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Myocardial Perfusion Contrast Echocardiography:
The Adenosine Bolus Protocol

Fernando Morcerf, MD; Alvaro Moraes, MD;
Caio Medeiros, MD; Marcia Carrinho, MD

ECOR e Serviço de Ecocardiografia do Hospital Pró-Cardíaco,
Rio de janeiro, Brasil

   Visualization of myocardial ultrasound contrast enhancement after a peripheral vein injection of microbubbles is now possible. (1, 2, 3, 4)

   Perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles (5, 6, 7) as well as other contrast agents (8, 9, 10, 11, 12) have been used for this purpose. In significant coronary artery disease, a myocardial perfusion defect (MPD) is usually demonstrated in the underperfused wall, (13) mainly after dipyridamole (14) or dobutamine (15) stress, what may be useful in identifying myocardial ischemia, (16) area at risk (17) and myocardial infarct size. (16)

   A hallmark of the physiological significance of a coronary obstruction is a reduction in the coronary flow reserve in the involved coronary bed while this flow can be more than three times its rest values in the normal bed. (18) Even though a pharmacological stress with dipyridamole or dobutamine may demonstrate a decreased coronary flow reserve, their mechanism of action has been related primarily to other reasons. (19) For both drugs, myocardial ischemia is a frequent and necessary end point or side effect for the demonstration of the MPD. These drugs do not depict an increase in coronary flow in the normally perfused wall with the available protocols for intravenous myocardial contrast echocardiography (MCE) for human investigation.

   We hypothesized that an IV bolus injection of adenosine during MCE may elicit not only a MPD in the underperfused coronary bed but also a further contrast enhancement in the normal region due to its prompt and short action in decreasing coronary resistance.

   In addition, we established and tested a protocol to detect coronary artery disease (CAD) during rest and pharmacological stress with bolus injection of adenosine in 81 humans beings using intravenous MCE. This protocol showed very high sensitivity and specificity. (20)

   In this initial publication the studied group consisted of 81 patients (mean age 60.3 + 11 years, ranging from 30 to 83; 64 men and 17 women) selected from a cohort of 532 patients who had MCE study while being investigated for symptoms suggestive of coronary artery disease at Pró-Cardíaco Hospital and had a coronary angiography within 1 month of the MCE study.

   Thirty-one patients had evidence of a previous acute myocardial infarction based on clinical history, the presence of pathologic Q waves on the resting ECG, and the presence of regional wall motion abnormalities on left ventriculography and on the 2-D echocardiogram. The walls of the infarct-related coronary arteries were excluded from analysis for the MCE study. In addition, 4 walls (in 4 patients) were excluded from analysis owing to the lack of adequate 2-D echocardiographic visualization. All patients were clinically stable between the MCE study and the angiographic procedure.

   In 9 patients the coronary angiography was considered normal. Of the 72 patients with coronary artery disease, 12 had three-vessels disease, 19 had two-vessels disease, 31 had single-vessel disease, and 10 patients with no residual lesion after a complete revascularization procedure (coronary artery bypass graft in 1, percutaneous transluminal coronary angioplasty alone in 4 and associated to stent in 5 pts).

   For each patient, 3 overlapping left ventricular territories or coronary perfusion beds were considered. The anterior interventricular septum and the anterior wall were considered part of the left anterior descendent (LAD) territory. The antero-lateral wall was considered as belonging to the LAD or to the circumflex artery (Cx) territory and the postero-lateral, posterior and posterior interventricular septum to the CX or the right coronary artery territory. Each wall was further divided in three segments (basal, mid and apical). (21)

   These 81 patients had 70 territories related to a flow limiting coronary lesion (> 75% obstruction), 138 territories related to a normal or no-flow limiting coronary lesion, 31 territories related to prior acute myocardial infarction, and 4 non-visualized territories. In case of more than one obstruction in series, only the most severe stenosis was considered.

   So in these 81 patients, a total of 208 territories not associated to an infarct-related coronary vessels were analyzed. One hundred thirty-eight coronary arteries or territories were normal or had <50% stenoses, and 70 arteries or territories had severe obstruction (> 75% stenoses). Of the 70 coronary obstruction analyzed, there were 18 left anterior descending, 33 left circumflex or proximal obtuse marginal, and 19 right coronary artery territories.

   The visually normal perfusion pattern at rest and after Adenosine bolus injection (figure 1) was observed in 136 of 138 territories (98.5 %) with normal or less than 50% obstructed coronary, while in 2 territories the perfusion pattern was considered abnormal (false positive).

