Chronic total occlusion due to diffuse in-stent restenosis: is brachytherapy the solution?

Percutaneous coronary intervention of chronic total occlusions (CTO) is associated with a significantly higher incidence of reocclusion and restenosis compared with non-total occlusions. Randomized and observational trials have demonstrated the effectiveness of intracoronary brachytherapy (ICBT) for the prevention of recurrent in-stent restenosis. However, limited data are available on the effectiveness of ICBT in patients with totally occluded in-stent restenosis. The authors assessed the long-term outcome of patients treated with intracoronary gamma radiation for totally occluded in-stent restenotic lesions. Percutaneous coronary intervention and subsequent catheter-based irradiation with iridium-192 was performed in 100 patients (103 vessels) with diffuse in-stent restenosis. At baseline, CTO of the target vessel at the site of the stent was present in 15 vessels (14.5%). Follow-up data were collected during follow-up visits and from telephone interviews. Repeat coronary angiography was performed in symptomatic patients with clinical restenosis. Clinical and angiographic characteristics were similar between the two groups, although there was a trend towards more unstable angina at the index procedure in CTO patients (66.7% versus 41.4%; p = 0.12) compared with patients without non-total occlusions. A higher percentage of patients (53.3%) with CTO required longer radiation sources (14 seeds, covering a length of 55 mm), compared with 23.9% of patients with non-total occlusion (p = 0.04). With a mean follow-up period of 47.5 +/- 24.0 months, major adverse cardiac events (MACE) were observed in 10 of 15 patients (66.7%) with CTO compared with 25 out of 88 patients (28.4%) without CTO (p = 0.009). According to multivariate analysis, total occlusion of the target vessel at baseline was the single independent predictor of MACE at one-year follow-up (relative risk 16.2, 95% confidence interval 4.2-62.9; p < 0.0001). This study shows that the use of gamma radiation for the prevention of recurrence of in-stent restenosis in patients with CTO does not seem to be as effective as in patients with non-total occlusions. Furthermore, CTO was an independent predictor of worse outcome at long-term follow-up in this study.

Haptoglobin phenotype as a predictor of restenosis after percutaneous transluminal coronary angioplasty.

We have demonstrated that a genetic polymorphism in the antioxidant protein haptoglobin is important in determining which patients develop restenosis after percutaneous transluminal coronary angioplasty. Knowledge of the haptoglobin phenotype may be useful in the assessment and utilization of new therapies to reduce restenosis, particularly in patients who are homozygous for the haptoglobin 2 allele.

One-year clinical follow-up with the serpentine balloon expandable stent: report of the first 100 patients.

BACKGROUND: We recently reported a high technical and 30-day clinical success rate among the first 100 patients treated with the tubular, serpentine design, stainless steel, balloon-expandable stent (beStent) in Israel. The present study examined the clinical results in these patients after the first year. METHODS: Seventy-eight men and 22 women were included in the study. Previous myocardial infarction, bypass surgery and percutaneous transluminal coronary angioplasty had occurred in 52%, 12% and 26% of the patients, respectively. Diabetes mellitus was present in 30 patients and hypertension in 34 patients. One hundred and forty-eight stents of 15, 25, and 35 mm lengths were used. The indications for stenting were suboptimal results (n = 85), bailout conditions (n = 10) or for the prevention of restenosis (n = 8), and lesion types were A (n = 10), B1 (n = 29), B2 (n = 20), and C (n = 44). All patients were clinically monitored with regular visits at 1, 3, 6, 9 and 12 months. RESULTS: Overall, the 12-month event-free survival rate was 82%. Subacute thrombosis occurred in two patients. There were two non-cardiac deaths, one O-wave myocardial infarction, six elective bypass surgeries and 12 target lesion revascularizations. Event-free survival was significantly higher for those with lesions shorter than 15 mm than for those with lesions longer than 15 mm (90% versus 67%, P = 0.003), and for women compared with men (96% versus 78%, P = 0.02). CONCLUSIONS: The initial experience with the beStent shows favorable long-term results with an overall event rate of 18% for this subset of relatively complex lesions; higher event rates were observed for longer lesions.

Continued expansion of the nitinol self-expanding coronary stent: angiographic analysis and 1-year clinical follow-up.

