Prospective 'real world' registry for the use of the 'PCB only' strategy in small vessel de novo lesions.

BACKGROUND: This prospective registry assessed the safety and efficacy of paclitaxel coated balloon (PCB) angioplasty for small vessel coronary artery disease in Europe and Asia with the intention to treat lesions without additional stenting. The use of PCBs in small vessels seems to be associated with favourable outcomes; however, prospective data for the use of PCBs without stenting are limited. METHODS: The SeQuent Please Small Vessel 'PCB only' Registry was an international, prospective, multicentre registry enrolling patients with de novo lesions of small reference diameters (≥ 2.0 mm, ≤ 2.75 mm). The primary end point was clinically driven target lesion revascularisation (TLR) at 9 months. Secondary end points were acute technical success, in-hospital outcomes, 9-month major adverse cardiac events (MACE) (death, myocardial infarction, or TLR), and the occurrence of definite lesion and vessel thrombosis. RESULTS: A total of 479 patients (66.1 ± 10.9 years, 36.7% diabetics) were enrolled, 105 (23.5%) with an acute coronary syndrome, 41 (9.2%) with ST elevation myocardial infarction (STEMI), and 60 (14.8%) with non-STEMI. The initial procedural success rate was 99.0%; 27 patients (6%) needed additional bare metal stent implantation. TLR at 9.4±1.7 months occurred in 14 patients (3.6%), while three patients (0.6%) had vessel thrombosis in non-target lesions. There was no cardiac death or coronary artery bypass graft surgery. CONCLUSIONS: To date, this is the largest prospective study with PCBs in small vessel de novo lesions in unselected patients. Rates of TLR and MACE were low, suggesting the use of PCBs may be an attractive alternative treatment option to drug eluting stents in small vessels.

Collateral function in chronic total coronary occlusions is related to regional myocardial function and duration of occlusion.

BACKGROUND: Collateral circulation can maintain myocardial function and viability in chronic total coronary occlusion (TCO). The present study evaluates the relation of myocardial function and duration of occlusion to collateral function. METHODS AND RESULTS: A total of 50 patients underwent a successful recanalization of a TCO (>4 weeks' duration). Collateral function was assessed by intracoronary Doppler and pressure recordings before the first balloon inflation and after PTCA had been completed. Collateral function was assessed by Doppler- (CFI(D)) and pressure-derived collateral flow indices (CFI(P)), as well as indices of collateral (R(Coll)) and peripheral resistance (R(P)). Patients with normokinesia had lower R(Coll) (4.9+/-2.5 versus 11.8+/-8.2 mm Hg. cm(-1). s(-1); P=0.033) and lower R(P) (3.8+/-1.9 versus 6.1+/-4.1 mm Hg. cm(-1). s(-1); P=0.031) than those with akinesia. Patients with akinesia and a TCO duration of

Microvascular dysfunction in chronic total coronary occlusions.

BACKGROUND: Microvascular dysfunction is defined as reduced coronary flow reserve in the absence of an epicardial stenosis. This study determined its prevalence and relation to regional myocardial function in chronic total coronary occlusions (TCO). METHODS AND RESULTS: After recanalization and stenting of a TCO (duration, >4 weeks) in 42 patients, coronary flow velocity reserve (CFVR) was measured by intracoronary Doppler. In a subset of 27 patients, intracoronary pressure was recorded to obtain the fractional flow reserve (FFR). In 21 patients, the CFVR was reassessed after 24 hours. CFVR was <2.0 in 55% of all patients. In the subgroup with simultaneous pressure recordings, 52% of patients showed a CFVR<2.0 and a FFR>/=0.75, indicating microvascular dysfunction. Both reduced CFVR and reduced FFR occurred in only 2 patients (7.7%). CFVR and FFR were not correlated (r=0.03). A low CFVR was associated with a higher baseline average peak velocity (35.6+/-16.6 versus 22.4+/-11.5 cm/s; P=0.006). Doppler parameters did not change within 24 hours. Regional dysfunction had no influence on CFVR. Patients with diabetes and/or hypertension had a lower CFVR than those without this comorbidity (1.86+/-0.69 versus 2.36+/-0.45; P<0.05). CONCLUSIONS: Microvascular dysfunction was observed in 55% of TCOs, independent of the impairment of regional myocardial function. Dysfunction was observed more often in patients with diabetes and hypertension. Neither CFVR or FFR alone is appropriate for assessing angioplasty results in patients with a TCO; CFVR should be combined with FFR to differentiate microvascular dysfunction from residual coronary stenosis or diffuse disease.

Immediate changes of collateral function after successful recanalization of chronic total coronary occlusions.

