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Synopsis Stem cell regenerative therapies hold promise for treating diseases across the spectrum of medicine. Recent clinical trials have confirmed the safety of stem cell delivery to the heart with promising but variable results. While significant progress has been made in the preclinical stages, the clinical application of cardiac cell therapy is limited by technical challenges, including inability to isolate a pure population of cardiac-specific progenitors capable of robust engraftment and regeneration, lack of appropriate pre-clinical animal models, uncertainty about the best mode of delivery, paucity of adequate imaging modalities, and lack of knowledge about the fate of transplanted cells. The inability of transplanted cells to structurally and functionally integrate into the host myocardium may pose arrhythmogenic risk to patients. This is in part dependent on the type of cell transplanted, where the expression of gap junctions such as connexin-43 is essential not only for electromechanical integration, but has also been found to be protective against electrical instability post-transplant. Additionally, certain methods of cell delivery, such as intramyocardial injection, carry a higher rate of arrhythmias. Other potential contributors to the arrhythmogenicity of cell transplantation include re-entrant pathways due to heterogeneity in conduction velocities between graft and host as well as graft automaticity. In this paper, we discuss the arrhythmogenic potential of cell delivery to the heart.

A recent meta-analysis suggested that the use of rosiglitazone increases the risk of myocardial infarction (MI) in patients with type 2 diabetes mellitus. It is unclear whether this is a class effect of thiazolidinediones (TZD). We did a meta-analysis to evaluate cardiovascular outcomes with the use of pioglitazone. Randomized, controlled trials in which pioglitazone was compared with placebo or other hypoglycemic agents were considered for analysis. Studies were included if the data for MI were available. Studies were identified with use of relevant search words in Medline, Pubmed, EMBASE, CINAHL, and Cochrane databases. Data abstraction was done by 2 individual authors using a standardized protocol. The relative risk across all study groups was computed by the Mantel-Haenszel method, and interstudy heterogeneity was assessed by the chi method. All results were computed according to 95% confidence intervals. Five trials (N = 9965) met the inclusion criteria for analysis. The relative risk for MI was 0.86 (0.69-1.07; P = 0.17). The relative risks for stroke and revascularization were 0.79 (0.61-1.02; P = 0.07) and 0.40 (0.13-1.23; P = 0.11), respectively. Pioglitazone does not increase the risk for MI and may decrease the risk for stroke and revascularization.

Despite major advances in percutaneous coronary intervention (PCI) techniques, the current guidelines recommend against elective PCI at hospitals without on-site cardiac surgery backup. Nonetheless, an increasing number of hospitals without on-site cardiac surgery in the United States have developed programs for elective PCI. Studies evaluating outcome in this setting have yielded mixed results, leaving the question unanswered. Hence, a meta-analysis comparing outcomes of nonemergent PCI in hospitals with and without on-site surgical backup was performed. A systematic review of literature identified four studies involving 6817 patients. Three clinical end points were extracted from each study and included in-hospital death, myocardial infarction, and the need for emergency coronary artery bypass grafting. The studies were homogenous for each outcome studied. Therefore, the combined relative risks (RRs) across all the studies and the 95% confidence intervals (CIs) were computed using the Mantel-Haenszel fixed-effect model. A two-sided alpha error less than 0.05 was considered to be statistically significant. Compared with facilities with on-site surgical backup, the risk of in-hospital death (RR, 2.7; CI, 0.6-12.9; P = 0.18), nonfatal myocardial infarction (RR, 1.3; CI, 0.7- 2.2; P = 0.29), and need of emergent coronary artery bypass grafting (RR, 0.46; CI, 0.06- 3.1; P = 0.43) was similar in those lacking on-site surgical backup. The present meta-analysis suggests that there is no difference in the outcome with regard to risk of nonfatal myocardial infarction, need for emergency coronary artery bypass grafting, and the risk of death in patients undergoing elective PCI in hospitals with and without on-site cardiac surgery backup.

In CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events. However, due to the low positive predictive value, routine genetic testing cannot be recommended at present.

Regional right ventricular (RV) dysfunction (RRVD) is an echocardiographic feature in acute pulmonary embolism (PE), primarily reported in patients with moderate-to-severe RV dysfunction. This study investigated the clinical importance of RRVD by assessing its relationship with clot burden and biomarkers. We identified consecutive patients admitted to the emergency department between 1999 and 2014 who underwent computed tomographic angiography, echocardiography, and biomarker testing (troponin and NT-proBNP) for suspected acute PE. RRVD was defined as normal excursion of the apex contrasting with hypokinesis of the mid-free wall segment. RV assessment included measurements of ventricular dimensions, fractional area change, free-wall longitudinal strain and tricuspid annular plane systolic excursion. Clot burden was assessed using the modified Miller score. Of 82 patients identified, 51 had acute PE (mean age 66 ± 17 years, 43% male). No patient had RV myocardial infarction. RRVD was present in 41% of PEs and absent in all patients without PE. Among patients with PE, 86% of patients with RRVD had central or multi-lobar PE. Patients with RRVD had higher prevalence of moderate-to-severe RV dilation (81 vs. 30%, p < 0.01) and dysfunction (86 vs. 23%, p < 0.01). There was a strong trend for higher troponin level in PE patients with RRVD (38 vs. 13% in PE patients without RRVD, p = 0.08), while there was no significant difference for NT-proBNP (67 vs. 73%, p = 0.88). RRVD showed good concordance between readers (87%). RRVD is associated with an increased clot burden in acute PE and is more prevalent among patients with moderate-to-severe RV enlargement and dysfunction.