|Year : 2019 | Volume
| Issue : 3 | Page : 141-149
Prognostic Significance of Right Ventricular Ejection Fraction Assessed by Two-Dimensional Echocardiography in Hospitalized Patients with Dilated Cardiomyopathy
G. Ravi Kiran, Ch. Sarath Chandra, P. Chandrasekhar, Mohammed Ali
Department of Cardiology, Government General Hospital, Kurnool, Andhra Pradesh, India
|Date of Submission||30-Aug-2018|
|Date of Decision||27-Sep-2018|
|Date of Acceptance||25-Oct-2018|
|Date of Web Publication||18-Dec-2019|
G. Ravi Kiran
Room No. 52, Department of Cardiology, Government General Hospital, PG Quarters, Budhwarpet Road, Kurnool, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: The aim of this study was to evaluate the prognostic significance of two-dimensional transthoracic echocardiography right ventricle ejection fraction (2D-TTE-RV-EF) calculated using 2D-TTE and compare the results with conventional RV function parameters such as tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (RV-FAC) in hospitalized dilated cardiomyopathy (DCMP) patients. Methods: This is a prospective, observational study that includes 122 DCMP patients. RV was modeled as a part of an ellipsoid enabling calculation of RV volume by combining three echo measurements. RVEF is then calculated (2D-TTE-RV-EF). P < 0.05 is considered statistically significant, and multivariate logistic regression analysis was done to determine the predictors of inhospital outcomes. Results: The mean age of study population was 51.2 ± 9.2 years with male: female ratio of 1.8:1. Mean value of LV-EF (Simpson biplane model) and 2D-TTE-RV-EF (ellipsoid model) was 33.6% ± 7.1% and 38.1% ± 11.2%, respectively. About 41 (33.6%) patients experienced inhospital major adverse cardiac events (MACE). In multivariate regression analysis, New York Heart Association class III or IV status, reduced LV-EF, reduced 2D-TTE-RV-EF, and cardiogenic shock at presentation were found to be independent predictors of in MACE. Analysis of receiver operator characteristic curve demonstrated that the optimal cutoff value of 2D-TTE-RV-EF for predicting inhospital MACE was 32.8%. Conclusion: Quantitative assessment of RV function with 2D-TTE-RV-EF improves the risk stratification beyond provided by LV-EF; the prognostic value may be better than that provided by TAPSE and RV-FAC.
Keywords: Dilated cardiomyopathy, ellipsoid model, right ventricular ejection fraction, right ventricular fractional area change, right ventricular function, tricuspid annular plane systolic excursion
|How to cite this article:|
Kiran GR, Chandra CS, Chandrasekhar P, Ali M. Prognostic Significance of Right Ventricular Ejection Fraction Assessed by Two-Dimensional Echocardiography in Hospitalized Patients with Dilated Cardiomyopathy. J Indian Acad Echocardiogr Cardiovasc Imaging 2019;3:141-9
|How to cite this URL:|
Kiran GR, Chandra CS, Chandrasekhar P, Ali M. Prognostic Significance of Right Ventricular Ejection Fraction Assessed by Two-Dimensional Echocardiography in Hospitalized Patients with Dilated Cardiomyopathy. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2019 [cited 2020 May 29];3:141-9. Available from: http://www.jiaecho.org/text.asp?2019/3/3/141/273295
| Introduction|| |
Dilated cardiomyopathy (DCMP) is a frequent cause of heart failure (HF). Despite recent advances in treatment of HF, prognostic markers remain uncertain from one patient to another.,, The prognostic significance of right ventricular (RV) function is not well studied as robustly as left ventricular (LV) function,,,,, (LV ejection fraction [LVEF] and new variables of myocardial deformation) on outcome in HF, and one strong probable reason for this is the challenging nature of echocardiographic evaluation of RV performance in routine practice.,, The complex shape of the RV makes its function more challenging to assess as compared to the left ventricle, by transthoracic echocardiography (TTE).
