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Medical Technology SA Volume 25 No. 2 | December 2011 Peer reviewed ORIGINAL ARTICLE A COMPARATIVE DOPPLER-CATHETERIZATION STUDY OF THE LEFT VENTRICULAR END DIASTOLIC PRESSURE JK Adam1 (PhD Clinical Tecnology) | K Shein2 (FCP (SA), Certificate in Cardiology) | J Chetty2 (BTech) | WNS Rmaih1 (MBChB, MSc Pharmacology) 1 2 Durban University of Technology, Department of Biomedical and Clinical Technology, Durban, South Africa Inkosi Albert Luthuli Central Hospital, Department of Cardiology, Durban, South Africa. Corresponding author: WNS Rmaih | tel: +27 31 373 5291 | fax: +27 31 373 5295 | email: [email protected] Abstract Objectives To assess the correlation between the non-invasively measured ratio of early transmitral filling velocity to early diastolic mitral annular velocity (E/E’) and invasively measured left ventricular end diastolic pressure (LVEDP) in our context. Methods This is a prospective study of 66 patients (40 males and 26 females) who underwent elective coronary angiogram done at Inkosi Albert Luthuli Central Hospital. Transthoracic spectral Doppler and tissue Doppler echocardiography was performed to measure early diastolic transmitral flow velocities (E) and early diastolic medial and lateral mitral annular velocity (E’) respectively. LVEDP was directly measured during left ventriculography in a cardiac catheterization laboratory. Statistical analysis was done to compare E/E’ lateral and E/E’ medial to LVEDP in the study group and in different clinical subsets. Results Among 21 patients with E/E’ lateral and 27 patients with E/E’ medial of >8, 17 (81%) lateral group and 18 (67%) medial group had a LVEDP of >15mmHg, p value of 0.001 and 0.008 respectively. Raised E/E’ lateral ratio that is raised LVEDP was found in 90.9% of females, 52% in those with diabetes and 41.9% in those with hypertension which is statistically significant but not in smokers (30%) or those with dyslipidemia (31.3%) or a positive family history of premature coronary artery disease (20.5%). Conclusion This study confirmed that non-invasively measured E/E’ ratio correlates well with LVEDP in our study population. Keywords Early transmitral filling velocity, early diastolic mitral annular velocity, invasively measured left ventricular end diastolic pressure INTRODUCTION non-invasive means to assess the LVEDP is sought. Coronary artery disease (CAD) is the leading cause of cardiovascular mortality worldwide, with > 4.5 million deaths occurring in the developing world, and despite a recent decline in developed countries, both CAD mortality and the prevalence of CAD risk factors continue to rise rapidly in developing countries[1,2,3]. The evaluation and management of CAD in these countries needs to be addressed. Tissue Doppler Imaging (TDI) measures the velocity of myocardial motion using Doppler principles. While the usual Doppler echocardiography measures the velocity of blood flow using the Doppler signals from the fast moving blood cells, which are of low amplitude, tissue Doppler measures low velocity, high amplitude signals from the myocardial tissue motion[7]. The first changes of ischemia are metabolic and biochemical leading to impaired ventricular relaxation and diastolic dysfunction, impaired systolic function and Electrocardiographic (ECG) changes with ST segment changes, followed by increased end diastolic pressure with left ventricular dyssynchrony, hypokinesis, akinesis and dyskinesis and lastly painful symptoms of angina[4]. Myocardial perfusion imaging to detect metabolic and biochemical changes is not always feasible in acute settings[5]. Therefore diastolic dysfunction is one of the earliest manifestations that can be assessed for evidence of ischemia. Raised diastolic filling pressure of the left ventricle is a measure of left ventricular diastolic dysfunction[4]. Among the diastolic left ventricular filling pressure measurements, LVEDP is the only measurement routinely done during left ventriculography. LVEDP >16mmHg is one of the diagnostic criteria for LV diastolic dysfunction[6]. The role of assessing the LVEDP in the diagnosis of diastolic dysfunction and the degree of the ischemic burden cannot be over emphasized. Because of the invasively measured parameter, it cannot be done in routine clinical practice. Therefore a Doppler echocardiography is widely used for the noninvasive assessment of diastolic filling of the left ventricle (LV). Analysis of the mitral inflow velocity curve has provided useful information for determination of filling pressures and prediction of prognosis in selected patients. However, mitral flow is dependent on multiple interrelated factors, including the rate and extent of ventricular relaxation, suction, atrial and ventricular compliance, mitral valve inertance, and left atrial pressure. These factors may have confounding effects on the mitral inflow; thus, it has not been possible