Int J Cardiovasc Imaging DOI 10.1007/s10554-015-0653-7
ORIGINAL PAPER
Detection of coronary artery disease in diabetic hypertensive patients using conventional transthoratic echocardiography at rest Jie Zhang1 • Ji-Xu Fan1 • Cheng-Bo Sun1 • Yan Liu1 • Yan Wang1 Yang Guo1 • Hong-E Li1
•
Received: 11 January 2015 / Accepted: 28 March 2015 Ó Springer Science+Business Media Dordrecht 2015
Abstract To investigate the usefulness of conventional transthoratic echocardiography in identifying coronary artery disease (CAD) in diabetic hypertensive patients, transthoratic echocardiography and coronary angiography were performed in 122 diabetic hypertensive patients with suspected CAD. Correlation analysis, multivariate analysis and receiver operating characteristic curve (ROC) analysis were done. Diabetic hypertensive patients with CAD had significantly smaller coronary sinus diameter (Dcs), less velocity time integral (VTI), less coronary sinus flow (Flow) and less Flow divided by left ventricular mass (Flow/LVM) at rest versus normal participants (P \ 0.01) and diabetic hypertensive patients without CAD (P \ 0.05). The VTI, Dcs, Flow, LVM and Flow/LVM all showed significant correlations with the maximal percent stenosis of the coronary artery lesions (P \ 0.05). However, only Flow showed statistically significant correlations with the maximal percent stenosis of the coronary artery lesions (P \ 0.01) when multiple stepwise regression analysis was performed. For predicting CAD (angiographically proven, [50 %) in diabetic hypertensive patients, the area under the ROC (AUC) was 0.92 for Flow, and a cut-off of \220 ml/min had a 93.2 % sensitivity, 87.9 % specificity and 91.3 % accuracy. For predicting a
& Jie Zhang [email protected] 1
Department of Ultrasound, The First People’s Hospital of Lianyungang, 182 North Tongguan Road, Xinpu District, Lianyungang 222002, Jiangsu Province, People’s Republic of China
[70 % coronary artery stenosis, the AUC was 0.88 for Flow, and a cut-off of \147 ml/min had an 89.5 % sensitivity, 87.4 % specificity and 88.5 % accuracy. Conventional transthoratic echocardiography can effectively and sensitively detect the CAD in diabetic hypertensive patients at rest. The reduced coronary sinus flow is a sensitive and specific predictor of CAD in diabetic hypertensive patients. Keywords Diabetic hypertensive patients Coronary artery disease Coronary sinus flow Left ventricular mass Transthoratic echocardiography Coronary angiography Abbreviations 3D Three-dimensional echocardiography BSA Body surface area CAD Coronary artery disease d End diastole DBP Diastolic blood pressure Dcs The diameter of coronary sinus HR Heart rate LVEF Left ventricular ejection fraction LVM Left ventricular mass LVMI Left ventricular mass index PP Pulse pressure ROC Receiver operating characteristic curve RAP Right atrial pressure RT-3DE Real-time 3-dimensional echocardiography RVSP Right ventricular systolic pressure SBP Systolic blood pressure T2DM Type 2 diabetes mellitus TPG Transtricuspid pressure gradient TR Tricuspid regurgitation VTI Velocity time integral
123
Int J Cardiovasc Imaging
Introduction Diabetes and hypertension, the deadly duet, are two highly prevalent diseases we often face at the same time [1]. The co-existence of hypertension and diabetes dramatically and synergistically increases the risk of coronary heart disease (CAD) [2]. In diabetic patients, coronary atherosclerosis often develops without symptoms, once it has developed, it always brings about worse outcome as compared with nondiabetic patients. The presence of hypertension tends to exacerbate this situation of coronary atherosclerosis and myocardial ischemia. Therefore, early detection of CAD and prompt intervention are important to reduce mortality in the management of diabetes and hypertension. At present, there have been various techniques for detecting coronary circulation dysfunction, such as myocardial perfusion scintigraphy, magnetic resonance imaging, coronary angiography, computed tomography angiography and exercise electrocardiogram. However, these techniques are not always readily available, which are limited by the potential of significant adverse effects, technical difficulty, availability, and cost. Zheng et al. [3–5] have confirmed that the conventional transthoratic echocardiography is a convenient, flexible, noninvasive and inexpensive tool for identifying hypertensive and nonhypertensive individuals in the significant myocardial ischemia state (epicardial coronary artery stenosis) by depicting the changes in the coronary sinus flow, the global left ventricular perfusion and the difference of left ventricular mass (LVM) at end diastole and peak systole. However, whether conventional transthoratic echocardiography can effectively and sensitively detect coronary artery disease in diabetic hypertensive patients remains unknown. In this study, we compared the changes of coronary sinus flow among normal participants, diabetic hypertensive patients with and without CAD, and investigated the usefulness of conventional transthoratic echocardiography in predicting a coronary artery stenosis (angiographically proven [50 and [70 % stenosis) in diabetic hypertensive patients.
