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Biomedical subjects

A M Lincoff

Publications and source records attributed to A M Lincoff.

At least 109 records · Page 6Linked to original sources

Significance of a coronary artery with thrombolysis in myocardial infarction grade 2 flow "patency" (outcome in the thrombolysis and angioplasty in myocardial infarction trials). Thrombolysis and Angioplasty in Myocardial Infarction Study Group.

To determine whether pharmacologic reperfusion to Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow during acute myocardial infarction confers the same clinical benefit as restoration of TIMI 3 flow, in-hospital clinical and angiographic outcomes in 1,229 patients prospectively enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction trials were analyzed. Patients were treated with intravenous tissue plasminogen activator or urokinase, or both. Angiography of the infarct-related artery 90 minutes after initiation of thrombolytic therapy demonstrated TIMI grades 0, 1, 2, or 3 flow in 20%, 7%, 17%, and 55% of vessels, respectively. Rescue or adjunctive coronary angioplasty was performed in 80%, 27%, and 16% of patients with TIMI 0/1, 2, or 3 flow, respectively. Predischarge angiography was performed in 963 patients. A significant gradient of increasing mortality was seen in patients with lower TIMI flow (4.3%, 6.1%, and 10.1% with TIMI 3, 2, and 0/1 flow, respectively, p = 0.002). The incidence of congestive heart failure and recurrent ischemia was significantly higher in patients with TIMI 2 than with TIMI 3 perfusion (26% vs 19% for heart failure, p = 0.03; 23% vs 17% for recurrent ischemia, p = 0.05). Acute left ventricular ejection fraction and infarct zone regional wall motion were also significantly improved in patients with TIMI 3 than with TIMI 2 flow, with trends toward better improvement in global and regional function in the TIMI 3 group. These findings were not affected by the use of acute coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

Prospective case-control comparison of percutaneous transluminal coronary revascularization in patients with multivessel disease treated in 1986-1987 versus 1991: improved in-hospital and 12-month results. Multivessel Angioplasty Prognosis Study (MAPS) Group.

OBJECTIVES: This study sought to ascertain whether early and 12-month clinical outcomes after percutaneous coronary revascularization have improved between 1986-1987 and 1991. BACKGROUND: Since the mid-1980s, when the results of percutaneous revascularization were considered to be somewhat static, justifying large-scale clinical trials of percutaneous transluminal coronary angioplasty versus other modes of therapy, balloon technology has improved, and several new percutaneous revascularization techniques have become available. The clinical results of the current integrated approach to revascularization compared with those for coronary angioplasty alone in the late 1980s are not known. METHODS: In this prospective case-control study, 200 consecutively treated patients with multivessel disease in 1991 were studied prospectively and compared with 400 consecutive patients from the same centers during 1986-1987. Patients from 1991 were matched with earlier patients on the basis of four previously described prognostic determinants (left ventricular ejection fraction, presence of unstable angina, diabetes and target lesion morphology score) and the treating institution and were assessed for treatment outcome (completeness of revascularization, procedural success and event-free survival [freedom from death, myocardial infarction and further revascularization]). RESULTS: The 1991 cohort of patients was older (mean [+/- SD] age 62 +/- 11 vs. 58 +/- 11 years, p < 0.001) and tended to have slightly worse left ventricular function (ejection fraction 56 +/- 10% vs. 58 +/- 11%, p = 0.009) than the 1986-1987 cohort. Overall lesion morphology risk scores were similar. New devices (other than coronary angioplasty) were used in 26% of patients. The 1991 patient cohort had more frequent total revascularization (35% vs. 21%, p = 0.003), fewer emergency bypass operations (1.0% vs. 5.5%, p = 0.006) and an improved overall procedural success rate (90% vs. 84%, p = 0.04). In addition, at 12 months the event-free survival rate was superior in the 1991 cohort (73.3% vs. 63.6%, p = 0.02), although there was no difference in infarct-free survival rate (94.6% vs. 93.2%, p = NS). CONCLUSIONS: Improved results with percutaneous revascularization in 1991 have important implications for patient care and interpretation of ongoing randomized trials enrolling patients in the late 1980s and intending to compare standard coronary angioplasty with other forms of therapy.

