Reduced aortic distensibility and coronary flow velocity reserve in diabetes mellitus patients with a negative coronary angiogram

BACKGROUND: Structural and functional abnormalities of the aortic wall and disturbances of the coronary circulation with presumed microvascular complications have been reported in patients with diabetes mellitus. OBJECTIVES: To simultaneously establish the coronary flow velocity reserve (CFVR) and aortic distensibility indexes in type 2 diabetes mellitus patients who have normal epicardial coronary arteries by stress transesophageal echocardiography (STEE). METHODS: The elastic properties of the descending aorta and the CFVR were evaluated simultaneously in 18 type 2 diabetes mellitus patients who had negative coronary angiograms. These results were compared with those of 21 nondiabetic subjects with normal epicardial coronary arteries and 24 patients with left anterior descending coronary artery (LAD) stenosis. STEE was used for the evaluation of elastic moduli of the descending aorta. The CFVR was calculated as the ratio of the average peak diastolic flow velocity during hyperemia to that at rest. RESULTS: The CFVR of diabetic patients with normal epicardial coronary arteries and those with LAD stenosis was similarly decreased compared with the controls (2.10+/-0.63 and 1.78+/-0.47 versus 2.76+/-1.25, P<0.05 and P<0.001, respectively). The elastic modulus (in 103 mmHg) was similarly increased in patients with diabetes mellitus and normal epicardial coronary arteries, and in those with LAD stenosis, compared with the control subjects (0.94+/-0.82 and 0.91+/-0.59 versus 0.49+/-0.19, P<0.05 and P<0.05, respectively). CONCLUSIONS: It may be stated that reduced aortic distensibility (increased elastic modulus) and the CFVR were demonstrated simultaneously during STEE in diabetic patients compared with nondiabetic subjects with negative coronary angiograms.     

Decreased aortic distensibility and coronary flow velocity reserve in patients with significant aortic valve stenosis with normal epicardial coronary arteries

BACKGROUND AND AIM OF THE STUDY: A number of clinical and experimental studies have suggested that aortic valve stenosis (AS) is a manifestation of atherosclerotic process. Previous studies have revealed a decreased coronary flow velocity reserve (CFR) in AS patients in consequence of left ventricular hypertrophy. The hypothesis was tested that the elastic properties of the descending aorta of AS patients might indicate signs of stiffness of the aorta. METHODS: The CFR and indices of aortic distensibility as functional markers of the descending aorta were compared in three different patient populations: (i) control subjects without valvular and coronary artery disease; (ii) patients with AS with normal epicardial coronary arteries; and (iii) patients with significant left anterior descending coronary artery (LAD) stenosis. CFR measurements were carried out according to a standard protocol, using vasodilatory stimulation with dipyridamole (0.56 mg/kg for 4 min), and peak diastolic velocity measurements at 6 min. The elastic properties of the aorta were calculated from echocardiographic parameters and blood pressure data. RESULTS: The CFR in AS patients was decreased to a similar extent as in patients with LAD stenosis. The aortic distensibility indices were similarly significantly increased in patients with AS and normal epicardial coronary arteries and with LAD stenosis, as compared with controls. CONCLUSION: These results indicate that the descending aorta exhibits appreciable increased stiffness in AS patients with normal epicardial coronary arteries.     

Coronary flow velocity reserve and indices describing aortic distensibility in patients after coronary angiography

BACKGROUND: The purpose of this study was to assess the elastic properties of the descending aorta and the coronary flow velocity reserve (CFR) in patients after coronary angiography. METHODS AND PATIENTS: We recruited 112 subjects with stable angina pectoris without a previous myocardial infarction: 17 consecutive patients with anatomically normal coronary arteries, 24 patients with non-significant coronary artery disease (CAD), 31 patients with significant left anterior descending coronary artery (LAD) disease and 40 patients with multivessel disease (MVD). Transoesophageal echocardiography (TEE) is useful for evaluation of the elastic properties of the descending aorta. The physical behaviour of vessels in response to an intraluminal force is described by the elastic modulus (E(p)) and Young's circumferential static elastic modulus (E(s)). Coronary flow velocities can be measured in the LAD under baseline conditions and during dipyridamole stress. The CFR was calculated as the ratio of the average peak diastolic flow velocity during hyperaemia to that at rest. RESULTS: The indices of aortic distensibility, CFR and mean CFR, were different in patients with LAD disease and in those with normal coronary angiograms. There were no further changes in these parameters in cases with MVD. In patients with non-significant CAD, the CFR, mean CFR and stiffness moduli lie between those for negative cases and those for patients with LAD disease/MVD. CONCLUSIONS: When there was significant stenosis of the LAD, the CFR was significantly decreased, while indices of aortic distensibility were increased as compared with the negative controls. Interestingly, not only the CFR, but also E(p) and E(s) displayed no further changes in cases with MVD as compared with LAD disease.     