Cardiac magnetic resonance (CMR) imaging is considered to be the gold standard for the evaluation of RV function, and RVEF is used as a measure of RV function. However, two-dimensional (2D)-TTE due to its easy availability and versatility is used often for evaluation of RV function. At present, 3-dimensional echocardiography for evaluation of RV function is still at its incipient stage and is only used in centers having good experience with this imaging modality. RV strain is a novel technique that enables direct quantification of myocardial deformation and is a sensitive tool to detect RV dysfunction. However, limited availability, less versatility, intervendor variability limits its quantification, even the cutoffs are too unreliable to be applied universally. Traditional 2D-TTE measures of RV function such as tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging (TDI) of tricuspid annulus, which rely predominantly on assessing the RV free wall function, may not fully assess the RV function in failing LV. There are contradictory conclusions in the literature on how well 2D-TTE-derived TAPSE correlates to CMR-derived RVEF. There are examples where the correlation between TAPSE and RVEF varies from no correlation, to statistically significant correlation.,, This discordant data on TASPE was to some extent answered by another 2D parameter fractional area change (FAC). A challenge when using TTE for RV evaluation is the position of the RV behind the sternum. When imaging the RV in apical four-chamber (4CH) view shadows from rib, sternum sometimes causes difficulty in imaging RV apical parts. Thus, limiting the FAC estimation in some patients, in addition, its estimation has high interobserver variability and does not take into account the contribution of RVOT in estimation of RV function. Thus, there is a practical unmet need for an echocardiographic variable which is easy, versatile, and rapid and does not need the entire visualization of RV for evaluation of its function.
Very recently, a novel study has described a method of estimation of RVEF from 2D-TTE in healthy adults, where the RV is approximated by an ellipsoid composed of three distances, which are easily measured by 2D-TTE. This method does not need entire visualization of RV, which was a main hindrance for routine application of RV FAC. The results from that study showed that the ellipsoid model underestimates RV volumes compared to reference CMR-derived RV volumes, but there was a good agreement between the ellipsoid model-derived RVEF and RVEF obtained from CMR, because RVEF is calculated as a fraction; thus, RVEF can be estimated accurately even though the volumes are underestimated., To our knowledge, there was no study that documented in literature about prognostic value of 2D-TTE-derived RVEF in any cardiac or pulmonary disease. The main aim of our study was to determine the inhospital prognostic significance of RVEF calculated by 2D-TTE in hospitalized DCMP patients and compare its performance with other echocardiographic variables of RV function.
| Methods|| |
This is a prospective observational study that included patients who had been diagnosed with DCMP and were treated at Kurnool General Hospital (GGH, Kurnool). This is a busy government-run tertiary care institution with nonselective intake of cardiac patients. This study was carried over a period of 3 months (from February 2, 2018, to April 20, 2018).
This study did not alter the standard care given to the patients in the hospital. The study was approved by the Institutional Ethics Review Committee. DCMP is characterized by dilation and impaired contraction of one or both ventricles, and affected patients have impaired systolic function and may or may not develop overt HF. Dilation is defined as above upper limit of normative values for South Asians, i.e., 146.47–0.8888 × age (ml) or 65.90–0.2863 × age (ml/m2), and impaired contraction is defined as LVEF <45% by modified Simpson biplane method, [Appendix]. As this is an observational study on critically ill patients which involves no intervention, consent was not taken.
- Diagnosed as having DCMP during the study period.
- Known heart diseases which are known to affect RV function such as history of valvular heart disease or pulmonary thromboembolism
- Known pulmonary diseases which cause pressure overload on RV thus may affect the RV function assessment such as obstructive airway diseases, pulmonary tuberculosis, and spinal deformities
- Full inhospital data not available
- Suboptimal 2D echocardiographic image for proper data acquisition and analysis
- Does not fit into study definition for DCMP.
Assessment with history, physical examination, and anthropometric measurements were made. Biochemical investigations, electrocardiogram (ECG) and 2D-TTE, were performed for every patient included in the study. All the patients were evaluated serially throughout their hospital course to identify complications such as need of inotropic support and/or ventilator support, death, and ventricular and atrial arrhythmias.