BACKGROUND: This study sought to report the first-year clinical outcome with the nitinol self-expanding coil stent and to provide angiographic data on the effect of self-expansion during implantation and follow-up. Self-expanding stents do not reach their nominal diameter at implantation. The long-term effects may therefore depend, in part, on continued expansion after initial implantation. METHODS: Between January 1995 and January 1996, 86 stents were deployed in 64 patients for indication of suboptimal results. All patients were clinically followed up for 1 year, and 72% had follow-up angiography. RESULTS: The majority (55%) of the lesions were class B2 or C. Balloon angioplasty increased the minimal lumen diameter from 1.07 +/- 0.73 mm to 2.24 +/- 0.57 mm; stent deployment further increased the diameter to 2.63 +/- 0.48 mm, and within-stent balloon dilatation to 2.96 +/- 0.62 mm. Angiographic follow-up performed at 7.8 +/- 1.1 months (range 7-9 months) showed that the minimal lumen diameter was 2.15 +/- 0.80 mm (late lumen loss of 0.81 +/- 0.69 mm), and the mean stent diameter expanded to 3.58 +/- 0.48 mm (self-expanding late stent gain of 0.62 +/- 0.55 mm). The extent of this expansion was inversely related to the late lumen loss (r = 0.67, slope 0.81, P <.01). At 1 year 51 (80%) of 64 patients were event free; 3 had undergone coronary artery bypass grafting, 2 had had a myocardial infarction, and 9 had repeat angioplasty. In the subgroup of a simple lesion (<15 mm) covered by 1 stent, 18 (86%) of 21 patients were event free. CONCLUSIONS: The self-expanding nitinol stent exerts its acute effect on minimal lumen diameter through its intrinsic radial force aided by balloon expansion. The stent continues to expand until it reaches its nominal diameter over the follow-up period. The extent of this expansion is inversely related to the late lumen loss, leading to an acceptable rate of long-term clinical events in this first cohort of patients with complex disease morphology.

First clinical experience with the premounted balloon-expandable serpentine stent: acute angiographic and intermediate-term clinical results.

The beStent-Artist coronary stent is a newly developed, stainless steel coronary stent with a serpentine tubular design and terminal stent markers, premounted on a semicompliant balloon. During this pilot evaluation we aimed to test the acute clinical and angiographic results, short-term (30 days) and 6-month clinical results. A total of 57 stents were used to treat 43 lesions in 40 patients. Deployment strategy included predilatation, stent deployment, balloon repositioning to match the distal end of the balloon to the distal stent marker, and subsequent 12-14 atm postdilatation. There were two cases of stent dislodgment, but no procedural complications. In four cases, stent recrossing with another balloon was necessary. In two of these cases, distal dissections were observed and treated with another stent. The minimal lumen diameter (MLD) increased from 0.84+/0.52 mm at baseline to 2.7+/-0.62 mm at the end of the procedure (a corresponding decrease in diameter stenosis from 78.6 > 16.4 to 18.2+/-10.7%). The acute gain was 1.89+/-0.61mm. No adverse events occurred by 30 days. During six months, 7/40 (18.5%) of patients required target vessel revascularization due to in-stent restenosis. In summary, the premounted beStent-Artist can be delivered and deployed with favorable immediate results and high success rate with favorable long-term recurrent event rates.

Acute and 30-day results of the serpentine balloon expandable stent implantation in simple and complex coronary arterial narrowings.

We report the acute and 30-day results with a new serpentine-design, tubular, stainless steel, balloon-expandable stent (beStent) in the first 100 patients. One hundred forty-eight stents were used to treat 103 narrowings in the left anterior descending (n = 46), left circumflex (n = 20), and right coronary (n = 37) arteries. There were 85 de novo and 18 restenotic lesions (lesion length: < 10 mm [31], 10 to 20 mm [43] > 20 mm [29]; lesion type: A [10] B1 [29], B2 [20], C [44]; total occlusions, 23. More than 1 stent was used in 31 patients for treatment of long lesions that could not be covered by 1 stent. The stents used were 15-mm (n = 106), 25-mm (n = 38), or 35-mm (n = 4) long. Stent implantation strategy involved predilatation, deployment, and high-pressure dilatation, using the same balloon if possible. Clinical in-hospital success was 97% (2 patients had stent thrombosis that was recanalyzed, with myocardial infarction developing in 1, and 1 patient died on day 14 from retroperitoneal bleeding treated with surgery and complicated by sepsis). One-month event-free survival was 96%, with 1 death on day 21 due to hypertensive crisis. There were no other major adverse cardiac events in this first complex cohort of patients. In conclusion, the initial experience with this stent demonstrates its safety and efficiency for treating simple and complex coronary disease, with a relatively low rate of complications. Long-term clinical follow-up awaits further investigation.

Self-expandable and highly flexible nitinol stent: immediate and long-term results in dogs.