Comparison of coronary flow velocity reserve and aortic distensibility in diabetic versus non-diabetic patients with and without aortic atherosclerosis

Coronary flow velocity reserve (CFR) and aortic distensibility are altered both in diabetes and in the presence of aortic atherosclerosis (AA). Transoesophageal echocardiography has been demonstrated to be a suitable method for simultaneous evaluation of these functional parameters. In the present study no significant difference could be observed in CFR and aortic distensibility in diabetic patients compared to non-diabetic subjects with or without AA.     

Simultaneous echocardiographic evaluation of coronary flow velocity reserve and aortic distensibility indices in hypertension

The coronary flow velocity reserve (CFVR), a measure of endothelial function in coronary circulation, can be measured semi-invasively in the left anterior descending coronary artery by using stress transesophageal echocardiography (TEE). During the same stress TEE, aortic distensibility indices (elastic modulus [E(p)] and Young's circumferential static elastic modulus [E(s)]) can be assessed. The purpose of the present study was to examine whether stress TEE is valuable method for parallel evaluation of CFVR, E(p), and E(s) in patients with hypertension. A total of 38 patients with chest pain but with a negative coronary angiogram were enrolled into the present study, which included examination of the presence or absence of hypertension. Significant coronary stenosis was considered present in the event of a luminal diameter reduction of >50% on use of the “worst view method.” Patients with significant coronary or valvular heart disease, atrial fibrillation, heart failure, unstable angina pectoris, acute myocardial infarction, or diabetes mellitus were excluded from the study. Stress TEE was performed in each case to evaluate CFVR, E(p), and E(s). Coronary flow velocity reserve and diastolic coronary flow velocities measured at peak stress were decreased in hypertensive patients as compared with normotensive subjects. E(p) and E(s) were significantly increased in hypertensive patients. In conclusion, it can be stated that Stress TEE is a useful tool for the simultaneous evaluation of the CFVR, E(p), and E(s) in hypertension. The CFVR and aortic distensibility are decreased in hypertension. The topic of this paper was presented at the EUROECHO9 Congress, 2005, Florence, Italy     

Coronary reserve and exercise ECG in patients with chest pain and normal coronary angiograms.

BACKGROUND. Coronary vasodilator reserve is reduced in some patients with a history of chest pain and angiographically normal coronary arteries. ECG changes suggestive of myocardial ischemia during exercise also can be demonstrated in a subset of these patients. METHODS AND RESULTS. We have investigated the correlation between coronary vasodilator reserve, assessed with 13N-labeled ammonia and positron emission tomography, and the ECG during exercise stress in 45 patients with a history of chest pain, angiographically normal coronary arteries, and a negative ergonovine test. ST segment depression on the ECG during exercise was present in 29 of 45 patients. Mean resting left ventricular blood flow was 1.04 +/- 0.22 ml.min-1.g-1; it increased to 1.32 +/- 0.47 ml.min-1.g-1 (p less than 0.01 versus baseline value) during atrial pacing and to 2.52 +/- 0.96 ml.min-1.g-1 (p less than 0.01 versus baseline value) after dipyridamole (0.56 mg/kg i.v.). No regional flow defects could be demonstrated in any patient during pacing or after dipyridamole. Myocardial flows after dipyridamole, however, did not show a normal frequency distribution (Kolmogorov-Smirnov test), and two patient populations could be identified. Twenty-nine (67%) patients had a mean left ventricular flow of 3.02 +/- 0.33 ml.min-1.g-1 after dipyridamole (range, 2.13-5.46 ml.min-1.g-1), and 14 (33%) patients had a mean flow of 1.48 +/- 0.29 ml.min-1.g-1 (range, 1.06-2.04 ml.min-1.g-1, p less than 0.01 versus the "high-flow group"). CONCLUSIONS. Approximately one third of patients in our series showed a reduced coronary vasodilator reserve. Although 12 of 14 patients in the "low-flow group" had ST segment depression during exercise stress, 16 of 29 patients in the high-flow group also had ST segment depression during exercise stress. Therefore, despite a good sensitivity (86%) in identifying patients with a blunted increment of coronary flow, the ECG response during exercise stress appears to have a rather low specificity (45%). This suggests that factors other than reduced coronary reserve and myocardial ischemia may play a role in the genesis of the ST segment depression in these patients.     

