Preliminary Animal and Clinical Experiences Using an Electromechanical Endocardial Mapping Procedure to Distinguish Infarcted From Healthy Myocardium

Kornowski, Ran; Hong, Mun K.; Gepstein, Lior; Goldstein, Steven A.; Ellahham, Samer; Ben‐Haim, Shlomo A.; Leon, Martin B.

doi:10.1161/01.cir.98.11.1116

Cited by 151 publications

(138 citation statements)

References 22 publications

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“…12,29 Moreover, the identical LV anatomic site that was observed to be improved by EMM was consistently observed to be improved by SPECT Tc 99m sestamibi myocardial perfusion imaging as well. Initial experience with catheterbased GTx in the single-blind study referred to above confirmed these findings by demonstrating reproducibility of the SPECT and EMM maps from baseline to post-mock procedure, followed by site-specific improvement in both SPECT and EMM 90 days after the patient crossed over to VEGF2 GTx.…”

Section: Discussionmentioning

confidence: 70%

“…In each of these studies, interpretation of symptomatic outcome in particular was complicated by the lack of a placebo-treated control group. Inclusion of a control group was recently facilitated by the advent of catheter-based GTx, which minimized the ethical dilemma of blinded placebo controls, 7,8,12 whereas a previous 6-patient pilot trial using this approach showed reduction in anginal symptoms and nitroglycerin use in VEGF2 versus placebo patients. This trial was limited because it was a single-blind design in which patients randomized to the control arm underwent a mock procedure (the catheter was advanced to the LV, but no injection was performed).…”

Section: Discussionmentioning

confidence: 99%

“…Serial myocardial isoenzymes (CPK-MB) were measured for the first 24 hours. Serial ECGs and standard transthoracic echocardiograms were performed preoperatively, within 24 hours after the procedure, and at each follow-up visit (weeks 2,4,8,12).…”

Section: Clinical Outcomesmentioning

confidence: 99%

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Phase 1/2 Placebo-Controlled, Double-Blind, Dose-Escalating Trial of Myocardial Vascular Endothelial Growth Factor 2 Gene Transfer by Catheter Delivery in Patients With Chronic Myocardial Ischemia

et al. 2002

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Background — This phase 1/2 study investigated the safety of percutaneous catheter-based gene transfer of naked plasmid DNA encoding for vascular endothelial growth factor 2 (phVEGF2) to left ventricular (LV) myocardium in a prospective, randomized, double-blind, placebo-controlled, dose-escalating study of inoperable patients with class III or IV angina. Methods and Results — A steerable deflectable 8F catheter with a 27-gauge needle at its distal tip was advanced percutaneously to the endocardial surface of the LV in 19 patients (age, 61±2 years) with chronic myocardial ischemia who were not candidates for conventional revascularization. Patients were randomized in a double-blind fashion to receive 6 injections (total volume, 6.0 mL) of placebo or phVEGF2 in doses of 200 μg (n=9), 800 μg (n=9), or 2000 μg (n=1) guided by LV electromechanical (NOGA) mapping with a gene-to-placebo ratio of 2:1. A total of 114 LV injections were delivered and caused no hemodynamic alterations, sustained ventricular arrhythmias, ECG evidence of infarction, or ventricular perforation. End-point analysis at 12 weeks disclosed a statistically significant improvement in Canadian Cardiovascular Society (CCS) angina class in phVEGF2-treated versus placebo-treated patients (−1.3 versus −0.1, P =0.04). Remaining efficacy end points—including change in exercise duration (91.8 versus 3.9 seconds), functional improvement by ≥2 CCS classes (9 of 12 versus 1 of 6), and Seattle Angina Questionnaire data—all showed strong trends favoring efficacy of phVEGF2 versus placebo treatment. Conclusions — This phase 1/2, double-blind, randomized trial provides preliminary data that support safety of phVEGF2 catheter-mediated myocardial gene transfer. The statistically significant reduction in anginal class and strong positive trends for remaining end points suggest that a larger phase 2/3 trial is warranted.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Phase 1/2 Placebo-Controlled, Double-Blind, Dose-Escalating Trial of Myocardial Vascular Endothelial Growth Factor 2 Gene Transfer by Catheter Delivery in Patients With Chronic Myocardial Ischemia

