Biomedical subjects
Publications and source records attributed to Ran Kornowski.
We describe four successful cases demonstrating the use of a novel filter-guidewire (FilterWire EX) during complex percutaneous coronary interventions in saphenous vein grafts (n = 3) and native coronary artery (n = 1) for prevention of distal embolization and consequently myonecrosis.
Recent experimental studies based on innovative hypothesis utilizing cell therapy for the damaged myocardium are recently becoming increasingly promising. The naturally occurring myocardial reparative process is apparently complex and relatively inefficient. It consists of up-regulation of progenitor cell release from the bone marrow after myocardial infarction, homing of these cells to the injured tissue, and differentiation of these progenitor cells into vascular cells and cardiomyocytes within the infarcted tissue. Accordingly, there are two main strategies to regenerate myocardium with autologous stem cells: (1) Extracting stem cells from the bone marrow and injecting these cells into the damaged area, (2) Increasing the efficiency of the naturally occurring reparative process by increasing the mobilization of bone marrow-derived stem cells after myocardial infarction. This review summarizes the growing field of autologous stem cell utilization over the past decade and outlines scientific and clinical hurdles that need to be overcome before this therapy can fully reach its clinical potential.
BACKGROUND: Percutaneous coronary intervention (PCI) in octogenarian patients has been associated with increased cardiovascular morbidity and mortality. This study aimed to assess acute and intermediate-term clinical outcomes among octogenarians undergoing PCI. METHODS: The authors identified 97 consecutive patients aged > or =80 years who underwent PCI using stents between November 2000 and February 2002 at their institution. The patients were divided into three groups according to clinical presentation: (1) acute myocardial infarction (AMI, n = 31); (2) unstable angina pectoris (UAP, n = 28); and (3) stable angina pectoris (SAP, n = 38). Procedural data, and in-hospital and six-month clinical outcomes were obtained and adjudicated for all patients. RESULTS: Overall mean age was 84 +/- 3 years, 67% of patients were males and 73% had multivessel coronary disease. In-hospital outcomes varied according to clinical presentation: procedural success was 78% in AMI patients (including shock patients), 93% in UAP, and 95% in SAP patients. Likewise, hospital mortality was 26% in AMI, 3.6% in UAP, and 0% in SAP patients (p = 0.0003). Among AMI patients, hospital mortality was extremely high in patients with cardiogenic shock (67% versus 4.6% in AMI without shock, p < 0.0001). Cumulative event rate at six months also varied according to clinical presentation: mortality/MI and target vessel revascularization (TVR) rates were 29%, 3.6%, and 0% in AMI, 7.1%, 7.4%, and 11% in UAP and 0%, 5.3%, and 7.9% in SAP patients. Multivariate analysis identified cardiogenic shock as the most powerful risk factor for predicting mortality (odds ratio = 42, p = 0.03). CONCLUSIONS: These results show that clinically stable octogenarian patients undergoing PCI have favorable procedural and intermediate-term prognosis. In contrast, cardiogenic shock has a profound negative prognostic impact on octogenarians despite 'aggressive' PCI attempts.
BACKGROUND: Collateral circulation is severely compromised in patients who have a limited degree of spontaneous myocardial angiogenesis and arteriogenesis. METHOD: To determine the clinical characteristics associated with angiographic apparent collaterals (AAC) and myocardial blush score (MBS), this study compared the clinical variables in various AAC and MBS grades (0 = no, 1 = minimal, 2 = moderate and 3 = maximal collaterals defined by the two variables) among a consecutive group of 112 patients (aged 62 +/- 12 years, 76% men) with a native artery chronic total coronary occlusion studied by selective coronary angiograms. RESULTS: By univariate analysis, including variables such as age, sex, diabetes, hypertension, hypercholesterolemia, smoking and ejection fraction, the only variable that was found more frequently in patients with greater AAC grade was hypercholesterolemia (59%, 63%, 71% and 78% in patients with AAC grade 0, 1, 2 and 3, P = 0.003). Ejection fraction tended to be more preserved in patients with greater AAC score (46%, 48%, 51% and 54% in patients with AAC grade 0, 1, 2 and 3, respectively, P = 0.052). Diabetes mellitus was the only factor that was negatively associated with MBS (23%, 22%, 18% and 16% in patients with MBS grade 0, 1, 2 and 3, P = 0.01). Using a multivariate logistic regression analysis to predict maximal AAC grade, the only independent predictor found was hypercholesterolemia (odds ratio = 1.3, confidence limits = 1.05-1.9, P = 0.048). Diabetes mellitus was the only predictor found to be negatively associated with MBS (odds ratio = 0.72, confidence limits = 0.46-0.98, P = 0.04). It is concluded that collateral grade is associated with hypercholesterolemia and myocardial blush is negatively associated with diabetes mellitus. These findings may reflect a conflicting impact of hypercolesterolemia and diabetes mellitus upon collateral formation, leading to enhanced or depressed angiogenesis in response to obstructive coronary artery disease.
