Coronary stenting in diabetic patients: Results from the ROSETTA registry.

OBJECTIVE: Diabetes mellitus is associated with high rates of restenosis and adverse outcomes after percutaneous transluminal coronary angioplasty (PTCA). It is unclear whether coronary stenting reduces adverse events in diabetic patients after PTCA. Our purpose was to determine whether coronary stenting improves clinical event rates in diabetic patients after PTCA. METHODS: The Routine Versus Selective Exercise Treadmill Testing After Angioplasty (ROSETTA) registry was a prospective multicenter observational study examining functional testing and adverse outcomes after successful PTCA. RESULTS: Among the 791 patients enrolled, 180 were diabetic. A total of 90 diabetics received stents while the remaining 90 patients did not. Baseline clinical characteristics were similar between the 2 groups of patients. However, patients with stents were more likely to have complex lesions, whereas those without stents were more likely to undergo atherectomy and have greater residual coronary stenosis. At 6-month follow-up, the composite end point defined as cardiac death, unstable angina, myocardial infarction, need for repeat PTCA, or coronary artery bypass graft surgery (CABG) occurred in 25.0% of stented and 22.2% of nonstented diabetic patients (P not significant [NS]). A multivariate logistic regression analysis showed that coronary stenting was not associated with a reduced incidence of the composite end point among diabetic patients (odds ratio 0.97, 95% CI 0.46-2.05, P NS). CONCLUSION: Coronary stenting does not improve clinical event rates in diabetic patients after PTCA.

Inhibition of carotid artery neointimal formation with intravenous microbubbles.

Because therapeutic gene products such as synthetic antisense oligodeoxynucleotides (ODN) bind to albumin-coated microbubbles, we sought to determine whether IV perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles could target their delivery to the carotid artery following balloon injury. In 5 pigs, the concentration of ODN taken up within the carotid vascular wall was found to be significantly increased when the IV antisense (ODN) was administered bound to PESDA (ODN-PESDA), and while transcutaneous low-frequency (20 kHz) ultrasound was applied over the carotid artery. Based on these results, a chronic model was then developed, in which 21 pigs received either IV ODN-PESDA, ODN alone, or control, following carotid balloon injury. At 30 days following balloon injury, percent area stenosis was only 8 +/- 2% in the ODN-PESDA groups compared to 19 +/- 8% and 28 +/- 3% in the other groups (p < 0.01). IV PESDA may be a method of noninvasively targeting the delivery of therapeutic genes.

Use of routine functional testing after percutaneous transluminal coronary angioplasty: results from the ROSETTA Registry.

BACKGROUND: The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for exercise testing suggest that only selected groups of high-risk patients should undergo routine functional testing after percutaneous transluminal coronary angioplasty (PTCA) for the detection of restenosis. OBJECTIVES: Our purpose was (1) to document the patterns of use of post-PTCA functional testing and (2) to determine whether the choice of functional testing strategy is related to clinical characteristics of patients or whether physicians use a similar strategy for all their patients. METHODS: The Routine Versus Selective Exercise Treadmill Testing After Angioplasty (ROSETTA) Registry is a prospective study examining the use of functional testing among 788 patients at 13 centers in 5 countries. RESULTS: During the 6-month period after a successful PTCA, 49% of patients underwent functional testing (range among centers 10%-81%). Among patients who underwent functional testing, 39% had a clinical indication and 61% had functional testing as a routine follow-up. The first functional test was performed a median of 7 weeks after PTCA, with 13% of patients having second tests at a median of 14 weeks and 4% having additional tests at a median of 20 weeks. Univariate and multivariate analyses demonstrated that the chief determinant of the use of routine functional testing was clinical center. Aside from age (P <.0001), no baseline clinical or procedural characteristics were consistently associated with the use of routine functional testing after PTCA. CONCLUSIONS: Physicians do not appear to be adhering to the ACC/AHA guidelines for exercise testing regarding the routine use of post-PTCA functional testing. None of the clinical characteristics identified by the ACC/AHA guidelines were associated with the routine use of post-PTCA functional testing, and the primary determinant of functional testing was the location of the center at which the patient had the PTCA.

Coronary angiography as a prognostic tool.