et al. 2002

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“…19 -21 It can be postulated that LELI can be delivered to the myocardium in humans via fiber optics in the catheter of the nonfluoroscopic in vivo navigation and mapping technology 19 currently in use in experimental animals and in humans. 20,21 The LELI energy can also be applied during or after the procedure of balloon angiography by use of a catheter with a central canal bearing a fiber optic, through which the laser energy can be delivered transversely (360°) to the infarcted area. Furthermore, as an adjunct procedure to other, increasingly popular approaches for repairing ischemic myocardium (angioplasty, stenting, grafting, transmyocardial revascularization, etc), the cardioprotective effect of LELI may likewise be beneficial at minimal or no additional risk.…”

Section: Discussionmentioning

confidence: 99%

Low-Energy Laser Irradiation Reduces Formation of Scar Tissue After Myocardial Infarction in Rats and Dogs

et al. 2001

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Background-Low-energy laser irradiation (LELI) has been found to attenuate various biological processes in tissue culture and experimental animal models. The aim of the present study was to investigate the effect of LELI on the formation of scar tissue in experimentally induced chronic infarct in rats and dogs. Methods and Results-Myocardial infarction (MI) was induced in 50 dogs and 26 rats by ligation of the left anterior descending coronary artery. After induction of MI, the laser-irradiated (LI) group received laser irradiation (infrared laser, 803-nm wavelength) epicardially. Control MI-induced non-laser irradiated (NLI) dogs were sham-operated, and laser was not applied. All dogs were euthanized at 5 to 6 weeks after MI. Infarct size was determined by TTC staining and histology. The laser treatment (PϽ0.05) lowered mortality significantly, from 30% to 6.5%, after induction of MI. The infarct size in the LI dogs was reduced significantly (PϽ0.0001) (52%) compared with NLI dogs. Histological observation of the infarct revealed a typical scar tissue in NLI dogs and cellularity in most of the LI dogs. Only 14Ϯ3% of the mitochondria in the cardiomyocytes in the ischemic zone (4 hours after MI) of LI MI-induced rats were severely damaged, compared with 36Ϯ1% in NLI rats. Accordingly, ATP content in that zone was 7.6-fold (significantly) higher in LI than in NLI rats. Conclusions-Our observations indicate that epicardial LELI of rat and dog hearts after chronic MI caused a marked reduction in infarct size, probably due to a cardioprotective effect of the LELI. Key Words: ischemia Ⅲ myocardial infarction Ⅲ antioxidants Ⅲ lasers T he approach to acute myocardial infarction (MI) has moved in the past decade from simple monitoring of coronary events to aggressive interventions in the processes underlying coronary thrombosis. Cardiac repair after infarct is a complex process involving diverse inflammatory components, extracellular matrix remodeling, and responses of the cardiomyocytes to the ischemia. 1,2 The sequential events that take place in the myocardium after occlusion of the left anterior descending coronary artery (LAD) in experimental animals (including dogs) have been well documented. 1,2 After necrosis of the cardiomyocytes and a rather long inflammatory phase, the ischemic zone is subsequently replaced by fibrotic tissue.Many studies have been directed toward the use of drugs, growth factors, and various interventional technologies in reducing myocardial infarct size and improvement of heart function after MI in experimental animals and humans. For example, recombinant adenovirus-mediated transfer of genes encoding antioxidants to the myocardium has been demonstrated to attenuate after ischemic dysfunction in neonatal mice. 3 Novel approaches to enhancing angiogenesis in the ischemic myocardium by introducing growth factors (mainly of the vascular endothelial growth factor family) were adapted and found to have a beneficial effect on patients with severe angina. 4 Low-energy laser irradiation (LELI) has b...

