Home-Based Exercise Training Improves Left Ventricle Diastolic Function in Survivors of Childhood ALL: A Tissue Doppler and Velocity Vector Imaging Study.

BACKGROUND: Advanced echocardiographic methods may reveal signs of late anthracycline cardiac toxicity (ACT) even in asymptomatic patients. We studied echocardiographic tissue Doppler imaging (TDI) and velocity vector imaging (VVI) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) before and after an exercise intervention. METHODS: Twenty-one asymptomatic, anthracycline-treated, long-term childhood ALL survivors with matched controls were studied at baseline. Seventeen of the survivors participated in a 3-month home-based exercise program. Echocardiography with TDI and VVI was performed. RESULTS: At baseline, ejection fraction (60.7 ± 4.7% vs. 62.3 ± 3.7%, P = 0.22) and fractional shortening (32.6 ± 3.1% vs. 34.0 ± 2.8%, P = 0.13) were similar in survivors and controls. Lateral early diastolic mitral annulus velocity E' (32.81 ± 5.71 cm/sec vs. 38.03 ± 6.21 cm/sec, P = 0.01), E'/A' (1.60 ± 0.48 vs. 2.07 ± 0.63, P = 0.01), and E/E' (2.78 ± 0.35 vs. 2.42 ± 0.62, P = 0.04) were impaired compared to controls. Peak circumferential strain and strain rate were attenuated at apex (-24.50 ± 3.46% vs. -28.06 ± 4.39%, P = 0.01 and -1.47 ± 0.22 sec(-1) vs. -1.68 ± 0.33 sec(-1) , P = 0.02) compared to controls. After the intervention, early diastolic mitral inflow velocity E (87.76 ± 12.54 cm/s vs. 95.28 ± 10.48 cm/s, P = 0.04) and E' increased (31.78 ± 5.50 cm/s vs. 34.96 ± 5.41 cm/s, P < 0.01). Peak circumferential systolic and diastolic strain rates at mid-level (-1.22 ± 0.21 sec(-1) vs. -1.35 ± 0.24 sec(-1) , P = 0.04 and 1.25 ± 0.25 sec(-1) vs. 1.48 ± 0.35 sec(-1) , P < 0.01) improved after the exercise program. CONCLUSIONS: A simple home-based exercise program improved cardiac function in asymptomatic childhood ALL survivors. Adding TDI in routine echocardiographic examination may improve the recognition of early signs of ACT, and VVI may bring additional information. The improvements in cardiac function after the exercise program emphasize the importance of physical activity in this population.

The effects of myocardial bridging on two-dimensional myocardial strain during dobutamine stress echocardiography.

Myocardial bridging (MB) is a common anatomic variant in coronary arteries with unclear functional significance. We evaluated regional myocardial strain by speckle tracking during dobutamine stress echocardiography (DSE) in patients with MB in the left anterior descending coronary artery (LAD). We studied 11 patients with MB in the LAD and no obstructive coronary artery disease (CAD), 7 patients without MB, but obstructive CAD in the LAD, and 12 controls without MB or obstructive CAD. MB was defined as either > 1 mm (superficial) or > 2 mm (deep) intramyocardial course of the LAD in coronary CT angiography. Regional longitudinal, radial and circumferential strains and strain rates as well as post-systolic strain index (PSI) were measured at rest, peak stress, and early recovery (1 min after stress). Strain parameters during DSE were similar in the myocardium distal to MB and other myocardial regions of the same patients as well as the LAD territory in controls. However, patients with obstructive CAD showed impaired LS and strain rate as well as increased PSI at peak stress. None of the MB was associated with systolic compression in invasive coronary angiography and strain parameters were similar between superficial and deep MB. Stress myocardial blood flow by positron emission tomography correlated with LS and RS at peak stress in the myocardium distal to MB (r = - 0.73, p = 0.03, and r = 0.64, p = 0.04, respectively). Myocardial strain is not reduced during DSE in patients with MB in the LAD and no significant systolic compression.