Figura 1: Apical 4 chambers at rest and after bolus injection of Adenosine. A normal perfusion pattern is a further enhancement of
the contrast observed at rest in all segments of the left ventricle
walls.
repouso - before or at rest; Adenosine - after bolus injection.

   A decrease in contrast enhancement before adenosine injection in at least one segment in the territory of a > 75% or totally obstructed coronary compared with those in the normal or < 50% obstructed perfusion bed were considered present by consensus of the two reviewer in 68 of 70 territories (97.2 %):

· after adenosine bolus injection the segments with decreased contrast at rest remained the same size in 32 territories or increased in 20 (fixed defects - figure 2) and,
· in 16 territories with homogenous contrast prior to the injection, a new segment with decreased contrast appeared (reversible defect - figure 3).

Figura 2: Apical 4 chambers at rest and after bolus injection of Adenosine. Example of fixed defect in the basal segment of the lateral wall. It is dark at rest and there is no change after Adenosine. All the other segments are normal (further enhancement of the contrast).
repouso - before or at rest; Adenosine - after bolus injection.


Figura 3: Apical 2 chambers at rest and after bolus injection of Adenosine. Example of reversible defect in the apical region that is normal at rest. After Adenosine there are darkening of this segment. Note that all the other segments have normal perfusion (further enhancement of the contrast).
repouso - before or at rest; Adenosine - after bolus injection.

   In 2 territories only it was observed a normal perfusion pattern at rest and after Adenosine bolus injection (false negative).

   The sensitivity was 97.1 % (68 of 70 territories related to a flow limited obstruction), the specificity was 98.6 % (136 of 138 territories related to a non-flow limited obstruction or normal coronary), and the global accuracy was 98.1 % (204 of 208 analyzed territories). The predictive positive and predictive negative values were 97.1 % and 98.6 % respectively. The odds ratio for an abnormal test was 0.694 and for a normal test was 0.34 (p < 0.001).

   The concordance (in a territory basis) for the presence or absence of coronary obstruction and perfusion defect using the Chi-square test was statistically significant (186.21, p < 0.001), with two discordance in a normal and two in an abnormal territory. The interobserver and intraobserver agreement were excellent, with kappa of 0.94 and 0.91, respectively.

   The Adenosine Protocol will be now exposed in details:

1. Patient Preparation:
   Patients refrained from caffeine containing beverages or theophylline containing medications for 12 hours prior to the exam. If in Dipyridamole medication, it was interrupted the day before the examination. Any other medication was not discontinued.

2. PESDA Administration:
   The PESDA solution was dissolved in 80 ml 5% dextrose and administered in a peripheral vein by continuous infusion, without IV ump, with the dripping rate depending on the contrast effect achieved as described bellow.

3. Initial Settings:
   The initial settings for a commercially available scanner (HDI 3000, ATL, Bothell, WA, USA) were:

· operating in second harmonic;
· 1/1 trigger mode, gated to the peek of the T wave or the R wave on the ECG, whichever allowed the best view;
· 2D map = 8;
· dynamic range = 60 dB;
· output set to produce a mechanical index (MI) = 0.7 or 0.8;
· focus set in the level of the mitral valve in a 4 chamber apical view.

4. Setting The Dripping Rate:
   The initial rate was set to 30 - 40 drops/min. After a waiting period of 1 minute the dripping rate was increased if the contrast in the left ventricular cavity was not maximal (close to white in the gray scale) or decreased if there was a shadow within the LV cavity, produced by the microbubbles, that starts anywhere in front of the mitral valve (in an apical 4-chamber view) so that the beginning of the shadow is kept inside the left atrial cavity.

5. Obtaining The Rest Images:
    Once the dripping rate was established, the controls were adjusted to achieve optimal wall enhancement (figure 4):

· MI was kept = 0.7 or 0.8 and the gain increased until wall enhancement was satisfactory;
· TGC was then adjusted to produce a smooth enhancement from LV apex to base, with no undue greater contrast in the proximal regions;
· Power was then decremented step by step, decreasing MI, noticing if there was any non homogenous contrast dimming in any segment, always comparing segments at the same depth from the transducer, for instance: in a 4-chamber apical view the
contrast intensity of the basal lateral wall only can be compared with the basal IV septum. Power was lowered until all the segments are black;
· Power was then incremented until MI = 0.6 or 0.7. With this setting the walls should show contrast enhancement but there would be room for further increase, or decrease, in contrast following the use of adenosine.