Angioplasty, Balloon, Coronary↗

Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: insights from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT).

OBJECTIVES: We examined the results of the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) to determine the characteristics and consequences of creatine kinase (CK) and creatine kinase, MB myocardial isoenzyme fraction (CK-MB) elevations after percutaneous coronary intervention. BACKGROUND: Enzyme elevations after interventional procedures have usually been thought to be without long-term clinical consequences. However, recent preliminary reports have suggested that there are important long-term clinical sequelae in patients with even mild enzyme elevations after coronary procedures. METHODS: Patients with new native lesions undergoing coronary intervention at 35 clinical sites were randomized to undergo percutaneous coronary angioplasty (n = 500) or directional coronary atherectomy (n = 512). Cardiac enzyme levels were measured 12 and 24 h after the interventional procedure and when clinically indicated for recurrent myocardial ischemia. Enzyme profiles were analyzed using a ratio that compared the peak enzyme level and the local laboratory upper limit of normal. Standard 12-lead electrocardiograms (ECGs) recorded before and after the procedure were interpreted by two independent readers who had no knowledge of the randomization data. Postprocedural myocardial infarction was defined as the appearance of new Q waves on the ECG, CK-MB levels three or more times the upper limit of normal or a total CK concentration two or more times the upper limit of normal when CK-MB levels were unavailable. Regression models were used to evaluate the predictive significance of a postintervention myocardial infarction with respect to clinical outcomes at 30 days and 1 year. RESULTS: There were 78 myocardial infarctions in the atherectomy group and 34 in the angioplasty group (15.2% vs. 6.8%, p = 0.001). Patients with a myocardial infarction more often had a repeat intervention or emergency coronary artery bypass surgery. Hospital length of stay was increased among patients with an infarction, as were mean hospital costs ($17,340.65 vs. $11,308.47, p = 0.0003). Postprocedural myocardial infarction was highly predictive of mortality, bypass surgery or repeat intervention within 30 days (p < 0.0001). CONCLUSIONS: Myocardial infarction occurred commonly after coronary intervention in CAVEAT and was associated with a worse clinical outcome. Although the incidence of myocardial infarction was higher with atherectomy than with angioplasty, the baseline characteristics and consequences of the infarctions were similar between the treatments with regard to 30-day outcome. Myocardial enzyme elevations after an otherwise successful interventional procedure may identify a population at risk for a future cardiac event.

Angioplasty, Balloon, Coronary↗

An overview of the results of the EPIC trial.

The Evaluation of 7E3 for the Prevention of Ischaemic Complications (EPIC) trial assessed the use of abciximab in the treatment of patients at high risk undergoing percutaneous revascularization procedures. Abciximab (c7E3) is a chimeric monoclonal antibody targeted to block the glycoprotein IIb/IIIa receptor on the surface of the platelet; this receptor is believed to be the final common pathway of platelet aggregation. Administered at the time of angioplasty or directional coronary atherectomy, abciximab had a beneficial effect in the population studied, which included patients considered to be at high risk from complications of the procedure, based on the presence of acute or recent myocardial infarction, severe unstable angina or adverse coronary morphological characteristics. Abciximab reduced the risk of the primary endpoint at 30 days (death, myocardial infarction, repeat angioplasty or bypass surgery for recurrent ischaemia, balloon pump or stent insertion for ischaemia) by 35%: from 12.8% in the placebo group to 8.3% in patients treated with abciximab bolus and infusion. This trend was observed as a whole and in each component of the primary endpoint. At 6 months follow-up, the effect of the treatment was modestly enhanced beyond 30 days. A variety of substudies have documented substantial evidence of treatment benefit in patients with acute myocardial infarction and unstable angina. Non-fatal infarction, observed as beyond that normally expected in other studies with directional coronary atherectomy, was not above normal in patients treated with abciximab, and there was evidence of a treatment benefit in the elderly, although more information would be helpful in patients over the age of 70. The substantial site-to-site variability indicates that standardization of percutaneous revascularization could enhance the benefit of abciximab, while reducing bleeding complications.