Echocardiographic data acquisition
All the participants were examined by 2D-TTE and performed using Philips CX50 and IE33 (Philips Medical Systems, Andover, MA, USA). The examinations were carried out as in clinical routine, with the participants in the left lateral recumbent position using a 5.1-MHz transducer. The 2D-TTE parameter “acquisition” was in accordance with the American Society of Echocardiography guidelines.
In short, the ellipsoid model represents the RV by an ellipsoid, whose volume can be measured using three echocardiographic measurements available in TTE images, i.e., RV inflow tract (RVIT3), RV long axis (RVLAX), and the LV maximum outer basal diameter (LVD). The RV volume (RVV) is then approximated as: RVV = π/6 × RVIT3 × RVLAX × LVD [Appendix and [Figure 1]. RVIT and RVLAX were measured in apical 4CH view (should be focused on the RV), while LVD was measured in apical 2-chamber view (2CH) view. Using this estimate of the RVV, for both diastolic and systolic measurements, RVEF can then be calculated: 100 × (RVEDV − RVESV)/RVEDV % (where RVEDV is RV end diastolic volume and RVESV is RV end systolic volume).
|Figure 1: Two-dimensional transthoracic echocardiography distances used for two-dimensional ejection fraction calculation. (a) Left ventricular basal diameter. (b) Right ventricular long axis length. (c) Right ventricular inflow tract diameter. LV: Left ventricle, LA: Left atrium, RV: Right ventricle, RA: Right atrium, RVIT: Right ventricular inflow tract, TAD: Tricuspid annulus diameter, RVLAX: Right ventricular long axis length, LVD: Left ventricular diameter|
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In addition, other measures of RV function such as RVFAC and TAPSE were analyzed. All TTE measurements were calculated as the average of three cardiac cycles. TTE measurements were measured at index admission. To measure interobserver variability, every 5th patient echocardiogram was performed by another independent clinician who was blinded to the study.
The primary endpoint of the present study was incidence of inhospital major adverse cardiac events (MACE), which is a composite of inhospital death, need for inotropic/vasopressor support, need for ventilator support of any form, up-titrating the decongestive therapy, tachyarrhythmias, namely atrial fibrillation (AF), ventricular tachycardia, and ventricular fibrillation that are apparent clinically. The secondary endpoints were duration of intensive cardiac care unit (ICCU) stay, inhospital stay, and repeated ICCU admissions.
Statistical analyses were performed using Medcalc® (V.16.8.4) for Windows, by MedCalc software (https://www.medcalc.org/) and Microsoft Excel 2007 for Windows by Microsoft Cooperation. Categorical and numerical variables were expressed in percentage and mean (±standard deviation), respectively. Numerical variables were tested with independent samples t-test, and categorical variables were tested using Chi-square test. Multivariate logistic regression analysis was performed to determine the predictors of inhospital outcomes. This analysis included variables with statistical significance in the univariate logistic regression analysis and those with a known clinical impact. The statistical significance was considered for a P < 0.05. Receiver operator characteristic (ROC) curves were computed for 2D-TTE RV function indices to assess the optimal cutoff value to predict inhospital outcomes. The optimal cutoff value was defined as the value yielding maximal Youden index (Yi = b [sensitivity] + [specificity] −1). Pearson's R was used to test the correlation between observers, and intraclass correlation coefficients (ICCs) were used to measure interobserver variability. To remove bias, data was analyzed by a statistician who was otherwise not involved in the study. Pearson product moment correlation methods for correlation between continuous data and dummy-variable regression analysis for correlation between numerical and categorical data were used.
| Results|| |
Demographic and baseline characteristics
Two hundred and thirteen patients were admitted with a diagnosis of DCMP and treated in our hospital during this study period, and after considering inclusion and exclusion criteria, 122 patients were included in the study and 91 patients were excluded from the study. The age of patients ranged from 28 to 84 years with a mean age of 51.2 ± 9.2 years. There was a male dominance with 78 patients being male (64%) with male: female ratio of 1.8:1 [Table 1] and [Table 2].