to determine diastolic function from the mitral flow velocity curves in many subsets of patients[8]. To overcome these limitations of the mitral inflow parameters, combinations of the mitral flow velocity curves with other Doppler parameters have been used. These include the pulmonary venous velocity curves, color M-mode, and the response of the mitral inflow to altered loading conditions. Tissue Doppler imaging (TDI) of mitral annular motion has been proposed to correct for the influence of myocardial relaxation on transmitral flows. This has been shown to be an excellent predictor of diastolic filling in subsets of patients[8]. The ratio of early peak transmitral diastolic velocity (E), a measISSN 1011 5528 | www.smltsa.org.za 17 Medical Technology SA Figure 1: Left ventricular end diastolic pressure ure of the early diastolic filling, and late peak diastolic transmitral flow velocity (A), a measure of an atrial contraction (E/A) is used to assess diastolic function. Under normal conditions, E is greater than A and the E/A ratio is approximately 1.5[6]. In early diastolic dysfunction, relaxation is impaired and, with vigorous atrial contraction, the E/A ratio decreases to less than 1.0. As the disease progresses, left ventricular compliance is reduced, which increases left atrial pressure and, in turn, increases early left ventricular filling despite impaired relaxation. This paradoxical normalization of the E/A ratio is called pseudonormalization. In patients with severe diastolic dysfunction, left ventricular filling occurs primarily in early diastole, creating an E/A ratio greater than 2.0. The E- and A-wave velocities are affected by blood volume, mitral valve anatomy, mitral valve function, and atrial fibrillation, making standard echocardiography less reliable[9]. In these cases, tissue Doppler imaging is useful for measuring mitral annular motion. The early diastolic velocity of the longitudinal motion of the mitral annulus (E’) reflects the rate of myocardial relaxation[10]. In normal subjects E’ increases as transmitral gradient increases with exertion or increased preload, whereas in patients with impaired myocardial relaxation E’ is reduced at baseline and does not increase as much as in normal subjects with increased preload[10]. The E’ increases with increasing transmitral gradient in healthy individuals, so that E/E’ is similar at rest and with exercise (usually <8). Decreased E’ is one of the earliest markers for diastolic dysfunction and is present in all stages of diastolic dysfunction[10]. Because E’ velocity remains reduced and mitral E velocity increases with higher filling pressure, the ratio between transmitral E velocity and mitral annular E’ velocity (E/E’), correlates well with LV filling pressure, LVEDP[7]. This study is done to determine the application of these findings in our context. Volume 25 No. 2 | December 2011 Figure 2: Early diastolic mitral inflow (E) and early diastolic myocardial annular velocity (E’) A. On transthoracic apical four-chamber view the cursor is placed across the tips of the mitral valve to obtain the early diastolic mitral inflow (E) and peak diastolic myocardial velocity during atrial contraction (A). B. On apical four chamber view the cursor is placed at the mitral annulus to obtain the peak early diastolic mitral annular tissue velocity (E’), and peak late (atrial contraction) diastolic myocardial tissue velocity (A’). Figure 3: Lateral and medial tissue Doppler measurements A. Transthoracic apical four-chamber view showing cursor placement for TDI measurement of lateral myocardial tissue velocity (arrow). B. Tissue Doppler myocardial velocities obtained at lateral mitral annulus: E’= peak early diastolic myocardial tissue velocity, A’= peak late (atrial contraction) diastolic myocardial tissue velocity, systolic = peak systolic myocardial tissue velocity. C. Transthoracic apical four-chamber view showing cursor placement for TDI measurement of medial myocardial tissue velocity (arrow). D. Tissue Doppler myocardial velocities obtained at medial mitral annulus. E’= peak early diastolic myocardial tissue velocity, A’= peak late (atrial contraction) diastolic myocardial tissue velocity, systolic = peak systolic myocardial tissue velocity. METHODS to all prospective participants and informed consent in English or Zulu was taken from all the participants. Ethical clearance was obtained from the institutional ethical committee. This is a prospective study of sixty six patients admitted at Inkosi Albert Luthuli Central Hospital for elective coronary angiogram during January 2008 to July 2008. Fourty (61%) males and 26 (39%) females. The ages range from 41 to 76 years with mean age of 56+11 (mean age ± SD). An information sheet was given Those with valvular heart disease, mechanical valvular prosthesis and patients with poor acoustic windows for transthoracic imaging were excluded. The participants underwent full physical examination, electrocardiogram (resting and/or exercise), chest X-ray, echocardiography or other non-invasive tests. 