Lawrence W. Gimple

Quantitative planar rest-redistribution 201Tl imaging in detection of myocardial viability and prediction of improvement in left ventricular function after coronary bypass surgery in patients with severely depressed left ventricular function.

BackgroundAlthough many patients with multivessel coronary artery disease (CAD) and severely depressed left ventricular (LV) function will benefit from coronary artery bypass graft surgery (CABG), surgeons may be reluctant to perform CABG on these patients without evidence of myocardial viability in regions of severe asynergy. We hypothesized that quantitative planar rest-redistribution 201Tl imaging would identify viable myocardium and predict improved regional and global function after revascularization in patients with depressed LV function and CAD. Methods and ResultsTwenty-one patients (mean LV ejection fraction, 0.27±0.05) were studied. Regional and global LV functions were evaluated before and 8 weeks after CABG with radionuclide ventriculography. Segments were prospectively classified as showing normal, mildly reduced, or severely reduced viability on the basis of quantitative analysis of defect severity and redistribution on planar resting 201Tl imaging. By 201Tl criteria, 90% of hypokinetic segments were classified with normal or mildly reduced viability. Among akinetic or dyskinetic segments, 20% had normal 201TI uptake, 53% had mildly reduced viability, and only 27% had severely reduced viability. 201TI viability criteria identified segments that improved function after CABG. Sixty-two percent of severely asynergic segments with normal viability and 54% with mildly reduced viability improved function after surgery, but only 23% with severely reduced viability improved function (p=0.002). When only adequately revascularized segments were considered, the predictive value of a positive preoperative viability scan for functional improvement was 73%. The greatest improvement in global LV function after CABG occurred in patients with the greatest number of asynergic segments classified as viable before surgery (p<0.01). In 10 patients with more than seven viable, asynergic segments, mean LV ejection fraction increased significantly after CABG (0.29±0.07 to 0.41±0.11, p=0.002). In 11 patients with seven or fewer viable, asynergic segments, mean LV ejection fraction remained unchanged after revascularization (0.27±0.05 to 0.30±0.08, p=NS). ConclusionsIn patients with CAD and severely depressed LV function, preoperative quantitative planar rest-redistribution 201TI imaging identifies viability in many asynergic myocardial segments, and these segments frequently improve function after CABG. The presence of numerous asynergic but viable myocardial segments before surgery correlated significantly with improvement in global LV function after bypass surgery.

Improved Outcome After Coronary Bypass Surgery in Patients With Ischemic Cardiomyopathy and Residual Myocardial Viability

BACKGROUNDnAlthough residual myocardial viability in patients with coronary artery disease and extensive regional asynergy is associated with improved ventricular function after coronary bypass surgery, the relationship between viability and clinical outcome after surgery is unclear. We hypothesized that patients with poor ventricular function and predominantly viable myocardium have a better outcome after bypass surgery compared with those with less viability.nnnMETHODS AND RESULTSnSeventy patients with multivessel coronary artery disease and left ventricular ejection fractions < 40% who underwent preoperative quantitative 201Tl scintigraphy before coronary bypass surgery were analyzed retrospectively. 201Tl scintigrams were reviewed blindly, and each segment was assigned a score based on defect magnitude. Segmental viability scores were summed and divided by the number of segments visualized to determine a viability index. The viability index was significantly related to 3-year survival free of cardiac event (cardiac death or heart transplant) after bypass surgery (P=.011) and was independent of age, ejection fraction, and number of diseased coronary vessels. Patients with greater viability (group 1; viability index > 0.67; n=33) were similar to patients with less viability (group 2; viability index < or = 0.67; n=37) with respect to age, comorbidities, and extent of coronary artery disease. There were 6 cardiac deaths and no heart transplants in group 1 patients and 15 cardiac deaths and two transplants in group 2 patients. Survival free of cardiac death or transplantation was significantly better in group 1 patients on Kaplan-Meier analysis (P=.018).nnnCONCLUSIONSnWe conclude that resting 201Tl scintigraphy may be useful in preoperative risk stratification for identification of patients more likely to benefit from surgical revascularization.

