Prediction of long-term ischemic events by noninvasively assessed coronary flow reserve.

BACKGROUND: Coronary flow reserve (CFR) by adenosine echocardiography in left anterior descending (LAD) or posterior descending coronary arteries may predict clinical outcome. METHODS: We used models accounting (Cox's model) or not (logistic regression and neural network) for time to event and either considered (forced models) or not (stepwise logistic regression and neural network models) all among 21 covariates to predict 1-year composite events after LAD CFR. RESULTS: There were 553 consecutive patients with coronary artery disease (CAD): 89 patients had also posterior descending CFR. During 1-year follow-up 328 patients were event-free, 35 had composite ischemic events and 190 underwent short-term revascularization. LAD and posterior descending CFR (respectively, 1.53 ±â€Š0.83, N = 225 and 1.84 ±â€Š0.80, N = 42) were significantly (P < 0.0001) lower in patients with events (or with revascularization following CFR measurement) than in those without (respectively, 3.13 ±â€Š0.84, N = 328, and 2.53 ±â€Š0.72, N = 47). Using LAD CFR as a continuous covariate, by both forced Cox's and logistic regression, coefficients (t values, respectively, -14.11 and -10.19) were significant (both P < 0.00001) to predict outcome. Global predictive accuracies by neural network, adopting a receiver operating characteristic areas under the curve (ROC) assessment, were excellent (>0.91) and the role of LAD CFR among predictors was overwhelming. Other indices of myocardial ischemia and the presence of coronary stenoses or previous infarction did not modify the multivariable predictive role of LAD CFR. When patients with revascularization were discounted, the LAD CFR predictive role was the same. CONCLUSIONS: Thus, adenosine echocardiography-based LAD CFR predicts 1-year composite ischemic events in patients with CAD, independent of the multivariable model adopted. Posterior descending CFR also has a role.

Usefulness of coronary flow reserve measured by echocardiography to improve the identification of significant left anterior descending coronary artery stenosis assessed by multidetector computed tomography.

Multidetector computed tomography (MDCT) detects coronary artery disease. However, an overestimation of coronary artery stenosis and artifacts can prevent accurate identification of significant coronary narrowing. The combination of MDCT with coronary flow reserve (CFR), the hyperemic/baseline peak flow velocity ratio, measured by transthoracic Doppler echocardiography might be helpful. We studied 144 consecutive patients with CFR and quantitative coronary angiography, obtained using both MDCT and invasive coronary angiography (reference method). It was hypothesized that the CFR might provide an incremental value to MDCT in detecting significant (> or =70%) left anterior descending (LAD) coronary artery stenosis. A CFR cutoff of <2 was used to discriminate significant stenosis. CFR was feasible in 141 (98%) of 144 patients, and MDCT was feasible in 131 (91%) of 144 patients (p <0.02). In a univariate model, the prediction of significant LAD stenosis was slightly, but significantly (p <0.0001), better with CFR (sensitivity 90%, specificity 96%, positive predictive value 84%, negative predictive value 97%, and diagnostic accuracy 94%, chi-square = 97.5) than with MDCT (sensitivity 80%, specificity 93%, positive predictive value 71%, negative predictive value 95%, diagnostic accuracy 90%, chi-square = 63.2). When the findings from transthoracic Doppler echocardiography and MDCT agreed, the diagnostic accuracy increased (96%; chi-square = 86.1, p <0.0001). In a multivariate prediction of significant LAD stenosis using a logistic neural network, CFR overshadowed MDCT, and the area under the receiver operating curve was 0.99. Of the 13 patients missed by MDCT, the diagnostic accuracy of transthoracic Doppler echocardiography to predict significant LAD stenosis was 100%. Thus, CFR could improve the diagnostic accuracy of MDCT to detect significant LAD stenosis.

Clinical value of echocardiographic assessment of coronary flow reserve after left anterior descending coronary artery stenting in an unselected population.

