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

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Instytut Kardiologii

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2025-02-01·The American Journal of Cardiology

Cardiac Amyloidosis Screening and Management in Patients With Heart Failure With Preserved Ejection Fraction: An International Survey

Article

作者: Rustamova, Yasmin ; Komarova, Irina ; Sitnikova, Violetta ; Loncar, Goran ; Shchendrygina, Anastasia ; Oerlemans, Marish I F J ; Duval, Antoine Jobbe ; Tokmakova, Mariya ; Giverts, Ilya ; de Gracia, Sydney Goldfeder ; Niederseer, David ; Zaleska-Kociecka, Marta ; Palacio, Maria Isabel ; Kida, Keisuke ; Barasa, Anders ; Garnier-Crussard, Antoine ; Guidetti, Federica ; Saldarriaga, Clara ; Mewton, Nathan ; Mapelli, Massimo ; Suvorov, Alexandr ; Mežnar, Anja Zupan ; Shutov, Michail ; Skouri, Hadi ; Bahouth, Fadel ; Dyachuk, Irina ; Ruschitzka, Frank ; Oerlemans, Marish I.F.J. ; Milinkovic, Ivan

Cardiac amyloidosis (CA) is still an underdiagnosed cause of heart failure (HF) and early disease recognition and timely disease-modifying therapy (DMT) administration translate to better outcomes. We aimed to assess CA screening and management approaches for patients with HF preserved ejection fraction (HFpEF) among physicians worldwide. An independent academic web-based survey was distributed worldwide between May 2023 and July 2023. Overall, 1,460 physicians (61% were men, median age was 42 [34 to 49] years) from 95 countries completed the survey. A total of 2/3 of respondents had experience diagnosing CA and reported having 10% of patients with CA in patients with HFpEF. Systematic screening for CA of all patients with HFpEF was performed by 10% of responders, whereas 24% did not consider the screening. Most responders (39%) used left ventricular hypertrophy as a screening criterion. Serum protein electrophoresis with immunofixation of free light chain and urine protein electrophoresis or cardiac magnetic resonance were selected by half of the responders as a first-line diagnostic tool. The combination of serum protein electrophoresis with immunofixation free light chain, urine protein electrophoresis, and bone scintigraphy was considered by 32% of the participants. CA DMT was available for 48% of the physicians. About 82% of responders would administrate HF to patients with HFpEF with CA, with the most preferable drugs being diuretics, sodium-glucose cotransporter-2 inhibitors, and renin-angiotensin-aldosterone system inhibitors. In conclusion, the results reveal the uncertainties among physicians worldwide regarding the need for CA screening of patients with HFpEF. CA remains a disease with very heterogeneous management, particularly, in the screening and diagnostic workup. The HF community should aim to educate on CA and improve access to DMT.

2025-01-01·The Lancet Diabetes & Endocrinology

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort

Article

作者: Nakai, Kazuki ; Rossi, Gian Paolo ; Araujo-Castro, Marta ; Satoh, Fumitoshi ; Libianto, Renata ; Yang, Shumin ; Wu, Vin-Cent ; Song, Yi ; Hu, Jinbo ; Mulatero, Paolo ; Turcu, Adina F ; Freel, E Marie ; Pintus, Giovanni ; Burrello, Jacopo ; Kline, Gregory ; Uslar, Thomas ; Drake, William M ; Varsani, Chetna ; Li, Nanfang ; Puar, Troy H ; Ladygina, Daria ; Stowasser, Michael ; Yang, Jun ; Williams, Tracy Ann ; Deinum, Jaap ; Adolf, Christian ; Amar, Laurence ; Brown, Morris J ; Naruse, Mitsuhide ; Wu, Xilin ; Nishikawa, Tetsuo ; Hahner, Stefanie ; Asbach, Evelyn ; Ragnarsson, Oskar ; Reincke, Martin ; O'Toole, Samuel Matthew ; Hundemer, Gregory L ; Li, Qifu ; Fardella, Carlos E ; Lacroix, André ; Fuller, Peter J ; Brűdgam, Denise ; Young, William F ; Hong, Namki ; Quinkler, Marcus ; Larose, Stephanie ; Goi, Jessica ; Nayak, Drishya ; Sholinyan, Julieta ; Vaidya, Anand ; Zhu, Qing ; Prejbisz, Aleksander ; Ono, Yoshikiyo ; Kocjan, Tomaz