Intrapericardial, but not extrapericardial, fat is an independent predictor of impaired hyperemic coronary perfusion in coronary artery disease.

OBJECTIVE: To measure intrapericardial fat (IPF), extrapericardial fat (EPF), and myocardial perfusion (MBF) in patients with and without coronary artery disease (CAD), hypothesizing that perfusion is more strongly associated with IPF because it is in direct anatomic contiguity with the myocardium or coronary arteries. METHODS AND RESULTS: Fat surrounding the heart may increase the risk of CAD and calcification, but little is known about the role of MBF in this relationship. The study included 107 patients with an intermediate likelihood of CAD. Positron emission tomography/computed tomography was used to measure IPF and EPF volumes and coronary artery calcium level, together with MBF at rest and during adenosine-induced hyperemia. Subsequently, all subjects underwent coronary angiography and were grouped for presence/absence of CAD and severity of myocardial hypoperfusion. IPF and EPF levels were higher in men and in patients with CAD (n=85) than in those without CAD (n=22) (P<0.001). EPF was increased regardless of the degree of stenoses (n=45), whereas IPF was selectively increased in subjects with obstructive stenoses (n=40). IPF and EPF levels were both associated with coronary artery calcium scores (R=0.25 and R=0.26, respectively; P<0.02), coronary flow reserve (R=-0.37 and R=-0.38, respectively; P<0.001), and hyperemic MBF (R=-0.36 and R=-0.44, respectively; P<0.0005). Male sex was a strong negative predictor of MBF. After discounting for confounders, myocardial hyperemic perfusion was predicted independently by sex, coronary artery calcium score, and IPF, but not EPF. CONCLUSIONS: CAD is accompanied by augmented fat depots surrounding the heart, which are negatively related to coronary flow hyperemia. Among fat depots, IPF was the only independent predictor of hyperemic MBF, supporting the hypothesis of a direct paracrine/vasocrine effect.

High dose of red wine elicits enhanced inhibition of fibrinolysis.

BACKGROUND AND DESIGN: The purpose of this randomized controlled cross-over study was to determine the acute effects of high doses of alcoholic beverages on circulating markers related to atherosclerosis and fibrinolysis. METHODS: Twenty-two healthy men consumed a high dose (8.1+/-0.9 dl) of alcohol-containing red wine and dealcoholized red wine, and an equal ethanol dose of cognac (2.4+/-0.3 dl). Blood samples were taken before and shortly after interventions. RESULTS: Red wine, unlike dealcoholized red wine and cognac, increased tissue plasminogen activator inhibitor-1 levels significantly, indicating an acute inhibition of fibrinolysis after a high dose. CONCLUSION: Findings may explain the increased risk of cardiovascular mortality among binge drinkers.

Effects of cognac on coronary flow reserve and plasma antioxidant status in healthy young men.

BACKGROUND: The cardioprotective effects of certain alcoholic beverages are partly related to their polyphenol content, which may improve the vasodilatory reactivity of arteries. Effect of cognac on coronary circulation, however, remains unknown. The purpose of this randomized controlled cross-over study was to determine whether moderate doses of cognac improve coronary reactivity as assessed with cold pressor testing (CPT) and coronary flow reserve (CFR) measurement. METHODS: Study group consisted of 23 subjects. Coronary flow velocity and epicardial diameter was assessed using transthoracic echocardiography at rest, during CPT and adenosine infusion-derived CFR measurements before drinking, after a moderate (1.2 +/- 0.1 dl) and an escalating high dose (total amount 2.4 +/- 0.3 dl) of cognac. To explore the bioavailability of antioxidants, the antioxidant contents of cognac was measured and the absorption from the digestive tract was verified by plasma antioxidant capacity determination. RESULTS: Serum alcohol levels increased to 1.2 +/- 0.2 per thousand and plasma antioxidant capacity from 301 +/- 43.9 micromol/l to 320 +/- 25.0 micromol/l by 7.6 +/- 11.8%, (p = 0.01) after high doses of cognac. There was no significant change in flow velocity during CPT after cognac ingestion compared to control day. CFR was 4.4 +/- 0.8, 4.1 +/- 0.9 (p = NS), and 4.5 +/- 1.2 (p = NS) before drinking and after moderate and high doses on cognac day, and 4.5 +/- 1.4, and 4.0 +/- 1.2 (p = NS) on control day. CONCLUSION: Cognac increased plasma antioxidant capacity, but it had no effect on coronary circulation in healthy young men. TRIAL REGISTRATION: NCT00330213.