BACKGROUND: Transthoracic Doppler echocardiography is a valuable tool to measure coronary flow reserve (CFR) and detect in-stent restenosis (ISR) after percutaneous coronary angioplasty in selected series of patients. OBJECTIVES: To assess the usefulness of coronary flow reserve measured by echocardiography in detecting significant (> or =70%) ISR of the left anterior descending coronary artery in a large unselected population. METHODS: Two hundred and twenty-three patients (age 61 +/- 10 years; 168 men) treated with left anterior descending stenting underwent CFR measurement by transthoracic Doppler echocardiography and venous adenosine infusion 24-72 h before control coronary angiography. Coronary-active drugs were continued, and patients with multiple risk factors and old anterior-apical myocardial infarction were included. RESULTS: Significant ISR occurred in 56 patients (25%). Patients with ISR had higher basal coronary flow velocity (27 +/- 10 cm/s vs. 24 +/- 7 cm/s; P < 0.002) and lower CFR (1.5 +/- 0.5 vs. 2.7 +/- 0.6; P < 0.0001) than those without ISR. A linear relation was found between ISR and CFR (r = -0.73; P < 0.0001) and remained significant after adjustment for blood pressure and heart rate (r = -0.74; P < 0.0001). A CFR less than two identified significant ISR (sensitivity 88%, specificity 88%, area under the curve = 0.943; P < 0.001). In a multivariate model of CFR prediction, myocardial infarction and heart rate were slightly contributory (ss = -0.19, P < 0.01; ss = -0.16, P < 0.03, respectively), whereas ISR had a large influence (ss = -0.66; P < 0.0001). The inverse correlation between ISR and CFR persisted in patients with myocardial infarction (r = -0.64; P < 0.0001) and in those treated with beta-blockers (r = -0. 71; P < 0.0001). CONCLUSION: Echocardiographic measurement of CFR detects significant left anterior descending ISR in unselected patients with multiple risk factors, old anterior-apical myocardial infarction, and taking beta-blockers.

Electrocardiographic markers of structural heart disease and predictors of death in 2332 unselected patients undergoing outpatient Holter recording.

AIMS: To test the hypothesis that the QS interval of ventricular ectopic beats (VEBs) (ventricular ectopic QS interval, VEQSI) would provide a marker for the presence of structural heart disease and a predictor of mortality. METHODS AND RESULTS: We interviewed and examined 2332 patients undergoing Holter ECG monitoring for clinical indications. In persons with VEBs, the morphologies were counted and the QS interval was measured for each of these morphologies. The duration of the broadest VEB, measured from the QRS onset in the derivation showing the earliest onset to its end in the derivation showing the latest termination, was taken as that patient's VEQSI. Survival was ascertained from public health records. Of 15 electrocardiographic variables pre-selected as potential prognostic indicators, VEQSI demonstrated the strongest association with the presence of structural heart disease (P = 0.013). Thirty-four persons died in 16 +/- 4 months follow-up. Univariate predictors of mortality are age, history of myocardial infarction, maximum heart rate, QS interval, the number of VEB morphologies, and the VEQSI. On multivariate analysis, only age (P < 0.001) and the number of VEB morphologies (P = 0.02) predicted mortality. CONCLUSION: VEQSI predicts the presence of structural heart disease. The number of VEB morphologies in a Holter recording predicts all-cause mortality.

Functional assessment of the collateral-dependent circulation in chronic total coronary occlusion using transthoracic Doppler ultrasound and venous adenosine infusion.