冠状动脉造影正常的胸痛患者冠状动脉血流储备功能研究

目的 :评价冠状动脉血流储备 (CFR)功能的测定对阐明冠状动脉造影正常患者的胸痛机制的临床作用。方法 :4 0例冠状动脉造影正常的胸痛患者分为非心脏病组、X综合征组及高血压组 ,采用TIMI计帧法测定注射罂粟碱前后相关冠状动脉血流帧数的变化 ,并计算CFR。结果 :X综合征组用药前后血流速度均慢于非心脏病组 (P <0 .0 5 ,P <0 .0 1) ,高血压组静息血流速度快于非心脏病组 (P <0 .0 5 )。非心脏病组的CFR范围为2 .0～ 2 .8,X综合征组及高血压组的CFR低于非心脏病组 (P <0 .0 1)。结论 :TIMI计帧法可用于CFR的测定 ,X综合征及高血压患者CFR降低 ,原因可能与冠状动脉小血管的充血反应能力下降和 (或 )基础冠状动脉血流的增加有关     

Prognostic value of coronary flow reserve and aortic distensibility indices in patients with suspected coronary artery disease

In recent studies it has been demonstrated that a reduced coronary flow reserve (CFR) is independently associated with a less benign long-term outcome. Aortic stiffness is one of the most important cardiovascular risk factors predicting cardiovascular morbidity and mortality. Vasodilator stress transesophageal echocardiography (TEE) is a suitable method to evaluate simultaneously CFR and elastic properties of the descending thoracic aorta. The aim of the present study was to assess the relative prognostic value of simultaneously measured CFR and aortic elastic properties by pulsed-wave Doppler TEE in patients with suspected or known coronary artery disease (CAD). The study comprised 157 in-hospital patients with chest pain. In all patients, stress TEE was used for the simultaneous evaluation of CFR and aortic distensibility indices [elastic modulus E(p) and Young's circumferential static elastic modulus E(s)]. During a mean follow-up of 48 +/- 8 months, 13 patients suffered cardiovascular death. By univariate analysis older age, diabetes mellitus, increased left ventricular (LV) end-diastolic diameter, increased LV mass index, lower LV ejection fraction, and lower CFR were significant predictors of cardiovascular survival. Multivariate regression analysis showed that only CFR (hazard ratio [HR] 10.31, P = 0.04), age (HR 1.20, P = 0.001), and increased left ventricular (LV) end-diastolic diameter (HR 1.14, P = 0.02) were independent predictors of cardiovascular survival. Only in the small number of patients without CAD and abnormal CFR aortic distensibility seemed to provide complementary prognostic information over CFR. In the majority of patients aortic distensibility did not offer complementary prognostic information to CFR during vasodilator stress TEE testing.     

Endothelial function in patients with chest pain and normal coronary angiograms

BACKGROUND: A normal coronary angiogram is found in about 20% of patients who undergo coronary angiography due to chest pain. In some of them syndrome X is diagnosed. Endothelial dysfunction is one possible cause of this pathology. AIM: To compare the endothelial function estimated by two different methods in patients with typical or atypical anginal pain and with no chest pain. METHODS: Fifty-three patients who underwent coronary angiography due to suspected coronary artery disease and who had a normal coronary angiogram were included in the study: 34 patients had typical anginal pain (group 1) and 19 patients had atypical chest pain (group 2). The control group consisted with 20 subjects without chest pain. The plasma concentration of such endothelial markers as von Willebrand factor (vWF), thrombomodulin (TM), endothelin 1 (ET-1), tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) and C-reactive protein were measured. We also determined endothelial-dependent brachial arterial dilatation (flow-mediated dilation, FMD). RESULTS: The groups of patients were different with regard to the factors of known effects on endothelial function but endothelial markers were not different in all groups with two exceptions. The concentration of tPA was the highest in patients with typical chest pain and the concentration of PAI-1 was the highest in patients without chest pain. The FMD values were low in all patients and there were no significant differences in the FMD values between the three analysed groups. We did not find any correlation between the concentration of examined endothelial markers and FMD. A non-significant relationship between the presence of classical risk factors and decreased FMP was observed. We have found a significant relationship between the number of risk factors and FMD, tPA, PAI-1 and hsCRP. CONCLUSIONS: The assessment of endothelial function using FMD or estimation of endothelial markers is not useful to differentiate chest pain.     