Microvascular integrity indicates myocellular viability in patients with recent myocardial infarction. New insights using myocardial contrast echocardiography.

BACKGROUNDnPatency of the infarct-related artery (IRA) after acute myocardial infarction (AMI) may not reflect the magnitude of tissue perfusion. In animal models of AMI, myocardial cellular necrosis has been associated with extensive capillary damage. Because myocardial contrast echocardiography (MCE) can define the spatial distribution of microvascular perfusion, we hypothesized that it could be used in patients after recent AMI to distinguish myocardial regions that have an intact microvasculature and thus are viable from those without an intact microvasculature and thus are not viable.nnnMETHODS AND RESULTSnOne hundred five patients with a recent AMI (range, 1 day to 4 weeks; median, 8 days) who were undergoing cardiac catheterization were included in the study. Two-dimensional echocardiography was performed at baseline and repeated 1 month later to assess regional function within the infarct zone (scores of 1 to 5 indicating normal to dyskinetic segments, respectively). MCE was performed in the cardiac catheterization laboratory to assess microvascular perfusion within the infarct bed. A contrast score index was derived by assigning scores to individual segments within the infarct zone (0, 0.5, and 1 denoting no, intermediate, and homogeneous contrast effect, respectively) and deriving the average score within the infarct bed. Revascularization was performed as clinically indicated. Although the baseline wall motion score and the contrast score index were similar in the 90 patients with a patent IRA and the 15 patients with an occluded IRA (median +/- 1 interquartile range, 3 +/- 1 versus 3.5 +/- 1; P = .41), wall motion score 1 month later was significantly better in those with open IRAs compared with those with closed IRAs (2 +/- 2 versus 3 +/- 2, P = .05). In the 90 patients with an open IRA, a strong correlation was noted between wall motion score 1 month later and the contrast score index (rho = -.64, P < .001). On multivariate analysis, the best correlate of the 1-month wall motion score was the contrast score index.nnnCONCLUSIONSnIn patients studied in the cardiac catheterization laboratory between 1 day and 4 weeks after AMI, an intact microvasculature as identified by MCE indicates myocardial regions that improve function 1 month later. This study demonstrates that microvascular patency is closely associated with myocardial cellular viability after AMI in humans.

Effectiveness of recombinant desulphatohirudin in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.

BackgroundThe effectiveness of balloon angioplasty is limited by a restenosis rate of approximately 30%. Recombinant desulphatohirudin (r-hirudin [CGP 39393]) has been found to be highly effective in preventing acute platelet-rich thrombosis after deep arterial injury as compared with heparin. Methods and ResultsThis study evaluated the effect of intravenous r-hirudin, a selective inhibitor of thrombin, on restenosis after balloon angioplasty in 29 rabbits. Focal femoral atherosclerosis was induced by air desiccation endothelial injury followed by a 2% cholesterol diet for 1 month. At angioplasty (2.5-mm balloon with three 60-second, 10-atm inflations 60 seconds apart), the rabbits received heparin (150 units/kg bolus, n = 16) or r-hirudin (1 mg/kg bolus followed by infusions of 1 mg/kg for the first hour and 0.5 mg/kg for the second hour, n = 13). Angiograms performed before and after angioplasty and before death were analyzed quantitatively by a blinded observer. Rabbits were killed 2 hours (n =14) or 28 days (n =15) after angioplasty. Femoral arteries were fixed in situ by perfusion of 10% formaldehyde at 100 mm Hg. The mean luminal diameter of the arteries with successful angioplasty (.20%o increase in luminal diameter) in rabbits treated with heparin (n =8 arteries) increased from 1.18 ± 0.29 mm before angioplasty to 1.86 ± 0.24 mm immediately after angioplasty (p < 0.001) and decreased to 0.94 ± 0.69 mm (p =0.0004) at 28 days after angioplasty. In rabbits treated with r-hirudin (n =11 arteries), the mean luminal diameter increased from 1.14 ± 0.17 mm before angioplasty to 1.68 ± 0.20 mm immediately after angioplasty (p < 0.001) and decreased to 1.37 ± 0.47 mm (p = 0.01) at 28 days after angioplasty. The mean reduction in luminal diameter by angiography was less in the r-hirudin-treated group than in the heparin-treated group (0.3090.33 versus 0.92 ± 0.61 mm, p = 0.01). Blinded planimetric analysis of stained histological sections of the femoral arteries also showed less cross-sectional area narrowing by plaque in rabbits treated with r-hirudin compared with those treated with heparin (22 ± z16% versus 48to29 o, p=0.01). Both groups had similar numbers of arteries with histological evidence of balloon-induced plaque tear (12 of 13 versus 13 of 15). ConclusionsRabbits receiving r-hirudin at the time of experimental balloon angioplasty had significantly less restenosis by angiography and by quantitative histopathology than rabbits receiving heparin. (Circulation 1991;84:232–243)

