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C 2008, the Authors C 2008, Wiley Periodicals, Inc. Journal compilation DOI: 10.1111/j.1540-8175.2008.00718.x ORIGINAL INVESTIGATIONS Association of Coronary Sinus Diameter with Pulmonary Hypertension Yilmaz Gunes, M.D., Unal Guntekin, M.D., Mustafa Tuncer, M.D., Yuksel Kaya, M.D., and Aytac Akyol, M.D. Cardiology Department, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey Background: Impaired venous drainage secondary to increased right atrial pressure (RAP) may result in coronary sinus (CS) dilatation. Methods: Two hundred fifteen patients referred for transthoracic echocardiography were included in the study. CS diameters were measured from apical four-chamber view with the transducer being slightly tilted posteriorly to the level of the dorsum of the heart. Pulmonary artery systolic pressure (PASP) is estimated by measurement of tricuspid regurgitation velocity (v) and estimate RAP based on size and collapsibility of inferior vena cava (VCI) with the formula PASP: 4v2 +RAP. Patients with PASP >35 mmHg were considered to have pulmonary hypertension (PH). Results: CS diameter was measured in 80.3% of the patients with normal PASP (8.1 ± 2.4 mm) and 93.1% of the patients having PH (12.3 ± 2.5 mm). PASP was significantly correlated with CS diameter (r = 0.647, P < 0.001), RA volume index (r = 0.631, P < 0.001), RV volume index (r = 0.475, P < 0.001), VCI diameter (r = 0.365, P < 0.001), and left ventricular ejection fraction (LVEF) (r = –0.270, P < 0.001). CS diameter was also correlated significantly with estimated RAP (r = 0.557, P < 0.001), RA volume index (r = 0.520, P < 0.001), RV volume index (r = 0.386, P < 0.001), LVEF (r = –0.327, P < 0.001), and VCI diameter (r = 0.313, P < 0.001). Multivariate analyses, testing for independent predictive information of CS size, VCI diameter, RA and RV volume indexes, and estimated RAP for the presence of PH revealed that estimated RAP (beta = 0.465, P < 0.001) and CS size (beta = 0.402, P = 0.003) were the significant predictors. Conclusions: Coronary sinus is dilated in patients with pulmonary hypertension. Coronary sinus diameter significantly correlates with PASP, RAP, right heart chamber volumes, LVEF, and VCI diameter. (ECHOCARDIOGRAPHY, Volume 25, October 2008) coronary sinus, pulmonary hypertension, right atrial pressure, vena cava inferior The estimation of pulmonary artery systolic pressure (PASP) with Doppler echocardiography is a simple and reliable noninvasive method for the detection of pulmonary hypertension (PH).1,2 In daily practice, PASP is estimated from adding the mean right atrial pressure (RAP) of a floating constant of 5, 10, or 20 mmHg (depending on the size of right atrium and appearance of the inferior vena cava [VCI]) to right ventricular (RV) to right atrial (RA) pressure gradient derived from incorporation of peak tricuspid regurgitation (TR) velocity into modified Bernoulli equation. This method appears to result in satisfactory estimation of intercardiac pressure.2–4 However, discrepancy between estimated RAP (either assumption of a constant value or estimation by the pattern of VCI) and measured RAP by right heart catheterization has been reported.5–7 Venous system drains into coronary sinus (CS) and opens to right atrium. Therefore, we thought that CS size may be associated with RAP. Although, CS is often visualized on echocardiography in patients with rightsided heart disease relevance of this finding is undefined. In this study, we aimed to search the association of CS size with PASP, RAP, right heart chambers, and VCI diameter. Methods Address for correspondence and reprint requests: Yilmaz Gunes, M.D., Cardiology Department, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey. Fax: +904322168352; E-mail: [email protected] Vol. 25, No. 9, 2008 A total of 215 patients referred for transthoracic echocardiography were included in the study. Patients having severe valvular heart ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. 935 GUNES, ET AL. disease and unsatisfactory imaging of CS and/or VCI were excluded from the study. Transthoracic echocardiography was performed in accordance with the combined ASE/ESC guidelines8 using commercially available device (Vivid 3, General Electric, Chicago, IL, USA) with a 3 MHz transducer and with digital image storage. Volumes of the right heart chambers were measured from apical four- and two-chamber views and indexed for body surface area. From the four-chamber view plane, the transducer was slightly tilted posteriorly to the level of the dorsal wall of the heart. At this level, both ventricles, right atrium, right atrioventricular valve, and the floor of the left atrium could still be visualized. In the posterior aspect of the left atrioventricular junction, it was possible to identify the CS in its entire length from the most lateral aspect of the heart to its entry into the RA, just above the septal leaflet of the tricuspid valve (Fig. 