Vasodilation of epicardial coronary artery can be measured with transthoracic echocardiography.

Transthoracic Doppler echocardiography (TTE) has been introduced as a noninvasive tool to measure coronary flow velocity reserve (CFVR). Velocity measurement, however, fails to take into account epicardial coronary artery vasodilation during hyperemia and this may cause underestimation of CFVR measurements. Therefore, we sought to determine whether the vasodilation of epicardial coronary artery can be measured during cold pressor test (CPT) and adenosine infusion simultaneously with the flow velocity measurement using TTE. We studied 41 healthy nonsmoking men with a linear high-frequency 8.0-MHz transducer. The CPT and adenosine infusion dilated the diameter of the distal left anterior descending coronary artery (LAD) from 1.4 +/- 0.4 mm to 1.5 +/- 0.4 mm (14 +/- 13%, p < 0.01) and from 1.4 +/- 0.4 mm to 1.8 +/- 0.5 mm (31 +/- 19%, p < 0.01), respectively. The CPT increased flow velocity and calculated coronary blood flow rate (velocity time integral x cross-sectional area) from 0.23 +/- 0.05 m/s to 0.36 +/- 0.13 m/s (31 +/- 34%, p < 0.01) and from 8.1 +/- 4.2 mL/min to 11.4 +/- 6.0 mL/min (47 +/- 51%, p < 0.01). CFVR and calculated coronary blood flow rate reserve were 3.9 +/- 1.0 and 6.0 +/- 1.9, respectively. In Bland-Altman analysis, velocity measurements underestimated the vasodilation response of the CPT and adenosine compared with the measurements where epicardial diameter dilation was taken into account. Intra- and interobserver variability of diameter measurements was low (coefficient of variation [CV] 2.6 to 6.5%). Day-to-day, within-day and intersonographer variabilities were of similar magnitude (CV 4.6 to 8.2%), suggesting good reproducibility. This study demonstrates that TTE can be used to assess changes in both epicardial coronary artery diameter and flow velocity simultaneously in the distal LAD artery.

Two-Dimensional Speckle-Tracking during Dobutamine Stress Echocardiography in the Detection of Myocardial Ischemia in Patients with Suspected Coronary Artery Disease.

BACKGROUND: Two-dimensional speckle-tracking applied to dobutamine stress echocardiography (DSE) may aid in the detection of coronary artery disease (CAD). The aim of this study was to determine the value of strain, strain rate, and postsystolic strain index (PSI) measured by speckle-tracking during DSE in the evaluation of the presence, extent, and severity of myocardial ischemia. METHODS: Fifty patients 63 ± 7 years of age with intermediate probability of CAD were prospectively recruited. All patients underwent DSE, quantitative positron emission tomographic perfusion imaging, and invasive angiography. Regional peak systolic longitudinal strain, strain rate, and PSI were measured at rest, at a dobutamine dose of 20 µg/kg/min, at peak stress, and at early recovery (1 min after stress). Obstructive CAD was defined as >75% stenosis or 40% to 75% stenosis combined with either fractional flow reserve < 0.80 or abnormal findings on myocardial perfusion positron emission tomography. RESULTS: Obstructive CAD was detected in 22 patients and in 36 of 150 coronary arteries. Strain analyses showed the highest reproducibility at rest, at a dobutamine dose of 20 µg/kg/min, and at early recovery. Increased PSI and reduced strain during early recovery were the strongest predictors of obstructive CAD and were associated with the extent, localization, and depth of myocardial ischemia by positron emission tomography. On vessel-based analysis, strain, PSI, and visual analysis of wall motion provided comparable diagnostic accuracy, whereas the combination of strain or PSI with visual analysis provided incremental value over visual analysis alone. CONCLUSIONS: Assessment of systolic or postsystolic strain by speckle-tracking echocardiography during early recovery after DSE can help in the detection of hemodynamically significant coronary stenosis compared with visual wall motion analysis alone.

