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1.
Indian Heart J ; 68(4): 464-72, 2016.
Article in English | MEDLINE | ID: mdl-27543467

ABSTRACT

OBJECTIVE: To analyze trends in utilization of anti-thrombotic agents (ATA) and in-hospital clinical outcomes in non-ST-elevation myocardial infarction (NSTEMI) patients managed with an invasive strategy from 2007 to 2010. METHODS & RESULTS: Using ACTION Registry(®)-GWTG™ data, we analyzed trends in use of ATA and in-hospital clinical outcomes among 64,199 NSTEMI patients managed invasively between 2007 and 2010. ATA included unfractionated heparin (UFH), low molecular weight heparin (LMWH), glycoprotein IIb/IIIa inhibitors (GPI) and bivalirudin. Although the proportion of NSTEMI patients treated with PCI within 48h of hospital arrival was similar in 2007 and 2010, percentage use of bivalirudin (13.4-27.3%; p<0.01) and UFH increased (60.0-67.5%, p<0.01), and that of GPI (62.3-41.0%; p<0.01) and LMWH (41.5-36.8%; p<0.01) declined. Excess dosing of UFH (75.9-59.3%, p<0.01), LMWH (9.6-5.2%; p<0.01) and GPI (8.9-5.9%, p<0.01) was also significantly lower in 2010 compared with 2007. Though in-hospital mortality rates were similar in 2007 and 2010 (2.3-1.9%, p=0.08), the rates of in-hospital major bleeding (8.7-6.6%, p<0.01) and non-CABG related RBC transfusion (6.3-4.6%, p<0.01) were significantly lower in 2010 compared with 2007. CONCLUSION: Compared with 2007, patients with NSTEMI, who were managed invasively in 2010 received GPI and LMWH less often and bivalirudin and UFH more frequently. There were sizeable reductions in the rates of excess dosing of UFH (though still occurred in 67% of patients), GPI and LMWH. In-hospital major bleeding complications and post-procedural RBC transfusion were lower in 2010 compared with 2007.


Subject(s)
Angioplasty, Balloon, Coronary/methods , Fibrinolytic Agents/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Hirudins/administration & dosage , Non-ST Elevated Myocardial Infarction/drug therapy , Peptide Fragments/administration & dosage , Registries , Antithrombins/administration & dosage , Dose-Response Relationship, Drug , Electrocardiography , Female , Follow-Up Studies , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Hospital Mortality/trends , Humans , Incidence , Male , Middle Aged , Non-ST Elevated Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/mortality , Recombinant Proteins/administration & dosage , Retrospective Studies , Time Factors , United States/epidemiology
3.
Am Heart J ; 141(6): 964-70, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11376311

ABSTRACT

BACKGROUND: The SHOCK Registry prospectively enrolled patients with cardiogenic shock complicating acute myocardial infarction in 36 multinational centers. METHODS: Cardiogenic shock was predominantly attributable to left ventricular pump failure in 884 patients. Of these, 276 underwent percutaneous coronary intervention (PCI) after shock onset and are the subject of this report. RESULTS: The majority (78%) of patients undergoing angiography had multivessel disease. As the number of diseased arteries rose from 1 to 3, mortality rates rose from 34.2% to 51.2%. Patients who underwent PCI had lower in-hospital mortality rates than did patients treated medically (46.4% vs 78.0%, P < .001), even after adjustment for patient differences and survival bias (P = .037). Before PCI, the culprit artery was occluded (Thrombolysis In Myocardial Infarction grade 0 or 1 flow) in 76.3%. After PCI, the in-hospital mortality rate was 33.3% if reperfusion was complete (grade 3 flow), 50.0% with incomplete reperfusion (grade 2 flow), and 85.7% with absent reperfusion (grade 0 or 1 flow) (P < .001). CONCLUSIONS: This prospective, multicenter registry of patients with acute myocardial infarction complicated by cardiogenic shock is consistent with a reduction in mortality rates as the result of percutaneous coronary revascularization. Coronary artery patency was an important predictor of outcome. Measures to promote early and rapid reperfusion appear critically important in improving the otherwise poor outcome associated with cardiogenic shock.


Subject(s)
Angioplasty, Balloon, Coronary , Shock, Cardiogenic/mortality , Shock, Cardiogenic/therapy , Aged , Canada/epidemiology , Female , Humans , Male , Myocardial Infarction/mortality , Myocardial Infarction/therapy , Prospective Studies , Registries , Survival Analysis , United States/epidemiology
5.
Catheter Cardiovasc Interv ; 52(2): 260-6, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11170342

