Mechanisms of balloon angioplasty and directional coronary atherectomy as assessed by intracoronary ultrasound.

OBJECTIVE: This study was designed to use intracoronary ultrasound imaging to elucidate the physical effects of balloon angioplasty and directional coronary atherectomy in vivo in humans. BACKGROUND: The proposed mechanisms of coronary artery interventions such as balloon angioplasty and directional atherectomy are based on animal studies or pathologic findings and these data may not be applicable to living patients. Intracoronary ultrasound findings correlate highly with pathologic results and may allow in vivo assessment of the mechanisms of such interventions in humans. METHODS: Intracoronary ultrasound imaging was performed in 45 patients after a successful coronary intervention (balloon angioplasty in 30, directional coronary atherectomy in 15). Ultrasound images obtained at the treatment site and at an adjacent angiographically normal references site were analyzed quantitatively for minimal lumen diameter, cross-sectional lumen area, are enclosed by the internal elastic lamina, plaque area (internal elastic lamina area--lumen area) and percent area stenosis (plaque area/internal elastic lamina area). Qualitative analysis included assessment of presence of dissection, plaque composition and plaque topography. RESULTS: The results of the two procedures were similar with respect to minimal lumen diameter (angioplasty 2.6 +/- 0.5 vs. atherectomy 2.6 +/- 0.3 mm, p = NS), lumen area (0.07 +/- 0.03 vs. 0.07 +/- 0.02 cm2, p = NS) and percent area stenosis (59 +/- 14% vs. 51 +/- 21%, p = NS). However, after angioplasty, the internal elastic lamina area was significantly larger at the treated site than at the reference site (delta = +0.03 +/- 0.04 cm2, p = 0.01). There was no significant difference between the two sites after atherectomy (delta = -0.01 +/- 0.05 cm2, p = NS). In addition, dissection was seen significantly more often after balloon angioplasty than after atherectomy (50% vs. 7%, p less than 0.01). The results were similar when stratified for plaque composition and morphology. These data were confirmed in six additional patients who underwent ultrasound imaging before and after the intervention. CONCLUSIONS: Thus, the improvement in lumen dimensions after coronary balloon angioplasty is a result of both vessel stretch, demonstrated by a larger internal elastic lamina area at the treated site, and dissection. Both vessel stretch and dissection are uncommon after atherectomy, a finding consistent with plaque removal as the major mechanism for improved lumen area after this procedure.

Intracoronary ultrasound predictors of adverse outcomes after coronary artery interventions.

OBJECTIVES: The purpose of this study was to determine the association between qualitative and quantitative lesion characteristics as assessed by intracoronary ultrasound imaging and adverse outcomes after coronary artery interventions. BACKGROUND: Restenosis and other adverse outcomes after coronary artery interventions may be difficult to predict from clinical or angiographic data. Intracoronary ultrasound imaging provides additional data that could prove useful. METHODS: Immediately after successful coronary artery interventions (angiographic residual stenosis < or = 50%), 69 patients underwent intracoronary ultrasound imaging. Images were assessed qualitatively for plaque composition and topography and for dissection. Quantitative data included measurement of minimal lumen diameter, lumen area, plaque area and percent area stenosis at the treatment and adjacent reference sites. Adverse outcome was defined as death, coronary bypass surgery, myocardial infarction or angiographic restenosis. RESULTS: Of the 69 patients, 1 died, 3 had bypass surgery and 1 had a myocardial infarction before planned 6-month repeat catheterization. Two patients were lost to follow-up study. Of the remaining 62 patients, 56 (90%) agreed to follow-up catheterization and 25 (45%) of the 56 had restenosis. Thus, 30 patients had an adverse outcome and 37 had no adverse event. The incidence of dissection detected by ultrasound imaging after an intervention was significantly greater in patients with than in those without a subsequent adverse event (63% vs. 35%, p < 0.05). The severity of dissection also appeared to be related to outcome (p < 0.05). Other qualitative and quantitative variables were not significantly different between the two patient groups. CONCLUSIONS: Dissection, as assessed by intracoronary ultrasound imaging after a coronary artery intervention, can identify patients at increased risk of subsequent adverse events. Additional studies are warranted to explore whether such imaging may allow modification of interventional procedures to improve outcome.

Predicting the risk of abrupt vessel closure after angioplasty in an individual patient.

