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2.
Ann Cardiol Angeiol (Paris) ; 64(6): 427-33, 2015 Dec.
Article in French | MEDLINE | ID: mdl-26547524

ABSTRACT

Data on regional variations in the characteristics, management and early outcome of patients admitted with ST-elevation myocardial infarction (STEMI) in France are limited. We used data from the FAST-MI 2010 registry to determine whether regional specificities existed, dividing the French territory into 6 larger geographical regions. Variations in the patients' characteristics were found, partly related to regional variations in demography. Acute reperfusion strategy showed more use of primary percutaneous coronary intervention in the greater Paris area, compared to other regions, which would be expected owing to geography and local availability of catheterization laboratories. Overall, however, in-hospital management showed more similarities than differences across regions. Complications, and in particular in-hospital mortality, did not differ significantly among regions.


Subject(s)
Heart Conduction System/physiopathology , Myocardial Infarction/epidemiology , Myocardial Infarction/therapy , Myocardial Reperfusion/methods , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Drug Therapy, Combination , Female , France/epidemiology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Myocardial Infarction/mortality , Myocardial Infarction/physiopathology , Percutaneous Coronary Intervention/methods , Prevalence , Risk Factors , Treatment Outcome
4.
Phytomedicine ; 17(10): 714-20, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20171066

ABSTRACT

Thymoquinone (TQ) is the main constituent of Nigella sativa essential oil which shows promising in vitro and in vivo antineoplastic growth inhibition against various tumor cell lines. Because of the increasing interest to test it in pre-clinical and clinical researches for assessing its health benefits, we here evaluate the interactions between TQ and human serum albumin (HSA), a possible carrier of this drug in vivo. Binding to HSA was studied using different spectroscopic techniques. Fourier transform infrared (FT-IR) and circular dichroism (CD) spectroscopies suggest that the association between TQ and HSA does not affect the secondary structure of HSA. Using fluorescence spectroscopy, one mole of TQ was found to bind one mole of HSA with a binding constant of 2.39 +/- 0.2 10(4)M(-1). At 25 degrees C (pH 7.4), van't Hoff's enthalpy and entropy that accompany the binding were found to be -10.24 kJ/mol(-1) and 45 J/mol(-1)K(-1) respectively. The thermodynamic analysis of the TQ-HSA complex formation shows that the binding process is enthalpy driven and spontaneous, and that hydrophobic interactions are the predominant intermolecular forces stabilizing the complex. Furthermore, displacement experiments using warfarin and ibuprofen indicate that TQ could bind to site I of HSA, which is also in agreement with the results of the molecular modeling study.


Subject(s)
Benzoquinones/metabolism , Nigella sativa/chemistry , Serum Albumin/metabolism , Benzoquinones/isolation & purification , Binding Sites , Circular Dichroism , Humans , Models, Molecular , Protein Structure, Secondary , Spectrometry, Fluorescence , Spectroscopy, Fourier Transform Infrared
5.
Arch Cardiovasc Dis ; 101(1): 41-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18391872

ABSTRACT

BACKGROUND: Since the early reports on the incidence of mechanical complications of acute myocardial infarction (AMI) assessed by echocardiography published in the 1980s, the management of patients with AMI has changed considerably, in particular with the progressive development of early revascularisation. METHODS: The aim of this multicentre study was to assess the incidence of mechanical complications of AMI in the reperfusion era. Nine-hundred and eight consecutive patients were included. Echocardiography was performed on admission and at discharge. Seventy-eight percent of patients were revascularised at the acute phase. RESULTS: The following incidence rates of mechanical complications were observed: mitral regurgitation 28%, secondary to left ventricular (LV) remodelling (43%) or papillary muscle dysfunction (57%); pericardial effusion 6.6%, more frequent after anterior AMI and associated with a lower ejection fraction (EF); LV thrombus 2.4%, mainly after anterior AMI and associated with a lower EF (38+/-10% vs. 48+/-12%; p<0.001); early infarct expansion 4%; septal rupture 0.6%; and acute free wall rupture 0.8%. The following factors were independently associated with the occurrence of mechanical complications by multivariate logistic regression analysis: lack of early revascularisation (OR 3.48, 95%CI 1.36-8.95; p<0.001), LV-EF<50% (OR 1.95, 95%CI 1.42-2.67; p<0.001), Killip class>II (OR 1.91, 95%CI 1.27-2.87; p<0.002) and age > or =70 years (OR 1.42, 95%CI 1.03-1.97; p<0.03). CONCLUSION: This study demonstrates the favourable prognostic influence of early revascularisation as shown by the low incidence of mechanical complications after AMI, and underlines the persistent relationship between the development of these complications and depressed LV function.