BACKGROUND: Coronary collaterals are essential to maintain myocardial function in chronic total coronary occlusions (TCOs). The aim of the present study was to assess the collateral circulation in TCOs before coronary angioplasty and to determine the recruitable collateral perfusion after recanalization by use of intracoronary Doppler flow velocimetry. METHODS AND RESULTS: In 21 patients with TCOs (duration >4 weeks), Doppler recordings of basal collateral flow were obtained before the first balloon inflation. Angioplasty was performed with stent implantation in all lesions. At the end of the procedure, recruitable collateral flow was measured during a repeat balloon inflation. The collateral flow index (CFI) was calculated from the velocity integral during the occlusion/velocity integral of antegrade flow. In 17 of 21 patients, angiography was repeated after 24 hours, and CFI was reassessed. Average peak velocity of collateral flow was 10.9+/-5.6 cm/s with a predominantly systolic flow (diastolic/systolic velocity ratio <0.5) compared with antegrade flow (diastolic/systolic velocity ratio >1.5). After recanalization, the average peak velocity of recruitable collateral flow dropped by >50% to 4.7+/-2.5 cm/s. CFI fell from 0.48+/-0.25 to 0.21+/-0.16 (P:<0.001). There was no further change of CFI during the following 24 hours. CFI was higher in patients with preserved regional ventricular function than in those with akinetic myocardium (0.57+/-0.23 versus 0.38+/-0.12, P:<0.05). CONCLUSIONS: Collateral circulation in TCO provided 50% of antegrade coronary flow. A considerable fraction of collateral flow was immediately lost after recanalization, indicating that TCO may not remain protected from future ischemic events by a well-developed collateral function.

Determinants of stent restenosis in chronic coronary occlusions assessed by intracoronary ultrasound.

Chronic coronary occlusions have a high recurrence rate that can be reduced by stenting, but this rate remains higher than in nonocclusive lesions. To analyze possible determinants of restenosis in these lesions, intracoronary ultrasound was performed during the recanalization procedure. A chronic coronary occlusion of > or = 1 month duration (range 1 to 33 months; median 3.3) was successfully recanalized in 41 patients. Quantitative ultrasound analysis was performed before and after stent placement, with measurement of the luminal area, the extent of the plaque burden at the site proximal and distal to the occlusion, and within the occlusion and the subsequent stent. The degree of compensatory enlargement of the coronary artery within the occlusion was determined by comparing the average of the total vessel area of the proximal and distal reference with the lesion site. Early reocclusion (subacute stent thrombosis) was observed in 1 patient (2.4%). The angiographic control after 6 months showed restenosis in 9 patients with 1 late reocclusion. The overall recurrence rate was 24%. There was no difference in clinical and procedural characteristics between lesions with restenosis and without restenosis. The latter had a larger minimum stent area (7.59 +/- 1.96 mm2 vs 5.71 +/- 0.90 mm2; p <0.01), and there was evidence for more compensatory vessel enlargement in lesions without restenosis. Thus, intracoronary ultrasound showed that a smaller minimum stent area was a major predictor of angiographic restenosis, and it occurred more often in occlusions without compensatory vessel enlargement.

Risk factors for acute and subacute stent thrombosis after high-pressure stent implantation: a study by intracoronary ultrasound.

BACKGROUND: In the era of coronary stenting with high-pressure expansion, stent thrombosis remains a major life-threatening risk. Because of its superior imaging mode, intracoronary ultrasound could provide insight into potential risk factors for stent thrombosis. PATIENTS AND METHODS: In 215 patients with stent implantations controlled by intracoronary ultrasound, four occurrences of subacute stent thrombosis, two complete acute thrombotic occlusions, and four occurrences of incomplete acute thrombosis were observed. All stents were expanded with inflation pressures of at least 14 atm ( 17+/-3 atm). The clinical data and the qualitative and quantitative ultrasound information were compared between stents with thrombosis and stents without thrombosis. The luminal area and the plaque border of the reference segments, and of the smallest and largest site of the stented segment after the initial and final expansion, were measured. RESULTS: Stents in the left anterior descending artery were more often involved in stent thrombosis than other vessels, but the vessel dimensions in this target vessel were smaller than in the right coronary artery. The plaque burden was considerably larger after stent implantation with subsequent thrombosis compared with no thrombosis (74.1+/-8.8% vs 63.6+/-8.0%; p < 0.001), and the stent area was smaller (4.80%+/-1.33 mm2 vs 6.86+/-2.08 mm2; p < 0.01 ). In stents with thrombosis the plaque burden of the stent site with the smallest and largest lumen differed by 15.2%, whereas the difference in plaque burden in stents without thrombosis was 2.7%. Intracoronary ultrasound showed that the best risk predictor of thrombosis was the residual plaque burden of the stented segment (odds ratio 15.7 [confidence interval 2.4 to 104.7]), and a small stent area after implantation (odds ratio 6.8 [confidence interval 1.9 to 24.3]). CONCLUSION: In a multivariate risk analysis plaque burden was the strongest independent risk factor for stent thrombosis. The amount of residual plaque mass around the stent might be a potential trigger for thrombus formation.

Thrombus formation on transcatheter ASD occluder device in a patient with coagulation factor XII deficiency.

