Evaluation of left ventricular filling pressure using doppler echocardiography in severe heart failure patients with reduced ejection fraction – Le Thi Bich Van

Journal of military pharmaco-medicine n 0 8-2018 137 EVALUATION OF LEFT VENTRICULAR FILLING PRESSURE USING DOPPLER ECHOCARDIOGRAPHY IN SEVERE HEART FAILURE PATIENTS WITH REDUCED EJECTION FRACTION Le Thi Bich Van1; Pham Nguyen Vinh2 SUMMARY Objectives: To estimate left ventricular filling pressure using Doppler echocardiography according to American Society of Echocardiography guidelines in NYHA classes III - IV heart failure patients with an ejection fraction ≤ 40%. Subjects and methods: A descriptive cross- sectional study on 101 patients with NYHA class III - IV severe chronic heart failure with an ejection fraction ≤ 40%, from April 2016 to June 2018 at Hochiminh City Heart Institute. Left ventricular filling pressure was estimated using 5 Doppler echocardiographic parameters, including peak E-wave velocity, mean E/A ratio, mean E/e’ ratio, mean peak tricuspid regurgitation velocity and mean left atrial volume index. Results: We have identified 83 patients (82.2%) with elevated left ventricular filling pressure and 18 patients with normal left ventricular filling pressure (17.8%). Peak E-wave velocity = 86.7 ± 27.2 cm/s; mean E/A ratio = 1.99 ± 1.18; mean E/e’ ratio = 14.2 ± 5.9; peak tricuspid regurgitation velocity > 2.8 m/s (62.4%) and mean (left atrial) volume index > 34 mL/m 2 (96%). We recognized that an E-wave deceleration time ≤ 125 ms, which accounted for over 50% (52.4%) of patients in the ejection fraction ≤ 30% and was statistically higher than 30% of patients having ejection fraction ≤ 40% (28.9%) (p = 0.02). Only 41.6% of patients had mean E/e’ ratio > 14, while 82.2% of patients were shown to have elevated left ventricular filling pressure after integrating 5 echocardiographic parameters. Diastolic dysfunction grade I, II and III group each accounted for 17.8%, 37.6% and 44.6% of patients, respectively. As for the left ventricular filling pressure group, more than half of them (54.2%) had diastolic dysfunction grade III. Conclusion: By integrating these 5 parameters, the chance of missing elevated left ventricular filling pressure patients will be lowered by half, which would be otherwise undetectable if only E/e’ ratio was used. * Key words: Heart failure; Left ventricular filling pressure; Diastolic dysfunction. INTRODUCTION Clinical assessment of left ventricular filling pressure (LVFP) is not only essential for effective medical management of heart failure patients, especially in severe cases, but also important in selecting treatment methods and titrating individualized diuretic, vasopressor and inotropic dosage to relieve symptoms and avoid late complications such as renal failure, hypotension, fluid and electrolyte disturbances which can increase mortality rate. Moreover, it can prevent invasive and unnecessary procedures such as central venous catheterization and the use of pulmonary arterial wedge pressure. 1. Columbia Asia Hospital Binhduong 2. Tam Duc Heart Hospital, Pham Ngoc Thach University of Medicine Corresponding author: Le Thi Bich Van (bvanlevt@yahoo.com) Date received: 02/08/2018 Date accepted: 20/09/2018 Journal of military pharmaco-medicine n 0 8-2018 138 However, when LVFP can’t be measured reliably in 50% of cases on clinical settings [1], Doppler echocardiography is the most powerful tool in these cases. Doppler echocardiography surpasses clinical evaluation in accuracy and can determine LVFP 1.5 times more accurate when both are combined [2]. LVFP is considered elevated when PAWP > 12 mmHg or left ventricular end-diastolic pressure > 16 mmHg [3], both of which can change the following Doppler echocardiographic parameters and in turn are used to determine LVFP: peak E-wave velocity, E/A ratio, E/e’ ratio, peak tricuspid regurgitation velocity (TRV), left atrial (LA) volume