Materials and methods Study population Consecutive patients with T2DM and hypertension, as defined respectively by the WHO [6] and JNC7 [7] criteria were recruited from the inpatient department of our hospital from January 2012 to July 2014. All participants had a sinus rhythm, normal systolic function of the left and right ventricles, normal right ventricular systolic pressure, right atrial pressure and pulmonary artery pressure, and mitral
123
and tricuspid valvular regurgitation of less than grade 2. Those with a history of heart failure, significant valvular heart disease, cardiomyopathy, pulmonary hypertension and congenital heart disease particularly things that cause dilated CS or increased RA pressures like intracoronary shunts, anomalous pulmonary venous return, or persistent left subclavian were excluded. As a result, a total of 122 diabetic hypertensive patients with suspected CAD (chest pain or chest distress), were eligible for this study. The coronary angiography would be conducted to get the information of their coronary lesions in interventional catheterization laboratory of our hospital. The control group was recruited from the local health exhibition and consisted of 60 age-and sex-matched healthy participants with fasting blood glucose level \6.1 mmol/l, blood pressure \140/90 mmHg, and normal CT coronary angiography finding. They all have no any history and signs of diabetes or cardiovascular diseases. Our study was approved by the local human research ethics committee of The First People’s Hospital of Lianyungang, and free informed consent was obtained from all of the participants. Echocardiographic measurements A complete 2DE, 3DE and Doppler study was performed in all participants, using a commercially available Philips iE33 ultrasound machine (Philips Medical Systems, Andover, MA, USA) equipped with S 5-1 linear-array transducer and X3-1 matrix-array transducer. The participants were lying in the left lateral position with the electrocardiography recorded simultaneously. The right ventricular systolic pressure (RVSP) was estimated by adding the right atrial pressure (RAP) to the transtricuspid pressure gradient (TPG) [8–11]. The TPG was calculated from the peak tricuspid regurgitation (TR) velocity using the modified Bernoulli equation: TPG (mmHg) = 4V2, where V = highest continuous wave Doppler measurement of the TR velocity (m/s) in the parasternal short axis and fourchamber apical views. RAP was estimated to be 5, 10, or 15 mmHg based on the variation in the size of inferior vena cava [11]: complete collapse, RAP = 5 mmHg; partial collapse, RAP = 10 mmHg; and no collapse, RAP = 15 mmHg. RVSP was considered to be equal to the pulmonary artery systolic pressure in the absence of right ventricular outflow obstruction. The left ventricular mass was measured by a method previously described by Pan et al. [12] using 3-dimensional echocardiography. Firstly, a full-volume three-dimensional data set was acquired from the apical window over 4 consecutive cardiac cycles during end expiration breathhold, and stored digitally for off-line analysis. Secondly, these real time three-dimensional echocardiography data sets were analyzed using commercially available software
Int J Cardiovasc Imaging
(Qlab version 4.2, 3DQ Advanced). The left ventricular end-diastolic and end-systolic volume, left ventricular ejection fraction (LVEF), the left ventricular end-diastolic mass (LVM) were calculated finally. All values for each parameter were obtained by averaging measurements from three successive cardiac cycles. LVM index at end-diastolic (LVMI), calculated by dividing the LVM by the body surface area (BSA), was used in all statistical analyses. The coronary sinus flow was measured by a method previously described by Zheng et al. [5]. Firstly, the parasternal right ventricular inflow tract view was obtained. The transducer was manipulated to visualise the mouth of the coronary sinus. To avoid the influence of atrial contraction, the coronary sinus diameter (Dcs) was measured at a 1 cm distance from the mouth in the end diastolic phase before the P wave on electrocardiography using adjust M-mode tracing. Secondly, a pulsed-wave sample volume (3 mm) was placed at a 1 cm distance from the mouth, and then rotated by a small amount (Doppler angle between the ultrasound beam and vessels \30°) to obtain the optimum Doppler flow signals, and spectral recordings of the flow were made. The velocity time integral (VTI, cm) were determined through digitised Doppler spectral envelops. Thirdly, the coronary sinus flow per minute (Flow) was calculated according to the formula [13]: Flow (ml/min) = p 9 D2/4 9 VTI 9 heart rate (HR), where p is the ratio of the circumference of a circle to its diameter, and D is the diameter of the coronary sinus. Global left ventricular perfusion (ml/min g) = Flow/LVM [14]. Coronary angiography Invasive coronary angiography was performed in all participants by the femoral approach within 24 h of transthoratic echocardiography according to the standard method of Judkins [15] using the COROSKOP Plus angiographic complex (Siemens AG, Berlin, Germany) and standard catheters and conventional views. The severity of coronary artery lesions was determined by the own quantitative analysis software of digital subtraction angiography. Angiography results were divided into CAD group (C50 % obstruction in C1 coronary artery) and non-CAD group (\50 % obstruction in any coronary artery). Reproducibility Intraobserver variability was assessed in 30 participants by repeating the measurements on two occasions (5 days apart) under the same basal conditions. To test the interobserver variability, the measurements were performed on the same subject by a second blinded observer. Variability was calculated as the mean percentage error, derived as the
difference between the two sets of measurements, divided by the mean observations. Statistical analysis Data were expressed as the mean ± SD. The differences between the two groups were tested using an unpaired two tailed t test. Multiple regression analysis by two methods (enter and stepwise) was performed to determine the correlation between dependent and independent variables, respectively. A receiver operating characteristic curve (ROC) analysis was used to compare the performance of single variable or multivariable in discrimination between diabetic hypertensive patients with coronary artery disease (angiographically proven,[50 %) and healthy participants, in predicting a severe coronary artery stenosis ([70 %), and to determine the optimal cut-off points and validity parameters. A value of P \ 0.05 was considered statistically significant. All statistical analysis was performed with SPSS version 16.0 software for Windows (SPSS Inc, Chicago, IL).
Results Clinical and echocardiographic characteristics Clinical and echocardiographic characteristics of the 122 diabetic hypertensive patients with CAD are summarized in Table 1. Compared with normal participants, the diabetic hypertensive patients with CAD had significantly higher SBP, DBP and PP (P \ 0.05), so did the diabetic hypertensive patients without CAD. However, there were no statistically significant differences among normal subjects and diabetic hypertensive patients with or without CAD according to age, BSA, HR, and LVEF. The Dcs, VTI, Flow, Flow/LVM were all significantly lower in diabetic hypertensive patients with CAD than in normal participants (P \ 0.01), and they were also significantly lower than that in diabetic hypertensive patients without CAD (P \ 0.05), while LVM and LVMI in diabetic hypertensive patients with and without CAD were all significantly greater than those in normal participants (P \ 0.05). Coronary angiographic findings The coronary angiographic findings were shown in Table 2. The multivessel disease, left coronary artery lesions, and moderate to severe stenosis were usually found in diabetic hypertensive patients.
123
Int J Cardiovasc Imaging Table 1 Clinical and echocardiographic parameters of normal participants and diabetic hypertensive patients with or without coronary artery disease (CAD) Parameters
Normal participants (n = 60)
diabetic hypertensive patients without CAD (n = 62)
diabetic hypertensive patients with CAD (n = 60)
Clinical parameters Age (years)
55.69 ± 12.3
56.7 ± 12.7
55.5 ± 13.1
Males, n (%) Duration of DM (years)
36 (60)
37 (60) 16.9 ± 10.2
36 (60) 16.8 ± 8.3
18.6 ± 8.4
19.3 ± 7.5
Duration of Hypertension (years) BSA (m2)
1.82 ± 0.36
1.81 ± 0.44
1.82 ± 0.35
HR (beats/min)
75.5 ± 10.4
73.6 ± 11.9
73.9 ± 12.3
SBP (mmHg)
110.56 ± 6.72
157.94 ± 11.69*
158.87 ± 12.32*
DBP (mmHg)
74.33 ± 5.01
91.87 ± 10.35*
92.56 ± 11.66*
PP (mmHg)
36.49 ± 6.72
66.81 ± 8.49*
67.26 ± 9.25*
Echocardiographic parameters LVEF (%)
62.20 ± 7.63
61.78 ± 8.92
62.34 ± 7.66
Dcs (cm)
0.95 ± 0.13
0.68 ± 0.16*
0.43 ± 0.15*,#
VTI (cm)
13.11 ± 5.24
10.99 ± 3.24*
7.82 ± 2.97**,#
Flow (ml/min)
749.87 ± 198.47
379.67 ± 177.81**