Subject(s)
Echocardiography, Doppler , Heart Diseases/diagnostic imaging , Myocardial Infarction/therapy , Myocardial Reperfusion , Age Factors , Aged , Female , France , Heart Diseases/etiology , Heart Diseases/physiopathology , Heart Diseases/prevention & control , Humans , Incidence , Logistic Models , Male , Middle Aged , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/prevention & control , Myocardial Infarction/complications , Myocardial Infarction/diagnostic imaging , Myocardial Reperfusion/methods , Odds Ratio , Papillary Muscles/diagnostic imaging , Pericardial Effusion/diagnostic imaging , Pericardial Effusion/prevention & control , Prospective Studies , Registries , Research Design , Risk Assessment , Risk Factors , Severity of Illness Index , Stroke Volume , Thrombosis/diagnostic imaging , Thrombosis/prevention & control , Time Factors , Treatment Outcome , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/prevention & control , Ventricular Function, Left , Ventricular Remodeling , Ventricular Septal Rupture/diagnostic imaging , Ventricular Septal Rupture/prevention & control
6.
Biochim Biophys Acta ; 1780(4): 627-37, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18206117

ABSTRACT

The reactivity of thymoquinone towards different redox states of hemoglobin and myoglobin in the presence of GSH, NADH, and NADPH was evaluated by optical spectral analysis. Thymoquinone reduces the ferryl forms (HbIV/MbIV) of both met-hemoglobin (HbIII) and met-myoglobin (MbIII) to oxy-hemoglobin (HbIIO2) and oxy-myoglobin (MbIIO2) under physiological conditions. The reaction is mediated by the intermediate quinone forms of TQ, that is, glutathionyl-dihydrothymoquinone (DHTQ-GS) and dihydrothymoquinone (DHTQ), formed from direct interaction of TQ with GSH or NADH (NADPH). In vitro incubation of oxidized human erythrocytes with TQ, DHTQ, and the GSH/TQ mixture reduces the intracellular met-Hb at different rates. In the present study, we report that TQ and its reduced derivatives can also prevent lipid peroxidation induced by the MbFeIII/H2O2 system. In this system, lipid peroxidation is induced by MbIV or a putative MbIV/.MbVI composite; it is plausible that the antioxidant function of TQ derivatives is related to their ability to reduce these oxidizing species. This is of particular biological significance, as natural quinones may participate in reducing processes that lead to recovery of hemoglobin and myoglobin during oxidative stress.


Subject(s)
Benzoquinones/chemistry , Hemoglobins/chemistry , Myoglobin/chemistry , Erythrocytes/chemistry , Erythrocytes/cytology , Glutathione/chemistry , Hemoglobin A/chemistry , Humans , Metmyoglobin/chemistry , Models, Chemical , NAD/chemistry , NADP/chemistry , Oxidation-Reduction , Oxyhemoglobins/chemistry , Spectrophotometry
7.
Free Radic Res ; 41(2): 153-61, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17364941

ABSTRACT

Thymoquinone (TQ) is the bioactive constituent of the volatile oil of Nigella sativa L. and has been shown to exert antioxidant antineoplastic and anti-inflammatory effects. During the study of its possible mechanism of action, we found that TQ reacts chemically (i.e. nonenzymatically) with glutathione (GSH), NADH and NADPH. A combination of liquid chromatography/UV-Vis spectrophotometry/Mass spectrometry analyses was used to identify the products of these reactions. The reaction that occur in physiological conditions indicates the formation of only two products, glutathionyl-dihydrothymoquinone after rapid reaction with GSH, and dihydrothymoquinone (DHTQ) after slow reaction time with NADH and NADPH. Measurement of the antioxidant activity of reduced compounds against organic radicals such as 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) also revealed a potential scavenging activity for glutathionyl-dihydrothymoquinone similar to that of DHTQ. Under our experimental conditions, TQ shows lower scavenging activities than glutathionyl-dihydrothymoquinone and DHTQ; it is very interesting to observe that the reduced compounds apparently show an antioxidant capacity equivalent to Trolox. The results indicate a possible intracellular nonenzymatic metabolic activation of TQ dependent on GSH, NADH or NADPH that may represent a "cellular switch" able to modulate cellular antioxidant defences.