We sought to investigate the acute and long-term patency rates and the histologic response of coronary arteries to a self-expandable nitinol coil stent. Twenty-two stents were implanted. Angiographic patency was demonstrated acutely in all but one dog, in which the stent was released in a small branch (1 mm); mismatch in stent-to-artery diameters resulted in vessel closure. Two dogs died from anesthesia overdose and two from bleeding within 24 hours. All dogs were treated with aspirin (80 mg/day) and warfarin (2.5 mg/day) for up to 1 month. Sixteen dogs were monitored for 1 to 2 weeks, 1 month, 3 months, 6 months, and 1 year and underwent subsequent angiography and histopathologic examination. Angiographic artery dimensions measured immediately after stent implantation (2.72 +/- 0.4 mm) did not differ from those noted at follow-up (2.68 +/- 0.44 mm, p not significant). Histologic examination showed outward stent pressure compressing the internal elastic membrane and media in most cases. Intimal hyperplasia started at 2 weeks and was most apparent at 3 and 6 months. Mean intimal thickness was 30.7 +/- 10.9 mu, 141.8 +/- 105.4 mu, 227.1 +/- 104.1 mu, 211.8 +/- 99.1 mu, and 170.1 +/- 42.7 mu at 1 to 2 weeks and 1, 3, 6 and 12 months, respectively. Therefore the nitinol self-expandable stent provokes a moderate cellular proliferative response that reaches its maximum in 3 to 6 months without further progression.

Regional three-dimensional geometry and function of left ventricles with fibrous aneurysms. A cine-computed tomography study.

BACKGROUND: To assess the extent and nature of the dysfunction surrounding aneurysms of the left ventricle (LV), we examined the parameters of local and global three-dimensional shape, size, and function of LVs of eight patients with histologically confirmed anterior fibrous aneurysms. METHODS AND RESULTS: Three-dimensional reconstructions of each LV were made from 10-12 short-axis fast cine-angiographic computed tomography (cine-CT) slices encompassing the entire heart at end diastole and end systole. Regional three-dimensional wall thickness, thickening, motion, curvature, and stress index were calculated for 84 elements encompassing the entire LV. The aneurysmal border was defined by a sharp decrease in end-diastolic wall thickness and separated the LV into an aneurysmal zone and a normal zone that was further divided into adjacent normal (AN) and remote normal (RN) zones. As expected, thickening was negligible in both the aneurysmal and the border zones. Although both the AN and the RN zones had normal wall thickness (1.05 +/- 0.20 and 1.09 +/- 0.20 cm, respectively), thickening was depressed in the AN (0.22 +/- 0.08 cm) but not the RN (0.44 +/- 0.19 cm) zones. The size of the dysfunction zone (defined as less than 2 mm thickening) was found to be considerably greater than the anatomic size of the aneurysm (60.9 +/- 13.7% versus 33.6 +/- 7.6% of the left ventricular endocardial area, respectively; p less than 0.001). In addition, the AN zone had a smaller curvature and a higher stress index than the RN zone. CONCLUSIONS: LVs with fibrous aneurysms are characterized by a relatively large region of nonfunction that encompasses the thin aneurysmal area and its transitional border zone, a normally functioning remote zone, and an intermediate region of normal wall thickness but with reduced function, which may be attributed to its low curvature and high stress index.

Diagnostic and prognostic value of oral dipyridamole test using echocardiography.

The diagnostic and prognostic value of the oral dipyridamole test using echocardiography was evaluated in 47 consecutive patients undergoing coronary arteriography. The results of the tests were not communicated to the physicians treating the subjects during a 1-year follow-up. The test had a sensitivity of 54% and a specificity of 100% for predicting severe (greater than or equal to 70% luminal stenosis) coronary artery disease. Neither ST-T segment changes nor chest pain during the test were associated with the presence of severe coronary artery disease. In the subgroup of 34 patients with severe coronary artery disease, the appearance of left ventricular segmental systolic dysfunction or ST-T segment depression (greater than or equal to 1 mm) during the test has a strong predictive value for subsequent cardiac events during a 1-year follow-up.

Familial homozygous hypercholesterolemia: clinical and cardiovascular features in 18 patients.

Homozygous familial hypercholesterolemia (HFH) is a very rare autosomal dominant disease characterized by accelerated severe atherosclerosis. We examined 18 patients from 9 families with HFH. The age range was 6-30 years (mean = 16 years). Male to female ratio was equal. All patients had huge, multiple tuberous xanthomas on the skin and tendons. Mean +/- standard deviation of plasma cholesterol, triglycerides, low-density lipoproteins (LDL), and high-density lipoproteins (HDL) cholesterol levels were 608 +/- 89, 122 +/- 39, 550 +/- 88, and 26 +/- 8 mg/dl, respectively. Five patients (28%) had angina pectoris, two sustained a myocardial infarction, and one died at the age of 15 years. Two-dimensional echocardiography demonstrated supravalvular aortic stenosis in 3 of the 13 patients (23%). Coronary arteriography performed in 11 patients demonstrated significant obstruction in 6 patients, 2 each with single-, double-, and triple-vessel disease. Left main stenosis was present in 3 patients (27%). Supravalvular aortic narrowing was demonstrated in 6 patients (54%) and was associated with a gradient in 2 (25 and 35 mmHg, respectively). Segmental contraction abnormalities were detected in 2 of the 11 patients (18%). It is concluded that coronary artery disease is prevalent in patients with HFH and, based on the data presented, we recommend the performance of noninvasive technique, coronary arteriography and supravalvular aortography at an early age to detect and to follow the progression of the disease.