The measurement of collateral flow reserve (CFR; the hyperemic/baseline collateral flow velocity ratio) in patients with chronic total coronary occlusion requires invasive and expensive techniques. Noninvasive transthoracic coronary Doppler echocardiography may be an alternative option. Fifty-one patients with chronic total coronary occlusion were evaluated by transthoracic coronary Doppler echocardiography and venous adenosine infusion to measure CFR in occluded coronary arteries (the left anterior descending artery in 44 patients and the artery supplying the posterior descending artery in 7 patients). CFR data were plotted against 3 angiographic parameters: (1) grade of the epicardial filling of the occluded artery (1=absent, 2=partial, 3=complete), (2) stenosis of the donor artery, and (3) the extent of coronary artery disease (vessels with >or=70% stenosis). Collateral flow was maintained at stress in 34 patients (CFR>or=1, range 1.0 to 2.2) but was withdrawn in 17 patients (CFR<1, range 0.25 to 0.90). CFR increased with the degree of angiographic collateral flow (grade 1: 0.73+/-0.29; grade 2: 1.16+/-0.31; grade 3: 1.34+/-0.49; F=5.31, p=0.008). A multivariate model of CFR prediction showed a direct relation with angiographic collateral grade and the number of diseased vessels and an inverse relation with stenosis of the donor artery. In conclusion, CFR measurement is feasible by transthoracic coronary Doppler echocardiography. One third of the patients with chronic total coronary occlusion had collateral flow withdrawal at stress, which occurs when collateral circulation is poor and when the donor artery is stenotic. CFR correlates with angiographic collateral grade and with the extent of coronary artery disease.

Evaluation of flow in the left anterior descending coronary artery but not in the left internal mammary artery graft predicts significant stenosis of the arterial conduit.

OBJECTIVES: The purpose of this study was to evaluate which Doppler-derived flow index best predicts new distal left anterior descending coronary artery (LAD) stenosis in patients with left internal mammary artery (LIMA) graft. BACKGROUND: The LIMA flow measurement has been proposed to assess graft function, but it may be misleading in case of new distal LAD stenosis and/or competitive flow from native LAD. Distal LAD coronary flow reserve (CFR: hyperemic/baseline peak flow velocity ratio) may be more appropriate. METHODS: The LIMA and distal LAD flow was measured by transthoracic Doppler echocardiography in 96 patients undergoing diagnostic/therapeutic coronary angiography, 7 +/- 4 years after cardiac bypass surgery. The LIMA flow indexes (systolic-to-diastolic peak velocity ratio [SDPVr] >1, diastolic time velocity integral fraction [DTVIf] <0.5, and CFR <2) and LAD CFR <2 were used to predict > or =70% new LAD stenosis. RESULTS: The LAD CFR <2 predicted new LAD stenosis, found in 21 of 77 patients without competitive flow from native LAD, with significantly higher diagnostic accuracy (98%) than LIMA flow indexes (SDPVr >1 = 61%, DTVIf <0.5 = 69%, and CFR <2 = 72%). The LIMA flow indexes were abnormal in 17 of 19 patients with competitive graft flow, but only 5 had graft restriction, and none had significant LAD stenosis. In a multivariate model of new distal LAD stenosis prediction, competitive flow from native LAD reduced the predictive role of LIMA but not of LAD CFR. CONCLUSIONS: In patients without competitive flow from native LAD, LAD CFR is more accurate for the detection of LAD stenosis than LIMA CFR. In patients with competitive graft flow, abnormal LIMA flow patterns and blunted LIMA CFR do not reflect downstream LAD flow as LAD CFR does.

Coronary flow reserve of the angiographically normal left anterior descending coronary artery in patients with remote coronary artery disease.

Coronary artery disease (CAD) has been suggested to alter coronary flow reserve (CFR; the ratio between hyperemic and baseline coronary flow velocities) not only in territories supplied by stenotic arteries but also in angiographically normal, remote regions. However, few data exist regarding the left anterior descending (LAD) coronary artery as the normal index artery. The influence of remote CAD on CFR of the angiographically normal LAD was evaluated with transthoracic Doppler ultrasound to measure CFR in the LAD during 90 seconds of venous adenosine infusion (140 microg/kg/min) in 122 subjects who were assigned to 1 group; group 1 comprised 49 controls without angiographically detectable CAD, and group 2 consisted of 73 patients with an angiographically normal LAD and remote CAD. Group 2 was divided into 4 subgroups: 16 patients with previous remote percutaneous coronary intervention (group 2A); 13 patients with significant remote stenosis (group 2B); 23 patients with previous remote myocardial infarction and percutaneous coronary intervention (group 2C); and 21 patients with previous remote myocardial infarction but no percutaneous coronary intervention (group 2D). CFR in the LAD was not significantly different in groups 1 and 2 (3.08 +/- 0.61 and 3.03 +/- 0.69, respectively, p = NS). Decreased ejection fraction and increased wall motion score index in patients with remote CAD (p < 0.00001) and multivessel CAD did not affect CFR in the LAD (group 2A 3.18 +/- 0.77; group 2B 3.05 +/- 0.65; group 2C 3.07 +/- 0.79; group 2D 2.86 +/- 0.50, respectively; F = 0.63, p = NS). In conclusion, CFR of an angiographically normal LAD is preserved in patients with remote CAD, even in the presence of previous remote myocardial infarction and wall motion abnormalities.