Subject(s)
Antioxidants/metabolism , Benzoquinones/metabolism , Free Radical Scavengers/metabolism , Antioxidants/pharmacology , Benzoquinones/pharmacology , Benzothiazoles/metabolism , Biphenyl Compounds/metabolism , Chromans/pharmacology , Chromatography, High Pressure Liquid , Erythrocytes/metabolism , Free Radical Scavengers/pharmacology , Glutathione/metabolism , Humans , Hydrazines/metabolism , Molecular Structure , NAD/metabolism , NADP/metabolism , Oxidation-Reduction , Picrates , Sulfonic Acids/metabolism
8.
Eur J Heart Fail ; 4(5): 647-54, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12413509

ABSTRACT

BACKGROUND: In patients with congestive heart failure (CHF), clinical trials have demonstrated the benefit of a number of drugs on morbidity and mortality. Nevertheless so far, there is no published controlled study of long-term antithrombotic therapy in patients with CHF. The aim of this work was to identify the relationship between cardiovascular drug use, especially antithrombotic therapy, and survival of CHF patients in current clinical practice, using an observational, population-based database. METHODS: The EPICAL study (Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine) has identified prospectively all patients with severe CHF in the community of Lorraine. Inclusion criteria were age 20-80 years in 1994, at least one hospitalisation for cardiac decompensation, NYHA III/IV HF, ventricular ejection fraction < or =30% or cardiothoracic index > or =60% and arterial hypotension or peripheral and/or pulmonary oedema. A total of 417 consecutive patients surviving at hospital discharge were included in the database. The average follow-up period was 5 years. Univariate Cox models were used to test the relationship of baseline biological and clinical factors to survival. Cardiovascular drug prescriptions were tested in a multivariate Cox model adjusted by other known predictive factors. RESULTS: Duration of disease >1 year, renal failure, serum sodium > or =138 mmol/l, old age, serious comorbidity, previous decompensation, high doses of furosemide and vasodilators use were independently associated with poor prognosis at 1 and 5 years. Oral anticoagulants, aspirin, lipid lowering drugs and beta-blockers use were associated with better survival. There was no interaction between aspirin and angiotensin converting enzyme inhibitor use on survival. CONCLUSION: Antithrombotic therapy was associated with a better long-term survival in our study population of severe CHF. These results together with other previously published circumstantial evidence urge for a prospective, controlled and randomised trial specifically designed to evaluate optimal oral anticoagulants and aspirin in patients with congestive heart failure.


Subject(s)
Fibrinolytic Agents/therapeutic use , Heart Failure/drug therapy , Heart Failure/mortality , Ventricular Dysfunction, Left/drug therapy , Ventricular Dysfunction, Left/mortality , Adrenergic beta-Antagonists/therapeutic use , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Controlled Clinical Trials as Topic , Databases, Factual , Dose-Response Relationship, Drug , Female , Follow-Up Studies , France/epidemiology , Heart Failure/physiopathology , Humans , Hypolipidemic Agents/therapeutic use , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Survival Analysis , Systole/drug effects , Systole/physiology , Treatment Outcome , Ventricular Dysfunction, Left/physiopathology
9.
Catheter Cardiovasc Interv ; 54(3): 276-82, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11747149

ABSTRACT

The objectives of the Race Car study were to assess the safety and efficacy of the Medtronic AVE S670 stent, a new-generation stent with a modular design consisting of interconnected sinusoidal rings allowing improved flexibility with good conformability and scaffolding. A total of 285 stents were implanted in 267 patients with (un)stable angina pectoris who underwent angioplasty of a single de novo lesion in a native coronary artery with a diameter between 3.0 and 4.0 mm. Available stent lengths were 9, 12, and 15 mm. The primary endpoint was the 6-month restenosis rate. Secondary endpoints were device and procedural success and major adverse cardiac event (MACE)-free survival at 1 and 6 months. All patients received the study stents and no other stents were used (angiographic success: 100%). Eight patients experienced a MACE during hospital admission (Q-wave MI in 2, non-Q-wave MI in 4, TLR in 2). A procedural success was obtained in 97% of the patients. There were no additional events at 1 month. The clinical endpoints encountered at 6 months were Q-wave MI in 1, bypass surgery in 3, and repeat angioplasty in 25 (MACE-free survival: 86.5%). Quantitative angiographic results were the minimum lumen diameter increased from 1.05 +/- 0.32 before to 2.73 +/- 0.39 mm after stent implantation. At follow-up, the loss in diameter was 0.74 +/- 0.50 mm. The loss index was 0.45 +/- 0.31 and restenosis rate was 13.4%. This study has demonstrated that the S670 stent in patients with (un)stable angina pectoris requiring intervention of a single lesion has a low acute and 6-month major event rate and a low angiographic restenosis rate.


