Progression of Systolic Abnormalities in Patients With “Isolated” Diastolic Heart Failure and Diastolic Dysfunction
Background— The definition of diastolic heart failure (DHF) relies on the use of sensitive tools to exclude the presence of systolic dysfunction. The use of ejection fraction (EF) of 50% as the cutoff point may not be adequate to address such a task. We believe that systolic dysfunction is common in DHF.
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.
Received November 19, 2001; revision received December 26, 2001; accepted January 2, 2002.
Diastolic dysfunction (DD) refers to the presence of abnormalities in filling of the ventricle(s).1 It may occur in the left, right, or both ventricles.2–4⇓⇓ In patients with systolic heart failure (SHF), left ventricular DD commonly coexists and is more prevalent than right ventricular DD.3 Nevertheless, isolated DD has been described to occur in almost all cardiac diseases with or without the accompanying heart failure features. The former is called diastolic heart failure (DHF), in which systolic function is preserved, which is usually assessed by echocardiography or ventriculography. DHF has been described to be responsible for more than one third of heart failure hospitalization.5 Echocardiography with Doppler studies is a commonly used noninvasive diagnostic tool for the distinction between systolic and diastolic dysfunction.6,7⇓ Conventional definition of DHF usually relies on the preserved systolic function with left ventricular ejection fraction >50% and coexisting features of DD.8,9⇓ The former criteria are somewhat arbitrary and may not be able to differentiate patients with mild systolic dysfunction. Tissue Doppler imaging (TDI) is an emerging echocardiographic technique with the capacity to quantify systolic and diastolic functions both globally and regionally.10,11⇓ We and others have demonstrated that TDI is useful and more sensitive for the detection of left ventricular systolic dysfunction and DD than is conventional echocardiography12,13⇓ because it integrates detailed information of regional function to estimate global cardiac function. Systolic function is in fact one of the most important determinants of diastolic function.14,15⇓ Because systolic and diastolic functions are closely coupled in the cardiac cycle and both are energy-dependent processes,1 we hypothesized that systolic abnormality coexists in patients with DHF and possibly “isolated” DD. Therefore, the aim of this study was to compare systolic and diastolic functions in patients with SHF, DHF, and isolated DD and in normal control subjects by means of TDI.
Echocardiography was performed in 339 subjects in a University teaching hospital. These included 233 patients with known systolic and/or diastolic dysfunction who were recruited from the outpatient clinic and 106 healthy volunteers from a regional health festival. Among the patients, 92 had SHF with ejection fraction <50% by echocardiography and had signs and symptoms of heart failure; 73 had DHF with clinical features of heart failure, preserved systolic function (ejection fraction ≥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.
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:
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
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 pulse–Doppler 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.25–27⇓⇓ 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 6–basal 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.
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 Scheffé’s correction for significance. Linear regression was used to investigate the correlation between two parametric variables. Comparison of nonparametric data was performed by χ2 test. The results are expressed as mean±SD. A value of P<0.05 was considered statistically significant.
In the disease group, the mean age was 66.9±10.7 years, and 72% were men. This was not different from the control subjects (64.3±9.5 years, 60% men, both P=NS). The heart rate was not different between the disease group and control subjects (67.4±13.1 versus 64.7±10.8 beats/min, P=NS). The clinical data for patients with SHF, DHF, and DD are shown in Table 1. The distribution of New York Heart Association (NYHA) class for SHF (n=92) was: class II, 50%; class III, 33%; and class IV, 17% and was 82%, 17%, and 0%, respectively, in those with DHF (n=73).
By the general linear model, it was found that age, heart rate, and individual medications including β-blockers and calcium channel blockers were not significant covariates that affected echocardiographic parameters; statistical adjustment was therefore not performed.
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).
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
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).
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 (χ2=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).
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).
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).
This study observed that in patients with DHF, there is objective evidence of impaired left ventricular systolic function as demonstrated by TDI. In these patients, the regional SM and mean SM in the left ventricle were decreased. The diastolic abnormality was illustrated by the reduction in EM. Apparently, the reduction of SM was less severe in DHF than in SHF, though the reduction of EM was similar. On the other hand, the reduction of both SM and EM were less severe in patients with isolated DD.
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.25–27⇓⇓
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.
TDI in the Assessment of Systolic and Diastolic Functions
TDI offers a new horizon for the assessment of left ventricular function.10–13,20⇓⇓⇓⇓ Previous validation studies have been described in the Methods section.22,24–26⇓⇓⇓ 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
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.
- ↵Grossman W. Diastolic dysfunction in congestive heart failure. N Engl J Med. 1991; 325: 1557–1564.
- ↵Xie GY, Berk MR, Smith MD, et al. Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure. J Am Coll Cardiol. 1994; 24: 132–139.
- ↵Yu CM, Sanderson JE, Chan S, et al. Right ventricular diastolic dysfunction in heart failure. Circulation. 1996; 93: 1509–1514.
- ↵Chakko S, de Marchena E, Kessler KM, et al. Right ventricular diastolic function in systemic hypertension. Am J Cardiol. 1990; 65: 1117–1120.
- ↵Dougherty AH, Naccarelli GV, Gray EL, et al. Congestive heart failure with normal systolic function. Am J Cardiol. 1984; 54: 778–782.
- ↵DeMaria AN, Wisenbaugh TW, Smith MD, et al. Doppler echocardiographic evaluation of diastolic dysfunction. Circulation. 1991; 84: 1288–1295.
- ↵Thomas JD, Weyman AE. Echocardiographic Doppler evaluation of left ventricular diastolic function: physics and physiology. Circulation. 1991; 84: 977–990.
