Background: There is a need for a targeted, comprehensive, minimally invasive myocardial restoration treatment aimed at patients with chronic postinfarction heart failure that can provide a sustained ...effect and be conveniently adopted with transcatheter techniques. Here we evaluated the effectiveness of a platelet-rich plasma hydrogel-based, cell-free therapeutic compound delivered with the aid of a 3-dimensional electromechanical mapping and catheter-based technique (NOGA) in a porcine translational model. Methods: We assessed the feasibility of targeted, minimally invasive transcatheter NOGA-guided injections of the therapeutic compound in myocardial infarction (MI) survivors at 8 weeks post-MI. Results: Animals undergoing NOGA-guided hydrogel injections at 8 weeks post-MI demonstrated a significant improvement of the selected left ventricular parameters at a 12-week follow-up. Compared to nonintervention, the hydrogel-based therapy provided significant improvements in end-diastolic volume (−11.0% ± 11.1% vs 6.3% ± 15.2%; P = .008) and ejection fraction (−9.1% ± 16% vs 12.7% ± 18.6%; P = .009). In the slice closest to the apex, significant differences in scar area were observed; the treatment group demonstrated a smaller mean scar area in the infarcted zone compared with the control group (47.1% ± 7.0% vs 59% ± 8.2%; P = .013) and a smaller mean scar area in the border zone compared with the saline group (31.4% ± 8.3% vs 42.6% ± 9.0%; P = .016). Conclusions: The study implies a translational potential of the hydrogel-based therapy and should trigger clinical trials focused on establishing a restoration therapy that can be integrated into a clinical protocol.
NOGA/MyoStar system uses low magnetic fields and endomyocardial electrical parameters, allowing precise endomyocardial injections of therapeutic agents to ischemic yet viable myocardium which is most ...likely to respond to the treatment. Preclinical and clinical studies have shown that NOGA/MyoStar guided intramyocardial injections are safe, feasible and a minimally invasive way to deliver gene therapy to the heart. Here we describe how to perform electroanatomical mapping and injections to hibernating myocardium in the preclinical studies.
Definiranje razlika između dominantne (D) i nedominantne noge (ND) jedan je od načina utvrđivanja asimetrije između ekstremiteta a samim time i rizika od ozljeđivanja. Cilj ovog istraživanja usmjeren ...je na utvrđivanje razlika u specifičnim unilateralnim testovima kod mladih košarkaša i košarkašica. Uzorak ispitanika činilo je 17 košarkašica (prosječne visine 177,96 ± 6,38 cm; prosječne mase 69,53 ± 8,00 kg i dobi 15,50 ± 0,96 god) i 34 košarkaša (prosječne visine 194,29 ± 7,52 cm; prosječne mase 83,66 ± 9,66 kg i dobi 15,40 ± 1,28 god) kadetske i juniorske reprezentativne selekcije. Korišteni su testovi za procjenu eksplozivne snage donjih ekstremiteta: skok u vis iz koraka odrazom D i ND nogom sa zamahom ruku (S_vis_jedn_L; S_vis_jedn_D), košarkaški dvokorak odrazom D i ND nogom (Dvokorak_L, Dvokorak_D) i Drift protokol koji se sastoji od 5 uzastopnih jednonožnih skokova u mjestu (Drift_L, Drift_D). U testovima S_vis_jedn (p=0,02) i Dvokorak (p=0,03) prikazane su statistički značajne razlike uz pogrešku p˂0,05 kod košarkaša. Kod košarkašica su utvrđene značajne razlike u testu S_vis_jedn (p=0,03). U ostalim testovima nema značajnih razlika između skokova odrazom D i ND nogom. Prikazani rezultati ukazuju na razlike između ekstremiteta te predstavljaju bazu za korekciju plana i programa treninga. Metodologija u ovom radu je jednostavna za provedbu i analizu te je usmjerena na imitaciju situacijskih uvjeta
There is a need for a targeted, comprehensive, minimally invasive myocardial restoration treatment aimed at patients with chronic postinfarction heart failure that can provide a sustained effect and ...be conveniently adopted with transcatheter techniques. Here we evaluated the effectiveness of a platelet-rich plasma hydrogel-based, cell-free therapeutic compound delivered with the aid of a 3-dimensional electromechanical mapping and catheter-based technique (NOGA) in a porcine translational model.
We assessed the feasibility of targeted, minimally invasive transcatheter NOGA-guided injections of the therapeutic compound in myocardial infarction (MI) survivors at 8 weeks post-MI.