Subject(s)
Angina Pectoris/diagnostic imaging , Angina Pectoris/surgery , Coronary Angiography , Stents , Aged , Angina Pectoris/complications , Blood Vessel Prosthesis Implantation/instrumentation , Coronary Angiography/instrumentation , Coronary Stenosis/complications , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/surgery , Electrocardiography , Equipment Design , Europe/epidemiology , Evaluation Studies as Topic , Female , Follow-Up Studies , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome
10.
Presse Med ; 30(31 Pt 1): 1539-48, 2001 Oct 27.
Article in French | MEDLINE | ID: mdl-11721493

ABSTRACT

OBJECTIVE: This pharmacoeconomic study was conducted to determine the cost of using tinzaparin, a low-molecular-weight heparin (LMWH), administered intravenously, in comparison with non-fractionated heparin (NFH) for the treatment of acute pulmonary embolism (PE) in France. METHODS: A decision algorithm indicating the therapeutic schedules and their consequences was constructed from data collected during a large-scale multicentric study and from data obtained from interviews with French physicians implicated in the treatment of pulmonary embolism. This model was used to estimate costs and to compare per patient expenditures for the two therapeutic schedules. RESULTS: Cost of instituting treatment per patient (excluding costs common to both schedules) was 202 euros for NFH and 77 euros for tinzaparin (delta 125 euros in favor of tinzaparin). Including follow-up costs for the 90 day analysis period, tizaparin reduced costs by 123 euros per patient (211 versus 334 euros for patients treated with NFH). Taking into account the sole cost of management of the two critical events that occurred during NFH or tinzaparin (8 first days) treatment, tinzaparin reduced costs by 137 euros per patient (112 euros versus 249 euros respectively). CONCLUSION: Tinzaparin reduced health care costs for pulmonary embolism due to easier administration, less complex laboratory tests, and personnel time savings. The robustness of the results was confirmed by the sensitivity analysis.


Subject(s)
Fibrinolytic Agents/economics , Fibrinolytic Agents/therapeutic use , Heparin, Low-Molecular-Weight/economics , Heparin, Low-Molecular-Weight/therapeutic use , Pulmonary Embolism/drug therapy , Acute Disease , Costs and Cost Analysis , Decision Trees , France , Humans , Tinzaparin
11.
Circulation ; 104(14): 1604-8, 2001 Oct 02.
Article in English | MEDLINE | ID: mdl-11581136

ABSTRACT

BACKGROUND: Stenting has been demonstrated to be superior to balloon angioplasty in de novo focal lesions located in large native vessels. However, in small vessels, the benefit of stenting remains questionable. METHODS AND RESULTS: A total of 381 symptomatic patients with de novo focal lesion located on a small coronary segment vessel (<3 mm) were randomly assigned to either stent implantation (192 patients; 197 lesions) or standard balloon angioplasty (189 patients; 198 lesions). The primary end point was the angiographic restenosis rate at 6 months, as determined by quantitative coronary angiography. On intention-to-treat analysis, angiographic success rate and major adverse cardiac events were comparable: 97.9% and 4.6% versus 93.9% and 5.8% in the stent group and the balloon group, respectively. After the procedure, a larger acute gain was achieved with stent placement (1.35+/-0.45 versus 0.94+/-0.47 mm, P=0.0001), resulting in a larger minimal lumen diameter (2.06+/-0.42 versus 1.70+/-0.46 mm, P=0.0001). At follow-up (obtained in 91% of patients), angiographic restenosis rate was 21% in the stent group versus 47% in the balloon group (P=0.0001), a risk reduction of 55%. Repeat target lesion revascularization was less frequent in the stent group (13% versus 25%, P=0.0006). CONCLUSIONS: Elective stent placement in small coronary arteries with focal de novo lesions is safe and associated with a marked reduction in restenosis rate and subsequent target lesion revascularization rate at 6 months.


Subject(s)
Coronary Disease/prevention & control , Coronary Vessels , Myocardial Revascularization/methods , Stents , Angioplasty, Balloon, Coronary/methods , Coronary Angiography , Coronary Disease/diagnostic imaging , Coronary Disease/mortality , Female , Follow-Up Studies , Hospitalization , Humans , Male , Middle Aged , Survival Rate , Treatment Outcome
12.
J Cardiovasc Electrophysiol ; 12(4): 479-86, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11332572

