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Biomedical subjects

Shmuel Fuchs

Publications and source records attributed to Shmuel Fuchs.

At least 37 records · Page 2Linked to original sources
PubMed2004

Simple clinical risk stratification and the safety of ambulation two hours after 6 French diagnostic heart catheterization.

Heart catheterization is frequently applied in patients with coronary artery disease for diagnostic and therapeutic implications. Using the femoral approach, post-procedure bed rest of 4 to 6 hours is recommended to prevent groin complications. This extended strict bed rest is associated with patient discomfort and increased medical costs, and interferes with more efficient catheterization laboratory management of referred outpatients. Accordingly, we tested a simple clinical approach to identify low-risk patients who may benefit from ambulation within two hours after sheath removal. Ninety-eight outpatients were stratified to early (time=1.5 to 2.0 hours; n=74) or conventional ambulation (time=4 to 5 hours; n=24) based on difficulties in obtaining arterial access, presence of oozing or hematoma after completing manual compression. Ecchymosis was the most frequent complication, noted in one early ambulated and three conventionally ambulated patients at hospital discharge and in eleven early ambulated and six conventionally ambulated patients at one-week follow-up. No large hematomas, retroperitoneal bleeding or need for blood transfusion occurred in any patients. Using simple clinical parameters, most outpatients who undergo elective diagnostic catheterization may benefit from safe early ambulation.

Ambulatory Care↗
PubMed2004

Coronary bifurcation lesions: to stent one branch or both?

OBJECTIVE: The purpose of this study was to evaluate two different stent placement techniques for bifurcation lesions: 1) stenting of the main branch and balloon dilatation of the sidebranch versus 2) stenting of both branches. BACKGROUND: Percutaneous coronary intervention (PCI) of coronary bifurcation lesions remains challenging, and limited information is available regarding whether stent placement is necessary in both branches of the bifurcation using bare-metal stents. Methods. We prospectively followed all patients who underwent PCI for symptomatic bifurcation lesions at our center. All patients were carefully followed for subsequent clinical events. RESULTS: Between March 2001 and November 2002, a total of 50 patients were treated with either stenting of both vessels (double stent group; n = 32) or stenting of the parent vessel and balloon angioplasty of the sidebranch (single stent group; n = 18). Optimal angiographic success was 87.5% in the single stent group and 100% in the double stent group (p = 0.1). The post-procedure percent diameter stenosis of the sidebranch vessel was significantly higher in the single stent group (18 +/- 25% versus 4 +/- 8%; p = 0.005). At 6 months, the incidence of clinically driven repeat target lesion revascularization was 37.6% with 2 stents as compared to 5.6% using 1 stent (p = 0.01). Angiographic restenosis was documented in 40.6% using 2 bifurcation stents, as compared to 11% when using 1 stent (p = 0.05). By multivariable analysis adjusted for baseline differences, stenting the sidebranch was a borderline predictor for major adverse cardiac events at 6 months (odds ratio = 10.3; 95% confidence interval, 0.9-116; p = 0.053). CONCLUSION: For the treatment of true bifurcation lesions, a strategy of stenting both vessels using bare metal stents seems to be associated with worse long-term results, as compared to stenting only the parent vessel.

Angioplasty, Balloon↗
PubMed2004

Acute and intermediate-term results of percutaneus left main coronary artery interventions.