Impact of flow level on coronary flow velocity pattern. A doppler flow study in patients with first acute myocardial infarction.

Analysis of coronary flow velocity pattern has been used to assess microvascular function post acute myocardial infarction (AMI). This study sought to analyze whether the flow level has an impact on parameters of coronary flow velocity pattern. Parameters of coronary flow velocity pattern were determined at baseline and during increased flow due to maximal hyperemia induced by adenosine in 25 patients after PTCA for first AMI using Doppler flow wires. Patients were divided into those with depressed (global wall motion index (GWMI) > or = 1.5; n = 14) and those with preserved (GWMI < 1.5; n = 11) left ventricular (LV) function at 4 weeks. Coronary flow velocity pattern at rest was different between patients with depressed and patients with preserved LV function at follow-up. A difference in flow pattern between the groups remained at increased flow level. However, increase of flow altered parameters of flow pattern. Diastolic deceleration rate (DSR) increased for patients with preserved LV function (53.7+/-25.6 at baseline vs. 67.0+/-29.8 cm/s2 with adenosine) and depressed LV function (95.3+/-58.6 vs. 110.7+/-61.4 cm/s2, respectively, p = 0.0012). Induction of hyperemia resulted also in increased systolic and diastolic peak flow velocity and diastolic deceleration time (DDT). Higher flow had no impact on early systolic retrograde flow, systolic flow duration and diastolic-systolic velocity ratio (DSVR). The coronary flow velocity pattern allows prediction of LV function at 4 weeks after AMI. However, it should be considered that some parameters of the flow velocity pattern are affected by the coronary flow level.

Usefulness of coronary flow reserve measured by transthoracic coronary Doppler ultrasound to detect severe left anterior descending coronary artery stenosis.

Transthoracic coronary Doppler ultrasound during venous adenosine infusion showed damped (<1) coronary flow velocity reserve in patients with severe left anterior descending coronary artery stenosis. Damped coronary flow reserve discriminated severe from nonsevere stenosis with high sensitivity, specificity, and positive predictive accuracy, and is a unique noninvasive tool to identify high-risk patients.

Value of echocardiography in predicting future cardiac events after acute myocardial infarction.

Short- and long-term survival after acute myocardial infarction mainly depends on three factors: the amount of myocardium that had become necrotic, the area of myocardium at further risk of becoming necrotic, and the patency of the infarct-related artery. Echocardiography is a low-cost, safe, bedside, repeatable tool, particularly useful for prognostic stratification after myocardial injury. Two-dimensional echocardiography analyzes left ventricular function, the most powerful predictor of survival immediately after acute myocardial infarction. Myocardial contrast echocardiography measures the infarct size and detects viable myocardium. Stress echocardiography stratifies patients with viable myocardium and/or multivessel coronary artery disease who need further diagnostic and therapeutic interventions. Transthoracic coronary Doppler ultrasonography assesses effective recanalization and coronary flow reserve of the left anterior descending coronary artery. Further technologic advances are needed to allow direct noninvasive measurement of flow by transthoracic Doppler ultrasonography in other coronary arteries.

Noninvasive coronary flow reserve assessed by transthoracic coronary Doppler ultrasound in patients with left anterior descending coronary artery stents.