264.99 ± 134.15**,#
LVM (g)
155.41 ± 30.06
209.93 ± 41.52*
211.26 ± 43.66*
LVMI (g/m2)
88.76 ± 15.02
115.33 ± 31.79**
115.25 ± 34.63**
Flow/LVM (ml/min g)
4.83 ± 2.06
2.13 ± 0.97**
1.19 ± 0.76**,#
3D three-dimensional echocardiography, BSA body surface area, CAD coronary artery disease, d end diastole, DBP diastolic blood pressure, Dcs the diameter of coronary sinus, HR heart rate, LVEF left ventricular ejection fraction, LVM left ventricular mass, LVMI left ventricular mass index, SBP systolic blood pressure, PP pulse pressure, T2DM type 2 diabetes mellitus, VTI velocity time integral * P \ 0.05; ** P \ 0.01, unpaired t test, compared to the values of normal subjects #
P \ 0.05; unpaired t test, compared to the values of diabetic hypertensive patients without CAD
Table 2 Coronary angiographic findings in diabetic hypertensive patients with coronary artery disease
Diabetic hypertensive patients with CAD Single-vessel disease, n (%) Multivessel disease, n (%) Diffuse disease, n (%)
95 (35)
Left coronary artery lesions, n (%)
207 (69)
Right coronary artery lesions, n (%)
94 (31)
Mild stenosis (50–74 %), n (%) Moderate stenosis (75–94 %), n (%) Severe stenosis ([95 %), n (%)
The Pearson correlation analysis and multiple regression analysis As shown in Table 3, the VTI, Dcs, Flow, LVM and Flow/ LVM showed statistically significant correlations with the maximal percent stenosis of the coronary artery lesions (P \ 0.01). When multiple regression analysis by the enter method was performed, only the Flow and Flow/LVM showed statistically significant correlations with the maximal percent stenosis of the coronary artery lesions (P \ 0.01)
123
37 (14) 138 (51)
37 (15) 119 (47) 96 (38)
(Table 4). Moreover, when multiple regression analysis by the stepwise method was performed, only Flow showed statistically significant correlations with the maximal percent stenosis of the coronary artery lesions (P \ 0.01) (Table 5). Receiver operating characteristic curve (ROC) analysis With the use of angiographically proven [50 % epicardial coronary artery stenosis as the criteria to distinguish the
Int J Cardiovasc Imaging Table 3 The Pearson correlation analysis for the maximal percent stenosis of the coronary artery lesions and related echocardiographic parameters in diabetic hypertensive patients with coronary artery disease Parameters
Coefficient (r)
Sig. (P)
VTI (cm)
-0.323
\0.001
Dcs (cm)
-0.418
\0.001
Flow (ml/min)
-0.517
\0.001
0.352
\0.001
-0.457
\0.001
LVM (g) Flow/LVM (ml/min g)
Dcs the diameter of coronary sinus, Flow coronary sinus flow per minute, LVM left ventricular mass, VTI velocity time integral
Table 4 Multiple regression analysis (enter method) for the maximal percent stenosis of the coronary artery lesions and related parameters in diabetic hypertensive patients with coronary artery disease Independent variable
Beta
t
Sig.
Flow (ml/min)
-1.933
-2.297
0.025
Flow/LVM (ml/min g)
-0.672
0.917
0.043
R, 0.668; F, 7.235; P \ 0.0001 in the multiple regression equation of in diabetic hypertensive patients with coronary artery disease Beta standardized coefficient, Flow coronary sinus flow per minute, LVM left ventricular mass
Table 5 Multiple regression analysis (stepwise method) for the maximal percent stenosis of the coronary artery lesions and related parameters in diabetic hypertensive patients with coronary artery disease Independent variable
Beta
t
Sig.
Flow (ml/min)
-0.593
-3.935
0.000
R, 0.593; F, 21.418; P \ 0.0001 in the multiple regression equation of in diabetic hypertensive patients without coronary artery disease Beta standardized coefficient, Flow coronary sinus flow per minute
diabetic hypertensive patients with CAD from healthy participants, the area under the ROC (AUC) was 0.92 for Flow. With the use of angiographically proven [70 % epicardial coronary artery stenosis as the criteria to distinguish the diabetic hypertensive patients with severe CAD from those with mild CAD, the AUC was 0.88 for Flow (Fig. 1). Discriminant analysis On the basis of the data depicted as mentioned above, a discriminant analysis of the cut off value of Flow for predicting diabetic hypertensive patients with angiographically
proven [50 and [70 % epicardial coronary artery stenosis was conducted. A cut-off of \220 ml/min had a 93.2 % sensitivity, 87.9 % specificity and 91.3 % accuracy in predicting a [50 % epicardial coronary artery stenosis. A cutoff of \147 ml/min had an 89.5 % sensitivity, 87.4 % specificity and 88.5 % accuracy in predicting a [70 % epicardial coronary artery stenosis. Reproducibility Intraobserver and interobserver variability for the Dcs, VTI ranged from 2.9 to 6.7 %. Intraobserver and interobserver variability for the LVM were 6.9 ± 2.3, 7.2 ± 2.1 %, respectively.
Discussion The results presented here indicate that coronary sinus flow measured by transthoratic echocardiography can effectively, sensitively detect and predict coronary artery disease in diabetic hypertensive patients. Over the last decade, the coronary flow reserve in the coronary sinus has been used to diagnose severe coronary artery stenosis by transesophageal Doppler echocardiography because of inadequate visualization of the coronary arteries, especially the mid and distal parts of them [13, 16, 17]. However, transesophageal Doppler echocardiography is a semi-invasive procedure, and the vasodilator drugs used, such as adenosine, are not always harmless. As far as diabetic hypertensive patients with CAD, they may induce angina pectoris and even more serious conditions. In routine echocardiographic examination, we have found that coronary sinus can be adequately visualized from the parasternal right ventricular inflow tract view through TTE approach in almost all subjects, and the coronary sinus flow in this view can be monitored by TTE within a distance of 1–1.5 cm from the ostium with a\30° Doppler angle between the ultrasound beam and the vessel, which is similar to the same measurement obtained with TEE and ensures a precise measurement of coronary sinus flow. However, this can not be done from the apical four chamber view because of a [60° Doppler angle between the ultrasound beam and the vessel. Our previous study shows that coronary microvascular dysfunction often exists in diabetic patients without angiographically proven epicardial coronary artery stenosis [18], and Zheng et al. [3] had reported that hypertensive patients without CAD often have more coronary sinus flow than nonhypertensive patients. So, we think that in the diabetic hypertensive state, enhanced myocardial contraction always requires more coronary blood flow supply due to coronary microvascular dysfunction and elevated
123
Int J Cardiovasc Imaging Fig. 1 Receiver operating characteristic curve showing the performance of coronary sinus flow per minute in discrimination between diabetic hypertensive patients with coronary artery disease (angiographically proven, [50 %) and healthy participants (a), and in predicting a severe coronary artery stenosis ([70 %) (b)
afterload, only a normal coronary flow reserve can meet this requirement. Decreased blood flow in the coronary sinus indicates the presence of coronary artery lesions and an impaired coronary flow reserve in fact. In addition, LV diastolic function often attenuates in diabetic hypertensive patients, the decreased myocardial relaxation will provide less diastolic force than healthy subjects, which also results in the reduced drainage of coronary sinus flow. Thus, it can be seen that measurements of blood flow alone (not coronary flow reserve) in the coronary sinus by transthoratic Doppler echocardiography in diabetic hypertensive patients is valuable in the diagnosis of CAD. Increased left ventricular (LV) mass has been shown to be an independent predictor of a coronary event [19, 20]. Recent studies have also shown that nonobstructive CAD visualized by cardiac computed tomographic angiography is associated with increased LV mass independent of effects of clinical risk factors and calcium scoring, and a significant correlation of LV mass with total plaque and total segment scores can be found [21, 22]. Our study also confirmed that LVM correlated significantly with the maximal percent stenosis of the coronary artery lesions. These findings may have widespread implications regarding the applications of LV mass in the clinical diagnosis of CAD. In present study, diabetic hypertensive patients with CAD had smaller Dcs, greater LVM, less VTI, Flow and Flow/ LVM than those in diabetic hypertensive patients without CAD and normal participants. However, whether the multitude of parameters can all effectively and sensitively detect and predict angiographically proven epicardial coronary artery stenosis in diabetic hypertensive patients. Our further analysis answered the question. As a result, only the coronary sinus flow can detect and predict a [50 and [70 % coronary artery stenosis in diabetic hypertensive patients with higher sensitively, specificity and accuracy.
