SM was: control subjects>DD>DHF>SHF, where the comparison was highly significant between any two groups (all P
0.001) (Table 2 and Figure 2). There was also a modest correlation between the mean SM and left ventricular ejection fraction (r=0.73, P<0.001) (Figure 3). The relation between left ventricular ejection fraction and mean SM was shown by the regression equation
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To compare TDI-measured SM with the ejection fraction, the value of -2 SD from the mean SM in the control subjects (ie, 4.4 cm/s) was used as the cutoff point for abnormality. It was found that 14% of patients with DD and 52% of patients with DHF had an SM <4.4 cm/s and was 92% in the SHF group.
To further support that the results genuinely reflect abnormal systolic function in the disease groups, the midwall systolic stress and midwall fractional shortening were also assessed. It was highly abnormal in patients with SHF (both P<0.001) and DHF (P<0.05 and P<0.001 respectively) (Table 2).
Diastolic Parameters
In patients with isolated DD, by Doppler echocardiography, 88% of them had an abnormal relaxation pattern and 12% had a pseudonormal pattern, which was 84% and 16%, respectively, in DHF. On the other hand, for those with SHF, 48% had an abnormal relaxation pattern, 22% had a pseudonormal pattern, and 30% had a restrictive filling pattern (
2=21.3, P<0.001). As a result of a higher prevalence of restrictive filling pattern, patients with SHF had a significantly higher peak transmitral early diastolic filling velocity and early to atrial velocity ratio and a lower peak atrial filling velocity than those with DHF and DD (Table 3).
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On TDI measurement, the peak myocardial early diastolic velocity (EM) was significantly lower in all the myocardial segments in patients with SHF, DHF, and DD when compared with control subjects (Table 4 and Figure 1B). There was no difference in regional EM between patients with SHF and DHF, though the EM in the majority of the left ventricular segments were significantly lower in these patients than in those with DD. Similar abnormalities were present in the EM for short-axis fiber function in the anteroseptal and posterior segments (Table 4).
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The mean value of EM (mean EM) at the 6 basal segments was calculated to represent global left ventricular diastolic function. It was significantly lower in all the disease groups than in control subjects (all P<0.001). In addition, the mean EM in SHF and DHF was lower than in those with DD (both P<0.001). The order of magnitude of mean EM was: control subjects>DD>DHF=SHF (Table 4 and Figure 2).
| Discussion |
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Systolic Abnormalities in Diastolic Heart Failure and "Isolated" Diastolic Dysfunction
Conventionally, isolated DHF is defined as increased resistance to diastolic filling or presence of abnormalities of left ventricular filling, with preserved systolic function that commonly used an ejection fraction of >50% in the clinical setting of heart failure.8,9 This definition has methodological limitations. Although most investigators adopt this definition to differentiate systolic from diastolic heart failure,32,33 the present study found that by using this nomenclature, abnormalities of systolic function are in fact prevalent in those labeled as DHF. Despite the fact that patients with regional wall motion abnormalities (such as myocardial infarction) were excluded from the DHF group in the present study, reduction of regional SM was found in almost all the myocardial segments when compared with normal control subjects, indicating that systolic function is indeed impaired globally in these patients. The severity of abnormalities was also stratified by the current method, being more severe in SHF, least in DD, and DHF in between. It is intriguing to note that for patients with SHF, the degree of impairing EM was the same as those with DHF. This probably is explained by the fact that in the former group, diastolic dysfunction always coexists that is at least as severe as in those with DHF.3
The systolic and diastolic abnormalities seen in long-axis fiber function in the patient groups were also observed in the short-axis fibers by TDI and was further supported by the abnormally increased midwall systolic stress and decreased midwall fractional shortening. The changes observed in these parameters were similar to those of long-axis velocities by TDI. This indicated that both long- and short-axis fiber functions were equally jeopardized by cardiac diseases, which was supported by previous studies.2527
In this study, quantitative measurement of mean SM and EM from the six basal left ventricular segments offers further insight in differentiating the three disease groups. Patients with DHF had lower mean SM and EM than those with isolated DD, whereas in the case of SHF, the SM was the lowest, and the EM was as abnormal as to those with DHF.