Noninvasive measurement of coronary flow reserve (CFR) (hyperemic/flow velocity ratio at rest) by transthoracic Doppler echocardiography showed normalization of flow in the left anterior descending (LAD) coronary artery early after stenting. We hypothesized that noninvasive CFR may reveal in-stent restenosis at follow-up. Therefore, we studied 134 patients, 0 to 72 months after successful proximal-middle LAD stenting, and 38 controls. LAD flow velocity was measured by transthoracic Doppler echocardiography during 90 seconds venous adenosine infusion (140 microg/kg/min). CFR was measured in diastole. According to angiography, patients who received stents were divided into 3 groups: group I, <50% LAD in-stent restenosis (n = 83); group II, nonsignificant (50% to 69%) LAD in-stent restenosis (n = 17); and group III, significant (> or = 70%) LAD in-stent restenosis (n = 34). LAD CFR was similar in group I and controls (2.90 +/- 0.58 vs 3.05 +/- 0.81; p = NS), it was slightly lower in group II (2.42 +/- 0.33) compared with controls and group I (p <0.001 vs both), and clearly abnormal (<2) in group III (1.38 +/- 0.48) compared with controls, and groups I and II (p <0.001). A CFR <2 had 91% sensitivity, 95% specificity, and 96% positive and 97% negative predictive values to detect significant stenosis in patients with LAD stents. Our data show that noninvasive Doppler assessment of CFR allows identification of significant LAD in-stent restenosis, based on a cut-off value of <2.

Measurement of coronary flow reserve in the anterior and posterior descending coronary arteries by transthoracic Doppler ultrasound.

We describe for the first time transthoracic Doppler ultrasound assessment of coronary flow reserve (CFR) in both the posterior descending (PDA) and left anterior descending (LAD) coronary arteries. CFR (hyperemic/resting diastolic flow velocity ratio) was measured by 90-second intravenous adenosine infusion (140 microg/kg/min). Baseline PDA flow was detected in 62 of 81 subjects (76%), and the CFR was measurable in 44 of them (54%) because of adenosine-induced hyperventilation. According to angiography, these 44 subjects were divided into 3 groups: group 1 (0% to 29% stenosis), group 2 (30% to 69% stenosis), and group 3 (> or =70% stenosis). PDA CFR was 2.62 +/- 0.25 in 17 patients in group 1, 2.33 +/- 0.32 in 9 patients in group 2, and 1.40 +/- 0.54 in 18 patients in group 3 (F = 41.83, p <0.0001). LAD CFR was 3.31 +/- 0.54 in 15 patients in group 1, 2.49 +/- 0.71 in 10 patients in group 2, and 1.12 +/- 0.49 in 19 patients in group 3 (F = 65.68, p <0.0001). A cut-off of <2 identified > or =70% stenosis in both of the arteries supplying the PDA and in the LAD. Noninvasive measurement of PDA CFR is feasible and may improve with technologic advancement and the use of selective adenosine receptor agonists, thus preventing hyperventilation.

Coronary recanalization in anterior myocardial infarction: the open perforator hypothesis.

OBJECTIVE: Patent perforators, noninvasively imaged by transthoracic color-Doppler echocardiography, may reflect adequate reperfusion in anterior myocardial infarction (MI). BACKGROUND: The Thrombolysis In Myocardial Infarction (TIMI) classification may not fully reflect adequate myocardial reperfusion in MI. METHODS: We studied 61 patients with anterior MI undergoing thrombolysis (n = 28), primary stenting (n = 20), or neither one (n = 13). High-resolution color-Doppler ultrasound was used to image the left anterior descending coronary artery (LAD) and perforators in four segments of the anterior-apical wall and to build a new recanalization score (RS). The TIMI flow was assessed by angiography. Wall motion score index (WMSI), ejection fraction (EF), end-diastolic volume index, and end-systolic volume index (ESVI) were measured by echocardiography at baseline and at three-month follow-up. Linear regression equations, considering RS or TIMI flow as independent variables, were compared among these functional recovery parameters. A multivariate linear model, predicting percent changes of WMSI, EF, or ESVI, was used to investigate the contribution of several clinical covariates along with RS and TIMI flow. RESULTS: Sensitivity, specificity, and diagnostic accuracy of color-Doppler ultrasound in detecting LAD patency were 86%, 98%, and 97%, respectively. Mean and peak flow velocities discriminated (0.004 < p < 0.008) TIMI flow but not RS. Regression equations showed that RS discriminated better than TIMI flow recovery of ventricular function (p < 0.012). The RS was the best single multivariate predictor (p < 0.0001) of percent changes in WMSI, EF, and ESVI. CONCLUSIONS: Transthoracic color-Doppler ultrasound detects an open LAD after MI. Perforators reflect adequate myocardial reperfusion and are early noninvasive markers of myocardial viability.