Animals undergoing NOGA-guided hydrogel injections at 8 weeks post-MI demonstrated a significant improvement of the selected left ventricular parameters at a 12-week follow-up. Compared to nonintervention, the hydrogel-based therapy provided significant improvements in end-diastolic volume (−11.0% ± 11.1% vs 6.3% ± 15.2%; P = .008) and ejection fraction (−9.1% ± 16% vs 12.7% ± 18.6%; P = .009). In the slice closest to the apex, significant differences in scar area were observed; the treatment group demonstrated a smaller mean scar area in the infarcted zone compared with the control group (47.1% ± 7.0% vs 59% ± 8.2%; P = .013) and a smaller mean scar area in the border zone compared with the saline group (31.4% ± 8.3% vs 42.6% ± 9.0%; P = .016).
The study implies a translational potential of the hydrogel-based therapy and should trigger clinical trials focused on establishing a restoration therapy that can be integrated into a clinical protocol.
Nonobstructive general angioscopy (NOGA) can identify vulnerable plaques in the aortic lumen that serve as potential risk factors for cardiovascular events such as embolism. However, the association ...between computed tomography (CT) images and vulnerable plaques detected on NOGA remains unknown.
We investigated 101 patients (67±11 years; women, 13.8%) who underwent NOGA and contrast-enhanced CT before or after 90 days in our hospital. On CT images, the aortic wall thickness, aortic wall area (AWA), and AWA in the vascular area were measured at the thickest point from the 6th to the 12th thoracic vertebral levels. Furthermore, the association between these measurements and the presence or absence of NOGA-derived aortic plaque ruptures (PRs) at the same vertebral level was assessed. NOGA detected aortic PRs in the aortic lumens at 145 (22.1%) of the 656 vertebral levels. The presence of PRs was significantly associated with greater aortic wall thickness (3.3±1.7 mm versus 2.1±1.2 mm), AWA (1.33±0.68 cm
versus 0.89±0.49 cm
), and AWA in the vascular area (23.2%±9.3% versus 17.2%±7.6%) (
<0.001 for all) on the CT scans compared with the absence of PRs. The frequency of PRs significantly increased as the aortic wall thickness increased. Notably, a few NOGA-derived PRs were detected on CT in near-normal intima.
The presence of NOGA-derived PRs was strongly associated with increased aortic wall thickness, AWA, and AWA in the vascular area, measured using CT. NOGA can detect PRs in the intima that appear almost normal on CT scans.
Stabilization of aortic vulnerable plaques has not been fully elucidated. Non-obstructive general angioscopy (NOGA) is a novel method for the detailed evaluation of atheromatous plaques in the aortic ...intimal wall. A 57-year-old man presenting with acute myocardial infarction underwent percutaneous coronary intervention (PCI). NOGA was performed for the evaluation of aortic atherosclerosis, and vulnerable puff-chandelier plaques in the aortic arch were identified. After a strictly controlled low-density lipoprotein cholesterol lowering therapy with a strong statin for 8 months after the primary PCI, NOGA revealed stabilized aortic plaques in the same lesions. Therefore, NOGA may be helpful in evaluating the effects of lipid-lowering therapy on aortic plaque stabilization.
Based on recent success in using modified RNA in clinical applications, we tested the safety, feasibility, and efficacy of direct delivery of citrate-saline-formulated mRNA into an hibernating ...ischemic heart muscle using an electromechanical mapping and injection catheter system (NOGA/Myostar) in a porcine chronic myocardial ischemia model. Chronic ischemia was induced in domestic pigs (
= 24) using a bottleneck stent placed in the left anterior descending coronary artery. Low (1 mg) and high (7.5 mg) doses of citrate-saline-formulated vascular endothelial growth factor (VEGF)-A
mRNA were administered in the study. LacZ mRNA and citrate-saline buffer were used as controls. Ten intramyocardial injections (200 μL each) of the mRNAs or citrate-saline buffer were given endovascularly into the hibernating ischemic myocardium using the NOGA catheter. Positron emission tomography
O-radiowater imaging was performed 7 days after the induction of ischemia and 28 days after the mRNA delivery to measure quantitative myocardial blood perfusion. Coronary angiography, left ventricular function measurements, and clinical chemistry were obtained at each time point. Thirty-five days after the mRNA transfers, pigs were sacrificed, and infarct size and general histology were analyzed. LacZ mRNA pigs were sacrificed 24 h after the transduction. Citrate-saline-formulated mRNA delivery into the ischemic myocardium with endovascular injection catheter did not lead to meaningful transduction with the translation of VEGF-A
, nor therapeutic effects in the heart. VEGF-A
mRNA showed no statistically significant improvements in left ventricular ejection fraction (LVEF), cardiac output, myocardial perfusion, infarct size, collateral growth, or capillary area in the study groups. However, there was a trend in the high-dose group toward an improved LVEF and cardiac output at rest. No significant adverse effects were observed. In conclusion, the NOGA/Myostar injection catheter system is ineffective in delivering citrate-saline-formulated mRNAs into the heart muscle with the doses and methods used in a porcine chronic myocardial ischemia model.