OBJECTIVES: We proposed to examine the relation between angiographic morphologic characteristics and abrupt closure after coronary angioplasty and to develop an empirically based risk stratification system. BACKGROUND: Certain lesion morphologic characteristics are associated with higher rates of abrupt closure after coronary angioplasty. Previous approaches have been limited by relatively small sample sizes and an inability to combine multiple characteristics to predict risk in an individual patient. METHODS: Lesion morphology was determined for 779 lesions in 658 patients undergoing an elective first angioplasty. Abrupt closure occurred in 63 lesions (8.1%). Variables associated with abrupt closure were identified by univariate and stepwise multiple logistic regression analysis, and internal validity was assessed by use of bootstrapping. An empirically based scoring system was developed by assigning different weights to each predictive characteristic and was then validated. RESULTS: Almost all lesion characteristics previously labeled "adverse" were associated with an increased risk of abrupt closure, but only total occlusion, location at a branch point, increasing lesion length, evidence for thrombus and right coronary artery location were statistically significant independent predictors. Despite the large sample size, the study was underpowered to detect even a 50% increase in risk with many characteristics. Using a scoring system, we assigned each lesion a specific risk of abrupt closure. The distribution of risk was broad, with 20% of patients having < or = 2.5% risk and 25% having > 10% risk. Internal validation techniques revealed that when 10% of patients were randomly eliminated from the sample in multiple iterations, the risk estimates varied, again pointing to the need for a larger sample. CONCLUSIONS: Empirically based weighting of lesion characteristics could quantify the risk of abrupt closure for individual patients, but a very large sample will be required to understand the interplay of complex lesion characteristics in altering expected outcomes.

Amphotericin-B and monensin potentiation of murine erythropoiesis in vitro: a possible role for sodium ions.

To study the role of monovalent cation flux in erythropoiesis we cultured mouse bone marrow cells with amphotericin B (AmB), monensin, valinomycin, or Etruscomycin. At low doses the polyene antibiotic AmB has been shown to increase cell permeability to Na+ and K+ and we found that it potentiated erythropoietin (epo)-stimulated erythroid-colony (CFU-E) and burst (BFU-E) growth at concentrations ranging from 0.5-1.0 micrograms/ml. Monensin, a sodium-specific ionophore, potentiated epo-stimulated erythroid growth at concentrations of 1-30 nM. On the other hand, a potassium-specific ionophore, valinomycin, did not cause potentiation, but rather suppressed epo-dependent colony formation. Etruscomycin, another polyene, but one which in mammalian cells increases ion permeability only at toxic concentrations, was also suppressive. Potentiating concentrations of AmB and monensin increased the sensitivity of CFU-E and BFU-E to epo and at saturating epo levels increased the numbers of erythroid colonies and bursts by about 40%. Neither AmB nor monensin stimulated erythroid growth in the absence of epo. We found a 20-fold difference in the AmB concentrations comprising the maximally potentiating dose in C57BL/6 and AKR marrow cultures. This is consistent with observed differences between these two mouse strains with regard to other effects of AmB on them, including the immunoadjuvant properties of AmB. Our results showing potentiation due to sodium ion flux may be related to previous work showing potentiation of erythroid differentiation caused by calcium ion flux, since sodium ion movement may directly affect the intracellular calcium ion concentration.

Effect of balloon material and inflation strategy on arterial trauma and mechanisms of percutaneous transluminal coronary angioplasty as determined by intracoronary ultrasound.

Twenty-three patients were randomized to a minimally invasive strategy or to standard percutaneous transluminal coronary angioplasty followed by intracoronary ultrasound. There was no difference in intracoronary ultrasound-determined dissection after the procedure in the 2 groups, and the mechanism of lumen enlargement by percutaneous transluminal coronary angioplasty in both groups predominantly was due to vessel stretch.

Clinical risks of thrombolytic therapy.

Understanding the clinical risks of intravenous thrombolytic therapy is critical to appropriate patient selection. The major risks can be classified into 5 major categories: intracranial hemorrhage, systemic hemorrhage, immunologic complications, hypotension, and myocardial rupture. Although theoretical concern exists about thromboembolic complications, they rarely occur. Although cardiac rhythm disturbances are somewhat more likely to occur at the time of reperfusion, the clinical significance of "reperfusion arrhythmias" is minimal. Intracranial hemorrhage, the most devastating complication, occurs in 0.2-1% of patients treated with thrombolytic therapy. Factors associated with incremental risk are now being identified from large clinical trials. Systemic hemorrhage is uncommon in patients without major vascular punctures and seldom leads to serious adverse outcomes. Immunologic complications--including anaphylaxis, which is rare, and immune complex disease, which is more common--occur only with streptokinase or agents with a streptokinase moiety, including anistreplase (anisoylated plasminogen--streptokinase activator complex, APSAC). Hypotension, which can be managed easily in most patients, is also observed much more frequently with streptokinase and anistreplase. Myocardial rupture is increasingly being recognized as a possible complication of late thrombolysis. A proper perspective on clinical risk can only be gained in the context of potential benefit of therapy. In many cases individual patients considered to be at highest risk for complications also stand to gain the most from treatment. Many of the questions raised by currently available data about bleeding risk are being addressed in the ongoing Global Utilization of t-PA and Streptokinase (GUSTO) Trial. A paradigm for considering this decision making problem is presented.

