Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.     

Effect of exogenous surfactant on total respiratory system compliance

We measured total respiratory system compliance (Crs) before and after instilling 25 mg artificial surfactant in 1 ml saline down the endotracheal tube of preterm babies requiring resuscitation at birth, and compared results with data from 6 similar babies receiving saline only. Surfactant did not produce a significant improvement in Crs.     

Intravascular ultrasound parameters associated with stent thrombosis after drug-eluting stent deployment

Drug-eluting stent (DES) thrombosis (ST) can be devastating. The study aim was to evaluate intravascular ultrasound (IVUS) predictors for DES thrombosis by comparing IVUS studies after implantation in 13 patients with 14 DES thrombosis lesions with a group of controls (30 lesions in 27 patients) matched for history of chronic renal failure and type of DES. Five patients (38%) discontinued dual antiplatelet therapy at the time of ST. There were 3 in-stent restenosis lesions (21%) treated using DESs in the ST group compared with 0 in the control group (p <0.05). Compared with the control group, IVUS studies in the ST group showed a smaller minimum stent area (4.6 +/- 1.1 vs 5.6 +/- 1.7 mm(2), p = 0.0489). In the ST group, 11 of 14 stents had a minimum stent area < or =5.0 mm(2) compared with 12 of 30 in the control group (p = 0.0392). Minimum stent area in patients who stopped clopidogrel therapy and developed ST (5.30 +/- 1.15 mm(2)) tended to be larger compared with that in patients who developed ST while using clopidogrel (4.24 +/- 0.96 mm(2), p = 0.091). Within the 5-mm-long proximal and distal reference segments analyzed, the ST group had larger proximal reference maximum plaque burdens and smaller minimum lumen areas, along with a tendency toward similar findings in the distal reference segments. In conclusion, IVUS findings at the time of DES implantation in patients who subsequently developed ST showed a smaller minimum stent area (especially in patients who developed ST while using clopidogrel) and more residual disease at the stent edges.     

Clinical, angiographic, and intravascular ultrasound characteristics of early saphenous vein graft failure

OBJECTIVES: We sought to examine saphenous vein graft (SVG) lesions that fail within the first year after operation. BACKGROUND: Saphenous vein grafts remain patent for approximately 10 years; however, up to 15% to 20% of SVGs become occluded within the first year. METHODS: We studied 100 patients who underwent percutaneous coronary intervention (PCI) for early (<1 year post-implantation) SVG failure lesions and compared them with a diabetes- and hypercholesterolemia-matched cohort of late SVG failures (>1 year). Coronary angiography and intravascular ultrasound images were analyzed. RESULTS: The majority of patients in both groups were males who presented with unstable angina; 36% were diabetic. Graft ages were 6.0 +/- 2.9 months and 105.4 +/- 50.8 months, respectively. The early SVG failure lesion location was more often ostial or proximal (62% vs. 42%, respectively). Early SVG failures were angiographically smaller than late failures (reference: 2.47 +/- 0.86 mm vs. 3.26 +/- 0.83 mm, p < 0.001) but had similar lesion lengths. Intravascular ultrasound showed that early failure lesions had smaller proximal and distal reference lumen areas (7.3 +/- 6.8 mm2 vs. 10.6 +/- 3.8 mm2, p = 0.026) and greater reference plaque burden than late failures (52.3% vs. 36.1%, p < 0.001). After PCI, 20.6% of early and 30.6% of late failure lesions had creatine kinase-myocardial band (CK-MB) greater than twice normal. CONCLUSIONS: Early SVG failure is mostly proximal or ostial, lesions appear focal, and early SVGs appear smaller than late SVGs. Intravascular ultrasound shows significant reference segment plaque burden, suggesting more severe, diffuse SVG disease.     

Are we making progress with percutaneous saphenous vein graft treatment?: A comparison of 1990 to 1994 and 1995 to 1998 results

OBJECTIVES: We sought to determine whether strategies to reduce procedural distal embolization and late repeat revascularization have resulted in more favorable outcomes after saphenous vein graft (SVG) angioplasty. BACKGROUND: Angioplasty of SVG lesions has been associated with frequent procedural and late cardiac events. Therefore, evolving strategies have been attempted to improve outcomes after SVG angioplasty. METHODS: We compared our earlier experience (1990 to 1994) of 1,055 patients with 1,412 SVG lesions with a recent group (1995 to 1998) of 964 patients with 1,315 lesions. RESULTS: Baseline characteristics were similar between the groups. However, there were significantly more unfavorable lesion characteristics (older, longer and significantly more degenerated SVGs) in the recent series. Between the two periods, there was decreased use ofatheroablative devices, whereas stent use increased. The procedural success rates (96.6% vs. 96.1%) were similar. However, one-year outcome (event-free survival) was significantly improved in the more recent experience (70.7% vs. 59.1%, p < 0.0001), especially late mortality (6.1% vs. 11.3%, p < 0.0001). Multivariate analysis showed stent use to be the only protective variable for both periods. CONCLUSIONS: This study shows that despite higher risk lesions, strategies to reduce distal embolization have maintained high procedural success. Late cardiac events, including mortality, have also been substantially reduced.     

Bivalirudin versus heparin as an antithrombotic agent in patients who undergo percutaneous saphenous vein graft intervention with a distal protection device

Bivalirudin (Angiomax) is increasingly used as a substitute for heparin in a variety of percutaneous coronary interventions, and data on its usage in saphenous vein graft interventions are limited. This retrospective, observational study evaluated the efficacy and safety of bivalirudin compared with heparin as an antithrombotic regimen in patients who underwent saphenous vein graft intervention with distal protection devices. We found that bivalirudin use is clinically safe and feasible, with fewer vascular and ischemic complications compared with heparin.     

