Therapeutic Angiogenesis Using Human VEGF-A165/bFGF Plasmid Injected Percutaneously Into the Ischemic Myocardium of "No-option" Coronary Artery Disease Patients; Double-blind Placebo Controlled Study

Achieving therapeutic angiogenesis with gene therapy using a plasmid coding human VEGF-A165/bFGF injected into ischemic myocardium of refractory coronary artery disease patients, employing a percutaneous catheter-based technique- a double-blind placebo controlled study.
Some patients with persistent coronary artery disease cannot be effectively treated using methods available today ("no-option" patients). It is currently evident that an emerging therapy for them might be the stimulation of neoangiogenesis in the area of ischemic myocardium using growth factor genes. Agents attracting greatest interest are FGF (fibroblast growth factor) and VEGF (vascular-endothelial growth factor). A number of methods have been tested to deliver these agents to the area of interest.
Basic research has revealed that potent forms of angiogenic growth factors are the basic FGF (bFGF) and VEGF type A. Most clinical research on therapeutic angiogenesis is done using one of these two growth factors. This is to our knowledge the first clinical study using bicistronic VEGF-A 165/bFGF plasmid.
Patient population will comprise CCS III and CCS IV coronary artery disease patients who cannot be treated with standard revascularization methods. In the course of study we shall attempt to analyze the efficacy of therapeutic plasmid-induced angiogenesis in terms of myocardial perfusion increase and clinical symptom improvement. The feasibility and safety of plasmid delivery method will also be assessed. A percutaneous catheter-based technique (Myo-Star, Johnson & Johnson®) is used for plasmid delivery.
All patients enrolled will receive optimal medical treatment as judged by treating physician. An effort will be made to modify medical therapy during the study course only for clear reasons.
Standard angiography and ventriculography will be performed prior to plasmid injection therapy. Ischemic area of interest will be identified on inclusion by SPECT. Cardiac nuclear magnetic resonance (cNMR) with adenosine will also be performed to assess heart morphology, function and perfusion. Next, injections will be performed according to protocol.
Follow-up visits will be performed at month 4 and month 12 after injection therapy.
A change in myocardial perfusion at rest and on dipyridamole-stress SPECT evaluation after injection therapy will be the primary measure of efficacy. Changes in exercise tolerance will also be monitored along with a number of other efficacy and safety parameters.

开始日期2004-12-01

申办/合作机构

Instytut Kardiologii

[+1]

100 项与 Instytut Kardiologii 相关的临床结果

登录后查看更多信息

0 项与 Instytut Kardiologii 相关的专利（医药）

登录后查看更多信息

533

项与 Instytut Kardiologii 相关的文献（医药）

2025-06-01·American Heart Journal

Pharmaco-invasive strategy and dosing of tenecteplase in STEMI patients 60 to <75 years: An inter-trial comparison of the STREAM-1 and STREAM-2 trials

Article

作者: Averkov, Oleg V ; Van de Werf, Frans ; Ristić, Arsen D ; Bainey, Kevin R ; Zheng, Yinggan ; Lambert, Yves ; Westerhout, Cynthia M ; Temple, Tracy ; Welsh, Robert C ; Armstrong, Paul W ; Sinnaeve, Peter ; Ly, Eric ; Arias-Mendoza, Alexandra ; Bogaerts, Kris

BACKGROUNDPrevious studies indicate a safety risk with full-dose TNK in elderly patients. In a study of patients ≥60 years STREAM-2 (STrategic Reperfusion Early After Myocardial infarction-2), a pharmaco-invasive (PI) strategy with half-dose TNK was similar (in efficacy and safety) to primary percutaneous coronary intervention (PPCI) in ST-elevation myocardial infarction (STEMI) patients presenting <3 hours. While no treatment difference ± 75 years was observed, the role of this half-dose PI strategy in patients <75 years is unknown. In this comparison of STEAM-1 and -2, we analyzed PI strategies with full-dose (STREAM-1) versus half-dose TNK (STREAM-2) to evaluate their relative efficacy and safety in this younger STEMI cohort.METHODSWe evaluated patients 60 to <75 years from STREAM-1 and STREAM-2 receiving PI treatment versus PPCI for their resolution of ST-elevation after fibrinolysis and angiography, primary efficacy composite of 30-day all-cause death, myocardial infarction, heart failure, and shock, and safety events.RESULTSAmong 1103 patients, 327 received a full-dose PI strategy (STREAM-1), 289 a half-dose PI strategy (STREAM-2) and 487 PPCI (338 in STREAM-1; 149 in STREAM-2). Half- compared to full-dose TNK resulted in similar proportions of patients achieving ST resolution ≥50% (71.2% vs 68.7%, P = .519): their ICH risks were 2.1% vs 1.5%, P = .605 respectively). Following angiography, PI patients had nominally better ST resolution ≥50% compared to their PPCI counterpart (STREAM-1: 87.7% vs. 83.2%, P = .120; STREAM-2: 88.2% vs. 81.0%, P = .048) with similar primary composite outcome at 30 days (STREAM-1: 14.4% vs. 16.3%, 0.90 [0.62, 1.31]; STREAM-2: 9.0% vs 8.1%, 1.29 [0.64, 2.61]). Major (non-ICH) bleeding markedly declined in STREAM-2 compared to STREAM-1 in both treatment groups (STREAM-1: 7.1% vs. 6.0%; STREAM-2: 0.3% vs. 0.7%).CONCLUSIONSIn STEMI patients 60 to <75 years presenting within 3 hours of symptoms, half-dose PI treatment appears as efficacious as a full-dose PI strategy with a low systemic bleeding risk. Half-dose PI treatment deserves consideration when timely PPCI is not attainable in this important STEMI sub-group.CLINICALTRIALSGOV REGISTRATION NUMBERSNCT00623623, NCT02777580.