Figura 4: Apical 4 chambers at rest. A - before final preparation there are microbubbles within the left ventricular cavity (LV) but not yet in the walls. Absence of shadowing inside the LV indicates that the dripping rate of the microbubbles is satisfactory. B - after final adjustments, the contrast in the walls is homogenous and very intense. L - lateral wall; S - interventricular septum.

6. Injecting Adenosine:
   Once the settings were optimized they were held constant throughout. Images were stored on videotape. One ampoule (6 mg) of adenosine (Adenocard®, LIBBS Farmacêutica Ltda, São Paulo, Brazil) was then injected IV as a bolus, what produced a prompt augment of the contrast in all or at least a segment of LV wall. If no response was noted, 2 amps (12 mg) or a total of 3 amps (18 mg) were then injected. Its action starts about 20-60 seconds after the injection and remains for 20-30 seconds. Simultaneous with its action, the patient develops tachypnea that may hinder the examination. He should be alerted to this phenomenon and asked to keep shallow respiratory incursion at least for 5 seconds when he feels the beginning of the respiratory urge.

7. Echocardiographic Analysis:
   Ultrasound images were obtained by with the scanner connected to an ultrasound transducer operating at 2 MHz when in nominal frequency and at 1,67 MHz for emission and 3,34 MHz for reception when in second harmonic.

   All patients were studied in the apical 4-chamber and 2-chamber views. Whenever possible the parasternal short-axis and an off-axis apical view with the ultrasound beam entering at the apex and emerging at the LV infero-basal wall were also used.

   Image acquisition began after optimization of the settings and just before injection of adenosine and continued until its effect in the myocardium had dissipated.

   Visual grading of myocardial contrast enhancement before and after adenosine bolus injection was assessed by two independent reviewers from high fidelity videotape images in a loop format utilizing a dedicated software.

   Each reviewer evaluated whether there was contrast enhancement at rest in each LV wall seen at every echocardiographic view obtained after starting PESDA infusion, whether the contrast enhancement was homogenous, and analyzed for further enhancement, decrement or unchanging contrast intensity that might occur during maximal adenosine effect. So, it was defined:

7.A. NORMAL PERFUSION PATTERN (Video 1)
    A visually normal perfusion pattern at rest was considered present when there was an homogenous contrast enhancement of all segments of the LV walls visualized in a given echocardiographic section, always comparing the contrast intensity of a particular segment with the one situated at the same depth in the contralateral wall, and when this homogeneity persisted in all the images obtained during step decrease of the mechanical index until no further evidence of contrast was seen in the walls (figure 5). After adenosine bolus injection, a normal perfusion pattern was a further enhancement of the contrast observed at rest in all segments of the LV walls (figure 1).

Figura 5: Paraesternal short-axis at rest. The homogeneity persisted in all the images obtained during step decrease of the mechanical index until no further evidence of contrast was seen in the walls.
mi - mechanical index; LV - left ventricle; RV - right ventricle; S - interventricular septum.

7.A. ABNORMAL PERFUSION PATTERN
   A visually evident abnormal perfusion pattern at rest was considered when there was an heterogeneous contrast enhancement of the LV walls (figure 6) or when this heterogeneity could be induced or intensified by step decrease of the mechanical index, situation on which an abnormal segment may appear darker than its contralateral (figure 7). After adenosine, an abnormal perfusion pattern was a lack of enhancement of a segment which was not contrasted (figure 2) at rest or, more often, a decrease contrast of a previously normal or slightly enhanced wall at rest (figure 3).

Figura 6: Apical 4 chambers at rest. There is a visually evident abnormal perfusion pattern at rest, before adenosine, in the basal portion of the lateral wall (arrow).
S - interventricular septum; L - lateral wall; LV - left ventricle.

Figura 7: Apical 2 chambers at rest. Heterogeneity induced by step decrease of the mechanical index (mi). Decreasing mi from 0.8 to 0.7 makes the perfusion abnormality at the basal portion of the posterior wall apparent, and by further decreasing to 0.4 the whole posterior wall is depicted as abnormally perfused.
S - interventricular septum; P - posterior wall; LV - left ventricle

   With the Adenosine Protocol our group studied 1535 patients in the clinical scenario. This robust experience was presented in various scientific meetings:

1. Intravenous Infusion Myocardial Contrast Echocardiography to Assess Myocardial Revascularization Procedures (22 )
   Background. The accuracy of intravenous infusion (IVI) of PESDA solution to evaluate a myocardial revascularization procedure (CABG and/or PTCA) has not yet been evaluated in a large series of pts. Accordingly, we assessed the ability of IVI-PESDA to identify perfusion defects in revascularized pts submitted to coronary angiography (ANG) to investigate residual and/or a new coronary obstruction.