BACKGROUND: Left main coronary artery disease is considered a surgical indication in most centers. However, in some cases prohibited from surgery or in patients with prior bypass grafting, there is a need for percutaneous coronary intervention in LMCA disease scenarios. OBJECTIVES: To assess the clinical outcomes among patients undergoing stent-based LMCA angioplasty. METHODS: We identified 34 consecutive patients who underwent PCI in LMCA at our institution. Procedural data and clinical outcomes were obtained for all patients. RESULTS: The mean age was 71 +/- 12 years. There were 27 elective and 7 emergent procedures performed on 23 "protected" LMCA and 11 "unprotected" LMCA. In emergent procedures, the prevalence of cardiogenic shock (29% vs. 0%, P = 0.04) in patients with prior coronary bypass (29% vs. 8.5%, P = 0.007) was significantly higher compared to elective cases. Procedural success in emergent procedures was significantly lower than in elective procedures (71 vs. 100%, P = 0.04). In emergent versus elective procedures, the in-hospital mortality rate was higher (43 vs. 0%, P = 0.006). The rate of cumulative major adverse cardiac events at 1 and 6 months was 43% and 71% in emergent cases versus 0% and 33% in elective cases (P < 0.05 for both comparisons). In patients with "unprotected" LMCA the overall rate of major cardiac events at 1 month was higher compared to "protected" LMCA patients (27 vs. 0%, P = 0.02). Multivariate analysis revealed emergent procedure as an independent predictor for mortality and adverse cardiac events (odds ratio 6.7, 95% confidence interval 1.2-36; P = 0.02). CONCLUSIONS: Percutaneous interventions in LMCA are feasible and relatively safe in carefully selected cases. Procedural outcomes and clinical prognosis is highly dependent on the nature of disease prior to angioplasty (e.g., elective vs. emergent procedure) as well as on protection of the LMCA by patent grafts.

Aged↗
PubMed2003

Akt controls vascular smooth muscle cell proliferation in vitro and in vivo by delaying G1/S exit.

Constitutive activation of serine/threonine kinase Akt causes uncontrolled cell-cycle progression in different cell types and in malignancy. To investigate how Akt activation modulates cell-cycle progression in vascular smooth muscle cells (SMCs) in vitro and in the intact animal, we inhibited Akt-dependent signaling by adenovirus-mediated transfection of a dominant-negative Akt mutant (AA-Akt). We observed reduced proliferation rate (P<0.01), DNA synthesis (P<0.01), and a significant arrest in G1/S exit (P<0.01) both in vitro in response to serum stimulation and in vivo after vascular injury. In vivo transfection of the balloon-injured vessel with AA-Akt reduced SMC proliferation, resulting in decreased neointima compared with control virus (P<0.01). These effects were at least in part modulated, both in vitro and in vivo, by increased p21Cip1 expression, as demonstrated by lack of effect of AA-Akt on cell proliferation in p21-/- mouse SMCs. In conclusion, this study demonstrates that Akt-dependent signaling enhances cell-cycle progression of nontransformed SMCs in vitro and in response to vascular injury in the intact animal. These results suggest a role for Akt signaling in modulating the response of normal tissues to stress and the response of the arterial wall to acute and possibly repetitive injuries that ultimately contribute to restenosis and atherosclerosis.

Adenoviridae↗
PubMed2003

Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions.

Bleeding related to percutaneous coronary intervention (PCI) occurs relatively frequently. We retrospectively investigated the incidence, predictors, and prognostic impact of periprocedural bleeding and transfusion in 10,974 patients who underwent PCI. Bleeding definitions were based on Thrombolysis In Myocardial Infarction (TIMI) criteria: (1) major bleeding (n = 588; 5.4%): if patients had a hemorrhagic stroke or if hematocrit decreased >15 points or by 10 to 15 points with clinical bleeding; (2) minor bleeding (n = 1,394; 12.7%): if hematocrit decreased <10 points with clinical bleeding or by 10 to 15 points without clinical bleeding; and (3) no bleeding (n = 8,992; 81.9%): if hematocrit decreased <10 points without clinical bleeding. Patients with major bleeding were older than patients with minor or no bleeding (67.8 +/- 11 vs 65.9 +/- 11 vs 63.6 +/- 11 years, respectively; p <0.001) and more often experienced intraprocedural complications, such as emergency use of an intra-aortic balloon pump (13.6% vs 6.5% vs 2.3%, respectively; p <0.001). Multivariate logistic regression analysis identified the use of an intra-aortic balloon pump (odds ratio [OR] 3.0, p <0.0001), procedural hypotension (OR 2.9, p <0.001), and age >80 years (OR 1.9 compared with age <50 years, p = 0.001) as the strongest predictors for major bleeding. Patients who had major bleeding had higher in-hospital and 1-year mortality compared with patients with minor or no bleeding. Bleeding was an independent predictor of in-hospital death. Thus, periprocedural major bleeding occurs relatively frequently and is associated with adverse outcomes. Patients >80 years of age who experience intraprocedural complications are at particularly high risk.