Does creatine kinase‐MB (CK‐MB) isoenzyme elevation following percutaneous coronary intervention with drug‐eluting stents impact late clinical outcome?

BACKGROUND: The incidence of postprocedural creatine kinase (CK)-MB elevation to >3x the upper limit of normal after percutaneous coronary intervention (PCI) has been reported at rates of up to 18% in the bare metal stent era and is correlated with higher adverse cardiovascular outcomes. This study examined the incidence and prognostic significance of CK-MB elevations after drug-eluting stent (DES) implantation. METHODS: The records of 2,537 patients who underwent DES implantation and completed > or =6 months' follow-up were evaluated. Patients with acute myocardial infarction and those who presented in cardiogenic shock and had elevated cardiac enzymes at baseline were excluded from the analysis. Of these, 179 patients (7.1%) had > or =3x postprocedural CK-MB and 2,358 patients had <3x CK-MB elevation. The composite end point of target vessel revascularization-major adverse cardiac events (TVR-MACE) at 6 months was compared between groups. Univariate and multivariate regression analyses were performed to identify predictors of adverse cardiac outcomes. RESULTS: The patients with CK-MB > or =3x elevation had a higher number of diseased vessels (2.15 +/- 0.86 vs. 1.81 +/- 0.87; P < 0.001), higher prevalence of type C lesions (29.9% vs. 17.7%; P < 0.001), received a higher average number of stents, and total stented length (1.72 +/- 0.89 vs. 1.49 +/- 0.83; P < 0.001 and 37.4 +/- 23.0 mm vs. 30.8 +/- 20.7 mm; P = 0.0003, respectively), and had lower rates of clinical success (91.9% vs. 99.2%; P < 0.001). The 6-month and 1-year TVR-MACE rates were higher for the elevated CK-MB group (11.9% vs. 7.0%; P = 0.02 and 16.1% vs. 26.6%, respectively; P = 0.005). The rates of subacute thrombosis were also significantly higher in the group with elevated CK-MB (0.4% vs. 3.2%, P < 0.001). Though significant CK-MB release was a predictor of TVR-MACE after univariate analysis, multivessel PCI, subacute stent thrombosis, total stented length, and history of prior PCI were the only predictors after multivariate regression analysis. CONCLUSIONS: Postprocedural CK-MB > or =3x elevation following PCI with DES continues to be a marker for the complexity of coronary disease and lack of clinical success; and correlates with higher rates of subacute thrombosis as well as late adverse events at 6-months and 1-year postprocedure.     

Smaller LDL particle size in women with polycystic ovary syndrome compared to controls

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. The contribution of lipid abnormalities to this higher risk, in particular atherogenic modifications of low density lipoprotein (LDL) such as a shift towards smaller LDL, has not been properly explored. We aimed to examine LDL size variation in relation to androgens and other risk factors in women with PCOS. DESIGN: Comparison of clinical and biochemical measurements in women with PCOS and women with normal ovarian function, of similar age and body mass index (BMI). PATIENTS: Thirty-one women with PCOS and 27 controls were studied. Patients were recruited from the outpatient endocrine clinic. MEASUREMENTS: Fasting total cholesterol, triglycerides (TG), high density lipoprotein (HDL), LDL, glucose, insulin, gonadotrophins, androgens, oestradiol, 17 OH progesterone and SHBG were measured. LDL particle diameter was calculated based on distance travelled in polyacrylamide native gels. Recumbent blood pressure was measured automatically. RESULTS: LDL particle size appeared to be significantly smaller in hyperandrogenic PCOS as compared to regularly cycling women (P = 0006), independent of variations in lipid levels. SHBG was the only independent predictor of LDL size in this population, with a strong correlation, which persisted after adjustment for all confounding variables. CONCLUSIONS: Our results suggest that androgen excess and mild insulin-resistance (both responsible for lower SHBG) may have an early modifying effect on low density lipoprotein size in polycystic ovary syndrome women. The denser pattern observed in polycystic ovary syndrome women could by itself constitute a higher cardiovascular risk, even in the absence of overt dyslipidaemia, and contribute to the excess risk of cardiovascular disease reported in this syndrome.     

Impact of intracoronary radiation on in-stent restenosis involving ostial lesions.

The aim of this study was to compare 6-month clinical outcomes of patients with in-stent restenosis (ISR) involving the ostium treated with intracoronary radiation therapy (IRT) compared to placebo therapy, and also to nonostial lesions treated with IRT. Coronary interventions in ostial lesions have a high rate of recurrence of restenosis. The impact of IRT on ostial ISR has been inadequately characterized. We assessed patients enrolled in gamma (192-iridium) and beta (90-yttrium, 32-phosphorus) radiation trials for ISR at the Washington Hospital Center. Of patients receiving IRT, 105 (8%) patients had ostial ISR and 1,289 (92%) patients had nonostial ISR. Twenty-seven patients had ostial ISR and received placebo therapy. Baseline demographic and angiographic and procedural details were similar, except ostial IRT patients had a trend toward shorter lesions (15.4 +/- 10.8 vs. 24.1 +/- 12.2 mm; P < 0.001) and had a higher rate of saphenous vein graft disease (46% vs. 19%; P < 0.001) compared to nonostial IRT patients. At 6 months, ostial lesions treated with IRT for ISR had a reduced rate of target lesion revascularization (TLR) compared to ostial lesions treated with placebo (15% vs. 43%; P = 0.004). Outcomes at 6 months were similar for the ostial and nonostial IRT groups including TLR (15% vs. 14%; P = 0.80) and composite major adverse cardiac events (18% vs. 15%; P = 0.46). Intracoronary radiation therapy is effective for ostial in-stent restenotic lesions and should be comfortably used for this challenging anatomic location.