Coronary flow reserve in patients with chest pain and normal coronary arteries.

BACKGROUND--Many studies have shown that coronary flow reserve is reduced in patients with chest pain and angiographically normal coronary arteries. The methods used to assess coronary blood flow have varied, but in nearly all reports dipyridamole has been used to bring about vasodilatation. This study was designed to assess whether the apparent impairment of coronary flow reserve seen with dipyridamole could be reproduced with either papaverine or adenosine, which induce maximum coronary blood flow by different mechanisms. METHODS--25 patients with chest pain and angiographically normal coronary arteries were studied with an intracoronary Doppler flow probe and quantitative angiography to determine epicardial coronary artery area, coronary blood flow velocity, coronary flow reserve, and coronary vascular resistance index (CVRI, the ratio of resistance after intervention to basal resistance). All patients received papaverine 8 mg. Eight patients with positive exercise tests received intracoronary papaverine (8 and 10 mg), intracoronary adenosine (6, 20, 60 micrograms), and high-dose intravenous dipyridamole (0.84 mg/kg). RESULTS--The velocity ratio (peak after intervention: baseline) (mean (SEM)) after 8 mg papaverine was 3.3 (0.2) (n = 25) and the coronary flow reserve was 4.1 (0.3) (n = 25). There were no differences between patients with a positive (n = 16) or negative (n = 9) exercise test. In eight patients coronary flow reserve was measured after increasing doses of papaverine, adenosine, and dipyridamole. Coronary flow reserve was 4.5 (0.3) with papaverine, 4.8 (0.3) with adenosine, and 3.5 (0.4) with dipyridamole (p = 0.08 v papaverine and adenosine). CVRI was 0.22 (0.01) with papaverine, 0.21 (0.02) with adenosine, and 0.29 (0.03) with dipyridamole (p < 0.05 v papaverine, p = 0.09 v adenosine). CONCLUSIONS--These results indicate that measurement of coronary flow reserve and CVRI in patients with chest pain and normal coronary arteries depends on the pharmacological stimulus. Normal values were obtained with papaverine in all patients, irrespective of the exercise test response. In patients with a positive exercise test significantly lower values were obtained with dipyridamole than with papaverine, or adenosine. The reported impairment of coronary flow reserve in patients with angina and normal coronary arteries may reflect the variability in response to different pharmacological agents. The mechanism underlying this variability is unknown, but may involve an abnormality of adenosine metabolism in the myocardium.     

Role of transthoracic Doppler-determined coronary flow reserve in patients with chest pain.

BACKGROUND: The assessment of patients with chest pain is an important step to make a diagnosis and clinical decision. Coronary flow reserve (CFR) can be used for the screening of significant coronary stenosis. However, the feasibility and limitation of CFR in those patients remains unknown. METHODS AND RESULTS: A total of 100 patients with chest pain were examined. CFR was measured in all 3 major coronary arteries by using transthoracic Doppler echocardiography (TTDE). Coronary angiography was performed 1 to 3 days after TTDE. CFR in all 3 major coronary arteries could be measured in 83 (83%) of 100 patients. The echo-contrast agent was useful in 32 of 49 patients who had unclear color Doppler images. When CFR <2.0 was regarded as the cut-off point, the overall agreement rate between CFR and the results of coronary angiography was 83% (69 of the 83 patients). In addition, CFR could predict the presence of coronary artery disease satisfactorily (sensitivity 85%, specificity 81%, positive predictive value 89%, negative predictive value 93%). CONCLUSIONS: TTDE seems to be a promising tool for screening patients with chest pain. Moreover, an echo-contrast agent seems to be an effective and supportive tool for patients who have poor visualization of coronary flow.     