A telecare system (Medic4All) has been developed that relies on a wireless wristwatch-like sensor to measure the pulse wave from the radial artery. From this, the heart rate and respiration rate are derived. The system's performance was examined by comparing the results obtained from the pulse wave signal with those obtained from conventional electrocardiographic and spirometer devices. A total of 144 patients participated in the study; their mean (SD) age was 43 (18) years. There were 44 cardiac patients in group 1 and 100 healthy patients, who were studied in their homes, in group 2. There was a significant correlation between the heart rates measured by the two monitoring methods. A 'difference versus average' analysis showed that the error distribution had a mean (SD) value of -0.1 (3.3) beats/min. Similarly, the respiration rates measured by the two techniques were significantly correlated. The error distribution had a mean (SD) value of 0.1 (1.9) respirations/min. The present study suggests that the wrist-worn sensor represents a promising tool for online detection and monitoring of vital signs in the home.
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.
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BACKGROUND: Arterial access site management after percutaneous coronary intervention (PCI) is a matter of increasing importance in this era of potent antiplatelet pharmacotherapy. We evaluated the safety and efficacy of a 6 French (Fr) Perclose suturing device in achieving rapid hemostasis of the access site after PCI and thus improving patient comfort. METHODS: The 6 Fr Perclose (Prostar) device consists of a suture-based closure device delivered via introducer sheath designed for suturing of the arteriotomy puncture site. Over a 3-month period, the device was used in 48 consecutive PCI treated patients (age, 62 13 years; 70% male; 44% post myocardial infarction) and in-hospital groin complication rate was compared to 48 consecutive patients (age, 64 12 years; 64% male; 33% post myocardial infarction) who had manual compression hemostasis. RESULTS: Antiplatelet glycoprotein IIb/IIIa antagonists were used more frequently during and following the procedure in 58% of Perclose-treated patients versus 42% of the manual compression group (p = 0.019). Leg immobilization duration was 3 4 hours in all patients sutured by the device; in patients with manual compression, the sheath was removed at an average of 4.8 2.5 hours after termination of the PCI and an additional 6 hours of leg immobilization were subsequently required. No difference in overall major complication rate was found between groups (6.2% in suture-mediated patients versus 9.3% in manual compression group; p = 0.60). In 3 patients (6.2%) treated using the device, adjunctive manual compression was required in addition to groin suturing due to technical failure or residual oozing from the arteriotomy site. CONCLUSION: The 6 Fr Perclose device can be safely used to achieve rapid hemostasis and the device may hasten bed mobilization of PCI-treated patients despite frequent use of potent antiplatelet pharmacotherapy during coronary interventions.
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.
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.
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.
Coronary artery disease is more aggressive in diabetic patients than in nondiabetics; they have more diffuse disease, higher mortality rates and worse clinical outcomes after coronary interventions. Intravascular ultrasound (IVUS) produces transmural tomographic images of the coronary arteries in vivo. Recent IVUS studies have provided new insights into the mechanisms of stenosis formation and restenosis in both nondiabetic and diabetic patients. Arterial remodeling is defined as a change in arterial area. During atherogenesis, an increase in arterial area usually accompanies plaque accumulation to delay lumen compromise. Stenosis formation is related to: (a) the rate of plaque accumulation versus the rate of positive remodeling; and (b) the limits and ultimate failure of positive remodeling. However, there is a marked variability in remodeling. IVUS studies have suggested that remodeling may be impaired in some diabetic patients during atherogenesis. Following non-stent catheter-based interventions, serial (post-intervention and follow-up) IVUS studies have shown that the change in lumen area correlates better with the change in arterial area (remodeling) than with the change in plaque area (neointimal hyperplasia). In some patients, a positive remodeling response mitigates against the increase in plaque area to limit late lumen loss and restenosis. Neointimal hyperplasia is exaggerated in diabetic patients. Despite this, there is a reduced frequency of positive remodeling, potentially similar to the impaired positive remodeling in some diabetic patients during atherogenesis. Failed or inadequate arterial remodeling may contribute to the pathogenesis and natural history of atherosclerotic coronary artery disease in diabetic patients.
The current report demonstrates the feasibility and potential clinical application of a catheter-based approach for left-ventricular electromechanical mapping and on-line assessment of myocardial via bility in the catherization laboratory based on generated endocardial signals and three-dimensional left ventricular anatomical reconstruction.
