Robert-Jan van Suylen

Balloon angioplasty for the treatment of lesions in saphenous vein bypass grafts

OBJECTIVES The purpose of this review is to assess the value and limitations of balloon angioplasty for the treatment of saphenous vein bypass graft obstructions. The potential efficacy of new interventional techniques is discussed. BACKGROUND Treatment of ischemia due to saphenous vein bypass graft obstructions poses a difficult problem that will be encountered more often as the pool of surgically treated patients continues to accumulate. Reoperation is technically demanding and is associated with high mortality and morbidity rates. Balloon angioplasty may provide a suitable alternative. METHODS The review proposes a classification of patients with attempted saphenous vein graft angioplasty according to expected early and late outcome based on the data obtained from the relevant published data and personal experience. RESULTS Angioplasty of a nonocclusive obstruction in a saphenous vein bypass graft has an initial success rate of approximately 90% and is a safe procedure (procedural death rate < 1%, myocardial infarction rate < 4%). The overall average restenosis rate is 42%. Surgical standby is limited and technically difficult. Angioplasty of chronic total occlusions in old grafts is associated with poor initial and long-term results. The long-term clinical results are unfavorable because of the continuing progression of disease in nontreated vein graft segments and native coronary arteries, in addition to the high restenosis rate. New techniques, although promising, have shown neither better initial results nor reduction of restenosis. Stent placement may be useful in longer graft lesions containing friable material. CONCLUSIONS Patients may be classified into three groups according to expected early and late outcome on the basis of 1) unfavorable graft anatomy, 2) risk of cardiogenic shock in event of acute graft closure, and 3) age of grafts. The three groups are 1) those with an initial high success, low procedural risk and low restenosis rate; 2) those with an initial high success but high procedural risk and moderate to high restenosis rate; and 3) those with a low success, high risk and high restenosis rate. Balloon angioplasty to treat lesions in venous bypass grafts should be considered a palliative procedure, not a long-term solution, for ongoing progression of coronary artery and vein graft disease. The induced high restenosis rate remains a significant problem.

The Ross Procedure A Systematic Review and Meta-Analysis

Background— Reports on outcome after the Ross procedure are limited by small study size and show variable durability results. A systematic review of evidence on outcome after the Ross procedure may improve insight into outcome and potential determinants. Methods and Results— A systematic review of reports published from January 2000 to January 2008 on outcome after the Ross procedure was undertaken. Thirty-nine articles meeting the inclusion criteria were allocated to 3 categories: (1) consecutive series, (2) adult patient series, and (3) pediatric patient series. With the use of an inverse variance approach, pooled morbidity and mortality rates were obtained. Pooled early mortality for consecutive, adult, and pediatric patients series was 3.0% (95% confidence interval [CI], 1.8 to 4.9), 3.2% (95% CI, 1.5 to 6.6), and 4.2% (95% CI, 1.4 to 11.5). Autograft deterioration rates were 1.15% (95% CI, 1.06 to 2.06), 0.78% (95% CI, 0.43 to 1.40), and 1.38%/patient-year (95% CI, 0.68 to 2.80), respectively, and for right ventricular outflow tract conduit were 0.91% (95% CI, 0.56 to 1.47), 0.55% (95% CI, 0.26 to 1.17), and 1.60%/patient-year (95% CI, 0.84 to 3.05), respectively. For studies with mean patient age >18 years versus mean patient age ≤18 years, pooled autograft and right ventricular outflow tract deterioration rates were 1.14% (95% CI, 0.83 to 1.57) versus 1.69% (95% CI, 1.02 to 2.79) and 0.65% (95% CI, 0.41 to 1.02) versus 1.66%/patient-year (95% CI, 0.98 to 2.82), respectively. Conclusions— The Ross procedure provides satisfactory results for both children and young adults. Durability limitations become apparent by the end of the first postoperative decade, in particular in younger patients.

Directional atherectomy for treatment of restenosis within coronary stents: clinical, angiographic and histologic results

OBJECTIVES The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure.

Proliferation and extracellular matrix synthesis of smooth muscle cells cultured from human coronary atherosclerotic and restenotic lesions