Coronary angiography was introduced into clinical practice more than 40 years ago revolutionizing the clinical understanding of the coronary artery disease and setting the stage for all the modern treatments such as coronary bypass surgery (CABG), percutaneous coronary angioplasty (PTCA), and thrombolysis. Coronary angiography has well-known pitfalls and limitations in the detection of coronary atherosclerosis. It is not very unusual to see in the routine clinical practice that the coronary angiography is less well appreciated as a prognostic tool. One reason for this may be the traditional teaching of the coronary angiography that favors the technical aspects of the catheterization and the radiographic interpretation skills. In this paper, the prognostic significance of coronary angiographic findings is reviewed and the clinical issues encountered in daily practice are highlighted.

Intravenous thrombolytic treatment of mechanical prosthetic valve thrombosis: a study using serial transesophageal echocardiography.

OBJECTIVE: We analyzed the results of intravenous thrombolytic treatment under transesophageal echocardiographic (TEE) guidance in prosthetic valve thrombosis. BACKGROUND: Thrombotic occlusion of prosthetic valves continues to be an uncommon but serious complication. Intravenous thrombolytic treatment has been proposed as an alternative to surgical intervention. METHODS: In a four-year period, 32 symptomatic patients with prosthetic valve related thrombosis underwent 54 thrombolytic treatment sessions for the treatment of 36 distinct episodes. All patients had low international normalized ratio values at the presentation. Transesophageal echocardiography was performed at baseline and repeated after each thrombolytic treatment session (total 98 TEE examinations). Streptokinase was used as the initial agent with a repeat dose given within 24 h when necessary. Recurrent thrombosis was treated either with tissue plasminogen activator or urokinase. RESULTS: The initial success after first dose was only 53% (17/32) but increased up to 88% (28/32) after repeated thrombolytic sessions upon documentation of suboptimal results on TEE examination (p < 0.01). In addition, four asymptomatic patients with large thrombi were also successfully treated with single infusion. The TEE characteristics of thrombus correlated with clinical presentation and response to lytics. Success was achieved with single lytic infusion in 40% of the obstructive thrombi as compared with 75% of the nonobstructive ones (p < 0.05). The success rates of lytic treatment were similar for mitral versus aortic valves, and for tilting disk versus bileaflet valves. Rapid (3 h) and slow (15 to 24 h) infusion of streptokinase resulted in similar success rates. However, major complications (three patients) occurred only in the rapid infusion group. CONCLUSION: In patients with prosthetic valve thrombosis, intravenous slow infusion thrombolysis given in discrete, successive sessions guided by serial TEE and transthoracic echocardiography can be achieved with a low risk of complications and a high rate of success.

Diastolic Pressure Gradient in the Ascending Aorta Caused by the Mobile Intimal Flap of Dissecting Aneurysm.

Aortic regurgitation is a serious complication of ascending aortic dissection. We report a 65-year-old man with Type A aortic dissection and aortic regurgitation who presented with a diastolic aortic pressure gradient along the aortic root which was caused by a large intimal flap interrupting the diastolic regurgitant flow.

Effect of transducer standoff on the detection, spatial extent, and quantification of myocardial contrast defects caused by coronary stenoses.

Intermittent harmonic imaging during a continuous infusion of microbubbles may be able to quantify myocardial perfusion abnormalities. Measurements of the spatial extent of these perfusion abnormalities depends on homogenous destruction of the microbubbles in the elevation plane of the transducer. We hypothesized that uneven microbubble destruction caused by attenuation of beam intensity could alter quantitative measurements of perfusion abnormalities during stress. To test this hypothesis, we measured the spatial extent of perfusion defects at peak dobutamine stress with a continuous intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin and intermittent harmonic imaging in dogs with nonflow-limiting coronary stenoses in the left anterior descending artery. The spatial extent of perfusion defects was also measured during total occlusion of the artery. Measurements were made at standoffs of 2- to 3-cm and 4- to 5-cm distance from transducer surface to myocardium. These spatial extents were correlated with risk area determined after death. The risk area during left anterior descending occlusion at a standoff of 2 to 3 cm was significantly larger at a 1500-ms pulsing interval (6.5 +/- 2.6 cm(2) for 2- to 3-cm standoff versus 3.7 +/- 1.4 cm(2) for 4- to 5-cm standoff; P =.01). The spatial extent at the 2- to 3-cm standoff more closely approximated risk area measured with Monastral Blue (7.8 +/- 2.7 cm(2)). Myocardial perfusion abnormalities during peak dobutamine stress were significantly smaller with the 4- to 5-cm standoff and undetectable in 4 of the 5 dogs. We conclude that ultrasound beam attenuation can reduce the size of a myocardial perfusion abnormality observed with intermittent harmonic imaging during a continuous infusion of microbubbles. This may reduce the sensitivity of this technique when transthoracic imaging is used.