The Sensitivity of Exercise Echocardiography Can Be Improved by Taking the Delayed Myocardial Contraction into Account.

The purpose of this study was to test whether the systolic myocardial wall motion abnormalities at the early stages of ischemia are applicable to the diagnosis of coronary artery disease. Forty-four patients with suspected coronary artery disease were studied with the use of low-level exercise echocardiography. Exercise was stopped at the onset of first cardiac symptoms, and no patient exceeded 70% of the age-predicted maximal heart rate level. Forty patients had significant stenosis in at least one coronary artery on coronary angiography. Ten control subjects with a low probability of ischemic heart disease also were studied with exercise echocardiography. The first ischemic wall motion abnormality in systole, defined as delayed onset of the contraction (a regional delay of at least 100 milliseconds in a frame-by-frame analysis of echocardiograms) without any reduction in systolic movement, was regarded separately from hypokinesis (systolic wall motion excursion of less than 5 mm). When the delayed onset of the contraction also was taken into account, 37 of the 40 patients with coronary artery disease had an ischemic response after exercise. The sensitivity of the test thus was 93%. The reduction in systolic wall movement was detected in only 18 of these patients at the exercise level attained (70% or less of age-predicted maximal heart rate). There were two false-positive echocardiograms, but when the control group also was considered, the specificity of the test remained high at 86%. The sensitivity of exercise echocardiography can be increased by paying attention to the delayed onset of the systolic contraction, which occurs at the early stages of ischemia.

Resting coronary flow velocity in the functional evaluation of coronary artery stenosis: study on sequential use of computed tomography angiography and transthoracic Doppler echocardiography.

AIMS: Accelerated flow at the site of flow-limiting stenosis can be detected by transthoracic Doppler echocardiography (TTDE). We studied feasibility and accuracy of sequential coronary computed tomography angiography (CTA) and TTDE in detection of haemodynamically significant coronary artery disease (CAD). METHODS AND RESULTS: We prospectively enrolled 107 patients with intermediate (30-70%) pre-test likelihood of CAD. All patients underwent CTA using a 64-slice scanner. Using TTDE, the ratio of maximal diastolic flow velocity to pre-stenotic flow velocity (M/P ratio) was measured in the coronary segments with stenosis in CTA. In all patients, the results were compared with invasive coronary angiography, including measurement of fractional flow reserve when appropriate. All analyses were done blinded. TTDE was feasible in 276 of 285 evaluated coronary segments. Significant coronary stenoses were associated with a higher M/P ratio than non-significant stenoses (3.59 ± 1.82 vs. 1.28 ± 0.60, P < 0.001). The optimal M/P ratio for detection of significant stenosis was 2.2 (area under receiver operating characteristic curve 0.92, P < 0.001). Compared with the strategy of CTA alone, sequential CTA and focused TTDE had a better positive predictive value (PPV; 61 vs. 78%) and diagnostic accuracy (93 vs. 96%, P = 0.006) without impairment of the negative predictive value (97 vs. 97%). CONCLUSION: Sequential use of CTA and TTDE is feasible for combined anatomic and functional evaluation of coronary stenoses. Compared with coronary CTA alone, addition of TTDE improved PPV for detection of significant CAD.

Clinical value of absolute quantification of myocardial perfusion with (15)O-water in coronary artery disease.