ABSTRACT

Experimental studies indicate that administration of angiogenic proteins or genes by the epicardial or intracoronary route can stimulate development of new collateral vessels and improve myocardial perfusion. An endocardial catheter-based approach to this therapy would obviate the need for surgery, while preserving the effectiveness of direct intramyocardial administration. Fluoroscopic guidance and prototype, preformed, coaxial catheters were used to examine the feasibility of percutaneous catheter-based adenovirus (Ad)-mediated gene transfer and expression in normal swine myocardium. The feasibility of intramyocardial administration (100 microl/injection) of a radiocontrast agent and black tissue dye to all regions of the left ventricle (septum, anterior, lateral, and inferior wall) was confirmed fluoroscopically and on postmortem examination. Injections of replication-deficient adenovirus (10 injections of 10(11) particle units/100 microl each) coding for beta-galactosidase (Adbetagal) or vascular endothelial growth factor (Ad(GV)VEGF121.10) were administered to the left ventricular free wall to examine endocardial based gene transfer and expression. beta-Galactosidase activity was detected by histochemical staining and quantitative assay in targeted regions of the myocardium. Regional VEGF expression was found to be significantly greater in targeted regions (1.3 +/- 0.4 ng/mg protein) as compared with non-targeted regions (0.3 +/- 0.1 ng/mg protein) or regions injected with control (Adbetagal) virus (0.2 +/- 0.03 ng/mg protein, P < 0.001). Catheter-based Ad mediated endocardial gene transfer and expression is feasible using percutaneous, fluoroscopically guided, preformed, coaxial catheters. This approach should be clinically useful to administer angiogenic genes to the ischemic myocardium.


Subject(s)
Gene Transfer Techniques , Genetic Therapy , Myocardium , Neovascularization, Physiologic , Adenoviridae , Animals , Cardiac Catheterization , Endocardium , Feasibility Studies , Fluoroscopy , Gene Expression , Swine
6.
Lancet ; 356(9243): 1705-10, 2000 Nov 18.
Article in English | MEDLINE | ID: mdl-11095257

ABSTRACT

BACKGROUND: Percutaneous transmyocardial laser revascularisation (PTMR) is a proposed catheter-based therapy for refractory angina pectoris when bypass surgery or angioplasty is not possible. We undertook a randomised trial to assess the safety and efficacy of this technique. METHODS: 221 patients with reversible ischaemia of Canadian Cardiovascular Society angina class III (61%) or IV (39%) and incomplete response to other therapies were recruited from 13 centres. Patients were randomly assigned PTMR with a holmium:YAG laser plus continued medical treatment (n=110) or continued medical treatment only (n=111). The primary endpoint was the exercise tolerance at 12 months. Analyses were by intention to treat. FINDINGS: 11 patients died and 19 withdrew; 92 PTMR-group and 99 medical-treatment-group patients completed the study. Exercise tolerance at 12 months had increased by a median of 89.0 s (IQR -15 to 183) with PTMR compared with 12.5 s (-67 to 125) with medical treatment only (p=0.008). On masked assessment, angina class was II or lower in 34.1% of PTMR patients compared with 13.0% of those medically treated. All indices of the Seattle angina questionnaire improved more with PTMR than with medical care only. By 12 months there had been eight deaths in the PTMR group and three in the medical treatment group, with similar survival in the two groups. INTERPRETATION: PTMR was associated with increased exercise tolerance time, low morbidity, lower angina scores assessed by masked reviewers, and improved quality of life. Although there is controversy about the mechanism of action, and the contribution of the placebo effect cannot be quantified, this unmasked study suggests that this palliative procedure provides some clinical benefits in the defined population of patients.


Subject(s)
Angina Pectoris/surgery , Laser Therapy , Myocardial Revascularization , Adult , Aged , Aged, 80 and over , Angina Pectoris/drug therapy , Angina Pectoris/mortality , Cardiovascular Agents/therapeutic use , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Dropouts , Survival Analysis , Survival Rate , Treatment Outcome
7.
J Am Coll Cardiol ; 36(3 Suppl A): 1063-70, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10985706

ABSTRACT

OBJECTIVES: This SHOCK Study report seeks to provide an overview of patients with cardiogenic shock (CS) complicating acute myocardial infarction (MI) and the outcome with various treatments. The outcome of patients undergoing revascularization in the SHOCK Trial Registry and SHOCK Trial are compared. BACKGROUND: Cardiogenic shock is the leading cause of death in patients hospitalized for acute MI. The randomized SHOCK Trial reported improved six-month survival with early revascularization. METHODS: Patients with CS complicating acute MI who were not enrolled in the concurrent randomized trial were registered. Patient characteristics were recorded as were procedures and vital status at hospital discharge. RESULTS: Between April 1993 and August 1997, 1,190 patients with CS were registered and 232 were randomized in the SHOCK Trial. Predominant left ventricular failure (78.5%) was most common, with isolated right ventricular shock in 2.8%, severe mitral regurgitation in 6.9%, ventricular septal rupture in 3.9% and tamponade in 1.4%. In-hospital Registry mortality was 60%, with ventricular septal rupture associated with a significantly higher mortality (87.3%) than all other categories (p < 0.01). The risk profile and mortality were lower for Registry patients who were managed with thrombolytic therapy and/or intra-aortic balloon counter-pulsation, coronary angiography, angioplasty and/or coronary artery bypass surgery. After adjusting for these differences, the extent to which survival was improved with early revascularization was similar to that observed in the randomized SHOCK Trial. CONCLUSIONS: In this prospective Registry the etiology of CS was a mechanical complication in 12%. The similarity of the beneficial treatment effect in patients undergoing early revascularization in the SHOCK Trial Registry and SHOCK Trial provides strong support for the generalizability of the SHOCK Trial results.


