Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Physiological and Phenotypic Characteristics of Late Survivors of Tetralogy of Fallot Repair Who Are Free From Pulmonary Valve Replacement
- Risk of Lower and Upper Gastrointestinal Bleeding, Transfusions, and Hospitalizations With Complex Antithrombotic Therapy in Elderly Patients
- Monitoring of Monocyte Recruitment in Reperfused Myocardial Infarction With Intramyocardial Hemorrhage and Microvascular Obstruction by Combined Fluorine 19 and Proton Cardiac Magnetic Resonance Imaging
- Ischemic Postconditioning During Primary Percutaneous Coronary Intervention: The Effects of Postconditioning on Myocardial Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction (POST) Randomized Trial
- Purification of Cardiomyocytes From Differentiating Pluripotent Stem Cells Using Molecular Beacons That Target Cardiomyocyte-Specific mRNA
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Physiological and Phenotypic Characteristics of Late Survivors of Tetralogy of Fallot Repair Who Are Free From Pulmonary Valve Replacement
This article provides an account of the long-term survival (>45 years of follow-up) of a large, complete, consecutive cohort of patients with repaired tetralogy of Fallot from a single UK institution. Using the functionality of a unique identifier, the National Health Service number, we were able to locate patients lost to follow-up and to establish whether they were still alive. Their detailed survival data were compared with the age- and sex-matched normal population. Collaboration with specialist centers dealing with adult congenital heart disease nationally provided corresponding incidence data relating to the changing prevalence over time of secondary pulmonary valve replacement after Fallot repair. In the second part of the study, a subset of patients were chosen at random to represent those free from subsequent pulmonary valve replacement. These patients of all ages were assessed thoroughly with conventional noninvasive imaging and functional modalities to characterize their cardiac morphology and function. The currently published literature focuses primarily on patients who need reintervention, and less is formally documented about those who are "well." We also hoped to identify those characteristics that would suggest that the initial surgical repair has proved definitive, that is, patients with normal exercise capacity who are still free from pulmonary valve replacement at 35 years of age. The morphological characteristics of these patients with what seems to be an ideal outcome may serve as guide for today's surgeons and provide a good substrate for further longitudinal studies. See p 1861.
Risk of Lower and Upper Gastrointestinal Bleeding, Transfusions, and Hospitalizations With Complex Antithrombotic Therapy in Elderly Patients
This retrospective cohort analysis of >78 000 US veterans 60 to 99 years of age prescribed complex antithrombotic therapy (aspirin, antiplatelet, and anticoagulant in dual and triple combinations) between October 2002 and September 2009 highlights the real-life risk of upper and lower gastrointestinal bleeding associated with these regimens. The magnitude of risk is quantified as the number needed to harm for upper and lower gastrointestinal bleeding, and by quantifying 2 additional patient-centered outcomes, the need for transfusion and bleeding requiring hospitalization. This study demonstrates the real-world reality of antithrombotic bleeding in a national population of elderly, comorbid, cardiac patients. These data are important to consider when counseling elderly patients regarding the potential risk-benefit of dual and triple antithrombotic regimens, further highlighting the importance of risk stratification and risk modification of elderly patients, and minimizing the time on dual and triple antithrombotic regimens. See p 1869.
