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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项与 Instytut Kardiologii 相关的文献（医药）

2024-12-31·Annals of Medicine

Predictors for prescription of noninvasive ventilation in the postoperative period of cardiac surgery: a systematic review

Review

作者: Gomes de Jesus, Fernando ; Sarmento dos Santos, Thaísa ; Rega de Oliveira, Juliana ; de Medeiros, Victoria Maria Garcia ; Rosa de Oliveira, Claudia ; Mediano, Mauro Felippe Felix ; Rodrigues Junior, Luiz Fernando ; Gonçalves de Lima, Jéssica

INTRODUCTIONThe postoperative (PO) period after cardiac surgery is associated with the occurrence of respiratory complications. Noninvasive positive pressure ventilation (NIPPV) is largely used as a ventilatory support strategy after the interruption of invasive mechanical ventilation. However, the variables associated with NIPPV prescription are unclear.OBJECTIVETo describe the literature on predictors of NIPPV prescription in patients during the PO period of cardiac surgery.MATERIALS AND METHODSThis systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) platform in December 2021 (CRD42021291973). Bibliographic searches were performed in February 2022 using the PubMed, Lilacs, Embase and PEDro databases, with no year or language restrictions. The Predictors for the prescription of NIPPV were considered among patients who achieved curative NIPPV.RESULTSA total of 349 articles were identified, of which four were deemed eligible and were included in this review. Three studies were retrospective studies, and one was a prospective safety pilot study. The total sample size in each study ranged from 109 to 1657 subjects, with a total of 3456 participants, of whom 283 realized NIPPV. Curative NIPPV was the only form of NIPPV in 75% of the studies, which presented this form of prescription in 5-9% of the total sample size, with men around 65 years old being the majority of the participants receiving curative NIPPV. The main indication for curative NIPPV was acute respiratory failure. Only one study realized prophylactic NIPPV (28% of 32 participants). The main predictors for the prescription of curative NIPPV in the PO period of cardiac surgery observed in this study were elevated body mass index (BMI), hypercapnia, PO lung injury, cardiogenic oedema and pneumonia.CONCLUSIONSBMI and lung alterations related to gas exchange disturbances are major predictors for NIPPV prescription in patients during the PO period of cardiac surgery. The identification of these predictors can benefit clinical decision-making regarding the prescription of NIPPV and help conserve human and material resources, thereby preventing the indiscriminate use of NIPPV.

2024-12-01·Current Problems in Cardiology

Diagnostic and therapeutic practice for Heart Failure with preserved ejection fraction around the world: An international survey

Review

作者: Zieroth, Shelley ; Esperon, Guillermina ; Rosano, Giuseppe M.C. ; Milinkovic, Ivan ; Rakotonoel, Rolland ; Mejia, Maria Isabel Palacio ; Robledo, Gina Gonzalez ; Vishram-Nielsen, Julie ; Mohty, Dania ; Guidetti, Federica ; Ingimarsdóttir, Inga Jóna ; Tham, Novi ; Kida, Keisuke ; Rosano, Giuseppe M C ; Tun, Han Naung ; Mapelli, Massimo ; Barasa, Anders ; Ruschitzka, Frank ; Shchendrygina, Anastasia ; Saldarriaga, Clara ; de Gracia, Sydney Stephanie Goldfeder ; Mewton, Nathan ; Fauvel, Charles ; Rustamova, Yasmin ; Meznar, Anja Zupan ; Einarsson, Hafsteinn ; Tejero, Alberto ; Zaleska-Kociecka, Marta

BACKGROUND AND AIMSThere is a gap in knowledge about implementing diagnostic tools and therapy for heart failure with preserved ejection fraction (HFpEF) in clinical practice. This survey aimed to assess real-world practice in HFpEF diagnosis and treatment in the international medical community.METHODSAn independent academic web-based 29-question survey was designed by a group of heart failure specialists and posted by email and through scientific societies and social networks to a broad community of physicians worldwide.RESULTS1.460 physicians from 95 countries answered the survey, with a mean age of 42.2±10.4 years, 39.4 % females, and 85.1 % were cardiologists. The left ventricular ejection fraction cut-off value selected for HFpEF diagnosis was 50 % for 89 % of participants. The scores for the probability of diagnosis of HFpEF were used only by 47.2 %, and H2FPEF was the most used score (31 %). Natriuretic peptides were used by 87.4 % of participants for the diagnostic workup, while the diastolic stress test was only used by 26.2 %. 54.4 % of participants chose SGLT2 inhibitors as their first drug treatment, followed by diuretics (18.6 %) and ACE inhibitors (8.4 %).CONCLUSIONSIn an international academic survey on HFpEF management, the criteria for screening and diagnosis of HFpEF patients remain aligned with classic international guidelines with a low use of diagnostic scores. SGLT2i is the leading therapeutic drug class used for this heterogeneous patient population. These results raise the need to improve education and awareness on diagnosing and managing HFpEF patients.