OBJECTIVES The purpose of this study was to examine the proliferative capacity and extracellular matrix synthesis of human coronary plaque cells in vitro. BACKGROUND Common to both primary atherosclerosis and restenosis are vascular smooth muscle cell proliferation and production of extracellular matrix proteins. The applicability to humans of experimental animal models of these processes has been questioned. METHODS Primary atherosclerotic and restenotic lesions were excised by percutaneous directional coronary atherectomy in 93 patients. Smooth muscle cells were cultivated by an explant technique and identified by their morphology in culture, ultrastructural features under electron microscopy and immunostaining using monoclonal antibodies to smooth muscle cell alpha-actin. Proliferation in secondary culture was assessed with growth curves and the synthesis of collagen and sulfated glycosaminoglycans by the incorporation of 3H-proline and 35S-sulfate, respectively. These studies were also performed in cells derived from human umbilical artery media. RESULTS Success rates for primary (45%) and secondary (12%) culture of coronary cells were not influenced by clinical variables or lesion category. Primary culture success was improved by the presence of organized thrombus in the plaque and in relation to increased maximal cell density of the atherectomy specimen. Restenotic cells displayed more rapid growth than did cells of primary atherosclerotic origin, which grew in a manner similar to that of umbilical artery cells. Mean calculated population-doubling times for the three cell groups were 52 h (95% confidence interval [CI] 48 to 58 h), 71 h (95% CI 62 to 83 h) and 74 h (95% CI 65 to 84 h), respectively. Restenotic and primary atherosclerotic cells did not differ in the synthesis of collagen ([mean +/- SEM] 0.034 +/- 0.004 vs. 0.033 +/- 0.004 nmol isotope.microgram protein-1, p = NS) or sulfated glycosaminoglycans (11.47 +/- 1.07 vs. 15.37 +/- 3.10 nmol isotope.microgram protein-1, p = NS), but the coronary cells synthesized significantly more collagen and sulfated glycosaminoglycans than did umbilical artery cells (0.019 +/- 0.004 and 5.43 +/- 1.00 nmol isotope.microgram protein-1, respectively, both p < 0.05). CONCLUSIONS These data indicate that increased smooth muscle cell proliferation contributes to coronary restenosis in humans and support the concept that the extracellular matrix synthesis of adult smooth muscle cells is important to lesion formation.

Determinants of coronary reserve in rats subjected to coronary artery ligation or aortic banding

OBJECTIVE We investigated whether decreased coronary reserve in hearts after coronary artery ligation or in hearts from rats after aortic banding can be related to remodeling of resistance arteries. METHODS Maximal coronary flow (absolute flow) and cardiac perfusion (flow corrected for heart weight) were determined in isolated, perfused rat hearts after adenosine or nitroprusside, at 3 and 8 weeks after coronary artery ligation or 4-5 weeks after aortic banding. Perivascular collagen and medial thickness of resistance arteries were determined by morphometry. RESULTS maximal coronary flow of infarcted hearts had been restored to sham values at 3 weeks. Growth of cardiac muscle mass from 3 to 8 weeks exceeded the increase in maximal coronary flow, leading to a decreased perfusion at 8 weeks. A slight, transient increase in perivascular collagen, but no medial hypertrophy, was found after infarction. After aortic banding perivascular fibrosis and medial hypertrophy led to a decreased maximal coronary flow in both the hypertrophied left and the non-hypertrophied right ventricle. Consequently, perfusion of the left ventricle was most severely reduced. CONCLUSIONS Reduced maximal perfusion after aortic banding is determined by both cardiac hypertrophy and vascular remodeling. In contrast, during infarction-induced remodeling, reduction of perfusion is not determined by vascular remodeling, but mainly by disproportional cardiac hypertrophy relative to vascular growth.

Endothelin receptors in the human coronary artery, ventricle and atrium

SummaryIn the present experiments we investigated endothelin (ET) receptors in the human coronary artery, and in ventricular and atrial muscle using quantitative receptor autoradiography. Displacement of [125I]Sf6b (Sarafotoxin S6b) (30 pM)- and [125I]ET-1 (30 pM)-labeled binding sites was studied using ET-1, the ETA receptor selective ligand BQ-123 (cyclo[D-Asp-L-Pro-D Val-L-Leu-D-Trp-]), and the ETB receptor selective ligand [Ala1,3,11,15]ET-1.Specific binding was more dense in atrium and coronary artery (relative optical density (r.o.d.): 0.14±0.01 and 0.16±0.01, respectively) than in ventricular muscle (r.o.d.: 0.10±0.01). In the coronary artery, binding was especially dense in the media. ET-1 displaced [125I]ET-1 and [125I]Sf6b monophasically in atrium, ventricle and coronary artery. [Ala1,3,11,15]ET 1 and BQ-123 displaced [125I]ET-1 and [125I]Sf6b-labeled sites biphasically in the ventricle and in the atrium. In the human coronary artery, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1-labeled sites monophasically (pIC50): ET-1 (9.72±0.12) > BQ-123 (6.84±0.08) > [Ala1,3,11,15]ET-1 (6.40±0.12). In contrast, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I] Sf6b-labeled coronary artery sites biphasically (high affinity pIC50: BQ-123, 9.03±0.25;[Ala1,3,11,15]ET-1, 8.40±0.14; low affinity pIC50: BQ-123, 7.24±0.14; [Ala1,3,11,15]ET-1, 6.99±0.09).These data indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle. In the human coronary artery, both radioligands labeled ETA binding sites, but [125I] Sf6b also labeled a non-ETA, non-ETB binding site with relatively high affinity for both BQ-123 and [Ala1,3,11,15] ET-1.