BACKGROUND: The standard interpretation of perfusion imaging is based on the assessment of relative perfusion distribution. The limitations of that approach have been recognized in patients with multivessel disease and endothelial dysfunction. To date, however, no large clinical studies have investigated the value of measuring quantitative blood flow and compared that with relative uptake. METHODS AND RESULTS: One hundred four patients with moderate (30%-70%) pretest likelihood of coronary artery disease (CAD) underwent PET imaging during adenosine stress using (15)O-water and dynamic imaging. Absolute myocardial blood flow was calculated from which both standard relative myocardial perfusion images and images scaled to a known absolute scale were produced. The patients and the regions then were classified as normal or abnormal and compared against the reference of conventional angiography with fractional flow reserve. In patient-based analysis, the positive predictive value, negative predictive value, and accuracy of absolute perfusion in the detection of any obstructive CAD were 86%, 97%, and 92%, respectively, with absolute quantification. The corresponding values with relative analysis were 61%, 83%, and 73%, respectively. In region-based analysis, the receiver operating characteristic curves confirmed that the absolute quantification was superior to relative assessment. In particular, the specificity and positive predictive value were low using just relative differences in flow. Only 9 of 24 patients with 3-vessel disease were correctly assessed using relative analysis. CONCLUSIONS: The measurement of myocardial blood flow in absolute terms has a significant impact on the interpretation of myocardial perfusion. As expected, multivessel disease is more accurately detected.

Decreased endothelin-1 levels after acute consumption of red wine and de-alcoholized red wine.

BACKGROUND: Red wine consumption may influence on vasoconstrictive peptide endothelin-1 levels, and this may be one mechanism leading to improved vasodilation after red wine consumption. Endothelin-1 levels and their association with coronary epicardial diameter and flow rate, however, have not been studied in vivo after consumption of red wine and de-alcoholized red wine. The purpose of this randomized trial was to determine the acute effects of these beverages on endothelin-1 levels and compare them to coronary artery epicardial diameter and flow rate. METHODS: Twenty-two healthy men consumed a high dose (8.1+/-0.9 dL) of alcohol-containing red wine and de-alcoholized red wine in a cross-over design at one sitting with a two-week washout period. Endothelin-1 levels were determined and coronary artery diameter and flow rate assessed using transthoracic echocardiography before and acutely after intervention. RESULTS: Red wine and de-alcoholized red wine significantly decreased endothelin-1 levels (0.75+/-0.26 pg/mL to 0.61+/-0.20 pg/mL, p=0.002; 0.74+/-0.32 pg/mL to 0.63+/-0.24 pg/mL, p=0.04, respectively), but did not have a significant effect on epicardial diameter (1.1+/-0.3 mm vs. 1.1+/-0.3 mm, p=0.58; and 1.1+/-0.3 mm vs. 1.1+/-0.2 mm, p=0.10, respectively) or flow rate (7.8+/-4.0 mL/min to 6.4+/-3.6 mL/min, p=0.07; and 7.8+/-4.0 mL/min to 7.4+/-3.2 mL/min, p=0.53, respectively). CONCLUSIONS: Red wine and de-alcoholized red wine decreased plasma endothelin-1 levels after acute consumption, but this change was not reflected in coronary epicardial diameters or flow rate.

Echocardiography in Fabry disease: diagnostic value of endocardial border binary appearance.

BACKGROUND AND AIM: It has been reported that the endocardium in Fabry disease has a binary appearance on transthoracic echocardiography. It has been suggested that this sign could be used with good accuracy to differentiate Fabry disease from hypertrophic cardiomyopathy and even as a first filter to screen for suspected Fabry disease. METHODS: Therefore, we performed a blinded echocardiography in a non-selected population of patients with Fabry disease and matched controls. We included 23 echocardiographic studies of Fabry patients. RESULTS: Two of the Fabry patients had binary appearance of the endocardium. One of them had left ventricular hypertrophy (LVH) and the other had a normal left ventricular mass. Binary appearance of the endocardium was detected in four of the controls, and one of them had LVH. Subgroup analysis of patients who had LVH indicated a sensitivity of 12.5% and a specificity of 66.7% for binary appearance of the endocardium to detect Fabry disease as the underlying cause of LVH. Overall, binary appearance of the endocardium had a sensitivity and a specificity of 15.4 and 73.3%, respectively, to distinguish patients with Fabry disease from controls in our population. CONCLUSIONS: Binary appearance of the endocardium is not feasible for screening Fabry disease by echocardiography.