Monitoring of Monocyte Recruitment in Reperfused Myocardial Infarction With Intramyocardial Hemorrhage and Microvascular Obstruction by Combined Fluorine 19 and Proton Cardiac Magnetic Resonance Imaging
Timely restoration of obstructed coronary blood flow represents a pivotal component in the management of acute myocardial infarction (MI); however, microvascular obstruction (MVO) occurs in a sizable number of patients with acute MI. Because it deprives tissue of adequate perfusion in MI areas with severe ischemia-reperfusion injury, MVO negates the potential benefits of reperfusion therapy and strongly predicts worse long-term outcomes. In the present study, we visualized experimentally the spatiotemporal distribution of monocytes/macrophages in reperfused MI regions with MVO and intramyocardial hemorrhage in vivo noninvasively through the integration of fluorine-19 magnetic resonance imaging for cell tracking and proton magnetic resonance imaging for MI tissue characterization. Monocyte/macrophage infiltration was significantly impaired in MVO areas defined by magnetic resonance imaging, which was followed by worse pump function in the long term compared with the animals with intramyocardial hemorrhage but no MVO. Monocytes and macrophages are primary innate immune cells that orchestrate delicate MI healing. The attenuated monocyte/macrophage infiltration in MVO regions could result in delayed healing. Post-MI functional outcome is determined not only by MI size but also by the rate and quality of infarct healing. The prolonged exposure of extensive unhealed MI tissue to mechanical deformation forces could lead to greater infarct expansion and promote adverse ventricular remodeling. Therefore, enhanced recruitment of monocytes/macrophages focally in MVO regions may hold potential to improve long-term outcomes by accelerating MI healing. Moreover, 19F/1H magnetic resonance imaging could be clinically translatable to noninvasively identify target patients and longitudinally monitor therapies that optimize MI healing by modulating monocyte/macrophage recruitment. See p 1878.
Ischemic Postconditioning During Primary Percutaneous Coronary Intervention: The Effects of Postconditioning on Myocardial Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction (POST) Randomized Trial
Lethal reperfusion injury accounts for up to 50% of the final size of a myocardial infarct. Ischemic postconditioning is repetitive reversible brief ischemia during the early period of reperfusion after the prolonged ischemic insult. Animal studies have demonstrated that postconditioning has cardioprotective effects comparable to preconditioning. Several small human trials reported that ischemic postconditioning with primary percutaneous coronary intervention (PCI) significantly reduced enzymatic infarct size compared with conventional primary PCI in patients with ST-segment-elevation myocardial infarction. However, the results of studies using magnetic resonance imaging to evaluate the effects of postconditioning on infarct size were inconsistent. Moreover, most studies have not reflected current practice patterns such as thrombus aspiration, predilation before stenting, or use of glycoprotein IIb/IIIa inhibitors. Until now, cardioprotective effects of ischemic postconditioning have not been demonstrated in a large-scale trial. Therefore, in the Effects of Postconditioning on Myocardial Reperfusion in Patients With ST-segment Elevation Myocardial Infarction (POST) trial, we assessed the hypothesis that postconditioning improves myocardial reperfusion after primary PCI. In this prospective, randomized trial, ischemic postconditioning with primary PCI did not improve ST-segment resolution to a greater extent than conventional primary PCI. Moreover, the rates of 30-day major adverse cardiac events were not significantly different between the randomized groups. Cardioprotective effects of postconditioning were not found in any of the prespecified subgroups. Our results indicate that ischemic postconditioning is less likely to improve clinical outcomes in patients with ST-segment-elevation myocardial infarction undergoing primary PCI with current standard practice. See p 1889.
Purification of Cardiomyocytes From Differentiating Pluripotent Stem Cells Using Molecular Beacons That Target Cardiomyocyte-Specific mRNA
One of the major obstacles to the clinical use of human pluripotent stem cell-derived cardiomyocytes is their heterogeneity in culture. Although various methods for differentiating cardiomyocytes from human pluripotent stem cells have been developed, these systems generate mixed populations that include undifferentiated cells and noncardiomyocytes, which can induce tumors or aberrant differentiation. Because there is no specific surface protein for cardiomyocytes, it has been a challenge to purify them. Here, we developed an efficient method for cardiomyocyte purification in which fluorescent molecular beacons were hybridized with cardiomyocyte-specific mRNA in target cardiomyocytes, and these molecular beacon-labeled cardiomyocytes were sorted by fluorescence-activated cell sorting. This novel method yielded ≈98% cardiomyocytes from differentiating human pluripotent stem cells, and these cardiomyocytes displayed all the characteristics of functional cardiomyocytes. Accordingly, these human pluripotent stem cell-derived purified cardiomyocytes will be enormously useful for cell therapy for cardiac disease, cardiac tissue engineering, drug discovery, mechanistic studies, and disease modeling. See p 1897.
- © 2013 American Heart Association, Inc.
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