ABSTRACT

INTRODUCTION: The properties and substrates of slow and fast AV nodal pathway remain unclear. This applies particularly to the slow pathway (SP), which is largely concealed by fast pathway (FP) conduction. We designed a new FP ablation approach that exposes the SP over the entire cycle length range and allows for its independent characterization and ablation. METHODS AND RESULTS: Premature stimulation was performed before and after FP ablation with 5.4 +/- 1.9 lesions (300-microm diameter each; overall lesion size 1.4 +/- 0.5 mm) targeting the junction between perinodal and compact node tissues in seven rabbit heart preparations. The resulting SP recovery curve and control curve had the same maximum nodal conduction time (165 +/- 22 msec vs 164 +/- 24 msec; P = NS) and effective refractory period (101 +/- 10 msec vs 100 +/- 9 msec; P = NS). The two curves covered the same cycle length range. However, the SP curve was shifted up with respect to control one at intermediate and long cycle lengths and thus showed a longer minimum nodal conduction time (81 +/- 15 msec vs 66 +/- 10 msec; P < 0.01) and functional refractory period (180 +/- 11 msec vs 170 +/- 12 msec; P < 0.05). The SP curve was continuous and closely fitted by a single exponential function. Small local lesions (2 +/- 1) applied to the posterior nodal extension resulted in third-degree nodal block in all preparations. CONCLUSION: The posterior nodal extension can sustain effective atrial-His conduction at all cycle lengths and account for both the manifest and concealed portion of SP. Slow and FP conduction primarily arise from the posterior extension and compact node, respectively.


Subject(s)
Atrioventricular Node/physiology , Animals , Atrial Function , Bundle of His/physiology , Heart Arrest, Induced , In Vitro Techniques , Neural Conduction/physiology , Neural Pathways/physiology , Rabbits , Refractory Period, Electrophysiological , Time Factors
13.
Am J Cardiol ; 87(6): 693-8, 2001 Mar 15.
Article in English | MEDLINE | ID: mdl-11249885

ABSTRACT

The purpose of this study was to compare the effects of stent placement with and without balloon predilatation on duration of the procedure, reduction of procedure-related costs, and clinical outcomes. Although preliminary trials of direct coronary stenting have demonstrated promising results, the lack of randomized studies with long-term follow-up has limited the critical evaluation of the role of direct stenting in the treatment of obstructive coronary artery disease. Between January and September 1999, 338 patients were randomly assigned to either direct stent implantation (DS+; 173 patients) or standard stent implantation with balloon predilatation (DS-; 165 patients). Baseline clinical and angiographic characteristics were similar in the 2 groups. Procedural success was achieved in 98.3% of patients assigned to DS+ and 97.5% of patients assigned to DS- (p = NS), with a crossover rate of 13.9%. Compared with DS-, DS+ conferred a dramatic reduction in procedure-related cost ($956.4 +/- $352.2 vs $1,164.6 +/- $383.9, p <0.0001) and duration of the procedure (424.2 +/- 412.1 vs 634.5 +/- 390.1 seconds, p < 0.0001). At 6-month follow-up, the incidence of major adverse cardiac events including death, angina pectoris, myocardial infarction, congestive heart failure, repeat angioplasty, or coronary artery bypass graft surgery was 5.3% in DS+ and 11.4% in DS- (p = NS). Multivariate analysis demonstrated that major adverse cardiac events rates were related to stent length of 10 mm (relative risk [RR] 3.25, 95% confidence intervals [CI] 1.36 to 7.78; p = 0.008), stent diameter of 3 mm (RR 2.69, 95% CI 1.03 to 7.06; p = 0.043), and complex lesion type C (RR 2.83, 95% CI 1.02 to 7.85; p = 0.045). Thus, in selected patients, this prospective randomized study shows the feasibility of DS+ with reduction in procedural cost and length, and without an increase in in-hospital clinical events and major adverse cardiac events at 6-month follow-up.


Subject(s)
Angina Pectoris/therapy , Angioplasty, Balloon, Coronary , Stents , Angina Pectoris/diagnostic imaging , Angina Pectoris/economics , Angina Pectoris/mortality , Angioplasty, Balloon, Coronary/adverse effects , Angioplasty, Balloon, Coronary/economics , Coronary Angiography , Cost Savings , Feasibility Studies , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Risk Factors , Stents/adverse effects , Stents/economics , Survival Rate
14.
J Interv Cardiol ; 14(1): 1-5, 2001 Feb.
Article in English | MEDLINE | ID: mdl-12053317

