Francesco Pizzuto

Assessment of Flow Velocity Reserve by Transthoracic Doppler Echocardiography and Venous Adenosine Infusion Before and After Left Anterior Descending Coronary Artery Stenting

OBJECTIVES We sought to evaluate whether coronary flow velocity reserve (CFR) (the ratio between hyperemic and baseline peak flow velocity), as measured by transthoracic Doppler echocardiography during adenosine infusion, allows detection of flow changes in the left anterior descending coronary artery (LAD) before and after stenting. BACKGROUND The immediate post-stenting evaluation of CFR by intracoronary Doppler has shown mixed results, due to reactive hyperemia and microvascular stunning. Noninvasive coronary Doppler echocardiography may be a more reliable measure than intracoronary Doppler. METHODS Transthoracic Doppler echocardiography during 90-s venous adenosine infusion (140 microg/kg body weight per min) was used to measure CFR of the LAD in 45 patients before and 3.7 +/- 2 days after successful stenting, as well as in 25 subjects with an angiographically normal LAD (control group). RESULTS Adequate Doppler spectra were obtained in 96% of the patients. Pre-stent CFR was significantly lower in patients than in control subjects (diastolic CFR: 1.45 +/- 0.5 vs. 2.72 +/- 0.71, p < 0.01; systolic CFR: 1.61 +/- 1.02 vs. 2.41 +/- 0.68, p < 0.01) and increased toward the normal range after stenting (diastolic CFR: 2.58 +/- 0.7 vs. 2.72 +/- 0.75, p = NS; systolic CFR: 2.43 +/- 1.01 vs. 2.41 +/- 0.52, p = NS). Diastolic CFR was often damped, suggesting coronary steal in patients with > or =90% versus <90% LAD stenosis (0.86 +/- 0.23 vs. 1.69 +/- 0.43, p < 0.01). Coronary stenting normalized diastolic CFR in these two groups (2.45 +/- 0.77 and 2.64 +/- 0.69, respectively, p = NS), even though impaired diastolic CFR persisted in three of four patients with > or =90% stenosis. Stenosis of the LAD was better discriminated by diastolic (F = 49.30) than systolic (F = 12.20) CFR (both p < 0.01). CONCLUSIONS Coronary flow reserve, as measured by transthoracic Doppler echocardiography, is impaired in LAD disease; it may identify patients with > or =90% stenosis; and it normalizes early after stenting, even in patients with > or =90% stenosis.

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.

Noninvasive surrogate markers of atherosclerosis

Noninvasive imaging techniques offer a unique opportunity to study the relation of surrogate markers to the development of atherosclerosis. These noninvasive imaging modalities include: (1) carotid artery, coronary, and aorta imaging; (2) left ventricular echocardiography imaging; (3) electron-beam computed tomography; (4) magnetic resonance imaging; and (5) ankle-brachial index. Because the incidence of coronary artery disease is a function of the development and progression of atherosclerosis, the use of noninvasive surrogate markers of atherosclerosis can aid in the diagnosis of cardiovascular disease through the identification of subclinical disease. Noninvasive imaging techniques provide an approach for identifying high-risk individuals who may benefit from active intervention to prevent clinical disease.

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.

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.

Coronary flow: how far can we go with echocardiography?

The possibility of directly observing arterial flow in vivo has been the dream of scientists for centuries [(Fig. 1)][1], but more than that, both noninvasive imaging of coronary flow and measurement of flow reserve have been considered a chimera. ![Figure 1][2] Figure 1 John Marshall’s

Regression and shift in composition of coronary atherosclerotic plaques by pioglitazone: insight from an intravascular ultrasound analysis.

Background Plaque reduction with the use of pioglitazone and statin combination therapy has been observed in carotid plaque. We sought to investigate the effect of combination therapy with statins and pioglitazone on coronary plaque regression and composition with the use of intravascular ultrasound (IVUS) and intravascular ultrasound-virtual histology (IVUS-VH). Methods We analysed 29 plaques in 25 diabetic patients with angiographic evidence of nonsignificant coronary lesions with IVUS-VH. Patients were treated with 80 mg of atorvastatin and 30 mg of pioglitazone daily for 6 months. After 6 months of therapy, IVUS-VH of each lesion was reacquired. Results Mean elastic external membrane volume was significantly reduced between baseline and follow-up (343.9 vs. 320.5 mm3; P < 0.05) as was mean total atheroma volume (179.3 vs. 166.6 mm3; P < 0.05). Change in total atheroma volume showed a 6.3% mean reduction. Areas of fibrous tissue, fibrolipidic tissue and calcium decreased over the 6 months of follow-up, although not significantly. On the other hand, the necrotic core increased from 9 to 14% (P < 0.05). Conclusion Our data demonstrated that atorvastatin/pioglitazone association is able to induce significant regression of coronary atherosclerosis, acting on plaque composition. Our findings are preliminary results and will be confirmed in an ongoing randomized placebo-controlled multicenter trial (PIPER; Pioglitazone for Prevention of Restenosis in Diabetics with Complex Lesion; trial registration: clinical trials.gov. Identifier: NCT 00376870).

Clinical study: editorial commentCoronary flow: how far can we go with echocardiography?*

The possibility of directly observing arterial flow in vivo has been the dream of scientists for centuries [(Fig. 1)][1], but more than that, both noninvasive imaging of coronary flow and measurement of flow reserve have been considered a chimera. ![Figure 1][2] Figure 1 John Marshall’s

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.

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.