Objectives To investigate the value of tissue Doppler imaging (TDI) measurements of right ventricular (RV) systolic and diastolic function as a predictor of long term cardiovascular outcomes in patients with left ventricular (LV) systolic heart failure.
Background In patients with LV systolic heart failure, RV function has been shown to be an important predictor of outcome. TDI is probably a clinically useful method for assessing RV function. The studies published so far have had a rather short follow-up period and have excluded patients with atrial fibrillation.
Methods 156 patients admitted to the cardiology department due to decompensated heart failure were included in this observational cohort study. 19% had atrial fibrillation. An echocardiographic examination was performed at entry to the study. The patients were then followed for a mean of 829 days. The primary endpoint was cardiovascular mortality or hospitalisation for decompensated heart failure.
Results 43 patients (28%) died from cardiovascular causes and 55 patients (35%) patients were hospitalised. 80 patients (51%) reached the study endpoint. Only age and a combined systolic and diastolic TDI parameter (s'r + e'r < 18.5 cm/s) of the right ventricle were independent predictors of cardiovascular outcome (HR 1.99, p=0.007).
Conclusion A combined measure of RV systolic and diastolic function, using TDI, can be used as an independent predictor of outcome in patients with LV systolic heart failure.
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In an increasing number of studies, tissue Doppler imaging (TDI) parameters of myocardial function have been shown to be of prognostic importance in patients with a variety of cardiac conditions.1–6 In particular, the ratio of early diastolic transmitral flow velocity (E) and early diastolic myocardial velocity (e') has emerged as a strong and independent predictor of cardiovascular mortality and morbidity.4–6 E/e' has been shown to be a non-invasive tool for estimating left heart filling pressure.7 ,8 Relatively few studies have addressed the prognostic importance of right ventricular (RV) function in patients with left ventricular (LV) heart failure.9–11 There is no established gold standard echocardiographic method to assess RV systolic and diastolic function. The most common parameter in clinical praxis is tricuspid annular plane systolic excursion. TDI of the tricuspid annulus is a promising method since it is easy to obtain and understand and reveals properties of both systolic and diastolic function of the right ventricle. There is some evidence that TDI parameters of the right ventricle are of prognostic importance in patients with heart failure.12–16 The studies published so far have a rather short follow-up period and have excluded patients with atrial fibrillation.
The aim of the present study is to evaluate RV systolic and diastolic TDI parameters and to assess their importance as predictors of long term prognosis in a common left-sided heart failure population, including patients with non-valvular atrial fibrillation. We hypothesise that a combination of systolic and diastolic RV velocities would be an independent predictor of cardiovascular outcomes, providing incremental prognostic information to more established clinical and echocardiographic variables. The study is conducted as a hospital-based observational cohort study.
Patients who were admitted to the Department of Cardiology at Södersjukhuset AB (Stockholm South General Hospital) due to signs and symptoms related to congestive heart failure between September 1999 and April 2004 were consecutively screened for this study. They were asked to participate if LV ejection fraction (LVEF) was ≤40%. Exclusion criteria were severe valvular heart disease and age >85 years. Patients with atrial fibrillation were included. Eventually, 156 patients were included in the study. Before discharge and in a stable clinical condition (within 1 week, but after intravenous diuretics had been stopped), they underwent an echocardiographic examination in which conventional and TDI parameters were recorded. The patients were then followed up for a median of 829 days. At the end of the follow-up period, data from the National Registry of Deaths and hospital records were collected. The study endpoint was cardiovascular death or hospitalisation for decompensated heart failure. No subjects were lost to follow-up. The study was approved by the Regional Committee of Research Ethics. Informed consent was obtained from all patients.
A Hewlett-Packard Sonos 5500 (Andover, California, USA) was used to record echocardiograms. The LV dimensions were measured according to the recommendations of the American Society of Echocardiography.17 The ejection fraction (EF) was determined using the Simpson biplane method. Transmitral flow was recorded by pulsed-wave Doppler placed between the mitral leaflet tips in the apical four-chamber view. Early (E) and late (A) transmitral flow velocities were recorded. The ratio of early to late flow (E/A ratio) was calculated when possible. The pulsed-wave TDI was performed by activating the TDI function of the same echocardiography machine. Images were acquired by using a variable frequency phased array transducer (2–4 MHz). The filter settings were kept low (50 Hz), and gains were adjusted at the lowest possible level to minimise noise and eliminate the signals produced by the transmitral and transtricuspid flow. A 1.7 mm sample volume was used to obtain an optimal signal without noise. Four different sites around the mitral annulus and one at the tricuspid annulus were selected. In the apical four-chamber view, the cursor was placed near the septal and lateral sides of the mitral annulus in such a way that the annulus moved along the sample volume line. In the same view, the cursor was also positioned at the lateral side of the tricuspid annulus. In the apical two-chamber view, the cursor was placed at the inferior and anterior sites of the mitral annulus. A Doppler velocity range of -20–20 cm/s was selected. Three major velocities were recorded: the positive systolic velocity when the mitral and tricuspid annulus moves towards the apex (s') and two negative diastolic velocities when the annulus moves away from the apex. One diastolic velocity occurs in the early phase of diastole (e') and one in the late phase of diastole (a'). A mean value for the above four sites was used to assess global LV systolic and diastolic function. For the right ventricle, a summation of systolic and early diastolic peak velocity was calculated as S'r+E'r and was expressed as a combined systolic and diastolic parameter of RV function. In patients with atrial fibrillation, A and a' are absent due to a lack of atrial contractions. The other parameters were obtained by calculating the mean for five consecutive cycles in these patients. The ratio of early transmitral flow to early diastolic velocity (E/e') was calculated as an estimate of LV filling pressure.