Comparison between visual assessment and quantitative angiography versus fractional flow reserve for native coronary narrowings of moderate severity

We tested the hypothesis that experienced interventional cardiologists can identify patients with fractional flow reserve (FFR) <0.75 either by visual assessment of the angiogram or by quantitative coronary angiography (QCA). Estimation of the significance of moderate lesions is difficult. FFR can determine the physiologic significance of a stenosis. Data comparing visual assessment and QCA of moderate lesions with FFR are limited. FFR was measured in 83 moderate lesions defined as having a 40% to 70% stenosis by visual inspection. An FFR <0.75 was considered significant. Lesions were visually assessed by 3 experienced interventional cardiologists and their significance estimated. QCA was performed. Both analyses were compared with FFR. FFR averaged 0.82 +/- 0.11 and was <0.75 in 15 of 83 lesions (18%). The reviewers classification was concordant with the FFR in about half the lesions. Concordance between reviewers was poor (Spearmans rho = 0.36). Visual assessment resulted in good sensitivity (80%) and negative predictive value (91%), but poor specificity (47%) and positive predictive value (25%) compared with FFR. By QCA, no patient with stenosis <60% or minimal luminal diameter >1.4 mm had FFR <0.75. QCA did not discriminate the significance of lesions outside of these parameters. Thus, neither visual assessment of an angiogram by experienced interventional cardiologists nor QCA can accurately predict the significance of most moderate narrowings.

Percutaneous balloon pericardiotomy for the treatment of cardiac tamponade and large pericardial effusions: description of technique and report of the first 50 cases.

OBJECTIVESnThis study describes the technique, clinical characteristics and results of the first 50 patients undergoing percutaneous balloon pericardiotomy as part of a multicenter registry.nnnBACKGROUNDnPercutaneous balloon pericardiotomy involves the use of a percutaneous balloon dilating catheter to create a nonsurgical pericardial window.nnnMETHODSnPatients eligible for percutaneous balloon pericardiotomy had either cardiac tamponade (n = 36) or a moderate to large pericardial effusion (n = 14). In addition to clinical follow-up, serial echocardiograms and chest X-ray films were obtained.nnnRESULTSnThe procedure was considered successful in 46 patients after a mean follow-up period of 3.6 +/- 3.3 months. Two patients required an early operation, one for bleeding from a pericardial vessel and one for persistent pericardial catheter drainage. Two patients required a late operation for recurrent tamponade. Minor complications of the procedure included fever in 6 of the first 37 patients (studied before the prophylactic use of antibiotic agents), thoracentesis or chest tube placement in 8 and a small spontaneously resolving pneumothorax in 2. Despite the short-term success of this procedure, the long-term prognosis of the 44 patients with malignant pericardial disease remained poor (mean survival time 3.3 +/- 3.1 months).nnnCONCLUSIONSnPercutaneous balloon pericardiotomy is successful in helping to manage large pericardial effusions, particularly in patients with a malignant condition. It may become the preferred treatment to avoid a more invasive procedure for patients with pericardial effusion and a limited life expectancy.