Age Factors↗
PubMed2003

Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice.

BACKGROUND: T lymphocytes, components of the immune and inflammatory systems, are involved in such normal processes as wound healing and host defense against infection and in such pathological processes as tumor growth and atherosclerotic plaque development. Angiogenesis is a mechanism common to each. Because CD4+ T lymphocytes are active in regulating humoral and cellular responses of the immune system, we determined whether CD4+ cells contribute to collateral vessel development by using the mouse ischemic hindlimb model. METHODS AND RESULTS: One week after ischemia, CD4-/- mice showed reduced collateral flow induction, macrophage number, and vascular endothelial growth factor levels in the ischemic muscle compared with wild-type mice. There was also delayed recovery of hindlimb function and increased muscle atrophy/fibrosis. Spleen-derived purified CD4+ T cells infused into CD4-/- mice selectively localized to the ischemic limb and significantly increased collateral flow as well as macrophage number and vascular endothelial growth factor levels in the ischemic muscle. Muscle function and damage also improved. CONCLUSIONS: These results indicate an important role of CD4+ cells in collateral development, as demonstrated by a 25% decrease in blood flow recovery after femoral artery ligation. Our data also suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenic cytokines.

Acute Disease↗
PubMed2003

Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study.

OBJECTIVES: We conducted a pilot study to evaluate the feasibility of transendocardial delivery of autologous bone marrow (ABM) strategy in patients with severe symptomatic chronic myocardial ischemia not amenable to conventional revascularization. BACKGROUND: Transendocardial injection of ABM cells appears to enhance perfusion of ischemic porcine myocardium. METHODS: Ten patients underwent transendocardial injection of freshly aspirated and filtered unfractionated ABM using left ventricular electromechanical guidance. Twelve injections of 0.2 ml each were successfully delivered into ischemic noninfarcted myocardium pre-identified by single-photon emission computed tomography perfusion imaging. RESULTS: Autologous bone marrow injection was successful in all patients and was associated with no serious adverse effects; in particular, there was no arrhythmia, evidence of infection, myocardial inflammation, or increased scar formation. Two patients were readmitted for recurrent chest pain. At three months, Canadian Cardiovascular Society angina score significantly improved (3.1 +/- 0.3 vs. 2.0 +/- 0.94, p = 0.001), as well as stress-induced ischemia occurring within the injected territories (2.1 +/- 0.8 vs. 1.6 +/- 0.8, p < 0.001). Treadmill exercise duration, available in nine patients, increased, but the change was not significant (391 +/- 155 vs. 485 +/- 198, p = 0.11). CONCLUSIONS: This study provides preliminary clinical data indicating feasibility of catheter-based transendocardial delivery of ABM to ischemic myocardium.

Bone Marrow Transplantation↗
PubMed2003

Current perspectives in therapeutic myocardial angiogenesis.

The complex mechanisms mediating the development of new blood vessels are now beginning to be unraveled. In conjunction with major biotechnology advances, this has facilitated the initiation of translational research related to a novel treatment strategy for patients with myocardial or leg ischemia due to obstructive arterial disease--therapeutic angiogenesis. At present, at least 17 clinical trials of myocardial angiogenesis have been presented involving over 900 patients. Uncertainty exists as to the optimal delivery route and angiogenic agent, and this uncertainty is reflected in the diverse methodology of the trials published thus far. The majority of patients received an angiogenic protein via the intracoronary route. Other delivery techniques--such as direct intramyocardial injection via transepicardial or transendocardial routes--and other angiogenic agents, including master genes, have also been studied. Most recently, interest has grown in the potential angiogenesis effects of cell therapy--such as autologous bone marrow cells or cultured stem cells--and there are now several groups initiating Phase I/II trials in this area. This review summarizes the current evidence pertaining to the safety, feasibility, and efficacy of various angiogenic techniques aimed at enhancing myocardial blood flow and alleviating angina.