1). Maximal and minimal CS diameters were measured at the proximity of atrial junction and percent contraction of CS diameter was calculated by dividing minimum diameter to maximum diameter. Right ventricular to right atrial pressure gradient was calculated from velocity of tricuspid insufficiency flow (v) in the parasternal short-axis and apical four-chamber view, and the highest tricuspid regurgitation velocity was taken as study sample. RAP was gauged by measuring the size of VCI diameter adjacent to the RA and the percent reduction in its diameter during inspiration in the subcostal view. A diameter <1.5 cm estimated RAP 0–5 mmHg; a normal diameter (1.5–2.5 cm) with inspira- tory collapse >50% estimated RAP 5–10 mmHg; a normal diameter with 50%< collapse estimated RAP 10–15 mmHg; dilatation with 50%< collapse estimated RAP 15–20 mmHg and dilatation without inspiratory collapse estimated RAP >20 mmHg.9,10 PASP is estimated with the formula PASP: 4v2 +RAP.1,9 Patients with PASP >35 mmHg were considered to have PH. In the case of a large CS contrast injection of a bolus of saline was performed in a left arm peripheral vein to exclude the possibility of left persistent superior vena cava (filling of CS with bubbles before RA). Measurements were obtained by two experienced echocardiographers blinded to clinical information and averaged. The acquired images were reanalyzed independently to obtain the inter- and intraobserver variabilities. The study was approved by the ethics committee of the local institution and patients’ consents were obtained. Statistics Quantitative variables are expressed as mean ± standard deviation (SD), and qualitative variables as numbers and percentages. Differences between independent groups were assessed by Student’s t-test for normally distributed quantitative variables and MannWhitney’s U-test for variables without normal distribution of variances and Chi-square test for qualitative variables. Pearson correlation analysis was used to assess the correlations for PASP, RAP, and the maximum CS diameter. Multivariate linear regression analysis was used to analyze the value of different baseline characteristics as independent predictors of PH. All tests were performed in the SPSS for Windows, version 10.0 (SPSS, Chicago, IL, USA). All results were considered statistically significant at the level of P < 0.05. Results Figure 1. Coronary sinus (arrows) draining into right atrium. 936 Eight patients having PH and 26 patients with normal PASP were excluded from the study due to unsatisfactory imaging of CS. Therefore, CS diameter was measurable in 80.3% of the patients with normal PASP and 93.1% of the patients having PH. Intra- and interobserver variabilities for all measurements were less than 5% and nonsignificant. No patient was suspected of left persistent superior vena cava. Clinical and echocardiographic characteristics of the study group are seen in Table I. Patients with PH were older, had larger right ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. Vol. 25, No. 9, 2008 CORONARY SINUS IN PULMONARY HYPERTENSION TABLE I Characteristics of the Study Population Age (years) Male Body mass index Diabetes mellitus Hypertension Smoking COPD Atrial fibrillation Coronary artery disease LVEF Maximum CS diameter (mm) Minimum CS diameter (mm) CS contraction (%) VCI diameter (mm) RA volume (cm3 ) RA volume index (cm10−4 ) RV volume (cm3 ) RV volume index (cm10−4 ) Pulmonary Hypertension (N = 109) Normal PASP (N = 106) P-Value 60.7 ± 1.3 51 (46.8%) 25.3 ± 4.7 20 (18.3%) 43 (39.4%) 34 (31.2%) 36 (33.0%) 34 (31.2%) 30 (27.5%) 52.7 ± 13.9 12.3 ± 2.5 9.3 ± 2.5 75.2 ± 8.3 23.6 ± 4.8 81.5 ± 55.0 45.5 ± 31.8 53.4 ± 35.9 30.1 ± 22.2 44.4 ± 15.7 63 (59,4%) 25.9 ± 3.8 5 (4.7%) 22 (20.7%) 30 (28.3%) 4 (3.8%) 1 (0.9%) 20 (18.8%) 60.2 ± 7.7 8.1 ± 2.4 5.5 ± 2.1 66.8 ± 11.2 20.8 ± 3.4 36.5 ± 14.3 19.9 ± 7.1 32.1 ± 11.2 17.5 ± 5.8 <0.001 0.076 0.307 0.002 0.003 0.658 <0.001 <0.001 0.148 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 PASP = pulmonary artery systolic pressure; COPD = chronic obstructive pulmonary disease; LVEF = left ventricular ejection fraction; VCI = inferior vena cava; RA = right atrium; RV = right ventricle. heart chambers and wider CS (Fig. 2) and VCI diameters. PASP was significantly correlated with CS diameter (r = 0.647, P < 0.001), RA volume index (r = 0.631, P < 0.001), RV vol- ume index (r = 0.475, P < 0.001), VCI diameter (r = 0.365, P < 0.001), and left ventricular ejection fraction (LVEF) (r = –0.270, P < 0.001). Estimated RAP was significantly correlated with PASP (r = 0.710, P < 0.001), VCI diameter (r = 0.707, P < 0.001), RA volume index (r = 0.601, P < 0.001), CS diameter (r = 0.557, P < 0.001), RV volume index (r = 0.531, P < 0.001), and LVEF (r = –0.295, P < 0.001). Maximum CS diameter was correlated significantly with PASP (r = 0.647, P < 0.001), estimated RAP (r = 0.557, P < 0.001), RA volume index (r = 0.520, P < 0.001), RV volume index (r = 0.386, P < 0.001), LVEF (r = –0.327, P < 0.001), and VCI diameter (r = 0.313, P < 0.001). Multivariate analyses, testing for independent predictive information of CS size, VCI diameter, RA and RV volume indexes, and estimated RAP for the presence of PH revealed that estimated RAP (beta = 0.465, P < 0.001) and CS size (beta = 0.402, P = 0.003) were the significant predictors. Discussion Figure 2. Error bar of coronary sinus by pulmonary hypertension. Vol. 25, No. 9, 2008 In this study we evaluated size of CS and found significant association with PASP, RAP, VCI size, and right heart chambers. In the parasternal long-axis view of the left ventricle, the CS can be seen wedged into the ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. 