Long-term outcome in patients with angina-like chest pain and normal coronary angiograms

BACKGROUND: Short-term prognosis of patients with chest pain and angiographically smooth coronary arteries is good in terms of development of coronary events (fatal or nonfatal myocardial infarction, coronary death, new coronary heart disease), but long-term studies are rare. PATIENTS AND METHODS: 185 consecutive patients (mean age 54 +7.8 years, 59% male)with typical angina pectoris or atypical chest pain who underwent coronary angiography between 1980 and 1989 and had completely normal coronary arteries and left ventricular function (mean ejection fraction 68%) were followed over a period of 12.0 +/- 2.9 years. Exercise tests showed ischemia in 51 patients (ECG) and 21 patients (myocardial scintigraphy), respectively. 173 patients could be recruited for follow-up. RESULTS: One patient died from acute myocardial infarction (0.05% per year). Nine patients died potentially from cardiac causes (0.51% per year) and seven from extracardial diseases. No nonfatal myocardial infarctions were documented. Six patients developed an angiographically documented coronary heart disease with significant stenoses after a mean follow-up of 12.7 years (0.3% per year). These patients had significantly more coronary risk factors than patients without coronary heart disease (2.8 vs. 1.8; p < 0.05) but not more often pathologic findings in rest-ECG (28% vs. 36%; not significant [n.s.]) and exercise test-ing (14% vs. 32%; n.s.). Frequency and intensity of chest pain remained unchanged in 34% of the patients. Symptoms regressed in more patients with an initially negative exercise test compared to patients who had a positive exercise test (78% vs. 54%;p < 0.05). The decrease in patients taking nitrates did not differ significantly between both groups (-42% vs. -27%; n.s.). CONCLUSION: Patients suffering from angina-like chest pain with normal coronary angiograms have a good long-term prognosis which does not differ from the general population of the same age. Patients with positive stress tests will have less relief from their symptoms than patients with a negative stress test over many years.     

Cardiac energy metabolism in patients with chest pain and normal coronary angiograms

In 70 patients (94% were a consecutive series) with angina pectoris and normal coronary angiograms, we measured cardiac exchange of lactate, glucose, free fatty acids (FFAs), glutamate, alanine, citrate, and oxygen together with coronary sinus blood flow and blood pressure in response to pacing (150 beats/min). Twelve patients had an abnormal exercise stress test; 26 developed ST depression and 46 had chest pain in response to pacing. Sixteen patients had no ST changes (exercise/ pacing) and no pain during pacing. Pacing induced an increase in cardiac carbohydrate extraction and a decrease in FFA extraction in the entire group of patients. Less than 3% of patients had significant cardiac lactate release in response to pacing, and there were no consistent differences in the cardiac metabolic or hemodynamic responses between patient groups. The pacing-induced shift from FFA to carbohydrate extraction probably reflects the cardiac response to an acute workload. A definite sign of cardiac ischemia (lactate production) was a rare finding in these patients and not confined to the demonstration of electrocardiographic signs of ischemia.     

Haemodynamic response to exercise in patients with chest pain and normal coronary angiograms

A series of 42 patients with chest pain but normal coronary angiograms and normal haemodynamics at rest were prospectively classified as typical angina (group 1, N = 9) or atypical angina (group 2, N = 16) or non-anginal chest pain (group 3, N = 17). All patients underwent radionuclide ventriculography and measurement of pulmonary artery pressure at rest and during maximum exercise. Comparison of data during exercise revealed significantly higher (P less than 0.025) left ventricular filing pressures as reflected by the diastolic pulmonary artery pressure in group 1 (29 +/- 5 mmHg) than in both group 2 (22 +/- 6 mmHg) and group 3 (22 +/- 5 mmHg). The rest-to-exercise change in left ventricular ejection fraction was variable and not significant in group 1 (62 +/- 6% vs 63 +/- 14%). By contrast, both group 2 and group 3 had significant increases (63 +/- 6% vs 69 +/- 10%, P less than 0.02 and 63 +/- 5% vs 68 +/- 5%, P less than 0.01). The classification as 'typical angina' was predictive of an abnormal (greater than 25 mmHg) filling-pressure response to stress. The positive and negative predictive values were 78% and 70%, respectively. The clinical classification was not a predictor of an abnormal (delta less than 5%) ejection-fraction response. No correlation between radionuclide and filling-pressure data could be established. The data suggest that the majority of patients assigned to group 1 manifested an impaired left ventricular function with exercise. This was primarily related to abnormalities in diastolic filling while the systolic performance was not consistently depressed.