ABSTRACT

The Tenax coronary stent is laser sculpted from high precision 316 L stainless steel using advanced production procedures. An a-SiC: H (hydrogen-rich amorphous silicon carbide) coating reduces its thrombogenicity and improves its biocompatibility. From April to July 1998, 266 stents were implanted in 241 patients (aged 62.7 +/- 10.5 years) in five centers. The clinical indication for intervention was unstable angina (33.2%) and recent myocardial infarction (29.5%) in many cases. Most lesions (53.8%) had complex characteristics (Class B2 or C). The target vessel was the LAD in 42.5% and the right coronary artery in 36.8% of all cases. Four primary stent deployment failures occurred and implantation was successful in 259 (97.4%) of 266 stents. No death and no Q-wave myocardial infarction or emergency CABG occurred during hospital stay. Clinical success, defined as successful deployment without procedural or clinical event, was achieved in 230 (95.4%) of 241 patients. One-year clinical follow-up shows a low need for target lesion revascularization (17/237 [7.1%] patients) and a 15.8% rate of major adverse cardiac events (36/237 patients). The clinical and angiographic outcomes of our study suggest that the hybrid, amorphous hydrogenated silicon carbide coated design is promising and merits further evaluation in larger clinical trials.


Subject(s)
Angina, Unstable/therapy , Biocompatible Materials , Carbon Compounds, Inorganic , Coated Materials, Biocompatible , Coronary Vessels , Myocardial Infarction/therapy , Silicon Compounds , Stainless Steel , Stents , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged
15.
Eur Heart J ; 21(21): 1767-75, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11052841

ABSTRACT

BACKGROUND: We hypothesized that intramural delivery of nadroparin, a low molecular weight heparin, would prevent in-stent restenosis by inhibiting neointimal hyperplasia in an angioplasty model free of arterial remodelling. METHODS AND RESULTS: In a prospective randomized multicentre trial, 250 patients submitted to balloon angioplasty followed by stent implantation were randomized into control group (no local drug delivery) or intramural delivery of nadroparin (2 ml of 2500 anti-Xa-units/ml with a microporous catheter). An ancillary intravascular ultrasound substudy was performed to supplement angiographic data with specific measurements of in-stent neointimal hyperplasia. The primary end-point was the late loss in minimal luminal diameter on the 6 month follow-up angiogram. Secondary end-points included feasibility and safety of local nadroparin delivery, and major adverse cardiac events at 8 weeks and 6 months follow-up. Local delivery of nadroparin was successful in 124 patients (99.2% success rate) and was not associated with an increase in stent thrombosis, coronary artery dissection, side branch occlusion, distal embolization or abrupt arterial closure. At angiographic follow-up, the late loss in lumen diameter was 0.84 +/- 0.62 mm in the control group compared to 0.88 +/- 0.63 mm in the nadroparin group (P=0.56). Angiographic restenosis rate (defined as a >50% diameter stenosis) did not differ in the control group (20%) compared to the nadroparin group (24%). The average area of neointimal tissue within the stent was 2.86 +/- 0.64 mm(2) vs 2.90 +/- 0.53 mm(2) (P=0.57), control vs nadroparin groups. There was no difference in major adverse cardiac events at any time (88.8% vs 89.6% event free survival at 6 months, control vs nadroparin). CONCLUSION: Intramural delivery of nadroparin with a microporous catheter after stent deployment was feasible and safe but had no effect in reducing restenosis or the occurrence of major adverse clinical events over 6 months.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Coronary Disease/drug therapy , Hyperplasia/pathology , Nadroparin/administration & dosage , Stents/adverse effects , Tunica Intima/drug effects , Adult , Aged , Coronary Angiography , Coronary Disease/diagnostic imaging , Coronary Disease/therapy , Female , Follow-Up Studies , Humans , Injections, Intralesional , Male , Middle Aged , Probability , Prospective Studies , Reference Values , Secondary Prevention , Treatment Outcome , Tunica Intima/pathology , Ultrasonography, Interventional , Vascular Patency
16.
J Am Coll Cardiol ; 35(7): 1729-36, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10841218