18 www.smltsa.org.za | ISSN 1011 5528 Medical Technology SA Volume 25 No. 2 | December 2011 LVEDP was directly measured during left ventriculography using a pressure transducer in a cardiac catheterization laboratory (Figure 1). the invasively measured LVEDP. E/E’ lateral for males, females and different clinical subsets of patients such as diabetes mellitus, hypertension, family history, smoking and hypercholesterolemia were also analyzed. Non-invasive echocardiographic measurements RESULTS The Acuson Sequoia echocardiography machine was used for the non-invasive measurements. With patients in the left lateral decubitis position, transthoracic 2-D and Doppler echocardiography was performed. Non-invasive E/E’ ratio vs. invasive LVEDP Invasive catheterization measurements In the apical four chamber view the pulse wave Doppler sample gate was placed across the mitral valve at its tips and the early transmitral filling velocity (E) was measured (Figure 2). Tissue Doppler peak early diastolic velocities were acquired at the medial (septal) and lateral annular sites of the left ventricle from the apical four chamber view (Figure 3). Thereafter the E/E’ ratios were calculated. SPSS version 16.0 (SPSS inc., Chicago, Illinois, USA) was used to analyse the data. Bar graphs were used to display the variables. The student t test, Chi-Square test, Independent samples test and cross tabulations was used to analyze the data. The Chi-Square test was used in determining the p value. Statistical significance was defined as p < 0.05. The non-invasively measured E/E’ medial and E/E’ lateral were then compared with The study showed 81% of the patients in the E/E’ lateral group had a p < 0.001 and 66.7% of the patients in the E/E’ medial group had a p < 0.008 (Figure 4 & 5). The sensitivity and specificity for the non-invasively measured E/E’ lateral was 55% and 81% and for E/E’ medial was 58% and 74% respectively with positive predictive value of 81% for E/E’ lateral and 67% for E/E’ medial. Lateral E/E’ was significantly higher in patients with LVEDP ≥ 15 mmHg. The correlation of the LVEDP with lateral annulus was equivalent or better than the medial annulus. Non-invasive E/E’ ratio vs. invasive LVEDP with regards to gender The E/E’ lateral which correlates with high LVEDP were found in 90.1% of females and 70% of males (Figure 6). The E/E’ medial which correlates with high LVEDP was found in 75% of females and 60% of males. The sensitivity and specificity for the noninvasively measured E/E’ lateral in females was 67% and Figure 4: Non-invasive E/E’ lateral ratio vs. Invasive LVEDP. Figure 5: Non-invasive E/E’ medial ratio vs. Invasive LVEDP. ISSN 1011 5528 | www.smltsa.org.za 19 Medical Technology SA Figure 6: Non-invasive E/E’ lateral ratio vs. invasive LVEDP with regards to gender. Figure 7: The correlation between diabetes mellitus (DM) and E/E’ lateral. Figure 8: The correlation between hypertension (Hpt) and E/E’ lateral. 20 www.smltsa.org.za | ISSN 1011 5528 Volume 25 No. 2 | December 2011 Medical Technology SA 91% and for E/E’ medial was 60% and 73% respectively with positive predictive value of 91% for E/E’ lateral and 75% for E/E’ medial. The sensitivity and specificity for the non-invasively measured E/E’ lateral in males was 44% and 88% and for E/E’ medial was 56% and 75% respectively with positive predictive value of 70% for E/E’ lateral and 60% for E/E’ medial. Non-invasive E/E’ ratio vs. invasive LVEDP with regards to anthropometric and clinical profiles Age, height, weight and body mass index (BMI) was not found to be associated with high LVEDP. Study 52% (13/21) of patients with DM and 41.9% (18/21) with Hypertension had a high E/E’ lateral ratio and high LVEDP which is statistically significant (Figure 7 & 8). Positive family history of premature coronary artery disease (20.5%), dyslipidemia (31.3%) and smokers (30%) were not found to be associated with high E/E’ ratio and LVEDP (Figure 9 & 10). DISCUSSION There is a correlation between the non-invasively measured E/E’ and the invasively measured LVEDP. High LVEDP was found in 81% of the patients in the E/E’ lateral > 8 group and 66.7% of the patients in the E/E’ medial >8 group. This is considered statistically significant for this population. European society of cardiology concensus statement, 2007[6], recommended that E/E’ ≤ 8 suggests normal filling pressure, > 15 is abnormal filling Volume 25 No. 2 | December 2011 pressure. Nagueh[8] et al also showed E/E’ lateral > 10 correlated with raised left ventricular (LV) filling pressures (LVEDP). Although a small sample size was used over a selected study period, the findings of this study indicate a trend that is comparable to other similar studies. This study also showed diastolic dysfunction and raised LVEDP more common in females than in