Real-time visualization of myocardial perfusion and wall thickening in human beings with intravenous ultrasonographic contrast and accelerated intermittent harmonic imaging.

Previous work has demonstrated that at higher peak negative pressures, microbubbles are destroyed by diagnostic ultrasonography. At lower pressures (lower mechanical index), less destruction occurs but enhanced contrast persists. In animals, this lower mechanical index has resulted in enhanced contrast after administration of intravenous microbubbles with intermittent imaging at faster frame rates. We tested whether this accelerated intermittent imaging technique could produce myocardial contrast and detect myocardial perfusion abnormalities in 25 patients (10 with normal wall motion, 15 after myocardial infarction). Three independent reviewers detected persistent myocardial contrast defects within the infarct zone throughout the cardiac cycle in 9 of the 15 patients after acute myocardial infarction; the presence of such defects was predictive of a persistent regional wall motion abnormality at 4-week follow-up. Interobserver agreement on regional contrast enhancement ranged from 88% to 90%. We conclude that accelerated intermittent imaging permits real-time visualization of myocardial blood flow and wall thickening.

The clinical implications of no reflow demonstrated with intravenous perfluorocarbon containing microbubbles following restoration of Thrombolysis In Myocardial Infarction (TIMI) 3 flow in patients with acute myocardial infarction.

Intravenous injections or infusions of perfluorocarbon-exposed sonicated dextrose albumin microbubbles were given 2.4 +/- 1.6 days following acute myocardial infarction to 45 consecutive patients. Patients were divided into 3 groups: patients with Thrombolysis In Myocardial Infarction (TIMI) grade 3 angiographic flow but persistent myocardial contrast defects by echocardiography (no reflow), patients with TIMI 3 flow and myocardial contrast enhancement (reflow), and patients with TIMI grade 0 to 2 flow in the infarct vessel. Thirty-five patients had TIMI 3 flow at the time of contrast study. Of these, 25 had evidence of reflow with intravenous contrast, whereas 10 (29%) still had contrast defects. At follow-up, end-systolic volume index decreased significantly in patients who exhibited reflow (21 +/- 8 ml/m2 at baseline to 18 +/- 8 ml/m2 at follow-up; p = 0.04), whereas those with no reflow had a significant increase (26 +/- 9 ml/m2 at baseline to 32 +/- 9 ml/m2 at follow-up; p = 0.006). A persistent contrast defect in the infarct zone demonstrated with intravenous ultrasound contrast following restoration of TIMI grade 3 flow in the infarct vessel identified patients likely to have deterioration in both regional and global systolic function.

Predictors of left atrial thrombus and spontaneous echo contrast in rheumatic valve disease before and after mitral valve replacement.

In this study we aimed to analyze, with reference to mitral regurgitation (MR), the incidence and predictors of left atrial (LA) thrombus and spontaneous echo contrast in patients with rheumatic valve disease before and after mitral valve replacement. The incidence of LA thrombus is known to be less in patients with MR. The impact of mitral valve replacement on this beneficial effect has not been studied in detail. The study included 169 consecutive patients (59 men and 110 women, average age 40 +/- 13 years) with rheumatic mitral valve disease who underwent transesophageal echocardiographic examination 1 to 3 days before and within 7 days (mean 4.0 +/- 1.3) after mitral valve replacement using mechanical prostheses in a single institution. The preoperative incidence of echocardiographic LA spontaneous echo contrast (SEC) was 1.1%, 30%, and 54%, and the incidence of thrombus was 1.1%, 13%, and 17% in the groups with MR, combined mitral stenosis + MR, and isolated mitral stenosis, respectively. In the MR group, SEC and thrombus incidence increased significantly after surgery. The independent predictors for postoperative thrombus development were atrial fibrillation, postoperative SEC, and preoperative thrombus. Thrombus recurred after surgery in 64% of 14 patients who had surgical thrombectomy. The presence of postoperative MR was associated with decreased risk of postoperative SEC and thrombus development. The interaction between MR and SEC and thrombus both before and after surgery provides further support for the protective effect of MR against LA thrombus formation.