Low-density lipoprotein derived from atherosclerotic patients enhances macrophage cholesterol accumulation and in vitro platelet aggregation.

The aims of our study were to assess the differences between plasma lipoproteins separated from five angiographically normal subjects and five patients with proven CHD. The patients with CHD had significantly higher levels of LDL-cholesterol and apo-B, and reduced levels of HDL-cholesterol and apo-Al. The biological characteristics of LDL and HDL from both groups of patients demonstrated that the LDL from the CHD patients enhanced platelet aggregation and increased cholesterol content and cholesterol esterification in MPM compared to the normal patients. HDL had no significant effect on MPM; however, there was an increased platelet aggregation with HDL derived from the CHD patients, while the HDL from the normal group decreased platelet aggregation. The data suggest that lipoproteins isolated from CHD patients are more atherogenic than lipoproteins from normal patients.

Quantitative characterization and sorting of three-dimensional geometries: application to left ventricles in vivo.

A procedure for automatic sorting of three-dimensional (3-D) shapes is proposed. The procedure is applied to sort into normal and abnormal categories, human left ventricles (LV) using in vivo data from 19 subjects (ten normal and nine abnormal LV's) studied by ultrafast tomography (Cine-CT). The procedure starts by utilizing a vector in a helical coordinate system to describe the spatial geometry of each individual LV cavity. This individual vector is then anatomically aligned and normalized to eliminate effects due to size, yielding a dimensionless vector, denoted as "geometrical cardiogram" (GCG). The GCG characterizes the instantaneous 3-D geometrical information of the individual LV. For the group of healthy subjects, the Karhunen-Loeve Transform (KLT) is then applied to compress the geometric information contained in their individuals' GCG vectors, at end diastole (ED) and end systole (ES), and yield a unique set of basis vectors. The "normal shape domain" is next defined as a truncated set of the KLT basis vectors from which a normal GCG can be reconstructed with a mean squared error (MSE) smaller than a defined threshold. The calculated MSE of any individual GCG reconstructed in this domain is then used as a criterion for sorting the 3-D shapes. Hearts which yield MSE greater than the threshold are considered abnormal. When applied to the study group of 19 subjects a significant difference (p less than 0.0001) between the MSE values obtained for the normal LV's, and those obtained for the abnormal LV's was detected, thus leading to a successful sorting of all the studied LV's. Finally, the KLT is applied to yield a compact representation of the 3-D geometry of any LV (normal or abnormal).

Arterial blood derived low density lipoprotein increases platelet aggregation and macrophage cholesterol content in comparison to lipoprotein derived from veinous blood.

We studied the biochemical and biological properties of plasma lipoproteins taken from blood derived from either the aorta or femoral vein of patients with normal coronary arteriography. There were no significant differences in concentrations of cholesterol, triglycerides, apoprotein A-1 and apoprotein B derived from either source. The cholesterol content of very low density lipoprotein (VLDL) and high density lipoprotein (HDL) was similar in both aortic and venous blood. The low density lipoprotein (LDL) concentration, however, was significantly higher in the aortic blood sample. Arterial LDL significantly enhanced in vitro platelet aggregation when compared to venous LDL. (p less than 0.02). When incubated with mouse peritoneal macrophages (MPM) arterial LDL and VLDL caused an increased cholesterol accumulation and enhanced cholesterol esterification within these macrophages. The venous lipoproteins had little effect. The differences noted in the arterial lipoproteins in composition and biological function when compared to venous lipoproteins might be related to the much higher incidence of atherosclerosis found in the arterial tree.

Von Willebrand factor and mitral valve prolapse.

The levels of von Willebrand factor (vWF:Ag) were measured in 27 patients with mitral valve prolapse (MVP) and compared to 27 age matched controls. Decreased levels of vWF:Ag (less than 80%) were found in 59% (16/27) of those with MVP compared to only 7% (2/27) of the controls (p less than 0.001). Mean vWF: Ag levels were also significantly lower in those with MVP (68 +/- 30% versus 100 +/- 23%, p less than 0.001). In those with MVP and congestive heart failure secondary to rupture chordae tendineae, however, the mean level of vWF: Ag was not significantly different from control values (95 +/- 32). There was an increased incidence of recurrent nose bleeds in those with MVP and low levels of vWF:Ag. We conclude that there is a relationship between MVP and low levels of vWF:Ag which may explain the increased incidence of epistaxis in such patients. Increased release of vWF:Ag in those with MVP and concomitant congestive heart failure may account for the normal levels found in this subgroup.