Effects of cryopreservation on contractile properties of porcine isolated aortic valve leaflets and aortic wall

Human semilunar donor heart valves can be stored in banks, awaiting transplantation. To evaluate the result of the preservation protocols, a quantitative description of the tissue is necessary. In this study we investigated in a quantitative way the contractile properties of fresh and cryopreserved porcine isolated aortic heart valve leaflets in response to a number of endogenous vasoactive compounds. The responses of strips of the aortic wall were included for comparison. Contraction was measured isometrically in response to potassium (K+; 100 mmol/L), 5-hydroxytryptamine (1 nmol/L to 100 micromol/L), noradrenaline (1 nmol/L to 100 micromol/L), endothelin-1 (0.01 nmol/L to 0.3 micromol/L), and prostaglandin F(2alpha) (0.1 nmol/L to 10 micromol/L). The pharmacologic parameters E(MAX) (the maximal response expressed as a percentage of contraction to a 100 mmol/L dose of K+) and EC50 (the concentration that produces 50% of the maximal effect) were calculated for every compound (n = 6 to 7 each). We observed that all specimens contracted in response to potassium. Its magnitude in fresh leaflets equaled 1.6 +/- 0.14 mN compared with 26.6 +/- 2.6 mN in fresh aortic wall. Noradrenaline, endothelin-1, and prostaglandin F(2alpha) all caused contraction in valvular leaflets and aortic wall, whereas 5-hydroxytryptamine caused contraction in the valvular leaflets but relaxation in aortic wall. After cryopreservation, the response to K+ amounted to 24% of the response of the fresh specimens in valvular leaflets (n = 25) and 14% in aortic wall (n = 26). The values of E(MAX) and EC50 of the responses to noradrenaline, endothelin-1, and prostaglandin F(2alpha) remained unchanged. Although the physiologic relevance of contraction of valvular leaflets needs further study, its measurement may provide an additional model to verify the consequences of alternative methods of preservation.

Clinical and histological determinants of smooth-muscle cell outgrowth in cultured atherectomy specimens: importance of thrombus organization.

Background:Coronary atherectomy provides a unique opportunity to obtain plaque tissue from a wide variety of clinical syndromes. We investigated the relation between the clinical status and histopathological substrate of tissue retrieved during directional coronary atherectomy and the proliferative and migratory potential of smooth-muscle cells judged from successful outgrowth during cell culture. Methods:After directional coronary atherectomy, tissue samples were examined macroscopically, divided into two equal pieces, and separately subjected to cell culture and histopathological study. Cell culture was performed using an explant technique. In-vitro smooth-muscle cell outgrowth was related to clinical and histological variables. Results:Atherosclerotic tissue was obtained from 98 consecutive atherectomy procedures. Histological examination revealed a broad spectrum of appearances, ranging from complex atheroma containing dense fibrous tissue, calcium deposits, macrophages, and necrotic debris to neointimal proliferation and organized thrombi. Smooth-muscle cell outgrowth was observed in 43 of the 98 samples (44%). Although not affected by any of the clinical variables, cell outgrowth was influenced by histological variables, in particular the presence of organizing thrombi. Outgrowth was successful in eight out of 10 samples with thrombus (80%) and in only 35 out of 88 (40%) without (P=0.03). Conclusion:The presence of organizing thrombi in the retrieved tissue facilitates smooth-muscle cell outgrowth and suggests an enhanced proliferative and migratory potential. These findings may be relevant to the understanding of neointimal proliferation in coronary syndromes where mural thrombosis is likely to occur.

Analysis of VNTR loci amplified by the polymerase chain reaction for investigating the origin of intimal smooth muscle cells in a coronary artery lesion developing after heart transplantation in man

Focal intimal thickening is a feature of primary atherosclerotic coronary lesions and restenotic lesions following percutaneous transluminal coronary angioplasty and other forms of vascular intervention, where it is the nonspecific response of the vessel wall to injury. The principal cellular component of the coronary plaque is the smooth muscle cell.’ Whether the smooth muscle cell in human coronary lesions is derived from cells circulating in the blood or from the vessel wall itself remains a matter for debate. On the basis of animal studies, it is generally presumed that the tunica media or subintimal space is the source of intimal smooth muscle cells.2-5 However, there is sound experimental evidence that smooth muscle cells recognized in a vascular plaque may originate in mural thrombus and not in the adjacent vessel wall. 6-8 Regardless of their source, these cells would normally be indistinguishable. Atherosclerotic lesions developing in the coronary arteries after orthotopic heart transplantation provide a unique opportunity to pursue the origin of cells within the coronary atherosclerotic plaque, as the donor and recipient invariably differ in genotype. Genetic differences may be demonstrated by the electrophoretic analysis of alleles from the highly polymorphic variable number of tandem repeats (VNTR) gene loci that occur widely in the human genome.g,10 The Dl7S5/Dl7S30 VNTR locus, the DlS80/ DlS58 VNTR locus, and the Apo B 3’ VNTR locus (the hypervariable 3’ region of the apolipoprotein B gene) represent independent, highly polymorphic deoxyribonucleic

Directional atherectomy: Combining basic research and intervention

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