ABSTRACT

OBJECTIVES: In a multicenter, randomized trial, systematic stenting using the Wiktor stent was compared to conventional balloon angioplasty with provisional stenting for the treatment of acute myocardial infarction (AMI). BACKGROUND: Primary angioplasty in AMI is limited by in-hospital recurrent ischemia and a high restenosis rate. METHODS: A total of 211 patients with AMI <12 h from symptom onset, with an occluded native coronary artery, were randomly assigned to systematic stenting (n = 101) or balloon angioplasty (n = 110). The primary end point was the binary six-month restenosis rate determined by core laboratory quantitative angiographic analysis. RESULTS: Angiographic success (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3 and residual diameter stenosis <50%) was achieved in 86% of the patients in the stent group and in 82.7% of those in the balloon angioplasty group (p = 0.5). Compared with the 3% cross-over in the stent group, cross-over to stenting was required in 36.4% of patients in the balloon angioplasty group (p = 0.0001). Six-month binary restenosis (> or = 50% residual stenosis) rates were 25.3% in the stent group and 39.6% in the balloon angioplasty group (p = 0.04). At six months, the event-free survival rates were 81.2% in the stent group and 72.7% in the balloon angioplasty group (p = 0.14), and the repeat revascularization rates were 16.8% and 26.4%, respectively (p = 0.1). At one year, the event-free survival rates were 80.2% in the stent group and 71.8% in the balloon angioplasty group (p = 0.16), and the repeat revascularization rates were 17.8% and 28.2%, respectively (p = 0.1). CONCLUSIONS: In the setting of primary angioplasty for AMI, as compared with a strategy of conventional balloon angioplasty, systematic stenting using the Wiktor stent results in lower rates of angiographic restenosis.


Subject(s)
Angioplasty, Balloon , Myocardial Infarction/therapy , Stents , Angioplasty, Balloon, Coronary , Female , Follow-Up Studies , Humans , Male , Middle Aged
17.
J Cardiovasc Electrophysiol ; 10(11): 1439-51, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10571364

ABSTRACT

INTRODUCTION: The functional origin of AV nodal conduction, refractory, and dual pathway properties remains debated. The hypothesis that normal conduction and refractory properties of the compact node and its posterior nodal extension (PNE) play a critical role in the slow and the fast pathway, respectively, is tested with ablation lesions targeting these structures. METHODS AND RESULTS: A premature atrial stimulation protocol was performed before and after PNE ablation in six isolated rabbit heart preparations. Discrete (approximately 300 microm) histologically controlled PNE lesions amputated the AV nodal recovery curve from its left steep portion reflecting slow pathway conduction and prevented reentry without affecting the right smooth fast pathway portion of the curve. The ablation shortened A2H2max from 159 +/- 16 ms to 123 +/- 11 msec (P < 0.01) and prolonged the effective refractory period from 104 +/- 6 msec to 119 +/- 11 msec (P < 0.01) without affecting A2H2min (55 +/- 9 msec vs 55 +/- 8 msec; P = NS) and functional refractory period (174 +/- 7 msec vs 175 +/- 6 msec; P = NS). These results did not vary with the input reference used. In six other preparations, lesions applied to the compact node after PNE ablation shifted the fast pathway portion of the recovery curve to longer conduction times and prolonged the functional refractory period, suggesting a compact node involvement in the fast pathway. CONCLUSION: The normal AV nodal conduction and refractory properties reflect the net result of the interaction between a slow and a fast pathway, which primarily arise from the asymmetric properties of the PNE and compact node, respectively.


Subject(s)
Atrioventricular Node/physiology , Refractory Period, Electrophysiological/physiology , Animals , Atrioventricular Node/pathology , Atrioventricular Node/physiopathology , Cardiac Complexes, Premature/physiopathology , Cardiac Pacing, Artificial , Electrophysiology , In Vitro Techniques , Neural Pathways/physiology , Neural Pathways/physiopathology , Rabbits , Time Factors
18.
J Cardiovasc Electrophysiol ; 10(7): 954-64, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10413375

ABSTRACT

INTRODUCTION: The circuitry underlying AV nodal reentry remains debated. We developed a model of AV nodal reentry and assessed the role of nodal inputs, compact node, and its posterior nodal extension (PNE) in this phenomenon. METHODS AND RESULTS: A fine scanning of short coupling interval range with an atrial premature beat consistently initiated slow-fast AV nodal reentrant beats that occurred 37+/-31 msec (mean+/-SD) after His-bundle activation in 11 of 16 consecutive rabbit heart preparations. The repeated testing (>40 times) of a chosen coupling interval within reentry window (6+/-9 msec, n = 11) yielded reentrant intervals that varied by 2+/-1 msec (mean SD for 40 beats+/-SD, n = 11). The breakthrough point of reentrant activation, as assessed from four perinodal sites, varied in different preparations from diffuse (4) to anterior (1), medial (3), or posterior (3); mean reentrant interval did not differ between perinodal sites. Antegrade perinodal activation pattern did not differ at reentrant versus nonreentrant coupling intervals and thus was not a primary determinant of reentry. A PNE ablation (n = 4) interrupted the slow pathway conduction and prevented reentry without affecting antegrade perinodal activation or fast pathway conduction. CONCLUSION: A reproducible model of AV nodal reentrant beats was developed and used to study underlying circuitry. The AV nodal reentry involves unaltered antegrade perinodal activation, slow PNE conduction and retrograde broad invasion of perinodal tissues starting at a preparation-dependent breakthrough point. A PNE ablation abolishes the reentry.