Elevated Serum Lipoprotein(a) Is a Risk Factor for Clinical Recurrence After Coronary Balloon Angioplasty

BACKGROUNDnElevated lipoprotein (Lp) (a) concentrations are associated with coronary artery disease and myocardial infarction. Lp(a) is structurally related to proteins involved in lipid transport, fibrinolysis, coagulation, and cellular mitogenesis and is known to have important physiological interactions with the coagulation and fibrinolytic systems. Because these processes may be important to arterial healing after balloon injury, we hypothesized that elevated Lp(a) concentrations may be associated with recurrence of symptoms and restenosis after balloon angioplasty.nnnMETHODS AND RESULTSnWe assessed 240 consecutive patients undergoing coronary balloon angioplasty with measurements of Lp(a), total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A-I, and apolipoprotein B-100 concentrations from fresh specimens. Patients were evaluated 4 to 6 months after angioplasty for clinical recurrence by repeat angiography if angina had returned or by maximal exercise treadmill testing with thallium imaging if patients remained asymptomatic. Ninety-seven patients (40%) had clinical recurrence; 143 (60%) did not. Patients with recurrence had significantly greater Lp(a) concentrations compared with those without (median, 29 versus 14; P < .0001). Each patient quintile stratified by increasing Lp(a) concentrations had incrementally greater recurrence rates ranging from 27% (lowest quintile) to 60% (highest quintile). By multivariate logistic regression analysis, Lp(a) concentration was the only predictor of recurrence (P < .0001). A subset of frozen, stored serum samples showed a significant decrease in measured Lp(a) concentration over time (mean, 605 days; P < .01).nnnCONCLUSIONSnAn elevated Lp(a) concentration was a risk factor for clinical recurrence after percutaneous transluminal balloon coronary angioplasty. Other lipid levels or clinical characteristics were not significantly associated with recurrence. When serum was frozen and stored for a prolonged period, Lp(a) concentration decreased over time.

Specific factor Xa inhibition reduces restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.

BACKGROUNDnBalloon angioplasty of atherosclerotic arteries results in activation of the coagulation cascade. Several coagulation factors, including factor Xa and thrombin, are mitogenic for vascular smooth muscle cells in vitro and thus may play a role in restenosis after balloon angioplasty. Specific inhibition of factor Xa can be achieved with recombinant antistasin (rATS) or tick anticoagulant peptide (rTAP). We hypothesized that inhibition of Xa would limit restenosis after balloon angioplasty in an atherosclerotic rabbit model.nnnMETHODS AND RESULTSnFocal femoral atherosclerosis was induced by air desiccation injury and a high-cholesterol diet in 38 New Zealand White rabbits. Recombinant antistasin (n = 20 arteries) or rTAP (n = 14 arteries) was administered by intravenous bolus at the time of balloon angioplasty and followed by a 2-hour infusion; controls (n = 21 arteries) received bolus heparin alone (150 U/kg). Therapeutic prolongation of the activated partial thromboplastin time occurred, and antithrombotic drug levels were achieved in all animals. Luminal diameter in millimeters by quantitative angiography did not differ between treatment groups before (1.1 +/- 0.2 for controls, 1.1 +/- 0.2 for rATS, and 1.1 +/- 0.3 for rTAP) or after balloon angioplasty (1.5 +/- 0.3 for controls, 1.4 +/- 0.2 for rATS, and 1.4 +/- 0.2 for rTAP). At 28 days, treatment with factor Xa inhibitors tended to result in arteries with larger luminal diameter than controls (1.2 +/- 0.3 for rATS, 1.2 +/- 0.3 for rTAP versus 1.0 +/- 0.3 for control, P = .09 by one-way ANOVA). Restenosis, defined as reduction in angiographic luminal diameter (in mm) from 2 hours after angioplasty to 28 days after angioplasty was less in the rATS group than in controls (-0.2 +/- 0.1 versus -0.5 +/- 0.4, P < .001) and tended to be less in the rTAP group (-0.3 +/- 0.2 versus -0.5 +/- 0.4, P = .07). Quantitative histopathological analysis showed less percent cross-sectional area narrowing by plaque in both rATS- and rTAP-treated arteries compared with controls (42 +/- 21%, 47 +/- 18%, and 63 +/- 14%, respectively; P < .01 by one-way ANOVA).nnnCONCLUSIONSnWe conclude that a 2-hour infusion of rATS or rTAP reduced angiographic restenosis and resulted in less luminal cross-sectional narrowing by plaque compared with controls.