   Methods. In 29 pts (21 male, 62 + 11 years) submitted to myocardial revascularization (77 procedures: CABG in 50, PTCA plus stent in 16, and PTCA alone in 11), ANG and MCE with IVI-PESDA, within 4 weeks of each other, were obtained. PESDA, a sonicated mixture of 1 ml 20% serum albumin, 12 ml 5% dextrose and 8 ml decafluorobutane gas, diluted in 80 ml 5% dextrose, infused at a rate of 2-5 ml/m, associated with triggered (1 to 1 cardiac cycle) 2nd harmonic imaging technology, at rest and after a bolus injection of Adenosine, was the used protocol. ANG showed a successful revascularization (obstruction <30%) in 25/25 LIMA, in 20/25 SVG (right and left marginal branches of circumflex artery), in 11/16 PTCA plus stent and 4/11 PTCA alone. An unsuccessful procedure was considered if there was a residual obstruction > 75%.

   Results. For all successful procedures, a marked and homogeneous contrast enhancement (normal perfusion pattern) was obtained with IVI-PESDA in the walls related to the treated artery. Absence or heterogeneous enhancement in the walls (perfusion defect) was observed in all pts with unsuccessful procedure.

   Conclusion. A perfusion defect observed with MCE with IVI-PESDA at rest or after Adenosine bolus injection strongly correlates with the presence of an unsuccessful revascularization procedure.

2. The Ability of Myocardial Contrast Echocardiography to Identify Perfusion Defects is Independent of Rest Wall Motion Abnormalities (23)
   Background. Myocardial contrast echocardiography (MCE) using an intravenous infusion (IVI) of a PESDA solution is an emergent technology to assess myocardial perfusion. The aim of this study was to evaluate the role of a rest wall motion abnormality in the accuracy of MCE when it is used as a diagnostic tool in pts with coronary artery disease (CAD).

   Methods. In 68 pts (52 male, 64 + 13 years) submitted to coronary angiography (ANG) to investigate CAD, MCE following IVI-PESDA was obtained within 4 weeks from ANG. PESDA solution (obtained by sonication of a mixture of 1 ml 20% serum albumin, 12 ml 5% dextrose and 8 ml decafluorobutane gas and diluted into 80 ml 5% dextrose) infused at a rate of 2-5 ml/m) associated with triggered (1 to 1 cardiac cycle) 2nd harmonic imaging technology, at rest and after a bolus injection of Adenosine was the used protocol. A homogeneous appearance of contrast enhancement distribution was established as normal perfusion pattern (NP), and absence or heterogeneous enhancement as a perfusion defect (PD). ANG was normal in 8 pts, with residual lesion <30% after reperfusion in 9 pts, and with obstruction >75% in 51 pts. A rest wall motion abnormality was identified by 2-D echo in 31 pts.

   Results. MCE showed NP in all pts with normal or residual lesion <30% ANG. All 31 pts with WM abnormalities had a PD in the corresponding area. The remaining 20 pts without WM abnormalities and coronary obstruction >75% had also a PD.

   Conclusion. A PD detected with MCE associated to IVI-PESDA solution, at rest or after Adenosine bolus injection in pts with CAD was observed independently of the presence of WM abnormality.

3. Adenosine Contrast Echocardiography in Patients with Suspected Coronary Artery Disease: is there Equality Between the Sexes? (24)
   Background. Adenosine Contrast Echocardiography (ACE) using an intravenous infusion of PESDA solution is an emergent technology to assess myocardial perfusion. The aim of this study was to evaluate the role of sex in the accuracy of MCE when it is used as a diagnostic tool in pts with suspected coronary artery disease (CAD).