Abciximab↗

Early clinical experience with integrelin, an inhibitor of the platelet glycoprotein IIb/IIIa integrin receptor.

Aggregation of platelets leading to thrombosis is one of the hallmarks of unstable angina, acute myocardial infarction, and ischaemic complications following coronary angioplasty. Activated platelets bind to fibrinogen through the glycoprotein IIb/IIIa integrin receptor. New agents have been developed to bind this receptor and thus prevent aggregation of platelets. One such compound (integrelin) is a cyclical peptide that has been shown to be a potent inhibitor of the glycoprotein IIb/IIIa receptor in man. A number of phase I and phase II clinical trials have been completed to evaluate this agent for the indications of unstable angina, acute myocardial infarction, as well as an adjunct to coronary angioplasty. This article will focus on the clinical investigation of integrelin with particular emphasis on its use during angioplasty. It has been consistently shown across different trials that integrelin can inhibit between 70% and 95% of platelet aggregation responses to 20 mumols of ADP at a variety of dosages used in the phase II trials. Preliminaray data also suggest that a more clinically unstable patient may require a higher dose of integrelin to cause a near complete inhibition of the platelet aggregation response to ADP. Future studies will need to explore more definitely the relationship between dose of glycoprotein IIb/IIIa receptor blockers and clinical instability.

Angioplasty, Balloon, Coronary↗

Cell adhesion molecules in coronary artery disease.

To date, six families of cell adhesion molecules are known. These are cell surface receptors that mediate adhesion of cells to each other or to components of the extracellular matrix and include integrins, selectins, the immunoglobulin superfamily, cadherins, proteoglycans and mucins. These cell adhesion molecules play a key role in cell-cell interaction (such as among endothelium, monocytes, smooth muscle cells and platelets) and cell-extracellular matrix interaction (such as between leukocytes, platelets or fibroblasts and the extracellular matrix). The importance of these interactions has recently been demonstrated in clinical trials with the use of an antibody fragment directed against the platelet alpha IIb beta IIIa integrin, with reduction of arterial thrombosis and restenosis after percutaneous coronary interventions. A fundamental role for cell adhesion molecules has been suggested for several other relevant disease processes, including atherosclerosis, acute coronary syndromes, reperfusion injury and allograft vasculopathy. This review focuses on providing the clinically relevant biology of these families of adhesion molecules, setting the foundation for delineation of their emerging role in cardiovascular therapeutics.

Animals↗

Randomized evaluation of coronary angioplasty for early TIMI 2 flow after thrombolytic therapy for the treatment of acute myocardial infarction: a new look at an old study. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group.

BACKGROUND: Patients who have suffered acute myocardial infarction (AMI) and have been treated with intravenous thrombolytic agents resulting in early 'patent' [Thrombolysis in Myocardial Infarction (TIMI) 2-3 flow grade] arteries have been shown not to benefit from early percutaneous transluminal coronary angioplasty (PTCA). Recent data, however, suggest that the clinical outcome of patients with early TIMI 2 flow is decidedly inferior to that of patients with TIMI 3 flow, raising the question whether early PTCA might be beneficial for patients with TIMI 2 flow. The clinical utility of PTCA for this particular subset of patients has never been assessed. METHODS: We analyzed left ventricular ejection fraction (LVEF) recovery by contrast ventriculography and clinical outcome in Thrombolysis and Angioplasty in Myocardial Infarction Phase I (TAMI-I) study patients with initial TIMI 2 flow grade, determined by blinded core laboratory analysis. RESULTS: No differences were observed between baseline demographic data for the 49 patients randomly assigned to undergo early PTCA compared with that from the 59 patients randomly assigned to receive early medical therapy. Patients were 56 +/- 11 years of age (mean +/- SD), 80% were men, the time from onset of chest pain to catheterization was 268 +/- 71 min, 42% had anterior AMI, and 42% had multivessel disease. Ninety minute baseline LVEF to prehospital discharge LVEF was minimally better in the group randomly assigned to undergo PTCA (51 +/- 12 to 52 +/- 11% versus 55 +/- 10 to 53 +/- 12%, P = 0.06). This contrasted with findings in patients with TIMI 3 flow grade at baseline, which showed a relative benefit for patients randomly assigned to receive early medical therapy (54 +/- 10 to 54 +/- 8% for PTCA, versus 55 +/- 10 to 58 +/- 8% for medical therapy, P = 0.01). Among patients with TIMI 2 flow grade there were no differences in in-hospital death or congestive heart failure (6.1 versus 1.7%, P = 0.25 and 18.4 versus 23.7%, P = 0.50, PTCA versus medical therapy, respectively). CONCLUSION: We conclude that (1) PTCA of infarct-related arteries with TIMI 2 flow grade may modestly improve recovery of left ventricular function, and (2) widespread application of PTCA in this setting should be deferred, pending demonstration that this benefit outweighs the risks of PTCA.