Unrecognized left main coronary artery disease in patients undergoing interventional procedures.

Selective, coronary arteriographic, catheter-based, intravascular ultrasound images were obtained to determine the presence and extent of angiographically undetected or underestimated left main (LM) coronary arterial narrowing in patients receiving coronary interventional therapy. Coronary arteriograms were determined to be either normal or abnormal by visual inspection. Abnormal arteriograms were digitized and quantitated using a semiautomated edge-detection algorithm. Thirty-eight patients receiving percutaneous treatment of stenoses in the left coronary artery system were studied. Optimal LM coronary angiograms were obtained in 2 views, and intravascular ultrasound images were obtained after the coronary interventional procedure. Intravascular ultrasound detected plaque in 24 of 27 angiographically normal LM arteries (89%), whereas narrowing was observed in 11 of 11 angiographically abnormal LM arteries (100%). Eight of 38 patients (21%) had > 40% area stenosis by intravascular ultrasound. In patients with angiographic disease, there was no correlation between quantitative angiographic and ultrasound percent area stenosis (r = 0.12; p = 0.72; SEE 19%). The median plaque area was not different between angiographically normal (0.05 cm2; 0.03, 0.08 [25th, 75th percentile]) and abnormal (0.06 cm2; 0.03, 0.1) patients. The median percent area stenosis in arteriographically normal subjects (26%; 14, 32%) was less than that in abnormal ones (37%; 20, 46%) (p = 0.03). Unrecognized LM disease is widespread and often underestimated in patients with normal LM angiograms undergoing interventional procedures. Plaque area is similar for angiographically normal and insignificantly abnormal vessels. This study suggests that intravascular ultrasound overcomes the limitations of silhouette imaging and can be a clinically useful, adjunctive method to evaluate LM coronary artery disease.

In vivo validation of compensatory enlargement of atherosclerotic coronary arteries.

Necropsy examinations and epicardial ultrasound studies have suggested that atherosclerotic coronary arteries undergo compensatory enlargement. This increase in vessel size may be an important mechanism for maintaining myocardial blood flow. It also is of fundamental importance in the angiographic study of coronary disease progression and regression. The purpose of this study was to determine, using intracoronary ultrasound, whether coronary arteries undergo adaptive expansion in vivo. Forty-four consecutive patients were studied (30 men, 14 women; mean age 56 +/- 10 years). Eighty intravascular ultrasound images were analyzed (32 left main, 23 left anterior descending and 25 right coronary arteries). Internal elastic lamina area, a measure of overall vessel size increased as plaque area expanded (r = 0.57, p = 0.0001, SEE = 5.5 mm2). When the left main, left anterior descending and right coronary arteries were examined individually, there continued to be as great or greater positive correlation between internal elastic lamina and plaque area (left anterior descending: r = 0.75, p = 0.0001; right coronary arteries: r = 0.63, p = 0.0007; left main: r = 0.56, p = 0.0009), implying that each of the vessels and all in aggregate underwent adaptive enlargement. When only those vessels with < 30% area stenosis were examined, internal elastic lamina correlated well with plaque area (r = 0.79, and p = 0.0001), and for each 1 mm2 increase in plaque area, internal elastic lamina increased 2.7 mm2. This suggests that arterial enlargement may overcompensate for early atherosclerotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolytic therapy in patients requiring cardiopulmonary resuscitation.

Cardiopulmonary resuscitation (CPR) is often considered a contraindication to thrombolytic therapy for acute myocardial infarction. Of 708 patients involved in the first 3 Thrombolysis and Angioplasty in Myocardial Infarction trials of lytic therapy for acute infarction, 59 patients required less than 10 minutes of CPR before receiving lytic therapy (CPR greater than 10 minutes was an exclusion of the trials) or required CPR within 6 hours of treatment. The patients receiving CPR were similar to the remainder of the group with respect to baseline demographics. The indication for CPR was usually ventricular fibrillation (73%) or ventricular tachycardia (24%). The median duration of CPR was 1 minute, with twenty-fifth and seventy-fifth percentiles of 1 and 5 minutes, respectively. The median number of cardioversions/defibrillations performed was 2 (twenty-fifth and seventy-fifth percentiles of 1 and 3 minutes, respectively). Patients receiving CPR were more likely to have anterior infarctions (66 vs 39%), the left anterior descending artery as the infarct-related artery (63 vs 38%) and lower ejection fractions on the initial ventriculogram (46 +/- 11 vs 52 +/- 12%) than those not receiving CPR. In-hospital mortality was 12 vs 6% with most deaths due to pump failure (57%) or arrhythmia (29%) in the CPR group and pump failure (38%) or reinfarction (25%) in the non-CPR group. At 7 day follow-up the CPR group had a significant increase in ejection fraction (+5 +/- 9%) compared with no change in non-CPR group. There were no bleeding complications directly attributed to CPR.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of long coronary artery narrowings with long angioplasty balloon catheters.