123
Our study had some possible limitations. First, the number of participants was limited. New data need to be collected in subsequent studies. Second, the measurement of coronary sinus flow was sometimes difficult because of interference from heart movements. Thirdly, in diabetic hypertensive patients, myocardial restriction and diastolic disturbances may be a reason for decreased blood flow as well, which need be further confirmed. Even so, transthoratic echocardiography, being rapid, reliable, inexpensive, and noninvasive in the assessment of the coronary sinus flow, has potential for clinical implications. In the further study, all diabetic hypertensive patients (including asymptomatic ones) should undergo an assessment of coronary sinus flow, for the patients with abnormal coronary sinus flow, coronary angiography is necessarily performed.
Conclusions In this study we evaluated the usefulness of conventional transthoratic echocardiography for detecting and predicting angiographically proven coronary artery stenosis in diabetic hypertensive patients. We have shown that reduced coronary sinus flow is a sensitive and specific predictor of CAD ([50 % coronary artery stenosis) and a severe coronary artery stenosis ([70 %) in diabetic hypertensive patients. Although some limitations were mentioned above, this method still holds considerable clinical promise for the diagnosis of CAD in diabetic hypertensive patients. Acknowledgments The authors gratefully acknowledge the technical assistance and helpful discussion of X. Z. Zheng at the department of ultrasound, The First People’s Hospital of Yancheng, Jiangsu Province, People’s Republic of China. Conflict of interest conflicts of interest.
The authors have reported no other potential
Int J Cardiovasc Imaging
References 1. Deedwania PC (2005) Diabetes and hypertension, the deadly duet: importance, therapeutic strategy, and selection of drug therapy. Cardiol Clin 23:139–152 2. Deedwania PC (2001) Pharmacotherapy of hypertension in patients with diabetes mellitus. Expert Opin Pharmacother 2: 1805–1816 3. Zheng ZX, Ji P, Mao HW, Hu JQ (2012) Reduced antegrade flow in the coronary sinus is a predictor of coronary artery stenosis in hypertensive patients. J Ultrasound Med 31:7–14 4. Zheng XZ, Ji P, Mao HW (2012) Reduced difference of left ventricular mass at end diastole and peak systole is a predictor of significant stenosis of the left coronary artery territory. J Ultrasound Med 31:1437–1442 5. Zheng XZ, Yang B, Wu J (2013) Sex-specific assessment of reduced coronary sinus flow in non-hypertensive patients with coronary artery disease at rest. Libyan J Med 8:21553. doi:10. 3402/ljm.v8i0.21553 6. Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553 7. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr et al (2003) The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC7 report. JAMA 28:2560–2572 8. Denton CP, Cailes JB, Phillips GD et al (1997) Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension insystemic sclerosis. Br J Rheumatol 36:239–243 9. McQuillan BM, Picard MH, Leavitt M et al (2001) Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects. Circulation 104:2797–2802 10. Finkelhor RS, Lewis SA, Pillai D (2014) Limitations and strengths of Doppler/Echo pulmonary artery systolic pressure– right heart catheterization correlations: a systematic literature review. Echocardiography. doi:10.1111/echo.12594 11. Taleb M, Khuder S, Tinkel J, Khouri SJ (2013) The diagnostic accuracy of Doppler echocardiography in assessment of pulmonary artery systolic pressure: a meta-analysis. Echocardiography 30(3):258–265 12. Pan YS, Yu HY, Wang GY, Qin L, Zhao ML (2004) Evaluation of left ventricular mass in patients with coronary artery disease
13.
14.
15. 16.
17.
18.
19.
20.
21.
22.
using two-dimensional echocardiography and real-time three-dimensional echocardiography. J Med Imaging 4:481–483 Vrublevsky AV, Boshchenko AA, Karpov RS (2004) Reduced coronary flow reserve in the coronary sinus is a predictor of hemodynamically significant stenoses of the left coronary artery territory. Eur J Echocardiogr 5:294–303 Bloch KM, Carlsson M, Arheden H, Sta˚hlberg F (2009) Quantifying coronary sinus flow and global LV perfusion at 3T. BMC Med Imaging 9:9. doi:10.1186/1471-2342-9-9 Judkins MP (1967) Selective coronary arteriography, I: a percutaneous trans-femoral technic. Radiology 89:815–824 Vrublevsky AV, Boshchenko AA, Karpov RS (2004) Simultaneous transesophageal Doppler assessment of coronary flow reserve in the left anterior descending artery and coronary sinus allows differentiation between proximal and non-proximal left anterior descending artery stenoses. Eur J Echocardiogr 5:25–33 Ramos Filho J, Ramires JA, Turina M, Medeiros CJ, Lachat M, Tsutsui J (2002) Study of coronary sinus flow reserve through transesophageal Doppler echocardiography in normal subjects. Arq Bras Cardiol 79:97–106 Zhang J, Fan JX, Sun CB, Liu Y, Wang Y, Guo Y et al (2014) Left ventricular perfusion determination on conventional transthoratic echocardiography in diabetic patients without angiographically proven epicardial coronary artery stenosis. Exp Clin Cardiol 20:3587–3603 Levy DGR, Savage DD, Kannel WB, Castelli WP (1998) Left ventricular mass and incidence of coronary heart disease in an elderly cohort: the Framingham Heart Study. Ann Intern Med 110:101–107 Tang W, Arnett DK, Province MA, Lewis CE, North K, Carr JJ et al (2006) Racial differences in the association of coronary calcified plaque with left ventricular hypertrophy: the National Heart, Lung, and Blood Institute Family Heart Study and Hypertension Genetic Epidemiology Network. Am J Cardiol 97:1441–1448 Madaj PM, Pagali SR, Hamirani YS, Raina S, Nair S, Zeb I et al (2010) Coronary artery calcium and plaque association with left ventricular mass, assessed by multi-row detector computed tomography. Coron Artery Dis 21:428–434 Lin FY, Nicolo D, Devereux RB, Labounty TM, Dunning A, Gomez M et al (2011) Nonobstructive coronary artery disease as detected by 64-detector row cardiac computed tomographic angiography is associated with increased left ventricular mass. J Cardiovasc Comput Tomogr 5:158–164
123
ORIGINAL PAPER
Detection of coronary artery disease in diabetic hypertensive patients using conventional transthoratic echocardiography at rest Jie Zhang1 • Ji-Xu Fan1 • Cheng-Bo Sun1 • Yan Liu1 • Yan Wang1 Yang Guo1 • Hong-E Li1
•
Received: 11 January 2015 / Accepted: 28 March 2015 Ó Springer Science+Business Media Dordrecht 2015
Abstract To investigate the usefulness of conventional transthoratic echocardiography in identifying coronary artery disease (CAD) in diabetic hypertensive patients, transthoratic echocardiography and coronary angiography were performed in 122 diabetic hypertensive patients with suspected CAD. Correlation analysis, multivariate analysis and receiver operating characteristic curve (ROC) analysis were done. Diabetic hypertensive patients with CAD had significantly smaller coronary sinus diameter (Dcs), less velocity time integral (VTI), less coronary sinus flow (Flow) and less Flow divided by left ventricular mass (Flow/LVM) at rest versus normal participants (P \ 0.01) and diabetic hypertensive patients without CAD (P \ 0.05). The VTI, Dcs, Flow, LVM and Flow/LVM all showed significant correlations with the maximal percent stenosis of the coronary artery lesions (P \ 0.05). However, only Flow showed statistically significant correlations with the maximal percent stenosis of the coronary artery lesions (P \ 0.01) when multiple stepwise regression analysis was performed. For predicting CAD (angiographically proven, [50 %) in diabetic hypertensive patients, the area under the ROC (AUC) was 0.92 for Flow, and a cut-off of \220 ml/min had a 93.2 % sensitivity, 87.9 % specificity and 91.3 % accuracy. For predicting a