Clinical, biochemical, and electrocardiographic features
One hundred and fourteen (93.4%) patients presented with chief complaint of breathlessness. Thirty-eight (31.1%) patients were de novo detected as DCMP and remaining patients (84) were previously diagnosed as DCMP patients (of which alarmingly 58 [69%] patients were drug noncompliant at presentation). About 56 (46%) patients were presumed to be idiopathic and 38% (46) of patients were diagnosed as having ischemic cardiomyopathy (ICMP: based on the history, ECG, and 2D-TTE features) [Table 3], [Table 4], [Table 5]. Treatment received by study population is shown in [Table 6].
Mean serum creatinine was 1.1 ± 0.2 mg/dl, hemoglobin 10.2 ± 1.1 g/dl, and 25 patients had hyponatremia (Serum sodium <135 mmol/l) on index day investigations. At admission ECG, 26 (21.3%) patients had left bundle branch block (LBBB), 14 (11.5%) patients had right bundle branch block (RBBB), 47 patients had left ventricular hypertrophy (LVH) (38.5%), and 43 (35.2%) patients had left atrial dilatation.
Echocardiographic right ventricle data
Mean value of TAPSE was 16 ± 4.2 mm (ranging from 5 to 25.2 mm) and of RV FAC was 42.1% ± 6.3% (ranging from 10% to 65%), and TTE-RV-EF (2D ellipsoid) was 44.7% ± 8.2% (ranges from 18.1% to 57.3%). Among the study population, 34 patients had severe TR (27.9%) [Table 7]. The interobserver coefficient of variation (COV) in calculating 2D-TTE-RV-EF was 8.1% (95% confidence interval [CI]: 2.0%–3.3%), and correlation between 2D-TTE-RV-EF obs1 and 2DTTE-RV-EF obs2 was high r = 0.80 (P < 0.01). ICC between observers for 2D-TTE-RV-EF was very good (0.87; 95% CI: 0.76–0.93). Mean value of 2D-TTE-derived RV-EF in study population was 38.1% ± 11.2% (ranges from 15% to 54%).
Echocardiographic left ventricle data
Mean LVEF (biplane Simpson) was found to be 35.6% ± 5.1% (ranges from 16% to 44%). Severe mitral regurgitation (MR) was found in 29 patients [Table 8]. The interobserver COV in calculating 2D-TTE-RV-EF was 10.2% (95% CI: 4.1%–5.9%), and correlation between LVEF (Simpson) obs2 and LVEF (Simpson) obs2 was good r = 0.71 (P < 0.05). ICC between observers was good (0.80; 95% CI: 0.70–0.86).
In-hospital major adverse cardiac events
During hospitalization, 41 (33.6%) patients experienced MACE, requiring inotropic/vasopressor support as most common adverse event (24.6%) and notably 11 patients experienced clinically apparent sustained arrhythmias (AF as most common arrhythmia). The inhospital all-cause mortality was 5% (n = 6) [Table 9].
|Table 9: Frequency of inhospital major adverse cardiac events in study population|
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Mean duration of ICCU stay was 0.9 ± 0.5 days [Appendix], and inhospital stay was 3.1 ± 0.6 days. About 11 (9%) patients needed repeated (more than 1) ICCU admissions [Table 10].
Univariate logistic regression analysis showed a significant association between composite endpoint and patients with the New York Heart Association (NYHA) III and IV, systolic blood pressure, RVFAC, 2D-TTE-RV-EF, LV-EDV, LVEF, severe MR, and cardiogenic shock at presentation. However, in multivariate logistic regression analysis, there was a significant association between presence NYHA III or IV at presentation, reduced LVEF, reduced 2DTTE-RV-EF, and cardiogenic shock at presentation and inhospital MACE [Table 11]. It is notable that though RV FAC was associated with increased risk of MACE, in univariate analysis but not in multivariate analysis. This novel parameter RV-EF ratio was associated with increased risk of MACE (area under receiver operating characteristic - AUROC curve: 0.82, 95% CI: 0.72–0.88, P < 0.05) and 2D-RV-EF of 32.8% was found to be of optimal cutoff (sensitivity = 87.2% and specificity = 83.1%) for inhospital MACE [Figure 2]. Analysis showed that cardiogenic shock is the only predictor (P < 0.05) of prolonged ICCU and inhospital stay. NYHA III or IV is the only predictor (odds ratio: 2.66, 95% CI: 1.78–3.11, P = 0.041) of re-admission in our study population [Table 12].