Aged↗

Patients at high risk for ischemic complications.

The identification of the factors which predict increased risk for procedural complications in patients undergoing percutaneous revascularization allows a prospective stratification and evaluation of the risk benefit ratio in the individual patient. Such stratification may allow choice of other management options, such as medical therapy or bypass surgery, but probably more importantly allows the selective application of adjunctive pharmacotherapy or mechanical support techniques. It is important to recognize the limitations of all pre-procedural risk assessment however in that overall these criteria still have relatively low predictive value and to a great extent closure remains unforeseeable. Additionally, high risk characteristics are frequently encountered in clinical practice, and for many high risk patients the best option for revascularization may still be the percutaneous one.

Age Factors↗

Intracoronary stenting compared with conventional therapy for abrupt vessel closure complicating coronary angioplasty: a matched case-control study.

OBJECTIVES: A case-control analysis was performed to compare clinical outcome after intracoronary stenting with that after conventional therapy for abrupt vessel closure. BACKGROUND: Previous studies have demonstrated that stenting after abrupt vessel closure results in marked angiographic improvement and preservation of coronary flow, leading to the anticipation of similar improvement in clinical outcome. METHODS: Sixty-one of 92 consecutive patients treated at two clinical sites by intracoronary stenting for abrupt vessel closure were matched, according to angiographic features of closure and estimated left ventricular mass threatened by ischemia, with patients treated conventionally during the 18 months before stent availability. In 33 pairs of matched patients, vessel closure was established; in 28 pairs, it was threatened (coronary dissection or worsening stenosis with preservation of normal anterograde flow). Baseline clinical and angiographic characteristics were comparable in the two matched groups. Patients with indeterminate mechanisms of total occlusion (31%) or dissections < 15 mm long (43%) predominated; patients with visible thrombus (8%) or dissections > 15 mm long (18%) were infrequently represented. Stents were successfully deployed in 60 of 61 patients at a median of 52 min (range 3 to 269) after the onset of closure. RESULTS: When compared with conventional treatment, stenting resulted in less residual stenosis (26% vs. 49% diameter stenosis, p < 0.001), a greater likelihood of restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow (97% vs. 72%, p < 0.001) and a reduction in the need for emergency bypass surgery (4.9% vs. 18%, p = 0.02). However, the incidence of Q wave myocardial infarction was nearly the same in the two groups (32% vs. 20%, respectively, p = NS). In the group with stenting, peak creatine kinase level and the frequency of Q wave infarction after established vessel closure increased with the time to stent placement (p = 0.001 and 0.054, respectively); the incidence of procedure-related Q wave infarction in patients who underwent stenting within 45 min of closure was very low (3.9%). In-hospital death occurred in 3.3% of patients in each treatment group. At a mean of 6.3 months of follow-up after hospital discharge, survival free from late cardiac death, myocardial infarction, bypass surgery or coronary angioplasty was 74.9% and 81.3% in the stent and the control treatment group, respectively (p = NS). CONCLUSIONS: Although early treatment of established vessel closure by intracoronary stenting was associated with a low incidence of both myocardial infarction and emergency bypass surgery, the likelihood or severity of infarction was not reduced among those in whom stents were implanted later. Patients with threatened vessel closure could not be shown to benefit from stent treatment. These data provide preliminary indications for stent placement in the acute period to be validated in larger randomized studies.