& Jie Zhang [email protected] 1
Department of Ultrasound, The First People’s Hospital of Lianyungang, 182 North Tongguan Road, Xinpu District, Lianyungang 222002, Jiangsu Province, People’s Republic of China
[70 % coronary artery stenosis, the AUC was 0.88 for Flow, and a cut-off of \147 ml/min had an 89.5 % sensitivity, 87.4 % specificity and 88.5 % accuracy. Conventional transthoratic echocardiography can effectively and sensitively detect the CAD in diabetic hypertensive patients at rest. The reduced coronary sinus flow is a sensitive and specific predictor of CAD in diabetic hypertensive patients. Keywords Diabetic hypertensive patients Coronary artery disease Coronary sinus flow Left ventricular mass Transthoratic echocardiography Coronary angiography Abbreviations 3D Three-dimensional echocardiography BSA Body surface area CAD Coronary artery disease d End diastole DBP Diastolic blood pressure Dcs The diameter of coronary sinus HR Heart rate LVEF Left ventricular ejection fraction LVM Left ventricular mass LVMI Left ventricular mass index PP Pulse pressure ROC Receiver operating characteristic curve RAP Right atrial pressure RT-3DE Real-time 3-dimensional echocardiography RVSP Right ventricular systolic pressure SBP Systolic blood pressure T2DM Type 2 diabetes mellitus TPG Transtricuspid pressure gradient TR Tricuspid regurgitation VTI Velocity time integral
123
Int J Cardiovasc Imaging
Introduction Diabetes and hypertension, the deadly duet, are two highly prevalent diseases we often face at the same time [1]. The co-existence of hypertension and diabetes dramatically and synergistically increases the risk of coronary heart disease (CAD) [2]. In diabetic patients, coronary atherosclerosis often develops without symptoms, once it has developed, it always brings about worse outcome as compared with nondiabetic patients. The presence of hypertension tends to exacerbate this situation of coronary atherosclerosis and myocardial ischemia. Therefore, early detection of CAD and prompt intervention are important to reduce mortality in the management of diabetes and hypertension. At present, there have been various techniques for detecting coronary circulation dysfunction, such as myocardial perfusion scintigraphy, magnetic resonance imaging, coronary angiography, computed tomography angiography and exercise electrocardiogram. However, these techniques are not always readily available, which are limited by the potential of significant adverse effects, technical difficulty, availability, and cost. Zheng et al. [3–5] have confirmed that the conventional transthoratic echocardiography is a convenient, flexible, noninvasive and inexpensive tool for identifying hypertensive and nonhypertensive individuals in the significant myocardial ischemia state (epicardial coronary artery stenosis) by depicting the changes in the coronary sinus flow, the global left ventricular perfusion and the difference of left ventricular mass (LVM) at end diastole and peak systole. However, whether conventional transthoratic echocardiography can effectively and sensitively detect coronary artery disease in diabetic hypertensive patients remains unknown. In this study, we compared the changes of coronary sinus flow among normal participants, diabetic hypertensive patients with and without CAD, and investigated the usefulness of conventional transthoratic echocardiography in predicting a coronary artery stenosis (angiographically proven [50 and [70 % stenosis) in diabetic hypertensive patients.
Materials and methods Study population Consecutive patients with T2DM and hypertension, as defined respectively by the WHO [6] and JNC7 [7] criteria were recruited from the inpatient department of our hospital from January 2012 to July 2014. All participants had a sinus rhythm, normal systolic function of the left and right ventricles, normal right ventricular systolic pressure, right atrial pressure and pulmonary artery pressure, and mitral
123
and tricuspid valvular regurgitation of less than grade 2. Those with a history of heart failure, significant valvular heart disease, cardiomyopathy, pulmonary hypertension and congenital heart disease particularly things that cause dilated CS or increased RA pressures like intracoronary shunts, anomalous pulmonary venous return, or persistent left subclavian were excluded. As a result, a total of 122 diabetic hypertensive patients with suspected CAD (chest pain or chest distress), were eligible for this study. The coronary angiography would be conducted to get the information of their coronary lesions in interventional catheterization laboratory of our hospital. The control group was recruited from the local health exhibition and consisted of 60 age-and sex-matched healthy participants with fasting blood glucose level \6.1 mmol/l, blood pressure \140/90 mmHg, and normal CT coronary angiography finding. They all have no any history and signs of diabetes or cardiovascular diseases. Our study was approved by the local human research ethics committee of The First People’s Hospital of Lianyungang, and free informed consent was obtained from all of the participants. Echocardiographic measurements A complete 2DE, 3DE and Doppler study was performed in all participants, using a commercially available Philips iE33 ultrasound machine (Philips Medical Systems, Andover, MA, USA) equipped with S 5-1 linear-array transducer and X3-1 matrix-array transducer. The participants were lying in the left lateral position with the electrocardiography recorded simultaneously. The right ventricular systolic pressure (RVSP) was estimated by adding the right atrial pressure (RAP) to the transtricuspid pressure gradient (TPG) [8–11]. The TPG was calculated from the peak tricuspid regurgitation (TR) velocity using the modified Bernoulli equation: TPG (mmHg) = 4V2, where V = highest continuous wave Doppler measurement of the TR velocity (m/s) in the parasternal short axis and fourchamber apical views. RAP was estimated to be 5, 10, or 15 mmHg based on the variation in the size of inferior vena cava [11]: complete collapse, RAP = 5 mmHg; partial collapse, RAP = 10 mmHg; and no collapse, RAP = 15 mmHg. RVSP was considered to be equal to the pulmonary artery systolic pressure in the absence of right ventricular outflow obstruction. The left ventricular mass was measured by a method previously described by Pan et al. [12] using 3-dimensional echocardiography. Firstly, a full-volume three-dimensional data set was acquired from the apical window over 4 consecutive cardiac cycles during end expiration breathhold, and stored digitally for off-line analysis. Secondly, these real time three-dimensional echocardiography data sets were analyzed using commercially available software
Int J Cardiovasc Imaging