   Methods. In 101 men (GROUP A: 66±13 years) and 38 women (GROUP B: 64±16 years) submitted to coronary angiography (ANG) to investigate CAD, ACE following PESDA (infused at a rate of 1-2 ml/m) was obtained within 4 weeks from ANG. Triggered (1:1) 2nd harmonic imaging, at rest and after a bolus injection (6-18 mg) of Adenosine (ADN) was the used protocol. For each pt 3 LV territories (related to RCA, CX and LAD arteries) were considered. Normal perfusion was defined as a homogeneous appearance of contrast enhancement distribution at rest and after ADN, and absence or heterogeneous enhancement at rest or after ADN was established as a perfusion defect. 301 and 112 territories were analyzed in GROUPS A and B respectively (2 territories were excluded in each group). ACE was visually assessed.

   Results. ANG showed 101 and 38 flow limiting (Ž 75%%) lesions for GROUPS A and B respectively, and 200 and 74 no flow limiting lesions (< 75%) for GROUPS A and B respectively. Normal perfusion was found in 195/200 (98%) and 72/74 (97%) territories supplied by arteries with obstruction < 75% in GROUP A and B respectively. Perfusion defects were detected in 97/101 (96%) and 36/38 (95%) territories related to arteries with obstruction in GROUP A and B respectively. It was observed only 13 false results (3%). There were no complications.

   Conclusion: ACE following PESDA infusion is an accurate (97%) method to study myocardial perfusion and was independent of sex in these pts with suspected CAD.

4. Myocardial Contrast Echocardiography Perfusion Imaging for the Evaluation of Chest Pain in the Emergency Department (25)
   Background. We have previously shown that myocardial perfusion is accurately assessed by myocardial contrast echocardiography (MCE) with PESDA in pts with stable coronary artery disease (CAD). However its utility for pts undergoing a rapid evaluation for possible ischemia in a Chest Pain Center (CPC) has not yet been evaluated. Accordingly, we assessed the ability of MCE to identify the perfusion patterns in these pts.

   Methods. 49 pts (35 male, 59+14 years, 28-90) were admitted to a CPC to investigate possible ischemia due to CAD. First ECG and initial CK-MB were non-diagnostic. According to the chest pain characteristics 3 groups were formed: A- typical angina: 11 pts; B- suggestive of angina: 21 pts; and C- non-suggestive of angina: 17 pts. MCE with triggered (1:1) 2nd harmonic imaging, was visually assessed (2 independent investigators), at rest and after IV injection of adenosine (ADN), using PESDA (sonicated solution of 1ml 20% albumin, 12ml 5% dextrose and 8ml decafluorobutane gas), continuously infused at 1-2ml/min. A marked and homogeneous contrast enhancement after ADN was defined as normal perfusion, and absence or heterogeneous enhancement in the walls was considered a perfusion defect. Coronary angiography (ANG) was obtained in 26 pts (in 11/11, 12/20 and 3/16 pts from groups A, B, and C respectively) within 48 hours from MCE. For each patient 3 LV territories (related to right coronary, circumflex and left anterior descending arteries) were considered.

   Results. 78 territories were analyzed in pts with ANG with 33 related to coronary artery with obstruction > 75% (all but one with abnormal perfusion); and 45 territories supplied by normal or no flow limiting (< 75%) coronary artery (43 with normal perfusion). The sensitivity was 97%, the specificity was 95.5% and the global accuracy was 96.2%.

   Conclusion. MCE with ADN is an accurate method to study myocardial perfusion in pts admitted to a CPC to elucidate the etiology of a chest pain.

5. Is Intravenous Myocardial Contrast Echocardiography Preferable to Nuclear Scintigraphy in the Assessment of Myocardial Perfusion? Comparison in Patients with Suspected Coronary Artery Disease (26)
   Background. Myocardial contrast echocardiography (MCE) using an intravenous infusion (IV) of a PESDA solution is an emergent technology to assess myocardial perfusion. The aim of this study was to compare its accuracy with a nuclear scintigraphy test (NST) in pts submitted to a routine investigation for coronary artery disease (CAD).

   Methods. In 41 pts with suspected CAD (28 male, 58 + 11 years, 41-87) MCE and NST were performed (within 6 month of each other) as a part of an investigation procedure. MCE with triggered (1:1) second harmonic imaging, was visually assessed (2 independent investigators), at rest and after IV injection of adenosine (ADN), using PESDA (sonicated solution of 1ml 20% albumin, 12ml 5% dextrose and 8ml decafluorobutane gas diluted in 80 ml of 5% dextrose, and continuously infused at 1-2ml/min, titrated for best myocardial contrast). NST was performed using standard protocols. For each patient 3 LV territories (related to right coronary, circumflex and left anterior descending arteries) were considered, total of 123 analyzed territories. A marked and homogeneous contrast enhancement after ADN was defined as normal perfusion pattern, and absence or heterogeneous enhancement in the walls was a perfusion defect. Coronary angiography (ANG) were obtained in 24 pts: Group A - 72 territories, 25 related to an obstructed artery (> 75%) and 47 perfused by a normal or no flow limiting coronary artery (< 75%). 17 pts did not have ANG (51 territories-Group B).