Subject(s)
Intra-Aortic Balloon Pumping , Myocardial Revascularization , Registries , Shock, Cardiogenic/etiology , Thrombolytic Therapy , Aged , Cardiac Catheterization , Coronary Angiography , Diagnosis, Differential , Female , Humans , Incidence , Male , Myocardial Infarction/complications , Myocardial Infarction/diagnosis , Myocardial Infarction/mortality , Myocardial Infarction/therapy , Prospective Studies , Radionuclide Ventriculography , Registries/statistics & numerical data , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/epidemiology , Shock, Cardiogenic/therapy , Survival Rate , Treatment Outcome
8.
J Am Coll Cardiol ; 36(3 Suppl A): 1123-9, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10985715

ABSTRACT

OBJECTIVES: We sought to investigate the potential benefit of thrombolytic therapy (TT) and intra-aortic balloon pump counterpulsation (IABP) on in-hospital mortality rates of patients enrolled in a prospective, multi-center Registry of acute myocardial infarction (MI) complicated by cardiogenic shock (CS). BACKGROUND: Retrospective studies suggest that patients suffering from CS due to MI have lower in-hospital mortality rates when IABP support is added to TT. This hypothesis has not heretofore been examined prospectively in a study devoted to CS. METHODS: Of 1,190 patients enrolled at 36 participating centers, 884 patients had CS due to predominant left ventricular (LV) failure. Excluding 26 patients with IABP placed prior to shock onset and 2 patients with incomplete data, 856 patients were evaluated regarding TT and IABP utilization. Treatments, selected by local physicians, fell into four categories: no TT, no IABP (33%; n = 285); IABP only (33%; n = 279); TT only (15%; n = 132); and TT and IABP (19%; n = 160). RESULTS: Patients in CS treated with TT had a lower in-hospital mortality than those who did not receive TT (54% vs. 64%, p = 0.005), and those selected for IABP had a lower in-hospital mortality than those who did not receive IABP (50% vs. 72%, p < 0.0001). Furthermore, there was a significant difference in in-hospital mortality among the four treatment groups: TT + IABP (47%), IABP only (52%), TT only (63%), no TT, no IABP (77%) (p < 0.0001). Patients receiving early IABP (< or = 6 h after thrombolytic therapy, n = 72) had in-hospital mortality similar to those with late IABP (53% vs. 41%, n = 64, respectively, p = 0.172). Revascularization rates differed among the four groups: no TT, no IABP (18%); IABP only (70%); TT only (20%); TT and IABP (68%, p < 0.0001); this influenced in-hospital mortality significantly (39% with revascularization vs. 78% without revascularization, p < 0.0001). CONCLUSIONS: Treatment of patients in cardiogenic shock due to predominant LV failure with TT, IABP and revascularization by PTCA/CABG was associated with lower in-hospital mortality rates than standard medical therapy in this Registry. For hospitals without revascularization capability, a strategy of early TT and IABP followed by immediate transfer for PTCA or CABG may be appropriate. However, selection bias is evident and further investigation is required.


Subject(s)
Fibrinolytic Agents/therapeutic use , Intra-Aortic Balloon Pumping , Registries , Shock, Cardiogenic/therapy , Thrombolytic Therapy , Aged , Cardiac Catheterization , Coronary Angiography , Electrocardiography , Female , Hemodynamics , Hospital Mortality , Humans , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/therapy , Myocardial Revascularization , Prospective Studies , Shock, Cardiogenic/etiology , Shock, Cardiogenic/mortality , Shock, Cardiogenic/physiopathology , Treatment Outcome
9.
Am J Cardiol ; 85(8): 957-61, 2000 Apr 15.
Article in English | MEDLINE | ID: mdl-10760334