(Qlab version 4.2, 3DQ Advanced). The left ventricular end-diastolic and end-systolic volume, left ventricular ejection fraction (LVEF), the left ventricular end-diastolic mass (LVM) were calculated finally. All values for each parameter were obtained by averaging measurements from three successive cardiac cycles. LVM index at end-diastolic (LVMI), calculated by dividing the LVM by the body surface area (BSA), was used in all statistical analyses. The coronary sinus flow was measured by a method previously described by Zheng et al. [5]. Firstly, the parasternal right ventricular inflow tract view was obtained. The transducer was manipulated to visualise the mouth of the coronary sinus. To avoid the influence of atrial contraction, the coronary sinus diameter (Dcs) was measured at a 1 cm distance from the mouth in the end diastolic phase before the P wave on electrocardiography using adjust M-mode tracing. Secondly, a pulsed-wave sample volume (3 mm) was placed at a 1 cm distance from the mouth, and then rotated by a small amount (Doppler angle between the ultrasound beam and vessels \30°) to obtain the optimum Doppler flow signals, and spectral recordings of the flow were made. The velocity time integral (VTI, cm) were determined through digitised Doppler spectral envelops. Thirdly, the coronary sinus flow per minute (Flow) was calculated according to the formula [13]: Flow (ml/min) = p 9 D2/4 9 VTI 9 heart rate (HR), where p is the ratio of the circumference of a circle to its diameter, and D is the diameter of the coronary sinus. Global left ventricular perfusion (ml/min g) = Flow/LVM [14]. Coronary angiography Invasive coronary angiography was performed in all participants by the femoral approach within 24 h of transthoratic echocardiography according to the standard method of Judkins [15] using the COROSKOP Plus angiographic complex (Siemens AG, Berlin, Germany) and standard catheters and conventional views. The severity of coronary artery lesions was determined by the own quantitative analysis software of digital subtraction angiography. Angiography results were divided into CAD group (C50 % obstruction in C1 coronary artery) and non-CAD group (\50 % obstruction in any coronary artery). Reproducibility Intraobserver variability was assessed in 30 participants by repeating the measurements on two occasions (5 days apart) under the same basal conditions. To test the interobserver variability, the measurements were performed on the same subject by a second blinded observer. Variability was calculated as the mean percentage error, derived as the
difference between the two sets of measurements, divided by the mean observations. Statistical analysis Data were expressed as the mean ± SD. The differences between the two groups were tested using an unpaired two tailed t test. Multiple regression analysis by two methods (enter and stepwise) was performed to determine the correlation between dependent and independent variables, respectively. A receiver operating characteristic curve (ROC) analysis was used to compare the performance of single variable or multivariable in discrimination between diabetic hypertensive patients with coronary artery disease (angiographically proven,[50 %) and healthy participants, in predicting a severe coronary artery stenosis ([70 %), and to determine the optimal cut-off points and validity parameters. A value of P \ 0.05 was considered statistically significant. All statistical analysis was performed with SPSS version 16.0 software for Windows (SPSS Inc, Chicago, IL).
Results Clinical and echocardiographic characteristics Clinical and echocardiographic characteristics of the 122 diabetic hypertensive patients with CAD are summarized in Table 1. Compared with normal participants, the diabetic hypertensive patients with CAD had significantly higher SBP, DBP and PP (P \ 0.05), so did the diabetic hypertensive patients without CAD. However, there were no statistically significant differences among normal subjects and diabetic hypertensive patients with or without CAD according to age, BSA, HR, and LVEF. The Dcs, VTI, Flow, Flow/LVM were all significantly lower in diabetic hypertensive patients with CAD than in normal participants (P \ 0.01), and they were also significantly lower than that in diabetic hypertensive patients without CAD (P \ 0.05), while LVM and LVMI in diabetic hypertensive patients with and without CAD were all significantly greater than those in normal participants (P \ 0.05). Coronary angiographic findings The coronary angiographic findings were shown in Table 2. The multivessel disease, left coronary artery lesions, and moderate to severe stenosis were usually found in diabetic hypertensive patients.
123
Int J Cardiovasc Imaging Table 1 Clinical and echocardiographic parameters of normal participants and diabetic hypertensive patients with or without coronary artery disease (CAD) Parameters
Normal participants (n = 60)
diabetic hypertensive patients without CAD (n = 62)
diabetic hypertensive patients with CAD (n = 60)
Clinical parameters Age (years)
55.69 ± 12.3
56.7 ± 12.7
55.5 ± 13.1
Males, n (%) Duration of DM (years)
36 (60)
37 (60) 16.9 ± 10.2
36 (60) 16.8 ± 8.3
18.6 ± 8.4
19.3 ± 7.5
Duration of Hypertension (years) BSA (m2)
1.82 ± 0.36
1.81 ± 0.44
1.82 ± 0.35
HR (beats/min)
75.5 ± 10.4
73.6 ± 11.9
73.9 ± 12.3
SBP (mmHg)
110.56 ± 6.72
157.94 ± 11.69*
158.87 ± 12.32*
DBP (mmHg)
74.33 ± 5.01
91.87 ± 10.35*
92.56 ± 11.66*
PP (mmHg)
36.49 ± 6.72
66.81 ± 8.49*
67.26 ± 9.25*
Echocardiographic parameters LVEF (%)
62.20 ± 7.63
61.78 ± 8.92
62.34 ± 7.66
Dcs (cm)
0.95 ± 0.13
0.68 ± 0.16*
0.43 ± 0.15*,#
VTI (cm)
13.11 ± 5.24
10.99 ± 3.24*
7.82 ± 2.97**,#
Flow (ml/min)
749.87 ± 198.47
379.67 ± 177.81**
264.99 ± 134.15**,#
LVM (g)
155.41 ± 30.06
209.93 ± 41.52*
211.26 ± 43.66*
LVMI (g/m2)
88.76 ± 15.02
115.33 ± 31.79**
115.25 ± 34.63**
Flow/LVM (ml/min g)
4.83 ± 2.06
2.13 ± 0.97**
1.19 ± 0.76**,#
3D three-dimensional echocardiography, BSA body surface area, CAD coronary artery disease, d end diastole, DBP diastolic blood pressure, Dcs the diameter of coronary sinus, HR heart rate, LVEF left ventricular ejection fraction, LVM left ventricular mass, LVMI left ventricular mass index, SBP systolic blood pressure, PP pulse pressure, T2DM type 2 diabetes mellitus, VTI velocity time integral * P \ 0.05; ** P \ 0.01, unpaired t test, compared to the values of normal subjects #
P \ 0.05; unpaired t test, compared to the values of diabetic hypertensive patients without CAD
Table 2 Coronary angiographic findings in diabetic hypertensive patients with coronary artery disease
Diabetic hypertensive patients with CAD Single-vessel disease, n (%) Multivessel disease, n (%) Diffuse disease, n (%)
95 (35)
Left coronary artery lesions, n (%)
207 (69)
Right coronary artery lesions, n (%)
94 (31)
Mild stenosis (50–74 %), n (%) Moderate stenosis (75–94 %), n (%) Severe stenosis ([95 %), n (%)
The Pearson correlation analysis and multiple regression analysis As shown in Table 3, the VTI, Dcs, Flow, LVM and Flow/ LVM showed statistically significant correlations with the maximal percent stenosis of the coronary artery lesions (P \ 0.01). When multiple regression analysis by the enter method was performed, only the Flow and Flow/LVM showed statistically significant correlations with the maximal percent stenosis of the coronary artery lesions (P \ 0.01)
123
37 (14) 138 (51)