index as per 2016 American Society of Echocardiography (ASE) Guidelines [4]. Therefore we decided to conduct this study: To investigate several Doppler echocardiographic parameters and its integration in estimating LVFP including peak E-wave velocity, mean E/A ratio, mean E/e’ ratio, mean peak TRV, mean LA volume index in NYHA classes III - IV heart failure patients with an EF ≤ 40%. SUBJECTS AND METHODS 1. Subjects. We enrolled 101 inpatients with NYHA classes III - IV with an EF ≤ 40% (EF = 27.2 ± 8.2%) at Hochiminh Heart Institute, in which 65.3% and 34.7% of them were males and females, respectively, having an average age of 62 ± 15, from April 2016 to June 2018. * Inclusion criteria: Heart failure with reduced left-ventricular systolic function based on 2016 European Society of Cardiology’s (ESC) recommendations. Heart failure classes III - IV were categorized based on the New York Heart Association (NYHA) Functional Classification. 2. Methods. Descriptive cross-sectional study. Data collection: We’ve collected personal information, NYHA classes III - IV heart failure with EF ≤ 40% diagnoses, and 5 Doppler echocardiographic parameters including E wave, E/A ratio, E/e’ ratio, TRV, LA which are measured using Philips HD XE ultrasound imaging system and 3.5 MHz probe. * Statistical analyses: Our data is entered in Epi. Data version 3.1 and then analyzed using Stata version 14.2. RESULTS AND DISCUSSION 1. Characteristics of several Doppler echocardiographic parameters used to estimate LVFP. Over the last few years, the clinical and pathophysiological importance of the mitral inflow pattern comprising the E-wave and A-wave measured by echocardiography has been studied thoroughly. Table 1: Characteristics of several parameters used to estimate LVFP on Doppler echocardiography. Characteristics n = 101 (M ± SD) E (cm/s) 86.7 ± 27.2 E/A 1.99 ± 1.18 EDT (ms) 143 ± 72 PAPs (mmHg) 36.0 ± 11.8 Mean E/e’ 14.2 ± 5.9 Septal E/e' 18.1 ± 7.1 Lateral E/e' 12.5 ± 6.3 TRV (m/s) 2.96 ± 0.49 Journal of military pharmaco-medicine n 0 8-2018 139 The onset of E-wave on Doppler echocardiography reflects the end of isovolumetric relaxation period and the beginning of mitral valve opening, which occurs when the LA pressure is greater than that of LV and thereby increases the mitral flow; when the opposite happens, the mitral flow will decrease. Therefore alterations in LV end-systolic and/or end- diastolic volume, elastic recoil and/or diastolic pressure will all directly affect the E-wave velocity. The A-wave velocity indicates the LA-LV pressure gradient during late diastole, which is affected by the LV compliance and LA contractile function. Our study had an E/A ratio > 1.5, which concured with many others such as Dokainish (1.66 ± 0.82) [5] and Hansen’s (1.9 ± 1.6) findings [6]. E-wave deceleration time (EDT) iwa influenced by LV relaxation, LV diastolic pressure after mitral valve opening, LV compliance and therefore it demonstrated the correlation between LV pressure and volume. The shorter EDT was, the shorter the LV filling time will be and a shortened EDT ≤ 125 ms was strictly correlated with increased mortality risk and need of heart transplantation. Table 2: EDT characteristics in patients categorized according to EF. EDT EF > 30% n (%) EF ≤ 30% n (%) Overall n (%) p > 125 ms 27 (71.1) 30 (47.6) 57 (56.4) 0.02 ≤ 125 ms 11 (28.9) 33 (52.4) 44 (43.6) EDT (M ± SD) 160.2 ± 66.2 132.1 ± 73.0 142.7 ± 71.5 0.06 We recognized that an E-wave deceleration time ≤ 125 ms, which accounted for over 50% (52.4%) of patients in the EF ≤ 30% group and was statistically higher than 30% of patients having EF ≤ 40% (p = 0.02). The EDT in our study was 143 ± 72 (ms), lower than that of Rihal’s (172 ± 66 ms) [7] and higher than that of Pinamonti’s (134.9 ± 18.9 ms) [8]. Table 3: Characteristics of E/e’ ratio, TRV and LA. Doppler n = 101 Percentage % Mean E/e’ > 14 42 41.6 Mean E/e’ ≤ 14 59 58.4 TRV > 2.8 