Relation Between Systolic and Diastolic Abnormalities
Although it is generally believed that DD and even DHF occurs solely or before systolic dysfunction, our findings illustrated that systolic abnormalities probably coexist in DHF and to a much lesser extent in DD. This condition is not detected by conventional investigations that measure ejection fraction. Conversely, our previous studies and others found that DD invariably coexists in patients with SHF.2,34 Because systole and diastole are closely coupled in the cardiac cycle, it is possible that functional abnormalities of intracellular calcium handling and the interaction of myofilaments resulting in diastolic abnormalities also affect systolic function.1,35 Studies also confirmed that end-systolic volume or parameters of systolic contractility such as +dp/dt are important determinants of early diastolic function.14,15 We postulate that in the early course of cardiac diseases in which DD is evident by Doppler echocardiography, systolic dysfunction starts to develop. As DD progresses to clinical heart failure (ie, DHF), systolic function is further jeopardized (decrease in SM). Eventually, the disease progresses to a full-borne picture in which both systolic and diastolic dysfunctions are clinically evident (ie, SHF) (Figure 4). Because the severity of systolic and diastolic dysfunctions occurs in a continuous spectrum, some patients may have more dominant features of DD or DHF, whereas the others have combined SHF and DD. Depending also on the sensitivity of the diastolic tool on systolic and diastolic functions, the "diagnosis" of diastolic versus systolic dysfunction may be altered, as shown in the shaded area of Figure 4.
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TDI in the Assessment of Systolic and Diastolic Functions
TDI offers a new horizon for the assessment of left ventricular function.1013,20 Previous validation studies have been described in the Methods section.22,2426 The EM was previously shown to be reduced in the presence of cardiac diseases causing DD, such as ischemic heart disease and left ventricular hypertrophy.20,24,29,31 On the other hand, the relation between systolic and diastolic dysfunction was not examined. Based on our observation, a -2 SD of mean SM (<4.4 cm/s) accurately predicted an abnormal systolic function in approximately half of patients with DHF and 14% of patients with DD. From the regression equation, this value corresponds to an ejection fraction of 55%. In other words, SM starts to reveal abnormal systolic function much earlier than ejection fraction does, and hence in a proportion of these patients the systolic function was labeled as "normal" by conventional methods. Therefore, the SM appears to be a more sensitive index of early systolic dysfunction than is ejection fraction. Our recent experience also found that TDI is more sensitive than ejection fraction for the detection of transient subclinical left ventricular systolic dysfunction after cardioversion of atrial fibrillation.12 Recently, reduced SM was also observed in patients with hypertrophic cardiomyopathy and those mutation-positive nonhypertrophic subjects, despite perfectly "normal" ejection fraction when compared with normal subjects.28
Conclusions
Using TDI, abnormalities of systolic function is prevalent in patients previously labeled as isolated DHF and to a lesser extent as DD. By combining quantitative assessment of SM, EM, and clinical features, it allows a more insightful understanding of the severity of systolic and diastolic dysfunction and differentiates among the predominant pathophysiological pictures, that is, DD, DHF, and SHF.
Received November 19, 2001; revision received December 26, 2001; accepted January 2, 2002.