2025-05-01·Current Cardiology Reviews

Dyspnea and Heart Failure: The Role of the Diaphragm

Article

作者: Luiz Ribeiro, Mario ; de Andrade Martins, Wolney ; Lagoeiro Jorge, Antonio Jose ; Correa Nascimento, Pablo Marino ; Nascimento Lourenco, Bernardo ; Villacorta, Humberto ; de Novaes Rocha, Nazareth

Background:Dyspnea and exertional intolerance are the most common clinical manifestations of Heart Failure (HF). One of the possible mechanisms of both symptoms in HF patients is weakness of the inspiratory muscles.Aim:Because the diaphragm is the main inspiratory muscle, this review aimed to investigate the contribution of diaphragmatic function to the genesis of dyspnea or exercise intolerance in HF patients.Methods:Original articles, clinical trials, and cohort or case-control studies published between January 2003 and March 2023 were included. The population, variables, and outcome strategy were the basis of this review, including studies that assessed HF patients, diaphragmatic function, and dyspnea or exercise tolerance. The PubMed/MEDLINE, Embase, and BVS/LILACS databases were searched.Results:A total of 353 articles were identified from electronic databases. After removing duplicate articles and screening based on titles, abstracts, and full texts, nine articles were included in the qualitative synthesis of this review. These studies were quite heterogeneous in their methodologies; however, most, except two, demonstrated an association among diaphragmatic dysfunction, dyspnea, and exertional intolerance in HF patients.Conclusion:Although few studies have assessed the contribution of diaphragmatic function to dyspnea and exertional intolerance in HF individuals, the vast majority of articles included in this review found such an association, especially when diaphragmatic function was assessed using ultrasound.

2025-04-14·Cardiology journal

Short- and long-term outcomes of Impella-protected, high-risk, elective PCI in patients with multivessel coronary disease and low ejection fraction - Polish Impella Registry.

Article

作者: Grygier, Marek ; Pluciński, Mieszko ; Pawłowski, Tomasz ; Fiutowski, Marcin ; Ściborski, Krzysztof ; Pawlik, Artur ; Włodarczak, Szymon ; Romanek, Robert ; Hawranek, Michał ; Zarębiński, Maciej ; Pawluczuk, Piotr ; Gąsecka, Aleksandra ; Włodarczak, Adrian ; Kaczyński, Mateusz ; Kochman, Janusz ; Wojakowski, Wojciech ; Warniełło, Mateusz ; Wańczura, Piotr ; Sacha, Jerzy ; Gurba, Sebastian ; Pietrasik, Arkadiusz ; Protasiewicz, Marcin ; Kuliczkowski, Wiktor ; Kasprzyk, Piotr ; Peruga, Jan ; Lesiak, Maciej ; Bartuś, Stanisław ; Gąsior, Mariusz ; Ciećwierz, Dariusz ; Krajsman, Maciej ; Legutko, Jacek ; Ochała, Andrzej ; Balak, Wojciech ; Burzyńska, Paulina ; Skorupski, Wojciech J ; Kochanowska, Anna ; Kleczyński, Paweł ; Skorupski, Włodzimierz ; Sukiennik, Adam ; Łomiak, Michał ; Konsek, Karolina ; Bielawski, Gabriel ; Witkowski, Adam ; Telichowski, Artur ; Gil, Robert ; Rzeszutko, Łukasz ; Hiczkiewicz, Jarosław ; Reczuch, Krzysztof

BACKGROUNDThe Impella percutaneous mechanical circulatory support device provides improved support in treating patients with high-risk percutaneous coronary interventions (HR-PCI) or in cardiogenic shock. IMPELLA-PL is a multicenter registry developed to share clinical data and experiences using Impella technology in Poland. The retrospective analysis conducted in this study aims to fill the knowledge gap of Impella performance in patients with multivessel coronary artery disease (CAD) and depressed left ventricular ejection fraction (EF) (≤30%) treated with HR-PCI.METHODSRetrospective data were analyzed from patients presenting with multivessel coronary disease and low EF treated with Impella CP collected from 20 Polish interventional cardiology centers registered with IMPELLA-PL to assess the safety and efficacy in short- and long-term clinical outcomes.RESULTSA total of 115 patients with low EF received Impella CP support during HR-PCI. The success rate of Impella supported HR-PCI was high (99.1%) with an average hospital stay of 15.6 ± 10.7 days. The right femoral artery was the most common access (55.7%) followed by the left femoral artery (37.4%). The in-hospital mortality rate was 6.1%, and the all-cause mortality rate at one year was 13.9%.CONCLUSIONSHigh-risk PCI with Impella CP periprocedural support was safe and effective in patients with low EF (≤30%). The all-cause mortality rate (6.1% and 13.9%, respectively, for in-hospital and at 12-months) was comparable with other Impella registries.

100 项与 Instytut Kardiologii 相关的药物交易

登录后查看更多信息

100 项与 Instytut Kardiologii 相关的转化医学

登录后查看更多信息