Angiogenesis Inducing Agents↗
PubMed2002

Stroke complicating percutaneous coronary interventions: incidence, predictors, and prognostic implications.

BACKGROUND: Stroke associated with percutaneous coronary intervention (PCI) is an infrequent although devastating complication. We investigated the incidence, predictors, and prognostic impact of periprocedural stroke in unselected patients undergoing PCI. METHODS AND RESULTS: A total of 9662 patients who underwent 12 407 PCIs between January 1990 and July 1999 were retrospectively studied. Stroke was diagnosed in 43 patients (0.38% of procedures). Patients with stroke were older (72+/-11 versus 64+/-11 years, P<0.001), had lower left ventricular ejection fraction (42+/-12 versus 46+/-13%, P=0.04) and more diabetes (39.5% versus 27.2%, P=0.07), and experienced a higher rate of intraprocedural complications necessitating emergency use of intra-aortic balloon pump (IABP) (23.3% versus 3.3%, P<0.001). In-hospital mortality (37.2% versus 1.1%, P<0.001) and 1-year mortality (56.1% versus 6.5%, P<0.001) were higher in patients with stroke. Compared with hemorrhagic stroke, patients with ischemic stroke had higher rate of in-hospital major adverse cardiac events (57.1% versus 25%, P=0.037). Multivariate logistic regression analysis identified emergency use of IABP as the strongest predictors for stroke (OR=9.6, CI 3.9 to 23.9, P<0.001), followed by prophylactic use of IABP (OR=5.1), age >80 years (OR=3.2, compared with age <50 years), and vein graft intervention (OR=2.7). CONCLUSIONS: Stroke associated with contemporary PCI is associated with substantial increased mortality. Elderly patients who experience intraprocedural complications necessitating the use of IABP are at particularly high risk.

Aged↗
PubMed2002

The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox?

OBJECTIVES: The purpose of this study was to assess the impact of body mass index (BMI) on the short- and long-term outcomes after percutaneous coronary intervention (PCI). BACKGROUND: Obesity is associated with advanced coronary artery disease (CAD). However, the relation between BMI and outcome after PCI remains controversial. METHODS: We studied 9,633 consecutive patients who underwent PCI between January 1994 and December 1999. Patients were divided into three groups according to BMI: normal, BMI between 18.5 and 24.9 (n = 1,923); overweight, BMI between 25 and 30 (n = 4,813); and obese, BMI >30 (n = 2,897). RESULTS: Obese patients were significantly younger and had consistently worse baseline clinical characteristics than normal or overweight patients, with a higher incidence of hypertension, diabetes, hypercholesterolemia and smoking history (p < 0.0001). Despite similar angiographic success rates among the three groups, normal BMI patients had a higher incidence of major in-hospital complications, including cardiac death (p = 0.001). At one-year follow-up, overall mortality rates were significantly higher for normal BMI patients compared with overweight or obese patients (p < 0.0001). Myocardial infarction and revascularization rates did not differ among the three groups. By multivariate Cox regression analysis, diabetes, hypertension, age, BMI and left ventricular function were independent predictors of long-term mortality. CONCLUSIONS: In patients with known CAD who undergo PCI, very lean patients (BMI <18.5) and those with BMI within the normal range are at the highest risk for in-hospital complications and cardiac death and for increased one-year mortality.

Age Factors↗
PubMed2002

Prognostic value of cardiac troponin I elevation after percutaneous coronary intervention in patients with chronic renal insufficiency: a 12-month outcome analysis.