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B. Gruner Svealv, G. Fritzon, and B. Andersson Gender and age related differences in left ventricular function and geometry with focus on the long axis Eur J Echocardiogr, August 1, 2006; 7(4): 298 - 307. [Abstract] [Full Text] [PDF] |
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S. Klotz, I. Hay, G. Zhang, M. Maurer, J. Wang, and D. Burkhoff Development of Heart Failure in Chronic Hypertensive Dahl Rats: Focus on Heart Failure With Preserved Ejection Fraction Hypertension, May 1, 2006; 47(5): 901 - 911. [Abstract] [Full Text] [PDF] |
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L. van Heerebeek, A. Borbely, H. W.M. Niessen, J. G.F. Bronzwaer, J. van der Velden, G. J.M. Stienen, W. A. Linke, G. J. Laarman, and W. J. Paulus Myocardial Structure and Function Differ in Systolic and Diastolic Heart Failure Circulation, April 25, 2006; 113(16): 1966 - 1973. [Abstract] [Full Text] [PDF] |
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G. P. Aurigemma, M. R. Zile, and W. H. Gaasch Contractile Behavior of the Left Ventricle in Diastolic Heart Failure: With Emphasis on Regional Systolic Function Circulation, January 17, 2006; 113(2): 296 - 304. [Full Text] [PDF] |
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E. Boni, M. Bezzi, L. Carminati, L. Corda, V. Grassi, and C. Tantucci Expiratory Flow Limitation Is Associated With Orthopnea and Reversed by Vasodilators and Diuretics in Left Heart Failure Chest, August 1, 2005; 128(2): 1050 - 1057. [Abstract] [Full Text] [PDF] |
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D. Vinereanu, E. Nicolaides, A. C. Tweddel, and A. G. Fraser "Pure" diastolic dysfunction is associated with long-axis systolic dysfunction. Implications for the diagnosis and classification of heart failure Eur J Heart Fail, August 1, 2005; 7(5): 820 - 828. [Abstract] [Full Text] [PDF] |
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Q. Ruan and S. F Nagueh Effect of age on left ventricular systolic function in humans: a study of systolic isovolumic acceleration rate Exp Physiol, July 1, 2005; 90(4): 527 - 534. [Abstract] [Full Text] [PDF] |
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I. P. Clements Combined systolic and diastolic dysfunction in the presence of preserved left ventricular ejection fraction Eur J Heart Fail, June 1, 2005; 7(4): 490 - 497. [Abstract] [Full Text] [PDF] |
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D. Vinereanu, P. O. Lim, M. P. Frenneaux, and A. G. Fraser Reduced myocardial velocities of left ventricular long-axis contraction identify both systolic and diastolic heart failure--a comparison with brain natriuretic peptide Eur J Heart Fail, June 1, 2005; 7(4): 512 - 519. [Abstract] [Full Text] [PDF] |
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C. F. Baicu, M. R. Zile, G. P. Aurigemma, and W. H. Gaasch Left Ventricular Systolic Performance, Function, and Contractility in Patients With Diastolic Heart Failure Circulation, May 10, 2005; 111(18): 2306 - 2312. [Abstract] [Full Text] [PDF] |
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V. K. Munagala, C. Y.T. Hart, J. C. Burnett Jr, D. M. Meyer, and M. M. Redfield Ventricular Structure and Function in Aged Dogs With Renal Hypertension: A Model of Experimental Diastolic Heart Failure Circulation, March 8, 2005; 111(9): 1128 - 1135. [Abstract] [Full Text] [PDF] |
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P. M. Srivastava, L. M. Burrell, and P. Calafiore Lateral vs medial mitral annular tissue Doppler in the echocardiographic assessment of diastolic function and filling pressures: which should we use? Eur J Echocardiogr, March 1, 2005; 6(2): 97 - 106. [Abstract] [Full Text] [PDF] |
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A. Borbely, J. van der Velden, Z. Papp, J. G.F. Bronzwaer, I. Edes, G. J.M. Stienen, and W. J. Paulus Cardiomyocyte Stiffness in Diastolic Heart Failure Circulation, February 15, 2005; 111(6): 774 - 781. [Abstract] [Full Text] [PDF] |
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H. Von Bibra, I. S Thrainsdottir, A. Hansen, V. Dounis, K. Malmberg, and L. Ryden Tissue Doppler imaging for the detection and quantitation of myocardial dysfunction in patients with type 2 diabetes mellitus Diabetes and Vascular Disease Research, February 1, 2005; 2(1): 24 - 30. [Abstract] [PDF] |
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P. Bordachar, S. Lafitte, S. Reuter, P. Sanders, P. Jais, M. Haissaguerre, R. Roudaut, S. Garrigue, and J. Clementy Echocardiographic parameters of ventricular dyssynchrony validation in patients with heart failure using sequential biventricular pacing J. Am. Coll. Cardiol., December 7, 2004; 44(11): 2157 - 2165. [Abstract] [Full Text] [PDF] |