ABSTRACT

"Optimal" percutaneous transluminal coronary angioplasty (PTCA) may have a late restenosis rate similar to stenting. We sought to assess short- and long-term results of a provisional stenting/optimal PTCA approach compared with elective stenting in a prospective, randomized study. A total of 97 patients with discrete, de novo lesions in native coronary arteries > or =3 mm in diameter were randomized 2:1 in PTCA with prolonged perfusion balloon inflation (n = 66) versus elective stenting (n = 31). Recoil after PTCA was assessed by routine delayed angiograms (5 and 20 minutes). Cross over to stent was allowed for an inadequate result; there was no on-line quantitative angiography. An independent core angiographic laboratory assessed all results and evaluated the adequacy of the subjective interpretation. Within the PTCA arm, there were 24 (36%) crossovers to stenting (5 of 24 [21%] due to recoil), whereas 2 stents could not be delivered to the lesion and crossed over to PTCA. As assessed by quantitative angiography, baseline reference vessel diameters were similar between the PTCA and stent groups. The immediate lumen diameter achieved with PTCA was smaller than that achieved with stenting (2.18+/-0.49 vs. 2.44+/-0.38 mm, respectively, p = 0.01). There were no differences in angiographic results between elective and crossover stenting and there were no in-hospital complications in any patient. Target lesion revascularization at 8 months was 19% (n = 6) in the elective stent arm versus 21% (n = 14) in the PTCA arm, p = NS; respective rates in PTCA alone and crossed over-to-stent subsets were 23% (n = 10) versus 17% (n = 4), p = NS. Angiographic restenosis was 47% after elective stenting versus 38% after PTCA (intention to treat), p = NS. By received treatment, it was 41% (11 of 27) in the group treated with the PTCA versus 33% (5 of 15) in the crossover-to-stent arm (p = NS). Thus, provisional stenting can be safely performed in the treatment of discrete, native de novo lesions. Early recoil after PTCA cannot be reliably assessed without quantitative angiography.


Subject(s)
Angioplasty, Balloon, Coronary , Coronary Disease/therapy , Stents , Coronary Angiography , Coronary Disease/diagnostic imaging , Cross-Over Studies , Female , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Recurrence
10.
Ann Thorac Surg ; 69(1): 14-23; discussion 23-4, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10654479

ABSTRACT

BACKGROUND: Adenovirus (Ad) vector-mediated gene therapy strategies have emerged as promising modalities for the "biological revascularization" of tissues. We hypothesized that direct intramyocardial, as opposed to intracoronary, administration of an Ad vector coding for the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) would provide highly focal Ad genome levels, and increases in VEGF, ideal for inducing localized therapeutic angiogenesis. METHODS: Persistence and regional distribution of the vector were assessed by TaqMan real-time quantitative polymerase chain reaction technology and enzyme-linked immunosorbent assay, after intramyocardial Ad(GV)VEGF121.10 in the rat, and either intramyocardial or intracoronary (circumflex territory) vector in Yorkshire swine. Based on these results, we assessed the focal nature of the improved cardiac blood flow in a previously reported porcine myocardial ischemia model. RESULTS: Intramyocardial delivery of Ad(GV)VEGF121.10 in the rat resulted in local persistence of the Ad genome that decreased 1,000-fold over 3 weeks, with peak myocardial VEGF expression 24 to 72 h after vector delivery. After intramyocardial Ad(GV)VEGF121.10 in the circumflex distribution of pigs, Ad vector genome and VEGF protein levels were more than 1,000-fold and more than 90-fold higher, respectively, in this distribution than in other myocardial regions. In comparison, intracoronary injection yielded maximum myocardial Ad genome and VEGF levels 33-fold and 9-fold lower, respectively, than that after intramyocardial delivery. Angiograms obtained 28 days after intramyocardial Ad(GV)VEGF121.10 demonstrated rapid circumflex reconstitution via collaterals localized to the region of vector administration. CONCLUSIONS: These studies demonstrate that direct intramyocardial administration of Ad(GV)VEGF121.10 results in focal genome and VEGF levels, including focal angiogenesis, sufficient to normalize blood flow to the ischemic myocardium, findings that are relevant to designing human trials of gene therapy-mediated cardiac angiogenesis.


Subject(s)
Adenoviridae/genetics , Endothelial Growth Factors/genetics , Genetic Vectors , Lymphokines/genetics , Neovascularization, Physiologic/genetics , Protein Isoforms/genetics , Animals , Collateral Circulation/genetics , Coronary Angiography , Coronary Circulation/genetics , Coronary Circulation/physiology , Coronary Vessels , Disease Models, Animal , Endothelial Growth Factors/analysis , Gene Expression Regulation, Viral , Genetic Therapy , Genome, Viral , Humans , Lymphokines/analysis , Male , Myocardial Ischemia/pathology , Myocardial Ischemia/physiopathology , Myocardial Ischemia/therapy , Myocardium , Protein Isoforms/analysis , Rats , Rats, Sprague-Dawley , Swine , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
11.
Catheter Cardiovasc Interv ; 47(4): 397-403, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10470466

ABSTRACT

This study assessed safety of the distal occlusion washout (DOW) method for prevention of no-reflow during stenting of degenerated saphenous vein grafts (SVGs). The DOW method involves protection of distal native coronary circulation with an occlusive balloon during the pretreatment and washout steps prior to stenting. Outcomes of stenting of 23 grafts in 21 patients after pretreatment with the DOW method were evaluated. The mean graft age was 7.4 +/- 4.3 years. The mean treated lesion length was 53 +/- 28 mm. Total occlusions were treated in 6 grafts and thrombotic lesions in 10 nontotally occluded grafts. One non-Q-wave MI and one acute stent thrombosis were observed. No deaths, Q-wave MIs, or subacute thromboses occurred. Follow-up in 18/21 (85.7%) patients at 28 +/- 8 weeks demonstrated target graft revascularization in 1 (5%) patient. The DOW method prevented clinically significant no-reflow in all 23 degenerated SVGs stented.