Severe coronary artery stenoses and reduced coronary flow velocity reserve in atherosclerotic mouse model: Doppler echocardiography validation study.

OBJECTIVE: Genetically modified hyperlipidemic mice are increasingly used as an animal model of atherosclerosis, but their coronary artery disease remains poorly characterized. Furthermore, non-invasive tools to detect functional consequences of coronary lesions remain to be tested in mice. Coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography provides a hemodynamic measure of coronary artery stenosis severity in humans. Thus, we applied Doppler echocardiography in atherosclerotic mice to study the relationship between CFVR and histologically determined coronary artery narrowing. METHODS: Atherosclerotic LDLR/ApoB48 double knockout mice of 58-72 weeks age (n=12) and age-matched C57BL/6 mice (n=5) were studied. CFVR was measured in anesthetized mice by Doppler echocardiography in the middle left coronary artery (LCA) during adenosine-induced maximal vasodilatation. Histopathology of proximal and middle LCA was studied in serial tissue sections. RESULTS: All LDLR/ApoB48 double knockout mice had atherosclerotic lesions in the proximal, but not in the middle LCA causing various degrees of luminal narrowing (30-97%). No lesions were found in controls. Compared with controls, CFVR was significantly reduced in the atherosclerotic mice (2.3+/-0.5 vs. 1.7+/-0.5, p=0.02). There was a negative correlation between CFVR and the amount of luminal narrowing (r=-0.91, p=0.001). Average CFVR was consistently lower in mice that had >or=70% than <70% stenosis (1.3+/-0.1, n=7 vs. 2.2+/-0.4, n=5, p=0.0002). CONCLUSIONS: LDLR/ApoB48 double knockout mice are characterized with histologically severe coronary artery narrowings. Reduced CFVR is a consistent feature of these lesions. Doppler echocardiography of coronary artery flow can be used to detect flow-limiting stenosis in living atherosclerotic mice.

Coronary artery flow velocity profile measured by transthoracic Doppler echocardiography predicts myocardial viability after acute myocardial infarction.

OBJECTIVE: To study whether flow velocity profile in the left anterior descending coronary artery (LAD) measured by transthoracic Doppler echocardiography (TTDE) predicts myocardial viability after reperfused anterior acute myocardial infarction (AMI). PATIENTS AND METHODS: 15 patients who had their first anterior ST elevation AMI and were successfully reperfused by coronary angioplasty and five controls without coronary artery disease were selected. Blood flow velocity spectrum was measured from the mid-LAD by TTDE 3 days after coronary angioplasty. Myocardial viability in the LAD region was quantified 3 months after AMI by relative uptake of 18F-fluorodeoxyglucose (FDG) imaged with positron emission tomography. Myocardium was graded as viable, partially viable or non-viable (relative FDG uptake >85%, 67-85% and <67%, respectively). Main outcome measures were diastolic deceleration time (DDT) of LAD flow velocity 3 days after AMI and myocardial viability 3 months after AMI. RESULTS: DDT of LAD flow velocity correlated with myocardial FDG uptake in the LAD region (r = 0.91, p<0.01). DDT was markedly longer in patients with viable myocardium (876+/-76 ms, n = 3) than partially viable (356+/-89 ms, n = 6, p<0.01), or non-viable myocardium (128+/-13 ms, n = 6, p<0.01). In controls, DDT was comparable (909+/-76 ms, n = 5) to patients with viable myocardium. DDT <190 ms was always associated with non-viable myocardium. CONCLUSIONS: DDT of LAD flow velocity is strongly associated with myocardial viability after reperfused anterior AMI. Non-invasive TTDE of the LAD may be used in the acute phase to predict long-term viability of the jeopardised myocardium.