Atrial fibrillation (AF) is an independent risk factor for stroke and systemic embolism. Cardiogenic and aortogenic emboli are causes of stroke or systemic embolism. Non-obstructive general ...angioscopy (NOGA) can be used to diagnose aortic intimal findings, including thrombi and atherosclerotic plaques, but little is known about NOGA-derived aortic intimal findings in patients with AF. This study focused on aortic intimal findings in patients with AF and evaluated the association between AF and aortic thrombi detected using NOGA. We enrolled 283 consecutive patients with coronary artery disease who underwent NOGA of the aorta between January 2017 and August 2022. Aortic intimal findings were screened using NOGA after coronary arteriography. The patients were divided into two groups according to their AF history (AF, n = 50 and non-AF, n = 233). Patients in the AF group were older than those in the non-AF group. Sex, body mass index, and coronary risk factors were not significantly different between the two groups. In the NOGA findings, the presence of intense yellow plaques and ruptured plaques was not significantly different between the two groups. Aortic thrombi were more frequent in the AF group than in the non-AF group (92.0 vs. 71.6%, p < 0.001). Multivariate logistic regression found that AF was independently associated with aortic thrombi (odds ratio 3.87 95% CI 1.28–11.6, p = 0.016). The presence of aortic thrombi observed using NOGA was associated with AF in patients with coronary artery disease. The roles of aortic thrombi as well as cardiogenic embolism may require clarification.
Well (2020) is an installation by Israeli artists Noga Or Yam and Faina Feigin. It investigates the story of an underground passage in Tel Aviv designed by a British Mandate-era Jewish architect. ...Starting from this building, the artists’ archival research leads them to the story of a water source which does not figure in the architect’s plan. While the story of the well is unearthed, so is one about the tense relations between the Jewish architect and the Palestinian orange merchant who inhabited the site before 1948. By restaging a hypothetical archive, Well reminds us of the problems inherent in narrative formation and erasure in the context of the Palestinian–Israeli conflict. Noga Or Yam also examined space and water in an earlier work, Black Soldier, White Soldier (2018): with the background sound of water drilling in southern Israel, urban photographic landscapes of Palestinian rooftops covered with water tanks are projected onto the walls. Water, either concealed or lacking, emerges in both works as a vehicle for unearthing a historical narrative that counters the official one. This research article reflects on contemporary art’s engagement with the formation of history, and how such engagement shapes the identity of present-day art in postcolonial realities.
We have previously shown that distal anterior wall ischemia/reperfusion induces gene expression changes in the proximal anterior myocardial area, involving genes responsible for cardiac remodeling. ...Here we investigated the molecular signals of the ischemia non-affected remote lateral and posterior regions and present gene expression profiles of the entire left ventricle by using our novel and straightforward method of 2D and 3D image reconstruction. Five or 24h after repetitive 10min ischemia/reperfusion without subsequent infarction, pig hearts were explanted and myocardial samples from 52 equally distributed locations of the left ventricle were collected. Expressional changes of seven genes of interest (HIF-1α; caspase-3, transcription factor GATA4; myocyte enhancer factor 2C /MEF2c/; hexokinase 2 /HK2/; clusterin /CLU/ and excision repair cross-complementation group 4 /ERCC4/) were measured by qPCR. 2D and 3D gene expression maps were constructed by projecting the fold changes on the NOGA anatomical mapping coordinates. Caspase-3, GATA4, HK2, CLU, and ERCC4 were up-regulated region-specifically in the ischemic zone at 5 h post ischemia/reperfusion injury. Overexpression of GATA4, clusterin and ERCC4 persisted after 24 h. HK2 showed strong up-regulation in the ischemic zone and down-regulation in remote areas at 5 h, and was severely reduced in all heart regions at 24 h. These results indicate a quick onset of regulation of apoptosis-related genes, which is partially reversed in the late phase of ischemia/reperfusion cardioprotection, and highlight variations between ischemic and unaffected myocardium over time. The NOGA 2D and 3D construction system is an attractive method to visualize expressional variations in the myocardium.