Acute and long-term results of coronary stents and atherectomy in women and the elderly.

AIM: To determine the efficacy of new coronary interventions in women and the elderly. PATIENTS AND METHODS: We studied 504 patients who underwent a total of 567 procedures, comprising 275 directional coronary atherectomy and 292 Palmaz-Schatz stents over a 2 1/2 year period; 18% were women and 23% were aged > or = 70 years (elderly). RESULTS: High rates of success were obtained with these procedures in women and the elderly, although the rates were lower in women than in men (89 versus 96%, P = 0.005), and similarly lower in the elderly than in younger patients (91 versus 96%, P = 0.06). In addition to the lower success rates, there was a higher incidence of procedure-related non-Q myocardial infarction and vascular complications in both the women and the elderly, independently. The degree of angiographic restenosis (> or = 50% diameter stenosis), however, was similar in women (36 versus 28% in men, P = 0.22) and in the elderly (28 versus 29% in patients ages < 70 years, P = 0.8). There were no sex-related differences in survival, late myocardial infarction, or repeat revascularization. In the elderly, although the incidence of repeat revascularization was not increased, there was a decrease in late survival (P < 0.001) and an increase in the incidence of late myocardial infarction (P = 0.02), probably reflecting the presence of other co-morbid variables. CONCLUSION: Both directional coronary atherectomy and coronary stenting can be performed safely and effectively in women and the elderly with good long-term clinical results, despite a somewhat lower rate of success and similarly higher rates of acute complications.

Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis.

BACKGROUND: Cardiac hypertrophy is associated with elevated intracardiac angiotensin-converting enzyme activity, which may contribute to diastolic dysfunction. METHODS AND RESULTS: We infused enalaprilat (0.05 mg/min) for 15 minutes into the left coronary arteries of 20 adult patients with left ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve area, 0.7 +/- 0.2 cm2) and 10 patients with dilated cardiomyopathy (mean ejection fraction, 35 +/- 4%) and assessed (1) simultaneous changes in LV micromanometer pressure and dimensions, (2) LV regional wall motion analyzed by the area method, and (3) Doppler flow-velocity profiles. Systemic neurohormonal activation did not occur with the selective left coronary artery infusion; there were no changes in plasma renin activity, angiotensin-converting enzyme activity, or atrial natriuretic peptide. In patients with aortic stenosis, LV end-diastolic pressure declined from 25 +/- 2 to 20 +/- 2 mm Hg (P < .05). LV pressure-volume and LV pressure-dimension relations showed downward shifts by ventriculography and echocardiography, respectively, indicating improved diastolic distensibility. Regional area change during isovolumic relaxation increased in the anterior segments perfused with enalaprilat but decreased in the inferior segments, indicating acceleration of isovolumic relaxation in the anterior segments and reciprocal shortening in the inferior segments. Regional peak filling rate increased in the anterior segments but not in the inferior segments, and the regional area stiffness constant decreased in the anterior segments but not in the inferior segments. There were no changes in heart rate, cardiac output, or right atrial pressure, excluding alterations in right ventricular/pericardial constraint. In contrast, in the patients with dilated cardiomyopathy the decrease in LV end-diastolic pressure from 22 +/- 2 to 18 +/- 2 mm Hg (P < .05) was accompanied by a significant fall in right atrial pressure (9 +/- 1 to 6 +/- 1 mm Hg), implicating alterations in pericardial constraint. The patients with dilated cardiomyopathy showed no improvement in regional diastolic relaxation, filling, or distensibility. CONCLUSIONS: Intracoronary enalaprilat at a dosage that did not cause systemic neurohormonal activation improved LV diastolic chamber distensibility and regional relaxation and filling in patients with LV hypertrophy due to aortic stenosis. In contrast, these effects of intracoronary enalaprilat on diastolic function were not observed in patients with dilated cardiomyopathy who did not have concentric hypertrophy. These observations support the hypothesis that the cardiac renin-angiotensin system is activated in patients with concentric pressure-overload hypertrophy and that this activation may contribute to impaired diastolic function.

Is 40% to 70% diameter narrowing at the site of previous stenting or directional coronary atherectomy clinically significant?

Traditional binary definitions of coronary restenosis based on 6-month continuous angiographic measurements (e.g., > 50% diameter stenosis) may give confusing results for lesions whose late percent stenosis falls near the arbitrary threshold. To determine the long-term clinical consequences of such lesions, the overall correlation between follow-up percent stenosis and the performance of subsequent ischemia-driven target vessel revascularization (triggered by significant angina or a positive exercise study result, or both) was examined in 443 consecutive lesions treated with directional coronary atherectomy or Palmaz-Schatz coronary stenting. Follow-up angiograms (available in 355 lesions, 82%) were stratified into 3 groups: severe late stenosis (> 70% stenosis, n = 59), moderate late stenosis (40% to 70% stenosis, n = 72), and minimal late stenosis (< 40% stenosis, n = 224). With an average clinical follow-up of 933 +/- 394 days, 92% of lesions in the "severe late stenosis" group were treated with ischemia-driven target vessel revascularization, compared with 0% of the lesions in the "minimal late stenosis" group. Ischemia-driven target vessel revascularization was performed in 38% of patients in the "moderate late stenosis" group. However, patients in this group who did not undergo revascularization (despite the fact that 43% of them had a late stenosis of > 50%) showed a similarly favorable long-term clinical outcome to patients with a minimal late stenosis. These results support a strategy of conservative management for the 20% of patients who have a moderate (40% to 70%) late stenosis after stenting or atherectomy, but do not have evidence of ischemia.