Platelet activation during coronary angioplasty in humans.

BackgroundPrevious studies have indicated that balloon angioplasty is associated with local platelet activation. In addition, different contrast media have different effects on thrombus formation during angioplasty in humans. We hypothesized that coronary angioplasty in humans is associated with activation of platelets to specific platelet agonists and that this activation may be differently modified by different angiographic contrast agents. Methods and ResultsWe studied 25 patients referred for angioplasty of the left anterior descending or circumflex coronary arteries. All patients were pretreated with aspirin and received heparin. Blood samples for assessment of platelet aggregation to serotonin, ADP, epinephrine, and collagen were obtained from the coronary sinus before any contrast injection, after initial diagnostic contrast injections, and after three balloon inflations. Patients were randomized to receive iopamidol, diatrizoate, or ioxaglate. Contrast alone was not associated with altered platelet aggregation. However, balloon angioplasty was consistently associated with increased platelet aggregation to serotonin but not to ADP, epinephrine, or collagen. These effects were similar with the three contrast agents studied except that the use of iopamidol was associated with increased platelet responsiveness to all concentrations of ADP after balloon dilation.Conclsions. Coronary angioplasty in humans was associated with increased platelet aggregation in blood drawn from the coronary sinus. This effect was primarily seen when serotonin was used as an agonist.

Selective αvβ3-Receptor Blockade Reduces Macrophage Infiltration and Restenosis After Balloon Angioplasty in the Atherosclerotic Rabbit

Background&agr;v&bgr;3-Integrin receptors are upregulated in atherosclerotic arteries and play a key role in smooth muscle cell and possibly inflammatory cell migration. We hypothesized that after balloon angioplasty (BA) of atherosclerotic arteries, selective inhibition of the &agr;v&bgr;3-receptor by XT199, a small-molecule, non-peptide-selective &agr;v&bgr;3-receptor antagonist, would reduce restenosis. Methods and ResultsAfter induction of focal atherosclerosis, rabbits underwent femoral BA and received XT199 (2.5 mg/kg IV bolus plus 2.5 mg · kg−1 · d−1 IV; n=19) or vehicle (n=20) for 14 days. At 28 days after BA, the XT199 group had a larger lumen (0.75±0.26 versus 0.57±0.20 mm2, P =0.03) and a smaller neointimal area (0.49±0.18 versus 0.68±0.25 mm2, P =0.01) than the vehicle group. Angiographic analysis confirmed a 30% to 40% reduction in restenosis. Arteries harvested at 28 days after BA did not show a reduction in intima plus media smooth muscle cell content but did show a 50% reduction in macrophage cell density in the XT199 group (716±452 versus 1458±989 cells/mm2, P <0.006). Neovessel density at 28 days was also reduced (23±42 versus 58±46 vessel cross sections/mm2, P <0.02). Early after BA (ie, 3 to 7 days), there was a decrease in intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, indicative of a reduction in vascular cell activation. ConclusionsSelective &agr;v&bgr;3-receptor blockade for 14 days after BA in the focally atherosclerotic rabbit significantly reduced restenosis and limited macrophage infiltration and neovascularization in the vessel wall.