Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells.

Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury, but preclinical studies in large animal models are required to determine optimal cell preparation and delivery strategies to maximize functional benefits and to evaluate safety. Here, we utilized a porcine model of acute myocardial infarction (MI) to investigate the functional impact of intramyocardial transplantation of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells, in combination with a 3D fibrin patch loaded with insulin growth factor (IGF)-encapsulated microspheres. hiPSC-derived cardiomyocytes integrated into host myocardium and generated organized sarcomeric structures, and endothelial and smooth muscle cells contributed to host vasculature. Trilineage cell transplantation significantly improved left ventricular function, myocardial metabolism, and arteriole density, while reducing infarct size, ventricular wall stress, and apoptosis without inducing ventricular arrhythmias. These findings in a large animal MI model highlight the potential of utilizing hiPSC-derived cells for cardiac repair.

Risk of new-onset atrial fibrillation and stroke after radiofrequency ablation of isolated, typical atrial flutter.

BACKGROUND: Radiofrequency ablation (RFA) is considered a curative procedure for typical atrial flutter (AFL); however, patients remain at risk for developing new atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to determine the incidence and predictors of new-onset AF and stroke after RFA of isolated AFL in a multicenter cohort. METHODS: The study included 315 consecutive patients who underwent successful RFA of isolated, typical AFL from 2006 to 2013 at 4 community and teaching hospitals. Patients with any history of AF prior to RFA were excluded. RESULTS: During 2.5 ± 1.8 years of follow-up after RFA, 80 patients (25%) developed new AF. In multivariate analysis, after adjusting for baseline medical therapy, obstructive sleep apnea and left atrial enlargement were independently associated with the development of new AF. Presence of a cardiac implantable electronic device (CIED) was associated with a 3.6-fold (95% confidence interval 1.9-6.6, P <.0001) increase in the likelihood of AF detection. New AF was detected in 48% of patients with CIED and 35% of those who underwent Holter ECG vs 19% of those with clinical follow-up only (P <.0001). Anticoagulation was stopped in 58% patients an average of 3.3 ± 4.8 months after RFA. Stroke occurred in 3 patients (1%) during the follow-up period. CONCLUSION: New AF occurs in ≥25% of patients after RFA of isolated typical AFL, but stroke is relatively rare. Obstructive sleep apnea and left atrial enlargement are risk factors for AF. The presence of a CIED significantly enhances the likelihood of detecting new AF, demonstrating the importance of arrhythmia surveillance after RFA of AFL.

Long-term follow-up of older patients with Mobitz type I second degree atrioventricular block.

OBJECTIVE: To examine the long-term survival of older patients with Mobitz I second degree atrioventricular (AV) block. DESIGN: Retrospective cohort study. Propensity score adjustment for requiring a cardiac implantable electronic device (CIED) was performed. Multivariable Cox regression analysis was used. SETTING: Tertiary care referral centre. PATIENTS: We examined 299 older patients (age >45 years) with Mobitz I second degree AV block on ECG at the Minneapolis Veterans Affairs Medical Center from 1992 to 2010. MAIN OUTCOME MEASURE: Survival. RESULTS: The average age of patients was 75±9 years; 99% were male; 59% had coronary heart disease; 44% had heart failure. 141 (47%) patients required CIED, of which 17 were implantable cardioverter-defibrillators (ICDs). CIEDs were implanted a median of 110 days after the ECG for symptomatic bradycardia, high-degree AV block or prevention of sudden cardiac death. Patients with CIED had greater cardiac co-morbidity than those without CIED. After a median 3.3 years of follow-up (range 3 days to 19 years), 190 (64%) patients died. Patients with CIED had longer survival than those without CIED (p=0.001). In propensity-adjusted multivariable Cox regression analysis, CIED implantation was associated with a 46% reduction in mortality (HR 0.54, 95% CI 0.35 to 0.82; p=0.004). Excluding 17 patients with ICDs did not alter the results. CONCLUSIONS: In this retrospective cohort study of older male patients with Mobitz I AV block on ECG, CIED implantation was associated with longer survival.