2024-11-01·Journal of the American College of Cardiology

Effect of Aficamten on Cardiac Structure and Function in Obstructive Hypertrophic Cardiomyopathy

Article

作者: Merkely, Bela ; Kulac, Ian J ; Meng, Lisa ; Claggett, Brian L ; Abraham, Theodore P ; Michels, Michelle ; Wohltman, Amy ; Coats, Caroline J ; Kupfer, Stuart ; Kwong, Raymond Y ; Kramer, Christopher M. ; Kramer, Christopher M ; Maron, Martin S ; Claggett, Brian L. ; Jacoby, Daniel L. ; Lee, Matthew M.Y. ; Kulac, Ian J. ; Solomon, Scott D. ; Oreziak, Artur ; Cardoso, Rhanderson N ; Lee, Matthew M Y ; Abraham, Theodore P. ; Cardoso, Rhanderson N. ; Kwong, Raymond Y. ; Masri, Ahmad ; Solomon, Scott D ; Olivotto, Iacopo ; Hegde, Sheila M ; Heitner, Stephen B. ; Maron, Martin S. ; Malik, Fady I ; Malik, Fady I. ; Jacoby, Daniel L ; Heitner, Stephen B ; Coats, Caroline J. ; Hegde, Sheila M.

BACKGROUNDObstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) hypertrophy, LV outflow tract obstruction, and left atrial dilation, which can be associated with progressive heart failure, atrial fibrillation, and stroke. Aficamten is a next-in-class cardiac myosin inhibitor that reduces outflow tract obstruction by modulating cardiac contractility, with the potential to reverse pathological remodeling and, in turn, reduce cardiovascular events.OBJECTIVESThis study sought to investigate the effect of aficamten on cardiac remodeling compared with placebo using cardiovascular magnetic resonance (CMR) and its association with key clinical endpoints in the SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) CMR substudy.METHODSSEQUOIA-HCM was a phase 3 double-blind, placebo-controlled trial for adults with symptomatic oHCM who were randomized 1:1 to 24 weeks of aficamten (dose range: 5-20 mg) or placebo. Eligible participants were offered enrollment in the CMR substudy with studies performed at baseline and week 24. Image analysis was performed in a blinded fashion by a core laboratory.RESULTSOf the 282 randomized patients, 57 (20%) participated in the substudy, and of those, 50 (88%) completed both baseline and week 24 CMR. Baseline characteristics of the CMR cohort were similar to the overall study population. Of these 50 patients, 21 received aficamten and 29 received placebo. Relative to placebo, patients receiving aficamten demonstrated significant reductions (Δ least-squares mean) in LV mass index (-15 g/m²; 95% CI: -25 to -6 g/m²; P = 0.001), maximal LV wall thickness (-2.1 mm; 95% CI: -3.1 to -1.1 mm; P < 0.001), left atrial volume index (-13 mL/m²; 95% CI: -19 to -7 mL/m²; P < 0.001), native T1 relaxation time (-37 ms; 95% CI: -69 to -5 ms; P = 0.026), indexed extracellular volume fraction (-3.9 g/m²; 95% CI: -7.0 to -0.9 g/m²; P = 0.014), and indexed myocyte mass (-14 g/m²; 95% CI: -23 to -4 g/m²; P = 0.004), while there were no significant changes in LV chamber volumes, LV replacement fibrosis (late gadolinium enhancement mass -0.7 g; 95% CI: -2.9 to 1.6 g; P = 0.54), or extracellular volume (0.7%; 95% CI: -2.2% to 3.6%; P = 0.61).CONCLUSIONSThe CMR substudy of SEQUOIA-HCM demonstrated that treatment with aficamten relative to placebo for 24 weeks resulted in favorable cardiac remodeling. These changes, particularly with regard to LV mass, wall thickness, and left atrial size, could potentially lead to reduced cardiovascular events including heart failure and atrial fibrillation with longer follow-up. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818).

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