Subject(s)
Angioplasty, Balloon, Coronary/methods , Coronary Disease/therapy , Graft Occlusion, Vascular/therapy , Saphenous Vein/transplantation , Stents , Aged , Coronary Angiography , Coronary Circulation , Coronary Disease/diagnostic imaging , Coronary Disease/physiopathology , Female , Filtration , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/physiopathology , Humans , Male , Prospective Studies , Saphenous Vein/diagnostic imaging , Saphenous Vein/physiopathology , Therapeutic Irrigation , Treatment Outcome
12.
Am J Cardiol ; 84(6): 726-8, A8, 1999 Sep 15.
Article in English | MEDLINE | ID: mdl-10498144

ABSTRACT

Two hundred fifty consecutive patients underwent coronary stenting and received a 2-week course of clopidogrel (75 mg orally each day after a loading dose of 150 mg) and aspirin. There was 1 (0.4%) in-hospital death, 1 (0.4%) acute stent thrombosis, and 2 (0.8%) subacute stent thromboses. There were no Q-wave myocardial infarctions, vascular complications, or repeat interventions at 30-day follow-up.


Subject(s)
Angioplasty, Balloon, Coronary , Aspirin/administration & dosage , Coronary Disease/therapy , Platelet Aggregation Inhibitors/administration & dosage , Stents , Ticlopidine/analogs & derivatives , Aged , Aspirin/adverse effects , Clopidogrel , Combined Modality Therapy , Coronary Disease/mortality , Coronary Thrombosis/mortality , Coronary Thrombosis/therapy , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Hospital Mortality , Humans , Male , Middle Aged , Myocardial Infarction/mortality , Myocardial Infarction/therapy , Platelet Aggregation Inhibitors/adverse effects , Recurrence , Ticlopidine/administration & dosage , Ticlopidine/adverse effects , Treatment Outcome
13.
J Mol Cell Cardiol ; 31(9): 1627-42, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10471347

ABSTRACT

The degree of cellularity in vascular lesions is determined by the balance between the migration and proliferation of cells relative to their rate of egress and apoptosis. Transforming growth factor-beta(1) can act as a potent antiproliferative and apoptotic factor for proliferating vascular cells. Our laboratory has previously identified cells cultured from human vascular lesions that are resistant to the antiproliferative effect of TGF-beta(1) due to an acquired mutation in the Type II receptor for TGF-beta(1). In the present studies, the expression of the Type I and II receptors in coronary and carotid atherosclerotic lesions was analysed by immunostaining, RT-PCR, and in situ RT-PCR. Levels of the Type I and Type II receptors varied widely within lesions, with the highest levels in the fibrous cap and at discrete foci within the lesion. Regions of smooth muscle-like cells (SMC) were commonly found that were Type I positive but Type II receptor negative. In 43 cell lines cultured from 126 human lesions, 84% of the lesion-derived cell (LDC) cultures exhibited functional resistance to the antiproliferative effect of TGF-beta(1). This resistance was conferred against TGF-beta(1), TGF-beta(2), and TGF- beta(3), but not interferon-gamma or mimosine. While normal SMC exhibited a four-fold increase in the rate of apoptosis after TGF- beta(1) treatment, most LDC were resistant to apoptosis in response to TGF-beta(1). Resistant cells exhibited selective loss of Type II receptor expression, and retroviral transfection of Type II receptor cDNA partially corrected the functional deficit. Thus, resistance to apoptosis may lead to the slow proliferation of resistant cell subsets, thereby contributing to the progression of atherosclerotic and restenotic lesions.


Subject(s)
Activin Receptors, Type I , Arteriosclerosis/pathology , Carotid Stenosis/pathology , Carotid Stenosis/physiopathology , Coronary Disease/pathology , Coronary Disease/physiopathology , Protein Serine-Threonine Kinases/genetics , Receptors, Transforming Growth Factor beta/genetics , Apoptosis , Arteriosclerosis/genetics , Arteriosclerosis/physiopathology , Atherectomy , Carotid Stenosis/genetics , Cell Division/drug effects , Cloning, Molecular , Coronary Disease/genetics , Endarterectomy, Carotid , Humans , Immunohistochemistry , Models, Cardiovascular , RNA, Messenger/genetics , Receptor, Transforming Growth Factor-beta Type I , Receptor, Transforming Growth Factor-beta Type II , Recombinant Proteins/biosynthesis , Recurrence , Reverse Transcriptase Polymerase Chain Reaction , Transcription, Genetic , Transfection , Transforming Growth Factor beta/pharmacology
14.
Circulation ; 100(5): 468-74, 1999 Aug 03.
Article in English | MEDLINE | ID: mdl-10430759

ABSTRACT

BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.