Acute Disease↗

Thrombolytic therapy for women with myocardial infarction: is there a gender gap? Thrombolysis and Angioplasty in Myocardial Infarction Study Group.

OBJECTIVES: The goal of this study was to investigate whether female gender portends an adverse prognosis independent of the severity of the underlying disease after acute myocardial infarction treated by thrombolysis. A total of 348 women were compared with 1,271 men enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials. BACKGROUND: The reasons for gender differences in the management and prognosis of acute coronary artery syndromes remain poorly defined. The extent to which gender itself explains observed differences in outcome and use of diagnostic procedures remains unclear because confounding factors have not been specified. METHODS: Patients < 76 years of age presenting within 6 h of onset of ischemic symptoms with electrocardiographic ST segment elevation and without contraindications to thrombolysis, previous infarction in the same distribution or cardiogenic shock were prospectively enrolled in Phases 1 to 3, 5 and 7 of the TAMI trials. All patients received recombinant tissue-type plasminogen activator, urokinase or a combination of both agents. Protocol-mandated cardiac catheterization was performed during the hospital period. Rescue coronary angioplasty was carried out for reperfusion failure at angiography 90 min after initiation of thrombolytic therapy. Coronary artery bypass grafting or coronary angioplasty was performed for clinical indications. RESULTS: Women were older than men (61.0 +/- 9.7 vs. 55.8 +/- 10.1 years, mean +/- SD) and had a higher incidence of many risk factors for adverse outcome after myocardial infarction. There were no differences in baseline hemodynamic variables or time to thrombolytic treatment. Rates of acute and predischarge infarct-related artery patency and global and regional left ventricular function were similar in the two groups. Rates of in-hospital coronary angioplasty (52.6% and 54.1%) and bypass graft surgery (20.4% and 22.0%) were comparable in women and men, respectively. Women had higher unadjusted rates of mortality (9.2% vs. 5.4%, p = 0.014), reinfarction (6.4% vs. 2.6%, p = 0.005) and hemorrhagic stroke (2.0% vs. 0.55%, p = 0.017) than did men during the hospital period. When adjusted for clinical and angiographic variables, differences in mortality and hemorrhagic stroke did not reach statistical significance, and the risk of reinfarction was only marginally associated with gender. CONCLUSIONS: In selected patients undergoing thrombolytic therapy and cardiac catheterization for acute myocardial infarction, adjusted mortality rates and utilization of postlysis revascularization are similar in women and men. However, women may be at increased risk for reinfarction.

Age Factors↗

Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction?

Thrombolytic therapy significantly improves the natural history of acute myocardial infarction, but recent data suggest that current reperfusion strategies have yet to realize the maximum potential for reduction of mortality and salvage of ventricular function. Coronary patency rates as high as 85% assessed by angiography 90 minutes after initiation of treatment greatly overestimate the efficacy of thrombolytic regimens, as this conventional angiographic "snapshot" view does not satisfactorily reflect the dynamic processes of coronary artery recanalization and reocclusion or the adequacy of myocardial perfusion. In fact, only the unusual patient appears to achieve optimal reperfusion for acute myocardial infarction, with a substantial deterioration of benefit in many patients due to insufficiently early or rapid recanalization, incomplete patency with TIMI grade 2 flow or critical residual coronary stenoses, absence of myocardial tissue reflow despite epicardial artery patency, intermittent coronary patency, subsequent reocclusion, or reperfusion injury. Recently developed techniques to critically assess the quality of reperfusion, coupled with the introduction of novel pharmacological agents and an improved understanding of the roles and mechanisms of existing thrombolytic and adjunctive drugs, have provided the opportunity to overcome many of the present limitations of reperfusion therapy. Emerging strategies to achieve optimal reperfusion are directed at enhancement of the velocity and quality of thrombolysis, amelioration of the adverse effects of reperfusion, and use of alternative pathways to myocardial salvage.