37 (15) 119 (47) 96 (38)
(Table 4). Moreover, when multiple regression analysis by the stepwise method was performed, only Flow showed statistically significant correlations with the maximal percent stenosis of the coronary artery lesions (P \ 0.01) (Table 5). Receiver operating characteristic curve (ROC) analysis With the use of angiographically proven [50 % epicardial coronary artery stenosis as the criteria to distinguish the
Int J Cardiovasc Imaging Table 3 The Pearson correlation analysis for the maximal percent stenosis of the coronary artery lesions and related echocardiographic parameters in diabetic hypertensive patients with coronary artery disease Parameters
Coefficient (r)
Sig. (P)
VTI (cm)
-0.323
\0.001
Dcs (cm)
-0.418
\0.001
Flow (ml/min)
-0.517
\0.001
0.352
\0.001
-0.457
\0.001
LVM (g) Flow/LVM (ml/min g)
Dcs the diameter of coronary sinus, Flow coronary sinus flow per minute, LVM left ventricular mass, VTI velocity time integral
Table 4 Multiple regression analysis (enter method) for the maximal percent stenosis of the coronary artery lesions and related parameters in diabetic hypertensive patients with coronary artery disease Independent variable
Beta
t
Sig.
Flow (ml/min)
-1.933
-2.297
0.025
Flow/LVM (ml/min g)
-0.672
0.917
0.043
R, 0.668; F, 7.235; P \ 0.0001 in the multiple regression equation of in diabetic hypertensive patients with coronary artery disease Beta standardized coefficient, Flow coronary sinus flow per minute, LVM left ventricular mass
Table 5 Multiple regression analysis (stepwise method) for the maximal percent stenosis of the coronary artery lesions and related parameters in diabetic hypertensive patients with coronary artery disease Independent variable
Beta
t
Sig.
Flow (ml/min)
-0.593
-3.935
0.000
R, 0.593; F, 21.418; P \ 0.0001 in the multiple regression equation of in diabetic hypertensive patients without coronary artery disease Beta standardized coefficient, Flow coronary sinus flow per minute
diabetic hypertensive patients with CAD from healthy participants, the area under the ROC (AUC) was 0.92 for Flow. With the use of angiographically proven [70 % epicardial coronary artery stenosis as the criteria to distinguish the diabetic hypertensive patients with severe CAD from those with mild CAD, the AUC was 0.88 for Flow (Fig. 1). Discriminant analysis On the basis of the data depicted as mentioned above, a discriminant analysis of the cut off value of Flow for predicting diabetic hypertensive patients with angiographically
proven [50 and [70 % epicardial coronary artery stenosis was conducted. A cut-off of \220 ml/min had a 93.2 % sensitivity, 87.9 % specificity and 91.3 % accuracy in predicting a [50 % epicardial coronary artery stenosis. A cutoff of \147 ml/min had an 89.5 % sensitivity, 87.4 % specificity and 88.5 % accuracy in predicting a [70 % epicardial coronary artery stenosis. Reproducibility Intraobserver and interobserver variability for the Dcs, VTI ranged from 2.9 to 6.7 %. Intraobserver and interobserver variability for the LVM were 6.9 ± 2.3, 7.2 ± 2.1 %, respectively.
Discussion The results presented here indicate that coronary sinus flow measured by transthoratic echocardiography can effectively, sensitively detect and predict coronary artery disease in diabetic hypertensive patients. Over the last decade, the coronary flow reserve in the coronary sinus has been used to diagnose severe coronary artery stenosis by transesophageal Doppler echocardiography because of inadequate visualization of the coronary arteries, especially the mid and distal parts of them [13, 16, 17]. However, transesophageal Doppler echocardiography is a semi-invasive procedure, and the vasodilator drugs used, such as adenosine, are not always harmless. As far as diabetic hypertensive patients with CAD, they may induce angina pectoris and even more serious conditions. In routine echocardiographic examination, we have found that coronary sinus can be adequately visualized from the parasternal right ventricular inflow tract view through TTE approach in almost all subjects, and the coronary sinus flow in this view can be monitored by TTE within a distance of 1–1.5 cm from the ostium with a\30° Doppler angle between the ultrasound beam and the vessel, which is similar to the same measurement obtained with TEE and ensures a precise measurement of coronary sinus flow. However, this can not be done from the apical four chamber view because of a [60° Doppler angle between the ultrasound beam and the vessel. Our previous study shows that coronary microvascular dysfunction often exists in diabetic patients without angiographically proven epicardial coronary artery stenosis [18], and Zheng et al. [3] had reported that hypertensive patients without CAD often have more coronary sinus flow than nonhypertensive patients. So, we think that in the diabetic hypertensive state, enhanced myocardial contraction always requires more coronary blood flow supply due to coronary microvascular dysfunction and elevated
123
Int J Cardiovasc Imaging Fig. 1 Receiver operating characteristic curve showing the performance of coronary sinus flow per minute in discrimination between diabetic hypertensive patients with coronary artery disease (angiographically proven, [50 %) and healthy participants (a), and in predicting a severe coronary artery stenosis ([70 %) (b)
afterload, only a normal coronary flow reserve can meet this requirement. Decreased blood flow in the coronary sinus indicates the presence of coronary artery lesions and an impaired coronary flow reserve in fact. In addition, LV diastolic function often attenuates in diabetic hypertensive patients, the decreased myocardial relaxation will provide less diastolic force than healthy subjects, which also results in the reduced drainage of coronary sinus flow. Thus, it can be seen that measurements of blood flow alone (not coronary flow reserve) in the coronary sinus by transthoratic Doppler echocardiography in diabetic hypertensive patients is valuable in the diagnosis of CAD. Increased left ventricular (LV) mass has been shown to be an independent predictor of a coronary event [19, 20]. Recent studies have also shown that nonobstructive CAD visualized by cardiac computed tomographic angiography is associated with increased LV mass independent of effects of clinical risk factors and calcium scoring, and a significant correlation of LV mass with total plaque and total segment scores can be found [21, 22]. Our study also confirmed that LVM correlated significantly with the maximal percent stenosis of the coronary artery lesions. These findings may have widespread implications regarding the applications of LV mass in the clinical diagnosis of CAD. In present study, diabetic hypertensive patients with CAD had smaller Dcs, greater LVM, less VTI, Flow and Flow/ LVM than those in diabetic hypertensive patients without CAD and normal participants. However, whether the multitude of parameters can all effectively and sensitively detect and predict angiographically proven epicardial coronary artery stenosis in diabetic hypertensive patients. Our further analysis answered the question. As a result, only the coronary sinus flow can detect and predict a [50 and [70 % coronary artery stenosis in diabetic hypertensive patients with higher sensitively, specificity and accuracy.