Myocardial perforation in the cardiac catheterization laboratory: incidence, presentation, diagnosis, and management.

The introduction of balloon valvuloplasty and new devices for coronary intervention has increased the incidence and changed the site and clinical presentation of cardiac perforation. We reviewed all cases of cardiac perforation that occurred during 11,845 consecutive catheterization procedures during a 6-yr period (1986-91). Fourteen cardiac perforations (overall incidence 0.12%) occurred as a result of the following procedures: mitral valvuloplasty 7 of 150 (4.7%), aortic valvuloplasty 4 of 260 (1.5%), pericardiocentesis 1 of 90 (1.1%), temporary pacer 1 of 1,660 (0.06%), and diagnostic left heart catheterization 1 of 6,965 (0.01%). Perforation was recognized in the catheterization laboratory in 11 patients, within 1 hr of leaving the laboratory in two patients, and 15 hr later in one patient. Hemodynamic evidence of tamponade developed in 13 patients and was confirmed by fluoroscopy (immobile heart borders) or echocardiography. Pericardiocentesis is definitive therapy in nearly half of the cases; the remaining patients require pericardiocentesis plus surgical repair of the perforation.

Balloon postdilation can safely improve the results of successful (but suboptimal) directional coronary atherectomy.

This study investigates whether adjunctive balloon angioplasty can be safely used to improve acute results in cases where directional coronary atherectomy alone has provided a successful (but suboptimal) outcome. Between October 1, 1990, and October 1, 1992, directional coronary atherectomy was performed successfully in 198 of 228 lesions. Individual operators believed that most acute results were satisfactory after atherectomy alone (group I, n = 115) with a minimal lumen diameter that increased from 0.82 +/- 0.45 to 3.21 +/- 0.65 mm after atherectomy, for an acute gain in lumen diameter of 2.39 +/- 0.73 mm and a residual stenosis of 6 +/- 13%. In 42% of lesions (group II, n = 83), however, results were considered suboptimal after atherectomy alone, with a minimal lumen diameter that increased from 0.85 +/- 0.45 to 2.83 +/- 0.64 mm, a smaller acute gain of 1.96 +/- 0.72 mm, and a mean residual stenosis of 17 +/- 14% (although all residual stenoses were < 50%, 19% had a residual stenosis > 30%). Adjunctive balloon angioplasty in these group II lesions provided an additional gain of 0.34 +/- 0.38 mm, bringing the total acute gain for group II lesions to 2.32 +/- 0.78 mm and the residual stenosis to 9 +/- 13%, similar to that of group I patients who underwent atherectomy alone. This strategy resulted in a 7 +/- 13% overall residual stenosis for the study population, with no higher incidence of periprocedural complications or adverse late clinical outcomes in group II patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency and consequences of intimal hyperplasia in specimens retrieved by directional atherectomy of native primary coronary artery stenoses and subsequent restenoses.

Although intimal hyperplasia is a frequent occurrence after arterial interventional procedures, the overall frequency and significance of intimal hyperplasia in primary coronary lesions has not been previously addressed. The incidence of intimal hyperplasia was therefore examined using standard light microscopy in specimens obtained from native coronary arteries of patients undergoing directional coronary atherectomy. The associated clinical history, angiographic results and clinical outcomes were also tabulated. Intimal hyperplasia was identified in 51 of 55 patients (93%) treated with directional coronary atherectomy for restenosis after a prior intervention. These restenosis lesions had less acute gain in lumen diameter after directional coronary atherectomy, a smaller late lumen diameter, more severe late stenosis (p < 0.04), and tended to have more restenosis defined as late stenosis > or = 50% (restenosis rate 40% for prior restenosis vs 26% for primary lesions). Surprisingly, however, intimal hyperplasia was also identified in 45 of 102 (44%) primary stenoses. Primary lesions (n = 45) with intimal hyperplasia were more likely to occur in younger patients and in the left anterior descending artery than were either primary lesions without intimal hyperplasia (n = 57) or prior restenosis lesions. There were otherwise no differences in the baseline characteristics, angiographic findings or clinical outcome of primary lesions with or without intimal hyperplasia (restenosis rate 28 and 24%, respectively). The event-free survival (72% at 12 months) was similar in all 3 groups. Thus, even though intimal hyperplasia is an almost universal finding in restenosis lesions, intimal hyperplasia is not specific for restenosis since histologically identical hyperplasia may be found in nearly half of primary coronary artery stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural organization and chromosomal assignment of the gene encoding endothelin.

Endothelin is a 21-amino acid vasoconstrictor synthesized and secreted by vascular endothelial cells. The human peptide is derived from a 212-amino acid precursor, preproendothelin. A nearly full length clone containing DNA complementary to human preproendothelin mRNA was isolated, and its nucleotide sequence was determined. Using this cDNA as a probe, the genomic organization of the human endothelin gene was determined and the promoter region delineated. The gene contains five exons and four intervening sequences. Nucleotide sequences encoding endothelin are contained within the second exon, and the third exon specifies a portion of preproendothelin that is homologous to endothelin. The second and third exons may represent descendants of a common progenitor exon. The 3'-untranslated portion of the gene contains a 250-base pair region that is highly conserved between human and porcine genomes and may have an important role in endothelin mRNA stability. On the basis of DNA isolated from human-mouse somatic hybrid cell lines, the endothelin gene was assigned to human chromosome 6.