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S. K. Hamlin, P. S. Villars, J. T. Kanusky, and A. D. Shaw Role of Diastole in Left Ventricular Function, II: Diagnosis and Treatment Am. J. Crit. Care., November 1, 2004; 13(6): 453 - 466. [Abstract] [Full Text] [PDF] |
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K.-L. He, M. Dickstein, H. N. Sabbah, G.-H. Yi, A. Gu, M. Maurer, C.-M. Wei, J. Wang, and D. Burkhoff Mechanisms of heart failure with well preserved ejection fraction in dogs following limited coronary microembolization Cardiovasc Res, October 1, 2004; 64(1): 72 - 83. [Abstract] [Full Text] [PDF] |
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P. M. Mottram, B. Haluska, R. Leano, D. Cowley, M. Stowasser, and T. H. Marwick Effect of Aldosterone Antagonism on Myocardial Dysfunction in Hypertensive Patients With Diastolic Heart Failure Circulation, August 3, 2004; 110(5): 558 - 565. [Abstract] [Full Text] [PDF] |
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A Auricchio and C M Yu Beyond the measurement of QRS complex toward mechanical dyssynchrony: cardiac resynchronisation therapy in heart failure patients with a normal QRS duration Heart, May 1, 2004; 90(5): 479 - 481. [Abstract] [Full Text] [PDF] |
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F. J. Munoz, B. Thomas, and P. Andrew Diastolic Heart Failure Chest, April 1, 2004; 125(4): 1588 - 1589. [Full Text] [PDF] |
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S. J. Skaluba and S. E. Litwin Mechanisms of Exercise Intolerance: Insights From Tissue Doppler Imaging Circulation, March 2, 2004; 109(8): 972 - 977. [Abstract] [Full Text] [PDF] |
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H. Yamaguchi, J. Yoshida, K. Yamamoto, Y. Sakata, T. Mano, N. Akehi, M. Hori, Y.-J. Lim, M. Mishima, and T. Masuyama Elevation of plasma brain natriuretic peptide is a hallmark of diastolic heart failure independent of ventricular hypertrophy J. Am. Coll. Cardiol., January 7, 2004; 43(1): 55 - 60. [Abstract] [Full Text] [PDF] |
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N. H. Andersen, S. H. Poulsen, K. Helleberg, P. Ivarsen, S. T. Knudsen, and C. E. Mogensen Impact of Essential Hypertension and Diabetes Mellitus on Left Ventricular Systolic and Diastolic Performance Eur J Echocardiogr, December 1, 2003; 4(4): 306 - 312. [Abstract] [Full Text] [PDF] |
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J. Mayet and A. Hughes Cardiac and vascular pathophysiology in hypertension Heart, September 1, 2003; 89(9): 1104 - 1109. [Full Text] [PDF] |
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F. H. Rutten, D. E. Grobbee, and A. W. Hoes Differences between general practitioners and cardiologists in diagnosis and management of heart failure: a survey in every-day practice Eur J Heart Fail, June 1, 2003; 5(3): 337 - 344. [Abstract] [Full Text] [PDF] |
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J. Koyama, P. A. Ray-Sequin, and R. H. Falk Longitudinal Myocardial Function Assessed by Tissue Velocity, Strain, and Strain Rate Tissue Doppler Echocardiography in Patients With AL (Primary) Cardiac Amyloidosis Circulation, May 20, 2003; 107(19): 2446 - 2452. [Abstract] [Full Text] [PDF] |
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D. Burkhoff, M. S. Maurer, and M. Packer Heart Failure With a Normal Ejection Fraction: Is It Really a Disorder of Diastolic Function? Circulation, February 11, 2003; 107(5): 656 - 658. [Full Text] [PDF] |
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C-M Yu, H Lin, Q Zhang, and J E Sanderson High prevalence of left ventricular systolic and diastolic asynchrony in patients with congestive heart failure and normal QRS duration Heart, January 1, 2003; 89(1): 54 - 60. [Abstract] [Full Text] [PDF] |
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M. Bartnik, K. Malmberg, and L. Ryden Diabetes and the heart: compromised myocardial function -- a common challenge Eur. Heart J. Suppl., January 1, 2003; 5(suppl_B): B33 - B41. [Abstract] [PDF] |
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A. Hansen, B.-L. Johansson, J. Wahren, and H. von Bibra C-Peptide Exerts Beneficial Effects on Myocardial Blood Flow and Function in Patients With Type 1 Diabetes Diabetes, October 1, 2002; 51(10): 3077 - 3082. [Abstract] [Full Text] [PDF] |
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