m/s 63 62.4 TRV ≤ 2.8 m/s 38 37.6 LA > 34 mL/m 2 97 96 LA ≤ 34 mL/m 2 4 4 Mean E/e’ > 14 was one of the basic and non-invasive parameters that indicated the presence of an elevated LVFP. This ratio was more significant in predicting a patient’s prognosis and the existence of an elevated LVFP than several single tissue Doppler imaging parameters (e.g. e’ wave), other conventional echocardiographic parameters and pulmonary vein inflow. Pulmonary arterial pressure (PAP) is considered elevated when mean PAP > 25 mmHg measured at rest by cardiac catheterization. Based on pulmonary artery systolic pressure (PAPs) calculations from TR (PAPs = 4 x TR x TR) by means of Doppler echocardiography, PAP was considered elevated when PAPs > 35 mmHg, which was equivalent to a Journal of military pharmaco-medicine n 0 8-2018 140 TR > 2.8 m/s. In our study, we successfully measured TR in 100% of our patients, in which 62.4% had peak TRV > 2.8 m/s, while none had TR > 2.8 m/s in the control group; also mean PAPs in the diseased group was 2.96 ± 0.49 m/s, which agreed with the findings of the study by Dokainish [5] and they also showed that TR and PAPs were elevated in patients with heart failure with reduced EF. Left atrial hypertrophy (LAH) is associated with poor cardiac prognosis. Several etiologies of LAH include LV systolic- diastolic dysfunction as well as atrial fibrillation. LA size seems to reflect LVFP and may be caused by accumulation of diastolic dysfunction over time. Of the study population, 96% of the diseased group had LA volume > 34 mL/m2, which were also compatible with the findings of a dilated left atrium in heart failure patients in the study by Hansen [6]. 2. Estimated LVFP and diastolic function. Treatment efficacy in severe heart failure depends greatly on dose titration in a way that preload, afterload, LV systolic- diastolic function must all be balanced to maintain a suitable cardiac output. LVFP is not only an important factor that helps titrate dosage, but it also varies over time and changes according to treatment response. Echocardiography is an imaging modality of paramount importance in assessing LVFP. Recently, guidelines for LVFP evaluation by echocardiography based on experts’ consensus, are published together with ASE/EAE guidelines and proven to be exact using invasive LVFP measurement, which indicates the fact that LVFP evaluation by echocardiography is easily accessible, feasible and highly accurate. In this study, estimating LVFP was done by integrating echocardiographic parameters based on 2016 ASE clinical practice guidelines in NYHA classes III - IV heart failure patients with an EF ≤ 40%, in which there were 83 patients (82.2%) diagnosed with elevated LVFP and 18 patients (17.8%) with normal LVFP. The following table illustrates the LVFP and diastolic dysfunction group. Table 4: Characteristics of LVFP and diastolic dysfunction. Left ventricular filling pressure n = 101 Percentage % Elevated LVFP 83 82.2 Non-elevated LVFP 18 17.8 Diastolic dysfunction grade I 18 17.8 Diastolic dysfunction grade II 38 37.6 Diastolic dysfunction grade III 45 44.6 17.8%, 37.6% and 44.6% of the diseased group had diastolic dysfunction grade I, II and III, respectively. * Percentage of patients with diastolic dysfunction in the elevated LVFP group: As for the elevated LVFP group, 45.8% and 54.2% of patients had diastolic dysfunction grade II and grade III, respectively, no patient with diastolic dysfunction grade I. Journal of military pharmaco-medicine n 0 8-2018 141 CONCLUSIONS Of the study population, only 41.6% of our patients had mean E/e’ ratio > 14, while 82.2% of patients were shown to have elevated LVFP after integrating 5 echocardiographic parameters. Therefore, E/e’ ratio > 14 had limited usage in predicting elevated LVFP and will miss half of the cases. REFERENCES 1. Owan T.E, Hodge D.O, Herges R.M et al. 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