A moderate dose of red wine, but not de-alcoholized red wine increases coronary flow reserve.

BACKGROUND: Red wine consumption is associated with reduced cardiovascular disease mortality. Its cardioprotective properties may be partly related to its ability to improve endothelial function. The purpose of this randomized controlled cross-over study was to determine whether moderate doses of red wine and de-alcoholized red wine improve coronary flow velocity reserve (CFR). METHODS: Using transthoracic Doppler echocardiography, 176 CFR measurements were made in 22 healthy men before and after ingestion of a moderate (4.0+/-0.4 dl) and an escalating high dose (total amount 8.1+/-0.9 dl) of alcohol-containing red wine and de-alcoholized red wine, which contained similar amounts of phenolic substances. The difference in plasma antioxidant capacity was determined by colorimetric assay kit. RESULTS: Red wine increased CFR from 3.8+/-1.4 to 4.5+/-1.4 (p<0.01) and 4.0+/-1.2 (p=NS) after moderate and high doses, respectively; whereas de-alcoholized red wine had no significant effects on CFR (4.0+/-0.7, 4.3+/-1.3 and 4.5+/-1.4, respectively). Plasma antioxidant capacity increased significantly after high dose of red wine (27.5+/-14.7%, p<0.001), but not after de-alcoholized red wine (0.5+/-10.5%, p=NS) despite similar amounts of phenolic substances. Differences between CFR and plasma antioxidant capacities before and after drinking had no significant association. CONCLUSIONS: A moderate dose of red wine, but not de-alcoholized red wine increases CFR. The increase of CFR is probably mediated by other than direct antioxidant properties of polyphenols, because the simultaneous increase of CFR and plasma antioxidant capacity were not associated.

Coronary flow reserve and heart failure in experimental coxsackievirus myocarditis. A transthoracic Doppler echocardiography study.

The objective of this study was to apply transthoracic Doppler echocardiography (TTDE) in mice to study coronary flow reserve (CFR), an index of coronary microvascular function, in mild and severe forms of experimental viral myocarditis. Regarding methodology, BALB/c mice were infected with cardiotropic coxsackieviruses causing either a mild (Nancy strain) or a severe (Woodruff strain) myocarditis. Left ventricular dimensions, fractional shortening, and CFR (ratio of left coronary artery flow velocity during maximal adenosine-induced vasodilatation to rest) were measured by TTDE before infection and again 1 or 2 wk after infection. As a result, the resting flow velocity did not change after infection. In contrast, CFR reduced significantly 1 wk after infection with either virus variant [from 2.5 (SD 0.3) to 1.4 (SD 0.1) in severe and from 2.4 (SD 0.4) to 2.1 (SD 0.3) in mild myocarditis], being significantly lower in the severe than mild myocarditis. CFR remained low in severe myocarditis 2 wk after infection. Fractional shortening decreased to the same levels 1 wk after infection with either virus variant [from 0.54 (SD 0.02) to 0.43 (SD 0.03) in severe and from 0.51 (SD 0.03) to 0.44 (SD 0.02) in mild myocarditis, P < 0.05]. However, 2 wk after infection, mice with severe myocarditis had enlarged left ventricles and lower fractional shortening [0.31 (SD 0.03)] than mice with mild myocarditis [0.47 (SD 0.02), P < 0.01]. In conclusion, CFR measured with TTDE is reduced in coxsackievirus myocarditis in mice. Low CFR is associated with progressive heart failure, indicating that dysfunction of coronary microcirculation is a determinant of poor outcome in viral myocarditis.

Transesophageal echocardiography in the diagnosis of thrombosis associated with permanent transvenous pacemaker electrodes.