|Table 11: Logistic regression analysis for composite endpoint of inhospital major adverse cardiac events|
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|Figure 2: Area under the receiver operating characteristic curve showing performance of two-dimensional trans-thoracic echocardiography right ventricular ejection fraction is prediction of inhospital major adverse cardiac events in study (dilated cardiomyopathy) patients. AUROC: Area under the receiver operating curve, 2D RV EF: 2-dimensional right ventricular ejection fraction|
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| Discussion|| |
Reduced 2D-TTE-RV-EF was found to be an independent predictor of inhospital MACE in patients with DCMP of various etiologies; the prognostic significance of quantitative assessment of RV function by this method is above what provided by assessing LV function. We also found that this variable is statistically superior to traditional variables of RV function such as TAPSE and RVFAC in determining the prognosis of DCMP hospitalized patients with an optimal cutoff of 32.8%.
Determination of RV function is an important parameter in the assessment of prognosis in many congenital and acquired cardiovascular diseases. Prognostic impact of RV function in DCMP patients was documented in many studies. However, parameters used for evaluation of RV function were TAPSE, or RVFAC or TDI or 3D echocardiography CMR. Studies also show that regular assessment of RV function in DCMP patients helps in even better prognostication, and in fact, improvement of RV function precedes LV reverse remodeling. However, many of these studies had excluded the patients with suboptimal visualization of RV and thus may not have full applicability in real world; another drawback was these studies did not directly compare multiple variables of RV function to determine their relative superiority as prognostic indicators. Until today, there is no established method for measurement of RVV estimations (thus RV-EF) based on using 2D-TTE. Conventional 2D-TTE parameters of RV function do not completely evaluate its function, even latest method for RV evaluation by longitudinal speckle-tracking echocardiography (STE) strain enables quantification of the RV free wall which, compared to Doppler tissue imaging strain, is less angle dependent but the need for good image quality and full visualization of the RV free wall is still present and a well-known fact that RV longitudinal strain (RVLS) does not take into account the radial movement of the RV and that RV radial strain is difficult to measure by 2D-STE. Thus, this technique (at least at present) does not seem to add any extra value.
Our study is novel in three ways. First, this is the first study that evaluated the prognostic significance of 2D-TTE-RV-EF in any acquired heart disease, and also, we compared this novel variable with traditional variables such as TAPSE and RVFAC to determine its relative performance. Finally, treating doctor, principal investigator, second observer, and statistician were blinded, thus reducing the bias to maximum extent. Calculation of RV-EF includes combination of three conventional distance measurements in 2D-TTE which had shown a strong correlation with CMR in both normal and diseased heart. The distances can easily be measured in the 2D-TTE images and are not dependent on complete visualization of the RV free wall which remains an important obstacle in echocardiography for estimating TAPSE and RV FAC. The time for measuring these distances is, however, slightly time consuming than TAPSE but comparable to RV FAC, although it may be recognized that this method has relatively high applicability in this regard, since it does not require full visualization of the entire RV free wall. A note has to be made on 8% of patients excluded from the study because of suboptimal echo window; almost all of these patients were excluded due to inadequate visualization of the free wall which is prerequisite for calculation of TAPSE and RV FAC (in whom this new variable can be calculated easily). A recent study also pointed that there was no correlation between TAPSE and cardiac MRI; this indicates that the ellipsoid model provides a better estimate of global RV function compared to TAPSE.