123
Our study had some possible limitations. First, the number of participants was limited. New data need to be collected in subsequent studies. Second, the measurement of coronary sinus flow was sometimes difficult because of interference from heart movements. Thirdly, in diabetic hypertensive patients, myocardial restriction and diastolic disturbances may be a reason for decreased blood flow as well, which need be further confirmed. Even so, transthoratic echocardiography, being rapid, reliable, inexpensive, and noninvasive in the assessment of the coronary sinus flow, has potential for clinical implications. In the further study, all diabetic hypertensive patients (including asymptomatic ones) should undergo an assessment of coronary sinus flow, for the patients with abnormal coronary sinus flow, coronary angiography is necessarily performed.
Conclusions In this study we evaluated the usefulness of conventional transthoratic echocardiography for detecting and predicting angiographically proven coronary artery stenosis in diabetic hypertensive patients. We have shown that reduced coronary sinus flow is a sensitive and specific predictor of CAD ([50 % coronary artery stenosis) and a severe coronary artery stenosis ([70 %) in diabetic hypertensive patients. Although some limitations were mentioned above, this method still holds considerable clinical promise for the diagnosis of CAD in diabetic hypertensive patients. Acknowledgments The authors gratefully acknowledge the technical assistance and helpful discussion of X. Z. Zheng at the department of ultrasound, The First People’s Hospital of Yancheng, Jiangsu Province, People’s Republic of China. Conflict of interest conflicts of interest.
The authors have reported no other potential
Int J Cardiovasc Imaging
References 1. Deedwania PC (2005) Diabetes and hypertension, the deadly duet: importance, therapeutic strategy, and selection of drug therapy. Cardiol Clin 23:139–152 2. Deedwania PC (2001) Pharmacotherapy of hypertension in patients with diabetes mellitus. Expert Opin Pharmacother 2: 1805–1816 3. Zheng ZX, Ji P, Mao HW, Hu JQ (2012) Reduced antegrade flow in the coronary sinus is a predictor of coronary artery stenosis in hypertensive patients. J Ultrasound Med 31:7–14 4. Zheng XZ, Ji P, Mao HW (2012) Reduced difference of left ventricular mass at end diastole and peak systole is a predictor of significant stenosis of the left coronary artery territory. J Ultrasound Med 31:1437–1442 5. Zheng XZ, Yang B, Wu J (2013) Sex-specific assessment of reduced coronary sinus flow in non-hypertensive patients with coronary artery disease at rest. Libyan J Med 8:21553. doi:10. 3402/ljm.v8i0.21553 6. Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553 7. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr et al (2003) The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC7 report. JAMA 28:2560–2572 8. Denton CP, Cailes JB, Phillips GD et al (1997) Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension insystemic sclerosis. Br J Rheumatol 36:239–243 9. McQuillan BM, Picard MH, Leavitt M et al (2001) Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects. Circulation 104:2797–2802 10. Finkelhor RS, Lewis SA, Pillai D (2014) Limitations and strengths of Doppler/Echo pulmonary artery systolic pressure– right heart catheterization correlations: a systematic literature review. Echocardiography. doi:10.1111/echo.12594 11. Taleb M, Khuder S, Tinkel J, Khouri SJ (2013) The diagnostic accuracy of Doppler echocardiography in assessment of pulmonary artery systolic pressure: a meta-analysis. Echocardiography 30(3):258–265 12. Pan YS, Yu HY, Wang GY, Qin L, Zhao ML (2004) Evaluation of left ventricular mass in patients with coronary artery disease
13.
14.
15. 16.
17.
18.
19.
20.
21.
22.
using two-dimensional echocardiography and real-time three-dimensional echocardiography. J Med Imaging 4:481–483 Vrublevsky AV, Boshchenko AA, Karpov RS (2004) Reduced coronary flow reserve in the coronary sinus is a predictor of hemodynamically significant stenoses of the left coronary artery territory. Eur J Echocardiogr 5:294–303 Bloch KM, Carlsson M, Arheden H, Sta˚hlberg F (2009) Quantifying coronary sinus flow and global LV perfusion at 3T. BMC Med Imaging 9:9. doi:10.1186/1471-2342-9-9 Judkins MP (1967) Selective coronary arteriography, I: a percutaneous trans-femoral technic. Radiology 89:815–824 Vrublevsky AV, Boshchenko AA, Karpov RS (2004) Simultaneous transesophageal Doppler assessment of coronary flow reserve in the left anterior descending artery and coronary sinus allows differentiation between proximal and non-proximal left anterior descending artery stenoses. Eur J Echocardiogr 5:25–33 Ramos Filho J, Ramires JA, Turina M, Medeiros CJ, Lachat M, Tsutsui J (2002) Study of coronary sinus flow reserve through transesophageal Doppler echocardiography in normal subjects. Arq Bras Cardiol 79:97–106 Zhang J, Fan JX, Sun CB, Liu Y, Wang Y, Guo Y et al (2014) Left ventricular perfusion determination on conventional transthoratic echocardiography in diabetic patients without angiographically proven epicardial coronary artery stenosis. Exp Clin Cardiol 20:3587–3603 Levy DGR, Savage DD, Kannel WB, Castelli WP (1998) Left ventricular mass and incidence of coronary heart disease in an elderly cohort: the Framingham Heart Study. Ann Intern Med 110:101–107 Tang W, Arnett DK, Province MA, Lewis CE, North K, Carr JJ et al (2006) Racial differences in the association of coronary calcified plaque with left ventricular hypertrophy: the National Heart, Lung, and Blood Institute Family Heart Study and Hypertension Genetic Epidemiology Network. Am J Cardiol 97:1441–1448 Madaj PM, Pagali SR, Hamirani YS, Raina S, Nair S, Zeb I et al (2010) Coronary artery calcium and plaque association with left ventricular mass, assessed by multi-row detector computed tomography. Coron Artery Dis 21:428–434 Lin FY, Nicolo D, Devereux RB, Labounty TM, Dunning A, Gomez M et al (2011) Nonobstructive coronary artery disease as detected by 64-detector row cardiac computed tomographic angiography is associated with increased left ventricular mass. J Cardiovasc Comput Tomogr 5:158–164
123