OBJECTIVES: We sought to assess the value of transesophageal echocardiography (TEE) in the diagnosis of PM-lead-associated central venous thrombi. BACKGROUND: Venous thrombosis is not infrequent after pacemaker (PM) or implantable cardioverter-defibrillator (ICD) implantation. Previous incidence studies of thrombosis have been based on venography or Doppler ultrasound, but the role of TEE has not been systematically evaluated in this setting. METHODS: Study group comprised 66 consecutive patients (mean age 64 years, 67 % male) referred for implantation of their first PM or ICD and with a successful TEE, transthoracic echocardiography (TTE) and venography at 6 months after implantation. The total number of implanted leads was 110. During the 6 months of clinical follow-up, nuclear ventilation-perfusion scan or spiral computed tomography was performed when symptoms aroused a clinical suspicion of PE. RESULTS: TEE revealed a right atrium (RA) or lower superior vena cava (SVC) thrombus in 6 (9%) patients. These thrombi were not visualized by TTE or venography. Additionally, 12 (20%) patients were found to have venographic subclavian or innominate vein thrombi, but none of those could be diagnosed with TEE. Symptomatic pulmonary embolism (PE) was diagnosed in two and an asymptomatic PE in one individual and two of these occurred among the six patients with a thrombus in TEE. No clinical predictors for thrombosis were found. CONCLUSIONS: TEE is an excellent method to visualize electrodes within the RA and proximal SVC. Electrode-associated RA thrombi appear to be relatively common after PM implantation, and they may remain undetectable by venography or TTE. Although these thrombi are mostly asymptomatic, they can give rise to pulmonary embolism and should also be kept in mind in the differential diagnosis of endocarditis. TEE is the method of choice for the diagnosis of these lesions.

Determinants of coronary flow velocity reserve in healthy young men.

The objective of this study was to identify risk markers for attenuated coronary flow velocity reserve (CFVR) that exist in healthy young men without evident atherosclerotic risk factors. Coronary blood flow velocity was measured with transthoracic Doppler echocardiography at baseline and during adenosine infusion in 37 healthy nonsmoking men [mean age, 27 yr (SD 4.0)]. Body composition and distribution of fat tissue were assessed with anthropometric measures and regulation of fat metabolism by determination of adiponectin and leptin levels. Physical performance capacity was tested with ergospirometry. The mean body mass index was 23 kg/m2 (SD 1.9), waist-to-hip ratio was 0.84 (SD 0.04), and CFVR was 3.5 (SD 0.61). Obesity indexes at study outset, leptin, adiponectin, maximal load (Max load in W/kg) and maximal oxygen consumption (Vo2 peak in ml x kg(-1) x min(-1)) in ergospirometry, rate-pressure product, and heart rate at rest were significantly associated with CFVR. In multivariate analysis, Max load (in W/kg) and waist-to-hip ratio were the only independent predictors of CFVR. We found no relationship between CFVR and serum lipids or body mass index. We conclude that abdominal fat accumulation and low aerobic fitness are independently associated with CFVR in men.

Transthoracic Doppler echocardiography as a noninvasive tool to assess coronary artery stenoses--a comparison with quantitative coronary angiography.

We prospectively tested the diagnostic accuracy of Doppler transthoracic echocardiography in detection of coronary artery stenoses throughout the main coronary arterial tree. In all, 84 patients referred for diagnostic quantitative coronary angiography were studied. Coronary artery stenosis was identified with color Doppler as local spot of turbulence, and local flow velocity was measured using pulsed wave Doppler. Angiography showed significant stenoses (diameter reduction > 50%) in 33 patients. An abnormal maximal-to-prestenotic blood flow velocity ratio greater than 2.0 in subtotal stenoses, or the detection of collateral blood flow in the absence of normal antegrade flow in the case of total occlusion (N = 6), resulted in overall sensitivity of 82% and specificity of 92%. The sensitivity and specificity were, respectively, 73% and 92% for left anterior descending coronary artery, 63% and 96% for right coronary artery, and 38% and 99% for left circumflex coronary artery stenoses. Transthoracic echocardiography is a promising noninvasive technique to diagnose significant coronary artery stenoses.