Serum cardiac troponin I (cTnI) is a highly specific marker for myocardial damage in patients with chronic renal insufficiency (CRI), unlike creatine kinase myocardial band fraction (CK-MB), which may be elevated in the absence of myocardial injury in patients with CRI. We studied 116 consecutive CRI patients (serum creatinine +/- 1.8 mg/dL, not on dialysis) with normal baseline cTnI levels who underwent successful percutaneous coronary intervention (PCI). Patients were divided into two groups: group 1, elevated postprocedural cTnI (n = 50), and group 2, normal cTnI (n = 66). Patients with elevated cTnI were older and had a higher incidence of postinfarction angina and lower creatinine clearance compared to patients who did not have cTnI elevation. Atheroablative devices (rotational and directional atherectomy and excimer laser coronary angioplasty) were more frequently used in group 1 patients (27.1% vs. 18.5%; P = 0.04). In-hospital mortality, cardiac mortality, and Q-wave myocardial infarction rates did not differ between the two groups. At 12-month follow-up, total mortality rates were significantly higher in group 1 (28.0% vs. 9.9%; P = 0.002). Multivariate analysis showed that cTnI was an independent predictor of late mortality (OR = 2.26; CI = 1.07-4.77; P = 0.03). Thus, in patients with CRI, elevated cTnI levels after successful PCI is an important predictor of poor long-term outcome. Our data suggest that patients with cTnI elevation > 3 times above normal values are particularly at higher risk.

Age Factors↗
PubMed2001

Anti-angiogenesis: A new potential strategy to inhibit restenosis.

Microvessels are an integral component of the neointima developing in response to the acute vascular injury resulting from angioplasty. These vessels originate from the vasa vasorum of the adventitia, and as such appear similar to the microvessels present in atherosclerotic plaques. Several angiogenic factors have been found in atherosclerotic plaques and have been associated with increased microvascularity. In addition, most of these agents - either directly or indirectly - also induce smooth muscle cell (SMC) proliferation, an essential component of the developing neointima. We therefore propose: (1) these newly formed blood vessels are necessary for the development, maintenance, and expansion of the neointimal lesions present in restenosis; (2) the initiation, regulation and maintenance of these vessels is, at least in part, due to the coordinate sequential expression of hypoxia-inducible factor 1 (HIF-1), vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), and/or other angiogenic factors such as the fibroblast growth factor (FGF) family of proteins; (3) targeted disruption of the signal transduction pathways modulated by these molecules may reduce vasa vasorum expansion and SMC proliferation. These effects, in turn, may inhibit neointimal expansion and thus the development of restenosis, especially following stenting.

Journal Article↗
PubMed2001

Percutaneous Approach to Achieve Therapeutic Myocardial Angiogenesis.

Myocardial therapeutic angiogenesis is a novel approach for treating the large number of patients with advanced symptomatic coronary artery disease not amenable to conventional revascularization approaches. Proof of concept has been demonstrated in animal models of myocardial ischemia, and preliminary results suggest possible benefit in clinical trials of direct surgical (transepicardial) delivery of proteins and recombinant genes encoding angiogenic growth factors. Catheter-based intramyocardial gene delivery strategies have been tested in parallel, with the assumption that the less invasive nature and the potential for multiple treatment sessions would make this technique more applicable. Currently, most of the data relating to the catheter-based transendocardial delivery of angiogensis factors are derived from the experience with a single device (Biosense; Johnson & Johnson, Skillman, NJ). Using this injection platform, catheter-based gene delivery was demonstrated in animals to be safe and feasible, with a transfection yield similar to that achieved by the direct transepicardial approach. At the time of this review, more than 45 patients have been enrolled in Phase I clinical trials that evaluate the safety and feasibility of transendocardial delivery of adenovirus and plasmid-mediated gene transfection as well as cellular elements.

Journal Article↗
PubMed2000

Catheter-based transendocardial gene delivery for therapeutic myocardial angiogenesis.

Currently it is unknown which is the most effective and safest delivery strategy for therapeutic myocardial angiogenesis. The enhancing effect of direct intramyocardial injection of angiogenic factors using either open-chest or catheter-based approaches on collateral function has been reported to occur in experimental models and among patients. This report reviews the rationale and current experience of using a catheter-based approach as a promising platform for proangiogenic intramyocardial gene delivery strategy.

Journal Article↗