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BACKGROUND: Left internal mammary artery (LIMA) grafting to the left anterior descending artery (LAD) is known to have long-term patency. However, myocardial ischemia in the territories supplied by LIMA to LAD is still demonstrated. The aim of this study is to examine the relationships between the extent, location, and clinical outcome of myocardial ischemia in LAD territories (ILAD) by use of myocardial perfusion imaging (MPI) and angiographic characteristics of such a bypass conduit. METHODS AND RESULTS: We studied 38 consecutive patients with prior coronary artery bypass grafting who showed stress-induced ischemia in LIMA to LAD territories by MPI single photon emission computed tomography between the years 1996-2000. All patients underwent quantitative coronary angiography within 6 months of the nuclear study. Single photon emission computed tomography parameters of ILAD were assessed by location (septum, apex, anterior, and anterolateral) and included extension score (1-4 per patient), severity score (0-3 per territory), and total sum score. LIMA to LAD quantitative coronary angiography parameters included minimal lumen diameter, lesion length, reference diameter, and diameter stenosis (percentage). LAD and LIMA diameters and ratio (in normal segments) were determined within 10 mm proximal and distal to the anastomotic site. The study group was compared with 18 control subjects without ischemia or stenosis treated with LIMA to LAD. The patients were followed up for cardiac death at an interval of 3.2 +/- 1.5 years from the time of MPI testing. The patients' mean age was 66 +/- 12 years (31 men and 7 women); the mean period after surgery was 6.2 +/- 1.5 years. The ILAD distribution was as follows: septum, 12 (32%); apex, 20 (52%); anterior, 24 (63%); and anterolateral, 18 (47%). The mean extension score was 1.9 +/- 1.0, and the mean total sum score was 3.4 +/- 2.3. Of 38 patients with ILAD, only 17 (45%) had greater than 50% luminal stenosis (2 LIMA and 15 anastomosis or distal). Among clinical variables during stress testing, the prevalence of angina was significantly higher in the luminal stenotic patients versus patients without stenosis (P =.04). A significant correlation was found between anterior wall ischemia and reference diameter (r = -0.7, P =.002) and between total sum score and minimal lumen diameter (r = -0.48, P =.05). Of note, the LAD-to-LIMA ratio was significantly lower in patients with ILAD and without luminal stenosis compared with the control group (0.73 +/- 0.16 vs 0.87 +/- 0.15, P =.004). Cardiac death occurred in 8 patients (21%), 5 patients with luminal stenosis versus 3 patients without stenosis (P = not significant). CONCLUSIONS: In patients with LIMA to LAD anastomosis, myocardial ischemia could occur even without angiographic luminal stenosis and apparently reflects a mismatch between LAD and LIMA diameters at distal anastomotic sites. Regarding the similar prevalence of cardiacdeath, invasive evaluation and aggressive treatment are recommended in all patients with ischemia in LIMA/LAD territories.
BACKGROUND: Controversy exists whether transmyocardial laser revascularization (TMR) is associated with angiogenesis or neuromodulation and whether these are time-dependent phenomena. Accordingly, we performed a time-course analysis of the expression of angiogenic and neuronal factors following experimental percutaneous TMR. METHODS AND RESULTS: Five weeks after placing ameroid constrictors on the circumflex coronary artery, 16 pigs underwent left ventricular mapping guided TMR using Ho:YAG laser (2 J x 1 pulse) at 30 sites directed at the ischemic zones and 11 animals were ischemic controls. Histology and immunostaining were obtained at 1 and 2 weeks (4 TMR and 3 controls at each time point) and at 4 weeks (8 TMR and 5 controls) for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), nerve growth factor (betaNGF), substance P (SP), and monocyte chemoattractant protein-1 (MCP-1). Immunoreactivity was scored using a digital image analysis system. Factor VIII staining was used for blood vessel counting. Enhanced regional expression of VEGF, bFGF and MCP-1 in the TMR group was noted at 1 and 2 weeks with a threefold increase at 4 weeks following TMR compared to controls. BetaNGF expression in the TMR group was enhanced at 1 and 2 weeks with subsequent decline at 4 weeks to the controls level. SP expression was not significantly different between groups at all time points. There was a twofold increase in the number of blood vessels in the TMR group at 4 weeks, which was not apparent earlier. CONCLUSIONS: These immunohistological findings suggest that cytokines expression compatible with angiogenesis and neuromodulation occurs early after TMR. Up-regulation of angiogenic and inflammatory cytokines may be more sustained than neuromodulation.