937 GUNES, ET AL. atrioventricular sulcus. Because the CS courses around the posterior aspect of the left atrioventricular groove in a plane perpendicular to the longitudinal plane of the heart, it is seen in its short axis as a circular structure adjacent to the posterior mitral valve. Except for a dilated CS, this echocardiographic section does not always provide a clear definition of the CS. The apical position has been considered as the best section for the visualization of the coronary sinus in a normal heart.11 Transthoracic echocardiography (TTE) is an excellent noninvasive method to detect PH. TTE estimates PASP and provides additional information about causes and consequences of PH. PASP is equivalent to right ventricular systolic pressure (RVSP) in the absence of right ventricular or pulmonary outflow obstruction. RVSP is estimated by measurement of tricuspid regurgitation velocity (v) and estimate RAP with the formula RVSP: 4v2 +RAP.1,9 The echocardiographic studies with patients having diverse disorders showed that predictions of RVSP correlated well with catheterization values.2–4 RAP is either a standard value of 5– 15 mmHg or estimated value from characteristics of VCI or from the height of jugular venous distension.12 Additional echocardiographic and Doppler parameters, including right and left ventricular dimensions and function, valvular abnormalities, right ventricular ejection and left ventricular filling characteristics, and VCI dimensions, are for the diagnosis confirmation and assessment of severity of PASP.1 Use of the size and inspiratory collapsibility of the VCI is the most widely adopted method for the estimation of RAP.9 Although, a number of studies report a high correlation (0.57–0.93) between TTE and right heart catheterization measurements of PASP,1 discrepancies have been observed between RAP estimated by the pattern of VCI collapse and measured by right heart catheterization.6,7,13,14 Vena cava measurements depend on the image being obtained perpendicular to the vessel, and in addition, there may be differences in the collapsibility of the VCI based on variations in inspiratory effort. Decreased respiratory effort, by causing smaller swings of intrapleural pressure, can simulate VCI plethora. Conversely, increased respiratory effort, as may occur due to various cardiac or respiratory causes, might prevent VCI plethora from being manifest even when the central venous pressure is high.15 Brennan et al.6 evaluated echocardiographic imag- 938 ing of the VCI for estimation of RAP in 102 patients undergoing right heart catheterization and found that traditional classification of RAP into 5 mmHg ranges based on VCI size and collapsibility performed poorly (43% accurate). The VCI size cutoff with optimum predictive use for RAP above or below 10 mmHg was 2.0 cm (sensitivity 73% and specificity 85%) and the optimal VCI collapsibility cutoff was 40% (sensitivity 73% and specificity 84%). Therefore, assessment of additional criteria like right heart chamber volumes and CS diameter may be useful for the prediction of RAP. Machraouni et al.13 found a good correlation between pulmonary artery mean pressure and the area index of the two right heart cavities (r = 0.83) and between RAP and RA area index (r = 0.64). In the study of Raymond et al.,16 RA area index was also closely correlated with RAP (r = 0.72, P < 0.001). In the present study, we found that patients with PH had larger right heart chambers and wider CS and VCI diameters and there were significant correlations between PASP, estimated RAP, right heart chamber volume indexes, VCI diameter, and CS diameter. Therefore, assessment of all of these parameters may be useful during evaluation of PH on echocardiographic examination. Andrade et al.11 studied 400 patients of 5 to 80 years of age and defined CS diameter as 0.4– 0.8 cm. Kronzon et al.17 were able to measure CS diameter at the right atrial communication by TTE in 16 of 40, and in all patients by transesophageal echocardiography (maximal diameter 6 to 14 mm, mean 9 ± 2). Dilated CS can result from increased blood flow due to abnormal venous drainage found in persistent left superior vena cava, total anomalous intracardiac pulmonary venous drainage, impaired right ventricular function, severe tricuspid regurgitation, unroofed left atrium, CS diverticulum, or coronary artery to CS fistula.11,18,19 In the absence of primary abnormalities of the tricuspid valve, right atrial enlargement is generally a manifestation of high RAP due to functional tricuspid regurgitation or elevated right ventricular diastolic pressure. A previous study demonstrated that pericardial effusion size is correlated with RAP in patients with PH20 and a likely mechanism of pericardial effusion observed in patients with primary PH was explained to be impaired venous and lymphatic drainage resulting from elevated RAP.16,18 Accordingly, impaired venous drainage secondary to increased RAP may result in CS dilatation. ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. Vol. 25, No. 9, 2008 CORONARY SINUS IN PULMONARY HYPERTENSION Patients with poor left ventricular systolic function show mild CS dilatation21 and attenuation of CS contraction has been described in patients with congestive heart failure with marked venous congestion.22 In the present study, there was a moderate but significant correlation between CS diameter and LVEF and CS contraction was attenuated in patients with PH. This attenuation may be an echocardiographic sign of elevated right heart pressures and central venous pressure. Ehtisham et al.23 visualized CS in 81% of 43 patients who underwent right heart catheterization for the evaluation of PH. Coronary sinus size correlated significantly with RA size (r = 0.60, P < 0.001) and RA pressure (r = 0.59, P < 0.001) but not with RV size, degree of tricuspid regurgitation, right ventricular pressure, mean pulmonary artery pressure, or pulmonary vascular resistance. Lee et al.24 assessed the anatomical changes of the CS with coronary venography in patients with LV dysfunction having moderate or severe mitral regurgitation. They found significant positive correlation between the CS perimeter and the PASP and magnitude of mitral regurgitation. No other significant correlations were observed between CS dimensions and left ventricular diameters, mitral annulus diameter, left atrial diameter, and right heart filling pressures. We were able to measure CS diameter in 80.3% of the patients with normal PASP (8.1 ± 2.4 mm) and 93.1% of the patients having PH (12.3 ± 2.5 mm). We found that CS size was significantly correlated with PASP, RAP, RA, and RV volumes, LVEF and VCI diameter and a dilated CS is a significant predictor of PH. Limitations The gold standard for determination of PASP is right heart catheterization. Right heart catheterization is not performed due to ethical concerns and is the major limitation of the study. As exact pressures are not measured by catheterization, evaluation of accuracy and cutoff values of echocardiographic findings to predict PASP and RAP were not possible. However, because this procedure is invasive, expensive, and potentially risky, determining PASP noninvasively has been a current matter for years. Although, PASP cannot be determined by echocardiography in some patients it is an inexpensive and reliable method allowing serial measurements and is the most commonly used noninvasive tool to determine PASP.1,9 Vol. 25, No. 9, 2008 Conclusions Our findings show that coronary sinus is dilated in patients with PH. Coronary sinus diameter significantly correlates with PASP, RAP, right heart chamber volumes, LVEF, and VCI diameter. Therefore, echocardiographic evaluation of CS may be considered an integral component of the assessment of PH on echocardiographic examination. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Galie N, Torbicki A, Barst R, et al: Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 2004;25:2243– 2278. Berger M, Haimowitz A, Van Tosh A, et al: Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. J Am Coll Cardiol 1985;6:359–365. Yock PG, Popp RL: Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984;70:657–662. Currie PJ, Seward JB, Chan KL, et al: Continuous wave Doppler determination of right ventricular pressure: A simultaneous Doppler-catheterization study in 127 patients. J Am Coll Cardiol 1985;6:750–756. 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Echocardiography 1997;14:579– 588. 20. Hinderliter AL, Willis PW, IV, Long WA, et al: Pericardial effusion in patients with primary pulmonary hypertension. Am J Cardiol 1999;84:481–484. 21. D’Cruz IA, Shala MB, Johns C, et al: Echocardiography of the coronary sinus in adults. Clin Cardiol 2000;23:149–154. 22. D’Cruz IA, Shirwany A: Update on echocardiography of coronary sinus anatomy and physiology. Echocardiography 2003;20:87–95. 23. Ehtisham M, Raisinghani A, Keramati S, et al J Am Soc Echocardiogr 2001;14:44–49 (Abstract). 24. Lee MS, Shah AP, Dang N, et al: Coronary sinus is dilated and outwardly displaced in patients with mitral regurgitation: Quantitative angiographic analysis. Catheter Cardiovasc Interv 2006;67:490–494. ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. Vol. 25, No. 9, 2008