Balloon angioplasty of long coronary artery narrowings has been associated with a lower rate of acute success, and a higher rate of acute complications and restenosis than that observed for short narrowings. Angioplasty catheters with longer length balloons (30 and 40 mm) are now available, and the objective of this study was to determine the acute and long-term success for patients with long coronary artery narrowings treated with these longer balloons. All patients with long narrowings (> or = 10 mm) treated with long balloons at 1 institution over a 1-year period were identified (93 narrowings in 89 patients), and acute and long-term outcomes were carefully documented. Procedural success (residual stenosis < or = 50%) was 97%. Abrupt closure occurred in 6% and major dissection in 11% of narrowings. Clinical success (procedural success without in-hospital death, bypass surgery or myocardial infarction) was achieved in 90% of patients. Repeat catheterization was performed in 61 patients (76% of those eligible), and restenosis was found in 50 to 55%, depending on the definition used. The treatment of long coronary artery narrowings using angioplasty catheters with longer balloons leads to high rates of acute success. However, there is a high rate of restenosis. New interventional devices for long lesions should be compared with long balloons in a randomized controlled trial.

Long-term outcome following successful reopening of abrupt closure after coronary angioplasty.

Abrupt closure after coronary angioplasty is often successfully treated by repeat dilation. Long-term follow-up, including 6-month repeat catheterization and 12-month clinical evaluation, was obtained in 1,056 patients treated with acute (n = 335) or elective (n = 721) coronary angioplasty to evaluate the long-term impact of successful reopening of abrupt closure. Abrupt closure occurred in 13.5% of patients and was successfully reopened in 58%. Adverse outcomes including restenosis, death, bypass surgery, myocardial infarction and repeat angioplasty were compared between patients with successfully treated abrupt closure and those with successful procedures (residual diameter stenosis < or = 50%) without abrupt closure. For patients with acute angioplasty, the restenosis rates (> 50% diameter stenosis at follow-up) were 64% for those with successfully treated abrupt closure versus 36% for those with successful procedures without abrupt closure (p < 0.01). In addition, subsequent myocardial infarction (12 vs 3%; p = 0.01) and repeat angioplasty (21 vs 10%; p = 0.03) were more frequent in the group with abrupt closure. For patients with elective angioplasty, restenosis was 43% in those with successfully treated abrupt closure versus 45% in those without abrupt closure (p = NS). Subsequent death and myocardial infarction were more frequent in patients with abrupt closure (death: 12 vs 3% [p < 0.01]; myocardial infarction: 13 vs 3% [p < 0.01]). Long-term adverse events are increased in patients with successfully treated abrupt closure compared to those with successful procedures without abrupt closure.

Design of the therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (TRAFFIC) trial.

The Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 for Intermittent Claudication (TRAFFIC) is a large, randomized, placebo-controlled, regimen-finding trial of intra-arterial recombinant fibroblast growth factor-2 in patients with intermittent claudication. This report describes the major design considerations and end points in TRAFFIC.

Levels of expression of P-selectin, E-selectin, and intercellular adhesion molecule-1 in coronary atherectomy specimens from patients with stable and unstable angina pectoris.

Unstable angina occurs when atherosclerotic plaque ruptures. Recent evidence suggests a role for inflammation in this process. Leukocyte-endothelial cell interactions are important in inflammation and are regulated by cell adhesion molecules. This study was designed to examine the vascular expression of cell adhesion molecules and cytokines in patients with unstable angina. Directional coronary atherectomy was performed in patients with unstable and stable angina. Expression of the cell adhesion molecules P-selectin, E-selectin, and intercellular adhesion molecule-1 in the tissue obtained was examined using immunohistochemistry. In addition, expression of the cytokines tumor necrosis factor-alpha and interleukin-1beta, which participate in the regulation of cell adhesion molecule expression, was also examined. Atherectomy specimens had significantly greater P-selectin expression from patients with unstable angina than from patients with stable angina. P-selectin expression was observed primarily on endothelial cells. There were no differences in any of the other factors between patients with unstable and stable angina. In addition, other clinical and angiographic variables were not associated with differential expression of any of the cell adhesion molecules or cytokines. These results indicate a possible role for P-selectin in the process of unstable angina.