Correlation between quantitative angiographic lesion severity and myocardial contrast intensity during a continuous infusion of perfluorocarbon-containing microbubbles.

The purpose of this study was to determine whether quantitative measurements of myocardial videointensity (MVI) during continuous intravenous infusions of microbubbles could detect differences in coronary artery stenosis severity during dobutamine stress echocardiography. Coronary artery stenoses were created in seven dogs by progressively tightening a snare around the coronary artery. Intravenous infusions of perfluorocarbon microbubbles were given during dobutamine stress. The initial rate of myocardial contrast enhancement (slope), peak myocardial contrast (peak MVI) at the longest pulsing interval, and the product (slope * peak MVI) were compared as ratios in the stenosed versus adjacent normal perfusion beds. Twenty-two coronary stenoses were compared (range 16% to 80% in diameter). There was a strong correlation between both slope ratios and slope * peak MVI ratios and percent stenosis (r = -0.89 for both, p<0.001). The rate of contrast replenishment during a continuous infusion of microbubbles can be used to determine both the presence and severity of coronary stenoses during stress echocardiography.

Effect of significant two-vessel versus one-vessel coronary artery stenosis on myocardial contrast defects observed with intermittent harmonic imaging after intravenous contrast injection during dobutamine stress echocardiography.

OBJECTIVES: We sought to determine the effect of multivessel as opposed to single-vessel coronary artery stenosis on myocardial contrast defects observed with intermittent harmonic imaging and intravenous perfluorocarbon-exposed sonicated dextrose albumin contrast injection. BACKGROUND: Intermittent harmonic imaging has permitted the detection of myocardial perfusion abnormalities with an intravenous ultrasound contrast agent. The effect of multivessel disease on inducibility of these perfusion abnormalities is unknown. METHODS: In 10 dogs, intravenous injections of contrast agent were given at rest and during dobutamine stress echocardiography when a single coronary artery stenosis was present (> or = 50% diameter by quantitative angiography) and again when a second stenosis (range 44% to 92% diameter) was present in the vessel supplying the adjacent perfusion bed. The peak myocardial contrast was visually and quantitatively assessed in the mid and lateral regions of the perfusion bed of the first stenosis (original stenosis zone) in the presence of one- and two-vessel stenosis. RESULTS: Peak myocardial contrast defects in both the mid and lateral segments of the original stenosis zone during dobutamine stress echocardiography was significantly lower when two-vessel stenosis was present (p = 0.015), especially in the lateral segment. The spatial extent of the perfusion defect in the original stenosis zone risk area increased significantly when two-vessel stenosis was present, and correlated closely with actual risk area (r = 0.99). Previous total occlusion followed by reperfusion of the vessel supplying the original stenosis zone significantly increased the amount of collateral activity between perfusion beds. CONCLUSIONS: Collateral flow limits the spatial extent of inducible ischemia within the risk area of single-vessel stenosis. Restoring blood flow to one perfusion bed reduces the extent of a perfusion abnormality that can be induced in an adjacent stenosed bed.

Hemostatic assessment of patients undergoing intraaortic balloon pump therapy.

