Potential Hazards and Technical Considerations Associated With Myocardial Cell Transplantation Protocols for Ischemic Myocardial Syndrome

Cell transplantation has recently emerged as a promising therapeutic approach to ischemic cardiomyopathy syndromes. Clinical studies suggest important benefits, including improved myocardial perfusion and function. The safety profile so far seems to be high overall, although the technique may harbor several adverse effects, such as ventricular arrhythmia, acceleration of atherosclerosis or restenosis, and induction of ischemic events. Multiple factors may affect the safety of cell infusion into the diseased heart, including the mode of delivery, the type of cells injected, compound characterization, and the heart status, function, and arrhythmogenic potential. Also, any adjunctive treatment used to enhance cellular homing and/or transdifferentiation increases the likelihood of unexpected local or systemic toxicity or side effects. In the present review, we discuss the potential hazards of this novel treatment and its relationship to technical considerations

Clinical significance of myocardial involvement in acute idiopathic pericarditis

Background: Acute idiopathic pericarditis (AIP) is frequently accompanied by myocardial involvement (AIPM). Although in acute myocarditis, the myocardial inflammation can lead to life-threatening complications, the outcome of patients with AIPM has been described as good. It remains unclear if a good prognosis of patients with AIPM reflects mild myocardial involvement or good medical management. Methods: A retrospective analysis of life-threatening complications and life-saving interventions in a cohort of 248 consecutive patients admitted to a single medical center between 2006 and 2017 with AIP (n = 169) or AIPM (n = 79). Major adverse cardiac events (MACE) included cardiac tamponade, cardiogenic shock, ventricular tachycardia, pericardiocentesis, pericardiectomy, large pericardial effusion and death. Results: Patients with AIPM were younger than patients with AIP (p < 0.001), and more often had left ventricular dysfunction (31.6% vs. 1.2%, p < 0.001) and less often had large pericardial effusion (1.3% vs. 13.6%, p = 0.002), and MACE (5.1% vs. 14.8%, p = 0.014). Cardiac tamponade occurred in 5.3% of the patients with AIP as opposed to 1.3% of the patients with AIPM (p = 0.176). Severe left ventricular dysfunction with cardiogenic shock occurred exclusively among patients with AIPM but the rate was low (2.5%). Life-saving interventions were used in both groups at comparable rates (2.5% vs. 5.3%, p = 0.510). There were no in-hospital deaths. Conclusions: Myocardial involvement in acute pericarditis is associated with a low rate of severe left ventricular dysfunction and cardiogenic shock and a reduced rate of large pericardial effusion, resulting in a lower rate of MACE. Life-saving interventions were used at comparable rates in patients with and without myocardial involvement having excellent survival rates

Heme Oxygenase-1 Induction Improves Cardiac Function following Myocardial Ischemia by Reducing Oxidative Stress

Background Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation. Methods In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured. Results HO-1 induction lowered release of lactate dehydrogenase (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non-diabetic mice (35±1%vs.41±2, respectively p\u3c0.05). CoPP-treated diabetic animals improved cardiac function (43±2% p\u3c0.01), reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P\u3c0.01, P\u3c0.001, P\u3c0.01 respectively). CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p\u3c0.05). The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p\u3c0.05). CoPP significantly increased the expression levels of pAKT and pGSK3β (p\u3c0.05) in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP\u27s cardioprotective effects. Conclusions HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by the increased levels of pAKT with a concomitant inhibition of pGSK3β leading to preserved mitochondrial membrane potential

Multicenter Evaluation of Edwards SAPIEN Positioning During Transcatheter Aortic Valve Implantation With Correlates for Device Movement During Final Deployment

ObjectivesThis study sought to evaluate the exact location of Edwards SAPIEN (Edwards Lifesciences, Irvine, California) devices in different stages of implantation and to quantify possible operator-independent device movement during final deployment.BackgroundAccurate device positioning during transcatheter aortic valve implantation is crucial in order to achieve optimal results.MethodsThis multicenter study consisted of 68 procedures with reliable pacemaker capture. Device positions were assessed using fluoroscopic images and the C-THV system (Paieon Medical, Rosh Ha'Ayin, Israel).ResultsThe location after implantation was significantly higher than in the final stage of rapid pacing: 16.7 ± 16.3% of device height below the plane of the lower sinus border versus 32.6 ± 13.8%, p < 0.0001. Operator-independent device-center upper movement during final deployment was 2 ± 1.43 mm, range: −1.3 to 4.6 mm. Device movement was asymmetrical, occurring more in the lower part of the device than in its upper part (3.2 ± 1.4 mm vs. 0.75 ± 1.5 mm, p < 0.001), resulting in device shortening. Multivariate analysis revealed that moderate and severe aortic valve calcification had 49% higher upward movement than mild calcification (p = 0.03), and aortic sinus volume was negatively correlated with movement size (r = −0.35, p = 0.005). This movement was independent of device version (SAPIEN vs. SAPIEN XT), procedural access (transfemoral vs. transapical), and interventricular septum width.ConclusionsThe final Edwards SAPIEN position is mostly aortic in relation to the lower sinus border. There is an operator-independent upward movement of the device center during the final stage of implantation. Anticipated upward movement of the device should influence its positioning before final deployment

Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease A feasibility study

AbstractObjectivesWe conducted a pilot study to evaluate the feasibility of transendocardial delivery of autologous bone marrow (ABM) strategy in patients with severe symptomatic chronic myocardial ischemia not amenable to conventional revascularization.BackgroundTransendocardial injection of ABM cells appears to enhance perfusion of ischemic porcine myocardium.MethodsTen patients underwent transendocardial injection of freshly aspirated and filtered unfractionated ABM using left ventricular electromechanical guidance. Twelve injections of 0.2 ml each were successfully delivered into ischemic noninfarcted myocardium pre-identified by single-photon emission computed tomography perfusion imaging.ResultsAutologous bone marrow injection was successful in all patients and was associated with no serious adverse effects; in particular, there was no arrhythmia, evidence of infection, myocardial inflammation, or increased scar formation. Two patients were readmitted for recurrent chest pain. At three months, Canadian Cardiovascular Society angina score significantly improved (3.1 ± 0.3 vs. 2.0 ± 0.94, p = 0.001), as well as stress-induced ischemia occurring within the injected territories (2.1 ± 0.8 vs. 1.6 ± 0.8, p < 0.001). Treadmill exercise duration, available in nine patients, increased, but the change was not significant (391 ± 155 vs. 485 ± 198, p = 0.11).ConclusionsThis study provides preliminary clinical data indicating feasibility of catheter-based transendocardial delivery of ABM to ischemic myocardium

Anti-immunoglobulin-like transcript 3 induced acute myocarditis—A case report

To the best of our knowledge, this is the first published report of anti-immunoglobulin-like transcript 3 (ILT3)-induced myocarditis. A 48-year old female patient with refractory acute myeloid leukemia who was given a single dose of anti-ILT3 monotherapy presented with fever, hypotension, chest pain, and elevated cardiac biomarkers. Systolic bi-ventricular function was in normal limits. The patient was promptly treated with pulse dose steroids with a rapid hemodynamic and clinical improvement and declining levels of cardiac biomarkers. The diagnosis of acute myocarditis was confirmed using cardiac magnetic resonance imaging applying the revised Lake Lewis criteria. While larger-scale data are needed in order to assess the incidence, management and prognosis of anti-ILT-3 induced myocarditis, we believe a high level of suspicion for adverse non-target cardiac effects is required in patients receiving this novel class of drugs

TCT-4 Efficacy and Safety of Concurrent Administration of Clopidogrel-loading (600mg) and Prasugrel-loading (60mg) in Patients with Acute ST-Segment Elevation Myocardial Infarction

Background: Current STEMI guideline recommendations limit the use of prasugrel to clopidogrel-naïve patients. However, in daily clinical practice a considerable proportion of STEMI patients undergoing primary PCI are preloaded with clopidogrel. Whether the use of prasugrel in clopidogrel pretreated STEMI patients is safe remains unknown. Similarly, the efficacy of a combined loading dose regimen has not been evaluated. Methods: Between 1 September 2009 and 15 October 2012, a total of 1,157 STEMI patients were included in the randomized COMFORTABLE AMI trial (NCT 00962416) and 891 STEMI patients in the SPUM ACS registry (NCT 01000701) at 12 centers. Patients were divided into three groups according to type of peri-procedural antiplatelet loading: (1) Clopidogrel and subsequent Prasugrel loading dose [CP], (2) Prasugrel loading dose alone [P] (3) Clopidogrel loading dose alone [C]; 23 patients were excluded because they were not exposed to Clopidogrel and Prasugrel. The primary safety endpoint was the rate of BARC type 3, 4 and 5 bleeding at 30 days. The primary efficacy endpoint was the composite of cardiac death, nonfatal MI and nonfatal stroke at 30 days. Outcomes were analyzed using Cox's Regressions (crude) and multinomial ITPW weighted Cox's Regressions. Results: A total of 2,025 patients were analysed of whom 428 (21.1%) had received CP, 447 (22.1%) patients P alone, and 1,150 (56.8%) patients C alone. The primary safety endpoint was observed among 1.2% of CP, 1.6% of P, and 1.5% of C patients (CP vs C ad. HR 0.99 (0.36-2.72), PC vs P ad. HR 0.73 (0.22-2.41). The primary safety endpoint occurred less frequently among CP (1.9%) compared with C patients (5.0%, adjusted HR 0.47 (0.22-1.00), but with similar frequency among P and C patients (2.9% vs 5.0%, ad. HR 0.68 (0.27-1.73). The net clinical benefit outcome parameter tended to be lower among CP (2.8%) compared with C patients (6.3%, ad. HR 0.56 (0.30-1.05), whereas no significant difference was observed between P and C patients (3.8% vs 6.3%, ad. HR 0.85 (0.39-1.86). Conclusions: Among STEMI patients preloaded with Clopidogrel, the concurrent administration of a Prasugrel loading dose appears safe and potentially more effective than Clopiogrel alone