Imaging in catheter ablation for atrial fibrillation: enhancing the clinician's view.

Catheter ablation is an effective treatment for symptomatic atrial fibrillation. A thorough understanding of the left atrium anatomy and its adjacent structures is critical for the success of the procedure and for avoiding complications. Pre-procedural imaging aims at determining left atrial size, anatomy, and function and is also used to rule out an atrial thrombus. During the procedure, while fluoroscopy remains the gold standard imaging modality for guiding transseptal catheterization and catheter ablation, numerous other imaging modalities have been developed to improve 3D navigation and ablation. Finally, post-operative imaging intends to monitor heart function and to search for potential complications like pulmonary vein stenosis or the rare but dramatic atrio-oesophageal fistula. This review discusses the relative merits of all imaging modalities available in the context of catheter ablation of atrial fibrillation.

Mast cell tryptase may modulate endothelial cell phenotype in healing myocardial infarcts.

Mast cells and macrophages infiltrate healing myocardial infarcts and may play an important role in regulating fibrous tissue deposition and extracellular matrix remodelling. This study examined the time-course of macrophage and mast cell accumulation in healing infarcts and studied the histological characteristics and protease expression profile of mast cells in a canine model of experimental infarction. Although macrophages were more numerous than mast cells in infarct granulation tissue, macrophage density decreased during maturation of the scar, whereas mast cell numbers remained persistently elevated. During the inflammatory phase of infarction, newly recruited leucocytes infiltrated the injured myocardium and appeared to be clustered in close proximity to degranulating cardiac mast cells. During the proliferative phase of healing, mast cells had decreased granular content and were localized close to infarct neovessels. In contrast, macrophages showed no selective localization. Mast cells in healing canine infarcts were alcian blue/safranin-positive cells that expressed both tryptase and chymase. In order to explain the pro-inflammatory and angiogenic actions of tryptase--the major secretory protein of mast cells--its effects on endothelial chemokine expression were examined. Chemokines are chemotactic cytokines that play an important role in leucocyte trafficking and angiogenesis and are highly induced in infarcts. Tryptase, a proteinase-activated receptor (PAR)-2 agonist, induced endothelial expression of the angiogenic chemokines CCL2/MCP-1 and CXCL8/IL-8, but not the angiostatic chemokine CXCL10/IP-10. Endothelial PAR-2 stimulation with the agonist peptide SLIGKV induced a similar chemokine expression profile. Mast cell tryptase may exert its angiogenic effects in part through selective stimulation of angiogenic chemokines.

Acute Congestive Heart Failure and Tumor Necrosis Factor Alpha.

Congestive heart failure is prevalent in the elderly; recurrent hospital admissions for acute deterioration is a major health care problem. We examined tumor necrosis factor alpha levels in 31 congestive heart failure patients who were admitted to the hospital due to acute cardiogenic pulmonary edema. Blood samples were taken within 24 hours of admission and at the time of discharge after recovery. Tumor necrosis factor alpha levels were also measured in 10 stable congestive heart failure outpatients and 16 healthy controls. Tumor necrosis factor alpha level at admission was higher than at time of discharge (4.6Â+/-1.9 vs. 3.4Â+/-1.1 (rg/mL, p is less than 0.02). Mean tumor necrosis factor alpha level of stable congestive heart failure outpatient was 2.6Â+/-0.7 rg/mL healthy controls had significantly lower tumor necrosis factor alpha levels (1.7Â+/-0.7 rg/mL) than congestive heart failure patients (p is less than 0.01). tumor necrosis factor alpha levels were highest among acute congestive heart failure patients. Elevated tumor necrosis factor alpha appears to be related to the exacerbation of congestive heart failure and may be a marker for deterioration. (c) 2000 by CVRR, Inc.