   Results. Considering both groups the concordance between tests was 76% (94/123 territories: 74 normal and 20 abnormal). In Group A the NST correctly identified 54/72 (75%) territories (15/25 - 60% territories related to obstructed artery and 39/47 - 83% territories normally perfused), while MCE correctly identified 69/72 (96%) territories (24/25 - 96% abnormal and 45/47 - 96% normal perfusion).

   Conclusion. MCE with ADN is a more accurate method to study myocardial perfusion in humans than nuclear scintigraphy tests.

6. Adenosine Contrast Echocardiography in 936 Consecutive Patients with Suspected Coronary Artery Disease: Experience of a Single Center (27)
   Background. We have previously shown that myocardial perfusion is accurately assessed by Adenosine Contrast Echocardiography (ACE) following PESDA infusion in a relatively small group of pts with stable coronary artery disease (CAD). The aim of this study was to assess the safety and tolerance of this protocol in the clinical scenario of CAD.

   Methods. 936 consecutive pts (660 male, 12 to 91 years) were submitted to the ACE protocol to investigate myocardial perfusion using continuous infusion of PESDA (1-2 ml/m), associated with triggered (fixed 1:1) 2nd harmonic imaging technology, at rest and after a bolus injection of Adenosine (ADN - at least 1 ampoule of 2ml/6mg was used for each echocardiographic view). Images were obtained at the standard apical 4-chamber and 2-chamber views. Myocardial perfusion was visually analyzed (2 independent investigators) in the territory of LAD, RCA and Cx arteries.

   Results. PESDA infusion produced myocardial contrast and ADN bolus injection enhanced it further in at least 1 LV segment wall in all pts. 580 pts (62%) required 1 amp of ADN per view to achieve further increment of the wall contrast. 300 pts (32%) and 56 pts (6%) required 2 and 3 amp respectively to obtain the same result. A transient, asymptomatic 3rd degree AV block lasting less than 10s was noted in 84 pts - 9% (19, 27 and 38 pts who had 1, 2 or 3 amp of ADN respectively). 122 pts (13%) complained of lightheadedness, 66 pts (7%) of headache, and, 47 pts (5%) of non-angina chest discomfort. All patients developed tachypnea. Symptoms lasted less than 30 s and did not required therapy or precluded further ADN injection is needed.

   Conclusion. ACE protocol with PESDA infusion is safe and very well tolerated by pts with suspected CAD.

7. Is Adenosine Contrast Echocardiography Useful in the Assessment of the Culprit Artery Patency in Patients with Acute Myocardial Infarction? (28)
   Background. We have previously shown that myocardial perfusion is accurately assessed by Adenosine Contrast Echocardiography (ACE) following PESDA infusion in pts with stable coronary artery disease (CAD). The aim was to assess the ability of ACE to identify perfusion defects in pts with 1st AMI and to correlate the perfusion patterns with the patency of the culprit coronary artery.

   Methods. In 21 pts (18 male, 64 ± 11 years) with 1st Q-wave AMI (inferior in 16 pts) submitted to coronary angiography (ANG) to investigate the extension of CAD, ACE with PESDA was visually assessed (2 independent investigators), at rest and after IV bolus injection of 6-18 mg of adenosine (ADN) using triggered (1:1) 2nd harmonic imaging. ANG (within 15 days from ACE) showed single-vessel disease in 9 pts, 2 vessels in 8 pts and 3 vessels in 4 pts. For each pt 3 LV territories (LAD, RCA and CX arteries) were considered.