Transcatheter occlusion of cardiac defects has become an effective and less invasive alternative to open heart surgery. Thromboembolic complications are rare events, after both surgical and transcatheter closure of atrial septal defects [Galal et al.: Eur Heart J 15:1381-1384, 1994]. We report on a case of thrombus formation on the atrial septal defect occluder system (ASDOS) [Sievert et al.: Cathet Cardiovasc Diagn 36:232-240, 1995; Hausdorf et al.: Heart 75:83-88, 1996]. Two days after transcatheter occlusion, the patient suffered an acute stroke due to embolism despite anticoagulation with intravenous heparin. A coagulation disorder with reduced factor XII concentration was deduced as the likely cause. Repeated transesophageal echocardiographic (TEE) studies revealed an involution of the intracardial thrombus within weeks of subsequent anticoagulatory treatment. First off, this case shows that patients with factor XII deficiency are at risk for thromboembolism. Second, it again clarifies that even large amounts of intraartrial thrombotic material may not be seen by transthoracic echocardiography (TTE) and underscores the necessity of performing TEE. Screening patients for coagulation disorders (Quick's value (Q), partial thromboplastin time (PTT)) before they are selected for treatment with thrombogenic devices is indispensable. With regard to their personal history (earlier thromboembolism) and the result of this screening (e.g., prolongation of PTT), quantitative determination of coagulation factors is reasonable. If patients endangered by thromboembolic complications nevertheless undergo ASD occlusion procedures, anticoagulation monitoring requires exceptional attention. Furthermore, it is recommended that TEE should be carried out in these patients 2 days after treatment, since transthoracic echocardiography (TTE) might be unable to detect thrombus formation on the device.

Additional luminal area gain by intravascular ultrasound guidance after coronary stent implantation with high inflation pressure.

AIMS: Studies by intravascular ultrasound demonstrated inadequate expansion in a large number of stents, which lead to the increase of inflation pressure for stenting. The present study examined whether routine use of high-pressure inflation would be sufficient for an optimum stent expansion without sonographic guidance. METHODS AND RESULTS: Two types of single coronary stents (Palmaz-Schatz in 54, and Wiktor in 25) were implanted with inflation pressures of 16-20 atm in 79 nonocclusive coronary lesions. IVUS before stenting was used in 78% to select the adequate stent size. Intravascular ultrasound after stenting was used to asses the minimum stent are and diameter, the reference areas, and the strut apposition to the vessel wall. The difference between the area of the expanding balloon and the stent area was calculated as the luminal deficit of the stent. Completeness of stent expansion required full strut apposition and lesion coverage, and a minimum stent area that was larger than the distal reference, and larger than 60% of the proximal reference. Intravascular ultrasound before stenting lead to an increase of the stent size in 47%. After high-pressure expansion, even with the optimized balloon size, 8% of stents had struts protruding into the lumen. The stent area (6.87 +/- 1.93 mm2) was significantly smaller than both the proximal (9.59 +/- 2.91 mm2; p < 0.001) and distal reference area (8.23 +/- 3.03 mm2; p < 0.001). The criteria for complete expansion were met in 48%. The expansion with a larger high-pressure balloon in 28 stents lead to an increase of the stent area by 19% (8.19 +/- 2.24; p < 0.001), and full stent apposition in all cases. The criteria of stent expansion were met in 82%. A wide range of the luminal deficit upto 48% was observed, which was not related to sonographic lesion characteristics, except in lesions with complete circumferential calcifications. The different stent designs were characterized by a slightly lower luminal deficit in slotted-tube stents (23 +/- 13% vs. 28 +/- 12%; p = 0.11) and a better index of stent symmetry as compared with the coil stent (0.87 +/- 0.08 vs. 0.82 +/- 0.09; p < 0.05). CONCLUSION: Routine use of high-pressure stent expansion did not lead to a sufficient stent expansion, even when the initial stent size had been guided by intravascular ultrasound. Further stent dilatation with larger balloons under ultrasound guidance would be required to optimize the luminal area gain.

Sequence, expression, and chromosomal assignment of a human sperm outer dense fiber gene.

Outer dense fibers (ODFs) are located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail. We have identified and describe here a human gene that is homologous to the Mst(3)CGP gene family of Drosophila melanogaster and encodes an ODF protein of 241 amino acids. The transcribed region has a size of approximately 1 kb and contains two exons of 416 bp and 406 bp, respectively, not including the 3' untranslated region. The gene is expressed in testis but not in human spleen, kidney, or brain and resembles in this respect the expression of the Drosophila Mst(3)CGP gene family in the male germline. An antiserum raised against a synthetic peptide derived from the N-terminus of the encoded sequence identified a protein of approximately 32 kDa in an extract of human sperm flagella. By Southern-blot analyses and in situ hybridization, the ODF gene was localized to band q22 of chromosome 8. The isolation of a human gene encoding a sperm tail protein may provide the ability to identify and investigate, on the molecular level, possible reasons for human male infertility that are dependent on flagellar disturbances.