Subject(s)
Atrioventricular Node/physiopathology , Catheter Ablation , Tachycardia, Atrioventricular Nodal Reentry/physiopathology , Animals , Atrioventricular Node/surgery , Bundle of His/physiopathology , Bundle of His/surgery , Disease Models, Animal , Electrocardiography , Heart Rate , Rabbits , Reproducibility of Results , Tachycardia, Atrioventricular Nodal Reentry/etiology , Tachycardia, Atrioventricular Nodal Reentry/surgery
19.
Arch Mal Coeur Vaiss ; 92(4): 427-30, 1999 Apr.
Article in French | MEDLINE | ID: mdl-10326151

ABSTRACT

The authors report the case of a 28 year old woman admitted as an emergency at 15 weeks' amenorrhea for malaise with transient aphasia and orthopnoea due to massive thrombosis of a St Jude aortic valve prosthesis implanted two years previously. This complication occurred after relay of oral anticoagulants with subcutaneous heparin therapy. After a medico-surgical and obstetrical discussion, the indication for thrombolytic therapy with 50 mg of rt-PA over two hours was decided with an excellent clinical and echocardiographic, immediate and lasting result, without any maternal or foetal complication. This enabled pregnancy to be continued to term under oral anti-coagulant therapy. Caesarean section was performed at 8 months leading to the birth of a healthy child. Echocardiographic and radioscopic parameters in the post-partum period showed good prosthetic valve function with no indication for reoperation. This case is original by the absence of neurological and obstetrical complications of thrombolysis, the continuation of pregnancy to term and complete lysis of the thrombus without replacement of the valvular prosthesis.


Subject(s)
Fibrinolytic Agents/therapeutic use , Heart Valve Prosthesis/adverse effects , Plasminogen Activators/therapeutic use , Pregnancy Complications, Cardiovascular/surgery , Thrombosis/etiology , Tissue Plasminogen Activator/therapeutic use , Adult , Aortic Valve Stenosis/surgery , Cesarean Section , Echocardiography , Female , Heparin/adverse effects , Humans , Pregnancy , Pregnancy Complications, Cardiovascular/diagnostic imaging , Pregnancy Outcome , Prosthesis Failure , Recombinant Proteins/therapeutic use , Thrombosis/drug therapy
20.
Circulation ; 98(2): 164-74, 1998 Jul 14.
Article in English | MEDLINE | ID: mdl-9679723

ABSTRACT

BACKGROUND: The AV node is frequently the site of reentrant rhythms. These rhythms arise from a slow and a fast pathway for which the anatomic and functional substratum remain debated. This study proposes a new explanation for dual-pathway physiology in which the posterior nodal extension (PNE) provides the substratum for the slow pathway. METHODS AND RESULTS: The anatomic and functional properties of the PNE were studied in 14 isolated rabbit heart preparations. A PNE was found in all studied preparations. It appeared as an elongated bundle of specialized tissues lying along the lower side of Koch's triangle between the coronary sinus ostium and compact node. No well-defined boundary separated the PNE, compact node, and lower nodal cell bundle. The electric properties of the PNE were characterized with a premature protocol and surface potential recordings from histologically controlled locations. The PNE showed cycle-length-dependent posteroanterior slow activation with a shorter refractory period (minimum local cycle length) than that of the compact node. During early premature beats resulting in block in transitional tissues, the markedly delayed PNE activation could propagate to maintain or resume nodal conduction and initiate reentrant beats. A shift to PNE conduction resulted in different patterns of discontinuity on conduction curves. Transmembrane action potentials recorded from PNE cells in 6 other preparations confirmed the slow nature of PNE potentials. CONCLUSIONS: The PNE is a normal anatomic feature of the rabbit AV node. It constitutes a cycle-length-dependent slow pathway with a shorter refractory period than that of the compact node. Propagated PNE activation can account for a discontinuity in conduction curves, markedly delayed AV nodal responses, and reentry. Finally, the PNE provides a substratum for the slow pathway in dual-pathway physiology.


Subject(s)
Atrioventricular Node/anatomy & histology , Atrioventricular Node/physiology , Action Potentials/physiology , Animals , Electrophysiology , In Vitro Techniques , Neural Pathways/anatomy & histology , Neural Pathways/physiology , Rabbits , Refractory Period, Electrophysiological/physiology
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