Patients undergoing intraaortic balloon pump (IABP) therapy are at risk for developing coagulopathies due to the adverse effects of prolonged exposure of the synthetic surface of the polyurethane balloon to blood components. Hemorrhagic risk has been attributed to a number of factors including thrombocytopenia, vascular injury, and/or platelet degranulation which increase the potential of receiving autogeneic blood transfusions. The present study is a prospective evaluation of coagulation using a viscoelastic monitor (Thrombelastograph--TEG) that measures functional aspects of clot development and stabilization in patients being treated with IABP therapy. Following Institutional Review Board approval, six patients undergoing IABP therapy for hemodynamic instability were enrolled in this study. Blood samples were taken prior to balloon insertion, at 8, 16, 24, 48, 72, and 96 hours on IABP therapy, and 24 hours following the removal of the balloon when applicable. Samples were incubated with heparinase to degrade heparin and TEG profiles were subsequently determined in duplicate. Measured parameters on the TEG included R-time, K-time, maximum amplitude, alpha angle, and lysis at 30 and 60 minutes with calculation of the TEG index. Mortality was 33% following IABP discontinuation. Transfusion of packed red blood cells occurred in 50% of the patients during their balloon pump therapy. Patients demonstrated a significant deviance in fibrinolytic potential from pre-IABP lysis (1.6% +/- 1.8) at both 24 hours (18.8% +/- 22.9) and 48 hours (21.9% +/- 28.5) of therapy (p < 0.05) which returned to baseline shortly after balloon removal. Activation of coagulation factors appeared evident by a steadily increasing alpha angle from pre-IABP data (3.1 +/- 9.2) throughout the duration of therapy and 24 hour recovery (53 +/- 14; p < .005), and by a steadily trending increase in the TEG index pre-IABP (.251 +/- 1.4) to post-IABP (2.6 +/- 1.7; p < 0.05). The results indicate that IABP therapy induces an increase in fibrinolytic potential at 24 to 48 hours of balloon pump therapy with a paradoxical trend toward increased coagulability, potentially predisposing the patient to hemorrhagic risk.

Detection of myocardial perfusion abnormalities during dobutamine and adenosine stress echocardiography with transient myocardial contrast imaging after minute quantities of intravenous perfluorocarbon-exposed sonicated dextrose albumin.

We have recently discovered that if ultrasound transmission is briefly suspended (triggered to just one frame per cardiac cycle) after very small doses of intravenous perfluorocarbon-exposed sonicated dextrose albumin, the myocardial contrast produced is significantly enhanced. The objective of this study was to test whether this technique (termed transient response imaging) could identify myocardial perfusion abnormalities during adenosine and dobutamine stress echocardiography. In 10 open-chest dogs with a significant (> 50%) coronary stenosis determined by quantitative angiography, intravenous perfluorocarbon-exposed sonicated dextrose albumin (0.005 to 0.01 ml/kg) was given at rest during peak dobutamine stress (20 to 30 micrograms/kg/min). Adenosine stress (100 to 140 micrograms/kg/min) was also given in seven of these dogs. The peak myocardial videointensity and spatial extent of contrast defect with transient response imaging (TRI) were compared with conventional 30 Hz frame rates, as well as wall thickening and coronary flow responses. In all 10 dogs there was visually evident myocardial contrast with TRI. In comparison, myocardial contrast was visually evident in only one of these dogs with conventional imaging. The peak myocardial videointensity ration in the stenosed perfusion bed divided by the normally perfused bed when TRI was used decreased in all dogs during dobutamine stress and correlated with minimal coronary lumen diameter (r = 0.70; p = 0.02). Visually evident myocardial contrast defects were detectable in nine of 10 dogs at peak dobutamine stress but only in one of the dogs with conventional imaging. All seven dogs that received adenosine demonstrated contrast defects with TRI, whereas none demonstrated contrast defects with conventional imaging. We conclude that the myocardial contrast produced with transient response imaging can be used to detect functionally significant coronary stenoses.

Provocation of coronary spasm by dobutamine stress echocardiography in a patient with angiographically minimal coronary artery disease.

Dobutamine stress echocardiography (DSE) has been widely used for the noninvasive diagnosis of obstructive coronary artery disease. The ST-segment elevation during DSE has been reported as an infrequent event, caused by old myocardial infarction and/or critical coronary narrowings. The patient presented here was a 35-year-old man with a recent history of nonexertional chest pain. He had hypercholesterolemia and a history of heavy smoking as risk factors. The patient developed ST-segment elevation with chest pain during 40 mcg/min dobutamine infusion for the stress echocardiographic examination. Subsequent coronary angiograms revealed only mild coronary atherosclerosis. It is speculated that coronary spasm occurred in this patient as a paradoxical response to increased coronary blood flow with dobutamine administration.