Coronary Vessels↗

Differences in cardioprotective efficacy of adrenergic receptor antagonists and Ca2+ channel antagonists in an animal model of dilated cardiomyopathy. Effects on gross morphology, global cardiac function, and twitch force.

Turkey poults fed furazolidone (Fz) in high concentrations (700 ppm) develop dilated cardiomyopathy (Fz-DCM). We tested whether five cardioactive agents were cardioprotective in this model of heart failure, ie, whether they prevented dilatation and wall thinning and improved contractile performance. We compared the effects of chronic administration of a beta 1-selective and a nonselective beta-receptor antagonist, an alpha-receptor antagonist, and two Ca2+ channel antagonists in the presence of Fz administration. The greatest cardioprotection was found with treatment with either propranolol or nifedipine. At the gross morphological level, the effect of propranolol (a nonselective beta-adrenergic antagonist) was greater than the effect of atenolol (a selective beta 1-adrenergic antagonist), and the effect of nifedipine was greater than that of verapamil (Ca2+ channel antagonists), with all agents more cardioprotective than phenoxybenzamine (an alpha 1-adrenergic > alpha 2-adrenergic antagonist). Differences in cardioprotective efficacy of each agent increased with increased concentration. These data indicate that the dose and choice of a specific type of Ca2+ channel antagonist or beta-receptor antagonist might be important in the treatment of dilated cardiomyopathy. All agents that were cardioprotective caused similar functional improvements at both the whole heart and isolated muscle levels. Compared with control animals, Fz-DCM animals showed a significant reduction in peak left ventricular (LV) developed pressure (92 +/- 17 versus 143 +/- 24 mm Hg, P < .05), +dP/dt (1151 +/- 219 versus 2454 +/- 549 mm Hg/s), and -dP/dt (1128 +/- 291 versus 1875 +/- 396 mm Hg/s), with a significant increase in LV end-diastolic volumes (2.8 +/- 0.7 versus 0.16 +/- 0.1 mL for control animals, P < .05). In contradistinction, LV + dP/dt and -dP/dt values for animals receiving Fz plus a cardioactive agent that demonstrated cardioprotection were not significantly different from control values. Peak LV developed pressures were also similar for Fz animals receiving an agent that demonstrated cardioprotection and control animals not receiving any pharmacologic agent. Isolated muscles from Fz-DCM animals as well as animals receiving Fz plus cardioprotective pharmacologic agents responded normally with regard to increasing extracellular Ca2+ concentrations. Peak twitch forces were greater for animals receiving cardioprotective agents plus Fz than control animals not receiving any pharmacologic agents or Fz alone. At higher stimulation rates, Fz-DCM muscles demonstrated a significantly reduced peak twitch force (4 +/- 0.5 versus 1.5 +/- 0.4 g/mm2 for control muscles versus Fz-DCM muscles, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Abrupt vessel closure complicating coronary angioplasty: clinical, angiographic and therapeutic profile.

To assess the clinical, angiographic and procedural correlates of outcome after abrupt vessel closure during coronary angioplasty, results were analyzed of 109 patients (8.3%) who had abrupt vessel closure during 1,319 consecutive coronary angioplasty procedures performed between July 1, 1988 and June 30, 1990. These 109 patients had a mean age of 59 +/- 11 years; 63% were male, 57% had had a prior myocardial infarction and 61% had multivessel disease. Coronary angioplasty was performed in the settings of acute myocardial infarction (14%), recent myocardial infarction (36%), unstable angina (34%) and stable ischemia (29%). Abrupt vessel closure occurred at a median of 27 min (range 0 min to 5 days) from the first balloon inflation. By angiographic criteria, thrombus or coronary dissection was identified in 20% and 28% of cases, respectively; both thrombus and dissection were present in 7% of closures, and 45% were due to indeterminate mechanisms. Successful reversal of abrupt vessel closure, defined as restoration of normal Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow without resultant Q wave myocardial infarction, emergency bypass surgery or death, was achieved in 47 patients (43%). By hierarchal analysis, the incidence of death, emergency coronary bypass surgery, Q wave and non-Q wave myocardial infarction was 8%, 20%, 9% and 11%, respectively. Univariate analysis using 23 clinical, morphologic and procedural variables demonstrated that successful outcome after abrupt closure was associated with prolonged balloon inflations (greater than 120 s) (odds ratio = 6.87, p less than 0.001), unstable angina (odds ratio = 2.37, p = 0.034) and placement of an intracoronary stent (odds ratio = 5.33, p = 0.062). By multivariate analysis, independent correlates of successful outcome were prolonged balloon inflations (odds ratio = 5.11, p = 0.001) and intracoronary stenting (odds ratio = 4.37, p = 0.049). Thus, although prolonged balloon inflations and intracoronary stents may improve outcome after abrupt vessel closure, the cumulative risk of morbidity or mortality remains significant and mandates investigation into improved strategies for its prevention and treatment.