males. Age, height, weight and body mass index (BMI) was not found to be associated with high LVEDP. Other studies have shown that the older age group (≥60 years)[11] and obesity are associated with a high LVEDP but not in this study. This can be explained by the younger age group in this study with a mean age of 56 ± 11 and exclusion of patients with poor acoustic windows who may be obese. It is well known and also identified in this study that diabetes mellitus (DM), hypertension (Hpt) and females are associated with diastolic dysfunction, that is raised LVEDP. Patients with traditional risk factors and higher LVEDP are at a greater risk for adverse cardiovascular outcome[1]. Therefore non-invasive tissue Doppler measurement of E/E’ can be used to risk stratify. Clinical risk factors such as family history, dyslipidemia and smoking were not found to be associated with high LVEDP. Therefore high LVEDP in these patients are possibly due to ischemia. Occlusive coronary artery disease was confirmed in 53 patients, while 13 patients had non-occlusive normal coronary arteries. Figure 9: The correlation between dyslipidemia (dyslipid) and E/E’ lateral. Figure 10: The correlation between non-smokers, current smokers, ex-smokers (Ex) and E/E’ lateral. ISSN 1011 5528 | www.smltsa.org.za 21 Medical Technology SA Volume 25 No. 2 | December 2011 LIMITATIONS CONCLUSIONS The number of cases selected in this study was small and limited to patients with coronary artery disease (53/66), especially in the Indian community. Therefore it cannot be extrapolated to other population groups and other clinical subsets such as valvular heart disease. Although E/E’ ratio can be easily measured, it is not easily performed on those with poor acoustic window such as patients who are obese, have crowded ribs, scars on the anterior chest wall and those with chronic obstructive airway disease. Tissue Doppler also requires proper alignment of the sample gate. The influence of regional wall motion abnormality on the mitral annulus movement is still unknown, therefore we cannot exclude that it could have affected E/E’ ratio. The trend /observations developed in this study suggests that non-invasively measured E/E’ ratio correlates well with high LVEDP in our study population. Therefore it may be used to estimate the LVEDP in routine clinical practice, which in turn provides information regarding diastolic function and severity of CAD. E/E’ lateral > 8 correlates with raised LVEDP > 15mmHg was found in females (90.9%), those with diabetes (52%) or hypertension (41.9%)but not in smokers (30%), those with dyslipdemia (31.3%) or family history of premature coronary disease (20.5%). REFERENCES to diagnose diastolic heart failure? A consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction (HFNEF) by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007; 28: 2539-2550 7. Francis J. Tissue Doppler Imaging. 2010. Available at http:// cardiophile.org/2010/03/tissue-doppler-imaging-tdi.html. [Accessed at 11/11/2011]. 8. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000; 102: 1788-1794. 9. Chhabisatpathy, MD, Trinath, K, and Mishra, MD. Diagnosis and Management of Diastolic Dysfunction and Heart Failure. Am Fam Physician 2006; 73: 841-6. 10. Cheuk, M.Y., Sanderson, J.E., Marwick, T.H and Jae, K. Tissue Doppler imaging, A new prognostic for cardiovascular disease. J Am Coll Cardiol. 2007; 49: 1903-1914. 11. Srivastava, P.M., Burrell, L.M and Calafiore, P. Lateral vs medial mitral annular tissue Doppler in the echocardiographic assessment of diastolic function and filling pressures: which should we use? European Journal of Echocardiography. 2005; 6: 97-106. 1. Okrainec, K., Banerjee, D.K., Eisenberg, M.J. Coronary artery disease in the developing world. Am Heart J. 2004; 148: 7-15. 2. World Health Organization Statistical Information System Core Health Indicators World Health Statistics 2006 Available online: http://www.who.int/en/ (accessed on September 20, 2009). 3. Abu-Baker N, Haddad L, Mayyas O. Smoking Behavior among Coronary Heart Disease Patients in Jordan: A Model from a Developing Country. Int J Environ Res Public Health. 2010 March; 7(3): 751-764. Published online 2010 February 26. doi: 10.3390/ijerph7030751 4. Kern, J. Morton. Artherosclerotic cardiovascular disease: Coronary blood flow and myocardial ischemia. In: Braunwalds (7th edition) Heart disease: A textbook for cardiovascular medicine, Elsevier Saunders, USA. 2005. pp 1103-1139. 5. Hamon M, Fau G, Née G, Ehtisham J, Morello R. Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease. J Cardiovasc Magn Reson. 2010 May 19; 12(1): 29. Epub 2010 May 19. 6. Paulus WJ, Tschöpe C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbély A, Édes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How 22 www.smltsa.org.za | ISSN 1011 5528 Further larger studies are needed to confirm our finding in different racial groups and clinical subsets.