   Results. 63 territories were analyzed being 21 related to AMI, 16 to other coronary artery with obstruction > 75%, and 26 to a normal (or obstruction < 75%) coronary artery. A marked and homogeneous contrast enhancement after ADN (normal perfusion) was obtained with ACE in all territories supplied by arteries with obstruction < 75%. Absence or heterogeneous enhancement in the walls (perfusion defect) was observed in all non-infarcted territories perfused by arteries with obstruction > 75%. In the AMI territories, there were 2 different types of findings: Type A (myocardial enhancement by 2nd harmonic only even before PESDA and no variation with ADN); Type B (normal aspect with 2nd harmonic only, decrease of myocardial contrast with PESDA and no enhancement with ADN). Type A was seen in 9/10 territories with a completely obstructed artery and Type B in 11/11 territories related to a reperfused artery.

   Conclusion. ACE is a safe and accurate method to study myocardial perfusion in humans with evolving AMI, and may be important to evaluate patency of the culprit artery after 1st Q-wave AMI.

8. Accuracy of Intravenous Myocardial Contrast Echocardiography to Detect Single-vessel Coronary Artery Disease (29)
   Background. The overall accuracy of noninvasive diagnostic tests depends on the population being studied. Stress echocardiography has a relative low sensitivity to detect single-vessel (SV) coronary artery disease (CAD). Myocardial contrast echocardiography (MCE) using an intravenous infusion (IV) of a PESDA solution is an emergent technology to assess myocardial perfusion. The aim of this study was to evaluate the accuracy of MCE when it is used as a diagnostic tool in pts with SV CAD.

   Methods. 56 pts (48 male, 62 + 13 years, 41-83) with SV CAD were studied by MCE following IV PESDA (sonication of a mixture of 1 ml 20% serum albumin, 12 ml 5% dextrose and 8 ml decafluorobutane gas, diluted into 80 ml 5% dextrose) solution infused at a rate of 1-2 ml/m. Images were obtained using triggered (1 to 1 cardiac cycle) 2nd harmonic technology at rest and after a bolus injection of adenosine (ADN). MCE was visually assessed by 2 independent investigators. A marked and homogeneous contrast enhancement after ADN was defined as normal perfusion, and absence or heterogeneous enhancement in the walls was considered a perfusion defect. For each patient 3 LV territories related to right coronary (RCA), circumflex (Cx) and left anterior descending (LAD) arteries were considered. Obstruction (> 75%) was present at coronary angiography in RCA, Cx and LAD arteries in 29, 14 and 13 pts respectively.

   Results. 55/56 territories related to an obstructed artery were analyzed (1 pt was excluded due to a limited echocardiographic window) and all but one (98%) had a perfusion defect. 111/112 (99%) territories supplied by a normal or no flow limiting lesion (< 75%) had a normal perfusion. In a patient-by-patient basis the sensitivity of MCE was 94.6%.

   Conclusion. MCE with ADN is a highly accurate method to detect a single-vessel coronary artery disease in humans.

9. Prediction of Myocardial Viability by Adenosine Contrast Echocardiography in Patients with Single-Vessel Coronary Artery Disease: Comparison with Dobutamine Stress Echocardiography (30)
   Background. In order to analyze myocardial perfusion echocardiography for evaluation of myocardial viability, 20 patients who underwent one-vessel percutaneous transluminal coronary angioplasty and had wall motion abnormality were studied.

   Methods. This group was submitted 2 to 7 (3,65 ± 1,69) days prior the angioplasty and 2 to 5 (4,00 ± 0,80) days after to dobutamine stress echocardiography and myocardial perfusion echocardiography with venous peripherical contrast. To determine the presence of myocardial viability, a two-dimensional echocardiogram was performed after 3 months. PESDA was the contrast agent employed, under continuous peripherical infusion; harmonic mode and intermittent imaging were used. Left anterior descending artery was revascularized in 12 patients, right coronary in 6 and circumflex artery in 1.

   Results. There was concordance between methods (kappa=81.97%, p< 0.0001). Among 240 segments, 69 (28.75%) had wall motion abnormalities, 44 were hypokinetic, 20 akinetic and 5 dyskinetic. Dobutamine stress echocardiography had a sensitivity rate of 90.00%, specificity of 82.76%, accuracy of 86.96% and 92.50%, 86.21% and 89.86% for perfusion. The only patient with circumflex procedure showed 100% concordance among methods; for left anterior descending artery, sensitivity was 88.89%, specificity was 94.12% and accuracy was 88.64% for dobutamine echocardiography and 88.89%, 94.12% and 90.91% when perfusion was employed. Among right coronary artery patients, sensitivity was 92.31%, specificity was 57.14% and accuracy was 80.00% for dobutamine echocardiography and 100,00%, 71.43% and 90.00% for perfusion. All dyskinetic segments were non-viable, as shown by perfusion; the 2 viable akinetic segments were detected by perfusion and 1 by dobutamine echocardiography. Among 44 hypokinetic segments, perfusion showed viability in 92,31% and dobutamine in 89,74%.