Acute Disease↗

Percutaneous support devices for high risk or complicated coronary angioplasty.

Indications for coronary angioplasty have expanded to include patients with unstable acute ischemic syndromes, severe multivessel coronary artery disease and impaired left ventricular function. Several mechanical approaches have been developed as adjuncts to high risk coronary angioplasty to improve patient tolerance of coronary balloon occlusion and maintain hemodynamic stability in the event of complications. These percutaneous techniques include intraaortic balloon counterpulsation, anterograde transcatheter coronary perfusion, coronary sinus retroperfusion, cardiopulmonary bypass, Hemopump left ventricular assistance and partial left heart bypass. The intraaortic balloon pump provides hemodynamic support and ameliorates ischemia by decreasing myocardial work; it may be inserted for periprocedural complications or before angioplasty in patients with ischemia or hypotension. Anterograde distal coronary artery perfusion may be accomplished passively through an autoperfusion catheter or by active pumping of oxygenated blood or fluorocarbons through the central lumen of an angioplasty catheter. Synchronized coronary sinus retroperfusion produces pulsatile blood flow via the cardiac veins to the coronary bed distal to a stenosis. Both perfusion techniques limit development of ischemic chest pain and myocardial dysfunction in patients undergoing prolonged balloon inflations. Percutaneous cardiopulmonary bypass provides complete systemic hemodynamic support which is independent of intrinsic cardiac function or rhythm and has been employed prophylactically in very high risk patients before coronary angioplasty or emergently for abrupt closure. These and newer support devices, while associated with significant complications, may ultimately improve the safety of coronary angioplasty and allow its application to those who would otherwise not be candidates for revascularization.

Angioplasty, Balloon, Coronary↗

Experimental determination and mathematical model of the transient incorporation of cholesterol in the arterial wall.

Experimental data of the radial incorporation of labeled cholesterol [14C-4] into the artery wall is regressed against a mathematical model that predicts macromolecular transport in this biological system. Data is obtained using excised canine carotid arteries that are perfused in vitro under pulsatile hemodynamic conditions for 2 hr. Vessels are exposed to either normotensive hemodynamics, hypertensive hemodynamics, or simulations in which the rate of flow or vessel compliance is deliberately altered. Several arteries are studied under normotensive conditions following balloon catheter deendothelialization. Transmural concentration profiles of [14C-4] activity are determined by microcryotomy of longitudinal sections of perfused vessels. Nonlinear Marquardt regression on 12 experimental cases yields parameter estimates of effective diffusivity, D and solute filtration velocity, V. Results of this experimental investigation support our hypothesis that hemodynamics and the endothelial lining influence wall flux in intact vessels. Exposure to altered (vs normotensive) hemodynamics is associated with increased incorporation of labeled cholesterol. A similar observation is made for deendothelialized vessels (e.g. a greater accumulation of label and a rise in convective flux). Based upon our companion measurements of vessel wall forces and endothelial cellular morphology accompanying hemodynamic simulations, we suggest that hemodynamically induced alterations to endothelial structures lead to the increased permeability, convection and incorporation that we observe in this work.

Animals↗