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“…A comparação desta via com a cirúrgica foi posteriormente realizada, em um grupo pequeno de pacientes, revelando resultados similares em relação à eficácia 23 . Outra opção de acesso foi demonstrada com a utilização do sistema de mapeamento eletromecânico tridimensional, o qual fornece a vantagem de permitir a diferenciação entre tecido miocárdico viável e cicatricial, facilitando a injeção precisa no segmentoalvo 24,25 . Neste estudo, foram realizadas injeções transendocárdicas com uso de cateter Myostar (sistema NOGA -Biosense Webster) e acesso vascular percutâneo em cinco pacientes com IAM anterior prévio 20 .…”

Section: Mioblastosunclassified

Terapia celular no tratamento da insuficiência cardíaca isquêmica

Fernandes¹,

Silva²

2007

Rev. Bras. Cardiol. Invasiva

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In this article the authors discuss the state of the art on cell therapy for ischemic heart failure. The principal cell types and their specific characteristics for the treatment of this pathology are presented. DESCRIPTORS:Tissue therapy. Myocardium. Myoblasts. Cell transplantation, methods. Heart failure, congestive. Myocardial ischemia. RESUMONeste artigo, os autores discutem o estado da arte da terapia celular no tratamento da insuficiência cardíaca isquêmica. São apresentados os principais tipos celulares disponíveis e suas particularidades no tratamento desta doença. A s recentes mudanças propostas pelo American College of Cardiology/American Heart Association (ACA/AHA), expostas nas diretrizes para diagnós-tico e tratamento de insuficiência cardíaca 1 , chamam a atenção da comunidade médica para a identificação precoce desta doença. De acordo com tais diretrizes, nova definição foi criada, incluindo pacientes assintomáticos, com ou sem lesão cardíaca estrutural manifesta (classe A e B, respectivamente), porém sob risco de desenvolvimento de insuficiência cardíaca. Apesar de não se desconsiderar a classificação universalmente aceita e utilizada na prática clínica proposta pela New York Heart Association (NYHA), tais mudanças expõem uma preocupação crescente com a identificação precoce dos pacientes em risco. O racional por traz desta estratégia baseia-se no fato de que, uma vez estabelecida, a injúria ventricular torna-se irreversível, fazendo portanto parecer algo tardio o diagnóstico da insuficiência cardíaca já sintomática. Atualmente, as opções terapêuticas disponíveis são voltadas para o controle da hiperativação do sistema neurohumoral, tratamento da etiologia, quando possível, e prevenção da morte súbita (cardioversores-desfibriladores implantáveis), quando indicado. DESCRITORES:Recentemente, a capacidade reparativa cardíaca foi demonstrada em estudos pré-clínicos 2-4 . A demonstração de células de origem extracardíaca, identificadas pela presença de cromossomo Y em pacientes do sexo masculino transplantados a partir de doadoras do sexo feminino, nos leva a questionar o paradigma vigente, o qual se baseia na incapacidade regenerativa do coração e na conseqüente substituição por tecido fibrótico após exposição a injúria miocárdica e morte celular 4 . Talvez, mais adequado seja pensarmos que a higidez do coração, bem como de todo sistema, é resultante de um equilíbrio entre exposição a fatores agressores e capacidade reparativa. Portanto, o dano estrutural resulta do desequilíbrio de tal homeostasia, seja por uma maior exposição à agressão crônica ou aguda (insultos isquêmicos agudos ou crônicos cumulativos), seja por uma redução da reserva reparativa (idade, diabetes) 5-7 .Entretanto, é inegável a ineficácia de eventuais mecanismos naturais de reparo em condições de agressão extrema, como no caso de infarto agudo do miocárdio e, posteriormente à injúria estabelecida, no processo de remodelamento ventricular. Após a perda de cardiomiócitos, seja por insulto isquêmico e resultante necrose, seja por aum...

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Preliminary Animal and Clinical Experiences Using an Electromechanical Endocardial Mapping Procedure to Distinguish Infarcted From Healthy Myocardium

Cited by 151 publications

References 22 publications

Phase 1/2 Placebo-Controlled, Double-Blind, Dose-Escalating Trial of Myocardial Vascular Endothelial Growth Factor 2 Gene Transfer by Catheter Delivery in Patients With Chronic Myocardial Ischemia

Phase 1/2 Placebo-Controlled, Double-Blind, Dose-Escalating Trial of Myocardial Vascular Endothelial Growth Factor 2 Gene Transfer by Catheter Delivery in Patients With Chronic Myocardial Ischemia

Low-Energy Laser Irradiation Reduces Formation of Scar Tissue After Myocardial Infarction in Rats and Dogs

Terapia celular no tratamento da insuficiência cardíaca isquêmica

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