Data are expressed as the mean±SD or number and percentage. Continuous variables were compared between groups with the unpaired t test (variables with normal distribution). Proportions were compared using the χ2 test and Fisher's exact test. A univariate Cox proportional hazards analysis was performed to investigate the significance of a number of relevant variables for predicting outcome (table 3). Variables that might be associated with outcome (ie, with a p value <0.10) were inserted into a multivariate Cox regression model to identify independent predictors of cardiovascular death and heart failure hospitalisation. The output of this analysis is expressed as HRs with 95% CIs. Continuous variables were categorised according to cut-off values defined by receiver operating characteristic curves. Cumulative event curves were obtained by using the Kaplan–Meier method. A p value of <0.05 was considered significant. We used the SPSS V.18.0 as statistical software.
Interobserver variability was tested for TDI parameters (s', e', E/e') in 40 randomly selected patients and was found to be non-significant: κ value 0.96.
Table 1 shows the clinical characteristics of the study population. A majority of the patients had ischaemic cardiomyopathy (defined by previous myocardial infarction, documented coronary disease either by angiography, or non-invasively). About one-fifth had atrial fibrillation. Table 2 shows the results of the echocardiographic examination at entry to the study. The patients were followed for a median of 829 days (15–1884 days). During the follow-up period 43 patients (28%) died from cardiovascular causes and 55 patients (35%) were hospitalised due to decompensated heart failure. Since only the first event was counted, 80 patients (51%) reached the study endpoint. The results of the univariate Cox proportional hazards analysis are shown in table 3. Age, left bundle branch block, ischaemic aetiology, duration of heart failure, left ventricular end-diastolic diameter, E/e' and TDI parameters of the right ventricle were possible predictors of cardiovascular events. In the multivariate Cox proportional hazard analysis, only age and the combined systolic and diastolic velocities of the tricuspid annulus (S'r+E'r) were independent predictors (table 4). In the group with S'r+E'r <18.5 cm/s 63% of patients (n=41) reached the study endpoint compared to 34% of patients (n=29) in the S'r+E'r >18.5 cm/s group. Kaplan-Meier analysis showed a significantly (p=0.008) worse long term prognosis for the patients with low S'r+E'r (figure 1). This cut-off value indicated a risk for cardiovascular death or hospitalisation with a sensitivity of 57% and a specificity of 68%. When cardiovascular mortality was analysed separately, none of the variables came out as independent predictors (tables 5 and 6).
Our study shows that a combined systolic and diastolic TDI parameter of the right ventricle is an independent predictor of cardiovascular outcome in patients with LV systolic heart failure. This is not surprising since in a population where all have systolic impairment; LVEF cannot be the great prognosis predictor. Therefore, the answer lies in other factors, such as diastolic function, left-sided filling pressures, and RV function. Some studies have previously shown that TDI parameters of the right ventricle are of prognostic importance,12–16 but they have all excluded patients with atrial fibrillation and the follow-up period was rather short. Atrial fibrillation is a very common disorder that coexists with heart failure, and it is of great clinical importance to include these patients in prognostic studies. In the present study approximately one-fifth of the patients had atrial fibrillation at the time of inclusion. This subgroup is not big enough to extrapolate the results of this study to all patients with atrial fibrillation. Nevertheless, it is an important principle to have a study population that resembles that seen in clinical reality.
Surprisingly, the estimation of left-sided filling pressure, E/e', did not emerge as an independent predictor of cardiovascular outcome in this study. There are at present numerous reports showing the opposite, including a study from our group.6 There might be several possible explanations for this. It is possible that there is a lack of power in our study, something that is contradicted by the high event rate. It might also be so that the timing of the recordings are too close to the acute episode of decompensation in some patients, and therefore diluting the prognostic power of E/e' by reflecting a transient state of decompensation. Another possible explanation is that RV function is a better predictor of long term outcome than E/e'. It could be the case that elevated left heart filling pressure is a more transient state than RV dysfunction, and that the latter reflects a more advanced stage of the same disease. This, of course, has to be studied in more detail in other studies. Nevertheless, LV E/e' will continue to be an important marker for symptoms and prognosis in patients with several different cardiac conditions.
Implications and strengths
The implications of this study are that the assessment of RV systolic and diastolic function should be included in patients with LV systolic dysfunction, and that TDI is an excellent method for doing this. The strengths of our study are the robust methodology, the long follow-up and the fact that it reflects a common population with systolic heart failure, including patients with atrial fibrillation.
The lack of invasive measurement is a limitation for scientific reasons. In the clinical context, only a small portion of this population would have had an indication for catheterisation. The patients have not been followed clinically throughout the study, and we lack data about changes in medication, receiving a cardiac resynchronisation therapy or implantable cardioverter defibrillator and newly diagnosed comorbidities, which could be confounding factors. The timing of the recordings could have been too close to the acute episode of decompensation in a few patients, and this may have affected the results of the study.
Assessment of RV function in patients with LV systolic heart failure is important. A combined measure of RV systolic and diastolic function, using TDI, can be used as an independent predictor for long term outcome in a common population with systolic heart failure.
The authors thank Eva Andersson and Johan Wardell for their valuable technical help.
Funding This study was partly supported by a grant of Stockholms läns landsting (ALF medicine).
Competing interests None.
Patient consent Obtained.
Ethics approval Regional Committee of Research Ethics, Stockholm.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The raw material, such as tissue Doppler imaging recordings, Excel and Predictive Analytics SoftWare (version 18.0) files are available on request by researchers, but will be changed before sharing to avoid identification of individual patients.