Subject(s)
Adenoviridae , Coronary Circulation , Coronary Disease/therapy , Endothelial Growth Factors/genetics , Genetic Therapy/methods , Genetic Vectors , Lymphokines/genetics , Neovascularization, Physiologic/genetics , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Coronary Artery Bypass , Coronary Disease/physiopathology , Coronary Disease/surgery , DNA, Complementary/biosynthesis , Exercise Test , Female , Humans , Injections , Male , Middle Aged , Myocardium , Severity of Illness Index , Treatment Outcome , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
15.
N Engl J Med ; 341(9): 625-34, 1999 Aug 26.
Article in English | MEDLINE | ID: mdl-10460813

ABSTRACT

BACKGROUND: The leading cause of death in patients hospitalized for acute myocardial infarction is cardiogenic shock. We conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock. METHODS: Patients with shock due to left ventricular failure complicating myocardial infarction were randomly assigned to emergency revascularization (152 patients) or initial medical stabilization (150 patients). Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty. Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups. The primary end point was mortality from all causes at 30 days. Six-month survival was a secondary end point. RESULTS: The mean age of the patients was 66+/-10 years, 32 percent were women and 55 percent were transferred from other hospitals. The median time to the onset of shock was 5.6 hours after infarction, and most infarcts were anterior in location. Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography, and 87 percent underwent revascularization; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication. Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups (46.7 percent and 56.0 percent, respectively; difference, -9.3 percent; 95 percent confidence interval for the difference, -20.5 to 1.9 percent; P=0.11). Six-month mortality was lower in the revascularization group than in the medical-therapy group (50.3 percent vs. 63.1 percent, P=0.027). CONCLUSIONS: In patients with cardiogenic shock, emergency revascularization did not significantly reduce overall mortality at 30 days. However, after six months there was a significant survival benefit. Early revascularization should be strongly considered for patients with acute myocardial infarction complicated by cardiogenic shock.


Subject(s)
Myocardial Infarction/therapy , Myocardial Revascularization , Shock, Cardiogenic/therapy , Aged , Angioplasty, Balloon, Coronary/mortality , Coronary Artery Bypass/mortality , Emergency Treatment , Female , Humans , Intra-Aortic Balloon Pumping , Logistic Models , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/mortality , Myocardial Revascularization/mortality , Shock, Cardiogenic/etiology , Shock, Cardiogenic/mortality , Survival Rate , Thrombolytic Therapy , Time Factors
16.
Med Care ; 37(1): 68-77, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10413394

ABSTRACT

OBJECTIVE: The study sought to determine if there were race/ethnicity or gender differences in access to coronary artery bypass graft (CABG) surgery among patients who have been designated as appropriate and as necessary for that surgery according to the RAND methodology. METHODS: RAND appropriateness and necessity criteria were used to identify a race/gender stratified sample of postangiography patients who would benefit from coronary artery bypass graft surgery. These patients were tracked for 3 months to determine if they had undergone coronary artery bypass graft surgery in New York State. Subjects were a total of 1,261 postangiography patients in eight New York hospitals in 1994 to 1996. Measures included percentages of patients for whom coronary artery bypass graft surgery was appropriate and necessary undergoing surgery by race/ethnicity and gender, as well as multivariate odds ratios for race/ethnicity and gender. RESULTS: After controlling for age, payer, number of vessels diseased, and presence of left main disease, African-American and Hispanic patients were found to be significantly less likely to undergo coronary artery bypass graft surgery than white non-Hispanic patients (respective odds ratios 0.64 and 0.60). When "necessity" was used as a criterion instead of "appropriateness," significant differences in access for African-American patients remained. The gatekeeper physician recommended surgery only 10% of the time that patients did not undergo "appropriate" coronary artery bypass graft surgery, and this percentage did not vary significantly by race/ethnicity or gender of the patient. CONCLUSIONS: Even after controlling for appropriateness and necessity for coronary artery bypass graft surgery in a prospective study, African-American patients had significant access problems in obtaining coronary artery bypass graft surgery. These problems appeared not to be related to patient refusals.


Subject(s)
Black or African American/statistics & numerical data , Coronary Artery Bypass/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Hispanic or Latino/statistics & numerical data , White People/statistics & numerical data , Aged , Coronary Angiography , Female , Health Services Accessibility/standards , Health Services Research , Humans , Male , Middle Aged , Multivariate Analysis , New York , Patient Selection , Practice Guidelines as Topic , Prospective Studies , Referral and Consultation/statistics & numerical data , Severity of Illness Index , Sex Factors
17.
J Invasive Cardiol ; 11 Suppl B: 6B-13B, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10745611