Intravascular ultrasound and balloon percutaneous transluminal coronary angioplasty.

Intracoronary ultrasound provides unique information during percutaneous transluminal coronary angioplasty (PTCA), including more accurate measurement of vessel size and plaque burden as well as plaque characteristics such as composition and distribution. As a research tool, it has been useful in determining the mechanisms of PTCA, which primarily involves vessel stretch, plaque fracture/dissection, and plaque redistribution. It may be clinically useful in assessing lesion severity in patients with indeterminate clinical and angiographic findings. Plaque characteristics as determined by intracoronary ultrasound may also be helpful in developing an individualized interventional approach for each lesion. Finally, certain intracoronary ultrasound findings after PTCA, such as large dissections and large residual stenosis, are associated with increased risk of short-term and long-term adverse outcomes.

Intracoronary ultrasound: insights into mechanisms and results of coronary interventions.

Intracoronary ultrasound imaging is a modality which allows in vivo cross-sectional visualization of coronary arteries similar to that obtained by pathology. Compared with coronary angiography, intracoronary ultrasound provides more detail on plaque morphology and topography and more accurate quantification of lumen and plaque area. Thus, it has evolved into a valuable research tool. For example, intracoronary ultrasound imaging has increased understanding of the mechanisms of action of balloon angioplasty and new interventions such as atherectomy and laser treatment. It may prove to have clinical utility by helping to individualize device selection and sizing and by assessing treatment results more accurately. Coronary imaging may be performed at low risk. Future developments will include smaller catheters, combined ultrasound and therapeutic catheters, and three-dimensional reconstruction of images.

Patients' perceptions of the cosmetic impact of melanoma resection.

This study investigated the relationship between primary versus grafted closure for melanoma and the cosmetic impact on the patient of the resulting scar. A total of 176 patients with melanoma completed a multiple-choice questionnaire designed for this study. Two factors were significantly related to negative cosmetic impact: severity of scar indentation (but not scar length) and the extent to which patients were unprepared for the actual size of their scars. Patients whose scars were deeply indented as well as those whose scars were larger than anticipated displayed greatest distress about their appearance. Cosmetic impact was greater for women than for men. These observations suggest that primary closures, rather than closures requiring skin grafts, have important psychological benefits for patients and that physicians can assist postoperative adjustment by giving patients accurate information about the expected appearance of their scars.

Spontaneous coronary artery spasm documented in a young woman. A case report.

A 35-year-old woman with coronary risk factors presented with nonexertional atypical burning chest pain of 1 week's duration. A myocardial perfusion study with Tc-99m MIBI revealed a severe stress induced anteroseptal perfusion defect that completely reperfused on a subsequent resting Tc-99m MIBI study. Coronary angiography showed mild nonobstructive coronary artery disease. At the termination of the procedure, a spontaneous episode of burning chest pain occurred. Left main coronary artery reinjection of contrast revealed proximal diffuse left anterior descending coronary artery spasm. The patient was followed for 2 years with no further episodes of chest pain, while on calcium channel-blocker medication. The phenomenon of vasospastic angina and the role of myocardial perfusion scintigraphy is discussed.

Angioplasty for acute coronary syndromes.

The acute ischemic syndromes (unstable angina and acute myocardial infarction) are often treated with percutaneous transluminal coronary angioplasty. Angioplasty should be considered in patients with unstable angina refractory to medical therapy and in those with evidence for ischemia after medical stabilization. Direct or primary angioplasty is indicated in patients with acute myocardial infarction with contraindications to thrombolytic therapy and is a reasonable alternative even in those eligible for thrombolytics. While there is no role for immediate angioplasty of a patent infarct-related artery following thrombolysis, rescue angioplasty of persistently occluded arteries may be beneficial, although further studies are needed.

A psychological comparison of patients with malignant melanoma and other dermatologic disorders.

A study of 168 patients with melanoma and 135 patients with other dermatologic disorders was conducted to define and compare emotional reactions in these populations. A self-report test of mental health developed by the Rand Corporation and previously applied to large segments of the general public was used to measure psychologic status. Melanoma patients were approximately equal to the general public and strikingly superior to other dermatology patients in terms of emotional well-being. Profoundly diminished self-esteem among nonmelanoma dermatology patients and intensified utilization of psychic resources among melanoma patients are postulated as an explanation for this finding.