Proposed RVEF calculation but not RV FAC was found to be independent predictor for inhospital MACE; this can be explainable because calculation of 2D-TTE-RV-EF involves assessing changes in three dimensions (X-axis [RVIT3], Y-axis [LVD], and Z-axis [RV-LAX]) whereas calculation of RV FAC involves assessing changes in two dimensions only (X-axis and Z-axis). Geometry of the LV is also important for reliability of this parameter, this is especially relevant in patients with ischemic origin of DCMP, i.e., in ischemic cardiomyopathy patients. In fact, subgroup analysis had found that this group of DCMP and RV-EF shows lesser correlation (AUROC = 0.71, P = 0.027) with inhospital MACE compared to remaining population (AUROC = 0.88, P = 0.0021). This is because this method of RV-EF calculation employs changes in LV basal diameter and ICMP patients with preserved basal segment contraction may lessen the reliability of this method of calculation. However, when ICMP population is considered as a whole the reliability of this method still holds good and shows statistically significant association with inhospital MACE. Furthermore, good interobserver agreement to this method adds additional value. All variables of RV performance including 2D-TTE-RV-EF failed to show any significant correlation with any of the secondary endpoints; the reason for this is not known and would be of interest in future studies. We found that cardiogenic shock is the only predictor of prolonged stay and NYHA III or IV at presentation is the only predictor of re-admission in our study population.
We believe that this new method of RV function evaluation by RVEF calculations using TTE may provide better prognostic information than other conventional RV function parameters. Studies correlating RV-EF-TTE and RV-EF-CMR in DCMP patients would be of interest for future studies.
The assumption of RV as a part of an ellipsoid is not a physiological method, even distances used in this model (RVIT3, RVLAX, and LVD) are not the actual radiuses of the ellipsoid, but these measures were selected to be used in the model because they have previously been defined and validated for calculation by ellipsoid method. Our study had five main limitations: first, this is a single-center study, and thus, the treatment decisions and discharge indications employed at our institute may not apply universally. Second, our sample is very small, and thus, though 10 predictors were identified in univariate analysis, only 4 variables were ultimately found to be associated with primary endpoint; this might be due to inadequate power. Another limitation is that among admitted patients with DCMP, only 58% of patients were included in the study which might affect the generalizability of study results. The fourth limitation was that the 2D-TTE-RV-EF in patients with DCMP was only calculated and no measurement in healthy participants was made. Thus, no information for comparison between these groups exists, which may be useful in future studies. Finally, intraobserver variation in calculation of this index is not evaluated which may have provided more insight into reproducibility of this new echocardiographic variable.
| Conclusion|| |
2D-TTE-RV-EF RV is a new, simple, versatile, easily reproducible parameter of RV function and is an independent predictor of inhospital MACE in hospitalized patients with DCMP. Quantitative assessment of RV function with RV-EF improves the risk stratification beyond provided by LV-EF, and an optimal cutoff of 32.8% was found to be an independent prognostic marker in this population. Importantly, it shows prognostic superiority over traditional variables of RV function such as TAPSE and RVFAC.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| Appendix|| |
| Upper Reference Values of Normal Left Ventricular Volumes|| |
LVEDV (M): 146.47–0.8888 (age).
LVESV (M): 62.97–0.4152 (age).
LVEDV (F): 97.59–0.3576 (age).
LVESV (F): 52.54–0.3583 (age).
(M: Males and F: Females).
| Ellipsoid Model|| |
The volume of a quarter of an ellipsoid, V1/4, can be calculated as:
Where a, b, and c (in X, Y, Z axis respectively) are the radiuses of the ellipsoid. i.e. [Figure 3] (Ellipsoid model) The volume of shaded region can be expressed as the difference between a quarter of the volume of the larger ellipsoid and a quarter of the volume of the smaller ellipsoid.
|Figure 3: (a) Ellipsoid model: Right ventricle is assumed geometrically as an ellipse warped around another ellipsoid (left ventricle). (b) Ellipsoid model: Right ventricular volume in shaded gray part. RVIT: Right ventricular inflow tract, RVLAX: Right ventricular long axis length, LVD: Left ventricular diameter|
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i.e.,: V-shaded part (approximately) = (a2-a1) ×
If a2-a1 is approximated by RVIT3, b approximated by LVD/2 and c approximated by RVLAX, an estimate of RVV is given [Table 1A].
RVV = π/6 × RVIT × RVLAX × LVD.
| Duration of Intensive Cardiac Care Unit Stay|| |
ICCU stay is calculated using 0.25 day, 0.5 day, and 0.75 day for patients transferred to step down unit or general ward within
6 h, 12 h, and more than 12 h (but <24 h) of ICCU admission, respectively.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12]