ABSTRACT

OBJECTIVES: A new percutaneous collagen hemostasis device was compared with conventional compression techniques after diagnostic catheterization and angioplasty. Background. Peripheral vascular complications after diagnostic catheterization or more complex interventional procedures, as well as the discomfort of manual compression and prolonged bed rest, represent significant morbidity for invasive cardiac procedures. METHODS: A prospective, multicenter, randomized trial was designed to compare the hemostasis time in minutes and the incidence of vascular complications in patients receiving a vascular hemostasis device with those undergoing conventional compression techniques. RESULTS: After diagnostic catheterization, hemostasis time was significantly less with the vascular hemostasis device than with conventional manual compression (4.1 +/- 2.8 min [n=90 patients] vs. 17.6 +/- 9.2 min [n= 75], p < 0.0001). This difference was greater in patients undergoing angioplasty and was unrelated to the anticoagulation status (4.3 +/- 3.7 min [n = 71 not receiving the heparin], 7.6 +/- 11.6 min [n= 85 receiving heparin], 33.6 +/- 24.2 min [n= 134 control patients not receiving heparin], p < 0.0001 vs. control patients). The time from the start of the procedure to ambulation was slightly less after diagnostic catheterization in patients treated with the device (13.3 +/- 12.1 hours vs. 19.2 +/- 17.8 hours, p < 0.05). It was also less in patients who underwent angioplasty when the device was used after discontinuation of anticoagulation (23.0 +/- 11.1 hours, without heparin), as compared with control compression techniques (32.7 +/- 18.8 hours, p < 0.0001). Time to ambulation was even shorter (16.1 +/- 11.1 h, p < 0.0001) in patients in whom the device was placed immediately after angioplasty while they were still fully anticoagulated with a prolonged activated clotting time (336 +/- 85 s). There were no major complications (surgery or transfusion) after diagnostic catheterization and a low incidence of major complications in patients who underwent angioplasty (0.7% in control patients, 1.4% with the device without heparin, 1.2% with the device and heparin, p = NS). After angioplasty, there was a trend toward fewer hematomas when the device was used in the absence of heparin (4.2% vs. 9.7% in control patients, p = 0.14). CONCLUSION: A new vascular hemostasis device can significantly reduce the puncture site hemostasis time and the time to ambulation without significantly increasing the risk of peripheral vascular complications The role of this technology in reducing complications, length of hospital stay and cost remains to be determined.


Subject(s)
Angioplasty, Balloon/adverse effects , Cardiac Catheterization/adverse effects , Hemostatic Techniques , Postoperative Hemorrhage/prevention & control , Pressure , Aged , Collagen/therapeutic use , Equipment and Supplies , Female , Femoral Artery/injuries , Hemostatics/therapeutic use , Humans , Male , Middle Aged , Needlestick Injuries/etiology , Needlestick Injuries/therapy , Postoperative Hemorrhage/etiology , Prospective Studies
18.
J Thorac Cardiovasc Surg ; 115(1): 168-76; discussion 176-7, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9451061

ABSTRACT

OBJECTIVES: Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, can be delivered to targeted tissues by means of a replication-deficient adenovirus (Ad) vector. We hypothesized that direct administration of Ad vector expressing the VEGF121 complementary deoxyribonucleic acid (AdGVVEGF121.10) into regions of ischemic myocardium would enhance collateral vessel formation and improve regional perfusion and function. METHODS: Yorkshire swine underwent thoracotomy and placement of an Ameroid constrictor (Research Instruments & MFG, Corvallis, Ore.) on the circumflex coronary artery. Three weeks later, myocardial perfusion and function were assessed by single photon emission computed tomography imaging (SPECT) with 99mTc-labeled sestamibi and by echocardiography during rest and stress. AdGVVEGF121.10 (n = 7) or the control vector, AdNull (n = 8), was administered directly into the myocardium at 10 sites in the circumflex distribution (10(8) pfu/site). Four weeks later, these studies were repeated and ex vivo angiography was performed. RESULTS: SPECT imaging 4 weeks after vector administration demonstrated significant reduction in the ischemic area at stress in AdGVVEFG121.10-treated animals compared with AdNull control animals (p = 0.005). Stress echocardiography at the same time demonstrated improved segmental wall thickening in AdGVVEGF121.10 animals compared with AdNull control animals (p = 0.03), with AdGVVEGF121.10 animals showing nearly normalized function in the circumflex distribution. Collateral vessel development assessed by angiography was also significantly greater in AdGVVEGF121.10 animals than in AdNull control animals (p = 0.04), with almost complete reconstitution of circumflex filling in AdGVVEGF121.10 animals. CONCLUSIONS: An Ad vector expressing the VEGF121 cDNA induces collateral vessel development in ischemic myocardium and results in significant improvement in both myocardial perfusion and function. Such a strategy may be useful in patients with ischemic heart disease in whom complete revascularization is not possible.