Intravenous myocardial contrast echocardiography predicts left ventricular remodeling in patients with acute myocardial infarction.

BACKGROUND: This study evaluated the ability of intravenous myocardial contrast echocardiography (MCE) performed in the setting of acute myocardial infarction for prediction of left ventricular (LV) remodeling. METHODS: Intravenous MCE was performed immediately before, 1 hour, and 24 hours after primary percutaneous transluminal coronary angioplasty (PTCA) in 35 patients with a first myocardial infarction. The MCE was used to define the relative perfusion defect size (in %; relMCD). Two-dimensional echocardiography was performed directly after angioplasty and after 4 weeks to determine LV end-diastolic volumes (LVEDV). The increase in LVEDV at 4 weeks defined a remodeling (> 15% increase) and a nonremodeling group (< or = 15% increase). RESULTS: Patients with remodeling had larger relMCD before (22.0 +/- 16.1 vs 8.0 +/- 11.9, P =.015), 1 hour (20.0 +/- 13.0 vs 4.9 +/- 11.6, P =.001), and 24 hours after PTCA (22.9 +/- 14.1 vs 1.2 +/- 2.8, P <.001). There was a significant correlation between relMCD 24 hours after PTCA and the increase in LVEDV at 4 weeks (r = 0.648; P <.001). Receiver operating characteristic (ROC) curve analysis revealed a relMCD at 24 hours of 5.1% or more to predict remodeling with a sensitivity of 94% and a specificity of 87% (area under ROC curve = 0.917; SE = 0.054). Multivariate analysis demonstrated relMCD at 24 hours to be the only predictor of remodeling (odds ratio = 173.4; P =.022). CONCLUSION: The size of the persistent MCE perfusion defect after revascularization for acute myocardial infarction has a high predictive value for LV remodeling during a 4-week follow-up period.

Alfentanil and sufentanil in fast-track anesthesia for coronary artery bypass graft surgery.

OBJECTIVE: To evaluate alfentanil, sufentanil, and the combination of both opioids in patients undergoing cardiac surgery. DESIGN: Prospective, randomized study. SETTING: University hospital. PARTICIPANTS: Patients undergoing coronary artery bypass graft (CABG) surgery (n = 195), randomly assigned to 3 groups of 65 each. INTERVENTIONS: Patients in group A received alfentanil, induction (15 microg/kg) and maintenance (15 microg/kg/hr); patients in group S received sufentanil, induction (1 microg/kg) and maintenance (1 microg/kg/h); and patients in group AS received alfentanil and sufentanil, induction with alfentanil (15 microg/kg) and maintenance with sufentanil (1 microg/kg/hr). MEASUREMENTS AND MAIN RESULTS: Hemodynamic data showed a reduction of all parameters at induction in the 3 groups (p < 0.05). Cardiac index decreased at induction in all groups (p < 0.05) but increased in groups S and AS toward baseline values at the end of surgery. The intubation time and length of stay in the intensive care unit were less in group AS (2.3 +/- 1.2 hours; p < 0.001 and 20 +/- 8 hours; p < 0.05), than in groups A (4.2 +/- 1.7 hours and 28 +/- 13 hours) and S (3.1 +/- 1.1 hours; p < 0.05 and 26 +/- 12 hours). Length of hospital stay and patients' outcome were similar in the 3 groups. CONCLUSION: Although the differences among groups regarding extubation time, intensive care unit length of stay, and some hemodynamic data were statistically significant, the differences were clinically small. All 3 anesthetic protocols were shown to be safe and appropriate for patients undergoing elective coronary artery bypass graft surgery and early postoperative tracheal extubation.