   Conclusion. Myocardial perfusion echocardiography was useful for evaluation of myocardial viability in patients with single-vessel disease.

10. Adenosine Contrast Echocardiography in Patients with Suspected Coronary Artery Disease and Complete left Bundle Branch Block (31)
   Background. Assessment of ischemia in the anterior circulation (LAD territory) in pts with suspected coronary artery disease (CAD) and impaired septum movement due to complete left bundle branch block (LBBB) suffers from high interobserver disagreement and low sensitivity and specificity. The aim was to assess the role of Adenosine Contrast Echocardiography (ACE) following PESDA infusion in these pts.

   Methods. In 31 pts (12 male, 64 ± 13 years) with LBBB and suspected CAD with no clinically recognized prior myocardial infarction, ACE with triggered (1:1) 2nd harmonic imaging was visually assessed (2 independent investigators), at rest and after IV injection of adenosine (ADN), using PESDA (sonicated solution of 1 ml 20% albumin, 12 ml 5% dextrose and 8 ml decafluorobutane gas), continuously infused at 1-2ml/min. A marked and homogeneous contrast enhancement after ADN was defined as normal perfusion, and absence or heterogeneous enhancement in the walls was considered a perfusion defect. Coronary angiography (ANG) was obtained in 6 pts (2 with normal coronary arteries and 4 with obstruction > 75%: 1 with 3 vessels, 1 with 2 vessels - RCA/CX and 2 with single vessel - RCA) within 6 months from ACE. For each patient 3 LV territories (related to RCA, CX and LAD) were considered.

   Results. 93 territories were analyzed. LAD obstruction was detected in only 1 pt that had abnormal perfusion. Despite the impaired septal movement all other territories supplied by normal LAD were correctly identified by ACE. The RCA and/or CX territories were also correctly identified. There were no false results.

   Conclusion. ACE following PESDA infusion seems to be an accurate method to identity perfusion abnormalities in the LAD territory in pts with LBBB and suspected CAD.

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9. Meza M, Greener Y, Aristizabal D, Perry B, Hunt R, Revall S, Murgo JP, Cheirif J. Myocardial contrast echocardiography safety of FS069, a new transpulmonary echocardiographic contrast agent. J Am Soc Echocardiogr 1994;7:S36.

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13. Moraes A, Morcerf F, Nogueira AC, Castier M, Salek F, Pereira W, Dohmann H. Myocardial contrast echocardiography for the detection of coronary artery disease. J Am Coll Cardiol 1998; 31 (suppl C): 272C.

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28. Moraes A, Morcerf F, Carrinho M, Salek F, Nogueira AC, Palheiro FC, Dohmann H. Is adenosine contrast echocardiography useful in the assessment of the culprit artery patency in patients with acute myocardial infarction? J Am Coll Cardiol 2000; 35 (suppl A): 426A.

29. Moraes A, Morcerf F, Carrinho M, Salek F, Nogueira AC, Palheiro FC, Dohmann H. Accuracy of Intravenous Myocardial Contrast Echocardiography to Detect Single-vessel Coronary Artery Disease. J Am Soc Echocardiogr 1999; 12: 364.

30. Castier M, Moraes A, Carrinho M, Morcerf F, Medeiros C, Albanese FM, Dohmann H. Prediction of myocardial viability by adenosine contrast echocardiography in patients with single-vessel coronary artery disease: comparison with dobutamine stress echocardiography. J Am Soc Echocardiogr 2000; 13: 460.

31. Carrinho M, Moraes A, Morcerf F, Nogueira AC, Palheiro FC, Salek F, Pandian N, Dohmann H. Adenosine contrast echocardiography in patients with suspected coronary artery disease and complete left bundle branch block. Proceedings of the 11th Congress of International Cardiac Doppler Society 2000.

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2nd Virtual Congress of Cardiology

Dr. Florencio Garófalo
Steering Committee
President
Dr. Raúl Bretal
Scientific Committee
President
Dr. Armando Pacher
Technical Committee - CETIFAC
President
fgaro@fac.org.ar
fgaro@satlink.com
rbretal@fac.org.ar
rbretal@netverk.com.ar
apacher@fac.org.ar
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