Subject(s)
DNA, Complementary/therapeutic use , Endothelial Growth Factors/therapeutic use , Gene Transfer Techniques , Genetic Vectors , Lymphokines/therapeutic use , Myocardial Ischemia/therapy , Neovascularization, Physiologic/drug effects , Adenoviridae/genetics , Animals , Echocardiography , Exercise Test , Humans , Myocardial Contraction/physiology , Myocardial Ischemia/diagnosis , Myocardial Ischemia/physiopathology , Radiopharmaceuticals , Swine , Technetium Tc 99m Sestamibi , Tomography, Emission-Computed, Single-Photon , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
19.
J Clin Invest ; 100(9): 2182-8, 1997 Nov 01.
Article in English | MEDLINE | ID: mdl-9410894

ABSTRACT

Cells proliferating from human atherosclerotic lesions are resistant to the antiproliferative effect of TGF-beta1, a key factor in wound repair. DNA from human atherosclerotic and restenotic lesions was used to test the hypothesis that microsatellite instability leads to specific loss of the Type II receptor for TGF-beta1 (TbetaR-II), causing acquired resistance to TGF-beta1. High fidelity PCR and restriction analysis was adapted to analyze deletions in an A10 microsatellite within TbetaR-II. DNA from lesions, and cells grown from lesions, showed acquired 1 and 2 bp deletions in TbetaR-II, while microsatellites in the hMSH3 and hMSH6 genes, and hypermutable regions of p53 were unaffected. Sequencing confirmed that these deletions occurred principally in the replication error-prone A10 microsatellite region, though nonmicrosatellite mutations were observed. The mutations could be identified within specific patches of the lesion, while the surrounding tissue, or unaffected arteries, exhibited the wild-type genotype. This microsatellite deletion causes frameshift loss of receptor function, and thus, resistance to the antiproliferative and apoptotic effects of TGF-beta1. We propose that microsatellite instability in TbetaR-II disables growth inhibitory pathways, allowing monoclonal selection of a disease-prone cell type within some vascular lesions.


Subject(s)
Arteriosclerosis/genetics , Receptors, Transforming Growth Factor beta/genetics , Arteriosclerosis/pathology , Atherectomy , Base Sequence , Cells, Cultured , Coronary Vessels , Humans , Mammary Arteries , Microsatellite Repeats , Mutation , Protein Serine-Threonine Kinases , Receptor, Transforming Growth Factor-beta Type II , Risk Factors
20.
Am J Cardiol ; 80(10A): 99K-105K, 1997 Nov 20.
Article in English | MEDLINE | ID: mdl-9409697

ABSTRACT

In the New Approaches to Coronary Intervention (NACI) registry, 887 patients were electively treated with excimer laser coronary angioplasty (ELCA) for coronary artery disease. The Advanced Interventional System (AIS) system was used in 487 cases; the Spectranetics system, in 400. The mean age was 63.4 years. Most patients had unstable angina (60.3%); 43.7% had a prior myocardial infarction; and 18.6% were high risk or inoperable patients. Mean ejection fraction was 55.4%. A total of 1,000 lesions were treated in the 887 patients. Of the 1,000 lesions treated with ELCA in the 887 patients, 36% were in the right coronary artery; 33%, left anterior descending; 13%, circumflex; 3%, left main; and 16.6%, vein graft. By angiographic core laboratory analysis available for 752 (85%) patients with 839 lesions, lesions were 12.76 mm long. The minimum lumen diameter increased to 1.29 mm after the laser and finally to 1.95 mm after adjunctive percutaneous transluminal coronary angioplasty (PTCA) (which was performed in 93% of all lesions), with a final residual stenosis of 32.1% and Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in 95%. Dissections of grades B, C, or D were seen after 22.0% of initial laser attempts, and postlaser perforations were noted in 2.6%. Additional such dissections accumulated after adjunctive PTCA but the perforation rate remained low. Procedural success was achieved in 84% of patients, but 1.2% died, 0.7% experienced Q-wave myocardial infarction (MI), and 2.7% required emergency bypass surgery. Multiple logistic regression analysis could not identify any independent predictors of these in-hospital complications. One-year mortality was 5.7% and the cumulative incidence of Q-wave MI was 1.5%. Coronary artery bypass graft (CABG) surgery was performed in 15.0% of patients whereas 25.5% required repeat percutaneous intervention with a target lesion revascularization rate of 31%. Independent predictors of death, Q-wave MI, or target lesion revascularization (which, combined, occurred in 35.6% of patients) were the absence of prior MI, ELCA in the circumflex, perforation after the procedure, and small (<2 mm) final minimal lumen diameter. Considering the large number of patients with high-risk lesions, laser angioplasty was performed with excellent procedural success rates and a reasonable incidence of major complications.


Subject(s)
Angioplasty, Laser/methods , Coronary Disease/surgery , Registries , Aged , Angioplasty, Balloon, Coronary/statistics & numerical data , Angioplasty, Laser/instrumentation , Angioplasty, Laser/statistics & numerical data , Coronary Disease/mortality , Coronary Disease/therapy , Female , Follow-Up Studies , Humans , Logistic Models , Male , Middle Aged , Predictive Value of Tests , Treatment Outcome
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