- ↵Vasan RS, Levy D. Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation. 2000; 101: 2118–2121.
- ↵Anonymous. How to Diagnose Diastolic Heart Failure. European Study Group on Diastolic Heart Failure. Eur Heart J. 1998; 19: 990–1003.
- ↵Gulati VK, Katz WE, Follansbee WP, et al. Mitral annular descent velocity by tissue Doppler echocardiography as an index of global left ventricular function. Am J Cardiol. 1996; 77: 979–984.
- ↵Sohn DW, Chai IH, Lee DJ, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol. 1997; 30: 474–480.
- ↵Yu CM, Wang Q, Lau CP, et al. Reversible impairment of left and right ventricular systolic and diastolic function during short-lasting atrial fibrillation in patients with an implantable atrial defibrillator: a tissue Doppler imaging study. Pacing Clin Electrophysiol. 2001; 24: 979–988.
- ↵Farias CA, Rodriguez L, Garcia MJ, et al. Assessment of diastolic function by tissue Doppler echocardiography: comparison with standard transmitral and pulmonary venous flow. J Am Soc Echocardiogr. 1999; 12: 609–617.
- ↵Courtois M, Mechem CJ, Barzilai B, et al. Factors related to end-systolic volume are important determinants of peak early diastolic transmitral flow velocity. Circulation. 1992; 85: 1132–1138.
- ↵Dent JM, Spotnitz WD, Nolan SP, et al. Mechanism of mitral leaflet excursion. Am J Physiol. 1995; 269: H2100–H2108.
- ↵Sahn DJ, DeMaria A, Kisslo J, et al. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation. 1978; 58: 1072–1083.
- ↵Yu CM, Sanderson JE, Shum IO, et al. Diastolic dysfunction and natriuretic peptides in systolic heart failure: higher ANP and BNP levels are associated with the restrictive filling pattern. Eur Heart J. 1996; 17: 1694–1702.
- ↵Masuyama T, Lee JM, Nagano R, et al. Doppler echocardiographic pulmonary venous flow-velocity pattern for assessment of the hemodynamic profile in acute congestive heart failure. Am Heart J. 1995; 129: 107–113.
- ↵Shimizu G, Hirota Y, Kita Y, et al. Left ventricular midwall mechanics in systemic arterial hypertension: myocardial function is depressed in pressure-overload hypertrophy. Circulation. 1991; 83: 1676–1684.
- ↵Pai RG, Gill KS. Amplitudes, durations, and timings of apically directed left ventricular myocardial velocities, II: systolic and diastolic asynchrony in patients with left ventricular hypertrophy. J Am Soc Echocardiogr. 1998; 11: 112–118.
- ↵Garcia MJ, Rodriguez L, Ares M, et al. Myocardial wall velocity assessment by pulsed Doppler tissue imaging: characteristic findings in normal subjects. Am Heart J. 1996; 132: 648–656.
- ↵Fleming AD, McDicken WN, Sutherland GR, et al. Assessment of colour Doppler tissue imaging using test-phantoms. Ultrasound Med Biol. 1994; 20: 937–951.
- ↵Nagueh SF, Kopelen HA, Lim DS, 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: 1346–1350.
- ↵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.
- ↵Mishiro Y, Oki T, Yamada H, et al. Evaluation of left ventricular contraction abnormalities in patients with dilated cardiomyopathy with the use of pulsed tissue Doppler imaging. J Am Soc Echocardiogr. 1999; 12: 913–920.
- ↵Oki T, Iuchi A, Tabata T, et al. Left ventricular systolic wall motion velocities along the long and short axes measured by pulsed tissue Doppler imaging in patients with atrial fibrillation. J Am Soc Echocardiogr. 1999; 12: 121–128.
- ↵Oki T, Tabata T, Yamada H, et al. Left ventricular diastolic properties of hypertensive patients measured by pulsed tissue Doppler imaging. J Am Soc Echocardiogr. 1998; 11: 1106–1112.
- ↵Nagueh SF, Bachinski LL, Meyer D, 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: 128–130.
- ↵Rodriguez L, Garcia M, Ares M, et al. Assessment of mitral annular dynamics during diastole by Doppler tissue imaging: comparison with mitral Doppler inflow in subjects without heart disease and in patients with left ventricular hypertrophy. Am Heart J. 1996; 131: 982–987.
- ↵Nagueh SF, Middleton KJ, Kopelen HA, et al. 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.
- ↵Garcia-Fernandez MA, Azevedo J, Moreno M, et al. Regional diastolic function in ischaemic heart disease using pulsed wave Doppler tissue imaging. Eur Heart J. 1999; 20: 496–505.
- ↵Marantz PR, Tobin JN, Wassertheil-Smoller S, et al. The relationship between left ventricular systolic function and congestive heart failure diagnosed by clinical criteria. Circulation. 1988; 77: 607–612.
- ↵Aronow WS, Ahn C, Kronzon I. Prognosis of congestive heart failure in elderly patients with normal versus abnormal left ventricular systolic function associated with coronary artery disease. Am J Cardiol. 1990; 66: 1257–1259.
- ↵Yu CM, Sanderson JE. Different prognostic significance of right and left ventricular diastolic dysfunction in heart failure. Clin Cardiol. 1999; 22: 504–512.
- ↵Perreault CL, Meuse AJ, Bentivegna LA, et al. Abnormal intracellular calcium handling in acute and chronic heart failure: role in systolic and diastolic dysfunction. Eur Heart J. 1990; 11 Suppl C: 8–21X.