BACKGROUNDPrimary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response.METHODSAn international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism. Clinical data at baseline and 6-12 months post-treatment were collected from patients with primary aldosteronism who started targeted medical treatment between 2016 and 2021 at 28 participating centres.FINDINGSConsensus was reached for defining complete, partial, or absent biochemical or clinical response. Of 1258 patients (with a mean age of 52 years [SD 11·5] and of whom 610 [48·5%] were female and 648 [51·5%] were male), 1057 (84·0%) had biochemical outcome data (559 [52·9%] had a complete biochemical response). The median daily dose of spironolactone was significantly higher for those with a complete biochemical response than for those without (40 mg [IQR 25-50] vs 25 mg [20-50]; p=0·011). Of the 1248 patients with clinical outcome data, 228 [18·3%] had a complete clinical response whereas 227 (18·2%) had an absent response. Patients with a complete clinical response were more likely than those with partial or absent clinical response to be women (OR 2·099, 95% CI 1·485-2·968; p<0·001), require lower doses of antihypertensive drugs at baseline (0·687, 0·603-0·782; p<0·001), and were less likely to have microalbuminuria or left ventricular hypertrophy (0·584, 0·391-0·873; p=0·009).INTERPRETATIONThe Primary Aldosteronism Medical Treatment Outcome (PAMO) criteria represent an internationally developed outcome standard that can guide clinical practice and research into primary aldosteronism. Efforts to optimise treatment intensity and minimise factors associated with an absent treatment response are needed to improve patient outcomes.FUNDINGNone.TRANSLATIONSFor the Chinese (simple), Chinese (complex), Japanese, Korean, German, French, Spanish, Dutch, Swedish, Slovenian, Polish, Italian and Russian translations of the abstract see Supplementary Materials section.

2025-01-01·EuroIntervention

High-risk percutaneous coronary intervention in patients with reduced left ventricular ejection fraction deemed not suitable for surgical revascularisation. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the ESC Working Group on Cardiovascular Surgery

Review

作者: Tarantini, Giuseppe ; Capodanno, Davide ; Baumbach, Andreas ; Gottardi, Roman ; Lefevre, Thierry ; Alasnag, Mirvat ; Collet, Carlos ; Naber, Christoph ; Mieghem, Nicolas Van ; Colleran, Roisin ; Schäfer, Andreas ; Al-Lamee, Rasha ; Rudolph, Tanja K ; Dudek, Dariusz ; Schoenhoff, Florian S ; Buszman, Piotr P ; Cayla, Guillaume ; Witkowski, Adam ; Giacoppo, Daniele ; Burzotta, Francesco ; Banning, Adrian ; Werner, Nikos ; Thielmann, Matthias ; Stefanini, Giulio ; Czerny, Martin ; Roguin, Ariel ; MacCarthy, Philip

This clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions was developed in association with the European Society of Cardiology Working Group on Cardiovascular Surgery. It aims to define procedural and contemporary technical requirements that may improve the efficacy and safety of percutaneous coronary intervention (PCI), both in the acute phase and at long-term follow-up, in a high-risk cohort of patients on optimal medical therapy when clinical and anatomical high-risk criteria are present that entail unacceptable surgical risks, precluding the feasibility of coronary artery bypass grafting (CABG). This document pertains to patients with surgical contraindication according to the Heart Team, in whom medical therapy has failed (e.g., residual symptoms), and for whom the Heart Team estimates that revascularisation may have a prognostic benefit (e.g., left main, last remaining vessel, multivessel disease with large areas of ischaemia); however, there is a lack of data regarding the size of this patient population. This document aims to guide interventional cardiologists on how to proceed with PCI in such high-risk patients with reduced left ventricular ejection fraction after the decision of the Heart Team is made that CABG - which overall is the guideline-recommended option for revascularisation in these patients - is not an option and that PCI may be beneficial for the patient. Importantly, when a high-risk PCI is planned, a multidisciplinary decision by interventional cardiologists, cardiac surgeons, anaesthetists and non-invasive physicians with expertise in heart failure management and intensive care should be agreed upon after careful consideration of the possible undesirable consequences of PCI, including futility, similar to the approach for structural interventions.

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